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1. The efficacy of wrapping with polyglycolic acid mesh and fibrin glue in preventing clinically relevant pancreatic fistula after minimally invasive distal pancreatectomy (WRAP Study): study protocol for a multicenter randomized controlled trial in Japan

Author

Hayato Baba, Atsushi Oba, Kimitaka Tanaka, Takayuki Miura, Daisuke Ban, Motonori Edanami, Yoshiya Ishikawa, Katsuhisa Ohgi, Haruyoshi Tanaka, Ryuta Shintakuya, Naoki Ikenaga, Tetsuya Ijichi, Yoshitaka Kiya, Ryo Muranushi, So Yamaki, Naoki Miyazaki, Shintaro Takeuchi, Shuichi Aoki, Takahiro Mizui, Masayuki Tanaka, Hiroki Ueda, Hideyuki Dei, Hideki Takami, Kenjiro Okada, Kohei Nakata, Yuko Mataki, Hiroaki Osakabe, Kazuto Shibuya, Daisuke Hashimoto, Yosuke Inoue, Satoshi Hirano, Michiaki Unno, Minoru Esaki, Minoru Kitago, Keiichi Akahoshi, Teiichi Sugiura, Tomoki Ebata, Kenichiro Uemura, Masafumi Nakamura, Takao Otsuka, Yuichi Nagakawa, Tsutomu Fujii, Sohei Satoi, and Yu Takahashi

Subjects
Distal pancreatectomy, Fibrin glue, Minimally invasive surgery, Polyglycolic acid mesh, Pancreatic fistula, Surgery, RD1-811
Abstract

Abstract Background Postoperative pancreatic fistula (POPF) continues to be the most common complication after distal pancreatectomy (DP). Recent advancements in surgical techniques have established minimally invasive distal pancreatectomy (MIDP) as the standard treatment for various conditions, including pancreatic cancer. However, MIDP has not demonstrated a clear advantage over open DP in terms of POPF rates, indicating the need for additional strategies to prevent POPF in MIDP. This trial (WRAP study) aims to evaluate the efficacy of wrapping the pancreatic stump with polyglycolic acid (PGA) mesh and fibrin glue in preventing clinically relevant (CR-) POPF following MIDP. Methods This multicenter, randomized controlled trial will include patients scheduled for laparoscopic or robotic DP for tumors in the pancreatic body and/or tail. Eligible participants will be centrally randomized into either the control group (Group A) or the intervention group (Group B), where the pancreatic stump will be reinforced by PGA mesh and fibrin glue. In both groups, pancreatic transection will be performed using a bioabsorbable reinforcement-attached stapler. A total of 172 patients will be enrolled across 14 high-volume centers in Japan. The primary endpoint is the incidence of CR-POPF (International Study Group of Pancreatic Surgery grade B/C). Discussion The WRAP study will determine whether the reinforcement of the pancreatic stump with PGA mesh and fibrin glue, a technique whose utility has been previously debated, could become the best practice in the era of MIDP, thereby enhancing its safety. Trial registration This trial was registered with the Japan Registry of Clinical Trials on June 15, 2024 (jRCTs032240120).

Published
2024
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2. Is multidisciplinary treatment effective for invasive intraductal papillary mucinous carcinoma?

Author

Seiko Hirono, Ryota Higuchi, Goro Honda, Satoshi Nara, Minoru Esaki, Naoto Gotohda, Hideki Takami, Michiaki Unno, Teiichi Sugiura, Masayuki Ohtsuka, Yasuhiro Shimizu, Ippei Matsumoto, Toshifumi Kin, Hiroyuki Isayama, Daisuke Hashimoto, Yasuji Seyama, Hiroaki Nagano, Kenichi Hakamada, Satoshi Hirano, Yuichi Nagakawa, Shugo Mizuno, Hidenori Takahashi, Kazuto Shibuya, Hideki Sasanuma, Taku Aoki, Yuichiro Kohara, Toshiki Rikiyama, Masafumi Nakamura, Itaru Endo, Yoshihiro Sakamoto, Akihiko Horiguchi, Takashi Hatori, Hirofumi Akita, Toshiharu Ueki, Tetsuya Idichi, Keiji Hanada, Shuji Suzuki, Keiichi Okano, Hiromitsu Maehira, Fuyuhiko Motoi, Yasuhiro Fujino, Satoshi Tanno, Akio Yanagisawa, Yoshifumi Takeyama, Kazuichi Okazaki, Sohei Satoi, and Hiroki Yamaue

Subjects
invasive IPMC, multidisciplinary treatment, neoadjuvant therapy, postoperative adjuvant therapy, recurrence, Surgery, RD1-811, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. Methods This retrospective multi‐institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. Results Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease‐specific survival (DSS), and recurrence‐free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19–9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un‐matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p

Published
2024
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3. Global evaluation and outcomes of cholecystectomy: protocol for a multicentre, international, prospective cohort study (GlobalSurg 4)

Author

Janet Martin, Ewen M Harrison, Philip Alexander, Dhruv Ghosh, Catherine Shaw, Robert Sutcliffe, Ewen Harrison, Ewen Griffiths, Malcolm Cameron, Sivesh K Kamarajah, Riinu Pius, Ajith Siriwardena, Antonio Ramos-De la Medina, Keith Roberts, John Primrose, Sohei Satoi, Rachel Guest, Dion G Morton, Omar Kouli, Amanda Dawson, Sivesh Kathir Kamarajah, Nicolas Avellaneda, Alex Dermanis, Parvez Haque, Laura Kehoe, Souliath Lawani, Ana Minaya Bravo, and Ng Wee Han

Subjects
Medicine
Abstract

Introduction Cholecystectomy is one of the most common operations performed worldwide. Although laparoscopic surgery has been the ‘gold-standard’ approach for this operation, there is a paucity of global evidence around the variations of safe provision of cholecystectomy, including low-income and middle-income countries. This international collaborative study will allow contemporaneous data collection on the quality of cholecystectomies using measures covering infrastructure, care processes and outcomes, with the primary aim define the global variation in compliance with preoperative, intraoperative and postoperative audit standards.Methods and analysis Global Evaluation of Cholecystectomy Knowledge and Outcomes is a prospective, international, multicentre, observational cohort study delivered by the GlobalSurg Collaborative. Consecutive patients undergoing cholecystectomy between 31 July 2023 and 19 November 2023 will be recruited, with follow-up at 30 days and 1-year postoperatively. The study will be undertaken at any hospital providing emergency or elective surgical services for biliary disease. The primary endpoint of this study is compliance with preoperative, intraoperative and postoperative audit standards. Secondary outcomes include rates of 30-day complications, achievement of critical view of safety and rates of gallbladder cancer.Ethics and dissemination This project will not affect clinical practice and has been classified as clinical audit following research ethics review at University Hospital Birmingham NHS Trust. The protocol will be disseminated through the international GlobalSurg and CovidSurg network.Trial registration number NCT06223061.

Published
2024
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4. Development of a nomogram to predict survival in advanced biliary tract cancer

Author

Hiroshi Imaoka, Masafumi Ikeda, Shogo Nomura, Chigusa Morizane, Takuji Okusaka, Masato Ozaka, Satoshi Shimizu, Kentaro Yamazaki, Naohiro Okano, Kazuya Sugimori, Hirofumi Shirakawa, Nobumasa Mizuno, Sohei Satoi, Hironori Yamaguchi, Rie Sugimoto, Kunihito Gotoh, Keji Sano, Akinori Asagi, Kazuyoshi Nakamura, and Makoto Ueno

Subjects
Medicine, Science
Abstract

Abstract The prognosis of advanced biliary tract cancer (BTC) patients remains poor due to limited efficacy of chemotherapy and difficulties in management. Thus, prediction of survival is crucial for the clinical management of advanced BTC. The aim was to develop and validate a nomogram to predict 6-month and 12-month survival in advanced BTC patients treated with chemotherapy. A multivariable Cox regression model was used to construct a nomogram in a training set (JCOG1113, a phase III trial comparing gemcitabine plus S-1 [GS] and gemcitabine plus cisplatin, n = 351). External validity of the nomogram was assessed using a test set (JCOG0805, a randomized, phase II trial comparing GS and S-1 alone, n = 100). Predictive performance was assessed in terms of discrimination and calibration. The constructed nomogram included lymph node metastasis, liver metastasis, carbohydrate antigen 19-9, carcinoembryonic antigen, albumin, and C-reactive protein. Uno’s concordance index was 0.661 (95% confidence interval [CI] 0.629–0.696) in the training set and 0.640 (95% CI 0.566–0.715) in the test set. The calibration plots for 6-month and 12-month survival showed good agreement in the two analysis sets. The present nomogram can facilitate prediction of the prognosis of advanced BTC patients treated with chemotherapy and help clinicians’ prognosis-based decision-making.

Published
2023
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5. Efficacy and safety of neoadjuvant nab‐paclitaxel plus gemcitabine therapy in patients with borderline resectable pancreatic cancer: A multicenter single‐arm phase II study (NAC‐GA trial)

Author

Ken‐ichi Okada, Kenjiro Kimura, Yo‐Ichi Yamashita, Kazuto Shibuya, Ippei Matsumoto, Sohei Satoi, Kazuhiro Yoshida, Yasuhiro Kodera, Takahiro Akahori, Seiko Hirono, Hidetoshi Eguchi, Mitsuhiro Asakuma, Masaji Tani, Etsuro Hatano, Hisashi Ikoma, Go Ohira, Hiromitsu Hayashi, Ke Wan, Toshio Shimokawa, Manabu Kawai, Hiroki Yamaue, and The NAC‐GA investigators

Subjects
borderline resectable, gemcitabine, nab‐paclitaxel, pancreatic cancer, phase II clinical trial, Surgery, RD1-811, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background Nab‐paclitaxel plus gemcitabine is a standard treatment for metastatic/locally advanced pancreatic cancer. The effectiveness of neoadjuvant therapy with nab‐paclitaxel plus gemcitabine (GnP‐NAT) in patients with borderline resectable pancreatic cancer (BRPC) remains unclear. Patients and Methods This single‐arm phase II trial included 61 patients with BRPC that were treated with two cycles of GnP‐NAT, (nab‐paclitaxel 125 mg/m2 and gemcitabine 1000 mg/m2), on days 1, 8, and 15 over a 4‐week period, which comprised one cycle. The primary endpoint was overall survival time. In the absence of disease progression, patients underwent planned pancreatectomy. Results Median overall survival, the primary endpoint, was 25.2 months, and the median recurrence‐free survival was 12.3 months. The overall rate of grade 3/4 events was 73.8%. One patient, who had a history of radiation therapy for past esophageal cancer, died from exacerbation via pneumonia. The overall resection rate was 73.8% (n = 45), and the R0 resection rate was 63.9% (n = 39). Overall, postoperative complications were found in 19 patients (42%) with 24 events, and nine patients (20%) with nine events ≥ grade IIIa, based on Dindo's classification. Conclusions This protocol treatment is thought to be a feasible, safe, and promising treatment regimen, but we caution against its use in patients with a history of interstitial lung disease and/or prior pulmonary irradiation. The survival data from this study suggest the need for further investigations of GnP‐NAT efficacy in patients with BRPC, as well as prospective evaluation of adverse events. Clinical Trial Registration UMIN Clinical Trials Registry, UMIN000024154 and ClinicalTrials.gov, NCT02926183.

Published
2023
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6. Reevaluation of regional lymph nodes in patients with pancreatic ductal adenocarcinoma in the pancreatic body and tail

Author

Yuki Matsui, Daisuke Hashimoto, Sohei Satoi, Tomohisa Yamamoto, So Yamaki, Mitsuaki Ishida, Satoshi Hirooka, Tsukasa Ikeura, and Mitsugu Sekimoto

Subjects
distal pancreatectomy, lymph node, lymph node metastasis, lymphadenectomy, pancreatic ductal adenocarcinoma, Surgery, RD1-811, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Introduction In patients with pancreatic ductal adenocarcinoma (PDAC) in the pancreatic body (Pb) and tail (Pt), the appropriate area for lymphadenectomy is controversial. This study aimed to reevaluate the extent of lymph node (LN) metastasis in Pb‐ and Pt‐PDAC, and to define the optimal area of LN dissection. Patients and methods This single‐center retrospective study evaluated patients with Pb‐ and Pt‐PDAC who underwent distal pancreatectomy with extended lymphadenectomy between 2006 and 2020. LN metastasis in >3.0% of patients were defined as new regional LN. Results The study cohort included 135 patients with Pb‐PDAC and 42 patients with Pt‐PDAC. In patients with Pb‐PDAC, LNs around the splenic artery (SPA) had the highest metastasis‐positive rate (54.1%). LNs along the left gastric artery, common hepatic artery, celiac axis (CA), superior mesenteric artery (SMA), and splenic hilus were defined as new regional LNs. In patients with Pt‐PDAC, LNs at the splenic hilum had the highest metastasis‐positive rate (38.1%). The station and LN around the SPA were defined as new regional LNs in those with Pt‐PDAC. Metastasis beyond the newly defined regional LNs was not associated with survival. The incidence of LN metastasis was lower in patients who received preoperative chemotherapy than in those who underwent upfront surgery in both Pb‐ and Pt‐PDAC. Conclusion Although it needs to be verified in future multicenter studies, LN of both the CA and SMA systems should be dissected in patients with Pb‐PDAC. However, only those around the SPA and splenic hilus should be dissected routinely in those with Pt‐PDAC.

Published
2023
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7. Randomized phase III trial of intravenous and intraperitoneal paclitaxel with S-1 versus gemcitabine plus nab-paclitaxel for pancreatic ductal adenocarcinoma with peritoneal metastasis (SP study)

Author

Tomohisa Yamamoto, Tsutomu Fujii, Satoshi Hirano, Fuyuhiko Motoi, Goro Honda, Kenichiro Uemura, Joji Kitayama, Michiaki Unno, Yasuhiro Kodera, Hiroki Yamaue, Toshio Shimokawa, Daisuke Hashimoto, So Yamaki, Hideyuki Yoshitomi, Fumihiko Miura, Hideki Ueno, Mitsugu Sekimoto, Sohei Satoi, and on behalf of the Study Group of Pancreatic Ductal Adenocarcinoma with Peritoneal Metastasis

Subjects
Pancreatic ductal carcinoma, Peritoneal metastasis, Peritoneal desemination, Intraperitoneal Paclitaxel, Randomized phase3 trial, Medicine (General), R5-920
Abstract

Abstract The prognosis of pancreatic ductal carcinoma (PDAC) with peritoneal metastasis remains dismal. Systemic chemotherapy alone may not be effective, and the combination of intraperitoneal chemotherapy with systemic chemotherapy is expected to prolong the overall survival in patients with peritoneal metastasis. We have designed a randomized phase III trial to confirm the superiority of intravenous (i.v.) and intraperitoneal (i.p.) paclitaxel (PTX) with S-1 relative to gemcitabine plus nab-PTX (GnP), which is the current standard therapy for patients with metastatic PDAC. A total of 180 patients will be accrued from 30 institutions within 3 years. Patients will be randomly assigned in a 1:1 ratio to receive either i.v. and i.p. PTX with S-1 or GnP (target of 90 patients per group). The primary endpoint is overall survival; secondary endpoints are progression-free survival, response rate, proportion with negative peritoneal washing cytology during chemotherapy, proportion requiring conversion surgery, and adverse event profiles. Japan Registry of Clinical Trials jRCTs051180199 ( https://jrct.niph.go.jp/ ).

Published
2022
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8. Efficacy of active hexose correlated compound on survival of patients with resectable/borderline resectable pancreatic cancer: a study protocol for a double-blind randomized phase II study

Author

Daisuke Hashimoto, Sohei Satoi, Hideki Ishikawa, Yasuhiro Kodera, Keiko Kamei, Satoshi Hirano, Tsutomu Fujii, Kenichiro Uemura, Akihiko Tsuchida, Suguru Yamada, Tomohisa Yamamoto, Kiichi Hirota, and Mitsugu Sekimoto

Subjects
Active hexose correlated compound, Functional food, Pancreatic cancer, Chemotherapy, Operation, Medicine (General), R5-920
Abstract

Abstract Background The prognosis of pancreatic ductal adenocarcinoma remains very poor. One possible reason for the short survival of patients with this disease is malnutrition, which can be present at the initial diagnosis, and continue after pancreatectomy. Then, it is important to improve nutritional status and to decrease adverse events during neoadjuvant and adjuvant chemotherapy. Active hexose correlated compound (AHCC) is a standardized extract of cultured Lentinula edodes mycelia, and is considered a potent biological response modifier in the treatment of cancer. To evaluate the survival impact of AHCC on the patients with pancreatic ductal adenocarcinoma, we plan to perform this trial. Methods This is a prospective multicenter phase II trial in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma to investigate the efficacy of AHCC regarding survival. Patients will begin taking AHCC or placebo on the first day of neoadjuvant therapy. AHCC or placebo will be continued until 2 years after surgery. The primary endpoint will be 2-year disease-free survival. The secondary endpoints are the completion rate, dose intensity, and adverse event profile of preoperative chemotherapy; response rate to preoperative chemotherapy; rate of decrease in tumor marker (carbohydrate antigen 19-9, carcinoembryonic antigen) concentrations during preoperative chemotherapy; entry rate, completion rate, dose intensity, and adverse event profile of adjuvant chemotherapy; safety of the protocol therapy (adverse effect of AHCC); 2-year overall survival rate; and nutrition score before and after preoperative chemotherapy, and before and after adjuvant chemotherapy. We will enroll 230 patients, and the study involves eight leading Japanese institutions that are all high-volume centers in pancreatic surgery. Discussion AHCC is expected to function as a supportive food in patients with pancreatic ductal adenocarcinoma, to reduce the proportion of severe adverse events related to neoadjuvant chemotherapy, and to increase the completion proportion of multimodal treatments, resulting in improved survival. Trial registration The trial protocol has been registered in the protocol registration system at the Japan Registry of Clinical Trials (Trial ID: jRCTs051200029 ). At the time of the submission of this paper (October 2020), the protocol version is 2.0. The completion date is estimated to be November 2024.

Published
2022
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9. Implementation of an educational program for pancreaticoduodenectomy in a university hospital: a retrospective observational study

Author

Sohei Satoi, Tomohisa Yamamoto, So Yamaki, Satoshi Hirooka, Daisuke Hashimoto, Tatsuma Sakaguchi, Hironori Ryota, Rintaro Yui, Kazuto Sakuramoto, Hideyuki Matsushima, Hiroaki Yanagimoto, Hideyoshi Toyokawa, Taku Michiura, Kentaro Inoue, and Mitsugu Sekimoto

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract. Objective:. No ideal training system exists for pancreaticoduodenectomy (PD). We developed an educational system that uses an objective structured assessment of technical skills. Methods:. This retrospective observational study was conducted using the data of consecutive trainees and patients who underwent PD from 2007 to 2013 in Kansai Medical University Hospital. The total score on the task checklist (21 parameters) for measuring technical performance during PD by self assessment and instructor assessment was compared between junior (JN) and hepatobiliary pancreatic (HBP) trainees at a university hospital. Surgical outcomes of 303 PDs (2007–2013) were also compared among JN trainees, HBP trainees, and instructors, and the present position of the trainees was investigated. This study was approved by the institutional review board of Kansai Medical University on May 26, 2020. Results:. The self-assessment score on the task checklist was significantly higher for the HBP trainees than for the JN trainees on all parts of PD (P

Published
2021
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10. Multicenter randomized phase II trial of prophylactic right‐half dissection of superior mesenteric artery nerve plexus in pancreatoduodenectomy for pancreatic head cancer

Author

Suguru Yamada, Sohei Satoi, Hideki Takami, Tomohisa Yamamoto, Isaku Yoshioka, Fuminori Sonohara, So Yamaki, Kazuto Shibuya, Masamichi Hayashi, Daisuke Hashimoto, Masahiko Ando, Kenta Murotani, Mitsugu Sekimoto, Yasuhiro Kodera, and Tsutomu Fujii

Subjects
pancreatic head cancer, pancreatoduodenectomy, phase II trial, superior mesenteric artery nerve plexus, Surgery, RD1-811, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Aim Right‐half dissection of the superior mesenteric artery (SMA) nerve plexus in pancreatoduodenectomy for pancreatic cancer was initiated to accomplish R0 resection; however, subsequent refractory diarrhea was a major concern. This study aimed to evaluate the necessity of this technique. Methods From April 2014 to June 2018, 74 patients with pancreatic head cancer were randomly allocated to either Group A, in which right‐half dissection of the SMA nerve plexus was performed (n = 37), or Group B, in which total preservation of the nerve plexus was performed (n = 37). Short‐term, long‐term, and survival outcomes were prospectively compared between the groups. Results The patient demographics, including the R0 resection rate, were not significantly different between the groups. Postoperative diarrhea occurred in 26 (70.3%) patients in Group A and 18 (48.6%) patients in Group B. There was a tendency for the development of severe diarrhea in Group A within 1 year postoperatively, and the frequency of diarrhea gradually decreased within 2 years, although that did not affect tolerance to adjuvant chemotherapy. There was no difference in either locoregional recurrence (27.0% vs 32.4%) or systemic recurrence (46.0% vs 46.0%). The median overall survival time in Groups A and B was 37.9 and 34.6 months, respectively (P = 0.77). Conclusion We did not demonstrate a clinical impact of right‐half dissection of the SMA nerve plexus on locoregional recurrence or survival. Therefore, the prophylactic dissection of the SMA nerve plexus is unnecessary given that refractory diarrhea could be induced by this technique (UMIN000012241).

