Gastrointestinal neuroendocrine tumors in 2020

Gastrointestinal neuroendocrine tumors are rare slow-growing tumors with distinct histological,biological,and clinical characteristics that have increased in incidence and prevalence within the last few decades.They contain chromogranin A,synaptophysin and neuron-specific enolase which are necessary for making a diagnosis of neuroendocrine tumor.Ki-67 index and mitotic index correlate with cellular proliferation.Serum chromogranin A is the most commonly used biomarker to assess the bulk of disease and monitor treatment and is raised in both functioning and non-functioning neuroendocrine tumors.Most of the gastrointestinal neuroendocrine tumors are non-functional.World Health Organization updated the classification of neuroendocrine tumors in 2017 and renamed mixed adenoneuroendocrine carcinoma into mixed neuroendocrine neoplasm.Gastric neuroendocrine tumors arise from enterochromaffin like cells.They are classified into 4 types.Only type I and type II are gastrin dependent.Small intestinal neuroendocrine tumor is the most common small bowel malignancy.More than two-third of them occur in the terminal ileum within 60 cm of ileocecal valve.Patients with small intestinal neuroendrocrine tumors frequently show clinical symptoms and develop distant metastases more often than those with neuroendocrine tumors of other organs.Duodenal and jejunoileal neuroendocrine tumors are distinct biologically and clinically.Carcinoid syndrome generally occurs when jejuno-ileal neuroendocrine tumors metastasize to the liver.Appendiceal neuroendocrine tumors are generally detected after appendectomy.Colonic neuroendocrine tumors generally present as a large tumor with local or distant metastasis at the time of diagnosis.Rectal neuroendocrine tumors are increasingly being diagnosed since the implementation of screening colonoscopy in 2000.Gastrointestinal neuroendocrine tumors are diagnosed and staged by endoscopy with biopsy,endoscopic ultrasound,serology of biomarkers,imaging studies and functional somatostatin scans.Various treatment options are available for curative and palliative treatment of gastrointestinal neuroendocrine tumors.

Metformin and pancreatic neuroendocrine tumors:A systematic review and meta-analysis

BACKGROUND Most patients with advanced pancreatic neuroendocrine tumors(pNETs)die due to tumor progression.Therefore,identifying new therapies with low toxicity and good tolerability to use concomitantly with the established pNET treatment is relevant.In this perspective,metformin is emerging as a molecule of interest.Retrospective studies have described metformin,a widely used agent for the treatment of patients with type 2 diabetes mellitus(T2DM),to be effective in modulating different tumor-related events,including cancer incidence,recurrence and survival by inhibiting mTOR phosphorylation.This systematic review evaluates the role of T2DM and metformin in the insurgence and post-treatment outcomes in patients with pNET.AIM To systematically analyze and summarize evidence related to the diagnostic and prognostic value of T2DM and metformin for predicting the insurgence and posttreatment outcomes of pNET.METHODS A systematic review of the published literature was undertaken,focusing on the role of T2DM and metformin in insurgence and prognosis of pNET,measured through outcomes of tumor-free survival(TFS),overall survival and progression free survival.RESULTS A total of 13 studies(5674 patients)were included in this review.Analysis of 809 pNET cases from five retrospective studies(low study heterogeneity with I^(2)=0%)confirms the correlation between T2DM and insurgence of pNET(OR=2.13,95%CI=1.56-4.55;P<0.001).The pooled data from 1174 pNET patients showed the correlation between T2DM and post-treatment TFS in pNET patients(hazard ratio=1.84,95%CI=0.78-2.90;P<0.001).The study heterogeneity was intermediate,with I^(2)=51%.A few studies limited the possibility of performing pooled analysis in the setting of metformin;therefore,results were heterogeneous,with no statistical relevance to the use of this drug in the diagnosis and prognosis of pNET.CONCLUSION T2DM represents a risk factor for the insurgence of pNET and is a significant predictor of poor post-treatment TFS of pNET patients.Unfortunately,a few studies with heterogeneous results limited the possibility of exploring the effect of metformin in the diagnosis and prognosis of pNET.

