Treatment of liver metastases in patients with neuroendocrine tumors

Background: Hepatic metastases of neuroendocrine tumors demand differentiated therapeutic management due to the unique natural course and hormone secretion of the tumors. Aim: The purpose of the prospective nonrandomized study was to review the institutional experience with surgical treatment of hepatic neuroendocrine metastases. Patients and methods: From September 1992 until March 1996 29 consecutive patients with neuroendocrine tumors have been evaluated for surgical treatment of liver metastases. Of them, 11 (37.9%) fulfilled criteria for surgical treatment of hepatic secondary tumors. Extensive preoperative workup was carried out. Patients were divided in groups for curative or palliative resection. Liver transplantation was carried out in selected patients with disseminated liver metastases. Results: Of 29 patients 4 (13.7%) underwent curative resection and in 3 patients (10.3%) palliative resection was performed. The patients who underwent curative resection are all biochemically and clinically tumor free at a mean postoperative follow-up of 22.3 months. Two patients who underwent palliative resection are alive at 40 and 29 months, respectively. From 12 patients evaluated for liver transplantation 4 were considered as suitable candidates. Conclusions: Liver resection can be recommended in patients with hepatic metastases of neuroendocrine tumors in terms of potential survival prolongation and palliation. Liver transplantation is generally acceptable treatment in highly selected group of these patients. Long-term results have to be awaited before definitive proof of the beneficial effect of surgical treatment. Received: 14 November 1997     

Intraductal papillary mucinous neoplasm of the pancreas associated with neuroendocrine tumor: A case report

IntroductionIntraductal papillary mucinous neoplasm is an uncommon cystic tumor of pancreas that can be associated with ductal adenocarcinoma. Coexistence of pancreatic IPMN and neuroendocrine tumor is very rare. Here, we report the imaging features of mixed type intraductal papillary mucinous neoplasia of the pancreas with high grade dysplasia together with neuroendocrine carcinoma and perform review of the literature.PresentationA 68-year old patient has been evaluated for possible IPMN that was suspected during ultrasound. MRI revealed main and side branch duct dilatations. At the head, a contrast enhancing nodular lesion was identified. Due to the presence of high risk stigmata according to guidelines, surgery was performed. Histopathological examination revealed an unusual association, including mixed type IPMN and neuroendocrine carcinoma.DiscussionThe concomitant occurrence of pancreatic IPMN and neuroendocrine tumor has been reported in case studies and brief reviews. Yet, the imaging findings and underlying molecular mechanisms of this entity has not been fully understood. In addition to this unusual association, pancreatic intraepithelial neoplasia was also detected in the present case. Although majority of neuroendocrine tumor associated IPMNs were reported to be having low grade dysplasia, our patient had high grade dysplasia. Further studies and reviews with larger groups are needed to establish imaging features and underlying molecular mechanisms of this rare association.ConclusionAlthough the major concern during work-up of IPMN is presence of associated pancreatic ductal adenocarcinoma, the possibility of neuroendocrine tumor, in the presence of a hypervascular solid foci on imaging studies should be kept in mind.     

MSCT诊断胰腺无功能性囊性神经内分泌肿瘤

目的探讨胰腺无功能性囊性神经内分泌肿瘤(NF-CNETP)的MSCT表现。方法回顾性分析10例经手术病理证实的NF-CNETP的MSCT表现,对照病理进行分析。结果 10例NF-CNETP中,位于胰头5例,胰尾4例,同时位于胰体尾部1例;肿瘤最大径2.5~6.2cm。10例肿瘤均边界清楚,其中9例见完整包膜。平扫肿瘤密度不均匀,实性囊壁呈等或稍低密度,10例中2例可见钙化。增强扫描动脉期9例呈明显环状不均匀强化,1例含壁结节者明显强化,门静脉期均呈持续性强化。肿瘤囊壁动脉期平均CT值为(128.00±62.62)HU,门静脉期为(132.40±44.66)HU。4例胰管轻度扩张。1例胰周淋巴结转移。6例接受能谱CT双能扫描,肿瘤囊壁动脉期及门静脉期的碘浓度值与腹主动脉的碘浓度值进行标准化后分别为0.40±0.16、0.79±0.22。结论 NF-CNETP的MSCT强化方式及包膜显示具有一定特征性,对诊断与鉴别诊断有一定意义。     

