Neuroendocrine Tumor Liver Metastases Research Articles

The comparative analysis of immunohistochemical parameters of primary liver cancer and liver metastases of malignant tumors of solid, trabecular, tubular-glandular structure in puncture trephine biopsy

Aim. In puncture trephine biopsy of the liver differential immunohistochemical (IHC) parameters of hepatocellular carcinoma (HCC) in 30 patients, cholangiocellular cancer (CC) of the liver in 15 patients, and liver metastases of malignant tumors of solid, trabecular structure [melanoma (12), breast cancer (10), neuroendocrine tumors (12), prostate cancer (2)] and tubuloglandular structure [ductal carcinoma of the pancreas (12), adenocarcinoma of the stomach (10), colorectal cancer (17), RCC (6), cancer lung (4)] were studied.Methods and results. It is established that melanoma metastases of solid-trabecular microstructure in the liver, as opposed to HCC, are characterized by expression of S100, HMB45, tyrosinase and lack of the expression of hepatocyte markers (HepPar-1, α-FTP). Liver metastases of neuroendocrine tumors of solid, trabecular microstructure have the IHC profile S100 + / ChG + / Syn + / CD56 +, to distinguish them from primary HCC and CC as well as liver metastases of other tumors. In view of the ultrasound and clinical-laboratory data of mammary (breast) cancer metastases were identified by CK7 + / CK20- / Er + / Mgl + immunophenotype, metastases of prostate cancer - by CK7- / CK20- / Andr + / PSA + immunophenotype. Liver metastases of adenocarcinoma of the stomach and colorectal cancers of tubular and glandular-acinar structure have the similar IHC expression profile of CK20, CDX2, CA 19-9, and CA 125 mucin, MUC2 and MUC5AC, the differential value has no CK7 expression in metastases of colorectal cancer and its presence in metastases of adenocarcinoma of the stomach.Conclusions. For the differential diagnosis in trephine biopsy of the liver which have the similar IHC profile of metastases of ductal pancreatic cancer, gastric adenocarcinoma and colorectal cancer, additional clinical data and instrumental studies of patients (ultrasound, computed tomography, gastroscopy and colonoscopy) are necessary.

Radioembolization with yttrium-90 resin microspheres for neuroendocrine tumor liver metastases.

We aimed to evaluate the effectiveness and safety of radioembolization with yttrium-90 (90Y) microspheres in cases with unresectable neuroendocrine tumor liver metastases (NETLMs). Thirty patients (mean age, 55 years) underwent resin-based 90Y radioembolization for unresectable NETLM at a single institution between April 2008 and June 2013. Post-treatment tumor response was assessed by cross-sectional imaging using the Response Evaluation Criteria in Solid Tumors (RECIST). Prognostic variables that affected survival were determined. The mean follow-up was 23.0±19.4 months and the median overall survival was 39 months (95% CI, 12.6-65.4 months), with one- and two-year survival rates of 71% and 45%, respectively. Imaging follow-up using RECIST at three-month intervals demonstrated partial response in 43%, complete remission in 3%, stable disease in 37%, and progressive disease in 17% of patients. Extent of tumor involvement was found to have a statistically significant influence on overall survival (P = 0.03). The existence of extrahepatic disease at the time of radioembolization, radiographic response, age, and primary neuroendocrine tumor site were not significant prognostic factors. The current study demonstrates the effectiveness and safety of radioembolization for the treatment of unresectable NETLMs. We identified that the extent of tumor involvement has a significant effect on overall survival. The use of imaging methods reflecting metabolic activity or cellularity such as scintigraphy or diffusion-weighted MRI would be more appropriate, for the response evaluation of liver metastases after radioembolization.

Surgical resection improves the outcome of the patients with neuroendocrine tumor liver metastases: large data from Asia.

