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Purpose: Radical antegrade modular pancreatosplenectomy (RAMPS) has been reported to achieve high rates of a negative margin and resected metastatic lymph nodes. However, many studies have used historical controls and the results remain controversial. We conducted this study to compare the surgical and long-term outcomes of RAMPS vs. conventional distal pancreatectomy (DP)., Methods: The subjects of this multicenter retrospective study were 106 patients who underwent curative resection for left-sided pancreatic cancer between 2012 and 2017. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using Kaplan-Meier estimates., Results: The RAMPS group had more advanced T (T3/T4) and N stages (N1/N2) and a larger tumor size than the conventional group (T stage, p = 0.04; N stage, p = 0.02; tumor size, p = 0.04). The RAMPS group had more harvested metastatic lymph nodes (p = 0.02). After propensity-score matching, 37 patients from each group were included in the final analysis. There was no significant difference in RFS (p = 0.463) or OS (p = 0.383) between the groups. Multivariate analyses revealed the completion of chemotherapy to be an independent factor for RFS and OS (both p < 0.001)., Conclusions: There was no difference in the RFS or OS between RAMPS and conventional DP in this series. RAMPS may be an option for R0 resection of advanced tumors; however, postoperative chemotherapy has a greater influence than the surgical procedure on the prognosis of patients with pancreatic cancer., (© 2021. Springer Nature Singapore Pte Ltd.)

Objective: The aim of this study was to evaluate whether neoadjuvant therapy (NAT) critically influenced microscopically complete resection (R0) rates and long-term outcomes for patients with pancreatic ductal adenocarcinoma who underwent pancreatoduodenectomy (PD) with portomesenteric vein resection (PVR) from a diverse, world-wide group of high-volume centers., Summary of Background Data: Limited size studies suggest that NAT improves R0 rates and overall survival compared to upfront surgery in R/BR-PDAC patients., Methods: This multicenter study analyzed consecutive patients with R/BR-PDAC who underwent PD with PVR in 23 high-volume centers from 2009 to 2018., Results: Data from 1192 patients with PD and PVR were collected and analyzed. The median age was 68 [interquartile range (IQR) 60-73] years and 52% were males. Some 186 (15.6%) and 131 (10.9%) patients received neoadjuvant chemotherapy (NAC) alone and neoadjuvant chemoradiotherapy, respectively. The R0/R1/R2 rates were 57%, 39.3%, and 3.2% in patients who received NAT compared to 46.6%, 49.9%, and 3.5% in patients who did not, respectively (P =0.004). The 1-, 3-, and 5-year OS in patients receiving NAT was 79%, 41%, and 29%, while for those that did not it was 73%, 29%, and 18%, respectively (P <0.001). Multivariable analysis showed no administration of NAT, high tumor grade, lymphovascular invasion, R1/R2 resection, no adjuvant chemotherapy, occurrence of Clavien-Dindo grade 3 or higher postoperative complications within 90 days, preoperative diabetes mellitus, male sex and portal vein involvement were negative independent predictive factors for OS., Conclusion: Patients with PDAC of the pancreatic head expected to undergo venous reconstruction should routinely be considered for NAT., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: With continued technical advances in surgical instruments and growing expertise, several surgeons have performed laparoscopic pylorus preserving pancreaticoduodenectomy (L-PPPD) safely with good results, and the laparoscopic approach is being performed more frequently. We performed over 100 cases of L-PPPD and compared their outcomes to those of open PPPD (O-PPPD) using the large sample size. The aim of the present study was to evaluate the safety and feasibility of L-PPPD compared with O-PPPD., Methods: From September 2012 to June 2017, PPPD was performed for 217 patients at Yonsei University Severance Hospital by a single surgeon. Patients were divided into two groups: those who underwent O-PPPD (n = 113) and those who underwent L-PPPD (n = 104). We performed a 1:1 propensity score-matched (PSM) analysis and retrospectively analyzed the demographic and surgical outcomes. We also reviewed all previous studies of more than 100 cases., Results: The L-PPPD group had lesser intraoperative blood loss than the O-PPPD group (548.1 ml vs. 244.7 ml; p < 0.001). Both groups showed similar rates of negative resection margins (99.1% vs. 96.2%; p = 0.196). Overall complication rates did not differ significantly between O-PPPD and L-PPPD (39.8% vs. 35.6%; p = 0.519). The clinically relevant postoperative pancreatic fistula (POPF) rates in the O-PPPD and L-PPPD groups were 18.8% and 13.5%, respectively (p = 0.311). There was no difference in 30- and 90-day mortality rates between the two groups (p = 0.479). Similar results were obtained after PSM analysis., Conclusions: L-PPPD can be a good alternative option for well-selected patients with periampullary lesions requiring PPPD.

