Faculty Profiles - HORIGUCHI Shigeru

Papers - HORIGUCHI Shigeru

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The efficacy of pancreatic juice cytology with liquid-based cytology for evaluating malignancy in patients with intraductal papillary mucinous neoplasm. International journal

Kazuya Miyamoto, Kazuyuki Matsumoto, Hironari Kato, Ryuichi Yoshida, Yuzo Umeda, Hirohumi Inoue, Takehiro Tanaka, Akihiro Matsumi, Yosuke Saragai, Yuki Fujii, Tatsuhiro Yamazaki, Daisuke Uchida, Takeshi Tomoda, Shigeru Horiguchi, Takahito Yagi, Hiroyuki Okada

BMC gastroenterology 20 ( 1 ) 319 - 319 2020.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Pancreatic juice cytology (PJC) is a tool for diagnosing malignant intraductal papillary mucinous neoplasm (IPMN); however, the accuracy is insufficient using the conventional method. Liquid-based cytology (LBC) improves the cell recovery rate, and almost all cells can be evaluated. We evaluated the efficacy of PJC with LBC for malignant IPMN. METHODS: We retrospectively analyzed 90 patients with suspected malignant IPMN who underwent PJC before pancreatectomy. PJC with smear and LBC methods was conducted in 52 patients (between June 2003 to December 2011) and 38 patients (between January 2012 to December 2018). Based on the imaging studies, all of the patients were classified according to the international consensus guidelines for IPMN revised in 2017. RESULTS: Of the 90 patients, 43 (48%) had malignant IPMN (high-grade dysplasia or invasive carcinoma), and the remaining patients had non-malignant IPMN (intermediate- or low-grade dysplasia). LBC increased the accuracy of PJC for the diagnosis of malignant IPMN (smear method: 56% [29/52] vs. LBC method: 76% [29/38]; P = 0.044). In a multivariate analysis, LBC was a significant factor influencing the accurate diagnosis of PJC (odds ratio: 3.52; P = 0.021). Furthermore, LBC increased the accuracy of PJC for malignant IPMN in patients with worrisome features (smear method: 66% [19/29] vs. LBC method: 93% [14/15]; P = 0.043). CONCLUSIONS: LBC increases the accuracy of PJC for diagnosing malignant IPMN compared with the conventional smear method.

DOI： 10.1186/s12876-020-01465-y

Utility of Endoscopic Ultrasound-Guided Fine Needle Aspiration in the Diagnosis of Local Recurrence of Pancreaticobiliary Cancer after Surgical Resection. International journal

Kazuyuki Matsumoto, Hironari Kato, Shigeru Horiguchi, Takeshi Tomoda, Akihiro Matsumi, Yuki Ishihara, Yosuke Saragai, Saimon Takada, Shinichiro Muro, Daisuke Uchida, Hiroyuki Okada

Gut and liver 14 ( 5 ) 652 - 658 2020.9

Language：English Publishing type：Research paper (scientific journal)

Background/Aims: Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA; EUS-FNA) allows for diagnostic tissue specimens from various regions to be analyzed. However, diagnosing recurrent pancreaticobiliary cancer after surgery is sometimes difficult. We evaluated the efficacy of EUS-FNA in the diagnosis of local recurrence of pancreaticobiliary cancer and analyzed the factors associated with falsenegative results. Methods: Fifty-one consecutive patients who underwent EUS-FNA due to suspected recurrence of pancreaticobiliary cancer after surgery in an academic center were retrospectively analyzed. The criteria for EUS-FNA were a resected margin or remnant pancreas mass, round swollen lymph node (≥10 mm in diameter), and soft-tissue enhancement around a major artery. Patients with suspected liver metastasis or malignant ascites were excluded. Results: Thirty-nine of the 51 patients had pancreatic cancer; the remaining 12 had biliary cancer. The target sites for EUS-FNA were the soft tissue around a major artery (n=22, 43%), the resected margin or remnant pancreas (n=12, 24%), and the lymph nodes (n=17, 33%). The median size of the suspected recurrent lesions was 15 mm (range, 8 to 40 mm). The overall sensitivity, specificity and accuracy of EUS-FNA for the diagnosis of recurrence was 84% (32/38), 100% (13/13), and 88% (45/51), respectively. FNA of the soft tissue around major arteries (odds ratio, 8.23; 95% confidence interval, 1.2 to 166.7; p=0.033) was significantly associated with a falsenegative diagnosis in the multivariate analysis. Conclusions: EUS-FNA is useful for diagnosing recurrent cancer, even after pancreaticobiliary surgery. The diagnoses of recurrence at soft-tissue sites should be interpreted with caution.

