Clinical features and outcomes of primary hepatic neuroendocrine carcinomas

Background and Aim: Primary hepatic neuroendocrine carcinomas (PHNECs) are extremely rare, with only about 150 cases having been reported in the English‐language literature. Because of the rarity of PHNECs, its clinical features and treatment outcomes are not well understood. Here, we report our experiences with PHNECs. Methods: We identified patients diagnosed with PHNEC and analyzed their demographics, baseline laboratory data, tumor characteristics, treatment modalities and outcomes. Results: A total of 218 consecutive patients were identified with pathologically confirmed neuroendocrine carcinoma. Of these, 12 patients were diagnosed with PHNECs; the median age was 66.5 years (range, 37 to 80 years), and seven patients (58.3%) were male. Two patients who each had a single hepatic mass underwent curative surgical resection. One patient who was of inoperable status at the initial diagnosis because of multiple intrahepatic metastases showed a partial response after the ninth round of systemic chemotherapy and then underwent surgical resection. The median overall survival in the 12 patients was 16.5 months (range, 0.7 to 41.7 months). Three patients who underwent surgical treatment are alive without recurrence for 15.2 months, 18.0 months, and 36.9 months, respectively. Conclusions: Primary hepatic neuroendocrine carcinoma should be considered as a possible differential diagnosis in the management of hepatic tumors. The liver can be the primary origin of neuroendocrine tumors, and if the tumors are diagnosed as primary hepatic neuroendocrine tumors, surgical resection must be considered for curative treatment.     

Primary hepatic carcinoid tumours

BACKGROUND: Carcinoid tumours of the liver are predominantly metastases from the gastrointestinal tract. Primary hepatic carcinoids are extremely rare. DISCUSSION: In contrast to metastases, primary hepatic carcinoids are usually solitary and resectable. It is important that these tumours are differentiated from metastases. Complete surgical resection should be contemplated and is generally curative.     

原发性肝类癌1例

1临床资料患者女,45岁。因反复发作右上腹不适1个月,发现右肝占位性病变2周入院。无发热、黄疸、腹痛。查体未见明显阳性体征。B超示：肝右叶可见一个8.5 cm×7.4 cm强回声区,边界不清晰,内部回声分布不均匀,内可见1.61 cm×1.63 cm的无回声区。     

Long-term survival after surgical management of neuroendocrine hepatic metastases

Background:

Surgical cytoreduction and endocrine blockade are important options for care for neuroendocrine liver metastases. We investigated the long-term survival of patients surgically treated for hepatic neuroendocrine metastases.

Methods:

Patients (n= 172) undergoing operations for neuroendocrine liver metastases from any primary were identified from a prospective liver database. Recorded data and medical record review were used to analyse the type of procedure, length of hospital stay, peri-operative morbidity, tumour recurrence, progression,and survival.

Results:

The median age was 56.8 years (range 11.5–80.7 years). 48.3% of patients were female. Median overall survival was 9.6 years (range 89 days to 22 years). On multivariate analysis, lung/thymic primaries were associated with worse survival [hazard ratio (HR): 15.6, confidence interval (CI): 4.3–56.8, P= 0.002]. Severe post-operative complications were also associated with worse long-term survival (P < 0.001). A positive resection margin status (R1) was not associated with a worse overall survival probability (P∼ 0.8).

Discussion:

Early and aggressive surgical management of hepatic metastases from neuroendocrine tumours is associated with significant long-term survival rates. Radiofrequency ablation is a reasonable option if a lesion is unresectable. R1 resections, unlike many other cancers, are not associated with a worse overall survival.     

