A rare surgical case of multiple liver resections for recurrent liver metastases from pancreatic gastrinoma: liver and vena cava resection

Pancreatic gastrinoma is a rare non-β islet cell tumor. Approximately 60% of gastrinomas are malignant; despite the fact that they are usually slow growing, liver metastases have a major impact on prognosis. Most authors have advocated aggressive surgical management as being the only potentially curative therapy to improve survival as well as to provide outstanding relief from symptoms. We present a case of a 57-year-old man referred to our hospital with a diagnosis of liver metastases from pancreatic gastrinoma, with suspected involvement of the inferior vena cava (IVC). At the age of 37 years, he was diagnosed in his local hospital as having a pancreatic gastrinoma, with liver metastases, and he underwent distal pancreatectomy, splenectomy and enucleation of liver metastases. A liver tumor recurred twice, 7 and 9 years after the first surgery, for which double liver resections were performed: the first time he underwent enucleation of multiple liver metastases in segments II, III, IV, V, VI, VII and VIII, with resection of the right hepatic vein and partially resection of the diaphragm; the second time he underwent enucleation of multiple liver metastases in segments II, III, IV, and V. In our hospital, 8 years after the last surgery, the patient underwent right extended trisectionectomy, resection of segment I, combined resection of the IVC, and partial removal of the diaphragm. To the best of our knowledge, from a review of the literature, this is the first case to achieve successful long-term survival through aggressive surgical management of this type of metastatic endocrine tumor. The patient described here is still alive, free of disease and leading a normal life, 20 years after the initial diagnosis and 3 years after the last surgery.     

Primary hepatic gastrinoma: Report of a case and review of literature

Primary hepatic gastrinoma is a very rare ectopic gastrinoma with less than 20 cases reported worldwide. We report the case of a patient with hypergastrinemia who was subjected to exhaustive preoperative and intraoperative imaging and also careful surgical exploration of the duodenum and pancreas which failed initially to identify the primary tumour. Eventually the patient was subjected to left liver lobectomy,as a small palpable lesion was noted intraoperatively. The diagnosis of gastrinoma requires a high index of clinical suspicion and the flawless cooperation of many specialties.     

大剂量旋覆代赭汤治疗脾胃虚弱型糖尿病胃轻瘫临床观察

目的:观察旋覆代赭汤对糖尿病胃轻瘫(Diabetic gastroparesis,DGP)患者促胃肠动力作用量效关系研究。方法:将108例脾胃虚弱型患者随机分为治疗组:大剂量54例(一两为15.625g)和对照组54例,对照组药物口服吗丁啉,10mg,每日3次,连用4周;治疗组药物口服旋覆代赭汤,每日1剂,连用4周。免疫组化法观察治疗前后血浆中胃动素(MOT)、血管活性肠肽(VIP)、胃泌素(GAS)的分布变化。结果:治疗组血浆中MOT的含量显著升高(P<0.01)、VIP的表达明显减少(P<0.01)、显著降低血浆GAS表达(P<0.05)。结论:旋覆代赭汤的促胃肠动力作用可能与血浆中MOT的含量显著升高和VIP与GAS的表达降低有密切关系。     

Gastrinomas: A historical perspective

The journey of gastrinomas had its beginnings in 1955 when Zollinger and Ellison published their seminal paper (Zollinger and Ellison, Ann Surg 1955; 142: 709–723). The evolution of the diagnosis and management of this syndrome has paralleled many important advances in medicine, including the development of various diagnostic tools to the major impact of medical treatment on the management of an inherently surgical pathology. There are numerous excellent review articles on the most current developments and treatment options of gastrinomas available in the literature today. The purpose of this paper is to present a historical perspective on this most fascinating condition. This article will illustrate the way in which the discovery of gastrinomas evolved and how its management has developed with it. The evolution of the surgical treatment of gastrinomas has evolved over the last 50 years. J. Surg. Oncol. 2009;100:425–433. © 2009 Wiley‐Liss, Inc.     

Multiple gastrinoma successfully resected with the aid of intraoperative arterial secretin injection test

Since gastrinoma is likely to develop in multiple sites, we should pay special attention to the removal of all daughter tumors, as well as the main tumor, during surgery for this disease. In a 24-year-old woman with pituitary prolactinoma, multiple gastrinomas were detected in a limited area of the pancreaticoduodenal region by preoperative imaging techniques, selective arterial secretin injection (SASI) test, and intraoperative inspection using ultrasonography. A pancreatoduodenectomy was performed, and it was intraoperatively confirmed that the serum gastrin concentration in the portal vein had decreased from 753 to 83 pg/ml (normal,<120pg/ml). However, intraoperative SASI test for the remnant pancreas showed a positive response, which prompted us to perform a histological examination of frozen sections obtained from the body and tail of the pancreas, despite the normal appearance. Many islet cell microtumors were discovered, and the remnant pancreas was completely removed. Postoperativelly, all of the tumors were immunohistochemically proven to be microgastrinomas. The patient is still disease-free, 2 years after the surgery, with a serum gastrin level of less than 30pg/ml. This report stresses the role of the intraoperative SASI test in preventing residual microgastrinomas before closure of the abdomen.     

