Small bowel neuroendocrine tumors (SBNETs) often present with nonspecific clinical manifestations, which can complicate diagnosis and treatment when coexisting comorbidities in the perioperative period. This report discusses a rare case involving SBNETs associated with scoliosis, aiming to provide a comprehensive understanding of the epidemiological characteristics, clinicopathologic features, and treatment strategies related to SBNETs.

A 69-year-old male presented with a 10-month history of abdominal pain, nausea, vomiting, and weight loss. He had been admitted to the other medical institutions multiple times due to recurrent abdominal pain and was diagnosed with small bowel obstruction over the past 10 months. He had a history of scoliosis. Radiographic spine imaging revealed severe scoliosis. At the same time, contrast-enhanced abdominal CT scans indicated slight thickening and enhancement of the small intestinal wall and identified a mass in the mesentery. An enteroscopy did not reveal any significant abnormalities.

Histopathological examination of the tumor specimens confirmed the diagnosis of a small bowel neuroendocrine tumor.

The case was reviewed in a multidisciplinary team discussion, which led to the decision for an exploratory laparotomy. During the surgical procedure, a segment of the small intestine and the associated regional mesenteric lymph nodes were successfully resected.

The patient had an uneventful recovery after surgery, and a follow-up 6 months later showed no signs of recurrence.

Contrast-enhanced abdominal CT is pivotal in the preoperative diagnosis and perioperative staging of SBNETs. Surgical resection remains the gold standard for treatment. In special cases when coexisting with comorbidities such as scoliosis, an individualized treatment strategy should be made after being reviewed by a multidisciplinary discussion.

The Iowa Neuroendocrine Tumor (NET) Clinic was founded and developed by two remarkable physicians, Thomas and Sue O'Dorisio. Tom was an Endocrinologist and close friend and colleague of Aaron Vinik. Both men were pioneers in studies of gastrointestinal hormones and the management of patients with NETs. Sue was a Pediatric Oncologist and research scientist with great expertise in new drug development and clinical trials. She and Tom were leaders in bringing somatostatin analogs and somatostatin-conjugated radioligands to the clinic for the therapy and diagnosis of NETs. All three physicians received lifetime achievement awards for their contributions to the field of NETs. This is the story of how the Iowa NET Clinic developed over the years to become a model for the multidisciplinary mantagement of patients with NETs, culminating in its designation as a European Neuroendocrine Tumor Society NET Center of Excellence, and the receipt of a Specialized Project of Research Excellence (SPORE) grant for the study of NETs from the National Institutes of Health.

The mesenteric extension of small neuroendocrine tumors is the surgical limiting factor because of the risk of postoperative short bowel syndrome due to superior mesenteric artery involvement. Recent pathological studies have shown that this vascular involvement is due to mesenteric tumor deposits, differentiated from lymph node metastases. The aim of this study was to evaluate the performances of computed tomography (CT) for the surgical planning of small intestine neuroendocrine tumors. This was a retrospective observational study, and all patients undergoing surgery for small intestine neuroendocrine tumor between January 2014 and March 2019 were included. Preoperative CTs were reviewed, blinded from surgical and pathological data, by two radiologists. Diagnostic accuracy and interobserver reliability analysis were performed. We included 45 patients (mean age: 61 years (28-84 years); 23 men). The CT sensitivity to identify the mesenteric mass was 97% (37/38) with a ĸ of 0.73. The positive predictive value of CT to anticipate a right colic resection was 86% (18/21). The negative predictive value of CT was high (97% (34/35) to 100% (35/35)) for duodenal resection (ĸ = 0.78). Regarding retropancreatic lymph node invasion, the CT sensitivity was poor (24%, 4/17), with a high ĸ (0.88). The level of involvement by the mesenteric mass was correlated with the length and the percentage of the remaining small bowel. CT is essential for the surgical planning of small intestine neuroendocrine tumors, being accurate in defining the mesenteric tumor deposits, allowing one to anticipate, with a good reproducibility, the length and percentage of the remaining small bowel and the necessity for a right colectomy.

The incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) is increasing at a rapid pace and is becoming an increasingly important consideration in clinical care. Epidemiological data from multiple countries indicate that the incidence of gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) exhibits regional, site-specific, and gender-based variations. While the genetics and pathogenesis of some GEP NEN, particularly pancreatic NENs, have been investigated, there are still many mechanisms that require further investigation. The management of GEP NEN is diverse, but surgery remains the primary option for most cases. Peptide receptor radionuclide therapy (PRRT) is an effective treatment, and several clinical trials are exploring the potential of immunotherapy and targeted therapy, as well as combination therapy.

Neuroendocrine tumors (NETs) are rare, slow-growing tumors originating from the diffuse neuroendocrine cell system, predominantly affecting the digestive tract. Small bowel neuroendocrine tumors (SBNETs) may present with nonspecific symptoms, such as abdominal pain, or with intermittent intestinal obstruction. This case outlines the diagnostic journey of a septuagenarian male with prolonged abdominal symptoms and weight loss. Despite extensive investigation, a definitive cause remained elusive. Recurrent partial intestinal obstruction led to surgical exploration and segmental resection. Pathology confirmed a NET. The case underscores the importance of considering intestinal neoplasia in older patients with recurrent partial small bowel obstruction.

Gastrointestinal midgut neuroendocrine neoplasms (NENs) are a heterogeneous group of uncommon malignancies. For well-differentiated NENs, known as neuroendocrine tumors (NETs), surgery is a cornerstone of management in localized and metastatic disease. Because of heterogeneous tumor behaviour, association with endocrine syndrome, and prognosis, the management of NETs must be individualized to all these factors in addition to the primary site. With the fast pace of advancement in the field, both for therapies and understanding of tumoral etiology and behaviour, it is important for surgical oncologists to remain updated on guidelines recommendations and suggested treatment pathways. Those guidelines provide important guidance for management of NETs but are largely based on expert opinions and interpretation of retrospective evidence. This article reviews highlights of most recent practice guidelines for midgut (gastric, duodenal, small intestinal, and appendiceal) NETs.

Small bowel neuroendocrine tumors (SB-NETs) are increasingly identified and have become the most frequent entity among small bowel tumors. An increasing incidence, a high prevalence, and a prolonged survival with optimal modern multidisciplinary management makes SB-NETs a unique set of tumors to consider for surgical oncologists. The major goals of surgical treatment in the setting of SB-NET include control of tumor volume, control of endocrine secretion, and prevention of locoregional complications. Key considerations include assessment of multifocality and resection of mesenteric nodal masses with the use of mesenteric-sparing approaches and acceptance of R1 margins if necessary to clear disease while avoiding short bowel syndrome. A description through eight steps for consideration is presented to allow for systematic surgical planning and execution of resection. Moreover, some controversies and evolving considerations to the surgical principles and technical procedures remain. The role of primary tumor resection in the presence of (unresectable) liver metastasis is still unclear. Reports of feasibility of minimally invasive surgery are emerging, with undetermined selection criteria for appropriateness or long-term outcomes. Resection of SB-NETs should be considered in all patients fit for surgery and should follow principles to achieve surgical oncological control that is appropriate for the stage and tumor burden, considering the age and comorbidity of the individual patient.

Neuroendocrine neoplasms (SI-NEN) are the commonest malignancies of the small intestine. Traditionally, surgical treatment for SI-NEN has been open surgery.

The purpose of this study was to compare minimally invasive surgery (MIS) with the traditional open surgery approach for treating SI-NEN in a Swedish population.

Patients with histopathological confirmed SI-NEN who underwent open surgery or MIS resection within 2009-2021 were extracted from the hospital's medical records.

65 patients were included in this study, with 35 (54 %) undergoing MIS and 30 (46 %) undergoing open surgery. We found no statistically significant difference (p = 0.173) in the frequency of R0 resections (MIS group n = 34 (97 %), open surgery group n = 26 (87 %)). Nor was there a significant difference (p = 0.101) when comparing the median number of resected lymph nodes (MIS group n = 13.5, open surgery group n = 10). A post-operative paralytic ileus was more often reported (p = 0.052) in the MIS group (n = 9, 26 %) compared to the open surgery group (n = 2, 7 %). In light of this, the days of hospital stay did not differ significantly (MIS group median = 6, IQR (5-8), open surgery group median = 6, IQR (5-9)). The Kaplan-Meier analysis did not reveal differences concerning cancer-related deaths (p = 0.109).

