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The improvement of effective multidrug agents has allowed more patients to undergo resection for pancreatic cancer (PC). In the conversion cases of initially unresectable PC after induction chemotherapy, pancreatic surgeons often encounter challenging vein resections cases such as those of long-segment portal vein (PV)/superior mesenteric vein (SMV) encasement or occlusion of the distal (caudal) SMV. Given the lack of consensus for the optimal approach for major vein resections and reconstructions in these situations, this review summarizes the literature on this topic and provides the best currently available approaches for challenging vein reconstruction cases. For long-segment PV/SMV encasement, tips for direct end-to-end anastomosis without grafts and the splenic vein (SpV) reconstruction to prevent left-side portal hypertension will be introduced. For distal SMV encasement, several bypass techniques to deal with collateralizations will be introduced. Even though some high-volume PC centers are obtaining favorable outcomes for challenging vein resection cases, existing evidence on this topic is limited. It is essential to organize the well-designed international multicenter studies for the small population of challenging vein resection cases. With the emergence of effective chemotherapies, the number of PC patients who can undergo curative resection is increasing. Achieving more successful vessel resection and reconstruction in the treatment of PC is a common goal that pancreatic surgeons should focus on together.

Neoadjuvant therapy is used for borderline resectable pancreatic ductal adenocarcinoma (PDAC) with high risk of incomplete resection and early recurrence. Because distal PDAC is rare, the optimal criteria for neoadjuvant therapy specific for distal PDAC remain unclear. We hypothesized large distal PDAC would recur earlier than small distal PDAC. The aim of this study was to identify the risk factors for failure of upfront resection for resectable distal PDAC. The study cohort comprised 158 patients with resectable distal PDAC who underwent radical resection. The long-term outcomes were recurrence-free survival (RFS), disease-specific survival (DSS), and post-recurrence survival (PRS). R0 resection was achieved in 92% of patients, and median DSS for the entire cohort was 31 months. Among 103 patients who developed recurrence, 32 (31%) developed recurrence within 6 months. The median PRS and DSS for those with early recurrence was 6 and 10 months, respectively, compared with 11 and 30 months, respectively, for those with late recurrence (p = 0.017 and p 4 cm had higher rates of R1 resection (16%) and concomitant resection of another organ (19%) than those with smaller tumors (4% and 2%, p = 0.009 and p 4 cm remained a significant predictor of early recurrence (p 4 cm is a reliable predictor of early recurrence after resection of distal PDAC, and neoadjuvant therapy may help select patients who can benefit from radical resection.

Background Use of neoadjuvant therapy for elderly patients with pancreatic cancer has been debatable. With FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan, oxaliplatin) or gemcitabine plus nab-paclitaxel (GnP) showing tremendous effects in improving the overall survival of patients with borderline resectable and locally advanced pancreatic cancer, there is no definitive consensus regarding the use of this regimen in the elderly. Methods This study evaluated the eligibility of elderly patients with borderline resectable or locally advanced pancreatic cancer for neoadjuvant therapy. Patients registered in the database of pancreatic cancer at the University of Colorado Cancer Center, who underwent neoadjuvant treatment between January 2011 and March 2019, were separated into three age groups (less than 70, 70–74, 75 or more years) and respective treatment outcomes were compared. Results The study included 246 patients with pancreatic cancer who underwent neoadjuvant treatment, of whom 154 and 71 received chemotherapy with FOLFIRINOX and GnP respectively. Among these 225 patients, 155 were younger than 70 years, 36 were aged 70–74 years, and 34 were aged 75 years or older. Patients under 70 years old received FOLFIRINOX most frequently (124 of 155 versus 18 of 36 aged 70–74 years, and 12 of 34 aged 75 years or more; P Conclusion The safety and efficacy of multiagent chemotherapy in patients aged 75 years or over were similar to those in younger patients. Modern multiagent regimens could be a safe and viable treatment option for clinically fit patients aged at least 75 years.

