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.

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.

Prediction of the lymphatic,microvascular,and perineural invasion of pancreatic neuroendocrine tumors using preoperative magnetic resonance imaging

BACKGROUND Significant correlation between lymphatic,microvascular,and perineural invasion(LMPI)and the prognosis of pancreatic neuroendocrine tumors(PENTs)was confirmed by previous studies.There was no previous study reported the relationship between magnetic resonance imaging(MRI)parameters and LMPI.AIM To determine the feasibility of using preoperative MRI of the pancreas to predict LMPI in patients with non-functioning PENTs(NFPNETs).METHODS A total of 61 patients with NFPNETs who underwent MRI scans and lymphadenectomy from May 2011 to June 2018 were included in this retrospective study.The patients were divided into group 1(n=34,LMPI negative)and group 2(n=27,LMPI positive).The clinical characteristics and qualitative MRI features were collected.In order to predict LMPI status in NF-PNETs,a multivariate logistic regression model was constructed.Diagnostic performance was evaluated by calculating the receiver operator characteristic(ROC)curve with area under ROC,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV)and accuracy.RESULTS There were significant differences in the lymph node metastasis stage,tumor grade,neuron-specific enolase levels,tumor margin,main pancreatic ductal dilatation,common bile duct dilatation,enhancement pattern,vascular and adjacent tissue involvement,synchronous liver metastases,the long axis of the largest lymph node,the short axis of the largest lymph node,number of the lymph nodes with short axis>5 or 10 mm,and tumor volume between two groups(P<0.05).Multivariate analysis showed that tumor margin(odds ratio=11.523,P<0.001)was a predictive factor for LMPI of NF-PNETs.The area under the receiver value for the predictive performance of combined predictive factors was 0.855.The sensitivity,specificity,PPV,NPV and accuracy of the model were 48.1%(14/27),97.1%(33/34),97.1%(13/14),70.2%(33/47)and 0.754,respectively.CONCLUSION Using preoperative MRI,ill-defined tumor margins can effectively predict LMPI in patients with NF-PNETs.

Comprehensive treatment of a functional pancreatic neuroendocrine tumor with multifocal liver metastases

A 64-year-old man was admitted to the Sun Yat-Sen University Cancer Center with chief complaints of recurrent abdominal pain and diarrhea for about 3 years and with a history of surgical repair for intestinal perforation owing to stress ulcer. Positron emission tomography （PET）/computed tomography （CT） demonstrated a primary tumor on the pancreatic tail with multifocal liver metastases. Pathological and immunohistochemistry staining revealed the lesion to be a pancreatic neuroendocrine tumor （pNET）. According to the latest World Health Organization （WHO, 2013） classification, the tumor was classified as stage IV fimctional G1 pNET. After referral to the multidisciplinary treatment board （MDT）, the patient was started on periodic dose of omeprazole, somatostatin analogues and Interferon α （IFNα） and had scanning follow-ups. Based upon the imaging results, CT-guided radioactive iodine-125 （1251） seeds implantation therapy, radiofrequency ablation therapy （RFA） or microwave ablation technique were chosen for the treatment of the primary tumor. Transarterial chemoembolization （TACE）, RFA and microwave ablation techniques were decided upon for liver metastases. The patient showed beneficial response to the treatment with clinically manageable low-grade side effects and attained partial remission （RECIST criteria） with a good quality of life.

