Monthly Archives: August 2020

Recent Articles on Pancreatobiliary #Pathology – 2020-08-31

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

Predicting Positive Margins in Pancreatic Head Adenocarcinoma After Neoadjuvant Therapy: Investigating Disparities in Quality Care Using the National Cancer Database

Annals of surgical oncology 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32856228

BACKGROUND: In pancreatic cancer, surgical resection with neoadjuvant therapy improves survival, but survival relies significantly on the margin status of the resected tissue. This study aimed to develop a model that predicts margin positivity, and then to identify facility-specific factors that influence the observed-to-expected (O/E) ratio for positive margins among facilities.
METHODS: This retrospective review analyzed patients in the National Cancer Database (2004-2016) with pancreatic head adenocarcinoma [tumor-node-metastasis (TNM) stage 1 or 2] who received neoadjuvant therapy for a pancreaticoduodenectomy. Logistic regression was used to develop a model that predicts margin positivity. This model then was used to identify outlier facilities with regard to the O/E ratio. Hospital volume was defined as the total number of pancreaticoduodenectomies per year.
RESULTS: The study enrolled 4085 patients, and 16.8% of these patients had positive margins. Most of the patients (64%) had a tumor size of 2 to 4 cm, and approximately 51% of the patients did not have positive lymph nodes at resection. A logistic regression model showed that the predictors of positive margins after resection with neoadjuvant therapy were male sex, larger tumor size, and positive lymph nodes. This model was validated to yield a bootstrap-corrected concordance index of 0.632. The study calculated O/E ratios with the model, identifying 12 low- and 17 high O/E-ratio outlier facilities among 401 studied hospitals. The outlier hospitals did not differ in facility type (i.e., academic vs integrated network), but did differ significantly in terms of yearly hospital volume (low outlier of 20.6 vs high outlier of 10.7; p = 0.008).
CONCLUSIONS: An association of lower-volume facilities with higher than expected rates of positive margins was found to indicate a disparity in care. This disparity was identified via an O/E ratio as a quality indicator for facilities. Facilities can gauge the efficiency of their own practices by referencing their O/E ratios, and they also can improve their practices by analyzing the framework of low O/E-ratio facilities.

doi: https://doi.org/10.1245/s10434-020-08766-2

DNA damage repair as a target in pancreatic cancer: state-of-the-art and future perspectives

Gut 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32855305

Complex rearrangement patterns and mitotic errors are hallmarks of most pancreatic ductal adenocarcinomas (PDAC), a disease with dismal prognosis despite some therapeutic advances in recent years. DNA double-strand breaks (DSB) bear the greatest risk of provoking genomic instability, and DNA damage repair (DDR) pathways are crucial in preserving genomic integrity following a plethora of damage types. Two major repair pathways dominate DSB repair for safeguarding the genome integrity: non-homologous end joining and homologous recombination (HR). Defective HR, but also alterations in other DDR pathways, such as BRCA1, BRCA2, ATM and PALB2, occur frequently in both inherited and sporadic PDAC. Personalised treatment of pancreatic cancer is still in its infancy and predictive biomarkers are lacking. DDR deficiency might render a PDAC vulnerable to a potential new therapeutic intervention that increases the DNA damage load beyond a tolerable threshold, as for example, induced by poly (ADP-ribose) polymerase inhibitors. The Pancreas Cancer Olaparib Ongoing (POLO) trial, in which olaparib as a maintenance treatment improved progression-free survival compared with placebo after platinum-based induction chemotherapy in patients with PDAC and germline BRCA1/2 mutations, raised great hopes of a substantially improved outcome for this patient subgroup. This review summarises the relationship between DDR and PDAC, the prevalence and characteristics of DNA repair mutations and options for the clinical management of patients with PDAC and DNA repair deficiency.

doi: https://doi.org/10.1136/gutjnl-2019-319984

Evaluation of allowable pancreatic resection rate depending on preoperative risk factors for new-onset diabetes mellitus after distal pancreatectomy

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

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32855059

BACKGROUND: Although more patients have long-term survival after pancreatectomy, the details of pancreatogenic diabetes mellitus (DM) are still unclear. We aimed to investigate the incidence of new-onset DM (NODM) after distal pancreatectomy (DP) and to clarify the risk factors, including allowable pancreatic resection rate (PR), for NODM.
METHODS: The incidence, onset time, and risk factors for NODM were retrospectively evaluated in 150 patients who underwent DP without preoperative DM and with >5 years of postoperative follow-up between 2005 and 2015.
RESULTS: The incidence rate of NODM was 39%, and 60% of this incidence was noted within 6 months postoperatively. In the multivariate analysis, hemoglobin A1c ≥ 5.8% (odds ratio [OR] 7.6), impaired glucose tolerance and/or impaired fasting glucose (OR 4.2), homeostasis model assessment of insulin resistance ≥1.4 (OR 5.5), and insulinogenic index <0.7 (OR 3.9) were the preoperative risk factors for NODM. Based on these four preoperative risk factors of NODM, we made the new scoring system to predict the NODM after DP. The NODM incidence was 0%, 8%, 48%, 60%, and 86% in patients with risk scores 0 (n = 25), 1 (n = 36), 2 (n = 33), 3 (n = 35), and 4 (n = 21), respectively. PRs ≥42.1% and ≥30.9% were allowable in the preoperative risk-score 0-1 and 2-4 groups. In the former group, the NODM incidence for PR ≥ 42.1% and <42.1% was significantly different (20% vs 0%, P < 0.05). In the latter group, the NODM incidence for PR ≥ 30.9% vs <30.9% was significantly different (75% vs 23%, P < 0.05).
CONCLUSIONS: We clarified the preoperative risk factors and allowable PR for NODM and recommended the use of a risk scoring system for predicting NODM preoperatively.

doi: https://doi.org/10.1016/j.pan.2020.08.005

Metastatic pancreatic adenocarcinomas could be classified into M1a and M1b category by the number of metastatic organs

BMC gastroenterology 2020 Aug;20(1):289

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32854631

BACKGROUND: With the improvement of treatment and prognosis for patients with late malignant diseases, certain malignancies with distant metastasis (M1 category) have been further classified into M1a (single metastatic site) and M1b (multiple metastatic sites) category in the staging system. We aimed to assess the feasibility of sub-classifying metastatic pancreatic adenocarcinoma (mPA) into M1a and M1b category depending on the number of metastatic organs.
METHODS: Patient records were collected from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2015). Univariable and multivariable analyses were performed using the Cox regression model. Then survival analysis was determined using the Kaplan-Meier method.
RESULTS: A total of 11,885 patients were included in this analysis, including 9425 patients with single metastasis and 2460 patients with multiple metastases. Multivariable analysis showed that gender, age, marital status, grade, surgery, chemotherapy, and radiotherapy were independent prognostic factors for patients with single metastasis; gender, age, marital status, grade, chemotherapy and radiotherapy were independent prognostic factors for patients with multiple metastases. Notably, surgery was an independent prognostic factor for patients with single metastasis (P < 0.001) but not for patients with multiple metastases (P = 0.134). Kaplan-Meier analysis showed that patients with single metastasis (M1a) had better survival outcomes than patients with multiple metastases (M1b) (P < 0.001).
CONCLUSIONS: PA patients with M1 diseases could be divided into M1a (single metastasis) category and M1b (multiple metastases) category by the number of metastatic organs. The subclassification would facilitate individualized treatment for late PA patients. Surgery was associated with lower mortality in M1a patients but not significantly in M1b patients.

doi: https://doi.org/10.1186/s12876-020-01431-8

Therapeutic Potentials of MicroRNAs for Curing Diabetes Through Pancreatic ��-Cell Regeneration or Replacement

Pancreas 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32852323

MicroRNAs are a type of noncoding RNAs that regulates the expression of target genes at posttranscriptional level. MicroRNAs play essential roles in regulating the expression of different genes involved in pancreatic development, β-cell mass maintenance, and β-cell function. Alteration in the level of miRNAs involved in β-cell function leads to the diabetes. Being an epidemic, diabetes threatens the life of millions of patients posing a pressing demand for its urgent resolve. However, the currently available therapies are not substantial to cure diabetic epidemic. Thus, researchers are trying to find new ways to replenish the β-cell mass in patients with diabetes. One promising approach is the in vivo regeneration of β-cell mass or increasing the efficiency of β-cell function. Another clinical strategy is the transplantation of in vitro developed β-like cells. Owing to their role in pancreatic β-cell development, maintenance, functioning and their involvement in diabetes, overexpression or attenuation of different miRNAs can cause β-cell regeneration in vivo or can direct the differentiation of various kinds of stem/progenitor cells to β-like cells in vitro. Here, we will summarize different strategies used by researchers to investigate the therapeutic potentials of miRNAs, with focus on miR-375, for curing diabetes through β-cell regeneration or replacement.