Background and Aim: The aim of this study is to identify the predictive factors for futile surgery in patients with radiologically resectable or borderline resectable pancreatic cancer and to develop a prediction model., Methods: This retrospective study included patients who underwent pancreatic surgery for pancreatic cancer between 2006 and 2017. To identify independent risk factors for futile surgery, logistic regression and random forest analyses were performed in the training cohort, based on which a nomogram was established. The predictive accuracy and discriminative ability of the nomogram were validated in the validation cohort., Results: Of 389 patients who underwent pancreatic surgery, the laparotomy was futile in 40 patients (10.3%). In the training cohort, the univariate and multivariate logistic regression analyses revealed that serum carbohydrate antigen 19-9 level of ≥ 150 U/mL (P = 0.003), the presence of suspicious lymph node (P = 0.013), and more extensive peripancreatic tumor infiltration (P < 0.001) were independent predictive factors for futile surgery. The bootstrap-corrected concordance index of the nomogram was high in the training cohort, 0.826 with a 95% confidence interval of 0.745-0.907. This model also showed a good discriminative performance in the validation cohort, with a concordance index of 0.831., Conclusions: We established and validated a novel nomogram that predicts the risk of futile surgery due to occult distant metastasis in patients with radiologically resectable or borderline resectable pancreatic cancer., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Solid pseudopapillary neoplasms (SPN) of the pancreas are rare pancreatic neoplasms where complete resection is the cornerstone in management. It has been demonstrated in previous studies that minimally invasive surgical approaches are effective management options in treating SPNs of the distal pancreas. The purpose of this study is to evaluate the feasibility of minimally invasive surgery in treating SPNs of the uncinate, head, and neck of the pancreas., Methods: Data from 2005 to 2017 at Severance Hospital of the Yonsei University Health systems in Seoul, South Korea, were retrospectively collected for 25 patients who were diagnosed with SPN of the uncinate, head, and neck of the pancreas and who underwent curative resection. Three groups of patients were considered, depending on the year of surgery, in order to determine trends in the surgical management of SPN. The patients were also divided into two groups corresponding to the type of operation done (minimally invasive surgery vs. open surgery). Perioperative patient data, including age, gender, body mass index (BMI), tumor size, and operation done, were compared and analyzed statistically. Long-term nutritional effects were measured using the Controlling Nutritional Status (CONUT) scoring system., Results: There were no statistically significant differences in age, gender, BMI, symptomatic presentation, operation type, tumor size, and tumor stage between the three time periods. In comparing between minimally invasive and open surgery, there were no statistically significant differences in age, gender, symptomatic presentation, BMI, tumor size, preoperative stage, type of operation, operation time, pancreatic duct size, post-operative pancreatic fistula (POPF) grade, death associated with disease, recurrence, pathological parameters, and change in CONUT score. There was a significant difference in tumor size (4.5 ± 1.8 vs. 2.6 ± 1.0 cm, p = 0.004), blood loss (664.2 ± 512.4 vs. 277.7 ± 250.8 mL, p = 0.024), need to transfuse (33% vs. 0%, p = 0.023), hospital length of stay (27.4 ± 15.3 vs. 11.5 ± 5.3 days, p = 0.002), and complication rate (75% vs. 30.8%, p = 0.027) between the two groups., Conclusions: In appropriately selected patients with SPNs of the uncinate, head, and neck of the pancreas, a minimally invasive surgical approach offers at least equal oncologic and nutritional outcomes, while demonstrating decreased complications and decreased hospital length of stay compared with that of an open surgical approach.

Background: The purpose of this study was to validate the predictive value of the oncologic outcome in addition to the validation of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator in patients treated with pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PPPD) for pancreatic head cancer., Methods: From June 2005 to December 2014, 199 patients underwent PD or PPPD for pancreatic head cancer. Medical records were retrospectively reviewed for investigating general patient characteristics and any comorbid diseases. The calculated perioperative complication risks from the ACS NSQIP calculator were compared with observed complication rates. In a propensity score matching analysis, disease-free survival (DFS) and overall survival (OS) were estimated according to calculated severe complication rate (CSCR)., Results: The CSCR > 17.9% (n = 69) and CSCR < 17.9% (n = 130) groups were significantly different considering number of the retrieved lymph nodes (22.95 ± 14.0 vs 18.80 ± 10.1, p = 0.029), histologic grade (p = 0.0235), and incidence of lymphovascular invasion (p = 0.026). The CSCR < 17.9% group had longer DFS (17.0 vs. 11.0 months, p = 0.015), but the OS was similar between the groups (39.0 vs. 23.0 months, p = 0.48). In the 1:2 propensity score analysis, the CSCR < 17.9% group had longer DFS and OS (DFS 26.0 vs. 11.0 months, p = 0.009; OS 44.0 vs. 26.0 months, p = 0.023)., Conclusion: The ACS NSQIP surgical risk calculator predicts surgical risk in patients with pancreatic head cancer who undergo PD or PPPD. Furthermore, this tool can help predict the prognosis of surgically treated pancreatic head cancer.

