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

Solid pseudopapillary neoplasms (SPNs) of the pancreas have low malignant potential. However, malignant SPNs are not fully understood.To evaluate risk factors affecting malignant potential, the clinicopathologic features of 375 surgically resected SPNs were compared.Fifty (13.3%) had malignant histologic features. Twenty-seven and 22 had perineural and lymphovascular invasions, respectively. Adjacent organ invasion was noted in 9 cases. Recurrence occurred in 8 cases. The median recurrence time after surgical resection was 67 months and was associated with a higher pT category (P = 0.001), lymphovascular invasion (P 0.001), and synchronous metastasis (P 0.001). SPN patients with malignant histologic features had worse recurrence-free survival (RFS; 10-year survival rate, 73.2%) than those without malignant histologic features (96.3%; P = 0.01). Patients with a higher pT category (P = 0.04), synchronous metastasis (P 0.01), and lymphovascular invasion (P 0.01) had worse RFS. Lymphovascular invasion (P = 0.042) and a higher T category (P = 0.002) were poor prognostic factors for recurrence.Lymphovascular invasion and a higher T category were worse prognostic factors for recurrence in SPN patients with malignant histologic features. For SPN patients with malignant histologic features, a longer follow-up may be required.

BACKGROUND Owing to concerns regarding adequate oncological outcomes and perioperative complications, minimally invasive distal pancreatectomy (MIDP) for pancreatic ductal adenocarcinoma (PDAC) has limited generalizability. The aim of this study was to assess the perioperative and oncologic outcomes of MIDP compared with open distal pancreatectomy (ODP) for resectable PDAC after propensity score matching (PSM). METHODS The patients who underwent MIDP and ODP for PDAC between January 2010 and December 2017 were retrospectively reviewed. Demographics, perioperative outcomes, pathological outcomes, and overall and disease-free survival data were collected to compare MIDP and ODP. After PSM, perioperative and oncologic outcomes were analyzed. RESULTS A total of 156 MIDP patients were compared with 156 ODP patients for resectable PDAC after PSM. Tumor size, TNM stage, differentiation, harvested lymph nodes, and positive lymph nodes were not different except for R1 resection and lymphovascular invasion between the MIDP and ODP groups. Operation times, overall complications, POPF, and adjuvant treatment were also not different between the two groups. The MIDP group had shorter hospital stays (10.0 vs 13.4 days, P

BACKGROUND Though robotic pancreaticoduodenectomy(R-PD) is gradually adopted, learning curve and its feasibility is still controversial. We analyzed our first 70 R-PD cases, comparing surgical outcomes and feasibility to those of open pancreaticoduodenectomy (O-PD). METHODS Medical records of 70 patients of R-PD and 269 patients of O-PD between 2015 and 2019 were retrospectively analyzed. Cumulative sum analysis was used to determine learning curve. Surgical outcomes were compared between early(1-35) and late cases(36-70). Additional analyses with O-PD using propensity score-matching were done. RESULTS Learning curve of R-PD completed after 30 cases. Shorter operative time, lower estimated blood loss, and shorter length of stay were noted in later cases. Complication rate tended to decrease over time. In comparison with O-PD after matching, R-PD showed longer operation time(414.5 minutes vs 244.7 minutes; P

Purpose This study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma.Materials and Methods Data from 646 patients who underwent surgical resection at Asan Medical Center between 2000 and 2017 were retrospectively reviewed.Results The median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111).Conclusion AC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.

Objectives Histopathologic characteristics of choledochal cysts and their clinical implications have not been previously comprehensively studied. Methods Smooth muscle distribution patterns and other histologic findings (inflammation, metaplasia, dysplasia, and heterotopia) in 233 surgically resected choledochal cysts were evaluated. Results Mean patient age was 23.3 ± 19.8 years, with male:female ratio of 0.3. Most cases were Todani type I (175 cases, 75.1%) or IVa (56 cases, 24.1%). Choledochal cysts with thin scattered/no muscle fiber (175 cases, 75.1%) were the predominant pattern and were associated with more frequent postoperative biliary stricture (P = .031), less frequent pyloric metaplasia (P = .016), and mucosal smooth muscle aggregates (P 20 years vs ≤20 years), suggesting that chronic irritation in association with developmental anomalies involves tumorigenesis from choledochal cysts. Conclusion Smooth muscle distribution pattern of choledochal cyst may predict postoperative complication, raising clinical implications of smooth muscle patterns in postoperative management of choledochal cysts.

Previous studies on changes in body composition of pancreatic cancer patients have only focused on short-term survivors. We studied longitudinal body composition changes and factors affecting them in long-term survivors by analyzing many abdominal computed tomography images using artificial intelligence technology. Of 302 patients who survived for &gt, 36 months after surgery were analyzed. Multivariate logistic regression analysis for factors affecting body composition changes and repeated-measures analysis of variance to observe differences in the course of change according to each factor were performed. In logistic analysis, preoperative sarcopenia and recurrence were the main factors influencing body composition changes at 1 and 3 years after surgery, respectively. In changes of longitudinal body composition, the decrease in body composition was the greatest at 3–6 months postoperatively, and the preoperative status did not recover even 3 years after surgery. Especially, males showed a greater reduction in skeletal muscle (SKM) after surgery than females (p &lt, 0.01). In addition, SKM (p &lt, 0.001) and subcutaneous adipose tissue (p &lt, 0.05) mass rapidly decreased in case of recurrence. In conclusion, long-term survivors of pancreatic cancer did not recover their preoperative body composition status, and preoperative sarcopenia and recurrence influenced body composition changes.

Fibrin sealants and topical glue have been studied to reduce the incidence of postoperative pancreatic fistulas (POPF) after pancreatico-enteric anastomosis, but a definitive innovation is still needed. We aim to evaluate the effectiveness of fibrin sealant patch applied to pancreatico-enteric anastomosis to reduce postoperative complications, including POPF. This study was a single-center, prospective, randomized, phase IV trial involving three pancreaticobiliary surgeons. The primary outcome was POPF; secondary outcomes included complications, drain removal days, hospital stay, readmission rate, and cost. Risk factors for POPF were identified by logistic regression analysis. A total of 124 patients were enrolled. Biochemical leakage (BL) or POPF occurred in 16 patients (25.8%) in the intervention group and 23 patients (37.1%) in the control group (no statistical significance). Clinically relevant POPF occurred in 4 patients (6.5%) in both the intervention and control groups (p = 1.000). Hospital stay (11.6 days vs. 12.1 days, p = 0.585) and drain removal days (5.7 days vs. 5.3 days, p = 0.281) were not statistically different between two groups. Complication rates were not different between the two groups (p = 0.506); nor were readmission rates (12.9% vs. 11.3%, p = 1.000) or cost ($13,549 vs. $15,038, p = 0.103). In multivariable analysis, age and soft pancreas texture were independent risk factors for BL or POPF in this study. Applying fibrin sealant patch is not a negative risk factor, but the p value may indicate a likelihood of reducing the incidence of BL (p = 0.084). Fibrin sealant patches after pancreaticojejunostomy did not reduce the incidence of POPF or other postoperative complications. This study was registered at clinicaltrials.gov (NCT03269955).

