記述言語：日本語   掲載種別：研究論文（学術雑誌）  

Pancreatic ductal adenocarcinoma(PDAC)is lethal malignancy with abundant stroma. Cancer-associated fibroblasts (CAFs) exist in the PDAC stroma and contribute to progression of malignant transformation, treatment resistance, and recurrence. However, effective treatment to control PDAC stroma has not been established. We have developed tumor suppressor gene p53-armed oncolytic adenovirus(OBP-702), and have clarified therapeutic effects on PDAC cells. In this study, we investigate the therapeutic effect of OBP-702 on PDAC CAF.

PubMed

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記述言語：日本語   出版者・発行元：(株)癌と化学療法社  

膵臓癌は豊富な間質を有する予後不良な悪性疾患である。膵臓癌の間質環境にはがん関連線維芽細胞(CAFs)が存在し,悪性化の進展,治療抵抗性や再発に寄与している。しかし膵臓癌間質を制御する有効な治療法は未だ確立していない。著者らは,癌抑制遺伝子p53を搭載した腫瘍融解アデノウイルス製剤(OBP-702)を開発し,膵臓癌に対する治療効果を明らかにしてきた。本研究では,膵臓癌CAFに対するOBP-702の治療効果を検討する。(著者抄録)

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

PURPOSE: It remains unknown whether stroke volume variation (SVV), pulse pressure variation (PPV), and dynamic arterial elastance (Eadyn) are suitable for monitoring fluid management during thoracoscopic esophagectomy (TE) in the prone position with one-lung ventilation and artificial pneumothorax. Our study aimed to evaluate the accuracy of SVV, PVV, and Eadyn in predicting the fluid responsiveness in these patients. METHODS: We recruited 24 patients who had undergone TE. Patients with a mean arterial blood pressure ≤ 65 mmHg received a 200-ml bolus of 6% hydroxyethyl starch over 10 min. Fluid responders showed the stroke volume index ≥ 15% 5 min after the fluid bolus. Receiver operating characteristic (ROC) curves were generated and area under the ROC curve (AUROC) was calculated. RESULTS: We obtained 61 fluid bolus data points, of which 20 were responders and 41 were non-responders. The median SVV before the fluid bolus in responders was significantly higher than that in non-responders (18% [interquartile range (IQR) 13-21] vs. 12% [IQR 8-15], P = 0.001). Eadyn was significantly lower in responders than in non-responders (0.55 [IQR 0.45-0.78] vs. 0.91 [IQR 0.67-1.00], P < 0.001). There was no difference in the PPV between the groups. The AUROC was 0.76 for SVV (95% confidence interval [CI] 0.62-0.89, P = 0.001), 0.56 for PPV (95% CI 0.41-0.71, P = 0.44), and 0.82 for Eadyn (95% CI 0.69-0.95, P < 0.001). CONCLUSIONS: SVV and Eadyn are reliable parameters for predicting fluid responsiveness in patients undergoing TE.

DOI： 10.1007/s00540-023-03256-7

PubMed

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その他リンク： https://link.springer.com/article/10.1007/s00540-023-03256-7/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

The programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) axis plays a crucial role in tumor immunosuppression, while the cancer-associated fibroblasts (CAFs) have various tumor-promoting functions. To determine the advantage of immunotherapy, the relationship between the cancer cells and the CAFs was evaluated in terms of the PD-1/PD-L1 axis. Overall, 140 cases of esophageal cancer underwent an immunohistochemical analysis of the PD-L1 expression and its association with the expression of the α smooth muscle actin, fibroblast activation protein, CD8, and forkhead box P3 (FoxP3) positive cells. The relationship between the cancer cells and the CAFs was evaluated in vitro, and the effect of the anti-PD-L1 antibody was evaluated using a syngeneic mouse model. A survival analysis showed that the PD-L1+ CAF group had worse survival than the PD-L1- group. In vitro and in vivo, direct interaction between the cancer cells and the CAFs showed a mutually upregulated PD-L1 expression. In vivo, the anti-PD-L1 antibody increased the number of dead CAFs and cancer cells, resulting in increased CD8+ T cells and decreased FoxP3+ regulatory T cells. We demonstrated that the PD-L1-expressing CAFs lead to poor outcomes in patients with esophageal cancer. The cancer cells and the CAFs mutually enhanced the PD-L1 expression and induced tumor immunosuppression. Therefore, the PD-L1-expressing CAFs may be good targets for cancer therapy, inhibiting tumor progression and improving host tumor immunity.

DOI： 10.1007/s00262-023-03531-2

PubMed

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The involvement of neutrophil extracellular traps (NETs) in cancer metastasis is being clarified, but the relationship between intrahepatic cholangiocarcinoma (iCCA) and NETs remains unclear. The presence of NETs was verified by multiple fluorescence staining in clinically resected specimens of iCCA. Human neutrophils were co-cultured with iCCA cells to observe NET induction and changes in cellular characteristics. Binding of platelets to iCCA cells and its mechanism were also examined, and their effects on NETs were analyzed in vitro and in in vivo mouse models. NETs were present in the tumor periphery of resected iCCAs. NETs promoted the motility and migration ability of iCCA cells in vitro. Although iCCA cells alone had a weak NET-inducing ability, the binding of platelets to iCCA cells via P-selectin promoted NET induction. Based on these results, antiplatelet drugs were applied to these cocultures in vitro and inhibited the binding of platelets to iCCA cells and the induction of NETs. Fluorescently labeled iCCA cells were injected into the spleen of mice, resulting in the formation of liver micrometastases coexisting with platelets and NETs. These mice were treated with dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor, which dramatically reduced micrometastases. These results suggest that potent antiplatelet therapy prevents micrometastases of iCCA cells by inhibiting platelet activation and NET production, and it may contribute to a novel therapeutic strategy.

DOI： 10.1016/j.canlet.2023.216260

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: In Japan, about 6% of esophageal cancers are adenocarcinomas, although most of them arise from Barrett's epithelium. Adenocarcinoma arising from heterotopic gastric mucosa (HGM) is very rare. Due to its rarity, there is no unified view on its treatment strategy and prognosis. CASE PRESENTATION: A 57-year-old man presented with a protruding lesion in the cervicothoracic esophagus that was detected by an upper gastrointestinal series at a medical checkup. Esophagoscopy revealed a 30 mm Type 1 tumor circumferentially surrounded by widespread HGM. Computed tomography (CT) and fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed no metastasis or invasion of the surrounding organs. We diagnosed the lesion as cT2N0M0 cStageIIB [Union for International Cancer Control (UICC) 8th Ed] cancer and performed subtotal esophagectomy with three-field lymph node dissection. The tumor was determined to be a well-differentiated adenocarcinoma arising from HGM, with deep invasion of the submucosa. The patient underwent no adjuvant therapy and has currently survived without any evidence of recurrence for 15 months. CONCLUSIONS: Although the treatment for adenocarcinoma arising from HGM is basically the same as that for squamous cell carcinoma (SCC) of the esophagus, it is important to determine the treatment strategy based on the characteristics of the adenocarcinoma arising from HGM.

DOI： 10.1186/s40792-023-01707-7

PubMed

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記述言語：英語  

Salvage surgery for esophageal cancer after definitive chemoradiotherapy (dCRT) is effective, but it is associated with a high rate of perioperative complications. The indications for robot-assisted minimally invasive esophagectomy (RAMIE) are expanding. However, there are few reports of salvage RAMIE. A 73-year-old man was referred to our hospital for residual esophageal cancer with a mediastinal fistula after dCRT. The perioperative diagnosis was T3N1M0-Stage III, and the salvage RAMIE was performed. Although the dissection was difficult due to fibrosis caused by dCRT and the esophageal mediastinal fistula, RAMIE was performed safely with no complications. Multiple features of RAMIE contributed to stable surgery. The monopolar dissection is effective for hard scar tissue caused by CRT and inflammation.

DOI： 10.1111/ases.13155

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Surgical resection of esophageal cancer is frequently performed to achieve a complete cure. However, the postoperative recurrence rate is 36.8-42.5%, leading to poor prognosis. Radiation therapy has been used to treat recurrences; solitary recurrence has been proposed as a prognostic factor for radiation therapy, though its significance is unclear. 18F-fluorodeoxyglucose positron emission tomography is a highly accurate diagnostic modality for esophageal cancer. This retrospective study aimed to analyze the outcomes of solitary postoperative recurrences of esophageal squamous cell carcinoma diagnosed with 18F-fluorodeoxyglucose positron emission tomography and treated with definitive radiation therapy. METHODS: We examined 27 patients who underwent definitive radiation therapy for single or multiple postoperative recurrences of esophageal squamous cell carcinoma between May 2015 and April 2021. 18F-fluorodeoxyglucose positron emission tomography/computed tomography was performed within 3 months before the commencement of radiation therapy. Kaplan-Meier, univariate, and multivariate analyses were performed to examine the overall survival and identify potential prognostic factors. RESULTS: The 1-, 2-, and 3-year overall survival rates were 85.2%, 62.6%, and 47.3%, respectively, and solitary recurrence was the only significant factor associated with overall survival (P = 0.003). The 1-, 2-, and 3-year overall survival rates in patients with solitary recurrence were 91.7%, 80.2%, and 80.2%, respectively, and in patients with multiple recurrences they were 80.0%, 50.3%, and 25.1%, respectively. Multivariate analysis also showed solitary recurrence as a significant factor for overall survival. CONCLUSIONS: When diagnosed with 18F-fluorodeoxyglucose positron emission tomography/computed tomography, solitary recurrence appears to have a more favorable prognosis than multiple recurrences.

DOI： 10.1007/s10388-023-01000-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The prognosis of esophageal cancer (EC) with organ invasion is extremely poor. In these cases, definitive chemoradiotherapy (CRT) followed by salvage surgery can be planned; however, the issue of high morbidity and mortality rates persists. Herein, we report the long-term survival of a patient with EC and T4 invasion who underwent a modified two-stage operation after definitive CRT. CASE PRESENTATION: A 60-year-old male presented with type 2 upper thoracic EC with tracheal invasion. First, definitive CRT was performed, which resulted in tumor shrinkage and improvement in the tracheal invasion. However, an esophagotracheal fistula subsequently developed, and the patient was treated with fasting and antibiotics. Although the fistula recovered, severe esophageal stenoses made oral intake impossible. To improve quality of life and cure the EC, a modified two-stage operation was planned. In the first surgery, an esophageal bypass was performed using a gastric tube with cervical and abdominal lymph node dissections. After confirming improved nutritional status and absence of distant metastasis, the second surgery was performed with subtotal esophagectomy, mediastinal lymph node dissection, and tracheobronchial coverage of the fistula. The patient discharged without major complications after radical resection and has been recurrence-free for 5 years since the start of treatment. CONCLUSION: A standard curative strategy could be difficult for EC with T4 invasion due to differences in the invaded organs, presence of complications, and patient condition. Therefore, patient-tailored treatment plans are needed, including a modified two-stage operation.

DOI： 10.1186/s40792-023-01692-x

PubMed

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: This study aimed to determine whether nutritional education, from the preoperative to postoperative period, and nutritional management designed to improve nutritional status alone, could improve patients' health-related self-management and nutritional management skills during the postoperative period. METHODS: We evaluated 101 hospitalised patients with oesophageal cancer who underwent surgery between 2015 and 2016 and received perioperative nutritional education (PERIO-N). The control group included 52 patients who underwent surgery between 2014 and 2015 and were supported only by normal interventions according to the Enhanced Recovery After Surgery protocol. The PERIO-N group paid specific attention to nutrition risk screening, nutrition assessment, nutrition monitoring, and lifestyle education. RESULTS: The patients in the PERIO-N group were 1.8 times more likely to be able to consume food orally than the control group (p=0.010). In the PERIO-N group, 50.5% of the patients could orally consume food, 42.6% received a combination of oral and enteral nutrition, and 6.9% only underwent enteral nutrition. In comparison, in the control group, 28.8% of the patients could orally consume food, 53.8% received a combination of oral and enteral nutrition, and 17.3% were only administered enteral nutrition (p=0.004). In addition, patients in the PERIO-N group were discharged at a 1.5 times higher rate than those in the control group (p=0.027). The readmission rate for malnutrition within 3 months was 4% in the PERIO group (5.4% for home discharge only) and 5.8% in the control group (10.5% for home discharge only) (p=0.61). CONCLUSION: This study found that perioperative nutrition education in patients who underwent oesophageal cancer surgery led to increase in the amount of oral intake at discharge. Moreover, the group that received nutrition education did not have an increased probability of hospitalisation due to the risk of malnutrition within 3 months after discharge.

