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Background: The optima preoperative biliary drainage before pancreaticoduodenectomy in patients with biliary tract and pancreatic cancer remains controversial., Methods: A total of 898 patients who underwent preoperative biliary drainage via endoscopic retrograde biliary drainage, endoscopic transnasal biliary drainage, or percutaneous transhepatic biliary drainage before pancreaticoduodenectomy for biliary tract and pancreatic cancer were included. Perioperative and long-term outcomes were analyzed., Results: The Clavien-Dindo grade ≥3 morbidity rates after pancreaticoduodenectomy were higher in the endoscopic retrograde biliary drainage (21.9%; P = .001) or endoscopic transnasal biliary drainage (20.2%; P = .007) than in the percutaneous transhepatic biliary drainage (9.7%) groups. In biliary tract cancer, the frequency of dissemination after pancreaticoduodenectomy was higher in the percutaneous transhepatic biliary drainage (15.3%) than in the endoscopic retrograde biliary drainage (0.7%; P = .001) and endoscopic transnasal biliary drainage (4.1%; P = .037) groups; percutaneous transhepatic biliary drainage was an independent factor associated with worse disease-free survival (P = .04), whereas in pancreatic cancer the frequency of dissemination and survival was comparable among the 3 preoperative biliary drainage methods. Albumin <3.9 g/dL was independently associated with worse overall survival in patients with both pancreatic (P = .038) and biliary tract (P = .002) cancers, respectively. During biliary drainage, external drainage (P = .038) was independently associated with albumin <3.9 g/dL; albumin was higher in endoscopic retrograde biliary drainage group than in endoscopic transnasal biliary drainage or percutaneous transhepatic biliary drainage groups after 21 days from tube insertion., Conclusion: In biliary tract cancer, percutaneous transhepatic biliary drainage may carry the risk of increasing the incidence of disseminative recurrence. In pancreatic cancer, percutaneous transhepatic biliary drainage is preferable owing to fewer complications without influencing recurrence. However, if patients cannot undergo surgery immediately, endoscopic retrograde biliary drainage will be applicable to help the preservation of nutritional status, which can have an impact on survival., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Preoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking., Objective: To investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy., Design, Setting, and Participants: This observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months., Exposures: Preoperative chemotherapy (with or without radiotherapy) followed by resection., Main Outcomes and Measures: The incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively., Results: Overall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P < .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89)., Conclusions and Relevance: This international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

Purpose: We describe details and outcomes of a novel technique for optimizing the surgical field during robotic distal pancreatectomy (RDP) for distal pancreatic lesions, which has become common with potential advantages over laparoscopic surgery., Methods: For suprapancreatic lymph node dissection and splenic artery ligation, we used the basic center position with a scope through the midline port. During manipulation of the perisplenic area, the left position was used by moving the scope to the left medial side. The left lateral position is optionally used by moving the scope to the left lateral port when scope access to the perisplenic area is difficult. In addition, early splenic artery clipping and short gastric artery dissection for inflow block were performed to minimize bleeding around the spleen. We evaluated retrospectively the surgical outcomes of our method using a scoring system that allocated one point for blood inflow control and one point for optimizing the surgical view in the left position., Results: We analyzed 34 patients who underwent RDP or R-radical antegrade modular pancreatosplenectomy (RAMPS). The left position was applied in 14 patients, and the left lateral position was applied in 6. Based on the scoring system, only the 0-point group (n = 8) had four bleeding cases (50%) with splenic injury or blood pooling; the other 1-point or 2-point groups (n = 13, respectively) had no bleeding cases (p = 0.0046)., Conclusion: Optimization of the surgical field using scope transition and inflow control ensured safe dissection during RDP., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Advancements in multiagent chemotherapy have expanded the surgical indications for pancreatic cancer. Although pancreaticoduodenectomy (PD) with portal vein resection (PVR) has become widely adopted, distal pancreatectomy (DP) with PVR remains rarely performed because of its technical complexity. This study was designed to assess the feasibility of DP-PVR compared with PD-PVR for pancreatic body cancers, with a focus on PV complications and providing optimal reconstruction techniques when DP-PVR is necessary., Methods: A retrospective review was conducted on consecutive pancreatic body cancer patients who underwent pancreatectomy with PVR between 2005 and 2020. An algorithm based on the anatomical relationship between the arteries and PV was used for optimal surgical selection., Results: Among 119 patients, 32 underwent DP-PVR and 87 underwent PD-PVR. Various reconstruction techniques were employed in DP-PVR cases, including patch reconstruction, graft interposition, and wedge resection. The majority of PD-PVR cases involved end-to-end anastomosis. The length of PVR was shorter in DP-PVR (25 vs. 40 mm; p < 0.001). Although Clavien-Dindo ≥3a was higher in DP-PVR (p = 0.002), inpatient mortality and R0 status were similar. Complete PV occlusion occurred more frequently in DP-PVR than in PD-PVR (21.9% vs. 1.1%; p < 0.001). A cutoff value of 30 mm for PVR length was determined to be predictive of nonrecurrence-related PV occlusion after DP-PVR. The two groups did not differ significantly in recurrence or overall survival., Conclusions: DP-PVR had higher occlusion and postoperative complication rates than PD-PVR. These findings support the proposed algorithm and emphasize the importance of meticulous surgical manipulation when DP-PVR is deemed necessary., (© 2023. Society of Surgical Oncology.)

Background: Pancreatic ductal adenocarcinomas (PDACs) are sometimes diagnosed accompanied by rapidly impaired diabetes (PDAC-RID). Although this type of PDAC may have unusual biological features, these features have not been explained., Methods: Patients with PDAC who underwent upfront pancreatectomy between 2010 and 2018 were retrospectively reviewed. PDAC-RID was defined as a glycated hemoglobin (HbA1c) value of ≥ 8.0% of newly diagnosed diabetes, and acute exacerbation of previously diagnosed diabetes. Other patients were classified as PDAC with stable glycometabolism (PDAC-SG). Clinicopathological factors, long-term survival rates, and recurrence patterns were evaluated., Results: Of the 520 enrolled patients, 104 were classified as PDAC-RID and 416 as PDAC-SG. There was no significant difference regarding TNM staging, resectability, or adjuvant chemotherapy rate between the groups. However, 5-years cancer-specific survival (CSS) was significantly higher in the PDAC-RID group than in the PDAC-SG group (45.3% vs. 31.1%; p = 0.02). This survival difference was highlighted in relatively early-stage PDAC (≤ pT2N1) (CSS: 60.8% vs. 43.6%; p = 0.01), but the difference was not significant for advanced-stage PDAC. A multivariate analysis of early-stage PDAC showed that PDAC-SG was an independent risk factor of shorter CSS (hazard ratio 1.76; p = 0.02). The hematogenous metastatic rate in early-stage PDAC was lower in the PDAC-RID group than in the PDAC-SG group (18.3% vs. 35.8%; p = 0.01)., Conclusions: PDAC-RID showed a favorable long-term survival rate after curative resection with low hematogenous metastases, which may be due to its unique biology., (© 2023. Society of Surgical Oncology.)

