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Objective: To determine the interobserver variability for complications of pancreatoduodenectomy as defined by the International Study Group for Pancreatic Surgery (ISGPS) and others., Background: Good interobserver variability for the definitions of surgical complications is of major importance in comparing surgical outcomes between and within centers. However, data on interobserver variability for pancreatoduodenectomy-specific complications are lacking., Methods: International cross-sectional multicenter study including 52 raters from 13 high-volume pancreatic centers in 8 countries on 3 continents. Per center, 4 experienced raters scored 30 randomly selected patients after pancreatoduodenectomy. In addition, all raters scored 6 standardized case vignettes. This variability and the "within centers" variability were calculated for 2-fold scoring (no complication/grade A vs grade B/C) and 3-fold scoring (no complication/grade A vs grade B vs grade C) of postoperative pancreatic fistula, postpancreatoduodenectomy hemorrhage, chyle leak, bile leak, and delayed gastric emptying. Interobserver variability is presented with Gwet AC-1 measure for agreement., Results: Overall, 390 patients after pancreatoduodenectomy were included. The overall agreement rate for the standardized cases vignettes for 2-fold scoring was 68% (95% CI: 55%-81%, AC1 score: moderate agreement), and for 3-fold scoring 55% (49%-62%, AC1 score: fair agreement). The mean "within centers" agreement for 2-fold scoring was 84% (80%-87%, AC1 score; substantial agreement)., Conclusions: The interobserver variability for the ISGPS-defined complications of pancreatoduodenectomy was too high even though the "within centers" agreement was acceptable. Since these findings will decrease the quality and validity of clinical studies, ISGPS has started efforts aimed at reducing the interobserver variability., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The connection between early postoperative fever and clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy remains unclear. This study aimed to investigate this association and assess the predictive value of early postoperative fever for CR-POPF., Methods: This retrospective observational study included adult patients who underwent pancreaticoduodenectomy at a tertiary teaching hospital between 2007 and 2019. Patients were categorized into those with early postoperative fever (≥ 38 °C in the first 48 h after surgery) and those without early postoperative fever groups. Weighted logistic regression analysis using stabilized inverse probability of treatment weighting (sIPTW) and multivariable logistic analysis were performed. The c-statistics of the receiver operating characteristic curves were calculated to evaluate the impact on the predictive power of adding early postoperative fever to previously identified predictors of CR-POPF., Results: Of the 1997 patients analyzed, 909 (45.1%) developed early postoperative fever. The overall incidence of CR-POPF among all the patients was 14.3%, with an incidence of 19.5% in the early postoperative fever group and 9.9% in the group without early postoperative fever. Early postoperative fever was significantly associated with a higher risk of CR-POPF after sIPTW (adjusted odds ratio [OR], 1.73; 95% confidence interval [CI], 1.34-2.22; P < 0.001) and multivariable logistic regression analysis (adjusted OR, 1.88; 95% CI, 1.42-2.49; P < 0.001). The c-statistics for the models with and without early postoperative fever were 0.76 (95% CI, 0.73-0.79) and 0.75 (95% CI, 0.72-0.78), respectively, showing a significant difference between the two (difference, 0.02; 95% CI, 0.00-0.03; DeLong's test, P = 0.005)., Conclusions: Early postoperative fever is a significant but not highly discriminative predictor of CR-POPF after pancreaticoduodenectomy. However, its widespread occurrence limits its applicability as a predictive marker., (© 2024. The Author(s).)

Background: The aim of this study is to investigate the perioperative composite textbook outcomes of pancreatic surgery after minimally invasive pancreatoduodenectomy (MIPD)., Materials and Methods: The cohort study was conducted across 10 institutions and included 1552 patients who underwent MIPD registered with the Korean Study Group on Minimally Invasive Pancreatic Surgery between May 2007 and April 2020. We analyzed perioperative textbook outcomes of pancreatic surgery after MIPD. Subgroup analyses were performed to assess outcomes based on the hospital volume of MIPD., Results: Among all patients, 21.8% underwent robotic pancreatoduodenectomy. High-volume centers (performing >20 MIPD/year) performed 88.1% of the procedures. The incidence of clinically relevant postoperative pancreatic fistula was 11.5%. Severe complications (Clavien-Dindo grade ≥IIIa) occurred in 15.1% of the cases. The 90-day mortality rate was 0.8%. The mean hospital stay was 13.7 days. Textbook outcomes of pancreatic surgery success were achieved in 60.4% of patients, with higher rates observed in high-volume centers than in low-volume centers (62.2% vs. 44.7%, P <0.001). High-volume centers exhibited significantly lower conversion rates (5.4% vs. 12.5%, P =0.001), lower 90-day mortality (0.5% vs. 2.7%, P =0.001), and lower 90-day readmission rates (4.5% vs. 9.6%, P =0.006) than those low-volume centers., Conclusion: MIPD could be performed safely with permissible perioperative outcomes, including textbook outcomes of pancreatic surgery, particularly in experienced centers. The findings of this study provided valuable insights for guiding surgical treatment decisions in periampullary disease., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Textbook outcome (TO) is a composite variable that can define the quality of pancreatic surgery. The aim of this study is to evaluate TO after pancreatoduodenectomy (PD) for nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs)., Patients and Methods: All patients who underwent PD for NF-PanNETs (2007-2016) in different centers were included in this retrospective study. TO was defined as the absence of severe postoperative complications and mortality, length of hospital stay ≤ 19 days, R0 resection, and at least 12 lymph nodes harvested., Results: Overall, 477 patients were included. The TO rate was 32%. Tumor size [odds ratio (OR) 1.696; p = 0.013], a minimally invasive approach (OR 12.896; p = 0.001), and surgical volume (OR 2.062; p = 0.023) were independent predictors of TO. The annual frequency of PDs increased over time as well as the overall rate of TO. At a median follow-up of 44 months, patients who achieved TO had similar disease-free (p = 0.487) and overall survival (p = 0.433) rates compared with patients who did not achieve TO. TO rate in patients with NF-PanNET > 2 cm was 35% versus 27% in patients with NF-PanNET ≤ 2 cm (p = 0.044). Considering only NF-PanNETs > 2 cm, patients with TO and those without TO had comparable 5-year overall survival rates (p = 0.766) CONCLUSIONS: TO is achieved in one-third of patients after PD for NF-PanNETs and is not associated with a benefit in terms of long-term survival., (© 2024. Society of Surgical Oncology.)

Background: Although the association between an increase in anastomotic leakage (AL) and non-steroidal anti-inflammatory drugs (NSAIDs) has been reported in gastrointestinal surgeries, this issue has rarely been addressed for pancreaticoduodenectomy (PD). We aimed to investigate the association between postoperative NSAIDs administration and clinically relevant AL (CR-AL) following PD., Methods: We retrospectively evaluated 2,163 consecutive patients who underwent PD between 2007 and 2019. The patients were divided into two groups; patients who received and did not receive NSAIDs by postoperative day (POD) 5. We conducted a propensity score analysis using inverse probability of treatment weighting (IPTW) to adjust the baseline differences between both groups. We compared the occurrence of CR-AL and other postoperative outcomes before and after IPTW. Further, we used the multivariable binary logistic regression method for a sensitivity analysis for CR-AL., Results: A total of 2,136 patients were included in the analysis. Of these, 222 (10.4%) received NSAIDs by POD 5. The overall occurrence rate of CR-AL was 14.9%. After IPTW, postoperative NSAIDs were significantly associated with CR-AL (odds ratio [OR]: 1.24, 95% CI [1.05, 1.47], P = 0.012), prolonged postoperative hospitalization (OR: 1.31, 95% CI [1.14, 1.50], P < 0.001), and unplanned readmission within 30 days postoperatively (OR 1.48: 95% CI [1.15, 1.91], P = 0.002). However, this association was not consistent in the sensitivity analysis., Conclusions: Postoperative NSAIDs use was significantly associated with an increase in CR-AL incidence following PD. However, sensitivity analysis failed to show its association, which precludes a firm conclusion of its detrimental effect.