Percutaneous transhepatic intraportal biopsy using gastroscope biopsy forceps for diagnosis of a pancreatic neuroendocrine neoplasm:A case report

BACKGROUND Pancreatic neuroendocrine neoplasms(PNENs)are a rare group of neoplasms originating from the islets of the Langerhans.Portal vein tumor thrombosis has been reported in 33%of patients with PNENs.While the histopathological diagnosis of PNENs is usually based on percutaneous biopsy or endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA),these approaches may be impeded by gastric varices,poor access windows,or anatomically contiguous critical structures.Obtaining a pathological diagnosis using a gastroscope biopsy forceps via percutaneous transhepatic intravascular pathway is an innovative method that has rarely been reported.CASE SUMMARY A 72-year-old man was referred to our hospital for abdominal pain and melena.Abdominal contrast-enhanced magnetic resonance imaging revealed a wellenhanced tumor(size:2.4 cm×1.2 cm×1.2 cm)in the pancreatic tail with portal vein invasion.Traditional pathological diagnosis via EUS-FNA was not possible because of diffuse gastric varices.We performed a percutaneous transportal biopsy of the portal vein tumor thrombus using a gastroscope biopsy forceps.Histopathologic examination revealed a pancreatic neuroendocrine neoplasm(G2)with somatostatin receptors 2(+),allowing systemic treatment.CONCLUSION Intravascular biopsy using gastroscope biopsy forceps appears to be a safe and effective method for obtaining a histopathological diagnosis.Although welldesigned clinic trials are required to obtain more definitive evidence,this procedure may help improve the diagnosis of portal vein thrombosis and related diseases.

Diagnostic accuracy of endoscopic ultrasound in pancreatic neuroendocrine tumors: A systematic review and meta analysis

AIM: To detect pancreatic neuroendocrine tumors (PNETs) has been varied. This study is undertaken to evaluate the accuracy of endoscopic ultrasound (EUS) in detecting PNETs.METHODS: Only EUS studies confirmed by surgery or appropriate follow-up were selected. Articles were searched in Medline, Ovid journals, Medline nonindexed citations, and Cochrane Central Register of Controlled Trials and Database of Systematic Reviews. Pooling was conducted by both fixed and random effects model). RESULTS: Initial search identified 2610 reference articles, of these 140 relevant articles were selected and reviewed. Data was extracted from 13 studies (n = 456) which met the inclusion criteria. Pooled sensitivity of EUS in detecting a PNETs was 87.2% (95%CI: 82.2-91.2). EUS had a pooled specificity of 98.0% (95%CI: 94.3-99.6). The positive likelihood ratio of EUS was 11.1 (95%CI: 5.34-22.8) and negative likelihood ratio was 0.17 (95%CI: 0.13-0.24). The diagnostic odds ratio, the odds of having anatomic PNETs in positive as compared to negative EUS studies was 94.7 (95%CI: 37.9-236.1). Begg-Mazumdar bias indicator for publication bias gave a Kendall's tau value of 0.31 (P = 0.16), indication no publication bias. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. CONCLUSION: EUS has excellent sensitivity and specificity to detect PNETs. EUS should be strongly considered for evaluation of PNETs.

Recent standardization of treatment strategy for pancreatic neuroendocrine tumors

Recent advances in localization techniques,such as the selective arterial secretagogue injection test(SASI test) and somatostatin receptor scintigraphy have promoted curative resection surgery for patients with pancreatic neuroendocrine tumors(PNET).For patients with sporadic functioning PNET,curative resection surgery has been established by localization with the SASI test using secretin or calcium.For curative resection of functioning PNET associated with multiple endocrine neoplasia type 1(MEN 1) which are usually multiple and sometimes numerous,resection surgery of the pancreas and/or the duodenum has to be performed based on localization by the SASI test.As resection surgery of PNET has increased,several important pathological features of PNET have been revealed.For example,in patients with Zollinger-Ellison syndrome(ZES),duodenal gastrinoma has been detected more frequently than pancreatic gastrinoma,and in patients with MEN 1 and ZES,gastrinomas have been located mostly in the duodenum,and pancreatic gastrinoma has been found to co-exist in 13% of patients.Nonfunctioning PNET in patients with MEN 1 becomes metastatic to the liver when it is more than 1 cm in diameter and should be resected after careful observation.The most important prognos-tic factor in patients with PNET is the development of hepatic metastases.The treatment strategy for hepatic metastases of PNET has not been established and aggressive resection with chemotherapy and trans-arterial chemoembolization have been performed with significant benefit.The usefulness of octreotide treatment and other molecular targeting agents are currently being assessed.