Objective: Pancreatic cancer with lung oligometastasis may have favourable overall survival. The aim of this study was to evaluate outcomes of pancreatic cancer with lung oligometastases including both synchronous and metachronous metastases., Methods: Consecutive pancreatic cancer patients with lung metastasis treated at our institution between February 2015 and December 2021 were identified from our prospectively maintained database. Clinical characteristics and outcomes were compared and analysed according to the extent of lung metastases. Predictors for overall survival were analysed using the Cox proportional hazards model., Results: A totoal of 171 patients were included (oligometastasis/polymetastasis/multi-organ metastasis: 34/50/87). Patients with oligometastases were more likely to undergo surgical resection (41% vs. 0% vs. 2%) and showed a longer median overall survival (41.3 vs. 17.6 vs. 13.1 months) compared with those with other types of metastases. Oligometastasis (hazard ratio, 0.43; 95% confidence interval, 0.24-0.76; P = 0.004) was identified as an independent factor predicting favourable overall survival in patients with lung-only metastasis. Disease status (synchronous vs. metachronous) was not associated with survival in patients with oligometastasis (29.4 vs. 41.3 months, P = 0.527) and polymetastasis (17.9 vs. 16.7 months, P = 0.545). Selected patients who underwent surgical resection showed a median overall survival of 52.7 months., Conclusions: Patients with lung oligometastases presented a favourable prognosis. Surgical resection in selected patients was associated with a long median overall survival., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Various approaches have been reported for the resection of the nervous and lymphatic tissues around the superior mesenteric artery (SMA) during pancreaticoduodenectomy (PD) for pancreatic cancer. We developed a new procedure for circumferential lymph node dissection around the SMA to minimize local recurrence., Methods: We included 24 patients who underwent PD with circumferential lymph node dissection around the SMA (circumferential dissection) and 94 patients who underwent classical mesopancreatic dissection (classical dissection) between 2019 and 2021. The technical details of this new method are described in the figures and videos, and the clinical characteristics and outcomes of this technique were compared with those of classical dissection., Results: The median follow-up durations in the circumferential and classical dissection groups were 39 and 36 months, respectively. The patients' characteristics, including tumor resectability, preoperative and adjuvant chemotherapy rates, postoperative complication rates, and tumor stage, were similar between the two groups. No differences were observed in recurrence-free survival and overall survival between the two groups; however, the classical dissection group tended to have more local recurrences than the circumferential dissection group (8.3% vs. 33.3%, P = 0.168). Although no case of nodular-type recurrence after circumferential dissection was observed, 61.1% of local recurrences after classical dissection were of the nodular-type, and 36.4% were located on the left side of the SMA., Conclusions: Performing circumferential lymph node dissection around the SMA during PD can be conducted safely with minimal risks of local recurrence and may enhance the completeness of local resection., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: In pancreaticoduodenectomy (PD), the approach to superior mesenteric artery (SMA) is a critical process that supports adequate surgical margins and radicality for pancreatic tumors. In most of the reports on laparoscopic PD, the right-sided approach in which the jejunum is pulled out to the right side for peri-SMA dissection is used, since the left side of the SMA is difficult to dissect, and the only way to do this is to dissect the vein first., Methods: We devised a method to simplify and safely perform peri-SMA dissection by reversing the process, starting from the left side of the SMA. The first step involves the mobilization of the pancreatic head, which allows for rotation around the SMA. The second step involves the dissection of the left side of the SMA and transection of the jejunum. The key point is to change the incision line between the anterior and posterior mesojejunum. The third process includes the inferior pancreatoduodenal artery (IPDA) and first jejunal artery (J1A) dissection, which can be easily performed from the left side because the SMA rotates by simply continuing the dissection along the previously exposed SMA, and the IPDA/J1A are safely dissected at the root because they are drawn to the left side. The remaining processes are performed on the right side., Results: This method was performed in 16 cases, and in most cases IPDA/J1A were divided from the left side., Conclusion: The technique for SMA dissection from the left posterior side was described with illustrations and video. Our method allows safe oncologic dissection around SMA avoiding anatomical misorientation during laparoscopic PD., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The optimal procedure during distal pancreatectomy (DP) for patients who have undergone distal gastrectomy (DG) remains unclear. Several papers on remnant gastric ischemia have reported that the preserved splenic vessels are essential for the proximal remnant stomach. 1-4 We evaluated the outcomes of DP for post-DG patients in our hospital and introduced robotic splenic vessels preserving DP (R-SPDP)., Methods: Postoperative short-term outcomes of DP for post-DG patients during 2014 and 2021 were evaluated. Next, R-SPDP was performed for a post-DG patient with the intention of preserving the remnant stomach safely. The double bipolar method was used to dissect the adhesions around the splenic vessels. 5,6 The splenic artery was clamped at the root side to prevent bleeding. 7 All short gastric arteries and veins, which were the main feeders of the remnant stomach, were preserved and resection was completed. After resection, the indocyanine green (ICG) fluorescence angiography confirmed blood flow in the short gastric arteries and veins and good return blood flow to the splenic vein. 8 RESULTS: Of four patients (50.0%, of 8 DP patients) in whom the remnant stomach was preserved, one conventional DP case had poor ICG perfusion and presented with remnant stomach ischemia postoperatively. The R-SPDP case with good ICG perfusion had a total operation time of 371 minutes and intraoperative blood loss of 10 mL. The oral diet was started on postoperative Day 3, and the postoperative course was uneventful., Conclusions: R-SPDP can be a good option for post-DG patients to preserve the remnant stomach safely., (© 2023. Society of Surgical Oncology.)

Background: The role of paraaortic lymph node (PALN) sampling for pancreatic cancer (PC) remains controversial. This study aimed to assess the yield of PALN sampling and its impact on long-term outcomes., Methods: Patients treated from 2005 to 2018 were included. Since 2015, patients with borderline resectable or unresectable (BR/UR) tumours received standardized neoadjuvant therapy (NAT), whereas patients with resectable tumours underwent upfront resection., Results: Among 771 patients with PALN excision, metastasis was confirmed in 76 patients (10%) and 59 proceeded to planned resection. PALN metastasis was associated with early recurrence and shorter survival after upfront resection (1-year recurrence-free rate: 23% vs 57% for resectable tumours, P < 0.001, 9% vs 52% for BR/UR tumours, P = 0.006; median overall survival (OS): 19 vs 31 months for resectable tumours, P < 0.001, 17 vs 23 months for BR/UR tumours, P = 0.057). In contrast, they were both similar between patients with/without PALN metastasis following NAT for BR tumours (1-year recurrence-free rate, 50% vs 58%, P = 0.88; median OS, 28 vs 35 months, P = 0.45, respectively)., Conclusions: Occult metastasis to PALNs is not uncommon in patients with potentially resectable PC. Its prognostic impact depends on the treatment strategy, and the intraoperative decision for resection should be individualized., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Although the importance of adjuvant chemotherapy (AC) has been recognized in pancreatic cancer (PC) patients, there are few studies to address the underlying mechanisms of failure to complete AC. This study aims to investigate the relationship between nutritional state represented by sarcopenia and failure to complete AC in patients after curative-intent surgery for PC. This study included 110 patients who underwent pancreaticoduodenectomy for potentially resectable pancreatic cancers with intention of adjuvant S-1. Sarcopenia was defined using the psoas muscle mass index with cutoff values of 6.36 cm 2 /m 2 for men and 3.92 cm 2 /m 2 for women, which were calculated with a 3-D volumetric software. The relation between sarcopenia and successful AC and long-term survival were investigated. Twenty-nine (26%) patients were diagnosed as having sarcopenia (Sarcopenia group). Sarcopenia group comprised significantly older patients than Non-sarcopenia group (72 vs. 67 years old, p = 0.0087). AC was successfully completed in 14 patients (48%) in Sarcopenia group compared to 72 patients (89%) in Non-sarcopenia group (p < 0.0001). Multivariate analysis identified age ≥ 70 years and sarcopenia as significant risk factors for failure of AC. Among patients ≥ 70 years old, rate of successful AC was significantly higher in sarcopenia groups than non-sarcopenia group (17% vs. 78%, p < 0.001). In conclusions, age and sarcopenia were critical risk factors for the failure of 6 months of adjuvant chemotherapy. Among elderly patients, sarcopenia can predict the poor success rate of AC.

