Immune checkpoint inhibitor-induced myocarditis, myositis, myasthenia gravis and transaminitis: a case series and review.

Immune checkpoint inhibitors have been incorporated into the treatment of various malignancies. An increasing body of literature is reporting rare but potentially fatal adverse events associated with these agents. In this case series, the authors report the clinical features and outcomes of seven patients who received immune checkpoint inhibitors for different solid organ malignancies and developed a tetrad of immune-related myocarditis, myositis, myasthenia gravis and transaminitis. Herein the authors review the literature and describe the current diagnostic and management approach for this overlapping syndrome. The authors' series highlights the importance of a high index of clinical suspicion, prompt comprehensive investigations, early multidisciplinary team involvement and initiation of immunosuppressive therapy when immune-related adverse events are suspected.

Cancer immunotherapy is used in the treatment of different cancer types. Immunotherapy activates the immune system to detect and attack cancer cells, but side effects may arise from the immune system inadvertently attacking normal tissues and organs. The increased use of immunotherapy has led to an increase in the reporting of rare but potentially life-threatening treatment-related side effects. In this case series, the authors report the clinical features and outcomes of seven patients who developed inflammation of the heart, muscles, nerve and muscle junctions and liver following treatment with immunotherapy. The authors review the scientific literature and discuss the current understanding of and management approach to this rare syndrome. The authors' report highlights the importance of a high degree of clinical suspicion, prompt comprehensive testing to confirm diagnosis, early involvement of experts from different specialties and early initiation of treatment in the management of this unique syndrome.

Pancreatitis and Biliary Obstruction Secondary to Duodenal Metastasis from Rapidly Progressing Lung Adenocarcinoma Treated with Common Bile Duct Stenting.

Non-small cell lung cancer (NSCLC) is characterised by diffuse metastases, with common sites being the brain, liver, bones, and adrenal glands. Small bowel metastasis from NSCLC is a rare phenomenon, particularly in patients with an adenocarcinoma histology. We report the case of a 56-year-old lung adenocarcinoma patient with a duodenal metastasis diagnosed on FDG/PET-CT and confirmed on duodenal biopsy. Although initially asymptomatic, he subsequently presented with obstructive jaundice secondary to rapid local disease progression at the duodenal metastasis, requiring endoscopic intervention for biliary drainage. He was commenced on single agent pembrolizumab, with disease response on subsequent follow-up. This case highlights a rare case of gastrointestinal metastasis from NSCLC requiring endoscopic intervention due to rapid progression of the disease at the site of metastasis.

Euglycemic Ketoacidosis in a Patient with Metastatic Non-Small-Cell Lung Adenocarcinoma and Concomitant Pulmonary Embolism.

Euglycemic ketoacidosis is a recognised side effect secondary to sodium-glucose cotransporter 2 inhibitor use in the treatment of type 2 diabetes mellitus; however, there is scarce evidence to suggest whether preexisting comorbid conditions contribute to the development of this potentially life-threatening complication. We describe a case of euglycemic ketoacidosis in a patient with type 2 diabetes mellitus in the context of empagliflozin use after a recent diagnosis of metastatic lung adenocarcinoma. The diagnosis was complicated by a pulmonary embolism and hospital-acquired pneumonia, and was subsequently established after an anion-gap metabolic acidosis was identified on arterial blood gas and serum ketone measurement. The patient required admission to the intensive care unit for fluid resuscitation and regular intravenous insulin to ensure resolution of acidosis and maintenance of normoglycaemia. The patient was discharged to home for outpatient single-agent pembrolizumab for treatment of his lung adenocarcinoma. This article highlights the importance or awareness of oral hypoglycaemic medications and their side effects, along with providing further evidence for the potential contribution of malignancy to the development of euglycemic ketoacidosis in a patient with type 2 diabetes mellitus.

Transient jejuno-jejunal intussusception in an anabolic steroid user-A case report.