Efficacy of endoscopic ultrasonography-guided fine needle aspiration for pancreatic neuroendocrine tumor grading

AIM: To evaluate the efficacy of endoscopic ultrasonography-guided fine needle aspiration(EUS-FNA) for grading pancreatic neuroendocrine tumors(PNETs).METHODS: A total of 22 patients were diagnosed with PNET by EUS-FNA between October 2001 and December 2013 at Fukushima Medical University Hospital.Among these cases,we targeted 10 PNET patients who were evaluated according to the World Health Organization(WHO) 2010 classification.Surgery was performed in eight patients,and chemotherapy was performed in two patients due to multiple liver metastases.Specimens obtained by EUS-FNA were first stained with hematoxylin and eosin and then stained with chromogranin,synaptophysin,CD56,and Ki-67.The specimens were graded by the Ki-67 index according to the WHO 2010 classification.Specimens obtained by surgery were graded by the Ki-67 indexand mitotic count(WHO 2010 classification).For the eight specimens obtained by EUS-FNA,the Ki-67 index results were compared with those obtained by surgery.In the two cases treated with chemotherapy,the effects and prognoses were evaluated.RESULTS: The sampling rate for histological diagnosis by EUS-FNA was 100%.No adverse effects were observed.The concordance rate between specimens obtained by EUS-FNA and surgery was 87.5%(7/8).Fo r t h e t w o c a s e s t re a t e d w i t h c h e m o t h e ra p y,case 1 received somatostatin analog therapy and transcatheter arterial infusion(TAI) targeting multiple liver metastases.Subsequent treatment consisted of everolimus.During chemotherapy,the primary tumor remained unconfirmed,although the multiple liver metastases diminished dramatically.Case 2 was classified as neuroendocrine carcinoma(NEC) according to the Ki-67 index of a specimen obtained by EUS-FNA; therefore,cisplatin and irinotecan therapy was started.However,severe adverse effects,including renal failure and diarrhea,were observed,and the therapy regimen was changed to cisplatin and etoposide.TAI targeting multiple liver metastases was performed.Although the liver metastases diminished,the primary tumor remained unconfirmed.These chemotherapy regimens had immediate effects for both unresectable neuroendocrine tumor(NET) and NEC cases.These two subjects are still alive.CONCLUSION: EUS-FNA was effective for PNET diagnosis and Ki-67 index grading for WHO 2010 classification,enabling informed decisions on unresectable PNET treatment by identifying NET or NEC.

Laparoscopic resection of pancreatic neuroendocrine tumors

Pancreatic neuroendocrine tumors(PNETs)are a rare heterogeneous group of endocrine neoplasms.Surgery remains the best curative option for this type of tumor.Over the past two decades,with the development of laparoscopic pancreatic surgery,an increasingly larger number of PNET resections are being performed by these minimally-invasive techniques.In this review article,the various laparoscopic surgical options for the excision of PNETs are discussed.In addition,a summary of the literature describing the outcome of these treatment modalities is presented.

Pancreatic neuroendocrine tumors:A review of serum biomarkers,staging,and management

Pancreatic neuroendocrine tumors(pNETs)are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading,clinical staging,and presence of symptoms related to hormonal secretion.With regard to diagnosis,remarkable advances have been made:Chromogranin A is recommended as a general marker for pNETs.But other new biomarker modalities,like circulating tumor cells,multiple transcript analysis,microRNA profile,and cytokines,should be clarified in future investigations before clinical application.Therefore,the currently available serum biomarkers are insufficient for diagnosis,but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs.Surgical resection is still the only curative therapeutic option for localized pNETs.However,a debulking operation has also been proven to be effective for controlling the disease.As for drug therapy,steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor,while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs.Great progress has been achieved in the combination of systematic therapy with local control treatments.The optimal timing of local control intervention,planning of sequential therapies,and implementation of multidisciplinary care remain pending.

