Aggressive surgery for metastatic liver neuroendocrine tumors

BACKGROUND: Neuroendocrine tumors of the gastrointestinal tract (carcinoids, pancreatic endocrine tumors) have low malignant potential but can decrease survival rates if they spread to the liver (LNET). METHODS: The records of 16 patients with LNET primarily from gastrointestinal carcinoids treated surgically were retrospectively reviewed. RESULTS: There were 12 women and 4 men. Median age was 56 years (range 25 to 75). Thirteen (81%) had a carcinoid tumor and 5 had gastrinoma. Two patients with multiple endocrine neoplasia type 1 had both a gastric carcinoid and a jejunal gastrinoma. Eight patients (50%) had the carcinoid syndrome. Each patient had all identifiable LNET either resected or ablated. Ten patients had liver wedge resections, 1 right trisegmentectomy, 5 left hepatic lobectomies, and 2 radiofrequency ablations. Thirteen (81%) patients had concomitant bowel resections. Two patients had concomitant total gastrectomies to remove stomach primaries. The final patient had an extraintestinal pelvic primary or a liver primary. There were no operative deaths, and all 8 (100%) patients with the carcinoid syndrome had amelioration of symptoms. The 5-year actuarial survival rate was 82% with a median follow-up of 32 months. CONCLUSIONS: This study demonstrates that liver and concomitant extrahepatic surgery can be performed safely in patients with liver metastases because of carcinoids or pancreatic endocrine tumors. It results in excellent long-term survival and amelioration of symptoms. Surgery should be the first-line therapy for patients with LNET.     

Cytoreductive hepatic surgery for neuroendocrine tumors.

We retrospectively reviewed 37 patients who underwent hepatic resection between 1970 and 1989 to evaluate the role of cytoreductive hepatic surgery in patients with metastatic neuroendocrine tumors (carcinoid, 24; islet cell, 13). Seventeen resections were curative (no gross residual tumor); nine patients had symptomatic endocrinopathies and seven patients had symptoms caused by the primary tumor. Eight of nine patients with symptomatic endorcrinopathies obtained complete relief of symptoms; five are alive with no evidence of disease at 2 to 82 months (mean, 26 months). Six of seven patients with symptoms caused by the primary tumor obtained complete relief; five are alive with no evidence of disease at 5 to 28 months (mean, 14 months). One symptom-free patient underwent curative hepatic resection 5 years after abdominoperineal resection for a rectal carcinoid. Twenty resections were palliative (gross residual tumor); 16 patients had symptomatic endocrinopathies and 4 patients had symptoms caused by the primary tumor. Eight of 16 patients with symptomatic endocrinopathies obtained complete relief; five are alive at 2 to 30 months (mean, 11 months), with a mean duration of complete relief of 6 months (3 to 12 months). All four patients who underwent resection for symptoms caused by the primary tumor obtained complete relief; two are alive and symptom free at 10 and 101 months. Our experience suggests that curative surgery should be considered in all patients with completely resectable metastatic disease and that palliative surgery, despite the short duration of complete relief, should be considered in selected patients because it delays and may reduce the subsequent need for medical therapy.     

Radioguided surgery in the treatment of gastro-entero-pancreatic neuroendocrine tumors]

Neuroendocrine tumors are rare neoplasms. In most cases conventional imaging techniques (US,CT,RMN) are not able to identify primitive tumors. This fact conditions the approach to the treatment of these tumors. 111In-Pentetreotide scintigraphy (Octreoscan) permits to visualize occult primary tumor by somatostatin receptors, changing the clinical history of patients. This method can be used in guided surgery with a hand-held gamma probe allowing to improve the detection of occult tumor (inverse square law), giving to the patient further possibilities of survival. Intraoperative gamma probe was still utilized with success in the management of other tumors, as relapsed colorectal cancer, while reports about gamma probe in neuroendocrine tumors are poor because of the rarity of disease. In two cases we have utilized a gamma probe (ORIS model 2) in neuroendocrine tumors: in a case we have observed liver recurring localizations originating from pancreas, with high proliferative index (Ki-67 = 2033 x 10 HPF), and in a case liver metastatic carcinoid of lung. The difference between tumor and background counts was significant exceeds 2 standard deviation count rate. Gamma probe permits a radical cure in many cases and completes intraoperative ultrasound in order to provide the surgeon with other information on the intraoperative staging of the patient.     

