Hepatic Neuroendocrine Tumor Research Articles

12年間の経過で増大し切除した肝原発神経内分泌腫瘍の1例

症例は76歳，女性．64歳時に他疾患の精査で肝S4に12mm大の単発腫瘤を指摘された．血管腫を疑い，以後不定期の経過観察で緩徐な増大傾向を認めていた．今回，4年の間隔があり，顕著な増大を認めたため，紹介となった．CTで腫瘍内部は大部分が充実性で，壊死または嚢胞を疑う低吸収域もみられ，MRIではT1強調像で低信号，T2強調像で低信号～強い高信号の領域が混在し，いずれの検査も早期より不均一に濃染された．他病変は認めず，原発性肝腫瘍と診断したが，肝細胞癌や血管肉腫などはいずれも非典型的であり，診断的治療目的に中央2区域切除術を施行した．病理組織学的診断は，肝原発神経内分泌腫瘍G2であった．肝原発神経内分泌腫瘍は非常に稀で，12年間に及ぶ緩徐な増大の経過を観察した．肝原発神経内分泌腫瘍G1およびG2について文献的考察を加え報告する．

Rare Primary Hepatic Neuroendocrine Tumor: Case Report and Literature Review

Neuroendocrine tumors are well-differentiated low grade malignant neoplasms. Their pathogenesis is thought to be secondary to the unrestricted proliferation of neuroendocrine cells. They most commonly arise in the bronchopulmonary or gastrointestinal tract but can originate from almost any organ. While the liver is a common site of metastases, primary hepatic neuroendocrine tumors are an exceedingly rare pathology, of which fewer than 100 cases have been described in world literature. Thus, there exists a paucity of data regarding the clinical presentation, diagnosis and management of this disease. We present a case of a 35 year old patient who presented to our facility for evaluation of a cough and cervical lymphadenopathy. Two biopsies of the lymph nodes were negative, however on workup for an occult malignancy a hypodense heterogeneous hypervascular lesion measuring 3.7cm x 2.7cm in segment IVb of the liver was noted on CT scan. The levels of laboratory studies such as LFT's, ALP, chromogranin A, 24 hour 5-HIAA and tumor markers including AFP were not elevated. An MRI confirmed the mass, and the patient underwent CT guided biopsy of the hepatic lesion. Staining from the biopsy resulted in cells reactive for synaptophysin, chromogranin, CAM 5.2, MOC31, CD 56 wand MUC confirming a nonsecretory neuroendocrine tumor. Patient underwent octreotide scan, PET scan, CT chest, MRI head along with EUS, EGD and colonoscopy to evaluate for a primary source, however, none was found. The well localized presentation without extensive hepatic invasion made the patient a candidate for surgical resection which was successfully performed. The patient remains disease free over 25 months after initial presentation. Primary hepatic neuroendocrine tumors are an exceedingly rare entity whose variable presentation necessitates provider familiarity with this condition. Once identified, excluding other primary locations with thorough investigation and treatment with surgical resection has been shown to provide the most patient benefit.Figure 1Figure 2

Diagnosis and treatment of primary hepatic neuroendocrine carcinoma

To investigate the clinical features, diagnostic and therapeutic methods of primary hepatic neuroendocrine carcinoma. The clinicopathological data of fourteen patients with primary hepatic neuroendocrine carcinoma confirmed by pathology were analyzed retrospectively and related literatures were reviewed. The fourteen patients, including eight males and six females, had an age range of 23-58 years (mean 45.9 years). Four tumors were located in the right liver lobe, four in the left liver lobe and six in both. The clinical manifestations were nonspecific and variable. The most common clinical manifestation was abdominal distention or right upper quadrant pain. Radiological findings were not specific and could not distinguish primary hepatic neuroendocrine tumor from hepatocellular carcinoma. Diagnosis of primary hepatic neuroendocrine tumor was confirmed by pathology using immunohistochemical staining and by the absence of extrahepatic primary lesions. Extrahepatic primary neuroendocrine carcinoma was ruled out by ultrasonography, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), preoperative gastrointestinal endoscopy and long-term postoperative follow up. Three patients received surgical treatment, two cases received surgical resection and radiofrequency ablation (RFA), six patients received transarterial chemoembolization, one case received orthotopic liver transplantation, one case only received exploratory laparotomy, and one case received chemotherapy. All 14 patients were followed up and seven of them are still alive, the others died of liver failure or recurrence. Primary hepatic neuroendocrine carcinomas are extremely rare. Its diagnosis should be confirmed by pathology. Preoperative fine needle biopsy is strongly recommended. Prognosis is relatively favorable. Surgical resection is treatment of first choice, and TACE, RFA, and chemotherapy can be used for unresectable patients.

