Recent Articles on Pancreatobiliary #Pathology – 2020-08-11

These are the recent articles on Pancreatobiliary Pathology:

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

New Pancreas Articles


  • Effect of single operator cholangioscopy on accuracy of bile duct cytology

Diagnostic cytopathology 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32770823

INTRODUCTION: This is the first study to evaluate the accuracy of bile duct brushings since the introduction of single operator cholangioscopy SpyGlass DS system in 2015. The primary aim of our study was to compare the accuracy of cytology brushings against biopsies obtained at endoscopic retrograde cholangiopancreatography (ERCP) and cholangioscopy.
METHOD: A retrospective search for bile duct brushing specimens was performed and the charts reviewed. The gold standard for definitive diagnosis of malignancy was surgical tissue or compelling clinical evidence of malignancy. Definite negative diagnosis relied on lack of clinical/imaging features of malignancy on follow-up.
RESULTS: There was no significant difference in diagnostic accuracy of cytology specimens obtained at different procedures. Overall sensitivity for all methods was 59%, specificity 90% and accuracy of 82%. Notably, all four false-positive cases except for one were from patients with primary sclerosing cholangitis or primary biliary sclerosis. There was no significant difference in sensitivity or specificity between biopsies procured by the two methods. The combined biopsy sensitivity for all modalities was 44% with a specificity of 100%. There was 70% concordance between cytology and biopsy cases. The overall specificity and sensitivity of the combined cytology and biopsy result was 85% and 65.3%, respectively. Ranking of factors that predict clinical diagnosis shows cytology results to surpass other parameters including pancreatic mass, age and stenosis length. Similarly, the presence of two cell populations and three-dimensional clusters was not nearly as predictive of malignancy as single malignant cells.
CONCLUSION: Biliary brush cytology specimens performed better than biopsies irrespective of whether they are procured during ERCP or cholangioscopy. The combination of cytology and biopsy had the best accuracy than either one alone.

doi: https://doi.org/10.1002/dc.24553



  • Symptom Burden of Nonresected Pancreatic Adenocarcinoma: An Analysis of 10,753 Patient-Reported Outcome Assessments

Pancreas 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32769858

OBJECTIVES: Pancreatic adenocarcinoma (PAC) is a debilitating disease. We sought to analyze symptom burden and trajectories after diagnosis of PAC and identify predictors of severe symptoms for nonresected patients.
METHODS: This was a retrospective review of linked administrative health care databases examining patients with PAC not undergoing resection. Primary outcome was severe patient-reported symptoms (Edmonton Symptom Assessment System ≥7). Multivariable modified Poisson regression models were used to identify factors associated with reporting severe symptoms.
RESULTS: A total of 10,753 symptom assessments from 2168 patients were analyzed. The median age was 67 years, and 47% were female; median survival was 7 months. Most common severe symptoms were tiredness (54.7%), anorexia (53.6%), overall impaired wellbeing (45.3%), and drowsiness (37.1%). Severity of symptoms decreased 1 month after diagnosis and plateaued 4 months after diagnosis. Female sex, comorbidities, and older age were associated with reporting severe symptoms; recent radiation treatment and residence in a rural community were associated with reporting less severe symptoms.
CONCLUSIONS: The prevalence of severe symptoms in patients with nonresected PAC was high, but potentially modifiable. We identified vulnerable groups of patients that may benefit from focused interventions. This information is important for patient counseling and design of supportive care strategies.

doi: https://doi.org/10.1097/MPA.0000000000001629



  • Multimodal Device and Computer Algorithm-Based Monitoring of Pancreatic Microcirculation Profiles In Vivo

