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Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer type that urgently requires effective therapeutic strategies. Andrographolide, a labdane diterpenoid compound abundant in Andrographis paniculata, has anticancer effects against various cancer types, but its anticancer activity and mechanism against PDAC remain largely uncharacterized., Purpose: This study explores novel drug target(s) and underlying molecular mechanism of andrographolide against PDAC., Study Design and Methods: The malignant phenotypes of PDAC cells, PANC-1 and MIA PaCa-2 cells, were measured using MTT, clonogenic assays, and Transwell migration assays. A PDAC xenograft animal model was used to evaluate tumor growth in vivo. Western blot, immunofluorescence and immunohistochemistry were used for measuring protein expression. The TCGA database was analyzed to evaluate promoter methylation status, gene expression, and their relationship with patient survival rates. RT-qPCR was used for detecting mRNA expression. Reporter assays were used for detecting signal transduction pathways. Promoter DNA methylation was determined by sodium bisulfite treatment and methylation-specific PCR (MSP). The biological function and role of specific genes involved in drug effects were measured through gene overexpression., Results: Andrographolide treatment suppressed the proliferation and migration of PDAC cells and impaired tumor growth in vivo. Furthermore, andrographolide induced the mRNA and protein expression of zinc finger protein 382 (ZNF382) in PDAC cells. Overexpression of ZNF382 inhibited malignant phenotypes and cancer-associated signaling pathways (AP-1, NF-κB and β-catenin) and oncogenes (ZEB-1, STAT-3, STAT-5, and HIF-1α). Overexpression of ZNF382 delayed growth of PANC-1 cells in vivo. ZNF382 mRNA and protein expression was lower in tumor tissues than in adjacent normal tissues of pancreatic cancer patients. Analysis of the TCGA database found the ZNF382 promoter is hypermethylated in primary pancreatic tumors which correlates with its low expression. Furthermore, andrographolide inhibited the expression of DNA methyltransferase 3 beta (DNMT3B) and increased the demethylation of the ZNF382 promoter in PDAC cells. Overexpression of DNMT3B attenuated the andrographolide-suppressed proliferation and migration of PDAC cells., Conclusion: Our finding revealed that ZNF382 acts as a tumor suppressor gene in pancreatic cancer and andrographolide restores ZNF382 expression to suppress pancreatic cancer, providing a novel molecular target and a promising therapeutic approach for treating pancreatic cancer., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shu-ling Fu reports financial support was provided by the National Science and Technology Council in Taiwan. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: In patients with hepatic artery variation (HAV), feasibility and justification of robotic pancreatoduodenectomy (RPD) for periampullary lesions have been not been well established., Methods: A total of 600 patients with periampullary lesions receiving RPD or open pancreaticoduodenectomy (OPD) were identified from our prospectively collected computer database. Surgical outcomes, oncological radicality, and survival outcomes after RPD in HAV ( +) and (-) patients were compared., Results: The incidence of HAV was 16%, including 12.7% in patients with RPD and 23.0% in those with OPD. In the HAV ( +) group, vascular injury rate had no statistical difference between the RPD (3.7%) and OPD (9.1%) patients, P = 0.404. Among the RPD patients, those with HAV ( +) had longer operation time (8.5 ± 2.5 vs. 7.7 ± 2.0 h, P = 0.013) and higher vascular injury (3.8% vs. 0.6%, P = 0.024) when compared with the HAV (-) patients. There was no significant difference between the HAV ( +) and (-) patients with RPD regarding blood loss, open conversion, vascular resection, and surgical mortality and morbidity. There was no survival difference between the HAV ( +) and (-) patients with pancreatic head adenocarcinoma after RPD. There was no survival difference between RPD and OPD in the HAV ( +) group., Conclusions: When compared with OPD, RPD is feasible and justifiable without increasing vascular injury rate for patients with HAV ( +). Hepatic artery variation has no negative impact on surgical, oncological, and survival outcomes following an RPD, if it is accurately identified pre-operatively and appropriately managed intraoperatively., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: We aimed to assess the diagnostic utility of an immunohistochemical panel including calcium-binding protein P, p53, Ki-67, and SMAD family member 4 and K-ras mutation for diagnosing pancreatic solid lesion specimens obtained by endoscopic ultrasound-guided fine-needle biopsy and to confirm their usefulness in histologically inconclusive cases., Methods: Immunohistochemistry and peptide nucleic acid-clamping polymerase chain reaction for K-ras mutation were performed on 96 endoscopic ultrasound-guided fine-needle biopsy specimens. The diagnostic efficacy of each marker and the combination of markers was calculated. The diagnostic performances of these markers were evaluated in 27 endoscopic ultrasound-guided fine-needle biopsy specimens with histologically inconclusive diagnoses. A classification tree was constructed., Results: K-ras mutation showed the highest accuracy and consistency. Positivity in more than two or three of the five markers showed high diagnostic accuracy (94.6 % and 93.6 %, respectively), and positivity for more than three markers showed the highest accuracy for inconclusive cases (92.0 %). A classification tree using K-ras mutation, Ki-67, S100P, and SMAD4 showed high diagnostic performance, with only two misclassifications in inconclusive cases., Conclusions: K-ras mutation detection via peptide nucleic acid-clamping polymerase chain reaction is a stable and accurate method for distinguishing between pancreatic ductal adenocarcinoma and non-pancreatic ductal adenocarcinoma lesions. A classification tree using K-ras mutation, Ki-67, S100P, and SMAD4 helps increase the diagnostic accuracy of cases that are histologically difficult to diagnose., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Introduction: Pancreatic cancer cells generally accumulate large numbers of lipid droplets (LDs), which regulate lipid storage. To promote rapid diagnosis, an automatic pancreatic cancer cell recognition system based on a deep convolutional neural network was proposed in this study using quantitative images of LDs from stain-free cytologic samples by optical diffraction tomography., Methods: We retrieved 3D refractive index tomograms and reconstructed 37 optical images of one cell. From the four cell lines, the obtained fields were separated into training and test datasets with 10,397 and 3,478 images, respectively. Furthermore, we adopted several machine learning techniques based on a single image-based prediction model to improve the performance of the computer-aided diagnostic system., Results: Pancreatic cancer cells had a significantly lower total cell volume and dry mass than did normal pancreatic cells and were accompanied by greater numbers of lipid droplets (LDs). When evaluating multitask learning techniques utilizing the EfficientNet-b3 model through confusion matrices, the overall 2-category accuracy for cancer classification reached 96.7 %. Simultaneously, the overall 4-category accuracy for individual cell line classification achieved a high accuracy of 96.2 %. Furthermore, when we added the core techniques one by one, the overall performance of the proposed technique significantly improved, reaching an area under the curve (AUC) of 0.997 and an accuracy of 97.06 %. Finally, the AUC reached 0.998 through the ablation study with the score fusion technique., Discussion: Our novel training strategy has significant potential for automating and promoting rapid recognition of pancreatic cancer cells. In the near future, deep learning-embedded medical devices will substitute laborious manual cytopathologic examinations for sustainable economic potential., Competing Interests: Declaration of competing interest The authors declare no conflict of interest relevant to this work, (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The role of the robotic approach for pancreaticoduodenectomy has not been well established with robust data. This study aimed to reappraise feasibility and justification of robotic pancreaticoduodenectomy (RPD) over time., Methods: A total of 500 patients undergoing RPD were enrolled and divided into early (first 250 patients) and late (last 250 patients) groups for a comparative study., Results: The conversion rate was 8.8% overall and was significantly lower in the late group (5.6% vs. 12.0%; p = .012). The overall median intraoperative blood loss was 130 mL. Radicality of resection was similar between early and late groups. The overall surgical mortality after RPD was 1.3%. The overall surgical morbidity and major complication was 44.1% and 13.2%, respectively, and similar between early and late groups. Chyle leakage was the most common complication after RPD (25.0%), followed by postoperative pancreatic fistula (POPF). The POPF rate was 8.6% overall, with 5.9% in the early group and 11.0% in the late group, p = .051. The overall delayed gastric emptying rate was 3.5%. The late group had better survival outcomes than those of the early group after RPD for ampullary adenocarcinoma (p = .027) but not for pancreatic head adenocarcinoma., Conclusions: Reappraisal of this study has confirmed that RPD is not only technically feasible without increasing surgical risks but also oncologically justified without compromising survival outcomes for both pancreatic head and other periampullary cancers over time. Moreover, RPD is associated with the benefits of low surgical mortality, blood loss, and delayed gastric emptying., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background/objective: Robotic pancreaticoduodenectomy in ampullary cancer has never been studied. This study aimed to clarify the feasibility and justification of robotic pancreaticoduodenectomy in ampullary cancer in terms of surgical risks, and oncologic and survival outcomes., Methods: A propensity score-matching comparison of robotic and open pancreaticoduodenectomy based on seven factors commonly used to predict the survival outcomes in ampullary cancer patients., Results: A total of 147 patients were enrolled, of which 101 and 46 underwent robotic and open pancreaticoduodenectomies, respectively. After propensity score-matching with a 2:1 ratio, 88 and 44 patients in the robotic and open pancreaticoduodenectomy groups were included. The operation time was of no significant difference after matching. The median intraoperative blood loss was much less in those who underwent robotic pancreaticoduodenectomy, both before (median, 120 vs. 320 c.c. P < 0.001) and after (100 vs. 335 mL P < 0.001) score-matching. There were no significant differences in terms of surgical risks, including surgical mortality, surgical morbidity, Clavien-Dindo severity classification, postoperative pancreatic fistula, delayed gastric emptying, post-pancreatectomy hemorrhage, chyle leak, bile leak, and wound infection, both before or after score-matching. The survival outcomes were also similar between the two groups, regardless of matching., Conclusions: Robotic pancreaticoduodenectomy for ampullary cancer is not only technically feasible and safe without increasing surgical risks, but also oncologically justifiable without compromising surgical radicality and survival outcomes., Competing Interests: Declaration of competing interest Bor-Shiuan Shyr, Shin-E Wang, Shih-Chin Chen, Yi-Ming Shyr, Bor-Uei Shyr have no conflicts of interest or financial ties to disclose., (Copyright © 2024 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare that they have no conflict of interest.