Background: Immunologic factors such as neutrophil-lymphocyte ratio and platelet-lymphocyte ratio play an important role in predicting the oncologic outcome of patients in pancreatic ductal adenocarcinoma (PDAC). It is hypothesized that host immunity represented by total lymphocyte count at diagnostic stage would influence oncologic outcome in left-sided PDAC., Methods: Between January 1992 and August 2017, total of 112 patients who underwent distal pancreatectomy for left-sided PDAC were included and analysed., Results: At the time of the diagnosis, total lymphocyte count at diagnosis of left-sided PDAC was 1.8 ± 0.7 10 3 /μL (mean value ± standard deviation). Among different cut-off values, 1.7 showed most powerful significant differences in long-term oncologic outcomes. The patients with preoperative lymphocyte count (≤1.7) was associated with early recurrence (median 8.4 months versus 18.1 months, P = 0.011) and shorter survival (median 18.6 months versus 35.9 months, P = 0.028). Patients with preoperative total lymphocyte count over 1.7 showed higher white blood cell count (P < 0.001), platelet count (P = 0.039), neutrophil count (P = 0.004) and monocyte count (P = 0.001). However, more interestingly, neutrophil-lymphocyte ratio (P < 0.001) and platelet-lymphocyte ratio (P < 0.001) were found to be significantly higher in those with total lymphocyte count less than 1.7. Lymphocyte to monocyte ratio was inversely related to preoperative total lymphocyte count (P < 0.001). Only age was identified to be significantly different (P = 0.007). However, other clinicopathological parameters generally known to be related to tumour aggressiveness, were not different between two groups., Conclusion: In conclusion, preoperative total lymphocyte at diagnostic stage is simple, and good prognostic factor in left-sided pancreatic cancer., (© 2019 Royal Australasian College of Surgeons.)

Specific protein 1 (SP1) is associated with aggressive behavior, invasive clinical phenotype and poor clinical outcomes in various cancers. We studied whether SP1 exerts its effect on invasiveness and promotion of the epithelial-mesenchymal transition (EMT) by regulating lysyl oxidase-like 2 (LOXL2) in pancreatic ductal adenocarcinoma (PDAC) cell lines. We showed that silencing of SP1 in MIA Paca-2 cell significantly decreased cell invasion and migration. In MIA Paca-2 cells, silencing of SP1 induced a reduction of LOXL2 expression, whereas LOXL2 silencing did not lead to a decrease in the expression of SP1. Chromatin immunoprecipitation assay demonstrated the binding of SP1 to LOXL2 promoter. Wound healing and transmigration assays also showed that transfection of both SP1 and LOXL2 siRNA induced most significant decrease of cell invasion and migration compared to either SP1 or LOXL2-only silenced cells. Finally, we investigated the prognostic value of SP1 in patients with PDAC and SP1/LOX2 expression was examined by immunochemistry. Univariate and multivariate analyses showed that tumor differentiation and co-expression of SP1 and LOXL2 were independent factors for disease-free survival. In summary, our study demonstrates that SP1 modulates EMT and is involved in tumor invasion and migration of PDAC cells through the regulation of LOXL2.

Background: Laparoscopic distal pancreatectomy (LDP) is generally the treatment of choice for diseases of the pancreatic body and tail. Most surgeons prefer the spleen- and splenic vessel-preserving technique (SPVP-LDP) in benign/borderline pancreatic disease because complications of splenic infarction and gastric varices can arise after Warshaw technique. This study was aimed to determine the true learning curve of the SPVP-LDP procedure not LDP including Warshaw technique., Methods: Data were collected retrospectively from all patients who underwent a LDP between June 2007 and April 2017 at Gangnam Severance Hospital. We used cumulative sum control chart (CUSUM) analysis to assess the learning curve for the SPVP-LDP technique., Results: Eight-three patients were performed LDP and we excluded patients who underwent robotic approach (N = 10) and open conversion DP (N = 8). Patients who underwent SPVP-LDP procedures were categorized into Group 1 (primary end-point). Those who underwent LDP procedures with splenectomy and the Warshaw technique were categorized into Group 2. We found that the 16th case was the cutoff point and the mean length of hospital stay was 13.0 days in the first period and 8.7 days in the second period (p = < 0.001)., Conclusions: These results indicated that the frequency of SPVP-LDPs had increased and that technological progress had been made over time. The true learning curve for SPVP-LDP was indicated as 16 cases in a group of surgeons with no experience of laparoscopic pancreatic surgery.