INTRODUCTION: Adult intussusception (AI) is both a challenging and rare diagnosis, with predisposing factors including malignancy, surgery and infection to name a few. Transient jejunal intussusception is a subset of AI which is usually diagnosed radiologically, with diagnostic laparoscopy utilised to determine whether a malignant cause is identifiable and subsequently treatable. PRESENTING CASE: We present the case of a previously healthy 36-year-old male diagnosed with transient jejunal intussusception on computed tomography after presenting with abdominal pain. Blood tests on admission were normal apart from polycythaemia. His only significant history was that of chronic anabolic steroid use. He had a subsequent normal gastroscopy and colonoscopy with diagnostic laparoscopy demonstrating thickening of the small bowel. Histopathological analysis of the intraoperative specimen was normal. The patient improved and was discharged with no further complications. CONCLUSION: This case highlights the potential association between anabolic steroid use resulting in polycythaemia, and AI or transient jejunal intussusception, along with further validating a conservative approach in the management of AI in patients deemed to be low risk of malignancy on pre-operative evaluation.

Macrophage inhibitory cytokine-1/growth differentiation factor-15 in premalignant and neoplastic tumours in a high-risk pancreatic cancer cohort.

BACKGROUND: Pancreatic cancer (PC) is a leading cause of cancer related mortality worldwide, with poor survival due to late diagnosis. Currently, biomarkers have limited use in early diagnosis of PC. Macrophage inhibitory cytokine-1 or growth differentiation factor-15 (MIC-1/GDF15) has been implicated as a potential serum biomarker in PC and other malignancies. AIM: To determine the role of MIC-1/GDF15 in detecting pre-malignant pancreatic lesions and neoplastic tumours in an asymptomatic high-risk cohort part of Australian Pancreatic Cancer Screening Program. METHODS: A feasibility prospective single centre cohort study was performed. Participants recruited for yearly surveillance with endoscopic ultrasound (EUS) had serial fasting blood samples collected before EUS for MIC-1/GDF15, C-reactive protein and carbohydrate antigen 19-9. Patients were stratified into five groups based on EUS findings: Normal; pancreatic cysts, branch-duct intraductal papillary mucinous neoplasm; diffuse non-specific abnormalities; and neoplastic tumours. MIC-1/GDF15 serum levels were quantified using ELISA. Participants in whom EUS demonstrated abnormalities but not malignancy were closely followed up with magnetic resonance imaging (MRI) or computed tomography. RESULTS: One hundred twenty participants were prospectively recruited from 2011-2018. Forty-seven participants (39.2%) had an abnormal EUS and five participants (4.2%) were diagnosed with neoplastic tumours, three by EUS (two pancreatic and one liver) and two by MRI/computed tomography (breast cancer, bladder cancer), which were performed for follow up of abnormal EUS. Baseline serum MIC-1/GDF15 was a significant predictor of neoplastic tumours on receiver operator characteristic curve analysis [area under curve (AUC) = 0.814, P = 0.023]. Baseline serum MIC-1/GDF15 had moderate predictive capacity for branch-duct intraductal papillary mucinous neoplasm (AUC = 0.644) and neoplastic tumours noted on EUS (AUC = 0.793), however this was not significant (P = 0.188 and 0.081 respectively). Serial serum MIC-1/GDF15 did not demonstrate a significant percentage change between a normal and abnormal EUS (P = 0.213). Median baseline MIC-1/GDF15 was greater in those with neoplastic tumours (Median = 1039.6, interquartile range = 727.0-1977.7) compared to those diagnosed with a benign lesion (Median = 570.1, interquartile range = 460.7-865.2) on EUS and MRI (P = 0.012). CONCLUSION: In this pilot study MIC-1/GDF15 has predictive capacity for neoplastic tumours in asymptomatic individuals with a genetic predisposition for PC. Further imagining may be warranted in patients with abnormal EUS and raised serum MIC-1/GDF15. Larger multicentric prospective studies are required to further define the role of MIC-1/GDF15 as a serological biomarker in pre-malignant pancreatic lesions and neoplastic tumours.