Background: Central pancreatectomy (CP) has been established as the most common type of parenchyma-sparing pancreatectomy; 1 however, CP is associated with higher morbidity and a higher pancreatic fistula (PF) rate than distal pancreatectomy or pancreaticoduodenectomy. 2,3 The jejunum patch technique (JPT) for distal pancreatectomy has recently been applied, which efficiently decreases the incidence of PF. 4 We have adapted this technique to CP as well as distal pancreatectomy with celiac axis resection. 5 Here, we retrospectively evaluated the usefulness of JPT for open CP cases, and report the experience of robot-assisted CP using the JPT., Methods: Among 37 consecutive cases who underwent CP at our institution between 2011 and 2022, clinical characteristics and postoperative short-term outcomes were compared between patients who underwent CP with and without the JPT. In robot-assisted CP using the JPT, after resection of the middle of the pancreas the transected jejunum was elevated through the retrocolic route in a Roux-en-Y fashion. The pancreatic stump was covered by the JPT using a modified Blumgart technique, following pancreaticojejunostomy for the distal side. 6 RESULTS: Among the entire cohort, 19 patients underwent CP using the JPT. The clinically relevant PF rate of the JPT group was significantly lower (47.4%) than the no-JPT group (83.3%, p = 0.022), and the length of drainage and hospital stay were shorter in the JPT group (p= 0.010 and p = 0.017, respectively). The blood loss of robot-assisted CP using the JPT was 20 mL, and the JPT took only 15 min., Conclusion: Robot-assisted CP using the JPT is an easy-to-use and promising procedure, based on experience and outcomes from open surgery., (© 2023. Society of Surgical Oncology.)

Alterations in KRAS, CDKN2A (p16), TP53, and SMAD4 genes have been major drivers of pancreatic carcinogenesis. The clinical course of patients with pancreatic cancer in relation to these driver alterations has not been fully characterised in large populations. We hypothesised that pancreatic carcinomas with different combinations of KRAS mutation and aberrant expression of CDKN2A, p53, and SMAD4 might show distinctive recurrence patterns and post-operative survival outcomes. To test this hypothesis, we utilised a multi-institutional cohort of 1,146 resected pancreatic carcinomas and assessed KRAS mutations by droplet digital polymerase chain reaction and CDKN2A, p53, and SMAD4 expression by immunohistochemistry. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed according to each molecular alteration and the number of altered genes using the Cox regression models. Multivariable competing risks regression analyses were conducted to assess the associations of the number of altered genes with specific patterns of recurrence. Loss of SMAD4 expression was associated with short DFS (multivariable HR, 1.24; 95% CI, 1.09-1.43) and OS times (multivariable HR, 1.27; 95% CI, 1.10-1.46). Compared to cases with 0-2 altered genes, cases with three and four altered genes had multivariable HRs for OS of 1.28 (95% CI, 1.09-1.51) and 1.47 (95% CI, 1.22-1.78), respectively (p trend  < 0.001). Patients with an increasing number of altered genes were more likely to have short DFS time (p trend  = 0.003) and to develop liver metastasis (p trend  = 0.006) rather than recurrence at local or other distant sites. In conclusion, loss of SMAD4 expression and an increasing number of altered genes were associated with unfavourable outcomes in pancreatic cancer patients. This study suggests that the accumulation of the four major driver alterations can confer a high metastatic potential to the liver, thereby impairing post-operative survival among patients with pancreatic cancer., (© 2023 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.)

Background: The efficacy of neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC-GS) in the prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC) has been reported. NAC-GS is now assumed to be a standard regimen for resectable PDAC in Japan. However, the reason for this improvement in prognosis remains unclear., Methods: In 2019, we introduced NAC-GS for resectable PDAC. From 2015 to 2021, 340 patients were diagnosed with resectable PDAC (anatomical and biological [carbohydrate antigen (CA) 19-9 < 500 U/mL]) and were divided according to the treatment period (upfront surgery [UPS] group, 2015-2019, n = 241; NAC-GS group, 2019-2021, n = 80). We used "intention-to-treat" analysis to compare the clinical outcomes of NAC-GS to those of UPS., Results: Of the 80 patients with NAC-GS, 75 (93.8%) completed two cycles of NAC-GS, and the resection rate of the NAC-GS group was comparable to that of the UPS group (92.5 vs. 91.3%, P = 0.73). The R0 resection rate was significantly higher in the NAC-GS group than in the UPS group (91.3 vs. 82.6%, P = 0.04), even though the surgical burden was smaller. Progression-free survival tended to be better (hazard ratio [HR] = 0.70, P = 0.06), and overall survival was significantly better in the NAC-GS group than in the UPS group (HR 0.55, P = 0.02)., Conclusions: NAC-GS provided improvements in microscopic invasion leading to a high R0 rate and smooth administration and completion of adjuvant therapy, which might lead to an improved prognosis in patients with resectable PDAC., (© 2023. Society of Surgical Oncology.)