Primary Hepatic Neuroendocrine Tumor after 4 years Tumor-free Follow-up

Background: A primary hepatic neuroendocrine tumour (PHNET) is a very rare disease. The liver represents the preferential site for neuroendocrine tumors' metastases.Case presentation: A 45-year old Caucasian female who presented with nausea, vomiting, diarrhea, accompanied by diffuse abdominal pain was found to have on contrast-enhanced computer tomography an encapsulated, partially cystic liver mass. The patient underwent an uneventful left atypical hepatic resection. Histopatological and immunohistochemical examination revealed a slowly growing (G1) hepatic neuroendocrine tumour. Post surgery, the specific neuroendocrine markers (serum Chromogranin A and 24h urinary 5 hydroxy-indolacetic acid) were within normal range. Further functional imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. The patient is presently after 4 years of follow-up with no local recurrence or distant metastases.Conclusions: The diagnosis of PHNET is a medical challenge that requires a thorough longterm follow-up in order to exclude an occult primary neuroendocrine tumour.

To be or not to be a primary hepatic neuroendocrine tumour

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

造影超音波検査が有用であった肝原発神経内分泌腫瘍の1例

症例は40歳，女性．皮膚の紅斑を主訴に皮膚科を受診し，鑑別として皮膚筋炎が考えられ，悪性疾患の精査目的に施行した腹部造影CT検査にて，肝S4/8に動脈相で辺縁部から濃染し，平衡相で軽度wash outされる径32 mmの腫瘤を認めた．腹部超音波検査Bモードでは，腫瘤のほとんどは境界明瞭な高エコーを呈し，内部の一部に嚢胞状の低エコー域を認めた．腹部造影超音波検査では，腫瘍は14秒後から染影されはじめ，38秒後に全体が均一に濃染された．門脈相では均一で肝実質とほぼ等エコーであった．嚢胞状の部位は染影しなかった．後血管相のadvanced dynamic flowで明瞭なdefectを呈した．肝腫瘍生検の病理診断では，肝原発神経内分泌腫瘍（primary hepatic neuroendocrine tumor: PHNET）が考えられたため，経皮経肝的門脈塞栓術を施行後に肝右葉3区域と尾状葉切除術を施行した．肝腫瘍は免疫組織学的に，chromogranin Aとsynaptophysinが陽性で，MIB-I indexは1.4％であった．肝外に原発巣を認めなかったことから，肝原発神経内分泌腫瘍 Grade 1と診断した．PHNETは稀な疾患であり，造影超音波検査で評価した報告例は少なく，文献的考察を踏まえて報告する．

Genetic analysis of an orbital metastasis from a primary hepatic neuroendocrine carcinoma

AbstractPurpose To give an overview of neuroendocrine carcinoma metastases to the eye region.Methods Critical review of the present literature demonstrated by a patient case.Results A 71‐year‐old female with a known history of primary hepatic neuroendocrine carcinoma, presented with a visual defect, proptosis and restricted eye movements of the right eye. Biopsies from the orbit and from the primary hepatic neuroendocrine carcinoma showed similar morphological and immunohistochemical features and high‐resolution, array‐based comparative genomic hybridization demonstrated loss of one copy each of chromosomes 3 and 18, and gain of 1q both in the primary hepatic neuroendocrine carcinoma and in the orbital tumour. The orbital mass was diagnosed as a metastasis from the primary hepatic neuroendocrine carcinoma.Conclusion Primary hepatic neuroendocrine tumours are very rare, and the orbit is an extremely rare location for a neuroendocrine carcinoma metastasis. This is the first reported case of an orbital metastasis with origin from a primary hepatic neuroendocrine carcinoma.

