Scoring of tumour response after neoadjuvant therapy in resected pancreatic cancer: systematic review.

BACKGROUND: Preoperative chemo(radio)therapy is used increasingly in pancreatic cancer. Histological evaluation of the tumour response provides information on the efficacy of preoperative treatment and is used to determine prognosis and guide decisions on adjuvant treatment. This systematic review aimed to provide an overview of the current evidence on tumour response scoring systems in pancreatic cancer. METHODS: Studies reporting on the assessment of resected pancreatic ductal adenocarcinoma following neoadjuvant chemo(radio)therapy were searched using PubMed and EMBASE. All original studies reporting on histological tumour response in relation to clinical outcome (survival, recurrence-free survival) or interobserver agreement were eligible for inclusion. This systematic review followed the PRISMA guidelines. RESULTS: The literature search yielded 1453 studies of which 25 met the eligibility criteria, revealing 13 unique scoring systems. The most frequently investigated tumour response scoring systems were the College of American Pathologists system, Evans scoring system, and MD Anderson Cancer Center system, investigated 11, 9 and 5 times respectively. Although six studies reported a survival difference between the different grades of these three systems, the reported outcomes were often inconsistent. In addition, 12 of the 25 studies did not report on crucial aspects of pathological examination, such as the method of dissection, sampling approach, and amount of sampling. CONCLUSION: Numerous scoring systems for the evaluation of tumour response after preoperative chemo(radio)therapy in pancreatic cancer exist, but comparative studies are lacking. More comparative data are needed on the interobserver variability and prognostic significance of the various scoring systems before best practice can be established.

Microscopic resection margin status in pancreatic ductal adenocarcinoma - A nationwide analysis.

INTRODUCTION: First, this study aimed to assess the prognostic value of different definitions for resection margin status on disease-free survival (DFS) and overall survival (OS) in pancreatic ductal adenocarcinoma (PDAC). Second, preoperative predictors of direct margin involvement were identified. MATERIALS AND METHODS: This nationwide observational cohort study included all patients who underwent upfront PDAC resection (2014-2016), as registered in the prospective Dutch Pancreatic Cancer Audit. Patients were subdivided into three groups: R0 (≥1 mm margin clearance), R1 (<1 mm margin clearance) or R1 (direct margin involvement). Survival was compared using multivariable Cox regression analysis. Logistic regression with baseline variables was performed to identify preoperative predictors of R1 (direct). RESULTS: 595 patients with a median OS of 18 months (IQR 10-32 months) months were analysed. R0 (≥1 mm) was achieved in 277 patients (47%), R1 (<1 mm) in 146 patients (24%) and R1 (direct) in 172 patients (29%). R1 (direct) was associated with a worse OS, as compared with both R0 (≥1 mm) (hazard ratio (HR) 1.35 [95% and confidence interval (CI) 1.08-1.70); P < 0.01) and R1 (<1 mm) (HR 1.29 [95%CI 1.01-1.67]; P < 0.05). No OS difference was found between R0 (≥1 mm) and R1 (<1 mm) (HR 1.05 [95% CI 0.82-1.34]; P = 0.71). Preoperative predictors associated with an increased risk of R1 (direct) included age, male sex, performance score 2-4, and venous or arterial tumour involvement. CONCLUSION: Resection margin clearance of <1 mm, but without direct margin involvement, does not affect survival, as compared with a margin clearance of ≥1 mm. Given that any vascular tumour involvement on preoperative imaging was associated with an increased risk of R1 (direct) resection with upfront surgery, neoadjuvant therapy might be considered in these patients.

Gemcitabine-based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score-matched cohort study.

BACKGROUND: Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis. METHODS: An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses. RESULTS: Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy. CONCLUSION: Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype.

ANTECEDENTES: Actualmente se desconoce si la quimioterapia adyuvante ofrece un beneficio en la supervivencia de los pacientes que se someten a resección de un adenocarcinoma ampular. El objetivo de este estudio fue comparar la supervivencia mediante la concordancia estimada por emparejamiento por puntaje de propensión, entre pacientes con y sin quimioterapia adyuvante después de la resección de un adenocarcinoma ampular. MÉTODOS: Se realizó un estudio internacional de cohortes multicéntrico, que incluyó a los pacientes que se sometieron a una duodenopancreatectomía por adenocarcinoma ampular (2006-2017) en 13 centros de seis países. Los puntajes de propensión se usaron para emparejar a los pacientes que recibieron quimioterapia adyuvante con los que no; tanto en la cohorte completa como en dos subgrupos (subtipo pancreaticobiliar / mixto e intestinal). La supervivencia se evaluó utilizando el método de Kaplan-Meier y las regresiones de Cox. RESULTADOS: En total, 1.163 pacientes fueron sometidos a una duodenopancreatectomía por adenocarcinoma ampular. Después de excluir a 179 pacientes, la mediana de supervivencia de los 976 pacientes restantes fue de 67 meses (i.c. del 95%, 56-78), de los cuales un total de 520 pacientes (53%) recibieron quimioterapia adyuvante. En una cohorte de emparejamiento por puntaje de propensión (194 versus 194 pacientes), la mediana de supervivencia fue mejor en los pacientes tratados con quimioterapia adyuvante en comparación con aquellos sin quimioterapia adyuvante (no se alcanzó la mediana de supervivencia versus 60 meses, respectivamente; P = 0,051). En el subtipo pancreaticobiliar/mixto se observó un beneficio en la supervivencia; no se alcanzó la mediana de supervivencia en pacientes que recibieron quimioterapia adyuvante versus 32 meses en el grupo sin quimioterapia, P = 0,020. El subtipo intestinal no mostró beneficio en la supervivencia de la quimioterapia adyuvante. CONCLUSIÓN: Los pacientes con adenocarcinoma ampular resecado pueden beneficiarse de la quimioterapia adyuvante basada en gemcitabina, pero este efecto podría reservarse para aquellos pacientes con subtipo de tumor pancreaticobiliar y/o mixto.

Accuracy of aPTT monitoring in critically ill patients treated with unfractionated heparin.

INTRODUCTION: The anticoagulant effect of unfractionated heparin (UFH) is usually monitored by means of the activated partial thromboplastin time (aPTT). In critically ill patients, however, increased levels of acute phase proteins may decrease the accuracy of the aPTT, leading to inadequate UFH dosing. In these circumstances, the anti-Xa assay is recommended for monitoring. OBJECTIVE: We aimed to analyse the accuracy of the aPTT for the monitoring of UFH dosing in critically ill patients. METHODS: In critically ill patients treated with therapeutic doses of UFH, we compared aPTT levels with simultaneously measured anti-Xa levels as the gold standard. Sensitivity and specificity of the aPTT were determined for different cut-off points, receiver operating characteristic (ROC) curves were constructed and their areas under the curve (AUCs) were calculated. RESULTS: A total of 171 paired blood samples from 58 patients were analysed. Concordant aPTT and anti-Xa values were observed in 108 (63.2%) data pairs. In 33 data pairs (19.3%) the aPTT was discordantly high and in 30 data pairs (17.5%) discordantly low. The sensitivity of the aPTT in detecting UFH underdosing and overdosing was 0.63 and 0.37, respectively. When considering alternative thresholds, ROC curves for underdosing and overdosing had AUCs of 0.71 and 0.81, respectively. CONCLUSION: In this small cohort of critically ill patients, the aPTT was accurate in 63.2% of the blood samples. Its sensitivity to detect UFH underdosing and overdosing was low (0.63 and 0.37, respectively). We conclude that in critically ill patients, the aPTT is not accurate enough to detect UFH underdosing and overdosing.