Background Previous studies on borderline resectable (BR) pancreatic cancer (PC) included patients with heterogenous preoperative states; however, the definition of resectability for PC has evolved. We aimed to investigate the prognostic factors for PC other than anatomical resectability in those who underwent upfront resection and discuss the optimal treatment strategy for PC. Methods We retrospectively examined 431 patients who underwent upfront surgery with curative intent between 2007 and 2014. The association between clinical characteristics and survival outcomes was assessed by stratifying patients according to risk factors. The patients were categorized into four groups based on anatomical (resectable [R]/BR) and biological features (CA19-9 ≤500/>500 U/mL): anatomical R with CA19-9 ≤500 U/mL (favorable-R); anatomical BR with CA19-9 ≤500 U/mL (favorable-BR); anatomical R with CA19-9 >500 U/mL (risky-R); and anatomical BR with CA19-9 >500 U/mL (risky-BR). Results Overall, 320 and 111 patients had anatomical R- and BR-PC, respectively. A modified Glasgow prognostic score = 2 (hazard ratio [HR]: 1.73), NLR>5 (hazard ratio [HR]: 1.54), CA19-9 >500 U/mL (HR: 1.86), and anatomical BR (HR: 1.38) were independent prognostic factors for overall survival. The risky-R group had likely worse prognosis (16 months vs. 19 months, P = 0.0605) and a significantly higher early recurrence rate (36% vs 18%, P = 0.0231) than the favorable-BR group. Conclusions It is essential to stratify and distinguish PC patients at a high risk of worse prognosis. Risky-R was an unfavorable prognostic factor and should thus be considered in the decision-making for treatment with neoadjuvant chemotherapy, in addition to anatomical BR-PC.

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

Adjuvant chemotherapy and/or chemoradiation [chemo(radiation)] is considered the standard of care for resected patients with pancreatic adenocarcinoma. However, invasive carcinoma arising from an intraductal papillary mucinous neoplasm (IPMN) seems to have different biologic behavior and prognosis. Retrospective data suggest a survival benefit of adjuvant chemo(radiation) for resected invasive IPMNs with metastatic nodal disease; however, it is unclear whether this remains valid for node-negative patients. To compare the outcome of patients with invasive IPMNs who received adjuvant chemo(radiation) with that of those treated with surgery alone, we queried the National Cancer Database regarding data of patients who underwent pancreatic resection for invasive IPMN between 2006 and 2015. A propensity score analysis was conducted to balance covariates between treatment groups. For the study, 492 patients were eligible, of whom 267 (54.3%) received adjuvant chemo(radiation). Estimated 1- and 3-year overall survival rates were 88.9% and 73.5% versus 93.2% and 72.8% for patients who did or did not receive adjuvant chemo(radiation), respectively. Among patients with negative nodal stage, there was no difference in overall survival between patients who received versus patients who did not receive adjuvant chemo(radiation) (P = 0.973). In contrast, among patients with positive nodal disease, those who received adjuvant chemo(radiation) had significantly better OS compared with those who did not (P = 0.001). In patients with resected invasive IPMNs, adjuvant chemo(radiation) was associated with significantly improved overall survival only in presence of nodal metastases. This finding can help clinicians to select adjuvant treatment in a patient-tailored fashion.

Supplemental Digital Content is available in the text, Objective: The aim of this study was to clarify the role of pancreatic surgery during the COVID-19 pandemic to optimize patients’ and clinicians’ safety and safeguard health care capacity. Summary Background Data: The COVID-19 pandemic heavily impacts health care systems worldwide. Cancer patients appear to have an increased risk for adverse events when infected by COVID-19, but the inability to receive oncological care seems may be an even larger threat, particularly in case of pancreatic cancer. Methods: An online survey was submitted to all members of seven international pancreatic associations and study groups, investigating the impact of the COVID-19 pandemic on pancreatic surgery using 21 statements (April, 2020). Consensus was defined as >80% agreement among respondents and moderate agreement as 60% to 80% agreement. Results: A total of 337 respondents from 267 centers and 37 countries spanning 5 continents completed the survey. Most respondents were surgeons (n = 302, 89.6%) and working in an academic center (n = 286, 84.9%). The majority of centers (n = 166, 62.2%) performed less pancreatic surgery because of the COVID-19 pandemic, reducing the weekly pancreatic resection rate from 3 [interquartile range (IQR) 2–5] to 1 (IQR 0–2) (P < 0.001). Most centers screened for COVID-19 before pancreatic surgery (n = 233, 87.3%). Consensus was reached on 13 statements and 5 statements achieved moderate agreement. Conclusions: This global survey elucidates the role of pancreatic surgery during the COVID-19 pandemic, regarding patient selection for the surgical and oncological treatment of pancreatic diseases to support clinical decision-making and creating a starting point for further discussion.