DOI： 10.31557/APJCP.2023.24.6.2037

PubMed

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Esophageal cancer is one of the most aggressive tumors, and the outcome remains poor. One contributing factor is the presence of tumors that are less responsive or have increased malignancy when treated with conventional chemotherapy, radiotherapy, or a combination of these. Cancer-associated fibroblasts (CAFs) play an important role in the tumor microenvironment. Focusing on conventional cancer therapies, we investigated how CAFs acquire therapeutic resistance and how they affect tumor malignancy. In this study, low-dose chemotherapy or radiotherapy-induced normal fibroblasts showed enhanced activation of CAFs markers, fibroblast activation protein, and α-smooth muscle actin, indicating the acquisition of malignancy in fibroblasts. Furthermore, CAFs activated by radiotherapy induce phenotypic changes in cancer cells, increasing their proliferation, migration, and invasion abilities. In in vivo peritoneal dissemination models, the total number of tumor nodules in the abdominal cavity was significantly increased in the co-inoculation group of cancer cells and resistant fibroblasts compared to that in the co-inoculation group of cancer cells and normal fibroblasts. In conclusion, we demonstrated that conventional cancer therapy causes anti-therapeutic effects via the activation of fibroblasts, resulting in CAFs. It is important to select or combine modalities of esophageal cancer treatment, recognizing that inappropriate radiotherapy and chemotherapy can lead to resistance in CAF-rich tumors.

DOI： 10.3390/cancers15112971

PubMed

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記述言語：日本語   出版者・発行元：金原出版(株)  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

This retrospective study aimed to investigate the validity of a 30-sec chair stand test (CS-30) as a simple test to assess exercise tolerance and clinical outcomes in 53 Japanese patients with esophageal cancer. There was a strong correlation between the results of CS-30 and the 6-min walk test (6MWT), the gold standard for assessing exercise tolerance (r=0.759). Furthermore, fewer patients whose CS-30 score was greater than 16 (the cutoff value defined based on 6MWT) experienced pneumonia in their postoperative course. These results suggest that exercise tolerance could be assessed using CS-30, and its cutoff value may be useful in predicting postoperative pneumonia risk.

DOI： 10.18926/AMO/65149

PubMed

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(株)南江堂  

＜文献概要＞近年,自動縫合器を使用した臓器の切離,および再建が普及している.一方で,従来行われていた手縫い吻合と異なり,各臓器において使用の際のピットフォールが存在すると思われる.今回,当科で行っている食道および胃切除術時のサーキュラーステープラおよびリニアステープラの使い方およびそのピットフォールを説明する.

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00393&link_issn=&doc_id=20230414270006&doc_link_id=10.15106%2Fj_geka85_345&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_geka85_345&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The use of virtual reality for simulations plays an important role in the initial training for robotic surgery. This randomized controlled trial aimed to investigate the impact of educational video on the performance of robotic simulation. Participants were randomized into the intervention (video) group that received an educational video and robotic simulation training or the control group that received only simulation training. The da Vinci® Skills Simulator was used for the basic course, including nine drills. The primary endpoint was the overall score of nine drills in cycles 1-10. Secondary endpoints included overall, efficiency, and penalty scores in each cycle, as well as the learning curves evaluated by the cumulative sum (CUSUM) analysis. Between September 2021 and May 2022, 20 participants were assigned to the video (n = 10) and control (n = 10) groups. The video group had significantly higher overall scores than the control group (90.8 vs. 72.4, P < 0.001). Significantly higher overall scores and lower penalty scores were confirmed, mainly in cycles 1-5. CUSUM analysis revealed a shorter learning curve in the video group. The present study demonstrated that educational video training can be effective in improving the performance of robotic simulation training and shortening the learning curve.

DOI： 10.1007/s11701-023-01556-4

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記述言語：日本語   出版者・発行元：(一社)日本マイクロサージャリー学会  

症例は44歳女性で、胸部下部食道癌の右肺下葉浸潤により食道肺瘻を生じ、繰り返す肺炎のため頸部食道離断術および食道瘻、胃瘻造設がなされた。腫瘍切除に伴い右肺下葉切除後の気管支断端および下行大動脈留置ステントが露出予定となったため、再建目的に当科紹介となった。ステント露出部は広背筋弁で被覆し、右肺下葉気管支断端は縫合切離速度自動調整機能付き自動縫合器Signiaステープリングシステムで切離された後に、断端部を十分な面積の前鋸筋弁で被覆した。術後2日目に造影CTにて胸腔内所見および移植組織の血流が問題ないことを確認し、術後23日目には転院となった。移植組織は全生着し、術後のCTでは気管支断端とステント露出部は筋弁で適切に被覆されており、術後経過は良好であった。

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担当区分：責任著者   記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cancer-associated fibroblasts (CAFs) are a critical component of the tumor microenvironment and play a central role in tumor progression. Previously, we reported that CAFs might induce tumor immunosuppression via interleukin-6 (IL-6) and promote tumor progression by blocking local IL-6 in the tumor microenvironment with neutralizing antibody. Here, we explore whether an anti-IL-6 receptor antibody could be used as systemic therapy to treat cancer, and further investigate the mechanisms by which IL-6 induces tumor immunosuppression. In clinical samples, IL-6 expression was significantly correlated with α-smooth muscle actin expression, and high IL-6 cases showed tumor immunosuppression. Multivariate analysis showed that IL-6 expression was an independent prognostic factor. In vitro, IL-6 contributed to cell proliferation and differentiation into CAFs. Moreover, IL-6 increased hypoxia-inducible factor 1α (HIF1α) expression and induced tumor immunosuppression by enhancing glucose uptake by cancer cells and competing for glucose with immune cells. MR16-1, a rodent analog of anti-IL-6 receptor antibody, overcame CAF-induced immunosuppression and suppressed tumor progression in immunocompetent murine cancer models by regulating HIF1α activation in vivo. The anti-IL-6 receptor antibody could be systemically employed to overcome tumor immunosuppression and improve patient survival with various cancers. Furthermore, the tumor immunosuppression was suggested to be induced by IL-6 via HIF1α activation.

DOI： 10.1007/s00262-023-03378-7

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

症例は66歳の男性で,Fabry病による慢性腎不全に対して維持透析中であった.右肺癌に対して肺部分切除を施行後膿胸の増悪のため,ICUで全身管理中に小腸穿孔,汎発性腹膜炎を来し当科紹介となった.原因不明の小腸穿孔として緊急手術を施行した.術中所見では,Treitz靱帯より約200cmの部位での小腸穿孔,腸間膜側から腹腔内への穿破を認め,腹腔内汚染は著明であった.小腸を約20cm切除し,洗浄ドレナージ,回腸人工肛門造設を行った.切除標本では粘膜面に多発潰瘍を認め,その1ヶ所に穿孔を認めた.病理組織学的検査では,サイトメガロウイルス(cytomegalovirus;以下,CMVと略記)免疫染色検査で潰瘍部に一致して陽性細胞が検出され,CMV感染による小腸穿孔と診断した.CMV感染による消化管穿孔はまれであるが,免疫不全患者ではその存在を常に念頭に置く必要があり,早期診断・治療が重要である.(著者抄録)

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

症例は66歳の男性で,Fabry病による慢性腎不全に対して維持透析中であった.右肺癌に対して肺部分切除を施行後膿胸の増悪のため,ICUで全身管理中に小腸穿孔,汎発性腹膜炎を来し当科紹介となった.原因不明の小腸穿孔として緊急手術を施行した.術中所見では,Treitz靱帯より約200cmの部位での小腸穿孔,腸間膜側から腹腔内への穿破を認め,腹腔内汚染は著明であった.小腸を約20cm切除し,洗浄ドレナージ,回腸人工肛門造設を行った.切除標本では粘膜面に多発潰瘍を認め,その1ヶ所に穿孔を認めた.病理組織学的検査では,サイトメガロウイルス(cytomegalovirus;以下,CMVと略記)免疫染色検査で潰瘍部に一致して陽性細胞が検出され,CMV感染による小腸穿孔と診断した.CMV感染による消化管穿孔はまれであるが,免疫不全患者ではその存在を常に念頭に置く必要があり,早期診断・治療が重要である.(著者抄録)

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その他リンク： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01117&link_issn=&doc_id=20230308270006&doc_link_id=10.5833%2Fjjgs.2022.0036&url=https%3A%2F%2Fdoi.org%2F10.5833%2Fjjgs.2022.0036&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: It has recently been recognized that preoperative sarcopenia contributes to postoperative complications and overall survival in gastric cancer (GC). However, few studies have investigated the relationship between postoperative skeletal muscle loss (SML) and survival in GC, despite the inevitability of body weight loss after gastrectomy in most GC patients. Herein, we studied the impact of postoperative SML on GC prognosis. PATIENTS AND METHODS: A total of 370 patients with GC who underwent curative gastrectomy were retrospectively evaluated in this study. Postoperative SML was assessed on computed tomography (CT) images taken before surgery and 1 year after surgery. The impact of postoperative SML on survival was evaluated. RESULTS: Postoperative severe SML was significantly associated with presence of comorbidities, higher tumor stage, higher postoperative complication rate and longer hospital stay. Univariate and multivariate analyses of prognostic factors for overall survival revealed that SML was an independent indicator of poor prognosis, along with age, tumor stage, preoperative sarcopenia, and operation time (hazard ratio, 2.65; 95% confidence interval, 1.68-4.20, p<0.0001). There was a strong association of severe postoperative SML with decreased overall survival in patients with preoperative sarcopenia. CONCLUSION: To improve the prognosis of GC patients after surgery, it is important to prevent postoperative SML as well as preoperative sarcopenia. Perioperative multimodal interventions including nutritional counseling, oral nutritional supplements, and exercise are required to prevent SML after gastrectomy.

DOI： 10.21873/anticanres.16153

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記述言語：日本語   出版者・発行元：日本外科代謝栄養学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Cancer-associated fibroblasts (CAFs) reportedly enhance the progression of gastrointestinal surgery; however, the role of CAFs in ampullary carcinomas remains poorly examined. This study aimed to investigate the effect of CAFs on the survival of patients with ampullary carcinoma. MATERIALS AND METHODS: A retrospective analysis of 67 patients who underwent pancreatoduodenectomy between January 2000 and December 2021 was performed. CAFs were defined as spindle-shaped cells that expressed α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP). The impact of CAFs on survival, including recurrence-free (RFS) and disease-specific survival (DSS), as well as prognostic factors associated with survival, was analyzed. RESULTS: The high-α-SMA group had significantly worse 5-year RFS (47.6% vs. 82.2%, p = 0.003) and 5-year DSS (67.5% vs. 93.3%, p = 0.01) than the low-α-SMA group. RFS (p = 0.04) and DSS (p = 0.02) in the high-FAP group were significantly worse than those in the low-FAP group. Multivariable analyses found that high α-SMA expression was an independent predictor of RFS [hazard ratio (HR): 3.68; 95% confidence intervals (CI): 1.21-12.4; p = 0.02] and DSS (HR: 8.54; 95% CI: 1.21-170; p = 0.03). CONCLUSIONS: CAFs, particularly α-SMA, can be useful predictors of survival in patients undergoing radical resection for ampullary carcinomas.

DOI： 10.3389/fonc.2023.1072106

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIMS: Ulcerative colitis (UC) can develop colitis-associated colorectal neoplasm (CAN). Adenine-to-inosine RNA editing, which is regulated by adenosine deaminase acting on RNA (ADAR), induces the posttranscriptional modification of critical oncogenes, including antizyme inhibitor 1 (AZIN1), leading to colorectal carcinogenesis. Therefore, we hypothesized that ADAR1 might be involved in the development of CAN in UC. METHODS: We systematically analyzed a cohort of 139 UC cases (40 acute phase, 73 remission phase, 26 CAN). The degree of inflammation was evaluated using the Mayo endoscopic score (MES). RESULTS: The type 1 IFN-related inflammation pathway was upregulated in the rectum of active UC, rectum of UC-CAN, and tumor site of UC-CAN patients. ADAR1 expression was upregulated in the entire colon of CAN cases, while it was down-regulated in non-CAN MES0 cases. ADAR1 expression in the rectum predicted the development of CAN better than p53 or β-catenin, with an area under the curve of 0.93. The high expression of ADAR1 and high AZIN1 RNA editing in UC was triggered by type 1 IFN stimulation from UC-specific microbiomes, such as Fusobacterium in vitro analyses. The induction of AZIN1 RNA editing by ADAR1, whose expression is promoted by Fusobacterium, may induce carcinogenesis in UC. CONCLUSIONS: The risk of CAN can be evaluated by assessing ADAR1 expression in the rectum of MES0 UC patients, freeing UC patients from unnecessary colonoscopy and reducing their physical burden. RNA editing may be involved in UC carcinogenesis, and may be used to facilitate the prevention and treatment of CAN in UC.

