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Robert T Jensen - One of the best experts on this subject based on the ideXlab platform.
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surgery for Gastrinoma and insulinoma in multiple endocrine neoplasia type 1
Journal of The National Comprehensive Cancer Network, 2006Co-Authors: Jeffrey A. Norton, Tony D Fang, Robert T JensenAbstract:The surgical management of pancreatic endocrine tumors in patients with multiple endocrine neoplasia type 1 remains controversial. Gastrinoma and insulinoma are the 2 most common functional pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. Gastrinomas cause gastric acid hypersecretion and peptic ulcer disease that are best managed using proton pump inhibitors. Surgery to remove the Gastrinoma in patients with multiple endocrine neoplasia type 1 is seldom curative unless a more extensive Whipple pancreaticoduodenectomy is performed. Because the prognosis is excellent, aggressive resections such as a Whipple procedure are only indicated for large, locally metastatic, advanced tumors. Furthermore, surgery to remove imageable tumors that are 2 cm in diameter is associated with excellent outcomes and decreased probability of liver metastases. Because Gastrinomas are commonly multiple and most originate in the duodenum and develop lymph node metastases, the duodenum should be opened and all tumors and lymph nodes excised. Insulinomas cause hypoglycemia that results in neuroglycopenic symptoms. Medical management of the hypoglycemia is less effective than that of the gastric acid hypersecretion. Fortunately, the insulinoma is usually clearly identified using routine pancreatic imaging studies. There is a high likelihood of cure when the insulinoma is excised surgically. However, recurrent hypoglycemia may occur, and careful follow-up is indicated.
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surgery increases survival in patients with Gastrinoma
Annals of Surgery, 2006Co-Authors: Jeffrey A. Norton, Douglas L Fraker, David Venzon, Fathia Gibril, H R Alexander, David J Liewehr, Robert T JensenAbstract:The role of routine surgical exploration for Gastrinoma resection has remained controversial since almost the initial description of this syndrome in 1955 by Zollinger and Ellison.1 Initially, the controversy was between whether to only perform a total gastrectomy or whether attempted tumor resection was an alternative either alone or combined with a total gastrectomy or a lesser acid-reducing procedure.2–4 With the development of effective gastric antisecretory drugs first with histamine H2 antagonists in the 1970s and 1980s and later proton pump inhibitors (PPIs) the nature of the debate has changed; however, the controversy has only increased.5–9 The nature of the debate changed to whether medical treatment alone should be carried out or whether surgery for Gastrinoma resection should be considered in patients with potentially resectable disease for all such patients or a subset.5–8 The controversy not only continued but increased because medical therapy is highly effective,7,9,10 in many patients over the short-term the tumor pursues a benign course,7,11 and until recently the long-term natural history of Gastrinomas or the ability to cure these patients was largely unclear.12 Even though recently the natural history has been better defined, and it clearly established that an increasing proportion of these patients are dying from the malignant nature of the Gastrinoma,13,14 as well as that up to 40% of patients can be cured long-term,8,12,15–17 the place of routine surgical resection for possible cure still remains controversial.7,18 This has occurred in large part because no study has demonstrated that routine surgical exploration with Gastrinoma resection leads to increased survival. A previous study by us in 199419 showed that routine surgery decreased the rate of development of liver metastases, the most important prognostic factor for survival in most studies;13,14 however, the follow-up duration and number of patients were not sufficient to show an effect on survival. We now report our experience with a larger group of patients (n = 160) who were followed for a mean of 12 years after surgery. These patients' survival is compared with a nonsurgical group (n = 35) who had potentially resectable disease but did not undergo surgery for a variety of reasons; however, they did not differ from the surgical group in clinical, laboratory features or imaging results in initial evaluations.
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current surgical management of zollinger ellison syndrome zes in patients without multiple endocrine neoplasia type 1 men1
Surgical Oncology-oxford, 2003Co-Authors: Jeffrey A. Norton, Robert T JensenAbstract:Abstract The role of surgery in the management of patients with sporadic (not part of multiple endocrine neoplasia type 1) Zollinger–Ellison syndrome (ZES) is controversial. In this setting, 60–90% of Gastrinomas are malignant and medical therapy can control the gastric acid hypersecretion in virtually every patient. Therefore, the progression of tumor is the major determinant of survival. Surgery will cure approximately one-third of patients with sporadic ZES. It will decrease the development of liver metastases and may improve survival. Somatostatin receptor scintigraphy is the best preoperative localization study. Its results are as good as all other imaging studies combined. Operative techniques should always include duodenotomy (opening the duodenum) and meticulous dissection of lymph nodes in the Gastrinoma triangle, because duodenal primary tumors are often missed and lymph node primary tumors or metastases are common. Postoperative evaluation should include secretin test because it is the most sensitive method to document cure and detect tumor recurrence.
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management and outcome of patients with sporadic Gastrinoma arising in the duodenum
Annals of Surgery, 2003Co-Authors: Theresa G Zogakis, Robert T Jensen, Jeffrey A. Norton, Fathia Gibril, Steven K Libutti, Donald E White, Richard H AlexanderAbstract:Zollinger Ellison Syndrome (ZES) is characterized by hypersecretion of gastrin from a neuroendocrine tumor resulting in profound gastric acid hypersecretion and a spectrum of clinical presentations including symptoms of refractory peptic ulcer disease, severe diarrhea, or intestinal perforation.1 In the past, surgical intervention consisted mainly of palliative gastrectomy to prevent the morbid consequences associated with uncontrolled gastric acid hypersecretion. With improvement in medical management using proton pump inhibitors, gastric acid hypersecretion can be effectively controlled in 100% of individuals in most series,2,3 which has effectively eliminated the need for emergent or palliative surgical intervention in patients diagnosed with the condition. Currently, surgical management is directed towards identification and resection of the primary tumor and regional metastases to lymph nodes or liver to prevent malignant progression of disease. In addition, cure as defined as 10-year biochemically confirmed disease-free survival can be achieved in 34% of patients with sporadic Gastrinoma undergoing resection with curative intent.4 Primary duodenal Gastrinomas are now recognized to be a more common etiology of sporadic ZES than previously thought and the use of routine duodenotomy during surgical exploration has resulted in improved identification and resection of these frequently very small primary tumors.5–7 Our institution has previously reported that small primary duodenal Gastrinomas are associated with lymph node metastases in over 50% of individuals at operation,6 but the long-term outcome of patients with primary duodenal tumors and the significance of associated lymph node metastases are not known. The current study was undertaken to characterize our current results for patients who have sporadic Gastrinomas arising in the duodenum who underwent resection with curative intent. Primary tumor size and location, the frequency and location of associated lymph node metastases, and overall and disease-free survival were analyzed.