DOI： 10.5009/gnl19200

当院における肝門部領域良性胆道狭窄に対するInside stentの有用性の検討

皿谷洋祐, 加藤博也, 上田英次郎, 松三明宏, 宮本和也, 藤井佑樹, 山崎辰洋, 内田大輔, 友田健, 堀口繁, 堤康一郎, 岡田裕之

胆道 34 ( 3 ) 582 - 582 2020.8

EUSガイド下エタノール注入療法を施行したインスリノーマの1例

松本和幸, 加藤博也, 稲垣兼一, 宮本和也, 山崎辰洋, 藤井祐樹, 内田大輔, 友田健, 堀口繁, 岡田裕之

膵臓 35 ( 3 ) A449 - A449 2020.7

Serum REIC/Dickkopf-3 Protein Level Predicts Disease-Free Survival in Patients with Hepatocellular Carcinoma. Reviewed

Atsushi Oyama, Daisuke Uchida, Hidenori Shiraha, Hiroaki Sawahara, Ryo Kato, Masaya Iwamuro, Shigeru Horiguchi, Hiroyuki Okada

Acta medica Okayama 74 ( 3 ) 237 - 243 2020.6

Language：English Publishing type：Research paper (scientific journal)

The physiological role of the reduced expression of immortalized cells (REIC)/Dickkopf-3 (Dkk-3) protein in patients with hepatocellular carcinoma (HCC) remains unclear. In this study, we evaluated the effect of the REIC/Dkk-3 protein on HCC cell proliferation and assessed the relationship between the serum REIC/Dkk-3 protein level and the prognosis in patients with HCC. We evaluated the REIC/Dkk-3 protein-induced anticancer effects on Huh7 and Hep3B cells (HCC cell lines) in the presence of peripheral blood mononuclear cells (PBMCs), and found that combination treatment with REIC/Dkk-3 protein and PBMCs reduced the proliferation of HCC cells (Hep3B: 82.0%±16.3%; Huh7: 72.6%±9.1%). We also studied 194 HCC patients who underwent primary liver resection or primary radiofrequency ablation from 2008 to 2017. Serum REIC/Dkk-3 protein levels were measured by an enzyme-linked immunosorbent assay and compared to the prognostic data. The 3-year disease-free survival of the REIC/Dkk-3 high group was significantly higher than that in the REIC/Dkk-3 low group. In conclusion, this is the first study investigating the relationship between HCC patient survival and serum REIC/Dkk-3 protein levels in a large population. Based on the results, the serum REIC/Dkk-3 protein level should be considered a new prognostic marker for patients with HCC.

DOI： 10.18926/AMO/59957

Correction to: Outcomes of endoscopic treatment for malignant biliary obstruction in patients with surgically altered anatomy: analysis of risk factors for clinical failure. Reviewed International journal

Takeshi Tomoda, Hironari Kato, Kazuya Miyamoto, Akihiro Matsumi, Eijiro Ueta, Yuuki Fujii, Yousuke Saragai, Tatsuhiro Yamazaki, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Surgical endoscopy 35 ( 1 ) 239 - 240 2020.2

Outcomes of endoscopic treatment for malignant biliary obstruction in patients with surgically altered anatomy: analysis of risk factors for clinical failure. Reviewed International journal

Takeshi Tomoda, Hironari Kato, Kazuya Miyamoto, Akihiro Matsumi, Eijiro Ueta, Yuuki Fujii, Yousuke Saragai, Tatsuhiro Yamazaki, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Surgical endoscopy 35 ( 1 ) 232 - 238 2020.1