How to properly manage neuroendocrine liver metastasis (NELM) remains debatable, and only limited clinical data have been published from Asian population. The objective of this study is to identify possible prognostic factors affecting overall survival time and to provide a guideline for future clinical practice.A retrospective study was performed on 1286 patients who had neuroendocrine tumors in our specialized center, and data from 130 patients who had NELM were summarized. Demographic and clinicopathologic data, tumor grade, treatment method, and prognosis were statistically analyzed.Most of the NELMs originated from pancreas (65.4%). Important prognostic factors that included tumor location and size were identified with multivariate analysis. Patients with either primary tumor resection or liver metastasis resection showed a 5-year survival of 35.7% or 33.3%, respectively, whereas resection of both resulted in a 50% 5-year survival. More importantly, resection was performed on 7 patients with grade 3 (G3) tumors, and resulted in 1-year, 3-year, and 5-year survival of 100%, 42.8%, and 28.6%, respectively, whereas the other 9 G3 patients without resection died within 3 years. P = 0.49 comparing the resected group with nonresected group in G3 patients. Besides, the overall 5-year survival rates for resected and nonresected patients were 40.5% and 5.4%, respectively.Multiple prognostic factors influenced the overall outcome of NELM including patient age, tumor location, and size, etc. Aggressive surgical approaches could be considered for maximum survival time disregarding the pathological grade of the tumor. Study with larger sample size should be considered to reevaluate the recommendation of the WHO guidelines for G3 neuroendocrine tumors.

Relationship between the level of serum chromogranin A and liver metastases of non-functional pancreatic neuroendocrine tumors

Objective To investigate the relationship between the level of serum chromogranin A (CgA) and liver metastases of non-functional pancreatic neuroendocrine tumors (pNETs).Methods The clinical data of 64 patients with non-functional pNETs who were admitted to the Zhongshan Hospital of Fudan University from December 2011 to December 2013 were retrospectively analyzed.Thirty-nine patients had complete clinical and follow-up data,and 25 patients only have clinical data.The levels of serum CgA were detected in 58 patients before liver metastases,and the levels of serum CgA were detected in 51 patients after liver metastases.Patients were re-examined every 3-6 months after the discharge.The level of serum CgA was increased or decreased by more than 50％ of the level of serum CgA before the treatment was defined as increase or decrease of serum CgA,otherwise,stable level of serum CgA.The levels of serum CgA were detected by enzyme-linked immunosorbent assay,and the liver metastatic tumor load was assessed by three-dimensional reconstruction with the data of computed tomography.The efficacy of treatment was evaluated by response evaluation criteria in solid tumors.Patients were followed up via out-patient examination till March 2014.Complete or partial remission was defined as disease remisson,stable condition was defined as stable disease,and disease progression or tumor recurrence was defined as disease progression.The measurement data were presented by (P25,P75).The count data were analyzed using the Fisher exact probability,and the measurement data were analyzed using the Kruskal-Wallis test or MannWhitney test.The correlation was tested by Spearman rank correlation.Results The levels of serum CgA of pNETs patients with liver metastases was 94.8 μg/L (67.4μg/L,181.4 μg/L),which was significantly higher than 59.9 μg/L (39.1 μg/L,88.5 μg/L) of pNETs patients without liver metastases (Z =-3.96,P ＜0.05).There was a positive correlation between the tumor load and the level of the serum CgA before liver metastases in 51 non-functional pNETs patients (r =0.486,P ＜ 0.05).Thirty-five patients were followed up for a median time of 10 months.In the 14 patients with disease remission,the ratios of patients with increased and stable level of serum CgA were 11/14 and 3/14,respectively.In the 12 patients with a stable condition,the ratios of patients with decreased,stable and increased level of serum CgA were 4/12,7/12 and 1/12,respectively.In the 9 patients with disease progression,the ratios of patients with stable and increased levels of serum CgA were 2/9 and 7/9,respectively.There were significant differences in the ratios of patients with decreased and increased levels of CgA among the 3 groups of patients (F =11.02,18.82,P ＜0.05),while no significant difference was detected in the ratio of patients with stable level of CgA among the 3 groups of patients (F =5.68,P ＞ 0.05).The ratio of patients with decreased level of serum CgA in patients with disease remission was significant higher than patients with disease progression or in a stable condition (P ＜ 0.05).The ratio of patients with increased level of serum CgA in patients with disease progression was significantly higher than patients with disease remission or in a stable condition (P ＜ 0.05).Conclusions Increased level of serum CgA might indicate that the efficacy of treatment is poor for non-functional pNETs patients with liver metastases.The tumor load is increased as the increase of the serum CgA level. Key words: Non-functional pancreatic neuroendocrine neoplasms; Pancreas; Liver metastases; Chromogranin A

Clinical applications of PET/MRI: current status and future perspectives.