Multiple gastrinoma successfully resected with the aid of intraoperative arterial secretin injection test

Since gastrinoma is likely to develop in multiple sites, we should pay special attention to the removal of all daughter tumors, as well as the main tumor, during surgery for this disease. In a 24-year-old woman with pituitary prolactinoma, multiple gastrinomas were detected in a limited area of the pancreaticoduodenal region by preoperative imaging techniques, selective arterial secretin injection (SASI) test, and intraoperative inspection using ultrasonography. A pancreatoduodenectomy was performed, and it was intraoperatively confirmed that the serum gastrin concentration in the portal vein had decreased from 753 to 83 pg/ml (normal,<120pg/ml). However, intraoperative SASI test for the remnant pancreas showed a positive response, which prompted us to perform a histological examination of frozen sections obtained from the body and tail of the pancreas, despite the normal appearance. Many islet cell microtumors were discovered, and the remnant pancreas was completely removed. Postoperativelly, all of the tumors were immunohistochemically proven to be microgastrinomas. The patient is still disease-free, 2 years after the surgery, with a serum gastrin level of less than 30pg/ml. This report stresses the role of the intraoperative SASI test in preventing residual microgastrinomas before closure of the abdomen.     

Morphology and immunohistochemically-defined endocrine function of pancreatic islet cell tumours

Thirty pancreatic islet cell tumours were histologically classified and analysed for their possible peptide hormone content using the immunohistoperoxidase method. Seven tumours contained insulin, six tumours contained gastrin and eight tumours contained glucagon. One tumour contained all three hormones. In the insulin and gastrin-containing tumours, the cells were usually arranged in solid nests of cells, with tubular and acinar formations in about half the cases. In the glucagon-containing tumours the cells were mainly arranged in anastomosing ribbons consisting of one of two layers of small cells. Most of the hormone-containing tumours were argyrophilic using Grimelius' silver reaction. All but one of the glucagon-containing tumours were incidental findings at autopsy. About half of the other tumours had metastasized. It is concluded that a relation exists between the histological pattern of growth and immunohistochemically defined endocrine function of pancreatic islet cell tumours.     

Ultrastructural and Immunocytochemical Study of a Primary Gastrinoma of the Liver

A primary hepatic gastrinoma found in a 13-year-old boy was studied by light microscopy, immunohistochemistry, electron microscopy, and immunoelectron microscopy. Results were consistent with a neuroendocrine neoplasm with abundant gastrin-immunoreactive cells. Unlike all previously reported cases of primary hepatic neuroendocrine tumors, which have been endocrinologically asymptomatic, the patient had a Zollinger-Ellison syndrome apparently cured by surgical resection of the tumor.     

Spatial profiling reveals tissue-specific neuro-immune interactions in gastroenteropancreatic neuroendocrine tumors

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous malignancies that arise from complex cellular interactions within the tissue microenvironment. Here, we sought to decipher tumor-derived signals from the surrounding microenvironment by applying digital spatial profiling (DSP) to hormone-secreting and non-functional GEP-NETs. By combining this approach with in vitro studies of human-derived organoids, we demonstrated the convergence of cell autonomous immune and pro-inflammatory proteins that suggests their role in neuroendocrine differentiation and tumorigenesis. DSP was used to evaluate the expression of 40 neural- and immune-related proteins in surgically resected duodenal and pancreatic NETs (n = 20) primarily consisting of gastrinomas (18/20). A total of 279 regions of interest were examined between tumors, adjacent normal and abnormal-appearing epithelium, and the surrounding stroma. The results were stratified by tissue type and multiple endocrine neoplasia I (MEN1) status, whereas protein expression was validated by immunohistochemistry (IHC). A tumor immune cell autonomous inflammatory signature was further evaluated by IHC and RNAscope, while functional pro-inflammatory signaling was confirmed using patient-derived duodenal organoids. Gastrin-secreting and non-functional pancreatic NETs showed a higher abundance of immune cell markers and immune infiltrate compared with duodenal gastrinomas. Compared with non-MEN1 tumors, MEN1 gastrinomas and preneoplastic lesions showed strong immune exclusion and upregulated expression of neuropathological proteins. Despite a paucity of immune cells, duodenal gastrinomas expressed the pro-inflammatory and pro-neural factor IL-17B. Treatment of human duodenal organoids with IL-17B activated NF-κB and STAT3 signaling and induced the expression of neuroendocrine markers. In conclusion, multiplexed spatial protein analysis identified tissue-specific neuro-immune signatures in GEP-NETs. Duodenal gastrinomas are characterized by an immunologically cold microenvironment that permits cellular reprogramming and neoplastic transformation of the preneoplastic epithelium. Moreover, duodenal gastrinomas cell autonomously express immune and pro-inflammatory factors, including tumor-derived IL-17B, that stimulate the neuroendocrine phenotype. © 2024 The Pathological Society of Great Britain and Ireland.