Purpose: After the popularization of serum immunoglobulin G4 (IgG4) measurement and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in our institute, surgical resection for non-neoplastic diseases of the pancreas became less common. Although the incidence of such false-positive cases was clarified in the 10-year period after the introduction of these measures (2009-2018), these data were not compared with the 30 years before 2009 (1979-2008). This study was performed to determine the percentage of autoimmune pancreatitis (AIP) that was included during the latter period and how the numbers of false-positive cases differed between the two periods., Methods: From 1979 to 2008, 51 patients had clinical suspicion of pancreatic carcinoma (false-positive disease). Among these 51 patients, 32 non-alcoholic patients who had tumor-forming chronic pancreatitis (TFCP) were clinically, histologically, and immunohistochemically compared with 11 patients who had TFCP during the latter 10-year period., Results: Retrospective IgG4 immunostaining of false-positive TFCP revealed 14 (35.0%) cases of AIP in the former 30 years versus 5 (45.5%) in the latter 10 years. There were 40 (5.9%) cases of TFCP among 675 patients in the former 30 years and 11 (0.9%) among 1289 patients in the latter 10 years., Conclusions: When the TFCP ratio of pancreatic resections and the AIP ratio of false-positive TFCPs were compared between the two periods, the TFCP ratio was 5.9% versus 0.9% and the AIP ratio was 35.0% versus 45.5%, respectively. It can thus be speculated that IgG4 measurement and EUS-FNA are absolutely imperative for the diagnosis of TFCP., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This study investigates the use of serum DUPAN-2 in predicting the PC progression in CA19-9 nonsecretors., Background: Although we previously reported that serum CA19-9 >500U/ mL is a poor prognostic factor and an indication for enhanced neoadjuvant treatment, there is not a biomarker surrogate that equivalently predicts prognosis for CA19-9 nonsecretors., Methods: We evaluated consecutive PC patients who underwent pancreatectomy from 2005 to 2019. All patients were categorized as either nonsecretor or secretor (CA19-9 ≤ or >2.0U/mL)., Results: Of the 984 resected PC patients, 94 (9.6%) were nonsecretors and 890 (90.4%) were secretors. The baseline characteristics were not statistically different between the 2 groups except for the level of DUPAN-2 (720 vs. 100U/mL, P < 0.001). Survival curves after resection were similar between the 2 groups (29.4 months vs. 31.3 months, P = 0.900). Survival curves of patients with DUPAN-2 >2000U/mL in the nonsecretors and patients with CA19-9 >500U/mL in the secretors were nearly equivalent as well (hazard ratio 2.08 vs. 1.89). In the multivariate analysis, DUPAN-2 >2000U/mL (hazard ratio 2.53, P = 0.010) was identified as independent prognostic factor after resection., Conclusion: DUPAN-2 >2000U/mL in CA19-9 nonsecretors can be an unfavorable factor that corresponds to CA19-9 >500U/mL in CA19-9 secretors which is an indicator for enhanced neoadjuvant treatment. The current results shed light on the subset of nonsecretors with poor prognosis that were traditionally categorized in a group with a more favorable prognosis group., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Laparoscopic (Lap-) radical antegrade modular pancreatosplenectomy (RAMPS) is an attractive radical procedure that aims to achieve negative posterior retroperitoneal margin in pancreatic ductal adenocarcinoma (PDAC) resections. However, only few institutions are adapting Lap-RAMPS due to the technical difficulties and the lack of supporting evidence for the clinical applications., Methods: A retrospective cohort study was performed on consecutive patients who underwent RAMPS for distal resectable PDACs. We analyzed the short- and long-term outcomes including local control and the induction of adjuvant chemotherapy compared between Lap- and Open-RAMPS., Results: Of the 118 RAMPS patients, 43 patients underwent Lap-RAMPS and 75 patients underwent Open-RAMPS. The blood loss was lower (125 vs. 390 mL, p < 0.001), and postoperative hospital stay was shorter (17 vs. 21 days, p = 0.018) in the Lap-RAMPS group. There was no difference in the postoperative complications and no mortality in both groups. R0 resection rate was 100.0% in the Lap-RAMPS and 90.7% in the Open-RAMPS (p = 0.039). Among the patients eligible for adjuvant chemotherapy, the Lap-RAMPS group showed a favorable induction rate (100.0 vs. 89.6%, p = 0.037). Both groups showed a favorable 3-year local recurrence rate (8.7 vs. 10.0%, p = 0.976) and 3-year overall survival (69.8 vs. 71.1%, p = 0.996)., Conclusions: The safety and efficacy of Lap-RAMPS were comparable to those of Open-RAMPS in terms of achieving local control and adjuvant chemotherapy induction. A higher early induction of adjuvant chemotherapy is an advantage of minimally invasive surgery., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Neoadjuvant treatment has significant survival benefits for patients with pancreatic cancer. However, local recurrence remains a serious issue, even after neoadjuvant treatment. This study investigated local recurrence after pancreaticoduodenectomy and determined the optimal resection level after neoadjuvant treatment., Methods: This retrospective study analyzed consecutive patients who underwent pancreaticoduodenectomy for borderline resectable pancreatic cancer after 4 cycles of neoadjuvant treatment-gemcitabine plus nab-paclitaxel between April 2015 and March 2020. Patients with borderline resectable-artery pancreatic cancer were classified according to the dissection level around the artery: level 3 group, hemi-, or whole circumferential arterial nerve plexus was dissected; and level 2 group, the nerve plexus was preserved., Results: Fifty-six patients with borderline resectable-artery pancreatic cancer underwent pancreaticoduodenectomy after neoadjuvant treatment (level 3 group, n = 40; level 2 group, n = 16). The resection level in the level 2 group was changed based on post-neoadjuvant treatment computed tomography images or intraoperative frozen section diagnosis. The overall and local recurrence rates were significantly higher in the level 2 group than in the level 3 group (overall recurrence, 93.8% vs 70.0%; P = .037) (local recurrence, 50.0% vs 5.0%; P < .001). Ten patients experienced local recurrence, of which 8 belonged to the level 2 group. Among them, 4 patients were confirmed as cancer-negative by surgical margin analysis or intraoperative frozen section diagnosis but experienced recurrence around the arteries., Conclusion: For treating borderline resectable-artery pancreatic cancer, changing the resection level based on post-neoadjuvant treatment computed tomography images increased the risk of local recurrence. All patients with borderline resectable-artery should undergo level 3 dissection, regardless of the response to neoadjuvant treatment., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Liver oligometastatic pancreatic cancer (PC) may have favorable outcomes. This study aims to evaluate outcomes and factors associated with overall survival (OS) of these patients., Methods: We retrospectively investigated consecutive PC patients with liver metastasis treated at our institution between 2013 and 2020. Clinical characteristics and outcomes were compared and analyzed according to the extent of liver metastasis. Cox proportional hazards model was used to identify prognostic factors for OS., Results: A total of 417 patients were included (multi-organ metastasis/polymetastasis/oligometastasis 174/158/85). Oligometastasis showed a longer OS compared to other types of metastases (7.7 vs 8.2 vs 13.1 months). Age <70 years, performance status of 0, modified Glasgow prognostic score of 0, carbohydrate antigen 19-9 <1000 U/mL were identified as significant prognostic factors for OS. A prognostic index consisting of these four factors successfully stratified the prognosis of these patients (prognostic index; high vs low, 19.9 vs 8.3 months). Highly selected patients who underwent surgical resection showed a median OS of 54.6 months., Conclusions: Oligometastasis presented a relatively favorable outcome. Our new prognostic index was useful in stratifying the prognosis of these patients. Multimodal treatment including surgery may have additional survival benefits for highly selected patients., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Radical antegrade modular pancreatosplenectomy (RAMPS) was developed to enhance curability in patients with left-sided pancreatic cancer. However, no evidence is available regarding the prognostic superiority of RAMPS compared with conventional distal pancreatectomy (cDP). Here, we aimed to assess the oncological benefit of RAMPS by comparing surgical outcomes between patients who underwent cDP and RAMPS with propensity score (PS) adjustment., Methods: Clinical data of 174 patients undergoing cDP and RAMPS between 2009 and 2016 at two high-volume centers were analyzed with PS matching. Recurrence-free survival (RFS), overall survival (OS), and local recurrence rates were compared between patients who underwent cDP and RAMPS., Results: The cDP and RAMPS groups were successfully matched with baseline characteristics. No differences were found in the 3-year RFS and OS rates between the two groups (3-year RFS: cDP 46% vs RAMPS 40%, p = 0.451, 3-year OS: cDP 57% vs RAMPS 53%, p = 0.692). However, the 3-year local recurrence rate was lower in the RAMPS (10%) than that in the cDP group (34%) (hazard ratio 0.275, 95% confidence interval 0.090-0.842, p = 0.02)., Conclusion: RAMPS is oncologically superior to conventional procedure in achieving local control of the disease in patients with left-sided pancreatic cancer., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Neoadjuvant chemotherapy (NAC) is widely used to treat borderline resectable pancreatic cancer. This study aimed to evaluate the serum carbohydrate antigen (CA)19-9 response, in association with survival, after four cycles of NAC-gemcitabine plus nab-paclitaxel., Methods: From 2015 to 2018, patients with borderline resectable pancreatic cancer were treated with NAC. Patients were stratified into two groups after excluding CA19-9 non-secretor: Group L (CA19-9 ≥2 and ≤500 U/mL) and Group H (CA19-9 >500 U/mL). The CA19-9 decrease during NAC was evaluated as a response of NAC and was assessed in association with survival concomitant with other prognosis factors., Results: Eighty-seven patients were evaluated (Group L: n = 43, Group H: n = 44). In intention-to-treat-based analysis, Group L exhibited significantly better progression-free survival (PFS) than Group H (median PFS: 24 vs 14months). In resection cohort, no correlation was detected between the CA19-9 decrease and survival in Group L. In Group H, the CA19-9 decrease ≤80% was associated with unfavorable survival in multivariate analysis [Hazard ratio: 4.738 (P = 0.007)]., Conclusion: In patients with pre-treatment CA19-9 >500 U/mL, the CA19-9 decrease ≤80% was strongly associated with poor survival and new strategy should be reconsidered for these patients., Competing Interests: Conflict of interest All authors have no conflicts of interest related to this article. As a relevant financial activity outside this work, Naoki Sasahira received research funding from Taiho Pharmaceutical., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background/aim: Carbohydrate antigen 19-9 (CA19-9) levels may aid in the determination of subsequent treatment in patients with unresectable locally-advanced pancreatic cancer (LAPC) treated with chemotherapy. However, the relationship between the timing and magnitude of CA19-9 changes and clinical outcomes remains unclear. This study was conducted to identify the timing and magnitude of CA19-9 changes, which are most strongly associated with outcomes in LAPC patients., Patients and Methods: We retrospectively analyzed consecutive LAPC patients treated with gemcitabine plus nab-paclitaxel (GnP) or modified FOLFIRINOX (mFFX) as the first-line chemotherapy between March 2014 and December 2018 in our hospital. Multivariate analyses were performed to identify prognostic factors of chemotherapy in LAPC., Results: Ninety-four patients were included (GnP/mFFX: 72/22). The median overall survival was 20.3 months, and the median progression-free survival was 8.8 months. CA19-9 values before treatment did not affect prognosis. However, CA19-9 <100 U/ml or more than a 70% reduction in CA19-9 four months after commencing treatment was associated with a good prognosis (hazard ratio=0.17; 95% confidence interval=0.09-0.33; p<0.01)., Conclusion: CA19-9 values 4 months after commencing treatment are a significant prognostic factor in LAPC patients undergoing chemotherapy., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