Limitations and suggestions for type 2 diabetes mellitus and pancreatic neuroendocrine tumors based on meta-analysis

We read with great interest the systematic review and meta-analysis by Cigrovski Berkovic et al published recently,which evaluated the association between type 2 diabetes mellitus(T2DM)and pancreatic neuroendocrine tumors(pNETs).The study identified T2DM as a risk factor for the development of pNETs and linked it to poor tumor-free survival.However,due to the limited number of studies and high heterogeneity,the role of metformin in the diagnosis and prognosis of pNETs remained inconclusive.We believe the study has some limitations regarding literature search,risk of bias assessment,and analysis of heterogeneity and publication bias.Expanding the search to more databases,applying more appropriate bias assessment tools,and using better statistical methods to evaluate heterogeneity and publication bias would strengthen the study’s conclusions.Addressing these concerns could provide more robust evidence for understanding the diagnostic and prognostic impact of T2DM in pNETs.

Temozolomide and capecitabine regimen as first-line treatment in advanced gastroenteropancreatic neuroendocrine tumors at a Latin American reference center

BACKGROUND Numerous studies have indicated that the temozolomide and capecitabine regimen(TEMCAP)exhibits a certain level of efficacy in treating advanced,welldifferentiated gastroenteropancreatic neuroendocrine tumors(GEP-NET).However,published data from Peru are limited.We hypothesize that this regimen could be a viable therapeutic option for advanced GEP-NET in the Peruvian population.AIM To evaluate overall survival(OS)in patients diagnosed with advanced GEP-NET treated with TEMCAP at the Instituto Nacional de Enfermedades Neoplásicas(INEN)in Lima-Perú.METHODS A retrospective review was conducted to identify patients with GEP-NEN treated with the TEMCAP regimen between 2011 and 2021 at the INEN.A total of thirtyeight patients were included in the final analysis:Thirty-five received TEMCAP as a first-line treatment,and three as a second-line treatment.The primary objective was to evaluate OS.The efficacy and safety of TEMCAP were assessed until the occurrence of unacceptable toxicity or disease progression.Survival outcomes were estimated using the Kaplan-Meier method.RESULTS The median age of the patients was 52 years(range 24-77 years),and 53.3%were female.The most common symptoms at diagnosis were abdominal pain in 31 patients(81.6%).Primary tumors included 12 in the rectum(31.6%),11 in the pancreas(28.9%),3 in the ileum(7.9%),2 in the mesentery(5.3%),2 in the small intestine(5.3%),1 in the appendix(2.6%),1 in the stomach(2.6%)and 6 cases of liver metastasis of unknown primary(15.8%).Five were neuroendocrine tumors(NET)G1(13.2%),33 were NET G2(86.8%),five had Ki67<3%(13.2%),and 33 had Ki67 between 3%and 20%(86.8%).TEMCAP was administered to 35(92.1%)patients as first-line treatment.OS at 12,36,and 60 months was estimated in 80%,66%,and 42%,respectively,with a median OS of 49 months.CONCLUSION TEMCAP therapy is a viable first-line option regarding efficacy and tolerability in areas where standard therapy is inaccessible.

Pancreatic neuroendocrine tumors:Are tumors smaller than 2 cm truly indolent?

BACKGROUND Pancreatic neuroendocrine tumors(PNETs)are relatively rare but rank as the second most common pancreatic neoplasm.They can be functional,causing early metabolic disturbances due to hormone secretion,or non-functional and diagnosed later based on tumor size-related symptoms.Recent diagnoses of PNETs under 2 cm in size have sparked debates about their management;some practitioners advocate for surgical removal and others suggest observation due to the tumors’lower potential for malignancy.However,it is unclear whether managing these small tumors expectantly is truly safe.AIM To evaluate poor prognostic factors in PNETs based on tumor size(>2 cm or<2 cm)in surgically treated patients.METHODS This cohort study included 64 patients with PNETs who underwent surgical resection between 2006 and 2019 at a high-complexity reference hospital in Medellín,Colombia.To assess patient survival,quarterly follow-ups were conducted during the first year after surgery,followed by semi-annual con-sultations at the hospital's hepatobiliary surgery department.Qualitative variables were described using absolute and relative frequencies,and quantitative variables were expressed using measures of central tendency and their corresponding measures of dispersion.RESULTS The presence of lymph node involvement,neural involvement,and lymphovascular invasion were all associated with an increased risk of mortality,with hazard ratios of 5.68(95%CI:1.26–25.61,P=0.024),6.44(95%CI:1.43–28.93,P=0.015),and 24.87(95%CI:2.98–207.19,P=0.003),respectively.Neural involvement and lymphovascular invasion were present in tumors smaller than 2 cm in diameter and those larger than 2 cm in diameter.The recurrence rates between the two tumor groups were furthermore similar:18.2%for tumors smaller than 2 cm and 21.4%for tumors larger than 2 cm.Patient survival was additionally comparable between the two tumor groups.CONCLUSION Tumor size does not dictate prognosis;lymph node and lymphovascular involvement affect mortality,which high-lights that histopathological factors-rather than tumor size-may play a role in management.