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: To evaluate the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) for malignant biliary obstruction (MBO) using short-type double-balloon enteroscope (sDBE) in patients with surgically altered anatomy. METHODS: A total of 45 patients with surgically altered anatomy underwent ERCP using sDBE for the treatment of MBO between April 2011 and March 2019. We retrospectively evaluated the clinical and technical success (insertion and biliary intervention success), adverse events, and risk factors for clinical failure. RESULTS: The scope was successfully inserted in the target site in 82.2% of patients (37/45), and among them, biliary intervention success was achieved in 86.4% (32/37). The overall technical success rate was 71.1% (32/45) and clinical success rate was 68.9% (31/45), with an adverse event rate of 11.1%. In multivariate analysis, the presence of peritoneal dissemination (odds ratio, 7.3; 95% confidence interval, 1.5-43.5, p = 0.02) was as an independent risk factor for clinical failure. The clinical success rate was 38.5% in patients with peritoneal dissemination and 81.3% in those without peritoneal dissemination. CONCLUSION: Endoscopic treatment using sDBE in patients without peritoneal dissemination provided favorable outcomes, and it can be an initial treatment for MBO in patients with surgically altered anatomy.

DOI： 10.1007/s00464-020-07385-y

Single-session esophagogastroduodenoscopy and endoscopic ultrasound using a forward-viewing radial scan ultrasonic endoscope. International journal

Daisuke Uchida, Hironari Kato, Kazuyuki Matsumoto, Yuki Ishihara, Akihiro Matsumi, Yosuke Saragai, Saimon Takada, Shuntaro Yabe, Shinichiro Muro, Takeshi Tomoda, Shigeru Horiguchi, Hiroyuki Okada

BMC gastroenterology 19 ( 1 ) 220 - 220 2019.12

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Endoscopic ultrasound is useful for obtaining high-resolution images of pancreaticobiliary diseases, but is not readily available for physical checkups. In this study, we evaluated the safety and efficacy of single-session esophagogastroduodenoscopy and endoscopic ultrasound in the detection of upper-gastrointestinal and pancreaticobiliary diseases using a forward-viewing radial scan ultrasonic endoscope. METHODS: A total of 148 patients who were scheduled for upper-gastrointestinal screening using an endoscope were prospectively included. All patients were examined by EUS in combination with EGD using a forward-viewing radial scan ultrasonic endoscope. The primary endpoint was the safety of the procedures. The secondary endpoints were the prevalence of diseases, the basal imaging capability of EUS, the procedure time, total dose of propofol, and the correlation between background factors and the prevalence of pancreatic disease. The imaging capability at each region was scored as 0 (invisible) to 2 (sufficient visualization to evaluate the organs). RESULTS: Intraoperative hypotension occurred as an adverse event of intravenous anesthesia in one patient. There were 82 pancreaticobiliary findings and 165 upper-gastrointestinal findings (malignancy not included). Follicular lymphoma of the intra-abdominal lymph nodes was detected in one patient. The mean imaging scores of each section were 1.95 (pancreatic head and papilla), 2.0 (pancreatic body), 1.99 (pancreatic tail), and 1.89 (common bile duct and gallbladder). Age, history of diabetes mellitus, and smoking history were significantly associated with the prevalence of pancreatic diseases. CONCLUSION: The simultaneous performance of EGD and EUS using a new ultrasonic endoscope is tolerable and safe for upper-gastrointestinal and pancreaticobiliary screening.

DOI： 10.1186/s12876-019-1141-7

The relationship between the PD-L1 expression of surgically resected and fine-needle aspiration specimens for patients with pancreatic cancer.

Kazuyuki Matsumoto, Toshiaki Ohara, Masayoshi Fujisawa, Akinobu Takaki, Masahiro Takahara, Noriyuki Tanaka, Hironari Kato, Shigeru Horiguchi, Ryuichi Yoshida, Yuzo Umeda, Soichiro Fushimi, Takahito Yagi, Akihiro Matsukawa, Hiroyuki Okada