詳細な画像検討を施行した肝原発神経内分泌腫瘍の一切除例

症例は57歳女性．検診で肝腫瘤を指摘された．腹部CT，MRIで血管腫と診断したが，増大傾向を認めたため入院した．肝胆道系酵素，腫瘍マーカーの上昇は認めず，肝炎ウイルスは陰性であった．腫瘤はUSで不均一な低輝度，単純CTで低吸収，造影CTにて辺縁優位に濃染，MRIではT1強調像で低信号，T2強調像で内部に不均一な低信号を伴う高信号，肝細胞相では低信号となった．Single-level dynamic CT Angiography（CTA）ではリング状濃染を認め，造影効果は持続した．腫瘍内部は早期から濃染され速やかに消褪し，後期相では低吸収となった．診断に難渋したため肝腫瘍生検を施行した．その結果，免疫組織化学的にNCAM，chromogranin A，synaptophysinは陽性であり神経内分泌腫瘍と診断した．上部，下部消化管内視鏡検査，PET-CTも施行したが肝以外に異常所見を認めず，肝原発神経内分泌腫瘍と診断し，外科的切除を施行した．肝原発の神経内分泌腫瘍は非常にまれな疾患であるが，詳細な画像検査を施行し，若干の文献的考察を加え報告する．

Diagnostic imaging of primary hepatic neuroendocrine tumors: a case and discussion of the literature.

Neuroendocrine tumors (NETs) are derived from neuroendocrine cells that are capable of producing functional peptide hormones. These tumors occur most frequently in the GI tract and lungs. GI NETs frequently metastasize into the liver, though NETs of primary hepatic origin are extremely rare. Ultrasound, CT, and MRI are typically all employed for characterization of these lesions but their appearance on diagnostic imaging can be highly variable. Reported here is an interesting case of a primary hepatic neuroendocrine tumor (PHNET), along with a discussion of the imaging characteristics of these tumors. Additionally, the current standards for definitive diagnosis and treatment of PHNETs are discussed.

Factors Affecting Periprocedural Morbidity and Mortality and Long-term Patient Survival after Arterial Embolization of Hepatic Neuroendocrine Metastases

PurposeTo identify factors affecting periprocedural morbidity and mortality and long-term survival following hepatic artery embolization (HAE) of hepatic neuroendocrine tumor (NET) metastases. Materials and MethodsThis single-center, institutional review board–approved retrospective review included 320 consecutive HAEs for NET metastases performed in 137 patients between September 1996 and September 2007. Forty-seven HAEs (15%) were performed urgently to manage refractory symptoms in inpatients (urgent group), and 273 HAEs (85%) were elective (elective group). Overall survival (OS) was estimated by Kaplan–Meier methodology. Complications were categorized per Common Terminology Criteria for Adverse Events, version 4.0. Univariate and multivariate analyses were performed to determine independent predictors for OS, complications, and 30-day mortality. The independent factors were combined to develop clinical risk score groups. ResultsUrgent HAE (P = .007), greater than 50% liver replacement by tumor (P < .0001), and extrahepatic metastasis (P = .007) were independent predictors for shorter OS. Patients with all three risk factors had decreased OS versus those with none (median, 8.5 vs 86 mo; P < .001). Thirty-day mortality was significantly lower in the elective (1%) versus the urgent group (8.5%; P = .0009). There were eight complications (3%) in the elective group and five (10.6%) in the urgent group (P = .03). Male sex and urgent group were independent factors for higher 30-day mortality rate (P = .023 and P =.016, respectively) and complications (P = .012 and P =.001, respectively). ConclusionsUrgent HAE, replacement of more than 50% of liver by tumor, and extrahepatic metastasis are strong independent predictors of shorter OS. Male sex and urgent HAE carry higher 30-day mortality and periprocedural morbidity risks.

Primary hepatic neuroendocrine tumor: Gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging

We present a case of a 71-year-old man with prostate cancer who had no prior underlying liver disease. During metastatic evaluation, a solid mass in the liver was identified by computed tomography and ultrasound. Gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging demonstrated a well-defined, peripheral enhancing hepatic mass containing small cystic component. This lesion was diagnosed as hepatic neuroendocrine tumor. Primary neuroendocrine tumors of the liver are extremely rare. This case is interesting because of the rarity of this neoplasm and the unique radiologic findings despite its small size. Reviews of previously reported cases in the literature are also presented.