Advancements in medical treatment for pancreatic neuroendocrine tumors:A beacon of hope

This editorial highlights the remarkable advancements in medical treatment strategies for pancreatic neuroendocrine tumors(pan-NETs),emphasizing tailored approaches for specific subtypes.Cytoreductive surgery and somatostatin analogs(SSAs)play pivotal roles in managing tumors,while palliative options such as molecular targeted therapy,peptide receptor radionuclide therapy,and chemotherapy are reserved for SSA-refractory patients.Gastrinomas,insul-inomas,glucagonomas,carcinoid tumors and VIPomas necessitate distinct thera-peutic strategies.Understanding the genetic basis of pan-NETs and exploring immunotherapies could lead to promising avenues for future research.This review underscores the evolving landscape of pan-NET treatment,offering renewed hope and improved outcomes for patients facing this complex disease.

Clinical experience sharing on gastric microneuroendocrine tumors: A case report

BACKGROUND The majority of gastric neuroendocrine tumors(G-NENs)are present in various lesions under endoscopy,and they can be polypoid uplifts,submucosal tumors or papules,erosions,and ulcers.The lesions are mostly confined to the mucosal or submucosal layer,usually less than 2 cm,and exclusively localized to the gastric body or fundus.In type 1 G-NENs,about 22%of cases have no visible lesions under an endoscope,and such lesions can only be detected via biopsies(microcar-cinoids).CONCLUSION In the case under study,the patient did not have any visible raised lesions under a gastroscope,and the lesions were found only after a random biopsy.This article combines the endoscopic manifestations and clinical features of the lesions in this case to improve the diagnosis of G-NENs.

Role of ablation therapy in conjunction with surgical resection for neuroendocrine tumors involving the liver

BACKGROUND Resection of hepatic metastasis from neuroendocrine tumors(NETs)improves quality of life and prolongs 5-year survival.Ablation can be utilized with surgery to achieve complete resection.Although several studies report long-term out-comes for patients undergoing ablation,none have explored perioperative effects of ablation in patients with metastatic NETs.AIM To determine if intra-operative ablation during hepatectomy increases risk of ad-verse outcomes such as surgical site infections(SSIs),bleeding,and bile leak.METHODS A retrospective analysis of the hepatectomy National Surgical Quality Impro-vement Program database from 2015-2019 was performed to determine the odds of SSIs,bile leaks,or bleeding in patients undergoing intraoperative ablation when compared to hepatectomy alone.RESULTS Of the 966 patients included in the study,298(30.9%)underwent ablation during hepatectomy.There were 78(11.7%)patients with SSIs in the hepatectomy alone group and 39(13.1%)patients with a SSIs in the hepatectomy with ablation group.Bile leak occurred in 41(6.2%)and 14(4.8%)patients in the two groups,respec-tively;bleeding occurred in 117(17.5%)and 33(11.1%),respectively.After con-trolling for confounding variables,ablation did not increase risk of SSI(P=0.63),bile leak(P=0.34)or bleeding(P=0.07)when compared to patients undergoing resection alone on multivariate analysis.CONCLUSION Intraoperative ablation with hepatic resection for NETs is safe in the perioperative period without significant increased risk of infection,bleeding,or bile leak.Surgeons should utilize this modality when appropriate to a-chieve optimal disease control and outcomes.