DOI： 10.1093/ecco-jcc/jjac186

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本臨床栄養代謝学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pancreatic ductal adenocarcinoma (PDAC) is often refractory to treatment with gemcitabine (GEM) and immune checkpoint inhibitors including anti-programmed cell death ligand 1 (PD-L1) antibody. However, the precise relationship between GEM-resistant PDAC and development of an immunosuppressive tumor microenvironment (TME) remains unclear. In this study, we investigated the immunosuppressive TME in parental and GEM-resistant PDAC tumors and assessed the therapeutic potential of combination therapy with the telomerase-specific replication-competent oncolytic adenovirus OBP-702, which induces tumor suppressor p53 protein and PD-L1 blockade against GEM-resistant PDAC tumors. Mouse PDAC cells (PAN02) and human PDAC cells (MIA PaCa-2, BxPC-3) were used to establish GEM-resistant PDAC lines. PD-L1 expression and the immunosuppressive TME were analyzed using parental and GEM-resistant PDAC cells. A cytokine array was used to investigate the underlying mechanism of immunosuppressive TME induction by GEM-resistant PAN02 cells. The GEM-resistant PAN02 tumor model was used to evaluate the antitumor effect of combination therapy with OBP-702 and PD-L1 blockade. GEM-resistant PDAC cells exhibited higher PD-L1 expression and produced higher granulocyte-macrophage colony-stimulating factor (GM-CSF) levels compared with parental cells, inducing an immunosuppressive TME and the accumulation of myeloid-derived suppressor cells (MDSCs). OBP-702 significantly inhibited GEM-resistant PAN02 tumor growth by suppressing GM-CSF-mediated MDSC accumulation. Moreover, combination treatment with OBP-702 significantly enhanced the antitumor efficacy of PD-L1 blockade against GEM-resistant PAN02 tumors. The present results suggest that combination therapy involving OBP-702 and PD-L1 blockade is a promising antitumor strategy for treating GEM-resistant PDAC with GM-CSF-induced immunosuppressive TME formation.

DOI： 10.1007/s00262-022-03334-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cancer-associated fibroblasts (CAFs) play a significant role in tumor progression within the tumor microenvironment. Previously, we used near-infrared photoimmunotherapy (NIR-PIT), a next-generation cancer cell-targeted phototherapy, to establish CAF-targeted NIR-PIT. In this study, we investigated whether dual-targeted NIR-PIT, targeting cancer cells and CAFs, could be a therapeutic strategy. A total of 132 cases of esophageal cancer were analyzed for epidermal growth factor receptor (EGFR), human epidermal growth factor 2 (HER2), and fibroblast activation protein (FAP) expression using immunohistochemistry. Human esophageal cancer cells and CAFs were co-cultured and treated with single- or dual-targeted NIR-PIT in vitro. These cells were co-inoculated into BALB/c-nu/nu mice and the tumors were treated with single-targeted NIR-PIT or dual-targeted NIR-PIT in vivo. Survival analysis showed FAP- or EGFR-high patients had worse survival than patients with low expression of FAP or EGFR (log-rank, P < 0.001 and P = 0.074, respectively), while no difference was observed in HER2 status. In vitro, dual (EGFR/FAP)-targeted NIR-PIT induced specific therapeutic effects in cancer cells and CAFs along with suppressing tumor growth in vivo, whereas single-targeted NIR-PIT did not show any significance. Moreover, these experiments demonstrated that dual-targeted NIR-PIT could treat cancer cells and CAFs simultaneously with a single NIR light irradiation. We demonstrated the relationship between EGFR/FAP expression and prognosis of patients with esophageal cancer and the stronger therapeutic effect of dual-targeted NIR-PIT than single-targeted NIR-PIT in experimental models. Thus, dual-targeted NIR-PIT might be a promising therapeutic strategy for cancer treatment.

DOI： 10.1038/s41598-022-24313-3

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記述言語：日本語   出版者・発行元：(一社)日本肥満学会  

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記述言語：日本語   出版者・発行元：(一社)日本肥満学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1245/s10434-022-12645-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The standard treatment for locally advanced esophageal cancer is preoperative chemotherapy with cisplatin and 5-fluorouracil (CF), followed by surgery. Although docetaxel plus cisplatin and 5-fluorouracil (DCF) has been reported to have favorable outcomes, no study has compared its therapeutic efficacy to that of standard treatment. This study aimed to compare the therapeutic effects of CF and DCF in the real world by matching patient background factors using propensity scores. METHODS: We retrospectively reviewed the data of 237 patients with esophageal squamous cell carcinoma who underwent esophagectomy between January 2008 and December 2018. Patients were divided into two groups based on the preoperative chemotherapy regimens of CF (79 patients) or DCF (158 patients), and 49 matched pairs were finally analyzed using propensity score matching. Short- and long-term outcomes were compared between groups. RESULTS: After matching, although no significant differences in survival were observed among the groups, patients receiving DCF showed a significantly high histological response (P < 0.001). Subgroup analyses demonstrated that DCF therapy had better overall survival (P = 0.046) and relapse-free survival (P = 0.010) among pathological T3 and T4 cases. Whereas, adverse effects of chemotherapy were more frequent in the DCF group. CONCLUSIONS: Patients receiving DCF had higher pathological response and better survival than those receiving CF, especially in pathological T3 and T4 cases matched using propensity scores. Thus, the DCF regimen might be an effective treatment for locally advanced esophageal cancer. However, the adverse side effects of chemotherapy remain high and should be handled appropriately.

DOI： 10.1007/s10388-022-00934-5

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記述言語：日本語   出版者・発行元：(一社)日本胸部外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本胸部外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本胸部外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科感染症学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本胸部外科学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Body weight loss (BWL) and skeletal muscle loss (SML) are inevitable after gastrectomy for gastric cancer (GC) and can decrease patients' quality of life (QOL) and survival. OBJECTIVE: The aim of this retrospective study was to evaluate the effect of perioperative and post-discharge patient participation in continuous nutritional counseling (CNC) on post-gastrectomy BWL and SML. METHODS: Ninety-three patients with GC who underwent curative gastrectomy between March 2018 and July 2019 were analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 49) or patient-participation CNC (CNC group, n = 44) after gastrectomy. Differences between percentage BWL (%BWL), percentage SML (%SML), and nutrition-related blood parameters between the preoperative values and those at 12 months after surgery were compared between the groups. RESULTS: Compared with the control group, %BWL was significantly lower in the CNC group at 1 month (-6.2 ± 2.5% vs. -7.9 ± 3.3%, p = 0.005), 6 months (-7.8 ± 6.6% vs. -12.3 ± 6.4%, p = 0.001) and 12 months (-7.9 ± 7.6% vs. -13.2 ± 8.2%, p = 0.002), and %SML was significantly lower in the CNC group at 12 months (-5.3 ± 10.3% vs. -12.8 ± 12%, p = 0.002). Regarding nutrition-related blood parameters, change in total cholesterol was significantly lower in the CNC group than the control group at 12 months after surgery (p = 0.02). Multivariate analysis identified no CNC as an independent risk factor for severe BWL (p = 0.001) and SML (p = 0.006) at 12 months after surgery. CONCLUSIONS: Following gastrectomy, patient-participation CNC prevented postoperative BWL and SML after surgery. These results support the induction of such a CNC program in these patients.

DOI： 10.1245/s10434-022-12572-3

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(株)へるす出版  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To investigate if early exercise can help prevent skeletal muscle loss and improve the clinical outcomes of esophageal cancer patients receiving preoperative neoadjuvant chemotherapy (NAC). METHODS: This was a single-center, retrospective observational cohort study of 110 patients with advanced esophageal cancer. We analyzed the effect of early exercise on the risk of skeletal muscle loss (defined as > 2.98%) during NAC and the subsequent clinical outcomes. Patients in the early exercise group (n = 71) started exercise therapy 8 days earlier than those the late exercise group (n = 39). RESULTS: The median age of the patients was 65.4 years, the mean BMI was 21.1 kg/m2, and 92 (84%) of the 110 patients were men. Skeletal muscle loss occurred in 34% and 67% of the early and late exercise groups, respectively (p < 0.001). There was a lower risk of surgical site infection in the early exercise group (1% vs 16%, p = 0.021). Multivariate analysis revealed that early exercise reduced the risk of skeletal muscle loss (OR = 0.25, 95% CI 0.09-0.65, p = 0.006). CONCLUSIONS: Our results suggest that early exercise reduces the risk of both skeletal muscle loss during NAC and subsequent surgical site infection in patients with esophageal cancer.

DOI： 10.1007/s00595-021-02449-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Verrucous carcinoma of the esophagus (VCE) is a rare tumor that is difficult to diagnose. In most cases, biopsies show nonspecific inflammatory and hyperkeratotic changes and do not show malignant findings. Most VCEs are slowly growing, locally advanced tumors with few metastases. Treatments for VCE are the same as for normal esophageal cancer, involving combined chemotherapy, surgical resection, and radiation therapy. However, it has been reported that VCE has a poor response to radiation or chemoradiotherapy (CRT). A case of VCE with complete response (CR) after CRT is presented. CASE PRESENTATION: A 70-year-old man was found to have white, irregular esophageal mucosa 4 years earlier. He had been followed up as an outpatient as having candidal esophagitis. However, his tumor grew gradually, and biopsy was performed by endoscopic mucosal resection (EMR). He was finally diagnosed with VCE. He had no metastases to distant organs, but some lymph node metastases were suspected. The tumor invaded his left bronchus. The esophagostomy and gastrostomy were constructed as emergent procedures. The patient then underwent definitive CRT. 4 weeks after the end of CRT, two-stage esophagectomy was performed. First, he underwent esophagectomy with thoracic lymph node dissection. A latissimus dorsi flap was patched to the bronchus after primary suture of the hole. 6 weeks later, reconstruction of the gastric tube was performed through the antethoracic route. The pathological findings showed CR to CRT, with no proliferative cancer cells in the specimen. The patient has had no recurrence for three and half years after the resection. CONCLUSIONS: We presented a locally advanced VCE that achieved CR to CRT. In cases that have some difficulty for local resection, CRT might be an appropriate treatment for VCE.

DOI： 10.1186/s40792-022-01486-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND/AIM: Postoperative body weight loss (BWL) and skeletal muscle loss (SML) after gastrectomy are associated with a decline in quality of life and worse longterm prognosis in gastric cancer (GC) patients. This study aimed to evaluate the efficacy of amino acids nutrition on BWL and SML in the early period following gastrectomy. PATIENTS AND METHODS: The parameters of body composition were measured by bioelectrical impedance analysis in the patients undergoing radical gastrectomy for GC and analyzed retrospectively. Patients received either peripheral parenteral nutrition (PPN) of 4.3% glucose fluid with regular diet (control group, n=43) or PPN of 7.5% glucose fluid containing amino acids plus oral nutritional supplement (ONS) rich in protein with regular diet (amino acids group, n=40) following gastrectomy. The percentages of BWL and SML from preoperative values to those at 7 days and 1 month after surgery were compared between the two groups. RESULTS: The %BWL and %SML at 7 days after surgery were significantly lower in the amino acids group than those in the control group (%BWL, -2.4±1.7% vs. -4.2±1.8%; p<0.0001, %SML, -4.1±3.8 vs. -6.5±3.8; p=0.006). Moreover, the %BWL at 1 month after surgery was significantly lower in the amino acids group compared to that in the control group (- 4.6±2.9% vs. -6.1±2.6%; p=0.01); however, the %SML was similar between the two groups. The hematological nutritional parameters were similar between the two groups. CONCLUSION: Amino acids nutrition by PPN and ONS following gastrectomy prevented postoperative BWL and SML in the early period after surgery in GC patients.

DOI： 10.21873/anticanres.15852

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are associated with the establishment and progression of peritoneal metastasis. This study investigated the efficacy of replicative oncolytic adenovirus-mediated p53 gene therapy (OBP-702) against CAFs and peritoneal metastasis of gastric cancer (GC). Higher CAF expression in the primary tumor was associated with poor prognosis of GC, and higher CAF expression was also observed with peritoneal metastasis in immunohistochemical analysis of clinical samples. And, we found transcriptional alteration of p53 in CAFs relative to normal gastric fibroblasts (NGFs). CAFs increased the secretion of cancer-promoting cytokines, including interleukin-6, and gained resistance to chemotherapy relative to NGFs. OBP-702 showed cytotoxicity to both GC cells and CAFs but not to NGFs. Overexpression of wild-type p53 by OBP-702 infection caused apoptosis and autophagy of CAFs and decreased the secretion of cancer-promoting cytokines by CAFs. Combination therapy using intraperitoneal administration of OBP-702 and paclitaxel synergistically inhibited the tumor growth of peritoneal metastases and decreased CAFs in peritoneal metastases. OBP-702, a replicative oncolytic adenovirus-mediated p53 gene therapy, offers a promising biological therapeutic strategy for peritoneal metastasis, modulating CAFs in addition to achieving tumor lysis.

