FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review.

BACKGROUND: Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC. METHODS: We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based. RESULTS: A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC. CONCLUSIONS: In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

Fate of Patients With Intraductal Papillary Mucinous Neoplasms of Pancreas After Resection According to the Pathology and Margin Status: Continuously Increasing Risk of Recurrence Even After Curative Resection Suggesting Necessity of Lifetime Surveillance.

OBJECTIVE: This study evaluated the associated factors and prognosis according to pathology and margin after surgical resection of intraductal papillary mucinous neoplasms (IPMN). BACKGROUND: There is limited information on recurrence patterns according to pathology and margin in IPMN. METHODS: Total 577 patients who underwent operation for IPMN at a tertiary center were included. Factors associated with recurrence, survival, and recurrence outcomes according to pathology and margin were analyzed. RESULTS: Among 548 patients analyzed, 353 had low-grade dysplasia (LGD), 78 had high-grade dysplasia (HGD), and 117 had invasive IPMN. Total 50 patients developed recurrences, with 4 resection margins, 10 remnant pancreas, 11 locoregional, and 35 distant recurrences. Invasive IPMN showed worse 5-year cumulative recurrence risk (LGD vs HGD vs invasive: 0.7% vs 4.3% vs 37.6%, P < 0.001) and 5-year survival rate (89.0% vs 84.0% vs 48.4%, P < 0.001). Recurrence risk increased after 5 years, even in LGD and HGD. Malignant margin (HGD and invasive) had worse 5-year cumulative recurrence rate (R0 vs LGD vs malignant: 8.3% vs 5.9% vs 50.6%, P < 0.001) and 5-year survival rate (80.7% vs 83.0% vs 30.8%, P < 0.001). Carbohydrate antigen 19-9 >37 ( P = 0.003), invasive IPMN ( P < 0.001), and malignant margin ( P = 0.036) were associated with recurrence. CONCLUSIONS: Invasive IPMN developed more recurrences and had worse survival than LGD or HGD, indicating the need for more efficient postoperative treatment strategies. Patients with LGD and HGD also need regular follow-up for recurrence after 5 years. Malignant margins need additional resection to achieve negative or at least LGD margin.

Parallel Analysis of Pre- and Postoperative Circulating Tumor DNA and Matched Tumor Tissues in Resectable Pancreatic Ductal Adenocarcinoma: A Prospective Cohort Study.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising biomarker for early tumor detection and minimal residual disease (MRD) assessment in early-stage cancer, but quantifying minute amounts of ctDNA is challenging and well-designed studies on ctDNA in early-stage cancer are still lacking. Here, we adapted a sensitive next-generation sequencing (NGS) technology and performed parallel analysis of pre- and postoperative ctDNA and matched tumor tissues in a prospective cohort of patients with resectable pancreatic ductal adenocarcinoma (PDAC). METHODS: In total, 70 consecutive patients undergoing curative resection for resectable PDAC were enrolled. We performed integrated digital error suppression-enhanced cancer personalized profiling by deep sequencing NGS of triple-matched samples (pre/postoperative plasma cell-free DNA [cfDNA], tumor tissue, and genomic DNA) targeting 77 genes. RESULTS: Preoperative ctDNA was detected in 37.7% of the evaluable patients, with a median variant allele frequency of 0.09%. Twelve additional oncogenic mutations were detected exclusively in preoperative ctDNA but not in tissue. When quantitative concentrations of ctDNA were estimated in haploid genome equivalents per milliliter (hGE/mL), the risk of early recurrence was high in patients with postoperative ctDNA >1 hGE/mL. cfDNA variants from 24.5% of patients had features compatible with clonal hematopoiesis. CONCLUSIONS: An optimized NGS approach might add value beyond tissue analysis through the highly sensitive detection of minute amounts of ctDNA in resectable PDAC. Postoperative ctDNA concentration could be a tool for MRD assessment. Moreover, parallel analyses of matched tissues and leukocytes might be required to accurately detect clinically relevant ctDNA.

Oncological outcome of proximal and middle extrahepatic bile duct cancer according to surgical extent (Is hilar resection oncologically acceptable in proximal and middle extrahepatic bile duct cancer?).