Liver transplantation for neuroendocrine tumors

Liver transplantation for the treatment of metastatic neuroendocrine tumors (NETs) is radical. Although cure is not impossible, it is improbable. The reported experience with transplantation for NETs is limited to less than 150 cases with widely varying results and few 5-year disease-free survivors. We reviewed our experience with transplantation for patients with NETs. Fourteen symptomatic patients with unresectable NET liver metastases who had failed medical management were listed for transplantation. Two patients listed for transplantation underwent prior right lobectomies. Three patients were listed but did not undergo transplantation: one was lost to follow-up, one died 14 months after listing, and one remains waiting over 4 years. Eleven patients underwent liver transplantation, three with living donor grafts. There were four men (36.4%) and seven women (63.6%) who had a mean age of 51.2 ± 6.3 years. Three patients had distal pancreatectomies and one patient had a Whipple procedure at the time of transplantation. There were six nonfunctioning tumors (54.6%), three carcinoid tumors (27.3%), and two (18.2%) Vipomas. In one patient, with fulminant hepatic failure, the NET was an incidental finding in the explant. The 1- and 5-year survival among transplanted patients is 73% and 36%, respectively, with a mean follow-up of 34 ± 40 months (range 0 to 119 months). Of the three patients surviving more than 5 years, only one was disease free. In carefully selected patients with metastatic NETs, liver transplantation may be an appropriate option. Presented in part at the Fourth Americas Congress of the American Hepato-Pancreatico-Biliary Association, Miami, Florida, February 28, 2003.     

Long-term results of surgery for small intestinal neuroendocrine tumors at a tertiary referral center

Background  

Small intestinal neuroendocrine tumors (SI-NETs) are uncommon, with an annual incidence of about 1 per 100,000 individuals. The primary tumor (PT) is generally small, but nevertheless the majority of patients have mesenteric lymph node metastases and liver metastases at diagnosis. Our aim was to identify prognostic factors for survival and to evaluate outcome after surgery in SI-NET patients.     

Outcome of laparoscopic pancreatic surgery: endocrine and nonendocrine tumors

Laparoscopic pancreatic surgery (LapPS) for management of benign pancreatic tumors has still not been defined. This paper evaluates the feasibility and outcome of LapPS in patients with endocrine pancreatic tumors (EPTs) and cystic neoplasms of the pancreas (CyNP). Eighteen patients with benign pancreatic tumors underwent LapPS between January 1998 and May 2001. The indications were 10 EPTs (6 sporadic insulinomas, 1 multiple insulinoma of multiple endocrine neoplasia type 1, 2 nonfunctioning tumors, 1 VIPoma) and 8 CyNPs (3 serous cystadenomas, 5 mucinous cystic neoplasms). The laparoscopic procedure was performed using four ports with patients in the half-lateral position. Laparoscopic ultrasonography (LapUS) was used in all cases. Laparoscopic enucleation (LapE) was planned in five patients and performed in four (one conversion for tumor not found during laparoscopy). Laparoscopic pancreatic resection (LapPR) with spleen salvage was planned in 13 patients and performed in 12 (one conversion for metastatic VIPoma), with splenic vessel preservation in 11 patients and short gastric vessel preservation in 1. The average operating time was 3.5 hours after enucleation, 4.0 hours after distal pancreatectomy, and 5.0 hours after subtotal pancreatectomy. Pancreatic fistula was observed in two patients after LapE and in three patients after LapPR. Splenectomy for splenic abscess was performed 1 week after surgery in a patient with short gastric vessel splenic preservation. The average hospital stay was 5 days. We concluded that LapPS is a safe method for removing EPTs and CyNPs, although the incidence of pancreatic fistulas remains high. In selected patients LapPS offers significant benefit to patients: reduced trauma to the abdominal wall, short hospital stay, and a quick postoperative recovery.     

