Recent Articles on Pancreatobiliary #Pathology – 2020-07-14

These are the recent articles on Pancreatobiliary Pathology:

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New Pancreas Articles


  • Complex Genetics in Pancreatitis: Insights Gained From a New Candidate Locus Panel

Pancreas 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32658084

OBJECTIVES: Chronic pancreatitis is the end stage of a pathologic inflammatory syndrome with multiple etiological factors, including genetic. We hypothesized that some pancreatitis etiology originates in pancreatic acinar or duct cells and requires both injury and compensatory mechanism failure.
METHODS: One hundred pancreatitis patients were assessed using a DNA sequencing panel for pancreatitis. Cooccurrence of variants within and between genes was measured. Gene coexpression was confirmed via published single-cell RNA sequencing.
RESULTS: One hundred and twenty-one variants were identified in 2 or more patients, 15 of which were enriched compared with reference populations. Single cell RNA-sequencing data verified coexpression of GGT1, CFTR, and PRSS1 in duct cells, PRSS1, CPA1, CEL, CTRC, and SPINK1 in acinar cells, and UBR1 in both. Multiple-risk variants with injury/stress effects (CEL, CFTR, CPA1, PRSS1) and impaired cell protection (CTRC, GGT1, SPINK1, UBR1) cooccur within duct cells, acinar cells, or both.
CONCLUSIONS: Pancreatitis is a complex disorder with genetic interactions across genes and cell types. These findings suggest a new, non-Mendelian genetic risk/etiology paradigm where a combination of nonpathogenic genetic risk variants in groups of susceptibility genes and injury/dysfunction response genes contribute to acquired pancreatic disease.

doi: https://doi.org/10.1097/MPA.0000000000001612



  • Risk Factors Analysis and Nomogram Development for Pancreatic Pseudocyst in Idiopathic Chronic Pancreatitis

Pancreas 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32658083

OBJECTIVE: The study concerns identifying risk factors and developing nomogram for pancreatic pseudocyst (PPC) in idiopathic chronic pancreatitis (ICP) to facilitate early diagnosis.
METHODS: From January 2000 to December 2013, ICP patients admitted to our center were enrolled. Cumulative incidence of PPC was determined by Kaplan-Meier method. Patients were randomized into training group and validation group in a 2:1 ratio. Risk factors of PPC were determined through Cox proportional hazards regression model based on training cohort. The nomogram was constructed according to risk factors.
RESULTS: Totally, 1633 ICP patients were included with a median follow-up duration of 9.8 years. Pancreatic pseudocyst was observed in 14.7% (240/1633) of patients after ICP onset. The cumulative incidences of PPC were 8.2%, 10.4%, and 12.9% at 3, 5, and 10 years after ICP onset, respectively. Male sex, smoking history, history of severe acute pancreatitis, and chronic pain at/before diagnosis of ICP and complex pathologic changes in main pancreatic duct were recognized as risk factors of PPC development. The nomogram constructed with these risk factors achieved good concordance indexes.
CONCLUSIONS: Risk for PPC could be estimated through the nomogram. High-risk patients were suggested to be followed up closely to help early diagnosis of PPC.

doi: https://doi.org/10.1097/MPA.0000000000001610



  • Angiotensin-(1-7) Treatment Restores Pancreatic Microcirculation Profiles: A New Story in Acute Pancreatitis

