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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

In recent years, automatic ontology generation has received significant attention in information science as a means of systemizing vast amounts of online data. As our initial attempt of ontology generation with a neural network, we proposed a recurrent neural network-based method. However, updating the architecture is possible because of the development in natural language processing (NLP). By contrast, the transfer learning of language models trained by a large, unlabeled corpus has yielded a breakthrough in NLP. Inspired by these achievements, we propose a novel workflow for ontology generation comprising two-stage learning. Our results showed that our best method improved accuracy by over 12.5%. As an application example, we applied our model to the Stanford Question Answering Dataset to show ontology generation in a real field. The results showed that our model can generate a good ontology, with some exceptions in the real field, indicating future research directions to improve the quality.

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.

Patients with pancreatic cancer (PC) have poor prognosis and a high incidence of recurrence. Since further treatment is applicable for specific recurrent events, it is important to predict recurrence patterns after surgery. This study aimed to identify and predict early and late recurrence patterns of PC using a histology-based machine learning model.Patients who underwent upfront curative surgery for PC between 2001 and 2014 were included. The timing of recurrence and prognosis of each first recurrence site were examined. A histology-based supervised machine learning method, which combined convolutional neural networks and random forest, was used to predict the recurrence and respective sites of metastasis. Accuracy was evaluated using area under the receiver operating characteristic curve (AUC).In total, 524 patients were included. Recurrence in the liver accounted for 47.8% of all recurrence events in the first year after surgery. Meanwhile, recurrence in the lung occurred later and could become apparent more than 5 years post-surgery, with indications for further surgery. In terms of substantial distant organ metastases, liver and lung metastases were identified as representative early and late recurrence events. The predictive AUCs of the machine learning model for training and test data were 1.000 and 0.861, respectively, and for predicting nonrecurrence were 1.000 for both.We identified the liver and lung as early and late recurrence sites, which could be distinguished with high probability using a machine learning model. Prediction of recurrence sites using this model may be useful for further treatment of patients with PC.

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

Background Previous studies have documented potential advantages of laparoscopic hepatectomy in decreasing blood loss compared with open surgery. This study aimed to compare intraoperative blood loss estimated using four different methods in open versus laparoscopic hepatectomy. Methods Patients undergoing liver resection between 2014 and 2017 were evaluated prospectively, differentiating between the laparoscopic and open approach. Groups were compared using univariable and multivariable analyses. Intraoperative blood loss was estimated using three formulas based on the postoperative decreases in haematocrit, haemoglobin or red blood cell volume, and using the conventional method of the sum of suction fluid amounts and gauze weight. In addition, blood loss per hepatic transection area was calculated to compare groups. Results Some 125 patients who underwent hepatectomy were selected, including 56 open hepatectomies and 69 laparoscopic liver resections. Intraoperative blood loss per hepatic transection area estimated by the conventional method was significantly less in the laparoscopic than the open group (3·6 (range 0·2–50·0) versus 6·6 (1·2–82·5) ml/cm2 respectively; 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.

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 0.001, respectively). Patients with tumors 4 cm had higher rates of R1 resection (16%) and concomitant resection of another organ (19%) than those with smaller tumors (4% and 2%, p = 0.009 and p 0.001, respectively). In multivariate analysis, tumor 4 cm remained a significant predictor of early recurrence (p 0.001, hazard ratio [HR] 6.51), shorter RFS (p = 0.018, HR 1.71), and shorter DSS (p = 0.002, HR 2.07).Tumor size 4 cm is a reliable predictor of early recurrence after resection of distal PDAC, and neoadjuvant therapy may help select patients who can benefit from radical resection.

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.