肝脏原发高级别神经内分泌癌1例报告

1病例资料患者男性,61岁,因“腹痛、乏力7 d”于2019年4月30日入本院,无恶心、呕吐,既往体健。入院查体:皮肤巩膜轻度黄染,右上腹部压痛明显,无其他阳性体征。入院血生化检查:TBil 31.8μmol/L,DBil 9.3μmol/L,IBil 22.5μmol/L,ALT 135.9 U/L,AST 163.3 U/L,GGT 115.1 U/L,余未见异常。肿瘤标志物:AFP 3.12 ng/ml,细胞角蛋白19片段20.47 ng/ml,神经元特异性烯醇化酶(neuron-specific enolase,NSE)176.25 ng/ml。实验室指标:各项肝炎指标正常。腹部平扫+增强CT:肝内多发占位性病变,考虑恶性,肝门区/腹主动脉周围多发淋巴结肿大,考虑转移可能。为明确诊断行经皮肝穿刺活组织检查术,病理结果提示:高级别神经内分泌癌(neuroendocrine carcinoma,NEC),免疫组化结果提示:CD56(+),CK7(灶状+),Ki-67(+70%),CK-pan(灶状+),Syn(灶状+)(图1)。结合影像学检查未发现其他组织来源NEC的证据,故诊断为原发性肝脏NEC伴肝内多发转移及肝外淋巴结转移。本病例因存在多发病灶无法手术切除,选择依托泊苷和顺铂方案(EP方案)行全身化疗,现已完成4疗程。复查肿瘤标志物:AFP 4.49 ng/ml,细胞角蛋白19片段2.89 ng/ml,NSE 7.66 ng/ml,恢复至正常。腹部平扫+增强CT:肝内多发占位性病变与前相比明显变少变小,肝门区、门腔间隙见多发淋巴结显示,部分肿大,较前片体积略减小(图2、3)。     

Primary hepatic carcinoid tumor

A primary hepatic carcinoid tumor arising in a 49-year-old woman is reported. The patient was admitted with multiple hepatic tumors and treated by a left lobectomy and cholecystectomy. Cut sections of the specimen revealed a solid and necrotic mass, measuring 10 × 12 × 13 cm, with multiple small satellite nodules. Histologically, the tumor cells had small oval-shaped nuclei and presented with a trabecular arrangement and rosette-like formation. Both Grimelius and Fontana-Mason stainings were positive. The tumor cells were positive for chromogranin A and negative for other antigens. Ultrastructural studies of the tumor cells revealed duct-like formation with microvilli and a cluster of dense small immature neurosecretory granules in the cytoplasm. These findings were consistent with those of carcinoid tumors. Postoperatively, the patient was treated with repeated transcatheter arterial chemoembolization for any remnant tumors. However, she died of the disease 5 years after the initial surgery. The autopsy findings suggested the primary site to be the liver. (Received Dec. 22, 1997; accepted Aug. 28, 1998)     

7例原发性肝脏神经内分泌癌患者的影像学特征分析

目的探讨原发性肝脏神经内分泌癌的影像学特征。方法回顾性分析我院2009年5月—2016年12月经病理确诊的7例原发性肝脏神经内分泌癌患者的临床及影像学资料。结果 7例原发性肝脏神经内分泌癌患者中男5例,女2例,年龄30~65岁,平均年龄45.6岁,其中1例行CT平扫及增强扫描,6例行CT平扫及MRI增强扫描。7例患者共9个病灶,多发神经内分泌癌2例,均有2个病灶,其中1例合并布加综合征,1例伴发肝细胞肝癌。血清神经元特异性烯醇化酶(neuron-specific enolase,NSE)阳性4例,癌胚抗原及糖类抗原19-9阳性2例,AFP均阴性。其影像学特征性表现包括病灶呈"快进快出"5例,病灶内可见多发偏中心囊性变区6例,延迟期可见包膜4例,粗大肿瘤血管4例,引流静脉显影4例,所有病例均未见门静脉癌栓、淋巴结转移及胆管扩张征象。结论神经内分泌癌的影像学表现具有一定的特征性,无明确肝病史的肝脏富血供占位、病灶内含有单发或多发的偏中心性囊变区、肿瘤表面粗大肿瘤血管与引流静脉的出现,结合血清AFP阴性及NSE的升高,放射科医师应考虑到原发性肝脏神经内分泌癌的可能性,确诊仍需要活检取得病理组织学证据。     