Background: Adjuvant therapy prolongs survival in patients with pancreatic ductal adenocarcinoma. However, no clear guidelines are available regarding the oncologic effects of adjuvant therapy (AT) in resected invasive intraductal papillary mucinous neoplasms (IPMN). The aim was to investigate the potential role of AT in patients with resected invasive IPMN., Materials and Methods: From 2001 to 2020, 332 patients with invasive pancreatic IPMN were retrospectively reviewed in 15 centres in eight countries. Propensity score-matched and stage-matched survival analyses were conducted., Results: A total of 289 patients were enroled in the study after exclusion (neoadjuvant therapy, unresectable disease, uncertain AT status, and stage IV). A total of 170 patients were enroled in a 1:1 propensity score-matched analysis according to the covariates. In the overall cohort, disease-free survival was significantly better in the surgery alone group than in the AT group ( P =0.003), but overall survival (OS) was not ( P =0.579). There were no significant differences in OS in the stage-matched analysis between the surgery alone and AT groups (stage I, P =0.402; stage II, P =0.179). AT did not show a survival benefit in the subgroup analysis according to nodal metastasis (N0, P =0.481; N+, P =0.705). In multivariate analysis, node metastasis (hazard ratio, 4.083; 95% CI, 2.408-6.772, P <0.001), and cancer antigen 19-9 greater than or equal to 100 (hazard ratio, 2.058; 95% CI, 1.247-3.395, P =0.005) were identified as adverse prognostic factors in resected invasive IPMN., Conclusion: The current AT strategy may not be recommended to be performed with resected invasive IPMN in stage I and II groups, unlike pancreatic ductal adenocarcinoma. Further investigations of the potential role of AT in invasive IPMN are recommended., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: Whether to execute pancreaticoduodenectomy or not for older people could pose a dilemma. This study clarifies the safety and justification of robotic pancreaticoduodenectomy (RPD) for older individuals over 80., Methods: A total of 500 patients undergoing RPD were divided into group O (≥ 80 y/o) and group Y (< 80 y/o) for comparison., Results: There were 62 (12.4%) patients in group O. Surgical mortality was 1.6% for overall patients and higher in group O, 6.5% vs 0.9%; p = 0.001. The surgical complication was comparable between groups O and Y. Delayed gastric emptying and bile leakage were higher in group O, 9.7% vs 2.5%; p = 0.004, and 6.5% vs 0.9%; p = 0.001, respectively. Length of stay was also longer in group O, with a median of 26 vs 19 days; p = 0.001. Survival outcome after RPD was poorer in group O for overall periampullary adenocarcinomas, with a 5-year survival of 48.1% vs 51.2%; p = 0.025 and also for the subgroup of pancreatic head adenocarcinoma, with a 3-year survival of 27.4% vs 42.5%; p = 0.030., Conclusion: RPD is safe and justified for the selected octogenarians and even nonagenarians, whoever is fit for a major operation. Nevertheless, pancreatic head cancer and higher mortality risk for the aged over 80 with advanced ASA score ≥ 3 should be informed as part of counselling in offering RPD., Competing Interests: All authors report no conflicts of interest in this work., (© 2023 Shyr et al.)

Background: The torque and fanning techniques allow for multiple areas within pancreatic lesions to be targeted using different maneuvers and can, hence, enhance diagnostic outcomes. We compared the diagnostic performance of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) for pancreatic masses using the torque and fanning techniques., Methods: This multicenter randomized trial enrolled a total of 160 consecutive patients who underwent EUS-FNB for solid pancreatic tumors using either the torque or fanning technique. Three passes were permitted for each lesion, and the technique sequence was randomly assigned as either torque first or fanning first with the standard technique as a reference., Results: The median quality score of the histological samples was significantly higher in the torque and fanning group than in the standard group (p < .001). Furthermore, the torque technique provided improved sensitivity of 93.38% and accuracy of 94.30%. The standard technique provided diagnostic sensitivity of 68.84% and accuracy of 72.96%, while the fanning technique showed sensitivity of 91.85% and accuracy of 93.04%., Conclusions: The new torque technique enables the acquisition of better-quality samples and can potentially increase the diagnostic outcomes in the EUS-FNB of pancreatic solid masses, with the same recommendations as those for the fanning technique., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Although we previously proposed a nomogram to predict malignancy in intraductal papillary mucinous neoplasms (IPMN) and validated it in an external cohort, its application is challenging without data on tumor markers. Moreover, existing nomograms have not been compared. This study aimed to develop a nomogram based on radiologic findings and to compare its performance with previously proposed American and Korean/Japanese nomograms., Methods: We recruited 3708 patients who underwent surgical resection at 31 tertiary institutions in eight countries, and patients with main pancreatic duct >10 mm were excluded. To construct the nomogram, 2606 patients were randomly allocated 1:1 into training and internal validation sets, and area under the receiver operating characteristics curve (AUC) was calculated using 10-fold cross validation by exhaustive search. This nomogram was then validated and compared to the American and Korean/Japanese nomograms using 1102 patients., Results: Among the 2606 patients, 90 had main-duct type, 900 had branch-duct type, and 1616 had mixed-type IPMN. Pathologic results revealed 1628 low-grade dysplasia, 476 high-grade dysplasia, and 502 invasive carcinoma. Location, cyst size, duct dilatation, and mural nodule were selected to construct the nomogram. AUC of this nomogram was higher than the American nomogram (0.691 vs 0.664, P = .014) and comparable with the Korean/Japanese nomogram (0.659 vs 0.653, P = .255)., Conclusions: A novel nomogram based on radiologic findings of IPMN is competitive for predicting risk of malignancy. This nomogram would be clinically helpful in circumstances where tumor markers are not available. The nomogram is freely available at http://statgen.snu.ac.kr/software/nomogramIPMN., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background/objective: Pancreatic neuroendocrine tumors (P-NETs) are highly heterogeneous with wide spectrum of biological behaviors and growth patterns. Here, we aimed to assess the impact of tumor grading on P-NETs prognosis and survival outcomes., Methods: Patients with P-NET were recruited to determine correlations between grades and clinicopathological factors, survival outcomes and prognostic factors., Result: A total of 152 patients with P-NETs were enrolled. G1 P-NET were associated with significantly lower rates of perineural invasion, lymphovascular invasion, lymph node involvement and distant metastasis. The pancreatic head was the most common location of P-NETs. The 1-year, 5-year and 10-year overall survival rates of the patients were 94.4%, 89.1% and 78.8%, respectively. Majority of pancreatic neuroendocrine carcinoma (P-NEC) were unresectable (90.9%), and P-NECs patients had poor survival rates (1-year, 20% and no 5-year). Male sex, tumor size ≥2.5 cm, perineural invasion, lymph node invasion, metastasis, and advanced stage were significantly associated with poorer survival outcomes. Tumor grade and sex were independent survival predictors. Moreover, tumor grade was the most powerful prognostic factor., Conclusions: Tumor grade, sex, perineural invasion, tumor size, lymph node involvement, metastasis, and stage are survival predictors for patients with P-NETs. Tumor grade is the most powerful independent prognostic factor., Competing Interests: Declaration of competing interest Bor-Shiuan Shyr, Bor-Uei Shyr, Shih-Chin Chen, Yi-Ming Shyr, Shin-E Wang have no conflicts of interest or financial ties to disclose., (Copyright © 2022 Asian Surgical Association and Taiwan Robotic Surgery Association. Published by Elsevier B.V. All rights reserved.)

