Pancreatic neuroendocrine tumor liver metastases (PanNET LMs) are traditionally classified into three types based on their distribution. Surgery is generally considered for patients with type I/II LMs, while those with type III LMs are typically regarded as unresectable; however, type III LMs encompass a wide range of clinical scenarios, some of which may allow surgical resection.

The aim of this study was to identify preoperative predictors of early progression following surgery (≤6 months) in patients with PanNETs and LMs.

Consecutive patients with PanNETs and LMs who underwent surgery at San Raffaele Hospital (2010-2023) were included.

After a median follow-up of 56 months, 18/54 patients (34%) experienced early disease progression. Female gender was identified as a protective factor (hazard ratio [HR] 0.373, p = 0.049), while age ≥ 70 years emerged as a significant risk factor (HR 2.744, p = 0.042) for early postoperative progression. When overall disease progression was considered as an outcome, female gender was confirmed as protective (HR 0.426, p = 0.010), while type III LMs significantly increased the risk of progression (HR 2.500, p = 0.012). In the subgroup of patients with type III LMs (n = 37), female gender was confirmed as the only predictor of longer progression-free survival (HR 0.332, p = 0.006).

This study highlights the potential role of surgery for patients with resectable or potentially resectable PanNETs and LMs. For patients with type III LMs, the role of surgery remains controversial. Nevertheless, surgery may still be an option in selected cases, particularly in younger patients and females, as part of a multidisciplinary treatment strategy.

Non-functional gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare tumors, and liver metastasis is the leading cause of death in patients with GEP-NENs. Due to the difficulty in conducting large cohort studies, no reliable tool currently exists to predict the risk of liver metastasis in these patients. This study aimed to develop and validate a nomogram model based on large cohort clinical data to accurately predict the risk of liver metastasis in patients with non-functional GEP-NENs.

A retrospective cohort study was conducted, encompassing 838 patients with non-functional GEP-NENs diagnosed between 2009 and 2023. Independent risk factors for liver metastasis were identified through univariate and multivariate logistic regression analyses. A nomogram was constructed based on significant predictors, including T stage, N stage, Ki-67 index, primary tumor site, and BMI. The model's performance was evaluated using the C-index, calibration curves, and decision curve analysis (DCA) for both training and validation cohorts.

The nomogram demonstrated excellent predictive performance, with C-index values of 0.839 and 0.823 for the training and validation sets, respectively. Risk stratification using the nomogram's total score effectively differentiated high-risk from low-risk patients. Kaplan-Meier survival analysis revealed significant survival differences between these groups (P < 0.0001). Moreover, the calibration curves indicated strong agreement between predicted and observed outcomes.

The developed nomogram is a reliable tool for predicting the risk of liver metastasis in non-functional GEP-NENs. It facilitates early identification of high-risk patients, thereby enabling personalized treatment and timely intervention. Future research should focus on multicenter validation and the integration of molecular markers to enhance the robustness and clinical applicability of the model.

The study aimed to describe patients' fundamental care needs and their experiences of nursing care, throughout surgical treatment of small intestinal neuroendocrine tumours.

A qualitative descriptive study was performed.

Patients' interviews (n = 19) were conducted in Sweden from May 2021 to January 2022 and analysed using directed qualitative content analysis guided by the Fundamentals of Care framework.

The results are presented in three descriptive categories chronologically throughout the care chain. In the preoperative phase of care, the category was 'Feeling safe but lonely and frightened, and struggling with existential thoughts'; experiences in the postoperative phase of care resulted in the category 'Feeling cared for but suffering from physical symptoms and feelings of loneliness'; and the category in the discharge phase was 'Lacking self-care information and feeling worried about the future'.

There were deficiencies in the delivery of fundamental care for patients with a rare tumour diagnosis throughout surgical treatment. Nursing care is mostly task focused and fragmented, and there is a lack of psychosocial and relational care across the care chain. Registered nurses and nursing managers need to take responsibility for their leadership in nursing care to fulfil patients' fundamental care needs. The Fundamentals of Care framework could be used for work improvements to include all aspects of nursing care.

High-quality nursing care is needed throughout the care chain, including self-care after discharge, for patients with this rare tumour diagnosis. A higher awareness of patients' experiences and the importance of psychosocial support is warranted. Registered nurses and nursing managers must revise and improve routines to support patients' psychosocial needs. Registered nurses need to take responsibility for their leadership in nursing care to fulfil patients' fundamental care needs.

What problem did the study address? This study highlights patients' fundamental care needs and experiences of nursing care throughout surgical treatment of small intestinal neuroendocrine tumours. What were the main findings? There are deficiencies in fulfilling patients' fundamental care needs across the care chain and in all dimensions of the Fundamental of Care framework throughout surgical treatment of small intestinal neuroendocrine tumours. Patients struggled with loneliness and existential thoughts, as well as worries about the future. Patients experienced a lack of information about plans for the day, self-care, and follow-ups. Where and on whom will the research have an impact? For clinicians to develop an understanding of, and improve, fundamental care needs for patients with small intestinal neuroendocrine tumours in a surgical context. For registered nurses to understand the importance of their leadership and nursing responsibility to fulfil fundamental care needs.

The consolidated criteria for reporting qualitative research (COREQ): a 32-item checklist for interviews and focus groups.

The patients shared their experiences during the interviews, which has contributed to a deeper knowledge and understanding of the phenomena under study.