Pancreas 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32769856

OBJECTIVES: Pancreatic microcirculation has an essential role in orchestrating pancreatic homeostasis. Inherent complexity and technological limitation lead to interobserver variability and 1-sided microcirculatory data. Here, we introduce a multimodal device and computer algorithm-based platform for monitoring and visualizing integrated pancreatic microcirculation profiles.
METHODS: After anesthetizing and exposing pancreas tissue of BALB/c mice, probes of Oxygen to See, Microx TX3, and MoorVMS-LDF2 were positioned at pancreas in situ to capture the pancreatic microcirculatory oxygen (hemoglobin oxygen saturation, relative amount of hemoglobin, and partial oxygen pressure) and microhemodynamic data (microvascular blood perfusion and velocity). To assess and visualize pancreatic microcirculation profiles, raw data of pancreatic microcirculation profiles were processed and transformed using interquartile range and min-max normalization by Python and Apache ECharts.
RESULTS: The multimodal device-based platform was established and 3-dimensional microcirculatory modules were constructed. Raw data sets of pancreatic microcirculatory oxygen and microhemodynamic were collected. The outlier of data set was adjusted to the boundary value and raw data set was preprocessed. Normalized pancreatic microcirculation profiles were integrated into the 3-dimensional histogram and scatter modules, respectively. The 3-dimensional modules of pancreatic microcirculation profiles were then generated.
CONCLUSIONS: We established a multimodal device and computer algorithm-based monitoring platform for visualizing integrated pancreatic microcirculation profiles.

doi: https://doi.org/10.1097/MPA.0000000000001627



  • Left Ventricular Assist Device Therapy and Acute Pancreatitis: Higher Incidence and Worse Clinical Outcomes

Pancreas 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32769855

OBJECTIVE: The aim of the study was to compare incidence and outcomes of acute pancreatitis among advanced heart failure therapies.
METHODS: Two retrospective cohorts are as follows: A, patients with heart failure presenting to our hospitals and B, the US National Inpatient Sample. Three groups were compared: left ventricular assist device (LVAD) recipients, transplant recipients, and controls who did not qualify for advanced therapies. Primary outcomes were pancreatitis incidence and mortality. Secondary outcomes included kidney failure, multiorgan failure, shock, and health care utilization.
RESULTS: Cohort A included 1344 heart failure patients, and cohort B included 677,905 patients with acute pancreatitis. In cohort A, annual pancreatitis incidence was 6.7 cases per 1000 LVAD recipients, 4.1 per 1000 LVAD bridge-to-transplant, 2.3 per 1000 transplant recipients, and 3.2 per 1000 heart failure controls (P = 0.03). Combined, the incidence was 5.6 per 1000 LVAD users and 2.7 in 1000 non-LVAD users (relative risk, 2.1; P = 0.009). In cohort B, increased mortality was seen in LVAD users, but not in transplant recipients. Left ventricular assist device patients had higher odds of kidney failure, multiorgan failure, shock, and intensive care.
CONCLUSIONS: Patients with LVAD have double risk of pancreatitis, worse clinical outcomes, and increased healthcare utilization. Studies elucidating the mechanisms behind pancreatic injury in advanced heart failure are suggested.

doi: https://doi.org/10.1097/MPA.0000000000001624



  • Prospective Analysis of the Impact of 68Ga-DOTATOC Positron Emission Tomography-Computerized Axial Tomography on Management of Pancreatic and Small Bowel Neuroendocrine Tumors

Pancreas 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32769854

OBJECTIVES: A prospective clinical trial evaluated the effect of Ga-DOTATOC positron emission tomography-computerized axial tomography (PET-CT) on change in management of patients with lung, pancreatic, and small bowel neuroendocrine tumors. The primary eligibility criterion was a histologically proven tumor with positive somatostatin receptor subtype 2A immunohistochemistry. The primary and secondary end points were change in patient management and safety.
METHODS: Referring physicians completed questionnaires pre- and post-Ga-DOTATOC PET-CT, stating current and planned patient management, respectively, with tumor board adjudication of final management decisions. Change in management was categorized as follows: no change; minor change (additional imaging, supportive care); or major change (octreotide/lanreotide therapy, tumor biopsy, surgery, peptide receptor radiotherapy, chemotherapy, biological therapy, liver embolization).
RESULTS: A major change in management was recommended for 54 (47.37%) of 114 subjects and a minor change for 6 (5.26%) of 114 subjects, with no change for 54 (47.37%) of 114 subjects. Grade 1 adverse events were observed in 26 of 114 subjects (nausea, headache, back pain, diarrhea); one grade 2 (petechiae) and one grade 3 (abdominal pain) adverse event were observed. No grade 2 or 3 adverse events were related to study drug and none required intervention.
CONCLUSIONS: Imaging with Ga-DOTATOC PET-CT has a significant impact on management of patients with neuroendocrine tumors.