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possible primary lymph node Gastrinoma occurrence natural history and predictive factors a prospective study
Annals of Surgery, 2003Co-Authors: Jeffrey A. Norton, Douglas L Fraker, Richard H Alexander, David Venzon, Fathia Gibril, Robert T JensenAbstract:The existence of primary lymph node (LN) Gastrinomas is controversial. 1–9 Even though a literature review 1 in 1994 identified 63 cases of apparent lymph node primary Gastrinoma, their existence and, if they occur, their characteristics remain unclear. This has occurred because most reports are case studies, follow-up is limited, and surveillance of disease activity postresection is often not systematically done. Furthermore, recent studies show that a secretin provocative test is essential to rule out recurrence postresection, especially in patients with normal fasting serum levels of gastrin, 10,11 and this was frequently not done. Therefore, continued disease-free status after only removal of an LN Gastrinoma, a criterion for diagnosing primary LN tumors, was often not fulfilled. 12 To address the issue of the possible existence of lymph node primary Gastrinoma and their characteristics, we analyzed our results in a large series of patients with possible LN primaries who were found in our prospective study of patients with Zollinger-Ellison syndrome (ZES) undergoing surgery for potential cure.
Jeffrey A. Norton - One of the best experts on this subject based on the ideXlab platform.
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current management of the zollinger ellison syndrome
Advances in Surgery, 2013Co-Authors: Geoffrey W Krampitz, Jeffrey A. NortonAbstract:Abstract In summary, ZES is a syndrome caused by Gastrinoma, usually located within the Gastrinoma triangle and associated with symptoms of peptic ulcer disease, GERD, and diarrhea. The diagnosis of ZES is made by measuring fasting levels of serum gastrin, BAO, and the secretin stimulation test. Because of the high association of ZES and MEN1, HPT must be excluded by obtaining a serum calcium and parathyroid hormone level. Treatment of ZES consists of medical control of symptoms with PPIs and evaluation for potentially curative surgical intervention. Noninvasive imaging studies including SRS, CT, and MRI should be performed initially to evaluate for metastases and identify resectable disease. Invasive imaging modalities such as EUS may be performed to further evaluate primary tumors. IOUS, palpation, and duodenotomy are used for intraoperative localization of Gastrinomas. In patients with MEN1, surgical resection should be pursued only if there is an identifiable tumor larger than 2 cm and after surgery for the primary hyperparathyroidism (3 1/2-gland parathyroidectomy). All patients with resectable localized sporadic Gastrinoma should undergo surgical exploration, even those with biochemical evidence but negative imaging studies. Tumor is most commonly found in the duodenum, and the cure rate is high. In patients with liver metastases, surgery should be considered if all identifiable tumor can be safely removed. A multidisciplinary approach including surgical and nonsurgical therapies should be taken in patients with advanced disease.
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surgery for Gastrinoma and insulinoma in multiple endocrine neoplasia type 1
Journal of The National Comprehensive Cancer Network, 2006Co-Authors: Jeffrey A. Norton, Tony D Fang, Robert T JensenAbstract:The surgical management of pancreatic endocrine tumors in patients with multiple endocrine neoplasia type 1 remains controversial. Gastrinoma and insulinoma are the 2 most common functional pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. Gastrinomas cause gastric acid hypersecretion and peptic ulcer disease that are best managed using proton pump inhibitors. Surgery to remove the Gastrinoma in patients with multiple endocrine neoplasia type 1 is seldom curative unless a more extensive Whipple pancreaticoduodenectomy is performed. Because the prognosis is excellent, aggressive resections such as a Whipple procedure are only indicated for large, locally metastatic, advanced tumors. Furthermore, surgery to remove imageable tumors that are 2 cm in diameter is associated with excellent outcomes and decreased probability of liver metastases. Because Gastrinomas are commonly multiple and most originate in the duodenum and develop lymph node metastases, the duodenum should be opened and all tumors and lymph nodes excised. Insulinomas cause hypoglycemia that results in neuroglycopenic symptoms. Medical management of the hypoglycemia is less effective than that of the gastric acid hypersecretion. Fortunately, the insulinoma is usually clearly identified using routine pancreatic imaging studies. There is a high likelihood of cure when the insulinoma is excised surgically. However, recurrent hypoglycemia may occur, and careful follow-up is indicated.