Background: Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare tumors considered to be benign although 10% to 15% of SPNs have been reported to be aggressive. Due to its rarity, there have only been a few cases reported regarding the clinical course of patients with aggressive SPNs. The goal of this study is to describe the clinical course of patients diagnosed with aggressive SPNs., Methods: A PubMed search was done looking for articles describing the clinical course of patients diagnosed with SPN that locally invaded, recurred, or metastasized. Institutional experience was also added to the pooled data. Patient information was extracted from the articles. Survival and recurrence curves were plotted and factors associated with survival and recurrences were analyzed., Results: A total of 59 patients were identified to have aggressive SPN. Seven patients were males and 52 were females and the mean age was 37.44 ± 2.21 years. Systemic metastasis constituted 81.4% while recurrence and deep tissue invasion were found in 11.9% and 6.8% of the patients, respectively. Disease-free survival was 45 ± 6.28 months and disease-specific survival was 152.67 ± 12.8 months. In survival analysis, age, gender, tumor size, tumor location, combined resection, type of recurrence, and stage IV on diagnosis were not significant factors in predicting survival. However, an unresectable tumor (hazards ratio [HR] = 4.871, 95% confidence interval [CI] 1.480-16.03, P = .009), and metastasis within 36 months (HR = 6.399, 95% CI: 1.390-29.452, P = .017) were identified as independent variables in predicting survival., Conclusion: SPNs of the pancreas carry a favorable course. Despite having aggressive properties, patients can still survive for more than 10 years as long as the tumor can be resected completely.

Purpose: This study investigated the effectiveness of meaning-centered psychotherapy (MCP), which is known to be a helpful psychotherapeutic intervention in distressing conditions, for patients with pancreatobiliary cancer., Materials and Methods: We recruited 37 patients with pancreatobiliary cancer from three university general hospitals and assessed their psychological characteristics. Patients who reported clinically significant emotional distress were recommended to undergo MCP. Patients who consented to MCP were provided four sessions of the therapy. Patient psychological characteristics were assessed again 2 months after MCP. For statistical comparison, outcome variables included anxiety, depression, mental adjustment to cancer, and quality of life (QoL), as well as the degree of stress and physical symptoms., Results: Sixteen patients completed the MCP and the final assessment 2 months later. In the initial assessment, the patients receiving MCP showed higher levels of anxiety and depression than those not receiving MCP, and QoL was also lower in terms of role function, emotional function, social function, and global QoL. At the 2-month follow-up, the MCP group showed a significant improvement in anxiety ( p =0.007), depression ( p =0.010), and anxious preoccupation ( p <0.001). In addition, QoL significantly improved in the MCP group, while there was no significant change in the non-MCP group., Conclusion: In this study, MCP showed potential therapeutic benefits against emotional distress in patients with pancreatobiliary cancer, improving their QoL., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018.)

Objective: This study was performed to determine whether neoadjuvant treatment increases survival in patients with BRPC., Summary Background Data: Despite many promising retrospective data on the effect of neoadjuvant treatment for borderline resectable pancreatic cancer (BRPC), no high-level evidence exists to support the role of such treatment., Methods: This phase 2/3 multicenter randomized controlled trial was designed to enroll 110 patients with BRPC who were randomly assigned to gemcitabine-based neoadjuvant chemoradiation treatment (54 Gray external beam radiation) followed by surgery or upfront surgery followed by chemoradiation treatment from four large-volume centers in Korea. The primary endpoint was the 2-year survival rate (2-YSR). Interim analysis was planned at the time of 50% case enrollment., Results: After excluding the patients who withdrew consent (n = 8) from the 58 enrolled patients, 27 patients were allocated to neoadjuvant treatment and 23 to upfront surgery groups. The overall 2-YSR was 34.0% with a median survival of 16 months. In the intention-to-treat analysis, the 2-YSR and median survival were significantly better in the neoadjuvant chemoradiation than the upfront surgery group [40.7%, 21 months vs 26.1%, 12 months, hazard ratio 1.495 (95% confidence interval 0.66-3.36), P = 0.028]. R0 resection rate was also significantly higher in the neoadjuvant chemoradiation group than upfront surgery (n = 14, 51.8% vs n = 6, 26.1%, P = 0.004). The safety monitoring committee decided on early termination of the study on the basis of the statistical significance of neoadjuvant treatment efficacy., Conclusion: This is the first prospective randomized controlled trial on the oncological benefits of neoadjuvant treatment in BRPC. Compared to upfront surgery, neoadjuvant chemoradiation provides oncological benefits in patients with BRPC.