Can imaging patterns of neuroendocrine hepatic metastases predict response yttruim-90 radioembolotherapy?

To evaluate the response to treatment in patients with neuroendocrine tumor liver metastases following yttrium-90 ((90)Y) radioembolotherapy, as a function of image patterns at presentation for (90)Y radioembolotherapy. The study cohort consisted of patients with hepatic metastatic neuroendocrine tumors treated with (90)Y at our institution during a two-year time period. Hepatic metastases were evaluated on a pre-therapy study assessing relative arterial enhancement compared to liver, lesion size, necrosis of the lesion, and associated tumor burden in the liver. We used six response criteria: Response Evaluation Criteria in Solid Tumors (RECIST) size, World Health Organization (WHO) size, European Association for the Study of the Liver (EASL) necrosis guidelines, Choi size, Choi necrosis and combination of Choi size and necrosis. About 65 lesions in 17 patients met study criteria and formed the cohort. Statistically significant response was found for lesions < 5 cm vs those ≥ 5 cm with RECIST (P = 0.04), WHO (P = 0.002) and combined Choi criteria (P = 0.02). Hyperenhancing lesions demonstrated greater response only with the Choi size criteria (P = 0.04). Lesions with ≤ 50% necrosis on the pre-scan had statistically significant greater response with the Choi necrosis criteria (P = 0.01). There was no statistical significance for response comparing lesions < 2 cm vs ≥ 2 cm or in comparing the degrees of tumor burden. Based on our findings in this study, it is suggested that initial imaging findings, as listed above, are not a good predictor of response to (90)Y radioembolization.

肝右三区域切除を施行した肝内転移を伴う肝原発神経内分泌腫瘍の1例

肝右三区域切除を施行した肝内転移を伴う肝原発神経内分泌腫瘍の1例

Advances in research of primary hepatic neuroendocrine tumors

Advances in research of primary hepatic neuroendocrine tumors

著明な石灰化を伴った肝原発神経内分泌腫瘍の1例

著明な石灰化を伴った肝原発神経内分泌腫瘍の1例

Liver Transplantation to Giant Hepatic Neuroendocrin Tumor

Neuroendocrine tumors (NET) comprise a heterogeneous group of rare neoplasms. Liver metastatic or primer hepatic NETs are amenable to various therapeutic modalities including liver transplantation (LT). Case: 45 years old woman, from another country, suffers from dyspepsia, weight loss and early satiety. She underwent blood analysis, it revealed, gamaglutamyl transferase and alkaline phosphatase as high as 1172 and 369 respectively. She was cachectic and gross hepatomegaly detected in physical examination. Computerized tomography of the abdomen revealed 12×18cm in right and 8×6cm tumor in the left liver lobe. Intrahepatic bile ducts were dilated and there was moderate amount of ascites in the abdomen. The tumor had been accepted as unresectable from another center. She admitted to our center. Liver biopsy was performed and sample was consisted with NET type I, Ki67 1%. Histology revealed trabeculated pattern coexisting PGP 9.5 cytokeratin-19 and CD56 positivity and chromografin low positivity. Also CEA, HCC, Insulin, Gastrin, TTF-1 and CDX-2 staining were negative. The pathology yielded primary liver NET or metastasis of pancreatic NET. PET CT was performed and no tumor other than liver was founded. Endoscopic ultrasound (EUS) was performed, but did not find any pathology. We considered her for living donor liver transplantation based on unresectable primer liver NET, no extrahepatic disease and well-differentiated tumor (Ki67 < 10%) reasons. After her older brother was prepared for living donor liver transplantation, right lob liver transplantation was succesfully performed. Liver specimen revealed same with the pre-surgical biopsy. No lymph node metastasis was found in the hilum of the liver. She has been doing very well free of metastasis 1 year after surgery. Conclusion: The use of LT for NET is controversial. As organs are in short supply, it is important to select patients who are most likely to benefit from this demanding procedure. Beyond the consensual criteria, i.e., it has been shown that the use of stringent criteria to select patients for LT could achieve spectacular overall and disease-free survival rates.