Background: Therapy using lutetium-177 dotatate (177LU) was approved in Europe for the treatment of advanced neuroendocrine tumors (NETs) in 2017. Since then, it has become part of the strategies in the treatment of NETs, making it now possible to evaluate real-life results. Research Design and Methods: Single-arm, retrospective, multicenter, cohort study of all the patients with metastatic NETs treated with 177LU (four cycles of 200 mCi every 8 weeks) in the two medical centers dedicated to the treatment of NETs from the region of Aragón, Spain, from 2017 to 2024. Descriptive analysis of demographic characteristics, efficacy, and survival analysis were performed using the statistics software Jamovi 2.6.14. Results: Sixty-eight patients were included. The majority were male, and the most frequent primary location was the pancreas. The ORR was 30.9%. The DCR was 88%. The median OS was 47.4 months [95% CI, 25.6-NE]. The median PFS was 26.1 months [95% CI, 18.5-68.3]. High-grade tumors, multiple previous treatments, and pancreatic location presented worse OS. In total, 42.6% presented any grade adverse event (17.2% hematologic, 30.9% GI symptoms). Conclusions: The efficacy of 177LU in our study is like that observed in similar studies. Acceptable tolerance has been shown. Pancreatic tumors, previous treatments, and higher grades demonstrated worse outcomes. The new research line must consider the use of treatment with 177LU in earlier lines for metastatic disease as well as its possible use in local or locally advanced disease.

Gastric neuroendocrine carcinomas (NECs) exhibit aggressive features, such as rapid growth, higher rate of metastasis, and a generally unfavorable prognosis compared to gastric adenocarcinoma. As a result, therapeutic options for NECs remain limited, contributing to the poor prognosis of patients. Immunotherapy has emerged as a promising treatment strategy and demonstrated the potential to partially improve the survival and prognosis of patients with NECs. Nevertheless, the unique clinical response termed pseudoprogression (PsP) has garnered considerable attention in the context of immunotherapy.

Presented here is a case of NEC recurrence five and a half months after radical gastric surgery. The 45-year-old male patient underwent combination treatment involving a PD-1 blocker and tyrosine kinase inhibitors and encountered two instances of PsP during treatment. The patient ultimately achieved a durable treatment response without altering his treatment regimens, resulting in a substantial therapeutic benefit.

This case report aimed to provide the authors' experience with the diagnosis of PsP and treatment strategies for PsP in ongoing immunotherapy.

Neuroendocrine liver metastases (NELM) significantly reduce survival in patients with neuroendocrine tumor. The management of NELM is challenged by a low rate of resectability and a high rate of recurrence. Indocyanine green (ICG) fluorescence imaging offers potential advantages in real-time tumor visualization and margin assessment. This study evaluates the impact of ICG fluorescence on perioperative outcomes and recurrence-free survival (RFS) in NELM patients undergoing laparoscopic parenchyma-sparing hepatectomy (LPSH).

A retrospective cohort study was performed on patients with NELM who underwent LPSH from August 2013 to May 2023 at our single center. Data on sociodemographic characteristics, laboratory parameters, surgical results and follow-up outcomes were collected.

A total of 51 NELM patients were included. No significant differences in baseline characteristics were observed between the ICG and non-ICG groups. Postoperative complications occurred in 52.9% of patients, with bile leakage being most common. No perioperative mortality was reported. Pathologically positive margins were significantly lower in the ICG group (1.3 vs. 16.4%, p < 0.001). After a median follow-up of 36 months, 62.7% of patients experienced recurrence, mostly intrahepatic. Median recurrence-free survival (RFS) was longer in the ICG group, though not statistically significant (38.0 vs. 29.0 months, p = 0.086).

The use of ICG fluorescence imaging in LPSH may improve surgical margins and potentially enhance RFS in NELM patients. These findings are clinically significant, highlighting the need for larger prospective studies to confirm its impact on long-term prognosis.

Neuroendocrine neoplasms (NENs) represent heterogeneous tumors arising from neuroendocrine cells in different organs. Despite growing interest in the nutritional aspects of NEN management, research in this area is limited. Aim of this review is to summarize the current state of knowledge, highlight research gaps, and underscore the significance of nutrition in the comprehensive care of NEN patients.

We conducted an extensive bibliographic search focusing on studies (including retrospective and prospective studies, systematic reviews, case series, and guidelines) exploring the relationship between nutritional assessments, dietary interventions, micronutrient deficiencies, and their impact on NEN outcomes.

Significant gaps exist in current research, particularly in understanding the specific nutritional needs of NEN patients and how tailored nutritional interventions can improve clinical outcomes. Evidence suggests that a high-fat Western diet may promote the growth of NEN, while a Mediterranean diet may help lower insulin levels and strengthen the immune system, potentially preventing tumor development. The ketogenic diet and intermittent fasting may also have positive impacts. Addressing common micronutrient deficiencies, such as vitamin D and niacin, is crucial to mitigate disease progression. There's a crucial need for future studies to include a comprehensive nutritional assessment incorporating patient-reported outcomes, to fully capture the impact of nutritional strategies.

Nutritional management, an important but under-researched facet of NEN treatment, significantly improves patients' quality of life and survival. Integrating nutrition into personalized cancer care is essential, highlighting the role of nutritional strategies in optimizing patient outcomes.