Published
2021
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11. Surgical indication for and desirable outcomes of conversion surgery in patients with initially unresectable pancreatic ductal adenocarcinoma

Author

Sohei Satoi, Tomohisa Yamamoto, So Yamaki, Tatsuma Sakaguchi, and Mitsugu Sekimoto

Subjects
conversion surgery, overall survival, resectability, surgical indication, unresectable pancreatic ductal adenocarcinoma, Surgery, RD1-811, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Aim of this review is to propose an acceptable surgical indication for conversion surgery in patients with initially unresectable (UR) pancreatic ductal adenocarcinoma (PDAC) by considering desirable outcomes, including resectability, overall survival (OS), and disease‐free survival (DFS). A comprehensive literature search of PubMed was conducted through July 15, 2019. Eligible studies were those reporting on patients with UR‐PDAC who underwent surgery. We excluded case reports with fewer than 10 patients, insufficient descriptions of survival data, and palliative surgery. When patients with UR‐PDAC with no progression after chemo(radiation) therapy were offered surgical exploration, resectability and median survival time (MST) of those who underwent conversion surgery ranged from 20% to 69% (median, 52%) and from 19.5 to 33 months (median, 21.9 months), respectively. When conversion surgery was carried out in patients with expected margin‐negative resection or with clinical response by Response Evaluation Criteria In Solid Tumors (RECIST), resectability and MST ranged from 18% to 27% (median, 20%) and from 21 to 35.3 months (median, 30 months), respectively. Among patients who underwent conversion surgery based on clinical response and decreased CA19‐9 level after multimodal treatment, resectability and MST ranged from 2% to 24% (median, 4.1%) and from 24.1 to 64 months (median, 36 months), respectively. Decreased CA19‐9 level was a predictor of resectability, OS and DFS by multivariate analysis. In conclusion, decision‐making for conversion surgery based on clinical response and decreased CA19‐9 level after multimodal treatment may be appropriate. With regard to desirable outcomes of OS and DFS, conversion surgery may provide improved survival for patients with initial UR‐PDAC.

Published
2020
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12. The efficacy of polyglycolic acid felt reinforcement in preventing postoperative pancreatic fistula after pancreaticojejunostomy in patients with main pancreatic duct less than 3 mm in diameter and soft pancreas undergoing pancreatoduodenectomy (PLANET-PJ trial): study protocol for a multicentre randomized phase III trial in Japan and Korea

Author

Kazuto Shibuya, Jin-Young Jang, Sohei Satoi, Masayuki Sho, Suguru Yamada, Manabu Kawai, Hongbeom Kim, Song Cheol Kim, Jin Seok Heo, Yoo-Seok Yoon, Joon Seong Park, Ho Kyoung Hwang, Isaku Yoshioka, Toshio Shimokawa, Hiroki Yamaue, and Tsutomu Fujii

Subjects
Pancreatoduodenectomy, Pancreaticojejunostomy, Postoperative pancreatic fistula, Polyglycolic acid felt, International multicentre study, Medicine (General), R5-920
Abstract

Abstract Background Partial pancreatoduodenectomy is performed for malignant and benign diseases of the pancreatic head region. The procedure is considered highly difficult and highly invasive. Postoperative pancreatic fistula (POPF) is an important complication because of several consequent complications, including intraabdominal haemorrhage, often increasing hospital stays and surgical mortality. Although many kinds of pancreaticojejunostomy aimed at reducing POPF have been examined to date, the technique has not yet been standardized. We devised a new method using double-coated polyglycolic acid felt after pancreaticojejunostomy. The aim of the PLANET-PJ trial is to evaluate the superiority of polyglycolic acid felt reinforcement in preventing POPF after pancreaticojejunostomy in patients undergoing partial pancreatoduodenectomy to previous anastomosis methods. Methods Patients diagnosed with pancreatic or periampullary lesions in whom it is judged that the main pancreatic duct diameter was 3 mm or less on the left side of the portal vein without pancreatic parenchymal atrophy due to obstructive pancreatitis are considered eligible for inclusion. This study is designed as a multicentre randomized phase III trial in Japan and the Republic of Korea. Eligible patients will be centrally randomized to either group A (polyglycolic acid felt reinforcement) or group B (control). In total, 514 patients will be randomized in 31 high-volume centres in Japan and Republic of Korea. The primary endpoint is the incidence of POPF (International Study Group of Pancreatic Surgery grade B/C). Discussion The PLANET-PJ trial evaluates the efficacy of a new method using double-coated polyglycolic acid felt reinforcement for preventing POPF after pancreaticojejunostomy. This new method may reduce POPF. Trial registration ClinicalTrials.gov, NCT03331718. University Hospital Medical Information Network Clinical Trials Registry, UMIN000029647. Registered on 30 November 2017. https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000033874

Published
2019
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13. A double-blind randomized comparative clinical trial to evaluate the safety and efficacy of dendritic cell vaccine loaded with WT1 peptides (TLP0-001) in combination with S-1 in patients with advanced pancreatic cancer refractory to standard chemotherapy

Author

Masahiro Katsuda, Motoki Miyazawa, Toshiyasu Ojima, Akio Katanuma, Kenichi Hakamada, Kentaro Sudo, Shingo Asahara, Itaru Endo, Makoto Ueno, Kazuo Hara, Suguru Yamada, Tsutomu Fujii, Sohei Satoi, Tatsuya Ioka, Masaichi Ohira, Takahiro Akahori, Masayuki Kitano, Hiroaki Nagano, Masayuki Furukawa, Tomohiko Adachi, and Hiroki Yamaue

Subjects
Dendritic cells, Immunotherapy, Pancreatic cancer, S-1, Vaccine, Wilms’ tumor gene 1, Medicine (General), R5-920
Abstract

Abstract Background Pancreatic cancer is a refractory malignancy, and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms’ tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy. Methods This is an investigator-initiated, double-blind, comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines. Discussion Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety, as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety. Trial registration University Hospital Medical Information Network Clinical Trials Registry, UMIN000027179. Registered on 9 April 2017.

Published
2019
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14. Decreased serum carbohydrate antigen 19–9 levels after neoadjuvant therapy predict a better prognosis for patients with pancreatic adenocarcinoma: a multicenter case-control study of 240 patients

Author

Shuichi Aoki, Fuyuhiko Motoi, Yoshiaki Murakami, Masayuki Sho, Sohei Satoi, Goro Honda, Kenichiro Uemura, Ken-ichi Okada, Ippei Matsumoto, Minako Nagai, Hiroaki Yanagimoto, Masanao Kurata, Takumi Fukumoto, Masamichi Mizuma, Hiroki Yamaue, Michiaki Unno, and for the Multicenter Study Group of Pancreatobiliary Surgery (MSG-PBS)

Subjects
Carbohydrate antigen 19–9, Neoadjuvant therapy, Pancreatic cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Carbohydrate antigen (CA) 19–9 levels after resection are considered to predict prognosis; however, the significance of decreased CA19–9 levels after neoadjuvant therapy has not been clarified. This study aimed to define the prognostic significance of decreased CA19–9 levels after neoadjuvant therapy in patients with pancreatic adenocarcinoma. Methods Between 2001 and 2012, 240 consecutive patients received neoadjuvant therapy and subsequent resection at seven high-volume institutions in Japan. These patients were divided into three groups: Normal group (no elevation [≤37 U/ml] before and after neoadjuvant therapy), Responder group (elevated levels [> 37 U/ml] before neoadjuvant therapy but decreased levels [≤37 U/ml] afterwards), and Non-responder group (elevated levels [> 37 U/ml] after neoadjuvant therapy). Analyses of overall survival and recurrence patterns were performed. Uni- and multivariate analyses were performed to clarify the clinicopathological factors influencing overall survival. The initial metastasis sites were also evaluated in these groups. Results The Responder group received a better prognosis than the Non-responder group (3-year overall survival: 50.6 and 41.6%, respectively, P = 0.026), but the prognosis was comparable to the Normal group (3-year overall survival: 54.2%, P = 0.934). According to the analysis of the receiver operating characteristic curve, the CA19–9 cut-off level defined as no elevation after neoadjuvant therapy was ≤103 U/ml. The multivariate analysis revealed that a CA19–9 level ≤ 103 U/ml, (P = 0.010, hazard ratio: 1.711; 95% confidence interval: 1.133–2.639), tumor size ≤27 mm (P = 0.040, 1.517; (1.018–2.278)), a lack of lymph node metastasis (P = 0.002, 1.905; (1.276–2.875)), and R0 status (P = 0.045, 1.659; 1.012–2.627) were significant predictors of overall survival. Moreover, the Responder group showed a lower risk of hepatic recurrence (18%) compared to the Non-responder group (31%), though no significant difference in loco-regional, peritoneal or other distant recurrence were observed between groups (P = 0.058, P = 0.700 and P = 0.350, respectively). Conclusions Decreased CA19–9 levels after neoadjuvant therapy predicts a better prognosis, with low incidence of hepatic recurrence after surgery.

Published
2019
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15. Does modified Blumgart anastomosis without intra-pancreatic ductal stenting reduce post-operative pancreatic fistula after pancreaticojejunostomy?

Author

Sohei Satoi, Tomohisa Yamamoto, Hiroaki Yanagimoto, So Yamaki, Hisashi Kosaka, Satoshi Hirooka, Masaya Kotsuka, Hironori Ryota, Taku Michiura, Kentaro Inoue, and Yoichi Matsui

Subjects
Surgery, RD1-811
Abstract

Summary: Background: Post-operative pancreatic fistula (POPF) is one of the most common and serious complications after pancreaticoduodenectomy (PD). The aim of this study is to retrospectively compare clinically relevant (CR) POPF and other complications after pacreaticojejunostomy (PJ) after modified Kakita (m-Kakita) or modified Blumgart (m-Blumgart) anastomoses without stenting in a single institution. Methods: One hundred twenty-eight patients underwent PJ using m-Kakita anastomoses (two interrupted penetrating sutures) between January 2009 and December 2011. One hundred eighteen patients underwent m-Blumgart anastomoses (two transpancreatic/jejunal seromuscular sutures to cover the pancreatic stump with jejunal serosa) between January 2014 and December 2015. Demographics, clinical characteristics, and post-operative mortality and morbidity were retrospectively compared between the two groups. Results: There were no significant differences in demographics or clinical characteristics between the two groups except operative time. A significantly lower rate of CR-POPF was found in the m-Blumgart group relative to the m-Kakita group (10% vs. 19%, p = 0.038). Univariate and multivariate analyses revealed that the m-Blumgart anastomosis and fistula risk category (Negligible, Low) were independently protective against CR-POPF (p

Published
2019
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16. Interdisciplinary Approach of Establishing PDAC Resectability: Biochemical, Radiological and NAT Regimen Prognostic Factors—Literature Review

Author

Aiste Gulla, Daisuke Hashimoto, Doris Wagner, Ryte Damaseviciute, Kestutis Strupas, and Sohei Satoi

Subjects
pancreatic adenocarcinoma, neoadjuvant treatment, surgical resectability, Medicine (General), R5-920
Abstract

Background and Objectives: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal tumors, with a 5-year overall survival rate of less than 10%. To date, curative surgical resection remains the only favorable option for improving patients’ survival. However, there is no consensus on which prognostic biochemical, radiological markers or neoadjuvant therapy regimens would benefit patients the most. Materials and Methods: A literature review was performed focusing on overall survival, R0 resection, 30-day mortality, adverse events (AEs), and elevated biomarkers. The electronic databases were searched from 2015 to 2020. Results: We reviewed 22 independent studies. In total, 20 studies were retrospective single- or multi-center reviews, while 2 studies were prospective Phase II trials. Conclusions: Patients with borderline resectable or locally advanced PDAC, who received neoadjuvant therapy (NAT) and surgery, have significantly better survival rates. The CA 19-9 biomarker levels in the neoadjuvant setting should be evaluated and considered as a specific biomarker for tumor resectability and overall survival.

Published
2022
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18. MAPLE-PD trial (Mesenteric Approach vs. Conventional Approach for Pancreatic Cancer during Pancreaticoduodenectomy): study protocol for a multicenter randomized controlled trial of 354 patients with pancreatic ductal adenocarcinoma

Author

Seiko Hirono, Manabu Kawai, Ken-ichi Okada, Tsutomu Fujii, Masayuki Sho, Sohei Satoi, Ryosuke Amano, Hidetoshi Eguchi, Yuko Mataki, Masafumi Nakamura, Ippei Matsumoto, Hideo Baba, Masaji Tani, Yasunari Kawabata, Yuichi Nagakawa, Suguru Yamada, Yoshiaki Murakami, Toshio Shimokawa, and Hiroki Yamaue

Subjects
Mesenteric approach, Artery-first approach, Conventional approach, Pancreaticoduodenectomy, R0 resection, Pancreatic ductal adenocarcinoma, Medicine (General), R5-920
Abstract

Abstract Background The mesenteric approach is an artery-first approach to pancreaticoduodenectomy for pancreatic cancer, which starts with the dissection of connective tissues around the superior mesenteric artery. The procedure aims for early confirmation of resectability by checking the surgical margin around the superior mesenteric artery first during the operation. It also aims to decrease intraoperative blood loss by early ligation of the inferior pancreaticoduodenal artery and to increase R0 rate by complete clearance of the lymph nodes around the superior mesenteric artery and pancreatic head plexus II, the most favorable positive margin site for pancreatic ductal adenocarcinoma. Furthermore, it aims to avoid the spread of cancer cells during operation (nontouch isolation technique). The MAPLE-PD (Mesenteric Approach vs. Conventional Approach for Pancreatic Cancer during Pancreaticoduodenectomy) trial investigates whether the mesenteric approach can prolong the survival of patients with pancreatic ductal adenocarcinoma who undergo pancreaticoduodenectomy compared with the conventional approach. Methods/design The MAPLE-PD trial is a Japanese multicenter randomized controlled trial that compares the surgical outcomes between the mesenteric and conventional approaches to pancreaticoduodenectomy. Patients with pancreatic ductal adenocarcinoma scheduled to undergo pancreaticoduodenectomy are randomized before operation to either a conventional approach (arm A) or a mesenteric approach (arm B). In arm A, the operation starts with Kocher’s maneuver. At the final step of the removal procedure, the connective tissues around the superior mesenteric artery are dissected. In arm B, the operation starts with dissection of the connective tissues around the superior mesenteric artery and ends with Kocher’s maneuver. In total, 354 patients from 15 Japanese high-volume centers will be randomized. The primary endpoint is overall survival by intention-to-treat analysis. Secondary endpoints include intraoperative blood loss, R0 rate, and recurrence-free survival. Discussion If the MAPLE-PD trial shows the oncological benefits of the mesenteric approach for patients with pancreatic ductal adenocarcinoma, this procedure may become a standard approach to pancreaticoduodenectomy. Trial registration ClinicalTrials.gov, NCT03317886. Registered on 23 October 2017. University Hospital Medical Information Network Clinical Trials Registry, UMIN000029615. Registered on 15 January 2018.

Published
2018
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19. Splenic vein resection together with the pancreatic parenchyma versus separated resection after isolation of the parenchyma during distal pancreatectomy (COSMOS-DP trial): study protocol for a randomised controlled trial

Author

Suguru Yamada, Tsutomu Fujii, Manabu Kawai, Toshio Shimokawa, Masafumi Nakamura, Yoshiaki Murakami, Sohei Satoi, Hidetoshi Eguchi, Yuichi Nagakawa, Yasuhiro Kodera, and Hiroki Yamaue

Subjects
Distal pancreatectomy, Splenic vein, Intra-abdominal haemorrhage, Pancreatic fistula, Mechanical stapler, Medicine (General), R5-920
Abstract

Abstract Background In distal pancreatectomy (DP), it is customary to ligate and divide the splenic vein after isolating it from the pancreatic parenchyma. This is considered essential to prevent disruption of the stump of the splenic vein and consequent intra-abdominal haemorrhage in the event of pancreatic fistula (PF). However, this procedure can be technically demanding, especially when the vein is firmly embedded in the pancreatic parenchyma. The objective of the COSMOS-DP trial is to confirm the non-inferiority of resection of the splenic vein embedded in the pancreatic parenchyma compared with the conventional technique of isolating the splenic vein before resection during DP using a mechanical stapler. Methods Patients with diseases of the pancreatic body and tail whose pancreatic parenchyma and splenic vein can be divided concurrently during open or laparoscopic DP are considered eligible for inclusion. This study is designed as a multicentre prospective randomised phase III trial. Eligible patients will be centrally randomised to either Arm A (resection of the splenic vein after isolation from the pancreatic parenchyma) or Arm B (co-resection of the vein together with the pancreas). This study aims to establish the non-inferiority of the safety of Arm B compared with that of Arm A; the primary endpoint is the incidence of PF (ISGPF grade B/C). Discussion The COSMOS-DP trial will establish the safety of this procedure, such that it can be recommended with more confidence. The use of this procedure will likely result in significant reductions in operative time and blood loss during DP. Trial registration ClinicalTrials.gov, NCT02871804. Registered on 27 July 2016.

Published
2018
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20. Evaluation of relative criteria for single-incision laparoscopic cholecystectomy

Author

Yoichi Matsui, So Yamaki, Satoshi Hirooka, Tomohisa Yamamoto, Hiroaki Yanagimoto, Sohei Satoi, and Masanori Kon

Subjects
Surgery, RD1-811
Abstract

Summary: Background/Objective: Although single-incision laparoscopic cholecystectomy (SILC) has no advantage over conventional laparoscopic cholecystectomy (LC), except for better cosmesis, few reports have discussed the criteria for SILC. The aim of this study was to evaluate the suitability of our criteria for SILC. Methods: During the study period, SILC was performed at our institution under the following criteria. The inclusion criteria were elective surgery, age of < 60 years, and body mass index of < 30 kg/m2. The exclusion criteria were a thick gallbladder wall, history of choledocholithiasis, previous abdominal surgery, and serious concomitant disease. We reviewed data regarding consecutive patients who underwent LC at our institution from November 2009 to March 2016. The data were assessed with respect to patient characteristics, operative data, and postoperative outcomes. Results: A total of 1093 patients underwent elective LC, and 232 (21.2%) of these patients underwent SILC using our criteria. Fourteen patients (6.0%) who underwent SILC required extra ports. Among the patients aged < 60 years, 50.2% (232/462) underwent SILC. There were few adverse events, including intra- and postoperative complications, among the patients who underwent SILC. Conclusion: The above-mentioned criteria are safe, necessary, and sufficient for SILC over conventional LC. Keywords: criteria, indication, single-incision laparoscopic cholecystectomy

Published
2018
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21. Antibiotic prophylaxis in laparoscopic cholecystectomy: a randomized controlled trial.