The results from this study support that a MIS approach for the treatment of SI-NEN may not be inferior to open surgery. The higher number of resected lymph nodes and R0 resections may even speak in favor for a MIS approach. More studies with a longer time of observation are needed to further support this conclusion.

We assessed the accuracy of preoperative gallium-68 DOTA-Tyr3-octreotate (DOTATATE) positron emission tomography (PET) imaging in estimating multifocality and nodal metastases of small bowel neuroendocrine tumors (sbNETs).

A multicenter analysis was performed on patients with sbNETs who underwent preoperative DOTATATE PET imaging and surgical resection, with manual palpation of the entire length of the small bowel, between January 2016 and August 2022. Preoperative imaging reports and blinded secondary imaging reviews were compared to the final postoperative pathology reports. Descriptive statistics were applied.

One-hundred and four patients met inclusion criteria. Pathology showed 53 (51%) patients had multifocal sbNETs and 96 (92%) had nodal metastases. The original preoperative DOTATATE PET imaging identified multifocal sbNET in 28 (27%) patients and lymph node (LN) metastases in 80 (77%) patients. Based on original radiology reports, sensitivity for multifocal sbNET identification was 45%, specificity was 92%, positive predictive value (PPV) was 86%, and negative predictive value (NPV) was 62%. For the identification of LN metastases, sensitivity was 82%, specificity was 88%, PPV was 99%, and NPV was 29%.

Although DOTATATE PET imaging is specific and relatively accurate, sensitivity and NPV are insufficient to guide surgical planning. Preoperative use should not replace open palpation to identify additional synchronous lesions or to omit regional lymphadenectomy.

The concept of surgical centralization is becoming more and more accepted for specific surgical procedures.

The aim of this study was to evaluate the relationship between procedure volume and the outcomes of surgical small intestine (SI) neuroendocrine tumor (NET) resections.

We conducted a retrospective national study that included patients who underwent SI-NET resection between 2019 and 2021. A high-volume center (hvC) was defined as a center that performed more than five SI-NET resections per year. The quality of the surgical resections was evaluated between hvCs and low-volume centers (lvCs) by comparing the number of resected lymph nodes (LNs) as the primary endpoint.

A total of 157 patients underwent surgery in 33 centers: 90 patients in four hvCs and 67 patients in 29 lvCs. Laparotomy was more often performed in hvCs (85.6% vs. 59.7%; p < 0.001), as was right hemicolectomy (64.4% vs. 38.8%; p < 0.001), whereas limited ileocolic resection was performed in 18% of patients in lvCs versus none in hvCs. A bi-digital palpation of the entire SI length (95.6% vs. 34.3%, p < 0.001), a cholecystectomy (93.3% vs. 14.9%; p < 0.001), and a mesenteric mass resection (70% vs. 35.8%; p < 0.001) were more often performed in hvCs. The proportion of patients with ≥8 LNs resected was significantly higher (96.3% vs. 65.1%; p < 0.001) in hvCs compared with lvCs, as was the proportion of patients with ≥12 LNs resected (87.8% vs. 52.4%). Furthermore, the number of patients with multiple SI-NETs was higher in the hvC group compared with the lvC group (43.3% vs. 25.4%), as were the number of tumors in those patients (median of 7 vs. 2; p < 0.001).

Optimal SI-NET resection was significantly more often performed in hvCs. Centralization of surgical care of SI-NETs is recommended.