Journal of gastroenterology 54 ( 11 ) 1019 - 1028 2019.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Recently, therapeutic antibodies against programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) have shown promising clinical results for several solid tumors, including pancreatic cancer. In this study, we evaluated the relationship between the PD-L1 expression of surgical resected and fine-needle aspiration (FNA) specimens for patients with pancreatic cancer. METHODS: Of 121 patients who underwent endoscopic ultrasound-guided (EUS)-FNA before surgery for pancreatic cancer in an academic center, the 94 (78%) with adequate FNA specimens for a histological evaluation were retrospectively analyzed. All the patients had undergone upfront surgery without any chemotherapy or radiotherapy. We performed immunohistochemistry (IHC) staining to investigate the PD-L1 expression in both resected and FNA specimens. The positive-stained cells were counted, and their percentage was used for the investigation. RESULTS: Of the 94 patients, 16 (17%) and 11 (10%) were defined as positive on resected cancer specimens using cutoff points of 5% and 10% positively stained cancer cell counts, respectively. The concordance rates for the positive frequency of PD-L1 expression between resected and FNA specimens were 44% (7/16) and 55% (6/11) when the positivity was set to ≥ 5% and ≥ 10%, respectively. The concordance rates for the negative frequency of PD-L1 expression between two specimens were 97% (76/78) and 99% (82/83) when the positivity was set to ≥ 5% and ≥ 10%, respectively. CONCLUSIONS: Approximately, half of the patients with PD-L1 expression positive and almost all the patients with PD-L1 expression negative could be diagnosed on FNA specimens.

DOI： 10.1007/s00535-019-01586-6

Contrast-enhanced harmonic endoscopic ultrasound using time-intensity curve analysis predicts pathological grade of pancreatic neuroendocrine neoplasm.

Saimon Takada, Hironari Kato, Yosuke Saragai, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Noriyuki Tanaka, Hiroyuki Okada

Journal of medical ultrasonics (2001) 46 ( 4 ) 449 - 458 2019.10

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Histological grading is important for the treatment algorithm in pancreatic neuroendocrine neoplasms (PNEN). The present study examined the efficacy of contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) and time-intensity curve (TIC) analysis of PNEN diagnosis and grading. METHODS: TIC analysis was performed in 30 patients using data obtained from CH-EUS, and a histopathological diagnosis was made via EUS-guided fine-needle aspiration or surgical resection. The TIC parameters were analyzed by dividing them into G1/G2 and G3/NEC groups. Then, patients were classified into non-aggressive and aggressive groups and evaluated. RESULTS: Twenty-six patients were classified as G1/G2, and four as G3/NEC. From the TIC analysis, five parameters were obtained (I: echo intensity change, II: time for peak enhancement, III: speed of contrast, IV: decrease rate for enhancement, and V: enhancement ratio for node/pancreatic parenchyma). Three of these parameters (I, IV, and V) showed high diagnostic performance. Using the cutoff value obtained from the receiver-operating characteristic (ROC) analysis, the correct diagnostic rates of parameters I, IV, and V were 96.7%, 100%, and 100%, respectively, between G1/G2 and G3/NEC. A total of 21 patients were classified into the non-aggressive group, and nine into the aggressive group. Using the cutoff value obtained from the ROC analysis, the accurate diagnostic rates of I, IV, and V were 86.7%, 86.7%, and 88.5%, respectively, between the non-aggressive and aggressive groups. CONCLUSION: CH-EUS and TIC analysis showed high diagnostic accuracy for grade diagnosis of PNEN. Quantitative perfusion analysis is useful to predict PNEN grade diagnosis preoperatively.

DOI： 10.1007/s10396-019-00967-x

Potential Factors Affecting Results of Short-Type Double-Balloon Endoscope-Assisted Endoscopic Retrograde Cholangiopancreatography. Reviewed International journal

Daisuke Uchida, Koichiro Tsutsumi, Hironari Kato, Akihiro Matsumi, Yosuke Saragai, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Hiroyuki Okada