Introduction The efficacy of laparoscopic simultaneous resection of primary colorectal cancer and synchronous colorectal liver metastases (SCRLM) remains unclear. Methods We retrospectively evaluated data from 258 patients who had undergone simultaneous curative resection of the primary tumor and SCRLM from 2006 to 2017. We compared surgical outcomes between open, hybrid (laparoscopic colorectal resection and open hepatectomy), and pure laparoscopic approaches. Surgical outcomes were also evaluated between the open hepatectomy (OH) group (ie, open/hybrid surgery) and the laparoscopic hepatectomy (LH) group (ie, pure laparoscopic surgery) in 141 patients later in the study period (2013-2017), when the clinical indications for laparoscopic hepatectomy were restricted to simple wedge resection and/or left lateral sectionectomy in our center. Results The pure laparoscopic approach was associated with significantly less intraoperative blood loss and a significantly shorter postoperative hospital stay than the open and hybrid approaches. Late in the study period, operative outcomes in the LH group (n = 37) were more favorable than for the OH group (n = 104) in terms of intraoperative blood loss and postoperative hospital stay. In patients with rectal cancer, however, earlier postoperative recovery in the LH group did not differ significantly from the OH group. Conclusion Laparoscopic simultaneous resection of SCRLM with the primary tumor by simple hepatectomy is safe and may enhance patients' postoperative recovery, especially in patients with colon cancer.

Objective To identify objective preoperative prognostic factors that are able to predict long-term survival of patients affected by PDAC. Summary of background data In the modern era of improved systemic chemotherapy for PDAC, tumor biology, and response to chemotherapy are essential in defining prognosis and an improved approach is needed for classifying resectability beyond purely anatomic features. Methods We queried the National Cancer Database regarding patients diagnosed with PDAC from 2010 to 2016. Cox proportional hazard models were used to select preoperative baseline factors significantly associated with survival; final models for overall survival (OS) were internally validated and formed the basis of the nomogram. Results A total of 7849 patients with PDAC were included with a median follow-up of 19 months. On multivariable analysis, factors significantly associated with OS included carbohydrate antigen 19-9, neoadjuvant treatment, tumor size, age, facility type, Charlson/Deyo score, primary site, and sex; T4 stage was not independently associated with OS. The cumulative score was used to classify patients into 3 groups: good, intermediate, and poor prognosis, respectively. The strength of our model was validated by a highly significant randomization test, Log-rank test, and simple hazard ratio; the concordance index was 0.59. Conclusion This new PDAC nomogram, based solely on preoperative variables, could be a useful tool to patients and counseling physicians in selecting therapy. This model suggests a new concept of resectability that is meant to reflect the biology of the tumor, thus partially overcoming existing definitions, that are mainly based on tumor anatomic features.

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

Simple Summary Extensive portal vein (PV) resection, including porto-mesenterico-splenic confluence (PMSC) during pancreaticoduodenectomy (PD) may sometimes be necessary for pancreatic head cancer, if the tumor is close to the portal venous system. However, as a late-onset postoperative complication, this extensive PV resection may result in sinistral portal hypertension (SPH) and cause variceal bleeding due to congested venous flow from the spleen. Since the prognosis of patients with pancreatic cancer has improved, owing to the development of chemotherapy and surgical techniques, SPH is no longer a negligible matter in the field of pancreatic cancer surgery. This review clarifies the pathogenesis and frequency of SPH after PD with PMSC resection and discusses its prediction and prevention. Abstract To achieve curative resection for pancreatic cancer during pancreaticoduodenectomy (PD), extensive portal vein (PV) resection, including porto-mesenterico-splenic confluence (PMSC), may sometimes be necessary if the tumor is close to the portal venous system. Recently, this extended resection has been widely accepted in high-volume centers for pancreatic resection due to its favorable outcomes compared with non-operative treatment. However, in patients with long-term survival, sinistral portal hypertension (SPH) occurs as a late-onset postoperative complication. These patients present gastrointestinal varices due to congested venous flow from the spleen, which may cause critical variceal bleeding. Since the prognosis of patients with pancreatic cancer has improved, owing to the development of chemotherapy and surgical techniques, SPH is no longer a negligible matter in the field of pancreatic cancer surgery. This review clarifies the pathogenesis and frequency of SPH after PD through PMSC resection and discusses its prediction and prevention.