良恶性胰腺神经内分泌肿瘤的影像学表现及鉴别诊断

目的探讨胰腺神经内分泌肿瘤的影像学表现及鉴别良恶性肿瘤的价值。方法回顾性分析18例经手术病理证实的胰腺神经内分泌肿瘤的影像学及病理资料,比较良恶性肿瘤的特征差异。结果 18例共检出18个病灶,包括神经内分泌瘤13个,神经内分泌癌5个;功能性肿瘤6个、无功能性12个。13例病灶形态规则,12例肿瘤边缘清晰;增强扫描动脉期16例肿瘤呈高密度强化,等密度、低密度强化各1例。良恶性肿瘤间最大径、肿瘤形态、边缘、强化方式及侵袭性差异均有统计学意义(P均0.05);功能性与无功能性肿瘤最大径差异有统计学意义(P0.05)。结论胰腺神经内分泌肿瘤的影像学表现有一定特点,对鉴别诊断良恶性肿瘤具有一定价值。     

Neuroendocrine metastases to the ovaries are significantly associated with small bowel neuroendocrine tumors and carcinomatosis

IntroductionNeuroendocrine tumors (NETs) metastatic to the ovary are traditionally considered rare, but data are lacking. This study seeks to better characterize the prevalence and outcomes of patients with neuroendocrine ovarian metastases (NOM).MethodsWomen with well-differentiated lung and gastroenteropancreatic NETs 2007–2017 were identified by medical record query. Clinicopathologic data were reviewed among patients with and without NOM.ResultsOf 242 patients, 27 (11.2%) developed NOM. NOM developed in 24.8% of SBNET patients and 65.7% of patients with carcinomatosis and intact ovaries. 33.3% had associated small bowel obstructions; 11.1% had ureteral obstruction. NOM were not apparent on imaging in 29.6% nor visible intraoperatively in 8.3%. Five-year survival rate was 61.5%. Those who underwent oophorectomy had a lower rate of subsequent ureteral obstruction (p < 0.01).ConclusionsNOM are more prevalent than previously reported and associated with significant morbidity. Empiric oophorectomy may be considered for SBNET patients and strongly advised in carcinomatosis.     

Differences in survival for patients with resectable versus unresectable metastases from pancreatic islet cell cancer

Well-differentiated islet cell tumors can be associated with aggressive biology, resulting in early metastases to the liver. This study was carried out to determine whether survival for patients with malignant islet cell tumors and synchronous liver metastases is affected by complete surgical resection. Thirty-one patients with synchronous liver metastases from islet cell cancer underwent surgical exploration with the intent for complete tumor resection, and all patients underwent resection of the pancreatic primary. The patients were divided into two groups, those with resectable versus unresectable liver metastases. Twenty-six of 31 (84%) patients underwent complete resection of both the primary tumor and all liver metastases, and 5 (16%) patients underwent only complete resection of the pancreatic primary without liver resection. To extirpate the primary tumor, a pancreaticoduodenectomy was performed in 11 of the 26 (42%) completely resected patients and in 4 of the 5 (80%) incompletely resected patients, P = NS. The remainder of the patients underwent distal pancreatectomy. There were no statistical differences in primary tumor size, lymph node metastases, or adjuvant treatments between patients with resected and unresected liver metastases. The median overall survival for the completely resected group was 78 months, longer than the 17 months for the group with unresectable liver metastases (P = 0.06). Complete tumor resection (or the tumor biology that allows such complete resection) affords a survival advantage to patients with metastatic islet cell tumors of the pancreas. Patterns of liver metastases from islet cell tumors, specifically multiple bilobar metastases that are not amenable to resection and/or ablation, predict a poor outcome despite resection of the primary pancreatic tumor. Presented at the Thirty-Eighth Annual Meeting of The Pancreas Club, New Orleans, LA., May 16, 2004.     