Surgery for primary pancreatic neuroendocrine tumors

Conclusions Currently, surgery for insulinoma is curative in nearly every patient, even those with MEN1, and fu-ture direction seems to be to make it more cosmeti-cally acceptable and less morbid by trying to accomplish the same procedure laparoscopically. Surgery for gastrinoma and nonfunctional NE tu-mors is curative in approximately 50% of patients. Duodenotomy is indicated during surgery for gastri-noma, because it increases tumor detection and cure rate. Patients with MEN1 with gastrinoma remain a challenge. With our current approach in these pa-tients, the cure rate is low, but the long-term survival remains excellent. The role of routine pancreaticoduodenectomy for sporadic and MEN1 NE tumors is currently unclear. It may increase cure rate, but it may also increase morbidity in pa-tients with a low, long-term tumor death rate.     

Liver transplantation for metastatic neuroendocrine tumors.

OBJECTIVE: This article describes the experience with liver transplantation in patients with irresectable neuroendocrine hepatic metastases. SUMMARY BACKGROUND DATA: Liver transplantation has become an established therapy in primary liver cancer. On contrast, there is little experience with liver transplantation in secondary hepatic tumors. So far, in the majority of patients being transplanted for irresectable liver metastases, long-term results have been disappointing because of early tumor recurrence. Because of their biologically less aggressive nature, the metastases of neuroendocrine tumors could represent a justified indication for liver grafting. METHODS: In a retrospective study, the data of 12 patients who underwent liver transplantation for irresectable neuroendocrine hepatic metastases were analyzed regarding survival, tumor recurrence, and symptomatic relief. RESULTS: Nine of 12 patients currently are alive with a median survival of 55 months (range, 11.0 days to 103.5 months). The operative mortality was 1 of 12, 2 patients died because of septic complications or tumor recurrences or both 6.5 months and 68.0 months after transplantation. all patients had good symptomatic relief after hepatectomy and transplantation. Four of the nine patients who are alive have no evidence of tumor with a follow-up of 2.0, 57.0, 58.0, and 103.5 months after transplantation. CONCLUSIONS: In selected patients, liver transplantation for irresectable neuroendocrine hepatic metastases may provide not only long-term palliation but even cure. Regarding the shortage of donor organs, liver grafting for neuroendocrine metastases should be considered solely in patients without evidence of extrahepatic tumor manifestation and in whom all other treatment methods are no longer effective.     

无功能性胰腺神经内分泌肿瘤的CT诊断

目的探讨无功能性胰腺神经内分泌肿瘤(NF-PNETs)的CT表现及诊断价值。方法对9例经病理学证实的NF-PNETs的CT及临床资料进行回顾性分析。结果 9例均为单发,位于胰腺头部4例,体、颈部3例,尾部2例;4例呈类圆形,5例分叶状。肿瘤最大直径约27~109 mm,平均76 mm,边界相对较清。4例实性、5例囊实性,CT平扫实性部分呈不均匀等及较低混杂密度,囊变、坏死区为低密度。增强扫描实性成分多呈明显或较明显强化,以动脉期明显。肿瘤边缘可见完整或不完整环形包膜,增强较明显,延迟强化。4例伴肝脏转移,3例腹膜后淋巴结转移并周边广泛侵犯,4例伴胆总管和/或主胰管稍增宽。结论 NF-PNETs以单发较大肿块常见,CT对其诊断及鉴别有较大价值,平扫多数呈较低密度,边界相对较清晰,增强早期较明显强化并见包膜延迟强化,容易血行转移但胰管扩张相对较少见。     