Digestive diseases and sciences 65 ( 5 ) 1460 - 1470 2019.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Short-type double-balloon endoscope (DBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) has been developed as an alternative approach for cases with a surgically altered gastrointestinal anatomy. However, this technique is sometimes technically challenging and carries a risk of severe adverse events. AIMS: To evaluate the factors affecting the technical success rate and adverse events of DBE-ERCP. METHODS: A total of 319 patients (805 procedures) with a surgically altered gastrointestinal anatomy underwent short DBE-ERCP. The factors affecting the technical success rate and adverse events, and the learning curve of the trainees were retrospectively evaluated. RESULTS: The technical success rate of all procedures was 90.7%. Adverse events occurred in 44 (5.5%) procedures. A multivariate analysis indicated that Roux-en-Y reconstruction and first-time short DBE-ERCP were factors affecting the technical failure and adverse event rates, while the modified Child method after subtotal stomach-preserving pancreaticoduodenectomy reconstruction was a non-risk factor for adverse events. The trainee caseload did not affect the technical success or adverse event rates significantly; however, trainees tended to perform cases involving the modified Child method after subtotal stomach-preserving pancreaticoduodenectomy reconstruction. The success rate of scope insertion increased according to experience; however, the overall success rate did not differ to a statistically significant extent. CONCLUSION: Short DBE-ERCP was useful and safe for managing cases with a surgically altered anatomy; however, trainees should concentrate on accumulating experience with easy cases, such as those with the modified Child method after subtotal stomach-preserving pancreaticoduodenectomy reconstruction or a history of DBE-ERCP.

DOI： 10.1007/s10620-019-05857-3

Successful removal of impacted large bile duct stones using electrohydraulic lithotripsy with an ultraslim endoscope after Billroth II gastrectomy. International journal

Kazuyuki Matsumoto, Hironari Kato, Shigeru Horiguchi, Daisuke Uchida, Takeshi Tomoda, Shinichiro Muro, Hiroyuki Okada

Endoscopy 51 ( 9 ) E265-E266 2019.9

Diagnostic Ability of Convex-Arrayed Endoscopic Ultrasonography for Major Vascular Invasion in Pancreatic Cancer. International journal

Yuki Fujii, Kazuyuki Matsumoto, Hironari Kato, Yosuke Saragai, Saimon Takada, Sho Mizukawa, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Shigeru Horiguchi, Noriyuki Tanaka, Hiroyuki Okada

Clinical endoscopy 52 ( 5 ) 479 - 485 2019.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/AIMS: This study aimed to examine the diagnostic ability of endoscopic ultrasonography (EUS) for major vascular invasion in pancreatic cancer and to evaluate the relationship between EUS findings and pathological distance. METHODS: In total, 57 consecutive patients who underwent EUS for pancreatic cancer before surgery were retrospectively reviewed. EUS image findings were divided into four types according to the relationship between the tumor and major vessel (types 1 and 2: invasion, types 3 and 4: non-invasion). We also compared the EUS findings and pathologically measured distances between the tumors and evaluated vessels. RESULTS: The sensitivity, specificity, and accuracy of EUS diagnosis for vascular invasion were 89%, 92%, and 91%, respectively, in the veins and 83%, 94%, and 93%, respectively, in the arteries. The pathologically evaluated distances of cases with type 2 EUS findings were significantly shorter than those of cases with type 3 EUS findings in both the major veins (median [interquartile range], 96 [0-742] µm vs. 2,833 [1,076-5,694] µm, p=0.012) and arteries (623 [0-854] µm vs. 3,097 [1,396-6,000] µm, p=0.0061). All cases with a distance of ≥1,000 µm between the tumors and main vessels were correctly diagnosed. CONCLUSION: Tumors at a distance ≥1,000 µm from the main vessels were correctly diagnosed by EUS.

DOI： 10.5946/ce.2018.163

A "Back Light System" for Identification of Sites for Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Solid Pancreatic Masses: A Prospective, Randomized Study with a Crossover Design. Reviewed International journal

Ryo Harada, Hironari Kato, Soichiro Fushimi, Hirofumi Inoue, Daisuke Uchida, Yutaka Akimoto, Takeshi Tomoda, Kazuyuki Matsumoto, Yasuhiro Noma, Naoki Yamamoto, Shigeru Horiguchi, Koichiro Tsutsumi, Hiroyuki Okada