doi: https://doi.org/10.1097/MPA.0000000000001655

Undertreatment of Pancreatic Cancer: Role of Surgical Pathology

Annals of surgical oncology 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32851518

BACKGROUND: Current guidelines recommend treatment of early-stage pancreatic cancer with surgical resection and chemotherapy. Undertreatment can occur after resection when patients fail to receive adjuvant chemotherapy. Final pathologic results have the potential to bias providers to omit adjuvant chemotherapy, however, the association of surgical pathology and adjuvant chemotherapy is unknown.
METHODS: Data from the National Cancer Database identified patients who underwent surgery for stage I or II pancreatic cancer. Chi-square tests and logistic regression were used to determine differences between patients receiving surgery followed by chemotherapy and those who had resection alone. Survival analysis of subgroups with favorable pathology (node-negative disease, tumor size ≤ 2 cm, well-differentiated histology) was performed by the Kaplan-Meier method and the Cox proportional hazards model.
RESULTS: Of the 22,131 patients included in this study, 28% were considered undertreated (surgery alone). Favorable pathologic traits of negative lymph nodes, tumor 2 cm in size or smaller, and well-differentiated histology were associated with a 15-35% lower probability that adjuvant chemotherapy would be given than less favorable pathologic results (p < 0.001). Multivariable survival analysis showed significantly lower odds of mortality for patients who received resection and chemotherapy than for those who were undertreated among two subgroups: patients with node-negative disease (hazard ratio [HR] 0.774) and those with a tumor 2 cm in size or smaller (HR 0.771).
CONCLUSION: The patients who had early-stage pancreatic cancer with favorable pathology after pancreatectomy were less likely than those with unfavorable pathology to receive adjuvant chemotherapy. This omission had significant survival consequences for subgroups with node-negative disease and tumors 2 cm in size or smaller. Recognition of patients with favorable pathology as an undertreated group is required for efforts to be directed toward encouraging guideline-concordant care and to combat undertreatment of pancreatic cancer.

doi: https://doi.org/10.1245/s10434-020-09043-y

Intraductal papillary squamous neoplasm of the pancreas: Cyto-histologic correlation of a novel entity

Annals of diagnostic pathology 2020 Aug;48():151583

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32847795

We correlate the cytologic and histologic features of a squamous-lined pancreatic cystic lesion with a complex papillary architecture and an associated KRAS mutation, which to our knowledge has not been previously described. A 69 year-old woman presented with intermittent left upper quadrant pain. CT imaging revealed a 1 cm solid lesion in the pancreatic tail with peripheral calcification. Endoscopic ultrasound-guided fine needle biopsy showed a proliferation of epithelial cells with fibrovascular cores. An immunohistochemical stain for p40 was positive in the lesional cells. A distal pancreatectomy revealed a unilocular, cystic, well-circumscribed, soft and friable mass measuring 1.0 × 1.0 × 0.8 cm. Histologically, the cyst was lined by nonkeratinizing stratified squamous epithelium with a complex papillary architecture, filling the cyst lumen. Molecular sequencing revealed a KRAS G12V missense mutation. While the lesion shared some histologic features with the previously described “squamoid cyst of the pancreatic ducts”, the complex papillary architecture and presence of a KRAS mutation are unique to the entity we describe herein and we propose the name “intraductal papillary squamous neoplasm of the pancreas.” Reporting the cytomorphologic features of this novel entity may help in identification of similar lesions and understanding of the clinicopathologic significance.

doi: https://doi.org/10.1016/j.anndiagpath.2020.151583

A Randomized Trial of Closed-Loop Control in Children with Type 1 Diabetes

The New England journal of medicine 2020 08;383(9):836-845

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32846062

BACKGROUND: A closed-loop system of insulin delivery (also called an artificial pancreas) may improve glycemic outcomes in children with type 1 diabetes.
METHODS: In a 16-week, multicenter, randomized, open-label, parallel-group trial, we assigned, in a 3:1 ratio, children 6 to 13 years of age who had type 1 diabetes to receive treatment with the use of either a closed-loop system of insulin delivery (closed-loop group) or a sensor-augmented insulin pump (control group). The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring.
RESULTS: A total of 101 children underwent randomization (78 to the closed-loop group and 23 to the control group); the glycated hemoglobin levels at baseline ranged from 5.7 to 10.1%. The mean (±SD) percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter increased from 53±17% at baseline to 67±10% (the mean over 16 weeks of treatment) in the closed-loop group and from 51±16% to 55±13% in the control group (mean adjusted difference, 11 percentage points [equivalent to 2.6 hours per day]; 95% confidence interval, 7 to 14; P<0.001). In both groups, the median percentage of time that the glucose level was below 70 mg per deciliter was low (1.6% in the closed-loop group and 1.8% in the control group). In the closed-loop group, the median percentage of time that the system was in the closed-loop mode was 93% (interquartile range, 91 to 95). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either group.
CONCLUSIONS: In this 16-week trial involving children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with the use of a closed-loop system than with the use of a sensor-augmented insulin pump. (Funded by Tandem Diabetes Care and the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number, NCT03844789.).

doi: https://doi.org/10.1056/NEJMoa2004736

New GallBladder Articles

Today there is no new Gallbladder Article.

New BileDuct Articles

Today there is no new Bile Duct Article.

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/

Recent Articles on Pancreatobiliary #Pathology – 2020-08-27

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

A case of inflammatory pseudotumour of the gallbladder presenting as a big mass of uncertain behavior

BMC gastroenterology 2020 Aug;20(1):282

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32838747

BACKGROUND: Inflammatory pseudotumour has been used to describe an inflammatory or fibrosing tumoral process of an undetermined cause that may involve a variety of organ systems, including the lungs, spleen, liver, lymph nodes, pancreas and extrahepatic bile duct with potential for recurrence and persistent local growth. In this article, we report a patient with a big mass of uncertain nature and behavior.
CASE PRESENTATION: A 60-year-old woman presented with a 1-week history of abdominal pain, fever and jaundice. Six months before she had had right upper quadrant pain that was interpreted as biliary colic. A contrast-enhanced CT scan showed a big mass of soft tissue with diffuse infiltration of the gallbladder, displacement of the transverse colon, hepatic flexure and duodenum. For diagnostic distinction between a chronic inflammatory disease or a neoplasm, exploratory laparotomy was required. Intraoperative exploration disclosed a big mass of hard texture involving the gallbladder, with multiple concrements, hepatoduodenal ligament, right and transverse mesocolon, stomach and duodenum. Cholecystectomy was performed, preserving adjacent organs with macroscopic desmoplastic reaction. Histopathologic examination of the gallbladder showed a spindle cell proliferation with diffuse chronic inflammatory infiltrate of lymphocytes, plasma cells and hyalinized fibrous stroma. No vascular invasion or cellular atypia were evident.
CONCLUSION: Inflammatory pseudotumour is a rare condition and diagnostic distinction from a chronic inflammatory disease or other neoplasm is only possible by histopathologic examination. There is a limited number of case reports in the literature indicating tumor location in the gallbladder.

doi: https://doi.org/10.1186/s12876-020-01408-7

Pancreatic Inflammation and Proenzyme Activation Are Associated With Clinically Relevant Postoperative Pancreatic Fistulas After Pancreas Resection

Annals of surgery 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32833754

OBJECTIVE: We investigated the activation of pancreatic proenzymes and signs of peripancreatic inflammation in patients with clinically relevant postoperative pancreatic fistulas (POPFs).
SUMMARY BACKGROUND DATA: An increase of systemic amylase concentration was associated with POPFs. This suggested parallels in the pathomechanisms between the development of POPFs and pancreatitis.
METHODS: Trypsinogen, procathepsin B, and IL-6 concentrations as well as cathepsin B, myeloperoxidase and trypsin activities were determined throughout the first 7 postoperative days in drain fluids of 128 consecutive patients after pancreas resection. Histology and immunohistochemistry were performed in pancreatic specimens after total pancreatectomy due to complications and after placing experimental pancreatic sutures in the pancreatic tail of C57/Bl6 mice.
RESULTS: Trypsin activity, cathepsin B activity and myeloperoxidase activity on the first postoperative day were elevated and predictive for clinically relevant pancreatic fistulas. Drain fluid stabilized trypsin activity and prevented the activation of the cascade of digestive enzymes. Leukocytes were the source of cathepsin B in drain fluid. Findings differed between fistulas after distal pancreatectomy and pancreatoduodenectomy. Immunohistochemistry of the pancreatic remnant revealed an inflammatory infiltrate expressing cathepsin B, independent of the presence of pancreatic fistulas. The infiltrate could be reproduced experimentally by sutures placed in the pancreatic tail of C57/Bl6 mice.
CONCLUSIONS: Trypsinogen activation, increased cathepsin B activity and inflammation around the pancreato-enteric anastomosis on post operative day 1 are associated with subsequent clinically relevant POPFs after pancreatoduodenectomy. The parenchymal damage seems to be induced by placing sutures in the pancreatic parenchyma during pancreatic surgery.

