Management of Acute Cholecystitis during Neoadjuvant Therapy in Patients with Pancreatic Adenocarcinoma.

BACKGROUND: Patients with localized pancreatic cancer (PC) can develop acute cholecystitis during neoadjuvant therapy; optimal management remains undefined. METHODS: Consecutive patients with localized PC who had indwelling biliary stents and received neoadjuvant therapy were reviewed. Time from stent placement to the development of acute cholecystitis was calculated. Patients were categorized as having surgical versus nonoperative management of cholecystitis. Time to PC resection was defined as the time from the start of treatment to pancreatic resection. RESULTS: Of the 283 patients with indwelling biliary stents, acute cholecystitis occurred in 17 (6%) patients. The median time from the date of stent placement to the development of cholecystitis was 2.3 months [interquartile range (IQR) 4.6 months]. Acute cholecystitis was managed with cholecystostomy tube placement in 15 (88%) patients and cholecystectomy in 2 (12%). In total, 189 (67%) of the 283 patients completed all intended neoadjuvant therapy and surgery; 10 (59%) of the 17 patients with cholecystitis (10 of 15 managed with a cholecystostomy tube and 0 of 2 managed with cholecystectomy) and 179 (67%) of the 266 patients without cholecystitis (p = 0.47). The median time to PC resection was 3.2 months for the 179 patients without cholecystitis and 3.6 months for the 10 patients with cholecystitis (p = 1.00). CONCLUSIONS: Acute cholecystitis occurred in 6% of patients with indwelling biliary stents during neoadjuvant therapy. Management with a cholecystostomy tube did not delay the completion of neoadjuvant therapy and surgery and should be considered the optimal management of this complication.

Impact of Neoadjuvant Chemoradiation on Pathologic Response in Patients With Localized Pancreatic Cancer.

Introduction/Background: Multimodal neoadjuvant therapy has resulted in increased rates of histologic response in pancreatic tumors and adjacent lymph nodes. The biologic significance of the collective response in the primary tumor and lymph nodes is not understood. Methods: Patients with localized PC who received neoadjuvant therapy and surgery with histologic assessment of the primary tumor and local-regional lymph nodes were included. Histopathologic response was classified using the modified Ryan score as follows: no viable cancer cells (CR), rare groups of cancer cells (nCR), residual cancer with evident tumor regression (PR), and extensive residual cancer with no evident tumor regression (NR). Nodal status was defined by number of lymph nodes (LN) with tumor metastases: N0 (0 LN), N1 (1-3), N2 (≥4). Results: Of 341 patients with localized PC who received neoadjuvant therapy and surgery, 107 (31%) received chemoradiation alone, 44 (13%) received chemotherapy alone, and 190 (56%) received chemotherapy and chemoradiation. Histopathologic response consisted of 15 (4%) CRs, 59 (17%) nCRs, 188 (55%) PRs, and 79 (23%) NRs. Patients who received chemotherapy alone had the worst responses (n = 21 for NR, 48%) as compared to patients who received chemoradiation alone (n = 25 for NR, 24%) or patients who received both therapies (n = 33 for NR, 17%) (Table 1; p = 0.001). Median overall survival for all 341 patients was 39 months; OS by histopathologic subtype was not reached (CR), 49 months (nCR), 38 months (PR), and 34 months (NR), respectively (p = 0.004). Of the 341 patients, 208 (61%) had N0 disease, 97 (28%) had N1 disease, and 36 (11%) had N2 disease. In an adjusted hazards model, modified Ryan score of PR or NR (HR: 1.71; 95% CI: 1.15-2.54; p = 0.008) and N1 (HR: 1.42; 95% CI: 1.1.02-2.01; p = 0.04), or N2 disease (HR: 2.54, 95% CI: 1.64-3.93; p < 0.001) were associated with increased risk of death. Conclusions: Neoadjuvant chemotherapy alone is associated with lower rates of pathologic response. Patients with CR or nCR have a significantly improved OS as compared to patients with PR or NR. Nodal status is the most important pathologic prognostic factor. Neoadjuvant chemoradiation may be an important driver of pathologic response.