DOI： 10.1016/j.omto.2022.04.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Conventional imaging techniques are available for clinical identification of tumor sites. However, detecting metastatic tumor cells that are spreading from primary tumor sites using conventional imaging techniques remains difficult. In contrast, fluorescence-based labeling systems are useful tools for detecting tumor cells at the single-cell level in cancer research. The ability to detect fluorescent-labeled tumor cells enables investigations of the biodistribution of tumor cells for the diagnosis and treatment of cancer. For example, the presence of fluorescent tumor cells in the peripheral blood of cancer patients is a predictive biomarker for early diagnosis of distant metastasis. The elimination of fluorescent tumor cells without damaging normal tissues is ideal for minimally invasive treatment of cancer. To capture fluorescent tumor cells within normal tissues, however, tumor-specific activated target molecules are needed. This review focuses on recent advances in tumor-targeted fluorescence labeling systems, in which indirect reporter labeling using tumor-specific promoters is applied to fluorescence labeling of tumor cells for the diagnosis and treatment of cancer. Telomerase promoter-dependent fluorescence labeling using replication-competent viral vectors produces fluorescent proteins that can be used to detect and eliminate telomerase-positive tumor cells. Tissue-specific promoter-dependent fluorescence labeling enables identification of specific tumor cells. Vimentin promoter-dependent fluorescence labeling is a useful tool for identifying tumor cells that undergo epithelial-mesenchymal transition (EMT). The evaluation of tumor cells undergoing EMT is important for accurately assessing metastatic potential. Thus, tumor-targeted fluorescence labeling systems represent novel platforms that enable the capture of tumor cells for the diagnosis and treatment of cancer.

DOI： 10.1111/cas.15369

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：日本語   出版者・発行元：日本外科系連合学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The epithelial-mesenchymal transition (EMT), a normal biological process by which epithelial cells acquire a mesenchymal phenotype, is associated with migration, metastasis, and chemoresistance in cancer cells, and with poor prognosis in patients with esophageal cancer. However, therapeutic strategies to inhibit EMT in tumor environments remain elusive. Here, we show the therapeutic potential of telomerase-specific replication- competent oncolytic adenovirus OBP-301 in human esophageal cancer TE4 and TE6 cells with an EMT phenotype. Transforming growth factor-β (TGF-β) administration induced the EMT phenotype with spindleshaped morphology, upregulation of mesenchymal markers and EMT transcription factors, migration, and chemoresistance in TE4 and TE6 cells. OBP-301 significantly inhibited the EMT phenotype via E1 accumulation. EMT cancer cells were susceptible to OBP-301 via massive autophagy induction. OBP-301 suppressed tumor growth and lymph node metastasis of TE4 cells co-inoculated with TGF-β-secreting fibroblasts. Our results suggest that OBP-301 inhibits the TGF-β-induced EMT phenotype in human esophageal cancer cells. OBP-301-mediated E1A overexpression is a promising antitumor strategy to inhibit EMT-mediated esophageal cancer progression.

DOI： 10.18926/AMO/63425

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

OBJECTIVES: An increasing number of patients visiting the dental office have a growing need for perioperative oral management (POM) to prevent postoperative complications. Therefore, it is necessary to determine which patients should receive preferential POM. This study investigated the dental status of patients scheduled to undergo surgery and addressed the priority for POM. METHODS: This retrospective study included a total of 150 patients who were scheduled to undergo surgery at the Department of Respiratory Surgery (DRS), Department of Neurological Surgery (DNS), Department of Gynecological Surgery (DGS), Department of Breast and Endocrine Surgery (DBES), and Department of Esophageal Surgery (DES) managed by the Perioperative Management Center of Okayama University Hospital. We compared the general and dental status of patients among the five groups. RESULTS: The DES group had significantly fewer teeth than the DBES group (p = 0.012), more severe periodontitis than both the DBES (p = 0.005) and DNS groups (p = 0.020), and poorer molar occlusal support status than both the DBES (p = 0.002) and DGS groups (p = 0.041). The DES group exhibited a significantly higher median age (p = 0.002), a higher ratio of males (p < 0.001), a higher prevalence of malignant tumors (p < 0.001), and higher proportions of smokers (p < 0.001) and drinkers (p < 0.001) than the other groups. CONCLUSION: Patients who underwent surgery at the DES had more dental problems than other surgery patients. Accordingly, these patients should be given the highest priority for POM triage.

DOI： 10.1007/s11748-021-01757-4

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その他リンク： https://link.springer.com/article/10.1007/s11748-021-01757-4/fulltext.html

記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: Although D2 lymphadenectomy is currently considered a standard procedure for advanced gastric cancer (GC) worldwide, there is room for discussion about the appropriate range of suprapancreatic D2 lymphadenectomy. Focusing on the posterior hepatic plexus (PHP), which is not well recognized, we developed a surgical technique of suprapancreatic D2 lymphadenectomy, which we have called PHP-D2, and its short-term and long-term efficacies were evaluated in comparison with non-PHP-D2. METHODS: GC patients who underwent distal gastrectomy with D2 lymphadenectomy between July 2006 and May 2013 were enrolled, from which patients who had peritoneal metastasis and/or were peritoneal cytology-positive during surgery were excluded. Their medical records were retrospectively reviewed. RESULTS: Ninety-two patients (non-PHP-D2: 48, PHP-D2: 44) were enrolled. Shorter operation time (330 min vs 275 min, p < 0.0001) and less blood loss (290 mL vs 125 mL, p < 0.0001) were observed in PHP-D2, and no pancreatic fistulas were observed in PHP-D2. More lymph nodes of #11p (1 vs 1.5, p = 0.0328) and #12a lymph nodes (0 vs 1, p = 0.0034) were retrieved in PHP-D2, with no significant differences in #8a and #9 lymph nodes. Lymphatic recurrence was significantly less in PHP-D2 (p = 0.0166), and univariate and multivariate analyses showed that non-PHP-D2 was a significant risk factor for lymphatic recurrence (p = 0.0158), although there were no significant differences between non-PHP-D2 and PHP-D2 in 5-year overall survival and 5-year relapse-free survival. CONCLUSION: PHP-D2 was a safe and feasible procedure that had the potential to reduce lymphatic recurrence, and it can be a standard procedure of D2 lymphadenectomy for advanced GC.

DOI： 10.1007/s00423-022-02437-4

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記述言語：英語   出版者・発行元：(一社)日本胃癌学会  

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記述言語：英語   出版者・発行元：(一社)日本胃癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

BACKGROUND: We have recently standardized upper mediastinal lymph node dissection (UMLND) using a microanatomy-based concept in thoracoscopic esophagectomy in the prone position (TEPP), and introduced robot-assisted minimally invasive esophagectomy (RAMIE) using the same concept as in TEPP while aiming at solo surgery. The purpose of this study was to investigate the outcomes of RAMIE using the microanatomy-based concept in the initial introduction phase. METHODS: We have performed more than 500 TEPP procedures as minimally invasive esophagectomy (MIE). After performing about 400 cases of MIE, we established a microanatomy-based standardization of UMLND. In October 2018, we introduced RAMIE, and have performed 75 procedures in 20 months. Two groups were analyzed: a group after microanatomy-based standardization in TEPP (100 cases after completing 400 cases of TEPP) and a RAMIE group (75 cases). Finally, 51 paired cases were matched using a propensity score. Furthermore, the change in postoperative short-term outcome for RAMIE in the initial introduction phase was analyzed. RESULTS: Although there were no significant differences between the two groups in the number of upper mediastinal lymph nodes dissected, there was a significant decrease (P = 0.036) in intraoperative blood loss volume with RAMIE, representing a definite benefit for patients. The thoracoscopic operative time for RAMIE decreased by almost 100 min following less than 50 cases of experience, reaching the same level as that for recent TEPP, but with only one-tenth the operator experience. There were no significant differences in the total postoperative morbidity rate including the recurrent laryngeal nerve palsy rate. CONCLUSION: RAMIE has been introduced safely and smoothly using the microanatomy-based concept established in TEPP.

DOI： 10.1007/s00464-020-08154-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

PURPOSE: The Endoscopic Surgical Skill Quantification System for qualified surgeons (QSs) was introduced in Japan to improve surgical outcomes. This study reviewed the surgical outcomes after initial experience performing laparoscopic distal gastrectomy (LDG) and evaluated the improvement in surgical outcomes following accreditation as a QS. METHODS: Eighty-seven consecutive patients who underwent LDG for gastric cancer by a single surgeon were enrolled in this study. The cumulative sum method was used to analyze the learning curve for LDG. The surgical outcomes were evaluated according to the two phases of the learning curve (learning period vs. mastery period) and accreditation (non-QS period vs. QS period). RESULTS: The learning period for LDG was 48 cases. Accreditation was approved at the 67th case. The operation time and estimated blood loss were significantly reduced in the QS period compared to the non-QS period (230 vs. 270 min, p < 0.001; 20.5 vs. 59.8 ml, p = 0.024, respectively). Furthermore, the major complication rate was significantly lower in the QS period than in the non-QS period (0 vs. 10.6%, p = 0.044). CONCLUSIONS: Experience performing approximately 50 cases is required to reach proficiency in LDG. After receiving accreditation as a QS, the surgical outcomes, including the complication rate, were improved.

DOI： 10.1007/s00595-021-02309-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

BACKGROUND: Although the main manifestation of giant paraesophageal hernia (PEH) is disordered meal passage due to gastric torsion, the contents of the hernia sometimes squeeze the heart and lungs and induce the symptoms of respiratory or heart failure. Furthermore, the quality of life (QOL) of patients with a heavy cardiac load deteriorates. In this study, changes in a heart failure marker and symptoms of cases with a giant PEH from before to after laparoscopic surgery were examined. METHODS: Levels of brain natriuretic peptide (BNP) as a heart failure marker were measured before and after radical laparoscopic surgery in cases of type III, IV type of giant PEH. Changes of the symptoms due to heart failure were also investigated. RESULTS: A total of 75 hiatal hernia surgeries were performed in 2012-2019. Of them, 50 had a giant PEH, and 20 (40.0%) had heart failure symptoms such as fatigue and exertional dyspnea. In the giant PEH cases, BNP could be measured before and after surgery to evaluate the presence of heart failure in 23 cases; postoperative BNP levels decreased from the preoperative values in 18 of them. Furthermore, in many cases, chest symptoms also improved. CONCLUSIONS: Radical laparoscopic surgery can reduce heart failure due to giant PEH. Therefore, in addition to conventional surgical indication criteria such as vomiting and food loss, increased cardiac load may be added to the new surgical indication criteria.

DOI： 10.1007/s00464-020-08202-2

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記述言語：英語  

Approximately 4% of patients with esophageal cancer develop a second primary malignancy in the upper gastrointestinal trunk. However, hepatectomy following esophagectomy for esophageal cancer has rarely been reported. We report the case of a 70-year-old man who underwent an esophagectomy for esophageal cancer with retrosternal gastric tube reconstruction. Nine years later, he developed hepatocellular carcinoma with tumor thrombus involving the left portal vein, and was successfully treated with left hemihepatectomy. Special attention should be paid to avoiding incidental injury of the gastric tube as well as the right gastroepiploic artery during the hepatectomy.

DOI： 10.18926/AMO/62818

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

BACKGROUND: Multidisciplinary team (MDT) approach has become a standard for perioperative patient care, including in esophageal cancer. In our institution, the Perioperative Management Center (PERiO) has been doing an MDT approach for patients undergoing esophageal cancer surgery since 2009. On the other hand, neoadjuvant therapy has also been becoming standard for many malignancies, including esophageal cancer. In Japan, neoadjuvant chemotherapy (NAC) for esophageal cancer is standard now. However, there have been no reports about when is the best time to start the MDT approach for patients with neoadjuvant therapy. In this study, the best start time for the MDT approach for esophageal cancer patients with NAC was examined from the perspective of adverse events during chemotherapy and perioperative period. METHODS: All cases underwent thoracoscopic esophagectomy in the prone position (TEPP) after NAC. The PERiO Intervention group that started before NAC (n = 100) was compared with the PERiO Intervention group that started after NAC (n = 77). Eventually, 54 paired cases were matched by propensity score matching. RESULTS: The adverse event rate during chemotherapy, especially oral complications, was significantly decreased in the PERiO Intervention started before the NAC group (P = 0.007). Furthermore, weight loss during the period from chemotherapy to surgery was significantly reduced in the group that started before NAC (P = 0.033). CONCLUSION: The MDT approach should be started before NAC in patients undergoing esophageal cancer surgery to prevent adverse events during chemotherapy and provide safe perioperative conditions.

DOI： 10.1007/s10388-021-00844-y

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本胸部外科学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：日本語   出版者・発行元：日本臨床外科学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCI LTD  

PURPOSE: OBP-301 (Telomelysin) is an attenuated type-5 adenovirus that contains the human telomerase reverse transcriptase promoter to regulate viral replication. OBP-301 sensitises human cancer cells to ionising radiation by inhibiting DNA repair, and radiation enhances coxsackievirus and adenovirus receptor-mediated OBP-301 infection on the contrary. We assessed OBP-301 with radiotherapy in oesophageal cancer patients unfit for standard chemoradiation treatments. METHODS: A phase I dose-escalation study of OBP-301 with radiotherapy was conducted in 13 histologically confirmed oesophageal cancer patients deemed unfit to undergo surgery or chemotherapy. Study treatment consisted of OBP-301 administration by intratumoural needle injection using a flexible endoscope on days 1, 18 and 32. Radiotherapy was administered concurrently over 6 weeks, beginning on day 4, to a total of 60 Gy. RESULTS: Of the 13 patients, 7, 3 and 3 patients were treated with 1010, 1011 and 1012 virus particles, respectively. Study group comprised 10 males and 3 females, with a median age of 82 years (range, 53-91 years). All patients developed a transient, self-limited lymphopenia. Distribution studies revealed transient virus shedding in the plasma. Eight patients had local complete response (CR); all of them exhibited no pathologically viable malignant cells in biopsy specimens, and 3 patients had a partial response. The objective response rate was 91.7%. The clinical CR rate was 83.3% in stage I and 60.0% in stage II/III. Histopathological examination revealed massive infiltration of CD8+ cells and increased PD-L1 expression. CONCLUSION: Multiple courses of endoscopic intratumoural OBP-301 injection with radiotherapy are feasible and provide clinical benefits in patients with oesophageal cancer unfit for standard treatments.