Laparoscopic distal pancreatectomy (LDP) has gained popularity for the treatment of left-sided pancreatic tumors. Robotic systems represent the most recent advancement in minimally invasive surgical treatment for such tumors. Theoretically, robotic systems are considered to have several advantages over laparoscopic systems. However, there have been few studies comparing both systems in the treatment of distal pancreatectomy. We compared perioperative and oncological outcomes between the two treatment modalities. A retrospective analysis was conducted of all consecutive minimally invasive distal pancreatectomy cases performed by a single surgeon at a high-volume center between January 2015 and December 2017. The analysis included 228 consecutive patients (LDP, n = 182; Robotic-assisted laparoscopic distal pancreatectomy [R-LDP], n = 46). Operative time was significantly longer in the R-LDP group than in the LDP group (166.4 vs. 140.7 min; p = 0.001). In a subgroup analysis of patients who underwent the spleen-preserving approach, the spleen preservation rate associated with R-LDP was significantly higher than that associated with LDP (96.8% vs. 82.5%; p = 0.02). In another subgroup analysis of patients with pancreatic cancer, there were no significant differences in median overall and disease-free survival between the two groups. R-LDP is a safe and feasible approach with perioperative and oncological outcomes comparable to those of LDP. R-LDP offers an added technical advantage that enables the surgeon to perform a complex procedure with good ergonomic comfort.

AIMS Mucinous cystic neoplasms (MCNs) of the pancreas are cystic neoplasms lined by mucinous lining epithelium (MLE) with associated ovarian-type stroma. Although a non-MLE (NMLE) can be observed in some MCNs, whether cystic neoplasms with ovarian-type stroma and NMLE should be classified as MCNs or separately designated is debated. METHODS AND RESULTS To test this, NMLEs were defined as flat or cuboidal epithelial cells without intracytoplasmic mucin. A total of 112 MCNs were reviewed, and the epithelium was classified as NMLE or MLE. A total of 110 females and two males with a mean age of 46.5 ± 12.3 years were included in this study. At least focal NMLE was noted in 76.8% (86/112) of MCNs. The mean percentage of the neoplastic epithelium that was NMLE in these 86 cases was 46%. NMLE was predominant (>50%) in 38.4% (43/112) of cases. MCNs with NMLE were smaller (42 ± 21 mm) than those with MLE (60 ± 36 mm, P

The efficacy and outcomes of laparoscopic resection for pancreatic neuroendocrine tumors (PNETs) are well established; however, specific data regarding the outcomes of laparoscopic pancreaticoduodenectomy (L-PD) are limited. The purpose of the present study was to compare the clinical and oncological outcomes following L-PD versus open PD (O-PD) in patients with PNETs. This retrospective study included 149 patients with PNETs who underwent PD at the Asan Medical Center between January 2006 and December 2017. In 58 patients, a laparoscopic approach was used (L-PD group), and in 91, an open technique was used (O-PD group). The mean operative time was longer in the L-PD group than in the O-PD group (417.4 min vs. 362.2 min; p = 0.002), and the mean duration of postoperative stay was shorter in the L-PD group (12.6 days vs. 17.8 days; p

This study aimed to evaluate the evolving trends in clinicopathological features of pancreatic neuroendocrine tumors and to analyze the predictors of recurrence after curative resection. Data collected retrospectively from a single center between January 1990 and December 2017 were analyzed. Patients were categorized chronologically into three groups for evolving time-trend analysis. Overall, 542 patients (300 female, 55.4%) underwent surgical resection for pancreatic neuroendocrine tumors, including 435 (80.3%) with non-functional tumors. Time-trend analysis revealed that the surgically resected pancreatic neuroendocrine tumor number increased consistently; however, the incidental non-functional pancreatic neuroendocrine tumor number also increased over time (P P P = 0.009), lymphovascular invasion (hazard ratio 3.62; P = 0.004), perineural invasion (hazard ratio 2.61; P = 0.004) and resection margin (hazard ratio 4.20; P = 0.003) were independent prognostic factors of disease-free survival. The surgically resected pancreatic neuroendocrine tumor number increased over time mainly because of an increase in incidentally discovered non-functional pancreatic neuroendocrine tumors. Grade G3 pancreatic neuroendocrine tumors, lymph node metastasis, lymphovascular invasion, perineural invasion and a positive resection margin were significant predictors of worse disease-free survival in patients with surgically resected pancreatic neuroendocrine tumors.

Background Recurrence of pancreatic cancer after primary pancreatectomy occurs in the vast majority of patients. The role of surgical treatment for recurrent pancreatic cancer is not well established. Methods Patients who underwent primary pancreatectomy with curative intent from 2000 to 2014 at a single large-volume centre were evaluated retrospectively. CT or PET was used to select patients with an isolated recurrence. The clinicopathological features and survival outcomes were compared according to treatment modalities. Results Of the 1610 patients with pancreatic cancer who underwent resection, 1346 (83·6 per cent) were diagnosed with recurrent pancreatic cancer. Recurrence was locoregional in 366 patients (27·2 per cent), distant multifocal in 251 (18·6 per cent), distant isolated in 188 (14·0 per cent), locoregional plus distant in 153 (11·4 per cent) and peritoneal seeding in 388 (28·8 per cent). Of the 1346 patients with recurrence, 197 (14·6 per cent) had isolated recurrence; of these, 48 (24·4 per cent of all isolated recurrences; 3·6 per cent of all recurrences) underwent resection. Median survival of the 197 patients after diagnosis of isolated recurrence was 14·7 months; it was longer in patients who underwent surgical resection than among those treated non-surgically (23·5 versus 12·0 months; P = 0·014). Multivariable analysis showed that chemotherapy and resection for recurrence were associated with better prognosis. Median survival after recurrence was longest in the 23 patients with isolated pulmonary recurrence (33·3 months). Survival after recurrence was better in patients who underwent resection of isolated recurrence in the remnant pancreas (median 28·0 versus 12·0 months, P = 0·010) and lung (median 36·5 versus 9·5 months; P = 0·010) than in those who did not undergo resection. Conclusion Surgical resection may be considered an option for treatment of patients with isolated recurrent pancreatic cancer.

Background We evaluated whether distal pancreatectomy (DP) with adjacent organ resection (AOR) affected perioperative outcomes and survival in patients with left-sided pancreatic ductal adenocarcinoma (PDAC). Methods Retrospective cohort study was conducted at single large volume academic medical center from January 2000 to December 2016. Results Five hundred and twenty-three patients had undergone standard DP (without additional vessel/organ resection) and 40 had undergone DP with AOR due to adjacent organ infiltration. There were no differences of postoperative morbidity and hospital stay between the two groups. In the patients with AJCC 8th stage I and II PDAC, there were significant differences of median disease-specific and progression-free survivals between the standard and AOR groups (37.9 vs. 20.2 months; P = 0.05, 20 vs. 10 months; P = 0.028, respectively). DP with AOR was identified as independent prognostic factor of stage I and II PDAC by multivariate Cox regression analysis. Conclusions Distal pancreatectomy with AOR could be an acceptable surgical treatment for left-sided PDAC. However, AOR group shows poor prognosis than that of the standard group in patients with AJCC 8th stage I and II PDAC. AOR should be considered indicative of a more aggressive tumor in AJCC 8th stage I and II PDAC.