KRAS mutation is a major driver of pancreatic carcinogenesis and will likely be a therapeutic target. Due to lack of sensitive assays for clinical samples of pancreatic cancer with low cellularity, KRAS mutations and their prognostic association have not been fully examined in large populations. In a multi-institutional cohort of 1162 pancreatic cancer patients with formalin-fixed paraffin-embedded tumor samples, we undertook droplet digital PCR (ddPCR) for KRAS codons 12/13/61. We examined detection rates of KRAS mutations by clinicopathological parameters and survival associations of KRAS mutation status. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease-free survival (DFS) and overall survival (OS) were computed using the Cox regression model with adjustment for potential confounders. KRAS mutations were detected in 1139 (98%) patients. The detection rate did not differ by age of tissue blocks, tumor cellularity, or receipt of neoadjuvant chemotherapy. KRAS mutations were not associated with DFS or OS (multivariable HR comparing KRAS-mutant to KRAS-wild-type tumors, 1.04 [95% CI, 0.62-1.75] and 1.05 [95% CI, 0.60-1.84], respectively). Among KRAS-mutant tumors, KRAS variant allele frequency (VAF) was inversely associated with DFS and OS with HRs per 20% VAF increase of 1.27 (95% CI, 1.13-1.42; p trend  <0.001) and 1.31 (95% CI, 1.16-1.48; p trend  <0.001), respectively. In summary, ddPCR detected KRAS mutations in clinical specimens of pancreatic cancer with high sensitivity irrespective of parameters potentially affecting mutation detections. KRAS VAF, but not mutation positivity, was associated with survival of pancreatic cancer patients., (© 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: The prognosis of initially unresectable pancreatic cancer (UR-PC) has improved since the introduction of FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GNP) treatment. Nonetheless, the indications and optimal timing for conversion to resection remain unclear for UR-PC. The aim of this study is to evaluate the characteristics of cases with initially UR-PC who received modified FFX or GNP treatment., Methods: This retrospective study reviewed 454 consecutive Japanese UR-PC cases who received modified FFX/GNP treatment. Cases were categorized according to resection status, and overall survival (OS) was evaluated using a multivariable prognostic scoring model (0-4 points, higher score indicating more favorable prognostic factors)., Results: The overall resection rate was 16% for locally advanced UR-PC (UR-LA) and 5% for metastatic UR-PC (UR-M). The resection group had better OS than the nonresection group (median OS time: not reached versus 13.0 months, P < 0.001). The independent prognostic factors were normalized CA19-9 concentration, modified Glasgow prognostic score of 0, tumor shrinkage after chemotherapy, chemotherapy duration ≥ 8 months, and resection. Cases were grouped according to their prognostic score, and the results suggested that candidates for resection might have prognostic scores of 4 points in UR-M cases or 2-4 points in UR-LA cases., Conclusions: Stratification according to prognostic score was useful in predicting the outcomes of UR-PC cases and may aid in identifying cases who might benefit from surgical treatment after responding to chemotherapy., (© 2022. Society of Surgical Oncology.)

The symposium "New criteria of resectability for pancreatic cancer" was held during the 33nd meeting of the Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) in 2021 to discuss the potential modifications that could be made in the current resectability classification. The meeting focused on setting the foundation for developing a new prognosis-based resectability classification that is based on the tumor biology and the response to neoadjuvant treatment (NAT). The symposium included selected experts from Western and Eastern high-volume centers who have discussed their concept of resectability status through published literature. During the symposium, presenters reported new resectability classifications from their respective institutions based on tumor biology, conditional status, pathology, and genetics, in addition to anatomical tumor involvement. Interestingly, experts from all the centers reached the agreement that anatomy alone is insufficient to define resectability in the current era of effective NAT. On behalf of the JSHBPS, we would like to summarize the content of the conference in this position paper. We also invite global experts as internal reviewers of this paper for intercontinental cooperation in creating an up-to-date, prognosis-based resectability classification that reflects the trends of contemporary clinical practice., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Laparoscopic radical antegrade modular pancreatosplenectomy (Lap-RAMPS) for left-sided pancreatic cancer remains a technically challenging procedure. How to approach the splenic artery in laparoscopic surgery has not been discussed in adequate detail, and the implications of an artery-first approach in left-sided pancreatic cancer remain unclear., Patients and Methods: Forty-five consecutive patients with left-sided resectable pancreatic cancer underwent Lap-RAMPS between July 2018 and September 2020. They were divided according to whether Lap-RAMPS was performed using an anterocranial splenic artery-first (ASF) approach (ASF group, n = 23) or via another approach (non-ASF group, n = 22). Clinical, pathological, and short-term outcomes were reviewed and compared between the groups., Results: The ASF approach was performed safely in all patients with resectable left-sided pancreatic cancer, and none required conversion to laparotomy. The ASF group had better outcomes in terms of conspicuous bleeding from the spleen during splenic mobilization (P = 0.016) and blood pooling during posterior dissection (P = 0.035). Consequently, blood loss was significantly less and operation time was significantly shorter in the ASF group than in the non-ASF group. There was no significant between-group difference in other short-term outcomes, including mortality, length of hospital stay, or Clavien-Dindo classification., Conclusions: The ASF approach was safe when performed for resectable left-sided pancreatic cancer and may help to prevent congestion of the pancreas and lessen intraoperative blood loss., (© 2022. Society of Surgical Oncology.)