doi: https://doi.org/10.1097/MPA.0000000000001625



  • The Effect of Age on Short- and Long-Term Outcomes in Patients With Pancreatic Ductal Adenocarcinoma Undergoing Laparoscopic Pancreaticoduodenectomy

Pancreas 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32769853

OBJECTIVE: The aim of the study was to evaluate the effect of age on outcomes with pancreatic ductal adenocarcinoma (PDAC) undergoing laparoscopic pancreaticoduodenectomy (LPD).
METHODS: We retrospectively collected clinical data of consecutive patients with PDAC undergoing LPD from January 2012 to April 2019. The patients were divided into 2 groups according to age at admission for LPD: younger than 70 and 70 years or older.
RESULTS: A total of 147 patients were included (<70 years, n = 96; ≥70 years, n = 51). The elderly LPD patients had lower serum albumin levels (mean, 37.9 [standard deviation, 4.8] g/L vs 40.7 [standard deviation, 6.8] g/L, P = 0.004) and a larger frequency of comorbidities (62.7% vs 36.5%, P = 0.002) than younger patients. The short-term outcomes showed no significant differences. The median overall survival time of the younger patients was not significantly greater than that of the elderly patients (20.0 [95% confidence interval, 16.1-23.9] months vs 19.0 [95% confidence interval, 13.8-24.2] months, P = 0.902).
CONCLUSIONS: The short- and long-term outcomes of elderly patients with PDAC after LPD were similar to those of younger patients, despite a higher prevalence of multiple chronic illnesses and poorer nutritional conditioning among the elderly patients. These results show that LPD can be applied safely to elderly patients.

doi: https://doi.org/10.1097/MPA.0000000000001620



  • Cost-effectiveness of Abdominal Ultrasound Versus Magnetic Resonance Imaging for Pancreatic Cancer Screening in Familial High-Risk Individuals in Japan

Pancreas 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32769852

OBJECTIVE: The aim of the study was to assess cost-effectiveness of abdominal ultrasound, magnetic resonance imaging, endoscopic ultrasound, computed tomography, positron emission tomography, and no screening for pancreatic cancer screening in familial high-risk individuals (HRIs).
METHODS: We developed decision trees with Markov models for a hypothetical cohort of familial HRIs at the age of 50 year using a healthcare sector perspective and a lifetime horizon. Main outcomes were costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios.
RESULTS: In a base-case analysis, abdominal ultrasound was the most cost-effective (US $11,035, 17.4875 QALYs). Magnetic resonance imaging yielded the best benefits. Cost-effectiveness was sensitive to the incidence of pancreatic cancer. Endoscopic ultrasound was more cost-effective than abdominal ultrasound when the incidence of pancreatic cancer was greater than 0.008 and under 0.016. Magnetic resonance imaging was more cost-effective than endoscopic ultrasound when the incidence of pancreatic cancer was greater than 0.016. Probabilistic sensitivity analysis using Monte-Carlo simulation for 10,000 trials demonstrated that abdominal ultrasound was cost-effective 76% of the time at a willingness-to-pay threshold of US $50,000/QALY gained.
CONCLUSIONS: Abdominal ultrasound is the most cost-effective and recommended for pancreatic cancer screening in familial HRIs in Japan. Evaluating the risk of pancreatic cancer among familial HRIs as a target for screening is significant.