BACKGROUND: For proximal to middle bile duct cancer, it is controversial whether bile duct resection alone is sufficient, or whether hepatic or pancreatic resection should be accompanied by initial planning. This study aimed to determine the optimal surgical extent based on oncological outcomes in patients with proximal to middle bile duct cancer. METHODS: Patients who underwent surgery for proximal to middle extrahepatic bile duct cancer, hilar resection, or combined resection of other organs were included. Clinicopathological characteristics and survival analyses were compared according to operation type. RESULTS: Among 156 patients in total, R0 rate was 56.7% for hilar resection and 82.7% for other organ resection. Although hilar resection was associated with shorter hospital stay and fewer overall complications, operation type did not affect overall survival (p = 0.259) and disease-free-survival (p = 0.774). Overall survival differed according to R status (5YSR 49.8 vs. 27.1%; p = 0.012). CONCLUSION: In proximal to middle extrahepatic bile duct cancer, surgery should be tailored to achieve R0 resection according to the extent of the disease rather than uniformly resecting extensively with other organ resections. Hilar resection could be selected if R0 resection is feasible, considering the lower morbidity with similar long-term survival.

Comparison of oncologic outcomes between open and laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma using data from the KOTUS-BP national database: overcoming selection bias and the necessity of definite indications.

BACKGROUND: Despite the lack of high-level evidence, laparoscopic distal pancreatectomy (LDP) is frequently performed in patients with pancreatic ductal adenocarcinoma (PDAC) owing to advancements in surgical techniques. The aim of this study was to investigate the long-term oncologic outcomes of LDP in patients with PDAC via propensity score matching (PSM) analysis using data from a large-scale national database. METHODS: A total of 1202 patients who were treated for PDAC via distal pancreatectomy across 16 hospitals were included in the Korean Tumor Registry System-Biliary Pancreas. The 5-year overall (5YOSR) and disease-free (5YDFSR) survival rates were compared between LDP and open DP (ODP). RESULTS: ODP and LDP were performed in 846 and 356 patients, respectively. The ODP group included more aggressive surgeries with higher pathologic stage, R0 resection rate, and number of retrieved lymph nodes. After PSM, the 5YOSRs for ODP and LDP were 37.3% and 41.4% (p = 0.150), while the 5YDFSRs were 23.4% and 27.2% (p = 0.332), respectively. Prognostic factors for 5YOSR included R status, T stage, N stage, differentiation, and lymphovascular invasion. CONCLUSION: LDP was performed in a selected group of patients with PDAC. Within this group, long-term oncologic outcomes were comparable to those observed following ODP.

Radiological tumour invasion of splenic artery or vein in patients with pancreatic body or tail adenocarcinoma and effect on recurrence and survival.

BACKGROUND: Major vessel invasion is an important factor for determining the surgical approach and long-term prognosis for patients with pancreatic head cancer. However, clinical implications of vessel invasion have seldom been reported in pancreatic body or tail cancer. This study aimed to evaluate the clinical relevance of splenic vessel invasion with pancreatic body or tail cancer compared with no invasion and investigate prognostic factors. METHODS: This study enrolled patients who underwent upfront distal pancreatectomy from 2005 to 2018. The circular degree of splenic vessel invasion was investigated and categorized into three groups (group 1, no invasion; group 2, 0-180°; group 3, 180° or more). Clinicopathological variables and perioperative and survival outcomes were evaluated, and multivariable Cox proportional analysis was performed to evaluate prognostic factors. RESULTS: Among 249 enrolled patients, tumour size was larger in patients with splenic vessel invasion (3.9 versus 2.9 cm, P = 0.001), but the number of metastatic lymph nodes was comparable to that in patients with no vessel invasion (1.7 versus 1.4, P = 0.241). The 5-year overall survival rates differed significantly between the three groups (group 1, 38.4 per cent; group 2, 16.8 per cent; group 3, 9.7 per cent, P < 0.001). Patients with both splenic artery and vein invasion had lower 5-year overall survival rates than those with one vessel (7.5 versus 20.2 per cent, P = 0.021). Cox proportional analysis revealed adjuvant treatment, R0 resection and splenic artery invasion as independent prognostic factors for adverse outcomes in pancreatic body or tail cancer. CONCLUSION: Splenic vessel invasion was associated with higher recurrence and lower overall survival in pancreatic body or tail cancers suggesting a need for a neoadjuvant approach.

Preoperative assessment of the resectability of pancreatic ductal adenocarcinoma on CT according to the NCCN Guidelines focusing on SMA/SMV branch invasion.