恶性内分泌肿瘤肝转移的肝移植治疗

在机体的肺、胃肠道等处广泛、散在地分布着许多具有内分泌作用的细胞,称为神经内分泌细胞（neuroendocrine cell）,起源于胃肠道和胰腺神经内分泌细胞的肿瘤称为胃肠胰内分泌肿瘤（gastroenteropancreatic neuroendocnne,GEP）．GEP分为类癌和胰腺内分泌肿瘤,该类肿瘤常发生肝转移．现就该领域的肝移植治疗作一综述。     

Surgical therapy for neuroendocrine tumors of the thymus

Summary. Neuroendocrine tumors of the thymus, also known as thymic carcinoids, are rare tumors of the anterior mediastinum. They occur sporadically or in association with the MEN I syndrome. We present five patients (four male, one female; age of first manifestation 19–53 years) who were operated on at our hospital between 1984 and 1995 for neuroendocrine thymic tumors. A hormone-producing tumor presented with Cushing's syndrome in two patients. Two patients had MEN I syndrome. Only in the female patient the primary tumor was confined to the thymus. We found lymph node metastases in three patients and a distant metastasis in one. The neuroendocrine tumors have a high rate of local recurrences and thus we performed 11 operations using a transthoracic or transsternal approach. Since there was no operative mortality and adjuvant therapies are of limited value, we recommend surgery even in case of recurrence.      

胰腺神经内分泌肿瘤患者腹腔镜术后住院时间延长的危险因素分析

目的 探究胰腺神经内分泌肿瘤（pNETs）患者行腹腔镜手术后住院时间延长的危险因素。方法 回顾性分析2015年1月至2022年8月在浙江省人民医院行腹腔镜手术治疗的91例pNETs患者的临床资料。以术后住院时间是否超过中位住院时间12 d将患者分为住院时间正常组（NLOS组,≤12 d,n=50）和住院时间延长组（PLOS组,>12 d,n=41）。通过单因素和多因素Logistic回归分析患者术后住院时间延长的危险因素,用AUC和Brier分数评价区分度和校准度。结果 单因素及多因素分析显示,手术时间>210 min(OR=8.850,95%CI 2.699～29.013,P<0.001)和腹腔镜手术方式[腹腔镜胰十二指肠切除术（LPD）:OR=5.753,95%CI 1.062～31.155,P=0.042;腹腔镜胰腺体尾切除术（LDP:OR=8.547,95%CI1.908～38.291,P=0.005]是患者住院时间延长的独立危险因素。此时相应的AUC为0.785,Brier分数为0.182。结论 手术时间和手术方式是预测pNETs患者腹腔镜术后住院时间是否延...     

Prognosis after surgery for multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors: Functionality matters

BackgroundMetastasized pancreatic neuroendocrine tumors are the leading cause of death in patients with multiple endocrine neoplasia type 1. Aside from tumor size, prognostic factors of pancreatic neuroendocrine tumors are largely unknown. The present study aimed to assess whether the prognosis of patients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors differs from those with resected multiple endocrine neoplasia type 1-related insulinomas and assessed factors associated with prognosis.MethodsPatients who underwent resection of a multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors between 1990 and 2016 were identified in 2 databases: the DutchMEN Study Group and the International MEN1 Insulinoma Study Group databases. Cox regression was performed to compare liver metastases-free survival of patients with a nonfunctioning pancreatic neuroendocrine tumors versus those with an insulinoma and to identify factors associated with liver metastases-free survival.ResultsOut of 153 patients with multiple endocrine neoplasia type 1, 61 underwent resection for a nonfunctioning pancreatic neuroendocrine tumor and 92 for an insulinoma. Of the patients with resected lymph nodes, 56% (18/32) of nonfunctioning pancreatic neuroendocrine tumors had lymph node metastases compared to 10% (4/41) of insulinomas (P = .001). Estimated 10-year liver metastases-free survival was 63% (95% confidence interval 42%–76%) for nonfunctioning pancreatic neuroendocrine tumors and 87% (72%–91%) for insulinomas. After adjustment for size, World Health Organization tumor grade, and age, nonfunctioning pancreatic neuroendocrine tumors had an increased risk for liver metastases or death (hazard ratio 3.04 [1.47–6.30]). In pancreatic neuroendocrine tumors ≥2 cm, nonfunctioning pancreatic neuroendocrine tumors (2.99 [1.22–7.33]) and World Health Organization grade 2 (2.95 [1.02–8.50]) were associated with liver metastases-free survival.ConclusionPatients with resected multiple endocrine neoplasia type 1-related nonfunctioning pancreatic neuroendocrine tumors had a significantly lower liver metastases-free survival than patients with insulinomas. Postoperative counseling and follow-up regimens should be tumor type specific and at least consider size and World Health Organization grade.     

