Advances in the Diagnosis and Treatment of Appendiceal Mucinous Neoplasms

Primary appendiceal neoplasms represent a relatively low percentage of all gastrointestinal cancers. A subset of these neoplasms, those of epithelial origin, are characterised by the production of a considerable amount of mucus, which is referred to as appendiceal mucinous neoplasms (AMN). Appendiceal mucinous neoplasms (AMN) have a low incidence, are easily misdiagnosed, depend on postoperative examination for confirmation of the diagnosis, are prone to form a “diagnosis”, and have a high incidence of the disease. Furthermore, they are prone to form peritoneal pseudomyxoma peritonei (PMP), are controversial in surgical decision-making, are prone to recurring after surgery alone, and are tricky to manage clinically. In this paper, we review the pathological characteristics, diagnosis and treatment of appendiceal mucinous tumours in the light of recent literature reports, with a view to providing certain references for the clinical diagnosis and treatment of this disease. .

Exploration and optimization of surgical techniques for laparoscopic transhiatal lower mediastinal lymph node dissection for adenocarcinoma of esophagogastric junction: A prospective IDEAL 2a study with qualitative design

Objective: To explore the change and feasibility of surgical techniques of laparoscopic transhiatal(TH)-lower mediastinal lymph node dissection(LMLND) for adenocarcinoma of the esophagogastric junction(AEG)according to Idea, Development, Exploration, Assessment, and Long-term follow-up(IDEAL) 2a standards.Methods: Patients diagnosed with AEG who underwent laparoscopic TH-LMLND were prospectively included from April 14, 2020, to March 26, 2021. Clinical and pathological information as well as surgical outcomes were quantitatively analyzed. Semistructured interviews with the surgeon after each operation were qualitatively analyzed.Results: Thirty-five patients were included. There were no cases of transition to open surgery, but three cases involved combination with transthoracic surgery. In qualitative analysis, 108 items under three main themes were detected: explosion, dissection, and reconstruction. Revised instruction was subsequently designed according to the change in surgical technique and the cognitive process behind it. Three patients had anastomotic leaks postoperatively, with one classified as Clavien-Dindo Ⅲa.Conclusions: The surgical technique of laparoscopic TH-LMLND is stable and feasible;further IDEAL 2b research is warranted.

Video-assisted Thoracoscopic Surgery for the Treatment of Mediastinal Lymph Node Tuberculous Abscesses

The mediastinal lymph node tuberculous abscesses（MLNTAs） are secondary to mediastinal tuberculous lymphadenitis. Surgical excision is often required when cold abscesses form. This study was aimed to examine video-assisted thoracoscopic surgery（VATS） for the treatment of MLNTA. Clinical data of 16 MLNTA patients who were treated in our hospital between December 1, 2013 and December 1, 2015 were retrospectively analyzed. All of the patients underwent the radical debridement and drainage of abscesses, and intrathoracic lesions were removed by VATS. They were also administered the intensified anti-tuberculosis treatment（ATT）, and engaged in normal physical activity and follow-up for 3 to 6 months. The results showed that VATS was successfully attempted in all of the 16 MLNTA patients and they all had good recovery. Two patients developed complications after surgery, with one patient developing recurrent laryngeal nerve injury, and the other reporting poor wound healing. It was concluded that VATS is easy to perform, and safe, and has high rates of success and relatively few side-effects when used to treat MLNTA.

Surgical management of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms are a rare and complex group of neoplastic lesions that develop from pancreatic islet cells.Their incidence has dramatically increased during the last two decades.Due to its complex nature and pathophysiological behaviour,surgical management continues to evolve.Surgery remains the cornerstone of treatment for most non-functional and functional pancreatic neuroendocrine tumours,while lymphadenectomy remains a controversial subject.Different techniques,such as pancreas-preserving and minimally invasive approaches,continue to evolve and offer the same overall outcomes as open surgery.This comprehensive review describes in detail the current and most up-todate classification and staging of pancreatic neuroendocrine tumours,explores the rationale for nonsurgical and surgical management,and focuses on surgical treatment and more specifically,on minimally invasive approaches.