Background: Early-onset pancreatic cancer (≤50 years, EOPC) is uncommon. This study aims to characterize the clinical and survival characteristics of EOPC in comparison to late-onset pancreatic cancer (>50 years, LOPC)., Methods: We retrospectively investigated consecutive PC patients treated at our institution between 2010 and 2019. We analyzed and compared clinicopathological characteristics, treatments, and outcomes of EOPC and LOPC., Results: Of 1646 PC patients identified (768 resectable/borderline resectable; 248 locally advanced; 630 metastatic), 127 (8%) had EOPC. Current smoking and heavy drinking were associated with EOPC. EOPC presented at a more advanced stage and had higher neutrophil-to-lymphocyte ratios than LOPC. Survival outcomes were similar between the two groups, both in the entire cohort and in each resectability group. In patients undergoing resection, EOPC tended to have a higher N stage (p = 0.099) and had a higher pathological stage (stage IV, 20% vs. 7%, p = 0.005) and a lower rate of macroscopically curative resection (80% vs. 93%, p = 0.006). Liver recurrence was more commonly observed in EOPC (42% vs. 23%, p = 0.015). In the metastatic cohort, combination chemotherapy regimens were more frequently administered in EOPC as first-line treatment (79% vs. 64%, p = 0.028). Both median PFS (4.4 vs. 5.3 months, p = 0.647) and OS (11.5 vs. 9.5 months, p = 0.183) were not significantly different between the two groups., Conclusions: EOPC presented with a more aggressive tumor biology. Survival outcomes were similar to LOPC due to more intensive treatment., (Copyright © 2022 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: For pancreatic ductal adenocarcinoma (PDAC) surgery, extended dissection of the nerve plexus (pl) around the superior mesenteric artery (SMA) or celiac artery (CA) is sometimes necessary. This consequently results in postoperative refractory diarrhea. This study aimed to evaluate the clinical impact of extended nerve plexus dissection around major arteries on postoperative diarrhea., Methods: Patients who underwent pancreatoduodenectomy (PD) for PDAC between January 2013 and December 2016 were included. The frequency of diarrhea (defined as a condition requiring opioid antidiarrheal drug for at least 6 months after surgery) and its short- and long-term outcomes were reviewed., Results: Of 200 consecutive patients who underwent PD, 78 (39.0%) developed postoperative refractory diarrhea (diarrhea group), and 73 of them (93.6%) underwent hemi-circumferential or more nerve dissection for SMA or CA; both plSMA and plCA dissection were associated with diarrhea. Borderline resectable artery (BR-A) PDAC was included more in the diarrhea group (32.0% vs. 13.1%, P = 0.001); however, the local recurrence rate in the diarrhea group was significantly lower than that in the non-diarrhea group (14.1% vs. 26.2%, P = 0.036). The completion of adjuvant chemotherapy and overall survival were comparable between the two groups. The pre-albumin level improved in 2 years, and 61.3% of patients with diarrhea could stop opioid antidiarrheal drugs within 3 years of surgery., Conclusions: Although the frequency of diarrhea increased following nerve plexus dissection around arteries, diarrhea was controllable and resulted in a reduced local recurrence rate. Aggressive dissection of the nerve plexus may be justified for local disease control in BR-A PDAC., (© 2022. The Author(s) under exclusive licence to Société Internationale de Chirurgie.)

Background/aim: This study evaluated the efficacy of adjuvant chemotherapy (AC) for intraductal papillary mucinous carcinoma (IPMC)., Patients and Methods: We retrospectively analyzed patients who underwent pancreatectomy for invasive IPMC from January 2007 to June 2020. We evaluated outcomes of AC in the entire cohort and in patients with known prognostic factors., Results: A total of 51 patients with invasive IPMC underwent surgery, of which 35 received AC. In the entire cohort, there was no significant difference in median overall survival (OS) between the AC and surgery alone (SA) group [hazard ratio (HR)=0.54; p=0.232]. For patients with poorly differentiated adenocarcinoma, median OS was significantly longer in the AC group (HR=0.27; p=0.022). For patients with lymph node metastasis, median OS was significantly higher in the AC group (HR=0.07; p<0.001)., Conclusion: AC may be effective for selected invasive IPMC patients., (Copyright © 2022 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: The most appropriate venous reconstruction method remains debatable when a long section of portal vein (PV) and/or superior mesenteric vein (SMV) must be resected in patients undergoing a pancreaticoduodenectomy (PD). The aim of the present study was to describe the technical details of the parachute technique, a modified end-to-end anastomotic maneuver that can be used in the above-mentioned circumstances, and to investigate its safety and feasibility., Study Design: Patients who underwent venous reconstruction using the parachute technique after receiving a PD with PV resection for pancreatic cancer between January 2014 and March 2019 were retrospectively reviewed. For the parachute technique, the posterior wall was sutured in a continuous fashion while the stitches were left untightened. The stitches were then tightened from both sides after the running suture of the posterior wall had been completed, thereby dispersing the tension applied to the stitched venous wall when the venous ends were brought together and solving any problems that would otherwise have been caused by over-tension. The postoperative outcomes and PV patency were then investigated., Results: Fifteen patients were identified. The median length of the resected PV/SMV measured in vivo was 5 cm (range, 3-6 cm). The splenic vein was resected in all the patients and was reconstructed in 13 patients (87%). The overall postoperative complication rate (≥ Clavien-Dindo grade I) was 60%, while a major complication (≥ Clavien-Dindo grade IIIa) occurred in 1 patient (7%). No postoperative deaths occurred in this series. The PV patency at 1 year was 87%., Conclusion: The parachute technique is both safe and feasible and is a simple venous reconstruction procedure suitable for use in cases undergoing PD when the distance between the resected PV and SMV is relatively long., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Neoadjuvant therapy is used for borderline resectable pancreatic ductal adenocarcinoma (PDAC) with high risk of incomplete resection and early recurrence. Because distal PDAC is rare, the optimal criteria for neoadjuvant therapy specific for distal PDAC remain unclear. We hypothesized large distal PDAC would recur earlier than small distal PDAC., Objective: The aim of this study was to identify the risk factors for failure of upfront resection for resectable distal PDAC., Methods: The study cohort comprised 158 patients with resectable distal PDAC who underwent radical resection. The long-term outcomes were recurrence-free survival (RFS), disease-specific survival (DSS), and post-recurrence survival (PRS)., Results: R0 resection was achieved in 92% of patients, and median DSS for the entire cohort was 31 months. Among 103 patients who developed recurrence, 32 (31%) developed recurrence within 6 months. The median PRS and DSS for those with early recurrence was 6 and 10 months, respectively, compared with 11 and 30 months, respectively, for those with late recurrence (p = 0.017 and p < 0.001, respectively). Patients with tumors > 4 cm had higher rates of R1 resection (16%) and concomitant resection of another organ (19%) than those with smaller tumors (4% and 2%, p = 0.009 and p < 0.001, respectively). In multivariate analysis, tumor > 4 cm remained a significant predictor of early recurrence (p < 0.001, hazard ratio [HR] 6.51), shorter RFS (p = 0.018, HR 1.71), and shorter DSS (p = 0.002, HR 2.07)., Conclusion: Tumor size > 4 cm is a reliable predictor of early recurrence after resection of distal PDAC, and neoadjuvant therapy may help select patients who can benefit from radical resection., (© 2021. Society of Surgical Oncology.)