Fully integrated positron emission tomography (PET)/magnetic resonance imaging (MRI) scanners have been available for a few years. Since then, the number of scanner installations and published studies have been growing. While feasibility of integrated PET/MRI has been demonstrated for many clinical and preclinical imaging applications, now those applications where PET/MRI provides a clear benefit in comparison to the established reference standards need to be identified. The current data show that those particular applications demanding multiparametric imaging capabilities, high soft tissue contrast and/or lower radiation dose seem to benefit from this novel hybrid modality. Promising results have been obtained in whole-body cancer staging in non-small cell lung cancer and multiparametric tumor imaging. Furthermore, integrated PET/MRI appears to have added value in oncologic applications requiring high soft tissue contrast such as assessment of liver metastases of neuroendocrine tumors or prostate cancer imaging. Potential benefit of integrated PET/MRI has also been demonstrated for cardiac (i.e., myocardial viability, cardiac sarcoidosis) and brain (i.e., glioma grading, Alzheimer's disease) imaging, where MRI is the predominant modality. The lower radiation dose compared to PET/computed tomography will be particularly valuable in the imaging of young patients with potentially curable diseases.However, further clinical studies and technical innovation on scanner hard- and software are needed. Also, agreements on adequate refunding of PET/MRI examinations need to be reached. Finally, the translation of new PET tracers from preclinical evaluation into clinical applications is expected to foster the entire field of hybrid PET imaging, including PET/MRI.

Survival following Y90 radioembolization for neuroendocrine tumor liver metastases: A retrospective, single-center analysis.

e15166 Background: Y90 radioembolization has become an increasingly common palliative measure for patients with unresectable metastatic neuroendocrine tumors (NETs) in the liver. The amount by whic...

Hepatic parenchymal preserving technique in the management of diffuse bilateral neuroendocrine tumour liver metastases: a feasible approach

Aggressive surgical resection of neuroendocrine tumour liver metastases (NET-LM) is associated with symptomatic relief. Debulking up to 90% of tumour burden, even with positive margins, may be beneficial. However, patients with diffuse hepatic metastases may not qualify for resection owing to associated insufficient remnant liver parenchyma. The purpose of this study is to describe an early experience with a hepatic parenchymal preserving (HPP) approach. We retrospectively reviewed our institutional neuroendocrine tumours database to identify patients with NET-LM, including symptomatic patients with extensive bilobar involvement, who underwent virtual volumetric assessment (VVA) combined with HPP resection between October 2008 and July 2011. Our study involved 9 patients. The median number of liver metastases resected was 10 (range 4-50). Symptomatic improvement was observed in all patients. Immediate postoperative normalization of 5-HIAA 24-hour urine levels occurred in 89% of patients. Symptomatic and biochemical response remained stable or improved in 75% of patients at 12 months of follow-up. Four patients had postoperative complications. There was no 90-day mortality. The described HPP approach is feasible and safe. Most patients experienced symptomatic and biochemical improvement. This reproducible approach could expand surgical resection options for patients with NET-LM and diffuse bilobar involvement.

Alternative Lengthening of Telomeres Predicts Site of Origin in Neuroendocrine Tumor Liver Metastases

The determination of the primary tumor origin in patients with neuroendocrine tumor liver metastases (NELM) can pose a considerable management challenge. Recent studies have shown that the alternative lengthening of telomeres (ALT) is prevalent in some human tumors, including pancreatic neuroendocrine tumors (PanNET), and can be useful in predicting tumor biology. In this study, we aimed to evaluate the use of ALT as a biomarker in patients with NELM, in particular to predict the site of origin of metastases. Tissue microarrays (TMAs) were constructed using tumor tissue from NELM patients undergoing liver resection between 1998 and 2010. These included 43 PanNET and 47 gastrointestinal carcinoid tumors. The TMAs were tested for ALT using telomere-specific fluorescent in situ hybridization. The association between ALT positivity and clinicopathologic features and long-term outcomes was investigated. Alternative lengthening of telomeres was positive (ALT+) in 26 (29%) of the 90 tumors included in the TMAs. Pancreatic neuroendocrine tumors were ALT+ in 56% of patients, compared with only 4% ALT+ among gastrointestinal carcinoid tumors (p < 0.001). The specificity of ALT for detecting pancreatic origin was 96% and the positive predictive value was 92%, and sensitivity was 56% and the negative predictive value was 70%. Additionally, ALT was associated with the pattern of metastatic disease: ALT+ NELM were more likely to have oligometastases (p = 0.001) and less likely to be bilateral in distribution (p = 0.05) than were ALT tumors. In addition, ALT+ was associated with improved prognosis in the PanNET patient population. Alternative lengthening of telomeres was found to be a useful biomarker in patients with NELM. This marker can be helpful in guiding therapy by identifying the site of origin in patients in whom the primary site is unknown.