Endoscopic ultrasound guided radiofrequency ablation,for pancreatic cystic neoplasms and neuroendocrine tumors

AIM: To outline the feasibility, safety, adverse events and early results of endoscopic ultrasound (EUS)-radiofrequency ablation (RFA) in pancreatic neoplasms using a novel probe.METHODS: This is a multi-center, pilot safety feasibility study. The intervention described was radiofrequency ablation (RF) which was applied with an innovative monopolar RF probe (1.2 mm Habib EUS-RFA catheter) placed through a 19 or 22 gauge fine needle aspiration (FNA) needle once FNA was performed in patients with a tumor in the head of the pancreas. The Habib™ EUS-RFA is a 1 Fr wire (0.33 mm, 0.013”) with a working length of 190 cm, which can be inserted through the biopsy channel of an echoendoscope. RF power is applied to the electrode at the end of the wire to coagulate tissue in the liver and pancreas.RESULTS: Eight patients [median age of 65 (range 27-82) years; 7 female and 1 male] were recruited in a prospective multicenter trial. Six had a pancreatic cystic neoplasm (four a mucinous cyst, one had intraductal papillary mucinous neoplasm and one a microcystic adenoma) and two had a neuroendocrine tumors (NET) in the head of pancreas. The mean size of the cystic neoplasm and NET were 36.5 mm (SD ± 17.9 mm) and 27.5 mm (SD ± 17.7 mm) respectively. The EUS-RFA was successfully completed in all cases. Among the 6 patients with a cystic neoplasm, post procedure imaging in 3-6 mo showed complete resolution of the cysts in 2 cases, whilst in three more there was a 48.4% reduction [mean pre RF 38.8 mm (SD ± 21.7 mm) vs mean post RF 20 mm (SD ± 17.1 mm)] in size. In regards to the NET patients, there was a change in vascularity and central necrosis after EUS-RFA. No major complications were observed within 48 h of the procedure. Two patients had mild abdominal pain that resolved within 3 d.CONCLUSION: EUS-RFA of pancreatic neoplasms with a novel monopolar RF probe was well tolerated in all cases. Our preliminary data suggest that the procedure is straightforward and safe. The response ranged from complete resolution to a 50% reduction in size.     

Neuroendocrine tumors of the pancreas

Background: The benefits of associating magnetic resonance imaging (MRI) and laparoscopy for localizing and treating neuroendocrine pancreatic tumors (NEPTs) have been poorly documented. Methods: In a retrospective study, eight patients with a mean age of 48 years were operated on for a NEPT. MRI was used to localize the lesions. In all patients a laparoscopic resection was carried out. Laparoscopic ultrasonography (LUS) was used during most operations. Results: The tumor was clearly localized by MRI in seven patients, and LUS showed the lesion in another patient whose preoperative MRI had been unsuitable. Three enucleations, three spleen-preserving caudal pancreatectomies, and two caudal pancreatectomies with splenectomy were carried out. There were no conversions and the mean operating time was 260 min, with a mean blood loss of 180 ml. The mean hospital stay was 7 days. There were no minor nor major complications during the hospitalization period. However, a pancreatic abscess was diagnosed in one patient 1 month later, requiring an urgent laparotomy. Conclusion: MRI as well as LUS are indeed suitable techniques to localize NEPTs. Moreover, the minimally invasive approach ensured an adequate treatment with a more comfortable and short postoperative recovery.     