Background: Factors aggravating remnant pancreas atrophy following pancreatoduodenectomy and the effects of atrophy have not been extensively studied. This study aimed to evaluate the clinical factors affecting remnant pancreas atrophy and assess the effects of atrophy on quality of life, nutritional status, and pancreatic exocrine and endocrine functions., Methods: Data collected prospectively from 122 patients who completed 12 months of follow-up, including computed tomography and the quality-of-life questionnaire, were analyzed. Pancreas volume was measured using a computed tomography volumetry program. Endocrine and exocrine functions were evaluated., Results: Malignancy and adjuvant chemoradiotherapy were associated with severity of atrophy. At 12 postoperative months, quality-of-life scores and nutritional indexes were mostly not associated with atrophy, but stool elastase level decreased significantly and incidence of new-onset diabetes mellitus was higher in the severe atrophy group. Postprandial 2-hour blood glucose and glycosylated hemoglobin levels were also higher in this group., Conclusions: Remnant pancreas atrophy was more severe in patients with malignant disease who received adjuvant chemoradiotherapy and was associated with pancreatic exocrine and endocrine functions. More careful monitoring and active management of exocrine and endocrine deficiencies are necessary for patients who underwent pancreatoduodenectomy for malignant disease and received chemoradiotherapy., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The anatomical structure around the pancreatic head is very complex and it is important to understand its precise anatomy and corresponding anatomical approach to safely perform minimally invasive pancreatoduodenectomy (MIPD). This consensus statement aimed to develop recommendations for elucidating the anatomy and surgical approaches to MIPD., Methods: Studies identified via a comprehensive literature search were classified using the Scottish Intercollegiate Guidelines Network method. Delphi voting was conducted after experts had drafted recommendations, with a goal of obtaining >75% consensus. Experts discussed the revised recommendations with the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting., Results: Three clinical questions were addressed, providing six recommendations. All recommendations reached at least a consensus of 75%. Preoperatively evaluating the presence of anatomical variations and superior mesenteric artery (SMA) and superior mesenteric vein (SMV) branching patterns was recommended. Moreover, it was recommended to fully understand the anatomical approach to SMA and intraoperatively confirm the SMA course based on each anatomical landmark before initiating dissection., Conclusions: MIPD experts suggest that surgical trainees perform resection based on precise anatomical landmarks for safe and reliable MIPD., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: This study aimed to investigate the association between sugammadex use and the occurrence of delayed passage of first flatus and oral intake tolerance following open pancreaticoduodenectomy (PD)., Methods: We reviewed consecutive patients who underwent open PD between 2015 and 2019; subsequently, they were divided into the sugammadex (group S) and neostigmine with anticholinergics (group N) groups based on the reversal agent used. We performed stabilized inverse probability of treatment weighting (IPTW) analysis to adjust for baseline differences between the groups. We compared the delayed passage of first flatus, oral intake tolerance, and other postoperative outcomes between the groups before and after IPTW., Results: Of the 736 included patients, 309 (42.0%) received sugammadex. Stabilized IPTW revealed a significantly lower occurrence of delayed passage of first flatus in group S (19.3%) compared to group N (28.3%) (OR 0.61, 95% CI: 0.43-0.86, P=0.005). Further, there was a significantly lower occurrence of delayed oral intake tolerance in group S (19.9%) than in group N (27.7%) (OR 0.65, 95% CI: 0.46-0.92, P=0.016)., Conclusions: Compared to previous reversal agents, sugammadex use was significantly associated with a decrease in the occurrence of prolonged time to first flatus and oral intake tolerance following open PD.

Background: The role of portal vein resection for pancreatic cancer is well established but not for pancreatic neuroendocrine neoplasms. Evidence from studies providing information on long-term outcome after venous resection in pancreatic neuroendocrine neoplasms patients is lacking., Methods: This is a multicenter retrospective cohort study comparing pancreaticoduodenectomy with vein resection with standard pancreaticoduodenectomy in patients with pancreatic neuroendocrine neoplasms. The primary endpoint was to evaluate the long-term survival in both groups. Progression-free survival and overall survival were calculated using the method of Kaplan and Meier, but a propensity score-matched cohort analysis was subsequently performed to remove selection bias and improve homogeneity. The secondary outcome was Clavien-Dindo ≥3., Results: Sixty-one (11%) patients underwent pancreaticoduodenectomy with vein resection and 480 patients pancreaticoduodenectomy. Five (1%) perioperative deaths were recorded in the pancreaticoduodenectomy group, and postoperative clinically relevant morbidity rates were similar in the 2 groups (pancreaticoduodenectomy with vein resection 48% vs pancreaticoduodenectomy 33%). In the initial survival analysis, pancreaticoduodenectomy with vein resection was associated with worse 3-year progression-free survival (48% pancreaticoduodenectomy with vein resection vs 83% pancreaticoduodenectomy; P < .01) and 5-year overall survival (67% pancreaticoduodenectomy with vein resection vs 91% pancreaticoduodenectomy). After propensity score matching, no significant difference was found in both 3-year progression-free survival (49% pancreaticoduodenectomy with vein resection vs 59% pancreaticoduodenectomy; P = .14) and 5-year overall survival (71% pancreaticoduodenectomy with vein resection vs 69% pancreaticoduodenectomy; P = .98)., Conclusion: This study demonstrates no significant difference in perioperative risk with a similar overall survival between pancreaticoduodenectomy and pancreaticoduodenectomy with vein resection. Tumor involvement of the superior mesenteric/portal vein axis should not preclude surgical resection in patients with locally advanced pancreatic neuroendocrine neoplasms., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Robotic surgery is a novel approach that scores over conventional minimally invasive approaches, even in pancreatic surgery. We investigated clinical outcomes of robot-assisted minimally invasive (hybrid laparoscopic and robotic) pancreatoduodenectomy (RA-MIPD)., Methods: Total 150 patients who underwent RA-MIPD between 2015 and 2018 were compared with 710 patients who underwent open pancreatoduodenectomy (PD) during the same period. Demographics and surgical outcomes were analyzed, and propensity score-matched (PSM) analysis was performed to evaluate complications including clinically relevant postoperative pancreatic fistula (CR-POPF) and oncologic outcomes in patients with malignancy., Results: PSM analysis was performed based on the pancreatic fistula risk. Patients undergoing RA-MIPD were younger (RA-MIPD vs. open PD: 61.2 vs. 65.5 years, P < 0.001); however, no significant intergroup difference was observed in sex (P = 0.091) and body mass index (P = 0.281). Operation time was longer in the RA-MIPD group (361.2 vs. 305.7 min, P < 0.001); however, estimated blood loss did not significantly differ (515.6 vs. 478.0 mL, P = 0.318). Overall complication (24.7% vs. 30.9%, P = 0.178) and CR-POPF rates (6.7% vs. 6.9%, P > 0.999) were similar. The RA-MIPD group showed lower pain scores and shorter length of postoperative hospitalization (11.5 vs. 17.2 days, P < 0.001). After PSM analysis for cancer and staging among patients with malignancies, no significant intergroup difference was observed in the R0 resection rate (96.7% vs. 93.3%, P = 0.527), tumor size (2.59 vs. 2.60 cm, P = 0.954), total number of retrieved lymph nodes (17.0 vs. 16.6, P = 0.793), and 2-year survival rates (84.4% vs. 77.8%, P = 0.898)., Conclusions: Compared with open PD, RA-MIPD is associated with better or at least similar early perioperative and equivalent midterm survival outcomes. RA-MIPD is safe and feasible and enables early postoperative recovery. RA-MIPD is expected to play a key role in near future.