doi: https://doi.org/10.1097/SLA.0000000000004257

Insulitis and lymphoid structures in the islets of Langerhans of a 66-year-old patient with long-standing type 1 diabetes

Virchows Archiv : an international journal of pathology 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32833039

Insulitis is a characteristic inflammatory lesion consisting of immune cell infiltrates around and within the pancreatic islets of patients with recent-onset type 1 diabetes (T1D). The infiltration is typically mild, both in terms of the number of infiltrating cells and the number of islets affected. Here, we present an unusual histopathological case study of a 66-year-old female patient with long-standing T1D, insulitis, and islet-associated lymphoid tissue. Most islets in the head of the pancreas of this patient were insulin-deficient, whereas the islets in the tail appeared normal. Insulitis was present in 0.84% of the insulin-containing islets and three islets had large lymphocytic infiltrates resembling tertiary lymphoid structures (TLS). Of note, this is the first description of potential TLS in the endocrine pancreas of a patient with T1D. Their association with a marked residual beta cell mass is of interest and may hint at new insights into disease progression and regulation of autoimmunity.

doi: https://doi.org/10.1007/s00428-020-02915-4

A case report of pancreatic panniculitis due to acute pancreatitis with intraductal papillary mucinous neoplasm

BMC gastroenterology 2020 Aug;20(1):286

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32831035

BACKGROUND: Pancreatic panniculitis is a rare skin manifestation in pancreatic disease patients that most frequently develops on the lower legs. We report the unique case of a 68-year-old man who suffered from pancreatic panniculitis on his trunk associated with acute pancreatitis due to an intraductal papillary mucinous neoplasm.
CASE PRESENTATION: A 68-year-old man complained of a 2-day history of a tender subcutaneous nodule on his trunk. Laboratory tests and abdominal contrast computed tomography were consistent with acute pancreatitis due to an intraductal papillary mucinous neoplasm. A skin biopsy of the nodule histologically displayed lobular panniculitis with characteristic “ghost cells”, which indicated pancreatic panniculitis.
CONCLUSIONS: In order to avoid a missed or delayed diagnosis, clinicians should bear in mind that pancreatic panniculitis can be the first manifestation of pancreatic disease when encountering subcutaneous nodules on the trunk.

doi: https://doi.org/10.1186/s12876-020-01430-9

Pancreatic duct guidewire placement for biliary cannulation as a risk factor for stone residue after endoscopic transpapillary stone removal

BMC gastroenterology 2020 Aug;20(1):285

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32831030

BACKGROUND: Recent improvements in stone extraction implements and apparatus have lessened the complexity of the endoscopic bile duct stone treatment. However, despite confirmation of complete removal, cases of residual stones have been reported, which can result in recurrent biliary symptoms, cholangitis, and pancreatitis and considerably increase cost given the need for repeat imaging and/or procedures. To date, risk factors for residual bile duct stones following endoscopic retrograde cholangiopancreatography (ERCP) extraction have not been thoroughly evaluated. This study retrospectively investigated the incidence and risk factors of residual bile duct stones following extraction via ERCP.
METHODS: We retrospectively reviewed all ERCP cases that underwent endoscopic bile duct stone extraction between April 2014 and March 2019. A total of 505 patients were enrolled and evaluated for the incidence and risk factors of residual bile duct stones after ERCP.
RESULTS: The rate of residual stones was 4.8% (24/505). Residual stones were detected by computed tomography (12/24) or magnetic resonance cholangiopancreatography (12/24). In univariate analyses, a large number of stones (P = 0.01), long procedure time (P = 0.005), and performance of the pancreatic duct guidewire placement method (P-GW) for selective bile duct cannulation (P = 0.01) were the factors involved in residual stones. In multiple logistic regression analysis, performing P-GW was retained as the only independent factor of residual stones (adjusted odds ratio, 3.44; 95% CI, 1.19-9.88; P = 0.02).
CONCLUSIONS: When removing bile duct stones with a pancreatic guidewire in place, paying attention to residual stones is necessary.

doi: https://doi.org/10.1186/s12876-020-01428-3

Insulin-like growth factor binding protein 3 chemosensitizes pancreatic ductal adenocarcinoma through its death receptor

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

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32830034

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human malignancies. Gemcitabine and doxorubicin are commonly used as the chemotherapy agents, but most of PDAC tumors eventually acquired resistance to chemotherapy. Accumulating evidence indicates that Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role against tumor growth but its expression has commonly suppressed. The present study was designed to evaluate IGFBP-3 effects in chemotherapy sensitization of PDAC cells. Here, we report that the re-sensitization of chemoresistant PDAC cells was occurred by IGFBP-3 through recruitment of its death receptor (IGFBP-3R). Using gemcitabine, doxorubicin-resistant PDAC cell lines, we found that IGFBP-3 sensitized chemoresistant cells by activating apoptosis (as evaluated by Bax up-regulation, Bcl-2 down-regulation as well as Caspase-3 and Caspase 8 activation). IGFBP-3R was also found to have higher expression level in resistant AsPc-1 and MIA PaCa-2 cells in comparison to parental cells. IGFBP-3R was also highly expressed in PDAC tumor which exposed to chemotherapy in comparison to un-treated PDAC tumors. In addition, we confirmed our finding by using specific siRNA to knocking down of IGFBP-3R which prevents IGFBP-3 Chemosensitization. Taken together, the present study for the first time indicates the clinical relevance for combining IGFBP-3 with chemotherapy to reduce chemoresistance in PDAC.

doi: https://doi.org/10.1016/j.pan.2020.07.406

New GallBladder Articles

A case of inflammatory pseudotumour of the gallbladder presenting as a big mass of uncertain behavior

BMC gastroenterology 2020 Aug;20(1):282

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32838747

doi: https://doi.org/10.1186/s12876-020-01408-7

New BileDuct Articles

A case of inflammatory pseudotumour of the gallbladder presenting as a big mass of uncertain behavior

BMC gastroenterology 2020 Aug;20(1):282

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32838747

doi: https://doi.org/10.1186/s12876-020-01408-7

Pancreatic duct guidewire placement for biliary cannulation as a risk factor for stone residue after endoscopic transpapillary stone removal

BMC gastroenterology 2020 Aug;20(1):285

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32831030

doi: https://doi.org/10.1186/s12876-020-01428-3

Usefulness of peroral cholangioscopy in the differential diagnosis of IgG4-related sclerosing cholangitis and extrahepatic cholangiocarcinoma: a single-center retrospective study

BMC gastroenterology 2020 Aug;20(1):287

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32831026

BACKGROUND: In the diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC), differentiation from extrahepatic cholangiocarcinoma (ECC) is extremely important but is still a clinical challenge. This study aimed to elucidate the usefulness of peroral cholangioscopy (POCS) for the differential diagnosis between IgG4-SC and ECC.
METHODS: POCS findings for bile duct stricture were retrospectively evaluated in 17 patients with IgG4-SC diagnosed at the Hiroshima University Hospital and 53 patients with surgically resected infiltrating ECC. Mucosal surface, dilated vessels (tortuosity, caliber alteration, and disruption), and easily bleeding were compared between the groups.
RESULTS: The stricture sites of IgG4-SC evaluated by POCS were 10 extrapancreatic bile ducts and 9 intrapancreatic bile ducts. In patients with IgG4-SC, smooth mucosal surface was observed in 89% (17/19), dilated vessels in 58% (11/19) [tortuosity 82% (9/11), caliber alteration 18% (2/11), and disruption 9% (1/11)], and easily bleeding in 0%. Irregular mucosal surface and easily bleeding were observed significantly more frequently in ECC (both P < 0.001). The frequency of caliber alteration and disruption of dilated vessels was significantly less in IgG4-SC (P < 0.001 and 0.005, respectively). The sensitivity and specificity of POCS in the diagnosis of ECC were 96 and 89%, respectively. Dilated vessels in IgG4-SC were observed significantly more frequently in the extrapancreatic bile duct, especially the hilar bile duct (P = 0.006). Concerning image evaluation, the interobserver agreement was κ = 0.719, and the intraobserver agreement was κ = 0.768 and 0.754.
CONCLUSIONS: Characteristic POCS findings of the stricture sites in IgG4-SC were smooth mucosal surface, dilated vessels without caliber alteration and disruption, and lack of easily bleeding. These POCS findings are extremely useful for distinguishing between IgG4-SC and ECC.

doi: https://doi.org/10.1186/s12876-020-01429-2

New Ampulla Articles

A case of inflammatory pseudotumour of the gallbladder presenting as a big mass of uncertain behavior