Although endoscopic naso-biliary drainage (ENBD) is a popular preoperative biliary drainage (PBD) method for patients with perihilar biliary malignancy (PHBM), patient discomfort caused by the nasal tube remains a problem. This study aimed to analyze the safety and efficacy of PBD with the placement of a plastic stent above the papilla [inside-stent (IS)] as a bridging therapy.The outcomes of 78 patients with potentially resectable PHBM, of whom 29 underwent IS placement and 49 underwent ENBD were evaluated.The stent-associated complication rates were not different between the two groups (7% in the IS group and 10% in the ENBD group, P = 0.621). Catheter dislocation occurred less frequently (0% vs. 22%, P = 0.016), and the median time to recurrent biliary obstruction was longer (not reached vs. 32 days, P = 0.039) in the IS group than in the ENBD group. Among the patients who underwent resection, their postoperative severe complication rates were not substantially different (26% vs. 25%, P = 0.923).IS placement is a possible alternative to ENBD as a bridge to a definitive operation for patients with resectable PHBM and a prospective trial to prove its feasibility and safety is therefore warranted.

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

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.

To identify objective preoperative prognostic factors that are able to predict long-term survival of patients affected by PDAC.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.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.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.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.

Background/objectives Pancreatic cystic neoplasms (PCNs) are common, among which 13%–23% are serous cystic neoplasms (SCNs). However, diffuse and multifocal variants of SCNs are extremely rare. The differential diagnosis of SCNs from other PCNs is important as the former entities are benign and do not become invasive. Objective This study analyzes the clinical characteristics of multifocal/diffuse SCN through a systematic review of the literature and a case report. Methods A comprehensive literature search was executed in the Ovid MEDLINE, Embase, and Google Scholar databases. The search strategy was designed to capture the concept of multifocal/diffuse SCN cases with sufficient clinical information for detailed analysis. Using the final included articles, we analyzed tumor characteristics, diagnostic modalities used, initial management and indications, and patient outcomes. Results A review of 262 articles yielded 19 publications with 22 cases that had detailed clinical information. We presented an additional case from our institution database. The systematic review of 23 cases revealed that the diffuse variant is more common than the multifocal variant (15 vs 8 cases, respectively). Patients were managed with surgical intervention, conservative treatment, or conservative treatment followed by surgical intervention. Indications for surgery following conservative management mainly included new onset or worsening of symptoms. Only one case reported significant tumor growth after attempting an observational approach. No articles reported recurrence of SCN after pancreatectomy, and no articles reported mortality related to multifocal/diffuse SCNs. Conclusion Despite their expansive-growing and space-occupying characteristics, multifocal/diffuse SCNs should be treated similarly to their more common unifocal counterpart.

Background and Aims: It has become clear that vein resection and reconstruction for pancreatic ductal adenocarcinoma (PDAC) is the standard of care as supported by multiple guidelines. However, resection of large peri-pancreatic arteries remains debatable. Materials and Methods: This review examines the current state of vascular resection with curative intent for PDAC in the last 5 years. Herein, we consider venous (superior mesenteric vein, portal vein), as well as arterial (superior mesenteric artery, celiac trunk, hepatic artery) resection or both with or without reconstruction. Results: Improvement of multidrug chemotherapy has revolutionized care for PDAC that should shift traditional surgical thinking from an anatomical classification of resectability to a prognostic and biological classification. Conclusion: The present review gives an overview on the results of pancreatectomy associated with vascular resection, with consideration of new perspectives offered by the availability of better systemic therapies.