DOI： 10.1016/j.ejca.2021.04.043

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Esophageal cancer is a disease showing poor prognosis. Although combination chemotherapy using cisplatin and 5-fluorouracil is standard for unresectable esophageal cancer, the response rate is 35%. Cancer stem cells (CSCs) and inflammation are reportedly responsible for the poor prognosis of esophageal cancer. However, comprehensive analyses have not been conducted and proposals for progress remain lacking. Iron is known to be a key factor in the stemness of CSCs. This study focused on the therapeutic potential of iron control using iron chelators for CSCs in esophageal cancer. Among 134 immunohistochemically analyzed cases, Nanog expression was high in 98 cases and low in 36 cases. High Nanog expression correlated with low overall and disease-free survivals. The iron chelators deferasirox (DFX) and SP10 suppressed the proliferation and expression of stemness markers in TE8 and OE33 cells. DFX and SP10 did not induce compensatory interleukin (IL)-6 secretion, although cisplatin did result in high induction. Moreover, BBI608 and SSZ, as other CSC-targeting drugs, could not suppress the expression of stemness markers. Together, Nanog expression appears related to poor prognosis in esophageal cancer patients, and inhibition of stemness and compensatory IL-6 secretion by iron chelators may offer a novel therapeutic strategy for esophageal cancer.

DOI： 10.1002/ijc.33544

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

INTRODUCTION: Intracorporeal Billroth I (B-I) reconstruction using an endoscopic linear stapler (ELS) is widely performed in total laparoscopic distal gastrectomy. However, conventional procedures require many ELSs for anastomosis. Here, we introduce the novel intracorporeal semi-hand-sewn (SHS) B-I reconstruction. MATERIALS AND SURGICAL TECHNIQUE: After the transection of stomach and duodenum using ELS following adequate lymph node dissection, small entry holes were made on the anterior wall in the greater curvature of the stomach and the duodenal stump. The posterior walls of both the remnant stomach and the duodenum were attached with the ELS and fired to create the posterior wall of the B-I anastomosis. All the transection line of the duodenum and one-third of the transection line of the stomach were dissected; finally the anterior wall suturing at the anastomotic site was performed by the laparoscopic hand-sewn technique. DISCUSSION: SHS procedure was performed for 17 gastric cancer patients. There were no intraoperative complications or conversions to open surgery. One intra-abdominal abscess was observed although there was no anastomotic leakage. The median reconstruction time was 48 minutes (32-63). The SHS procedure was safe, feasible, and economical, although it requires sufficient laparoscopic suturing and ligation skill.

DOI： 10.1111/ases.12887

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記述言語：英語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(株)へるす出版  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

BACKGROUND: Gastric yolk sac tumor (YST)-like carcinoma is extremely rare, and its prognosis is poor, because most patients have widespread metastases at the time of diagnosis. We report a case of gastric YST-like carcinoma with an adenocarcinoma component without metastases in which curative resection was performed. CASE PRESENTATION: A 77-year-old man complaining of melena and dizziness due to anemia was diagnosed with poorly differentiated adenocarcinoma in the gastric cardia, with a benign ulcer in the gastric body. He underwent total gastrectomy with D2 lymph node dissection for the tumor. Histological examination of the resected specimens revealed a mixture of reticular and glandular neoplastic components morphologically. In the reticular area, an endodermal sinus pattern and some Schiller-Duval bodies were confirmed. Gastric YST-like carcinoma with adenocarcinoma components, T2N0M0 Stage IB, was diagnosed. Immunohistochemical analysis showed that the YST was positive for carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP) and p53. In contrast, the adenocarcinoma was positive for p53 and negative for CEA and AFP. The patient remained healthy as of 7 years postoperatively, with no recurrence. CONCLUSIONS: Routine medical examinations or endoscopic examinations for accidental symptom may be helpful for early diagnosis and good prognosis for gastric YST-like carcinoma, although the prognosis is generally poor.

DOI： 10.1186/s40792-021-01199-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

An aberrant right subclavian artery (ARSA) is one of the famous anatomical abnormalities with a prevalence of 0.16-4.4%. In esophagectomy, anatomical abnormalities of the ARSA could cause complications with some surgical procedures. An 85-year old man was referred to our department for esophageal adenocarcinoma that was at a slightly high position for esophagectomy with the abdominal approach. However, he had a significant past medical history. This risk factor made it difficult to perform thoracoscopic esophagectomy. He underwent mediastinoscopic esophagectomy (ME) with the left cervical and laparoscopic approach. The ARSA presented no difficulties with the ME surgical technique including the dissection of the left recurrent laryngeal nerve lymph node. Although this patient had a respiratory dysfunction and some difficulties in a prone position, ME enabled a safe esophagectomy with lymph node dissection.

DOI： 10.1111/ases.12859

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：英語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：英語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Surgery is the only curative treatment option for pancreatic cancer, but patients often develop postoperative recurrence. Surgical invasiveness might be involved in the mechanism of recurrence. The associations among inflammation caused by surgery, neutrophils, and cancer metastasis were investigated. At first, neutrophil extracellular traps (NETs) were examined in clinical specimens, and NETs were observed around metastatic tumors. To explore how NETs were induced, neutrophils were cultured with pancreatic cancer or in cancer-conditioned medium. Neutrophils formed NETs when they were cultured with pancreatic cancer or even its conditioned medium. The effects of NETs on cancer cells were further investigated in vitro and in vivo. NETs induced the epithelial to mesenchymal transition in cancer cells and thereby promoted their migration and invasion. HMGB1 derived from NETs appeared to potentiate the malignancy of cancer cells. In a mouse model of liver metastasis with inflammation, NETs participated in the metastatic process by enhancing extravasation. Interestingly, thrombomodulin degraded HMGB1 and consequently inhibited the induction of NETs, thereby preventing pancreatic cancer metastasis to the liver. In conclusion, NETs interact reciprocally with pancreatic cancer cells, which play a pivotal role in inflammation-associated metastasis. Targeting NETs with thrombomodulin can be a novel strategy to improve the surgical outcome of pancreatic cancer patients.

DOI： 10.1016/j.canlet.2020.10.015

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE RESEARCH  

Cancer-associated fibroblasts (CAFs) have an important role in the tumor microenvironment. CAFs have the multifunctionality which strongly support cancer progression and the acquisition of therapeutic resistance by cancer cells. Near-infrared photoimmunotherapy (NIR-PIT) is a novel cancer treatment that uses a highly selective monoclonal antibody (mAb)-photosensitizer conjugate. We developed fibroblast activation protein (FAP)-targeted NIR-PIT, in which IR700 was conjugated to a FAP-specific antibody to target CAFs (CAFs-targeted NIR-PIT: CAFs-PIT). Thus, we hypothesized that the control of CAFs could overcome the resistance to conventional chemotherapy in esophageal cancer (EC). In this study, we evaluated whether EC cell acquisition of stronger malignant characteristics and refractoriness to chemoradiotherapy are mediated by CAFs. Next, we assessed whether the resistance could be rescued by eliminating CAF stimulation by CAFs-PIT in vitro and in vivo. Cancer cells acquired chemoradiotherapy resistance via CAF stimulation in vitro and 5-fluorouracil (FU) resistance in CAF-coinoculated tumor models in vivo. CAF stimulation promoted the migration/invasion of cancer cells and a stem-like phenotype in vitro, which were rescued by elimination of CAF stimulation. CAFs-PIT had a highly selective effect on CAFs in vitro. Finally, CAF elimination by CAFs-PIT in vivo demonstrated that the combination of 5-FU and NIR-PIT succeeded in producing 70.9% tumor reduction, while 5-FU alone achieved only 13.3% reduction, suggesting the recovery of 5-FU sensitivity in CAF-rich tumors. In conclusion, CAFs-PIT could overcome therapeutic resistance via CAF elimination. The combined use of novel targeted CAFs-PIT with conventional anticancer treatments can be expected to provide a more effective and sensible treatment strategy.

DOI： 10.1038/s41598-021-81465-4

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

BACKGROUND: Although thoracoscopic esophagectomy in the prone position (TEPP) has become a standard procedure for esophageal cancer surgery, upper mediastinal lymph node dissection (UMLND) on the left side remains an issue. We have recently developed a new standardized approach to left UMLND in TEPP based on the microanatomy of the membranes and layers with the aim of achieving quick and safe surgery. The purpose of this study was to establish and evaluate our new standardized procedure in left UMLND. PATIENTS AND METHODS: Patients were divided into 2 groups: a pre-standardization group (n = 100) and a post-standardization group (n = 100). Eventually, 83 paired cases were matched using propensity score matching. In our new standardized procedure, left UMLND was performed while focusing on the visceral sheath, vascular sheath, and the fusion layer between them using a magnified view. RESULTS: The thoracoscopic operative time was significantly shorter (P < 0.001) in the post-standardization group [n = 83; 209.0 (176.0-235.0) min] than in the pre-standardization group [n = 83; 235.5 (202.8-264.5) min]. No significant differences were found in the number of mediastinal lymph nodes dissected or intraoperative blood loss between the two groups. There was a tendency for the total postoperative morbidity to decrease in the post-standardization group. Furthermore, the left recurrent laryngeal nerve palsy rate was significantly lower in the post-standardization group (18.1% to 8.7%, P = 0.015). CONCLUSION: Microanatomy-based standardization contributes to safe and efficient left UMLND.

DOI： 10.1007/s00464-020-07407-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

BACKGROUND: Incidence of esophagogastric junction (EGJ) carcinoma has been increasing worldwide. Several studies revealed that the distance from the EGJ to the proximal edge of the primary tumor (esophageal invasion: EI) may be a significant indicator of metastasis in the mediastinal lymph nodes in patients with Siewert type II carcinomas. However, few studies have been conducted in patients with carcinomas located at Siewert type II sequentially to upper carcinomas (Siewert type I) for mediastinal metastasis regardless of histological types. METHODS: This was a single-center retrospective cohort study. EGJ carcinomas located at Siewert type I and II regions including both squamous cell carcinoma (SCC) and adenocarcinoma were analyzed in terms of lymph node metastasis patterns. RESULTS: We included 121 patients in this study. Thirty-three (27.3%) patients had SCC. In multivariate analysis, the distance of EI (> 20 mm) was an independent risk factor (OR 11.80, p = 0.005) for lower mediastinal lymph node metastasis. In terms of above the middle mediastinal metastasis, the distance of EI (> 30 m), histological type (SCC), and tumor size (> 40 mm) were risk factors in univariate analysis. Furthermore, EI was significant (OR 13.50, p = 0.026) in multivariate analysis. CONCLUSIONS: The distance of EI was the independent risk factor for mediastinal lymph node metastasis, especially > 20 mm related with a higher risk for mediastinal lymph node metastasis. Furthermore, EGJ carcinoma patients who have EI > 30 mm, large SCC carcinoma, and multiple lymph node metastasis might be considered the middle-upper mediastinal lymph node dissection by transthoracic approach.

DOI： 10.1007/s00423-020-02017-4

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記述言語：英語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CELL PRESS  

Peritoneal metastasis is the most frequent form of distant metastasis and recurrence in gastric cancer, and the prognosis is extremely poor due to the resistance of systemic chemotherapy. Here, we demonstrate that intraperitoneal (i.p.) administration of a green fluorescence protein (GFP)-expressing attenuated adenovirus with oncolytic potency (OBP-401) synergistically suppressed the peritoneal metastasis of gastric cancer in combination with paclitaxel (PTX). OBP-401 synergistically suppressed the viability of human gastric cancer cells in combination with PTX. PTX enhanced the antitumor effect of OBP-401 due to enhanced viral replication in cancer cells. The combination therapy increased induction of mitotic catastrophe, resulting in accelerated autophagy and apoptosis. Peritoneally disseminated nodules were selectively visualized as GFP-positive spots by i.p. administration of OBP-401 in an orthotopic human gastric cancer peritoneal dissemination model. PTX enhanced the deep penetration of OBP-401 into the disseminated nodules. Moreover, a non-invasive in vivo imaging system demonstrated that the combination therapy of i.p. OBP-401 administration with PTX significantly inhibited growth of peritoneal metastatic tumors and the amount of malignant ascites. i.p. virotherapy with PTX may be a promising treatment strategy for the peritoneal metastasis of gastric cancer.