Uniportal video-assisted thoracoscopic surgery for complex mediastinal mature teratoma:A case report

BACKGROUND Mediastinal mature teratoma is the most common histological type of primary extragonadal germ cell tumor.In this report,we describe a rare case of giant mature teratoma located primarily in the anterior mediastinum and causing partial atelectasis of the upper and middle lobes of the right lung,as well as extrinsic compression of the right atrium.CASE SUMMARY A 31-year-old male with a giant mediastinal mature teratoma presented with progressive exertional dyspnea and chest pain for 1 mo.Computed tomography of the chest indicated the diagnosis of anterior mediastinal teratoma.The patient underwent right uniportal anterior approach video-assisted thoracoscopic surgery(VATS).En bloc resection of the giant teratoma,wedge resection of the upper and middle lobes of the right lung,resection of the thymus and partial excision of the pericardium were successfully performed.The pathological diagnosis revealed a mature cystic teratoma with foreign-body reaction that was closely related to the right lung,atrium dextrum,superior vena cava and ascending aorta.An atrophic thymic tissue was also discovered at the external teratoma surface.The patient was discharged on postoperative day 7.CONCLUSION This is the first report of the use of uniportal VATS for complete resection of a teratoma in combination with wedge resection of the right upper and middle lung lobes and partial resection of the pericardium.

Life-threatening delayed mediastinal and subcutaneous emphysema after general anesthesia in a rheumatoid arthritis patient: a case report

Background:Delayed mediastinal emphysema with subcutaneous emphysema after extubation is rarely reported in current literature.Symptomatic treatment is considered effective for management.Case presentation:We report a case of a 56-year-old female with longstanding rheumatoid arthritis under corticosteroid therapy who developed mediastinal emphysema with subcutaneous emphysema 2 days after recovering from general anesthesia for orthopedic surgery treating a femoral neck fracture.The patient received aggressive subcutaneous decompression and symptomatic management.Results:The patient’s condition improved after treatment.Based on computed tomography scan results,we hypothesize that the longstanding rheumatoid arthritis may have resulted in fragile lung tissue.Violent postoperative coughing likely caused rupture of small airways,leading to mediastinal emphysema.Conclusions:It is crucial to preoperatively assess the risk of airway injury in high-risk patients with longstanding rheumatoid arthritis.Delayed postoperative mediastinal emphysema should be carefully evaluated and managed aggressively to avoid exacerbation or life-threatening scenarios.Further research is warranted to elucidate the pathology and guide perioperative management in these patients.

Solid pseudopapillary tumor of the pancreas:A systematic review of clinical,surgical and oncological characteristics of 1384 patients underwent pancreatic surgery

Background:Pancreatic solid pseudopapillary tumors(SPTs)are rare clinical entity,with low malignancy and still unclear pathogenesis.They account for less than 2%of exocrine pancreatic neoplasms.This study aimed to perform a systematic review of the main clinical,surgical and oncological characteristics of pancreatic SPTs.Data sources:MEDLINE/PubMed,Web of Science and Scopus databases were systematically searched for the main clinical,surgical and oncological characteristics of pancreatic SPTs up to April 2021,in accordance with the preferred reporting items for systematic reviews and meta-analyses(PRISMA)standards.Primary endpoints were to analyze treatments and oncological outcomes.Results:A total of 823 studies were recorded,86 studies underwent full-text reviews and 28 met inclusion criteria.Overall,1384 patients underwent pancreatic surgery.Mean age was 30 years and 1181 patients(85.3%)were female.The most common clinical presentation was non-specific abdominal pain(52.6%of cases).Mean overall survival was 98.1%.Mean recurrence rate was 2.8%.Mean follow-up was 4.2 years.Conclusions:Pancreatic SPTs are rare,and predominantly affect young women with unclear pathogenesis.Radical resection is the gold standard of treatment achieving good oncological impact and a favorable prognosis in a yearly life-long follow-up.