Background: This study aimed to clarify the feasibility and justification of pancreatic head sparing (PHS) enucleation for patients with agenesis of the dorsal pancreas (ADP) associated with a solid pseudopapillary tumor (SPT)., Methods: Data of the SPT patients with and without ADP, including clinical presentations, surgical options, and surgical and survival outcomes, were recruited for comparison., Results: A total of 31 patients with SPTs were included, three of whom displayed ADP and underwent PHS enucleation. Surgical complications were comparable between the groups. Overall, the 5- and 10-year disease-free survival rates were 100% and 90%, respectively. The 20- and 25-year overall survival rates were 100% and 66.7%, respectively. Only one patient (3.2%) developed tumor recurrence 7.3 years after pancreatectomy for an SPT with lymph node involvement, and the patient survived 24.5 years after the initial operation. No tumor recurrence occurred in any patient with ADP after PHS enucleation., Conclusion: PHS enucleation seems to be feasible and justifiable for SPT patients with ADP in terms of surgical and survival outcomes, and this approach could be recommended to avoid pancreatic insufficiency., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2022, the Chinese Medical Association.)

Objective: This study aimed to identify risk factors for recurrence after pancreatic resection for intraductal papillary mucinous neoplasm (IPMN)., Summary Background Data: Long-term follow-up data on recurrence after surgical resection for IPMN are currently lacking. Previous studies have presented mixed results on the role of margin status in risk of recurrence after surgical resection., Methods: A total of 126 patients that underwent resection for noninvasive IPMN were followed for a median of 9.5 years. Dedicated pathological and radiological reviews were performed to correlate clinical and pathological features (including detailed pathological features of the parenchymal margin) with recurrence after surgical resection. In addition, in a subset of 32 patients with positive margins, we determined the relationship between the margin and original IPMN using driver gene mutations identified by next-generation sequencing., Results: Family history of pancreatic cancer and high-grade IPMN was identified as risk factors for recurrence in both uni- and multivariate analysis (adjusted hazard ratio 3.05 and 1.88, respectively). Although positive margin was not significantly associated with recurrence in our cohort, the size and grade of the dysplastic focus at the margin were significantly correlated with recurrence in margin-positive patients. Genetic analyses showed that the neoplastic epithelium at the margin was independent from the original IPMN in at least 9 of 32 cases (28%). The majority of recurrences (74%) occurred after 3 years, and a significant minority (32%) occurred after 5 years., Conclusion: Sustained postoperative surveillance for all patients is indicated, particularly those with risk factors such has family history and high-grade dysplasia., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is highly aggressive and has poor prognosis. There are few biomarkers to inform treatment decisions, and collecting tumour samples for testing is challenging., Methods: Circulating tumour cells (CTCs) from patients with PDAC liquid biopsies were expanded ex vivo to form CTC-derived organoid cultures, using a laboratory-developed biomimetic cell culture system. CTC-derived organoids were tested for sensitivity to a PDAC panel of nine drugs, with tests conducted in triplicate, and a weighted cytotoxicity score (CTS) was calculated from the results. Clinical response to treatment in patients was evaluated using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 criteria at the time of blood sampling and 3 months later. The correlation between CTS and clinical response was then assessed., Results: A total of 41 liquid biopsies (87.8% from patients with Stage 4 disease) were collected from 31 patients. The CTC-derived organoid expansion was achieved in 3 weeks, with 87.8% culture efficiency. CTC-derived organoid cultures were positive for EpCAM staining and negative for CD45 staining in the surface marker analysis. All patients had received a median of two lines of treatment prior to enrolment and prospective utility analysis indicated significant correlation of CTS with clinical treatment response. Two representative case studies are also presented to illustrate the relevant clinical contexts., Conclusions: CTCs were expanded from patients with PDAC liquid biopsies with a high success rate. Drug sensitivity profiles from CTC-derived organoid cultures correlated meaningfully with treatment response. Further studies are warranted to validate the predictive potential for this approach., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Long-Sheng Lu, Yin-Ju Chen, Peng-Yuan Wang and Thierry Burnouf share patent inventorship for eSelect. Yuan-Hung Wu owns stock shares of CancerFree Biotech Ltd, which licenses eSelect technology from Taipei Medical University. Yi-Hsuan Chen is a current employee of CancerFree Biotech Ltd. The other authors declare no relevant conflicts of interest., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This study is to clarify the feasibility of and justification for robotic pancreaticoduodenectomy (RPD) in patients with pancreatic adenocarcinoma., Methods: A 1-to-1 propensity score-matched comparison of RPD and open pancreaticoduodenectomy (OPD) was performed based on six covariates commonly used to predict the survival outcome for pancreatic adenocarcinoma., Results: A total of 130 patients were enrolled, with 65 in each study group after propensity score matching. The median operating time was longer for RPD (8.3 h vs. 7.0 h, P = 0.002). However, RPD was associated with less blood loss, lower overall surgical complication rate, and lower incidence of delayed gastric emptying. The resection radicality was oncologically similar between these two groups, but the median lymph node yield was higher for RPD (18 vs. 16, P = 0.038). Before propensity score matching, the 5-year survival was better in RPD (27.0% vs. 17.6%, P = 0.006). After matching, there was still a trend towards improved overall survival in the RPD group; however, the difference in 5-year survival between RPD and OPD was not significant (24.5% vs. 19.7%, P = 0.088)., Conclusion: RPD is not only technically feasible with no increase in surgical risk but also oncologically justifiable without compromising survival outcome. However, unlike randomized control trials, the limitations in this propensity score-matched analysis only accounted for 6 observed covariates commonly used to predict the survival outcome in patients with pancreatic adenocarcinoma, and confounders not included in this study could also affect our results., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Surgical views with high resolution and magnification have enabled us to recognize the precise anatomical structures that can be used as landmarks during minimally invasive distal pancreatectomy (MIDP). This study aimed to validate the usefulness of anatomy-based approaches for MIDP before and during the Expert Consensus Meeting: Precision Anatomy for Minimally Invasive HBP Surgery (February 24, 2021)., Methods: Twenty-five international MIDP experts developed clinical questions regarding surgical anatomy and approaches for MIDP. Studies identified via a comprehensive literature search were classified using Scottish Intercollegiate Guidelines Network methodology. Online Delphi voting was conducted after experts had drafted the recommendations, with the goal of obtaining >75% consensus. Experts discussed the revised recommendations in front of the validation committee and an international audience of 384 attendees. Finalized recommendations were made after a second round of online Delphi voting., Results: Four clinical questions were addressed, resulting in 10 recommendations. All recommendations reached at least a 75% consensus among experts., Conclusions: The expert consensus on precision anatomy for MIDP has been presented as a set of recommendations based on available evidence and expert opinions. These recommendations should guide experts and trainees in performing safe MIDP and foster its appropriate dissemination worldwide., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Minimally invasive pancreaticoduodenectomy (MIPD) has recently been safely performed by experts, and various methods for resection have been reported. This review summarizes the literature describing surgical approaches for MIPD., Methods: A systematic literature search of PubMed (MEDLINE) was conducted for studies reporting robotic and laparoscopic pancreaticoduodenectomy; the reference lists of review articles were searched. Of 444 articles yielded, 23 manuscripts describing the surgical approach to dissect around the superior mesenteric artery (SMA), including hand-searched articles, were assessed., Results: Various approaches to dissect around the SMA have been reported. These approaches were categorized according to the direction toward the SMA when initiating dissection around the SMA: anterior approach (two articles), posterior approach (four articles), right approach (16 articles), and left approach (three articles). Thus, many reports used the right approach. Most articles provided a technical description. Some articles showed the advantage of their method in a comparison study. However, these were single-center retrospective studies with a small sample size., Conclusions: Various approaches for MIPD have been reported; however, few authors have reported the advantage of their methods compared to other methods. Further discussion is needed to clarify the appropriate surgical approach to the SMA during MIPD., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background or Purpose: Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). However, the diagnostic adequacy of EUS-FNA is often limited by low cellularity leading to inconclusive results. We aimed to investigate the feasibility and added utility of targeted next-generation sequencing (NGS) on PDAC EUS-FNAs., Methods: EUS-FNAs were prospectively performed on 59 patients with suspected PDAC (2014-2017) at a high-volume center. FNAs were analyzed for the presence of somatic mutations using NGS to supplement cytopathologic evaluations and were compared to surgical specimens and circulating tumor DNA (ctDNA)., Results: Fifty-nine patients with suspected PDAC were evaluated, and 52 were diagnosed with PDAC on EUS-FNA. Four of the remaining seven patients had inconclusive EUS-FNAs and were ultimately diagnosed with PDAC after surgical resection. Of these 56 cases of PDAC, 48 (85.7%) and 18 (32.1%) harbored a KRAS and/or TP53 mutation on FNA NGS, respectively. Particularly, in the four inconclusive FNA PDAC diagnoses (false negatives), half harbored KRAS mutations on FNA. No KRAS/TP53 mutation was found in remaining three non-PDAC cases. All EUS-FNA detected KRAS mutations were detected in 16 patients that underwent primary tumor NGS (100% concordance), while 75% KRAS concordance was found between FNA and ctDNA NGS., Conclusion: Targeted NGS can reliably detect KRAS mutations from EUS-FNA samples and exhibits high KRAS mutational concordance with primary tumor and ctDNA. This suggests targeted NGS of EUS-FNA samples may enable preoperative ctDNA prognostication using digital droplet PCR and supplement diagnoses in patients with inconclusive EUS-FNA., (© 2021. The Society for Surgery of the Alimentary Tract.)

