Rapamycin Prevents Surgery-Induced Immune Dysfunction in Patients with Bladder Cancer.

The mechanistic target of rapamycin (mTOR) integrates environmental inputs to regulate cellular growth and metabolism in tumors. However, mTOR also regulates T-cell differentiation and activation, rendering applications of mTOR inhibitors toward treating cancer complex. Preclinical data support distinct biphasic effects of rapamycin, with higher doses directly suppressing tumor cell growth and lower doses enhancing T-cell immunity. To address the translational relevance of these findings, the effects of the mTOR complex 1 (mTORC1) inhibitor, rapamycin, on tumor and T cells were monitored in patients undergoing cystectomy for bladder cancer. MB49 syngeneic murine bladder cancer models were tested to gain mechanistic insights. Surgery-induced T-cell exhaustion in humans and mice and was associated with increased pulmonary metastasis and decreased PD-L1 antibody efficacy in mouse bladder cancer. At 3 mg orally daily, rapamycin concentrations were 2-fold higher in bladder tissues than in blood. Rapamycin significantly inhibited tumor mTORC1, shown by decreased rpS6 phosphorylation in treated versus control patients (P = 0.008). Rapamycin reduced surgery-induced T-cell exhaustion in patients, evidenced by a significant decrease in the prevalence of dysfunctional programmed death-1 (PD-1)-expressing T cells. Grade 3 to 4 adverse event rates were similar between groups, but rapamycin-treated patients had a higher rate of wound complications versus controls. In conclusion, surgery promoted bladder cancer metastasis and decreased the efficacy of postoperative bladder cancer immunotherapy. Low-dose (3 mg daily) oral rapamycin has favorable pharmacodynamic and immune modulating activity in surgical patients and has the potential to decrease surgery-induced immune dysfunction.

Cavernous hemangioma of adult pancreas: A case report and literature review.

Pancreatic hemangioma is a rare type of benign vascular tumor. Low clinical suspicion and inability of current cross sectional imaging techniques to differentiate it from other pancreatic lesions, contribute to the difficulty in making the correct diagnosis. Without a definitive diagnosis, and due to concern for malignancy, in many instances, surgery is performed. We report a case of pancreas cavernous hemangioma in an 18-year-old female. The patient presented with three-month history of epigastric pain. Physical examination and routine blood tests were normal. Abdominal Computed Tomography scan revealed a 5 cm × 6 cm complex non-enhancing cystic mass in the head of pancreas. Magnetic resonance imaging, endoscopic ultrasonography (EUS) and EUS guided fine needle aspiration cytology were non-diagnostic. Because of uncontrolled symptoms, the patient underwent surgical resection. Histopathology and Immunohistochemical staining confirmed the diagnosis of cavernous hemangioma of pancreas.

The utility of UroVysion fluorescence in situ hybridization in pancreatic fine-needle aspiration samples directed and obtained by endoscopic ultrasonography.

CONTEXT: The diagnosis of pancreatic adenocarcinoma can be challenging for the pathologist. Endoscopic ultrasound-guided, fine-needle aspiration (EUS-FNA) can be used to obtain samples of pancreatic masses. UroVysion fluorescence in situ hybridization (UFISH) has been reported to increase the sensitivity and to be very specific for the diagnosis of adenocarcinoma when combined with cytology in the diagnosis of biliary brushings and washings. OBJECTIVES: To determine the sensitivity and specificity of UFISH on tissues obtained from pancreatic lesions suggestive of adenocarcinoma obtained by EUS-FNA, compared against fine-needle aspiration (FNA) results. Additionally, to use patient follow-up data to evaluate UFISH results in FNA samples that showed significant atypia but did not meet the criteria for malignancy. DESIGN: Sixty consecutive cases of pancreatic EUS-FNA from our institution submitted for UFISH testing. RESULTS: Polysomic UFISH has a sensitivity of 93% and a specificity of 100% when compared against FNA results. Follow-up studies showed that adding UFISH to FNA increased the sensitivity for patients with true-positive results from 83% to 94% and increased specificity from 85% to 100%. For 7 patients with suspicious FNA results who had sufficient follow-up, UFISH was 100% sensitive and 100% specific. CONCLUSIONS: UFISH can be used to confirm the diagnosis of malignancy in pancreatic adenocarcinoma. Because of the high specificity, polysomic UFISH may help establish a diagnosis of malignancy when the FNA features are suggestive of, but not conclusive for, malignancy. The most common cause for a false-negative UFISH result was insufficient numbers of malignant cells.