Pancreas 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32658081

OBJECTIVES: The aim of this study was to investigate the changes of pancreatic microvascular vasomotion and blood distribution pattern in acute pancreatitis (AP), and whether Angiotensin (Ang)-(1-7) treatment could restore pancreatic microcirculation profiles.
METHODS: Mice were randomly separated into control, AP, and Ang-(1-7)-treated AP (A-AP) group. Acute pancreatitis was induced in mice by intraperitoneal injection of cerulein and lipopolysaccharide. Pancreatitis was confirmed by histopathology, serum amylase and high-sensitive C-reactive protein. Pancreatic microvascular vasomotion and blood distribution pattern in AP progression were assessed by laser Doppler. Meanwhile, ultrastructural changes of pancreatic microcirculation, including microvascular cavity and wall and endothelial mitochondria, were evaluated by transmission electron microscopy.
RESULTS: Acute pancreatitis mice exhibited pathological pancreatic injuries with lower blood distribution pattern and decreased average blood perfusion, relative velocity, effective frequency, and amplitude of microvascular vasomotion. The pancreatic pathological injuries in Ang-(1-7)-treated mice were significantly alleviated. Consistently, Ang-(1-7) treatment led to a restoration in pancreatic microcirculation profiles. Furthermore, non-Ang-(1-7)-treated mice showed an irregular microvascular wall, narrow cavity, and swelling mitochondria, and these ultrastructural impairments were reversed by Ang-(1-7) administration.
CONCLUSIONS: Pancreatic microcirculation profiles are abnormal in the progression of AP. Angiotensin-(1-7) administration could restore functional status of pancreatic microcirculation.

doi: https://doi.org/10.1097/MPA.0000000000001609



  • Functional ��-Cell Differentiation of Small-Tail Han Sheep Pancreatic Mesenchymal Stem and the Therapeutic Potential in Type 1 Diabetic Mice

Pancreas 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32658079

OBJECTIVES: This study aims to investigate the characteristics of sheep pancreatic mesenchymal stem cells (PSCs) and therapeutic potential of differentiated β-like cells in streptozotocin-induced diabetic mice.
METHODS: Pancreatic mesenchymal stem cells were isolated from 3- to 4-month-old sheep embryos, and their biological characteristics were explored. The function and therapeutic potential of differentiated β-like insulin-producing cells were also investigated in vitro and in vivo. Differentiated cells were identified through dithizone staining and immunofluorescence staining. Insulin secretion was analyzed using an enzyme-linked immunosorbent assay kit. The preliminary therapeutic potential of induced β-like cells in diabetic mice was detected by blood glucose and body weight.
RESULTS: Primary PSCs were isolated and subcultured up to passage 36. Immunofluorescence staining presented PSC-expressed important markers such as Pdx1, Nkx6-1, Ngn3, and Nestin. Primary PSCs could be induced into functional pancreatic β-like islet cells with a 3-step protocol. The induced β-like islet cells could ameliorate blood glucose in diabetic mice.
CONCLUSIONS: The method proposed for generating pancreatic islet β cells provided a preliminary phenotypic investigation of induced cell treatment in diabetic mice, and also laid a foundation in the identification of pharmaceutical targets to treat insulin-dependent diabetes.

doi: https://doi.org/10.1097/MPA.0000000000001604



  • The Role of Laparoscopic Cholecystectomy After Severe and/or Necrotic Pancreatitis in the Setting of Modern Minimally Invasive Management of Pancreatic Necrosis

Pancreas 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32658078

OBJECTIVES: The trend toward minimally invasive procedures (MIP) in necrotizing pancreatitis is increasing. The optimal timing and technique of cholecystectomy in severe/necrotizing pancreatitis is unclear. This study aims to determine the role of laparoscopic cholecystectomy after severe/necrotizing pancreatitis in the context of MIP.
METHODS: Retrospective analysis of a prospective database was performed for consecutive patients after cholecystectomy for gallstone pancreatitis between January 2011 and January 2018 at Monash Health, Melbourne, Australia.
RESULTS: Three hundred fifty-five patients with gallstone pancreatitis underwent laparoscopic cholecystectomy with 2 conversions. Patients with severe pancreatitis were older (P = 0.002), with a more even sex distribution when compared with mild pancreatitis. Females predominated in the mild pancreatitis group.Patients with moderate/severe pancreatitis (P = 0.002) and necrosis (P > 0.001) were more likely to have delayed cholecystectomy compared with mild pancreatitis. There was no increase in biliary presentations while awaiting cholecystectomy. Length of stay for patients with severe/necrotizing pancreatitis (P = 0.001) was increased, surgical complications appeared similar.
CONCLUSIONS: Laparoscopic cholecystectomy can be performed safely and effectively for pancreatitis, irrespective of severity. The paradigm shift in the management of severe necrotizing pancreatitis away from open necrosectomy toward MIP can be extended to encompass laparoscopic cholecystectomy.