Background: Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD)., Methods: We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402)., Results: After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139-3.455]; P < 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753-3.209]; P < 0.001)., Conclusion: Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: It is currently unknown whether bile duct segmental resection (BDSR) is an acceptable method for localized middle bile duct cancer (mid-BDC) when R0 resection can be achieved. This study aimed to investigate the short- and long-term outcomes of mid-BDC patients treated with pancreaticoduodenectomy (PD) compared to those for BDSR., Methods: This was a retrospective, Japanese and Korean multi-center collaboration study based on patients' medical records., Results: A total of 663 patients, including 245 BDSR and 418 PD cases, were enrolled. The incidence of postoperative pancreatic fistula (3.3% vs 44.1%, P < .0001), surgical site infection in the organ space (6.1% vs 17.7%, P < .0001) and clinically problematic morbidities (15.9% vs 32.8%, P < .0001) was significantly higher in the PD group. There was no difference in the mortality rate (0.8% vs 1.7%, P = .3566). Local (33.9% vs 14.4%, P < .0001) and lymph node (22.4% vs 11.0%, P < .0001) recurrence rates were significantly higher in the BDSR group. Relapse-free survival (25.0 vs 34.0 months, P = .0184) and overall survival (41.2 vs 60.1 months, P = .0019) were significantly longer in the PD group. The PD group had significantly better prognosis in stage IA/IB cases (58.3 vs 111.5 months, P = .0067), which were the best indicators for BDSR, even when R0 resection was achieved. In multivariate analysis, BDSR was an independent poor prognostic factor., Conclusion: Despite the inferior perioperative short-term outcomes, our data advocate that PD should be the standard procedure for mid-BDCs and that BDSR should be avoided even if R0 resection can be achieved. (UMIN000017914)., (© 2020 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The objective of this study was to validate and update the Amsterdam prediction model including tumor grade, lymph node ratio, margin status and adjuvant therapy, for prediction of overall survival (OS) after pancreatoduodenectomy for pancreatic cancer., Methods: We included consecutive patients who underwent pancreatoduodenectomy for pancreatic cancer between 2000 and 2017 at 11 tertiary centers in 8 countries (USA, UK, Germany, Italy, Sweden, the Netherlands, Korea, Australia). Model performance for prediction of OS was evaluated by calibration statistics and Uno's C-statistic for discrimination. Validation followed the TRIPOD statement., Results: Overall, 3081 patients (53% male, median age 66 years) were included with a median OS of 24 months, of whom 38% had N2 disease and 77% received adjuvant chemotherapy. Predictions of 3-year OS were fairly similar to observed OS with a calibration slope of 0.72. Statistical updating of the model resulted in an increase of the C-statistic from 0.63 to 0.65 (95% CI 0.64-0.65), ranging from 0.62 to 0.67 across different countries. The area under the curve for the prediction of 3-year OS was 0.71 after updating. Median OS was 36, 25 and 15 months for the low, intermediate and high risk group, respectively (P < 0.001)., Conclusions: This large international study validated and updated the Amsterdam model for survival prediction after pancreatoduodenectomy for pancreatic cancer. The model incorporates readily available variables with a fairly accurate model performance and robustness across different countries, while novel markers may be added in the future. The risk groups and web-based calculator www.pancreascalculator.com may facilitate use in daily practice and future trials., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: It remains controversial whether central pancreatectomy (CP) can preserve the exocrine and endocrine function of the pancreas or not. This study aimed to evaluate the safety and efficacy of CP compared with distal pancreatectomy (DP) and pancreaticoduodenectomy (PD) for benign and low-grade malignant neoplasms., Methods: This retrospective study enrolled 219 patients who underwent elective CP (n = 55), DP (n = 70), or PD (n = 94) for benign and low-malignant neoplasms in a single university hospital between January 2000 and December 2015. Patients who underwent CP were propensity score matched to patients who underwent DP or PD at a 1:1 ratio, respectively. Peri- and postoperative outcomes, long-term endocrine/exocrine function, and pancreatic volume change 12 months postoperatively were prospectively evaluated., Results: Of the 165 patients, 55 were included in each of the CP, DP, and PD groups. Significant differences between the CP and DP groups were observed in overall morbidity (CP: n = 18, 33% vs DP: n = 8, 14%; P = 0.041), clinically relevant postoperative pancreatic fistula (CP: n = 13, 24% vs DP: n = 4, 7%; P = 0.022), stool elastase level 12 months after surgery (CP: 151 μg/g vs DP: 245 μg/g; P = 0.003), and percentage change in the remnant pancreatic volume 12 months after surgery (CP: - 9.4% vs DP: + 7.5%; P < 0.001)., Conclusions: The indications for CP to treat benign and low-grade malignant pancreatic neoplasms should be limited to cases in which the distal pancreatic volume can be considerably saved and PD can be prevented because CP has a higher postoperative morbidity without a marked functional superiority over DP.

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&#95;view.cgi?recptno=R000033874.

Background: Few studies of the oncological outcomes of ampullary cancer have addressed recurrence, and many treatment-related issues remain unresolved. This study evaluated optimal surgical treatment strategies based on recurrence patterns after pancreaticoduodenectomy (PD) for ampullary cancer., Methods: Two hundred and fifty-nine patients who underwent PD with R0 resection for ampullary cancer from January 2000 to June 2012 were included. Generally, lymph node (LN) dissection extended to the right superior mesenteric artery (SMA). Recurrence was defined based on imaging studies. The first detected recurrence sites and patterns were analyzed., Results: During a mean follow-up of 51.3 months, recurrence occurred in 89 (34.4%) cases, most commonly in the liver. Poor differentiation, advanced T stage, and LN metastasis were identified as risk factors for recurrence. Locoregional and systemic recurrences occurred alone or simultaneously in 20.2%, 73.0%, and 6.7% of patients, respectively. Locoregional and systemic recurrences tended to occur in early- and advanced-stage cases, respectively. A nodal-type recurrence around mesenteric vessels was the most common locoregional recurrence pattern, and 58.8% (10/17) were located left of the SMA., Conclusion: As nodal-type metastasis around the mesenteric vessels was the dominant recurrence pattern, careful LN dissection around the SMA should be considered for early and advanced ampullary cancers., (© 2019 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: To determine the most appropriate pancreatic drainage method, by investigating differences in 12-month clinical outcomes in patients implanted with external and internal pancreatic stents as an extension to a previous study on short-term outcome., Methods: This prospective randomized controlled trial enrolled 213 patients who underwent pancreaticoduodenectomy with duct to mucosa pancreaticojejunostomy between August 2010 and January 2014 (NCT01023594). Of the 185 patients followed-up for 12 months, 97 underwent external and 88 underwent internal stenting. Their long-term clinical outcomes were compared., Results: Overall late complication rates were similar in the external and internal stent groups (P = 0.621). The percentage of patients with >50% atrophy of the remnant pancreatic volume after 12 months was similar in both groups (P = 0.580). Factors associated with pancreatic exocrine or endocrine function, including stool elastase level (P = 0.571) and rate of new-onset diabetes (P = 0.179), were also comparable. There were no significant between-group differences in quality of life, as evaluated by the EORTC QLQ-C30 and QLQ PAN26 questionnaires., Conclusion: External and internal stents showed comparable long-term, as well as short-term clinical outcomes, including late complication rates, preservation of pancreatic duct diameters, pancreatic volume changes with functional derangements, and quality of life after surgery., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: This study investigated the clinical outcomes according to the preoperative nutritional status and to identify factors influencing long-term unrecovered nutritional status., Methods: Data were prospectively collected from 355 patients who underwent PD between 2008 and 2014. Nutritional status was evaluated by Mini Nutrition Assessment (MNA) and patients were classified into group A (malnourished), group B (risk-of-malnutrition), or group C (well-nourished). MNA score, complications, body mass index (BMI), stool elastase level, biochemical parameters, and quality-of-life (QOL) were collected serially for 1 year., Results: Preoperatively, 60 patients were categorized into group A, 224 into group B, and 71 into group C. Overall complication and pancreatic fistula were higher in groups A and B compared with group C (P = 0.003 vs P = 0.004). QOL, biochemical parameters, BMI and stool elastase level were lowest in group A preoperatively. BMI and stool elastase level remained low after surgery in all groups. Advanced age, low BMI, pre-existing diabetes mellitus, jaundice, exocrine insufficiency and adjuvant therapy were factors influencing long-term unrecovered nutritional status., Conclusion: Preoperative malnourished patients suffer from poor clinical outcomes. Therefore, those with risk factors of malnutrition should be monitored and vigorous efforts are needed to improve their nutrition., (Copyright © 2018 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: There are only limited data on the failure patterns after surgical resection for duodenal cancer, and the role of adjuvant chemoradiotherapy (CRT) also remains controversial. In this study, the treatment outcomes of surgery alone were compared to those of surgery plus adjuvant CRT for duodenal cancer., Methods: Between January 1991 and February 2013, a total of 47 patients with duodenal cancer had pancreaticoduodenectomy, and their age ranged from 31 to 80 (median 62). Twenty-five patients (53%) underwent surgery alone, while 22 (47%) underwent surgery plus adjuvant CRT. Postoperative radiotherapy with concomitant 5-fluorouracil was given to tumor bed and regional lymph nodes up to 40-55.4 Gy. Median duration of follow-up was 31 months (range 6-286) for all patients and 90 months (range 14-286) for survivors., Results: CRT (+) group included more patients with advanced nodal stage and overall stage group (p = 0.003 and 0.002, respectively). The 5-year overall survival rates were not different between CRT (-) and CRT (+) groups (50.1 vs. 46.7%, p = 0.794). CRT (+) group achieved a superior 5-year loco-regional relapse-free survival rate compared with CRT (-) group, but the difference did not reach a statistical significance (80.1 vs. 68.4%, p = 0.267). On multivariate analysis, however, the addition of CRT was the only favorable prognosticator predicting loco-regional relapse-free survival (p = 0.046). Two patients experienced grade 3 neutropenia during CRT., Conclusions: Adjuvant CRT after pancreaticoduodenectomy was correlated with an improved loco-regional control in duodenal cancer. Considering the high loco-regional recurrence in surgery alone group, CRT may be considered as adjuvant treatment.