A 65-year-old male presented after a positive Cologuard testing. He was asymptomatic at presentation, with no reported complaints of fever, chills, abdominal pain, diarrhea, constipation, hematochezia, or unexpected weight loss. CT imaging of the abdomen and pelvis revealed a 2 cm mass at the rectosigmoid junction with a single enlarged lymph node nearby measuring 2.7 x 1.6 cm, raising suspicion for regional metastatic adenopathy. He underwent a colonoscopy, which confirmed a rectosigmoid mass. Biopsy results showed adenocarcinoma of the colon. Consequently, the patient was scheduled for a laparoscopic sigmoidectomy with low anterior resection. The pathology of the surgical specimen confirmed adenocarcinoma, moderately differentiated, associated with a component of poorly differentiated large cell neuroendocrine carcinoma, with the neuroendocrine component best developed in the lymph node metastasis. Although the patient did not meet the standard criteria for mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) tumors, treatment was administered using chemotherapeutic agents typically reserved for MiNENs. He was treated with platinum-based doublet with good response and has been in remission for one and a half years. This report highlights the importance of flexible therapeutic approaches when pathology marginally deviates from the standard established criteria, illustrating that tailoring treatment to the specific pathology can provide considerable patient benefits.

Introduction: Middle ear adenomatous neuroendocrine tumors (MEANTs) are rare middle ear lesions characterized by nonspecific symptoms, signs, and imaging findings. Diagnosis typically relies on postoperative pathological assessment. This study investigated the diagnostic utility of the predilection sites and clinical characteristics of MEANTs. Methods: A retrospective analysis was conducted on clinical data from 10 patients with histologically confirmed MEANTs, admitted to Eye & ENT Hospital of Fudan University between March 2016 and March 2023. Results: The median age of the patients at diagnosis was 39.3 years. Hearing loss (n = 8) and ear pain (n = 6) were the most prevalent clinical symptoms in the patients diagnosed with MEANTs. Endoscopic examination revealed diverse symptoms, predominantly presenting as non-pulsatile masses with distinct boundaries and quasi-circular shapes within the external auditory canal, often accompanied by abundant blood vessels (n = 4). Tumors were typically confined to the middle/lower tympanic chambers or eustachian tube and were frequently associated with tympanic sclerosis, particularly around the pharyngeal tube (n = 3). Pathologically, MEANTs exhibited CD56 positivity or weak positivity, along with positive staining for CKpan and Syn, negativity for S100, and Ki67 ≤3%. Personalized surgical interventions were chosen by all the patients based on lesion severity, with no subsequent radiotherapy or chemotherapy administered postoperatively. No tumor progression was noted during the postoperative follow-up. In addition, a noteworthy case was presented in which MEANT initially manifested in the middle or lower tympanic cavity and eustachian tubes. Over 2 years, the tumor progressively grew, invading the middle tympanum and surrounding ossicles, ultimately achieving complete resection with no recurrence observed during subsequent follow-up. Conclusions: A possible diagnosis of middle ear adenoma should be considered when encountering non-pulsatile tumors with clearly demarcated inner boundaries within the external auditory canal accompanied by abundant quasi-circular vessels and the presence of new bone or neoplasm at the pharyngeal tympanic canal orifice observed during preoperative examinations or surgical procedures.

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.

Both the incidence and prevalence of well-differentiated neuroendocrine tumours from the small intestine (Si-NET) are gradually increasing. Most patients have non-functioning tumours with subtle GI symptoms and tumours are often discovered incidentally by endoscopy or at advanced disease stages by imaging depicting mesenteric lymph node and /or liver metastases while around 30% of the patients present with symptoms of the carcinoid syndrome. Adequate biochemical assessment and staging including functional imaging is crucial for treatment-related decision-making that should take place in an expert multidisciplinary team setting. Preferably, patients should be referred to specialised ENETS Centres of Excellence or centres of high expertise in the field. This guidance paper provides the current evidence and best knowledge for the management of Si-NET grade (G) 1-3 following 10 key questions of practical relevance for the diagnostic and therapeutic decision making.

Neuroendocrine tumors (NETs) of the pancreas are rare neoplasms that present complex challenges to diagnosis and treatment due to their indolent course. The incidence of pancreatic neuroendocrine tumors has increased significantly over the past two decades. A limited number of pancreatic neuroendocrine cell lines are currently available for the research. Here, we present 3D-iNET ORION, a novel 3-dimensional (spheroid) cell line, isolated from human pancreatic neuroendocrine tumor liver metastasis. Three-dimensionally grown (3D) cancer cell lines have gained interest over the past years as 3D cancer cell lines better recapitulate the in vivo structure of tumors, and are more suitable for in vitro and in vivo experiments. 3D-iNET ORION cancer cell line showed high potential to form tumorspheres when embedded in Matrigel matrix and expresses synaptophysin and EpCAM. Electron microscopy analysis of cancer cell line proved the presence of dense neurosecretory granules. When xenografted into athymic mice, 3D-iNET ORION cells produce slow-growing tumors, positive for chromogranin and synaptophysin. Human Core Exome Panel Analysis has shown that 3DiNET ORION cell line retains the genetic aberration profile detected in the original tumor. In conclusion, our newly developed neuroendocrine cancer cell line can be considered as a new research tool for in vitro and in vivo experiments.

A 40-year-old male patient was admitted due to abdominal distension and discomfort in the upper abdomen persisting for three days. Enhanced CT of the upper abdomen revealed an irregularly dense soft tissue area in the body and tail of the pancreas, approximately 7.6 × 3.1 cm in size, with blurred boundaries, and indistinct separation from the splenic artery and vein. Multiple liver lesions of varying sizes and slightly lower densities were also observed. Liver tumor biopsy considering a neuroendocrine tumor G2, combined with the medical history, led to a diagnosis of pancreatic neuroendocrine tumor G2 with liver metastasis. Physical examination showed mild tenderness in the upper abdomen but no other significant positive signs. During treatment, the patient developed multiple red papular rashes around the mouth, on both lower limbs, and the perineum, accompanied by itching. The glucagon level was 1138.3 pg/L. The patient underwent resection of the pancreatic body and tail, splenectomy, partial liver tumor resection, and cholecystectomy. Within five days post-surgery, the skin lesions began to crust and flake off. On the 14th day post-surgery, the serum glucagon level was rechecked at 136.4 pg/L. As of April 2024, progression of liver lesions was noted, with no significant skin symptoms during the period.