Recently, laparoscopic distal pancreatectomy (LDP) has become the standard procedure for resection of left-sided pancreatic tumors. Fluid collection (FC) at the resection margin of the pancreatic stump after LDP is a frequent radiological finding. However, there have been few treatment guidelines and the optimal management for this clinical finding is unclear. The aim of present study is to define the incidence of FC and suggest the optimal management for FC after LDP. A total of 1227 patients who underwent LDP between March 2005 and December 2015 were collected. FC was considered present when the longest diameter of the lesion on CT scan was > 3 cm. A follow-up with at least two CT image was available for 1102 patients. Of these, 689 (62.5%) patients showed initial fluid collection (IFC) at the pancreas resection site in immediate postoperative CT. IFC (+) group had higher proportion of men, BMI, and higher rate of concomitant splenectomy than IFC (−) group. Among patients with FC after LDP, the treatment group had more frequent leukocytosis and accompanying symptoms than the observation group. Seventy-seven patients underwent therapeutic interventions for FC after LDP. Among them, 55 (71.4%) patients underwent endoscopic ultrasonography-guided gastrocystostomy (EUS-GC). EUS-GC group had a higher success rate (85.6 vs. 63.6%, p

Purpose To evaluate the diagnostic performance of CT in the determination of pancreatic cancer resectability according to the National Comprehensive Cancer Network (NCCN) criteria to predict R0 resection. Materials and Methods Structured reports of pancreatic CT clinically prepared by board-certified abdominal radiologists from January 2014 to March 2017 were retrospectively reviewed to assess resectability (resectable, borderline resectable, or unresectable) according to NCCN criteria (version 1.2017) in 616 patients (369 men, 247 women; mean age, 63 years ± 10 [standard deviation]) with pancreatic cancer. Negative resection margin (R0) rates were assessed based on CT resectability status in patients who underwent upfront surgery. R0 resection-associated factors were identified by using logistic regression analysis. Results In 371 patients who underwent surgery, R0 resection rates were 73% (171 of 235), 55% (57 of 104), and 16% (five of 32) for resectable, borderline resectable, and unresectable disease, respectively (P < .001). At multivariable analysis, tumor diameter larger than 4 cm (P < .001) and abutment to the portomesenteric vein (P < .001) were significantly associated with margin-positive resection in patients with resectable disease at CT. R0 resection rates were 80% (123 of 154) for resectable disease without portomesenteric vein abutment, 59% (48 of 81) for resectable disease with portomesenteric vein abutment, 83% (57 of 69) for resectable disease 2 cm or smaller, and 29% (five of 17) for tumors larger than 4 cm. Conclusion CT resectability is used to stratify patients with pancreatic cancer according to the possibility of R0 resection. Larger tumor size and tumor abutment to the portomesenteric vein are associated with margin-positive resection in patients with resectable pancreatic cancer. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Fowler in this issue.

Simple Summary For decades, there has been no globally accepted neoadjuvant or adjuvant therapy in resectable biliary tract cancer. Based on the results of the BILCAP trial, adjuvant capecitabine has been widely regarded as standard adjuvant therapy. Focusing on the management of resectable biliary tract cancer, this article reviews each therapeutic strategy including surgery, chemotherapy and radiotherapy, and summarises published and ongoing clinical trials of neoadjuvant and adjuvant therapy. Abstract Biliary tract cancers (BTCs) are a group of aggressive malignancies that arise from the bile duct and gallbladder. BTCs include intrahepatic cholangiocarcinoma (IH-CCA), extrahepatic cholangiocarcinoma (EH-CCA), and gallbladder cancer (GBCA). BTCs are highly heterogeneous cancers in terms of anatomical, clinical, and pathological characteristics. Until recently, the treatment of resectable BTC, including surgery, adjuvant chemotherapy, and radiation therapy, has largely been based on institutional practice guidelines and evidence from small retrospective studies. Recently, several large randomized prospective trials have been published, and there are ongoing randomized trials for resectable BTC. In this article, we review prior and recently updated evidence regarding surgery, adjuvant and neoadjuvant chemotherapy, and adjuvant radiation therapy for patients with resectable BTC.

Background: Prediction of post-pancreaticoduodenectomy (PD) morbidity is difficult, especially in the early postoperative period when CT (Computed Tomography) scans are not available. Elevated serum amylase and lipase in postoperative day 0 or 1 may be used to define postoperative acute pancreatitis (POAP), but the existing literature does not agree on whether POAP is significantly associated with postoperative pancreatic fistula (POPF). Methods: We analyzed the data obtained from a previously published randomized controlled trial. POAP was defined as elevations in serum amylase above 110 U/L on postoperative day 0 or 1. Clinically relevant POAP (CR-POAP) was defined as elevations in C-reactive protein level (CRP) on postoperative day 2 in those with POAP. Postoperative complications including severe complications (Clavien–Dindo ≥ IIIa), POPF, and clinically relevant POPF (CR-POPF) were analyzed. Results: In 246 patients, POAP did not show significant associations with total postoperative complications (odds ratio (OR) 0.697, 95% CI, 0.360–1.313, p = 0.271), severe complications (OR 0.647, 95% CI, 0.258–1.747, p = 0.367), and CR-POPF (OR 0.998, 95% CI, 0.310–3.886, p = 0.998) in multivariable analysis. Conclusions: In patients undergoing PD, POAP was not significantly associated with postoperative complications including POPF. Caution should be taken when using POAP as a predictor of POPF.

Early recurrence in pancreatic ductal adenocarcinoma (PDAC) is a decisive factor in determining a patient's prognosis. We determined in our current study whether circulating tumour cells (CTCs) exist in the blood of PDAC patients and can be used as a predictor of recurrence patterns (i.e. time and site) after surgical resection. Between December 2017 and November 2018, the mononuclear cell layer was obtained from the peripheral blood of 36 patients diagnosed with PDAC. CTCs were then isolated using the CD-PRIME™ platform and detected via immunostaining. The patient records were analyzed to correlate these data with survival and recurrence patterns. Twelve patients were CTC-positive (33.3%) and showed a significantly frequent rate of systemic recurrence (distant metastases and peritoneal dissemination) (p = 0.025). On multi-variable logistic regression analysis, CTC positivity was an independent risk factor for early recurrence (p = 0.027) and for systemic recurrence (p = 0.033). In summary, the presence or absence of CTC in the blood of the patients with PDAC could help predict the recurrence pattern after surgery. PDAC patients with CTC positivity at tumour diagnosis should therefore undergo a comprehensive strategy for systemic therapy and active monitoring to detect possible early recurrence.

Supplemental Digital Content is available in the text, Pancreatectomy for pancreatic cancer with arterial invasion is controversial and performed infrequently. As its indication evolves and neoadjuvant chemotherapy also evolves, it is meaningful to identify short- and long-term outcomes of pancreatectomy with arterial resection (AR). This study aimed to retrospectively analyze the clinical outcomes of pancreatectomy with AR for pancreatic ductal adenocarcinoma. Patients with pancreatic ductal adenocarcinoma treated with pancreatectomy with AR at our institute between January 2000 and April 2017 were retrospectively reviewed. Operative outcome and survival were compared according to the presence of neoadjuvant chemotherapy. This study included 109 patients (38 underwent surgery after neoadjuvant chemotherapy, 71 underwent upfront surgery). The median hospital stay was 17 (interquartile range, 12–26.5) days. Clinically relevant postoperative pancreatic fistula (grade B or C) occurred in 14 patients (12.8%). The major morbidity (≥grade III) and mortality rates were 26.6% and 0.9%, respectively. R0 resection was achieved in 80 patients (73.4%). Microscopic actual tumor invasion into the arterial wall was identified in 25 patients (22.9%). The median overall survival (OS) of all patients was 18.4 months. The neoadjuvant chemotherapy group showed better OS than the upfront surgery group, without statistical significance (25.3 vs 16.2 months, P = .06). Progression-free survival was better in patients with neoadjuvant chemotherapy (13.2 vs 7.1 months, P = .01). Patients with partial response to neoadjuvant chemotherapy showed better OS than those with stable disease (33.7 vs 17.5 months, P = .04). Pancreatectomy with AR for advanced pancreatic cancer showed acceptable procedure-related morbidity and mortality. A survival benefit of neoadjuvant chemotherapy was identified, compared to upfront surgery.