Bisecreting Pituitary Neuroendocrine Tumors: About 9 Cases at the Abass Ndao Hospital Center in Dakar

Introduction: Pituitary neuroendocrine tumor (PitNET) may present multisecreting forms. Identifying its forms helps to guide management. This management is a real challenge, given the limited resources in our regions. In view of advances in the management of these multisecreting pituitary neuroendocrine tumors and the lack of published data in Africa, and in Senegal particularly, this survey was carried out with the aim of describing the epidemiological, clinical and therapeutic aspects of multisecreting PitNETs. Patients and Method: It was a multicenter, retrospective, descriptive and analytical study carried out on files collected from 1st January 2008 to 31 December 2022 in the neurosurgery departments of the Fann and Principal hospitals in Dakar and the endocrinology department of the Abass Ndao hospital in Dakar. Results: Of the 242 patients treated for PitNET, 09 presented (the mean age of our patients was 41.7 ± 11 years) with bihormonal PitNET, i.e. a proportion of 3.71%. Two types of association were found: 08 tumors with GH (Growth Hormon) + PRL (prolactin) secretion and 01 PitNET with ACTH (Adreno Corticotropic Homon) + prolactin secretion. Clinically, gonadotropic insufficiency was found in all patients (100%). Dysmorphic syndrome was found in 6 patients (66.7%) and tumor syndrome in 7 patients (77.8%). Ophthalmological evaluation revealed a decrease in visual acuity in 66.6% of patients. All had macroadenomas, with extension noted in 02 patients. All patients underwent transsphenoidal surgery with complications such as transient diabetes insipidus (3 patients, 33.3%), followed by cerebrospinal fluid leaks (1 patient, 11.1%). Remission was noted in all 5 patients tested. A comparison between the different secretory forms did not reveal any significant difference in the frequency of postoperative complications. Conclusion: Despite the lack of immunohistochemistry, two types of association were found: ACTH-PRL and GH-PRL. All were macroadenomas, the majority with an associated tumor syndrome. The latter was significantly less frequent in bisecreting PitNETs compared with monosecreting and non-functional forms. However, there was no significant difference in the occurrence of post-operative complications between the three secretory forms of PitNETs.

Management of gastric and duodenal neuroendocrine tumors

Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, like all NETs. However, the incidence of GI-NETS has been increasing in recent years. Gastric NETs (G-NETs) and duodenal NETs (D-NETs) are the common types of upper GI-NETs based on tumor location. G-NETs are classified into three distinct subgroups: type&#x02005;I, II, and III. Type&#x02005;I&#x02005;G-NETs, which are the most common subtype (70%-80% of all G-NETs), are associated with chronic atrophic gastritis, including autoimmune gastritis and Helicobacter pylori associated atrophic gastritis. Type II G-NETs (5%-6%) are associated with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome (MEN1-ZES). Both type&#x02005;I&#x02005;and II G-NETs are related to hypergastrinemia, are small in size, occur in multiple numbers, and are generally benign. In contrast, type III G-NETs (10%-15%) are not associated with hypergastrinemia, are large-sized single tumors, and are usually malignant. Therefore, surgical resection and chemotherapy are generally necessary for type III G-NETs, while endoscopic resection and follow-up, which are acceptable for the treatment of most type&#x02005;I&#x02005;and II G-NETs, are only acceptable for small and well differentiated type III G-NETs. D-NETs include gastrinomas (50%-60%), somatostatin-producing tumors (15%), nonfunctional serotonin-containing tumors (20%), poorly differentiated neuroendocrine carcinomas (&#x0003c; 3%), and gangliocytic paragangliomas (&#x0003c; 2%). Most D-NETs are located in the first or second part of the duodenum, with 20% occurring in the periampullary region. Therapy for D-NETs is based on tumor size, location, histological grade, stage, and tumor type. While endoscopic resection may be considered for small nonfunctional D-NETs (G1) located in the higher papilla region, surgical resection is necessary for most other D-NETs. However, there is no consensus regarding the ideal treatment of D-NETs.