Risk of appendiceal neoplasm in patients with appendix disorders

The most common appendicular disease is acute appendicitis,with a lifetime risk of 7%–8%.Complicated cases,which can occur in 2%–7%of patients,can signi-ficantly impact the severity of the condition and may require different manage-ment approaches.Nonoperative management with possible delayed appende-ctomy has been suggested for selected patients,however,there is a non-negligible risk of missing an underlying malignancy,which is reported to be as high as 11%.Diagnostic work-up is paramount to achieve optimal treatment with good results.

Combining surgery with 125I brachytherapy for recurrent mediastinal dedifferentiated liposarcoma: A case report and review of literature

BACKGROUND Dedifferentiated liposarcoma in the mediastinum is an extremely rare malignant neoplasm.A few previous case reports indicate that surgical resection is the major treatment,but frequent recurrence occurs locally.Due to its rarity,its clinical characteristics,optimal treatment and clinical outcomes remain unclear.Here,we report a case of multifocal recurrent dedifferentiated liposarcoma in the posterior mediastinum treated by combining surgery with 125I brachytherapy,and summarize its clinical features,treatment and prognosis.CASE SUMMARY A 75-year-old man was admitted to our hospital with a history of gradual dysphagia for one year and aggravated dysphagia for 3 mo.Contrast-enhanced computed tomography(CT)revealed several large cystic-solid masses with lipomatous density,and calcification in the posterior-inferior mediastinum.The patient received a wide excision by video-assisted thoracoscopic surgery.Pathological analysis confirmed the tumors were dedifferentiated liposarcomas.The tumor locally relapsed 24 mo later,and another operation was performed by video-assisted thoracoscopic surgery.Fifteen months after the second surgery,the tumor recurred again,and the patient received CT-guided radioactive seeds 125I implantation.After 8 mo,follow-up chest CT showed an enlarged tumor.Finally,his condition exacerbated with severe dysphagia and dyspnea,and he died of respiratory failure in July 2018.CONCLUSION We reviewed the literature,and suggest that surgical resection provides beneficial effects for dedifferentiated liposarcoma in the mediastinum,even in cases with local recurrence.125I brachytherapy may be beneficial for recurrent unresectable patients.

Mediastinal lymphadenectomy influences postoperative immune response after lung cancer surgery

The aim of the study was to calculate the amount of surgical injury caused by systematic lymphadenectomy of mediastinum in patients operated on due to non-small cell lung cancer,with uneventful postoperative course.The study group consisted of 11 patients with cancer of the right lung(Group 1).The control group consisted of 12 patients with left lung cancer(Group 2).In patients with right lung cancer systematic lymphadenectomy,while in patients with left lung cancer systematic sampling was performed.Serum IL-6 and IL-1ra concentration was measured before and after surgery,and on postoperative day 1,3,and 7,as well as in sputum at the end of surgery and in pleural fluid on postoperative day 1,by ELISA test.Peripheral blood lymphocyte(PBL) count was measured with flow cytometry.Time of surgery was higher in patients with right than left lung cancer(154.1±31.29) vs(119.6±24.81) min;P=0.008) .The number of resected mediastinal lymph nodes was higher in patients with right than left lung cancer(27.6±7.6) vs(11.1 ±8.1);P=0.00006) .Postoperative decrease of PBL was significantly higher in group 1 than 2(1.25±0.37) vs(1.75 ±0.64) ×103/μL;P=0.04) .No significant differences were found in serum,pleural fluid and sputum concentration of IL-6 and IL -1ra between groups.Negative correlation between concentration of these cytokines in pleural fluid and number of resected mediastinal lymph nodes was found(Spearman test for IL-6:r=-0.723;P<0.001;for IL-1ra:r=-0.768;P<0.001).Number of "positive" N2 lymph nodes did not correlate with pleural fluid concentration of cytokines.Systematic lymphadenectomy of the mediastinum causes immunosuppression,as measured by decreased count of PBL and a negative correlation between number of resected mediastinal lymph nodes and concentration of cytokines in pleural fluid.

