Abstract
Grade 3, well-differentiated, gastric neuroendocrine tumors (NET G3) are extremely rare. Herein, we report the case of a 64-year-old man with a grade 3 neuroendocrine tumor of the stomach who experienced intra-abdominal bleeding during the course of drug treatment. The patient was referred to our hospital for examination of a gastric tumor that was initially diagnosed by a local medical doctor. Esophagogastroduodenoscopy revealed an elevated lesion with a central ulcer in the upper body of the stomach, and biopsy specimens confirmed the pathological diagnosis of NET G3. Abdominal contrast-enhanced computed tomography (CT) showed a 25-cm, well-defined mass lesion showing heterogeneous enhancement in the liver. A clinical diagnosis of NET G3 with multiple liver metastases was given, after which everolimus was administered in combination with a somatostatin analogue. However, the patient developed sudden-onset epigastric abdominal pain and general fatigue 2 months later, and emergency abdominal contrast-enhanced CT confirmed the presence of intra-abdominal hemorrhage. Following blood transfusion, the patient’s symptoms and general condition improved. Although the patient was treated with streptozocin, abdominal CT indicated progression of the liver metastases. Unfortunately, despite receiving best supportive care, the patient died 8 months after the initial of the treatment. To the best of our knowledge, this is the first case of a patient who developed spontaneous hemoperitoneum during drug treatment for a NET G3 to be reported in the English literature. It is essential that additional data be obtained to determine the optimal treatment for this disease.
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References
Cives M, Strosberg JR. Gastroenteropancreatic neuroendocrine tumors. CA Cancer J Clin. 2018;68:471–87.
Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26:3063–72.
Sorbye H, Baudin E, Borbath I, et al. Munich advisory board participants unmet needs in high-grade gastroenteropancreatic neuroendocrine neoplasms (WHO G3). Neuroendocrinology. 2016;108:54–62.
Pellat A, Coriat R. Well differentiated grade 3 neuroendocrine tumors of the digestive tract: a narrative review. J Clin Med. 2020;9:1677.
Hatanaka T, Naganuma A, Saito T, et al. Intratumoral hemorrhage of liver metastasis from a rectal neuroendocrine tumor. Intern Med. 2019;58:217–23.
Murakami R, Taniai N, Kumazaki T, et al. Rupture of a hepatic metastasis from renal cell carcinoma. Clin Imaging. 2000;24:72–4.
Kadowaki T, Hamada H, Yokoyama A, et al. Hemoperitoneum secondary to spontaneous rupture of hepatic metastasis from lung cancer. Intern Med. 2005;44:290–3.
Sakai M, Oguri T, Sato S, et al. Spontaneous hepatic rupture due to metastatic tumor of lung adenocarcinoma. Intern Med. 2005;44:50–4.
Chen HC, Chen CJ, Jeng CM, et al. Malignant fibrous histiocytoma presenting as hemoperitoneum mimicking hepatocellular carcinoma rupture. World J Gastroenterol. 2007;13:6441–3.
Gulati A, Vyas S, Lal A, et al. Spontaneous rupture of hepatic metastasis from choriocarcinoma: a review of imaging and management. Ann Hepatol. 2009;8:384–7.
Bakhshi GD, Borisa AD, Bhandarwar AH, et al. Primary hepatic choriocarcinoma: a rare cause of spontaneous haemoperitoneum in an adult. Clin Pract. 2012;2:e73.
Yoon JH. A spontaneously ruptured hepatic metastasis from a gastric gastrointestinal stromal tumor that presented as hemoperitoneum. J Investig Med High Impact Case Rep. 2013;1:2324709613512475.
Duan YF, Tan Y, Yuan B, et al. Spontaneous rupture of hepatic metastasis from small cell neuroendocrine carcinoma of maxillary sinus. World J Surg Oncol. 2014;12:126.
Rahul A, Robin F, Adarsh H. Spontaneous rupture of hepatic metastasis from pancreatic adenocarcinoma. Case Rep Oncol Med. 2016;2016:6968534.
Kim HJ, Park YE, Ki MS, et al. Spontaneous rupture of hepatic metastasis from a thymoma: a case report. World J Gastroenterol. 2016;22:9860–4.
Mochimaru T, Minematsu N, Ohsawa K, et al. Hemoperitoneum secondary to rupture of a hepatic metastasis from small cell lung cancer during chemotherapy: a case with a literature review. Intern Med. 2017;56:695–9.