This study is to clarify the feasibility and justification of robotic pancreaticoduodenectomy (RPD) by comparing the outcomes between RPD and open pancreaticoduodenectomy (OPD) groups. All perioperative data and outcomes were prospectively collected. There were 304 (63.9%) RPD and 172 (36.1%) OPD. The median operation time was longer in RPD group than OPD (7.5 vs 7.0 h). The blood loss was much lower in RPD group, with a median of 130 vs. 400 c.c. in OPD group. Based on Clavien-Dindo classification, grade 0 (no complication) was 51.8% in RPD group, higher than 43.2% in OPD. Delayed gastric emptying was only 3.5% in RPD group, much lower than 13.6% in OPD. Wound infection rate was also lower in RPD group, 3.2% vs. 7.7% in OPD. The postoperative hospital stay was shorter in RPD group, with a median of 20 days, vs. 24 days in OPD. There was no significant difference regarding the lymph node yield, surgical mortality, postoperative pancreatic fistula, postpancreatectomy hemorrhage, chyle leakage and bile leakage between RPD and OPD groups. For pancreatic head adenocarcinoma, the survival outcome was better in RPD group, with 1-year, 3-year, and 5-year survival of 82.9%, 45.3%, and 26.8% respectively, as compared with 63.8%, 26.2%, and 17.4% in OPD. RPD is not only feasible but also justified without increasing the surgical risks and compromising the survival outcomes. Moreover, RPD might provide benefits of less blood loss, less delayed gastric emptying, lower wound infection rate and shorter length of postoperative stay, as compared with OPD.

Objective: Circulating cell-free DNA (cfDNA) analysis is recently reported as a promising prognostic biomarker in various types of cancer. This study aimed to evaluate the role of cfDNA in pancreatic head adenocarcinoma., Methods: Data for pancreatic head adenocarcinoma undergoing pancreaticoduodenectomy were studied for cfDNA. Prognostic factors were determined, and their correlation with cfDNA level was evaluated., Results: The median of cfDNA for 97 cases was 7724 copies/mL, with a mean of 10,467, and ranging from 1856 to 44,203. Cell-free DNA was significantly higher in positive lymph node involvement and advanced stage III. Poor prognostic factors included high cfDNA level (>7724 copies/mL), abnormal carbohydrate antigen 19-9, abnormal carcinoembryonic antigen, and advanced stage. The 1- and 5-year survivals for those with high cfDNA were poorer, 70.2% and 21.2%, respectively, as compared with 93.4% and 23.7% for those with low cfDNA level. Only cfDNA level and stage were independent prognostic factors after multivariate analysis., Conclusions: The level of cfDNA was correlated with tumor burden. Therefore, it could be an emerging survival predictor for resectable pancreatic head adenocarcinoma, and its detection might be a promising liquid biopsy to monitor both tumor progression and treatment response., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chyle leakage is a well-known but poorly characterized complication after pancreaticoduodenectomy (PD). No study examined the chyle leakage after robotic PD (RPD)., Methods: Data regarding chyle leakage were prospectively collected and analyzed from patients undergoing RPD or open PD (OPD)., Results: The study included 118 RPD and 165 OPD. Overall chyle leakage rate was 12.0%, with 13.6% for RPD and 10.9% for OPD. Chyle leakage was eventually resolved in all patients through conservative treatment. The drainage volumes were significantly higher in chyle leakage group from postoperative days (PODs) 1-7, with a median of 240 mL on POD 1 and POD 7, as compared to 160 mL on POD 1 and 70 mL on POD 7 for those without chyle leakage. The number of lymph nodes involved and resected and pancreatic head adenocarcinoma affected the risk of developing chyle leakage, whereas the surgical approach used (RPD or OPD) did not., Conclusions: Chyle leakage after PD is not rare, and it can eventually be resolved through conservative treatment. The extent and radicality of the surgery probably have a significant effect on the risk of developing chyle leakage, but the surgical approach used does not., (© 2020 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background and Aim: Although several techniques for improved outcomes in endoscopic ultrasound (EUS)-guided tissue acquisition have been reported, the reported diagnostic yield for pancreatic masses is not satisfactory. The effects of novel technique (torque method) on twisting the scope in the clockwise or counterclockwise direction during EUS-fine needle biopsy (EUS-FNB) are unknown. We compared the diagnostic yield of EUS-FNB for pancreatic masses using the torque and standard techniques., Methods: From April 20, 2017, to March 16, 2018, 124 consecutive patients with solid pancreatic mass who underwent EUS-FNB using either the torque or standard technique were randomly assigned. Three passes were made with each technique, comprising 10 uniform to-and-fro movements on each pass with a 10-mL syringe suction. The primary outcome was procurement rates of histologic cores, and the secondary outcomes were the diagnostic performance and technical failure., Results: There were significant differences between the groups regarding the procurement rate of the histologic core and optimal quality core (standard vs torque: 87.1% [54/62] vs 98.4% [61/62], P = 0.038 and 79.0% [49/62] vs 93.5% [58/62], P = 0.037). The sensitivity, specificity, positive predictive value, and negative predictive values of EUS-FNB were 85.45%, 100%, 100%, and 46.67%, respectively, for the standard technique and 96.49%, 100%, 100%, and 71.43%, respectively, for the torque technique. The diagnostic accuracies of the standard and torque techniques were 87.10% and 96.77%, respectively., Conclusions: The torque technique for EUS-FNB offered acceptable technical feasibility and superior diagnostic performance, including optimal histologic core procurement, compared with the standard technique., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: To evaluate the surgical, oncological, and survival outcomes after pancreaticoduodenectomy (PD) with superior mesenteric vein (SMV)/portal vein (PV) resection by either robotic PD (RPD) or open PD (OPD)., Methods: Data of patients with periampullary lesions undergoing PD were retrieved from a prospectively collected computer database. Surgical risks as well as oncological and survival outcomes were compared between patients with (vein resection group) and without SMV/PV resection (without vein resection group)., Results: A total of 391 patients undergoing pancreaticoduodenectomy were enrolled, including 43 (11.0%) and 384 (89.0%) patients with and without vein resection, respectively. Eleven (25.6%) of PDs with vein resection were performed using the robotic approach. Operation time in the vein resection group was significantly longer (median of 8 vs. 7 h). Blood loss, curative resection (R0) rate, and harvested lymph node number were similar between these two groups. Surgical outcomes including postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), chyle leakage, wound infection, and hospital stay were not significantly different between the two groups. There was no survival difference between these groups, with 1- and 3-year survival rates of 92.6% and 26.5%, respectively, for vein resection group, vs. 70.3% and 37.2%, respectively, for the without vein resection group., Conclusions: PD with vein resection is technically feasible by OPD and RPD in selected patients. Additional SMV/PV would not increase the surgical risks of PD and could achieve similar survival outcomes for pancreatic head adenocarcinoma when compared to PD without vein resection.