Background: During laparoscopic pancreaticoduodenectomy (LPD), dissecting uncinate process from the superior mesenteric artery (SMA) will determine one of the important surgical margins (retroperitoneal margin) for predicting oncological outcomes and the quality of LPD. However, clear identification of the division line for retroperitoneal margin is not easy as the uncinate process of the pancreas is anatomically very close to SMA and intermingled with the nerve plexus and soft tissues around SMA. In this study, we present data regarding the potential usefulness of indocyanine green (ICG)-enhanced approach in obtaining retroperitoneal margin during LPD., Methods: From January to September 2017, medical records of patients who underwent LPD for periampullary pathological conditions were retrospectively reviewed. ICG (5 mg/2 cm 3 ) was prepared and intravenously injected when dissecting uncinate process of the pancreas. Perioperative outcomes, including gender, age, diagnosis, body mass index, operation time, estimated blood loss, transfusion, presence of postoperative pancreatic fistulas (POPFs), and length of hospital stay, were evaluated., Results: During the study period, a total of 37 patients underwent LPD for periampullary pathological lesions. Among them, ICG-enhanced dissection of uncinate process of the pancreas was applied in 10 patients (27%). All patients were able to obtain margin-negative resection. There were no significant differences between the perioperative outcomes of patients who did and did not undergo ICG-enhanced approach., Discussion: ICG perfusion-based laparoscopic dissection of retroperitoneal margin is feasible and safe in LPD. This intraoperative visual difference can provide the surgeon with very helpful real-time visual information. Further study is mandatory.

Background: Anoctamin (ANO)/transmembrane member 16 (TMEM16) proteins mediate diverse physiological and pathophysiological functions including cancer cell proliferation. The present study aimed to identify the role of ANOs in pancreatic cancer., Methods: In an initial screen of ANOs, ANO9/TMEM16J was overexpressed in pancreatic cancer cells, and its role in the pathogenesis of pancreatic cancer was evaluated using an integrated in vitro and in vivo approach. To determine clinical relevance of the experimental findings, the prognostic value of ANO9 was evaluated in patients with pancreatic cancer., Results: The ANO9 mRNA and protein levels were increased in pancreatic cancer-derived cells. Exogenous expression of ANO9 in PANC-1 cells significantly increased cell proliferation in cell cultures and in mice. In contrast, knockdown of ANO9 in AsPC-1, BxPC-3, and Capan-2 cells strongly inhibited cell proliferation. Mechanistic analysis suggested that physical association of ANO9 with epidermal growth factor receptor (EGFR) underlies ANO9-induced cell proliferation. Knockdown of ANO9 augmented the effects of the EGFR inhibitor and the cytotoxic agent on pancreatic cancer cell proliferation. In addition, high ANO9 expression is a poor prognostic factor in patients with pancreatic cancer., Conclusions: The ANO9/TMEM16J appears to be a clinically useful prognostic marker for pancreatic cancer and a potential therapeutic target.