OBJECTIVES: For patients with pancreatic adenocarcinoma (PAC), adequate determination of disease extent is critical for optimal management. We aimed to evaluate diagnostic accuracy of CT in determining the resectability of PAC based on 2020 NCCN Guidelines. METHODS: We retrospectively enrolled 368 consecutive patients who underwent upfront surgery for PAC and preoperative pancreas protocol CT from January 2012 to December 2017. The resectability of PAC was assessed based on 2020 NCCN Guidelines and compared to 2017 NCCN Guidelines using chi-square tests. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using log-rank test. R0 resection-associated factors were identified using logistic regression analysis. RESULTS: R0 rates were 80.8% (189/234), 67% (71/106), and 10.7% (3/28) for resectable, borderline resectable, and unresectable PAC according to 2020 NCCN Guidelines, respectively (p < 0.001). The estimated 3-year OS was 28.9% for borderline resectable PAC, which was significantly lower than for resectable PAC (43.6%) (p = 0.004) but significantly higher than for unresectable PAC (0.0%) (p < 0.001). R0 rate was significantly lower in patients with unresectable PAC according to 2020 NCCN Guidelines (10.7%, 3/28) than in those with unresectable PAC according to the previous version (31.7%, 20/63) (p = 0.038). In resectable PAC, tumor size ≥ 3 cm (p = 0.03) and abutment to portal vein (PV) (p = 0.04) were independently associated with margin-positive resection. CONCLUSIONS: The current NCCN Guidelines are useful for stratifying patients according to prognosis and perform better in R0 prediction in unresectable PAC than the previous version. Larger tumor size and abutment to PV were associated with margin-positive resection in patients with resectable PAC. KEY POINTS: • The updated 2020 NCCN Guidelines were useful for stratifying patients according to prognosis. • The updated 2020 NCCN Guidelines performed better in the prediction of margin-positive resection in unresectable cases than the previous version. • Tumor size ≥ 3 cm and abutment to the portal vein were associated with margin-positive resection in patients with resectable pancreatic adenocarcinoma.

Perioperative and oncologic outcome of robot-assisted minimally invasive (hybrid laparoscopic and robotic) pancreatoduodenectomy: based on pancreatic fistula risk score and cancer/staging matched comparison with open pancreatoduodenectomy.

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.

A comparison of outcomes in patients with intracholecystic papillary neoplasms or conventional adenocarcinomas of the gallbladder.

BACKGROUND: Intracholecystic papillary neoplasm (ICPN) of the gallbladder (GB) is an exophytic intraepithelial neoplasm. This study aimed to investigate clinicopathologic findings, prognosis and recurrence patterns of patients with ICPN as compared to those patients with conventional adenocarcinoma of the gallbladder (GBC). METHODS: Patients who underwent surgical resection for suspected GB cancer between 2000 and 2018 were included. ICPN was defined as an exophytic papillary mass within the GB lumen with a size ≥1.0 cm. RESULTS: Of 607 patients, 241 patients (40%) were pathologically diagnosed with ICPN. Of the 241 patients with ICPNs, 110 (46%) were T1 or less. Following T stage-matched analysis, the rate of lymph node metastases were comparable (50 [52%] vs. 37 [49%], P = 0.581). The five-year survival rate was higher in ICPN, but after T stage-matching, they were comparable (69.1 vs. 63.2%, P = 0.171). Overall recurrence rates were also comparable, with the exception of lower peritoneal seeding in patients with ICPN. CONCLUSION: Patients with ICPN who underwent resection were more likely to have an earlier T stage. There was no significant difference in prognosis and recurrence between ICPN and conventional GBC after stage matching. Therefore, the treatment strategy for ICPN should follow the same protocols used for conventional GBC.

Adverse oncologic effects of preoperative biliary drainage on early stage ampulla of Vater cancer.

BACKGROUND: The preoperative biliary drainage (PBD) in ampulla of Vater (AoV) cancer is indiscriminately performed without logical backgrounds. This study was performed to evaluate the effect of PBD on short and long-term outcomes in AoV cancer. METHODS: 313 patients who underwent pancreaticoduodenectomy and were pathologically diagnosed as AoV cancer between January 2000 and December 2014 were reviewed. RESULTS: 167 patients (53.4%) underwent PBD: Endoscopic drainage was performed in 106 patients (33.9%) and percutaneous drainage in 61 (19.5%). The postoperative complication rate of PBD group was significantly higher than that of upfront surgery group (48.5% vs. 38.4%, p = 0.045). The 5-year disease-free survival rate (5Y-DFSR) was significantly lower in PBD group compared to upfront surgery group (53.8% vs. 74.3%, p < 0.001). Worse 5Y-DFSR of PBD group was more evident in T1/T2 stage (59.2% vs. 84.1%, p < 0.001). In multivariate analysis with T1/T2 staged patients, PBD was independently associated with worse outcome (hazard ratio 2.145 [95% confidence interval, 1.202-3.826], p = 0.010). CONCLUSION: For T1/T2 AoV cancer, PBD adversely affected the short-term postoperative complication rate as well as the long-term oncologic outcomes. Therefore, especially in patients with T1/T2 AoV cancer, routine practice of PBD should be refrained and be reserved for selected cases such as cholangitis.