This study aimed to clarify the key factors for minimizing unsuitable surgical interventions for patients with radiologically occult metastatic pancreatic cancer (ROMPC), defined as a distant metastasis detected during surgery or within 6 months after resection. This study involved 502 patients planned to undergo curative resection for pancreatic cancer between 2008 and 2015. Patients were divided into ROMPC and non-ROMPC groups and evaluated preoperative factors associated with ROMPC. Overall survival (OS) was significantly lower in the ROMPC group (n = 145) than the non-ROMPC group (n = 357, median survival time [MST] 10.8 vs. 35.3 months, P

A 53-year-old man with prior history of resection of liposarcoma in his leg presented with gallbladder mass. Computed tomography showed 4-cm tumor at gallbladder fundus with weak enhancement with IV contrast. Differential diagnoses included hemangioma and liposarcoma, and laparoscopic cholecystectomy was recommended. In the operating room, the tumor appeared without serosal and liver invasions and uncomplicated laparoscopic cholecystectomy was completed. Histopathological examination revealed the tumor as myxoid liposarcoma with round cells. Adjuvant chemotherapy was not given, and he was placed on imaging surveillance. At 16 months after the operation, he developed recurrence of liposarcoma in the left popliteal fossa.

Objective: The aim of this study was to establish clinically relevant outcome benchmark values using criteria for pancreatoduodenectomy (PD) with portomesenteric venous resection (PVR) from a low-risk cohort managed in high-volume centers. Summary Background Data: PD with PVR is regarded as the standard of care in patients with cancer involvement of the portomesenteric venous axis. There are, however, no benchmark outcome indicators for this population which hampers comparisons of patients undergoing PD with and without PVR resection. Methods: This multicenter study analyzed patients undergoing PD with any type of PVR in 23 high-volume centers from 2009 to 2018. Nineteen outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of the centers (NCT04053998). Results: Out of 1462 patients with PD and PVR, 840 (58%) formed the benchmark cohort, with a mean age was 64 (SD11) years, 413 (49%) were females. Benchmark cutoffs, among others, were calculated as follows: Clinically relevant pancreatic fistula rate (International Study Group of Pancreatic Surgery): ≤14%; in-hospital mortality rate: ≤4%; major complication rate Grade≥3 and the CCI up to 6 months postoperatively: ≤36% and ≤26, respectively; portal vein thrombosis rate: ≤14% and 5-year survival for patients with pancreatic ductal adenocarcinoma: ≥9%. Conclusion: These novel benchmark cutoffs targeting surgical performance, morbidity, mortality, and oncological parameters show relatively inferior results in patients undergoing vascular resection because of involvement of the portomesenteric venous axis. These benchmark values however can be used to conclusively assess the results of different centers or surgeons operating on this high-risk group.

Pancreatic cancer (PC) is likely to become the second leading cause of malignancy-associated mortality within the next 10 years and surgery remains the best hope for cure. The introduction of effective neoadjuvant treatment (NAT) has increased the resection rate of PC in the era of contemporary pancreatology. This review summarizes the surgical selection criteria for locally advanced PC (LAPC), by focusing on the commonly used predictors for resectability and better overall survival outcome. Based on the currently available evidence, the role of change in carbohydrate antigen 19-9 (CA 19-9) and patient's tumor response to NAT are critical in surgical candidacy selection. Although, consensus on surgical candidacy selection for LAPC still needs to be made, several data have shown that surgery provides the most optimistic chance of cure for PC. Surgery is, therefore, recommended whenever the benefits of pancreatectomy outweigh surgical complications, and the chance of local or distant metastases in the postoperative setting is low. This review also provided our insight for and experience in selecting surgical candidates by focusing on optimizing the overall survival of LAPC patients. Nevertheless, a collaborative approach to formulating standardized criteria for surgical candidate selection and treatment guidelines for LAPC is a common goal that pancreatologists worldwide should focus on.