Clinical endoscopy 52 ( 4 ) 334 - 339 2019.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/AIMS: We applied a back light system (BLS) with a magnifying glass to improve the ability to assess the adequacy of specimen sampling using endosonography. We conducted this study to evaluate the efficacy of the BLS in sampling of specimens by endoscopic ultrasound-guided fine needle aspiration of solid pancreatic masses. METHODS: This was a prospective, randomized, crossover, single-center clinical trial. An endosonographer evaluated adequacy on gross visual inspection and identified whitish specimen sampling sites with and without the BLS according to a randomization sequence in the first and second passes with a 25-G needle. On cytological evaluation, the presence of well-defined pancreatic ductal epithelium was evaluated by a cytopathologist who was blinded to any clinical information. RESULTS: A total of 80 consecutive patients were eligible during the study period. Adequacy was observed for 52 specimens (65%) with the BLS and 54 (68%) without the BLS (p=0.88). In assessment of specimen adequacy on gross examination, only fair agreement was observed both with and without BLS (kappa score 0.40 and 0.29, respectively). CONCLUSION: The BLS did not influence the ability to identify specimen sampling sites or reliable assessment of specimen site adequacy using gross visual inspection.

DOI： 10.5946/ce.2019.004

Comparison Between Endoscopic Biliary Stenting Combined with Balloon Dilation and Balloon Dilation Alone for the Treatment of Benign Hepaticojejunostomy Anastomotic Stricture. Reviewed International journal

Takeshi Tomoda, Hironari Kato, Kazuya Miyamoto, Yousuke Saragai, Sho Mizukawa, Shuntaro Yabe, Saimon Takata, Shinichiro Muro, Daisuke Uchida, Kazuyuki Matsumoto, Shigeru Horiguchi, Koichiro Tsutsumi, Ken Hirao, Tsuneyoshi Ogawa, Hiroyuki Okada

Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 24 ( 6 ) 1352 - 1358 2019.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Hepaticojejunostomy anastomotic stricture (HJAS) is an important complication of biliary reconstructive surgery but has no standard treatment. We aimed to evaluate the outcomes of endoscopic treatment for benign HJAS and identify the risk factors for its recurrence. METHODS: This study retrospectively analyzed 176 patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for HJAS between April 2008 and March 2016. The outcome of endoscopic biliary stenting combined with balloon dilation (EBS group) and balloon dilation alone (balloon group) was evaluated. RESULTS: The scope was successfully inserted into the HJ site in 93.8% patients (165/176), and 139 patients underwent endoscopic treatment after HJAS was confirmed. Successful biliary drainage was achieved in 137 patients by using ERCP and rendezvous procedures. Among these, 103 patients were included in balloon group and 34 patients were in EBS group. HJAS was resolved in 132 patients; five died from recurrence of primary disease. The 1 (3)-year bile duct patency rates in the balloon and EBS groups were 62.5% (46.6%) and 89.4% (84.7%), respectively (p = 0.015). Univariate analysis showed that balloon dilation (p = 0.009) and early HJAS formation (time from surgery to ERCP < 1 year) (p = 0.02) were risk factors for HJAS recurrence. In the multivariate analysis, balloon dilatation was identified as independent risk factors for HJAS recurrence. CONCLUSIONS: Balloon dilation without stent deployment and early HJAS formation are risk factors for HJAS recurrence after endoscopic treatment. Stent deployment might be recommended for definite resolution of HJAS.

DOI： 10.1007/s11605-019-04297-8

Biliary cannulation technique with ultraslim endoscope for a patient with Billroth II gastrectomy. International journal

Yosuke Saragai, Daisuke Uchida, Hironari Kato, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Hiroyuki Okada

Endoscopy 51 ( 2 ) E38-E39 2019.2

Utility of liquid biopsy using urine in patients with pancreatic ductal adenocarcinoma. International journal

Hiroyuki Terasawa, Hideaki Kinugasa, Soichiro Ako, Mami Hirai, Hiroshi Matsushita, Daisuke Uchida, Takeshi Tomoda, Kazuyuki Matsumoto, Shigeru Horiguchi, Hironari Kato, Kazuhiro Nouso, Hiroyuki Okada

Cancer biology & therapy 20 ( 10 ) 1348 - 1353 2019

Language：English Publishing type：Research paper (scientific journal)

