Arterial stimulation with simultaneous venous sampling for localizing insulinomas

Purpose: The present study aimed to assess the accuracies of arterial stimulation with simultaneous venous sampling(ASVS) in preoperative localization of insulinomas. Materials and Methods: A cohort consisting of 6 males and 14 females(median age, 48.5y; range, 28–62y) with pathologically proven insulinomas were included in this study. Selective angiographies were performed with the superior mesenteric artery(SMA), gastroduodenal artery(GDA), proximal splenic artery, and midsplenic artery in all individuals. Then ASVS procedures were followed after angiographies for these arteries. Clinical characteristics of the patient and the tumor number, location, and size were recorded. The accuracy of preoperative localization of insulinomas was tested. Results: A total of 22 tumors were identified by histopathological diagnosis. The mean size of the tumor was 1.40±0.60 cm. Five tumors were in the head/neck region and 17 in the body/tail region. ASVS accurately localized 17/20(85%) cases with only biochemical data and 19/20(95%) cases with biochemical data and angiography images. Variant pancreatic arterial anatomy was revealed in 2 false cases with inferior pancreatic artery replaced by the superior mesenteric artery. Conclusion: ASVS was highly accurate in localizing insulinomas and should be performed in most of the patients with suspected insulinomas before the operation.

Pancreatic insulinomas:laparoscopic management

Insulinomas are rare pancreatic neuroendocrine tumors that are most commonly benign,solitary,and intrapancreatic. Uncontrolled insulin overproduction from the tumor produces neurological and adrenergic symptoms of hypoglycemia. Biochemical diagnosis is confirmed by the presence of Whipple's triad,along with corroborating measurements of blood glucose,insulin,proinsulin,C-peptide,β-hydroxybutyrate,and negative tests for hypoglycemic agents during a supervised fasting period. This is accompanied by accurate preoperative localization using both invasive and non-invasive imaging modalities. Following this,careful preoperative planning is required,with the ensuing procedure being preferably carried out laparoscopically. An integral part of the laparoscopic approach is the application of laparoscopic intraoperative ultrasound,which is indispensable for accurate intraoperative localization of the lesion in the pancreatic region. The extent of laparoscopic resection is dependent on preoperative and intraoperative findings,but most commonly involves tumor enucleation or distal pancreatectomy. When performed in an experienced surgical unit,laparoscopic resection is associated with minimal mortality and excellent long-term cure rates. Furthermore,this approach confers equivalent safety and efficacy rates to open resection,while improving cosmesis and reducing hospital stay. As such,laparoscopic resection should be considered in all cases of benign insulinoma where adequate surgical expertise is available.

Pancreatic insulinomas: diagnosis and surgical treatment of 74 patients

Objective: To summarize retrospectively the experi- ence in diagnosis and surgical treatment of pancreatic insulinoma. Method: 74 patients who had been operated on and confirmed pathologically from July 1967 to July 2001 were enrolled. They were 37 men and 37 women, aged 41.91 years on average. Results: In all patients with typical Whipple's triad, the ratio of insulin to glucose was measured over 0.3 for at least one time. 52.70 % of the patients were once misdiagnosed, and only 20.27 % of them were correctly diagnosed in a year after onset of symp- toms. Their average course of the disease was 3.36 years. B-ultrasonography and endoscopic ultrasonog- raphy (EUS) showed a low positive rate for localiza- tion of insulinoma. CT and magnetic resonance ima- ging (MRI) could correctly detected 63.41% and 63.64 % of tumors respectively, in sharp contrast to a localization rate of 90 % for arterial stimulation and venous sampling (ASVS). Single insulinoma was ob- served in 66 patients (89.19 %), multiple insulinoma in 2 (2.70 %), hyperplasia in 4 (5.41%), and malig- nant insulinoma in 2 (2. 70%). Most (85. 29%) of the benign insnlinomas were less than 2 cm in diame- ter. Simple enucleation was the major operative pro- cedure for benign tumors. In 88. 52% of the pa- tients, glycemia increased to normal in 30 minutes after tumor excision, and in the remaining patients within 2 hours. 97. 26% of the patients experienced temporary hyperglycemia but recovered in a week. The major complications of insnlinoma included pan- creatic fistulae (27.27 %) and pancreatitis (5. 19 %). Conclusions: Better recognization of insulinoma and its rational examination are essential to early diagno- sis. CT can be first used for localization, otherwise ASVS is used. Surgery is the major choice for the treatment of insulinoma, but cautions should be taken to pancreatic fistulae after operation.