Background: The aim of this study was to evaluate the safety and efficacy of a flowable hemostatic matrix, and their effects for postoperative pancreatic fistula (POPF) after pancreatectomy. Methods: This was a randomized, clinical, single-center, single-blind (participant), non-inferiority, phase IV, and parallel-group trial. The primary endpoint was the incidence of POPF. The secondary endpoints were risk factors for POPF, drain removal days, incidence of complication, 90-day mortality, and length of hospital stay. Results: This study evaluated a total of 53 patients, of whom 26 patients were in the intervention group (flowable hemostatic matrix) and 27 patients were in the control group (thrombin-coated collagen patch). POPF was more common in the control group than in the intervention group (59.3% vs. 30.8%, p = 0.037). Among participants who underwent distal pancreatectomy, POPF (33.3% vs. 92.3%, p = 0.004), and clinically relevant POPF (8.3% vs. 46.2%, p = 0.027) was more common in the control group. A multivariate logistic regression model identified flowable hemostatic matrix use as an independent negative risk factor for POPF, especially in cases of distal pancreatectomy (DP) (odds ratio 17.379, 95% confidential interval 1.453&ndash, 207.870, p = 0.024). Conclusion: Flowable hemostatic matrix application is a simple, feasible, and effective method of preventing POPF after pancreatectomy, especially for patients with DP. Non-inferiority was demonstrated in the efficacy of preventing POPF in the intervention group compared to the control group.

Objective: To propose a decision tool considering both malignancy probability and surgical risk for intraductal papillary mucinous neoplasm (IPMN). Background Data Summary: Surgical risk and malignancy probability are both critical factors in making decisions about surgical resection of IPMN. Methods: We included 800 patients who underwent pancreatic resection for branch duct and mixed-type IPMN (April 1995 to June 2018). A nomogram was used to obtain the malignancy probability (MP-N). The surgical risks were estimated as the postoperative complication rate and serious complication from the ACS NSQIP surgical risk calculator (SC-ACS NSQIP). The risk&ndash, benefit analysis was conducted in two ways: calculation of the cutoff value of MP-N using the complication rate and directly comparing the MP-N and SC-ACS NSQIP results. Results: The optimal cutoff value of MP-N was 32% and 21% in the pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) groups, respectively, when using the major complication rate (Clavien grades III over). When we applied the optimal cutoff value to the two surgical methods, surgery was reduced by 51.7% in the PD group and 56% in the DP group, and the AUC value of the malignant predictions were 0.7126 and 0.7615, respectively. According to the direct comparison of MP-N and SC-ACS NSQIP, surgery was reduced by 31.7%, and the AUC value of malignant prediction was 0.6588. Conclusion: Our risk&ndash, benefit analysis model considering both malignancy probability and surgical risk is relatively acceptable, and it may help surgeons and patients make treatment decisions for a disease with a broad spectrum of malignancy rates.

Postoperative abdominal fluid collections (PAFCs) are a potentially fatal complication of pancreatobiliary surgery. Endoscopic ultrasound (EUS)-guided drainage has recently been shown to be effective in treating PAFCs of more than 4 weeks old. Little is currently known, however, regarding the EUS-guided drainage of PAFCs of less than 4 weeks. This study assessed the efficacy and safety of the early drainage (

Background No preoperative model is available for predicting postsurgical prognosis of patients with resectable pancreatic ductal adenocarcinoma (PDAC). Purpose To develop and validate a preoperative risk scoring system using clinical and CT variables to predict recurrence-free survival (RFS) after upfront surgery in patients with resectable PDAC. Materials and Methods In this retrospective study, consecutive patients with resectable PDAC underwent upfront surgery from January 2014 to December 2015 (development set) and from January 2016 to January 2017 (test set). In the development set, multivariable Cox proportional hazard modeling with bootstrapping was used to select clinical and CT variables associated with RFS and to construct a risk scoring system. The discrimination capability of the risk score was assessed by using the Harrell C-index and compared with that of pathologic American Joint Committee on Cancer tumor stage. The risk score was validated in the test set. Results A total of 395 patients were evaluated, including 262 patients (mean age ± standard deviation, 64 years ± 10; 155 men) in the development set and 133 (mean age, 64 years ± 9; 79 men) in the test set. Five independent variables predicted risk of recurrence or death: tumor size (hazard ratio [HR], 1.23; 95% confidence interval [CI]: 1.05, 1.44; P = .009), hypodense tumor in the portal venous phase (HR, 1.66; 95% CI: 1.01, 2.73; P = .04), tumor necrosis (HR, 2.04; 95% CI: 1.38, 3.03; P < .001), peripancreatic tumor infiltration (HR, 1.50; 95% CI: 1.07, 2.11; P = .02), and suspicious metastatic lymph nodes (HR, 1.94; 95% CI: 1.38, 2.72; P < .001). In the test set, the risk score showed good discrimination capability (C-index of 0.68; 95% CI: 0.63, 0.74) and outperformed the pathologic tumor stage (C-index of 0.60; 95% CI: 0.55, 0.66; P = .03). Patients were categorized into favorable, intermediate, and poor prognosis groups with 1-year RFS of 0.87, 0.58, and 0.26, respectively. Conclusion The presented preoperative risk score can predict recurrence-free survival after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Pandharipande and Anderson in this issue.

The prognosis for patients with pancreatic cancer is extremely poor, as they are resistant to first line chemotherapy. The long-term goal of this study was to identify effective combination chemotherapy for pancreatic cancer using pancreatic cancer surgical specimens in the histoculture drug response assay (HDRA) based on three-dimensional culture of tumour fragments, which maintains nature tumour histology in vitro. From 2015 to 2017, the HDRA was performed with tumour specimens from 52 pancreatic cancer patients from Asan Medical Hospital. First, combination drug regimens showed higher drug efficacy and less patient variation than single drugs. Initially, 5-Fluorouracil(5-FU)/Belotecan/Oxaliplatinum and Tegafur/Gimeracil (TS-1)/Oxaliplatinum/Irinotecan were found to be effective. Second, we were able to correlate the efficacy of some drugs with tumour stage. Third, when designing new combination regimens containing 5-FU or gemcitabine, we could identify more effective drug combinations. This is the first study to demonstrate usefulness of the HDRA for pancreatic cancer. Using this technique, we could identify novel candidate combination drug regimens that should be effective in treating pancreatic cancer.

Several studies have compared laparoscopic pancreaticoduodenectomy (LPD) and open pancreaticoduodenectomy (OPD) in patients with periampullary carcinoma, however, only a few studies have made such a comparison on patients with ampulla of Vater cancer (AVC). We compared the perioperative and oncologic outcomes between LPD and OPD in patients with AVC using propensity-score-matched analysis. A total of 359 patients underwent PD due to AVC during the study period (76 LPD, 283 OPD). After propensity score matching, the LPD group showed significantly longer operation time than did the OPD group (400.2 vs. 344.6 min, p &lt, 0.001). Nevertheless, the LPD group had fewer painkiller administrations (8.3 vs. 11.1, p &lt, 0.049), fewer Grade II or more severe postoperative complications (15.9% vs. 34.8%, p = 0.012), and shorter postoperative hospital stays (13.7 vs. 17.3 days, p = 0.048), compared with the OPD group. There was no significant difference in recurrence-free outcomes and overall survival between the two groups (p = 0.754 and 0.768, respectively). Compared with OPD, LPD for AVC had comparative oncologic outcomes with less pain, less postoperative morbidity, and shorter hospital stays. LPD may serve as a promising alternative to OPD in patients with AVC.