Importance: Postoperative morbidity associated with pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA) remains as high as 70%. However, to our knowledge, few studies have examined quality of life in this patient population., Objective: To identify symptom burden and trajectories and factors associated with high symptom burden following PD for PA., Design, Setting, and Participants: This population-based cohort study of patients undergoing PD for PA diagnosed between 2009 and 2015 linked population-level administrative health care data to routinely prospectively collected Edmonton Symptom Assessment System (ESAS) scores from 2009 to 2015, with a data analysis undertaken in 2018., Exposures: Baseline characteristics, including age, sex, income quintile, rurality, immigration status, and comorbidity burden, as well as treatment characteristics, including year of surgery and receipt of chemotherapy., Main Outcome and Measures: The outcome of interest was moderate to severe symptoms (defined as ESAS ≥4) for anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and impaired well-being. The monthly prevalence of moderate to severe symptoms was presented graphically for each symptom. Multivariable regression models identified factors associated with the reporting of moderate to severe symptoms., Results: We analyzed 6058 individual symptom assessments among 615 patients with PA who underwent resection (285 women [46.3%]) with ESAS data. Tiredness (443 [72%]), impaired well-being (418 [68%]), and lack of appetite (400 [65%]) were most commonly reported as moderate to severe. The proportion of patients with moderate to severe symptoms was highest immediately after surgery (range, 14%-66% per symptom) and decreased over time, stabilizing around 3 months (range, 8%-42% per symptom). Female sex, higher comorbidity, and lower income were associated with a higher risk of reporting moderate to severe symptoms. Receipt of adjuvant chemotherapy was not associated with the risk of moderate to severe symptoms., Conclusions and Relevance: There is a high prevalence of symptoms following PD for PA, with improvement over the first 3 months following surgery. In what to our knowledge is the largest cohort reporting on symptom burden for this population, we have identified factors associated with symptom severity. These findings will aid in managing patients' perioperative expectations and designing strategies to improve targeted symptom management.

Background: Gangliocytic paraganglioma (GP) is rare and difficult to be differentiated from other periampullary neoplasms. The clinical characteristics and optimal treatment of periampullary GPs have not been clarified., Methods: The data pool for the analysis comprised of cases of periampullary GP encountered in our institution and sporadic cases reported in the English literature., Results: A total of 117 cases with periampullary GP were studied, including 2 from our institute, and among them, duodenal GP was the most common (53.0%). GP size ranged from 0.7 to 19.0 cm, with a median of 2.2 cm. The most common presenting symptom for overall periampullary GPs was epigastric pain in 49.5% cases, followed by gastrointestinal bleeding in 35.4% cases. Most (84.1%) of the periampullary GPs were benign, whereas 15.9% were malignant. Metastasis was noted in 26.3% of periampullary GPs, with 14.5% showing lymph node metastasis and 1.8% showing liver metastasis. Of the periampullary GP cases included, 30.1% were treated with pancreaticoduodenectomy, 40.6% with local excision, and 17.7% with endoscopic resection., Conclusions: Periampullary GP should be considered as a tumor with malignant potential. Endoscopic resection is the treatment of choice for most of the duodenal GPs, whereas pancreaticoduodenectomy is recommended for GPs with possible malignancy, such as large size, with submucosal invasion, or pancreatic GP.

Background: This study is to clarify the feasibility of robotic pancreaticoduodenectomy in terms of surgical risks, clinically relevant postoperative pancreatic fistula, and oncologic outcomes compared with open pancreaticoduodenectomy by using propensity score matching. Traditional open pancreaticoduodenectomy and robotic pancreaticoduodenectomy have been compared only in small, retrospective, and nonrandomized cohort studies with variable quality., Methods: Prospectively collected data for pancreaticoduodenectomy were evaluated. Comparison between robotic pancreaticoduodenectomy and open pancreaticoduodenectomy was carried out after propensity-score matching. A total of 117 robotic pancreaticoduodenectomy and 128 open pancreaticoduodenectomy cases were performed during the study period. After propensity score matching, 87 cases were included for comparison in each cohort., Results: Longer operation time, less blood loss, more lymph nodes harvested, and less delayed gastric emptying were noted in the robotic pancreaticoduodenectomy cases. We found no significant difference regarding the overall postoperative complications by Clavien-Dindo classification, postpancreatectomy hemorrhage, wound infection rate, and postoperative hospital stay. Clinically relevant postoperative pancreatic fistula was not significantly different between robotic pancreaticoduodenectomy and open pancreaticoduodenectomy, regardless of the Callery risk factor, with overall clinically relevant postoperative pancreatic fistula of 8.0% by robotic pancreaticoduodenectomy and 12.6% by open pancreaticoduodenectomy after propensity score matching. We found no survival difference between robotic pancreaticoduodenectomy and open pancreaticoduodenectomy when the comparison was specifically performed for each primary periampullary malignancy., Conclusion: Robotic pancreaticoduodenectomy is associated with less blood loss, less delayed gastric emptying, and more lymph node yield. Propensity scored-matched analysis revealed that robotic pancreaticoduodenectomy is not inferior to open pancreaticoduodenectomy in terms of clinically relevant postoperative pancreatic fistula, surgical risks, and survival outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Endocan expression has been reported to be associated with aggressive tumor progression and poor outcomes in various cancers, such as breast cancer, renal cell cancer, lung cancer, gastric cancer, and pituitary adenomas. However, the prognostic significance of endocan in neuroendocrine tumors remains unknown. Thus, the aim of this study was to determine the correlation between endocan expression in pancreatic neuroendocrine tumor (PNET) tissues and progression-free survival. This study included 73 patients with confirmed PNETs who were treated in a single tertiary center in north Taiwan between 1992 and 2015. Immunohistochemical endocan expression and microvessel density (MVD) were examined, and the relationships between these parameters and other clinicopathological characteristics were analyzed. The abovementioned patients were divided into groups according to their endocan expression levels (≥1% or <1%) and median MVDs. Negative endocan expression (P = .002) and a high MVD (P < .001) were significant and favorable prognostic factors for progression-free survival. However, positive endocan expression was significantly associated with a low MVD (P = .037) and tumor mitosis (Ki-67 index) (P = .028). Multivariate Cox regression analysis showed that positive endocan expression (hazard ratio: 4.778, P = .018) and lymph node involvement (hazard ratio: 5.121, P = .005) were independent prognostic factors for tumor recurrence.In conclusion, endocan expression was correlated with poor clinical outcomes in PNETs. Our data indicated that endocan expression may be a reliable marker for predicting tumor recurrence in patients with PNETs.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive type of pancreatic cancer with clinical characteristics of local invasion and early metastasis. Recent cohort studies indicate high fructose intake is associated with an increase in pancreatic cancer risk. However, the mechanisms by which fructose promotes pancreatic tumorigenesis remain unclear. Herein, Kras+/LSLG12D mice were crossed with Elas-CreER transgenic mice to determine whether fructose intake directly contributes to tumor formation. Orthotopic tumor-xenograft experiments were performed to determine whether fructose substitution enhances the metastatic potential of PDAC cells. The mechanisms underlying the effects of fructose were explored by RNAseq analysis in combination with high-performance anion exchange chromatography. Dietary fructose was initially found to promote the development of aggressive pancreatic cancer in mice conditionally expressing KrasG12D in the adult pancreas. We further revealed that fructose substitution enhanced the metastatic potential of human PDAC cell via selective outgrowth of aggressive ABCG2-positive subpopulations and elevating N-acetylmannosamine levels that upregulated β-galactoside α2,6-sialyltransferase 1 (ST6Gal1), thereby promoting distant metastasis. Finally, we observed that PDAC patients expressing higher levels of ST6Gal1 and GLUT5 presented poorer prognosis compared to other groups. In conclusion, our findings have elucidated a crucial role of ST6Gal1 in regulating the invasiveness of PDACs in a fructose-responsive manner.