This prospective trial revealed the additional diagnostic value of staging laparoscopy with contrast-enhanced intraoperative ultrasonography and indocyanine green-fluorescence imaging, detecting radiologically occult liver metastases and other occult metastases effectively for patients with high-risk resectable or borderline resectable pancreatic cancer. The 2-year survival rate of patients without occult metastasis was significantly better than that of patients with occult metastasis. These favourable results for patients without occult metastasis indicate that an enhanced screening strategy and modern multidisciplinary treatment may improve the outcome even of patients affected by high-risk advanced pancreatic cancer. State-of-the-art staging worth the effort

We describe the short- and long-term outcomes for PDAC patients after tailored mesopancreas dissection using supracolic artery-first approach followed by adjuvant therapy. This study analyzed 233 consecutive patients who underwent artery-first pancreaticoduodenectomy for PDAC. Dissection extent for the superior mesenteric artery (SMA) was categorized into three levels: level 2 (LV2) including regional lymph nodes, level 3 (LV3) with hemicircumferential nerve plexus dissection, and extended-level 3 (E-LV3) including borderline resectable cases for the SMA. All clinical, pathological, and survival outcomes were reviewed. LV2/3/E-LV3 dissection was performed in 77/115/41 patients. The short-term outcomes were similar among groups without mortality. Although postoperative diarrhea requiring opioids was significantly more frequent in the E-LV3 group (76%) than other groups (vs. LV2 (21%), P

Background Clinical implication of disappearing liver metastases (DLMs) from colorectal cancer after chemotherapy needs to be reviewed in the era of modern imaging studies. Methods Between 2010 and 2015, 184 patients underwent curative hepatectomy for colorectal liver metastases following preoperative chemotherapy. The sites of metastases detected on pre-chemotherapy CE-CT were examined post-chemotherapy using CE-CT, gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI), and contrast-enhanced intraoperative ultrasonography (CE-IOUS). DLMs were defined as tumors that disappeared on CE-CT post chemotherapy. The detection rate of DLMs with EOB-MRI and CE-IOUS were assessed, and the outcome of DLMs resected and those left in place were reviewed. Results A total of 275 DLMs were noted in 59 patients. On EOB-MRI, 71 lesions (26%) were visible and were resected, 92% (65/71) of which contained viable disease. Using CE-IOUS, an additional 94 lesions were identified. A total of 165 DLMs (60%) were identified and resected by sequential use of EOB-MRI and CE-IOUS, 77% (127/165) of which contained viable disease. Of 110 DLMs not identified, 68 were resected, 4% (3/68) of which contained viable disease. Among 42 lesions left in place, 6 (14%) recurred during the median follow-up period of 27 (9–72) months. Discussion EOB-MRI and CE-IOUS exploration identified clinically relevant DLMs containing viable disease with a high level of accuracy.

Recently, several studies have revealed the usefulness of biomarkers to predict the response to chemotherapy for pancreatic ductal adenocarcinoma (PDAC). Among them, human antigen R (HuR) is reported as a powerful marker for response to gemcitabine chemotherapy for PDAC. The present report describes a patient with PDAC who underwent gemcitabine therapy before resection and after recurrence, and HuR expression was examined at multiple stages. A 72-year-old man was diagnosed with locally advanced unresectable PDAC invading the common hepatic artery. After 9 cycles of gemcitabine treatment, a computed tomography (CT) scan demonstrated a partial response. He underwent distal pancreatectomy with portal vein resection. The pathologic assessment for response to the chemotherapy was grade Ib by Evans's criteria, and HuR expression was high. Serum carbohydrate antigen 19-9 (CA19-9) level rose rapidly at 4 months after the first resection. A CT scan and needle biopsy revealed a solitary recurrence in the abdominal wall, and HuR expression remained high. After 4 cycles of gemcitabine and S-1 combination therapy, a CT scan demonstrated a partial response, and serum CA19-9 decreased. However, after 2 additional cycles of the therapy, a CT scan demonstrated progressive disease, and serum CA19-9 increased slightly. By laparotomy, an abdominal wall recurrence and multiple peritoneal dissemination were found. HuR expression in the biopsy specimen obtained during the laparotomy was decreased. Although gemcitabine therapy was reinitiated, the disease progressed rapidly so the treatment was stopped. In this case, a correlation between the acquisition of resistance to gemcitabine therapy and change in HuR expression was demonstrated.