Neuroendocrine tumours (NETs) are increasing in incidence, often diagnosed at advanced stages, and individuals may experience years of diagnostic delay, particularly when arising from the small intestine (SI). Clinical prediction models could present novel opportunities for case finding in primary care.

An open cohort of adults (18+ years) contributing data to the Optimum Patient Care Research Database between 1st Jan 2000 and 30th March 2023 was identified. This database collects de-identified data from general practices in the UK. Model development approaches comprised logistic regression, penalised regression, and XGBoost. Performance (discrimination and calibration) was assessed using internal-external cross-validation. Decision analysis curves compared clinical utility.

Of 11.7 million individuals, 382 had recorded SI NET diagnoses (0.003%). The XGBoost model had the highest AUC (0.869, 95% confidence interval [CI]: 0.841-0.898) but was mildly miscalibrated (slope 1.165, 95% CI: 1.088-1.243; calibration-in-the-large 0.010, 95% CI: -0.164 to 0.185). Clinical utility was similar across all models.

Multivariable prediction models may have clinical utility in identifying individuals with undiagnosed SI NETs using information in their primary care records. Further evaluation including external validation and health economics modelling may identify cost-effective strategies for case finding for this uncommon tumour.

Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs.

In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort.

In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate.

NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms presenting unique challenges in diagnosis and management. Traditional markers such as chromogranin A (CgA), pancreatic polypeptide (PP), and neuron-specific enolase (NSE) have limitations in terms of specificity and sensitivity. Specific circulating markers such as serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) and various gastrointestinal hormones such as gastrin, glucagon, somatostatin, and vasoactive intestinal peptide (VIP) have a role in identifying functional NENs. Recent advances in molecular and biochemical markers, also accounting for novel genomic and proteomic markers, have significantly improved the landscape for the diagnosis and monitoring of NENs. This review discusses these developments, focusing on both traditional markers such as CgA and NSE, as well as specific hormones like gastrin, insulin, somatostatin, glucagon, and VIP. Additionally, it covers emerging genomic and proteomic markers that are shaping current research. The clinical applicability of these markers is highlighted, and their role in improving diagnostic accuracy, predicting surgical outcomes, and monitoring response to treatment is demonstrated. The review also highlights the need for further research, including validation of these markers in larger studies, development of standardized assays, and integration with imaging techniques. The evolving field of biochemical markers holds promise for improving patient outcomes in the treatment of NENs, although challenges in standardization and validation remain.

Toll-like receptors (TLRs) are pattern recognition receptors of the innate immunity. TLRs are known to mediate both antitumor effects and tumorigenesis. TLRs are abundant in many cancers, but their expression in small bowel neuroendocrine tumors (SB-NETs) is unknown. We aimed to characterize the expression of TLRs 1-9 in SB-NETs and lymph node metastases and evaluate their prognostic relevance. The present study included 125 patients with SB-NETs, of whom 95 had lymph node metastases, from two Finnish hospitals. Tissue samples were stained immunohistochemically for TLR expression, assessed based on cytoplasmic and nucleic staining intensity and percentage of positively stained cells. Statistical methods for survival analysis included Kaplan-Meier method and Cox regression adjusted for confounding factors. Disease-specific survival (DSS) was the primary outcome. TLRs 1-2 and 4-9 were expressed in SB-NETs and lymph node metastases. TLR3 showed no positive staining. In primary SB-NETs, TLRs 1-9 were not associated with survival. For lymph node metastases, high cytoplasmic TLR7 intensity associated with worse DSS compared to low cytoplasmic intensity (26.4% vs. 84.9%, p = 0.028). Adjusted mortality hazard (HR) was 3.90 (95% CI 1.07-14.3). The expression of TLRs 1-6 and 8-9 in lymph node metastases were not associated with survival. SB-NETs and their lymph node metastases express cytoplasmic TLR 1-2 and 4-9 and nucleic TLR5. High TLR7 expression in SB-NET lymph node metastases was associated with worse prognosis. The current research has future perspective, as it can help create base for clinical drug trials to target specific TLRs with agonists or antagonists to treat neuroendocrine tumors.

Summarizing the clinical features of children with intussusception secondary to small bowel tumours and enhancing awareness of the disease.

Retrospective summary of children with intussusception admitted to our emergency department from January 2016 to January 2022, who underwent surgery and were diagnosed with small bowel tumours. Summarize the types of tumours, clinical presentation, treatment, and prognosis.

Thirty-one patients were included in our study, 24 males and 7 females, with an age of onset ranging from 1 m to 11y 5 m. Post-operative pathology revealed 4 types of small intestinal tumour, 17 lymphomas, 10 adenomas, 4 inflammatory myofibroblastomas and 1 lipoma. The majority of tumours in the small bowel occur in the ileum (83.9%, 26/31). Abdominal pain, vomiting and bloody stools were the most common clinical signs. Operative findings indicated that the small bowel (54.8%, 17/31) and ileocolic gut were the main sites of intussusception. Two types of procedure were applied: segmental bowel resection (28 cases) and wedge resection of mass in bowel wall (3 cases). All patients recovered well postoperatively, with no surgical complications observed. However, the primary diseases leading to intussusception showed slight differences in long-term prognosis due to variations in tumor types.