Background: Small bowel carcinoids are insidious tumors that are often metastatic when diagnosed. Limited mutation landscape studies of carcinoids indicate that these tumors have a relatively low mutational burden. The development of targeted therapies will depend upon the identification of mutations that drive the pathogenesis and metastasis of carcinoid tumors. Methods: Whole exome and RNA sequencing of 5 matched sets of normal tissue, primary small intestine carcinoid tumors, and liver metastases were investigated. Germline and somatic variants included: single nucleotide variants (SNVs), insertions/deletions (indels), structural variants, and copy number alterations (CNAs). The functional impact of mutations was predicted using Ensembl Variant Effect Predictor. Results: Large-scale CNAs were observed including the loss of chromosome 18 in all 5 metastases and 3/5 primary tumors. Certain somatic SNVs were metastasis-specific; including mutations in ATRX, CDKN1B, MXRA5 (leading to the activation of a cryptic splice site and loss of mRNA), SMARCA2, and the loss of UBE4B. Additional mutations in ATRX, and splice site loss of PYGL, leading to intron retention observed in primary and metastatic tumors. Conclusions: We observed novel mutations in primary/metastatic carcinoid tumor pairs, and some have been observed in other types of neuroendocrine tumors. We confirmed a previously observed loss of chromosome 18 and CDKN1B. Transcriptome sequencing added relevant information that would not have been appreciated with DNA sequencing alone. The detection of several splicing mutations on the DNA level and their consequences at the RNA level suggests that RNA splicing aberrations may be an important mechanism underlying carcinoid tumors.

Neuroendocrine tumors (NETs) represent a heterogeneous group of tumors, with variable presentation based on the location of origin and degree of metastatic spread. There are no randomized control trials to guide surgical management; however, surgery remains the mainstay of treatment for most gastroenteropancreatic NETs based on retrospective studies. Metastatic disease is common at the time of presentation, particularly in the liver. There is a role for cytoreduction for improvement of both symptoms and survival. Robust prospective randomized data exists to support the use of medical therapies to improve progression-free and overall survival in patients with advanced, metastatic, and unresectable NETs.

Neuroendocrine neoplasms of the small bowel are a diverse group of tumors with a broad spectrum of imaging findings and clinical implications. Most tumors originate in close proximity to the ileocecal valve and most commonly metastasize to the mesentery and liver. This review will highlight the imaging findings of primary and metastatic small bowel neuroendocrine neoplasm that are most relevant to the surgical team.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common type of neuroendocrine tumors and are being increasingly identified in clinical practice. The diagnosis, staging, management, and surveillance of GEP-NETs rely heavily on endoscopy, and consequently, it is important for gastroenterologists to have a solid understanding of these tumors. This article reviews the presentation, diagnosis, and management of both localized and advanced GEP-NETs, with increased emphasis on the role of endoscopy, to enable gastroenterologists and other practitioners to have the necessary tools for the care of patients with these tumors.

Complete surgical resection is the only hope to cure small intestine neuroendocrine neoplasms (SiNENs). However, inadequate lymphadenectomy or entire small bowel palpation for multiple primary tumours renders at least 20% of resections suboptimal. This study was undertaken to investigate reintervention outcomes after initial suboptimal resections (ISORs), and agreement between residual tumour identification on interval imaging and during reintervention. This retrospective, multicentre study included all patients undergoing reintervention within 18 months post ISOR. Disease-free survival (DFS) was defined as the time from reintervention resection date to recurrence or any-cause of death. The kappa coefficient assessed agreement rates between suspected residual tumour on interval imaging and its presence at reintervention. A total of 21 patients underwent reintervention for nonmetastatic SiNENs (median follow-up 2.3 [IQR 0.6-3.75] years). Residual tumour, suspected in 17/21 (81%) patients based on interval imaging, was found in 20/21 (95%) during reintervention. Interval imaging-intraoperative detection agreement was fair for residual primary tumours (kappa = 0.28, 95% CI: 0.05-0.62; p = .09) and residual lymph node metastases (kappa = 0.17, 95% CI: 0.28-0.62; p = .45). Reintervention achieved complete tumour clearance in 16/21 (76%) patients, among whom 5/16 (31%) developed liver metastases during follow-up. Median DFS was 70.6 months (IQR 39.7-not reached). Reintervention post-ISOR can obtain tumour clearance and prolonged remission. It should be systematically discussed after suspected ISOR, even when postoperative imaging does not find any residual tumour. To maximize detection of potentially resectable residual disease, imaging modalities after "curative" surgery should be redefined.