Author

Yoichi Matsui, Sohei Satoi, Masaki Kaibori, Hideyoshi Toyokawa, Hiroaki Yanagimoto, Kosuke Matsui, Morihiko Ishizaki, and A-Hon Kwon

Subjects
Medicine, Science
Abstract

Recent meta-analyses concluded that antibiotic prophylaxis is not warranted in low-risk laparoscopic cholecystectomy. However, most trials in the meta-analyses had a relatively small sample size and were statistically underpowered. In addition, many of the trials mentioned potential cost savings owing to the elimination of prophylactic antibiotics. However, no trial has statistically estimated the cost effectiveness. To evaluate the results of meta-analyses, we conducted a randomized controlled trial on the role of prophylactic antibiotics in low-risk laparoscopic cholecystectomy with an adequate sample size.From March 2007 to May 2013, at the Department of Surgery, Kansai Medical University, patients who were scheduled for elective laparoscopic cholecystectomy were randomly assigned to one of two arms: those who were and were not administered prophylactic antibiotics. The primary endpoint was the occurrence of postoperative infections and secondary endpoints were postoperative hospital stay and medical costs.During the study period, 518 patients were assigned to the Antibiotics group and 519 to the No antibiotics group. Occurrences of surgical site infections, distant infections and overall infections were significantly lower in the Antibiotics group than in the No antibiotics group (0.8 vs. 3.7%, p = 0.001, OR: 0.205 (95%CI: 0.069 to 0.606); 0.4 vs. 3.1%, p = 0.0004, OR: 0.122 (95%CI: 0.028 to 0.533); 1.2 vs. 6.7%; p

Published
2014
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22. Impact of neoadjuvant therapy on gut microbiome in patients with resectable/borderline resectable pancreatic ductal adenocarcinoma

Author

Ayaka Takaori, Daisuke Hashimoto, Tsukasa Ikeura, Takashi Ito, Koh Nakamaru, Masataka Masuda, Shinji Nakayama, So Yamaki, Tomohisa Yamamoto, Kosuke Fujimoto, Yoshiyuki Matsuo, Shohei Akagawa, Mitsuaki Ishida, Kiyoshi Yamaguchi, Seiya Imoto, Kiichi Hirota, Satoshi Uematsu, Sohei Satoi, Mitsugu Sekimoto, and Makoto Naganuma

Subjects
Hepatology, Endocrinology, Diabetes and Metabolism, Gastroenterology
Published
2023
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24. Risk factors associated with hypoglycemic events after total pancreatectomy: A nationwide multicenter prospective study in Japan

Author

Hironobu Suto, Keiko Kamei, Hiroyuki Kato, Takeyuki Misawa, Michiaki Unno, Hiroyuki Nitta, Sohei Satoi, Yasunari Kawabata, Masayuki Ohtsuka, Toshiki Rikiyama, Takeshi Sudo, Ippei Matsumoto, Tomohiro Hirao, Keiichi Okano, Yasuyuki Suzuki, Naohiro Sata, Shuji Isaji, Masanori Sugiyama, and Yoshifumi Takeyama

Subjects
Blood Glucose, Glycated Hemoglobin, Cholesterol, Pancreatectomy, Japan, Risk Factors, Insulin, Short-Acting, Weight Loss, Humans, Hypoglycemic Agents, Insulin, Surgery, Prospective Studies
Abstract

The number of total pancreatectomy cases have increased worldwide, expanding the need for new insulin products and high-titer pancrelipases. However, the current data that is focused on hypoglycemic events after a total pancreatectomy from large nationwide series are still lacking. This study is aimed to assess the risk factors associated with hypoglycemic events after a total pancreatectomy.Data were prospectively collected from 216 consecutive patients who underwent total pancreatectomies between August 2015 and December 2017 from 68 Japanese centers. Of the 216 patients, 166 with a follow-up period of 1 year were analyzed. The risk factors for hypoglycemic events at 6 and 12 months (postoperative months 6 and 12) were investigated based on the results of a nationwide multicenter prospective study.Of the 166 patients, 57 (34%) and 70 (42%) experienced moderate or severe hypoglycemic events or hypoglycemia unawareness on a monthly basis at postoperative months 6 and 12, respectively. Multivariate analysis revealed that body weight loss after surgery ≥0.3 kg and total cholesterol level ≤136 mg/dL at postoperative month 6, and glycated hemoglobin level ≤8.9% and rapid-acting insulin use at postoperative month 12 were independent risk factors for hypoglycemic events after a total pancreatectomy. There were different independent risk factors depending on the postoperative period.Patients with body weight loss after surgery, low total cholesterol level, strict glycemic control, and using rapid-acting insulin should be aware of the occurrence of hypoglycemic events after their total pancreatectomy. In order to prevent hypoglycemic events after a total pancreatectomy, we need to consider optimal nutritional and glycemic control according to the postoperative period.

Published
2022
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26. A Retrospective Study Investigating the Safety and Efficacy of Nanoliposomal Irinotecan in Elderly Patients with Unresectable Pancreatic Cancer

Author

Tatsuki Ikoma, Toshihiko Matsumoto, Shogen Boku, Tomoyo Yasuda, Masataka Masuda, Takashi Ito, Koh Nakamaru, So Yamaki, Shinji Nakayama, Daisuke Hashimoto, Tomohisa Yamamoto, Nobuhiro Shibata, Tsukasa Ikeura, Makoto Naganuma, Sohei Satoi, and Takayasu Kurata

Subjects
General Medicine, nanoliposomal irinotecan (nal-IRI), pancreatic cancer, elderly patients, nutritional status
Abstract

Although nanoliposomal irinotecan combined with 5-fluorouracil and leucovorin (nal-IRI+5-FU/LV) has been used to treat first-line resistant unresectable pancreatic cancer, the efficacy and safety data among the elderly remain limited. We retrospectively analyzed clinical outcomes among elderly patients. Patients treated with nal-IRI+5-FU/LV were assigned to the elderly (≥75 years) and non-elderly (

Published
2023
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27. Clinical outcomes of organ‐preserving pancreatectomy for benign or low‐grade malignant pancreatic tumors: A multicenter nationwide survey in Japan

Author

Yukio Asano, Hiroyuki Kato, Satoshi Arakawa, Masahiro Ito, Takukazu Nagakawa, Akimasa Nakao, Tetsuo Ohta, Hiroki Yamaue, Masakazu Yamamoto, Sohei Satoi, Yasuhiro Kodera, Yoshifumi Takeyama, Masayuki Ohtsuka, Itaru Endo, Tadahiro Takada, and Akihiko Horiguchi

Subjects
Pancreatic Neoplasms, Pancreatic Fistula, Pancreatectomy, Postoperative Complications, Treatment Outcome, Japan, Hepatology, Quality of Life, Humans, Surgery, Pancreaticoduodenectomy, Retrospective Studies
Abstract

Whether organ-preserving pancreatic surgery has an advantage in postoperative short- and long-term outcomes or not is still unknown because only small case series studies have been available to date. In this multicenter retrospective study, we aimed to elucidate the clinical advantage and disadvantage of organ-preserving pancreatectomy among patients with low-grade malignant pancreatic tumors and benign pancreatic diseases.We included patients diagnosed with benign or low-malignant pancreatic tumor who underwent pancreaticoduodenectomy (PD) in 621 cases, duodenum-preserving pancreatic head resection (DPPHR) in 31 cases, middle pancreatectomy (MP) in 148 cases, distal pancreatectomy (DP) in 814 cases, and spleen-preserving distal pancreatectomy (SPDP) in 259 cases between January 1, 2013, and December 31, 2017. Preoperative backgrounds, surgical outcomes and pre- and postoperative (3, 6, 12, 24, and 36 months) nutritional status were compared between these procedures.In terms of short-term outcomes, the incidence of pancreatic fistula in patients who underwent MP was significantly higher than in patients with standard pancreatectomy. As for the long-term pancreatic functions in the cases of head or body lesion, both exocrine and endocrine functions after MP were significantly favorable compared with the PD group from 3 to 36 months after surgery. In pancreatic body or tail lesion, significant advantage of endocrine function, but not exocrine function, was found in the MP group compared to standard DP at all time points.MP may contribute to the improvement of postoperative quality of life for patients with pancreatic body low-malignant tumors, rather than PD or DP; however, reducing the incidence of short-term complications such as pancreatic fistula is a future challenge.

Published
2022
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28. Insights from managing clinical issues in distal pancreatectomy with en bloc coeliac axis resection: experiences from 626 patients.

Author

Toru Nakamura, Ken-Ichi Okada, Masayuki Ohtsuka, Ryota Higuchi, Hidenori Takahashi, Kazuyuki Nagai, Michiaki Unno, Yoshiaki Murakami, Atsushi Oba, Moriaki Tomikawa, Atsushi Kato, Akihiko Horiguchi, Masafumi Nakamura, Shintaro Yagi, Sohei Satoi, Itaru Endo, Ryosuke Amano, Ippei Matsumoto, Ito, Yoichi M., and Takukazu Nagakawa

Subjects
PANCREATECTOMY, SPLENIC artery, PROPENSITY score matching, SURGERY, PANCREATIC surgery, THERAPEUTIC embolization
Abstract

Background: Distal pancreatectomy with en bloc coeliac axis resection (DP-CAR) for pancreatic body cancer has been reported increasingly. However, its large-scale outcomes remain undocumented. This study aimed to evaluate DP-CAR volume and mortality, preoperative arterial embolization for ischaemic gastropathy, the oncological benefit for resectable tumours close to the bifurcation of the splenic artery and coeliac artery using propensity score matching, and prognostic factors in DP-CAR. Methods: In a multi-institutional analysis, 626 DP-CARs were analysed retrospectively and compared with 1325 distal pancreatectomies undertaken in the same interval. Results: Ninety-day mortality was observed in 7 of 21 high-volume centres (1 or more DP-CARs per year) and 1 of 41 low-volume centres (OR 20.00, 95 per cent c.i. 2.26 to 177.26). The incidence of ischaemic gastropathy was 19.2 per cent in the embolization group and 7.9 per cent in the no-embolization group (OR 2.77, 1.48 to 5.19). Propensity score matching analysis showed that median overall survival was 33.5 (95 per cent c.i. 27.4 to 42.0) months in the DP-CAR and 37.9 (32.8 to 53.3) months in the DP group. Multivariable analysis identified age at least 67 years (HR 1.40, 95 per cent c.i. 1.12 to 1.75), preoperative tumour size 30 mm or more (HR 1.42, 1.12 to 1.80), and preoperative carbohydrate antigen 19-9 level over 37 units/ml (HR 1.43, 1.11 to 1.83) as adverse prognostic factors. Conclusion: DP-CAR can be performed safely in centres for general pancreatic surgery regardless of DP-CAR volume, and preoperative embolization may not be required. This procedure has no oncological advantage for resectable tumour close to the bifurcation of the splenic artery, and should be performed after appropriate patient selection. [ABSTRACT FROM AUTHOR]

Published
2023
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29. External validation of postoperative pancreatic fistula prediction scores in pancreatoduodenectomy: a systematic review and meta-analysis

Author

Euan J. Dickson, Ewen M Harrison, Thomas Thorne, Robert P. Sutcliffe, Stefan Stättner, Liam Phelan, Darius F. Mirza, Stephen R Knight, Kevin Cp Conlon, Nicola de Liguori Carino, Benjamin Loveday, Laura Magill, Rita J Perry, R. Pande, Ajith K. Siriwardena, Bobby Tingstedt, Keith J. Roberts, Thomas Pinkney, James R A Skipworth, M. Panikkar, James M. Halle-Smith, Saxon Connor, Sanjay Pandanaboyana, Sohei Satoi, Ali Arshad, Todd Hore, Francesco Giovinazzo, and James Hodson

Subjects
medicine.medical_specialty, Future studies, Framingham Risk Score, Hepatology, business.industry, Gastroenterology, External validation, MEDLINE, medicine.disease, Risk Assessment, Pancreaticoduodenectomy, Clinical Practice, Pancreatic Fistula, Postoperative Complications, Risk Factors, Pancreatic fistula, Meta-analysis, Internal medicine, Clinical validity, Humans, Medicine, business, Pancreas, Retrospective Studies
Abstract

Background Multiple risk scores claim to predict the probability of postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. However, it is unclear which scores have undergone external validation, and which score is the most accurate. Objective To identify risk scores for POPF, and assess the clinical validity of these scores. Methods Areas under receiving operator characteristic curve (AUROCs) were extracted from studies that performed external validation of POPF risk scores. These were pooled for each risk score, using intercept-only random-effects meta-regression models. Results Systematic review identified 34 risk scores, of which six had been subjected to external validation, and so were included in the meta-analysis, namely the Tokyo (N=2 validation studies), Birmingham (N=5), FRS (N=19), a-FRS (N=12), m-FRS (N=3) and ua-FRS (N=3) scores. The overall predictive accuracies were found to be similar for all six scores, with pooled AUROCs of 0.61, 0.70, 0.71, 0.70, 0.70 and 0.72, respectively. Considerably heterogeneity was observed, with I2 statistics ranging from 52.1-88.6%. Conclusion Most risk scores lack external validation; where this was performed, risk scores were found to have limited predictive accuracy. . Consensus is needed for which score to use in clinical practice. Due to the limited predictive accuracy, future studies to derive a more accurate risk score are warranted.

Published
2022
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30. Synopsis of a clinical practice guideline for pancreatic ductal adenocarcinoma with peritoneal dissemination in Japan; Japan Peritoneal Malignancy Study Group

Author

Tsutomu Fujii, Hideyo Miyato, Joji Kitayama, Daisuke Hashimoto, Hiroyuki Isayama, So Yamaki, Yasushi Tsuji, Hironori Yamaguchi, Suguru Yamada, Kei Saito, Masamichi Hayashi, Toru Watanabe, Shigeto Ishii, Hideaki Shimada, Yousuke Nakai, Hayato Baba, Keisuke Kurimoto, Tomohisa Yamamoto, Naminatsu Takahara, and Sohei Satoi

Subjects
medicine.medical_specialty, Pancreatic ductal adenocarcinoma, endocrine system diseases, Hepatology, business.industry, General surgery, Guideline, Discontinuation, Pancreatic Neoplasms, Peritoneal malignancy, Clinical Practice, Natural history, Japan, Ascites, medicine, Humans, Surgery, Poor performance status, medicine.symptom, business, Peritoneal Neoplasms, Carcinoma, Pancreatic Ductal
Abstract

BACKGROUND/PURPOSE Patients with pancreatic ductal adenocarcinoma (PDAC) with peritoneal dissemination have a dismal prognosis because discontinuation of systemic chemotherapy is required for massive ascites or poor performance status. The natural history, diagnosis and treatment of PDAC with peritoneal dissemination have not been fully investigated. METHODS We systematically reviewed published information on the clinical diagnosis and treatment of PDAC with peritoneal dissemination using the PubMed database (2000-2020) and provided recommendations in response to clinical questions. This guideline was created according to the "Minds Clinical Practice Guideline Development Guide 2017". The literature quality and body of evidence were evaluated with the GRADE System and classified into four levels ("strong", "medium", "weak", "very weak"). The strength of each final recommendation was decided by a vote of committee members based on the GRADE Grid method. RESULTS These guidelines address 3 subjects: diagnostic, chemotherapeutic, and surgical approaches. They include 9 clinical questions and statements with recommendation strengths, evidence levels, and agreement rates, in addition to one "column". CONCLUSIONS This is the English synopsis of the 2021 Japanese clinical practice guideline for PDAC with peritoneal dissemination. It summarizes the clinical evidence for the diagnosis and treatment of PDAC with peritoneal dissemination and provides future perspectives.

Published
2022
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31. High tumor budding predicts a poor prognosis in resected duodenal adenocarcinoma

Author

Tatsuma Sakaguchi, Sohei Satoi, Daisuke Hashimoto, Tomohisa Yamamoto, So Yamaki, Satoshi Hirooka, Mitsuaki Ishida, Tsukasa Ikeura, Kentaro Inoue, Makoto Naganuma, Hideki Ishikawa, and Mitsugu Sekimoto

Subjects
Duodenal Neoplasms, Lymphatic Metastasis, Humans, Neoplasm Invasiveness, Surgery, General Medicine, Adenocarcinoma, Neoplasm Recurrence, Local, Prognosis, Neoplasm Staging, Retrospective Studies
Abstract

Tumor budding is a histological characteristic defined as the presence of small clusters of cancer cells at the invasion front. Its significance in duodenal adenocarcinoma (DA) has not been fully described.A single-center, retrospective study was conducted. Patients who underwent curative surgery for histologically diagnosed DA from January 2006 to December 2018 at Kansai Medical University Hospital were included. Tumor budding was counted per 0.785 mmIn total, 47 patients were included. The 5-year overall survival and relapse-free survival rates were 77% and 72%, respectively. High tumor budding was seen in 15 patients (32%). Excluding patients with superficial type (pT1) DA (n = 22), high tumor budding [hazard ratio (HR) 13.4, p = 0.028], regional lymph node metastasis (HR 19.9, p = 0.039), and adjuvant chemotherapy (HR 0.056, p = 0.036) were independent factors related to the overall survival in multivariate analyses. Distant metastases occurred significantly more often in patients who had high tumor budding than in others (p = 0.039).The data suggest that high tumor budding is a predictor of a poor prognosis in resected DA.

Published
2022
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32. Academic value and impact of continuous global academic learning: the International HPB surgery journal club concept

Author

Aiste Gulla, Povilas Ignatavicius, Camilo Correa, Yosuke Inohue, Daisuke Hashimoto, Daisuke Ban, Ulrike Heger, Doris Wagner, Qinfen Xie, Perry Shen, Arthur L. Michel, Jan Lerut, Marco Del Chiaro, Thilo Hackert, Christopher L. Wolfgang, Jin He, Peter Kingham, Timothy M. Pawlik, Sohei Satoi, Peter Schemmer, Kestutis Strupas, and Ajith K. Siriwardena

Subjects
Hepatology, Gastroenterology
Published
2023
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33. The academic impact and value of an international online surgery lecture series

Author

Daisuke Hashimoto, Aiste Gulla, Sohei Satoi, Tomohisa Yamamoto, So Yamaki, Yuki Matsui, Chisato Ohe, Makoto Yamasaki, Madoka Hamada, Tsukasa Ikeura, Masaaki Shimatani, Raoul Breugelmans, Algirdas Utkus, Tomas Poskus, Arturas Samuilis, Marius Miglinas, Arvydas Laurinavicius, Koichi Tomoda, Vaiva Hendrixson, Mitsugu Sekimoto, and Kestutis Strupas

Subjects
Surgery, General Medicine
Published
2023
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34. Is perioperative COVID-19 really associated with worse surgical outcomes? A nationwide COVIDSurg propensity-matched analysis

