Surgical management of insulinoma: Diagnosis of tumor location and high incidence of malignancy

The findings in twenty-two patients with insulinoma were reviewed, as continuous efforts should be made to establish preoperative localization of the tumor. Superselective arteriography and percutaneous, transhepatic portal vein and pancreatic venous catheterization are highly recommended approaches. At the time of surgical intervention, a cautious exploration of the pancreas after thorough mobilization is most important. Recent use of intraoperative ultrasonography increases the likelihood of finding these occult tumors which locate deeply in the head of the pancreas. Apart from the diagnostic problems, we wish to emphasize the high incidence of malignancy (7/22, 31.8 per cent) in our series. Althout patients with malignant isulinoma had a much better prognosis compared to those with a pancreatic ductal malignancy, pancreatic resection with regional lymphnode dissection seems to be a rational procedure. Enucleation can be done when intraoperative findings of the tumor and regional lymphonode indicate no malignant features and no multiple lesions. However, at the first operation, enucleation is still a procedure of choice, even for the malignant insulinoma in the head with a well-defined capsule and no metastatic lesions, the objective being to avoid a duodenopancreatectomy or total pancreatectomy. These data were reported at the 30th Congress of Société Internationale de Chirurgie, Hamburg, Germany, 1983     

“胰岛素正常”的胰岛素瘤

目的分析胰岛素瘤胰岛素水平正常的原因，以提高其诊断水平。方法对我院1982年6月至2005年10月诊断为胰岛素瘤，且胰岛素水平检测结果在正常范围内的12例进行回顾性分析。结果12例患者均出现空腹或发作性低血糖症状，连续检测血糖，至少1次血糖值〈2．8mmol／L。同期检测外周静脉血中免疫反应性胰岛素（IRI）水平均〈25mU／L。周围静脉血中免疫反应性胰岛素／血糖比值（IGR）：〈0．3者5例，〉0．3者7例。12例中8例进行了血清C-肽检测，6例高于正常。结论少数胰岛素瘤患者的血胰岛素可在正常范围内，血胰岛素水平正常不能排除胰岛素瘤的诊断。     

Insulinoma: Selective arterial calcium injection performed to confirm localization and complete resection

A case of insulinoma is reported in a patient in whom selective arterial calcium injection (SACI) tests were performed both to confirm tumor localization before surgery and to confirm complete tumor removal during surgery. An 18-year-old woman with hypoglycemic episodes was diagnosed with an insulinoma in the pancreatic body demonstrated by celiac arteriography. In a preoperative SACI test, calcium was injected into the splenic artery (SpA), gastroduodenal artery (GDA), and superior mesenteric artery (SMA). Serum immunoreactive insulin (IRI) and proinsulin levels were measured in hepatic venous samples. IRI was markedly increased after the injection of calcium into the GDA and SMA, while there was no response in IRI levels when calcium was injected into the SpA. Therefore, no occult insulinoma was revealed in the distal area fed by the SpA, although the presence of insulinoma was uncertain in the proximal pancreas. In the intraoperative SACI test, calcium was injected into the celiac artery. Insulin (determined by enzyme immunoassay) and proinsulin levels were measured in portal venous samples before and after resection of the tumor. After resection, these levels decreased in response to the calcium stimuli, confirming complete removal of the insulinoma. The SACI test was helpful to localize the insulinoma and was useful to confirm the complete removal of the tumor.     

Multiple genetic alterations in malignant metastatic insulinomas

Proto-oncogenes, growth factors/receptors, and tumour suppressor genes were analysed in malignant metastatic insulinomas. Normal pancreas showed only a moderate immunoreaction for c-myc proto-oncogene and a strong reaction for insulin. Benign insulinomas were slightly or moderately positive for transforming growth factor a (TGFα), weakly positive for epidermal growth factor receptor (EGF-R), and strongly positive for c-myc and insulin. In malignant insulinomas, besides a strong immunoreaction for c-myc and TGFα, activation of c-K-ras and overexpression of p53 protein were found. Insulin reaction was moderate or strong. Three out of six malignant insulinomas displayed a c-K-ras point mutation at codon 12. All mutations were guanine to cytosine transversion, resulting in amino acid substitution, glycine to arginine. Mutations were present in metastatic insulinomas only. Patients with mutated c-K-ras oncogene had overexpression of p53 protein as well as c-myc and TGFα overexpression. Our results support the view that malignant progression is a consequence of more than one genetic lesion and suggest that activation of myc, TGFα, and ras genesα plays a role in a multistep process of tumour progression, perhaps serving as an initiating event.     