The precise contributions of histopathologic features in the determination of stage and prognosis in small intestinal neuroendocrine tumors (NETs) are still under debate, particularly as they pertain to primary tumor size, mesenteric tumor deposits (TDs), and number of regional lymph nodes with metastatic disease. This single-institution series reviewed 162 patients with small bowel NETs (84 females, mean age: 60.3±12.0 y). All cases examined (100%) were immunoreactive for both chromogranin A and synaptophysin. Primary tumor size >1 cm (P=0.048; odds ratio [OR]=3.06, 95% confidence interval [CI]: 1.01-9.24) and lymphovascular invasion (P=0.007; OR=4.85, 95% CI: 1.53-15.40) were associated with the presence of lymph node metastasis. Conversely, TDs (P=0.041; OR=2.73, 95% CI: 1.04-7.17) and higher pT stage (P=0.006; OR=4.33, 95% CI: 1.53-12.28) were associated with the presence of distant metastasis (pM). A cutoff of ≥7 positive lymph nodes was associated with pM (P=0.041), and a thusly defined modified pN stage (pNmod) significantly predicted pM (P=0.024), compared with the prototypical pN (cutoff of ≥12 positive lymph nodes), which did not. Over a median follow-up of 35.7 months, higher pNmod (P=0.014; OR=2.15, 95% CI: 1.16-3.96) and pM (P<0.001; OR=11.00, 95% CI: 4.14-29.20) were associated with disease progression. Proportional hazards regression showed that higher pNmod (P=0.020; hazard ratio=1.51, 95% CI: 1.07-2.15) and pM (P<0.001; hazard ratio=5.48, 95% CI: 2.90-10.37) were associated with worse progression-free survival. Finally, Kaplan-Meier survival analysis demonstrated that higher pNmod (P=0.003), pM (P<0.001), and overall stage group (P<0.001) were associated with worse progression-free survival, while higher pM also predicted worse disease-specific survival (P=0.025). These data support requiring either chromogranin or synaptophysin, but not both, for small bowel NET diagnosis, the current inclusion of a 1 cm cutoff in primary tumor size and the presence of TDs in staging guidelines, and would further suggest lowering the cutoff number of positive lymph nodes qualifying for pN2 to 7 (from 12).

Small-intestinal neuroendocrine tumors (siNETs) account for 25% of gastroenteropancreatic NETs. Multiple siNETs appear to develop in a limited segment of the small bowel (SB), 89% of them being located in the ileum, most often within 100 cm of the ileocecal valve (ICV). According to the European Neuroendocrine Tumor Society (ENETS) and the American Joint Committee on Cancer (AJCC), all localized siNETs should be considered for radical surgical resection with adequate lymphadenectomy irrespective of the absence of lymphadenopathy or mesenteric involvement. Surgical management of siNETs: The preoperative workout should include a precise evaluation of past medical and surgical history, focusing on the symptoms of carcinoid syndrome (flush, diarrhea, and cardiac failure). Morphological evaluation should include a CT scan including a thin-slice arterial CT, a PET/CT with 68 Ga, and a hepatic MRI in cases of suspected metastasis. Levels of 24 h urinary 5-hydroxyindoleacetic acid are needed. Regarding surgery, the limiting component is the number of free jejunal branches allowing a resection without risk of short small bowel syndrome. The laparoscopic approach has been poorly studied, and open laparotomy remains the gold standard to explore the abdominal cavity and entirely palpate the small bowel through bidigital palpation and compression. An extensive lymphadenectomy is required. A prophylactic cholecystectomy should be performed. In case of emergency surgery, current recommendations are not definitive. However, there is expert agreement that it is not reasonable to initiate resection of the mesenteric mass without comprehensive workup and mapping.

The surgery of siNETs is in constant evolution. The challenge lies in the ability to propose a resection without imposing short small bowel syndrome on the patients. The oncological benefits supported in the literature led to recent changes in the recommendations of academic societies. The next steps remain the dissemination of reproducible quality criteria to perform these procedures.