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surgery increases survival in patients with Gastrinoma
Annals of Surgery, 2006Co-Authors: Jeffrey A. Norton, Douglas L Fraker, David Venzon, Fathia Gibril, H R Alexander, David J Liewehr, Robert T JensenAbstract:The role of routine surgical exploration for Gastrinoma resection has remained controversial since almost the initial description of this syndrome in 1955 by Zollinger and Ellison.1 Initially, the controversy was between whether to only perform a total gastrectomy or whether attempted tumor resection was an alternative either alone or combined with a total gastrectomy or a lesser acid-reducing procedure.2–4 With the development of effective gastric antisecretory drugs first with histamine H2 antagonists in the 1970s and 1980s and later proton pump inhibitors (PPIs) the nature of the debate has changed; however, the controversy has only increased.5–9 The nature of the debate changed to whether medical treatment alone should be carried out or whether surgery for Gastrinoma resection should be considered in patients with potentially resectable disease for all such patients or a subset.5–8 The controversy not only continued but increased because medical therapy is highly effective,7,9,10 in many patients over the short-term the tumor pursues a benign course,7,11 and until recently the long-term natural history of Gastrinomas or the ability to cure these patients was largely unclear.12 Even though recently the natural history has been better defined, and it clearly established that an increasing proportion of these patients are dying from the malignant nature of the Gastrinoma,13,14 as well as that up to 40% of patients can be cured long-term,8,12,15–17 the place of routine surgical resection for possible cure still remains controversial.7,18 This has occurred in large part because no study has demonstrated that routine surgical exploration with Gastrinoma resection leads to increased survival. A previous study by us in 199419 showed that routine surgery decreased the rate of development of liver metastases, the most important prognostic factor for survival in most studies;13,14 however, the follow-up duration and number of patients were not sufficient to show an effect on survival. We now report our experience with a larger group of patients (n = 160) who were followed for a mean of 12 years after surgery. These patients' survival is compared with a nonsurgical group (n = 35) who had potentially resectable disease but did not undergo surgery for a variety of reasons; however, they did not differ from the surgical group in clinical, laboratory features or imaging results in initial evaluations.
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surgery and prognosis of duodenal Gastrinoma as a duodenal neuroendocrine tumor
Best Practice & Research in Clinical Gastroenterology, 2005Co-Authors: Jeffrey A. NortonAbstract:It has become increasingly clear that duodenal Gastrinomas are the most common cause of Zollinger-Ellison syndrome (ZES). However, attempts to find these tumors before and during surgery for ZES have had limited success until duodenotomy (opening the duodenum) was described. The routine use of duodenotomy in patients with non-familial Gastrinoma increases the number of duodenal tumors found, and the immediate and long-term cure-rate. The increase in cure-rate appears to be secondary to increased detection of small, previously undetectable duodenal Gastrinomas. Duodenotomy detects small tumors (<1 cm) in the proximal duodenum. It does not detect more duodenal Gastrinomas per patient, nor does it detect tumors in unusual duodenal locations. Duodenotomy decreases the death-rate associated with these tumors. However, it has not affected the rate of development of liver metastases. Duodenotomy is a critical method to find duodenal Gastrinomas. It should be routinely performed in all surgery to find and remove Gastrinoma for cure of ZES.
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surgical treatment and prognosis of Gastrinoma
Best Practice & Research in Clinical Gastroenterology, 2005Co-Authors: Jeffrey A. NortonAbstract:Zollinger–Ellison syndrome (ZES) is a clinical syndrome with severe peptic ulcer disease and diarrhea caused by gastric acid hypersecretion secondary to a neuroendocrine tumour that secretes excessive amounts of the hormone gastrin (Gastrinoma). Gastrinomas occur in a familial and a sporadic form. Patients with Gastrinoma in the familial setting of Multiple Endocrine Neoplasia type 1 (MEN-1) are seldom, if ever, cured of Zollinger–Ellison syndrome by the current non-Whipple operations to remove duodenal and pancreatic Gastrinoma. Surgery is currently used in these patients to deal with the malignant nature of pancreatic or duodenal neuroendocrine tumours. Malignant potential is best determined by tumour size. Tumours that are greater than 2cm in size should be excised. In the sporadic setting, cure occurs in a significant proportion of patients (50%) by surgical resection of Gastrinoma. Duodenotomy has improved both the tumour detection rate and the cure rate and should be routinely done. Whipple pancreaticoduodenectomy results in the highest probability of cure in both sporadic and MEN-1 Gastrinoma patients as it removes the entire Gastrinoma triangle. However, the excellent long-term survival of these patients with lesser operations and the increased operative mortality and long-term morbidity of Whipple make its current role unclear until further studies are done.
Masayuki Imamura - One of the best experts on this subject based on the ideXlab platform.
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a primary hepatic Gastrinoma accompanied by hyperplasia of multi nodular brunner s glands
Surgical Case Reports, 2017Co-Authors: Takaomi Hagi, Izumi Komoto, Yohei Hosoda, Shinji Uemoto, Susumu Hijioka, Yoshiro Taki, Kazuhiro Nishiyama, Masayuki ImamuraAbstract:Primary hepatic Gastrinoma causing severe ulcerogenic syndrome is extremely rare. Herein, we report a case of primary hepatic Gastrinoma accompanied by hyperplasia of multi-nodular Brunner’s glands in a patient who instead, preoperatively, was suspected of having multiple duodenal Gastrinomas and hepatic metastasis. A 57-year-old woman consulted a clinic complaining of melena, intermittent abdominal pain, diarrhea, and vomiting which had persisted for about 3 years. Six months before her presentation, she underwent segmental resection of the jejunum for acute peritonitis due to the spontaneous jejunal perforation. A blood test revealed that her serum immunoreactive gastrin (IRG) level was 12,037 pg/mL. Subsequently, she was transferred to our hospital. On computed tomography (CT), a hypervascular tumor of 23 mm in the segment 5 (S5) region of the liver was visualized. A selective arterial secretagogue injection test (SASI test) was performed twice. The first SASI test revealed that the hepatic tumor was a Gastrinoma, and there was no Gastrinoma in the duodeno-pancreatic region. Additionally, somatostatin receptor scintigraphy only visualized the tumor in the liver. However, the second SASI test, which was performed during the administration of a proton pump inhibitor and a somatostatin analog (octreotide acetate), revealed that there may have been Gastrinomas existing not only in the liver but also in the upper part of the duodenum or the head of the pancreas. Duodenal endoscopy revealed multiple submucosal tumors in the first and the second portion of the duodenum, although a pathological examination of biopsied specimens obtained from the duodenal lesions was negative for malignant cells. Multiple endocrine neoplasia type 1 (MEN1) was excluded from her family history, and serum levels of both intact parathyroid hormone (iPTH) and calcium were within normal ranges. An anterior segmentectomy of the liver and pancreas-preserving total duodenectomy were performed on September 9, 2013. Postoperatively, her serum immunoreactive gastrin level decreased to less than 50 pg/mL. Pathological study of the resected specimens revealed a Gastrinoma in the liver, but no Gastrinoma in the duodenum. Interestingly, the duodenal submucosal tumor-like lesions were hyperplastic Brunner’s glands. Postoperatively, she has been well without recurrence of hypergastrinemia for 4 years. We report a case of primary hepatic Gastrinoma in a patient who has been cured for 4 years postoperatively. The diagnosis was somewhat difficult due to the coexisting, multiple hyperplastic Brunner’s glands of the duodenum mimicking the submucosal neuroendocrine tumors, which might have developed due to long-term hypergastrinemia.