BMC gastroenterology 2020 Aug;20(1):282

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32838747

doi: https://doi.org/10.1186/s12876-020-01408-7

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

A very useful function: eval parse text paste

SCIENCE

A very useful function: eval parse text paste

When creating evolutions models and simulations in R, code can quickly become messy and slow. Functions that require fewer lines of code can speed up your program, and make it easier to follow what is happening. There are also often variables, such as number of alleles or loci, that need to be manipulated easily, without the requirement of changing multiple lines of code. This is where eval parse text paste becomes useful. The four stages of this can be understood by considering each of them individually, in reverse order.

paste simply converts something into text, and can combine several pieces of text together. For example. In the code below, we can paste the generation number of a program i next to the word generation. ,sep="" means there is no gap between the two pieces we are pasting together. We could make…

View original post 796 more words

Recent Articles on Pancreatobiliary #Pathology – 2020-08-24

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

The occurrence of prion protein in surgically resected pancreatic adenocarcinoma

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

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32828686

BACKGROUND: Among the several new targets for the comprehension of the biology of pancreatic ductal adenocarcinoma (PDAC), Prion proteins (PrPc) deserve particular mention, since they share a marked neurotropism. Actually, PrPc could have also a role in tumorigenesis, as recently demonstrated. However, only few in vitro studies in cell cultures showed the occurrence of PrPc in PDAC cells. We aim to evaluate the presence of PrPc in vivo in PDAC tissues as a potential new biomarker.
METHODS: Samples from tumors of 23 patients undergone pancreatic resections from July 2018 to May 2020 at our institution were collected and analyzed. Immunohistochemistry and western blotting of PDAC tissues were compared with control tissues. Immunohistochemistry was used also to evaluate the localization of PrPc and of CD155, a tumoral stem-cell marker.
RESULTS: All cases were moderately differentiated PDAC, with perineural invasion (PNI) in 19/23 cases (83%). According to western-blot analysis, PrPc was markedly expressed in PDAC tissues (273.5 ± 44.63 OD) respect to controls (100 ± 28.35 OD, p = 0.0018). Immunohistochemistry confirmed these findings, with higher linear staining of PrPc in PDAC ducts (127.145 ± 7.56 μm vs 75.21 ± 5.01 μm, p < 0.0001). PrPc and CD155 exactly overlapped in ductal tumoral cells, highlighting the possible relationship of PrPc with cancer stemness. Finally, PrPc expression related with cancer stage and there was a potential correspondence with PNI.
CONCLUSIONS: Our work provides evidence for increased levels of PrPc in PDAC. This might contribute to cancer aggressiveness and provides a potentially new biomarker. Work is in progress to decipher clinical implications.

doi: https://doi.org/10.1016/j.pan.2020.08.004

Whole-exome Sequencing Reveals New Potential Susceptibility Genes for Japanese Familial Pancreatic Cancer

Annals of surgery 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32826389

OBJECTIVE: The primary objective of this study was to identify novel genes that predispose people in the Japanese population to FPC.
SUMMARY OF BACKGROUND DATA: Familial history of pancreatic cancer is an important risk factor but, to date, few genes predisposing individuals to increased risk of developing FPC have been identified.
METHODS: We performed whole-exome sequencing of germline DNA from 81 Japanese FPC patients. We also investigated somatic gene alterations in 21 matched tumor tissues through whole-exome sequencing and copy number analysis.
RESULTS: Our germline variants identified previously known FPC susceptibility genes such as ATM and BRCA2, and several novel tumor suppressor genes with potentially deleterious variants for FPC. Interestingly, somatic whole-exome analysis demonstrated that most tumor samples with suspicious loss of heterozygosity of candidate genes were KRAS wild-types, implying that these cases may not have required KRAS activation as a driver event for carcinogenesis.
CONCLUSIONS: Our findings indicate that FPC patients harbor potentially deleterious causative germline variants in tumor suppressor genes, which are known to acquire somatic mutations in pancreatic cancer, and that somatic loss of heterozygosity of some FPC susceptibility genes may contribute to the development of FPC in the absence of somatic KRAS-activating mutation. Genetic testing for a wider variety of FPC-predisposition genes could provide better screening approach for high-risk groups of pancreatic cancer.

doi: https://doi.org/10.1097/SLA.0000000000004213

Reciprocal regulation of pancreatic ductal adenocarcinoma growth and molecular subtype by HNF4�� and SIX1/4

Gut 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32826305

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival of less than 5%. Transcriptomic analysis has identified two clinically relevant molecular subtypes of PDAC: classical and basal-like. The classical subtype is characterised by a more favourable prognosis and better response to chemotherapy than the basal-like subtype. The classical subtype also expresses higher levels of lineage specifiers that regulate endodermal differentiation, including the nuclear receptor hepatocyte nuclear factor 4 α (HNF4α). The objective of this study is to evaluate the role of HNF4α, SIX4 and SIX1 in regulating the growth and molecular subtype of PDAC.
DESIGN: We manipulate the expression of HNF4α, SIX4 and SIX1 in multiple in vitro and in vivo PDAC models. We determine the consequences of manipulating these genes on PDAC growth, differentiation and molecular subtype using functional assays, gene expression analysis and cross-species comparisons with human datasets.
RESULTS: We show that HNF4α restrains tumour growth and drives tumour cells toward an epithelial identity. Gene expression analysis of murine models and human tumours shows that HNF4α activates expression of genes associated with the classical subtype. HNF4α also directly represses SIX4 and SIX1, two mesodermal/neuronal lineage specifiers expressed in the basal-like subtype. Finally, SIX4 and SIX1 drive proliferation and regulate differentiation in HNF4α-negative PDAC.
CONCLUSION: Our data show that HNF4α regulates the growth and molecular subtype of PDAC by multiple mechanisms, including activation of the classical gene expression programme and repression of SIX4 and SIX1, which may represent novel dependencies of the basal-like subtype.

doi: https://doi.org/10.1136/gutjnl-2020-321316

Prehabilitation prior to surgery for pancreatic cancer: A systematic review

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

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32826168

INTRODUCTION: Prehabilitation aims to improve fitness and outcomes of patients undergoing major surgery. This systematic review aimed to appraise current available evidence regarding the role of prehabilitation in patients undergoing oncological pancreatic resection.
METHODS: A systematic literature search of PUBMED, MEDLINE, EMBASE databases identified articles describing prehabilitation programmes before pancreatic resection for malignancy. Data collected included timing of prehabilitation, programme type, duration, adherence and post-operative outcome reporting.
RESULTS: Six studies, including 193 patients were included in the final analysis. Three studies included patients undergoing neoadjuvant therapy followed by resection and 3 studies included patients undergoing upfront resection. Time from diagnosis to surgery ranged between 2 and 22 weeks across all studies. Two studies reported a professionally supervised exercise programme, and four described unsupervised programmes. Exercise programmes varied from 5 days to 6 months in duration. Adherence to exercise programmes was better with supervised programmes (99% reaching weekly activity goal vs 85%) and patients not undergoing neoadjuvant therapy (90% reaching weekly activity goal vs 82%). All studies reported improvement in muscle mass or markers of muscle function following prehabilitation. Two studies reported the impact of Prehabilitation on postoperative outcomes and Prehabilitation was associated with lower delayed gastric emptying and a shorter hospital stay with no impact on other postoperative outcomes.
CONCLUSION: Early evidence demonstrates that Prehabilitation programmes may improve postoperative outcomes following pancreatic surgery. However current Prehabilitaton programmes for patients undergoing pancreatic resection report diverse exercise regimens with no consensus regarding timing or length of Prehabilitation, warranting a need for standardisation of Prehabilitation programmes in pancreatic surgery.

doi: https://doi.org/10.1016/j.pan.2020.07.411

New GallBladder Articles

Today there is no new Gallbladder Article.

New BileDuct Articles

Today there is no new Bile Duct Article.