直肠神经内分泌肿瘤69例淋巴结转移和预后的影响因素分析

目的研究影响直肠神经内分泌肿瘤（NET）的淋巴结转移及预后因素。方法回顾性分析2003年4月至2011年10月辽宁省肿瘤医院大肠外科收治的69例直肠NET患者的临床资料,分析淋巴结转移及预后与直肠NET临床病理因素的关系。结果69例患者中有9例（13．0％）发生淋巴结转移,单因素分析结果显示：淋巴结转移与直肠NET大小、T分期及G分级有关（均P〈0．01）;多因素分析结果显示：T分期是独立影响淋巴结转移的因素（P=0．002,OR=46．000,95％CI：4．030～525．126）。全组患者的5年总生存率为90．3％,单因素分析结果显示：肿瘤大小、T分期、N分期、M分期、TNM分期及G分级与患者的总体生存率有关（分别为P〈0．01和P〈0．05）;多因素分析结果显示,M分期是长期生存的独立预后因素（P=0．000,HR=2．285,95％CI：1．484～3．518）。TNM分期Ⅰ期行局部和根治切除手术的患者,3年总生存率差异无统计学意义（P〉0．05）;Ⅱ期及以上分期患者,行非根治切除与根治切除手术者3年总生存率差异则有统计学意义（P=0．046）。结论直肠NET的T分期与淋巴结转移有关,TNM与M分期两者交互作用影响患者的预后,故可以作为淋巴结转移及预后的预测因素。TNM分期Ⅰ期的患者推荐行局部切除,Ⅱ期及以上的患者推荐行根治性手术治疗。     

Cytoreduction results in high perioperative mortality and decreased survival in patients undergoing pancreatectomy for neuroendocrine tumors of the pancreas

We reviewed our experience with pancreatectomy for neuroendocrine tumors (NE) to determine outcomes after R0/R1 or R2 resection and compare them to patients in whom resection was not attempted. Data were reviewed for all patients presenting with NE tumors of the pancreas between 1990 and 2005. Kaplan-Meier survival curves were compared by log-rank analysis. Multivariate analysis was completed using Cox proportional hazards to identify risk factors for poor survival after resection. Of 120 patients, 65 (54%) had functional tumors. Resection was undertaken in 83: distal pancreatectomy in 41, pancreaticoduodenectomy in 27, enucleation in 14, and central pancreatectomy in 1. Survival was significantly longer after resection (91 months versus 24, P<0.001). R0/R1 resection was accomplished in 64 (77%) and resulted in lower perioperative mortality (2% versus 21%, P<0.01) and longer survival (112 months versus 24, P<0.001) compared to R2 resection. Survival after R2 resection was no better than after no resection. Factors predictive of decreased survival were moderate/poor differentiation, R2 resection, and high-risk features. Long-term survival is possible following complete resection for NE tumors of the pancreas. However, cytoreduction resulting in incomplete tumor removal carries significant perioperative mortality without long-term survival benefit and should be discouraged. Presented at the Forty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, Los Angeles, California, May 22, 2006.     

The tail of neuroendocrine tumors from lung to pancreas: Two rare case reports

INTRODUCTION

Primary pancreatic neuroendocrine tumors are a well-established disease entity, however, neuroendocrine metastases to the pancreas from other sites have been scarcely documented. Specifically, pancreatic metastases from a pulmonary carcinoid tumor have only previously been described in a single case report.

PRESENTATION OF CASE

We sought to outline our institutional experience of two patients with pulmonary neuroendocrine tumors that developed metastases to the pancreas, confirmed by gross pathology and immunohistochemistry. In both cases, the pancreatic metastases were surgically resected and their pulmonary origin were discovered post-operatively.

DISCUSSION

Our findings should raise awareness to the possibility of metastatic disease when evaluating a pancreatic mass in a patient with a clinical history of pulmonary carcinoid tumor. Expert opinion on immunohistochemically differentiating a primary pancreatic neuroendocrine malignancy from a metastasis should be employed in these cases.

CONCLUSION

Establishing this diagnosis pre-operatively could affect the decision to proceed with surgical resection, given the morbidity of pancreatectomy and the unknown long-term clinical outcome of patients with pulmonary carcinoid tumors metastatic to the pancreas.     