Clinicopathologic characteristics and prognosis of gastroenteropancreatic neuroendocrine neoplasms: a multicenter study in South China

Background: Gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs) are a heterogeneous group of rare tumors. Many issues in terms of epidemiologic features, pathogenesis, and treatment of GEP-NENs are still under discussion. Our study aimed to analyze the clinicopathologic characteristics and prognosis of Chinese patients with GEP-NENs.Methods: Complete clinicopathologic data and survival information of 1183 patients with GEP-NENs treated between 2005 and 2015 were collected from five medical centers in Guangdong Province, China. Patient survival was estimated using the Kaplan–Meier method and analyzed using the log-rank test; prognostic factors were analyzed using the Cox proportional hazards model.Results: The most common tumor location was the rectum(37.4%), followed by the pancreas(28.1%), stomach(20.7%), small intestine(7.2%), appendix(3.4%), and colon(3.3%). After initial definitive diagnosis, 1016(85.9%) patients underwent surgery. The 1-, 3-, and 5-year overall survival(OS) rates for the entire cohort were 87.9%, 78.5%, and 72.8%, respectively. The 3-year OS rates of patients with G1, G2, and G3 tumors were 93.1%, 82.7%, and 43.1%, respectively(P < 0.001). The 3-year OS rates of patients with stage I, II, III, and IV tumors were 96.0%, 87.3%, 64.0%, and 46.8%, respectively(P < 0.001). Patients with distant metastasis who underwent palliative surgery had a longer survival than those who did not(P = 0.003). Similar survival benefits of palliative surgery were observed in patients with neuroendocrine tumor(P y, M category, and sur= 0.031) or neuroendocrine carcinoma(P gery were found to be independent prog= 0.046). In multivariate analysis, age, grade, N categornostic factors.Conclusions: Patients with GEP-NENs who are women, younger than 50 years old, have smaller tumor size, have lower tumor grade, have lower T/N/M category, and who undergo surgery can have potentially longer survival time. Our data showed that surgery can improve the prognosis of GEP-NEN patients with distant metastasis. However, randomized controlled trials need to be conducted to establish the optimal criteria for selecting patients to undergo surgery.

Current perspectives on pancreatic serous cystic neoplasms:Diagnosis, management and beyond

Pancreatic cystic neoplasms have been increasingly recognized recently. Comprising about 16% of all resected pancreatic cystic neoplasms, serous cystic neoplasms are uncommon benign lesions that are usually asymptomatic and found incidentally. Despite overall low risk of malignancy, these pancreatic cysts still generate anxiety, leading to intensive medical investigations with considerable financial cost to health care systems. This review discusses the general background of serous cystic neoplasms, including epidemiology and clinical characteristics, and provides an updated overview of diagnostic approaches based on clinical features, relevant imaging studies and new findings that are being discovered pertaining to diagnostic evaluation. We also concisely discuss and propose management strategies for better quality of life.

Differences between main-duct and branch-duct intraductal papillary mucinous neoplasms of the pancreas

In the last decade,intraductal papillary mucinous neoplasms(IPMNs) have become commonly diagnosed.From a morphological standpoint,they are classified in main-duct IPMNs(MD-IPMNs) and branch-duct IPMNs(BD-IPMNs),depending on the type of involvement of the pancreatic ductal system by the neoplasm.Despite the fact that our understanding of their natural history is still incomplete,recent data indicate that MD-IPMNs and BD-IPMNs show significant differences in terms of biological behaviour with MD-IPMNs at higher risk of malignant degeneration.In the present paper,clinical and epidemiological characteristics,rates of malignancy and the natural history of MD-IPMNs and BD-IPMNs are analyzed.The profile of IPMNs involving both the main pancreatic duct and its side branches(combined-IPMNs) are also discussed.Finally,general recommendations for management based on these differences are given.

Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis

BACKGROUND To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated. AIM To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters. METHODS The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis. RESULTS We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3%(25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8;heterogeneity: P = 0.126;I2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2;95%CI: 1.8-161.1;heterogeneity: P = 0.165;I2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2;95%CI: 0.3-11.6;heterogeneity: P = 0.304;I2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3;95%CI: 0.1-1.1;heterogeneity: P = 0.173;I2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively. CONCLUSION This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5- year disease-specific survival rates reported;hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.

Update on surgical treatment of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms(PNENs) are rare and account for only 2%-4% of all pancreatic neoplasms. All PNENs are potential(neurendocrine tumors PNETs) or overt(neuroendocrine carcinomas PNECs) malignant,but a subset of PNETs is low-risk. Even in case of low-risk PNETs surgical resection is frequently required to treat hormone-related symptoms and to obtain an appropriate pathological diagnosis. Low-risk PNETs in the body and the tail are ideal for minimallyinvasive approaches which should be tailored to the individual patient. Generally,surgeons must aim for parenchyma sparing in these cases. In high-risk and malignant PNENs,indications for tumor resection are much wider than for pancreatic adenocarcinoma,in many cases due to the relatively benign tumor biology. Thus,patients with locally advanced and metastatic PNETs may benefit from extensive resection. In experienced hands,even multi-organ resections are accomplished with acceptable perioperative morbidity and mortality rates and are associated with excellent long term survival. However,poorly differentiated neoplasms with high proliferation rates are associated with a dismal prognosis and may frequently only be treated with chemotherapy. The evidence on surgical treatment of PNENs stems from reviews of mostly singlecenter series and some analyses of nation-wide tumor registries. No randomized trial has been performed to compare surgical and non-surgical therapies in potentially resectable PNEN. Though such a trial would principally be desirable,ethical considerations and the heterogeneity of PNENs preclude realization of such a study. In the current review,we summarize recent advances in the surgical treatment of PNENs.

Transarterial embolization of metastatic mediastinal hepatocellular carcinoma

This paper introduces an innovative treatment for extrahepatic metastasis of hepatocellular carcinoma. A 71-yearold patient had a stable liver condition following treatment for hepatocellular carcinoma, but later developed symptomatic mediastinal metastasis. This rapidly growing mediastinal mass induced symptoms including cough and hoarseness. Serial sessions of transarterial embolization (TAE) successfully controlled this mediastinal mass with limited side effects. The patient's survival time since the initial diagnosis of the mediastinal hepatocellular carcinoma was 32 mo, significantly longer than the 12 mo mean survival period of patients with similar diagnoses: metastatic hepatocellular carcinoma and a liver condition with a Child-Pugh class A score. Currently, oral sorafenib is the treatment of choice for metastatic hepatocellular carcinoma. Recentstudies indicate that locoregional treatment of extrahepatic metastasis of hepatocellular carcinomas might also significantly improve the prognosis in patients with their primary hepatic lesions under control. Many effective locoregional therapies for extrahepatic metastasis, including radiation and surgical resection, may provide palliative effects for hepatocellular carcinoma-associated mediastinal metastasis. This case report demonstrates that TAE of metastatic mediastinal hepatocellular carcinoma provided this patient with tumor control and increased survival time. This finding is important as it can potentially provide an alternative treatment option for patients with similar symptoms and diagnoses.