DOI： 10.1016/j.omto.2020.06.021

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

OBJECTIVES: Although tracheobronchial diverticulum (DV) rarely cause problems, attention should be paid during esophagectomy, which requires careful dissection around the trachea and bronchi. Here, we retrospectively review cases of tracheobronchial DVs among esophageal cancer patients and report two cases of bronchial DV injury during thoracoscopic esophagectomy that were successfully repaired. METHODS: The thin-section CT images of esophageal cancer patients who underwent thoracoscopic esophagectomy from January 2013 to December 2015 were retrospectively reviewed. The localization, number, and size (largest axial diameter) of all detected DVs were recorded. RESULTS: A total of 180 patients were enrolled in this study. The incidence of tracheal DV was 5.0%, and that of bronchial DV was 40.0%. The median diameter of the tracheal diverticula was 2.45 [interquartile range (IQR) 2.00-8.17] mm and that of the bronchial diverticula was 1.90 (IQR 1.51-2.46) mm. All tracheal diverticula presented at the right tracheal wall 4.5-6.0 cm below the vocal cords; bronchial diverticula presented at the subcarinal lesions. We experienced two cases with bronchial diverticulum injuries during thoracoscopic esophagectomy, which were repaired by primary closure and confirmed that there was no air leak. No postoperative complications associated with bronchial injury occurred in either patient. CONCLUSION: Since tracheobronchial DVs are not as rare as previously thought, careful evaluation of thin-slice CT scans is necessary before thoracoscopic esophagectomy. If a tracheobronchial DV is injured during surgery, it is important to carefully repair it and confirm that there is no air leak to avoid complications.

DOI： 10.1007/s11748-020-01421-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMC  

BACKGROUND: The postoperative survival rate of patients with esophageal squamous cell carcinoma (ESCC) remains poor compared with other gastrointestinal cancers. We hypothesized that skeletal muscle loss in the postoperative acute phase might be a new predictor for long-term prognosis after highly invasive surgery such as ESCC surgery. METHODS: The following items were retrospectively investigated. First, whether skeletal muscle loss occurred in the postoperative acute phase of ESCC was verified. Second, the preoperative and intraoperative factors involved in skeletal muscle loss in the postoperative acute phase of ESCC were investigated. Then, whether skeletal muscle loss in the postoperative acute phase affected long-term prognosis was examined. The medical records of consecutive patients who underwent radical esophagectomy for ESCC between January 2010 and February 2015 were retrospectively reviewed; 72 cases were eligible for this study. The total psoas major muscle mass index (TPI) at the level of the third lumbar vertebra (L3) was measured using computed tomography (CT) before surgery and 3 days after surgery. The long-term prognosis was estimated by the Kaplan-Meier method and the multivariate logistic regression model. RESULTS: There was already a significant reduction of TPI in the acute phase up to POD 3 after ESCC surgery in comparison with the preoperative baseline TPI (P < 0.001). The TPI reduction rate was significantly milder in cases with less blood loss during surgery and in cases that underwent thoracoscopic esophagectomy than in cases that underwent open esophagectomy. The 3-year overall survival rate was significantly different between the TPI reduction rate severe group and the TPI reduction rate mild group. CONCLUSION: Skeletal muscle loss occurred even in the postoperative acute phase. Furthermore, it is very significant that skeletal muscle loss in the postoperative acute phase of ESCC surgery is involved in the long-term prognosis.

DOI： 10.1186/s12957-020-01908-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER JAPAN KK  

BACKGROUND: Locally advanced esophageal cancer (EC) invading surrounding organs (T4b) is difficult to treat. In general, definitive chemoradiotherapy (d-CRT) has been chosen as treatment for such cases. However, the outcome has not been good. Recently, the effectiveness of d-CRT with docetaxel, cisplatin, and 5-fluorouracil (DCF-RT) has been reported. Furthermore, surgery after d-CRT has a better prognosis than d-CRT alone in some reports, although it has a high risk of surgical complications. This study investigated the effectiveness and safety of induction DCF-RT. METHODS: The subjects were EC patients who underwent induction DCF-RT in Okayama University Hospital between January 2011 and December 2017. Their background characteristics, treatment details, histopathological factors, adverse events during CRT, postoperative complications, and overall survival (OS) were assessed. RESULTS: A total of 16 cases were performed induction DCF-RT. In 10 cases, death occurred, with 9 cancer-related deaths, and 1 death due to other disease. For all cases, OS was 37.5% at 3 years. 12 cases underwent esophagectomy after DCF-RT. Their OS was 50% at 3 years. 13 patients (81.3%) had Grade 3 febrile neutropenia. In 7 cases (62.5%), fasting for the treatment of diarrhea was needed. Three patients (25%) developed anastomotic leakage. Some recurrent laryngeal nerve paralysis was observed in 6 cases (50%). CONCLUSION: Although the rates of adverse events and surgical complications were slightly higher than in past reports, they were acceptable. It is useful to perform induction DCF-RT for T4b EC.

DOI： 10.1007/s10388-019-00709-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

Iron is a trace but vital element in the human body and is necessary for a multitude of crucial processes in life. However, iron overload is known to induce carcinogenesis via oxidative stress. Cancer cells require large amounts of iron for their rapid division and cell growth. Iron was recently found to play a role in cancer stem cells (CSCs); it maintains stemness during development. Iron also plays an important role in stemness by moderating reactive oxygen species. Thus, iron metabolism in CSCs is a promising therapeutic target. In this review, we summarize the roles of iron in cancer cells and CSCs. We also summarize anti-cancer therapeutic studies with iron chelators and describe our expectation of a new therapeutic strategy for CSCs on the basis of our findings.

DOI： 10.18926/AMO/57946

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Epithelial-mesenchymal transition (EMT) is a biological process by which epithelial cells acquire mesenchymal characteristics. In malignant tumors, EMT is crucial for acquisition of a mesenchymal phenotype with invasive and metastatic properties, leading to tumor progression. An inflammatory microenvironment is thought to be responsible for the development and progression of colorectal cancer (CRC); however, the precise role of inflammatory microenvironments in EMT-related CRC progression remains unclear. Here, we show the spatiotemporal visualization of CRC cells undergoing EMT using a fluorescence-guided EMT imaging system in which the mesenchymal vimentin promoter drives red fluorescent protein (RFP) expression. An inflammatory microenvironment including TNF-α, IL-1β, and cytokine-secreting inflammatory macrophages induced RFP expression in association with the EMT phenotype in CRC cells. In vivo experiments further demonstrated the distribution of RFP-positive CRC cells in rectal and metastatic tumors. Our data suggest that the EMT imaging system described here is a powerful tool for monitoring EMT in inflammatory microenvironment-CRC networks.

DOI： 10.1038/s41598-019-52816-z

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記述言語：日本語   出版者・発行元：(一社)日本外科感染症学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00464-018-6511-7

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.SABCS18-4330

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2019-LB-310

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2019-1155

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.SABCS18-2979

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.canlet.2018.12.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Lymph node metastasis is a pathognomonic feature of spreading tumors, and overcoming metastasis is a challenge in attaining more favorable clinical outcomes. Esophageal cancer is an aggressive tumor for which lymph node metastasis is a strong poor prognostic factor, and the tumor microenvironment (TME), and cancer-associated fibroblasts (CAFs) in particular, has been implicated in esophageal cancer progression. CAFs play a central role in the TME and have been reported to provide suitable conditions for the progression of esophageal cancer, similar to their role in other malignancies. However, little is known concerning the relevance of CAFs to the lymph node metastasis of esophageal cancer. Here, we used clinical samples of esophageal cancer to reveal that CAFs promote lymph node metastasis and subsequently verified the intercellular relationships in vitro and in vivo using an orthotopic metastatic mouse model. In the analysis of clinical samples, FAP+ CAFs were strongly associated with lymph node metastasis rather than with other prognostic factors. Furthermore, CAFs affected the ability of esophageal cancer cells to acquire metastatic phenotypes in vitro; this finding was confirmed by data from an in vivo orthotopic metastatic mouse model showing that the number of lymph node metastases increased upon injection of cocultured cancer cells and CAFs. In summary, we verified in vitro and in vivo that the accumulation of CAFs enhances the lymph node metastasis of ESCC. Our data suggest that CAF targeted therapy can reduce lymph node metastasis and improve the prognosis of patients with esophageal cancer in the future.

DOI： 10.1002/ijc.31953

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MDPI  

Excess iron causes cancer and is thought to be related to carcinogenesis and cancer progression including stemness, but the details remain unclear. Here, we hypothesized that stemness in cancer is related to iron metabolism and that regulating iron metabolism in cancer stem cells (CSCs) may be a novel therapy. In this study, we used murine induced pluripotent stem cells that expressed specific stem cell genes such as Nanog, Oct3/4, Sox2, Klf4, and c-Myc, and two human cancer cell lines with similar stem cell gene expression. Deferasirox, an orally available iron chelator, suppressed expression of stemness markers and spherogenesis of cells with high stemness status in vitro. Combination therapy had a marked antitumor effect compared with deferasirox or cisplatin alone. Iron metabolism appears important for maintenance of stemness in CSCs. An iron chelator combined with chemotherapy may be a novel approach via suppressing stemness for CSC targeted therapy.

DOI： 10.3390/cancers11020177

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：OKAYAMA UNIV MED SCHOOL  

Anterior cervical plate fixation is a common surgical treatment for cervical spine trauma, disc herniation, or cervical spondylosis. Esophageal perforation following anterior cervical plate fixation is a rare but serious complication. Management of esophageal perforation is controversial; however, we suggest treating most cases surgically because this condition is slow to heal and often fatal. We managed 2 cases of esophageal perforation following anterior cervical plate fixation by flap reconstruction with the pectoralis major muscle in one case and a jejunal free flap in the other. Here, we report our experience and review the surgical indications.

DOI： 10.18926/AMO/56462

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記述言語：英語   出版者・発行元：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/JCO.2019.37.4_suppl.130

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記述言語：英語   出版者・発行元：(一社)日本胃癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-V C H VERLAG GMBH  

Aim: As a result of the difficulty in effective prevention of gastroesophageal reflux, no standard reconstruction procedure after proximal gastrectomy (PG) has yet been established. The double-flap technique (DFT), or Kamikawa procedure, is an antireflux reconstruction procedure in esophagogastrostomy. The efficacy of DFT has recently been reported in several studies. However, these were all single-center studies with a limited number of cases. Methods: We conducted a multicenter retrospective study in which patients who underwent DFT, irrespective of disease type and reconstruction approach, at each participating institution between 1996 and 2015 were registered. Primary endpoint was incidence of reflux esophagitis at 1-year after surgery, and secondary endpoint was incidence of anastomosis-related complications. Results: Of 546 patients who were eligible for this study, 464 patients who had endoscopic examination at 1-year follow up were evaluated for reflux esophagitis. Incidence of reflux esophagitis of all grades was 10.6% and that of grade B or higher was 6.0%. Male gender and anastomosis located in the mediastinum/intra-thorax were independent risk factors for grade B or higher reflux esophagitis (odds ratio [OR]: 4.21, 95% confidence interval [CI]: 1.44-10.9, P = 0.0109). Total incidence of anastomosis-related complications was 7.2%, including leakage in 1.5%, strictures in 5.5% and bleeding in 0.6% of cases. Laparoscopic reconstruction was the only independent risk factor for anastomosis-related complications (OR: 3.93, 95% CI: 1.93-7.80, P = 0.0003). Conclusion: Double-flap technique might be a feasible option after PG for effective prevention of reflux, although anastomotic stricture is a complication that must be well-prepared for.

DOI： 10.1002/ags3.12216

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS INC  

Cancer-associated fibroblasts (CAFs) are strongly implicated in tumor progression, including in the processes of tumorigenesis, invasion, and metastasis. The targeting of CAFs using various therapeutic approaches is a novel treatment strategy; however, the efficacy of such therapies remains limited. Recently, near-infrared photoimmunotherapy (NIR-PIT), which is a novel targeted therapy employing a cell-specific mAb conjugated to a photosensitizer, has been introduced as a new type of phototherapy. In this study, we have developed a novel NIR-PIT technique to target CAFs, by focusing on fibroblast activation protein (FAP), and we evaluate the treatment efficacy in vitro and in vivo. Esophageal carcinoma cells exhibited enhanced activation of fibroblasts, with FAP over-expressed in the cytoplasm and on the cell surface. FAP-IR700-mediated PIT showed induced rapid cell death specifically for those cells in vitro and in vivo, without adverse effects. This novel therapy for CAFs, designed as local control phototherapy, was safe and showed a promising inhibitory effect on FAP+ CAFs. PIT targeting CAFs via the specific marker FAP may be a therapeutic option for CAFs in the tumor microenvironment in the future.