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A primary hepatic Gastrinoma accompanied by hyperplasia of multi-nodular Brunner’s glands
SpringerOpen, 2017Co-Authors: Takaomi Hagi, Izumi Komoto, Yohei Hosoda, Shinji Uemoto, Susumu Hijioka, Yoshiro Taki, Kazuhiro Nishiyama, Masayuki ImamuraAbstract:Abstract Background Primary hepatic Gastrinoma causing severe ulcerogenic syndrome is extremely rare. Herein, we report a case of primary hepatic Gastrinoma accompanied by hyperplasia of multi-nodular Brunner’s glands in a patient who instead, preoperatively, was suspected of having multiple duodenal Gastrinomas and hepatic metastasis. Case presentation A 57-year-old woman consulted a clinic complaining of melena, intermittent abdominal pain, diarrhea, and vomiting which had persisted for about 3 years. Six months before her presentation, she underwent segmental resection of the jejunum for acute peritonitis due to the spontaneous jejunal perforation. A blood test revealed that her serum immunoreactive gastrin (IRG) level was 12,037 pg/mL. Subsequently, she was transferred to our hospital. On computed tomography (CT), a hypervascular tumor of 23 mm in the segment 5 (S5) region of the liver was visualized. A selective arterial secretagogue injection test (SASI test) was performed twice. The first SASI test revealed that the hepatic tumor was a Gastrinoma, and there was no Gastrinoma in the duodeno-pancreatic region. Additionally, somatostatin receptor scintigraphy only visualized the tumor in the liver. However, the second SASI test, which was performed during the administration of a proton pump inhibitor and a somatostatin analog (octreotide acetate), revealed that there may have been Gastrinomas existing not only in the liver but also in the upper part of the duodenum or the head of the pancreas. Duodenal endoscopy revealed multiple submucosal tumors in the first and the second portion of the duodenum, although a pathological examination of biopsied specimens obtained from the duodenal lesions was negative for malignant cells. Multiple endocrine neoplasia type 1 (MEN1) was excluded from her family history, and serum levels of both intact parathyroid hormone (iPTH) and calcium were within normal ranges. An anterior segmentectomy of the liver and pancreas-preserving total duodenectomy were performed on September 9, 2013. Postoperatively, her serum immunoreactive gastrin level decreased to less than 50 pg/mL. Pathological study of the resected specimens revealed a Gastrinoma in the liver, but no Gastrinoma in the duodenum. Interestingly, the duodenal submucosal tumor-like lesions were hyperplastic Brunner’s glands. Postoperatively, she has been well without recurrence of hypergastrinemia for 4 years. Conclusion We report a case of primary hepatic Gastrinoma in a patient who has been cured for 4 years postoperatively. The diagnosis was somewhat difficult due to the coexisting, multiple hyperplastic Brunner’s glands of the duodenum mimicking the submucosal neuroendocrine tumors, which might have developed due to long-term hypergastrinemia
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biochemically curative surgery for Gastrinoma in multiple endocrine neoplasia type 1 patients
World Journal of Gastroenterology, 2011Co-Authors: Masayuki Imamura, Izumi Komoto, Shuichi Ota, Takuya Hiratsuka, Shinji Kosugi, Ryuichiro Doi, Masaaki Awane, Naoya InoueAbstract:AIM: To search for the optimal surgery for Gastrinoma and duodenopancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. METHODS: Sixteen patients with genetically confirmed multiple endocrine neoplasia type 1 (MEN 1) and Zollinger-Ellison syndrome (ZES) underwent resection of both Gastrinomas and duodenopancreatic neuroendocrine tumors (NETs) between 1991 and 2009. For localization of Gastrinoma, selective arterial secretagogue injection test (SASI test) with secretin or calcium solution was performed as well as somatostatin receptor scintigraphy (SRS) and other imaging methods such as computed tomography (CT) or magnetic resonance imaging (MRI). The modus of surgery for Gastrinoma has been changed over time, searching for the optimal surgery: pancreaticoduodenectomy (PD) was first performed guided by localization with the SAST test, then local resection of duodenal Gastrinomas with dissection of regional lymph nodes (LR), and recently pancreas-preserving total duodenectomy (PPTD) has been performed for multiple duodenal Gastrinomas. RESULTS: Among various types of preoperative localizing methods for Gastrinoma, the SASI test was the most useful method. Imaging methods such as SRS or CT made it essentially impossible to differentiate functioning Gastrinoma among various kinds of NETs. However, recent imaging methods including SRS or CT were useful for detecting both distant metastases and ectopic NETs; therefore they are indispensable for staging of NETs. Biochemical cure of Gastrinoma was achieved in 14 of 16 patients (87.5%); that is, 100% in 3 patients who underwent PD, 100% in 6 patients who underwent LR (although in 2 patients (33.3%) second LR was performed for recurrence of duodenal Gastrinoma), and 71.4% in 7 patients who underwent PPTD. Pancreatic NETs more than 1 cm in diameter were resected either by distal pancreatectomy or enucleations, and no hepatic metastases have developed postoperatively. Pathological study of the resected specimens revealed co-existence of pancreatic Gastrinoma with duodenal Gastrinoma in 2 of 16 patients (13%), and G cell hyperplasia and/or microGastrinoma in the duodenal Brunner’s gland was revealed in all of 7 duodenal specimens after PPTD. CONCLUSION: Aggressive resection surgery based on accurate localization with the SASI test was useful for biochemical cure of Gastrinoma in patients with MEN 1.