Background: Our previous randomized controlled trial revealed no difference in 2-year overall survival (OS) between extended and standard resection for pancreatic adenocarcinoma. The present study evaluated the 5-year OS and recurrence patterns according to the extent of pancreatectomy., Methods: Between 2006 and 2009, 169 consecutive patients were prospectively enrolled and randomized to standard (n = 83) or extended resection (n = 86) groups to compare 5-year OS rate, long-term recurrence patterns and factors associated with long-term survival., Results: The surgical R0 rate was similar between the standard and extended groups (85.5 vs. 90.7%, P = 0.300). Five-year OS (18.4 vs. 14.4%, P = 0.388), 5-year disease-free survival (14.8 vs. 14.0%, P = 0.531), and overall recurrence rates (74.7 vs. 69.9%, P = 0.497) were not significantly different between the two groups, although the incidence of peritoneal seeding was higher in the extended group (25 vs. 8.1%, P = 0.014)., Conclusions: Extended pancreatectomy does not have better short-term and long-term survival outcomes, and shows similar R0 rates and overall recurrence rates compared with standard pancreatectomy. Extended pancreatectomy does not have to be performed routinely for all cases of resectable pancreatic adenocarcinoma, especially considering its associated increased morbidity shown in our previous study., (© 2017 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The clinical relevance of fibrosis with regard to tumor progression is supported by the correlation between fibrosis and poor outcomes. Fecal elastase-1 (FE-1) level has been used to assess exocrine dysfunction of the pancreas and to predict pancreas fibrosis. The aim of this study was to assess the impact of FE-1 on the survival of pancreatic cancer patients., Methods: Between January 2006 and December 2014, 136 patients with pancreatic adenocarcinoma underwent R0 resection at Gangnam Severance Hospital, Korea. Preoperative FE-1 levels were available in 94 patients who were enrolled in the study. Patients were classified into two groups according to preoperative FE-1: "normal" (≥200 μg/g) or "reduced" (<200 μg/g)., Results: Median preoperative FE-1 level was 130.1 μg/g (IQR 32.0; 238.3). 62 patients (66.0%) had reduced pancreatic function and 32 patients (34.0%) had normal pancreatic function. The two groups had significantly different disease-free survival (P < 0.001). On multivariate analysis, normal FE-1, no lymph node metastasis and completion of adjuvant chemotherapy were found to be independent prognostic factors for better DFS (P = 0.001, P = 0.017, P = 0.038, respectively)., Conclusion: FE-1 is a simple and non-invasive predictive clinical marker for prognosis of pancreatic cancer after attempted curative resection., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Importance: The rate of postoperative pancreatic fistula (POPF) after distal pancreatectomy ranges from 13% to 64%. To prevent POPF, polyglycolic acid (PGA) mesh was introduced, but its effect has been evaluated only in small numbers of patients and retrospective studies., Objective: To evaluate the efficacy of PGA mesh in preventing POPF after distal pancreatectomy., Design, Setting, and Participants: Prospective randomized clinical, single-blind (participant), parallel-group trial at 5 centers between November 2011 and April 2014. The pancreatic parenchyma was divided using a stapling device; no patient was given prophylactic octreotide. Perioperative and clinical outcomes were compared including POPF, which was graded according to the criteria of the International Study Group For Pancreatic Fistulas. A total of 97 patients aged 20 to 85 years with curable benign, premalignant, or malignant disease of the pancreatic body or tail were enrolled (44 in the PGA group and 53 in the control group)., Interventions: Patients in the PGA group underwent transection of the pancreas and application of fibrin glue followed by wrapping the PGA mesh around the remnant pancreatic stump., Main Outcomes and Measures: The primary end point of this study was the development of a clinically relevant POPF (grade B or C by the International Study Group grading system). The secondary end point was the evaluation of risk factors for POPF., Results: The study therefore evaluated a total of 97 patients, 44 in the PGA group and 53 in the control group. Thirty-nine patients were women and 58 patients were men. There were no differences in mean (SD) age (59.9 [12.0] years vs 54.5 [14.1] years, P = .05), male to female ratio (1.0:1.3 vs 1.0:1.7, P = .59), malignancy (40.9% vs 32.1%, P = .37), mean (SD) pancreatic duct diameter (1.92 [0.75] mm vs 1.94 [0.95] mm, P = .47), soft pancreatic texture (90.9% vs 83.0%, P = .17), and mean (SD) thickness of the transection margin (16.9 [5.4] mm vs 16.4 [4.9] mm, P = .63) between the PGA and control groups. The rate of clinically relevant POPF (grade B or C) was significantly lower in the PGA group than in the control group (11.4% vs 28.3%, P = .04)., Conclusions and Relevance: Wrapping of the cut surface of the pancreas with PGA mesh is associated with a significantly reduced rate of clinically relevant POPF., Trial Registration: clinicaltrials.gov Identifier: NCT01550406.

Introduction: Gemcitabine-based regimens represent the standard systemic first line treatment in patients after pancreatic resection. However, the clinical impact of gemcitabine varies significantly in individuals because of chemoresistance. An in vitro adenosine triphosphate based chemotherapy response assay (ATP-CRA) was designed to evaluate the sensitivity of cancer cells to various chemotherapeutic agents. This study investigated the correlation between in vitro gemcitabine sensitivity of tumor cells and early recurrence after curative resection., Method: From January 2007 to December 2010, the ATP-CRA for gemcitabine was tested in 64 patients surgically treated for pancreas cancer at Gangnam Severance Hospital, Seoul, Korea. We analyzed the relationship between chemosensitivity and early systemic recurrence in patients with pancreas cancer to predict disease-free survival (DFS) after curative resection in pancreas cancer., Result: The mean cell death rate (CDR) was 20.0 (±14.5) and divided into two groups according to the mean values of the CDR. Lymphovascular invasion was more frequently shown in gemcitabine resistance group without statistical significance. In univariate and multivariate analysis, advanced tumor stage and gemcitabine sensitive group (CDR ≥ 20) were identified as independent prognostic factors for DFS., Conclusions: Gemcitabine sensitivity measured by ATP-CRA was well correlated with in vivo drug responsibility to predict early recurrence following gemcitabine-based adjuvant chemotherapy in patients with pancreas cancer., (© 2016 Wiley Periodicals, Inc.)