Liver-specific therapies for metastases of neuroendocrine pancreatic tumors

The presence or development of liver metastases in patients with neuroendocrine pancreatic tumors is the most important prognostic factor.Liver resection,transplantation and many different therapeutic approaches are discussed in this special review.

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.

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.

Tumor-infiltrating platelets predict postoperative recurrence and survival in resectable pancreatic neuroendocrine tumor

BACKGROUND Platelets have been reported to participate in tumor cell growth,extravasation,epithelial–mesenchymal transition,metastasis,and drug resistance.However,the importance of platelets in pancreatic neuroendocrine tumor(pNET)lacks adequate literature support.The predictive value of tumor-infiltrating platelets(TIPs)in pNET remains unclear.AIM To investigate the relationship between TIPs and the prognosis of patients with pNET following radical resection.METHODS In total,113 patients who had undergone radical surgical resection with a pathologic diagnosis of pNET were enrolled in this study.Immunohistochemical analysis of cluster of differentiation 42b(CD42b)expression in the tumor specimens was performed to determine the presence of TIPs.Univariate and multivariate analyses were used to analyze the prognostic value of TIPs.RESULTS TIPs were observed in intratumoral areas in 54 patients.Neither basic characteristics nor preoperative platelet-associated indicators showed a significant relationship with the presence of TIPs(all P>0.05).Patients with positive intratumoral CD42b expression had worse overall survival(P=0.005)and recurrence-free survival(P<0.001)than those with negative intratumoral CD42b expression.Multivariate analysis demonstrated that TIPs were independent prognostic factors for overall survival(P=0.049)and recurrencefree survival(P=0.003).Nevertheless,platelet count,mean platelet volume,and platelet-to-lymphocyte ratio were not associated with postoperative survival or recurrence in pNET patients(all P>0.05).CONCLUSION TIPs are a useful prognostic biomarker for patients with resectable pNET,and their detection represents a promising tool for pNET treatment strategy decisions.

Leveraging machine learning techniques for predicting pancreatic neuroendocrine tumor grades using biochemical and tumor markers

BACKGROUND The incidence of pancreatic neuroendocrine tumors (PNETs) is now increasing rapidly. The tumor grade of PNETs significantly affects the treatment strategy and prognosis. However, there is still no effective way to non-invasively classify PNET grades. Machine learning (ML) algorithms have shown potential in improving the prediction accuracy using comprehensive data. AIM To provide a ML approach to predict PNET tumor grade using clinical data. METHODS The clinical data of histologically confirmed PNET cases between 2012 and 2018 were collected. A method of minimum P for the Chi-square test was used to divide the continuous variables into binary variables. The continuous variables were transformed into binary variables according to the cutoff value, while the P value was minimum. Four classical supervised ML models, including logistic regression, support vector machine (SVM), linear discriminant analysis (LDA) and multi-layer perceptron (MLP) were trained by clinical data, and the models were labeled with the pathological tumor grade of each PNET patient. The performance of each model, including the weight of the different parameters, were evaluated. RESULTS In total, 91 PNET cases were included in this study, in which 32 were G1, 48 were G2 and 11 were G3. The results showed that there were significant differences among the clinical parameters of patients with different grades. Patients with higher grades tended to have higher values of total bilirubin, alpha fetoprotein, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 72-4. Among the models we used, LDA performed best in predicting the PNET tumor grade. Meanwhile, MLP had the highest recall rate for G3 cases. All of the models stabilized when the sample size was over 70 percent of the total, except for SVM. Different parameters varied in affecting the outcomes of the models. Overall, alanine transaminase, total bilirubin, carcinoembryonic antigen, carbohydrate antigen 19-9 and carbohydrate antigen 72-4 affected the outcome greater than other parameters. CONCLUSION ML could be a simple and effective method in non-invasively predicting PNET grades by using the routine data obtained from the results of biochemical and tumor markers.