4例原发性肝脏神经内分泌肿瘤临床分析及文献复习

目的 总结原发性肝脏神经内分泌肿瘤(PHNEN)患者的病例资料,分析其临床特征,以提高临床诊断和治疗水平。方法 回顾性分析、总结我院诊治PHNEN患者的临床表现、化验检查、影像学特点、病理学检查和治疗转归。结果 4例患者均为女性,中位年龄为56(40,73)岁;2例无不适主诉,2例有腹痛;血清ALT 28.3(18.0～49.8)U/L,TBIL 11.5(9.5～16.3)μmol/L,神经元特异性烯醇化酶(NSE)为44.1(20.2～77.1)ng/ml;腹部CT均提示肝内多发占位,增强扫描动脉期呈环形或不均匀强化,静脉期强化程度降弱;组织病理学检查示3例为神经内分泌癌,1例为神经内分泌瘤G2;1例患者接受对症治疗,采取手术、介入和/或药物等联合治疗另3例患者,随访11～81个月,2例死亡,2例生存。结论 PHNEN临床少见,缺乏特征性临床表现、辅助检查和病理学诊断标志,需排除其他病变后方可考虑诊断。早期发现和联合治疗是改善患者预后的重要策略。     

Treatment strategy for rectal carcinoids: A clinicopathological analysis of 229 cases at a single cancer institution

Background and Aim: A treatment strategy for tumors with only venous invasion and characteristics of small rectal carcinoids with metastasis have not been clearly documented. The present study aims to determine the risk factors for lymph node metastasis and to elucidate characteristics of small tumors with metastasis. Methods: We investigated a total of 229 patients with rectal carcinoids. The relationship between each clinicopathological variable and the presence of lymph node metastasis was evaluated. Results: Tumor size (larger than 10 mm), presence of central depression, depth of tumor invasion, lymphatic invasion, and venous invasion were significantly associated with the incidence of lymph node metastasis (P < 0.001). Multivariate analysis revealed that tumor size (odds ratio: 63.3, P < 0.001) and venous invasion (odds ratio: 40.9, P < 0.001) were independently predictive of lymph node metastasis. In 204 patients with small (no larger than 10 mm) tumors, 10 patients had lymph node metastasis. All 10 tumors had low proliferation values indicated by mitosis and Ki‐67 index. Multivariate analysis for the 204 patients revealed that only venous invasion was independently associated with metastasis (odds ratio: 40.1, P < 0.001). Five‐year disease free survival rates of the total patients with metastasis and without metastasis were 81.1% and 95.5%, respectively (P < 0.001, log‐rank test). Conclusions: Venous invasion as well as tumor size and lymphatic invasion indicates high malignant potential to metastasize to lymph node and would provide useful information in considering the addition of radical surgery. Postoperative pathological examinations of specimens obtained by local resection are very important to avoid underestimation.     

原发性肝类癌1例报告

正1病例资料患者男性,44岁,因反复发作右上腹不适4年余,加重1周入院。无发热、黄疸、腹痛。外院查甲胎蛋白(AFP)5.09IU/ml,癌胚抗原(CEA)1.86 ng/ml。血清K+3.0 mmol/L,肝功能正常,HBeA g及丙型肝炎抗体均阴性。B超示:肝脏大小正常,形态规则,肝内可见多个异常回声区,边界清晰,部分为无回声区,壁增厚,部分为高回声区,其一无回声大小约3.5cm×4.1 cm,余肝实质回声密集中等,分布均匀。PET-CT示     

胆囊混合性腺神经内分泌肿瘤合并肝转移1例报告

1病例资料患者女性,49岁,因“上腹部伴腰背持续性隐痛2个月”于2018年10月25日入本院。既往高血压病史3年,未治疗。肝胆胰CT平扫+三期增强(图1)提示:平扫下可见肝实质密度减低,低于脾脏,胆囊不大,壁不均匀增厚,反折处显著;增强扫描可见不均匀延迟强化,胆囊管低位汇入胆总管,胆总管未见扩张,胆囊周围、肝门区见多发结节样软组织密度影,其余未见明显异常。检查结论:脂肪肝,胆囊占位性病变考虑胆囊癌伴周围多发淋巴结肿大。     

直肠腺瘤合并原发性肝脏神经内分泌癌一例

原发性肝脏神经内分泌癌(PHNEC)较罕见,临床症状、体征、超声及影像学检查均不具特异性,病理表现和免疫表型是确诊的主要依据.本例患者因直肠和肝脏特殊的影像学表现,入院初考虑直肠癌伴肝转移,后经病理和免疫组化确诊PHNEC.该病例提示我们临床工作中应警惕因经验主义引起的误诊,应重视病理学诊断结果.     

