A CASE OF ACQUIRED GENERALIZED LIPODYSTROPHY ASSOCIATED WITH PEMBROLIZUMAB IN A PATIENT WITH METASTATIC MALIGNANT MELANOMA.

OBJECTIVE: To describe an unusual immune-related adverse event (irAE), acquired generalized lipodystrophy (AGL), from checkpoint inhibitor therapy in a patient treated with pembrolizumab. METHODS: This is a case report of a 67-year-old male with metastatic melanoma who was treated with pembrolizumab. Prior to pembrolizumab, the patient was treated with another immune-checkpoint inhibitor and developed autoimmune hemolytic anemia. After starting pembrolizumab, he developed a scrotal mass consistent with panniculitis and after several subsequent cycles, he developed AGL. RESULTS: Loss of subcutaneous fat, unexplained weight loss in combination with worsening insulin resistance and worsening hypertriglyceridemia after initiation of pembrolizumab were consistent with AGL. Autoimmune disorders and other etiologies were ruled out. Despite this irAE, the patient continued to receive pembrolizumab given stabilization of melanoma with treatment. CONCLUSION: We report the second case of a patient who developed AGL secondary to pembrolizumab, and the fourth case to report such complication secondary to antiprogrammed cell death receptor-1 inhibitors. As use of checkpoint inhibitors becomes more common to treat several types of cancer, it is vital for clinicians to recognize these rare irreversible complications that are not frequently reported in clinical trials.

Reduced risk of colorectal cancer with use of oral bisphosphonates: a systematic review and meta-analysis.

PURPOSE: The association between oral bisphosphonate (BP) intake and colorectal cancer (CRC) risk has been investigated in several recent studies with conflicting results. We summarized the evidence from the published studies in a categorical, dose-response meta-analysis. METHODS: Relevant studies were identified by a search of MEDLINE and EMBASE databases through January 15, 2012. We included studies that reported effect size estimates with 95% CIs for the association between exposure to oral BPs and risk of CRC. RESULTS: Three case-control studies with a total of 16,998 CRC cases and 108,197 controls and one cohort study with 94,405 individuals exposed to BPs and 283,181 unexposed to BPs were included in meta-analysis. The random effect model meta-analysis suggested reduced risk of CRC with exposure to oral BPs with pooled odds ratio (OR) of 0.87 (95% CI, 0.78 to 0.97). Significant inverse relationship was noted for 10 or more prescriptions categories, with pooled ORs of 0.71 (95% CI, 0.58 to 0.87). Similarly, the analysis for 1 to 3 years of use and more than 3 years of use of BPs suggested a significant inverse relationship, with pooled ORs of 0.76 (95% CI, 0.68 to 0.85) and 0.78 (95% CI, 0.61 to 0.99), respectively. CONCLUSION: This meta-analysis suggests that the use of oral BPs at a dose of 10 or more prescriptions or 1 or more years of duration is associated with reduced risk of CRC. Further randomized controlled trials are needed to prove this association.

Lung cancer-induced paraneoplastic syndromes.

PURPOSE OF REVIEW: Paraneoplastic syndromes occur commonly in patients with lung cancer, especially cancers of neuroendocrine origin. The syndromes can be the first clinical manifestation of malignant disease or a harbinger of cancer recurrence. To update the knowledge that would facilitate the care of lung cancer patients with paraneoplastic syndromes, this review focuses on the epidemiology, pathogenesis, clinical features, and current management of the more common and clinically relevant syndromes. RECENT FINDINGS: Certain combinations of clinical signs and symptoms (endocrine, neurologic, immunologic, dermatologic, metabolic, constitutional, and hematologic) are associated with lung carcinoma as a manifestation of the secretion of cytokines and hormones by these cells or as an associated immunologic response. These syndromes can be categorized by common causative mechanisms: hormonal syndromes, autoimmune syndromes, and other syndromes of less clear cause. Recent advances in medical technology have allowed better understanding of these syndromes and the development of novel diagnostic and therapeutic tools. SUMMARY: Increased awareness of paraneoplastic syndromes associated with lung cancer should lead to the earlier recognition and diagnosis of malignancies, thereby improving the overall prognosis of patients and alleviating associated comorbidities. Despite the recent advances in recognizing and treating paraneoplastic syndromes, many questions remain to be answered.