Clinical features of intussusception in children secondary to small bowel tumours: a retrospective study of 31 cases.

BACKGROUND: Summarizing the clinical features of children with intussusception secondary to small bowel tumours and enhancing awareness of the disease. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Prognostic factors for liver metastasis in patients with small intestinal stromal tumor: A retrospective analysis of surveillance, epidemiology, and end results.

BACKGROUND: Liver metastasis (LIM) is the most common distant site of metastasis in small intestinal stromal tumors (SISTs). The aim of this study was to determine the risk and prognostic factors associated with LIM in patients with SISTs. METHODS: Patients diagnosed with gastrointestinal stromal tumors between 2010 and 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate logistic regression models, as well as a Cox regression model were used to explore the risk factors associated with the development and prognosis of LIM. Additionally, the overall survival (OS) of patients with LIM was analyzed using the Kaplan-Meier method. Furthermore, a predictive nomogram was constructed, and the model's performance was evaluated using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). RESULTS: A total of 1582 eligible patients with SISTs were included, among whom 146 (9.2%) were diagnosed with LIM. Poor tumor grade, absence of surgery, later T-stage, and no chemotherapy were associated with an increased risk of developing LIM. The nomogram prediction model achieved an AUC of 0.810, 95% Confidence Interval (CI) 0.773-0.846, indicating good performance, and the calibration curve showed excellent accuracy in predicting LIM. The OS rate of patients with LIM was significantly lower than that of patients without LIM (p < 0.001). CONCLUSIONS: Patients with SISTs who are at high risk of developing LIM deserve more attention during follow-up, as LIM can significantly affect patient prognosis. The nomogram demonstrated good calibration and discrimination for predicting LIM.

Fulminant ectopic Cushing's syndrome caused by metastatic small intestine neuroendocrine tumour - a case report and review of the literature.

Cushing's syndrome (CS) secondary to adrenocorticotropic hormone (ACTH) producing tumours is a severe condition with a challenging diagnosis. Ectopic ACTH-secretion often involves neuroendocrine tumours (NET) in the respiratory tract. ACTH-secreting small intestine neuro-endocrine tumours (siNET) are extremely rare entities barely reported in literature. This review is illustrated by the case of a 75-year old woman with fulminant ectopic CS caused by a ACTH-secreting metastatic siNET. Severe hypokalemia, fluid retention and refractory hypertension were the presenting symptoms. Basal and dynamic laboratory studies were diagnostic for ACTH-dependent CS. Extensive imaging studies of the pituitary and thorax-abdomen areas were normal, while [68Ga]Ga-DOTATATE PET-CT revealed increased small intestine uptake in the left iliac fossa. The hypercortisolism was well controlled with somatostatin analogues, after which a debulking resection of the tumour was performed. Pathological investigation confirmed a well-differentiated NET with sporadic ACTH immunostaining and post-operative treatment with somatostatin analogues was continued with favourable disease control.

Expression and clinical value of CXCR4 in high grade gastroenteropancreatic neuroendocrine neoplasms.

Background: CXC chemokine receptor 4 (CXCR4) is associated with the progression and metastasis of numerous malignant tumors. However, its relationship with Gastroenteropancreatic Neuroendocrine Neoplasms Grade 3 (GEP-NENs G3) is unclear. The aim of this study was to characterize the expression of CXCR4 in GEP-NENS and to explore the clinical and prognostic value of CXCR4. Methods: This study retrospectively collected clinical and pathological data from patients with GEP-NENs who receiving surgery in Qilu Hospital of Shandong University from January 2013 to April 2021, and obtained the overall survival of the patients based on follow-up. Immunohistochemistry (IHC) was performed on pathological paraffin sections to observe CXCR4 staining. Groups were made according to pathological findings. Kaplan-Meier (K-M) curve was used to evaluate prognosis. SPSS 26.0 was used for statistical analysis. Results: 100 GEP-NENs G3 patients were enrolled in this study. There was a significant difference in primary sites (P=0.002), Ki-67 index (P<0.001), and Carcinoembryonic Antigen (CEA) elevation (P=0.008) between neuroendocrine tumor (NET) G3 and neuroendocrine carcinoma (NEC). CXCR4 was highly expressed only in tumors, low or no expressed in adjacent tissues (P<0.001). The expression level of CXCR4 in NEC was significantly higher than that in NET G3 (P=0.038). The K-M curves showed that there was no significant difference in overall survival between patients with high CXCR4 expression and patients with low CXCR4 expression, either in GEP-NEN G3 or NEC (P=0.920, P=0.842. respectively). Conclusion: Differential expression of CXCR4 was found between tumor and adjacent tissues and between NET G3 and NEC. Our results demonstrated that CXCR4 can be served as a new IHC diagnostic indicator in the diagnosis and differential diagnosis of GEP-NENs G3. Further studies with multi-center, large sample size and longer follow-up are needed to confirm the correlation between CXCR4 expression level and prognosis.