Pancreatic groove cancer is very rare and can be indistinguishable from groove pancreatitis. This study is to clarify the characteristics, clinical features, managements, and survival outcomes of this rare tumor.Brief descriptions were made for each case of pancreatic groove cancer encountered at our institute. Individualized data of pancreatic groove cancer cases described in the literature were extracted and added to our database to expand the study sample size for a more complete analysis.A total of 33 patients with pancreatic groove cancer were included for analysis, including 4 cases from our institute. The median tumor size was 2.7 cm. The most common symptom was nausea or vomiting (89%), followed by jaundice (67%). Duodenal stenosis was noted by endoscopy in 96% of patients. The histopathological examination revealed well differentiated tumor in 43%. Perineural invasion was noted in 90%, and lymphovascular invasion and lymph node involvement in 83%. Overall 1-year survival rate was 93.3%, and 3- or 5-year survival rate was 62.2%, with a median survival of 11.0 months. Survival outcome for the well-differentiated tumors was better than those of the moderate/poorly differentiated ones.Early involvement of duodenum causing vomiting is often the initial presentation, but obstructive jaundice does not always happen until the disease progresses. Tumor differentiation is a prognostic factor for survival outcome. The possibility of pancreatic groove cancer should be carefully excluded before making the diagnosis of groove pancreatitis for any questionable case., Competing Interests: The authors have no conflicts of interest to disclose.

Introduction: To address the issue of limited data on and inconsistent findings for genetic alterations in pancreatic neuroendocrine tumors (pNETs), we analyzed sequences of known pNET-associated genes for their impact on clinical outcomes in a Taiwanese cohort. Methods: Tissue samples from 40 patients with sporadic pNETs were sequenced using a customized sequencing panel that analyzed 43 genes with either an established or potential association with pNETs. Genetic mutations and clinical outcomes were analyzed for potential associations. Results: Thirty-three patients (82.5%) survived for a median 5.9 years (range, 0.3-18.4) of follow up. The median number of mutations per patient was 3 (range, 0-16). The most frequent mutations were in ATRX (28%), MEN1 (28%), ASCL1 (28%), TP53 (20%), mTOR (20%), ARID1A (20%), and VHL (20%). The mutation frequencies in the MEN1 (including MEN1 / PSIP1 / ARID1A ), mTOR (including m TOR / PIK3CA / AKT1 / PTEN / TS1 / TSC2 / ATM ), DAXX/ATRX, and angiogenesis (including VHL / ANGPT1 / ANGPT2 / HIF1A ) pathways were 48%, 48%, 38%, and 45%, respectively. Mutations in ATRX were associated with WHO grade I pNET (vs. grade II or III, p = 0.043), and so were those in genes involved in angiogenesis (p = 0.002). Patients with mutated MEN1 and DAXX/ATRX pathways showed a trend toward better survival, compared to patients with the wild-type genes (p = 0.08 and 0.12, respectively). Conclusion: Genetic profiles of Asian patients with pNETs were distinct from Caucasian patient profiles. Asian patients with pNETs were more frequently mutated for the mTOR and angiogenesis pathways. This could partially explain the better outcome observed for targeted therapy in Asian patients with pNETs., Competing Interests: The authors have declared that no competing interest exists.

Recent studies have implicated the prorenin receptor (PRR) is associated with pancreatic tumorigenesis. We therefore investigated the role of PRR in pancreatic tumorigenesis and assessed whether PRR can serve as a target for imaging diagnosis at early stages of PDAC. Here we show that aberrant expression of PRR in premalignant PanIN lesions, and human PDAC samples, and PDAC cell lines, particularly in Panc-1 cells. Interestingly, PRR expression was positively associated with PDAC progression. Moreover, overexpression of human PRR resulted in increased cell proliferation and decreased apoptosis, while knockdown of human PRR caused decreased cell proliferation and enhanced apoptosis in pancreatic cancer cells. We also observed that overexpression of human PRR enhanced MAPK and PI3K/Akt signaling pathways in PDAC cells, while knockdown of human PRR suppressed both of pathways. The confocal imaging analysis showed that human PRR was highly expressed in Panc-1, ASPC, and Miapaca cells, whereas BXPC-3, and HPAC cells had a significantly lower fluorescent signals. Consistently, the single-photon emission computed tomography (SPET/CT) showed that the uptake of anti-PRR labelled with 125 I was higher in Panc-1 and ASPC tumors-bearing mice after 96 hours injection. Importantly, tumors in pancreas of Pdx1-cre; LSL-Kras G12D mice had a significant increased PRR expression and accumulation of radioactivity at 96 h after injection. These data suggest that 125 I-anti-PRR can detect the orthotopic tumors in Pdx1-cre; LSL-Kras G12D mice. Therefore, anti-PRR labelled with 125 I is a promising radiotracer for imaging diagnosis at early stages of pancreatic cancer., Competing Interests: CONFLICTS OF INTEREST All authors declare that they have no competing financial interest.

Background: Obesity has been steadily increasing in the United States. The effect of body mass index (BMI) on surgical outcomes in pancreatic surgery is still controversial. Currently, there is no report related to obesity and robotic pancreatic surgery. The purpose of this study was to evaluate the impact of BMI on the surgical outcomes of both nonobese and obese patients undergoing robot-assisted distal pancreatectomy (RADP)., Methods: A prospectively collected database for RADP was retrieved for analysis. Patients were categorized as obese (BMI ≥30 kg/m(2)) and nonobese (BMI <30 kg/m(2)). Demographics, perioperative data, American Society of Anesthesiologists score, diagnosis, conversion rate, morbidity, surgical mortality, pancreatic fistula rate, and length of stay were compared., Results: A total for 85 RADP were included, with 57 (67%) in the nonobese group and 28 (33%) in the obese group. No differences were found between nonobese and obese patients regarding demographic, preoperative risk, and perioperative parameters and mortality. There was a trend in the obese group associated with a higher rate of postoperative complications, but it was statistically insignificant. Clinically significant pancreatic fistula (grade B) occurred in 28.5% of obese patients and in 7% of nonobese patients, but without statistical significance (P = .064)., Conclusions: Obesity does not have a significant impact on the perioperative outcomes and surgical risks for patients undergoing RADP, but high BMI may be a predictor for pancreatic fistula after RADP.