血清嗜铬粒蛋白A水平与无功能性胰腺神经内分泌瘤肝转移的关系

目的 探讨血清嗜铬粒蛋白A(CgA)水平与无功能性胰腺神经内分泌瘤(pNETs)肝转移肿瘤负荷及患者预后的关系.方法 回顾性分析2011年12月至2013年12月复旦大学附属中山医院收治的64例无功能性pNETs肝转移患者的临床资料.39例患者具有临床和随访资料,25例患者仅有临床资料.64例患者中,58例具有尚未发生肝转移时的血清CgA水平资料,51例具有已发生肝转移时的血清CgA水平资料.采用门诊方式进行随访,患者出院后每3～6个月定期复查实验室和影像学检查.患者血清CgA水平升高或降低程度≥50％治疗肝转移瘤前的血清CgA水平,定义为血清CgA水平升高或降低,其余定义为血清CgA水平稳定.随访时间截至2014年3月.采用ELISA法检测血清CgA.CT检查三维重建测定肝转移肿瘤负荷.采用国际实体瘤疗效评价标准评价无功能性pNETs肝转移患者疗效.将完全缓解和部分缓解归为治疗缓解,疾病稳定归为疾病稳定,疾病进展和肿瘤复发归为疾病进展.计量资料用M(P25,P75)表示,计数资料检验采用Fisher确切概率法,计量资料多组间比较采用Kruskal-Wallis检验,两两比较采用Mann-Whitney检验,采用Spearman等级相关分析进行相关性检验.结果 无功能性pNETs肝转移患者血清CgA水平为94.8 μg/L(67.4 μg/L,181.4 μg/L),显著高于尚未发生肝转移时的血清CgA水平59.9 μg/L(39.1μg/L,88.5 μg/L),两者比较,差异有统计学意义(Z=-3.96,P＜0.05).无功能性pNETs肝转移患者血清CgA水平与无功能性pNETs肝转移肿瘤负荷呈正相关(r=0.486,P＜0.05).39例具有临床和随访资料的患者中35例获得完整随访,中位随访时间为10个月.14例治疗缓解的患者中,血清CgA水平降低和稳定患者比例分别为11/14和3/14;12例疾病稳定的患者中,血清CgA水平降低、稳定和升高的患者比例分别为4/12、7/12和1/12;9例疾病进展的患者中,血清CgA水平稳定和升高患者比例分别为2/9和7/9.3种不同疗效的患者血清CgA水平降低和升高患者比例比较,差异均有统计学意义(F =11.02,18.82,P＜0.05);血清CgA水平稳定患者比例比较,差异无统计学意义(F=5.68,P＞0.05).治疗缓解的患者血清CgA水平降低患者比例显著高于其余两种疗效的患者,差异有统计学意义(P＜0.05);疾病进展的患者血清CgA水平升高患者比例显著高于其余两种疗效的患者,差异有统计学意义(P＜0.05).结论 高血清CgA水平可能提示无功能性pNETs患者发生肝转移,疗效不佳.血清CgA水平越高,可能提示肝转移肿瘤负荷越大.     

手术治疗胃肠胰腺神经内分泌瘤肝转移的Meta分析

目的 通过对胃肠胰腺神经内分泌瘤肝转移患者手术与非手术治疗对照研究的系统分析,探讨手术治疗胃肠胰腺神经内分泌瘤肝转移的价值.方法 检索Cochrane图书馆、PubMed、Medline、Embase、中国生物医学文献数据库、万方数据库中的相关随机研究,按照Cochrane推荐的文献纳入标准筛选文献,并对纳入文献进行质量评估,共有10组研究中心的1 567例患者的数据纳入进行Meta分析.结果 单纯手术切除治疗与药物（奥曲肽）治疗、全身放化疗、经动脉治疗、射频消融术等非手术治疗胃肠胰腺神经内分泌瘤肝转移相比较,3年生存率（OR：0.07,95％CI：0.02,0.22;Pheterogeneity=0.93,P＜0.00001）及5年生存率（OR：0.19,95％ CI：0.15,0.24;Pheterogeneity=0.11,P＜0.00001）差异具有统计学意义,手术治疗组的3、5年生存率明显优于非手术治疗组.结论 手术切除是治疗胃肠胰腺神经内分泌瘤肝转移的首选治疗方法,其安全有效且较其他非手术治疗在生存期方面具有较好的优势.     

