Amsterdam International Consensus Meeting: tumor response scoring in the pathology assessment of resected pancreatic cancer after neoadjuvant therapy.

Histopathologically scoring the response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant treatment can guide the selection of adjuvant therapy and improve prognostic stratification. However, several tumor response scoring (TRS) systems exist, and consensus is lacking as to which system represents best practice. An international consensus meeting on TRS took place in November 2019 in Amsterdam, The Netherlands. Here, we provide an overview of the outcomes and consensus statements that originated from this meeting. Consensus (≥80% agreement) was reached on a total of seven statements: (1) TRS is important because it provides information about the effect of neoadjuvant treatment that is not provided by other histopathology-based descriptors. (2) TRS for resected PDAC following neoadjuvant therapy should assess residual (viable) tumor burden instead of tumor regression. (3) The CAP scoring system is considered the most adequate scoring system to date because it is based on the presence and amount of residual cancer cells instead of tumor regression. (4) The defining criteria of the categories in the CAP scoring system should be improved by replacing subjective terms including "minimal" or "extensive" with objective criteria to evaluate the extent of viable tumor. (5) The improved, consensus-based system should be validated retrospectively and prospectively. (6) Prospective studies should determine the extent of tissue sampling that is required to ensure adequate assessment of the residual cancer burden, taking into account the heterogeneity of tumor response. (7) In future scientific publications, the extent of tissue sampling should be described in detail in the "Materials and methods" section.

Adequacy assessment of endoscopic ultrasound-guided, fine-needle aspirations of pancreatic masses for theranostic studies: optimization of current practices is warranted.

CONTEXT: Novel chemotherapy regimens now provide the opportunity for "personalized" care in pancreatic cancer. Little is known about our ability to procure adequate cells for theranostic studies using standard ultrasound-guided fine-needle aspirations and cytologic techniques. OBJECTIVE: To assess cellularity of cytology material in patients with solid pancreatic lesions. DESIGN: One hundred sixty-nine endoscopic ultrasound-guided fine-needle aspirations with positive diagnoses of solid epithelial pancreatic neoplasms were evaluated for smear and cell block cellularity. Cellularity was scored on a scale of 1 to 4; scores of 3 or 4 (>100 cells) were deemed adequate for ancillary studies. Clinicopathologic variables were recorded. A 3-month prospective analysis was also performed using a new collection algorithm. RESULTS: Only 12.4% (21 of 169) of the positive cases had a cell block cellularity score that was adequate for theranostic studies. This score was not associated with on-site evaluation, needle gauge, or number of passes. Adenocarcinoma was the most common diagnosis (88%) but yielded fewer adequate cell blocks, P = .006. Cellularity showed correlation with endoscopists, P = .04. Tumor size and fibrosis score of resected tumors tended to correlate with cellularity, but only larger size in endocrine tumors was significantly associated with adequacy (P = .02). Standardized collection did not improve overall cell block cellularity. CONCLUSIONS: Changes in practice, such as obtaining dedicated passes for ancillary studies, may not be enough to improve the theranostic utility of endoscopic ultrasound-guided fine-needle aspiration in pancreatic neoplasia. Other methods to improve tumor cell yield, including modified cytologic techniques and new needle designs, need to be further investigated.

Assessment of nuclear nanomorphology marker to improve the detection of malignancy from bile duct biopsy specimens.

OBJECTIVES: The accurate diagnosis of malignancy from small bile duct biopsy specimens is often challenging. This proof-of-concept study assessed the feasibility of a novel optical technology, spatial-domain low-coherence quantitative phase microscopy (SL-QPM), that assesses nanoscale structural alterations in epithelial nuclei for improving the diagnosis of malignancy in bile duct biopsy specimens. METHODS: The SL-QPM analysis was performed on standard histology specimens of bile duct biopsy specimens from 45 patients. We analyzed normal cells with benign follow-up, histologically normal cells with pancreaticobiliary malignancy, and malignant epithelial cells. RESULTS: The SL-QPM-derived nuclear nanomorphology marker can not only distinguish benign and malignant epithelial cells but can also detect features of malignancy in those cells normal by light microscopy with a discriminatory accuracy of 0.90. When combining pathology with SL-QPM, the sensitivity is improved to 88.5% from 65.4% of conventional pathology, while maintaining 100% specificity. CONCLUSIONS: SL-QPM-derived nuclear nanomorphology markers represent a novel approach for detecting malignancy from histologically normal-appearing epithelial cells, with potential as an adjunctive test in patients with negative or inconclusive pathologic diagnosis on bile duct biopsy specimens.

CD3 monitoring of antithymocyte globulin therapy in thoracic organ transplantation.

BACKGROUND: Antithymocyte globulin is frequently used as a component of induction therapy in thoracic organ transplantation. This study evaluates the utility of monitoring peripheral CD3 lymphocytes to rationally adjust antithymocyte globulin therapy in this patient population. METHODS: A total of 17 heart and 19 lung transplant recipients received antithymocyte globulin (ATGAM or thymoglobulin) as induction therapy or to treat steroid-resistant acute or chronic rejection. Absolute CD3 counts were maintained between 50 and 100 cells/microl. RESULTS: With CD3 monitoring, the doses of antithymocyte globulin were reduced from 10-15 mg/kg to 1-5 mg/kg during the course of therapy. The total amount of antithymocyte globulin given to each CD3 monitored patient was reduced by 48%. Dose reduction did not alter the number of acute rejection or infectious episodes, and hematological side effects were infrequent. CONCLUSION: CD3 monitoring of antithymocyte globulin therapy in thoracic organ recipients reduced the amount of drug received by each patient, while maintaining CD3 counts less than 100 cells/microl.