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/

Recent Articles on Pancreatobiliary #Pathology – 2020-08-21

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

;():*

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

doi: https://doi.org/

;():*

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

doi: https://doi.org/

;():*

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

doi: https://doi.org/

;():*

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

doi: https://doi.org/

;():*

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

doi: https://doi.org/

A preclinical trial and molecularly-annotated patient cohort identify predictive biomarkers in homologous recombination deficient pancreatic cancer

Clinical cancer research : an official journal of the American Association for Cancer Research 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32816949

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) arising in patients with a germline BRCA1 or BRCA2 (gBRCA) mutation may be sensitive to platinums and poly(adenosine diphosphate-ribose) polymerase inhibitors (PARPi). However, treatment stratification based on gBRCA mutational status alone is associated with heterogeneous responses.
EXPERIMENTAL DESIGN: We performed a 7-arm preclinical trial consisting of 471 mice, representing 12 unique PDAC patient-derived xenografts, of which 9 were gBRCA-mutated. From 179 patients whose PDAC was whole genome and transcriptome sequenced, we identified 21 cases with homologous recombination deficiency (HRD), and investigated prognostic biomarkers.
RESULTS: We found that biallelic inactivation of BRCA1/BRCA2 is associated with genomic hallmarks of HRD and required for cisplatin and talazoparib (PARPi) sensitivity. However, HRD genomic hallmarks persisted in xenografts despite the emergence of therapy resistance, indicating the presence of a genomic scar. We identified tumour polyploidy and a low Ki67 index as predictors of poor cisplatin and talazoparib response. In HRD PDAC patients, tumour polyploidy and a basal-like transcriptomic subtype were independent predictors of shorter survival. To facilitate clinical assignment of transcriptomic subtype, we developed a novel pragmatic two-marker assay (GATA6:KRT17).
CONCLUSIONS: In summary, we propose a predictive and prognostic model of gBRCA-mutated PDAC based on HRD genomic hallmarks, Ki67 index, tumour ploidy and transcriptomic subtype.

doi: https://doi.org/10.1158/1078-0432.CCR-20-1439

CDK1/2/5 inhibition overcomes IFNG-mediated adaptive immune resistance in pancreatic cancer

Gut 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32816920

OBJECTIVE: Adaptive immune resistance mediated by the cytokine interferon gamma (IFNG) still constitutes a major problem in cancer immunotherapy. We develop strategies for overcoming IFNG-mediated adaptive immune resistance in pancreatic ductal adenocarcinoma cancer (PDAC).
DESIGN: We screened 429 kinase inhibitors for blocking IFNG-induced immune checkpoint (indoleamine 2,3-dioxygenase 1 (IDO1) and CD274) expression in a human PDAC cell line. We evaluated the ability of the cyclin-dependent kinase (CDK) inhibitor dinaciclib to block IFNG-induced IDO1 and CD274 expression in 24 human and mouse cancer cell lines as well as in primary cancer cells from patients with PDAC or ovarian carcinoma. We tested the effects of dinaciclib on IFNG-induced signal transducer and activator of transcription 1 activation and immunological cell death, and investigated the potential utility of dinaciclib in combination with IFNG for pancreatic cancer therapy in vivo, and compared gene expression levels between human cancer tissues with patient survival times using the Cancer Genome Atlas datasets.
RESULTS: Pharmacological (using dinaciclib) or genetic (using shRNA or siRNA) inactivation of CDK1/2/5 not only blocks JUN-dependent immune checkpoint expression, but also triggers histone-dependent immunogenic cell death in immortalised or primary cancer cells in response to IFNG. This dual mechanism turns an immunologically 'cold' tumour microenvironment into a 'hot' one, dramatically improving overall survival rates in mouse pancreatic tumour models (subcutaneous, orthotopic and transgenic models). The abnormal expression of CDK1/2/5 and IDO1 was associated with poor patient survival in several cancer types, including PDAC.
CONCLUSION: CDK1/2/5 kinase activity is essential for IFNG-mediated cancer immunoevasion. CDK1/2/5 inhibition by dinaciclib provides a novel strategy to overcome IFNG-triggered acquired resistance in pancreatic tumour immunity.

doi: https://doi.org/10.1136/gutjnl-2019-320441

Diagnosis of pancreatic solid pseudopapillary neoplasms using cell blocks and immunohistochemical evaluation of endoscopic ultrasound-guided fine-needle aspiration biopsy specimens

Cytopathology : official journal of the British Society for Clinical Cytology 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32816310

BACKGROUND AND AIMS: Preoperative diagnostic imaging of pancreatic solid pseudopapillary neoplasms (SPN) is challenging. A few studies have investigated the role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the diagnosis of SPN. We investigated the diagnostic yield of cell blocks and immunohistochemistry (IHC) for SPN using EUS-FNA specimens without cytological evaluation.
PATIENTS AND METHODS: We retrospectively analyzed the histopathology records of patients with suspected SPN, who underwent EUS-FNA biopsy between January 1997 and January 2020. Diagnosis based on cell blocks (hematoxylin-eosin staining with complementary IHC) was compared with the definitive surgical diagnosis.
RESULTS: This study included 25 patients (24 were women). Patients' mean age was 33.7 years (range 12-78 years). The most common symptom was abdominal pain. SPN was an incidental finding in 52% of the patients. The mean lesion size was 4.3 cm (range 1.2-11.4 cm), and the most common endosonographic features included solid-cystic (56%) or solid (40%) tumors. Final diagnoses included SPNs (23) and non-functioning neuroendocrine tumors (2). The overall accuracy of EUS-FNA was 80%. Tumor cells showed immunopositivity for beta-catenin, CD10, CD99, and progesterone receptor (PR) in 93.7%, 87.5%, 83.3%, and 66.6% of patients, respectively. No SPN showed immunopositivity for chromogranin A.
CONCLUSIONS: Intention-to-diagnose analysis showed that the diagnostic accuracy of EUS-FNA for SPNs using cell blocks and complementary IHC without cytological evaluation was fairly good. Evaluation of beta-catenin, CD 10, CD99, and PR expression must be included in the IHC panel for diagnostic confirmation of SPNs using EUS-FNA biopsy specimens.

doi: https://doi.org/10.1111/cyt.12905

Effects of Diet versus Gastric Bypass on Metabolic Function in Diabetes

The New England journal of medicine 2020 Aug;383(8):721-732

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32813948

BACKGROUND: Some studies have suggested that in people with type 2 diabetes, Roux-en-Y gastric bypass has therapeutic effects on metabolic function that are independent of weight loss.
METHODS: We evaluated metabolic regulators of glucose homeostasis before and after matched (approximately 18%) weight loss induced by gastric bypass (surgery group) or diet alone (diet group) in 22 patients with obesity and diabetes. The primary outcome was the change in hepatic insulin sensitivity, assessed by infusion of insulin at low rates (stages 1 and 2 of a 3-stage hyperinsulinemic euglycemic pancreatic clamp). Secondary outcomes were changes in muscle insulin sensitivity, beta-cell function, and 24-hour plasma glucose and insulin profiles.
RESULTS: Weight loss was associated with increases in mean suppression of glucose production from baseline, by 7.04 μmol per kilogram of fat-free mass per minute (95% confidence interval [CI], 4.74 to 9.33) in the diet group and by 7.02 μmol per kilogram of fat-free mass per minute (95% CI, 3.21 to 10.84) in the surgery group during clamp stage 1, and by 5.39 (95% CI, 2.44 to 8.34) and 5.37 (95% CI, 2.41 to 8.33) μmol per kilogram of fat-free mass per minute in the two groups, respectively, during clamp stage 2; there were no significant differences between the groups. Weight loss was associated with increased insulin-stimulated glucose disposal, from 30.5±15.9 to 61.6±13.0 μmol per kilogram of fat-free mass per minute in the diet group and from 29.4±12.6 to 54.5±10.4 μmol per kilogram of fat-free mass per minute in the surgery group; there was no significant difference between the groups. Weight loss increased beta-cell function (insulin secretion relative to insulin sensitivity) by 1.83 units (95% CI, 1.22 to 2.44) in the diet group and by 1.11 units (95% CI, 0.08 to 2.15) in the surgery group, with no significant difference between the groups, and it decreased the areas under the curve for 24-hour plasma glucose and insulin levels in both groups, with no significant difference between the groups. No major complications occurred in either group.
CONCLUSIONS: In this study involving patients with obesity and type 2 diabetes, the metabolic benefits of gastric bypass surgery and diet were similar and were apparently related to weight loss itself, with no evident clinically important effects independent of weight loss. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT02207777.).

doi: https://doi.org/10.1056/NEJMoa2003697

Clinical Routine Application of the Second-generation Neuroendocrine Markers ISL1, INSM1, and Secretagogin in Neuroendocrine Neoplasia: Staining Outcomes and Potential Clues for Determining Tumor Origin

Endocrine pathology 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32813226

Neuroendocrine neoplasms (NENs) have traditionally been identified via expression of proteins associated to the regulation of secretory vesicles and granules. We report the clinical usage of the “second-generation” proteins ISL LIM homeobox 1 (ISL1), INSM transcriptional repressor 1 (INSM1), and secretagogin (SECG) as immunohistochemical markers of neuroendocrine differentiation since their introduction in clinical routine and compare the results with the established proteins chromogranin A (CGA) and synaptophysin (SYP). In total, 161 tumors, including 139 NENs and 22 “non-NENs” (unrelated tumors with an initial suspicion of NEN), were informatively stained for ISL1, and subsets were also interrogated for INSM1 and/or SECG. Diffuse or focal positive immunoreactivity was noted for ISL1 in 91/139 NENs (65%) and in 6/22 (27%) non-NENs, for INSM1 in 76/85 NENs (89%) and in 2/5 (40%) non-NENs, and for SECG in 49 out of 64 NENs (77%) and in 0/5 non-NENs (0%). Generally, ISL1, INSM1, and SECG exhibited sensitivities in line with or slightly below that of CGA and SYP-largely attributable to tissue-specific patterns regarding tumoral origin. Moreover, for pancreatic and small intestinal NENs, the two largest subgroups, ISL1 staining results were consistent irrespectively of tumor source and WHO grade. We verify previously suggested immunohistochemical schemes of neuroendocrine markers of first- and second-generations to facilitate the diagnostic process for NENs and confirm that the second-generation neuroendocrine markers display tissue-specific patterns. We therefore recommend their implementation in tertiary endocrine pathology centers, not least to aid in the identification of primary tumors when analyzing metastases.