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Changing Treatment Strategy for Gastrinoma in Patients with Zollinger-Ellison Syndrome
World Journal of Surgery, 2006Co-Authors: Masayuki Imamura, Izumi KomotoAbstract:We overviewed the recent development of curative surgery for Gastrinoma that has been rapidly improved since the development of new localization techniques, especially the selective arterial secretagogue injection test (SASI test) and somatostatin receptor scintigraphy (SRS). A number of new pathological findings of Gastrinomas in patients with Zollinger-Ellison syndrome have been accumulated in accordance with the increase of curative resection of Gastrinomas, and these new findings also have contributed to the progress of the treatment strategy for grastrinomas.
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intravenous calcium injection test is a novel complementary procedure in differential diagnosis for Gastrinoma
World Journal of Surgery, 2002Co-Authors: Michihiko Wada, Izumi Komoto, Ryuichiro Doi, Masayuki ImamuraAbstract:The current study evaluated efficacy of the intravenous calcium injection test as a new diagnostic approach to clarify the existence of Gastrinoma, which often goes undetected with routine testing. Twenty-six patients with hypergastrinemia were studied. For the calcium injection test, blood samples were taken from 12 patients with hypergastrinemia (HG), and three healthy volunteers, and one patient with nonfunctioning endocrine tumor in the pancreas (control). We compared results of the calcium injection test with those of the secretin test and the selective arterial secretagogue injection (SASI) test. The SASI test with secretin was performed in 24 of 26 patients with hypergastrinemia, including 22 of 24 patients with Zollinger-Ellison syndrome (ZES). Accuracy in the diagnosis of tumor localization by the SASI test was 95% (21 of 22) in ZES patients. The secretin test was negative in 3 of 21 patients with ZES (14%). Either the secretin test or the SASI test was positive in 22 of 23 patients (96%). The calcium injection test was administered to 12 patients in the HG group and 4 controls. The HG group showed significantly higher serum gastrin levels than those of the control group in the calcium injection test. Eight of 10 ZES patients (80%) had a positive calcium injection test. We could diagnose Gastrinomas in 100% of ZES patients by either the calcium injection test or the secretin test. We have thus confirmed the efficacy of the intravenous calcium injection test in the diagnosis of Gastrinoma. The calcium injection test could become an adjunct in the diagnosis of Gastrinoma, which often goes undetected with routine testing.
Izumi Komoto - One of the best experts on this subject based on the ideXlab platform.
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a primary hepatic Gastrinoma accompanied by hyperplasia of multi nodular brunner s glands
Surgical Case Reports, 2017Co-Authors: Takaomi Hagi, Izumi Komoto, Yohei Hosoda, Shinji Uemoto, Susumu Hijioka, Yoshiro Taki, Kazuhiro Nishiyama, Masayuki ImamuraAbstract:Primary hepatic Gastrinoma causing severe ulcerogenic syndrome is extremely rare. Herein, we report a case of primary hepatic Gastrinoma accompanied by hyperplasia of multi-nodular Brunner’s glands in a patient who instead, preoperatively, was suspected of having multiple duodenal Gastrinomas and hepatic metastasis. A 57-year-old woman consulted a clinic complaining of melena, intermittent abdominal pain, diarrhea, and vomiting which had persisted for about 3 years. Six months before her presentation, she underwent segmental resection of the jejunum for acute peritonitis due to the spontaneous jejunal perforation. A blood test revealed that her serum immunoreactive gastrin (IRG) level was 12,037 pg/mL. Subsequently, she was transferred to our hospital. On computed tomography (CT), a hypervascular tumor of 23 mm in the segment 5 (S5) region of the liver was visualized. A selective arterial secretagogue injection test (SASI test) was performed twice. The first SASI test revealed that the hepatic tumor was a Gastrinoma, and there was no Gastrinoma in the duodeno-pancreatic region. Additionally, somatostatin receptor scintigraphy only visualized the tumor in the liver. However, the second SASI test, which was performed during the administration of a proton pump inhibitor and a somatostatin analog (octreotide acetate), revealed that there may have been Gastrinomas existing not only in the liver but also in the upper part of the duodenum or the head of the pancreas. Duodenal endoscopy revealed multiple submucosal tumors in the first and the second portion of the duodenum, although a pathological examination of biopsied specimens obtained from the duodenal lesions was negative for malignant cells. Multiple endocrine neoplasia type 1 (MEN1) was excluded from her family history, and serum levels of both intact parathyroid hormone (iPTH) and calcium were within normal ranges. An anterior segmentectomy of the liver and pancreas-preserving total duodenectomy were performed on September 9, 2013. Postoperatively, her serum immunoreactive gastrin level decreased to less than 50 pg/mL. Pathological study of the resected specimens revealed a Gastrinoma in the liver, but no Gastrinoma in the duodenum. Interestingly, the duodenal submucosal tumor-like lesions were hyperplastic Brunner’s glands. Postoperatively, she has been well without recurrence of hypergastrinemia for 4 years. We report a case of primary hepatic Gastrinoma in a patient who has been cured for 4 years postoperatively. The diagnosis was somewhat difficult due to the coexisting, multiple hyperplastic Brunner’s glands of the duodenum mimicking the submucosal neuroendocrine tumors, which might have developed due to long-term hypergastrinemia.
