Sandeep A Padala

Pembrolizumab-induced severe rejection and graft intolerance syndrome resulting in renal allograft nephrectomy

Introduction Pembrolizumab is a selective anti-programmed cell death protein-1 (PD-1) humanized monoclonal antibody that inhibits PD-1 activity by binding to the PD-1 receptor that is found on activated T-cells. The goal of the treatment is to allow the immune system to target and destroy cancer cells by preventing cancer cells from binding to PD-1 receptors, leading to decreased tumor growth. The activation of T-cells by pembrolizumab not only leads to the destruction of malignant cells but also attacks the donor alloantigens that are present in a renal transplant, resulting in graft rejection. Case report We present a case of a 46-year-old African American female with history of renal transplant who was treated with pembrolizumab for stage IV B endometrial adenocarcinoma and experienced renal transplant rejection and severe graft intolerance syndrome. Management and outcome: Due to ongoing graft intolerance, a transplant nephrectomy was performed. Allograft pathology was consistent with non-viable kidney with tubulitis, interstitial fibrosis and necrosis consistent with transplant rejection without any evidence of malignancy. Discussion As emphasized in our case, there is a very high risk of graft rejection in patients who need to be placed on immunomodulators such as pembrolizumab, so the risk versus benefit needs to be assessed and discussed. Our case is unique because pembrolizumab not only caused graft rejection but also severe graft intolerance syndrome which led to transplant nephrectomy. Further guidelines are needed in renal transplant patients requiring PD-1 inhibitors to establish the ideal treatment plan of immunosuppression management and anti-cancer treatments.

A Rare Presentation of Choledochoduodenal Fistula Due to Ovarian Cancer Metastasis

Choledochoduodenal fistula (CDF) is an abnormal communication between the common bile duct and the duodenum. It accounts for about 5% to 25% of the total biliary fistulas and is usually due to a perforated duodenal ulcer, choledocholithiasis, and complications secondary to tuberculosis or could be iatrogenic. Primary intrabilliary tumors usually cause obstructive jaundice and rarely biliary metastasis arising from other organs like colon, breast, and lungs can cause obstructive jaundice. There has been a case report of metastasis from ovarian cancer to the major papilla of the duodenum but no reported cases of it causing a CDF. We report a rare case of an 83-year-old female with ovarian cancer who developed a metastatic lesion to the duodenum eventually resulting in a CDF.