Clinical outcomes of gastroduodenal neuroendocrine tumors according to their WHO grade: A single-institutional retrospective analysis

The management of gastroduodenal neuroendocrine tumor (NET) has been controversial between radical surgical resection and local excision including endoscopic resection. A gastroduodenal NET grade (G), measured by their mitotic rate and Ki67 proliferation index, is important to predict prognosis. In this study, we aimed to compare the clinical outcomes of gastroduodenal NET according to grades in order to identify poor prognostic factors of gastroduodenal NETs. Fifty-four gastroduodenal NETs diagnosed between December 2008 and December 2020 in a tertiary referral hospital were retrospectively reviewed. The clinical outcomes of gastroduodenal NETs, according to tumor grades and factors associated with NET G2-3, were analyzed. A total of 52 gastroduodenal NET patients was enrolled. The mean follow-up period was 56.2 ± 40.1 months. The mean size of gastric and duodenal NET was 7.9 ± 11.0 mm and 9.8 ± 7.6 mm, respectively. During the study period, 72.7% (16/22) of gastric NETs and 83.3% (25/30) of duodenal NETS were G1. All G1 gastroduodenal NETs showed no lymph node or distant metastasis during the study periods. All G3 gastroduodenal NETs showed metastasis (one lymph node metastasis and 3 hepatic metastases). Among metastatic NETs, the smallest tumor size was a 13 mm gastric G3 NET. Factors associated with G2-3 NETs were larger tumor size, mucosal ulceration, proper muscle or deeper invasion, and lymphovascular invasion. A small-sized gastroduodenal NET confined to submucosa without surface ulceration may be suitable for endoscopic resection. After local resection of a gastroduodenal NET (G1) without lymphovascular and muscle proper invasion, follow-up examination without radical surgical resection can be recommended. G3 NETs may be treated by radical surgical resection, regardless of tumor size.     

胆囊神经内分泌癌3例诊治分析并文献复习

原发性胆囊神经内分泌癌临床少见,约占全部神经内分泌癌的0.2%[1]。临床表现无特异性,表现出类癌综合征的极少,多以急慢性胆囊炎或胆囊肿物就诊,术前常规检查诊断困难,主要依靠术后病理结合免疫组化明确诊断。本文对本院就诊的3例胆囊神经内分泌癌患者进行分析总结以便该病的临床诊断及治疗经验的积累。     

Treatment outcomes of endoscopic resection for rectal carcinoid tumors: an analysis of the resectability and long-term results from 46 consecutive cases

Aim: In Japan, most of colorectal carcinoid tumors developed in rectum. The choice of treatment is important because surgical treatment may need to construct artificial anus. Although curative endoscopic resection (ER) is desirable from the point of quality of life, sufficient evidence of endoscopic treatment for rectal carcinoid tumors is not fully obtained.

Methods: Between April 2001 and August 2013, 46 rectal carcinoid tumors in 46 patients who underwent either with endoscopic mucosal resection with a ligation device (EMR-L) or endoscopic submucosal dissection (ESD) were analyzed retrospectively. The rates of en bloc resection, positive for lateral and/or vertical margin, curative resection, local recurrence, additional treatments, overall and disease-specific survival rate after ER were evaluated during follow-up (median observation period 61.6 months).

Results: Twenty-two lesions were treated by EMR-L and 24 lesions were treated by ESD. Both groups had similar mean tumor size (EMR-L: 6.2?mm, ESD: 6.0?mm). The rate of en bloc resection, negative for both lateral and vertical margins, and curative resection were, respectively, 73%, 63%, and 50% for EMR-L, 100%, 100%, and 83% for ESD. These results suggested that the rate of resectability and curability for ESD was significantly higher than EMR-L (p?Conclusion: The long-term outcomes of ER for rectal carcinoid tumors were excellent. ESD has advantage for resectability and curability compared with EMR-L; therefore, ESD is more favorable procedure as treatment for rectal carcinoid tumors.     