Background: The association between optimal carbohydrate antigen (CA) 19-9 concentration after neoadjuvant chemotherapy (NACT) and prognosis has not been confirmed in patients with borderline resectable (BRPC) and locally advanced pancreatic cancer (LAPC). Methods: This retrospective study included 122 patients with BRPC and 103 with LAPC who underwent surgery after NACT between 2012 and 2019 in a tertiary referral center. Prognostic models were established based on relative difference of the CA 19-9 (RDC), with their prognostic performance compared using C-index and Akaike information criterion (AIC). Results: CA 19-9 concentrations of 37&ndash, 1000 U/mL before NACT showed prognostic significance in patients with BRPC and LAPC (hazard ratio [HR]: 0.262, 95% confidence interval [CI]: 0.092&ndash, 0.748, p = 0.012). Prognostic models in this subgroup showed that RDC was independently prognostic of better overall survival (HR: 0.262, 95% CI: 0.093&ndash, 0.739, p = 0.011) and recurrence free survival (HR: 0.299, 95% CI: 0.140&ndash, 0.642, p = 0.002). The prognostic performances of RDC (C-index: 0.653, AIC: 227.243), normalization of CA 19-9 after NACT (C-index: 0.625, AIC: 230.897) and surgery (C-index: 0.613, AIC: 233.114) showed no significant differences. Conclusion: RDC was independently associated with better prognosis after NACT in patients with BRPC or LAPC. Decreased CA19-9 after NACT was a prognostic indicator of better survival and recurrence, as was normalization of CA 19-9 after both NACT and surgery.

BACKGROUND Although lymph node metastasis is a poor prognostic factor in patients with pancreatic ductal adenocarcinoma (PDAC), our understanding of lymph node size in association with PDAC is limited. Increased nodal size in preoperative imaging has been used to detect node metastasis. We evaluated whether lymph node size can be used as a surrogate preoperative marker of lymph node metastasis. METHODS We assessed nodal size and compared it to the nodal metastatic status of 200 patients with surgically resected PDAC. The size of all lymph nodes and metastatic nodal foci were measured along the long and short axis, and the relationships between nodal size and metastatic status were compared at six cutoff points. RESULTS A total of 4,525 lymph nodes were examined, 9.1% of which were metastatic. The mean size of the metastatic nodes (long axis, 6.9±5.0 mm; short axis, 4.3±3.1 mm) was significantly larger than that of the non-metastatic nodes (long axis, 5.0±4.0 mm; short axis, 3.0±2.0 mm; all p

Background In surgery for perihilar cholangiocarcinoma (PHCC), it is still controversial as to whether additional resection of the bile duct is needed on high grade (HG) biliary intraepithelial neoplasia (BilIN) margin. Methods Patients who underwent surgery for PHCC with curative intent between 2001 and 2015 were stratified by resection margin, and were analyzed comparing the clinical outcomes. Results Of the 306 study participants, 217 patients had negative margins (R0), 18 patients had HG BilIN, and 71 patients had positive margins (R1). The median overall survival was 36.0 months in the R0 group, 41.0 months in the HG BilIN group, and 25.0 months in the R1 group while overall survival rates at 5 years were 34.5% in the R0 group, 44.4% in the HG BilIN group, and 21.0% in the R1 group. The median disease-free survival was 15.0 months in the R0 group, 16.5 months in the HG BilIN group, and 12.0 months in the R1 group. Conclusions Although the HG BilIN group had neoplasia with malignant potential, survival and recurrence outcomes were comparable to those of the R0 group, which suggests that no additional resection is needed when the maximal bile duct margin in PHCC surgery contains HG BilIN.

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

OBJECT The objectives are to investigate the incidence and risk factors associated with symptomatic marginal ulcer (sMU) and analyze their relationship with the use of prophylactic proton pump inhibitors (PPIs) after pancreaticoduodenectomy. METHODS Clinical postoperative outcomes of 72 sMU and 1266 non-sMU were compared and analyzed. We performed a subanalysis of 72 patients with sMU diagnosed within (n = 18) and after 4 months (n = 54). The risk factors associated with sMU incidence were analyzed. RESULTS Of the 1338 patients, 72 (5.4%) were diagnosed as having sMU. Eighteen patients (25.0%) were diagnosed during the first 4 months, and 48 (66.7%), within 16 months. Cumulative sMU incidence differed according to the duration of prophylactic PPI use (≥4 months: 7.1% vs

Background The endovascular treatment is the first-line therapy for late massive arterial haemorrhage after pancreaticoduodenectomy (PD). This study aimed to evaluate the clinical features and outcomes of patients who experienced pseudoaneurysm (PA) bleeding after PD and treated with transcatheter arterial embolization (TAE) and stent-graft placement (SGP). Methods A total of 37 patients (TAE = 16, stent graft = 16, both = 5) had an endovascular treatment due to hepatic artery PA bleeding after PD at our institution from January 2008 to December 2018. Results There were 35 men and two women with a mean age of 62 years (range 45-82 years). The latency of bleeding ranged from postoperative days 3 to 46 (median day 21). The most common site of bleeding was gastroduodenal artery stump (n = 22). In TAE group (n = 16), the technical success rate was 100% and the clinical success rate was 87.5%. In SGP group (n = 16), the technical and clinical success rates were 100% and 93.8%. Five patients underwent SGP and TAE simultaneously; TAE was performed to prevent endoleak. A total of three patients experienced hepatic ischaemia (TAE = 2, SGP = 1). However, there was no statistically significant difference of hepatic ischaemia occurrence between the two groups P = 0.55). Conclusions In patients with suspected PA, urgent angiography should be considered immediately for diagnosis and treatment. The SGP can be performed first if it is technically feasible. However, TAE is also a safe and effective treatment in patients with intact portal flow, as well as those with preserved collateral pathways after hepatobiliary surgery.

PurposeThis study was conducted to evaluate the prognostic values of the 7th and 8th American Joint Committee on Cancer (AJCC) staging systems for patients with resected perihilar cholangiocarcinoma (PHCC).Materials and MethodsA total of 348 patients who underwent major hepatectomy for PHCC between 2008 and 2015 were identified from a single center. Overall survival (OS) was estimated using the Kaplan-Meier method and compared across stage groups with the log-rank test. The concordance index was used to evaluate the prognostic predictability of the 8th AJCC staging system compared with that of the 7th.ResultsIn the 8th edition, the stratification of each group of T classification improved compared to that in the 7th, as the survival rate of T4 decreased (T2, 31.2%; T3, 13.9%; T4, 15.1%; T1- T2, p=0.260; T2-T3, p=0.001; T3-T4, p=0.996). Both editions showed significant survival differences between each N category, except between N1 and N2 (p=0.063) in 7th edition. Differences of point estimates between the 8th and 7th T and N classification and overall stages were +0.028, +0.006, and +0.039, respectively (T, p=0.005; N, p=0.115; overall stage, p=0.005). In multivariable analysis, posthepatectomy liver failure, T category, N category, distant metastasis, histologic differentiation, intraoperative transfusion, and resection margin status were associated with OS.ConclusionThe prognostic predictability of 8th AJCC staging for PHCC improved slightly, with statistical significance, compared to the 7th edition, but its overall performance is still unsatisfactory.