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A primary hepatic Gastrinoma accompanied by hyperplasia of multi-nodular Brunner’s glands
SpringerOpen, 2017Co-Authors: Takaomi Hagi, Izumi Komoto, Yohei Hosoda, Shinji Uemoto, Susumu Hijioka, Yoshiro Taki, Kazuhiro Nishiyama, Masayuki ImamuraAbstract:Abstract Background Primary hepatic Gastrinoma causing severe ulcerogenic syndrome is extremely rare. Herein, we report a case of primary hepatic Gastrinoma accompanied by hyperplasia of multi-nodular Brunner’s glands in a patient who instead, preoperatively, was suspected of having multiple duodenal Gastrinomas and hepatic metastasis. Case presentation A 57-year-old woman consulted a clinic complaining of melena, intermittent abdominal pain, diarrhea, and vomiting which had persisted for about 3 years. Six months before her presentation, she underwent segmental resection of the jejunum for acute peritonitis due to the spontaneous jejunal perforation. A blood test revealed that her serum immunoreactive gastrin (IRG) level was 12,037 pg/mL. Subsequently, she was transferred to our hospital. On computed tomography (CT), a hypervascular tumor of 23 mm in the segment 5 (S5) region of the liver was visualized. A selective arterial secretagogue injection test (SASI test) was performed twice. The first SASI test revealed that the hepatic tumor was a Gastrinoma, and there was no Gastrinoma in the duodeno-pancreatic region. Additionally, somatostatin receptor scintigraphy only visualized the tumor in the liver. However, the second SASI test, which was performed during the administration of a proton pump inhibitor and a somatostatin analog (octreotide acetate), revealed that there may have been Gastrinomas existing not only in the liver but also in the upper part of the duodenum or the head of the pancreas. Duodenal endoscopy revealed multiple submucosal tumors in the first and the second portion of the duodenum, although a pathological examination of biopsied specimens obtained from the duodenal lesions was negative for malignant cells. Multiple endocrine neoplasia type 1 (MEN1) was excluded from her family history, and serum levels of both intact parathyroid hormone (iPTH) and calcium were within normal ranges. An anterior segmentectomy of the liver and pancreas-preserving total duodenectomy were performed on September 9, 2013. Postoperatively, her serum immunoreactive gastrin level decreased to less than 50 pg/mL. Pathological study of the resected specimens revealed a Gastrinoma in the liver, but no Gastrinoma in the duodenum. Interestingly, the duodenal submucosal tumor-like lesions were hyperplastic Brunner’s glands. Postoperatively, she has been well without recurrence of hypergastrinemia for 4 years. Conclusion We report a case of primary hepatic Gastrinoma in a patient who has been cured for 4 years postoperatively. The diagnosis was somewhat difficult due to the coexisting, multiple hyperplastic Brunner’s glands of the duodenum mimicking the submucosal neuroendocrine tumors, which might have developed due to long-term hypergastrinemia
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biochemically curative surgery for Gastrinoma in multiple endocrine neoplasia type 1 patients
World Journal of Gastroenterology, 2011Co-Authors: Masayuki Imamura, Izumi Komoto, Shuichi Ota, Takuya Hiratsuka, Shinji Kosugi, Ryuichiro Doi, Masaaki Awane, Naoya InoueAbstract:AIM: To search for the optimal surgery for Gastrinoma and duodenopancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. METHODS: Sixteen patients with genetically confirmed multiple endocrine neoplasia type 1 (MEN 1) and Zollinger-Ellison syndrome (ZES) underwent resection of both Gastrinomas and duodenopancreatic neuroendocrine tumors (NETs) between 1991 and 2009. For localization of Gastrinoma, selective arterial secretagogue injection test (SASI test) with secretin or calcium solution was performed as well as somatostatin receptor scintigraphy (SRS) and other imaging methods such as computed tomography (CT) or magnetic resonance imaging (MRI). The modus of surgery for Gastrinoma has been changed over time, searching for the optimal surgery: pancreaticoduodenectomy (PD) was first performed guided by localization with the SAST test, then local resection of duodenal Gastrinomas with dissection of regional lymph nodes (LR), and recently pancreas-preserving total duodenectomy (PPTD) has been performed for multiple duodenal Gastrinomas. RESULTS: Among various types of preoperative localizing methods for Gastrinoma, the SASI test was the most useful method. Imaging methods such as SRS or CT made it essentially impossible to differentiate functioning Gastrinoma among various kinds of NETs. However, recent imaging methods including SRS or CT were useful for detecting both distant metastases and ectopic NETs; therefore they are indispensable for staging of NETs. Biochemical cure of Gastrinoma was achieved in 14 of 16 patients (87.5%); that is, 100% in 3 patients who underwent PD, 100% in 6 patients who underwent LR (although in 2 patients (33.3%) second LR was performed for recurrence of duodenal Gastrinoma), and 71.4% in 7 patients who underwent PPTD. Pancreatic NETs more than 1 cm in diameter were resected either by distal pancreatectomy or enucleations, and no hepatic metastases have developed postoperatively. Pathological study of the resected specimens revealed co-existence of pancreatic Gastrinoma with duodenal Gastrinoma in 2 of 16 patients (13%), and G cell hyperplasia and/or microGastrinoma in the duodenal Brunner’s gland was revealed in all of 7 duodenal specimens after PPTD. CONCLUSION: Aggressive resection surgery based on accurate localization with the SASI test was useful for biochemical cure of Gastrinoma in patients with MEN 1.