Aggressive surgery improves long-term survival in neuroendocrine pancreatic tumors: an institutional experience

OBJECTIVE: To evaluate surgical strategies for neuroendocrine pancreatic tumors (NEPT) in the light of the new WHO classification from 2004 and to draw conclusions for future surgical concepts. BACKGROUND:: The extent of surgical resection in primary and recurrent NEPT is unclear. METHODS: Between 1987 and 2004, 62 patients with sporadic NEPT were treated at our institution and sections from biopsy and resection specimen were histopathologically reclassified. Clinical presentation, surgery, metastases, and pattern of recurrence were related to survival. RESULTS: Fifteen well-differentiated tumors (WDT, 24%), 39 low-grade carcinomas (LGC, 63%), and 8 high-grade carcinomas (HGC, 13%) were identified. Median observation time was 30.5 months; 48 of 62 patients (78%) were surgically resected, and in 45 patients R0/R1 status was achieved. Overall 2- and 5-year survival in the latter group was 80% and 64%, respectively. Retrospective WHO classification revealed that organ-preserving segmental resections had been performed in 10 LGC and 1 HGC. These patients showed equal outcome as radically resected counterparts (n = 19). Liver and other organ metastases were present in 19 of 62 patients (31%), and resection was accomplished in 7 of 19 patients, which conferred better overall survival (P = 0.026, log-rank test); 21 of 45 R0/R1-resected patients (47%) suffered from recurrence, and reoperation was accomplished in 9 patients, which resulted in better overall survival (P = 0.066). CONCLUSION: Organ-preserving resections offer sufficient local control in LGC; therefore, radical resections do not seem to be justified. On the other hand, radical resection is indicated even in metastasized patients or in case of loco-regional recurrence. The silent and slow course of the disease facilitates long-term surgical control.     

自制经肛单孔多通道装置在经肛门微创手术治疗低位直肠神经内分泌肿瘤中的应用

目的:评价经肛门微创手术中应用自制经肛单孔多通道装置治疗直肠神经内分泌肿瘤的临床价值。方法:回顾分析2016年7月至2017年12月收治的5例行直肠神经内分泌肿瘤局部切除患者的临床资料。结果:5例患者均顺利完成手术,术中术野稳定、清晰,无漏气、意外发生,术后病理报告示切缘(包括环周及垂直)阴性。中位手术时间55(40～75) min,中位失血量38(22～105) mL,术后中位住院时间5(4～7) d。术后1例患者发热,经对症治疗后治愈;未出现肛门括约肌功能异常。术后随访12个月,无局部复发病例,无排便困难、直肠狭窄发生。结论:自制经肛单孔多通道装置安全、可行,经济实惠,取材方便;此平台还可用于直肠良性肿瘤、T_1期直肠癌的治疗,虽然存在一定的技术不足,但仍具有一定的临床应用前景。