Background: Using a retrospective observational cohort approach, the overall survival (OS) following curative-intent resection of pancreatic adenocarcinoma (PC) was defined at the population level according to adjuvant treatment, and predictors of OS were identified., Methods: Patients undergoing resection of PC in the province of Ontario between 2005 and 2010 were identified using the provincial cancer registry, and linked to databases that include all treatments received and outcomes experienced in the province. Pathology reports were abstracted for staging and margin status. Patients were identified as having received chemotherapy (CT), chemoradiation therapy (CRT), or no adjuvant treatment (NAT). Kaplan-Meier survival analysis of patients surviving ≥ 6 months was performed, and predictors of OS identified by log-rank test. Cox multivariable analysis was used to define independent predictors of OS., Results: Among the 473 patients undergoing PC resection, the median survival was 17.8 months; for the 397 who survived ≥ 6 months following surgery, the 5-year OS for the CT, CRT, and NAT groups was 21%, 16%, and 17%, respectively (p = 0.584). Lymph node-negative patients demonstrated improved OS associated with chemotherapy on multivariable analysis (HR = 2.20, 95% CI = 1.25-3.83 for NAT vs. CT)., Conclusions: Following PC resection, only patients with negative lymph nodes demonstrated improved OS associated with adjuvant chemotherapy., (Copyright © 2016. Published by Elsevier Ltd.)

Background: Hepatoid carcinoma of the pancreas is extremely rare. This article tries to summarize the clinical features and outcomes of pancreatic hepatoid carcinoma., Methods: The data pool for analysis includes the case we encountered with hepatoid carcinoma of the pancreas and the reported cases in the literature., Results: Twenty-three cases of hepatoid carcinoma of the pancreas were analyzed. This tumor occurred more frequently in male than in female patients (69.6 vs. 30.4 %). Tumor sizes range from 0.5 to 11.0 cm with median of 6.0 cm. The most common symptom was epigastric pain (36.4 %). When the tumor locates at pancreatic head, nausea/vomiting (62.5 %) is more common, followed by jaundice and epigastric pain (50.0 %). For those at pancreatic body-tail, 42.9 % of the patients presented no symptom. Alpha-fetoprotein (AFP) was abnormally elevated in 60 % of the cases. Hepatoid carcinoma in the pancreas could be either pure form or mixed form with other malignancy (40.9 %), with the most common coexisted pathology of malignant neuroendocrine tumor (22.7 %). Metastasis occurred in 36.4 % of the cases at the diagnosis of this tumor, including liver metastasis in 31.8 % and lymph node metastasis in 21.1 %. The overall 1-year survival rate was 71.1 % and 5-year 40.4 %, with a median of 13.0 months. Unresectability, hepatic, and lymph node metastases are associated with negative impact on survival outcome., Conclusions: Elevation of serum AFP may be a clue leading to the diagnosis of pancreatic hepatoid carcinoma. This tumor could be mixed form with other malignancy. Surgical resection should be the treatment of choice whenever possible.

Background/aims: There are several methods for obtaining tissue samples to diagnose malignant biliary strictures during endoscopic retrograde cholangiopancreatography (ERCP). However, each method has only limited sensitivity. This study aimed to evaluate the diagnostic accuracy of a combined triple-tissue sampling (TTS) method (on-site bile aspiration cytology, brush cytology, and forceps biopsy)., Methods: We retrospectively reviewed 168 patients with suspicious malignant biliary strictures who underwent double-tissue sampling (DTS; n=121) or TTS (n=47) via ERCP at our institution from 2004 to 2011., Results: Among the 168 patients reviewed, 117 patients (69.6%) were eventually diagnosed with malignancies. The diagnostic sensitivity for cancer was significantly higher in the TTS group than the DTS group (85.0% vs 64.9%, respectively; p=0.022). Furthermore, the combination of brush cytology and forceps biopsy was superior to the other method combinations in the DTS group. With respect to cancer type (cholangiocarcinoma vs noncholangiocarcinoma), interestingly, the diagnostic sensitivity was higher for cholangiocarcinoma in the TTS group than the DTS group (100% vs 69.4%, respectively; p<0.001) but not for the non-cholangiocarcinoma patients (57.1% vs 57.1%, respectively)., Conclusions: TTS can provide an improved diagnostic accuracy in suspicious malignant biliary strictures, particularly for cholangiocarcinoma.

Objectives: The objectives of this study were to study the expression status of markers associated with epithelial-to-mesenchymal transition (EMT) and metastasis in pancreatic ductal adenocarcinomas (PDACs) and to explore the prognostic value of these markers., Methods: Immunohistochemical stains for CD24, CD44, E-cadherin, N-cadherin, Snail, S100A4, Vimentin, urokinase-type plasminogen activator receptor, Ezrin, and matrix metalloproteinase 2 were performed on 67 resected PDACs., Results: Proteins associated with EMT and metastasis were more frequently expressed in PDACs with poor differentiation, higher tumor stage, and lymphatic and perineural invasion. CD24 expression was associated with frequent expression of EMT markers (CD44 [P = 0.004], S100A4 [P < 0.001], Vimentin [P = 0.022], urokinase-type plasminogen activator receptor [P = 0.002], and Ezrin [P = 0.010]). CD24 and S100A4 expressions in PDAC were significant prognostic factors for early tumor recurrence (hazard risk [HR], 5.185 and 2.490, P = 0.048 and 0.009, respectively) and poor survival (HR, 11.977 and 3.202, P = 0.006 and 0.004, respectively). In addition, the interaction between CD24 and S100A4 expression status was a significant prognostic factor for poor survival (HR, 18.518, P = 0.003)., Conclusions: The expression of markers of EMT and metastasis in PDACs was significantly associated with pathologic features of aggressiveness. CD24 and S100A4 expressions were significant predictors of poor survival; thus, immunohistochemistry for these markers in resected specimens may help to identify PDAC patients with a poor prognosis.

Objectives: The aim of this study was to identify predictors for longterm survival following pancreaticoduodenectomy (PD) for pancreatic and other periampullary adenocarcinomas., Methods: Clinicopathological factors were compared between short-term (<5 years) and longterm (≥ 5 years) survival groups. Rates of actual 5-year and actuarial 10-year survival were determined., Results: There were 109 (21.8%) longterm survivors among a sample of 501 patients. Patients with ampullary adenocarcinoma represented 76.1% of the longterm survivors. Favourable factors for longterm survival included female gender, lack of jaundice, lower blood loss, classical PD, absence of postoperative bleeding or intra-abdominal abscess, non-pancreatic primary cancer, earlier tumour stage, smaller tumour size (≤ 2 cm), curative resection, negative lymph node involvement, well-differentiated tumours, and absence of perineural invasion. Independent factors associated with longterm survival were diagnosis of primary tumour, jaundice, intra-abdominal abscess, tumour stage, tumour size, radicality, lymph node status and cell differentiation. The prognosis was best for ampullary adenocarcinoma, for which the rate of actual 5-year survival was 32.8%, and poorest for pancreatic head adenocarcinoma, for which actual 5-year survival was only 6.5%., Conclusions: The majority of longterm survivors after PD for periampullary adenocarcinomas are patients with ampullary adenocarcinoma. The longterm prognosis in pancreatic head adenocarcinoma remains dismal., (© 2013 International Hepato-Pancreato-Biliary Association.)

Background: Gremlin 1 (GREM1) is a bone morphogenetic protein antagonist and a novel proangiogenic factor. Our aim was to evaluate the prognostic value of GREM1 expression and GREM1-related factors in tumor-associated angiogenesis in pancreatic neuroendocrine tumors (NETs)., Methods: The immunohistochemical expression of GREM1 and microvessel density (MVD) were examined in 35 patients with pancreatic NETs and then compared with other clinicopathologic characteristics, including the World Health Organization classification., Results: The presence of expression of GREM1 (p = 0.016) and high MVD (p = 0.020) were significant and favorable prognostic factors. Moreover, GREM1 expression was significantly associated with high MVD (p = 0.011). MVD was significantly higher in well-differentiated NETs than in well-differentiated or poorly differentiated neuroendocrine carcinomas (p < 0.001)., Conclusions: GREM1 expression was correlated with tumor-associated angiogenesis and was found to be a novel prognostic marker in pancreatic NETS. Our data support a tumor suppressor role of GREM1 in pancreatic NETs.