Thanks to the development of modern chemotherapeutic regimens, survival after surgery for pancreatic ductal adenocarcinoma (PDAC) has improved and pancreatologists worldwide agree that the treatment of PDAC demands a multidisciplinary approach. Neoadjuvant treatment (NAT) plays a major role in the treatment of PDAC since only about 20% of patients are considered resectable at the time of diagnosis. Moreover, increasing data demonstrating the benefits of NAT for borderline resectable/locally advanced PDAC are driving a shift from up-front surgery to NAT in the multidisciplinary treatment of even resectable PDAC. Our understanding of the role of NAT in PDAC has evolved from tumor shrinkage to controlling potential micrometastases and selecting patients who may benefit from radical resection. The present review gives an overview on the current literature of NAT concepts for BR/LA PDAC and resectable PDAC.

Simple Summary Intraductal papillary mucinous neoplasms (IPMN) are common but difficult to manage since accurate tools for diagnosing malignancy are unavailable. This study evaluates the diagnostic value of main pancreatic duct (MPD) diameter for detecting IPMN malignancy, using a meta-analysis of published data. The result suggests that malignancy is highly prevalent in IPMN with ductal dilatation of >5 mm. Abstract Intraductal papillary mucinous neoplasms (IPMN) are common but difficult to manage since accurate tools for diagnosing malignancy are unavailable. This study tests the diagnostic value of the main pancreatic duct (MPD) diameter for detecting IPMN malignancy using a meta-analysis of published data of resected IPMNs. Collected from a comprehensive literature search, the articles included in this analysis must report malignancy cases (high-grade dysplasia (HGD) and invasive carcinoma (IC)) and MPD diameter so that two MPD cut-offs could be created. The sensitivity, specificity, and odds ratios of the two cutoffs for predicting malignancy were calculated. A review of 1493 articles yielded 20 retrospective studies with 3982 resected cases. A cutoff of ≥5 mm is more sensitive than the ≥10 mm cutoff and has pooled sensitivity of 72.20% and 75.60% for classification of HGD and IC, respectively. Both MPD cutoffs of ≥5 mm and ≥10 mm were associated with malignancy (OR = 4.36 (95% CI: 2.82, 6.75) vs. OR = 3.18 (95% CI: 2.25, 4.49), respectively). The odds of HGD and IC for patients with MPD ≥5 mm were 5.66 (95% CI: 3.02, 10.62) and 7.40 (95% CI: 4.95, 11.06), respectively. OR of HGD and IC for MPD ≥10 mm cutoff were 4.36 (95% CI: 3.20, 5.93) and 4.75 (95% CI: 2.39, 9.45), respectively. IPMN with MPD of >5 mm could very likely be malignant. In selected IPMN patients, pancreatectomy should be considered when MPD is >5 mm.

BACKGROUND For the establishment of personalized therapy, we investigated biomarkers that can contribute to the selection of adjuvant therapy for pancreatic ductal adenocarcinoma (PDAC). METHODS Between 2005 and 2014, of 141 consecutive patients with PDAC who underwent R0 or R1 resection, 61 patients given gemcitabine and 31 patients given S-1 as adjuvant therapy were enrolled. We evaluated the correlation between treatment outcomes and the expressions of intratumoral human antigen R (HuR), human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD). RESULTS There were no significant differences in clinicopathological features between the gemcitabine and S-1 groups. Among those with high HuR expression and high hENT1 expression, the disease-free survival (DFS) was significantly higher with gemcitabine than with S-1 (MST: 26.2 vs. 11.8 months, P = 0.024; 20.2 vs. 10.2 months, P = 0.029, respectively). Moreover, high HuR/hENT1 (high HuR or high hENT1) was significantly associated with better outcome for gemcitabine (HR for DFS: 0.43, P = 0.027) and low HuR/hENT1 was significantly associated with worse outcome for gemcitabine (HR for DFS: 2.24, P = 0.021). TS and DPD expression levels were not informative in this examination. CONCLUSIONS HuR and hENT1 were good candidates as selective biomarkers and this study's concept could contribute to personalized therapy for PDAC patients.