Author

Argandykov, Dias, Dorken-Gallastegi, Ander, El Moheb, Mohamad, Gebran, Anthony, Proaño-Zamudio, Jefferson A, Bokenkamp, Mary, Renne, Angela M, Nepogodiev, Dmitri, Bhangu, Aneel, Kaafarani, Haytham M A, Kwabena, Siaw-Acheampong, Leah, Argus, Daoud, Chaudhry, Brett, E Dawson, James, C Glasbey, Rohan, R Gujjuri, Conor, S Jones, Sivesh, K Kamarajah, Chetan, Khatri, James, M Keatley, Samuel, Lawday, Elizabeth, Li, Harvinder, Mann, Ella, J Marson, Kenneth, A Mclean, Maria, Picciochi, Elliott, H Taylor, Abhinav, Tiwari, Joana F, F Simoes, Isobel, M Trout, Mary, L Venn, Richard J, W Wilkin, Aneel, Bhangu, Dmitri, Nepogodiev, Irida, Dajti, Arben, Gjata, Luis, Boccalatte, Mariamarta, Modolo, Daniel, Cox, Peter, Pockney, Philip, Townend, Felix, Aigner, Irmgard, Kronberger, Kamral, Hossain, Gabrielle, Vanramshorst, Ismail, Lawani, Gustavo, Ataide, Glauco, Baiocchi, Igor, Buarque, Muhammad, Gohar, Mihail, Slavchev, Arnav, Agarwal, Amanpreet, Brar, Janet, Martin, Maria Marta Modolo, Maricarmen, Olivos, Jose, Calvache, Carlos Jose Perez Rivera, Ana Danic Hadzibegovic, Tomislav, Kopjar, Jakov, Mihanovic, Jaroslav, Klat, René, Novysedlak, Peter, Christensen, Alaa, El-Hussuna, Sylvia, Batista, Eddy, Lincango, Sameh, H Emile, Mengistu Gebreyohanes Mengesha, Samuel, Hailu, Hailu, Tamiru, Joonas, Kauppila, Johanna, Laukkarinen, Alexis, Arnaud, Markus, Albertsmeiers, Hans, Lederhuber, Markus, Loffler, Stephen, Tabiri, Symeon, Metallidis, Georgios, Tsoulfas, Maria Aguilera Lorena, Gustavo, Grecinos, Tamas, Mersich, Daniel, Wettstein, Dhruv, Ghosh, Gabriele, Kembuan, Peiman, Brouk, Mohammad, Khosravi, Masoud, Mozafari, Ahmed, Adil, Helen, M Mohan, Oded, Zmora, Marco, Fiore, Gallo, Gaetano, Francesco, Pata, Gianluca, Pellino, Sohei, Satoi, Faris, Ayasra, Mohammad, Chaar, Ildar, R Fakhradiyev, Mohammad, Jamal, Muhammed, Elhadi, Aiste, Gulla, April, Roslani, Laura, Martinez, Antonio Ramos De La Medina, Oumaima, Outani, Pascal, Jonker, Schelto, Kruijff, Milou, Noltes, Pieter, Steinkamp, Willemijn van der Plas, Adesoji, Ademuyiwa, Babatunde, Osinaike, Justina, Seyi-Olajide, Emmanuel, Williams, Sofija, Pejkova, Knut Magne Augestad, Zainab Al Balushi, Ahmad, Qureshi, Raza, Sayyed, Mustafa Abu Mohsen Daraghmeh, Sadi, Abukhalaf, Moises, Cukier, Hugo, Gomez, Sebastian, Shu, Ximena, Vasquez, Marie Dione Parreno-Sacdalan, Piotr, Major, José, Azevedo, Miguel, Cunha, Irene, Santos, Ahmad, Zarour, Eduard-Alexandru, Bonci, Ionut, Negoi, Sergey, Efetov, Andrey, Litvin, Faustin, Ntirenganya, Ehab, Alameer, Dejan, Radenkovic, Frederick Koh Hong Xiang, Chew Min Hoe, James Ngu Chi Yong, Rachel, Moore, Ncamsile, Nhlabathi, Ruth Blanco Colino, Ana Minaya Bravo, Ana, Minaya-Bravo, Umesh, Jayarajah, Dakshitha, Wickramasinghe, Mohammed, Elmujtaba, William, Jebril, Martin, Rutegård, Malin, Sund, Arda, Isik, Sezai, Leventoğlu, Tom E, F Abbott, Ruth, Benson, Caruna, Ed, Sohini, Chakrabortee, Andreas, Demetriades, Anant, Desai, Thomas, D Drake, John, G Edwards, Jonathan, P Evans, Samuel, Ford, Christina, Fotopoulou, Ewen, Griffiths, Peter, Hutchinson, Michael, D Jenkinson, Tabassum, Khan, Stephen, Knight, Angelos, Kolias, Elaine, Leung, Siobhan, Mckay, Lisa, Norman, Riinu, Ots, Vidya, Raghavan, Keith, Roberts, Andrew, Schache, Richard, Shaw, Katie, Shaw, Neil, Smart, Grant, Stewart, Sudha, Sundar, Dale, Vimalchandran, Naomi, Wright, Sattar, Alshryda, Osaid, Alser, Kerry, Breen, Ian, Ganly, Haytham, Kaafarani, Brittany, Kendall, Hassan, Mashbari, Hamza Al Naggar, Dennis, Mazingi, J J, Wong, Napolitano, L, Hemmila, M, Amin, D, Abramowicz, S, S M, Roser, K A, Olson, Riley, C, Heron, C, Cardenas, T, Leede, E, Thornhill, M, A B, Haynes, Mcelhinney, K, Roward, S, M D, Trust, C E, Hill, P G, Teixeira, Etchill, E, Stevens, K, M R, Ladd, Long, C, Rose, J, Kent, A, Yesantharao, P, Vervoort, D, Jenny, H, Gabre-Kidan, A, Margalit, A, Tsai, L, Malapati, H, Yesantharao, L, Abdou, H, Diaz, J, Richmond, M, Clark, J, O'Meara, L, Hanna, N, Ying, Y, Fleming, J, Ovaitt, A, Gigliotti, J, Fuson, A, Cooper, Z, Salim, A, A Hirji, S, Brown, A, Chung, C, Hansen, L, U Okafor, B, Roxo, V, P Raut, C, S Jolissaint, J, A Mahvi, D, Kaafarani, H, Breen, K, Bankhead-Kendall, B, Alser, O, Mashbari, H, Velmahos, G, L R, Maurer, El Moheb, M, Gaitanidis, A, Naar, L, M A, Christensen, Kapoen, C, Langeveld, K, El Hechi, M, Mokhtari, A, H Haqqani, M, T Drake, F, Goldenberg-Sandau, A, Galbreath, B, Reinke, C, Ross, S, Thompson, K, Manning, D, Perkins, R, Eriksson, E, Evans, H, Masrur, M, Giulianotti, P, Benedetti, E, Chang, G, Ourieff, J, Dehart, D, Dorafshar, A, Price, T, R Bhama, A, Torquati, A, Cherullo, E, Kennedy, R, Myers, J, Rubin, K, S Ban, V, G Aoun, S, H Batjer, H, Caruso, J, Carmichael, H, G Velopulos, C, L Wright, F, Urban, S, C McIntyre Jr, R, J Schroeppel, T, A Hennessy, E, Dunn, J, Zier, L, Burlew, C, Coleman, J, P Colling, K, Hall, B, E Rice, H, S Hwang, E, A Olson, S, Moris, D, Verma, R, Hassan, R, Volpe, A, Merola, S, A O'Banion, L, Lilienstein, J, Dirks, R, Marwan, H, Almasri, M, Kulkarni, G, Mehdi, M, Abouassi, A, Abdallah, M, M San Andrés, Eid, J, Aigbivbalu, E, Sundaresan, J, George, B, Ssentongo, A, Ssentongo, P, S Oh, J, Hazelton, J, Maines, J, Gusani, N, Garner, M, Horvath, S, Zheng, F, Ujiki, M, Kinnaman, G, Meagher, A, Sharma, I, Holler, E, Mckenzie, K, Chan, J, Fretwell, K, W Nugent 3rd, Khalil, A, Chen, D, Post, N, Rostkowski, T, Brahmbhatt, D, Huynh, K, L Hibbard, M, Schellenberg, M, Martin, Rcg, Bhutiani, N, Giorgakis, E, Laryea, J, Bhavaraju, A, Sexton, K, Roberts, M, Kost, M, Kimbrough, M, Burdine, L, Kalkwarf, K, Robertson, R, Gosain, A, Camp, L, Lewit, R, P Kronenfeld, J, Urrechaga, E, Goel, N, Rattan, R, Hart, V, Allen, M, Gilna, G, Cioci, A, Ruiz, G, Rakoczy, K, Pavlis, W, Saberi, R, Morris, R, S Karam, B, Brathwaite, Cem, Liu, H, Petrone, P, Hakmi, H, H Sohail, A, Baltazar, G, Heckburn, R, M Nygaard, R, T Colonna, E, W Endorf, F, J Hill, M, Maiga, A, Dennis, B, H Levin, J, Lallemand, M, Choron, R, Peck, G, Soliman, F, Rehman, S, Glass, N, Juthani, B, Deisher, D, M Ruzgar, N, J Ullrich, S, Sion, M, Paranjape, C, M El Moheb, R Kar, A, Gillezeau, C, Rapp, J, Taioli, E, A Miles, B, Alpert, N, Podolsky, D, L Coleman, N, P Callahan, M, Ganly, I, Brown, L, Monson, Jrt, Dehal, A, Abbas, A, Soliman, A, Kim, B, Jones, C, Dauer, E, Renza-Stingone, E, Hernandez, E, Gokcen, E, Kropf, E, Sufrin, H, Hirsch, H, Ross, H, Engel, J, Sewards, J, Poggio, J, Sanserino, K, Rae, L, Philp, M, Metro, M, Mcnelis, P, Petrov, R, Pazionis, T, Till, B, Lamm, R, J Rios-Diaz, A, Palazzo, F, Rosengart, M, Nicholson, K, M Carrick, M, Rodkey, K, Suri, A, Callcut, R, Nicholson, S, Talathoti, N, Klaristenfeld, D, Biffl, W, Marsh, C, Schaffer, K, E Berndtson, A, Averbach, S, Curry, T, Kwan-Feinberg, R, Consorti, E, Gonzalez, R, Grolman, R, Liu, T, Merzlikin, O, K Abel, M, Ozgediz, D, Boeck, M, Z Kornblith, L, Nunez-Garcia, B, Robinson, B, Park, P, F Utria, A, E Rice-Townsend, S, Javid, P, Hauptman, J, Kieran, K, Nehra, D, Walters, A, Cuschieri, J, H Davidson, G, Nunez, J, Cosker, R, Eckhouse, S, Choudhry, A, Marx, W, Jamil, T, Seegert, S, Al-Embideen, S, Quintana, M, Jackson, H, D Wexner, S, Kent, I, and N Martins, P

Subjects
COVID-19, COVIDSurg, mortality, postoperative complications, Surgery, Critical Care and Intensive Care Medicine
Published
2023

35. Incidence and risk factors of nonalcoholic fatty liver disease after total pancreatectomy: A first multicenter prospective study in Japan

Author

Shuji Isaji, Takeshi Sudo, Keiichi Okano, Yoshifumi Takeyama, Ippei Matsumoto, Yasuyuki Suzuki, Hiroyuki Nitta, Yasunari Kawabata, Masanori Sugiyama, Sohei Satoi, Hiroyuki Kato, Hironobu Suto, Keiko Kamei, Takeyuki Misawa, Masayuki Ohtsuka, Michiaki Unno, Toshiki Rikiyama, and Naohiro Sata

Subjects
Diarrhea, medicine.medical_specialty, Multivariate analysis, Gastroenterology, Pancreaticoduodenectomy, Pancreatectomy, Japan, Non-alcoholic Fatty Liver Disease, Risk Factors, Pancrelipase, Internal medicine, Hounsfield scale, Nonalcoholic fatty liver disease, medicine, Humans, Prospective Studies, Prospective cohort study, Hepatology, business.industry, Incidence, Incidence (epidemiology), Perioperative, medicine.disease, Female, Surgery, business, Body mass index
Abstract

BACKGROUND/PURPOSE This study aimed to prospectively assess the current prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD) after total pancreatectomy (TP). METHODS Between August 2015 and December 2017, we prospectively collected data from 68 Japanese centers on 148 consecutive patients who underwent TP whose computed tomography (CT) attenuation values were evaluated for 12 months. We defined post-TP NAFLD as a liver parenchyma CT value of less than 40 Hounsfield units (HU). Data on perioperative variables were retrieved from all patients and evaluated using univariate and multivariate analyses to identify the perioperative risk factors of NAFLD. RESULTS In this prospective cohort study, supplementation of pancreatic exocrine enzymes was provided to all 148 patients, and 97% of them were treated with high-titer pancrelipase (median dosage: 1800 mg) postoperatively. Indeed, 29 patients (19.6%) developed NAFLD within a year after TP. Multivariate analysis revealed that female sex (p=0.002), higher body mass index (BMI) (p=0.001), and postoperative diarrhea (p=0.038) were independent risk factors for post-TP NAFLD. However, post-TP NAFLD ameliorated in 11 patients (37.9%) at 12 months after surgery. CONCLUSIONS Among patients with risk factors such as female sex, higher BMI, and postoperative diarrhea, attention should be paid to the occurrence of NAFLD after TP.

Published
2021
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36. Outcomes and Their State-level Variation in Patients Undergoing Surgery With Perioperative SARS-CoV-2 Infection in the USA

Author

Osaid, Alser, Ander Dorken Gallastegi, Anthony, Gebran, Kerry, Breen, Mohamad El Moheb, Apostolos, Gaitanidis, Leon, Naar, Brittany, Bankhead-Kendall, Hassan, Mashbari, Robert, D Sinyard, Lydia, R Maurer, Charu, Paranjape, George, C Velmahos, Dmitri, Nepogodiev, Aneel, Bhangu, Haytham M, A Kaafarani, Kwabena, Siaw-Acheampong, Leah, Argus, Daoud, Chaudhry, Brett, E Dawson, James, C Glasbey, Rohan, R Gujjuri, Conor, S Jones, Sivesh, K Kamarajah, Chetan, Khatri, James, M Keatley, Samuel, Lawday, Elizabeth, Li, Harvinder, Mann, Ella, J Marson, Kenneth, A Mclean, Maria, Picciochi, Elliott, H Taylor, Abhinav, Tiwari, Joana F, F Simoes, Isobel, M Trout, Mary, L Venn, Richard J, W Wilkin, Irida, Dajti, Arben, Gjata, Oussama, Kacimi, Luis, Boccalatte, Maria Marta Modolo, Daniel, Cox, Peter, Pockney, Philip, Townend, Felix, Aigner, Irmgard, Kronberger, Ahmed, Elgun, Amer, Alderazi, Kamral, Hossain, Greg, Padmore, Gabrielle, Vanramshorst, Ismail, Lawani, Duane, Wedderburn, Sonam, Dargay, Israël, Feraudy, Cerovac, Anis, Samir, Delibegovic, Alemayehu Ginbo Bedada, Gustavo, Ataide, Glauco, Baiocchi, Igor, Buarque, Muhammad, Gohar, Mihail, Slavchev, Jean Marie Vianney Butoyi, Chukwuemeka, Nwegbu, Arnav, Agarwal, Amanpreet, Brar, Janet, Martin, Maricarmen, Olivos, Dong-Lin, Ren, Wenhui, Lou, Jose, Calvache, Carlos Jose Perez Rivera, Ana Danic Hadzibegovic, Tomislav, Kopjar, Jakov, Mihanovic, Pablo, Avilés, Nikolaos, Gouvas, Jaroslav, Klat, René, Novysedlak, Nicolas, Amisi, Peter, Christensen, Alaa, El-Hussuna, Sylvia, Batista, Eddy, Lincango, Sameh, H Emile, Danilo Alfonso Arévalo Sandoval, Mengistu Gebreyohanes Mengesha, Samuel, Hailu, Hailu, Tamiru, Joonas, Kauppila, Johanna, Laukkarinen, Alexis, Arnaud, Roumanatou Bankole Sapin, Kebba, Marenah, Zaza, Demetrashvili, Andreas, A Schnitzbauer, Magdalena, Gruendl, Markus, Albertsmeiers, Hans, Lederhuber, Markus, Loffler, Bernard Ofori Appiah, Daniel, Acquah, Stephen, Tabiri, Symeon, Metallidis, Georgios, Tsoulfas, Maria Aguilera Lorena, Gustavo, Grecinos, Tamas, Mersich, Daniel, Wettstein, Atul, Suroy, Dhruv, Ghosh, Pranay, Pawar, Gabriele, Kembuan, Peiman, Brouk, Mohammad, Khosravi, Masoud, Mozafari, Ahmed, Adil, Helen, M Mohan, Oded, Zmora, Marco, Fiore, Gallo, G, Pata, Francesco, Gianluca, Pellino, Naoto, Kuroda, Sohei, Satoi, Yuki, Fujimoto, Faris, Ayasra, Mohammad, Chaar, Ildar, R Fakhradiyev, Intisar, Hisham, Jin-Young, Jang, Enver, Fekaj, Mohammad, Jamal, Anvar, Beisembaev, Muhammed, Elhadi, Aiste, Gulla, Luc, Samison, Jupsi, Neny, Palesa, Chisala, April, Roslani, Iran Irani Duran Sanchez, Laura Martinez Perez Maldonado, Antonio Ramos De La Medina, Jade, Nunez, Oumaima, Outani, Abd'Rashid, Nashidengo, Ashish Lal Shrestha, Rakesh, Shah, Pascal, Jonker, Schelto, Kruijff, Milou, Noltes, Pieter, Steinkamp, Willemijn van der Plas, Chris, Varghese, Deborah, Wright, Jorge, Neira, Adesoji, Ademuyiwa, Babatunde, Osinaike, Justina, Seyi-Olajide, Emmanuel, Williams, Sofija, Pejkova, Knut Magne Augestad, Kjetil, Soreide, Zainab Al Balushi, Ahmad, Qureshi, Raza, Sayyed, Mustafa Abu Mohsen Daraghmeh, Sadi, Abukhalaf, Moises, Cukier, Chris, Munguas, Hugo, Gomez, Sebastian, Shu, Ximena, Vasquez, Marie Dione Parreno-Sacdalan, Piotr, Major, José, Azevedo, Miguel, Cunha, Irene, Santos, Ahmad, Zarour, Eduard-Alexandru, Bonci, Ionut, Negoi, Sergey, Efetov, Andrey, Litvin, Faustin, Ntirenganya, Ehab, Alameer, Abdourahmane, Ndong, Dejan, Radenkovic, Ibrahim, Sesay, Frederick Koh Hong Xiang, Chew Min Hoe, James Ngu Chi Yong, Arpad, Panyko, Jurij, Kosir, Uros, Bele, Hassan, Ali, Rachel, Moore, Ncamsile, Nhlabathi, Ruth Blanco Colino, Ana Minaya Bravo, Umesh, Jayarajah, Dakshitha, Wickramasinghe, Mohammed, Elmujtaba, William, Jebril, Martin, Rutegård, Malin, Sund, Eleftherios, Gialamas, Karoline, Horisberger, Michel, Adamina, Muhammad, Alshaar, Abel, Huang, Ben, Mbwele, Varut, Lohsiriwat, Shane, Charles, Haithem, Jlassi, Arda, Isik, Sezai, Leventoğlu, Lekuya, Herve, Lekuya, Monka, Herman, Lule, Tom E, F Abbott, Ruth, Benson, Caruna, Ed, Sohini, Chakrabortee, Andreas, Demetriades, Anant, Desai, Thomas, D Drake, John, G Edwards, Jonathan, P Evans, Samuel, Ford, Christina, Fotopoulou, Ewen, Griffiths, Peter, Hutchinson, Michael, D Jenkinson, Tabassum, Khan, Stephen, Knight, Angelos, Kolias, Elaine, Leung, Siobhan, Mckay, Lisa, Norman, Riinu, Ots, Vidya, Raghavan, Keith, Roberts, Andrew, Schache, Richard, Shaw, Katie, Shaw, Neil, Smart, Grant, Stewart, Sudha, Sundar, Dale, Vimalchandran, Naomi, Wright, Slava, Kopetskiy, Sattar, Alshryda, Ian, Ganly, Haytham, Kaafarani, Brittany, Kendall, Fernando, Bonilla, Hamza Al Naggar, Mayaba, Maimbo, Dennis, Mazingi, J Wong, J, Napolitano, L, Hemmila, M, Amin, D, Abramowicz, S, M Roser, S, A Olson, K, Riley, C, Heron, C, Cardenas, T, Leede, E, Thornhill, M, B Haynes, A, Mcelhinney, K, Roward, S, D Trust, M, E Hill, C, G Teixeira, P, Etchill, E, Stevens, K, R Ladd, M, Long, C, Rose, J, Kent, A, Yesantharao, P, Vervoort, D, Jenny, H, Gabre-Kidan, A, Margalit, A, Tsai, L, Malapati, H, Yesantharao, L, Abdou, H, Diaz, J, Richmond, M, Clark, J, O'Meara, L, Hanna, N, Ying, Y, Fleming, J, Ovaitt, A, Gigliotti, J, Fuson, A, Cooper, Z, Salim, A, A Hirji, S, Brown, A, Chung, C, Hansen, L, U Okafor, B, Roxo, V, P Raut, C, S Jolissaint, J, A Mahvi, D, Kaafarani, H, Breen, K, Bankhead-Kendall, B, Alser, O, Mashbari, H, Velmahos, G, R Maurer, L, M El Moheb, Gaitanidis, A, Naar, L, A Christensen, M, Kapoen, C, Langeveld, K, M El Hechi, Mokhtari, A, H Haqqani, M, T Drake, F, Goldenberg-Sandau, A, Galbreath, B, Reinke, C, Ross, S, Thompson, K, Manning, D, Perkins, R, Eriksson, E, Evans, H, Masrur, M, Giulianotti, P, Benedetti, E, Chang, G, Ourieff, J, Dehart, D, Dorafshar, A, Price, T, R Bhama, A, Torquati, A, Cherullo, E, Kennedy, R, Myers, J, Rubin, K, S Ban, V, G Aoun, S, H Batjer, H, Caruso, J, Carmichael, H, G Velopulos, C, L Wright, F, Urban, S, C McIntyre Jr, R, J Schroeppel, T, A Hennessy, E, Dunn, J, Zier, L, Burlew, C, Coleman, J, P Colling, K, Hall, B, E Rice, H, S Hwang, E, A Olson, S, Moris, D, Verma, R, Hassan, R, Volpe, A, Merola, S, A O'Banion, L, Lilienstein, J, Dirks, R, Marwan, H, Almasri, M, Kulkarni, G, Mehdi, M, Abouassi, A, Abdallah, M, M San Andrés, Eid, J, Aigbivbalu, E, Sundaresan, J, George, B, Ssentongo, A, Ssentongo, P, S Oh, J, Hazelton, J, Maines, J, Gusani, N, Garner, M, Horvath, S, Zheng, F, Ujiki, M, Kinnaman, G, Meagher, A, Sharma, I, Holler, E, Mckenzie, K, Chan, J, Fretwell, K, W Nugent 3rd, Khalil, A, Chen, D, Post, N, Rostkowski, T, Brahmbhatt, D, Huynh, K, L Hibbard, M, Schellenberg, M, R C, G Martin, Bhutiani, N, Giorgakis, E, Laryea, J, Bhavaraju, A, Sexton, K, Roberts, M, Kost, M, Kimbrough, M, Burdine, L, Kalkwarf, K, Robertson, R, Gosain, A, Camp, L, Lewit, R, P Kronenfeld, J, Urrechaga, E, Goel, N, Rattan, R, Hart, V, Allen, M, Gilna, G, Cioci, A, Ruiz, G, Rakoczy, K, Pavlis, W, Saberi, R, Morris, R, S Karam, B, C E, M Brathwaite, Liu, H, Petrone, P, Hakmi, H, H Sohail, A, Baltazar, G, Heckburn, R, M Nygaard, R, T Colonna, E, W Endorf, F, J Hill, M, Maiga, A, Dennis, B, H Levin, J, Lallemand, M, Choron, R, Peck, G, Soliman, F, Rehman, S, Glass, N, Juthani, B, Deisher, D, M Ruzgar, N, J Ullrich, S, Sion, M, Paranjape, C, R Kar, A, Gillezeau, C, Rapp, J, Taioli, E, A Miles, B, Alpert, N, Podolsky, D, L Coleman, N, P Callahan, M, Ganly, I, Brown, L, J R, T Monson, Dehal, A, Abbas, A, Soliman, A, Kim, B, Jones, C, D Dauer, M, Renza-Stingone, E, Hernandez, E, Gokcen, E, Kropf, E, Sufrin, H, Hirsch, H, Ross, H, Engel, J, Sewards, J, Poggio, J, Sanserino, K, Rae, L, Philp, M, Metro, M, Mcnelis, P, Petrov, R, Pazionis, T, Till, B, Lamm, R, J Rios-Diaz, A, Palazzo, F, Rosengart, M, Nicholson, K, M Carrick, M, Rodkey, K, Suri, A, Callcut, R, Nicholson, S, Talathoti, N, Klaristenfeld, D, Biffl, W, Marsh, C, Schaffer, K, E Berndtson, A, Averbach, S, Curry, T, Kwan-Feinberg, R, Consorti, E, Gonzalez, R, Grolman, R, Liu, T, Merzlikin, O, K Abel, M, Ozgediz, D, Boeck, M, Z Kornblith, L, Nunez-Garcia, B, Robinson, B, Park, P, F Utria, A, E Rice-Townsend, S, Javid, P, Hauptman, J, Kieran, K, Nehra, D, Walters, A, Cuschieri, J, H Davidson, G, Nunez, J, Cosker, R, Eckhouse, S, Choudhry, A, Marx, W, Jamil, T, Seegert, S, Al-Embideen, S, Quintana, M, Jackson, H, D Wexner, S, Kent, I, N Martins, P, Xiao, Liu, and Alistair, Denniston