doi: https://doi.org/10.1097/MPA.0000000000001614



  • Risk Factors for Acute Kidney Injury in Acute Pancreatitis: A 7-Year Retrospective Analysis of Patients in a Large Tertiary Hospital

Pancreas 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32769851

OBJECTIVE: The aim of our study was to investigate the risk factors for acute kidney injury (AKI) in patients with acute pancreatitis (AP).
METHODS: Acute pancreatitis patients were retrospectively divided into 2 groups: AKI and non-AKI. We used logistic regression analysis to investigate the risk factors for AP patients with AKI. We also compared the incidence of complications and mortality between the non-AKI and AKI groups.
RESULTS: A total of 1255 AP patients without AKI and 430 AP patients with AKI were included. The risk factors for AKI in AP were hypertriglyceridemia (P = 0.001), severity (P = 0.001), etiology (P = 0.001), and Acute Physiology and Chronic Health Evaluation II scores (P = 0.001). The incidences of organ failure (P = 0.001), pancreatic necrosis (P = 0.001), and mortality (P = 0.001) were greater in the AKI group than in the non-AKI group.
CONCLUSIONS: Hypertriglyceridemia, severity, etiology, and Acute Physiology and Chronic Health Evaluation II scores are independent risk factors for AKI in AP patients. Those patients have serious outcomes such as high rate of organ failure, pancreatic necrosis, and debridement of necrosis.

doi: https://doi.org/10.1097/MPA.0000000000001613



  • Gene Expression Profiling of the Pancreas in Patients Undergoing Total Pancreatectomy With Islet Autotransplant Suggests Unique Features of Alcoholic, Idiopathic, and Hereditary Pancreatitis

Pancreas 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32769850

OBJECTIVES: To determine if RNA collected from pancreatic tissue, without the use of RNAlater, is useful for RNA sequencing (RNA-seq) despite degradation, and if so, then, via RNA-seq analysis, how does gene expression vary between pancreatitis etiologies.
METHODS: Data were assessed in 2 dimensions, based on RNA-seq signal shape assessed by RSeQC v.2.6.4 and RNA expression after accounting for different degrees of degradation.
RESULTS: Six measures of RNA characteristics (median RNA fragment size, reads per million kilobases saturation, transcript integrity number, distribution of hexamers, percentage of nucleotides that are guanine or cytosine, and duplicated reads) were significantly different between hereditary pancreatitis and idiopathic pancreatitis. Differential expression analysis revealed that 150 genes were differentially expressed between hereditary and idiopathic etiologies, 197 genes were differentially expressed between alcoholic and idiopathic etiologies, and 200 genes were differentially expressed between alcoholic and hereditary etiologies. We then determined that many enriched pathways between hereditary and idiopathic etiologies are related to the matrisome, and many of the enriched pathways between alcoholic and idiopathic etiology or hereditary etiology are related to ion transport.
CONCLUSIONS: We found distinct RNA-seq signals between different pancreatitis etiologies in both of the dimensions in critical pathways for pancreas biology.

doi: https://doi.org/10.1097/MPA.0000000000001607



  • Loss of HIF1A From Pancreatic Cancer Cells Increases Expression of PPP1R1B and Degradation of p53 to Promote Invasion and Metastasis