Primary large cell neuroendocrine carcinoma in the common bile duct: First Asian case report

Large cell neuroendocrine carcinoma (LCNEC) in the biliary system is a poorly differentiated, high-grade neuroendocrine tumor. These tumors exhibit aggressive behavior and an increased tendency for early nodal and distant metastases. Herein, we report an unusual case of a pure primary LCNEC of the common bile duct (CBD). A 75-year-old female presented with nausea and jaundice. The patient underwent a CBD excision with lymph node dissection. Upon histological and immunohistochemical examination, the tumor exhibited pure large cell-type neuroendocrine features. Metastases were noted in two of the eight lymph nodes. The patient was administered adjuvant chemotherapy. The patient’s cancer recurred 7 mo after surgery, and the patient died from liver failure 5 mo after recurrence. The prognosis of LCNEC of CBD remains poor despite curative resection and adjuvant chemotherapy. The role of additional therapies, such as multimodal treatment including radiation therapy, must be further studied to improve the prognoses of patients.     

Update in clinical management for gallbladder neuroendocrine carcinoma

Background:Gallbladder neuroendocrine carcinoma (GB-NEC) is rare and there are few reports at present. We sought to review the current knowledge of GB-NEC and provide recommendations for clinical management.Methods:A systemic literature research was conducted in the websites of Pubmed, Medline, Web of Science, CNKI, Wanfang Data using the keywords including gallbladder combined with neuroendocrine carcinoma or neuroendocrine tumor or neuroendocrine neoplasm. Two reviewers independently screened the articles by reading the title, abstract and full-text.Results:In computed tomography (CT) and magnetic resonance imaging (MRI) examination, a well-defined margin, gallbladder replacing type with larger hepatic and lymphatic metastases could be helpful for differential diagnosis of GB-NEC and gallbladder adenocarcinoma (GB-ADC). Older age, unmarried status, large tumor size (>5 cm), positive margins, and distant Surveillance, Epidemiology and End result (SEER) stage are independently associated with poor survival. Surgical resection remains as the preferred and primary treatment. The potential survival benefit of lymphadenectomy for patients remains controversial. Platinum-based postoperative adjuvant chemotherapy may improve the survival. The efficacy of other treatments including immunotherapy, targeted therapy and somatostatin analogue needs further investigation.Conclusion:Typical imaging features could be helpful for preoperative diagnosis. Age, margin status, tumor size, marital status, histopathologic subtype and SEER stage may be independent predictors for the survival. Remarkable advances regarding the treatment for GB-NEC have been achieved in recent years. Further studies are needed to investigate the survival benefit of lymphadenectomy for patients with GB-NEC.     

Preliminary results of a Japanese nationwide survey of neuroendocrine gastrointestinal tumors

Background We conducted a nationwide survey to estimate the incidence of neuroendocrine gastrointestinal tumors (NETs) newly diagnosed in Japan from 2002 through 2004. Methods Data on 1541 patients, 514 pancreatic endocrine tumors (PETs) and 1027 gastrointestinal carcinoids (GICs), were collected and analyzed. Results Nonfunctioning tumors (NF-PET) constituted 47.7% of PETs. Next in frequency were insulinoma (31.7%) and gastrinoma (8.6%). Malignancy was frequent in NF-PETs (46.1%) and gastrinomas (45.5%), but only 7.4% of insulinomas were malignant. The incidence of multiple endocrine neoplasia type-1 associated with PETs was 7.4%. The incidence of GICs was 28.8%, 5.2%, and 66.0% in foregut, midgut, and hindgut, respectively. Carcinoid syndrome and metastases were observed in only 1.7% and 5.6% of GICs, respectively. Conclusions The incidence of NETs in Japan was clarified by this preliminary study. Comparatively large differences in GICs between Japan and Western nations were present with regard to the location, symptomatic status, and prevalence of malignancy.