Background: The use of preoperative biliary drainage (PBD) for managing patients with periampullary cancer awaiting surgery remains controversial. The impact of PBD status and type on surgical outcomes has not been established, leading to a lack of consensus. We aimed to evaluate the impact of PBD on short-term surgical outcomes in curatively resected periampullary cancer., Methods: We retrospectively reviewed data from patients undergoing curative periampullary cancer resection. A propensity score-matched analysis was performed to adjust for clinical differences. Univariate and multivariate analyses were performed to determine independent risk factors for complications., Results: The overall complication rate was significantly higher in patients who underwent PBD (P = 0.027). Additionally, complication rates were significantly higher in the endoscopic biliary drainage (EBD) group than in the percutaneous transhepatic biliary drainage (PTBD) group (P < 0.001). After propensity score matching, overall complication rates in patients receiving EBD (P < 0.001) were significantly higher. PBD type and diagnosis were independent risk factors for complications (hazard ratios: 1.927 for EBD; 1.921 for biliary tract cancer)., Conclusions: Preoperative biliary drainage, especially EBD, should not be routinely performed in patients awaiting surgery for periampullary cancer, as it increases the risk of complications., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Robot surgery is a new method that maintains advantages and overcomes disadvantages of conventional methods, even in pancreatic surgery. This study aimed to evaluate safety and benefits of robot-assisted minimally invasive pancreaticoduodenectomy (robot PD)., Methods: This study included 237 patients who underwent PD between 2015 and 2017. Demographics and surgical outcomes were evaluated., Results: Fifty-one patients underwent robot PD and 186 underwent open PD. Robot PD group had younger age (60.7 vs. 65.4 years, P = 0.006) and lower body mass index (22.7 vs. 24.0, P = 0.007). Robot PD group had lower proportion of patients with firm or hard pancreatic texture (15.7% vs. 38.2%, P = 0.004) and smaller pancreatic duct size (2.3 vs. 3.3 mm, P = 0.002). Two groups had similar operation time (robot vs. open: 335.6 vs. 330.1 min) and complications (15.7% vs. 21.0%), including postoperative pancreatic fistula rate (6.0% vs. 12.0%). Robot PD group had lower postoperative pain score (3.7 vs. 4.1 points, P = 0.008), and shorter postoperative stay (10.6 vs. 15.3 days, P = 0.001)., Conclusion: Robot PD is comparable to open PD in early outcomes. Robot PD is safe and feasible and enables early recovery; indication for robot PD is expected to expand in the near future., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Laparoscopic surgery and robotic surgery have their own merits and demerits. The aim of this study was to evaluate early experiences of hybrid pancreaticoduodenectomy (PD) and to identify the learning curve of robotic surgery., Methods: Sixteen patients underwent hybrid PD from August 2015 to February 2016. The outcomes were compared with those of an open PD group by the same operator during the same period. The resection time and anastomosis time were analyzed., Results: Six patients in the hybrid PD group developed complications. The postoperative hospital stay in the hybrid surgery group was significantly shorter than the open PD group (10.9 ± 3.2 vs 16.9 ± 8.8 days). The total operative time of hybrid surgery was significantly longer than that of open surgery (414.7 ± 47.0 vs 266.0 ± 51.1 minutes). In hybrid surgery, the actual operation time reduced with experience, particularly anastomosis time., Conclusion: Hybrid PD is feasible and safe. The learning curve of hybrid surgery, particularly robotic anastomosis, is relatively short., (Copyright © 2017 John Wiley & Sons, Ltd.)

Purpose: This study was conducted to evaluate the long-term outcome in patients undergoing pancreaticoduodenectomy (PD) followed by adjuvant chemoradiotherapy for distal cholangiocarcinoma (DCC) in a high-volume center and to identify the prognostic impact of clinicopathologic factors., Materials and Methods: A total of 132 consecutive patients who met the inclusion criteria were retrieved from the institutional database from January 1995 to September 2009. All patients received adjuvant treatments at a median of 45 days after the surgery. Median follow-up duration was 57 months (range, 6 to 225 months) for all patients and 105 months for survivors (range, 13 to 225 months)., Results: The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 70.7%, 55.7%, 49.4%, and 48.1%, respectively. Univariate analysis revealed poorly differentiated (P/D) tumors and lymph node (LN) metastasis were significantly associated with DMFS and OS. Additionally, preoperative carbohydrate antigen 19-9 level was significantly correlated with DFS, LRRFS, and DMFS. Upon multivariate analysis for OS, P/D tumors (p=0.015) and LN metastasis (p=0.003) were significant prognosticators that predicted inferior OS. Grade 3 or higher late gastrointestinal toxicity occurred in only one patient (0.8%)., Conclusion: Adjuvant chemoradiotherapy after PD for DCC is an effective and tolerable strategy without significant side effects. During long-term follow-up, we found that prognosis of DCC was mainly influenced by histologic differentiation and LN metastasis. For patients with these risk factors, further research should focus on improving adjuvant strategies as well as other treatment approaches.

Background: It is considered natural that glucose tolerance worsens after pancreatectomy. However, diabetes mellitus (DM) resolves after metabolic bypass surgery and anatomic changes after PD resemble those after metabolic surgery. This study assessed the incidence of DM resolution after pancreatectomy and differences in metabolic parameters following pancreatoduodenectomy (PD) and distal pancreatectomy (DP)., Methods: Between 2007 and 2013, 218 consecutive patients with pancreatic diseases underwent PD (n = 112) or DP (n = 106) at Seoul National University Hospital. Factors associated with changes in glucose homeostasis were evaluated by assaying serum glucose concentrations in prospectively collected samples., Results: Of the 218 patients, 88 (40.4%) had preoperative DM, with 27 (30.7%) of the latter showing postoperative resolution of DM, a rate significantly higher in patients who had undergone PD than DP (40.4% vs. 12.9%, p = 0.008). Fasting blood glucose (p = 0.001), PP2 (p < 0.001), and HOMA-IR (p = 0.005) significantly decreased after PD but not after DP. Multivariate analysis revealed that PD was independently associated with DM resolution (odds ratio 7.790, p = 0.003). PD was associated with a significantly higher DM resolution rate than DP among the 37 pancreatic cancer patients with preoperative DM (34.6% vs. 0%, p = 0.036). DM resolution rates were similar in pancreatic cancer and other pancreatic diseases (p = 0.419)., Conclusion: More than 40% of patients with preoperative DM show resolution after PD. Decreased insulin resistance and suspected enhanced glucose stimulated insulin secretion decreasing PP2 seem to contribute improved glucose homeostasis after PD. BMI was unrelated to DM resolution, indicating that PD-associated physio-anatomical changes may help resolve DM independent of weight., (Copyright © 2016 IAP and EPC. Published by Elsevier India Pvt Ltd. All rights reserved.)

Background: The purpose of the present study was to analyze the outcome of chemoradiotherapy for extrahepatic bile duct (EHBD) cancer patients with gross residual disease after surgical resection., Patients and Methods: We retrospectively analyzed 30 patients with EHBD adenocarcinoma who underwent chemoradiotherapy after palliative resection (R2 resection). Postoperative radiotherapy was delivered to the tumor bed including residual tumor and regional lymph nodes (range=40-55.8 Gy). Most patients underwent chemoradiotherapy concurrently with 5-fluorouracil (5-FU) or gemcitabine., Results: The 2-year locoregional progression-free, distant metastasis-free and overall survival rates were 33.3%, 42.4% and 44.5%, respectively. High radiation dose≥50 Gy had a marginally significant impact on superior locoregional progression-free survival compared to 40 Gy (p=0.081). One patient developed grade 3 late gastrointestinal toxicity., Conclusion: Adjuvant chemoradiotherapy for EHBD cancer patients with gross residual disease after surgery was well-tolerated. There could be a chance for durable locoregional control and even long-term survival in selected patients., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Objective: To prospectively evaluate the survival benefit of dissection of the nerve plexus and lymphadenectomy in patients with pancreatic head cancer., Background: Despite randomized controlled trials on the extent of surgery in pancreatic cancer, attempts have been made to perform more extended resections., Methods: A total of 244 patients were enrolled; of these, 200 were randomized to undergo standard resection or extended resection, with the latter including the dissection of additional lymph nodes and the right half of the nerve plexus around the superior mesenteric artery and celiac axis. We evaluated 167 patients from 7 centers who fulfilled all of the required criteria., Result: Operation time was longer and estimated blood loss was higher in the extended resection group than in the standard resection group, but the R0 resection rate was comparable. The mean number of lymph nodes retrieved per patient was higher in the extended resection group than in the standard resection group (33.7 vs 17.3; P < 0.001). The morbidity rate was slightly higher in the extended resection group than in the standard resection group. Two patients in the extended resection group died in hospital. Median survival after R0 resection was similar in the extended resection and standard resection groups (18.0 vs 19.0 months; P = 0.239) regardless of lymph node metastasis. Adjuvant chemoradiation had a positive impact on overall survival., Conclusions: This study suggests that extended lymphadenectomy with dissection of the nerve plexus does not provide a significant survival benefit compared with standard resection in pancreatic head cancer. Standard resection can be performed safely and efficiently, without negatively affecting oncologic efficacy or long-term survival, when compared with extended pancreaticoduodenal resection. (NCT00679913)?