Salame H, Issa M, Nicolas G, et al. A rare case of a ruptured metastatic hepatic lesion from a jejunal gastrointestinal stromal tumor (gist) treated by arterial embolization. Am J Case Rep. 2018;19:1480–7.
Dolapsakis C, Pavli P, Panagopoulos A, et al. Haemoperitoneum due to spontaneous rupture of a liver metastasis. Eur J Case Rep Intern Med. 2019;6:001142.
Lin HM, Lei LM, Zhu J, et al. Risk factor analysis of perioperative mortality after ruptured bleeding in hepatocellular carcinoma. World J Gastroenterol. 2014;20:14921–6.
Bieze M, Phoa SS, Verheij J, et al. Risk factors for bleeding in hepatocellular adenoma. Br J Surg. 2014;101:847–55.
Darnis B, Rode A, Mohkam K, et al. Management of bleeding liver tumors. J Visc Surg. 2014;151:365–75.
Srinivasa S, Lee WG, Aldameh A, et al. Spontaneous hepatic haemorrhage: a review of pathogenesis, aetiology and treatment. HPB (Oxford). 2015;17:872–80.
Heetfeld M, Chougnet CN, Olsen IH, et al. Other knowledge network members characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms. Endocr Relat Cancer. 2015;22:657–64.
Gumuscu B, Norwood K, Parker GA, et al. Well-differentiated neuroendocrine tumor of the stomach: a rare case at an uncommon site. Medicin. 2016;95:e4260.
Min BH, Hong M, Lee JH, et al. Clinicopathological features and outcome of type 3 gastric neuroendocrine tumours. Br J Surg. 2018;105:1480–6.
Shen C, Chen H, Chen H, et al. Surgical treatment and prognosis of gastric neuroendocrine neoplasms: a single-center experience. BMC Gastroenterol. 2016;16:111.
Sato Y, Hashimoto S, Mizuno K, et al. Management of gastric and duodenal neuroendocrine tumors. World J Gastroenterol. 2016;22:6817–28.
Yang Z, Klimstra DS, Hruban RH, et al. Immunohistochemical characterization of the origins of metastatic well-differentiated neuroendocrine tumors to the liver. Am J Surg Pathol. 2017;41:915–22.
Hanazaki K, Sakurai A, Munekage M, et al. Surgery for a gastroenteropancreatic neuroendocrine tumor (GEPNET) in multiple endocrine neoplasia type 1. Surg Today. 2013;43:229–36.
Chung CS, Tsai CL, Chu YY, et al. Clinical features and outcomes of gastric neuroendocrine tumors after endoscopic diagnosis and treatment: a digestive endoscopy society of Taiwan (DEST). Medicine. 2018;97:e12101.
Namikawa T, Oki T, Kitagawa H, et al. Neuroendocrine carcinoma of the stomach: clinicopathological and immunohistochemical evaluation. Med Mol Morphol. 2013;46:34–40.
Namikawa T, Kobayashi M, Okabayashi T, et al. Primary gastric small cell carcinoma: report of a case and review of the literature. Med Mol Morphol. 2005;38:256–61.
Pavel ME, Hainsworth JD, Baudin E, et al. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011;378:2005–12.
Pavel ME, Baudin E, Öberg KE, et al. Efficacy of everolimus plus octreotide LAR in patients with advanced neuroendocrine tumor and carcinoid syndrome: final overall survival from the randomized, placebo-controlled phase 3 RADIANT-2 study. Ann Oncol. 2017;28:1569–75.
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Tsutomu Namikawa, Keiichiro Yokota, Sachi Yamaguchi, Ian Fukudome, Masaya Munekage, Sunao Uemura, Hiromichi Maeda, Hiroyuki Kitagawa, Kiyo Mibu, Michiya Kobayashi, and Kazuhiro Hanazaki declare that they have no conflict of interest.
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Namikawa, T., Yokota, K., Yamaguchi, S. et al. Spontaneous intra-abdominal hemorrhage of a well-differentiated, grade 3 gastric neuroendocrine tumor during drug-based treatment. Clin J Gastroenterol 14, 1244–1249 (2021). https://doi.org/10.1007/s12328-021-01433-3
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DOI: https://doi.org/10.1007/s12328-021-01433-3