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.

恶性胰岛素瘤多发肝转移一例

恶性胰岛素瘤是疑难罕见的神经内分泌肿瘤之一,常合并远处转移,其中以肝转移最常见,预后多不佳。本文报道1例恶性胰岛素瘤多发肝转移病例。患者男性,70岁,因“发作性意识障碍4个月余”入院,监测血糖发现其空腹、餐后及夜间均反复出现低血糖。胰腺灌注CT及肝脏动态增强MRI发现胰头钩突部占位、肝内多发转移灶,经皮肝穿刺活检病理证实为胰岛素瘤。经多学科讨论后,分期行肝内动脉介入栓塞及射频消融治疗,同时联合依维莫司治疗。复查增强CT可见部分肝转移灶缩小。患者规律加餐,血糖逐渐上升并维持在正常水平。本文讨论该病例的临床特征及多学科协作诊疗经过,旨在为恶性胰岛素瘤患者的临床综合诊治提供经验。

对比5.0T与3.0T平扫MRI显示胰岛素瘤质量

目的对比5.0T与3.0T平扫MRI显示胰岛素瘤质量。方法前瞻性对12例胰岛素瘤患者以5.0T和3.0T MR仪采集术前腹部T1WI、T2WI平扫并行弥散加权成像(DWI),对比5.0T与3.0T各序列MR图像质量主观评分及肿瘤-胰腺实质对比度评分,观察肿瘤信噪比(SNR)和对比度噪声比(CNR),比较各序列图像及总体肿瘤显示率。结果5.0T T1WI和DWI显示胰岛素瘤的主观评分均高于3.0T T1WI和DWI(P均<0.05),5.0T T2WI主观评分与3.0T T2WI差异无统计学意义(P=0.166)。针对肿瘤-胰腺实质对比度评分,5.0T T1WI高于3.0T T1WI(P=0.023),而5.0T T2WI与3.0T T2WI、5.0T DWI与3.0T DWI差异均无统计学意义(P均>0.05)。胰岛素瘤SNR在5.0T T2WI高于3.0T T2WI(P=0.015),5.0T T1WI与3.0T T1WI、5.0T DWI与3.0T DWI之间差异均无统计学意义(P均>0.05);胰岛素瘤CNR在5.0T与3.0T各序列图像差异均无统计学意义(P均>0.05)。5.0T T1WI、T2WI及DWI胰岛素瘤显示率分别为100%(12/12)、66.67%(8/12)及83.33%(10/12),3.0T T1WI、T2WI及DWI分别为75.00%(9/12)、58.33%(7/12)及66.67%(8/12);5.0T MRI胰岛素瘤总体显示率为100%(12/12),3.0T MRI为83.33%(10/12)。结论相比3.0T MRI,胰岛素瘤5.0T MRI显示胰岛素瘤更佳并有利于诊断。

老年胰岛素瘤1例病例报道及文献复习

胰岛素瘤是最常见的功能性胰腺神经内分泌肿瘤,以内源性胰岛素分泌过多及随之出现的低血糖症状为主要特征。作为老年低血糖及晕厥的罕见原因,胰岛素瘤常被临床医生忽略。与中青年患者比较,老年胰岛素瘤患者更易出现致命性低血糖及不可逆的脑功能损害,早期诊治可提高其生活质量和健康期望寿命。该院2021年6月21日收治1例73岁女性胰岛素瘤患者,通过分析其临床表现、定性及定位诊断、治疗及后续随访,为老年胰岛素瘤的诊治及临床管理提供诊疗思路。

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.

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.

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.

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.

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.

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)

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.

Role of preoperative endoscopic ultrasound-guided fine-needle tattooing of a pancreatic head insulinoma

Although insulinomas are rare, they are the most com-mon pancreatic neuroendocrine tumor, with an inci-dence of four cases per million population. Insulinomas are generally benign indolent intrapancreatic tumors. Surgical resection remains the main option for treat-ment. However, up to 67% of a pancreatic head insu-linomas are nonpalpable, thus surgical resection of the nonplapable insulinoma in this area could become prob-lematic resulting in prolonged surgical time, increased risk of pancreatic duct injury and need for pancreati-coduodenectomy. Endoscopic ultrasound-guided fine- needle tattooing(EUS-FNT), has been shown to have a crucial role for localization of pancreatic body and tail lesions, facilitating laparoscopic distal pancreatectomyand helping surgeons identify the location of the tumor. EUS-FNT might have a role for preoperative localiza-tion of pancreatic head insulinomas which are likely to be nonpalpable. We report a case of preoperative EUS-FNT for localization of a nonplapable pancreatic head insulinoma. This report demonstrates that EUS-FNT of pancreatic head insulinomas may facilitate surgical resection, reduce operative time and decrease surgical complications.

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.

Roles of sulfonylurea receptor 1 and multidrug resistance protein 1 in modulating insulin secretion in human insulinoma

BACKGROUND:Sulfonylurea receptor 1(SUR1)and multidrug resistance protein 1(MRP1)are two prominent members of multidrug resistance proteins associated with insulin secretion. The aims of this study were to investigate their expression in insulinomas and their sole and synergistic effects in modulating abnormal insulin secretion. METHODS:Fasting glucose,insulin and C-peptide were measured in 11 insulinoma patients and 11 healthy controls. Prolonged oral glucose tolerance tests were performed in 6 insulinoma patients.Insulin content,SUR1 and MRP1 were detected in 11 insulinoma patients by immunohistochemistry. SUR1 and MRP1 were also detected in 6 insulinoma patients by immunofluorescence. RESULTS:Insulinoma patients presented the typical demons-trations of Whipple’s triad.Fasting glucose of each insulinoma patient was lower than 2.8 mmol/L,and simultaneous insulin and C-peptide were increased in insulinoma patients. Prolonged oral glucose tolerance tests showed that insulin secretion in insulinoma patients were also stimulated by high glucose.Immunohistochemistry and immunofluorescence staining showed that SUR1 increased,but MRP1 decreased in insulinoma compared with the adjacent islets. CONCLUSIONS:The hypersecretion of insulin in insulinomas might be,at least partially,due to the enrichment of SUR1. In contrast,MRP1,which is down-regulated in insulinomas, might reflect a negative feedback in insulin secretion.

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.

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 sei- zure-free during the 4-year follow-up.This report highlights the need for careful reassessment of all seizures refractory to medi- cation,even for the patients associated with epileptiform discharges on EEG.

Pancreatic insulinoma combined with glucagon positive cell: A case report

We present a 70-year-old man who was referred for surgery with uncontrollable hypoglycemia. Ultrasonography and abdominal contrast computed tomography revealed a hypervascular tumor of 1 cm in diameter in the pancreatic tail. With a diagnosis of insulinoma, we performed a distal pancreatectomy. The patient showed a good postoperative course without any complications. The patient's early morning fasting hypoglycemia disappeared. The respective levels of C-peptide and insulin dropped from 14.9 ng/mL and 4860 μIU/mL preoperatively to 5.3 ng/mL and 553 μIU/mL after surgery. A histopathological examination demonstrated that the tumor was a pancreatic neuroendocrine tumor, grade 1. Immunostaining was negative for insulin and positive for CD56, chromogranin A, synaptophysin and glucagon. These findings suggested that the tumor was clinically an insulinoma but histopathologically a glucagonoma. Among all insulinoma cases reported between 1985 and 2010, only 5 cases were associated with independent glucagonoma. In this report, we characterize and discuss this rare type of insulinoma by describing the case we experienced in detail.