Lymphoma is the most common cause of intussusception in pediatric patients with small bowel tumours, followed by adenoma. Small bowel tumours in children tend to occur in the ileum. Therefore, the treatment of SBT patients not only requires surgeons to address symptoms through surgery and obtain tissue samples but also relies heavily on the expertise of pathologists for accurate diagnosis. This has a significant impact on the overall prognosis of these patients.

Currently, the primary treatment modalities for colorectal neuroendocrine tumors (CRNET) with a diameter between 10mm and 20mm are surgical resection (SR) and endoscopic resection (ER). However, it remains unclear which surgical approach yields the greatest survival benefit for patients.

This study included data from patients diagnosed with CRNET with tumor diameters ranging from 10mm to 20mm between the years 2004 and 2019, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized into ER and SR groups based on the respective surgical approaches. Inverse probability weighting (IPTW) was employed to mitigate selection bias. Kaplan-Meier analysis and log-rank tests were utilized to estimate overall survival (OS) and cancer-specific survival (CSS). Cox regression analysis (univariate and multivariate) was performed to evaluate potential factors influencing survival.

A total of 292 CRNET patients were included in this study (ER group: 108 individuals, SR group: 184 individuals). Prior to IPTW adjustment, Kaplan-Meier analysis and Cox proportional hazard regression analysis demonstrated that the OS and CSS of the SR group were inferior to those of the ER group. However, after IPTW adjustment, no statistically significant differences in prognosis were observed between the two groups. Subgroup analyses revealed that patients with muscular invasion, positive lymph nodes, or distant metastasis derived greater survival benefits from SR. Significant differences in OS and CSS between the two groups were also observed across different age groups.

For patients with mucosal-limited lesions and without local lymph node or distant metastasis, ER is the preferred surgical approach. However, for patients with muscular invasion or positive lymph nodes/distant metastasis, SR offers a better prognosis. The choice of surgical approach should be based on the specific clinical characteristics of patients within different subgroups.

The recent introduction of novel treatments for advanced neuroendocrine tumors (NETs) and the well-established impact of clinical case discussion within dedicated multidisciplinary teams indicates the need to promote the centralization of rare diseases, such as NENs (neuroendocrine neoplasms). Data on the real-life use of and indications for [68Ga]Ga-DOTANOC PET/CT were collected from a prospective monocentric 5-year electronic archive including consecutive patients with confirmed and suspected NETs (September 2017 to May 2022). Overall, 2082 [68Ga]Ga-DOTANOC PET/CT scans (1685 confirmed NETs, 397 suspected NETs) were performed in 1537 patients. A high positivity rate was observed across different clinical settings (approximately 70%). Approximately 910/2082 scans were requested by the local oncology ward (851 confirmed NETs, 59 suspected NETs). The following observations were found: (i) the detection rate across all indications was 73.2% (higher for staging, peptide receptor radioligand therapy (PRRT) selection, and treatment response assessment); (ii) in suspected NETs, PET was more often positive when based on radiological findings. This systematic data collection in a high-volume diagnostic center represents a reliable cohort reflecting the global trends in the use of [68Ga]Ga-DOTANOC PET/CT for different clinical indications and primary tumor sites, but prompts the need for further multicenter data sharing in such a rare and slowly progressive disease setting.

Pancreatic neuroendocrine neoplasms (p-NENs) are relatively rare and highly heterogeneous. Dyslipidemia may be related to the risk of developing p-NENs, although dyslipidemia in patients with p-NENs is rarely reported. In this study, the clinical characteristics of p-NENs patients with different lipid levels and their prognostic value in p-NENs patients were evaluated.

Patients (n=211) with p-NENs hospitalized at Jiangsu Neuroendocrine Tumor Centre of Jiangsu Province Hospital from December 2018 to December 2022 were enrolled. Clinical data related to p-NENs were collected. Based on the EGA database, the related lipoprotein, low-density lipoprotein receptor (LDLR) and high-density lipoprotein binding protein (HDLBP) mRNA in p-NENs and paratumoral tissues and the follow-up information of p-NENs were evaluated.

A total of 175 p-NENs patients ultimately met the inclusion criteria. The ki67 index was higher in p-NENs patients with elevated lipid with the proportion of≥5, and in those with AJCC stage III and stage IV than p-NENs patients with low-level lipid. In p-NENs patients, the expression of HDLBP mRNA was downregulated in p-NENs tissues compared to the paratumoral tissues. Survival analysis showed that serum lipids had no effect on the prognosis of p-NENs; however, high LDLR level p-NENs were at the risk of poor survival.

Serum lipid level in p-NENs can affect the grading and staging, but the correlation with the prognosis of p-NENs is not significant. However, dyslipidemia may be a potential predictor of p-NENs.

The prognosis and impact of different prognostic factors in pancreatic neuroendocrine neoplasms (pNEN) remain controversial.

To investigate prognostic factors for recurrence-free survival and disease-specific survival in patients with pNEN, divided into three groups: patients undergoing surveillance (tumor size < 2 cm, group 1), patients followed after curative-intended surgery (group 2), and patients with unresectable disease or residual tumors after resection (group 3).

A single-center retrospective study including consecutive patients over a 20-year period. Multivariate Cox regression analyses were performed to identify risk factors.