Risk factors for postoperative pancreatic fistula in patients with insulinomas:analysis of 292 consecutive cases

BACKGROUND: Pancreatic fistula (PF) remains the most challenging complication in pancreatic surgery, yet few published studies have focused on the risk factors for postoperative PF in patients undergoing surgery for insulinomas. METHODS: From January 1990 to February 2010, a total of 292 patients with insulinomas underwent surgery at Peking Union Medical College Hospital. Demographic data, intraoperative procedures, and postoperative data were collected. Particular attention was paid to variables associated with PF as defined by the International Study Group of Pancreatic Fistula (ISGPF). Univariate and multivariate analyses were used to identify possible risk factors for PP. RESULTS: PF was found in 132 (45.2%) patients, of whom 90 were classified into ISGPF grade A, 33 grade B, and 9 grade C. Multivariate analysis showed that male patients (OR=2.56; P=0.007) and operative time > 180 minutes (OR=3.756; P < 0.0001) were independent risk factors for clinical PF. Pancreatic resection with stapler was a protective factor for both total PF (OR=0.022; P=0.010) and clinical PF (OR=0.097; P=0.007). CONCLUSIONS: Male gender and operative time > 180 minutes were independent risk factors for clinical PF, while pancreatic resection with a stapler was a protective factor. Whether body mass index (BMI) and other variables during operation are risk factors of PF needs further study. (Hepatobiliary Pancreat Dis Int 2012;11:102-106)

Robotic versus laparoscopic surgery for sporadic benign insulinoma:Short-and long-term outcomes

Background:Minimally invasive surgery is the optimal treatment for insulinoma.The present study aimed to compare short-and long-term outcomes of laparoscopic and robotic surgery for sporadic benign insulinoma.Methods:A retrospective analysis of patients who underwent laparoscopic or robotic surgery for insulinoma at our center between September 2007 and December 2019 was conducted.The demographic,perioperative and postoperative follow-up results were compared between the laparoscopic and robotic groups.Results:A total of 85 patients were enrolled,including 36 with laparoscopic approach and 49 with robotic approach.Enucleation was the preferred surgical procedure.Fifty-nine patients(69.4%)underwent enucleation;among them,26 and 33 patients underwent laparoscopic and robotic surgery,respectively.Robotic enucleation had a lower conversion rate to laparotomy(0 vs.19.2%,P=0.013),shorter operative time(102.0 vs.145.5 min,P=0.008)and shorter postoperative hospital stay(6.0 vs.8.5 d,P=0.002)than laparoscopic enucleation.There were no differences between the groups in terms of intraoperative blood loss,the rates of postoperative pancreatic fistula and complications.After a median follow-up of 65 months,two patients in the laparoscopic group developed a functional recurrence and none of the patients in the robotic group had a recurrence.Conclusions:Robotic enucleation can reduce the conversion rate to laparotomy and shorten operative time,which might lead to a reduction in postoperative hospital stay.

Efficacy of Raw Corn Starch in Insulinoma-Related Hypoglycemia:A Promising Supportive Therapy