Experience in primary hepatic neuroendocrine tumor

We aimed to analyze the clinical characteristics, pathologic features, treatment approaches, and prognostic factors of primary hepatic neuroendocrine tumor. We retrospectively analyzed the clinical characteristics, pathologic features, treatment approaches, and prognostic factors of 9 patients with primary hepatic neuroendocrine tumor treated in our hospital from January 2003 to January 2010. The clinical manifestations were nonspecific and variable. The most common clinical manifestation was distention or right upper quadrant pain. Radiological findings are not specific and cannot distinguish primary hepatic neuroendocrine tumor from hepatocellular carcinoma. Diagnosis of primary hepatic neuroendocrine tumor was confirmed immunohistochemically and by the absence of extrahepatic primary sites. No extrahepatic primary lesions were found by ultrasonography, computed tomography, magnetic resonance imaging or positron emission tomography scan either preoperatively or during the follow-up period in our research. Immunohistologically, synaptophysin, chromogranin A and CD56 should be used as markers to precisely diagnose primary hepatic neuroendocrine tumor. The outcome of primary hepatic neuroendocrine tumor is mostly related to its resectability. Total resection of the neoplasm is most commonly proposed. A multimodality of treatments, including chemotherapy, transarterial chemoembolization and radiofrequency ablation, should be used preor postoperatively to improve the survival. Primary hepatic neuroendocrine tumor is a rare entity, and its diagnosis is difficult. Preoperative fine needle biopsy is strongly recommended, and primary surgery integrated with chemotherapy, transarterial chemoembolization or radiotherapy is considered to be an effective modality for primary hepatic neuroendocrine tumor.

Clinical features and outcomes of primary hepatic neuroendocrine carcinomas

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. We identified patients diagnosed with PHNEC and analyzed their demographics, baseline laboratory data, tumor characteristics, treatment modalities and outcomes. 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. 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 neuroendocrine tumor: Five cases with different preoperative diagnoses

Neuroendocrine tumors, also known as carcinoid tumors, behave like benign tumors; however, they show the characteristics of carcinoma. While more than 80% of the neuroendocrine tumors found in the liver are metastatic, primary hepatic neuroendocrine tumors are very rare. Five patients with hepatic mass who admitted to our clinic between August 2003 and July 2007 were treated surgically. Ultrasonography, computerized tomography and magnetic resonance imaging were performed in all patients. Endoscopy and colonoscopy were conducted to exclude malignancy of other sites. Hepatectomy was carried out in all patients. Diagnosis was confirmed with immunohistochemical examination. The five patients treated surgically were diagnosed as primary hepatic neuroendocrine tumor histopathologically. Abdominal pain was the most common complaint of all patients. Hepatectomy was conducted in all patients due to tumors originating from the liver lobes. Only one patient (Case 2) underwent transarterial chemoembolization before hepatectomy to reduce tumor bleeding. Owing to tumor recurrence on the left lobe of the liver in Case 2, transarterial chemoembolization was performed four years after hepatectomy. R0 resection was achieved in two patients (Cases 1 and 3). In conclusion, primary hepatic neuroendocrine tumors are very rare and asymptomatic tumors. Thus, high-sensitive laboratory and imaging examinations are required. At present, hepatectomy remains the main treatment for primary hepatic neuroendocrine tumor.

Primary and metastatic hepatic neuroendocrine carcinoma: a clinicopathological study

Objective To study the clinicopathological features of primary and metastatic hepatic neuroendocrine carcinoma.Methods The records of 35 patients with primary hepatic neuroendocrine carcinoma and 35 patients with metastatic hepatic neuroendocrine carcinoma were retrospectively reviewed.These patients served as the primary group(priNET,n=35)and the metastasis group (metNET,n=35),respectively.Results There were significant differences between the two groups of patients in gender,site,size and number of tumor(P＜0.05).Although there was no significant difference between the two groups in the distribution of the tumors in the two lobes of liver (P＞0.05),priNET had more tumors localized to one lobe of liver while metNET had more tumors involving both lobes of liver(P＜0.05).Conclusions Gender,size,site and number of tumor may play an important role in the differentiation of primary or metastatic hepatic neuroendocrine tumor. Key words: Liver tumor; Neuroendocrine tumor; Clinical pathology