Pancreatic neuroendocrine tumor Grade 1 patients followed up without surgery:Case series

Among the three grades of neuroendocrine tumors(NETs),the prognosis for Grade 1(G1) with surgery is very good.Therefore,we evaluated the prognoses of pancreatic NET(PNET) G1 patients without surgery.A total of 8 patients who were diagnosed with NET G1,with an observation period of more than 6 mo until surgery or without surgery,were recruited.The patients who underwent surgery were ultimately diagnosed using specimens obtained during the surgery,whereas the patients who did not undergo surgery were diagnosed using specimens obtained by endoscopic ultrasonography-guided fine needle aspiration.Overall,we mainly evaluated the observation period and tumor growth.The observation period for the five cases with surgery ranged from 6-80 mo,and tumor growth was observed in one case.In contrast,the observation period for the three cases without surgery ranged from 17-54 mo,and tumor growth was not observed.Therefore,although the first-choice treatment for NETs is surgery,our experience includes certain NET G1 patients who were followed up without surgery.

Correlation between radiologic features on contrastenhanced CT and pathological tumor grades in pancreatic neuroendocrine neoplasms

Contrast-enhanced computed tomography(CT)contributes to the increasing detection of pancreatic neuroendocrine neoplasms(PNENs).Nevertheless,its value for differentiating pathological tumor grades is not well recognized.In this report,we have conducted a retrospective study on the relationship between the 2017 World Health Organization(WHO)classification and CT imaging features in 94 patients.Most of the investigated features eventually provided statistically significant indicators for discerning PNENs G3 from PNENs G1/G2,including tumor size,shape,margin,heterogeneity,intratumoral blood vessels,vascular invasion,enhancement pattern in both contrast phases,enhancement degree in both phases,tumor-to-pancreas contrast ratio in both phases,common bile duct dilatation,lymph node metastases,and liver metastases.Ill-defined tumor margin was an independent predictor for PNENs G3 with the highest area under the curve(AUC)of 0.906 in the multivariable logistic regression and receiver operating characteristic curve analysis.The portal enhancement ratio(PER)was shown the highest AUC of 0.855 in terms of quantitative features.Our data suggest that the traditional contrastenhanced CT still plays a vital role in differentiation of tumor grades and heterogeneity analysis prior to treatment.

Non-functioning pancreatic neuroendocrine tumors: Surgery or observation?

Incidentally detected, sporadic, nonfunctional pancreatic neuroendocrine tumors are increasingly diagnosed on imaging studies performed for unrelated purposes. Although their resection is usually recommended, controversy still exists regarding their optimal management, due to their highly variable and difficult to predict biologic behavior. Recently, several studies and guidelines advocated an expectant management approach in small size, low grade, incidentally diagnosed nonfunctional pancreatic neuroendocrine tumors. The aim of this study is to review and summarize the available literature addressing nonfunctional pancreatic neuroendocrine tumors, with an emphasis on surgical management controversies.

Pancreatic neuroendocrine tumors: biology, diagnosis, and treatment

Pancreatic neuroendocrine tumors (PNETs), a group of endocrine tumors arising in the pancreas, are among the most common neuroendocrine tumors. The genetic causes of familial and sporadic PNETs are somewhat understood, but their molecular pathogenesis remains unknown. Most PNETs are indolent but have malignant potential. The biological behavior of an individual PNET is unpredictable; higher tumor grade, lymph node and liver metastasis, and larger tumor size generally indicate a less favorable prognosis. Endocrine testing, imaging, and histological evidence are necessary to accurately diagnose PNETs. A 4-pronged aggressive treatment approach consisting of surgery, locoregional therapy, systemic therapy, and complication control has become popular in academic centers around the world. The optimal application of the multiple systemic therapeutic modalities is under development; efficacy, safety, availability, and cost should be considered when treating a specific patient. The clinical presentation, diagnosis, and treatment of specific types of PNETs and familial PNET syndromes, including the novel Mahvash disease, are summarized.