Most models for predicting malignant pancreatic intraductal papillary mucinous neoplasms were developed based on logistic regression (LR) analysis. Our study aimed to develop risk prediction models using machine learning (ML) and LR techniques and compare their performances. This was a multinational, multi-institutional, retrospective study. Clinical variables including age, sex, main duct diameter, cyst size, mural nodule, and tumour location were factors considered for model development (MD). After the division into a MD set and a test set (2:1), the best ML and LR models were developed by training with the MD set using a tenfold cross validation. The test area under the receiver operating curves (AUCs) of the two models were calculated using an independent test set. A total of 3,708 patients were included. The stacked ensemble algorithm in the ML model and variable combinations containing all variables in the LR model were the most chosen during 200 repetitions. After 200 repetitions, the mean AUCs of the ML and LR models were comparable (0.725 vs. 0.725). The performances of the ML and LR models were comparable. The LR model was more practical than ML counterpart, because of its convenience in clinical use and simple interpretability.

Background To identify chronologic changes in clinical and survival features of pancreatic ductal adenocarcinoma based on diagnosis and treatment strategy development since 2000. Methods Among 2,029 patients enrolled in this study, 746 and 1,283 were treated between 2000 and 2009 (group 1) and between 2010 and 2016 (group 2), respectively. We used patient clinicopathologic, biologic, and molecular factors to assess the prognostic factors. Results Group 2 had a better survival outcome than group 1 (median survival time: 24.9 versus 18.4 months; 5-year survival rate: 27.6% versus 22.3%). The tendency for early diagnosis (lower CA19-9 levels, smaller size, and earlier T stage), use of neoadjuvant chemotherapy, decreased morbidity, early recovery (lesser hospital stay and more minimally invasive surgery), and standardization of surgical techniques appeared to improve patient survival. Multivariable analysis for prognosis revealed that tumor biologic factors (increased preoperative serum CA19-9 level, tumor size, tumor differentiation, N stage, and presence of lymphovascular invasion), operational factors (status of the resection margin, type of operation, and year of operation), and genetic factors (K-ras mutations) correlated with patient survival. Conclusion Early diagnosis and combined efforts, such as neoadjuvant chemotherapy and an established system of patient care, have gradually enhanced patient survival after operative resection for pancreatic ductal adenocarcinoma. Hence, multiplex prognostic parameters could provide additional information for improved prognostic estimation of pancreatic cancer exhibiting heterogeneous results.

The clinicopathologic characteristics of duodenal gastrointestinal stromal tumor (GIST) were unclear and the optimal surgical procedure for duodenal GIST remains poorly defined. We aimed to analyze clinicopathological characteristics, survival outcomes based on the surgical procedure, and recommend optimal surgical treatment for duodenal GIST. From July 2000 to April 2017, 118 patients with localized duodenal GIST underwent curative surgical resection at a single institution. We retrospectively reviewed the clinicopathological characteristics and survival outcomes. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 94.9 and 79.2%, respectively. On multivariate analysis, the mitotic count was a statistically significant prognostic factor for DFS. Limited resection (LR) was performed in 20 patients with GIST in the first or fourth portion of the duodenum. Both LR and pancreaticoduodenectomy (PD) were performed in 98 patients with GIST in second or third portion of the duodenum. The patients in the LR group had less late complications than in the PD group and no postoperative newly developed diabetes mellitus. The minimally invasive LR (MI-LR) group had a shorter duration of surgery and shorter length of postoperative hospital stay. LR is a feasible and effective surgical treatment for patients with small-sized and antimesenteric-sided duodenal GIST in terms of late complications and postoperative diabetic complications. MI-LR has better perioperative outcomes than open LR. Therefore, we should consider MI-LR as an optimal surgical treatment for selected patients with duodenal GIST.

Well-differentiated pancreatic neuroendocrine neoplasms/tumors (PanNETs) are rare neoplasms with diverse clinical behavior. Biomarker discovery is important for predicting clinical course and prognosis of PanNET patients. Carbonic anhydrase 9 (CA9) and vimentin are hypoxia and epithelial-mesenchymal transition-related proteins of which expression in many carcinomas has been associated with poor prognosis, but their significance in PanNET has yet to be determined. We assessed CA9 and vimentin expression in 164 PanNETs and compared this with clinicopathologic characteristics. CA9 expression was observed in normal islets, while neuroendocrine microadenomas and small (

We aimed to examine the predictive value of changes in perioperative carbohydrate antigen (CA) 19-9 levels for patients operated for perihilar cholangiocarcinoma (pCCA). A total of 322 patients who underwent curative resection for pCCA were divided into three groups: normal preoperative CA19-9 (CA19-9 ≤ 37 U/mL), normalization (preoperative CA19-9 &gt, 37 U/mL, postoperative CA19-9 ≤ 37 U/mL), and non-normalization (pre- and postoperative CA19-9 &gt, 37 U/mL) groups. The association of clinicopathological factors with overall survival (OS) was investigated. The non-normalization group (n = 82) demonstrated significantly worse OS than the normal CA19-9 (n = 114) and normalization (n = 126) groups (5-year OS, 16.9%, 29.4%, and 34.4%, respectively, both p ≤ 0.001). The cutoff points of 300 U/mL for preoperative (p = 0.001) and 37 U/mL for postoperative (p &lt, 0.001) CA19-9 levels showed the strongest prognostic values. In the non-normalization group, patients who underwent R1 resection displayed significantly worse OS than those who underwent R0 resection (median OS, 10.2 vs. 15.7 months, p = 0.016). Multivariate analysis revealed that lymph node metastasis (hazard ratio (HR), 2.07, p &lt, 0.001), postoperative CA19-9 &gt, 37 U/mL (HR, 1.94, 0.001), transfusion (HR, 1.74, p = 0.002), and T stage (T3,4) (HR, 1.67, p = 0.006) were related to worse OS. Persistent high CA19-9 level after resection of pCCA and R1 resection, especially in the non-normalization group, was associated with poor OS. A high postoperative CA19-9 level was an independent prognostic factor in resected pCCA.

Background Surgical resection is the only curative option in patients with pancreatic ductal adenocarcinoma. Little is known about the oncologic outcomes of laparoscopic distal pancreatectomy. This bi-institutional study aimed to examine the long-term oncologic results of standard laparoscopic distal pancreatectomy in a large cohort of patients with pancreatic ductal adenocarcinoma. Methods From January 2002 to March 2016, 207 patients underwent standard laparoscopic distal pancreatectomy for pancreatic ductal adenocarcinoma at Oslo University Hospital-Rikshospitalet (Oslo, Norway) and Asan Medical Centre (Seoul, Republic of Korea). After the exclusion criteria were applied (distant metastases at operation, conversion to an open operation, loss to follow-up), 186 patients were eligible for the analysis. Perioperative and oncologic variables were analyzed for association with recurrence and survival. Results Median overall and recurrence-free survivals were 32 and 16 months, while 5-year overall and recurrence-free survival rates were estimated to be 38.2% and 35.9%, respectively. Ninety-six (52%) patients developed recurrence: 56 (30%) extrapancreatic, 27 (15%) locoregional, and 13 (7%) combined locoregional and extrapancreatic. Thirty-seven (19.9%) patients had early recurrence (within 6 months of operation). In the multivariable analysis, tumor size >3 cm and no adjuvant chemotherapy were associated with early recurrence ( P = .017 and P = .015, respectively). The Cox regression model showed that tumor size >3 cm and lymphovascular invasion were independent predictors of decreased recurrence-free and overall survival. Conclusion Standard laparoscopic distal pancreatectomy is associated with satisfactory long-term oncologic outcomes in patients with pancreatic ductal adenocarcinoma. Several risk factors, such as tumor size >3 cm, no adjuvant chemotherapy, and lymphovascular invasion, are linked to poor prognosis after standard laparoscopic distal pancreatectomy.