Long Term Survival Analysis of Hepatectomy for Neuroendocrine Tumour Liver Metastases

Background. Liver is the commonest site for metastasis in patients with neuroendocrine tumour (NET). A vast majority of treatment strategies including liver directed nonsurgical therapy, liver directed surgical therapy, and nonliver directed therapy have been proposed. In this study we aim to investigate the outcome of liver resection in neuroendocrine tumour liver metastases (NELM). Method. 293 patients had hepatectomy for liver metastasis in our hospital between June 1996 and December 2010. Twelve patients were diagnosed to have NET in their final pathology and their data were reviewed. Results. The median ages of the patients were 48.5 years (range 20–71 years). Eight of the patients received major hepatectomy. Four patients received minor hepatectomy. The median operation time was 418 minutes (range 195–660 minutes). The median tumor size was 8.75 cm (range 0.9–21 cm). There was no hospital mortality. The overall one-year and three-year survivals were 91.7% and 55.6%. The one-year and three-year disease-free survivals were 33.3% and 16.7%. Conclusion. Hepatectomy is an effective and safe treatment for NELM. Reasonable outcome on long term overall survival and disease-free survival can be achieved in this group of patients with a low morbidity rate.

Transplantation and Surgical Strategies in Patients With Neuroendocrine Liver Metastases: Protocol of Four Systematic Reviews

BackgroundHepatic metastases of neuroendocrine tumors (NETs) are considered a major prognostic factor associated with significantly reduced survival compared to patients without liver metastases. Several surgical and nonsurgical strategies are present to treat resectable and nonresectable liver metastases, some of which have the potential to cure liver mestatases.ObjectiveThe aims of the four systematic reviews presented in the paper are to determine the effectiveness of liver resection versus nonsurgical treatment of patients with NET liver metastases, to investigate the impact of neoadjuvant and adjuvant treatment options on the tumor-free survival, to assess the role of liver transplantation in patients presenting with unresectable bilateral hepatic metastases, and to evaluate the role of primary tumor resection in presence of unresectable liver metastases.MethodsLiterature search was performed on Medical Literature Analysis and Retrieval System Online, Excerpta Medica Database, and the Cochrane Library (Cochrane Database of Systematic Reviews, Database of s of Reviews of Effects, and Cochrane Central Register of Controlled Trials). No language restrictions were applied. Randomized controlled trials, prospective and retrospective comparative cohort studies, and case-control studies will be used for the qualitative and quantitative synthesis of the systematic reviews. Case series will be only included in a separate database for descriptive purposes.ResultsThis study is ongoing and presents a protocol system of four systematic reviews that will assist in determining the effectiveness of liver resection versus nonsurgical treatment of patients with NET liver metastases. This study is also assumed to investigate the impact of neoadjuvant and adjuvant treatment options on the tumor-free survival, the role of liver transplantation, and the relevance of primary tumor resection in presence of unresectable liver metastasis.ConclusionsThe systematic reviews will show the current evidence based on the effectiveness of surgical strategies in patients with NET liver metastases and serve as basis for clinical practice guidelines.Trial RegistrationThe systematic reviews have been prospectively registered with the International Prospective Register of Systematic Reviews: liver resection (CRD42012002652); http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002652 (Archived by WebCite at http://www.webcitation.org/6LQUqMnqL,). neoadjuvant and adjuvant treatment strategies (CRD42012002656); http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002656 (Archived by WebCite at http://www.webcitation.org/6LQVvEHuf). liver transplantation (CRD42012002655); http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002655 (Archived by WebCite at http://www.webcitation.org/6LQW7WFo3,). resection of the locoregional primary NET (CRD42012002654); http://www.crd.york.ac.uk/prospero/display_record.asp?ID=CRD42012002654 (Archived by WebCite at http://www.webcitation.org/6LQWEIuGe).