doi: https://doi.org/10.1007/s12022-020-09645-y

Left-sided portal hypertension caused by peripancreatic lymph node tuberculosis misdiagnosed as pancreatic cancer: a case report and literature review

BMC gastroenterology 2020 Aug;20(1):276

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32811429

BACKGROUND: Left-sided portal hypertension (LSPH) is an extremely rare clinical syndrome, and it is the only form of curable portal hypertension. It is primarily caused by pancreatic disease, and is associated with complications that cause spleen vein compression. Specific symptoms are often lacking, rendering it difficult to diagnose. Splenectomy is the main treatment for cases complicated by variceal bleeding, and the effects of treatment primarily depend on the condition of the primary disease.
CASE PRESENTATION: The patient was a 29-year-old woman who was admitted to the hospital for repeated hematemesis and black stool. She had been misdiagnosed with pancreatic cancer 7 years prior. Combined imaging and endoscopic examination indicated varicose gastric fundus veins, a pancreatic mass, and enlarged peripancreatic lymph nodes. Laboratory investigations revealed reduced erythrocyte, platelet, and leukocyte counts, the interferon gamma release assay was positive, and liver function was normal. Abdominal exploration, splenectomy, varicose vein dissection, and lesion resection were performed via laparotomy. Postoperative biopsy analysis confirmed the diagnosis of lymph node tuberculosis. Based on the above-described factors, LSPH caused by peripancreatic lymph node tuberculosis was a diagnosed.
CONCLUSIONS: Herein we describe the first reported case of LSPH caused by peripancreatic lymph node tuberculosis. When left portal hypertension occurs simultaneously, peripancreatic lymph node tuberculosis is often misdiagnosed as pancreatic cancer. Further studies are necessary to develop a more favorable diagnostic method for pancreas masses and more advantageous therapy for LSPH, especially in cases caused by mechanical compression.

doi: https://doi.org/10.1186/s12876-020-01420-x

New GallBladder Articles

Post-mortem viral dynamics and tropism in COVID-19 patients in correlation with organ damage

Virchows Archiv : an international journal of pathology 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32815036

The persistence of SARS-CoV-2 after death of infected individuals is unclear. The aim of this study was to investigate the presence of SARS-CoV-2 RNA in different organs in correlation with tissue damage and post-mortem viral dynamics in COVID-19 deceased. Twenty-eight patients (17 males, 11 females; age 66-96 years; mean 82.9, median 82.5 years) diagnosed with COVID-19 were studied. Swabs were taken post-mortem during autopsy (N = 19) from the throat, both lungs, intestine, gallbladder, and brain or without autopsy (N = 9) only from the throat. Selective amplification of target nucleic acid from the samples was achieved by using primers for ORF1a/b non-structural region and the structural protein envelope E-gene of the virus. The results of 125 post-mortem and 47 ante-mortem swabs were presented as cycle threshold (Ct) values and categorized as strong, moderate, and weak. Viral RNA was detected more frequently in the lungs and throat than in the intestine. Blood, bile, and the brain were negative. Consecutive throat swabs were positive up to 128 h after death without significant increase of Ct values. All lungs showed diffuse alveolar damage, thrombosis, and infarction and less frequently bronchopneumonia irrespective of Ct values. In 30% the intestine revealed focal ischemic changes. Nucleocapsid protein of SARS-CoV-2 was detected by immunohistochemistry in bronchial and intestinal epithelium, bronchial glands, and pneumocytes. In conclusion, viral RNA is still present several days after death, most frequently in the respiratory tract and associated with severe and fatal organ damage. Potential infectivity cannot be ruled out post-mortem.

doi: https://doi.org/10.1007/s00428-020-02903-8

New BileDuct Articles

Today there is no new Bile Duct Article.

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/

Recent Articles on Pancreatobiliary #Pathology – 2020-08-14

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

Premature mortality of gastrointestinal cancer in Iran: trends and projections 2001-2030

BMC cancer 2020 Aug;20(1):752

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32787796

BACKGROUND: The present study was conducted to determine the trend and projection of premature mortality from gastrointestinal cancers (GI cancers) at national and subnational levels in Iran.
METHODS: Employing the data obtained from Iranian Death Registry System (DRS) and population data from census, the mortality rates of GI cancers was calculated among 30-70 age groups. The trends of esophageal, colon and rectum, gallbladder, pancreases, stomach, and liver cancer premature mortalities were estimated and projected at the national and subnational levels from 2001 to 2030. Then, Spatio-temporal model was used to project spatial and temporal correlations.
RESULTS: The overall mortality rate of GI cancers was higher in males than in females, indicating 6.1, 3.9 and 3.9% per 100,000 individuals among males in 2001, 2015 and 2030 respectively and 3.8, 3.1 and 3.7 per 100,000 individuals among females in the same time-frame. The overall mortality rate of GI cancers in males was decreasing until 2015 and will remain stationary into 2030; however, the rate will be increasing among females in both time-frames. Also, there was a considerable variation in the mortality trends of different cancers. Pancreatic, gallbladder, and liver cancers were shown to have an increasing trend while a drop was observed in the mortality rates of stomach, colon and rectum, and esophageal cancers.
CONCLUSION: Variation of GI cancers patterns and trends around the country indicated that a more comprehensive control plan is needed to include the predicted variations.

doi: https://doi.org/10.1186/s12885-020-07132-5

New GallBladder Articles

Premature mortality of gastrointestinal cancer in Iran: trends and projections 2001-2030

BMC cancer 2020 Aug;20(1):752

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32787796

doi: https://doi.org/10.1186/s12885-020-07132-5

New BileDuct Articles

Today there is no new Bile Duct Article.

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/

Recent Articles on Pancreatobiliary #Pathology – 2020-08-13

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

Neutrophil to lymphocyte ratio, not platelet to lymphocyte or lymphocyte to monocyte ratio, is predictive of patient survival after resection of early-stage pancreatic ductal adenocarcinoma

BMC cancer 2020 Aug;20(1):750

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32782024

BACKGROUND: NLR, PLR, and LMR have been associated with pancreatic ductal adenocarcinoma (PDAC) survival. Prognostic value and optimal cutpoints were evaluated to identify underlying significance in surgical PDAC patients.
METHODS: NLR, PLR, and LMR preoperative values were available for 277 PDAC patients who underwent resection between 2007 and 2015. OS, RFS, and survival probability estimates were calculated by univariate, multivariable, and Kaplan-Meier analyses. Continuous and dichotomized ratio analysis determined best-fit cutpoints and assessed ratio components to determine primary drivers.
RESULTS: Elevated NLR and PLR and decreased LMR represented 14%, 50%, and 50% of the cohort, respectively. OS (P = .002) and RFS (P = .003) were significantly decreased in resected PDAC patients with NLR ≥5 compared to those with NLR < 5. Optimal prognostic OS and RFS cutpoints for NLR, PLR, and LMR were 4.8, 192.6, and 1.7, respectively. Lymphocytes alone were the primary prognostic driver of NLR, demonstrating identical survival to NLR.
CONCLUSIONS: NLR is a significant predictor of OS and RFS, with lymphocytes alone as its primary driver; we identified optimal cutpoints that may direct future investigation of their prognostic value. This study contributes to the growing evidence of immune system influence on outcomes in early-stage pancreatic cancer.

doi: https://doi.org/10.1186/s12885-020-07182-9

New GallBladder Articles

Today there is no new Gallbladder Article.

New BileDuct Articles

Today there is no new Bile Duct Article.