Objective To investigate the efficacy of raw corn starch(RCS)in clinical management of insulinoma-induced hypoglycemia.Methods We retrospectively collected clinical data of insulinoma patients who received RCS-supplemented diet preoperatively,and analyzed the therapeutic effects of the RCS intervention on blood glucose control,weight change,and its adverse events.Results The study population consisted of 24 cases of insulinoma patients,7 males and 17 females,aged 46.08±14.15 years.Before RCS-supplemented diet,all patients had frequent hypoglycemic episodes(2.51±3.88 times/week),concurrent with neuroglycopenia(in 83.3% of patients)and autonomic manifestations(in 75.0% of patients),with the median fasting blood glucose(FBG)of 2.70(interquartile range[IQR]:2.50-2.90)mmol/L.The patients'weight increased by 0.38(IQR:0.05-0.65)kg per month,with 8(33.3%)cases developing overweight and 7(29.2%)cases developing obesity.All patients maintained the RCS-supplemented diet until they underwent tumor resection(23 cases)and transarterial chemoembolization for liver metastases(1 case).For 19 patients receiving RCS throughout the day,the median FBG within one week of nutritional management was 4.30(IQR:3.30-5.70)mmol/L,which was a significant increase compared to pre-nutritional level[2.25(IQR:1.60-2.90)mmol/L;P<0.001].Of them,10 patients receiving RCS throughout the day for over four weeks had sustained improvement in FBG compared to pre-treatment[3.20(IQR:2.60-3.95)mmol/L vs.2.15(IQR:1.83-2.33)mmol/L;P<0.001].Five patients who received RCS only at night also had a significant increase in FBG within one week of nutritional management[3.50(IQR:2.50-3.65)mmol/L vs.2.20(IQR:1.80-2.60)mmol/L;P<0.001],but only one patient who continued to receive RCS for over four weeks did not have a significant improvement in FBG.No improvement in weight gain was observed upon RCS supplementation.Mild diarrhea(2 cases)and flatulence(1 case)occurred,and were relieved by reduction of RCS dose.Conclusion The RCS-supplemented diet is effective in controlling insulinoma-induced hypoglycemia.

Preoperative Localization of Insulinoma by Intra-arterial Spiral CT

Objective To evaluate the value of intra-arterial dynamic spiral CT on preoperative localization of insulinoma. Methods Two patients with insulinoma proved by operative pathology were preoperatively localized by intra-arterial dynamic spiral CT. Results In intra-arterial spiral CT, two small insulinomas (1.5–2.0 cm in diameter) demonstrated as a significantly high dense nodule 20 s later after initiation of injection of contrast medium. The course of high density lasted nearly 4 min. Conclusion Intra-arterial dynamic spiral CT could clearly detect small insulinoma, and might be one of most effective preoperative localization methods for small insulinoma. Key words insulinoma - anteriography - CT

Endoscopic ultrasound radiofrequency ablation of pancreatic insulinoma in elderly patients:Three case reports

BACKGROUND Endoscopic ultrasound(EUS)-guided radiofrequency ablation(RFA)has recently been proposed as a local treatment for functional pancreatic neuroendocrine neoplasms in patients unfit for surgery,in order to obtain clinical syndrome regression.Data on the safety and long-term effectiveness of this approach are scarce,and EUS-RFA procedures are not standardized.CASE SUMMARY The present case series reports 3 elderly patients with a pancreatic insulinoma and comorbidities,locally treated by EUS-guided RFA with clinical success in terms of hypoglycemic symptoms.RFA procedures were performed during deep sedation,under EUS control with a 19 G needle,an electrode 5-mm in size at a power of 30 W and multiple RFA applications during the same session in order to treat the whole area of the lesions.Immediate relief of symptoms was evident in 2 patients after the first EUS-RFA,while in the third patient a second endoscopic treatment was needed.All 3 patients are symptom-free without need of medications after 24 mo of follow-up with imaging follow-up showing no disease recurrence.A single adverse event of intraprocedural bleeding occurred,which was successfully treated endoscopically.CONCLUSION EUS-RFA represents an effective and safe alternative to surgery for the treatment of insulinomas in elderly patients at high surgical risk.However,larger multicenter studies withlonger follow-up are needed in order to better assess its safety and clinical success.

Diagnosis and management of insulinoma

Insulinomas,the most common cause of hypoglycemia related to endogenous hyperinsulinism,occur in 1-4 people per million of the general population.Common autonomic symptoms of insulinoma include diaphroresis,tremor,and palpitations,whereas neuroglycopenenic symptoms include confusion,behavioural changes,personality changes,visual disturbances,seizure,and coma.Diagnosis of suspected cases is based on standard endocrine tests,especially the prolonged fasting test.Non-invasive imaging procedures,such as computed tomography and magnetic resonance imaging,are used when a diagnosis of insulinoma has been made to localize the source of pathological insulin secretion.Invasive modalities,such as endoscopic ultrasonography and arterial stimulation venous sampling,are highly accurate in the preoperative localization of insulinomas and have frequently been shown to be superior to noninvasive localization techniques.The range of techniques available for the localization of insulinomas means thatblind resection can be avoided.Intraoperative manual palpation of the pancreas by an experienced surgeon and intraoperative ultrasonography are both sensitive methods with which to finalize the location of insulinomas.A high proportion of patients with insulinomas can be cured with surgery.In patients with malignant insulinomas,an aggressive medical approach,including extended pancreatic resection,liver resection,liver transplantation,chemoembolization,or radiofrequency ablation,is recommended to improve both survival and quality of life.In patients with unresectable or uncontrollable insulinomas,such as malignant insulinoma of the pancreas,several techniques should be considered,including administration of ocreotide and/or continuous glucose monitoring,to prevent hypoglycemic episodes and to improve quality of life.