178 Background: Colorectal cancer with liver metastases (CLM) has high post operative recurrence rates, and optimizing the perioperative treatment is imperative. Post operative carcinoembryonic antigen (CEA) can help detecting minimal residual disease in colon cancer after curative resection. Methods: The aim of this study was to identify the potential role of serum CEA after liver resection in patients with CLM. This study was conducted at the Cancer Institute Hospital, Japanese Foundation for Cancer Research from 2004 to 2018. Patients with CLM who underwent complete resection of primary tumors and liver metastases were enrolled in this study. We studied the associations between the perioperative CEA levels and characteristics of recurrence. Results: Recurrence was detected during the median follow-up time of 50.9 months in 343 (54.1%) of the total 633 patients analyzed. Patients with postoperative CEA (>5) group had a significantly higher recurrence rate (75.7% vs 50.0%, p < 0.01), with a shorter time until recurrence (4.4 months vs 36.9 months, p < 0.01) than those with a postoperative CEA level (≤5) group. In multivariate analysis, a postoperative CEA level >5 ng/ ml was an independent predictor, with the highest hazard ratio for both recurrence free survival (RFS) and overall survival (OS) (RFS: 2.77, 95% confidence interval [CI] 2.14–3.60, p 5) group who did not have normalized CEA levels after adjuvant chemotherapy compared to normalized CEA group (3.3 months vs 18.5 months, p = 0.008). Conclusions: The postoperative CEA and postadjuvant chemotherapy CEA level in the CEA level (>5) group after surgery may be a predictor of RFS and OS.

290 Background: While systemic chemotherapy for gastric cancer has evolved significantly in the last decade, the role of surgery for liver metastasis remained controversial. The aims of this study were to examine the trend in outcomes of patients with gastric cancer liver metastasis (GCLM) undergoing resection at our center, and to define the optimal selection criteria for resection. Methods: One hundred and twenty-two consecutive patients who underwent liver resection for GCLMs with curative intent at our institution from 1993 through 2021 were included. The patients were grouped into 2 eras: era I, 1993 to 2010; era II, 2011 to 2021. Our criteria for liver resection included absence of extrahepatic disease, and the limited number of liver metastasis (often 3 or less). Median follow-up was 34 months for all and 71 months for the survivors. Results: There were 63 patients in era I and 59 in era II. The patients in era II received chemotherapy prior to liver resection more often (68% vs 41%, p = 0.004), and their primary tumor was less advanced (T3/4; 66% vs 85%, p = 0.021) with less regional lymph node metastasis (median No. of positive nodes; 4 vs 1, p = 0.034) compared to those in ear I. Median and 5-year disease-specific survival (DSS) were better in era II (not reached, 55%) than in era I (35 months, 35%, p = 0.025). In the multivariate analysis for the entire cohort, elevated CEA (> 50 ng/ml), primary T4, and primary at the proximal stomach emerged as independent factors associated with shorter DSS. Number of these risk factors are highly predictive for long-term survival; among the patients without or with a single factor alone, 5-year DSS was 50%, whereas none of those with multiple risk factors survived beyond 5 years ( p< 0.0001). Conclusions: Long-term outcomes for patients with oligo-GCLM has improved in the modern chemotherapy era. Liver resection should be considered unless they carry multiple risk factors.

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.

685 Background: For borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC), neoadjuvant (NAT) FOLFIRINOX or gemcitabine plus nab-paclitaxel (GnP) are standard treatment options and these regimens have shown a survival advantage over single-agent gemcitabine. However, the role of these modern therapeutic regimens in elderly patients is debatable. In this analysis, we evaluated the outcomes of neoadjuvant treatment (NAT) with combination chemotherapy in elderly patients. Methods: 230 consecutive patients who underwent neoadjuvant treatment for BRPC/LAPC discussed and planned for NAT at the University of Colorado Cancer Center from January 2011 to March 2019 were reviewed. 214 patients who received FOLFIRINOX (n = 143) or GnP (n = 71) were eligible for analysis. We divided all patients into three groups ( < 70, 70-74, ≥75 years) and compared the short-term and long-term outcomes. Results: Of 214 patients, patients < 70 (n = 147) received FOLFIRINOX more frequently than the other groups (p < 0.001): FOLFIRINOX: 115 cases, GnP: 32 cases, 70-74 years (n = 33): FOLFIRINOX: 15 cases, GnP: 18 cases, and ≥75 years (n = 34): FOLFIRINOX: 13 cases, GnP: 21 cases. Resection rates were not statistically different between three groups ( < 70: 62%, 70-74: 70%, ≥75 years: 56%, p = 0.504). There was a slight trend towards worse survival in the two older groups (Median Survival Time [MST]: < 70: 23.2 mo., 70-74: 19.5 mo., ≥75 years: 17.6 mo., p = 0.075) The FOLFIRINOX group was superior to GnP group in all three groups (MST: < 70: 25.6 vs 18.2 mo., p = 0.017; 70-74: 33.2 vs 16.1mo., p = 0.029; ≥75 years: not reached vs 16.1 mo., p = 0.135). There were no toxic deaths or 30 day mortality after pancreatectomy in the study population. Conclusions: Neoadjuvant combination chemotherapy regimens were safe and feasible for elderly patients. Neoadjuvant therapy with FOLFIRINOX was associated with a survival advantage vs GnP and is an good option for fit and elderly patients ≥75 years.