A novel morphological classification using resected specimens predicted malignant potential and prognosis in patients with pancreatic neuroendocrine tumors (P-NETs). The aim of this study was to examine the predictive ability of morphological diagnoses made using non-invasive multi-detector computed tomography (MDCT) in P-NETs. Between 2002 and 2015, 154 patients were diagnosed with P-NETs at the Tokyo Medical and Dental University, and 82 patients who underwent surgical treatment were enrolled. The primary tumors were classified by MDCT into three types: Type I, simple nodular tumor; Type II, simple nodular tumor with extra-nodular growth; and Type III, confluent multinodular tumor. Patients were stratified by 15 clinical specialists according to classification and without any other clinical or pathological information. Clinicopathological features and patient survival were reviewed retrospectively. The mean observation time was 1004 days. Forty-six, 22, and 14 patients had Type I, II, and III tumors, respectively. Morphological classification was significantly correlated with advanced features such as tumor size, Ki-67 index, and synchronous liver metastasis (p

We herein present a case of a 59-year-old man who had undergone pylorus preserving pancreaticoduodenectomy with regional lymph node dissection prior to episodes of melena. Series of conventional endoscopic investigations failed to identify the bleeding source. Enhanced computed tomography scan revealed complete obstruction of the main portal vein with numerous collateral veins running towards the hepatic hilus. Comprehensively, hemorrhage from the jejunal varices caused by postoperative portal hypertension was highly suspected. As the jejunal loop was out of reach, adult variable-stiffness colonoscope (AVSC) was utilized to solve the Roux-en-Y anatomy. Numerous telangiectasis and small varices at hepaticojejunostomy were observed and in the mean time, bleeding was noticed and endoclips were placed without any delay. Ectopic variceal bleeding in jejunal loop after pancreaticoduodenectomy is difficult to manage. We believe that AVSC is an alternative device when specialized jejunal endoscopy is not available.

Background & Aims Recent genomic studies have identified frequent mutations of AT-rich interactive domain 2 ( ARID2 ) in hepatocellular carcinoma (HCC), but it is not still understood how ARID2 exhibits tumor suppressor activities. Methods We established the ARID2 knockout human HCC cell lines by using CRISPR/Cas9 system, and investigated the gene expression profiles and biological functions. Results Bioinformatic analysis indicated that UV-response genes were negatively regulated in the ARID2 knockout cells, and they were sensitized to UV irradiation. ARID2 depletion attenuated nucleotide excision repair (NER) of DNA damage sites introduced by exposure to UV as well as chemical compounds known as carcinogens for HCC, benzo[a]pyrene and FeCl 3 , since xeroderma pigmentosum complementation group G (XPG) could not accumulate without ARID2. By using large-scale public data sets, we validated that ARID2 knockout could lead to similar molecular changes between in vitro and in vivo settings. A higher number of somatic mutations in the ARID2 -mutated subtypes than that in the ARID2 wild-type across various types of cancers including HCC was observed. Conclusions We provide evidence that ARID2 knockout could contribute to disruption of NER process through inhibiting the recruitment of XPG, resulting in susceptibility to carcinogens and potential hypermutation. These findings have implications for therapeutic targets in cancers harboring ARID2 mutations. Lay summary Recent genomic studies have identified frequent mutations of ARID2, a component of the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex, in hepatocellular carcinoma, but it is not still understood how ARID2 exhibits tumor suppressor activities. In current study, we provided evidence that ARID2 knockout could contribute to disruption of DNA repair process, resulting in susceptibility to carcinogens and potential hypermutation. These findings have far-reaching implications for therapeutic targets in cancers harboring ARID2 mutations.