Background: To describe the technical details and efficacy of distal pancreatectomy with celiac axis resection (DP-CAR) and left gastric artery (LGA) flow preservation for pancreatic ductal adenocarcinoma (PDAC)., Method: This single-center, retrospective analysis investigated short- and long-term outcomes of DP-CAR performed on 55 patients with PDAC from 2011 to 2019. Our method included LGA reconstruction after total resection of the CA (rDP-CAR group; 24 patients) or LGA preservation if the tumor invasion was away from its root (pDP-CAR group; 31 patients), a CA-first approach to reduce blood loss during dissection, and conservative drain management with or without jejunal serosal patching at the pancreatic stump., Results: Among the study patients, 23 had locally advanced PDAC and 22 had borderline resectable PDAC. Median operation duration was 443 min (248-810), estimated blood loss was 600 mL (150-2280), and incidence of transfusion was 2%. Ischemic complications occurred exclusively in the rDP-CAR group, including two patients with ischemic gastropathy (8%) and three patients with findings of liver ischemia on computed tomography (13%). One patient underwent relaparotomy for stomach perforations, and 19 patients (35%) had pancreatic fistula, including 8 patients who underwent conservative drain placement for more than 3 weeks without specific symptoms. There were no Clavien-Dindo grade 4 or higher postoperative complications. Preoperative therapy showed improved 3-year overall survival rates than without (54% vs. 37%, p = 0.027)., Conclusions: Using the standardized technique, DP-CAR was safely performed with no mortality and acceptable long-term survival., (© 2021. Society of Surgical Oncology.)

Pancreatic cancer is the fourth leading cause of cancer-related death in Japan. Pancreatic cancer is categorized as resectable, borderline resectable, or unresectable based on the degree of adjacent vascular invasion and the presence of distant metastases. Neoadjuvant chemotherapy with gemcitabine and S-1 (NAC-GS) has recently become a standard option for resectable pancreatic cancer in Japanese patients. According to previous reports, GS is considered to be relatively safe and feasible treatment for Japanese patients, including the elderly. However, NAC-GS is occasionally associated with severe adverse events which may ultimately render the patient unfit for surgery. A 60-year-old man with resectable pancreatic cancer suffered from severe necrotic enteritis during NAC-GS, which required surgical resection. Considering the time course and histological findings of the resected bowel, S-1 was believed to be the causative agent. The low urinary dihydrouracil to uracil ratio also suggested possible dihydropyrimidine dehydrogenase deficiency, which may have hindered the metabolism of S-1 and contributed to the development of necrotic enteritis. Life-threatening enteritis occurs in approximately 0.3% of all patients who receive S-1. As initial symptoms are non-specific, patients should be instructed to lower the hurdle for contacting the hospital during NAC-GS., (© 2021. Japanese Society of Gastroenterology.)

Background . A higher Ki-67 labeling index is associated with a poorer prognosis in gastroenteropancreatic neuroendocrine neoplasms. It has also been proposed that the Ki-67 labeling index may increase during disease progression from the primary site to metastatic sites. Although biopsy specimens are used to measure the Ki-67 labeling index, heterogeneity in lesions is thought to affect the assessment of the Ki-67 labeling index. To overcome tumor heterogeneity, we evaluated the variability in the Ki-67 labeling index between primary lesions and hepatic metastases by analyzing only surgically resected specimens. Methods. We conducted a single-center retrospective study to analyze the variability in the Ki-67 labeling index and the change in tumor grade between the primary site and metastatic hepatic sites in 19 patients diagnosed with gastroenteropancreatic neuroendocrine neoplasms at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from 1998 to 2018. Both the primary site and metastatic hepatic sites were surgically resected. Results. Among the 19 patients with gastroenteropancreatic neuroendocrine neoplasms, 12 patients (63%) showed higher levels of the Ki-67 labeling index at metastatic hepatic sites than at the primary site. The median Ki-67 labeling index levels for the primary lesion and metastatic hepatic lesions were 5% and 10%, respectively. The Ki-67 labeling index levels were significantly elevated in the metastatic hepatic lesions compared to the primary lesion ( P  = .002). Conclusions. This study addressed the heterogeneity of the Ki-67 labeling index by analyzing only surgically resected specimens. We observed a statistically significant increase in the Ki-67 labeling index in hepatic metastases compared to the primary lesion.