In recent years, liquid biopsy for blood and body fluid in cancer patients has attracted attention. However, there have been few reports of liquid biopsy focusing on urine of pancreatic ductal adenocarcinoma (PDAC). In 56 patients with PDAC, DNA was extracted from urine and plasma prior to treatment, and KRAS mutations were analyzed with droplet digital PCR to examine the mutation detection rate. Our study showed that KRAS mutations were found in 27 cases (48%) in urine and 27 cases (48%) in plasma. The detection rate of urine KRAS mutations varied by renal functions. The rates were 70% (14/20) and 36% (13/36) in the creatinine clearance rate (CCr) < 70 mL/min group and in the CCr ≥ 70 mL/min group, respectively (P = .024). Whereas, no influence of the CCr was observed in the detection rates of plasma KRAS mutations. The rates were 50% (10/20) and 47% (17/36) in cases with the CCr < 70 mL/min group and the CCr ≥ 70 mL/min group, respectively. Although the sample size was small, this study clearly indicated a new possibility of less invasive urine liquid biopsy in PDAC patients.

DOI： 10.1080/15384047.2019.1638685

Efficacy and safety of chemotherapy after endoscopic double stenting for malignant duodenal and biliary obstructions in patients with advanced pancreatic cancer: a single-institution retrospective analysis. Reviewed International journal

Kazuyuki Matsumoto, Hironari Kato, Shigeru Horiguchi, Koichiro Tsutsumi, Yosuke Saragai, Saimon Takada, Sho Mizukawa, Shinichiro Muro, Daisuke Uchida, Takeshi Tomoda, Hiroyuki Okada

BMC gastroenterology 18 ( 1 ) 157 - 157 2018.10

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Advanced pancreatic cancer is accompanied not only by bile duct obstruction, but also occasionally by duodenal obstruction. With new advances in chemotherapy and improvement in the management of stent dysfunction, the life expectancy of patients with pancreatic cancer has increased. This study aimed to evaluate the efficacy and safety of chemotherapy for advanced pancreatic cancer, as well as to analyze the prognostic factors, following endoscopic double stenting. METHODS: This retrospective study was conducted from January 1, 2007 to October 31, 2015 at an academic center. Fifty consecutive patients with pancreatic cancer who had undergone endoscopic double stenting, comprising duodenal and biliary stenting, were analyzed. We reviewed the patients records and analyzed the data of stent dysfunction rates after double stenting, reintervention for stent dysfunction, chemotherapy after double stenting, adverse events associated with chemotherapy after double stenting, survival times following double stenting, and overall survival times. The hospital's institutional review board for human research approved this study. RESULTS: The overall survival time and the survival time following double stenting were 10.9 months (IQR 6.0-18.4 months) and 2.4 months (IQR 1.4-5.2 months), respectively. After double stenting, duodenal stent dysfunction occurred in 6 patients (12%), and biliary stent dysfunction occurred in 12 patients (24%), respectively. All patients who experienced stent dysfunction underwent endoscopic reintervention, and all of the procedures were successful. Twenty-one (42%) patients were treated with chemotherapy post double stenting; 9 patients received chemotherapy as a first-line treatment, 9 as a second-line treatment, and 3 as a third-line treatment. During chemotherapy, 8 (38%) patients had grade 3-4 adverse events, which were manageable. Chemotherapy post double stenting (OR, 0.19; 95% CI, 0.059-0.60; P = .0051), reintervention for biliary stent dysfunction (OR, 0.21; 95% CI, 0.081-0.50; P = .0002), and performance status (< 2) (OR, 0.28; 95% CI, 0.098-0.71; P = .0064) were significant prognostic factors after double stenting. CONCLUSIONS: Systemic chemotherapy was manageable, even in patients with double stenting. Chemotherapy after double stenting and appropriate reintervention for stent obstructions potentially prolonged the survival of patients with advance pancreatic cancer.

DOI： 10.1186/s12876-018-0886-8

Multi-center clinical evaluation of streptozocin-based chemotherapy for advanced pancreatic neuroendocrine tumors in Japan: focus on weekly regimens and monotherapy. International journal

Hitoshi Shibuya, Susumu Hijioka, Yasunari Sakamoto, Tetsuhide Ito, Keijiro Ueda, Izumi Komoto, Noritoshi Kobayashi, Atsushi Kudo, Hiroaki Yasuda, Hayato Miyake, Junichi Arita, Sho Kiritani, Masafumi Ikeda, Hiroshi Imaoka, Makoto Ueno, Satoshi Kobayashi, Mitsuhiro Furuta, Yoshikuni Nagashio, Gou Murohisa, Taku Aoki, Shigemi Matsumoto, Masayo Motoya, Nobuaki Azemoto, Jun Itakura, Shigeru Horiguchi, Tatsuji Yogi, Tetsuro Kawagoe, Youichi Miyaoka, Fumito Imamura, Michio Senju, Hitoshi Arioka, Kazuo Hara, Masayuki Imamura, Takuji Okusaka