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Changing Treatment Strategy for Gastrinoma in Patients with Zollinger-Ellison Syndrome
World Journal of Surgery, 2006Co-Authors: Masayuki Imamura, Izumi KomotoAbstract:We overviewed the recent development of curative surgery for Gastrinoma that has been rapidly improved since the development of new localization techniques, especially the selective arterial secretagogue injection test (SASI test) and somatostatin receptor scintigraphy (SRS). A number of new pathological findings of Gastrinomas in patients with Zollinger-Ellison syndrome have been accumulated in accordance with the increase of curative resection of Gastrinomas, and these new findings also have contributed to the progress of the treatment strategy for grastrinomas.
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intravenous calcium injection test is a novel complementary procedure in differential diagnosis for Gastrinoma
World Journal of Surgery, 2002Co-Authors: Michihiko Wada, Izumi Komoto, Ryuichiro Doi, Masayuki ImamuraAbstract:The current study evaluated efficacy of the intravenous calcium injection test as a new diagnostic approach to clarify the existence of Gastrinoma, which often goes undetected with routine testing. Twenty-six patients with hypergastrinemia were studied. For the calcium injection test, blood samples were taken from 12 patients with hypergastrinemia (HG), and three healthy volunteers, and one patient with nonfunctioning endocrine tumor in the pancreas (control). We compared results of the calcium injection test with those of the secretin test and the selective arterial secretagogue injection (SASI) test. The SASI test with secretin was performed in 24 of 26 patients with hypergastrinemia, including 22 of 24 patients with Zollinger-Ellison syndrome (ZES). Accuracy in the diagnosis of tumor localization by the SASI test was 95% (21 of 22) in ZES patients. The secretin test was negative in 3 of 21 patients with ZES (14%). Either the secretin test or the SASI test was positive in 22 of 23 patients (96%). The calcium injection test was administered to 12 patients in the HG group and 4 controls. The HG group showed significantly higher serum gastrin levels than those of the control group in the calcium injection test. Eight of 10 ZES patients (80%) had a positive calcium injection test. We could diagnose Gastrinomas in 100% of ZES patients by either the calcium injection test or the secretin test. We have thus confirmed the efficacy of the intravenous calcium injection test in the diagnosis of Gastrinoma. The calcium injection test could become an adjunct in the diagnosis of Gastrinoma, which often goes undetected with routine testing.
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surgery increases survival in patients with Gastrinoma
Annals of Surgery, 2006Co-Authors: Jeffrey A. Norton, Douglas L Fraker, David Venzon, Fathia Gibril, H R Alexander, David J Liewehr, Robert T JensenAbstract:The role of routine surgical exploration for Gastrinoma resection has remained controversial since almost the initial description of this syndrome in 1955 by Zollinger and Ellison.1 Initially, the controversy was between whether to only perform a total gastrectomy or whether attempted tumor resection was an alternative either alone or combined with a total gastrectomy or a lesser acid-reducing procedure.2–4 With the development of effective gastric antisecretory drugs first with histamine H2 antagonists in the 1970s and 1980s and later proton pump inhibitors (PPIs) the nature of the debate has changed; however, the controversy has only increased.5–9 The nature of the debate changed to whether medical treatment alone should be carried out or whether surgery for Gastrinoma resection should be considered in patients with potentially resectable disease for all such patients or a subset.5–8 The controversy not only continued but increased because medical therapy is highly effective,7,9,10 in many patients over the short-term the tumor pursues a benign course,7,11 and until recently the long-term natural history of Gastrinomas or the ability to cure these patients was largely unclear.12 Even though recently the natural history has been better defined, and it clearly established that an increasing proportion of these patients are dying from the malignant nature of the Gastrinoma,13,14 as well as that up to 40% of patients can be cured long-term,8,12,15–17 the place of routine surgical resection for possible cure still remains controversial.7,18 This has occurred in large part because no study has demonstrated that routine surgical exploration with Gastrinoma resection leads to increased survival. A previous study by us in 199419 showed that routine surgery decreased the rate of development of liver metastases, the most important prognostic factor for survival in most studies;13,14 however, the follow-up duration and number of patients were not sufficient to show an effect on survival. We now report our experience with a larger group of patients (n = 160) who were followed for a mean of 12 years after surgery. These patients' survival is compared with a nonsurgical group (n = 35) who had potentially resectable disease but did not undergo surgery for a variety of reasons; however, they did not differ from the surgical group in clinical, laboratory features or imaging results in initial evaluations.
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management and outcome of patients with sporadic Gastrinoma arising in the duodenum
Annals of Surgery, 2003Co-Authors: Theresa G Zogakis, Robert T Jensen, Jeffrey A. Norton, Fathia Gibril, Steven K Libutti, Donald E White, Richard H AlexanderAbstract:Zollinger Ellison Syndrome (ZES) is characterized by hypersecretion of gastrin from a neuroendocrine tumor resulting in profound gastric acid hypersecretion and a spectrum of clinical presentations including symptoms of refractory peptic ulcer disease, severe diarrhea, or intestinal perforation.1 In the past, surgical intervention consisted mainly of palliative gastrectomy to prevent the morbid consequences associated with uncontrolled gastric acid hypersecretion. With improvement in medical management using proton pump inhibitors, gastric acid hypersecretion can be effectively controlled in 100% of individuals in most series,2,3 which has effectively eliminated the need for emergent or palliative surgical intervention in patients diagnosed with the condition. Currently, surgical management is directed towards identification and resection of the primary tumor and regional metastases to lymph nodes or liver to prevent malignant progression of disease. In addition, cure as defined as 10-year biochemically confirmed disease-free survival can be achieved in 34% of patients with sporadic Gastrinoma undergoing resection with curative intent.4 Primary duodenal Gastrinomas are now recognized to be a more common etiology of sporadic ZES than previously thought and the use of routine duodenotomy during surgical exploration has resulted in improved identification and resection of these frequently very small primary tumors.5–7 Our institution has previously reported that small primary duodenal Gastrinomas are associated with lymph node metastases in over 50% of individuals at operation,6 but the long-term outcome of patients with primary duodenal tumors and the significance of associated lymph node metastases are not known. The current study was undertaken to characterize our current results for patients who have sporadic Gastrinomas arising in the duodenum who underwent resection with curative intent. Primary tumor size and location, the frequency and location of associated lymph node metastases, and overall and disease-free survival were analyzed.