413 patients were included, with a mean (SD) age of 62 ± 14 years. In group 1 (n = 51), median (IQR) follow-up was 29 (21-34) months, and tumor size was 1.0 (0.8-1.4) cm. One progressed and had a tumor resection. In group 2 (n = 165), follow-up 59 (31-102) months, median tumor size 2 (1.2-3.4) cm, median Ki-67 index 5 (3-10)%, the 5-year recurrence rate was 21%. Tumor size (p < 0.001), Ki-67 index (p = 0.02), and location in the pancreatic head (p < 0.001) were independent risk factors. In group 3 (n = 197), follow-up 19 (6-46) months, median tumor size 4.2 (2.6-7.0) cm, Ki-67 index 17 (9-64)%, the median disease-specific survival was 22 (6-75) months-99 in NET G1; 54 in NET G2; 14 in NET G3; and 6 months in neuroendocrine carcinomas (NEC). Age (p = 0.029), plasma chromogranin A (p = 0.014), and proliferation, expressed by grade (p = 0.001) and Ki-67 index (p < 0.001), were risk factors.

Growth in pNET < 2 cm requiring surgery was observed in 1/51. Tumor size, Ki-67 index, and location in the head were prognostic factors for disease recurrence, while age, plasma chromogranin A, and proliferation predicted mortality in patients with unresectable disease or residual tumors after resection.

Determining neuroendocrine tumor (NET) primary sites is pivotal for patient care as pancreatic NETs (pNETs) and small bowel NETs (sbNETs) have distinct treatment approaches. The diagnostic power and prioritization of fluorescence in situ hybridization (FISH) assay biomarkers for establishing primary sites has not been thoroughly investigated using machine learning (ML) techniques. We trained ML models on FISH assay metrics from 85 sbNET and 59 pNET samples for primary site prediction. Exploring multiple methods for imputing missing data, the impute-by-median dataset coupled with a support vector machine model achieved the highest classification accuracy of 93.1% on a held-out test set, with the top importance variables originating from the ERBB2 FISH probe. Due to the greater interpretability of decision tree (DT) models, we fit DT models to ten dataset splits, achieving optimal performance with k-nearest neighbor (KNN) imputed data and a transformation to single categorical biomarker probe variables, with a mean accuracy of 81.4%, on held-out test sets. ERBB2 and MET variables ranked as top-performing features in 9 of 10 DT models and the full dataset model. These findings offer probabilistic guidance for FISH testing, emphasizing the prioritization of the ERBB2, SMAD4, and CDKN2A FISH probes in diagnosing NET primary sites.

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.

Small intestine neuroendocrine tumors are predominantly small but with high potential for distant metastases development. Diagnosis establishment in early-stage is often difficult and challenging. Small intestine neuroendocrine tumors often initially present with liver metastases. According to the Consensus Guidelines of the North American Neuroendocrine Tumor Society, in patients with liver metastases from unknown origin of primary neuroendocrine tumor, surgical exploration should be performed in order to identify the primary location, prevent small intestine obstruction, and treat one if already present. We present a case of a 69-year-old male patient diagnosed with liver and peritoneal metastases due to small bowel neuroendocrine tumor treated with surgery due to the presence of small intestine obstruction.

This study aimed to evaluate the safety, efficacy, and long-term outcomes of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for treating colorectal adenomas and tumors.

A systematic literature review was conducted using databases including PubMed, Web of Science, and Embase. Parameters such as number of patients or lesions, histological diagnosis, lesion size, surgery time, en-bloc resection, R0 resection, severe postoperative complications, and local recurrence were extracted and pooled for analysis.

A total of 12 retrospective studies involving 1289 patients and 1850 lesions were included in the analysis. EMR was found to have a shorter operation time by 53.6 minutes (95% CI: 51.3, 55.9, P<0.001) and fewer incidences of severe postoperative complications such as perforation and delayed bleeding (OR = 0.40, 95%CI: 0.23, 0.71, P<0.001). On the other hand, ESD had higher rates of en-bloc resection (OR = 0.15, 95%CI: 0.07, 0.30, P<0.001) and R0 resection (OR = 0.32, 95%CI: 0.16, 0.65, P<0.001). Recurrence after EMR was found to be significantly higher than that after ESD surgery (OR = 5.88, 95%CI: 2.15, 16.07, P = 0.037).

The study suggests that the choice of surgical method may have a greater impact on recurrence compared to the pathological type, and that ESD may be more suitable for the treatment of malignant lesions despite its higher rates of severe postoperative complications and longer operation time.

Neuroendocrine tumours (NET) arising from the small bowel are clinically challenging and are often diagnosed at advanced stages. Disease control with surgery alone can be demanding. Multimodal treatment concepts integrating surgery and non-surgical modalities could be of benefit.

Retrospective review of consecutive adult patients with SB NET treated at Imperial College Healthcare NHS Trust between 1 January 2010 and 31 December 2019. Data regarding clinicopathological characteristics, treatments, and disease trajectory were extracted and summarised. Overall and progression/recurrence-free survival were estimated at 5 and 10 years.

154 patients were identified, with a median age of 64 years (range 33-87); 135/154 (87.7%) had stage III/IV disease at diagnosis. Surgery was used in 125 individuals (81.2%), typically with either segmental small bowel resection (60.8%) or right hemicolectomy (33.6%) and mesenteric lymphadenectomy for the primary tumour. Systemic and/or liver-directed therapies were used in 126 (81.8%); 60 (47.6%) had more than one line of non-surgical treatment. Median follow-up was 67.2 months (range 3.1-310.4); overall survival at 5 and 10 years was 91.0% (95% CI: 84.9-94.7%) and 82.5% (95% CI: 72.9-88.9%), respectively. Imaging-based median progression-free survival was 42.7 months (95% CI: 24.7 to 72.4); 5-year progression-free survival was 63.4% (95% CI: 55.0-70.6%); 10-year progression-free survival was 18.7% (95% CI: 12.4-26.1). Nineteen patients (12.3%) reached 10 years follow-up without disease recurrence and therefore were considered cured.

