Clostridium difficile infection (CDI) is the primary cause of nosocomial diarrhea in the United States. Although C. difficile toxins A and B are the primary mediators of CDI, the overall pathophysiology underlying C. difficile-associated diarrhea remains poorly understood. Studies have shown that a decrease in both NHE3 (Na/H exchanger) and DRA (downregulated in adenoma, Cl/[Formula: see text] exchanger), resulting in decreased electrolyte absorption, is implicated in infectious and inflammatory diarrhea. Furthermore, studies have shown that NHE3 is depleted at the apical surface of intestinal epithelial cells and downregulated in patients with CDI, but the role of DRA in CDI remains unknown. In the current studies, we examined the effects of C. difficile toxins TcdA and TcdB on DRA protein and mRNA levels in intestinal epithelial cells (IECs). Our data demonstrated that DRA protein levels were significantly reduced in response to TcdA and TcdB in IECs in culture. This effect was also specific to DRA, as NHE3 and PAT-1 (putative anion transporter 1) protein levels were unaffected by TcdA and TcdB. Additionally, purified TcdA and TcdA + TcdB, but not TcdB, resulted in a decrease in colonic DRA protein levels in a toxigenic mouse model of CDI. Finally, patients with recurrent CDI also exhibited significantly reduced expression of colonic DRA protein. Together, these findings indicate that C. difficile toxins markedly downregulate intestinal expression of DRA which may contribute to the diarrheal phenotype of CDI. NEW & NOTEWORTHY Our studies demonstrate, for the first time, that C. difficile toxins reduce DRA protein, but not mRNA, levels in intestinal epithelial cells. These findings suggest that a downregulation of DRA may be a critical factor in C. difficile infection-associated diarrhea.

Carcinosarcomas of the pancreas are rare entities with a dismal prognosis. We report a rare case of pancreatic carcinosarcoma in a 49-year-old African American female who underwent a total abdominal hysterectomy with right salpingo-oophorectomy and exploration of the pancreatic mass. The surgery revealed a sclerotic mass in the body and tail of the pancreas that was surgically unresectable, and a pancreatic biopsy confirmed the pathology of pancreatic carcinosarcoma. Histologically, the lesion showed a high-grade spindle cell sarcoma and adjacent moderately differentiated adenocarcinoma. On immunohistochemical examination, the carcinomatous component was positive for epithelial markers, and the sarcomatous component was focally positive for SMA and desmin. In addition, the sarcomatous component showed diffuse immunoreactivity for CD10 with a surrounding myofibroblastic proliferation. Reports have associated expression of CD10 in pancreatic stellate cells with increased tumor aggressiveness. In this article, we report a case of pancreatic carcinosarcoma that shows sarcomatous CD10 immunoexpression with higher Ki67 labeling in the sarcoma than the carcinoma raising the question if the sarcomatous component could be potentiating the aggressiveness of the carcinomatous component.

Ovarian Brenner tumors, accounting for ∼5% of overall ovarian epithelial neoplasm, are often reported in association with mucinous neoplasm. Histogenetically, the two tumors are thought to arise from similar precursors. To date, fewer than 60 borderline Brenner tumors alone have been reported, and the concomitant presence of atypical proliferative components in Brenner and mucinous tumors is even rarer. Therefore, the clinicopathological characteristics and prognosis of patients with the borderline Brenner tumors alone or coexisting with mucinous neoplasm are extremely limited. Herein, we report a unique case of a 53-year-old woman with a unilateral ovarian borderline Brenner tumor associated with focal atypical mucinous epithelial proliferation and her clinical presentations. The clinicopathological features of the tumor are documented and the literature review along with the clinical molecular advances are summarized in this study.

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