The role of biliary events in treatment and survival of patients with advanced pancreatic ductal adenocarcinoma.

BACKGROUND: Systemic chemotherapy (CT) is the treatment of choice for advanced pancreatic ductal adenocarcinoma (PDAC). Biliary obstruction is common in this setting and may interfere with CT administration due to jaundice or cholangitis related to biliary stent malfunction. AIMS: To evaluate the impact of biliary events on CT administration and survival in patients with stage III-IV PDAC. METHODS: Patients enrolled in a randomized trial of nab-paclitaxel plus gemcitabine with/without capecitabine and cisplatin in advanced PDAC were included. Data on management of jaundice, biliary stents/complications and CT were prospectively collected and retrospectively analyzed. Modified overall (mOS) and progression-free (mPFS) survival were evaluated. RESULTS: Eighty-eight patients met the inclusion criteria (50% females; median age 65years). Seven of eight (87.5%) patients who placed plastic stents developed biliary complications versus 14/30 (46.7%) with metallic stents (p = 0.071). Patients without biliary complications completed planned CT in 64.2% versus 47.6% of cases (p = 0.207). CT completion was related to longer mOS (17 vs 12 months, p = 0.005) and mPFS (9 vs 6 months, p = 0.011). mOS was shorter when biliary complications occurred (12 vs 17 months, p = 0.937), as was mPFS (6 vs 8 months, p = 0.438). CONCLUSION: Complications related to biliary obstruction influence chemotherapy completion and survival in patients with advanced PDAC.

Management of clinically relevant postoperative pancreatic fistula-related fluid collections after distal pancreatectomy.

BACKGROUND: Distal pancreatectomy is burdened by a high rate of clinically relevant postoperative pancreatic fistula (CR-POPF). The presence of a fistula-related abdominal collection often requires additional treatment such as antibiotics, percutaneous drainage, and endoscopic drainage thus prolonging patient recovery. Aim of this study was to describe the management of abdominal collections related to CR-POPF and identify variables associated with the need for invasive procedures. METHODS: A retrospective review of clinical data for patients who underwent distal pancreatectomy between 2015 and 2020 was conducted. All postoperative CT-scan imaging performed for clinical signs related to POPF was reviewed. The main outcome of the study was the need for procedural management (percutaneous or endoscopic) of CR-POPF-related fluid collections at 90 days after surgery. A multivariate regression analysis was adopted to analyze factors influencing procedural management of the collection. RESULTS: Five hundred sixteen patients were included in the study. Laparoscopic resection was performed in 290 patients (56%). At 90 days after surgery, CR-POPF occurred in 207 (40.1%) patients. A symptomatic collection related to fistula was observed in 130 patients (25.2%). Factors associated with fluid collections were increased body mass index (BMI) (25.5 versus 24, p = 0.001) and intraoperative blood loss (median of 250 versus 200 ml, p < 0.001). Procedural management was required in 70 patients (13.6%); 52 patients required interventional radiology and 18 endoscopic drainage. At multivariate analysis, risk factors for invasive procedures were the following CT-scan parameters: fluid collection diameter greater than 5 cm (OR 6.366, 95%CI 2.29-17.66, p = 0.001), presence of blood in the fluid collection (OR 10.618, 95%CI 1.94-58.09, p = 0.006), and enhancement of its walls (OR 4.073, 95%CI 1.22-13.57, p = 0.022). CONCLUSION: CR-POPF-related fluid collections affect about a quarter of patients undergoing distal pancreatectomy. CT-scan provides important information which can guide the management of the collection in a "step-up" fashion.

Early biochemical predictors of clinically relevant pancreatic fistula after distal pancreatectomy: a role for serum amylase and C-reactive protein.

BACKGROUND: Recent evidence suggests that pancreatic inflammation plays a pivotal role in the occurrence of clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreaticoduodenectomy but few data are available for distal pancreatectomy (DP). The aim of this study was to evaluate the impact of early biochemical markers on the occurrence of CR-POPF after DP. METHODS: Clinical and laboratory data for 432 consecutive DP patients were reviewed. Serum amylase was evaluated on postoperative day (POD) 1, and drain fluid amylase (DFA) and C-reactive protein (CRP) were evaluated on POD 2 and 3. Receiver operator characteristic (ROC) curves were performed for all biochemical markers and an area under the curve (AUC) was computed. Multivariable regression analyses to identify the factors associated with CR-POPF and severe postoperative morbidity (Clavien-Dindo grade ≥ 3) were performed. RESULTS: At 90 days after surgery, CR-POPF occurred in 155 (36%) patients, severe complications in 66 (15%) patients. ROC curve analyses showed that DFA on POD2 had the largest AUC (0.753, p < 0.001), followed by serum amylase on POD 1 (0.651, p < 0.001), serum CRP on POD3 (0.644, p < 0.001), and CRP change between POD 2 and POD 3 (0.644, p < 0.001). Multivariable analysis identified male gender (OR 2.29, 95% CI 1.36-3.86; p = 0.002), DFA ≥ 1500 U/L on POD2 (OR 4.63, 95% CI 2.72-7.89; p < 0.001), serum amylase ≥ 100 U/L on POD 1 (OR 1.72, 95% CI 1.01-2.93; p = 0.046), and CRP increase by at least 25 mg/L on POD 3 compared to the previous day (OR 1.89, 95% CI 1.11-3.21; p = 0.019) as independent predictors of CR-POPF, yielding a valid regression model (AUC 0.765, 95% CI 0.714-0.816, p < 0.001). CONCLUSIONS: Postoperative serum amylase and CRP trajectory represent useful early biochemical markers for CR-POPF in addition to DFA. Our findings suggest that these laboratory tests should be incorporated into clinical practice to aid postoperative patient and drain management.

Management of neuroendocrine carcinomas of the pancreas (WHO G3): A tailored approach between proliferation and morphology.

Neuroendocrine carcinomas (NEC) of the pancreas are defined by a mitotic count > 20 mitoses/10 high power fields and/or Ki67 index > 20%, and included all the tumors previously classified as poorly differentiated endocrine carcinomas. These latter are aggressive malignancies with a high propensity for distant metastases and poor prognosis, and they can be further divided into small- and large-cell subtypes. However in the NEC category are included also neuroendocrine tumors with a well differentiated morphology but ki67 index > 20%. This category is associated with better prognosis and does not significantly respond to cisplatin-based chemotherapy, which represents the gold standard therapeutic approach for poorly differentiated NEC. In this review, the differences between well differentiated and poorly differentiated NEC are discussed considering both pathology, imaging features, treatment and prognostic implications. Diagnostic and therapeutic flowcharts are proposed. The need for a revision of current classification system is stressed being well differentiated NEC a more indolent disease compared to poorly differentiated tumors.