Risk factors, prognostic factors, and nomograms for distant metastases in patients with gastroenteropancreatic neuroendocrine tumors: a population-based study.

Background: Patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have a poor prognosis for distant metastasis. Currently, there are no studies on predictive models for the risk of distant metastasis in GEP-NETs. Methods: In this study, risk factors associated with metastasis in patients with GEP-NETs in the Surveillance, Epidemiology, and End Results (SEER) database were analyzed by univariate and multivariate logistic regression, and a nomogram model for metastasis risk prediction was constructed. Prognostic factors associated with distant metastasis in patients with GEP-NETs were analyzed by univariate and multivariate Cox, and a nomogram model for prognostic prediction was constructed. Finally, the performance of the nomogram model predictions is validated by internal validation set and external validation set. Results: A total of 9145 patients with GEP-NETs were enrolled in this study. Univariate and multivariate logistic analysis demonstrated that T stage, N stage, tumor size, primary site, and histologic types independent risk factors associated with distant metastasis in GEP-NETs patients (p value < 0.05). Univariate and multivariate Cox analyses demonstrated that age, histologic type, tumor size, N stage, and primary site surgery were independent factors associated with the prognosis of patients with GEP-NETs (p value < 0.05). The nomogram model constructed based on metastasis risk factors and prognostic factors can predict the occurrence of metastasis and patient prognosis of GEP-NETs very effectively in the internal training and validation sets as well as in the external validation set. Conclusion: In conclusion, we constructed a new distant metastasis risk nomogram model and a new prognostic nomogram model for GEP-NETs patients, which provides a decision-making reference for individualized treatment of clinical patients.

Emergent approach to small bowel tumors: diagnosis and treatment.

BACKGROUND: This study presents the diagnosis and treatment of rare small bowel tumors through clinical cases. METHODS: Patients treated between 2000 and 2023 were included in the study. The clinical records of the patients were analyzed retrospectively. RESULTS: A total of 34 patients were included in the study. Of these patients, 26 (75.5%) were male and eight (23.5%) were female. The mean age of the patients was 62.1 years. The most common symptoms and signs were abdominal pain (76.4%), bloating (38.2%), and nausea and vomiting (17.6%). Diagnostic methods included computed tomography (CT) (82.3%), upper gastrointestinal double balloon enteroscopy (35.2%), and capsule endoscopy (5.8%). Diagnoses included adenocarcinoma in 13 cases, gastrointestinal stromal tumors (GISTs) in 12 cases, and neuroendocrine tumors (NETs) in two cases. CONCLUSION: Small bowel tumors frequently present with abdominal pain, bloating, and nausea and vomiting. CT and endoscopic procedures are the primary diagnostic tools. Small bowel cancers are often diagnosed late due to subtle clinical findings and the limitations of endoscopic imaging. Targeted screening strategies may be beneficial for certain at-risk and symptomatic patient groups. Early surgical intervention offers significant advantages for diagnosed patients.

Lymph node metastases are more frequent in paediatric appendiceal NET ≥1.5 cm but without impact on outcome - Data from the German MET studies.

BACKGROUND: Paediatric appendiceal neuroendocrine tumours (appNET) are very rare tumours, mostly detected incidentally by histopathological evaluation after appendectomy. Treatment recommendations are based on adult data considering high-risk NET as defined by European Neuroendocrine Tumour Society (ENETS) guidelines for completion right-sided hemicolectomy (RHC). Recent data suggest that less aggressive therapy may be justified. PROCEDURE: Analysis of children and adolescents with appNET prospectively registered with the German Malignant Endocrine Tumour (MET) studies between 1997 and 2022. RESULTS: By December 2022, 662 patients (64.7% females, 35.3% male) had been reported. Median age was 13.3 years [4.5-17.9], median duration of follow-up 2.2 years [0-10.9]. No distant metastases were reported. Tumour size was <1 cm in 63.5%, 1-2 cm in 33.2%, and >2 cm in 3.2% of patients. WHO grade 1 and 2 tumours were diagnosed in 76.9% and 23.1% of patients, respectively. Lymphovascular invasion and lymph node metastases were associated with tumour size ≥1.5 cm. 27.0% of patients presented with high-risk NET according to ENETS criteria. Of those, only 55.9% underwent secondary oncological right hemicolectomy. Neither distant metastases, nor recurrences or disease-related deaths occurred in patients with appendectomy only as well as in patients with completion RHC. Overall and event-free survival were both 100%. CONCLUSIONS: Internationally harmonized consensus recommendations on treatment of children and adolescents with appendiceal NET are urgently needed to avoid completion RHC in high-risk patients.