Occult sporadic insulinoma: Localization and surgical strategy

Insulinomas continue to pose a diagnostic challenge to physicians, surgeons and radiologists alike. Most are intrapancreatic, benign and solitary. Biochemical diagnosis is obtained and imaging techniques to localize lesions continue to evolve. Surgical resection is the treatment of choice. Despite all efforts, an occult insulinoma (occult insulinoma refers to a biochemically proven tumor with indeterminate anatomical site before operation) may still be encountered. New localization preoperative techniques decreases occult cases and the knowledge of the site of the mass before surgery allows to determine whether enucleation of the tumor or pancreatic resection is likely to be required and whether the tumor is amenable to removal via a laparoscopic approach. In absence of preoperative localization and intraoperative detection of an insulinoma, blind pancreatic resection is not recommended.

Pancreatic insulinoma:current issues and trends

BACKGROUND:Although insulinomas are very rare tumors, they are the most common pancreatic neuroendocrine neoplasms.The incidence in general population is 1-4 per 1 000 000 yearly but the incidence is higher in autopsy studies. The malignancy of insulinomas is difficult to be predicted on the basis of their histological features,and the current WHO classification has been reevaluated.This review aimed to summarize classical knowledge with current trends in the diagnosis and treatment of insulinomas. DATA SOURCES:A Medline search using terms'insulinoma', 'treatment'and'neuroendocrine tumors'was conducted. Additional references were sourced from key articles. RESULTS:Surgery is the treatment of choice for insulinoma and has an extremely high success rate.Medical treatment is also available but only for patients who are unable or unwilling to undergo surgical treatment.Preoperative localization is necessary for planning the surgical approach.Many methods exist for localization of an insulinoma and can be invasive and non-invasive.The combination of biphasic thin section helical CT and endoscopic ultrasonography(EUS)has an almost 100% sensitivity in localizing insulinomas.Laparoscopic ultrasound is mandatory to localize intraoperatively these tumors.EUS-guided fine needle tattoing is an alternative method of localization in case of lack of laparoscopic ultrasound. CONCLUSION:Laparoscopic resection for benign insulinomas is the procedure of choice,whereas pancreatectomy is reserved for large,potentially malignant tumors.

Clinically detected gastroenteropancreatic neuroendocrine tumors are on the rise: Epidemiological changes in Germany

AIM:To study the epidemiologic changes of gastroenteropancreatic neuroendocrine tumors(GEP-NET)in Germany,we analyzed two time periods 1976-1988 and1998-2006.METHODS:We evaluated epidemiological data of GEP-NET from the former East German National Cancer Registry(DDR Krebsregister,1976-1988)and its successor,the Joint Cancer Registry(GKR,1998-2006),which was founded after German reunification.Due to a particularly substantial database the epidemiological data from the federal states of Mecklenburg-Western Pomerania,Saxony,Brandenburg and Thuringia,covering a population of more than 10.8 million people,were analyzed.Survival probabilities were calculated using life table analysis.In addition,GEP-NET patients were evaluated for one or more second(non-GEP-NET)primary malignancies.RESULTS:A total of 2821 GEP neuroendocrine neoplasms were identified in the two registries.The overall incidence increased significantly between 1976 and2006 from 0.31(per 100.000 inhabitants per year)to2.27 for men and from 0.57 to 2.38 for women.In the later period studied(2004-2006),the small intestine was the most common site.Neuroendocrine(NE)neoplasms of the small intestine showed the largest absolute increase in incidence,while rectal NE neoplasms exhibited the greatest relative increase.Only the incidence of appendiceal NET in women showed little change between 1976 and 2006.Overall survival of patients varied for sex,tumor site and the two periods studied but improved significantly over time.Interestingly,about 20%of the GEP-NET patients developed one or more second malignancies.Their most common location was the gastrointestinal tract.GEP-NET patients without second malignancies fared better than those with one or more of them.CONCLUSION:The number of detected GEP-NET increased about 5-fold in Germany between 1976 and2006.At the same time,their anatomic distribution changed,and the survival of GEP-NET patients improved significantly.Second malignancies are common and influence the overall survival of GEP-NET patients.Thus,GEP-NET warrant our attention as well as intensive research on their tumorigenesis.