Background: Hepatopancreatoduodenectomy has been performed to achieve radical resection in malignant biliary tumors. We reviewed clinical outcomes to evaluate the clinical feasibility of hepatopancreatoduodenectomy for the treatment of gallbladder and bile duct cancer., Methods: Twenty-three patients underwent hepatopancreatoduodenectomy from 1995 to 2007; 10 gallbladder cancer and 13 bile duct cancer. Median follow-up periods were 15.0 months., Results: R0 resection was performed in 17 of 23 patients (73.9%). Morbidity and mortality rates were 91.3% and 13.0%, respectively. Five-year survival rates were 10.0% for gallbladder cancer and 32.3% for bile duct cancer. Survival more than 3 years was possible for most patients with stage IIA or less, whereas all gallbladder cancer patients with stage III and all bile duct cancer with stage IIB or more died within 2 years. Bile duct cancer patients with pN0 survived longer than those with pN1 (p < 0.001)., Conclusions: To obtain negative proximal and distal ductal resection margins in the biliary tract cancer, R0 resection and long-term survival can be achieved by hepatopancreatoduodenectomy. However, its adoption in patients with lymph node metastasis or adjacent organ invasion cannot be recommended.

Objective: The purpose of this study was to determine whether patients who develop a pancreatic fistula after pancreatoduodenectomy are more likely to have higher pancreatic fat levels than matched controls and if so, to investigate whether preoperative dual gradient-echo magnetic resonance (MR) imaging can be used to measure pancreatic fat and predict the development of postoperative pancreatic fistula., Summary Background Data: Pancreatic fistula is a major complication and its most frequently reported risk factors tend to be anatomic features of the pancreatic remnant, such as a soft pancreatic texture., Methods: Between January 2007 and September 2007, a total of 96 cases of pancreatoduodenectomy were performed at Seoul National University Hospital. Of total, 20 patients (20.8%) who developed a pancreatic fistula were carefully matched for multiple parameters including age, gender, pancreatic pathology, surgeon, and type of operation with 20 control patients who did not develop a pancreatic fistula. In the pancreatic fistula group, 9 patients (45%) had a grade A fistula and 11 (55%) grade B fistula. Degrees of pancreatic fatty infiltration and fibrosis were assessed quantitatively. In-phase and opposed-phase images were obtained by dual-gradient-echo MR imaging. Percentage decreases in pancreatic signal intensity on opposed-phase images relative to those on in-phase images were calculated and defined as relative signal intensity decreases (RSID)., Results: More patients in the pancreatic fistula group had a soft pancreatic texture or a smaller pancreatic duct and total fat and RSID were significantly higher. In soft pancreatic texture group, intralobular, interlobular, and total fat were significantly elevated. Furthermore, pancreatic fat levels were found to be correlated positively with RSID (P=0.013). RSID was correlated with total pancreatic fat and when an RSID criterion more than 7.032 was used, pancreatic fistula could be predicted as 72.7% sensitivity and 75.9% specificity., Conclusion: Our findings suggest that increased pancreatic fat is a risk factor of postoperative pancreatic fistula. Preoperative measurements of pancreatic fat by MRI offer a noninvasive predicting the occurrence of pancreatic fistula.

Background: The objectives of this study were to investigate the clinicopathological features of branch intraductal papillary mucinous neoplasm (IPMN) and to determine safe criteria for its observation. Most clinicians agree that surgical resection is required to treat main duct-type IPMN because of its high malignancy rate. However, no definite treatment guideline (with respect to surgery or observation) has been issued on the management of branch duct type IPMN., Methods: We retrospectively reviewed the clinicopathological data of 138 patients who underwent operations for IPMN between 1993 and 2006 at five institutes in Korea., Results: Of 138 patients (mean age, 60.6 years; 87 men, 51 women), 76 underwent pancreatoduodenectomy, 39 distal pancreatectomy, 4 total pancreatectomy, and 20 limited pancreatic resection. There were 112 benign cases: 47 adenoma, 63 borderline cases, and 26 malignant cases, with 9 of these being noninvasive and 17 invasive. By univariate analysis, tumor size and the presence of a mural nodule were identified as meaningful predictors of malignancy. By receiver operating characteristic curve analysis, a tumor size of >2 cm was found to be the most valuable predictor of malignancy. When cases were classified according to tumor size and the presence of a mural nodule, the malignancy rate for a tumor 2 cm, >25%., Conclusions: Many branch duct IPMNs are malignant. Surgical treatment is recommended, except in cases that are strongly suspected to be benign or cases that present a high operative risk. Observation is only recommended in patients with a tumor size of

Background: Pancreatic surgeons often must make decisions regarding hepatic artery (HA) resection while performing a pancreatoduodenectomy (PD). The purpose of this report was to review and summarize HA resection experience with a focus on vascular preservation during PD and to develop a useful guideline for pancreatic surgeons in dealing with these needs., Methods: We reviewed 1324 cases that had available computed tomographic and angiographic findings and summarized the problematic HA variations encountered in PD. In reviewing our PD series (n = 254), we have created a set of guidelines that enable a pragmatic approach to the unique variations in HA and the risks of cancer invasion., Results: Challenging HA variations during PD were found in 20.1% of the cases and included the common HA arising from the superior mesenteric artery (SMA) (2.34%), a replaced right HA (RHA) from the SMA (9.82%), an RHA or left HA from the gastroduodenal artery (0.97%), and the right anterior or right posterior HA from the SMA (1.06%), among others. In our PD series, the problematic HAs (15.8%) were preserved, except for a single case (0.4%) in which PD involved en bloc resection of the RHA from the SMA due to a cancerous invasion and without right hemihepatectomy., Conclusions: Surgeons should have knowledge of the anatomically variable vasculature of the HA when planning for PD. Preoperative imaging studies can aid and should be performed in anticipation of the potential HA variations during PD.

Aim: The purpose of this study is to find a better operative technique by comparing interrupted stitches with continuous stitches for the outer layer of the pancreaticojejunostomy, i.e. the stitches between the stump parenchyma of the pancreas and the jejunal seromuscular layer, and other risk factors for the incidence of pancreatic leakage., Methods: During the period January 1997 to October 2004, 133 patients have undergone the end-to-side and duct-to-mucosa pancreaticojejunostomy reconstruction after pancreaticoduodenectomy with interrupted suture for outer layer of the pancreaticojejunostomy and 170 patients with a continuous suture at our institution by one surgeon., Results: There were no significant differences between the two groups in the diagnosis, texture of the pancreas, use of octreotide and pathologic stage. Pancreatic fistula occurred in 14 patients (11%) among the interrupted suture cases and in 10 (6%) among the continuous suture cases (P = 0.102). Major pancreatic leakage developed in three interrupted suture patients (2%) and zero continuous suture patients (P = 0.026). In multivariate analysis, soft pancreatic consistency (odds ratio, 5.5; 95% confidence interval 2.3-13.1) and common bile duct cancer (odds ratio, 3.7; 95% CI 1.6-8.5) were predictive of pancreatic leakage., Conclusion: Pancreatic texture and pathology are the most important factors in determining the fate of pancreaticojejunal anastomosis and our continuous suture method was performed with significantly decreased occurrence of major pancreatic fistula. In conclusion, the continuous suture method is more feasible and safer in performing duct-to-mucosa pancreaticojejunostomy.