Neuroendocrine Tumor Liver Metastases Treated With Yttrium-90 Radioembolization

Surgical resection remains the only curative option for neuroendocrine tumor liver metastases (NETLM). However, 90% of patients have unresectable disease. Limited data currently exists for yttrium-90 radioembolization (Y90-RE), an emerging treatment option for unresectable NETLM. This study evaluates the efficacy and tolerability of Y90-RE as well as prognostic factors in a group of NETLM patients treated with Y90-RE. Thirty-eight patients underwent glass-based Y90-RE from April 2004-February 2012. Patients were assessed radiographically (both RECIST criteria and change in tumor enhancement), serologically, and clinically at 1 month and then every 3 months post-treatment for tumor response, toxicity, and survival outcomes. Median length of follow-up was 17 months (IQR, 9-37). Median survival was 29 months. On imaging follow-up, 3 patients (9%) had a complete response (CR) to treatment, 6 (17%) had a partial response (PR), 21 (60%) had stable disease (SD), and 5 (14%) developed progressive disease (PD). Univariate analysis identified 2 significant factors associated with a good treatment response (CR/PR): location of primary tumor (p = 0.036) and histological subtype (p = 0.050). Trends towards improved survival were observed in patients who received systemic therapy before Y90-RE (p = 0.070) and in patients who received octreotide before treatment (p = 0.052). Patients requiring >1 Y90-RE treatment had worse survival (17.3 vs 39.7 months, p = 0.040). Grade 3 serologic toxicity was observed in 2 patients (one elevated bilirubin, one elevated alkaline phosphatase) after Y90-RE. No portal hypertension, liver abscess, or bilomas were reported. Grade 3 non-serologic toxicities included abdominal pain (11%), fatigue (11%), nausea/vomiting (5%), ascites (5%), dyspnea (3%), diarrhea (3%), and peripheral edema (3%). Our institutional experience demonstrates Y90-RE to be an efficacious, safe, and tolerable treatment for NETLM.

Hepatic pseudocystic metastasis of well-differentiated ileal neuroendocrine tumor: a case report with review of the literature

Imaging appearance of cyst-like changes is most frequently described in primary neuroendocrine lesions, especially pancreatic NETs.The imaging finding of a pseudocystic lesion of the liver puts in differential diagnosis many pathologies such as infectious diseases, simple biliary cysts up to biliary cystadenomas and eventually to primary or metastatic malignancies.Primary or metastatic hepatic malignancies with pseudocystic aspects are rare, and a pseudocystic aspect is reported only after neo-adjuvant treatment.Liver metastasis of untreated neuroendocrine tumors are usually solid and, to our knowledge, only two cases of neuroendocrine cystic hepatic metastases of ileal atypical carcinoids have been reported so far.We present a case of a 67 years old man with synchronous finding of an untreated hepatic pseudocystic lesion and an ileal mass histologically diagnosed as a well differentiated (G1) neuroendocrine tumor.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1443883503102967.

Gene expression in neuroendocrine tumor liver metastases accurately distinguishes between pancreas and small bowel primary tumors

Gene expression in neuroendocrine tumor liver metastases accurately distinguishes between pancreas and small bowel primary tumors

New Trends in the Multidisciplinary Treatment of Liver Tumors

The authors report on new trends in the multidisciplinary treatment of liver tumors from the 3rd Interdisciplinary Treatment of Liver Tumors Congress in Essen, Germany. Novel aspects of molecular target-oriented therapies of hepatocarcinoma were reported, such as the current position of radiofrequency and microwave ablation of tumors compared with the new electroporation technique. State-of-the-art and new surgical trends in cholangiocarcinoma treatment were also discussed. The correlation of the biological behavior involved in the differentiation of melanomas with the treatment of liver metastasis was better defined. The role of neoadjuvant chemotherapy and combined strategies for colorectal liver metastasis were focused on intra-arterial therapeutic options. New data on neuroendocrine tumor liver metastases were also shared, leading to a better orientation for patient selection for surgical treatment.