Purpose: This study focused on implementation of a prognostic scoring index based on clinico-laboratory parameters measured routinely on admission in metastatic pancreatic cancer patients., Materials and Methods: Records from 403 patients of metastatic disease were analyzed retrospectively. Continuous variables were dichotomized according to the normal range or the best cut-off values statistically determined by Contal and O'Quigley method, and then analyzed in association with prognosis-overall survival (OS), using Cox's proportional hazard model. Scores were calculated by summing the rounded chi-square scores for the factors that emerged in the multivariate analysis., Results: Performance status, hemoglobin, leucocyte count, neutrophil-lymphocyte ratio, and carcinoembryonic antigen were independent factors for OS. When patients were divided into three risk groups according to these factors, median survival was 11.7, 6.2, and 1.3 months for the low, intermediate, and high-risk groups, respectively (p < 0.001). Palliative chemotherapy has a significant survival benefit for low and intermediate-risk patients (median OS; 12.5 months vs. 5.9 months, p < 0.001 and 8.0 months vs. 2.0 months, p < 0.001, respectively)., Conclusion: We advocate the use of a multivariable approach with continuous variables for prognostic modeling. Our index is helpful in accurate patient risk stratification and may aid in treatment selection., Competing Interests: relevant to this article was not reported.

Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in cancer. We analyzed the prognostic impact of LOXL2 in pancreatic cancer patients and investigated the role of LOXL2 in pancreatic cancer cell lines. Immunohistochemical analysis was performed in samples from 80 patients and showed LOXL2 expression in 81.2% of patients with pancreatic cancer. Regarding recurrence patterns, LOXL2-positive tumors showed a significantly higher rate of distant recurrence. The 1-year and 3-year disease-free survival rates were 84.6% and 0.0%, respectively, for LOXL2-negative patients, and 27.8 % and 0.0 %, respectively, for LOXL2-positive patients. On univariate analysis, combined resection of major vessels, depth of invasion, tumor stage, and LOXL2- positive status were significant factors for poor prognosis. After identification of LOXL2 expression in pancreatic cancer cell lines, LOXL2-silenced and LOXL2-overexpressed cell lines were used to perform transwell invasion and transendothelial migration assays.In vitro studies indicated that LOXL2 silencing in MIA PaCa-2 and PANC-1 cells induced a mesenchymal-epithelial transition (MET)-like process associated with decreased invasive and migratory properties. LOXL2 overexpression in AsPC-1 and BxPC-3 cells enhanced the epithelial-mesenchymal transition (EMT)-like process and increased migratory and invasive activity. These clinical and preclinical data confirm that higher LOXL2 expression is associated with the invasiveness of pancreatic cancer cells and the low survival rate of pancreatic cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in pancreatic cancer., Competing Interests: All authors declare that we have no conflicts of interest in connection with this paper.

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

Purpose: Accurate indications and the extent of surgery for branch duct intraductal papillary mucinous neoplasm (IPMN) of the pancreas are still debatable. In particular, small tumor is located at the head portion of pancreas presents a dilemma. The purpose of this study is to compare the efficacy of enucleation (EN) with that of pancreaticoduodenectomy (PD) in patients with small (2 cm

Background/aims: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has a favorable prognosis, but seems to be associated with a high incidence of extrapancreatic tumors. The purpose of this study was to evaluate the incidence and clinicopathological features of extrapancreatic tumors associated with IPMN., Methods: Thirty-seven patients with IPMN of the pancreas, confirmed by surgical resection and typical findings of endoscopic ultrasonography and CT imaging between October 1, 1998 and August 31, 2006 were included. Seventeen patients were diagnosed with surgical resection and biopsy, and others by typical imaging findings of IPMN. These patients were examined for the development of extrapancreatic tumors., Results: Of 37 patients with IPMN, 14 (38%) had 18 extrapancreatic tumors, and 10 (27%) had 13 extrapancreatic malignancies. Five, six, and two extrapancreatic malignancies had been diagnosed before, during, and after the diagnosis of IPMN. Gastric adenocarcinoma (3 patients, 23%) and colorectal carcinoma (3 patients, 23%) were the most common neoplasms. Other extrapancreatic tumors included lung cancer (n=2), prostatic cancer (n=1), renal cell carcinoma (n=1), cholangiocellular carcinoma (n=1), urinary bladder cancer (n=1), and gallbladder cancer (n=1), respectively. As benign tumor, there were two gallbladder adenoma, one gastric adenoma, one colonic adenoma and one benign ovarian cystic neoplasm, respectively., Conclusions: IPMN is associated with high incidence of extrapancreatic tumors, particularly gastric and colorectal neoplasms. Upper gastrointestinal endoscopy and colonoscopy should be done, and systemic surveillance for the possible occurrence of other tumors may allow early detection of extrapancreatic tumor in patients with IPMN.