Background/aims: We compared the long-term functional outcomes of standard pancreatoduodenectomy (SPD) and pylorus-preserving pancreatoduodenectomy (PPPD) patients., Methodology: The subjects were 67 patients who underwent SPD (23) or PPPD (44) and who survived more than 3 years. General nutritional status, pancreatic functions, gastrointestinal (GI) symptoms, and quality of life (QOL) were assessed., Results: Postoperative relative body weights to preoperative body weight in the SPD group were generally lower, however, no significant difference was observed throughout the postoperative period, except at 6 postoperative months. Steatorrhea developed in 3 (13.0%) of the 23 SPD and in 6 (13.6%) of the 44 PPPD patients during the 3-year follow-up (p > 0.05). IFG or DM newly developed in 2 (10.5%) of the 19 SPD and in 5 (13.9%) of the 36 PPPD patients during the 3-year follow-up (p > 0.05). Symptoms such as flatus, diarrhea and fatigue were more frequently observed in SPD patients. The general health status/QOL score of the PPPD group (75.5) was somewhat higher than that of the SPD group (65.4) (p > 0.05)., Conclusions: The long-term functional outcomes of SPD and PPPD patients were generally comparable. However, PPPD was more favorable than SPD in terms of an earlier postoperative recovery and reduced rates of GI symptoms such as flatus and diarrhea.

Background/aims: Hemorrhage after pancreatoduodenectomy is a severe, life-threatening complication. This study was conducted to determine the guidelines appropriate for the prevention and management of hemorrhagic complications., Methodology: We reviewed the medical records of 456 patients who had undergone pancreatoduodenectomy at our hospital between 1991 and 2000., Results: Significant postoperative bleeding occurred in 21 patients (4.6%). Early bleeding (within the 5th postoperative day) caused by improper intraoperative hemostasis occurred in 5 of these cases; 3 of whom were saved by prompt operation and one by conservative management. The other 16 cases consisted of late bleeding (after the 5th postoperative day), of which 12 patients (75%) experienced pancreatic leaks and 8 pseudoaneurysms of major arteries. "Sentinel bleeding" was evident in 8 cases. Angiographic embolization was performed in 8 cases, 7 of which were successful. Reoperation was tried in 7 cases with complete hemostasis being achieved in 2. As a result, 15 of 21 patients obtained complete hemostasis and the mortality rate from hemorrhage was 28.6% (6/21)., Conclusions: Rapid decision-making is mandatory when bleeding stigmata such as pseudoaneurysm on CT and sentinel bleeding are noted. Prompt operation for early bleeding and angiographic embolization for late bleeding are recommended. In order to prevent hemorrhage after pancreatoduodenectomy, meticulously performed hemostasis and the avoidance of pancreatic anastomotic leaks are essential.

Background: Delayed gastric emptying (DGE) is the most frequent postoperative complication after pylorus-preserving pancreatoduodenectomy (PPPD). This study was undertaken to determine which factors influence the development of DGE after PPPD., Study Design: We studied 150 consecutive patients who underwent PPPD performed by one surgeon between 1996 and 2000. The variables analyzed were age, gender, diagnosis, laboratory data, operative time, transfusion, preoperative cholangitis, and complications. The operative factors included were route of the afferent jejunal limb (retromesenteric versus antemesenteric), type of pancreatoenteric anastomosis, and preservation of the right gastric artery. DGE was defined as nasogastric drainage for more than 10 days or delay of regular diet until 14 days postoperatively., Results: Univariate analysis showed preoperative cholangitis, intraabdominal complication, and the jejunal reconstruction method were significantly associated with DGE. Preservation of the right gastric artery was not associated with gastric emptying ability. Multivariate analysis by logistic regression showed that DGE was significantly more frequent among patients with preoperative cholangitis (15 of 36 [41.7%] versus 19 of 114 [16.7%], p=0.0031), postoperative intraabdominal complications (15 of 36 [41.7%] versus 10 of 114 [8.8%], p = 0.0001), and in the retromesenteric group (33 of 104 [31.7%] versus 3 of 46 [6.5%], p = 0.0174)., Conclusions: Preoperative cholangitis and postoperative leakage problems affect gastric emptying after PPPD during the early postoperative period. The retromesenteric route is not recommended for pancreato- and biliary-enteric anastomosis. We speculate that retromesenteric passage of afferent jejunum can cause venous congestion and bowel edema, which can in turn retard the recovery of jejunal peristalsis at the duodenojejunostomy site resulting in disturbance from food passage.

Objective: To investigate whether gastrin has regenerative effect on the pancreas and in particular whether it prevents the atrophy of the distal pancreas after resection of pancreas in humans., Summary Background Data: Although pancreatic regeneration after resection is well documented in animals, atrophy rather than regeneration of the distal remnant pancreas commonly occurs following pancreatoduodenectomy in humans. Of the many factors involving pancreatic regeneration, gastrin has been shown to have trophic effect on the pancreas in an animal model., Methods: Between March 1999 and May 2000, a randomized prospective study was performed in 56 patients who underwent pylorus-preserving pancreatoduodenectomy for periampullary neoplasms. Patients were allocated to either a lansoprazole group or a control group. The lansoprazole members were given oral lansoprazole (30 mg/d) over 12 weeks postoperatively to induce hypergastrinemia. During the study period, 19 patients were excluded for different reasons; in the end a total of 37 patients (lansoprazole, n = 18; control, n = 19) were eligible for study. The volume of the distal pancreas as determined using thin-sectioned spiral CT data, nutritional status, and endocrine (insulin level, glucose tolerance test) and exocrine function (stool elastase) of the pancreas and serum gastrin levels were measured before surgery and 3 months after surgery. The two groups were clinically comparable., Results: Serum gastrin level was elevated in the lansoprazole group. In this group, the mean volume of the distal pancreas was reduced by 10% after pylorus-preserving pancreatoduodenectomy, whereas severe pancreatic atrophy occurred in the control group. Postoperative insulin and stool elastase levels were higher in the lansoprazole group than in the control group., Conclusions: This study is the first prospective randomized trial of induced hypergastrinemia on the regeneration of the pancreas in humans. It may be possible to use induced hypergastrinemia in the treatment or prevention of pancreatic insufficiency following resection or injury.

The purpose of this study was to clarify the prognostic significance of transfusion following pancreatoduodenectomy for periampullary cancers. We analyzed 357 periampullary cancers from 1985 to 1997 (ampullary cancer 130 cases, distal bile duct cancer 141 cases, pancreatic head cancer 86 cases). A total of 215 (60%) of the 357 patients have received intraoperative transfusion. The 5-year survival rate of 130 ampullary cancer patients was 59%; altogether, 76 patients (58%) underwent intraoperative transfusion. The 5-year survival rate of patients without intraoperative transfusion was 79%, whereas that of patients with a transfusion was 47% (p = 0.029). Following multivariate analysis, intraoperative transfusion was found to be an independent poor prognostic factor for those with ampullary cancer (relative risk 2.174). Among those with common bile duct cancer, the overall 5-year survival rate was 33%, and the 5-year survival rates for patients with (n = 87) or without (n = 54) transfusion were 25% and 38%, respectively, which did not reach statistical significance (p = 0.0717). For those with pancreatic head cancer, the overall 5-year survival rate was 16%, and there was no survival difference between transfused (n = 52) and untransfused (n = 34) patients. In the present study the reason was not clear, although intraoperative transfusion was an independent significant prognostic factor for ampullary cancer. Careful dissection to minimize intraoperative bleeding is mandatory during pancreatoduodenectomy for ampullary cancer.

To determine if there is any difference in pancreatic function after pylorus-preserving pancreatoduodenectomy(PPPD) according to the type of pancreatoenterostomy [pancreatojejunostomy (P-J) or pancreatogastrostomy (P-G)], we evaluated the long-term functional status of 34 patients who underwent PPPD and survived for more than 1 year without clinical evidence of recurrence. Altogether 20 patients underwent P-J and 14 P-G. To compare the two groups, we analyzed the (1) general nutritional status; (2) quality of life using three scoring systems; (3) gastrointestinal symptoms; and (4) pancreatic exocrine function by the stool elastase I test and endocrine function by oral glucose tolerance test (GTT). After PPPD, body weight decreased in both groups, with no difference between the two groups. No statistical differences were found in triceps skinfold thickness or serum protein/albumin. Regarding the quality of life and postoperative gastrointestinal symptoms, there were no differences between the two groups except steatorrhea. There were 4 mild and 15 severe cases of pancreatic exocrine insufficiency among those who underwent P-J, whereas all of the patients who underwent P-G showed severe pancreatic insufficiency. On GTT, excluding preoperative diabetes patients, 43.8% (7/16) of the P-J group had abnormal results after surgery, whereas 75.0% (9/12) of the PG group had an abnormal postoperative GTT (p = 0.11). Severe exocrine and endocrine pancreatic insufficiency developed after PPPD in both the P-J and P-G groups, but there was more functional deterioration in the P-G group than in the P-J group. General nutritional status and quality of life were not affected by the pancreatoenterostomy method in either group.