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/

Recent Articles on Pancreatobiliary #Pathology – 2020-08-13

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

PAF1 Regulates Stem Cell Features of Pancreatic Cancer Cells, Independently of the PAF1 Complex, via Interactions with PHF5A and DDX3

Gastroenterology 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32781084

BACKGROUND & AIMS: It is not clear how pancreatic cancer stem cells (CSCs) are regulated, resulting in ineffective treatments for pancreatic cancer. PAF1, a RNA polymerase II-associated factor 1 complex (PAF1C) component, maintains pluripotency of stem cells, by unclear mechanisms, and is a marker of CSCs. We investigated mechanisms by which PAF1 maintains CSCs and contributes to development of pancreatic tumors.
METHODS: Pancreatic cancer cell lines were engineered to knockdown PAF1 using inducible small hairpin RNAs. These cells were grown as orthotopic tumors in athymic nude mice and PAF1 knockdown was induced by administration of doxycycline in drinking water. Tumor growth and metastasis were monitored via IVIS imaging. CSCs were isolated from pancreatic cancer cell populations using flow cytometry and characterized by tumor sphere formation, tumor formation in nude mice, and expression of CSC markers. Isolated CSCs were depleted of PAF1 using the CRISPR/Cas9 system. PAF1-regulated genes in CSCs were identified via RNA-seq and PCR array analyses of cells with PAF1 knockdown. Proteins that interact with PAF1 in CSCs were identified by immunoprecipitations and mass spectrometry. We performed chromatin immunoprecipitation sequencing of CSCs to confirm the binding of the PAF1 sub-complex to target genes.
RESULTS: Pancreatic cancer cells depleted of PAF1 formed smaller and fewer tumor spheres in culture and orthotopic tumors and metastases in mice. Isolated CSCs depleted of PAF1 downregulated markers of self-renewal (NANOG, SOX9, and BETA-CATENIN), of CSCs (CD44v6, and ALDH1), and the metastasis-associated gene signature, compared to CSCs without knockdown of PAF1. The role of PAF1 in CSC maintenance was independent of its RNA polymerase II-associated factor 1 complex component identity. We identified DDX3 and PHF5A as proteins that interact with PAF1 in CSCs and demonstrated that the PAF1-PHF5A-DDX3 sub-complex bound to the promoter region of Nanog, whose product regulates genes that control stemness. Levels of the PAF1-DDX3 and PAF1-PHF5A were increased and co-localized in human pancreatic tumor specimens, human pancreatic tumor-derived organoids, and organoids derived from tumors of KPC mice, compared with controls. Binding of DDX3 and PAF1 to the Nanog promoter, and the self-renewal capacity of CSCs, were decreased in cells incubated with the DDX3 inhibitor RK-33. CSCs depleted of PAF1 downregulated genes that regulate stem cell features (Flot2, Taz, Epcam, Erbb2, Foxp1, Abcc5, Ddr1, Muc1, Pecam1, Notch3, Aldh1a3, Foxa2, Plat, and Lif).
CONCLUSIONS: In pancreatic CSCs, PAF1 interacts with DDX3 and PHF5A to regulate expression of NANOG and other genes that regulate stemness. Knockdown of PAF1 reduces the ability of orthotopic pancreatic tumors to develop and progress in mice and their numbers of CSCs. Strategies to target the PAF1-PHF5A-DDX3 complex might be developed to slow or inhibit progression of pancreatic cancer.

doi: https://doi.org/10.1053/j.gastro.2020.07.053

IgG4-Related Disease of the Ovary

Turk patoloji dergisi 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32779156

Immunoglobulin G4-related disease is characterized by dense fibrosis, obliterative phlebitis, and lymphoplasmacytic infiltration that contains abundant IgG4 positive plasma cells. It causes tumefactive lesions in the involved organs and is most commonly seen in the salivary glands, pancreas, and retroperitoneum. Ovarian involvement has been reported in only two cases. In our case, a 58-year-old female patient presented with abdominal distention and pain. Pelvic computed tomography revealed a soft tissue lesion compatible with the omental cake, several intraabdominal implants, and bilateral adnexal fullness. A laparotomy was performed under suspicion of peritoneal carcinomatosis secondary to bilateral adnexal mass. In the histopathologic examination, abundant lymphoplasmacytic infiltration and dense fibrosis were observed in both ovaries and the peritoneum. In the areas of greatest density, the density of IgG4-positive plasma cells was found to range from 40 to 50 per high-power field. The patient was accepted as suffering from probable IgG4-related disease because of the bilateral involvement of the ovaries and the histopathological findings. In conclusion, we present this case to draw attention to the fact that IgG4-related disease can also be seen in the ovary.

doi: https://doi.org/10.5146/tjpath.2020.01500

Margin-Positive Pancreatic Ductal Adenocarcinoma during Pancreaticoduodenectomy: Additional Resection Does Not Improve Survival

Annals of surgical oncology 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32779052

BACKGROUND: The impact of resecting positive margins during pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDA) remains debated. Additionally, the survival benefit of resecting multiple positive margins is unknown.
METHODS: We identified patients with PDA who underwent PD from 2006 to 2015. Pancreatic neck, bile duct, and uncinate frozen section margins were assessed before and after resection of positive margins. Survival curves were compared with log-rank tests. Multivariable Cox regression assessed the effect of margin status on overall survival.
RESULTS: Of 501 patients identified, 17.3%, 5.3%, and 19.7% had an initially positive uncinate, bile duct, or neck margin, respectively. Among initially positive bile duct and neck margins, 77.8% and 67.0% were resected, respectively. Although median survival was decreased among patients with any positive margins (15.6 vs. 20.9 months; p = 0.006), it was similar among patients with positive bile duct or neck margins with or without R1 to R0 resection (17.0 vs. 15.6 months; p = 0.20). Median survival with and without positive uncinate margins was 13.8 vs. 19.7 months (p = 0.04). Uncinate margins were never resected. Resection of additional margins when the uncinate was concurrently positive was not associated with improved survival (p = 0.37). Patients with positive margins who received adjuvant therapy had improved survival, regardless of margin resection (p = 0.03). Adjuvant therapy was independently protective against death (hazard ratio 0.6, 95% CI 0.5-0.7).
CONCLUSIONS: Positive PD margins at any position are associated with reduced overall survival; however, resection of additional margins may not improve survival, particularly with concurrently positive uncinate margins. Adjuvant chemotherapy improves survival with positive margins, regardless of resection.

doi: https://doi.org/10.1245/s10434-020-09000-9

Targeting of the Hedgehog/GLI and mTOR pathways in advanced pancreatic cancer, a phase 1 trial of Vismodegib and Sirolimus combination

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

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32778368

BACKGROUND/OBJECTIVES: Preclinical data indicated a functional and molecular interaction between Hedgehog (HH)/GLI and PI3K-AKT-mTOR pathways promoting pancreatic ductal adenocarcinoma (PDAC). A phase I study was conducted of Vismodegib and Sirolimus combination to evaluate maximum tolerated dose (MTD) and preliminary anti-tumor efficacy.
METHODS: Cohort I included advanced solid tumors patients following a traditional 3 + 3 design. Vismodegib was orally administered at 150 mg daily with Sirolimus starting at 3 mg daily, increasing to 6 mg daily at dose level 2. Cohort II included only metastatic PDAC patients. Anti-tumor efficacy was evaluated every two cycles and target assessment at pre-treatment and after a single cycle.
RESULTS: Nine patient were enrolled in cohort I and 22 patients in cohort II. Twenty-eight patients were evaluated for dose-limiting toxicities (DLTs). One DLT was observed in each cohort, consisting of grade 2 mucositis and grade 3 thrombocytopenia. The MTD for Vismodegib and Sirolimus were 150 mg daily and 6 mg daily, respectively. The most common grade 3-4 toxicities were fatigue, thrombocytopenia, dehydration, and infections. A total of 6 patients had stable disease. No partial or complete responses were observed. Paired biopsy analysis before and after the first cycle in cohort II consistently demonstrated reduced GLI1 expression. Conversely, GLI and mTOR downstream targets were not significantly affected.
CONCLUSIONS: The combination of Vismodegib and Sirolimus was well tolerated. Clinical benefit was limited to stable disease in a subgroup of patients. Targeting efficacy demonstrated consistent partial decreases in HH/GLI signaling with limited impact on mTOR signaling. These findings conflict with pre-clinical models and warrant further investigations.

doi: https://doi.org/10.1016/j.pan.2020.06.015

Precision medicine phase II study evaluating the efficacy of a double immunotherapy by durvalumab and tremelimumab combined with olaparib in patients with solid cancers and carriers of homologous recombination repair genes mutation in response or stable after olaparib treatment