Neuroendocrine tumors (NETs) are a rare and heterogeneous disease group and constitute 0.5% of all malignancies. The annual incidence of NETs is increasing worldwide. The reason for the increase in the incidence of NETs is the detection of benign lesions, incidental detection due to the highest use of endoscopic and imaging procedures, and higher recognition rates of pathologists. There have been exciting developments regarding NET biology in recent years. Among these, first of all, somatostatin receptors and downstream pathways in neuroendocrine cells have been found to be important regulatory mechanisms for protein synthesis, hormone secretion, and proliferation. Subsequently, activation of the mammalian target of rapamycin pathway was found to be an important mechanism in angiogenesis and tumor survival and cell metabolism. Finally, the importance of proangiogenic factors (platelet-derived growth factor, vascular endothelial growth factor, fibroblastic growth factor, angiopoietin, and semaphorins) in the progression of NET has been determined. Using the combination of biomarkers and imaging methods allows early evaluation of the appropriateness of treatment and response to treatment.

Small bowel neuroendocrine tumors (SBNETS) are slow-growing neoplasms with a noted propensity toward metastasis and comparatively favorable prognosis. The presentation of SBNETs is varied, although abdominal pain and obstructive symptoms are the most common presenting symptoms. In patients with metastases, hypersecretion of serotonin and other bioactive amines results in diarrhea, flushing, valvular heart disease, and bronchospasm, termed carcinoid syndrome. The treatment of SBNETs is multimodal and includes surgery, liver-directed therapy, somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy.

Small intestinal neuroendocrine neoplasms (siNENs) are slowly growing tumours with a low malignant potential. However, more than half of the patients present with distant metastases (stage IV) and nearly all with locoregional lymph node (LN) metastases at the time of surgery. The value of locoregional treatment is discussed controversially.

In stage I to III disease, locoregional surgery was currently shown to be curative prolonging survival. In stage IV disease, surgery may prolong survival in selected patients with the chance to cure locoregional disease besides radical/debulking liver surgery. It may improve the quality of life and may prevent severe local complications resulting in a state of chronic malnutrition and severe intestinal ischaemia or bowel obstruction. Locoregional tumour resection offers the opportunity to be curative or to focus therapeutically on liver metastasis, facilitating various other therapeutic modalities. Risks and benefits of the surgical intervention need to be balanced individually.

The 8th edition AJCC Staging for small bowel neuroendocrine tumors created a novel N2 classification. This study investigates if it is independently prognostic.

Records of patients from 2008 to 2019 were reviewed. Survival rates were estimated by Kaplan-Meier method and compared by log-rank. The Cox Proportional Hazards model was used to determine factors associated with overall survival (OS) via multivariate analysis.

Among 300 patients, 225 were N2 and 60 were N1. No differences were seen in pathologic markers for N1 compared to N2. N2 were more likely to have liver metastases (LM) (p = 0.048) but rates of resectability were similar. Median OS for N1 with >70% liver cytoreduction was not yet reached compared to 121 months for N2 (p = 0.005). On multivariate analysis, LM was associated with shorter survival (p = 0.028), but nodal status was not.

Unlike LM, N2 status is not independently prognostic, but a marker for aggressive LM.

Surgical resection is the foundation for treatment of small bowel neuroendocrine tumors (SBNETs). Guidelines for surgical management of SBNETs rely on retrospective data, which suggest that primary tumor resection and cytoreduction improve symptoms, prevent future complications, and lengthen survival. In advanced NETs, improvement in progression-free survival has been reported in large, randomized, controlled trials of various medical treatments, including somatostatin analogues, targeted therapy, and peptide receptor radionuclide therapy. This review discusses important studies influencing the management of SBNETs and the limitations of current evidence regarding surgical interventions for SBNETs.

Small-intestinal neuroendocrine tumors (SI-NET) are situated preferentially within the ileum. The aim was to describe a potential difference in location between unifocal and multiple ileal-NET.

Between December 2010 and December 2019, all consecutive patients who underwent resection in our European Neuroendocrine Tumor Society Center of Excellence, of at least 1 non-duodenal SI-NET, were retrospectively included. The main objective was to prove that multiple ileal-NET were mostly located on the left side of the superior mesenteric artery (SMA) axis (defined as 40 cm from the ileocecal valve), and unifocal ones on the right side.