The diagnostic and prognostic values of inflammatory markers in intraductal papillary mucinous neoplasm.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is an broad-spectrum disease from benign to malignant. Inflammatory markers are known as prognostic predictors in various diseases. The purpose of this study was to determine the predictive value of inflammatory markers for prognosis in IPMN. METHODS: From April 1995 to December 2016, patients who underwent pancreatectomy with pathologically confirmed IPMN at four tertiary centers were enrolled. Patients with a history of pancreatitis or cholangitis, and other malignancies were excluded. Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and advanced lung cancer inflammation index (ALI) were calculated. RESULTS: Of all, ninety-eight patients (26.8%) were diagnosed as invasive IPMN. The NLR and PLR were significantly elevated in invasive IPMN than in non-invasive disease (2.0 vs 1.8, p = 0.004; 117.1 vs 107.4, p = 0.009, respectively). ALI was significantly higher in non-invasive IPMN than in invasive disease (58.1 vs 45.9, p < 0.001). In multivariate analysis, only NLR showed significant association among the inflammatory markers studied (p = 0.044). In invasive IPMN, the five-year recurrence-free survival rate for NLR less than 3.5 was superior to the rest (59.1 vs 42.2, p = 0.023). CONCLUSION: NLR may help to rightly select IPMN patients who will require surgery and may serve as a useful prognostic factor.

Optimal stapler cartridge selection to reduce post-operative pancreatic fistula according to the pancreatic characteristics in stapler closure distal pancreatectomy.

BACKGROUND: Postoperative pancreatic fistula (POPF) is associated with potentially fatal complications, but there is lack of data on relationship between pancreas thickness, and stapler size and the POPF rate. This study aimed to suggest optimal stapler that reduces POPF rate according to the pancreas thickness. METHODS: This retrospective cohort study was conducted in two tertiary high-volume pancreas centers. 599 patients who underwent distal pancreatectomy were assessed for stump reinforcement methods, pathology findings, pancreas thickness, and cartridge used. The cartridges were grouped as I, II, III according to the closed height ≤1.5 mm, 1.8 mm, and ≥2.0 mm, respectively. RESULTS: The POPF rate increased according to the thickness. The stapler Groups I, II, and III had an overall POPF rate of 66.4% vs. 61.7% vs. 57.8%, but Group II stapler cartridge showed a significant reduction in the POPF rate than other cartridges in pancreas with thickness <13 mm (53.5% vs. 21.7% vs. 36.0%, p = 0.031). There was no significant difference between the POPF rate according to stapler groups when the pancreas was thicker than 13 mm. CONCLUSION: Thickness is the strongest risk factor in predicting POPF. Use of Group II stapler cartridge for pancreas with a thickness of <13 mm can help reduce POPF.

Effects of Pancreatic Enzyme Replacement Therapy on Body Weight and Nutritional Assessments After Pancreatoduodenectomy in a Randomized Trial.

BACKGROUND & AIMS: We studied the effects of pancreatic enzyme replacement therapy (PERT) on body weight, nutritional status, and quality of life (QoL) in patients with pancreatic exocrine insufficiency after pancreatoduodenectomy. METHODS: We performed a randomized, double-blind trial of 304 patients who underwent pancreatoduodenectomy at 7 tertiary referral hospitals in South Korea. Patients with fecal levels of elastase of 200 µg/g or less, before and after surgery, were assigned randomly to groups that received PERT (a single capsule of 40,000 IU pancreatin, Norzyme (40,000 IU, Pankreatan; Nordmark Arzneimittel GmbH & Co, Uetersen, Germany), 3 times each day during meals for 3 months; n = 151) or placebo (n = 153). Protocol completion was defined as taking more than two thirds of the total dose without taking other digestive enzymes; the protocol was completed by 71 patients in the PERT group and 93 patients in the placebo group. Patients underwent a physical examination, oral glucose tolerance tests, and blood tests at baseline and at month 3 of the study period. The primary end point was change in body weight. Secondary end points were changes in bowel habits, nutritional parameters, and QoL. RESULTS: In the per-protocol analysis, 3 months after the study began, patients in the PERT group gained a mean of 1.09 kg in weight and patients in the placebo group lost a mean of 2.28 kg (difference between groups, 3.37 kg; P < .001). However, no difference in body weight was observed between groups in the intent-to-treat analysis. Three months after the study began, the mean serum levels of prealbumin increased by 10.9 mg/dL in the PERT group and increased by 7.8 mg/dL in the placebo group (P = .002). Poor compliance to PERT was a significant risk factor for weight loss (P < .001). There was no significant difference in QoL scores between groups. CONCLUSIONS: In the intent-to-treat analysis of data from a randomized trial, we found no significant effect of PERT on mean body weights of patients with pancreatic exocrine insufficiency after pancreatoduodenectomy. However, with active education and monitoring, PERT could increase body weight and nutritional parameters. ClinicalTrials.gov no: NCT02127021.

