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Colonic Perforation After Treatment With Nivolumab in Esophageal Cancer: A Case Report.

ABSTRACT: With the advent of checkpoint inhibitors, it has opened up opportunities for numerous cancer patients. However, as is the case with every treatment, complications need to be weighed. Gastrointestinal adverse effects, such as diarrhea and colitis are well-known complications for checkpoint inhibitors. In severe cases, colitis-induced colonic perforation may occur with an estimation of 1.0% to 1.5% in anti-CTLA-4 antibodies. However, only a handful of cases of such devastating complications have been reported in anti-PD-1 antibodies such as pembrolizumab and nivolumab. We here report a case of intestinal perforation in a patient treated with nivolumab.

SUBMITTER: Cho HJ

PROVIDER: S-EPMC8359691 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Colonic Perforation After Treatment With Nivolumab in Esophageal Cancer: A Case Report.

Cho Hye Jung HJ Kim Woo Ram WR Kim Joo-Hang JH Kim Duk Hwan DH Kim Dae Jung DJ Kang Haeyoun H

Annals of coloproctology 20210624 Suppl 1

With the advent of checkpoint inhibitors, it has opened up opportunities for numerous cancer patients. However, as is the case with every treatment, complications need to be weighed. Gastrointestinal adverse effects, such as diarrhea and colitis are well-known complications for checkpoint inhibitors. In severe cases, colitis-induced colonic perforation may occur with an estimation of 1.0% to 1.5% in anti-CTLA-4 antibodies. However, only a handful of cases of such devastating complications have b ...[more]

PMID: 34167190

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Project description:BackgroundEsophageal perforation is a rare but life-threatening condition associated with a high mortality rate and often presents with nonspecific clinical manifestations that can lead to delayed diagnosis and treatment. When combined with ST-segment elevation on electrocardiography (ECG), it can be particularly challenging to distinguish esophageal perforation from acute inferior myocardial infarction, as the two conditions may share similar ECG findings.Case descriptionWe report the case of a 65-year-old man with a significant history of long-term alcohol consumption who presented to our hospital (the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine) with persistent oppressive pain in the anterior and posterior left chest. Initially, the patient was diagnosed with acute coronary syndrome based on the ECG findings, which showed Q-wave and ST-segment elevation in the inferior leads. However, further dynamic monitoring of myocardial necrosis markers, including myoglobin and troponin I, yielded negative results inconsistent with acute myocardial infarction. Subsequent enhanced computed tomography revealed thickening and discontinuity of the wall of the thoracic esophagus with an irregular, mixed-density shadowing of the surrounding soft tissue confirming the diagnosis of esophageal rupture. Despite prompt recognition and transfer to a hospital with surgical capabilities, the patient tragically succumbed to esophageal rupture and hemorrhage while awaiting surgery.ConclusionsThis case highlights the importance of maintaining a broad differential, including esophageal rupture, in patients exhibiting necrotic Q waves and ST-segment elevation in the inferior wall of the ECG, especially in the absence of reciprocal changes in the lateral leads and the lack of abnormal markers of myocardial necrosis. Prompt recognition of this rare but potentially fatal condition is crucial for initiating appropriate treatment and improving patient outcomes. Emergency physicians should be aware of this atypical presentation of esophageal perforation mimicking an acute myocardial infarction and consider this differential diagnosis when faced with discordant clinical and diagnostic findings.