Background/purpose: We evaluated efficacy of neoadjuvant therapy with gemcitabine and nab-paclitaxel (GNP-NAT) in borderline resectable pancreatic cancer (BR-PC) patients compared to conventional upfront surgery (UPS)., Methods: This single-center retrospective study assessed 151 consecutive patients: 96 diagnosed in 2008-2014 underwent UPS (UPS group) and 55 diagnosed in 2015-2017 underwent GNP-NAT (GN group). Patient background, surgical, pathological, and survival outcomes were compared between groups., Results: Age, sex, and pretreatment carbohydrate antigen 19-9 were similar between groups. After four courses of NAT-GNP, 46 GN patients (84%) underwent surgery while all UPS patients underwent surgery. Only three GN patients (5%) underwent non-therapeutic procedures, compared to 23 (24%) in the UPS group (P = .004). In the whole cohort, R0-resection was achieved in 40 GN patients (73%) vs 46 UPS patients (48%; P = .004) and the 3-year overall survival was significantly higher in the GN group (median survival time, 31.9 vs 18.1 months, P = .014). In the resection cohort, the R0-resection rate was 93% (GN) vs 63% (UPS; P = .0007). There was no 90-day mortalities in either group., Conclusions: Intention-to-treat-based analysis indicated considerable benefits of GNP-NAT in BR-PCs for long-term survival, contributing to improved tumor suppression and patient selection., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Previous studies on borderline resectable (BR) pancreatic cancer (PC) included patients with heterogenous preoperative states; however, the definition of resectability for PC has evolved. We aimed to investigate the prognostic factors for PC other than anatomical resectability in those who underwent upfront resection and discuss the optimal treatment strategy for PC., Methods: We retrospectively examined 431 patients who underwent upfront surgery with curative intent between 2007 and 2014. The association between clinical characteristics and survival outcomes was assessed by stratifying patients according to risk factors. The patients were categorized into four groups based on anatomical (resectable [R]/BR) and biological features (CA19-9 ≤500/>500 U/mL): anatomical R with CA19-9 ≤500 U/mL (favorable-R); anatomical BR with CA19-9 ≤500 U/mL (favorable-BR); anatomical R with CA19-9 >500 U/mL (risky-R); and anatomical BR with CA19-9 >500 U/mL (risky-BR)., Results: Overall, 320 and 111 patients had anatomical R- and BR-PC, respectively. A modified Glasgow prognostic score = 2 (hazard ratio [HR]: 1.73), NLR>5 (hazard ratio [HR]: 1.54), CA19-9 >500 U/mL (HR: 1.86), and anatomical BR (HR: 1.38) were independent prognostic factors for overall survival. The risky-R group had likely worse prognosis (16 months vs. 19 months, P = 0.0605) and a significantly higher early recurrence rate (36% vs 18%, P = 0.0231) than the favorable-BR group., Conclusions: It is essential to stratify and distinguish PC patients at a high risk of worse prognosis. Risky-R was an unfavorable prognostic factor and should thus be considered in the decision-making for treatment with neoadjuvant chemotherapy, in addition to anatomical BR-PC., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: The prognosis of borderline resectable (BR) pancreatic cancer (PC) has improved by multidisciplinary therapy. However, the differences in clinical course between pancreatic head (Ph) and pancreatic body and tail (Pbt) cancer has not been fully elucidated. Therefore, we conducted this study to compare the clinical course of BR PC patients according to tumor location., Methods: We retrospectively investigated consecutive patients with BR PC who initiated neoadjuvant chemotherapy (NAC) between March 2015 and April 2019. We compared clinicopathological characteristics, treatment, recurrence pattern and post recurrence treatment between Ph and Pbt cancer patients. We also compared recurrence free survival (RFS) and overall survival (OS) according to tumor location., Results: A total of 108 patients with BR PC were included. Tumor location was Ph 74 and Pbt 34, respectively. Initial regimen of NAC was nab-paclitaxel/gemcitabine in 106 and gemcitabine in 2, respectively. Although Pbt location was associated with more advanced T stage, it showed similar N stage, pathological stage, RFS, OS, and details of adjuvant chemotherapy compared to Ph location. The most common site of postoperative recurrence was liver-only recurrence in Ph tumor (32% vs. 6%, p = 0.04) and peritoneal dissemination-only recurrence in Pbt tumor (35% vs. 11%, p = 0.06). Furthermore, Ph cancer patients received a higher rate of monotherapy compared to Pbt cancer patients (19% vs. 0%, p = 0.08)., Conclusions: In our experience tumor location was not a prognostic factor for OS in BR PC. Postoperative recurrence pattern and treatment after recurrence were different according to tumor location., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Although existing histopathologic protocols for pancreatic cancer have been standardized, the relevance between prognosis and resection margin clearance is still controversial. Reconstruction of specimens as in situ to appropriately assess the margin is desirable in these protocols., Methods: The three-dimensional fixation protocol defined specimen handling of pancreaticoduodenectomy (PD) with portal vein (PV) resection. The superior mesenteric artery (SMA) margin of the specimen was tidily fixed around an artificial SMA as if in an in situ setting. In this prospective study, patients undergoing PD with PV resection for pancreatic cancer in 2016 were enrolled. To evaluate the feasibility of the three-dimensional fixation protocol, the SMA margin distance and PV involvement of tumor assessed by computed tomography (CT) were compared with those assessed by pathology., Results: Thirty-three patients with/without preoperative chemotherapy were enrolled. The entire cohort did not present with high-quality diagnostic assessment of the medial margins around SMA and PV (correct estimation, 58% and 73%, respectively). In contrast, in 16 patients undergoing upfront surgery, the concordance value of the SMA margin, which assesses the agreement between CT and pathology measures, was 0.48 (moderate agreement). The PV involvement examined by imaging was significantly associated with that by pathology (P = 0.013)., Conclusions: The three-dimensional fixation protocol was applicable to all cases undergoing PD with PV resection. Focusing on the patients with upfront surgery demonstrated the feasibility of accurate pathological assessment of medial margins. We propose this protocol as a promising standard for the assessment of true surgical margin status.

Purpose: This study aimed to clarify the key factors for minimizing unsuitable surgical interventions for patients with radiologically occult metastatic pancreatic cancer (ROMPC), defined as a distant metastasis detected during surgery or within 6 months after resection., Methods: This study involved 502 patients planned to undergo curative resection for pancreatic cancer between 2008 and 2015. Patients were divided into ROMPC and non-ROMPC groups and evaluated preoperative factors associated with ROMPC., Results: Overall survival (OS) was significantly lower in the ROMPC group (n = 145) than the non-ROMPC group (n = 357, median survival time [MST] 10.8 vs. 35.3 months, P < 0.001). In the ROMPC group, OS tended to be worse for patients who had pancreatectomies (n = 84) than those who did not (n = 61, MST 10.1 vs. 13.2 months, P = 0.057), and the next chemotherapy started significantly later in patients who had pancreatectomies (P < 0.001). Moreover, OS was significantly lower for patients with (n = 82) than without (n = 63) liver metastases (MST 9.7 vs. 13.0 months, respectively, P = 0.020). The best indicator for patients at higher risk of ROMPC was a combination of carbohydrate antigen 19-9 concentration ≥ 300 U/ml and tumor size ≥ 30 mm., Conclusions: In the ROMPC group, patients who underwent pancreatectomy had a poorer prognosis than patients not undergoing pancreatectomy. Given that the liver was the most frequent distant metastatic site for ROMPC and had the poorest prognosis, establishing a strategy featuring new imaging modalities to detect radiologically occult liver metastases is necessary.

Background: Pancreaticoduodenectomy (PD) with splenic vein (SV) ligation may result in sinistral portal hypertension (SPH). The aim of this study was to compare the outcomes of various types of SV reconstruction to prevent SPH and to define the optimal reconstruction method., Methods: This study included patients who underwent PD with SV resection and reconstruction for pancreatic cancer between December 2013 and June 2017. The patency of various types of SV anastomosis and SPH was evaluated by follow up computed tomography., Results: The type of SV reconstruction was divided into two groups: (i) end-to-side anastomosis (n = 10), in which the SV was anastomosed with either the left renal vein (LRV; n = 8) or portal vein (n = 2); and (ii) end-to-end anastomosis (n = 20), in which the SV was anastomosed with another smaller vein or graft. The patency rate for Group 1 was 90% (9/10), compared with 45% (9/20) for Group 2 (P = 0.024). Half the patients in whom the SV anastomosis was occluded (6/12) developed gastrointestinal varices, whereas only 11% of patients with a patent SV anastomosis (2/9) had varices (P = 0.034)., Conclusion: SV-LRV reconstruction is widely applicable, effectively reduces the risk of SPH, and should be considered for the case of extended PD., (Copyright © 2019. Published by Elsevier Ltd.)

Background: We describe the short- and long-term outcomes for PDAC patients after tailored mesopancreas dissection using supracolic artery-first approach followed by adjuvant therapy., Methods: This study analyzed 233 consecutive patients who underwent artery-first pancreaticoduodenectomy for PDAC. Dissection extent for the superior mesenteric artery (SMA) was categorized into three levels: level 2 (LV2) including regional lymph nodes, level 3 (LV3) with hemicircumferential nerve plexus dissection, and extended-level 3 (E-LV3) including borderline resectable cases for the SMA. All clinical, pathological, and survival outcomes were reviewed., Results: LV2/3/E-LV3 dissection was performed in 77/115/41 patients. The short-term outcomes were similar among groups without mortality. Although postoperative diarrhea requiring opioids was significantly more frequent in the E-LV3 group (76%) than other groups (vs. LV2 (21%), P < .0001; vs. LV3 (34%), P < .0001; LV2 vs. LV3, P = 0.20), most cases of diarrhea were well controlled. Adjuvant chemotherapy was introduced similarly among groups (LV2, 76%; LV3, 81%; E-LV3, 88%, P = 0.29). The 3- and 5-year overall survival rates in the LV2/3/E-LV3 groups were 42/33/42% and 27/22/26%, respectively, showing no significant difference among groups., Discussion: Our tailored dissection and preemptive use of opioid antidiarrheal effectively prevents intractable diarrhea, increasing the success of adjuvant chemotherapy.