Most patients with SB NET present in a metastasised stage. Multimodal treatment concepts may be associated with excellent clinical outcomes. Future work should explore optimal approaches to treatment sequencing and patient selection.

Neuroendocrine tumours commonly metastasise to the liver, particularly those arising from the intestinal tract and pancreas. Whilst surgery offers the only approach with intent to cure, the vast majority of patients with neuroendocrine liver metastases are ineligible. Liver-directed interventional therapies seek to exploit the patho-anatomy of the blood supply of hepatic metastases to deliver therapy to liver deposits. This may involve percutaneous ablation, bland embolization, or the selective infusion of chemotherapeutics, targeted agents or radiolabelled embolic material. Retrospective case series evidence has characterised objective response rates, disease control rates, and longer-term outcomes associated with each approach. Recent advances in this field include ongoing comparative trials of different techniques, but more importantly, combinations of interventional liver-directed therapies and other systemic therapy in multimodal treatment concepts.

Neuroendocrine neoplasms (NENs) of the small bowel are typically slow-growing lesions that remain asymptomatic until reaching an advanced stage. Imaging modalities for lesion detection, staging, and follow-up in patients with known or suspected NEN include CT enterography, MR enterography, and PET/CT using a somatostatin receptor analog. FDG PET/CT may have a role in the evaluation of poorly differentiated NENs. Liver MRI, ideally with a hepatocyte-specific contrast agent, should be used in the evaluation of hepatic metastases. Imaging informs decisions regarding both surgical approaches and systematic therapy (specifically, peptide receptor radionuclide therapy). This AJR Expert Panel Narrative Review describes the multimodality imaging features of small-bowel NENs; explores the optimal imaging modalities for their diagnosis, staging, and follow-up; and discusses how imaging may be used to guide therapy.

Liver metastasis is one of the most important factors affecting the prognosis of patients with neuroendocrine neoplasms (NENs). Transhepatic artery embolization (TAE) is the main local treatment of NENs with liver metastasis (NENLM). This study aimed to elucidate the differences between pancreatic and rectal NENLM with a discrepancy in blood supply.

A total of 32 patients with NENLM of different primary sites received 102 TAE treatments at our hospital. Clinical features, such as age, sex, World Health Organization (WHO) tumour grade and progression-free survival (PFS), were compared between patients with pancreatic and rectal NENLM with different blood supplies. The total follow-up time is 1-5 years.

There were 12 cases with tumours originating from the rectum or pancreas, respectively. Other tumour-originated sites included the duodenum (two cases, 6.25%), the thymus and lung (four cases, 12.5%), and the unknown (two cases, 6.25%). The average age of patients was 51.59 years, and 17 (53.1%) were men. WHO grade 1, 2 or 3 tumours occurred in three (9.4%), 23 (71.9%) and six (18.7%) patients, respectively. Hepatic tumour burdens of low (<25%), middle (25%-50%) and high (>50%) levels were found in 13 (40.6%), eight (25%) and 11 (34.4%) patients, respectively. There were more patients with hypervascular pancreatic NENLM than with hypovascular rectal NENLM (p = 0.005). Tumour shrinkage in all cases with NENLM was 50% with an objective response rate of 37.5%, disease control rate of 75% and PFS of 12 months. Disease progression (p = 0.09), tumour shrinkage (p = 0.07) and death (p = 0.19) were more prominent in the pancreatic NENLM group than in the rectal NENLM group. Progression-free survival was not reached in the pancreatic NENLM group, which was more prominent than in the rectal NENLM group (7 months; hazard ration, 0.22; 95% confidence interval, 0.07-0.76; p = 0.016). The main adverse events were abdominal pain (71.9%) and transaminase elevation (50%), which were more common in pancreatic NENLM than in rectal NENLM.

Transhepatic artery embolization treatment is markedly effective and safe for treating NENLM, especially pancreatic NENLM.

Small-bowel tumors represent a rare entity comprising 0.6% of all new cancer cases in the US, and only 3% of all gastrointestinal neoplasms. They are a heterogenous group of neoplasms comprising of about forty different histological subtypes with the most common being adenocarcinoma, neuroendocrine tumors, stromal tumors and lymphomas. Their incidence has been reportedly increasing over recent years, partly owing to the advances and developments in the diagnostic modalities. Small-bowel capsule endoscopy, device assisted enteroscopy and dedicated small-bowel cross-sectional imaging are complimentary tools, supplementing each other in the diagnostic process. Therapeutic management of small-bowel tumors largely depends on the histological type and staging at diagnosis. The aim of the present review article is to discuss relevant advances in the diagnosis and management of small-bowel tumors.