Project description:BackgroundImmune checkpoint inhibitors (ICIs) have emerged as paradigm shifting treatment options for a number of cancers. Six antibodies targeting the immune checkpoint proteins programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1) or cytotoxic T-lymphocyte associated protein 4 (CTLA4) have been approved. In some cases, response rates have been impressive, but not uniformly so and not consistently; similarly, toxicity to this class of therapeutic is often unpredictable and can be life threatening. Predicting treatment response and toxicity are two main obstacles to truly individualize treatment with ICIs. One of the most severe and life-threatening adverse events is colitis induced colonic perforation, estimated to occur in 1.0 to 1.5% of patients treated with ICIs. An important question to address is, under what circumstances is it appropriate to reinitiate ICI treatment post-bowel perforation?Case presentationThe patient is a 62-year-old woman, who presented with stage IV lung cancer. Immunohistochemical staining indicated that 80% of the patient's tumor cells expressed PD-L1. The patient was started on a three-week cycle of pembrolizumab. Subsequent reducing in tumor burden was observed within ten weeks. Initially, pembrolizumab was tolerated fairly well, with the exception of immunotherapy related hypothyroidism. However, the patient experienced a second, more serious immune-related adverse event (irAE), in the form of enteritis, which led to small bowel perforation and necessitated exploratory laparotomy. The concerning part of the small bowel was resected, and a primary anastomosis was created. Based on the pathological and surgical findings, the patient was diagnosed with pembrolizumab-associated small bowel perforation. The patient recovered well from surgery and, considering the patient's remarkable response to treatment, a collective decision was made to reinitiate pembrolizumab on post-operative day twenty-eight. The patient is continuing her immunotherapy with ongoing partial response and is able to continue her full-time job.ConclusionsThis case report highlights the challenges of identifying patients likely to respond to ICIs and those that are likely to experience irAEs and it discusses the impressive work that has been done to start to address these challenges. Lastly, the topic of reinitiating pembrolizumab treatment even after colonic perforation is discussed.

Project description:BackgroundMetastatic neuroendocrine carcinoma has an extremely poor prognosis, and no effective second-line treatment is available. Herein, we describe a case of multiple metastases after primary resection of esophageal neuroendocrine carcinoma successfully treated with nivolumab plus radiotherapy in a short time.Case presentationA man in his 70s presented to our hospital after an abnormality was detected on an upper gastrointestinal series. Upper gastrointestinal endoscopy revealed a type 2 tumor spanning the endothelial cell junction to the abdominal esophagus. Histopathological examination of the biopsy confirmed a diagnosis of esophageal neuroendocrine carcinoma. The patient had no distant metastases. Thoracoscopic esophagectomy with three-field lymph node dissection was performed. Histopathological examination confirmed a diagnosis of esophageal neuroendocrine carcinoma with features of adenoid cystic-like carcinoma and squamoid pattern (pT2 [MP], INF a, ly1, v1 [EVG], pIM0, pDM0, pRM0, pN1 [1/28], M0; Stage II), which was positive for synaptophysin. The postoperative course was good, with no complications. The patient was treated with 100 mg of irinotecan and 100 mg of cisplatin, administered every 4 weeks, as postoperative adjuvant chemotherapy. Grade 3 loss of appetite was observed, and adjuvant chemotherapy was discontinued after four cycles of first-line treatment. A positron emission tomography-computed tomography scan 3 years after surgery showed abnormal uptake in the subaortic, left hilar, and left axillary lymph nodes, and in a mass in the right lung apex. The patient was diagnosed with metastatic esophageal neuroendocrine carcinoma postoperatively. First-line treatment could not be repeated due to toxicity from the initial treatment. Nivolumab (240 mg every 2 weeks) was administered as second-line treatment, and radiotherapy was started (56 Gy delivered in 28 fractions to the local [subaortic and hilar] lymph nodes). After 10 cycles of nivolumab in combination with radiotherapy (56 Gy), a positron emission tomography-computed tomography scan showed disappearance of all lesions. A complete response was achieved. Maintenance therapy (240 mg of nivolumab) was continued. No recurrence has been observed for 42 months.ConclusionsWe experienced a case in which nivolumab in combination with radiotherapy was effective for metastatic esophageal neuroendocrine carcinoma after primary resection.

Dataset Information

Colonic Perforation After Treatment With Nivolumab in Esophageal Cancer: A Case Report.

Publications

Colonic Perforation After Treatment With Nivolumab in Esophageal Cancer: A Case Report.

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