Background/aims: This study is to reappraise the clinical presentations, surgical and survival outcomes of pancreatic head adenocarcinoma., Methodology: Data of pancreatic head adenocarcinomas undergoing pancreaticoduodenectomy were reappraised and compared between period 1 (1984-1996) and period 2 (1997-2009)., Results: Surgical mortality was 3.6% in period 2 and 5.0% in period 2. The surgical morbidity was 35.7% in period 1, 35.3% in period 2. Pancreatic leakage was significantly lower (3.4%) in pancreaticogastrostomy group, as compared to 11.7% in pancreaticojejunostomy. There was 57.5% positive lymph node involvement and 77.4% perineural invasion. More patients underwent adjuvant or palliative chemotherapy in period 2 (42.2%) than in period 1 (14.8%). The 5-year survival for resected pancreatic head adenocarcinoma was 3.7% in period 1 and 11.1% in period 2. The 5-year survival after curative resection in period 1 was significantly lower than that in period 2 (4.2% vs. 14.7%)., Conclusions: Although surgical mortality has significantly decreased recently, pancreaticoduodenectomy continues to be a complex and technically-demanding procedure with high and unchanged surgical morbidity. The poor survival outcome of pancreatic head adenocarcinoma might be a combined reflection of difficulty in early detection, aggressive biological behavior of tumor itself and complex surgical anatomy for resection.

Objective: The objective of the study was to clarify the role of a palliative pancreaticoduodenectomy in both pancreatic and periampullary adenocarcinomas., Methods: Survival outcomes were compared between resections and bypass operations, and between curative (R0) and palliative resections, with a microscopically (R1) and a grossly (R2) positive resection margin., Results: There were 595 surgical patients, including 207 undergoing bypass operations and 388 undergoing pancreaticoduodenectomies, with 47.4% curative resections (R0) and 17.8% palliative resections (R1 + R2). The overall positive margin rate after a pancreaticoduodenectomy was 27.3% (R1 = 8.0%, R2 = 19.3%). For periampullary adenocarcinomas, there was a significant survival difference between the R0, palliative, and no resection groups. However, there was no significant survival difference between the R0 and palliative resection for pancreatic head adenocarcinoma. Note that the survival outcome after either a curative or a palliative pancreaticoduodenectomy was still better than the survival outcome of a bypass operation., Conclusions: There was a survival benefit after a pancreaticoduodenectomy regardless of the resection margin or primary origin of the periampullary adenocarcinoma, as compared with a bypass operation. The resection margin after a pancreaticoduodenectomy did not play a role in the survival outcome in pancreatic head adenocarcinoma. Therefore, we recommend that pancreaticoduodenectomies should be attempted whenever possible.

Background/aims: Periampullary lesions often present diagnostic and therapeutic dilemmas. This study is to clarify the justification of pancreaticoduodenectomy for the resectable periampullary lesion without histological confirmation of malignancy., Methodology: Clinical data for periampullary lesions with presumed malignancy were retrieved from our prospectively-collected computer database. The surgical risks and test performance characteristics in diagnosis were determined., Results: There were 636 patients undergoing pancreaticoduodenectomy, including 572 with malignancy and 64 (10.1% false positive rate) with benign lesions. No resection was attempted for 32 patients, but 8 (25% false negative rate) eventually turned out to be malignant. Our data showed a sensitivity of 98.6% (572/580), a specificity of 27% (24/88) and an accuracy of 89.2% (596/668) in detecting periampullary malignancy. The surgical risks after pancreaticoduodenectomy were significantly lower in the benign group, with 28.1% morbidity (vs. 43.7% in the malignant group), no pancreatic leakage (vs. 11.5% in malignant group) and no surgical mortality (vs. 7.3% in the malignant group)., Conclusions: Pancreaticoduodenectomy is justified for a periampullary lesion without histological confirmation whenever malignancy is suspected. Moreover, a nihilistic approach could be associated with a significant false negative rate (25%) if left unresected and might preclude a patient with periampullary malignancy from cure.

Neurofibromas arise from peripheral nerve cells. They are rarely found within the pancreas, especially not associated with type I neurofibromatosis. Here, we report a case of a neurofibroma in a 44-year-old woman who initially presented with epigastralgia. Imaging revealed one large cystic mass of 5.7 × 8 × 5.8 cm in the pancreatic body, which was resected with distal pancreatectomy. The postoperative course of treatment was without complication, and no signs of recurrence were observed after 1 year and 6 months' follow-up., (Copyright © 2012. Published by Elsevier B.V.)

Objectives: This study tried to clarify the role of pancreatic resection in the treatment of secondary malignancy with metastasis or local invasion to the pancreas in terms of surgical risk and survival benefit., Methods: Data of secondary malignancy of the pancreas from our 19 patients and cases reported in the English literature were pooled together for analysis., Results: There were 329 cases of resected secondary malignancy of the pancreas, including 241 cases of metastasis and 88 cases of local invasion. The most common primary tumor metastatic to the pancreas and amenable to resection was renal cell carcinoma (RCC) (73.9%). More than half (52.3%) of the primary cancers with local invasion to the pancreas were colon cancer, and nearly half (40.9%) were stomach cancer. The median metastatic interval was 84 months (7 years) for overall primary tumors and 108 months (9 years) for RCC. The 5-year survival for secondary malignancy of the pancreas after resection was 61.1% for metastasis and 58.9% for local invasion, with 72.8% for RCC metastasis, 69.0% for colon cancer, and 43.8% for stomach cancer with local invasion to the pancreas., Conclusions: Pancreatic resection should not be precluded for secondary malignancy of the pancreas because long-term survival could be achieved with acceptable surgical risk in selected patients.

Objective: To present our experience of 93 neuroendocrine tumors (NETs) in the pancreas and peripancreatic region, with emphasis on how resectability affects long-term survival and the impact of functional status on the survival outcome., Methods: Ninety-three patients with NETs in the pancreas and peripancreatic region were included to compare the clinical features between functional and nonfunctional NETs. Prognostic factors were determined by univariate and multivariate analyses., Results: There were 39 functional (41.9%) and 54 nonfunctional NETs (58.1%). According to World Health Organization (WHO) tumor categories, there were 57 well-differentiated tumors (61.3%), 26 well-differentiated carcinomas (28%), and 10 poorly differentiated carcinomas (10.8%). Univariate analysis showed that functional status of the tumor, tumor stage, lymph node status, and pathological classification were prognostic factors for both disease-free survival and disease-specific survival. Resectability did not influence the survival outcome, with the resectable and unresectable groups demonstrating a 5-year disease-specific survival of 86.4% and 65.6%, respectively (P = 0.210). Only the WHO pathological classification was an independent prognostic factor after multivariate analysis., Conclusions: Irresectability does not necessarily preclude long-term survival for both functional and nonfunctional NETs. It is the WHO pathological classification, instead of hormonal functional status, that is an independent prognostic factor and has impact on the survival outcome.

By comparing the clinicopathological features and survivals between the resected and non-resected intraductal papillary mucinous neoplasms (IPMNs) of the pancreas, this study tried to clarify the natural history of IPMNs, to provide a strategy for treatment, and to determine the justification of not performing resection for some patients. A total of 57 patients with IPMN, including 39 resected and 18 non-resected IPMNs, were recruited for study. Data on demographics, clinical presentations, diagnostic work-up, treatment modality, clinical course, and outcomes were evaluated and compared between the resected and non-resected IPMNs. The most common clinical presentation was abdominal pain (57% in total IPMNs, 67% in resected, 33% in non-resected), followed by body weight loss (32% in total IPMNs, 33% in resected, 28% in non-resected). The sensitivity in the diagnosis of IPMN was highest by magnetic resonance cholangiopancreatography (MRCP) (88%), followed by endoscopic retrograde cholangiopancreatography (ERCP) (68%), and computed tomography scan (CT scan) (42%) and sonography (10%). The median survival was 21.5 months for patients with resected IPMNs, ranging from 2 to 124 months, and 14 months in non-resected IPMN patients, ranging from 5.5 to 70 months. There is no significant survival difference between the resected and non-resected groups, with a 5-year survival of 69.8% in resected IPMNs and 59.8% in non-resected IPMNs, P = 0.347. The survival outcome of the unresectable non-resected IPMNs was much inferior to the resected IPMNs, P = 0.002 and resectable non-resected IPMNs, P = 0.001. Thus, the prime prognostic factor in predicting the survival outcome of IPMNs is resectability, instead of resection itself. Long-term survival could also be expected in resectable IPMNs without resection. No resection for the IPMN may be justified for patients with high surgical risks, especially for those who are asymptomatic and very aged.