Pancreatic neuroendocrine tumors: Therapeutic challenges and research limitations

Pancreatic neuroendocrine tumors(PNETs)are known to be the second most common epithelial malignancy of the pancreas.PNETs can be listed among the slowest growing as well as the fastest growing human cancers.The prevalence of PNETs is deceptively low;however,its incidence has significantly increased over the past decades.According to the American Cancer Society’s estimate,about 4032(>7%of all pancreatic malignancies)individuals will be diagnosed with PNETs in 2020.PNETs often cause severe morbidity due to excessive secretion of hormones(such as serotonin)and/or overall tumor mass.Patients can live for many years(except for those patients with poorly differentiated G3 neuroendocrine tumors);thus,the prevalence of the tumors that is the number of patients actually dealing with the disease at any given time is fairly high because the survival is much longer than pancreatic ductal adenocarcinoma.Due to significant heterogeneity,the management of PNETs is very complex and remains an unmet clinical challenge.In terms of research studies,modest improvements have been made over the past decades in the identification of potential oncogenic drivers in order to enhance the quality of life and increase survival for this growing population of patients.Unfortunately,the majority of systematic therapies approved for the management of advanced stage PNETs lack objective response or at most result in modest benefits in survival.In this review,we aim to discuss the broad challenges associated with the management and the study of PNETs.

Clinical characteristics and outcome of primary hepatic neuroendocrine tumors after comprehensive therapy

BACKGROUND Primary hepatic neuroendocrine tumors(PHNETs),a group of neuroendocrine neoplasms,are extremely rare.There are only few case reports about PHNETs in the literature.The lack of large samples and multicenter research results in poor diagnostic and therapeutic approaches.AIM To discuss the clinical characteristics,diagnosis,and treatment of PHNETs and risk factors related to survival.METHODS We retrospectively analyzed the clinical data,imaging features,immunohistochemistry data,and treatment efficacy of 40 patients who were pathologically diagnosed with PHNETs and admitted to The First Affiliated Hospital of Zhengzhou University from January 1,2014 to November 15,2019.Finally,survival analysis was performed to identify the risk factors for survival.RESULTS The main symptoms and signs included intermittent abdominal pain(19 patients,47.5%)and bloating(8 patients,20.0%).The positive rates of tested tumor markers were recorded as follows:Carbohydrate antigen 19-9(CA19-9)(6 patients,15.0%),CA72-4(3 patients,7.5%),carcinoembryonic antigen(7 patients,17.5%),and alpha-fetoprotein(6 patients,15.0%).Immunohistochemical staining results showed positivity for Syn in 38(97.4%)of 39 patients,for chromogranin A in 17(65.4%)of 26 patients,for CD56 in 35(94.6%)of 37 patients,for AE1/AE3 in 28(87.5%)of 32 patients,and for Ki-67 in all 40(100.0%)patients.The overall survival rate was significantly related to the tumor grade,AE1/AE3,and Ki-67.tumor number,tumor size,metastasis,and treatment)and overall survival.CONCLUSION Higher grade,negative AE1/AE3,and higher Ki-67 are associated with a worse survival rate.Kinds of treatment and other parameters have no significant influence on overall survival.

Gastric neuroendocrine tumors in a BRCA2 germline mutation carrier:A case report

BACKGROUND The molecular changes present in gastric neuroendocrine tumors(NETs)include a loss of heterozygosity or mutation of MEN1,CDKN1B gene mutation,P27 heterozygous mutation,and ATP4A gene missense mutation.We identified and are the first to report a case of type 1 histamine-producing enterochromaffin-like cell NETs(ECL-cell NETs)with a BRCA2 gene germline mutation.CASE SUMMARY The patient had a history of iron-deficient anemia for 5 years,and gastroscopic examination indicated multiple gastric tumors.Then,the patient underwent distal gastrectomy.Microscopically,multifocal tumor cells were found in the mucosa and submucosa;tumor cells were organoid and arranged in nests and cords,and the stroma was rich in sinusoids.The surrounding gastric mucosa showed atrophy with mild intestinal metaplasia or pseudopyloric gland metaplasia.Neuroendocrine cells could be seen with diffuse linear,nodular,and adenomatous hyperplasia.Immunohistochemically,the tumor cells diffusely expressed cytokeratin,chromogranin,synaptophysin,and CD56.Whole-genome highthroughput molecular sequencing revealed a pathogenic germline mutation in the BRCA2 gene,a heterozygous germline frameshift mutation in exon 11,c.6443_6444del(p.S2148Yfs*2).The final diagnosis was gastric type 1 ECL-cell NETs with a BRCA2 gene germline mutation,accompanied by autoimmune gastritis.CONCLUSION This is the first report of a case of type 1 gastric ECL-cell NETs with a pathogenic germline mutation of the BRCA2 gene.The findings of this report will expand the germline mutation spectrum of gastric NETs and increase the understanding of the molecular changes present in these tumors for their improved diagnosis in the future.