Ninety-four patients were included, 6 with unifocal jejunal-NET located 35 cm (range, 10-60) from the duodenojejunal angle (DJA), 44 (47%) with unifocal ileal-NET and 44 (47%) with multiple ileal-NET. The median number of tumors in multiple ileal-NET was 7 (range, 2-95), within a median small bowel segment of 105 cm (10-240). The median length between the proximal tumor and the DJA was 428 cm (300-635) and 540 cm (350-725) for the distal one; 40 (91%) of them were located on the left side of the SMA axis. In contrast, unifocal ileal-NET were located at a median distance of 577 cm (305-820) from the DJA (p < 0.001, compared to multiple ileal-NET); 30 (68%) of them were on the right side of the SMA axis (p < 0.001).

Multiple ileal-NET are mostly located on the left side of the SMA axis. Further studies are warranted to explore the embryological origin of unifocal versus multiple ileal-NET.

Small-intestinal neuroendocrine tumors (SI-NETs) are the most prevalent small bowel neoplasms with an increasing frequency. In the multimodal management of SI-NETs, surgery plays a key role, either in curative intent, even if R0 resection is feasible in only 20% of patients due to advanced stage at diagnosis, or palliative intent. Surgeons must be informed about the specific surgical management of SI-NETs according to their hormonal secretion, their usual dissemination at the time of diagnosis and the need for bowel-preserving surgery to avoid short bowel syndrome. The aim of this paper is to review the surgical indications and techniques, and perioperative and postoperative management of SI-NETs.

Tumor biomarkers (TBMs) reflect disease burden and correlate with survival for small bowel neuroendocrine tumors (SBNETs). This study sought to determine the performance of chromogranin A (CgA), pancreastatin (PST), neurokinin A (NKA), and serotonin (5HT) during follow-up assessment of resected SBNETs.

An institutional database identified patients undergoing surgery for SBNETs. Tumor biomarker levels were assessed as categorical (normal vs elevated) and continuous variables for association with progression-free survival (PFS) and overall survival (OS) via the Kaplan-Meier method with Cox multivariable models adjusted for confounders. Sensitivity, specificity, and predictive values of TBM levels in identifying imaging-confirmed progression were calculated.

In 218 patients (44% female, 92% node + , 73% metastatic, 97% G1 or G2), higher levels of CgA, PST, NKA, and 5HT correlated with higher-grade and metastatic disease at presentation (p < 0.05). Elevated pre- and postoperative CgA, PST, and NKA correlated with lower PFS and OS (p < 0.05; median follow-up period, 49.6 months). Normal CgA, PST, and NKA were present in respectively 20.3%, 16.9%, and 72.6% of the patients with progression, whereas elevated levels were present in respectively 69.5%, 24.8%, and 1.3% of the patients without progression. Using TBMs to determine progression showed superiority of PST (78.9% accuracy) over CgA (63.3% accuracy) or CgA and PST together (60.3% accuracy).

Although specific for progression, NKA was rarely elevated, limiting its usefulness. Pre- and postoperative PST and CgA correlated with disease burden and survival, with PST providing better discrimination of outcomes. During the follow-up period, use of PST most accurately detected progression. These results suggest that PST should replace CgA for SBNET surveillance.

This document is a summary of the French Intergroup guidelines regarding the management of digestive neuroendocrine neoplasms (NEN) published in February 2020 (www.tncd.org).

All French medical societies involved in the management of NEN took part in this work. Recommendations were graded into four categories (A, B, C or D), according to the level of evidence found in the literature until May 2019.