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possible primary lymph node Gastrinoma occurrence natural history and predictive factors a prospective study
Annals of Surgery, 2003Co-Authors: Jeffrey A. Norton, Douglas L Fraker, Richard H Alexander, David Venzon, Fathia Gibril, Robert T JensenAbstract:The existence of primary lymph node (LN) Gastrinomas is controversial. 1–9 Even though a literature review 1 in 1994 identified 63 cases of apparent lymph node primary Gastrinoma, their existence and, if they occur, their characteristics remain unclear. This has occurred because most reports are case studies, follow-up is limited, and surveillance of disease activity postresection is often not systematically done. Furthermore, recent studies show that a secretin provocative test is essential to rule out recurrence postresection, especially in patients with normal fasting serum levels of gastrin, 10,11 and this was frequently not done. Therefore, continued disease-free status after only removal of an LN Gastrinoma, a criterion for diagnosing primary LN tumors, was often not fulfilled. 12 To address the issue of the possible existence of lymph node primary Gastrinoma and their characteristics, we analyzed our results in a large series of patients with possible LN primaries who were found in our prospective study of patients with Zollinger-Ellison syndrome (ZES) undergoing surgery for potential cure.
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does the widespread use of proton pump inhibitors mask complicate and or delay the diagnosis of zollinger ellison syndrome
Alimentary Pharmacology & Therapeutics, 2001Co-Authors: V D Corleto, David Venzon, Fathia Gibril, B Annibale, S Angeletti, Jose Serrano, Delle G Fave, Robert T JensenAbstract:Background: Proton pump inhibitors are potent acid suppressants which, at normal doses, can result in hypergastrinaemia in patients with idiopathic oesophageal reflux disease and in the control of symptoms in most patients with Gastrinomas. Therefore, their use could delay or mask the diagnosis of Gastrinoma. Aim: To investigate whether the widespread use of proton pump inhibitors masks or complicates the diagnosis of Gastrinoma. Subjects and methods: Data from two centres with different referral criteria for suspected Gastrinomas were analysed (Gastroenterology Unit, Rome, Italy and National Institutes of Health, Bethesda, MD, USA). The number of referrals and the number of new patients with Gastrinoma diagnosed in the years prior to the widespread use of proton pump inhibitors (1986–1992) were compared with the numbers since proton pump inhibitors became widely available (1993–1998). Results: The decrease in referral rate (P=0.0009) and the decrease in the annual rate of Gastrinoma diagnosis (P=0.0020) at both centres correlated with the increased use of proton pump inhibitors. At the Italian centre, there was a 62% decrease in annual referrals (P < 0.0001) in the post-proton pump inhibitor period, relative to the pre-proton pump inhibitor period, whereas there was an increase in the rate of referral of other gastrointestinal endocrine tumours. The number of new cases of Gastrinoma diagnosed decreased by 40%. At the US centre, the referral rate decreased by 28% (P=0.024) in the post-proton pump inhibitor period. There was also a 43% decrease in the number of new cases diagnosed annually in the post-proton pump inhibitor period (P=0.0012). There was a 2.6-fold increase in the post-proton pump inhibitor period in the percentage of referrals with a false diagnosis of Gastrinoma as the cause of hypergastrinaemia (P=0.0040). Conclusions: In both referral centres, less patients have been referred with a possible diagnosis of Gastrinoma and fewer new patients with Gastrinoma have been diagnosed since proton pump inhibitors became widely available. These data support the conclusion that, since proton pump inhibitors have been released, the diagnosis of Gastrinoma has been masked and will probably be delayed, with the result that patients with Gastrinoma will be diagnosed at more advanced stages in their disease course.
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surgical treatment of localized Gastrinoma within the liver a prospective study
Surgery, 1998Co-Authors: Jeffrey A. Norton, Douglas L Fraker, Richard H Alexander, John L Doppman, Gerard M Doherty, David Venzon, Fathia Gibril, Robert T JensenAbstract:Abstract Background: Studies demonstrate that liver metastases of Gastrinoma significantly reduce survival. Methods: Since 1982 we have prospectively studied 213 patients with Zollinger-Ellison syndrome. For this report the results of surgery for localized liver Gastrinoma were analyzed. Results: Zollinger-Ellison syndrome was diagnosed biochemically in all patients and acid output was controlled with medications. Imaging studies demonstrated liver Gastrinoma in 69 patients (32%). Fifty-two had diffuse unresectable disease, whereas 17 (10%) had localized disease. All patients with localized liver Gastrinoma and 2 patients with diffuse disease who needed surgery are the subject of this report. Major hepatic lobectomy was performed in 10 patients and wedge resections in 9. Three patients had apparent liver primary Gastrinomas and 16 had metastatic disease. Seventeen of 19 patients were able to have all identifiable Gastrinoma resected. Extrahepatic tumor was also removed at the same procedure. Extirpation of liver Gastrinoma required hepatic lobectomy in 10 patients and wedge resections in the others. Five-year survival was 85%. Five of 17 completely resected patients (29%) remained disease free. Conclusions: Resectable localized liver Gastrinoma is rare. Primary liver Gastrinomas can occur. Surgical resection of localized liver Gastrinoma provides a cure rate similar to that of extrahepatic Gastrinoma and an excellent long-term survival. (Surgery 1998;124:1145-52.)