Background: Most studies on minimally invasive pancreatoduodenectomy (MIPD) combine patients with pancreatic and periampullary cancers even though there is substantial heterogeneity between these tumors. Therefore, this study aimed to evaluate the role of MIPD compared to open pancreatoduodenectomy (OPD) in patients with non-pancreatic periampullary cancer (NPPC). Methods: A systematic review of Pubmed, Embase, and Cochrane databases was performed by two independent reviewers to identify studies comparing MIPD and OPD for NPPC (ampullary, distal cholangio, and duodenal adenocarcinoma) (01/2015–12/2021). Individual patient data were required from all identified studies. Primary outcomes were (90-day) mortality, and major morbidity (Clavien-Dindo 3a-5). Secondary outcomes were postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), blood-loss, length of hospital stay (LOS), and overall survival (OS). Results: Overall, 16 studies with 1949 patients were included, combining 928 patients with ampullary, 526 with distal cholangio, and 461 with duodenal cancer. In total, 902 (46.3%) patients underwent MIPD, and 1047 (53.7%) patients underwent OPD. The rates of 90-day mortality, major morbidity, POPF, DGE, PPH, blood-loss, and length of hospital stay did not differ between MIPD and OPD. Operation time was 67 min longer in the MIPD group (P = 0.009). A decrease in DFS for ampullary (HR 2.27, P = 0.019) and distal cholangio (HR 1.84, P = 0.025) cancer, as well as a decrease in OS for distal cholangio (HR 1.71, P = 0.045) and duodenal cancer (HR 4.59, P < 0.001) was found in the MIPD group. Conclusions: This individual patient data meta-analysis of MIPD versus OPD in patients with NPPC suggests that MIPD is not inferior in terms of short-term morbidity and mortality. Several major limitations in long-term data highlight a research gap that should be studied in prospective maintained international registries or randomized studies for ampullary, distal cholangio, and duodenum cancer separately. Protocol registration: PROSPERO (CRD42021277495) on the 25th of October 2021. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to determine the relationship between the prognosis of ampullary cancer (AC) and the level of the tumor marker CA 19-9 (carbohydrate antigen 19-9), and to identify the optimal cutoff values for CA 19-9. The study enrolled 385 patients who underwent curative resection for AC. The C-tree method was used to determine the optimal cutoff value for CA 19-9, which was found to be 46 U/mL. This new cutoff value was a statistically significant prognostic factor for AC and may be used to evaluate the prognosis of AC and determine treatment strategies such as surgical treatments and adjuvant chemotherapy. Background: Carbohydrate antigen 19-9 (CA 19-9) is a representative tumor marker used for the diagnosis of pancreatic and biliary tract cancers. There are few published research results that can be applied to actual clinical practice for ampullary cancer (AC) alone. This study aimed to demonstrate the relationship between the prognosis of AC and the level of CA 19-9, and to determine the optimal thresholds. Methods: Patients who underwent curative resection (pancreaticoduodenectomy (PD) or pylorus preserving pancreaticoduodenectomy (PPPD)) for AC at the Seoul National University Hospital between January 2000 and December 2017 were enrolled. To determine the optimal cutoff values that could clearly stratify the survival outcome, the conditional inference tree (C-tree) method was used. After obtaining the optimal cutoff values, they were compared to the upper normal clinical limit of 36 U/mL for CA 19-9. Results In total, 385 patients were enrolled in this study. The median value of the tumor marker CA 19-9 was 18.6 U/mL. Using the C-tree method, 46 U/mL was determined to be the optimal cutoff value for CA 19-9. Histological differentiation, N stage, and adjuvant chemotherapy were significant predictors. CA 19-9 36 U/mL had marginal significance as a prognostic factor. In contrast, the new cutoff value, CA 19-9 46 U/mL, was found to be a statistically significant prognostic factor (HR: 1.37, p = 0.048). Conclusions: The new cutoff value of CA 19-9 46 U/mL may be used for evaluating the prognosis of AC. Therefore, it may be an effective indicator for determining treatment strategies such as surgical treatments and adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Pancreatic resection has higher postoperative mortality and morbidity rates than other abdominal operations. Some centers have reported remarkable postoperative outcomes of minimally invasive surgery. This study investigated the chronological trends of pancreatectomies by analyzing a large‐scale database. Methods: The medical records of 5175 patients who underwent pancreatic resection between 1961 and 2019 at a single institution were reviewed. To investigate the chronological change in survival outcomes of periampullary cancer, the survival data of 3,108 patients were analyzed. Results: Patient age and the proportion with pancreatic cancer have increased over time. From 2015 to 2019, pancreatic cancer was the most common cause for resection (35.9%), followed by pancreatic cysts (24.8%) and common bile duct cancer (13.4%). The incidence of postoperative complications tended to decrease over time (26.0% from 2000 to 2004; 20.8% from 2015 to 2019). A comparison of survival outcomes of periampullary malignancies by period revealed that patients with pancreatic cancer significantly improved (5‐year survival rate: 14.4% before 2000% vs 15.2% from 2000 to 2009% vs 29.0% after 2009, P <.001). Conclusions: Postoperative outcomes of pancreatic resection have improved over the past few decades. To improve outcomes in the future, an active multidisciplinary approach and postoperative management are required. [ABSTRACT FROM AUTHOR]

Background: Although perioperative hypothermia was found to be associated with gastrointestinal anastomotic leakage in preclinical studies, its association with postoperative pancreatic fistula (POPF) following pancreaticoduodenectomy was never evaluated. We investigated the association between intraoperative hypothermia and clinically relevant (CR)‐POPF following pancreaticoduodenectomy. Methods: We retrospectively reviewed 2163 consecutive patients who underwent pancreaticoduodenectomy during 2007‐2019. Based on intraoperative time‐weighted average core temperature, patients were grouped into normothermia (36.0‐37.5°C), mild hypothermia (35.0‐<36.0°C), and severe hypothermia (<35°C). We conducted multivariable logistic regression analysis for CR‐POPF, a propensity score analysis using inverse probability of treatment weighting (IPTW) to adjust the baseline differences between the three groups, followed by multivariable logistic regression with IPTW for CR‐POPF. Results: Among the 2008 patients analysed, 1118 (55.7%) and 120 (6.0%) had mild and severe hypothermia, respectively, and 14.2% overall incidence of CR‐POPF. Severe intraoperative hypothermia was significantly associated with CR‐POPF before and after IPTW (before: odds ratio [OR] 1.79, 95% confidence interval [CI]: 1.03‐3.09, P =.038; after: OR 2.48, 95% CI: 1.28‐4.81, P =.007); however, mild hypothermia had no significant associations. Conclusion: Severe intraoperative hypothermia is significantly associated with the occurrence of CR‐POPF following pancreaticoduodenectomy, suggesting that hypothermia is deleterious on pancreaticojejunal anastomotic healing. [ABSTRACT FROM AUTHOR]

Background/Purpose: The aim of the present study was to identify the types of recurrence in pancreatic ductal adenocarcinoma (PDAC) and discover the frequent location of the local recurrence. Methods: This study included 361 patients with PDAC who underwent curative‐intent surgery between 2007‐2014. Results: Among 361 patients, 75.1% (n = 271) developed recurrence during the follow‐up period. The 5‐year overall survival rate of recurred patients was 8.3%. The patterns of recurrence were classified as local (17.7%), systemic (62.0%), and loco‐systemic (20.3%). According to the preoperative tumor locations, patients with uncinate and head cancer showed higher rates of local recurrence than those with body and tail cancer (47.8% vs 17.2%, P <.001). When comparing uncinate and head cancer only, patients with uncinate cancer had much more frequent local recurrence around the superior mesenteric artery/vein (M zone) than around the hepatoduodenal ligament/common hepatic artery (H zone). Patients with head cancer had a higher rate of local recurrence in the H zone (H zone vs M zone; 53.5% vs 81.4% in uncinate cancer, P =.001; 66.7% vs 44.4% in head cancer, P =.056). Conclusion: Discovering the patterns of recurrence and frequent locations of recurrence may assist in local control as well as in the development of a customized individual approach for each patient. [ABSTRACT FROM AUTHOR]