OBJECTIVES This study aims to identify the computed tomography (CT) features that may differentiate nonfunctioning pancreatic neuroendocrine tumors (NF-PanNETs) with lymph node (LN) metastasis from NF-PanNETs without lymph node metastasis. METHODS We retrospectively analyzed 166 NF-PanNETs in 166 patients who had undergone surgical resection (median age, 53). Two radiologists evaluated the qualitative and quantitative CT findings. Through univariate and multivariate logistic regression analyses, we determined independent significant findings for differentiating NF-PanNETs with LN metastasis from NF-PanNETs without LN metastasis. Recurrence-free survival (RFS) and overall survival (OS) were compared between the 2 groups using Kaplan-Meier analysis and log-rank testing. RESULTS Of the 166 NF-PanNETs, 24 (14.5%) tumors demonstrated LN metastasis. Three CT findings, radiologic LN enlargement (adjusted odds ratio [OR], 11.76; P = 0.001), liver metastasis (OR, 10.31; P = 0.027), and portal enhancement ratio of

Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy. Analyses for germline BRCA mutations were performed if patients had one or more first-degree or second-degree relatives with breast or ovarian cancers or had a personal medical history of these diseases. DNA was extracted from whole blood, and all coding exons and their flanking intron regions of BRCA1 and BRCA2 were sequenced. Results A total of 175 patients were screened for personal and family history and 10 (5.7%) met the inclusion criteria for genetic sequencing. Pathogenic germline BRCA2 mutation [c.7480C>T (p.Arg2494*)] was identified in one male patient, resulting in a frequency of 10% for the risk-stratified patients and 0.6% for the unselected PDAC population. Two patients had germline BRCA2 variants of uncertain significance [c.1744A>C (p.Thr582Pro) and c.68-7T>A]. Conclusion Personal or family history of breast or ovarian cancers is a feasible, cost-effective risk categorization for screening germline BRCA mutations in Asian PDAC patients as 10% of this population had the pathogenic mutation herein. Future validation from a large, prospective cohort is needed.

OBJECTIVE Given the rarity of the disease, the post-resection clinical course of localized pancreatic acinar cell carcinoma (ACC) is largely unknown. Therefore, we aimed to analyze the outcomes of patients with localized pancreatic ACC who underwent curative surgical resection. METHODS We retrospectively analyzed the outcomes of 20 patients with resectable pancreatic ACC who underwent surgery. RESULTS Altogether 20 patients were included in the study, with a median age of 57 years and a male predominance. There were eight pure ACC, 10 mixed acinar–neuroendocrine carcinomas and two mixed acinar–ductal adenocarcinomas. Among the 15 patients who were staged histologically, 3, 8 and 4 were at stages IB, IIA and IIB, respectively. Eleven patients received adjuvant chemotherapy (5-fluorouracil-based [n = 9]; gemcitabine [n = 1]; etoposide plus cisplatin [n = 1]). In a median follow-up period of 27.1 months, disease recurred in 10 patients, most commonly in the liver (90%). Median recurrence-free survival and overall survival were 16.9 months and 75.0 months, respectively. Elevation of cancer antigen 19-9 (CA19-9), lymph node metastasis and neural invasion were significantly associated with poor overall survival (P = 0.007, P = 0.027 and P = 0.016, respectively). CONCLUSIONS Compared with ductal adenocarcinoma, resectable pancreatic ACC has a favorable prognosis after surgery. Considering that distant metastasis is the most common pattern of recurrence, further studies are necessary to define the role of adjuvant chemotherapy for improving survival outcomes.

BACKGROUND Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic neoplasms and there is no well-elucidated biomarker to stratify their detection and prognosis. Previous studies have reported that progesterone receptor (PR) expression status was associated with poorer survival in PanNET patients. METHODS To validate previous studies, PR protein expression was assessed in 21 neuroendocrine microadenomas and 277 PanNETs and compared with clinicopathologic factors including patient survival. RESULTS PR expression was gradually decreased from normal islets (49/49 cases, 100%) to neuroendocrine microadenoma (14/21, 66.6%) to PanNETs (60/277, 21.3%; p < .001). PanNETs with loss of PR expression were associated with increased tumor size (p < .001), World Health Organization grade (p = .001), pT classification (p < .001), perineural invasion (p = .028), lymph node metastasis (p = .004), activation of alternative lengthening of telomeres (p = .005), other peptide hormonal expression (p < .001) and ATRX/DAXX expression (p = .015). PanNET patients with loss of PR expression (5-year survival rate, 64.1%) had significantly poorer recurrence-free survival outcomes than those with intact PR expression (90%) by univariate (p = .012) but not multivariate analyses. Similarly, PanNET patients with PR expression loss (5-year survival rate, 76%) had significantly poorer overall survival by univariate (p = .015) but not multivariate analyses. CONCLUSIONS Loss of PR expression was noted in neuroendocrine microadenomas and was observed in the majority of PanNETs. This was associated with increased grade, tumor size, and advanced pT and pN classification; and was correlated with decreased patient survival time by univariate but not multivariate analyses. Loss of PR expression can provide additional information on shorter disease-free survival in PanNET patients.

Borderline resectable pancreatic cancer (BRPC) is a potentially resectable disease but is associated with poorer survival compared to primary resectable disease. There has been no prospective trial that compare the efficacy of FOLFIRNOX and gemcitabine-based regimen for BRPC. Between February 2013 and December 2014, 18 patients with BRPC receiving FOLFIRINOX were reviewed retrospectively. For comparative analysis, data for all BRPC patients (n=18) in our previous phase 2 study of neoadjuvant fixed-dose rate-gemcitabine plus capecitabine were pooled. Patients received a median 6 cycles (range, 3-13) of FOLFIRINOX. Surgical resection was performed in 12 patients (67%) and R0 resection in 9 patients. Median progression-free survival (PFS) and overall survival (OS) were 16.8 (95% confidence interval [CI], 9.4-24.2) and 21.2 (95% CI, 14.2-28.2) months, respectively. Patients who underwent surgical resection showed significantly better PFS (p=0.01) and OS (p=0.003) than those unresected. In the exploratory analysis, patients receiving FOLFIRINOX showed significantly longer PFS compared to those receiving fixed-dose rate-gemcitabine plus capecitabine (median 16.8 months [95% CI, 9.4-24.2] vs. 6.5 months [1.6-11.3]; p = 0.04). There was a trend toward improved OS in patients who received FOLFIRINOX (median 21.2 months [95% CI, 14.2-28.2]) compared to those who received fixed-dose rate-gemcitabine plus capecitabine (13.6 months [11.8-15.4]; p=0.12). FOLFIRINOX was feasible and effective as neoadjuvant chemotherapy for patients with BRPC and may have improved efficacy compared to a gemcitabine-based regimen.