Gastroenterology 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32768595

BACKGROUND & AIMS: Pancreatic ductal adenocarcinomas (PDACs) are hypovascular, resulting in the upregulation of hypoxia inducible factor 1 alpha (HIF1A), which promotes survival of cells under low-oxygen conditions. We studied the roles of HIF1A in development of pancreatic tumors in mice.
METHODS: We performed studies with KrasLSL-G12D/+;Trp53LSL-R172H/+; Pdx1-Cre (KPC) mice, KPC mice with labeled pancreatic epithelial cells (EKPC), and EKPC mice with pancreas-specific depletion of HIF1A. Pancreatic and other tissues were collected and analyzed by histology, and immunohistochemistry. Cancer cells were cultured from PDACs from mice and analyzed in cell migration and invasion assays and by immunoblots, real-time PCR, and liquid chromatography-mass spectrometry. We performed studies with the human pancreatic cancer cell lines PATU-8988T, BxPC-3, PANC-1 and MiaPACA-2, which have no or low metastatic activity, and PATU-8988S, AsPC-1, SUIT-2 and Capan-1, which have high-metastatic activity. Expression of genes was knocked down in primary cancer cells and pancreatic cancer cell lines using small hairpin RNAs; cells were injected intravenously into immune-competent and NOD/SCID mice and lung metastases were quantified. We compared levels of mRNAs in pancreatic tumors and normal pancreas in the Cancer Genome Atlas.
RESULTS: EKPC mice with pancreas-specific deletion of HIF1A developed more advanced pancreatic neoplasias and PDACs with more invasion and metastasis, and had significantly shorter survival times, than EKPC mice. Pancreatic cancer cells from these tumors had higher invasive and metastatic activity in culture than cells from tumors of EKPC mice. HIF1A-knockout pancreatic cancer cells had increased expression of protein phosphatase 1 regulatory inhibitor subunit 1B (PPP1R1B). There was an inverse correlation between levels of HIF1A and PPP1R1B in human PDAC tumors; higher expression of PPP1R1B correlated with shorter survival times of patients. Metastatic human pancreatic cancer cell lines had increased levels of PPP1R1B and lower levels of HIF1A compared with non-metastatic cancer cell lines; knockdown of PPP1R1B significantly reduced the ability of pancreatic cancer cells to form lung metastases in mice. PPP1R1B promoted degradation of p53 by stabilizing phosphorylation of MDM2 at Ser166.
CONCLUSIONS: HIF1A can act a tumor suppressor by preventing expression of PPP1R1B and subsequent degradation of the p53 protein in pancreatic cancer cells. Loss of HIF1A from pancreatic cancer cells increases their invasive and metastatic activity.

doi: https://doi.org/10.1053/j.gastro.2020.07.046


New GallBladder Articles

Today there is no new Gallbladder Article.

New BileDuct Articles


  • Effect of single operator cholangioscopy on accuracy of bile duct cytology

Diagnostic cytopathology 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32770823

INTRODUCTION: This is the first study to evaluate the accuracy of bile duct brushings since the introduction of single operator cholangioscopy SpyGlass DS system in 2015. The primary aim of our study was to compare the accuracy of cytology brushings against biopsies obtained at endoscopic retrograde cholangiopancreatography (ERCP) and cholangioscopy.
METHOD: A retrospective search for bile duct brushing specimens was performed and the charts reviewed. The gold standard for definitive diagnosis of malignancy was surgical tissue or compelling clinical evidence of malignancy. Definite negative diagnosis relied on lack of clinical/imaging features of malignancy on follow-up.
RESULTS: There was no significant difference in diagnostic accuracy of cytology specimens obtained at different procedures. Overall sensitivity for all methods was 59%, specificity 90% and accuracy of 82%. Notably, all four false-positive cases except for one were from patients with primary sclerosing cholangitis or primary biliary sclerosis. There was no significant difference in sensitivity or specificity between biopsies procured by the two methods. The combined biopsy sensitivity for all modalities was 44% with a specificity of 100%. There was 70% concordance between cytology and biopsy cases. The overall specificity and sensitivity of the combined cytology and biopsy result was 85% and 65.3%, respectively. Ranking of factors that predict clinical diagnosis shows cytology results to surpass other parameters including pancreatic mass, age and stenosis length. Similarly, the presence of two cell populations and three-dimensional clusters was not nearly as predictive of malignancy as single malignant cells.
CONCLUSION: Biliary brush cytology specimens performed better than biopsies irrespective of whether they are procured during ERCP or cholangioscopy. The combination of cytology and biopsy had the best accuracy than either one alone.

doi: https://doi.org/10.1002/dc.24553


New Ampulla Articles

Today there is no new Ampulla Article.

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