Subjects
Male, medicine.medical_specialty, Revised Cardiac Risk Index, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), pulmonary complications, Malignancy, Time-to-Treatment, Postoperative Complications, Sex Factors, Risk Factors, medicine, COVID-19, COVIDSurg, elective surgery, emergency surgery, mortality, pulmonary complications, Humans, In patient, Prospective Studies, emergency surgery, Elective surgery, Aged, Respiratory Distress Syndrome, SARS-CoV-2, business.industry, Pulmonary Complication, Age Factors, COVID-19, Pneumonia, Perioperative, Middle Aged, COVIDSurg, elective surgery, mortality, medicine.disease, United States, Surgery, Multicenter study, Elective Surgical Procedures, Female, business
Abstract

Objective To report the 30-day outcomes of patients with perioperative SARS-CoV-2 infection undergoing surgery in the USA. Summary background data Uncertainty regarding the postoperative risks of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exists. Methods As part of the COVIDSurg multicenter study, all patients aged ≥17 years undergoing surgery between January 1 and June 30, 2020 with perioperative SARS-CoV-2 infection in 70 hospitals across 27 states were included. The primary outcomes were 30-day mortality and pulmonary complications. Multivariable analyses (adjusting for demographics, comorbidities, and procedure characteristics) were performed to identify predictors of mortality. Results A total of 1,581 patients were included; more than half of them were males (n= 822, 52.0%) and older than 50 years (n=835, 52.8%). Most procedures (n=1,261, 79.8%) were emergent, and laparotomies (n= 538, 34.1%). The mortality and pulmonary complication rates were 11.0 and 39.5%, respectively. Independent predictors of mortality included age ≥70 years (OR 2.46, 95% CI [1.65-3.69]), male sex (2.26 [1.53-3.35]), ASA grades 3-5 (3.08 [1.60-5.95]), emergent surgery (2.44 [1.31-4.54]), malignancy (2.97 [1.58-5.57]), respiratory comorbidities (2.08 [1.30-3.32]), and higher Revised Cardiac Risk Index (1.20 [1.02-1.41]). While statewide elective cancelation orders were not associated with a lower mortality, a sub-analysis showed it to be associated with lower mortality in those who underwent elective surgery (0.14 [0.03-0.61]). Conclusions Patients with perioperative SARS-CoV-2 infection have a significantly high risk for postoperative complications, especially elderly males. Postponing elective surgery and adopting non-operative management, when reasonable, should be considered in the USA during the pandemic peaks.

Published
2021
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37. Effects of pre-operative isolation on postoperative pulmonary complications after elective surgery: an international prospective cohort study