Neuroendocrine tumors of the gastro-entero-pancreatic system

Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms, although their prevalence has increased substantially over the past three decades. Moreover, there has been an increased clinical recognition and characterization of these neoplasms. They show extremely variable biological behavior and clinical course. Most NETs have endocrine function and secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome; however, many are clinically silent until late presentation with mass effects. Investigation and management should be individualized for each patient, taking into account the likely natural history of the tumor and general health of the patient. Management strategies include surgery for cure or palliation, and a variety of other cytoreductive techniques, and medical treatment including chemotherapy, and biotherapy to control symptoms due to hormone release and tumor growth, with somatostatin analogues (SSAs) and alphainterferon. New biological agents and somatostatintagged radionuclides are under investigation. Advances in the therapy and development of centers of excellence which coordinate multicenter studies, are needed to improve diagnosis, treatment and therefore survival of patients with GEP NETs.

Rectal neuroendocrine tumors:Current advances in management,treatment,and surveillance

Rectal neuroendocrine neoplasms(r-NENs)are considered among the most frequent digestive NENs,together with small bowel NENs.Their incidence has increased over the past few years,and this is probably due to the widespread use of endoscopic screening for colorectal cancer and the advanced endoscopic procedures available nowadays.According to the current European Neuroendocrine Tumor Society(ENETS)guidelines,well-differentiated r-NENs smaller than 10 mm should be endoscopically removed in view of their low risk of local and distant invasion.R-NENs larger than 20 mm are candidates for surgical resection because of their high risk of distant spreading and the involvement of the muscularis propria.There is an area of uncertainty regarding tumors between 10 and 20 mm,in which the metastatic risk is intermediate and the endoscopic treatment can be challenging.Once removed,the indications for surveillance are scarce and poorly codified by international guidelines,therefore in this paper,a possible algorithm is proposed.

Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors

Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuro-endocrine tumors (NETs). In recent years, accumul ating data has supported their role as antiproliferative agents, capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies, including carci-noid and pancreatic endocrine tumors. A phase Ⅲ, ran-domized, placebo-controlled trial has now demonstrated that octreotide long-acting repeatable (LAR) 30 mg can significantly prolong time to tumor progression among patients with metastatic midgut NETs regardless of functional status, chromogranin A level or age. In addition to signif icantly lengthening time to tumor pro-gression in the overall study population, subset analysis suggests that patients with low tumor burden are most likely to experience disease stabilization with octreotide LAR 30 mg, supporting the early use of octreotide LAR in patients with metastatic disease. Further research efforts are underway to evaluate the use of somatostatin analogs as antiproliferative agents in other types of gastroenteropancreatic-NETs. Ongoing studies are also evaluating novel somatostatin analogs and somatostatin analogs in combination with other anti-tumor therapies.

Pathologic research update of colorectal neuroendocrine tumors

Colorectal neuroendocrine tumors (NETs) originate from neuroendocrine cells in the intestinal tract, and represent a small area within oncology, but one which has provided increasing new data during the past years. Although the World Health Organization has determined clinical and histological features to predict prognosis for such tumors, they may not be valid on an individual basis. We aim to give an overview of the recent findings with regard to pathology, molecular genetics and diagnosis of NETs.