Cancer chemotherapy and pharmacology 82 ( 4 ) 661 - 668 2018.10

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Streptozocin (STZ) is a key agent for treating advanced pancreatic neuroendocrine tumors (pNET). Most STZ regimens for pNET are daily and also include 5-fluorouracil (5FU), whereas STZ monotherapy and weekly regimens have also been applied in daily practice in Japan. The present study aimed to evaluate responses to weekly regimens and to STZ monotherapy, and to identify a predictive marker of a response to STZ. METHODS: Clinical data regarding STZ-based chemotherapy for pNET were collected between 2015 and 2017 at 25 facilities. We analyzed the effects, safety, progression-free survival (PFS), and factors that correlate with responses to STZ. RESULTS: The overall objective response rate (ORR) of 110 patients who underwent STZ-based chemotherapy (monotherapy, 81.8%; weekly regimen 46.4%) was 21.8%, and PFS was 9.8 months. The ORR of weekly vs. daily regimens was 21.6 vs. 22.0% (P = 1.000), and that of monotherapy vs. combination therapy was 21.1 vs. 25.0% (P = 0.766). A Ki67 proliferation index (Ki67) of > 5% was a predictive marker of a response to STZ (P = 0.017), whereas regimen type, mono- or combination therapy, treatment line and liver tumor burden were not associated with responses. The frequencies of Grade ≥ 3 nausea and hematological adverse events were significantly lower for monotherapy than combination therapy (P = 0.032). CONCLUSIONS: The effects of weekly STZ monotherapy on pNET are comparable to those previously reported and the toxicity profile was acceptable. Ki67 > 5% was the sole predictive marker of an objective response.

DOI： 10.1007/s00280-018-3656-y

Dipeptide γ-secretase inhibitor treatment enhances the anti-tumor effects of cisplatin against gastric cancer by suppressing cancer stem cell properties. Reviewed International journal

Ryo Kato, Masaya Iwamuro, Hidenori Shiraha, Shigeru Horiguchi, Emi Tanaka, Ken Matsumoto, Atsushi Ohyama, Hiroaki Sawahara, Teruya Nagahara, Daisuke Uchida, Koichiro Tsutsumi, Hiroyuki Okada

Oncology letters 16 ( 4 ) 5426 - 5432 2018.10

Language：English Publishing type：Research paper (scientific journal)

The γ-secretase inhibitor blocks Notch activity by preventing its cleavage at the cell surface. In the present study, the effect of the γ-secretase inhibitor on the viability of gastric cancer cells when administered in combination with cisplatin was investigated, with particular focus on CD44highLgr-5high cancer cells. The four gastric cancer cell lines, MKN45, MKN74, SC-6-JCK and SH-10-TC, were used for the experiments. In the MTT assay, treatment with 25 µM dipeptide γ-secretase inhibitor (DAPT) alone did not affect cell proliferation in any of the four cell lines. Gastric cancer cells subjected to combination treatment with DAPT and cisplatin exhibited decreased viability when compared with those treated with cisplatin alone. Flow cytometry was performed to evaluate the expression of cluster of differentiation (CD)-44 and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr-5), two cancer stem cell markers in gastric cancers. Treatment with cisplatin alone significantly increased the proportion of CD44highLgr-5high cells. However, the addition of DAPT to cisplatin reduced the CD44highLgr-5high fraction, suggesting that DAPT reduced the number of gastric cancer cells. In conclusion, the present study demonstrated the synergistic effects of DAPT in combination with cisplatin by decreasing the survival of gastric cancer cells. In addition, combination treatment with DAPT reduced the number of CD44highLgr-5high cells, which are thought to exhibit cancer stem cell properties. These results highlight the therapeutic potential of DAPT in gastric cancer treatment.

DOI： 10.3892/ol.2018.9301

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