The management of NEN is challenging because of their heterogeneity and the increasing complexity of diagnostic and therapeutic procedures. Pathological analysis is required for their diagnostic and prognostic characterization, which mainly relies on differentiation, grade and stage. The two main emergency situations are functioning syndromes and poorly-differentiated carcinoma. Chromogranin A is the main biochemical marker of NET, although of limited clinical interest. Initial characterization relies on morphological and isotopic imaging. The treatment of localized NET relies on watchful follow-up and local or surgical resection depending on its supposed aggressiveness. Treatment options for metastatic disease include surgery, somatostatin analogues, chemotherapy, targeted therapies, organ-driven locoregional therapies and peptide-receptor radionuclide therapy. As specific predictive factors of treatment efficacy are yet to be identified and head-to-head comparisons have not or only rarely been performed, the therapeutic strategy currently depends on prognostic factors. Cumulative toxicity and the impact of treatment on quality of life must be considered since survival is relatively long in most patients with NET.

These guidelines are proposed to achieve the most beneficial therapeutic strategy in clinical practice as the therapeutic landscape of NEN is becoming ever more complex. These recommendations are permanently being reviewed.

This review serves as a primer on contemporary neuroendocrine neoplasm classification, with an emphasis on gastroenteropancreatic well-differentiated neuroendocrine tumors. Topics discussed include general features of neuroendocrine neoplasms, general neuroendocrine marker immunohistochemistry, the distinction of well-differentiated neuroendocrine tumor from pheochromocytoma/paraganglioma and other diagnostic mimics and poorly differentiated neuroendocrine carcinoma from diagnostic mimics, the concepts of differentiation and grade and the application of Ki-67 immunohistochemistry to determine the latter, the various WHO classifications of neuroendocrine neoplasms including the 2019 WHO classification of gastroenteropancreatic tumors, organ-specific considerations for gastroenteropancreatic well-differentiated neuroendocrine tumors, immunohistochemistry to determine site of origin in metastatic well-differentiated neuroendocrine tumor of occult origin, immunohistochemistry in the distinction of well-differentiated neuroendocrine tumor G3 from large cell neuroendocrine carcinoma, and, finally, required and recommended reporting elements for biopsies and resections of gastroenteropancreatic neuroendocrine epithelial neoplasms.

Neuroendocrine tumors of the gastrointestinal tract or pancreas are rare. Their presentation overlaps with other intra-abdominal neoplasms, but can have unique features. The workup involves recognition of unusual clinical features associated with the tumors, imaging, analysis of blood or urine concentrations, and biopsy. Functional imaging takes advantage of the neuroendocrine tumor-specific expression of somatostatin receptors. There are characteristic features supporting the diagnosis on contrast-enhanced cross-sectional imaging. The use of tumor markers for biochemical diagnosis requires an understanding of the confounding variables affecting these assays. There are unique and specific immunohistochemical staining and grading requirements for appropriate diagnosis of these tumors.

To assess the metabolomic fingerprint of small intestine neuroendocrine tumors (SI-NETs) and related hepatic metastases, and to investigate the influence of the hepatic environment on SI-NETs metabolome. Ninety-four tissue samples, including 46 SI-NETs, 18 hepatic NET metastases and 30 normal SI and liver samples, were analyzed using 1H-magic angle spinning (HRMAS) NMR nuclear magnetic resonance (NMR) spectroscopy. Twenty-seven metabolites were identified and quantified. Differences between primary NETs vs. normal SI and primary NETs vs. hepatic metastases, were assessed. Network analysis was performed according to several clinical and pathological features. Succinate, glutathion, taurine, myoinositol and glycerophosphocholine characterized NETs. Normal SI specimens showed higher levels of alanine, creatine, ethanolamine and aspartate. PLS-DA revealed a continuum-like distribution among normal SI, G1-SI-NETs and G2-SI-NETs. The G2-SI-NET distribution was closer and clearly separated from normal SI tissue. Lower concentration of glucose, serine and glycine, and increased levels of choline-containing compounds, taurine, lactate and alanine, were found in SI-NETs with more aggressive tumors. Higher abundance of acetate, succinate, choline, phosphocholine, taurine, lactate and aspartate discriminated liver metastases from normal hepatic parenchyma. Higher levels of alanine, ethanolamine, glycerophosphocholine and glucose was found in hepatic metastases than in primary SI-NETs. The present work gives for the first time a snapshot of the metabolomic characteristics of SI-NETs, suggesting the existence of complex metabolic reality, maybe characteristic of different tumor evolution.