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

Background: Carcinoma of the ampulla of Vater has a relatively higher resection rate, lower recurrence rate, and more favorable prognosis than other malignant tumors of the periampullary region. Because of the relative low incidence of carcinoma of the ampulla of Vater, there have been few reports on the patterns and risk factors of recurrence after curative resection. The aim of this study was to evaluate the patterns and risk factors of recurrence after curative resection of ampulla of Vater carcinoma., Materials and Methods: Between January 1992 and December 2002, 102 patients received radical resection for ampulla of Vater carcinoma at Yonsei University Medical Center. Fifteen patients were excluded because of incomplete clinicopathologic data. Finally, 87 patients were reviewed and analyzed to assess predictors of tumor recurrence., Results: Among the 87 patients, 37 patients (42.5%) experienced recurrent disease. The mean length of time to recurrence was 29.3 +/- 35.3 months, and the most common sites of recurrence were the intra-abdominal organs: liver and loco-regional lymph nodes. The patients were divided into two groups: early recurrence (18 months). In the early recurrence group, ulcer formation tumors and poorly differentiated tumors were more common in comparison with the late recurrence group. Lymph node metastasis was identified as an independent factor of tumor recurrence after curative resection for ampulla of Vater carcinoma., Conclusion: Lymph node metastasis is the most important risk factor for recurrence after a curative resection. Also, the fact that a higher probability of recurrence is anticipated in cases of ulcer formation and poorly differentiated tumors, there exists a need for a close-up follow-up program., ((c) 2006 Wiley-Liss, Inc.)

Pancreatic cancer is a disease with poor prognosis mainly due to low resection rates and late diagnosis. To increase resectability and improve survival rates, a better understanding of pancreatic cancer pathogenesis and more effective screening techniques are required. New methods, such as genetic and molecular alterations, may suggest novel approaches for pancreatic cancer diagnosis and treatment. We immunohistochemically investigated 44 formalin-fixed, paraffin-embedded specimens of pancreatic ductal adenocarcinoma using monoclonal anti-p16 antibodies and monoclonal anti-p53 antibodies. The expressions of p16 and p53 proteins were compared using the Chi-square test with SPSS. Disease-free survival was analyzed using the Kaplan-Meier method, verified by the Log- Rank test. Loss of p16 expression was noted in 20 (45.5%) cases and aberrant p53 protein expression was detected in 14 (31.8%) cases. Loss of p16 expression was associated with a higher incidence of lymph node metastasis (p=0.040) and a more advanced stage (p=0.015), although there was no significant correlation between p16 expression and survival. Aberrant p53 protein expression correlated with histologic grade (p= 0.038). Disease-free survival rate was significantly lower in the aberrant p53 protein positive group compared to the negative group (p=0.029). From our results, we suggest that p53 is not a prognostic factor; however, p16 and p53 genes do play important roles in the progression of pancreatic ductal adenocarcinoma.

Background: Despite recently increasing numbers of reports on intraductal papillary mucinous tumors (IPMTs), difficulties still remain in terms of diagnosis, treatment, and prognosis. The purpose of this multicenter study was to evaluate the clinicopathologic features of IPMT in Korea and to suggest predictive criteria for malignancy in IPMT., Methods: We retrospectively reviewed the clinicopathologic data of 208 patients who underwent operations for IPMT between 1993 and 2002 at 28 institutes in Korea., Results: Of the 208 patients (mean age, 61 years), 147 were men and 61 were women. A total of 124 patients underwent pancreatoduodenectomy, 42 underwent distal pancreatectomy, 17 underwent total pancreatectomy, and 25 underwent limited pancreatic resection. There were 128 benign cases (adenoma, n = 62; borderline, n = 66) and 80 malignant cases (noninvasive, n = 29; invasive, n = 51). A significant difference in 5-year survival was observed between the benign and malignant groups (92.6% vs. 65.3%; P = .006). Of the six factors (age, location, duct dilatation, mural nodule, main duct type, and tumor size) that showed statistical differences by univariate analysis between the benign and malignant groups, three were significant by multivariate analysis--namely, mural nodule (P = .009), tumor size (P = .023), and a dilated duct size (P = .010)., Conclusions: A significant proportion of IPMTs are malignant, although the overall prognosis of IPMT is superior to that of ordinary pancreatic cancer. Radical surgery is recommended for IPMT with the predictors of malignancy: mural nodule, tumor size (> or =30 mm), and dilated duct size (> or =12 mm).