Recent standardization of treatment strategy for pancreatic neuroendocrine tumors

Recent advances in localization techniques,such as the selective arterial secretagogue injection test(SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancreatic neuroendocrine tumors(PNET).For patients with sporadic functioning PNET,curative resection surgery has been established by localization with the SASI test using secretin or calcium.For curative resection of functioning PNET associated with multiple endocrine neoplasia type 1(MEN 1) which are usually multiple and sometimes numerous,resection surgery of the pancreas and/or the duodenum has to be performed based on localization by the SASI test.As resection surgery of PNET has increased,several important pathological features of PNET have been revealed.For example,in patients with Zollinger-Ellison syndrome(ZES),duodenal gastrinoma has been detected more frequently than pancreatic gastrinoma,and in patients with MEN 1 and ZES,gastrinomas have been located mostly in the duodenum,and pancreatic gastrinoma has been found to co-exist in 13% of patients.Nonfunctioning PNET in patients with MEN 1 becomes metastatic to the liver when it is more than 1 cm in diameter and should be resected after careful observation.The most important prognos-tic factor in patients with PNET is the development of hepatic metastases.The treatment strategy for hepatic metastases of PNET has not been established and aggressive resection with chemotherapy and trans-arterial chemoembolization have been performed with significant benefit.The usefulness of octreotide treatment and other molecular targeting agents are currently being assessed.

An insulinoma with clinical and electroencephalographic features resembling complex partial seizures

We described a female patient with insulinoma who experienced recurrent episodes of automatism, confusion and convulsion. Furthermore, her electroencephalography （EEG） findings resembled the pattern in complex partial seizures with secondary generalization. The interictal EEG showed spikes and sharp waves, as well as focal slowing over the left temporal lobe, and the ictal EEG revealed generalized spikes and sharp waves associated with diffused slowing. She was initially misdiagnosed as pharmacoresistant epilepsy. After the insulinoma was found and surgically removed, her EEG turned normal and she was seizure-free during the 4-year follow-up. This report highlights the need for careful reassessment of all seizures refractory to medication, even for the oatients associated with eoileotiform discharges on EEG.

A case of occult insulinoma localized by pancreatic dynamic enhanced spiral CT

Insulinomas are the most common category of pancreatic endocrine tumors,with an annual incidence of 1-4 cases per million people.Most are intrapancreatic,benign and solitary.Therefore,they have an excellent prognosis after surgical resection.However,the localization diagnosis of insulinomas still poses a challenge to surgeons and radiologists.In this case,the tumor was occult and could not be found by either abdominal enhanced spiral computed tomography(CT)or ultrasonography.Therefore,we tried a new method of CT scanning and localized the tumor.

Hyperinsulinemic hypoglycemia due to adult nesidioblastosis in insulin-dependent diabetes

In neonates, persistent hyperinsulinemic hypoglycemia (PHH) is associated with nesidioblastosis. In adults, PHH is usually caused by solitary benign insulinomas. We report on an adult patient who suffered from insulin-de- pendent diabetes mellitus, and subsequently developed PHH caused by diffuse nesidioblastosis. Mutations of the MEN1 and Mody 2/3 genes were ruled out. Preoperative diagnostic procedures, the histopathological criteria and the surgical treatment options of adult nesidioblastosis are discussed. So far only one similar case of adult nesidioblastosis subsequent to diabetes mellitus Ⅱ has been reported in the literature. In case of conversion of diabetes into hyperinsulinemic hypoglycemia syndrome, nesidioblastosis in addition to insulinoma should be con- sidered.