胰腺导管内乳头状黏液性肿瘤的诊断与治疗

目的提高对胰腺导管内乳头状黏液性肿瘤(IPMTs)的认识,以改善其诊治水平。方法对1993年5月至2003年12月收治的15例IPMTs病人的临床、影像学表现及病理资料作回顾性分析。结果15例中男性12例,女性3例。年龄33～76岁,平均58岁。上腹痛为最常见症状。B超和CT检查,均提示有不同程度的胰管扩张和囊实性占位。11例行ERCP检查,发现十二指肠乳头肿大和黏液溢出者7例。14例行手术治疗(胰十二指肠切除术12例,胰体尾切除1例,全胰切除1例)。术后病理诊断胰头导管内乳头状黏液性腺癌3例、导管内乳头状黏液性腺瘤伴局部癌变6例、胰头导管内乳头状黏液性腺瘤伴不典型增生3例、胰头导管内乳头状黏液性腺瘤2例,术后除1例因肝广泛转移而死亡外,其余病人均健在,存活期最长1例已13年。结论胰腺有囊实性占位伴胰管全程扩张的病人应考虑IPMTs,ERCP发现十二指肠乳头增大有黏液溢出者可确诊该疾病。手术切除是最有效的治疗,术后预后良好。     

胰腺神经内分泌瘤基因组学和表观遗传学的研究进展

目前大量研究发现对染色质结构起调控作用的ATRX-DAXX和多发性内分泌肿瘤1型(MEN-1)基因,哺乳动物雷帕霉素靶蛋白(mTOR)信号通路相关基因的突变共同参与了胰腺神经内分泌肿瘤(pNETs)的发生和发展.这些突变基因主要通过DNA甲基化、组蛋白修饰、染色体重塑和替代性端粒延长机制激活等表观遗传学的异常改变使染色质变异以及pNETs相关信号通路的异常激活协同引起pNETs肿瘤形成和侵袭.这些证据表明基因组学和表观遗传学的异常改变共同激活了pNETs的肿瘤生物学行为.这些发现对胰腺神经内分泌肿瘤的临床诊治及预后判断有重要的现实意义,并可据此研究出特异性靶向治疗的新策略.分子靶向药物与根治性手术治疗联合应用将是未来针对pNETs主要的治疗手段.     

胃肠道神经内分泌肿瘤诊治的研究进展

胃肠道神经内分泌肿瘤是一组异质性肿瘤,曾被认为是一种罕见的肿瘤.根据近几年的数据,其发病率已明显升高.胃肠道神经内分泌肿瘤临床表现多样,嗜铬蛋白A是其最重要的生化标志物.传统的影像学检查以及生长抑素受体显影有利于诊断.治疗方法包括手术切除、生物治疗、放射性核素治疗以及化学疗法.本文对其诊断方法和治疗方法的研究进展进行综述.     

胰腺神经内分泌肿瘤的CT和MRI表现

目的探讨胰腺神经内分泌肿瘤的影像特征。方法分析43例经手术后病理证实的胰腺神经内分泌肿瘤的CT和MRI资料,并与手术病理结果对照。结果 43个病灶平均大小为(25.00±1.82)mm,23个病灶出现坏死囊变;CT平扫15个病灶呈等密度,28个病灶呈稍低密度;43个病灶T1WI均呈低/稍低信号,27个病灶T2WI呈高/稍高信号,16个病灶T2WI呈等信号;26个病灶见包膜;30个病灶显示清晰轮廓;24个病灶增强扫描动脉期病灶即明显强化,8个呈延迟强化,5个呈向心性强化,6个呈轻度强化。结论胰腺神经内分泌肿瘤形态及CT和MRI动态增强扫描具有特征性表现,影像学检查对诊断其具有重要价值。