DOI： 10.1080/15384047.2019.1617566

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記述言語：英語   出版者・発行元：WILEY  

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記述言語：英語   出版者・発行元：WILEY  

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記述言語：英語   出版者・発行元：WILEY  

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記述言語：英語   出版者・発行元：WILEY  

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記述言語：英語   出版者・発行元：WILEY  

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記述言語：英語   出版者・発行元：WILEY  

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記述言語：英語   出版者・発行元：WILEY  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1158/1078-0432.CCR-18-0205

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記述言語：日本語  

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.jamcollsurg.2018.04.025

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Tokyo  

Background: Gastric cancer is the second most common malignancy, overlapping with thoracic esophageal cancer (TEC). Among them, metachronous gastric tube cancers after TEC surgery have been increasing. The aims of this study were to examine the clinicopathological factors and treatment outcomes of gastric tube cancer (GTC) after TEC surgery. Methods: Thirty-three GTCs in 30 cases after TEC treated between 1997 and 2016 were investigated retrospectively. Results: Most cases were males. The median interval from TEC surgery to GTC occurrence was 57 (6.5–107.5) months. Almost 2/3 lesions occurred in the lower third of the gastric tube (21/33)
29 lesions (in 26 cases) were superficial cancers, and 4 lesions were advanced cancers. Twenty-two lesions of superficial cancer were differentiated type, and the remaining seven lesions were undifferentiated type. Treatment for superficial cancer had previously been performed with partial gastric tube resection (10 lesions), and the number of cases undergoing endoscopic submucosal dissection (ESD) had increased recently (19 lesions). Most cases with superficial cancer survived without relapse. Four lesions of advanced cancer were found after a relatively long interval following TEC surgery. Most lesions of advanced cancer were scirrhous, undifferentiated type, and they died due to GTC. Conclusion: GTCs may occur late in the postoperative course following TEC surgery. If they are discovered at an early stage, these lesions can be cured with ESD. Long-term periodic endoscopic examinations after TEC surgery are important.

DOI： 10.1007/s10388-018-0611-2

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2018-LB-045

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2018-4807

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2018-5066

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2018-1101

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2018-1741

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2018-2033

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2018-3831

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記述言語：英語   出版者・発行元：(一社)日本胃癌学会  

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記述言語：英語   出版者・発行元：WILEY  

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記述言語：英語   出版者・発行元：WILEY  

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

We report a case of an elderly patient with advanced esophageal cancer who underwent multidisciplinary treatment. An 86-year-old male consulted our hospital with complaints of pharynx discomfort and difficulty in swallowing. He was preoperatively diagnosed with esophageal cancer, T3N2M0, Stage III . We performed 2 courses of cisplatin plus 5-FU therapy as neoadjuvant chemotherapy. The primary tumor and metastatic lymph nodes reduced in size, and thoracoscopic esophagectomy in the prone position was performed. Pathological findings were esophageal cancer, pT3-Ad, INF b, ly2, v1, IM0, pPM0, pDM0, pRM1, pN3, pStage III . As the radical margin was positive, chemoradiotherapy was performed. We continued postoperative chemotherapy for approximately 1 year, and the patient has survived without relapse for 4 years from esophagectomy. Even in patients over 80 years old, long-term prognosis can be expected by performing radical surgery and chemoradiotherapy.

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記述言語：日本語   出版者・発行元：(一社)日本消化器内視鏡学会  

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2017-5809

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2017-1103

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DOI： 10.1158/1538-7445.AM2017-5905

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2017-5934

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記述言語：英語   出版者・発行元：AMER ASSOC CANCER RESEARCH  

DOI： 10.1158/1538-7445.AM2017-925

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記述言語：英語   出版者・発行元：(一社)日本胃癌学会  

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記述言語：日本語   出版者・発行元：岡山医学会  

&emsp;Esophageal achalasia is a disorder of the lower esophageal sphincter muscle. Patients present with dysphagia, chest pain, vomiting, and aspiration. Esophageal achalasia had traditionally been treated with esophageal achalasia balloon dilatation and the Heller-Dor method, but in recent years, the use of per-oral endoscopic myotomy (POEM) has increased. Our patient, a 39-yr-old male, began experiencing dysphagia 4 years prior to his referral to our hospital. Based on the results of esophagogastroduodenoscopy, esophageal radiography and high-resolution manometry, we made the diagnosis of esophageal achalasia (Chicago classification type I) . After informed consent from the patient and his family and approval from our hospital's ethics committee were obtained, we performed a POEM. The patient was discharged on the 4th day post-surgery. At the 1-year post-operative examination, no worsening of symptoms and no relapse were observed. POEM is an excellent treatment method for esophageal achalasia from the perspective of therapeutic effect and prevention of invasion. We recommend that it be considered as the first-choice treatment for achalasia. However, accessibility to the procedure itself is limited due to the few adequately trained operators worldwide. POEM should thus be performed by an expert operator at a high-volume center.

DOI： 10.4044/joma.129.115

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その他リンク： http://search.jamas.or.jp/link/ui/2017339773

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

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記述言語：日本語   出版者・発行元：(一社)日本胃癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1158/0008-5472.CAN-10-2333

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

AIMS: Metaplastic changes secondary to chronic inflammation at the gastro-oesophageal junction and at the pyloric antrum are recognized as the premalignant conditions of Barrett's oesophageal adenocarcinoma and intestinal-type gastric carcinoma (GC), respectively. Heparanase (HPSE) and cyclooxygenase (COX)-2 have been proved to play critical roles in inflammation as well as in cancer. The aim was to examine the meaning of their expression in inflammation-related carcinogenesis. METHODS AND RESULTS: First, expression of HPSE and COX-2 in 78 clinical tissues of Barrett's oesophagus was examined by immunohistochemistry and in situ hybridization. Their expression was increased during the metaplasia-dysplasia sequence with increased neovascularization. Successively, their expression in Barrett's dysplasia was compared with that of GC (22 cases of diffuse-type and 10 of intestinal-type). Interestingly, the expression pattern in Barrett's dysplasia was similar to that in intestinal-type GC, which mainly arises from chronic inflammation. Furthermore, cultured cell lines isolated from differentiated GC tissues, which are often found to be of intestinal-type, revealed up-regulated mRNA expression of HPSE and COX-2. CONCLUSIONS: HPSE and COX-2 are preferentially up-regulated in Barrett's oesophagus and intestinal-type GC. These molecules may play an important role during the development of inflammation-related adenocarcinoma of the upper gastrointestinal tract.

DOI： 10.1111/j.1365-2559.2010.03594.x

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

The HSP90 molecular chaperone family is highly conserved and expressed in various organisms ranging from prokaryotes to eukaryotes. HSP90 proteins play essential housekeeping functions, such as controlling the activity, turnover and trafficking of various proteins, promoting cell survival through maintaining the structural and functional integrity of some client proteins which control cell survival, proliferation and apoptosis, and play an important role in the progression of malignant disease. HSP90 proteins are ATP-dependent chaperones and the binding and hydrolysis of ATP are coupled to conformation changes of HSP90, which facilitate client protein folding and maturation. Many natural and synthetic molecular compounds have been proposed as promising cancer therapy via disrupting the formation of complex ATP-HSP90-client proteins.

DOI： 10.3892/or_00000787

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Autophagy is a cellular lysosomal degradation pathway involved in proteins and organelles recycling for promoting cell survival, development and homeostasis. It is a multistep process and genetic studies have identified many proteins that participate in autophagosome formation and fusion with lysosomes, and various signaling factors that associate with the regulation of autophagy. In general, autophagy acts as a cell protector and its dysfunction is correlated with diverse pathologies, such as neurodegeneration, liver, heart and muscle diseases, cancer, inflammation and ageing. However, its role in cell death increases the complexity of the autophagic degradation system. A broad understanding of autophagy, ranging from detailed processes, including induction, formation and degradation, to function in physiology and pathology, revealed by accumulating studies, may be helpful for formulating therapeutic strategies for autophagy-associated human diseases.

DOI： 10.3892/ijmm_00000369

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

The type 1 insulin-like growth factor receptor (IGF-IR) and its associated signaling system play a significant role in tumongenesis, tumor survival and progression, and cancer therapeutic resistance, and thus has provoked great interest as a promising target for cancer treatment In this report we present the role of IGF-IR in gasrointestinal carcinomas whose pathology has been identified as tightly correlated with an abnormal expression and activation of IGF-IR Reported data from experimental studies suggest the feasibility of targeted IGF-IR therapy in gastrointestinal carcinomas Many types of inhibitors against IGF-IR have been developed Inhibitors with anti-IGF-IR monoclonal antibodies and tyrosine kinase inhibitors currently undergoing preclinical and clinical evolution are also reviewed

DOI： 10.3892/ol_00000036

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BAISHIDENG PUBLISHING GROUP INC  

Focal adhesion kinase (FAK) is a 125-kDa non-receptor protein tyrosine. Growth factors or the clustering of integrins facilitate the rapid phosphorylation of FAK at Tyr-397 and this in turn recruits Src-family protein tyrosine kinases, resulting in the phosphorylation of Tyr-576 and Tyr-577 in the FAK activation loop and full catalytic FAK activation. FAK plays a critical role in the biological processes of normal and cancer cells including the gastrointestinal tract. FAK also plays an important role in the restitution, cell survival and apoptosis and carcinogenesis of the gastrointestinal tract. FAK is over-expressed in cancer cells and its over-expression and elevated activities are associated with motility and invasion of cancer cells. FAK has been proposed as a potential target in cancer therapy. Small molecule inhibitors effectively inhibit the kinase activity of FAK and show a potent inhibitory effect for the proliferation and migration of tumor cells, indicating a high potential for application in cancer therapy.

DOI： 10.3748/wjg.15.5916

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

Gastrointestinal stromal tumors often express gene mutations to c-KIT and platelet-derived growth factor receptor-alpha, both of which result in constitutive activations of their signaling pathways that are quite essential for the proliferation and survival of tumor cells in most clinical gastrointestinal stromal tumors. Targeting these molecules provides a dramatic improvement to therapeutic strategy. To identify a new therapeutic target for gastrointestinal stromal tumor treatment, we focused on focal adhesion kinase, which is reported to be all up-regulated gene in clinical gastrointestinal stromal tumors, because so fiar no one has examined its expression status at the protein level. In this study, Western blot analysis revealed that all 10 of the examined gastrointestinal stromal tumor tissues strongly expressed focal adhesion kinase protein and that phosphorylated focal adhesion kinase was detected in 9 of them. Next, we assessed the expression Status Of focal adhesion kinase and phosphorylated focal adhesion kinase in 51 cases of gastrointestinal stromal tumor by immunohistochemistry. Positive stainings for focal adhesion kinase and phosphorylated focal adhesion kinase were confirmed in 44 (86.3%) and in 40 cases (78.4%) of the 51 gastrointestinal stromal tumors, respectively. We further found that the focal adhesion kinase-positive staining rate became higher along with the increased status of malignant behavior. Moreover, when the 51 gastrointestinal stromal tumors were divided into 2 groups based upon their focal adhesion kinase expression status, the 5-year overall Survival of patients in the focal adhesion kinase-positive group (66.5%) was significantly poorer than that in the focal adhesion kinase-negative group (100%). These results indicate that the up-regulation of focal adhesion kinase protein may also contribute to the tumor progression of gastrointestinal stromal tumors and that focal adhesion kinase is a potential target for gastrointestinal stromal tumor treatment. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.humpath.2009.05.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPANDIDOS PUBL LTD  

Focal adhesion kinase (FAK) is a 125-kDa non-receptor and non-membrane protein tyrosine. FAK can function with integrins and growth factor receptors to promote cell survival dependent kinase activity and nuclear FAK promotes cell proliferation and survival through FERM (FAK, ezrin, radixin, moesin) domain-enhanced p53 degradation independent kinase activity. Many previous studies have indicated that FAK plays a critical role in the biological processes of normal and cancer cells and FAK has been proposed as a potential target in cancer therapy. Small molecule inhibitors (PF-573,228; PF-562,271 and NVP-226) for use as potential cancer therapies have been developed. However, the detailed mechanism of the role for FAK in tumor cell generation and progression remain unclear, so future work is needed to explore these issues. New inhibitors that can be effectively inhibit the function of FAK still need to be explored due to the low specificity, and resistance.

DOI： 10.3892/or_00000524

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記述言語：英語   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

Focal adhesion kinase (FAK) is often up-regulated in a variety of malignancies, including gastrointestinal stromal tumor (GIST), and its overexpression seems to be associated with tumor progressiveness and poor prognosis. GIST is well known to have a mutation to c-KIT; thus, a specific c-KIT inhibitor (imatinib) is recognized as the first-line chemotherapy for GIST, although a certain type of c-KIT mutation reveals a resistance to imatinib due to as yet uncertain molecular mechanisms. To assess the c-KIT mutation-related variation of cellular responses to imatinib, murine lymphocyte-derived Ba/F3 cells, which are stably transduced with different types of c-KIT mutation, were treated with either imatinib or a FAK inhibitor (TAE226), and their antitumor effects were determined in vitro and in vivo. A mutation at exon 11 (KITdel559-560) displayed a high sensitivity to imatinib, whereas that at exon 17 (KIT820Tyr) showed a significant resistance to imatinib in vitro and in vivo. KIT820Tyr cells appeared to maintain the activities of FAK and AKT under the imatinib treatment, suggesting that FAK might play a role in cell survival in imatinib-resistant cells. When FAK activity in those cells was inhibited by TAE226, cell growth was equally suppressed and the cells underwent apoptosis regardless of the c-KIT mutation types. Oral administration of TAE226 significantly diminished tumor growth in nude mice bearing KIT(820Tyr) xenografts. In summary, c-KIT mutation at exon 17 displayed a resistance to imatinib with maintained activations of FAK and subsequent survival signals. Targeting FAK could be a potential therapeutic strategy for imatinib-resistant GISTs.