BMC cancer 2020 Aug;20(1):748

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32778095

BACKGROUND: Tumors with deficient homologous repair are sensitive to PARP inhibitors such as olaparib which is known to have immunogenic properties. Durvalumab (D) is a human monoclonal antibody (mAb) which inhibits binding of programmed cell death ligand 1 (PD-L1) to its receptor. Tremelimumab (T) is a mAb directed against the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). This study is designed to evaluate the efficacy of combination of olaparib, durvalumab and tremelimumab in patients with a solid tumors with a mutation in homologous gene repair.
METHODS: This phase II study will assess the efficacy and safety of olaparib/D/T association in patients (n = 213) with several types of solid cancers (breast cancer, ovarian cancer, pancreatic cancer, endometrial cancer, prostate cancer and others) with at least one mutation in homologous repair genes (BRCA1, BRCA2, PALB2, ATM, FANCA, FANCB, FANCC, FANCE, FANCF, CHEK2, RAD51, BARD1, MRE11, RAD50, NBS1, HDAC2), LKB1/STK11, INPP4B, STAG2, ERG, CHEK1, BLM, LIG4, ATR, ATRX, CDK12). Good performance status patients and corresponding to specific inclusion criteria of each cohort will be eligible. STEP1: Patients will receive olaparib 300 mg BID. In absence of progression after 6 weeks of olaparib, they will follow STEP 2 with olaparib and immunotherapy by durvalumab (1500 mg Q4W) + tremelimumab (75 mg IV Q4W) during 4 months and will further pursue durvalumab alone until disease progression, death, intolerable toxicity, or patient/investigator decision to stop (for a maximum duration of 24 months, and 36 months for ovarian cohort). Primary endpoint is safety and efficacy according to progression-free survival (PFS) of olaparib + immunotherapy (durvalumab + tremelimumab) during 4 months followed by durvalumab alone as maintenance in patients with solid cancers and in response or stable, after prior molecular target therapy by olaparib; secondary endpoints include overall survival (OS), disease control rate (DCR), response rate after 6 weeks of olaparib, safety of olaparib/durvalumab/tremelimumab association. Blood, plasma and tumor tissue will be collected for potential prognostic and predictive biomarkers.
DISCUSSION: This study is the first trial to test the combination of olaparib and double immunotherapy based on molecular screening.
TRIAL REGISTRATION: NCT04169841 , date of registration November 20, 2019.

doi: https://doi.org/10.1186/s12885-020-07253-x

Diagnostic accuracy of contrast-enhanced diffusion-weighted MRI for liver metastases of pancreatic cancer: towards adequate staging and follow-up of pancreatic cancer – DIA-PANC study: study protocol for an international, multicenter, diagnostic trial

BMC cancer 2020 Aug;20(1):744

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32778061

BACKGROUND: At the time of surgery, approximately 10-20% of the patients with pancreatic cancer are considered unresectable because of unexpected liver metastasis, peritoneal carcinomatosis or locally advanced disease. This leads to futile surgical treatment with all the associated morbidity, mortality and costs. More than 50% of all liver metastases develop in the first six months postoperatively. These (subcentimeter) liver metastases are most likely already present at the time of diagnosis and have not been identified pre-operatively, due to the poor sensitivity of routine preoperative contrast-enhanced CT (CECT).
METHODS: The DIA-PANC study is a prospective, international, multicenter, diagnostic cohort study investigating diffusion-weighted, contrast-enhanced MRI for the detection of liver metastases in patients with all stages of pancreatic cancer. Indeterminate or malignant liver lesions on MRI will be further investigated histopathologically. For patients with suspected liver lesions without histopathological proof, follow up imaging with paired CT and MRI at 3-, 6- and 12-months will serve as an alternative reference standard.
DISCUSSION: The DIA-PANC trial is expected to report high-level evidence of the diagnostic accuracy of MRI for the detection of liver metastases, resulting in significant value for clinical decision making, guideline development and improved stratification for treatment strategies and future trials. Furthermore, DIA-PANC will contribute to our knowledge of liver metastases regarding incidence, imaging characteristics, their number and extent, and their change in time with or without treatment. It will enhance the worldwide implementation of MRI and consequently improve personalized treatment of patients with suspected pancreatic ductal adenocarcinoma.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03469726 . Registered on March 19th 2018 – Retrospectively registered.

doi: https://doi.org/10.1186/s12885-020-07226-0

Preoperative anthropomorphic and nutritious status and fistula risk score for predicting clinically relevant postoperative pancreatic fistula after pancreaticoduodenectomy

BMC gastroenterology 2020 Aug;20(1):264

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32770952

BACKGROUND: Postoperative pancreatic fistula (POPF) is a life-threatening postoperative complication. The aim of this study was to evaluate the efficacy of the fistula risk score (FRS) and preoperative body composition factors for predicting the occurrence of clinically relevant POPF (CR-POPF) after pancreaticoduodenectomy (PD).
METHODS: In this study, 136 consecutive patients who underwent PD between 2006 and 2018 were enrolled. The risk factors of CR-POPF (grades B and C) were analyzed. Preoperative visceral adipose tissue area (VATA), skeletal mass index (SMI), and subcutaneous adipose tissue area (SATA) were calculated from computed tomography data.
RESULTS: The overall 30-day mortality and morbidity rates were 0.7 and 38%, respectively. The incidence rates of grade B and C CR-POPF were 27 and 4%, respectively. A univariate analysis revealed that male sex, habitual smoking, prognostic nutritional index (PNI) < 45, VATA ≥90, VATA/SATA ≥0.9, VATA/SMI ≥ 1.4, and FRS > 4 were significantly associated with the incidence of CR-POPF. A multivariate analysis revealed that PNI < 45, VATA/SMI ≥ 1.4 and FRS > 4 were the independent risk factors of CR-POPF.
CONCLUSIONS: Preoperative anthropomorphic imbalance, PNI, and FRS were independent risk factors for CR-POPF. Patients with high-risk factors should be closely monitored during the postoperative period.

doi: https://doi.org/10.1186/s12876-020-01397-7

New GallBladder Articles

Today there is no new Gallbladder Article.

New BileDuct Articles

Margin-Positive Pancreatic Ductal Adenocarcinoma during Pancreaticoduodenectomy: Additional Resection Does Not Improve Survival

Annals of surgical oncology 2020 Aug;():

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32779052

doi: https://doi.org/10.1245/s10434-020-09000-9

New Ampulla Articles

Approaches to Biopsy and Resection Specimens from the Ampulla

Surgical pathology clinics 2020 Sep;13(3):453-467

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32773194

The ampulla of Vater gives rise to a versatile group of cancers of mixed/hybrid histologic phenotype. Ampullary carcinomas (ACs) are most frequently intestinal or pancreatobiliary adenocarcinomas but other subtypes, such as medullary, mucinous, or signet ring/poorly cohesive cell carcinoma, may be encountered. Ampullary cancer can also be subclassified based on immunohistochemical features, however these classification systems fail to show robust prognostic reliability. More recently, the molecular landscape of AC has been uncovered, and has been shown to have prognostic and predictive significance. In this article, the site-specific, histologic, and genetic characteristics of ampullary carcinoma and its precursor lesions are discussed.

doi: https://doi.org/10.1016/j.path.2020.05.005

Upper Gastrointestinal Manifestations of Inflammatory Bowel Disease

Surgical pathology clinics 2020 Sep;13(3):413-430

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32773192

Although the features of lower gastrointestinal tract inflammation associated with ulcerative colitis and Crohn disease are generally familiar to pathologists, there is less awareness of and familiarity with the manifestations of inflammatory bowel disease in the esophagus, stomach, and duodenum. Nonetheless, their diagnosis has therapeutic and possibly prognostic implications, potentially foretelling severe complications. The recognition that ulcerative colitis can affect gastrointestinal organs proximal to the large intestine and terminal ileum represents a revision of concepts ingrained among generations of physicians. This article reviews the pathologic features and clinical significance of esophagitis, gastritis, and duodenitis associated with inflammatory bowel disease.

doi: https://doi.org/10.1016/j.path.2020.05.003

Giardia Is Often Overlooked on Histopathologic Examination: A High-Volume, Single-Institution Experience

International journal of surgical pathology 2020 Aug;():1066896920947795

PubMed: https://www.ncbi.nlm.nih.gov/pubmed/?term=32772760

AIMS. GIARDIA: is sometimes missed by the pathologist, and we sought to determine how often this occurs at our institution-a large tertiary care center with a subspecialty gastrointestinal pathology service and what certain clinical and histologic clues can be used to flag cases with a higher likelihood of infection, targeting them for greater scrutiny.
METHODS AND RESULTS: We identified a set of patients who tested positive for Giardia with a stool-based test, and who also received a small bowel biopsy at a similar time-point. These biopsies were retrospectively reviewed for Giardia, finding 8 positive cases. The organism was prospectively detected in 4 cases (50%) but overlooked in the remaining 4 cases (50%). Three of the 4 cases missed cases showed only rare organisms. The detected cases tended to more frequently have prominent lymphoid aggregates (3 detected cases, 0 overlooked cases) and intraepithelial lymphocytosis (3 detected cases, 0 overlooked cases). Certain clinical and histologic clues can be used to flag cases with a higher likelihood of infection. Specifically, we found abnormalities of the mucosa (active inflammation, intraepithelial lymphocytosis, villous expansion, prominent lymphoid aggregates) in each case, and 4 of 8 cases were from immunocompromised patients. Finally, 2 of 8 cases were terminal ileum biopsies.
CONCLUSIONS: Biopsies with a histologic abnormality or those from immunocompromised patients should receive greater attention. Routinely looking for Giardia at that terminal ileum is necessary.

doi: https://doi.org/10.1177/1066896920947795

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

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