Author

Dmitri Nepogodiev, Joana Ff Simoes, Elizabeth Li, Maria Picciochi, James C Glasbey, Glauco Baiocchi, Ruth Blanco-Colino, Daoud Chaudhry, Ehab AlAmeer, Kariem El-Boghdadly, Funmilola Wuraola, Dhruva Ghosh, Rohan R Gujjuri, Ewen M Harrison, Herman Lule, Haytham Kaafarani, Mohammad Khosravi, Irmgard Kronberger, Sezai Leventoğlu, Harvinder Mann, Kenneth A Mclean, Mengistu Gebreyohanes Mengesha, Maria Marta Modolo, Faustin Ntirenganya, Lisa Norman, Oumaima Outani, Riinu Pius, Peter Pockney, Ahmad Uzair Qureshi, April Camilla Roslani, Sohei Satoi, Catherine Shaw, Aneel Bhangu, Omar M Omar, Waheed-Ul-Rahman Ahmed, Leah Argus, Alasdair Ball, Edward P Bywater, Amanpreet Brar, Brett E Dawson, Irani Duran, Muhammed Elhadi, Conor S Jones, Sivesh K Kamarajah, James M Keatley, Samuel Lawday, Ella J Marson, Riinu Ots, Irène Santos, Elliott H Taylor, Isobel M Trout, Chris Varghese, Mary L Venn, William Xu, Irida Dajti, Arben Gjata, Salah Eddine Oussama Kacimi, Luis Boccalatte, Daniel Cox, Philip Townend, Felix Aigner, Irmgard Elisabeth Kronberger, Elgun Samadov, Amer Alderazi, Kamral Hossain, Greg Padmore, Gabrielle van Ramshorst, Ismaïl Lawani, Anis Cerovac, Samir Delibegovic, Gustavo Mendonça Ataíde Gomes, Igor Lima Buarque, Muhammad Gohar, Mihail Slavchev, Chukwuemeka Nwegbu, Arnav Agarwal, Janet Martin, Joshua Ng-Kamstra, Maricarmen Olivos, Wenhui Lou, Dong-Lin Ren, Jose Andres Calvache, Carlos J Perez Rivera, Ana Danic Hadzibegovic, Tomislav Kopjar, Jakov Mihanovic, Pablo Mijahil Avilés Jiménez, Nikolaos Gouvas, Jaroslav Klat, René Novysedlák, Nicolas Amisi, Peter Christensen, Alaa El-Hussuna, Sylvia Batista, Eddy Lincango-Naranjo, Sameh Emile, Danilo Alfonso Arévalo Sandoval, Hailu Dhufera, Samuel Hailu, Mengistu G Mengesha, Joonas H Kauppila, Alexis P Arnaud, Zaza Demetrashvili, Markus Albertsmeier, Hans Lederhuber, Markus W Löffler, Daniel Kwesi Acquah, Bernard Ofori, Stephen Tabiri, Symeon Metallidis, Georgios Tsoulfas, Maria-Lorena Aguilera-Arevalo, Gustavo Recinos, Tamás Mersich, Dániel Wettstein, Gabriele Kembuan, Peiman Brouki Milan, Mohammad Hossein Khosravi, Masoud Mozafari, Ahmed Hilmi, Helen Mohan, Oded Zmora, Gaetano Gallo, Francesco Pata, Gianluca Pellino, Yuki Fujimoto, Naoto Kuroda, Mohamad K Abou Chaar, Faris Ayasra, Ildar Fakhradiyev, Intisar Hisham Said Hamdun, Jang Jin-Young, Mohammad Jamal, Lina Karout, Aiste Gulla, Fanjandrainy Rasoaherinomenjanahary, Luc Hervé Samison, Iran Irani Durán Sánchez, Diana Samantha Gonzalez, Laura Martinez, María José Martínez, Alejandra Nayen, Antonio Ramos-De la Medina, Jade Nunez, Pueya Rashid Nashidengo, Rakesh Shah, Ashish Lal Shrestha, Pascal Jonker, Schelto Kruijff, Milou Noltes, Pieter Steinkamp, Deborah Wright, Lukman Abdur-Rahman, Adesoji Ademuyiwa, Adewale Adisa, Babatunde Osinaike, Justina Seyi-Olajide, Omolara Williams, Emmanuel Williams, Sofija Pejkova, Zainab Al Balushi, Raza Sayyed, Mustafa Abo Mohsen, Sadi A Abukhalaf, Moises Cukier, Hugo Gomez-Fernandez, Sebastian Shu Yip, Ximena Paola Vasquez Ojeda, Marie Dione Sacdalan, Piotr Major, José Azevedo, Miguel F Cunha, Ahmad Zarour, Eduard-Alexandru Bonci, Ionut Negoi, Sergey Efetov, Viktor Kochetkov, Andrey Litvin, Jc Allen Ingabire, Georges Bucyibaruta, Ntirenganya Faustin, Sosthene Habumuremyi, Alphonsine Imanishimwe, Haragirimana Jean de Dieu, Emmanuel Munyaneza, Isaie Ncogoza, Ehab Alameer, Abdourahmane Ndong, Dejan Radenkovic, Min Hoe Chew, Frederick Koh, James Ngu, Arpád Panyko, Uros Bele, Jurij Aleš Košir, Hassan Daoud, Ana Maria Minaya Bravo, Umesh Jayarajah, Dakshitha Wickramasinghe, Mohammed Elmujtba Adam Essa Adam, Martin Rutegård, Malin Sund, Michel Adamina, Eleftherios Gialamas, Karoline Horisberger, Muhammad Alshaar, Abel Huang, Varut Lohsiriwat, Shane Charles, Haithem Jlassi, Arda Isik, Hervé Monka Lekuya, Slava Kopetskyi, Hayder Alsaadi, Sattar Alshryda, Osaid Alser, Brittany Bankhead-Kendall, Kerry Breen, Hassan Mashbari, Fernando Bonilla Cal, Hamza Al-Naggar, Mayaba Maimbo, Dennis Mazingi, Tom Abbott, Melika Akhbari, Ruth Benson, Shivam Bhanderi, Bruce Biccard, Edward Caruana, Sohini Chakrabortee, Reema Chapatwala, Ainhoa Costas-Chavarri, Andreas K Demetriades, Anant Desai, Salomone Di Saverio, Thomas Drake, John Edwards, Jonathan Evans, Marco Fiore, Samuel Ford, Christina Fotopoulou, Alexander Fowler, Kaori Futaba, Ian Ganly, Harelimana Grace James, Ewen Griffiths, Alessandro Gronchi, Peter Hutchinson, Gabriella Yael Hyman, Joseph Incorvia, Ritu Jain, Michael Jenkinson, Tabassum Khan, Stephen Richard Knight, Angelos Kolias, Søren Kudsk-Iversen, Tsun Yu Kwan, Elaine Leung, Julio Mayol, Siobhan McKay, John G Meara, Emily Mills, Susan Moug, Akshay Patel, Roberto Perinotti, Henry E Rice, Keith Roberts, Andrew Schache, Richard Shaw, Neil Smart, Matthew Stephens, Grant D Stewart, Ella Teasdale, Peter Vaughan-Shaw, Raghavan Vidya, Naomi Wright, Natalie Zimmelman, Ervis Agastra, Dariel Thereska, Sergio Martin Lucchini, Veronica Laudani, Carina Chwat, Ivana Ines Pedraza Salazar, Diana Alejandra Pantoja Pachajoa, Agustin Duro, José Alfredo Calderón Arancibia, Giuliana D'Aulerio, Nagendra Dudi-Venkata, Natasha Egoroff, Shebani Farik, Natalie Lott, Jana-Lee Moss, Sarah Rennie, Lorwai Tan, Uyen Giao Vo, David Watson, David Watters, Tim Bright, Paul Hollington, Xuanyu Zhou, Hidde M Kroon, Anthony Farfus, John Barker, Eleanor Watson, Sean Stevens, Haider Latif, Amanda Caroline Dawson, Alwin Chuan, Vijayaragavan Muralidharan, Enoch Wong, Travis Ackermann, Maurizio Pacilli, Russell Hodgson, Alexander Heriot, Peter Choong, Wendy Brown, Surjit Lidder, Justin Yeung, Luke Traeger, Guillermo Regalo, Ralph Gourlay, Sarit Badiani, Cherry Koh, Soni Putnis, Fayza Haider, Ashrarur Rahman Mitul, Niels Komen, Bert Dhondt, Serge Cappeliez, Manon Pigeolet, Martijn Schoneveld, Jasper Stijns, Wouter Oosterlinck, Nicolas Flamey, Cyrille Kpangon, Mouhamed Agbadebo, S Mèvo Romaric Tobome, Aldo Vieira Barros, Samuel Aguiar Júnior, Heloisa Galvão do Amaral Campos, Jefferson Gross, Felipe José Fernandez Coimbra, Luiz Paulo Kowalski, Fabiana Makdissi, Suely Nakagawa, Joao Pedreira Duprat Neto, Jose Guilherme Vartanian, Guilherme Yazbek, Stenio C Zequi, Ronald Flumignan, Natalia Jaworska, Angela Dell, Harsha Shanthanna, Abdollah Behzadi, Carolyn Nessim, Michelle Mozel, Pascal St-Germain, Crispin Russell, Gary Groot, Najib Safieddine, Duminda Wijeysundera, Antoine Eskander, Sami Chadi, Shawn MacKenzie, Alana Flexman, Fernando Heredia, Julio Villanueva, Sofia Waissbluth, Roberto Macchiavello, Mario I Escudero, Tyare Fuentes, Ximena Mimica, Dinimo Bolivar Saenz, Lina Caicedo, Juan Pablo Alzate, Joaquin Luna, Nestor Fabian Pedraza Alonso, Camilo Ortiz Silva, Juliana Rodriguez, Liliana Silva-Igua, Martha Luz Torres, Lina María Trujillo, Albaro José Nieto Calvache, Julián Balanta-Melo, Rafael Figueroa-Casanova, Oscar-Julián García-Montoya, Carlos Andres Marulanda Toro, Marcela Velez Botero, Maria Clara Mendoza Arango, Eneida Diaz Martinez, Valentina Gutiérrez Perdomo, Emileth Montenegro, Julia Rodriguez-Abreu, Dolores Mejía, Galal Abouelnagah, Sameh Shehata, Ahmed Hossam Eldin Fouad Rida, Ramy A Hassan, Mahmoud M Saad, Mohamed Reda Loaloa, Badr Mostafa, Mohamed Qassem, Mohamed Fahmy, Hesham Abozied, Ahmed Y Azzam, Sherief Ghozy, Asser Sallam, Ahmed Shehta, Mohamed Abdelkhalek, Rehab Samaka, Amr Morsy, Ahmed Elshawadfy Sherif, Abraham Negussie, Tigist Fisseha, Kibruyisfaw Shumbash, Metasebia Abebe, Seid Mohammed Yasin, Yemisirach Bizuneh Akililu, Abebe Megersa, Teshome Tefera, Melatework Assefa, Bahru Atnafu, Bereket Tsegaye, Yoseph Solomon Bezabih, Silamlak Sisay, Kebebe Bekele, Moa Jira, Habtamu Derilo, Eyueal Degefa, Anteneh Tadesse, Melkamu Nidaw, Elise Sarjanoja, Sylvie Testelin, Sophie Boucher, Lionel Jouffret, Zaher Lakkis, Alban Zarzavadjian Le Bian, Luke Harper, Marc Danguy des Déserts, Benoît André, Karem Slim, Romain Verhaeghe, Andrea Police, Edouard Girard, Alexandre Chebaro, Armande Subayi Nkembi, Laurent Arnalsteen, Quentin Ballouhey, Diane Mege, Clement Jeandel, Emilie Duchalais, Pierre-Alban Bouche, Gilles Manceau, Célia Crétolle, Erik Hervieux, Noémie Girard, Agathe Seguin-Givelet, Sebastien Gaujoux, Belinda De Simone, Matthieu Boisson, Damien Bergeat, Fabien Fredon, Francesco Nappi, Radwan Kassir, Aurélien Scalabre, Federico Migliorelli, Anne-Cecile Ezanno, Barbara Seeliger, Charlotte Vaysse, Helene Charbonneau, Vincent Misrai, Olivier Abbo, Martina Aida Angeles, Laurent Brunaud, Ali Modabber, Sebastian Wolf, Carsten Kamphues, Philipp Höhn, Tim R Glowka, Alexander Christopher Rokohl, Ulrich Bork, Georg Fluegen, Raymund E Horch, Andrea Schmedding, Andreas Schnitzbauer, Helge Eberbach, Daniel Schlager, Fritz Spelsberg, Lena Keppler, Andreas Hecker, Susanne Wolfer, Ulrich Ronellenfitsch, Christine Nitschke, Christian Peiper, Ibrahim Hakami, Stefan Welter, Karine Nikolaieva, Andreas Roth, Judith Lindert, Konstantinos Gousias, Anke Rissmann, Valerie Catherine Linz, Nuh Rahbari, Marie-Claire Rassweiler-Seyfried, Anna Eleonora Gut, Jens Gempt, Daniel Reim, Arthur Wagner, Alexander M Keppler, Mircea Gabriel Stoleriu, Tim Saier, Josef Stadler, Julia Christina Kaiser, Stefan M Brunner, Karin Pfister, Jonas Herzberg, Kai Nowak, Tobias Reinhard, Gregor A Stavrou, Alfred Königsrainer, Christian Konrads, Markus Quante, Simon Laban, Silke von Pusch, Markus Hirschburger, Johannes Doerner, Armin Wiegering, Ekaterini Christina Tampaki, Alitza Gutiérrez Ruiz, Alejandra Rodas, Ana Lucía Portilla, Jacqueline Carrera, Amalia Barrios Duarte, Megan Lowey, Sabrina Barillas, Atul Suroy, Dhaivat Vaishnav, Raghunandan Gorantlu Chowdappa, Irappa Madabhavi, Dhananjaya Bhat, Sunil Kumar Venkatappa, Sumit Thakar, Kavitha Jain, Aruna Kumar, Manoj Nagar, Tushar Mishra, Arunkumar Sekar, Anand Gupta, Lileswar Kaman, Madhivanan Karthigeyan, Manjul Tripathi, Ashwin Rammohan, Sudheer Othiyil Vayoth, Anupama Rajanbabu, Anbukkani Subbian, Rahul Gupta, Monish Raut, Nissi Evelyn, R Lavanya Kannaiyan, Anil Matai, Sanjeev Misra, Vishal Bhende, Sathish Muthu, Indranil Ghosh, Abhishek Sharma, Ankur Bajaj, Shiv Rajan, Gaurav Agarwal, Pranay Pawar, Philip Alexander, M Vijayakumar Vijayakumar, Zeeshan Hameed, L Badareesh, Navneet Kumar Chaudhry, Lipika Baliarsing, Satish Dharap, Amruta Kulkarni, Yuvaraja Thyavihally, Rahul Deo Sharma, C S Pramesh, Rajesh Soni, Surya Kumar Dube, Shilpa Sharma, Harvinder Singh, Lovenish Bains, Rahul Ghodke, Ashwani Kumar, Vivek Sodhai, Suvendu Maji, Somprakas Basu, Chandrashekhar Mahakalkar, Ravi Kannan, Asif Mehraj, N Ranganath, Ashish Phadnis, I Yadev, Alfie Kavalakat, Rohin Mittal, Karthik Chandra Vallam, Hamed Akhavizadegan, Esmaeil Rezghi Maleki, Naser Yousefzadeh Kandevani, Hilary Ikele, Catherine McNestry, Christina Fleming, Stephen O'Brien, Sami Abd Elwahab, Niall Davis, Mohsen Javadpour, Brendan McDonnell, Clare O Connor, Jarlath Bolger, Cillian Clancy, Stefanie M Croghan, Noel Donlon, Carolyn Cullinane, Ben Creavin, Muheilan Muheilan, Helen Earley, Syed Mohammad Umar Kabir, Muhammad Fahadullah, Éanna Ryan, Tara Connelly, Daisuke Hashimoto, Majdi Ali Alqudah, Amer Alajalen, Rand Y Omari, Abdulrahman Qasem, Yazan Alawneh, Amer Ahmad, Omar Aladawi, Bourhan Alrayes, Hanan Haidar, Shatha Husain, Faisal Qassem, Adnan Sumadi, Ala'a Abu Salhiyeh, Balqees Mahmoud Al-Manaseer, Zaid Alsunna, Hazim Ra'ed, Faten Reyad Bani Hamad, Amro Abuleil, Elmi Ahmed Mohamed Jimaale, Marah Abu-Mehsen, Noor Olaywah, Omar Wafi, Hazim Ababneh, Luai Abu-Ismail, Almu'atasim Khamees, Ahmad Alkhatib, Raikhan Bolatbekova, Mukhtar Kulimbet, Talgat Nurgozhin, Timur Saliev, Baurzhan Zhussupov, Ydyrys Almabayev, Dilyara Kaidarova, Khalil Tamoos, Ahmed Aqeelah, Alsnosy Abdullah Khalefa Mohammed, Faraj Al Maadany, Ghadah Alkadeeki, Milad Gahwagi, Wafa Aldressi, Mohamed Amnaina, Arowa Hassan Abdulrahman Alansari, Akram Alkaseek, Ghozlan Yagoub, Anass Ben Amer, Marwa Salem, Ayman Almugaddami, Dania Burgan, Mohammed Abdelkabir, Khayriyah Alshareef, Rayet Al Islam Ben Jouira, Ayman Meelad, Ahmad Bouhuwaish, Sumayya Essayah Dwaga, Houda Khalifa, Bushray Almiqlash, Taha Suliaman, Mohammed Alawami, Fras Elhajdawe, Hajir Aboazamazem, Ibrahim Ellojli, Ahmed Msherghi, Ismail Ali Saleh, Mohammed Alayan, Marcel Didier Ndayishyigikiye, Akutu Munyika, Philipp Plarre, David W Borowski, Cameron Wells, Rebecca Teague, Brodie Elliott, David Kieser, Omar Mohyieldin, Nick McIntosh, Cheyaanthan Haran, Jasmin King, Jeong Ha, Matthew James McGuinness, Opeoluwa Adesanya, Julius Olaogun, Akinola Akinmade, Kefas Bwala, Peter Agbonrofo, Akinwale Afolabi, Usang Usang, Sebastian Ekenze, Samson Olori, Taiwo Akeem Lawal, Abiodun Okunlola, Stephen Kache, Danjuma Sale, Lofty-John Anyanwu, Chukwuma Okereke, Musliu Adetola Tolani, Venko Filipce, Lazar Todorovic, Sotir Stavridis, John George Massoud, Sareyah Alsibai, Rizwan Sultan, Humera Naz Altaf, Abu Bakar Hafeez Bhatti, Shahzad Hussain Waqar, Aliya Aziz, Asad Ali Kerawala, Lajpat Rai, Mariyah Anwer, Aiman Tariq, Bushra Ayub, Sami Ullah Niazi, Muhammad Yasir Naseem, Muhammad Zeeshan Sarwar, Muhammad Imran Khokhar, Imdad Ahmad Zahid, Haroon Javaid Majid, Nabila Talat, Muhammad Asif, Muhammad Hamid Chaudhary, Umer Farooq, Siddique Ahmad, Waleed Mabood, Syed Imran Bukhari, Muhammad Tariq, Eesha Yaqoob, Saad Javed, Muhammad Usman Malik, Hassan Nawaz Yaqoob, Glenda Marina Falcon Pacheco, Robinson Mas Melendez, Arazzelly Del Pilar Paucar Urbina, Jose Rios Chiuyari, Carlos Eduardo Otiniano Alvarado, Lorena Fuentes Rivera Lau, Giuliano Borda-Luque, Milagros Niquen-Jimenez, Claudia Arias, Sergio Zegarra, Jenner Betalleluz Pallardel, Regina Amparo Ugarte Oscco, Gian Mendiola, Yahaira Tatiana Carpio Colmenares, Carlos Shiraishi Zapata, Maria Rosa Ortiz, Filipe Castro Borges, Octavio Viveiros, Pedro Serralheiro, Paulo Santos-Costa, Filipa Mendes, Miguel Rocha Melo, Paulo Cardoso, Ana Soares, Rita Gonçalves Pereira, Nelson Silva, André Caiado, Maria Luís Sacras, Pedro Azevedo, Rui Almeida-Reis, João Oliveira, Jorge Nogueiro, Mafalda Sampaio-Alves, Luciana Cidade Costa, Catarina Baía, Ana Cláudia Deus, Rita Branquinho, André Marçal, André Tojal, Silviu Tiberiu Makkai-Popa, Aurel Mironescu, Florin Grama, Elena Adelina Toma, Daniela Filipescu, Nicolae Bacalbasa, Natalia Motas, Sebastian Ionescu, Octav Ginghina, Radu Costea, Narcis Octavian Zarnescu, Radu Drasovean, Mihail-Gabriel Dimofte, Vlad Porumb, Mikhail Kirov, Yegor Molitvin, Vadim Pykhteev, Marianna Raevskaya, Aleksandr Butyrskii, Mushabab Alshahrani, Azah Althumairi, Nasser Alzerwi, Ahmed Al Ameer, Tariq Madkhali, Abddulrahman Saleh Almulhim, Salman Ghazwani, Abdu Ayoub, Othman Iskander, Mohammed Ghunaim, Mohammed Alharthi, Turki M Alzaidi, Mohammad Alyami, Abdulrahman Al Amri, Abdullah AlFakhri, Amal Alhefdhi, Sharfuddin Chowdhury, Thamer Nouh, Ameen Alshehri, Abdulrahman Alzahrani, Yousef Alalawi, Selmy Awad, Ibrahima Konate, Jacques Tendeng, Nan Zun Teo, Sabra Aqil, Cristina Barrena López, Ana Sánchez Mozo, Antonio Rodriguez Infante, Patricia Caja Vivancos, Mikel Prieto, Igor Alberdi San Roman, Laura Gomez Fernandez, Josep Maria Muñoz Vives, Anna Carreras-Castañer, Berta Díaz-Feijoo, Ramon Sieira-Gil, Victor Turrado-Rodriguez, Anna Sánchez López, Santiago Sánchez-Cabús, Marta Jimenez Toscano, MªPilar Canals Sin, Saura García Laura, Oriol Martin Sole, Pedro Palazon Bellver, Sonia Pérez-Bertólez, Jordi Prat-Ortells, Mireia Riba Martínez, Josep Rubio-Palau, Xavier Tarrado, Jorge Nuñez, Veronica Alonso Mendoza, Coro Bescós, Eloy Espin-Basany, Martin Espinosa-Bravo, Daniel Gil-Sala, Susana González-Suárez, Nuria Montferrer Estruch, Lucia Porteiro Mariño, Ana Rodríguez-Tesouro, Fabian Rojas Portilla, M Pilar Tormos Pérez, Inmaculada Vives, Unai Garcia De Cortazar, Kiara Tudela, Aitor Landaluce-Olavarria, Mercedes Estaire Gómez, Jorge Almoguera, Bakarne Ugarte-Sierra, Virginia Jimenez, Marta Bertrand, Laura Cárdenas Puiggrós, Olga Delisau-Puig, Jorge Garcia-Adamez, David Julià Bergkvist, Eloy Maldonado-Marcos, Lucia Diego García, Marta Roldón Golet, Iván Soto-Darias, Aida Cristina Rahy-Martín, Diego Enjuto, Adolfo Ramos-Luengo, Juan Delgado Fernandez, Carolina Lugo Duarte, Cristina Ojeda Thies, Lucila Marquez, Diana Crego Vita, Jana Dziakova, Jorge Caño Velasco, Olga Mateo-Sierra, Begoña Quintana-Villamandos, Cristina Rey Valcarcel, Javier Rio, Laura Román García de León, Marcello Di Martino, Jorge Prada, Javier Serrano González, Manuel Losada, Jose Tomas Castell Gomez, Ramon Corripio-Sanchez, Alexander Forero-Torres, José Manuel Morales-Puebla, Hanna Perez-Chrzanowska, Santiago Valderrabano Gonzalez, Alvaro Yebes, Ignacio Zapardiel, Manuel Diez Alonso, Nelson Morales Palacios, Alberto Cabañero Sánchez, Fátima Sánchez Fernández, Alfredo Abad Gurumeta, Ane Abad-Motos, Fernando Corella, Javier Ripollés-Melchor, Rosa Sanz-Gonzalez, Marta Alcaraz Fuentes, Maria Teresa Fernández Martín, Pablo Calvo Espino, Milagros Carrasco Prats, Antonio-José Fernández-López, Damián García Escudero, Vanesa Garcia Soria, Jesús Aarón Martínez Alonso, Miguel Ruiz-Marín, Beatriz Gómez Pérez, Joaquin Moya-Angeler, Daniel Fernández Martínez, Heura Llaquet Bayo, Enrique Colás-Ruiz, Susana Bella Romera, M Teresa Gavaldà Pellicé, Misericòrdia Jordà Solé, Enrique Jose Ruiz Velasquez, Bernardo Núñez, Raul Jimenez, Jon Zabaleta, Maria Jose González-Gimeno, Irene Ortega Vázquez, Antonio Perez Ferrer, Rubén Martín-Láez, Marcelo Moreno Suarez, Miguel Angel Freiria Eiras, Irene Ramallo-Solís, Juan-Carlos Gomez-Rosado, Jose Ramon Oliver Guillen, Mar Achalandabaso Boira, Juan Carlos Catalá Bauset, Julio Domenech, Rafael Badenes, Juan Carlos Bernal-Sprekelsen, Jorge Sancho-Muriel, Beatriz De Andrés-Asenjo, Francisco J Tejero-Pintor, Marc Vallve-Bernal, Alba Vazquez Melero, Laura Sánchez Blasco, Jorge Escartin, Victoria Duque Mallén, Selvaratnam Srishankar, Charitha Sooriyabandara, Oshan Basnayake, Nalaka Gunawansa, Prabuth Dulanjan Weeraddana, Thanusan Vimalakanthan, Shanthamoorthy Gishanthan, Pramodh Chandrasinghe, Marc-Olivier Sauvain, Ahmad Ghazal, Yusra Al-Sabbagh, Turki Alhassoun, Sara Maa Albared, Antoine Naem, Hareth Alnahr, Ghassan Jisry, Ali Hammed, Okedi Francis Xaviour, Gaston Turinawe, Isaac Mubezi, Franck K Sikakulya, Andrew Kakeeto, Wilberforce M Kabweru, Ronald Kiweewa, Paul Matovu, Otolia Isaac, Mohamed Mashhour, Amin El Helw, Safeena Kherani, Awadelkarim Mohamed, Ferial Mohamed Ali Abbas, Diary Mohammed, Ehab Aldlyami, Rakesh Kundra, Antony Louis Rex Michael, Kareem S Khalil, Rachel Dbeis, Shafaque Shaikh, Jenny Ferry, Aiman Jamal, Haleema Siddique, Rishi Das, Nikhil Ponugoti, Pornjittra Rattanasirivilai, Asma Sultana, Frances Mosley, Matthew Chan, Antony Bateman, Gareth Davies-Jones, Fanourios Georgiades, Navid Ahmadi, Aman Coonar, Mariam Baig, Chetan Khatri, Arthika Surendran, Julian Sonksen, Robert Sinnerton, Caitlin Brennan, Gemma Faulkner, Michael Greenhalgh, Hannah Emerson, Kiran Singisetti, Joshua Totty, Michael Wilson, Terence Lo, Harriet Corbett, Ijeoma Okonkwo, Gill Arbane, Cyrus Kerawala, Chetan Parmar, Michael Bath, Funlayo Odejinmi, Jayesh Sagar, Rishi Talwar, Samuel Newman, John Hammond, John Moir, Natalie Duric, Tamas Szakmany, Ahmar Iftikhar Talib, Mina Youssef, Christopher Lewis-Lloyd, Mariam Lami, Khurram Ayub, Benjamin Dean, Supriya Balasubramanya, Sathya Lakpriya, Luke Rogers, Paul Turner, Mark Maher, Kohila Sigamoney, Jihène El Kafsi, John Hardie, David Johnson, Christin Henein, Marianne Hollyman, Ketan Agarwal, Simon Powell, Govind Singh Chauhan, Rakesh Patel, Joel Gagnier, Heather Carmichael, Aurora, Kristofor A Olson, Eric Etchill, Sameer Hirji, Matthew Naunheim, Frederick Drake, Caroline Reinke, Anna Alecci, Dennis Vaysburg, Jennifer Rodriquez, Emily Shih, Vin Shen Ban, Julia Coleman, Krista Kaups-Fresno, Emmanouil Giorgakis, Maggie DiNome, Neal Bhutiani, Omar Alnachoukati, Taylor Aiken, Thomas Diehl, Ankush Gosain, Rishi Rattan, Muhammad Owais Abdul Ghani, Nensi Melissa Ruzgar, Anna Liveris, Nina Glass, Charu Paranjape, Theresa Chin, Antonio Meola, Kristina Nicholson, John Squiers, Stephanie Lueckel, Janani Reisenauer, Rachael Callcut, Ahmed Mansour, Allison Berndtson, Lucy Kornblith, Sara Seegert, Paulo Martins, Mohammed Al-Shehari, Ibrahim Al-Raimi, Allan Ngulube, Maphios Siamuchembu, Willard Mushiwokufa, Busisiwe Mlambo, Simbarashe Chinyowa, Enton Bollano, Kostandin Gjyli, Jola Kerpaci, Enxhi Vrapi, Lorena Zijaj, Bahraoui Djahida, Belabbes Fatima Zohra, Kouidri Khadidja, Oussama Bali, Nassim Benallel, Ismahene Lalmi, Meriem Abdoun, Nesrine Aouabed, Souad Bouaoud, Kamel Bouchenak, Assia Haif, Zineddine Soualili, Joaquin Bastet, Agustín Bianco, Daniel Capitaine, Jorge Centeno Lozada, Carlos Esquivel, Rodrigo Figueroa, Manuel Garcia, Pablo Martín García, José Ignacio Gerchunoff, Fernando Martinez Iascano, Jose Mondino, María Emilia Muriel, Carmignani Pablo, Martin Passadore, Alejandra Tornini, Rogelio Traverso, Lara Vargas, Gerardo Zanoni, Norberto Berber, Estefanía Cotta, Marcela Di Vincenzo, Esteban Sebastian Gallino, Cecilia Gigena, Bianca Grassano, Ignacio Lugones, Constanza Madrid, Maximiliano Maricic, Antonio Alberto Martinez, Andres Rosso, Pablo Scher, Sofia Tachella, Damaris Idara Anabel Zezular, Carla Abuawad, Agustin Albani Forneris, Carola Allemand, Laura Gisela Alvarez Calzaretta, Jorge G Boretto, Rocio Boudou, Rodrigo Brandariz, Martin Buljubasich, Arturo Burchakchi, Martin Buttaro, Juan Pablo Campana, Virginia Cano Busnelli, Tomas Carminatti, Agustina Florencia Castro Lalín, Julian Cereghini, María Sol Crespi Amor, Roberto Sebastián Croattini, Maria Sol Fernandez, Marcelo Figari, Uriel Fraidenraij, Diego Gallegos, Agustín Maria García-Mansilla, Marcos Gonzalez, Matias Ignacio Gonzalez, Esteban Gonzalez Salazar, Jeremias Goransky, Guillermo Hernandez Gauna, Felipe Higuera, Fernando Holc, Esteban Gabriel Jauregui, Juan Larrañaga, Juan Liyo, Lionel Llano, Pablo Lobos, Emilia Luzzi, Gustavo Mastroianni, Santiago Miguel Mata-Suarez, Horacio F Mayer, Santiago Mc Loughlin, Efrain Mendoza, 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Kache, Danjuma Sale, Lofty-John Anyanwu, Chukwuma Okereke, Musliu Adetola Tolani, Venko Filipce, Lazar Todorovic, Sofija Pejkova, Sotir Stavridis, John George Massoud, Sareyah Alsibai, Rizwan Sultan, Humera Naz Altaf, Abu Bakar Hafeez Bhatti, Shahzad Hussain Waqar, Aliya Aziz, Asad Ali Kerawala, Lajpat Rai, Mariyah Anwer, Aiman Tariq, Bushra Ayub, Sami Ullah Niazi, Muhammad Yasir Naseem, Muhammad Zeeshan Sarwar, Muhammad Imran Khokhar, Imdad Ahmad Zahid, Haroon Javaid Majid, Nabila Talat, Muhammad Asif, Muhammad Hamid Chaudhary, Umer Farooq, Siddique Ahmad, Waleed Mabood, Syed Imran Bukhari, Muhammad Tariq, Eesha Yaqoob, Saad Javed, Saad Javed, Muhammad Usman Malik, Hassan Nawaz Yaqoob, Moises Cukier, Glenda Marina Falcon Pacheco, Robinson Mas Melendez, Arazzelly Del Pilar Paucar Urbina, Jose Rios Chiuyari, Carlos Eduardo Otiniano Alvarado, Lorena Fuentes Rivera Lau, Giuliano Borda-Luque, Milagros Niquen-Jimenez, Claudia Arias, Sergio Zegarra, Jenner Betalleluz Pallardel, Regina Amparo Ugarte Oscco, Gian Mendiola, Yahaira Tatiana Carpio Colmenares, Carlos Shiraishi Zapata, Maria Rosa Ortiz, Marie Dione Sacdalan, Piotr Major, Filipe Castro Borges, Octavio Viveiros, Pedro Serralheiro, Paulo Santos-Costa, Filipa Mendes, Miguel Rocha Melo, Paulo Cardoso, Ana Soares, José Azevedo, Rita Gonçalves Pereira, Nelson Silva, André Caiado, Maria Luís Sacras, Pedro Azevedo, Rui Almeida-Reis, Miguel F Cunha, João Oliveira, Jorge Nogueiro, Mafalda Sampaio-Alves, Luciana Cidade Costa, Catarina Baía, Ana Cláudia Deus, Rita Branquinho, André Marçal, André Tojal, Ahmad Zarour, Ahmad Zarour, Silviu Tiberiu Makkai-Popa, Aurel Mironescu, Florin Grama, Elena Adelina Toma, Ionut Negoi, Daniela Filipescu, Nicolae Bacalbasa, Natalia Motas, Sebastian Ionescu, Octav Ginghina, Radu Costea, Narcis Octavian Zarnescu, Radu Drasovean, Eduard-Alexandru Bonci, Mihail-Gabriel Dimofte, Vlad Porumb, Mikhail Kirov, Yegor Molitvin, Andrey Litvin, Vadim Pykhteev, Marianna Raevskaya, Sergey Efetov, Aleksandr Butyrskii, Mushabab Alshahrani, Azah Althumairi, Nasser Alzerwi, Ahmed Al Ameer, Ahmed Al Ameer, Tariq Madkhali, Abddulrahman Saleh Almulhim, Salman Ghazwani, Abdu Ayoub, Othman Iskander, Mohammed Ghunaim, Mohammed Alharthi, Turki M Alzaidi, Azah Althumairi, Mohammad Alyami, Abdulrahman Al Amri, Azah Althumairi, Abdullah AlFakhri, Amal Alhefdhi, Sharfuddin Chowdhury, Thamer Nouh, Ameen Alshehri, Abdulrahman Alzahrani, Yousef Alalawi, Selmy Awad, Ibrahima Konate, Abdourahmane Ndong, Jacques Tendeng, Nan Zun Teo, Frederick Koh, Jurij Aleš Košir, Uros Bele, Sabra Aqil, Cristina Barrena López, Ana Sánchez Mozo, Antonio Rodriguez Infante, Patricia Caja Vivancos, Mikel Prieto, Igor Alberdi San Roman, Laura Gomez Fernandez, Josep Maria Muñoz Vives, Anna Carreras-Castañer, Berta Díaz-Feijoo, Ramon Sieira-Gil, Victor Turrado-Rodriguez, Anna Sánchez López, Santiago Sánchez-Cabús, Marta Jimenez Toscano, MªPilar Canals Sin, Saura García Laura, Oriol Martin Sole, Pedro Palazon Bellver, Sonia Pérez-Bertólez, Jordi Prat-Ortells, Mireia Riba Martínez, Josep Rubio-Palau, Xavier Tarrado, Jorge Nuñez, Veronica Alonso Mendoza, Coro Bescós, Eloy Espin-Basany, Martin Espinosa-Bravo, Daniel Gil-Sala, Susana González-Suárez, Nuria Montferrer Estruch, Jorge Nuñez, Lucia Porteiro Mariño, Ana Rodríguez-Tesouro, Fabian Rojas Portilla, M Pilar Tormos Pérez, Inmaculada Vives, Unai Garcia De Cortazar, Kiara Tudela, Aitor Landaluce-Olavarria, Mercedes Estaire Gómez, Jorge Almoguera, Bakarne Ugarte-Sierra, Virginia Jimenez, Marta Bertrand, Laura Cárdenas Puiggrós, Olga Delisau-Puig, Jorge Garcia-Adamez, David Julià Bergkvist, Eloy Maldonado-Marcos, Lucia Diego García, Marta Roldón Golet, Iván Soto-Darias, Aida Cristina Rahy-Martín, Diego Enjuto, Adolfo Ramos-Luengo, Juan Delgado Fernandez, Carolina Lugo Duarte, Cristina Ojeda Thies, Lucila Marquez, Diana Crego Vita, Jana Dziakova, Ana Maria Minaya Bravo, Jorge Caño Velasco, Olga Mateo-Sierra, Begoña Quintana-Villamandos, Cristina Rey Valcarcel, Javier Rio, Laura Román García de León, Marcello Di Martino, Jorge Prada, Javier Serrano González, Manuel Losada, Jose Tomas Castell Gomez, Ramon Corripio-Sanchez, Alexander Forero-Torres, José Manuel Morales-Puebla, Hanna Perez-Chrzanowska, Santiago Valderrabano Gonzalez, Alvaro Yebes, Ignacio Zapardiel, Manuel Diez Alonso, Nelson Morales Palacios, Alberto Cabañero Sánchez, Fátima Sánchez Fernández, Alfredo Abad Gurumeta, Ane Abad-Motos, Fernando Corella, Javier Ripollés-Melchor, Rosa Sanz-Gonzalez, Marta Alcaraz Fuentes, Maria Teresa Fernández Martín, Pablo Calvo Espino, Milagros Carrasco Prats, Antonio-José Fernández-López, Damián García Escudero, Vanesa Garcia Soria, Jesús Aarón Martínez Alonso, Miguel Ruiz-Marín, Beatriz Gómez Pérez, Joaquin Moya-Angeler, Daniel Fernández Martínez, Heura Llaquet Bayo, Enrique Colás-Ruiz, Susana Bella Romera, M Teresa Gavaldà Pellicé, Misericòrdia Jordà Solé, Enrique Jose Ruiz Velasquez, Bernardo Núñez, Raul Jimenez, Jon Zabaleta, Maria Jose González-Gimeno, Irene Ortega Vázquez, Antonio Perez Ferrer, Rubén Martín-Láez, Marcelo Moreno Suarez, Miguel Angel Freiria Eiras, Irene Ramallo-Solís, Juan-Carlos Gomez-Rosado, Jose Ramon Oliver Guillen, Mar Achalandabaso Boira, Juan Carlos Catalá Bauset, Julio Domenech, Rafael Badenes, Juan Carlos Bernal-Sprekelsen, Jorge Sancho-Muriel, Beatriz De Andrés-Asenjo, Francisco J Tejero-Pintor, Marc Vallve-Bernal, Alba Vazquez Melero, Laura Sánchez Blasco, Jorge Escartin, Victoria Duque Mallén, Selvaratnam Srishankar, Umesh Jayarajah, Charitha Sooriyabandara, Oshan Basnayake, Nalaka Gunawansa, Dakshitha Wickramasinghe, Prabuth Dulanjan Weeraddana, Thanusan Vimalakanthan, Shanthamoorthy Gishanthan, Pramodh Chandrasinghe, Eleftherios Gialamas, Marc-Olivier Sauvain, Ahmad Ghazal, Yusra Al-Sabbagh, Turki Alhassoun, Sara Maa Albared, Antoine Naem, Hareth Alnahr, Ghassan Jisry, Ali Hammed, Arda Isik, Okedi Francis Xaviour, Gaston Turinawe, Isaac Mubezi, Franck K Sikakulya, Andrew Kakeeto, Wilberforce M Kabweru, Hervé Monka Lekuya, Ronald Kiweewa, Herman Lule, Paul Matovu, Otolia Isaac, Mohamed Mashhour, Amin El Helw, Sattar Alshryda, Safeena Kherani, Awadelkarim Mohamed, Ferial Mohamed Ali Abbas, Diary Mohammed, Ehab Aldlyami, Rakesh Kundra, Mohamed Mashhour, Mohamed Mashhour, Antony Louis Rex Michael, Hayder Alsaadi, Kareem S Khalil, Rachel Dbeis, Shafaque Shaikh, Jenny Ferry, Aiman Jamal, Haleema Siddique, Rishi Das, Nikhil Ponugoti, Sivesh K Kamarajah, Pornjittra Rattanasirivilai, Asma Sultana, Frances Mosley, Matthew Chan, Antony Bateman, Gareth Davies-Jones, Fanourios Georgiades, Grant D Stewart, Navid Ahmadi, Aman Coonar, Mariam Baig, Chetan Khatri, Arthika Surendran, Julian Sonksen, Robert Sinnerton, Caitlin Brennan, Gemma Faulkner, Michael Greenhalgh, Hannah Emerson, Kiran Singisetti, Joshua Totty, Michael Wilson, Terence Lo, Harriet Corbett, Ijeoma Okonkwo, Gill Arbane, Kariem El-Boghdadly, Cyrus Kerawala, Chetan Parmar, Tom Abbott, Michael Bath, Funlayo Odejinmi, Jayesh Sagar, Rishi Talwar, Samuel Newman, John Hammond, John Moir, Natalie Duric, Tamas Szakmany, Ahmar Iftikhar Talib, Mina Youssef, Christopher Lewis-Lloyd, Christopher Lewis-Lloyd, Mariam Lami, Khurram Ayub, Benjamin Dean, Supriya Balasubramanya, Sathya Lakpriya, Luke Rogers, Paul Turner, Mark Maher, Kohila Sigamoney, John Edwards, Jihène El Kafsi, John Hardie, David Johnson, Christin Henein, Marianne Hollyman, Ketan Agarwal, Simon Powell, Govind Singh Chauhan, Rakesh Patel, Joel Gagnier, Heather Carmichael, Aurora, Kristofor A Olson, Eric Etchill, Joseph Incorvia, Sameer Hirji, Matthew Naunheim, Frederick Drake, Haytham Kaafarani, Caroline Reinke, Anna Alecci, Dennis Vaysburg, Jennifer Rodriquez, Emily Shih, Vin Shen Ban, Julia Coleman, Henry E Rice, Krista Kaups-Fresno, Emmanouil Giorgakis, Maggie DiNome, Neal Bhutiani, Omar Alnachoukati, Brittany Bankhead-Kendall, Taylor Aiken, Thomas Diehl, Ankush Gosain, Rishi Rattan, Muhammad Owais Abdul Ghani, Nensi Melissa Ruzgar, Anna Liveris, Nina Glass, Charu Paranjape, Theresa Chin, Antonio Meola, Kristina Nicholson, John Squiers, Stephanie Lueckel, Janani Reisenauer, Rachael Callcut, Ahmed Mansour, Allison Berndtson, Lucy Kornblith, Sara Seegert, Paulo Martins, Hamza Al-Naggar, Mohammed Al-Shehari, Ibrahim Al-Raimi, Allan Ngulube, Maphios Siamuchembu, Willard Mushiwokufa, Busisiwe Mlambo, Simbarashe Chinyowa, Ervis Agastra, Enton Bollano, Kostandin Gjyli, Dariel Thereska, Irida Dajti, Jola Kerpaci, Enxhi Vrapi, Lorena Zijaj, Bahraoui Djahida, Belabbes Fatima Zohra, Kouidri Khadidja, Oussama Bali, Nassim Benallel, Ismahene Lalmi, Meriem Abdoun, Nesrine Aouabed, Souad Bouaoud, Kamel Bouchenak, Assia Haif, Zineddine Soualili, Joaquin Bastet, Agustín Bianco, Daniel Capitaine, Jorge Centeno Lozada, Carlos Esquivel, Rodrigo Figueroa, Manuel Garcia, Pablo Martín García, José Ignacio Gerchunoff, Fernando Martinez Iascano, Jose Mondino, María Emilia Muriel, Carmignani Pablo, Martin Passadore, Alejandra Tornini, Rogelio Traverso, Lara Vargas, Gerardo Zanoni, Norberto Berber, Estefanía Cotta, Marcela Di Vincenzo, Esteban Sebastian Gallino, Cecilia Gigena, Bianca Grassano, Veronica Laudani, Ignacio Lugones, Constanza Madrid, Maximiliano Maricic, Antonio Alberto Martinez, Andres Rosso, Pablo Scher, Sofia Tachella, Damaris Idara Anabel Zezular, Carla Abuawad, Agustin Albani Forneris, Carola Allemand, Laura Gisela Alvarez Calzaretta, Luis Boccalatte, Jorge G Boretto, Rocio Boudou, Rodrigo Brandariz, Martin Buljubasich, Arturo Burchakchi, Martin Buttaro, Juan Pablo Campana, Virginia Cano Busnelli, Tomas Carminatti, Agustina Florencia Castro Lalín, Julian Cereghini, María Sol Crespi Amor, Roberto Sebastián Croattini, Maria Sol Fernandez, Marcelo Figari, Uriel Fraidenraij, Diego Gallegos, Agustín Maria García-Mansilla, Marcos Gonzalez, Matias Ignacio Gonzalez, Esteban Gonzalez Salazar, Jeremias Goransky, Guillermo Hernandez Gauna, Felipe Higuera, Fernando Holc, Esteban Gabriel Jauregui, Juan Larrañaga, Juan Liyo, Lionel Llano, Pablo Lobos, Emilia Luzzi, Gustavo Mastroianni, Santiago Miguel Mata-Suarez, Horacio F Mayer, Santiago Mc Loughlin, Efrain Mendoza, Ricardo Esteban Mentz, Pedro Mercado, Pablo Moyano, Florencia Noll, Diego Odetto, Agustina Rene Oliva, Rafael Perez Vidal, Catalina Poggi, Eduardo Jorge Premoli, María Lourdes Ramos, Patricio Rosas, Luciano Rossi, Gustavo Rossi, Jose Saadi, Jordán Scherñuk, Pablo Slullitel, María Verona Stang, María Victoria Taboada, Sebastian Tirapegui, Constanza Uffelmann, Carlos Vaccaro, Roberto Vagni, Ana Clara Valerio, Celeste Soledad Zarratea, Carina Chwat, Silvina Montal, Brian Morris, Pedro Valdez, Fernando Diaz-Couselo,Ricci C, Casadei R, Fruscio, R, Ornaghi, S, Felice Pecoraro, Emanuele Cammarata, Sofia Campanella, Daniela Canzonieri, Adriana Cordova, Federico De Michele, Ettore Dinoto, Mara Franza, Leo Licari, Daniele Matta, Domenico Mirabella, Roberto Pirrello, Pierfrancesco Pugliese, Fernando Rosatti, Giuseppe Salamone, Francesca Toia, Massimiliano Tripoli, Vito Chiantera, Mariano Catello Di Donna, Collaborative, Covidsurg, Collaborative, Globalsurg, Palmisano, Silvia, de Manzini, Nicolo', Simoes, J, Rosati, R, on behalf of COVIDSurg Collaborative, GlobalSurg Collaborative, Aldrighetti, L, Mortini, P, Olmi, S, Medical Oncology, Assoc Surg Training ASiT, European Soc Coloproctology ESCP, EuroSurg, G4 Alliance, GlobalPaedSurg, GICS, ItSURG, ISRC, Italian Soc Colorectal Surg SICCR, PTSurg, S-ECCO, South African Soc, and SpainSurg