Central Pancreatectomy Versus Distal Pancreatectomy and Pancreaticoduodenectomy for Benign and Low-Grade Malignant Neoplasms: A Retrospective and Propensity Score-Matched Study with Long-Term Functional Outcomes and Pancreas Volumetry.

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.

Propensity score-matched analysis of internal stent vs external stent for pancreatojejunostomy during pancreaticoduodenectomy: Japanese-Korean cooperative project.

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.

Robotic extended cholecystectomy in gallbladder cancer.

BACKGROUND: The application of minimally invasive surgery (MIS) in advanced gallbladder cancer (GBC) requiring extended cholecystectomy is challenging, in terms of achieving clinically safe and complete oncologic resection. Recently developed robotic systems, however, may provide advantages in overcoming difficulties faced by laparoscopic MIS. The purpose of this study is to investigate the feasibility and advantages of a robotic system to assist with extended cholecystectomy. METHODS: Patients diagnosed with clinically suspected stage T2 or above, GBC (as determined by preoperative computed tomography or ultrasonography) underwent robotic extended cholecystectomy (REC) from February 2018 to January 2020. The attached video shows the detailed procedure in the following order: the positioning of the patient and the trocars, Kocher maneuver, lymph node dissection (#8, 9, 12, 13), skeletonization of hepatoduodenal ligament, ligation of the cystic duct and liver resection. RESULTS: Of 16 patients who underwent REC, mean operation time was 198.3 min and the median estimated blood loss was 295 ml. 11 patients (68.8%) were pathologically diagnosed as stage T2 or above, and the metastatic lymph node was identified in 3 patients (18.8%). All cases had secured tumor-free resection margins, and 3 patients (18.8%) showed invasion to the hepatic parenchyma. The mean number of retrieved lymph nodes was 7.2. The median duration of hospital stay was 7 days. There were no mortality or recurrence within 90 days after the operation. CONCLUSION: This study suggests that robotic systems can be safely utilized in advanced stage GBC, facilitating oncologically sufficient lymph node dissection and rapid recovery.

Correction to: Comprehensive proteome and phosphoproteome profiling shows negligible influence of RNAlater on protein abundance and phosphorylation.

[This corrects the article DOI: 10.1186/s12014-019-9239-z.].

Comprehensive proteome and phosphoproteome profiling shows negligible influence of RNAlater on protein abundance and phosphorylation.

Certain tumors such as pancreatic ductal adenocarcinoma (PDAC) are known to contain a variety of hydrolytic enzymes including RNases and proteases that may lead to degradation of RNA and proteins during sample processing. For such tumor tissues with RNA instability, RNAlater containing a high concentration of quaternary ammonium sulfates that denature RNA-hydrolyzing enzymes is often used to protect RNAs from hydrolysis. Although a few studies have been carried out to determine the effect of RNAlater on DNA and RNA, whether RNAlater influences the proteome and phosphoproteome is largely unknown. In this study we carried out a systematic and comprehensive analysis of the effect of RNAlater on the proteome and phosphoproteome using high-resolution mass spectrometry. PDAC tissues from three patients were individually pulverized and the tissue powders of each patient were divided into two portions, one of which was incubated in RNAlater at 4 °C for 24 h (RNAlater tissue) while the other was kept at - 80 °C (frozen tissue). Comprehensive quantitative profiling experiments on the RNAlater tissues and the frozen tissues resulted in the identification of 99,136 distinct peptides of 8803 protein groups and 17,345 phosphopeptides of 16,436 phosphosites. The data exhibited no significant quantitative changes in both proteins and phosphorylation between the RNAlater tissues and the frozen tissue. In addition, the phosphoproteome data showed heterogeneously activated pathways among the three patients that were not altered by RNAlater. These results indicate that the tissue preservation method using RNAlater can be effectively used on PDAC tissues for proteogenomic studies where preservation of intact DNA, RNA and proteins is prerequisite. Data from this study are available via ProteomeXchange with the identifier PXD010710.

Comparison of long-term clinical outcomes of external and internal pancreatic stents in pancreaticoduodenectomy: randomized controlled study.

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.