Neuroendocrine tumors (NETs) of the ampulla of Vater are extremely rare. Here, we discuss the clinical presentation, diagnostic challenges, and treatment options of a recently experienced case of NET of the ampulla of Vater in light of the literature. A 56-year-old woman presented with recurrent upper abdominal pain. Ultrasonography (USG) of the whole abdomen showed multiple gallstones along with a dilated common bile duct (CBD). For evaluating the dilated CBD, a magnetic resonance cholangiopancreatography was performed, which revealed the double-duct sign. Subsequently, an upper gastrointestinal endoscopy showed a bulged-out ampulla of the Vater. Biopsy and histopathological examination of the growth yielded the diagnosis of adenocarcinoma. A Whipple procedure was performed. Macroscopically, a 2 cm growth was noted involving the ampulla of Vater, and microscopic findings were consistent with a well-differentiated NET, grade 1 (low grade). The diagnosis was further confirmed by immunohistochemical staining (pan-cytokeratin positive, synaptophysin positive, and focally chromogranin positive). Her postoperative course was uneventful except for delayed gastric emptying. A detailed evaluation and a high index of suspicion are required for the diagnosis of this rare tumor. Treatment is relatively easier after a proper diagnosis.

Surveillance guidelines following the resection of small bowel neuroendocrine tumors (SB-NETs) are inconsistent. We evaluated the impact of surveillance imaging on SB-NET recurrence and overall survival (OS).

Patients with completely resected SB-NETs referred to a provincial cancer center (2004-2015) were reviewed. Associations between imaging frequency, recurrence, post-recurrence treatment, and OS were determined using univariate and Cox-regression analyses.

Among 195 completely resected SB-NET patients, 31% were ≥70 years, 43% were female, and 80% had grade 1 disease. Imaging frequency was predictive of recurrence (hazard ratio 2.52, 95% confidence interval 1.84-3.46, p < 0.001). 72% underwent interventions for recurrent disease. Patients who were treated for the recurrent disease had comparable OS to those who did not recur (median 152 vs. 164 months; p = 0.25). Imaging frequency was not associated with OS in those with treated recurrent disease (p = 0.65). Patients who recurred underwent more computerized tomography (CT) scans than those who did not recur (CT: 1.47 ± 0.89 vs. 1.02 ± 0.81 scans/year, p < 0.001). Detection of disease recurrence was 5%-7% per year during the first 6 years of surveillance and peaked at 17% in Year 9.

Less frequent imaging over a longer duration should be emphasized to capture clinically relevant recurrences that can be treated to improve OS.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors with a broad range of local and systemic treatment options. Still a lack of data regarding treatment sequences exists. The aim of this study was to analyse outcomes in GEP-NETs depending on stage and treatment steps and compare our treatment decisions to the latest treatment recommendations of European Society of Medical Oncology (ESMO) 2020 for GEP-NETs.

Patients were included in this retrospective single-center analysis from 2012-2016. All patients suffering from a GEP-NET, who were screened, treated or evaluated at ENETS Center in Zurich, Switzerland were included in analysis. Patients with any other diagnosis of NET were not included. We used Kaplan Meier estimator as well as Cox regression to compare survival rates between different sites of localization, grades or stages and treatment sequences.

Overall, we identified 256 GEP-NETs, most in advanced stage (62%) and located in small intestine tract or pancreatic gland. Survival depended on stage, grade, primary site and duration of response for the early systemic treatment. On average patients underwent 2.6 different treatment modalities, mostly depending on stage and higher tumor grade. Surgery was performed early but also in advanced stages, usually followed by Somatostatine-Agonist modalities. In distant disease (Stage IV), we investigated a positive effect of PFS after treatment with Somatostatine Analogues (SSA) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.21 - 0.97; p = 0.04) and systemic treatment (HR, 0.51; 95% CI, 0.26 - 0.99; p = 0.047) if patients underwent prior surgery or endoscopic resection. Kaplan Meier distributions predict shorter OS in distant disease (Stage IV), (Figure. 1; HR, 2.06; 95% CI, 1.46 - 2.89; log-rank test, p < 0.001).

This retrospective analysis presents a great overview of all patients', disease and treatment characteristics of GEP-NETs at ENETS Center in Zurich, Switzerland. We illustrated survival (PFS) depending on implemented therapies. According to these findings, we formed a suggested treatment algorithm for advanced GEP-NETs, which does not differ from the latest treatment recommendation by ESMO guidelines for GEP-NETs. The results of this project may define GEP-NET patients' selection for upcoming clinical prospective studies.

Neuroendocrine tumors are part of a heterogeneous group of tumors located in organs such as the gastrointestinal tract (GIT), lungs, thymus, thyroid, and adrenal glands. The most prevalent sites are the small intestine, cecal appendix, and pancreas. More than 50% of these tumors are associated with metastases at the time of diagnosis. Neuroendocrine tumors are classified according to the degree of cell differentiation and the histopathological proliferation index of the lesion. Neuroendocrine tumors can be well differentiated or poorly differentiated. G3 tumors are characterized by Ki-67 expression greater than 20% and can be either well differentiated (G3 NET) or poorly differentiated (G3 NEC). Neuroendocrine carcinoma (NEC G3) is subdivided into small-cell and large-cell types. When neuroendocrine tumors present clinical and compressive symptoms, carcinoid syndrome is evident. Carcinoid syndrome occurs when the tumor produces neuroendocrine mediators that cannot be metabolized by the liver due to either the size of the tumor or their secretion by the liver itself. Several therapeutic strategies have been described for the treatment of metastatic neuroendocrine tumors, including curative or palliative surgical approaches, peptide receptor radionuclide therapy, percutaneous therapy, systemic chemotherapy, and radiotherapy. Liver surgery is the only approach that can offer a cure for metastatic patients. Liver metastases must be completely resected, and in this context, orthotopic liver transplantation has gained prominence for yielding very promising outcomes in selected cases. The aim of this study is to review the literature on OLT as a form of treatment with curative intent for patients with gastroenteropancreatic neuroendocrine tumors with liver metastasis.