Background We previously reported the usefulness of distal pancreatectomy with celiac axis resection (DP-CAR) with left gastric artery (LGA) reconstruction to prevent ischemic gastropathy. To evaluate the reconstruction quality, we performed intraoperative angiography with indocyanine green (ICG)-fluorescence imaging. Methods 21 consecutive patients planned for DP-CAR with LGA reconstruction were enrolled in this prospective, exploratory single-arm study from 2014 to 2017. After LGA reconstruction, intraoperative angiography revealed continuous arterial flow passing through the anastomotic sites and gradually increasing tissue perfusion in the stomach. Results Three patients were excluded. Among the remaining 18 patients, we obtained good flow in 11 patients and poor flow in 7 patients after initial LGA reconstruction. Among the seven patients with poor flow, five underwent LGA re-anastomosis, three recovered good flow. The incidence of grade B/C DGE was 14% (2/14) in the finally good flow group and 75% (3/4) in the poor flow group (p = 0.019). Ischemic gastropathy occurred in two patients (50%) in the poor flow group (p = 0.039), including one with a gastric perforation. Discussion Our data show that intraoperative angiography with ICG-fluorescence imaging can evaluate the reconstruction quality, thus contributing to improvements in the short-term outcome of DP-CAR with LGA reconstruction.

Background and aim To improve the prognosis of cholangiocarcinoma, we investigated potential biomarkers that may enable the selection of patients for whom postoperative adjuvant chemotherapy is likely effective. Methods The cohort of this retrospective study included 170 surgically resected cholangiocarcinoma patients, 26 with gemcitabine adjuvant chemotherapy (GEM group), 36 with S-1 adjuvant chemotherapy (S-1 group), and 103 receiving no adjuvant chemotherapy (NC group). Propensity score matching was performed to adjust patient backgrounds; 36 patients from the NC group then were selected. Immunohistochemistry of orotate phosphoribosyltransferase (OPRT) and human equilibrative nucleoside transporter 1 (hENT1) was performed to determine the correlation between their expression and disease-free survival (DFS). Results After matching, the backgrounds of these three groups were unbiased. No significant improvement of DFS by adjuvant chemotherapy was observed in the whole cohort. However, among the high-OPRT-expression patients, DFS of GEM, S-1, and NC groups at 5 years was 28.8%, 53.8%, and 25.5%, respectively. The DFS of the S-1 group was significantly longer than that of the NC group (P = 0.034). On the other hand, no significant differences in DFS were observed among the low OPRT expression patients. hENT1 expression was shown to have no predictive value. Multivariate analysis of the high-OPRT-expression patients demonstrated that S-1 adjuvant chemotherapy can reduce tumor recurrence (HR, 0.303; P = 0.013). Conclusion Cholangiocarcinoma patients with high OPRT expression would benefit from postoperative adjuvant S-1 therapy, which increases the DFS. Assessment of OPRT expression may contribute to the optimization of adjuvant chemotherapy for cholangiocarcinoma.

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.

For the establishment of personalized therapy, we investigated biomarkers that can contribute to the selection of adjuvant therapy for pancreatic ductal adenocarcinoma (PDAC).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).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.HuR and hENT1 were good candidates as selective biomarkers and this study's concept could contribute to personalized therapy for PDAC patients.

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.