Diagnosis and treatment of insulinoma: report of 105 cases

Objective: To study the methods for diagnosis andtreatment of insulinoma.Methods: Clinical data from 105 patients with insuli-noma who had been admitted to our hospital from Ju-ly 1966 to December 1999 were retrospectively re-viewed.Results: Fasting blood glucose values were less than2.75 mmol/L in all the patients. Fasting serum insulinvalues in 60 patients were higher than 25 mU/L, av-erage 65 mU/L. Before operation, carcinoma was de-tected in 2 of 45 patients by ultrasound scan, and in10 of 35 by CT. Enucleation of insulinoma was per-formed in 60 patients. Operations included insulinomaresection (35 patients), distal resection of the pancreas(8), and biopsy (2).Conclusion: Whipple's triad and the index of insulinrelease>0.3 are the major variables for diagno-sis Intraoperative exploration and ultrasound scan are themethods for the localization of insulinoma Enucleation ofbenign insulinoma is preferred, but proximal or distal re-sections of the pancreas are required only for large, deep ormultiple tumors

Risk factors for the occurrence of insulinoma: a case-control study

BACKGROUND: The etiology of insulinoma is poorly understood. Few studies investigated the possible roles of environmental factors and lifestyle in the pathogenesis of insulinoma. The aim of this study is to identify risk factors associated with occurrence of insulinoma in the Chinese population. METHODS: This study consisted of 196 patients with insulinoma and 233 controls. Demographic information of the patients and controls and risk factors of the disease were analyzed. Univariate and unconditional multivariable logistic regression analyses were made to estimate odds ratios (ORs) and possible risk factors. RESULTS: Approximately 68.88% (135/196) of the patients were from rural areas in contrast to 10.30% (24/233) of the controls (P【0.0001). This difference was confirmed by the multivariate analysis (OR=4.950; 95% CI: 2.928-8.370). Family history of pancreatic endocrine tumor (OR=16.754; 95% CI: 2.125-132.057) and other cancers (OR=2.360; 95% CI: 1.052-5.291) was also related to a high-risk population of insulinoma. CONCLUSION: Rural residents or people who have a family history of pancreatic endocrine tumor and other cancers are a high-risk population of insulinoma.

Laparoscope resection of retroperitoneal ectopic insulinoma: A rare case

Ectopic insulinoma is a very rare and dormant tumor.Here we report the case of a 79-year-old female who presented with repeated episodes of hypoglycemia and was diagnosed with insulinoma based on laboratory and imaging examinations.Computed tomography and positron emission tomography revealed a tumor in the retroperitoneum under and left of the hepatoduodenal ligament, which was resected successfully using a laparoscopic approach.Pathologic results revealed an ectopic insulinoma, which was confirmed immunohistochemically.Ectopic insulinomas are accompanied by hypoglycemia that can be misdiagnosed as drug- or disease-induced.These tumors are difficult to diagnose and locate, particularly in atypical cases or for very small tumors.Synthetic or targeted examinations, including low blood glucose, elevated insulin, proinsulin, and C-peptide levels, 48-h fasting tests, and relevant imaging methods should be considered for suspected cases of insulinoma.Surgery is the treatment of choice for patients with insulinoma, and laparoscopic resection is a feasible and effective method for select ectopic insulinoma cases.

Conservative resection for benign tumors of the proximal pancreas

AIM:To evaluate the safety and long-term prognosis of conservative resection (CR) for benign or borderline tumor of the proximal pancreas.METHODS: We retrospectively analyzed 20 patients who underwent CR at the Second Affi liated Hospital of Zhejiang University School of Medicine between April 2000 and October 2008. For pancreaticojejunostomy, a modified invagination method, continuous circular invaginated pancreaticojejunostomy (CCI-PJ) was used. Modified continuous closed lavage (MCCL) was performed for patients with pancreatic fistula.RESULTS: The indications were: serous cystadenomas in eight patients, insulinomas in six, non-functional islet cell tumors in three and solid pseudopapillary tumors in three. Perioperative mortality was zero and morbidity was 25%. Overall, pancreatic fistula was present in 25% of patients. At a mean follow up of 42.7 mo, all patients were alive with no recurrence and no new-onset diabetes mellitus or exocrine dysfunction.CONCLUSION: CR is a safe and effective procedure for patients with benign tumors in the proximal pancreas, with careful CCI-PJ and postoperative MCCL.