DOI： 10.1158/1535-7163.MCT-08-0884

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

Esophageal squamous cell carcinoma (ESCC) is an exceptionally drug-resistant tumor with a 5-year survival rate <5%. From an initial drug screen, we identified bortezomib as having robust activity in ESCC lines. Mechanistically, bortezomib induced a G2-M-phase cell cycle arrest and p53-independent apoptosis associated with caspase cleavage and Noxa induction. Bortezomib also showed excellent activity in organotypic culture and in vivo models of ESCC. Biochemically, bortezomib treatment activated the p38 and c-Jun NH2-termnial kinase stress-activated mitogen-activated protein kinase (MAPK) pathways and induced phospho-H2AX activity. Although H2AX is known to cooperate with c-Jun NH2-termnial kinase to induce apoptosis following UV irradiation, knockdown of H2AX did not abrogate bortezomib-induced apoptosis. Instead, blockade of p38 MAPK signaling, using either small interfering RNA or a pharmacologic inhibitor, reversed bortezomib-induced apoptosis and the up-regulation of Noxa. Radiation therapy is known to activate the p38 MAPK pathway and is a mainstay of ESCC treatment strategies. In a final series of studies, we showed that the coadministration of bortezomib with irradiation led to enhanced p38 MAPK activity and a significant reduction in colony formation. We therefore suggest that p38 MAPK pathway activation is an excellent potential therapeutic strategy in ESCC. It is further suggested that bortezomib could be added to existing ESCC therapeutic regimens.

DOI： 10.1158/1535-7163.MCT-08-0391

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：W B SAUNDERS CO-ELSEVIER INC  

BACKGROUND & AIMS: Esophageal squamous cell carcinoma (ESCC) is known to be a highly angiogenic tumor. Here, we investigated the role of the stromal fibroblasts in the ESCC-induced angiogenic response using a novel 3-dimensional model. METHODS: A novel assay was developed where cocultures of ESCC and esophageal fibroblasts induced human microvascular endothelial cell (HMVEC) vascular network formation in a 3-dimensional collagen gel. Biochemical studies showed that the ESCC-induced activation of the fibroblasts was required to induce vascular network formation via a transforming growth factor (TGF)-beta and vascular endothelial growth factor (VEGF)-dependent pathway. RESULTS: Conditioned media from a panel of 4 ESCC lines transdifferentiated normal esophageal fibroblasts into myofibroblasts via TGF-beta signaling. The presence of fibroblasts was essential for efficient HMVEC network formation, and the addition of ESCC cells to these cultures greatly enhanced the angiogenic process. The role of TGF-beta in this process was shown by the complete inhibition of network formation following TGF-beta inhibitor treatment. Finally, we showed that ESCC-derived TGF-beta regulates angiogenesis through the release of VEGF from the fibroblasts and that the VEGF release was blocked following TGF-beta inhibition. CONCLUSIONS: This study shows the essential role of fibroblasts in the ESCC angiogenic-induced response and suggests that the pharmacologic targeting of the TGF-beta signaling axis could be of therapeutic benefit in this deadly disease.

DOI： 10.1053/j.gastro.2008.02.061

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記述言語：英語   出版者・発行元：FEDERATION AMER SOC EXP BIOL  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：TAYLOR & FRANCIS LTD  

Anticancer drug discovery has long been hampered by the poor predictivity of the preclinical models. There is a growing realization that the tumor microenvironment is a critical determinant of the response of cancer cells to therapeutic agents. The past 5 years have seen a great deal of progress in our understanding of how the three-dimensional microenvironment modulates the signaling behavior of tumor cells. The present review discusses how three-dimensional in vitro cell culture models can benefit cancer drug discovery through an accurate modeling of the tumor microenvironment, leading to more physiologically relevant experimental outcomes.

DOI： 10.1517/17460441.3.1.1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: We evaluated the techniques of colonic interposition and supercharge for esophageal reconstruction and discussed the main considerations related to these procedures. PATIENTS AND METHODS: In this study, we performed 51 esophageal reconstructions using colonic interposition. Twenty-eight of the 51 patients had synchronous or allochronic gastric malignancy. We selected colonic interposition for high anastomosis in 11 patients and also for esophageal bypass in 3 patients. This procedure was also selected to preserve gastric function in 5 patients. We recently performed the supercharge technique for colonic interposition in 41 patients. RESULTS: Despite the long duration and multistep nature of the operation procedure, no perioperative complications were noted. The patients returned to a good quality of life. The incidence of postoperative weight loss did not differ significantly between the colonic reconstruction group and the gastric reconstruction group. In terms of heartburn and dumping syndrome, the outcome was markedly better in the colonic reconstruction group (no cases of heartburn or dumping syndrome) than that in the gastric reconstruction group. CONCLUSION: For reconstruction of the esophagus, the colonic interposition and supercharge technique is advantageous and contributes to the patient's quality of life.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Mutations of proto-oncogene c-kit in gastrointestinal stromal tumors (GISTs) are considered to cause a constitutive activation of KIT responsible for their oncogenesis. Imatinib has therapeutic potential for GISTs because of its inhibitory effect on KIT kinase activity. However, no study has been published concerning the effects of imatinib on GIST cells with various types of KIT mutation. To investigate the effects of imatinib on various c-kit mutations found in GISTs, cell proliferation and apoptosis assays were performed in two GIST cell lines with different KIT mutations. One of the cell lines, GIST-T1, revealed a heterozygous deletion of exon 11 in the c-kit, while the other cell line, GIST882, possessed a homozygous missense mutation of exon 13 in the c-kit gene. Imatinib inhibited proliferation and induced apoptosis in both cell lines. Imatinib potently suppressed proliferation of the GIST882 cell line at the concentration of 1.0 microM, whereas it inhibited the GIST-T1 at 0.1 microM. In two types of activating mutant KIT, imatinib could inhibit the constitutive activation of both types of KIT mutant, although the antiproliferative effect on GIST882 was weaker than on GIST-T1. Western blot analysis revealed that apoptosis related proteins were activated or suppressed by imatinib in both cell lines in the respective manner. Our results suggest that the apoptotic signal trans-duction caused by imatinib in GISTs is susceptible to various types of KIT mutation.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Amino acids, especially branched-chain amino acids such as l-leucine, have been shown to regulate activation of p70 S6 kinase and phosphorylation of 4E-BP1 through the mTOR signaling pathway. In our recent study, l-arginine was also shown to activate the mTOR signaling pathway in rat intestinal epithelial cells. l-Glutamine is an amino acid that is required for culturing of numerous cell types, including rat intestinal epithelial cells. In this study, we showed that l-glutamine inhibited the activation of p70 S6 kinase and phosphorylation of 4E-BP1 induced by arginine or leucine in rat intestinal epithelial cells. Although the molecular mechanism of l-glutamine-induced inhibition of the mTOR signaling pathway is still unknown, the presence of this novel signal pathway may indicate that individual amino acids play specific roles for cellular proliferation and growth.

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記述言語：日本語   出版者・発行元：岡山医学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Perforin is known as a pore-forming cytotoxic granule released from cytotoxic T cells. Previous experiments in vitro revealed the presence of precursor cells that are capable of producing perforin in the immune system cells. The present study was undertaken to examine whether perforin-positive cells could be induced in the digestive tract and to characterize their precursor cells. Expression of perforin-positive cells in the intestine of Balb/c mice induced by OK-432 was analyzed by immunohistochemical staining and RT-PCR. Oral treatment of Balb/c mice with OK-432 resulted in the occurrence of perforin-positive cells in the inferior segment of small intestine, the superior segment of large intestine, mesenteric lymph nodes and spleen. In the small intestine, perforin-positive cells were found in the lamina propria mucosa. The presence of perforin-positive cells was also noted following long-term OK-432 treatment. Similar results were obtained following treatment with biological response modifiers such as lipopolysaccharide. In mice with GVHD (graft-versus-host disease), the presence of perforin-positive cells was noted in the small intestine and spleen. When the serial sections of the small intestinal mucosa from OK-432-treated mice were immunostained with anti-perforin, anti-CD8 and anti-asialo-GM1 antibodies, the perforin-positive cells were found to be CD8-positive. The results suggest that CD8(+) cells in lamina propria mucosa play a significant role as effectors in the mucosal immune system which is activated by various stimuli.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: This study assessed the techniques of the free jejunal graft for the reconstruction of hypopharynx or cervical esophagus and discussed the main aspects related to those procedures. METHODS AND RESULTS: By using free jejunal grafts, we reconstructed 54 hypopharyngeal and cervical esophageal cancers. In this study, 23 out of 54 patients had a malignant tumor located in the hypopharynx and 31 in the cervical esophagus (27 primary cases and four secondary cases). Despite the multi-step and time-consuming procedure, we did not incur any trans-operative complication. Furthermore, we undertook the larynx preserving cervical esophagectomy and free jejunal graft reconstruction in six patients with cervical esophageal cancer, and those patients acquired a good quality of life. CONCLUSION: For the reconstruction of hypopharynx or cervical esophagus, the free jejunal graft is a very useful technique and improves the patient's quality of life.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In this study, we examined the distribution of heparanase protein in 75 esophageal squamous cell carcinomas by immunohistochemistry and analyzed the relationship between heparanase expression and clinicopathological characteristics. In situ hybridization showed that the mRNA expression pattern of heparanase was similar to that of the protein, suggesting that increased expression of the heparanase protein at the invasive front was caused by an increase of heparanase mRNA in tumor cells. Heparanase expression correlated significantly with depth of tumor invasion, lymph node metastasis, tumor node metastasis (TNM) stage and lymphatic invasion. Overexpression of heparanase in esophageal cancers was also associated with poor survival. In addition to its localization in the cytoplasm and cell membrane, heparanase was also identified in the nuclei of normal epithelial and tumor cells by immunohistochemistry. Furthermore, nuclear heparanase was detected in nuclear extract of cancer cell lines by Western blot and immunohistochemistry. Examination of the role of nuclear heparanase in cell proliferation and differentiation by double immunostaining for proliferating cell nuclear antigen (PCNA) and cytokeratin 10 (CK10) showed significant relationship between nuclear heparanase expression and differentiation (heparanase vs CK10), but not for proliferative state of esophageal cancer cells (heparanase vs PCNA). Our results suggest that cytoplasmic heparanase appears to be a useful prognostic marker in patients with esophageal cancer and that nuclear heparanase protein may play a role in differentiation. Inhibition of heparanase activity may be effective in the control of esophageal tumor invasion and metastasis.

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The accumulation of p53 protein, which is considered to be caused by a p53 gene mutation, is closely associated with poor prognosis in patients with certain types of carcinomas. The progression of esophageal squamous cell carcinoma (ESCC) is also suspected to depend on p53 gene status. We analyzed the relationship between p53 and p21 protein accumulation in ESCC, and simultaneously analyzed the frequency of apoptosis. Formalin-fixed paraffin-embedded sections were taken from 46 patients who underwent esophagectomy for ESCC. These sections were examined by immunostaining with monoclonal antibodies PAb1801 and EA10 to determine p53 and p21 protein accumulation, respectively. We also analyzed the frequency of apoptosis by TdT-mediated dUTP-biotin nick end-labeling (TUNEL). For estimation of the proportion of stained cells, we used computer analysis with NIH image analysis software. p21 protein accumulation showed an almost inverse distribution to that of p53 protein. In areas where both p53 and p21 proteins were accumulated, few apoptotic cells were observed. Particularly in cases of mucosal tumors, p53 protein was prominently accumulated in the lower layer of the tumor, whereas p21 protein accumulation was confined to the upper layer. Our results suggest that progression of esophageal squamous cell carcinoma is controlled by a p53-dependent pathway.

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：英語   出版者・発行元：(一社)日本癌治療学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(NPO)日本食道学会  

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記述言語：日本語   出版者・発行元：(一社)日本消化器外科学会  

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記述言語：日本語   出版者・発行元：(株)へるす出版  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：日本語   出版者・発行元：(一社)日本外科学会  

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記述言語：英語   出版者・発行元：(一社)日本胃癌学会  

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記述言語：英語   出版者・発行元：(一社)日本胃癌学会  

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記述言語：日本語   出版者・発行元：(一社)日本内視鏡外科学会  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）  

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記述言語：英語   掲載種別：研究発表ペーパー・要旨（国際会議）  

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