Retrospective analysis of interventional treatment of hepatic metastasis from gastroenteropancreatic neuroendocrine tumors

Objective： To analyze the angiography appearance of liver metastases from gastroenteropancreatic neuroendocrine tumors （GEP-NETs）, and evaluate the clinical efficacy and prognostic factors of interventional treatment for hepatic metastases. Methods： Fifty GEP-NETs patients with hepatic metastases were treated from January 2012 to December 2016, and received transarterial embolization （TAE） in the hepatic tumor or hepatic arterial infusion chemotherapy （HAIC）. All patients received 179 times of the intervention therapy in total. Results： Blood supplies were identified in the 50 eases with angiography, which showed that 35 cases had abundant vessels, while 15 eases had poor blood supply. Twenty-two cases were found either collateral blood supply, or portal vein invasion or arterial-portal vein fistula. The best curative efficacy was complete remission （CR） in 4 cases, partial remission （PR） in 28 cases and stable disease （SD） in 18 eases during the process of treatment. The angiography （P=0.047） and the frequency of intervention （P=0.037） showed significantly statistical difference with Kaplan-Meier analysis. The Cox analysis showed that more than 3 times of interventional therapy was an independent prognostic factor. Conclusions： Interventional treatment is safe and effective for GEP-NETs, and is beneficial to patients with main hepatic metastases after endocrine therapy.

Comparison of imaging-based and pathological dimensions in pancreatic neuroendocrine tumors

AIM To establish the ability of magnetic resonance(MR) and computer tomography(CT) to predict pathologic dimensions of pancreatic neuroendocrine tumors(Pan NET) in a caseload of a tertiary referral center.METHODS Patients submitted to surgery for Pan NET at the Surgical Unit of the Pancreas Institute with at least 1 preoperative imaging examination(MR or CT scan) from January 2005 to December 2015 were included and data retrospectively collected. Exclusion criteria were: multifocal lesions, genetic syndromes, microadenomas or mixed tumors, metastatic disease and neoadjuvant therapy. Bland-Altman(BA) and Mountain-Plot(MP) statistics were used to compare size measured by each modality with the pathology size. Passing-Bablok(PB) regression analysis was used to check the agreement between MR and CT.RESULTS Our study population consisted of 292 patients. Seventy-nine(27.1%) were functioning Pan NET. The mean biases were 0.17 ± 7.99 mm, 1 ± 8.51 mm and 0.23 ± 9 mm, 1.2 ± 9.8 mm for MR and CT, considering the overall population and the subgroup of non-functioning-Pan NET, respectively. Limits of agreement(LOA) included the vast majority of observations, indicating a good agreement between imaging and pathology. The MP further confirmed this finding and showed that the two methods are unbiased with respect to each other. Considering ≤ 2 cm non-functioning-Pan NET, no statistical significance was found in the size estimation rate of MR and CT(P = 0.433). PBR analysis did not reveal significant differences between MR, CT and pathology.CONCLUSION MR and CT scan are accurate and interchangeable imaging techniques in predicting pathologic dimensions of Pan NET.

New therapeutic approaches to metastatic gastroenteropancreatic neuroendocrine tumors:A glimpse into the future

Neuroendocrine(NE) gastroenteropancreatic tumors are a heterogeneous group of neoplasias arising from neuroendocrine cells of the embryological gut. Their incidence have increased significantly over the past 3 decades probably due to the improvements in imaging and diagnosis. The recent advances in molecular biology have translated into an expansion of therapeutic approaches to these patients. Somatostatin analogs, which initially were approved for control of hormonal syndromes, have recently been proven to inhibit tumor growth. Several new drugs such as antiangiogenics and others targeting mammalian target of rapamycin pathways have been approved to treat progressive pancreatic neuroendocrine tumors(NETs) although their role in nonpancreatic is still controversial. The treatment of NETs requires a coordinated multidisciplinary approach. The management of localized NETs primarily involves surgical resection followed by surveillance. However, the treatment of unresectable and/or metastatic disease may involve a combination of surgical resection, systemic therapy, and liver-directed therapies with the goal of alleviating symptoms of peptide release and controlling tumor growth. This article will review the current therapeutic strategies for metastatic gastroenteropancreatic NETs and will take a glimpse into the future approaches.