A rare case of carcinoid heart disease caused by neuroendocrine tumor of unknown primary site

Carcinoid syndrome is caused by chronic serotonin excess due to liver metastases of neuroendocrine tumours. Episodic flushing, bronchospasm, diarrhea and dyspnea are frequent among patients with carcinoid disease. Carcinoid heart disease affects the right heart in 95% of cases resulting in ventricular failure, tricuspid and pulmonary valve disease and may be fatal. Octreotide blocks hormonal release and can reduce the risk of developing carcinoid heart disease. We report a case of a 72-year old woman with metastasized neuroendocrine tumor of unknown primary site (NET-CUP), who was admitted to internal medicine for acute renal failure, flush, diarrhea, and dyspnea occurring after a third 90Y- DOTATOC treatment course. Urinary 5-HIAA levels were elevated (> 35 mg/24h) and chromogranin A levels were high at 7126 µg/l. ECG showed sinus tachycardia, low voltage QRS and right bundle block suggesting right heart failure. The transthoracic echocardiography revealed maximal tricuspid regurgitation, thickening and retraction of tricuspid leaflets. Consequently, the right ventricle was enlarged (RA 62 mm, RV 50 mm) and septal motility was abnormal. Trans-esophageal echocardiography revealed pulmonary stenosis I°. The findings represented an extreme example of carcinoid heart disease, which had not been diagnosed before in the patient. Due to advanced tricuspidal insufficiency balloon valvuloplasty was not an option and the patient declined cardiac valve surgery. Conservative therapy with loop diuretics, beta blockers, balanced fluid intake and short-acting somatostatin analogues relieved symptoms.

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.

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.

Contrast-enhanced ultrasound after devascularisation of neuroendocrine liver metastases: functional and morphological evaluation

To evaluate morphological and perfusion changes in liver metastases of neuroendocrine tumours by contrast-enhanced ultrasound (CEUS) after transarterial embolisation with bead block (TAE) or trans-arterial chemoembolisation with doxorubicin-eluting beads (DEB-TACE). In this retrospective study, seven patients underwent TAE, and ten underwent DEB-TACE using beads of the same size. At 1 day before embolisation, 2 days, 1 month and 3 months after the procedure, a destruction-replenishment study using CEUS was performed with a microbubble-enhancing contrast material on a reference tumour. Relative blood flow (rBF) and relative blood volume (rBV) were obtained from the ratio of values obtained in the tumour and in adjacent liver parenchyma. Morphological parameters such as the tumour's major diameter and the viable tumour's major diameter were also measured. A parameter combining functional and morphological data, the tumour vitality index (TVI), was studied. The Wilcoxon rank-sum test and Fisher's test were used to compare treatment groups. At 3 months rBF, rBV and TVI were significantly lower (P = 0.005, P = 0.04 and P = 0.03) for the group with doxorubicin. No difference in morphological parameters was found throughout the follow-up. One parameter, TVI, could evaluate the morphological and functional response to treatments.

Selective internal radiation therapy for neuroendocrine liver metastases

Selective internal radiation therapy (SIRT) with yttrium-90 (90Y) microspheres is a promising treatment option for unresectable neuroendocrine tumour liver metastases (NETLM). Liver metastases, which present in 46−93% of patients at time of diagnosis depending of origin of the primary tumour, are a cause of significant mortality and morbidity. For this reason, patients with NETLM require optimal clinical management, using the combined skills of a multidisciplinary team. The options available can be categorised as follows: • Surgical, with or without ablation, e.g. RFA • Medical, e.g. somatostatin analogues and/or chemotherapy • Nuclear medicine, e.g. Peptide Receptor Radionuclide Therapy (PRRT)

Overview of neuroendocrine liver metastases treatment

Although surgical resection is the only way to induce remission (if not cure) in patients with liver metastases (LM) of digestive neuroendocrine tumours (NETS), it cannot be performed in the vast majority of the patients due to the diffusion of hepatic disease. Indeed, despite evolving techniques that may include twostep resection procedures and liver transplantation, the proportion of patients who receive liver resection barely exceeds 15% in specialised centres. Medical and interventional radiological anti-tumour treatments are the mainstay for the management of patients with malignant NETS. The treatment approach is determined by: the tumour biology, location of the primary, natural history and extent of liver involvement. In patients with nonprogressive disease on 2 consecutive CT scans performed at 6-month intervals, with limited (<50% of the liver parenchyma), well-differentiated grade 1 or 2 LM, and