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

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New BileDuct Articles

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New Ampulla Articles

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