doi: https://doi.org/10.1097/MPA.0000000000001601



  • Patterns of Failure After Neoadjuvant Stereotactic Body Radiation Therapy or Fractionated Chemoradiation in Resectable and Borderline Resectable Pancreatic Cancer

Pancreas 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32658077

OBJECTIVES: The goal of this study was to compare outcomes of patients with borderline and resectable pancreatic cancer treated with neoadjuvant stereotactic body radiation therapy (SBRT) versus fractionated chemoradiation.
METHODS: Patients with borderline or resectable pancreatic cancer treated with neoadjuvant intent between November 2011 and December 2017 were reviewed. The SBRT volume/dose was 33 Gy in 5 fractions to gross tumor plus abutting vessel with or without 25 Gy in 5 fractions to pancreatic head/body and celiac/superior mesenteric artery. Fractionated chemoradiation volume/dose was 50.4 Gy in 28 fractions to gross tumor, superior mesenteric/celiac arteries, and enlarged lymph nodes with concurrent bolus 5-FU, leucovorin, oxaliplatin, irinotecan or gemcitabine/nab-paclitaxel. Failure patterns, local recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival were assessed.
RESULTS: Forty-three patients were reviewed (18 SBRTs and 25 fractionated). Among patients who underwent resection, patients treated with fractionated chemoradiation had improved LRFS (12-month LRFS, 86% vs 62%, P = 0.003) and PFS (median PFS, 23 months vs 11 months, P = 0.006) compared with SBRT. There was no difference in overall survival.
CONCLUSIONS: Stereotactic body radiation therapy may result in inferior LRFS and PFS compared with fractionated chemoradiation, likely because of under coverage of high-risk vascular targets.

doi: https://doi.org/10.1097/MPA.0000000000001602



  • Pancreatic Neuroendocrine Neoplasms and Gastrointestinal Stromal Tumors: A Single-Institution Experience of a Rare Association and Review of the Literature

Pancreas 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32658075

OBJECTIVE: Pancreatic neuroendocrine neoplasms (pNENs) and gastrointestinal stromal tumors (GISTs) represent rare neoplasms. Nonsyndromic cases of pNENs associated with a synchronous GIST were evaluated, and a review of the literature was performed.
METHODS: We evaluated clinicopathologic features, postoperative outcome, and follow-up of patients operated on for nonsyndromic synchronous pNENs and GISTs in our unit (2003-2017).
RESULTS: Five (3.2%) of 156 patients with a pNEN had an associated GIST (3 male/2 female; average age, 67 years). They were diagnosed with a pNEN preoperatively and underwent pancreatic surgery. In 4 patients, GISTs were detected intraoperatively. Histology showed 3 G1 and 2 G2 pNENs. All GISTs were low risk (median size, 0.9 cm). Two patients were alive without disease 108 and 132 months after surgery. In the literature, 7 cases were described. They had low-risk GISTs, with a gastric location in 6 cases (median size, 2.85 cm).
CONCLUSIONS: Sporadic pNENs coexisting with a GIST have been demonstrated in 12 cases. This association is considered fortuitous, and its true incidence may be underestimated. Surgery should be performed on the GIST during the pancreatic surgery. The prognosis strictly depends on the pancreatic NENs.

doi: https://doi.org/10.1097/MPA.0000000000001599



  • A Single-Institution Experience of Induction 5-Fluorouracil, Leucovorin, Irinotecan, and Oxaliplatin Followed by Surgery Versus Consolidative Radiation for Borderline and Locally Advanced Unresectable Pancreatic Cancer