Efficacy of contrast-enhanced ultrasound-guided percutaneous core needle biopsy in anterior mediastinal masses

Objective:To evaluate the efficacy and safety of percutaneous core needle biopsy(PCNB)using ultrasound(US)-guided and contrast-enhanced ultrasound(CEUS)-guided procedures for anterior mediastinal masses(AMMs).Methods:In total,284 consecutive patients(166 men,118 women;mean age,43.0±18.4 years)who underwent PCNB for AMMs were enrolled.Patients were divided into the US-guided group(n=133)and the CEUS-guided group(n=151).PCNB was performed using a core needle(16-gauge or 18-gauge).Internal necrosis,diagnostic yield,and diagnostic accuracy were compared between the two groups.Results:The predominant final diagnosis of the cases in this study was thymoma(29.7%),lymphoma(20.5%),thymic carcinoma(13.3%),and germ cell tumour(13.3%),respectively.There was no significant difference in patient age,sex,number of percutaneous biopsies,or display rate of internal necrosis on conventional US between the two groups.The rate of internal necrosis of the lesions was significantly higher after contrast agent injection(72.2%vs.41.7%;P<0.001).The CEUS-guided group had a higher diagnostic yield than the US-guided group(100%vs.89.5%,P<0.001).There was no significant difference between the diagnostic accuracy of the CEUSguided and US-guided groups(97.3%vs.97.4%;P=1.000).None of the patients experienced adverse reactions or complications after US-guided or CEUS-guided PCNB.Conclusions:CEUS-guided PCNB can improve the diagnostic yield by optimizing the biopsy procedure.

Endoscopic submucosal dissection for colorectal neoplasms

Although endoscopic submucosal dissection(ESD) gains acceptance as one of the standard treatments for esophageal and stomach neoplasms in Japan,it is still in the developing stage for colorectal neoplasms.In terms of indications,little likelihood of nodal metastasis and technical resectability are principally considered.Some of intramucosal neoplasms,carcinomas with minute submucosal invasion,and carcinoid tumors,which are technically unresectable by conventional endoscopic treatments,may become good candidates for ESD,considering substantial risks and obtained benefits.ESD as a staging measure to obtain histological information of the invasion depth and lymphovascular infiltration is acceptable because preoperative prediction is difficult in some cases.In terms of techniques,advantages of ESD in comparison with other endoscopic treatments are to be controllable in size and shape,and to be resectable even in large and fibrotic neoplasms.The disadvantages may be longer procedure time,heavier bleeding,and higher possibility of perforation.However,owing to refinement of the techniques,invention of devices,and the learning curve,acceptable technical safety has been achieved.Colorectal ESD is very promising and become one of the standard treatments for colorectal neoplasms in the near future.

Posterior Mediastinal Mature Teratoma: A Case Report and Literature Review

Mediastinal mature teratoma is the most common form of germ cell tumors, often located in the anterior mediastinum. A posterior mediastinum location has rarely been described. We report a case of a posterior mediastinal mature teratoma in a 37-year-old patient and a literature review, through which we describe the diagnostic and therapeutic difficulties inherent in this particular location of these tumors.

Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives

Although gastroenteropancreatic neuroendocrine neoplasms(GEP-NENs)have always been considered rare tumors,their incidence has risen over the past few decades.They represent a highly heterogeneous group of neoplasms with several prognostic factors,including disease stage,proliferative index(Ki67),and tumor differentiation.Most of these neoplasms express somatostatin receptors on the cell surface,a feature that has important implications in terms of prognosis,diagnosis,and therapy.Although International Guidelines propose algorithms aimed at guiding therapeutic strategies,GEP-NEN patients are still very different from one another,and the need for personalized treatment continues to increase.Radical surgery is always the best option when feasible;however,up to 80%of cases are metastatic upon diagnosis.Regarding medical treatments,as GEP-NENs are characterized by relatively long overall survival,multiple therapy lines are adopted during the lifetime of these patients,but the optimum sequence to be followed has never been clearly defined.Furthermore,although new molecular markers aimed at predicting the response to therapy,as well as prognostic scores,are currently being studied,their application is still far from being part of daily clinical practice.As they represent a complex disease,with therapeutic protocols that are not completely standardized,GEP-NENs require a multidisciplinary approach.This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.