无功能胰岛细胞瘤19例诊断与治疗

目的：探讨无功能胰岛细胞瘤的诊断和治疗。方法：回顾分析19例患者的病史资料,其中施行肿瘤摘除5例,胰体尾切除＋脾切除5例,胰十二指肠切除2例,胰体尾切除＋Roux-en-Y吻合术1例,全胰切除1例,胆囊空肠吻合术3例,活检2例。结果：肿瘤位于胰头6例,胰体2例,胰尾9例,累及全胰2例,多发1例;病理证实恶性8例,良性11例。除2例术后分别死亡肝功能衰竭和胰瘘、多器官衰竭外均获满意疗效。结论：手术切除肿瘤均可取得良好疗效。     

胰岛素瘤11例诊治体会

目的：提高胰岛素瘤的诊断与治疗水平。方法：对11例胰岛素瘤的诊治资料进行回顾性总结。结果：术前B超阳性率18％,CT阳性率27％,术中探查阳性率90．9％。种肿瘤摘除10例。远段胰腺切除1例。结论：Whipple三联征是诊断的主要依据。手术是治疗胰岛素瘤的最佳方法,术中仔细探查,监测血糖是保证疗效的关键。     

胰岛细胞瘤体素内不相干运动参数与CT灌注参数的相关性

目的评估胰岛素瘤体素内不相干运动(IVIM)相关参数和CT灌注参数及病理学分级的相关性。方法前瞻性收集北京协和医院怀疑胰岛素瘤且行IVIM和CT灌注扫描的患者共55例,对图像进行后处理得到IVIM相关参数[包括表观扩散系数(ADC)、真实扩散系数(D)、灌注相关扩散系数(D*)和灌注分数(f)]和CT灌注参数[包括血流量(BF)、血容量(BV)和渗透性(PM)]。对术后病理标本进行染色获得病理学指标(包括分级、ki-67指数和核分裂相)。比较正常胰腺不同解剖部位及正常胰腺与胰岛素瘤的IVIM相关参数差异。分析IVIM参数与CT灌注参数及病理学指标的相关性。结果胰尾ADC值及D值均明显减低,差异有统计学意义(P均<0.001)。胰岛素瘤及正常胰腺的所有IVIM参数差异均有统计学意义(P均<0.001)。正常胰腺的ADC值、f值与BF呈正相关(r=0.437,P=0.003;r=0.357,P=0.010),余IVIM相关参数与CT灌注参数均无相关性(P均>0.05)。IVIM参数与胰岛素瘤病理学分级指标间均无相关性(P均>0.05)。结论正常胰腺的不同解剖部位的I...     

胰岛素瘤患者动态血糖谱的特点及意义

目的分析胰岛素瘤患者动态血糖监测系统(CGMS)血糖谱的特点,探讨CGMS在胰岛素瘤诊断中的价值。方法应用CGMS对6例经病理证实的胰岛素瘤患者(胰岛素瘤组)进行连续3 d的血糖监测,分析CGMS的平均血糖水平(MBG)、M-valueof Schlichtkrull(M-value)、血糖分布频率及低血糖事件,监测结果与5例新诊断2型糖尿病伴低血糖患者(糖尿病组)及6例正常糖调节者(对照组)进行比较。结果①胰岛素瘤组M-value显著高于对照组(P<0.01),而MBG两组间无显著性差异(P>0.05)。糖尿病组M-value及MBG均高于胰岛素瘤组及对照组(P<0.05或P<0.01)。②6例胰岛素瘤患者CGMS监测期间共发生36次低血糖事件,持续时间为3.6 h/d,其中21次(58.3%)发生于夜间;5例糖尿病患者共发生7次低血糖事件,持续时间为0.17 h/d,其中4次(57.1%)发生于夜间。③对照组99.2%的血糖波动于3.9～7.8 mmol/L;胰岛素瘤组血糖2.8～3.9mmol/L及≤2.8 mmol/L的分布频率均显著高于糖尿病组(P<0.01),而7.8～11.1 mmol/L及≥11.1 mmol/L的分布频率则低于糖尿病组(P<0.05和P<0.01)。结论CGMS可进一步分析低血糖的时间分布、类型及原因,结合M-value等血糖参数,有助于胰岛素瘤诊断水平的提高。