Subjects
Lung Diseases, Male, Internationality, SARS-Cov-2, COVID-19, surgery, pathways, pre-operative isolation, Settore MED/18 - CHIRURGIA GENERALE, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Lung Disease, ESTUDOS PROSPECTIVOS, Cohort Studies, Patient Isolation, Postoperative Complications, 80 and over, Prospective Studies, Prospective cohort study, 610 Medicine & health, Aged, 80 and over, Incidence (epidemiology), Treatment Outcome, Elective Surgical Procedures, Female, Elective Surgical Procedure, Cohort study, Human, medicine.medical_specialty, Isolation (health care), Preoperative care, NO, Anesthesiology, Preoperative Care, medicine, Humans, Elective surgery, LS7_4, Aged, business.industry, pathway, Surgery, Reconstructive and regenerative medicine Radboud Institute for Health Sciences [Radboudumc 10], Prospective Studie, Anesthesiology and Pain Medicine, Human medicine, Postoperative Complication, Cohort Studie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p=0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3days, with an OR (95%CI) at 4–7days or ≥8days of 1.25 (1.04–1.48), p=0.015 and 1.31 (1.11–1.55), p=0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care. We aimed to determine the impact of pre-operative isolation on postoperative pulmonary complications after elective surgery during the global SARS-CoV-2 pandemic. We performed an international prospective cohort study including patients undergoing elective surgery in October 2020. Isolation was defined as the period before surgery during which patients did not leave their house or receive visitors from outside their household. The primary outcome was postoperative pulmonary complications, adjusted in multivariable models for measured confounders. Pre-defined sub-group analyses were performed for the primary outcome. A total of 96,454 patients from 114 countries were included and overall, 26,948 (27.9%) patients isolated before surgery. Postoperative pulmonary complications were recorded in 1947 (2.0%) patients of which 227 (11.7%) were associated with SARS-CoV-2 infection. Patients who isolated pre-operatively were older, had more respiratory comorbidities and were more commonly from areas of high SARS-CoV-2 incidence and high-income countries. Although the overall rates of postoperative pulmonary complications were similar in those that isolated and those that did not (2.1% vs 2.0%, respectively), isolation was associated with higher rates of postoperative pulmonary complications after adjustment (adjusted OR 1.20, 95%CI 1.05–1.36, p=0.005). Sensitivity analyses revealed no further differences when patients were categorised by: pre-operative testing; use of COVID-19-free pathways; or community SARS-CoV-2 prevalence. The rate of postoperative pulmonary complications increased with periods of isolation longer than 3days, with an OR (95%CI) at 4–7days or ≥8days of 1.25 (1.04–1.48), p=0.015 and 1.31 (1.11–1.55), p=0.001, respectively. Isolation before elective surgery might be associated with a small but clinically important increased risk of postoperative pulmonary complications. Longer periods of isolation showed no reduction in the risk of postoperative pulmonary complications. These findings have significant implications for global provision of elective surgical care.

Published
2021
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38. A simple risk score for detecting radiological occult metastasis in patients with resectable or borderline resectable pancreatic ductal adenocarcinoma

Author

So Yamaki, Sohei Satoi, Mitsuaki Ishida, Satoshi Hirooka, Tomohisa Yamamoto, Daisuke Hashimoto, Mitsugu Sekimoto, Kentaro Inoue, Tatsuma Sakaguchi, and Tsukasa Ikeura

Subjects
medicine.medical_specialty, Multivariate analysis, Framingham Risk Score, Hepatology, business.industry, Odds ratio, Adenocarcinoma, medicine.disease, Occult, Gastroenterology, Metastasis, Pancreatic Neoplasms, Risk Factors, Borderline resectable, Internal medicine, Radiological weapon, Cohort, Humans, Medicine, Surgery, business, Carcinoma, Pancreatic Ductal, Retrospective Studies
Abstract

BACKGROUND We advocated carbohydrate antigen (CA) 19-9 ≥ 150 U/mL and tumor size ≥30 mm as "high-risk markers" for predicting unresectability among patients with radiologically resectable (R) or borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC). The main aim is to establish a risk scoring system for occult abdominal metastasis (OAM) in R/BR PDAC. METHODS Predictors of OAM were investigated retrospectively in an experiment cohort from 2006 to 2018. The proposed risk scoring system was validated in another cohort from 2019 to 2020. RESULTS Five hundred and thirteen eligible patients were divided into the experimental (405 patients; OAM, 22%) and validation cohorts (108 patients). Multivariate analysis identified tumor location of body/tail (odds ratio [OR] 4.45, P

Published
2021
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39. Autophagy Inhibition Increased Sensitivity of Pancreatic Cancer Cells to Carbon Ion Radiotherapy.

Author

Makoto Sudo, Hiroko Tsutsui, Shuhei Hayashi, Koubun Yasuda, Keiko Mitani, Nana Iwami, Makoto Anzai, Toshiro Tsubouchi, Mitsuaki Ishida, Sohei Satoi, Tatsuaki Kanai, Seiko Hirono, Etsuro Hatano, and Jiro Fujimoto

Subjects
PANCREATIC cancer, CANCER cells, AUTOPHAGY, NEOADJUVANT chemotherapy, CELL death
Abstract

Background/Aims: Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer. Methods: We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone. Results: CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining. Conclusions: CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities. [ABSTRACT FROM AUTHOR]

Published
2023
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40. Sporadic nonfunctional pancreatic neuroendocrine tumors: Risk of lymph node metastases and aggressiveness according to tumor size: A multicenter international study

Author

Julie Perinel, Gennaro Nappo, Alessandro Zerbi, Charlotte M. Heidsma, Elisabeth J.M. Nieveen van Dijkum, Ho Seong Han, Yoo-Seok Yoon, Sohei Satoi, Ihsan Ekin Demir, Helmut Friess, Yogesh Vashist, Jakob Izbicki, Alexandra Charlotte Muller, Beat Gloor, Marta Sandini, Luca Gianotti, Fabien Subtil, Mustapha Adham, Surgery, CCA - Cancer Treatment and Quality of Life, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Pancreatic Neoplasms, Neuroendocrine Tumors, Pancreatectomy, Lymphatic Metastasis, Humans, Surgery, 610 Medicine & health, Retrospective Studies
Abstract

Background: Although the correlation between tumor size and aggressiveness is clearly established in sporadic nonfunctional pancreatic neuroendocrine tumors, the management of tumors ≤2 cm remains debated. In recent guidelines, the cut-off size to operate ranged from 1 to 2 cm. The aim of this retrospective study was to report the rate of lymph nodes metastases in resected sporadic nonfunctional pancreatic neuroendocrine tumors, according to tumor size and, second, to identify risk factors of lymph node metastases and disease-free survival. Methods: Resected sporadic nonfunctional pancreatic neuroendocrine tumors from 9 international expert centers were included (1999–2017). Functional pancreatic neuroendocrine tumors, genetic syndromes, and R2 resection were excluded. Aggressiveness was defined as microvascular invasion, perineural invasion, lymph node metastases, G3 grading, distant metastases, and/or recurrence. Results: Overall, 495 resected sporadic nonfunctional pancreatic neuroendocrine tumors were included. For tumors up to 5 cm, the risk of lymph node metastases was increased by 1.73 for every 1 cm increase in size (odds ratio = 1.73; 95% confidence interval = 1.46–2.03). Tumor size >2 cm (P < .001), perineural invasion (P = .002), microvascular invasion (P < .001), and distant metastases (P = .008) were independently associated with lymph node metastases. Tumor size >2 cm (P = .003), R1 status (P = .004), lymph node metastases (P < .001), and World Health Organization grade 3 (P = .002) were independently associated with disease-free survival. Aggressiveness rate was 13.1% in tumors ≤1 cm and 29% in tumors between 1.1 and 2 cm. Conclusion: In resected sporadic nonfunctional pancreatic neuroendocrine tumors, the risk of lymph node metastases is correlated to tumor size. Considering that sporadic nonfunctional pancreatic neuroendocrine tumors between 1.1 and 2 cm had a higher risk of lymph node metastases and recurrence compared to tumors ≤1 cm, the decision to perform surgery in this subgroup of patients should be individualized in surgically fit patients.