Pancreas 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32658074

OBJECTIVES: In the 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) era, the benefit of surgery versus definitive radiation for borderline resectable (BR) and locally advanced (LA) unresectable pancreatic ductal adenocarcinoma (PDAC) is not well defined. Our primary objective was to identify the survival impact of surgery for BR and LA unresectable PDAC treated with induction FOLFIRINOX.
METHODS: We performed a single-center retrospective review of BR and LA PDAC treated with FOLFIRINOX from 2010 to 2018. The overall survival of surgery and consolidative radiotherapy was estimated in the Kaplan-Meier method and compared via the log-rank test. Subgroup analyses were conducted for BR and LA patients.
RESULTS: We identified 101 BR and LA PDAC patients treated with induction FOLFIRINOX (41 surgeries and 60 consolidative radiotherapies). Surgery patients were 68.3% (28/41) BR and 31.7% (13/41) LA, whereas consolidative radiotherapy patients were 30% (18/60) BR and 70% (42/60) LA. The R0 resection rate was 100%, and 46.3% (19/41) received preoperative radiation. Median overall survival of surgery versus consolidative radiotherapy was 42.3 versus 19.6 months, respectively (P < 0.001). On multivariate analysis, surgery associated with improved survival.
CONCLUSIONS: Surgery after induction FOLFIRINOX is feasible and has a clinically meaningful survival benefit in BR and LA PDAC.

doi: https://doi.org/10.1097/MPA.0000000000001592



  • Medullary Pancreatic Carcinoma Due to Somatic POLE Mutation: A Distinctive Pancreatic Carcinoma With Marked Long-Term Survival

Pancreas 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32658072

Medullary pancreatic carcinoma (MPC) is a rare histological variant of pancreatic ductal adenocarcinoma (PDAC). Because of its rarity, data on the molecular background of MPC are limited. Previous studies have shown that a subset of MPCs is microsatellite instable due to mismatch repair deficiency. Here, we present a unique case of a female patient in her 60s who is a long-term survivor after surgery for pancreatic cancer. The patient had a microsatellite stable MPC with a somatic mutation of the polymerase epsilon gene (POLE). Both microsatellite instable and POLE-mutated cancers are usually associated with high tumor mutational burden and antigen load, resulting in a prominent antitumor immune response and overall better survival. The current case illustrates that, in addition to mismatch repair deficiency, MPC can develop because of a somatic POLE mutation, resulting in a tumor with a high tumor mutational burden and leading to a better prognosis compared with conventional PDAC. This new finding may have important implications in the management of patients with MPC and calls for further studies on the role of POLE in PDAC.

doi: https://doi.org/10.1097/MPA.0000000000001588



  • Evaluation of Pathologic Response on Overall Survival After Neoadjuvant Therapy in Pancreatic Ductal Adenocarcinoma

Pancreas 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32658070

OBJECTIVES: Single-institution studies have shown improved outcomes among patients with a pathologic complete response (pCR) following neoadjuvant therapy. We sought to evaluate the impact of pCR and near-complete response (nCR) on overall survival (OS) using a large national database.
METHODS: The National Cancer Database was queried for patients given a diagnosis of pancreatic cancer from 2004 to 2014. A pCR was defined as no tumor identified in the pancreas after surgical resection. An nCR was defined as a primary tumor less than 1 cm without lymph node metastases. The primary outcome was OS.
RESULTS: A total of 5364 patients underwent neoadjuvant chemotherapy and/or radiation followed by pancreatectomy. Forty-one patients (0.8%) had a pCR, 54 (1%) had an nCR, and the remaining 5266 (98.2%) had an otherwise incomplete response. Patients with pCR had a median OS of 43 months compared with 24 months for nCR and 23 months for incomplete response (P < 0.0001). Only pCR was associated with improved OS on adjusted Cox regression.
CONCLUSIONS: For patients given a diagnosis of pancreatic cancer who underwent neoadjuvant treatment and surgical resection, achieving a pCR was associated with improved OS compared with those with residual tumor. An association between nCR and improved survival was not observed.