The present study aimed to elucidate whether the stemness molecule, CD133, is expressed in well-differentiated pancreatic neuroendocrine tumors (PanNETs; World Health Organization grades 1 and 2) and establish its clinical relevance using 2 separate cohorts. In the first series (n = 178) in which tissue microarrays were available, immunohistochemistry revealed that CD133 was expressed in 14 cases (8%). CD133+ PanNETs had higher TNM stages (P < .01), more frequent lymphovascular invasion (P = .01), and higher recurrence rates (P = .01). In the second cohort (n = 56), the expression of CD133 and CK19 was examined in whole tissue sections. CD133 and CK19 were positive in 10 (18%) and 36 (64%) cases, respectively. CD133 expression correlated with higher pT scores (P < .01), the presence of microscopic venous infiltration (P = .03), and shorter disease-free periods (P < .01). When cases were divided into grade 1 and 2 neoplasms, patients with CD133+ PanNET continued to have shorter disease-free periods than did those with CD133- tumors in both groups (P < .01 and P = .02, respectively). Although CK19+ cases had shorter disease-free periods than did CK19- cases in the whole cohort (P = .02), this difference was less apparent in subanalyses of grade 1 and 2 cases. CD133 expression also appeared to be an independent predictive factor for tumor recurrence in a multivariate analysis (P = .018). The CD133 phenotype was identical between primary and metastatic foci in 17 of 18 cases from which tissues of metastatic deposits were available. In conclusion, the combination of CD133 phenotyping and World Health Organization grading may assist in stratifying patients in terms of the risk of progressive clinical courses.

Aim To analyze the outcomes in pancreatic cancer (PC) cases with a microscopically-positive resection margin (R1 resection) treated with postoperative radiotherapy (PORT). Patients and methods We retrospectively analyzed the outcomes in 62 patients who received PORT for PC with R1 resection between 2001 and 2012. All patients received three-dimensional conformal radiotherapy. Concurrent chemotherapy was administered to 58 patients. Results The median follow-up was 20.1 months. The median survival was 22.0 months and the 3-year overall survival rate was 25%. The 3-year disease-free survival and local recurrence-free survival rates were 12% and 54%, respectively. Local recurrence occurred in 23 patients (44%), distant failure in 45 (87%), and both in 16 (31%). By multivariate analysis, the postoperative cancer antigen 19-9 (CA19-9) level and adjuvant chemotherapy were independent prognostic factors for survival. Conclusion PORT is associated with a relatively favorable survival outcome in PC with R1 resection. Chemotherapy and postoperative CA19-9 level were significant prognostic factors for survival.

To compare perioperative and oncologic outcomes of pure (totally) laparoscopic pancreaticoduodenectomy (TLPD) or robot-assisted pancreaticoduodenectomy (RAPD) with those of conventional open pancreaticoduodenectomy (OPD). A systematic literature search was performed using PubMed, EMBASE, and Cochrane library databases. Studies comparing TLPD with OPD and RAPD with OPD were included; only original studies reporting more than 10 cases for each technique were included. Studies were combined using a random-effects model to report heterogeneous data, or a fixed-effects model was applied. TLPD involved longer operative time (weighted mean difference [WMD]: 116.85 min; 95% confidence interval [CI] 54.53–179.17) and significantly shorter postoperative hospital stay (WMD: −3.68 days; 95% CI −4.65 to −2.71). Overall morbidity and postoperative pancreatic fistula were not significantly different between TLPD and OPD. RAPD was associated with a longer operative time, less intraoperative blood loss, and shorter hospital stay. Oncologic outcomes were not significantly different among the procedure types. Compared to OPD, TLPD and RAPD were feasible and oncologically safe procedures. However, there are no prospective studies, and the majority of the studies on TLPD and RAPD have remained in the early training phase. In addition to randomized controlled trials or prospective studies, new data from the late training phase of learning experiences should also be analyzed.

Background & Aims Levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA-125) in blood are used as markers to determine the response of patients with cancer to therapy, but are not used to identify patients with pancreatic cancer. Methods We obtained blood samples from 504 patients undergoing pancreatic surveillance from 2002 through 2018 who did not develop pancreatic cancer and measured levels of the tumor markers CA19-9, CEA, CA-125, and thrombospondin-2. Single-nucleotide polymorphisms (SNPs) in FUT3, FUT2, ABO, and GAL3ST2 that have been associated with levels of tumor markers were used to establish SNP-defined ranges for each tumor marker. We also tested the association between additional SNPs (in FUT6, MUC16, B3GNT3, FAM3B, and THBS2) with levels of tumor markers. To calculate the diagnostic specificity of each SNP-defined range, we assigned the patients under surveillance into training and validation sets. After determining the SNP-defined ranges, we determined the sensitivity of SNP-adjusted tests for the tumor markers, measuring levels in blood samples from 245 patients who underwent resection for pancreatic ductal adenocarcinoma (PDAC) from 2010 through 2017. Results A level of CA19-9 that identified patients with PDAC with 99% specificity had 52.7% sensitivity. When we set the cut-off levels of CA19-9 based on each SNP, the test for CA19-9 identified patients with PDAC with 60.8% sensitivity and 98.8% specificity. Among patients with FUT3 alleles that encode a functional protein, levels of CA19-9 greater than the SNP-determined cut-off values identified 66.4% of patients with PDAC, with 99.3% specificity. In the validation set, levels of CEA varied among patients with vs without SNP in FUT2, by blood group, and among smokers vs nonsmokers; levels of CA-125 varied among patients with vs without the SNP in GAL3ST2. The use of the SNPs to define the ranges of CEA and CA-125 did not significantly increase the diagnostic accuracy of the assays for these proteins. Combining data on levels of CA19-9 and CEA, CA19-9 and CA-125, or CA19-9 and thrombospondin-2 increased the sensitivity of detection of PDAC, but slightly reduced specificity. Conclusions Including information on SNPs associated with levels of CA19-9, CEA, and CA-125 can improve the diagnostic accuracy of assays for these tumor markers in the identification of patients with PDAC. Clinicaltrials.gov no: NCT02000089 .

BACKGROUND/PURPOSE Clinical outcomes of octogenarians with acute cholecystitis treated with laparoscopic cholecystectomy are unclear. This study aimed to compare their outcomes according to preoperative severity and comorbidities. METHODS Medical charts of 120 octogenarians who underwent laparoscopic cholecystectomy for acute cholecystitis between January 2008 and December 2017 at Asan Medical Center, Seoul, Korea, were retrospectively reviewed. Based on the Tokyo Guidelines 2018 (TG 18), patients had mild (n = 35), moderate (n = 61), or severe (n = 24) disease. We investigated postoperative outcomes, comorbidities, and prognostic factors of ≥grade III complications. RESULTS Total antibiotic use duration (P = .024), operative times (P = .002), additional port insertion (P = .012), and postoperative hospital stay (P = .018) were significantly higher in the severe group. There were no statistically significant differences in total or grade III or higher complications (P = .304) or mortality (P = .476). On multivariate analysis, pulmonary disease predicted Clavien-Dindo classification ≥grade III complications (odds ratio 37.075; 95% confidence interval 5.734-239.695; P

There is little evidence on the safety and benefits of laparoscopic pancreaticoduodenectomy (LPD) in elderly patients; therefore, we evaluated the feasibility and efficacy of this procedure by comparing perioperative and oncological outcomes between LPD and open pancreaticoduodenectomy (OPD) in elderly patients. We retrospectively reviewed the data of 1,693 patients who underwent PD to manage periampullary tumours at a single institution between January 2014 and June 2017. Of these patients, 326 were elderly patients aged ≥70 years, with 56 patients allocated to the LPD group and 270 to the OPD group. One-to-one propensity score matching (56:56) was used to match the baseline characteristics of patients who underwent LPD and OPD. LPD was associated with significantly fewer clinically significant postoperative pancreatic fistulas (7.1% vs. 21.4%), fewer analgesic injections (10 vs. 15.6 times; p = 0.022), and longer operative time (321.8 vs. 268.5 minutes; p = 0.001) than OPD in elderly patients. There were no significant differences in 3-year overall and disease-free survival rates between the LPD and OPD groups. LPD had acceptable perioperative and oncological outcomes compared with OPD in elderly patients. LPD is a reliable treatment option for elderly patients with periampullary tumours.