Several studies comparing internal and external stents have been conducted with the aim of reducing pancreatic fistula after PD. There is still no consensus, however, on the appropriate use of pancreatic stents for prevention of pancreatic fistula. This multicenter large cohort study aims to evaluate whether internal or external pancreatic stents are more effective in reduction of clinically relevant pancreatic fistula after pancreaticoduodenectomy (PD). We reviewed 3149 patients (internal stent n = 1,311, external stent n = 1838) who underwent PD at 20 institutions in Japan and Korea between 2007 and 2013. Propensity score matched analysis was used to minimize bias from nonrandomized treatment assignment. The primary endpoint was the incidence of clinically relevant pancreatic fistula. This study was registered on the UMIN Clinical Trials Registry (UMIN000032402). After propensity score matched analysis, clinically relevant pancreatic fistula occurred in more patients in the external stents group (280 patients, 28.7%) than in patients in the internal stents group (126 patients, 12.9%) (OR 2.713 [95% CI, 2.139–3.455]; P < 0.001). In subset analysis of a high-risk group with soft pancreas and no dilatation of the pancreatic duct, clinically relevant pancreatic fistula occurred in 90 patients (18.8%) in internal stents group and 183 patients (35.4%) in external stents group. External stents were significantly associated with increased risk for clinically relevant pancreatic fistula (OR 2.366 [95% CI, 1.753–3.209]; P < 0.001). Propensity score matched analysis showed that, regarding clinically relevant pancreatic fistula after PD, internal stents are safer than external stents for pancreaticojejunostomy. A multicenter large cohort study by propensity score matched analysis showed that internal stents for pancreaticojejunostomy are safer than external stents regarding pancreatic fistula. The importance of this finding is that internal stents for pancreaticojejunostomy might reduce clinically relevant pancreatic fistula after pancreaticoduodenectomy. [ABSTRACT FROM AUTHOR]

Background: It is currently unknown whether bile duct segmental resection (BDSR) is an acceptable method for localized middle bile duct cancer (mid‐BDC) when R0 resection can be achieved. This study aimed to investigate the short‐ and long‐term outcomes of mid‐BDC patients treated with pancreaticoduodenectomy (PD) compared to those for BDSR. Methods: This was a retrospective, Japanese and Korean multi‐center collaboration study based on patients' medical records. Results: A total of 663 patients, including 245 BDSR and 418 PD cases, were enrolled. The incidence of postoperative pancreatic fistula (3.3% vs 44.1%, P <.0001), surgical site infection in the organ space (6.1% vs 17.7%, P <.0001) and clinically problematic morbidities (15.9% vs 32.8%, P <.0001) was significantly higher in the PD group. There was no difference in the mortality rate (0.8% vs 1.7%, P =.3566). Local (33.9% vs 14.4%, P <.0001) and lymph node (22.4% vs 11.0%, P <.0001) recurrence rates were significantly higher in the BDSR group. Relapse‐free survival (25.0 vs 34.0 months, P =.0184) and overall survival (41.2 vs 60.1 months, P =.0019) were significantly longer in the PD group. The PD group had significantly better prognosis in stage IA/IB cases (58.3 vs 111.5 months, P =.0067), which were the best indicators for BDSR, even when R0 resection was achieved. In multivariate analysis, BDSR was an independent poor prognostic factor. Conclusion: Despite the inferior perioperative short‐term outcomes, our data advocate that PD should be the standard procedure for mid‐BDCs and that BDSR should be avoided even if R0 resection can be achieved. (UMIN000017914). [ABSTRACT FROM AUTHOR]

Background: Few studies of the oncological outcomes of ampullary cancer have addressed recurrence, and many treatment‐related issues remain unresolved. This study evaluated optimal surgical treatment strategies based on recurrence patterns after pancreaticoduodenectomy (PD) for ampullary cancer. Methods: Two hundred and fifty‐nine patients who underwent PD with R0 resection for ampullary cancer from January 2000 to June 2012 were included. Generally, lymph node (LN) dissection extended to the right superior mesenteric artery (SMA). Recurrence was defined based on imaging studies. The first detected recurrence sites and patterns were analyzed. Results: During a mean follow‐up of 51.3 months, recurrence occurred in 89 (34.4%) cases, most commonly in the liver. Poor differentiation, advanced T stage, and LN metastasis were identified as risk factors for recurrence. Locoregional and systemic recurrences occurred alone or simultaneously in 20.2%, 73.0%, and 6.7% of patients, respectively. Locoregional and systemic recurrences tended to occur in early‐ and advanced‐stage cases, respectively. A nodal‐type recurrence around mesenteric vessels was the most common locoregional recurrence pattern, and 58.8% (10/17) were located left of the SMA. Conclusion: As nodal‐type metastasis around the mesenteric vessels was the dominant recurrence pattern, careful LN dissection around the SMA should be considered for early and advanced ampullary cancers. [ABSTRACT FROM AUTHOR]

Abstract: Background: Robot surgery is a new method that maintains advantages and overcomes disadvantages of conventional methods, even in pancreatic surgery. This study aimed to evaluate safety and benefits of robot‐assisted minimally invasive pancreaticoduodenectomy (robot PD). Methods: This study included 237 patients who underwent PD between 2015 and 2017. Demographics and surgical outcomes were evaluated. Results: Fifty‐one patients underwent robot PD and 186 underwent open PD. Robot PD group had younger age (60.7 vs. 65.4 years, P = 0.006) and lower body mass index (22.7 vs. 24.0, P = 0.007). Robot PD group had lower proportion of patients with firm or hard pancreatic texture (15.7% vs. 38.2%, P = 0.004) and smaller pancreatic duct size (2.3 vs. 3.3 mm, P = 0.002). Two groups had similar operation time (robot vs. open: 335.6 vs. 330.1 min) and complications (15.7% vs. 21.0%), including postoperative pancreatic fistula rate (6.0% vs. 12.0%). Robot PD group had lower postoperative pain score (3.7 vs. 4.1 points, P = 0.008), and shorter postoperative stay (10.6 vs. 15.3 days, P = 0.001). Conclusion: Robot PD is comparable to open PD in early outcomes. Robot PD is safe and feasible and enables early recovery; indication for robot PD is expected to expand in the near future. [ABSTRACT FROM AUTHOR]

Hypothesis: Duodenal-preserving resection of the head of the pancreas (DPRHP) and pancreas head resection with segmental duodenectomy (PHRSD) can be alternatives to standard pancreaticoduodenectomy for benign periampullary lesions. Design: Retrospective analysis of patients requiring surgery for benign and borderline malignant tumors of the periampullary region. Setting: Tertiary care referral center. Patients: Duodenal-preserving resection of the head of the pancreas (n = 8) and PHRSD (n = 7) were performed in 15 patients with a preoperative diagnosis of benign and borderline malignant tumors of the periampullary region (ie, 11 pancreas head lesions [2 intraductal papillary mucinous tumors, 4 serous cystadenomas, 2 insulinomas, 1 epidermal cyst, 1 metastatic renal cell carcinoma, 1 nonfunctioning islet cell tumor/parapaillary] and 4 duodenal lesions [3 adenomas and 1 adenocarcinoma]). Main Outcome Measures: Surgical factors (operation time and blood loss), postoperative complication, postoperative pancreatic insufficiency (eg, development of diabetes mellitus and steatorrhea or elevated stool elastase values), weight change, and recurrence of disease. Results: No differences were noted in the mean operation time and estimated blood loss between the 2 procedures. Major postoperative complication constituted the following: bile duct stricture (n = 1) in DPRHP and delayed gastric emptying (n = 1) and postoperative bleeding (n = 1) in PHRSD. Newly developed diabetes mellitus occurred in 1 patient. Exocrine pancreatic insufficiency (steatorrhea) was observed in 1 patient after PHRSD. Patients with early duodenal carcinoma and intraductal papillary mucinous tumors with a borderline malignancy are still alive without evidence of recurrence. There was no hospital or long-term mortality. Conclusions: Duodenal-preserving resection of the head of the pancreas is recommended first for a benign or low-grade, early malignant pancreatic head lesion; PHRSD can be an option... [ABSTRACT FROM AUTHOR]