doi: https://doi.org/10.1097/MPA.0000000000001590



  • Patient-derived Organoid Pharmacotyping is a Clinically Tractable Strategy for Precision Medicine in Pancreatic Cancer

Annals of surgery 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32657929

OBJECTIVE: PDAC patients who undergo surgical resection and receive effective chemotherapy have the best chance of long-term survival. Unfortunately, we lack predictive biomarkers to guide optimal systemic treatment. Ex-vivo generation of PDO for pharmacotyping may serve as predictive biomarkers in PDAC. The goal of the current study was to demonstrate the clinical feasibility of a PDO-guided precision medicine framework of care.
METHODS: PDO cultures were established from surgical specimens and endoscopic biopsies, expanded in Matrigel, and used for high-throughput drug testing (pharmacotyping). Efficacy of standard-of-care chemotherapeutics was assessed by measuring cell viability after drug exposure.
RESULTS: A framework for rapid pharmacotyping of PDOs was established across a multi-institutional consortium of academic medical centers. Specimens obtained remotely and shipped to a central biorepository maintain viability and allowed generation of PDOs with 77% success. Early cultures maintain the clonal heterogeneity seen in PDAC with similar phenotypes (cystic-solid). Late cultures exhibit a dominant clone with a pharmacotyping profile similar to early passages. The biomass required for accurate pharmacotyping can be minimized by leveraging a high-throughput technology. Twenty-nine cultures were pharmacotyped to derive a population distribution of chemotherapeutic sensitivity at our center. Pharmacotyping rapidly-expanded PDOs was completed in a median of 48 (range 18-102) days.
CONCLUSIONS: Rapid development of PDOs from patients undergoing surgery for PDAC is eminently feasible within the perioperative recovery period, enabling the potential for pharmacotyping to guide postoperative adjuvant chemotherapeutic selection. Studies validating PDOs as a promising predictive biomarker are ongoing.

doi: https://doi.org/10.1097/SLA.0000000000004200



  • Three-dimensional remnant pancreatic volume ratio indicates postoperative pancreatic exocrine insufficiency in pancreatic cancer patients after distal pancreatectomy

Pancreatology : official journal of the International Association of Pancreatology (IAP) … [et al.] 2020 Jul;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32654989

BACKGROUND: Pancreatectomy may cause serious pancreatic exocrine insufficiency (PEI), which can lead to some nutritional problems, including new-onset diabetes mellitus (DM) or non-alcoholic fatty liver disease (NAFLD). Recent studies have reported that remnant pancreatic volume (RPV) significantly influences postoperative PEI. However, the specific correlation between RPV and postoperative PEI remains unclear. Here, we compare various pre-, peri-, and postoperative risk factors in a retrospective cohort to address whether preoperatively measured RPV is a predictor of postoperative PEI in pancreatic cancer patients after distal pancreatectomy (DP).
METHODS: Sixty-one pancreatic cancer patients who underwent DP were retrospectively enrolled. Pancreatic volume was measured using preoperative 3D images, which simulated the actual intraoperative pancreatic parenchymal volume. We obtained the 3D-measured RPV and resected pancreatic volume. We calculated the ratio of the RPV to the total pancreatic volume and then divided the cohort into high- and low-RPV ratio groups based on a cut-off value (>0.35, n = 37 and ≤ 0.35, n = 24). Using multivariate analysis, the RPV ratio as well as pre-, peri- and postoperative PEI risk factors were independently assessed.
RESULTS: The multivariate analysis revealed that a low RPV ratio (odds ratio [OR], 5.911; p = 0.001), a hard pancreatic texture (OR, 3.313; p = 0.023) and TNM stage III/IV (OR, 3.515; p = 0.031) were strong predictors of the incidence of PEI.
CONCLUSIONS: The present study indicates that the RPV ratio is an additional useful predictor of postoperative nutrition status in pancreatic cancer patients.

doi: https://doi.org/10.1016/j.pan.2020.06.018


New GallBladder Articles

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New Ampulla Articles

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To see all journal watch articles please visit: http://pbpath.org/journal-watch-upcoming-issue/