Published
2022
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41. Nutritional impact of active hexose-correlated compound for patients with resectable or borderline-resectable pancreatic cancer treated with neoadjuvant therapy

Author

So Yamaki, Tatsuma Sakaguchi, Mitsugu Sekimoto, Mitsuaki Ishida, Tomohisa Yamamoto, Daisuke Hashimoto, Hironori Ryota, Sohei Satoi, Kentaro Inoue, and Satoshi Hirooka

Subjects
Male, Oncology, medicine.medical_specialty, medicine.medical_treatment, Shiitake Mushrooms, Nutritional Status, Phases of clinical research, 030230 surgery, Deoxycytidine, 03 medical and health sciences, 0302 clinical medicine, Polysaccharides, Borderline resectable, Surgical oncology, Internal medicine, Pancreatic cancer, Antineoplastic Combined Chemotherapy Protocols, Active hexose correlated compound, medicine, Humans, Neoadjuvant therapy, Aged, Tegafur, Aged, 80 and over, Chemotherapy, business.industry, General Medicine, Middle Aged, medicine.disease, Gemcitabine, Neoadjuvant Therapy, Pancreatic Neoplasms, Drug Combinations, Oxonic Acid, Nutrition Assessment, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Surgery, Nutrition Therapy, business, Carcinoma, Pancreatic Ductal, Phytotherapy, medicine.drug
Abstract

Active hexose-correlated compound (AHCC) is a standardized extract from cultured Lentinula edodes mycelia, used as a potent biological response modifier in cancer treatment. We evaluated the nutritional effect of AHCC, given during neoadjuvant therapy, to patients with pancreatic ductal adenocarcinoma (PDAC). Thirty patients with resectable or borderline-resectable PDAC received neoadjuvant therapy with gemcitabine plus S-1. We compared, retrospectively, the outcomes of 15 patients who received AHCC combined with neoadjuvant therapy with those of 15 patients who did not receive AHCC combined with neoadjuvant therapy. The median changes of the neutrophil-to-lymphocyte ratio (NLR) and prognostic nutrition index (PNI) were significantly better in the AHCC group. The relative dose intensity of neoadjuvant therapy was also significantly higher in the AHCC group. Thus, AHCC may improve the nutritional status during neoadjuvant therapy of patients with pancreatic ductal adenocarcinoma. To validate these results and examine the long-term impact of AHCC, a prospective phase II study for PDAC is ongoing.

Published
2021
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42. Implementation of an educational program for pancreaticoduodenectomy in a university hospital: a retrospective observational study

Author

Satoshi Hirooka, Daisuke Hashimoto, Kazuto Sakuramoto, Mitsugu Sekimoto, Tatsuma Sakaguchi, Hideyoshi Toyokawa, Rintaro Yui, Hiroaki Yanagimoto, Taku Michiura, So Yamaki, Hideyuki Matsushima, Kentaro Inoue, Hironori Ryota, Tomohisa Yamamoto, and Sohei Satoi

Subjects
medicine.medical_specialty, Hepatology, business.industry, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, General surgery, Retrospective cohort study, RC799-869, Diseases of the digestive system. Gastroenterology, Pancreaticoduodenectomy, University hospital, Endocrinology, medicine, business, Educational program
Abstract

Objective:. No ideal training system exists for pancreaticoduodenectomy (PD). We developed an educational system that uses an objective structured assessment of technical skills. Methods:. This retrospective observational study was conducted using the data of consecutive trainees and patients who underwent PD from 2007 to 2013 in Kansai Medical University Hospital. The total score on the task checklist (21 parameters) for measuring technical performance during PD by self assessment and instructor assessment was compared between junior (JN) and hepatobiliary pancreatic (HBP) trainees at a university hospital. Surgical outcomes of 303 PDs (2007–2013) were also compared among JN trainees, HBP trainees, and instructors, and the present position of the trainees was investigated. This study was approved by the institutional review board of Kansai Medical University on May 26, 2020. Results:. The self-assessment score on the task checklist was significantly higher for the HBP trainees than for the JN trainees on all parts of PD (P

Published
2021
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43. Development, validation, and comparison of a nomogram based on radiologic findings for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: An international multicenter study

Author

Hyung Il Seo, Michael D. Kluger, Ho-Seong Han, Wookyeong Song, Wonho Choo, Alex B. Blair, Wooil Kwon, Woo Jung Lee, Taesung Park, Nadine C.M. van Huijgevoort, Goro Honda, Takashi Hatori, Ching-Yao Yang, Shin E. Wang, Hyeong Seok Kim, Ki Byung Song, Satoshi Hirano, Hongbeom Kim, Tsutomu Fujii, Matthias Löhr, Yoo Seok Yoon, Song Cheol Kim, Yasushi Hashimoto, Hiroki Yamaue, Fuyuhiko Motoi, Marc G. Besselink, Masayuki Sho, Marco Del Chiaro, Jin He, Dong Wook Choi, Seong Ho Choi, Chang Moo Kang, Hiroaki Nagano, Hee Chul Yu, Yinmo Yang, Jin Seok Heo, Ippei Matsumoto, Sungyoung Lee, Wenhui Lou, Yi Ming Shyr, Christopher L. Wolfgang, Seungyeoun Lee, Yasuhiro Shimizu, Yuichi Nagakawa, Roberto Salvia, Jin-Young Jang, Jae Do Yang, Sang Geol Kim, Claudio Bassi, Youngmin Han, Sohei Satoi, Gloria H. Su, Jun Chul Chung, Giovanni Marchegiani, Masakazu Yamamoto, Roberto Valente, Seiko Hirono, Surgery, CCA - Imaging and biomarkers, CCA - Cancer Treatment and Quality of Life, Amsterdam Gastroenterology Endocrinology Metabolism, and Graduate School

Subjects
medicine.medical_specialty, genetic structures, urologic and male genital diseases, Malignancy, nomogram, 03 medical and health sciences, 0302 clinical medicine, medicine, cancer, Cyst, Pancreatic duct, Hepatology, Receiver operating characteristic, business.industry, Nomogram, medicine.disease, radiology, medicine.anatomical_structure, intraductal papillary mucinous neoplasms of the pancreas, Dysplasia, 030220 oncology & carcinogenesis, Cohort, 030211 gastroenterology & hepatology, Surgery, Radiology, Pancreas, business, malignancy prediction
Abstract

Background Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms. Methods We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct > 10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients. Results Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs. 0.664, p = 0.014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, p = 0.255). Conclusions A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN.

Published
2021
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44. Conversion surgery in patients with pancreatic cancer and peritoneal metastasis

Author

Hideki Takami, Yasuhiro Kodera, Tsutomu Fujii, Satoshi Hirano, Kenta Murotani, Fuminori Sonohara, Hideki Ishikawa, Suguru Yamada, Kazuto Shibuya, Yoshiak Murakami, Isaku Yoshioka, Joji Kitayama, Masamichi Hayashi, Fuyuhiko Motoi, So Yamaki, Mitsugu Sekimoto, Sohei Satoi, Daisuke Hashimoto, Hitoshi Inoue, and Tomohisa Yamamoto

Subjects
medicine.medical_specialty, Chemotherapy, Combination therapy, business.industry, medicine.medical_treatment, Gastroenterology, medicine.disease, Gemcitabine, Surgery, Clinical trial, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Oncology, Paclitaxel, chemistry, Tolerability, 030220 oncology & carcinogenesis, Pancreatic cancer, Cohort, medicine, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract

Background Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies globally. We have previously explored the clinical efficacy of intraperitoneal (IP) paclitaxel therapy for patients with PDAC and peritoneal metastasis, which demonstrated favourable response and disease control rates. However, the real implications of conversion surgery after IP therapy remain unclear. Methods We conducted two multicenter clinical trials of IP therapy with paclitaxel in patients with PDAC and peritoneal metastasis. We focused on patients who underwent conversion surgery and investigated the long-term outcomes, particularly, initial recurrence patterns and long-term survival. Results Seventy-nine patients with PDAC and peritoneal metastasis were treated, and 33 (41.8%) patients received SP (intravenous IP paclitaxel with S-1) and 46 (58.3%) were administered GAP (intravenous gemcitabine + nab-paclitaxel combined with IP paclitaxel) combination therapy. Of the 79 patients, 16 (20.3%) underwent conversion surgery. The median time to surgery was 9.0 (range, 4.1-13.0) months after the initiation of chemotherapy. Finally, 13 (81.3%) patients underwent R0 resection. Evans grade was IIA in nine patients, IIB in four patients, III in two patients, and IV in one patient. The median overall survival time in patients who underwent conversion surgery was 32.5 (range, 13.5-66.9) months. Twelve (75.0%) patients were found to have experienced recurrence after conversion surgery. Especially, peritoneal recurrence was observed in 50% of patients as the initial recurrence pattern. The median recurrence-free survival time was 9.2 (range, 5.1-32.8) months, and three patients have survived without recurrence to date. Conclusions Our IP therapy displays promising clinical efficacy with acceptable tolerability in patients with PDAC and peritoneal metastasis. Although we could observe some super-responders in the cohort, further improvements in IP therapy are warranted.

Published
2021
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47. Multicenter randomized phase II trial of prophylactic right‐half dissection of superior mesenteric artery nerve plexus in pancreatoduodenectomy for pancreatic head cancer

Author

Tsutomu Fujii, Masamichi Hayashi, Kenta Murotani, Fuminori Sonohara, Hideki Takami, Sohei Satoi, Kazuto Shibuya, Suguru Yamada, Isaku Yoshioka, So Yamaki, Masahiko Ando, Tomohisa Yamamoto, Mitsugu Sekimoto, Yasuhiro Kodera, and Daisuke Hashimoto

Subjects
medicine.medical_specialty, RD1-811, pancreatic head cancer, RC799-869, Refractory, medicine.artery, Pancreatic cancer, Medicine, Superior mesenteric artery, phase II trial, pancreatoduodenectomy, business.industry, superior mesenteric artery nerve plexus, Gastroenterology, Nerve plexus, Original Articles, Diseases of the digestive system. Gastroenterology, SMA, medicine.disease, Surgery, Dissection, Diarrhea, medicine.anatomical_structure, Original Article, medicine.symptom, business, Pancreatic head cancer
Abstract

Aim Right‐half dissection of the superior mesenteric artery (SMA) nerve plexus in pancreatoduodenectomy for pancreatic cancer was initiated to accomplish R0 resection; however, subsequent refractory diarrhea was a major concern. This study aimed to evaluate the necessity of this technique. Methods From April 2014 to June 2018, 74 patients with pancreatic head cancer were randomly allocated to either Group A, in which right‐half dissection of the SMA nerve plexus was performed (n = 37), or Group B, in which total preservation of the nerve plexus was performed (n = 37). Short‐term, long‐term, and survival outcomes were prospectively compared between the groups. Results The patient demographics, including the R0 resection rate, were not significantly different between the groups. Postoperative diarrhea occurred in 26 (70.3%) patients in Group A and 18 (48.6%) patients in Group B. There was a tendency for the development of severe diarrhea in Group A within 1 year postoperatively, and the frequency of diarrhea gradually decreased within 2 years, although that did not affect tolerance to adjuvant chemotherapy. There was no difference in either locoregional recurrence (27.0% vs 32.4%) or systemic recurrence (46.0% vs 46.0%). The median overall survival time in Groups A and B was 37.9 and 34.6 months, respectively (P = 0.77). Conclusion We did not demonstrate a clinical impact of right‐half dissection of the SMA nerve plexus on locoregional recurrence or survival. Therefore, the prophylactic dissection of the SMA nerve plexus is unnecessary given that refractory diarrhea could be induced by this technique (UMIN000012241)., The necessity of right‐half dissection of the SMA nerve plexus in pancreatoduodenectomy for pancreatic cancer was evaluated. We did not demonstrate the clinical impact of this technique on locoregional recurrence or survival. Therefore, the prophylactic dissection is unnecessary, given that refractory diarrhea could be induced by this technique.

Published
2021

48. Pancreatic Trauma: Proposal for Management Algorithm

Author

Sohei Satoi, Kazuhito Sakuramoto, Tomohisa Yamamoto, Rintaro Yui, Fujio Matsumura, So Yamaki, Daisuke Hashimoto, Hiroyuki Horiuchi, and Takaomi Okawa

Subjects
medicine.medical_specialty, Pancreatic trauma, business.industry, General surgery, medicine, Surgery, business, Management algorithm
Abstract

Introduction Pancreatic trauma is potentially lethal despite recent improvements in surgical techniques and conservative management. However, no guidelines for the management of pancreatic trauma have been established. In this report, we propose an algorithm for the management of pancreatic trauma based on our experience of 9 cases and 1 literature review. Case presentation This study included 9 patients with pancreatic trauma (5 men and 4 women). The patient median age was 40 years (range, 17–75 years). The overall mortality rate was 22.2%, and the postoperative mortality rate was 16.7%. Superficial trauma was present in 2 patients. Deep trauma without injury to the main pancreatic duct was present in 1 patient, and this patient was treated successfully with endoscopic nasopancreatic drainage. Active bleeding was present in 2 patients and controlled by interventional radiology. Deep trauma with injury to the main pancreatic duct was present in 6 patients. Among them, 1 patient died after conservative treatment with endoscopic nasopancreatic drainage. The other 5 patients underwent surgery (pancreatic resection in 4 and necrosectomy in 1). Conclusion The herein-described algorithm recommends interventional radiology for active arterial bleeding, conservative management for trauma without ductal injury, and surgery for trauma with ductal injury. This algorithm may provide a basis for future establishment of guidelines.

Published
2020
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49. Role of phosphorylated Smad3 signal components in intraductal papillary mucinous neoplasm of pancreas

Author

Koichi Matsuzaki, Takashi Yamaguchi, Tsukasa Ikeura, Katsunori Yoshida, Yuichi Hori, Mitsuaki Ishida, Kazuichi Okazaki, and Sohei Satoi

Subjects
Male, Poor prognosis, Pathology, medicine.medical_specialty, endocrine system diseases, Pancreatic Intraductal Neoplasms, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, Biomarkers, Tumor, Humans, Medicine, Smad3 Protein, Phosphorylation, Aged, Retrospective Studies, Invasive carcinoma, Hepatology, Intraductal papillary mucinous neoplasm, business.industry, Carcinoma, Gastroenterology, Middle Aged, medicine.disease, Immunohistochemistry, Up-Regulation, Pancreatic Neoplasms, medicine.anatomical_structure, Dysplasia, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Neoplasm Grading, business, Pancreas, Carcinogenesis, Immunostaining
Abstract

Malignant intraductal papillary mucinous neoplasm (IPMN) has poor prognosis. The carcinogenesis of IPMN is not clear. The aim of this study was to clarify transitions in phosphorylated Smad3 signaling during IPMN carcinogenesis.By using immunohistochemistry, we examined the expression of pSmad3C and pSmad3L from 51 IPMN surgical specimens resected at our institution between 2010 and 2013. We also examined the expression of Ki-67, c-Myc and p-JNK.The median immunostaining index of pSmad3C was 79.2% in low-grade dysplasia, 74.9% in high-grade dysplasia, and 42.0% in invasive carcinoma (P0.01), whereas that of pSmad3L was 3.4%, 4.3%, and 42.4%, respectively (P0.01). There was a negative relationship between the expression of pSmad3C and c-Myc (P0.001, r = -0.615) and a positive relationship between the expression of pSmad3L and c-Myc (P0.001, r = 0.696). Negative relationship between the expression of pSmad3C and Ki-67 (P0.01, r = -0.610) and positive relationship between the expression of pSmad3L and Ki-67 (P0.01, r = 0.731) were confirmed. p-JNK-positive cells were frequently observed among pSmad3L-positive cancer cells. The median of pSmad3L/pSmad3C ratio in the non-recurrence group and the recurrence group were 0.58 (range, 0.05-0.93), 3.83 (range, 0.85-5.96), respectively (P = 0.02). The median immunostaining index of c-Myc in the non-recurrence group and the recurrence group were 2.91 (range, 0-36.9) and 82.1 (range, 46.2-97.1), respectively (P = 0.02). The median immunostaining index of Ki-67 in the non-recurrence group and the recurrence group were 12.9 (range 5.7-30.8) and 90.9 (range 52.9-98.5), respectively (P = 0.02).pSmad3L was upregulated in malignant IPMN. pSmad3L/pSmad3C ratio may be a useful prognostic factor in IPMN.

Published
2020
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50. Global Survey on Pancreatic Surgery During the COVID-19 Pandemic

Author

Atsushi Oba, Thomas F. Stoop, Matthias Löhr, Thilo Hackert, Nicholas Zyromski, William H. Nealon, Michiaki Unno, Richard D. Schulick, Mohammed H. Al-Musawi, Wenming Wu, Yupei Zhao, Sohei Satoi, Christopher L. Wolfgang, Mohammad Abu Hilal, Marc G. Besselink, Marco Del Chiaro, Graduate School, Surgery, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
Male, Internationality, pancreatic cancer, duodenal adenocarcinoma, intensive care unit, 0302 clinical medicine, hospital volume, Interquartile range, Surveys and Questionnaires, Health care, Pandemic, pancreatic surgery, Practice Patterns, Physicians', minimally invasive surgery, Middle Aged, CA19-9, 030220 oncology & carcinogenesis, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, 030211 gastroenterology & hepatology, Original Article, Female, Patient Safety, Coronavirus Infections, neoadjuvant treatment, Adult, medicine.medical_specialty, Consensus, ampullary adenocarcinoma, Clinical Decision-Making, Pneumonia, Viral, MEDLINE, pancreatic neuroendocrine tumor, chronic pancreatitis, 03 medical and health sciences, Patient safety, Betacoronavirus, Pancreatic cancer, medicine, Humans, Adverse effect, Pandemics, respectability, business.industry, SARS-CoV-2, pandemic, Cancer, COVID-19, medicine.disease, intraductal papillary mucinous neoplasms, distal bile duct cancer, Pancreatic Neoplasms, pancreatic necrosis, Emergency medicine, Surgery, business
Abstract

Supplemental Digital Content is available in the text, Objective: The aim of this study was to clarify the role of pancreatic surgery during the COVID-19 pandemic to optimize patients’ and clinicians’ safety and safeguard health care capacity. Summary Background Data: The COVID-19 pandemic heavily impacts health care systems worldwide. Cancer patients appear to have an increased risk for adverse events when infected by COVID-19, but the inability to receive oncological care seems may be an even larger threat, particularly in case of pancreatic cancer. Methods: An online survey was submitted to all members of seven international pancreatic associations and study groups, investigating the impact of the COVID-19 pandemic on pancreatic surgery using 21 statements (April, 2020). Consensus was defined as >80% agreement among respondents and moderate agreement as 60% to 80% agreement. Results: A total of 337 respondents from 267 centers and 37 countries spanning 5 continents completed the survey. Most respondents were surgeons (n = 302, 89.6%) and working in an academic center (n = 286, 84.9%). The majority of centers (n = 166, 62.2%) performed less pancreatic surgery because of the COVID-19 pandemic, reducing the weekly pancreatic resection rate from 3 [interquartile range (IQR) 2–5] to 1 (IQR 0–2) (P < 0.001). Most centers screened for COVID-19 before pancreatic surgery (n = 233, 87.3%). Consensus was reached on 13 statements and 5 statements achieved moderate agreement. Conclusions: This global survey elucidates the role of pancreatic surgery during the COVID-19 pandemic, regarding patient selection for the surgical and oncological treatment of pancreatic diseases to support clinical decision-making and creating a starting point for further discussion.

Published
2020
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