Immune Checkpoint Inhibitor Induced Diabetes Mellitus Treated with Insulin and Metformin: Evolution of Diabetes Management in the Era of Immunotherapy.

Immune checkpoint inhibitors (ICPIs) are a breakthrough therapy in oncology and have been approved by the Food and Drug Administration for the treatment of several malignancies. ICPIs have been reported to cause immune-mediated damage of islet cells leading to ICPI-induced type 1 diabetes mellitus (T1DM). These reports described patients presenting with severe diabetic ketoacidosis (DKA). We present a case of a 69-year-old Caucasian male with type 2 diabetes suffering from non-small cell lung cancer and undergoing treatment with pembrolizumab, an anti-programmed cell death protein-1 antibody, who presented to our emergency department with complaints of nausea, vomiting, polyuria, and polydipsia. He was found to have high anion gap metabolic acidosis with ketosis and elevated blood glucose levels consistent with DKA. Lab workup was consistent with T1DM. Despite being on a tailored insulin regimen, his blood glucose remained elevated, necessitating the addition of metformin to his regimen which effectively controlled his blood glucose.

Not your usual hip pain: necrotising fasciitis secondary to sigmoid perforation.

Necrotising fasciitis (NF) resulting from sigmoid perforation is rare, but none the less remains life threatening. Early surgical intervention and empiric broad-spectrum antibiotic remains the standard of care. A 65-year-old man with history of stage 4 rectal cancer presented with bilateral hip pain. An X-ray of the hip and pelvis to rule out fracture revealed abnormal gas pattern overlying the right hip. CT imaging revealed distal sigmoid perforation with air extending from the pelvis to posterior aspect of the right hip and thigh. Aggressive surgical intervention and antibiotic initiation was associated with successful outcomes in our patient. Although less common, sigmoid perforation leading to NF in posterior thigh is a reminder of a potentially lethal complication.

Safety of endoscopy in cancer patients with thrombocytopenia and neutropenia.

BACKGROUND AND AIMS: Cancer patients are prone to thrombocytopenia and neutropenia, which increase the risk of bleeding and infection. We assessed the safety of endoscopic procedures in cancer patients with thrombocytopenia and/or neutropenia. METHODS: We studied consecutive cancer patients with thrombocytopenia and/or neutropenia who underwent endoscopic procedures from 2010 through 2015. Neutropenia was defined as an absolute neutrophil count (ANC) <1000 cells/µL, and thrombocytopenia as a platelet count <100 × 103/µL. Univariate and multivariate generalized estimating equation models were used to assess factors associated with risk of adverse events (AEs) or death. RESULTS: We identified 588 patients who underwent 783 procedures; 608 procedures were performed in the setting of thrombocytopenia and 675 procedures in the setting of neutropenia. Concurrent neutropenia and thrombocytopenia were recorded in 500 endoscopies. Twenty-four patients (4.1%) experienced infectious AEs, whereas 29 (4.9%) experienced bleeding AEs within 1 week of the procedure. On multivariate analysis, platelet count ≤50 × 103/µL was associated with risk of bleeding AEs. In contrast, poor performance status was associated with increased risk of infection AEs (P < .01). No association was observed between low ANC and infectious AEs. Poor performance status (P < .01) and platelet count ≤100 × 103/µL (P < .05) were associated with increased risk of 30-day mortality. A persistent platelet count <20 × 103/µL after the procedure, with a baseline platelet count of ≤20 × 103/µL before the procedure, was associated with significant risk of bleeding AEs compared with a platelet count >20 × 103/µL after the procedure (P < .01); furthermore, if the platelet count increased to >50 × 103/µL after the procedure, the bleeding risk after the procedure was greatly reduced (P < .01). CONCLUSIONS: Endoscopic procedures are relatively safe in cancer patients with platelet count >50 × 103/µL. Nevertheless, a platelet count of ≥20 × 103/µL could be an appropriate threshold for platelet transfusion if 50 × 103/µL is difficult to achieve. The functional status of the patient, in the absence of the need for urgent or necessary endoscopic interventions, should be considered when deciding whether to perform endoscopy. The risk of procedure and the ANC did not seem to affect the outcomes.

Immune-checkpoint inhibitor-induced diarrhea and colitis in patients with advanced malignancies: retrospective review at MD Anderson.

BACKGROUND: Immune checkpoint inhibitors (ICPIs) are gaining increasing popularity as an efficacious treatment for advanced malignancies. ICPI treatment can be complicated by diarrhea and colitis. Systemic steroids are the first line treatment. Infliximab is reserved for severe refractory cases. We aimed to assess the impact of ICPI-induced diarrhea and colitis and their immunosuppressive treatment on patients' outcomes. METHODS: This retrospective analysis was conducted in 327 cancer patients who received ICPIs between 2011 and 2017. Patients with ICPI-induced toxicities in other organs were excluded. We collected data about patient demographics, clinical variables, and overall survival. We used descriptive analysis to compare different groups based on the occurrence and the treatment of diarrhea and colitis. Kaplan-Meier and log-rank test were used to estimate and compare overall survival durations between groups. RESULTS: Diarrhea was recorded in 117 (36%) patients; 79 (24%) of them required immunosuppressive treatment of either systemic corticosteroid without infliximab (n = 44) or with infliximab (n = 35). Caucasian ethnicity, melanoma, stage 3 cancer, and ipilimumab were predictors of colitis that requires immunosuppression. Patients who required immunosuppressants had better overall survival than those who did not require treatment for colitis or diarrhea (P < 0.001). Immunosuppression for diarrhea or colitis did not affect the overall survival significantly (P = 0.232), nor did the choice of treatment (corticosteroids with vs. without infliximab; P = 0.768). Diarrhea was an independent predictor of a favorable overall survival (P < 0.001), irrespective of treatment need (P = 0.003). We confirmed the same results in a subgroup analysis for patients with stage IV malignancies only. Patients who received long duration of steroid treatment (> 30 days) had numerically higher infection rate than those who received steroid for shorter duration (40.4 vs. 25.8%, P = 0.160). Likewise, long duration of steroid without infliximab was associated with increased risk of infection compared to short duration of steroid with infliximab (42.9% vs. 14.3%, P = 0.089). CONCLUSIONS: Patients with ICPI-induced diarrhea or colitis have improved survival outcomes. Diarrhea is an independent predictor of an improved survival regardless of treatment requirement. Immunosuppressive treatment for diarrhea did not significantly affect overall survival, however, infection rates were numerically higher among patients who received steroids for a long duration. Therefore, early non-steroid immunosuppressive therapy may ensure a more favorable overall outcome.