Successful Endoscopic Submucosal Dissection Using Open Peroral Endoscopic Myotomy for Duodenal Neuroendocrine Tumor.

Duodenal neuroendocrine tumors (NETs) are subepithelial tumors that are difficult to remove endoscopically, particularly when located just beyond the pylorus. This paper reports a case of a successful endoscopic submucosal dissection (ESD) using open gastric peroral endoscopic myotomy (POEM) for a remnant duodenal NET detected after endoscopic mucosal resection (EMR). A 67-year-old male presented with a 5 mm remnant duodenal NET close to the pylorus after EMR for a duodenal polypoid lesion performed four months earlier. Duodenal ESD was performed under conscious sedation using I-type and IT II knives. The tumor adhered to the fibrotic tissue, and the submucosal cushion was insufficient. Open gastric POEM was performed concurrently during ESD, resulting in the complete resection of the NET. This case suggests that while challenging, open gastric POEM can serve as a valuable technique for endoscopic resection in cases of early gastric cancer or duodenal masses located around the pylorus.

Plasma tryptophan pathway metabolites quantified by liquid chromatography-tandem mass spectrometry as biomarkers in neuroendocrine tumor patients.

A good and accessible biomarker is of great clinical value in neuroendocrine tumor (NET) patients, especially considering its frequently indolent nature and long-term follow-up. Plasma chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) are currently used as biomarkers in NET, but their sensitivity and specificity are restricted. 5-HIAA is the main metabolite of serotonin, an important neurotransmitter of the tryptophan pathway. The aim of this study is to estabish a sensitive and accurate method for the quantification of tryptophan pathway metabolites in plasma. We further aimed to evaluate its utility as a clinical tool in NET disease. We obtained plasma samples from NET patients and healthy controls recruited from the University Hospital of North Norway, Tromsø. Samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and eight metabolites of the tryptophan pathway were quantified. We included 130 NET patients (72/130 small intestinal [SI] NET, 35/130 pancreatic NET, 23/130 other origin) and 20 healthy controls. In the SI-NET group, 26/72 patients presented with symptoms of carcinoid syndrome (CS). We found that combining tryptophan metabolites into a serotonin/kynurenine pathway ratio improved diagnostic sensitivity (92.3%) and specificity (100%) in detecting CS patients from healthy controls compared with plasma 5-HIAA alone (sensitivity 84.6%/specificity 100%). Further, a clinical marker based on the combination of plasma serotonin, 5-HIAA, and 5OH-tryptophan, increased diagnostic capacity identifying NET patients with metastasized disease from healthy controls compared with singular plasma 5-HIAA, serotonin, or CgA. In addition, this marker was positive in 61% of curatively operated SI-NET patients compared with only 10% of healthy controls (p < .001). Our results indicate that simultaneous quantification of several tryptophan metabolites in plasma, using LC-MS/MS, may represent a clinically useful diagnostic tool in NET disease.

Virtual Care for Patients with Advanced Well Differentiated Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET).

INTRODUCTION: The COVID-19 pandemic resulted in an unprecedent shift towards virtual cancer care, including the care of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The aim of this study was to evaluate the use of virtual care for GEP-NETs during the COVID-19 pandemic at a high-volume academic cancer center. METHODS: This retrospective, observational study performed at the Ottawa Hospital Cancer Center in Canada evaluated adult patients with GEP-NETs seen in consultation by medical oncology between 1 June 2019 and 31 December 2022. Demographic, clinicopathologic, cancer treatment and visit data were collected. Univariable and multivariable analyses assessed the relationship between patient characteristics and virtual care use. RESULTS: A total of 103 patients with well-differentiated GEP-NETS were included. Overall, 18/103 (17.5%) consults and 594/781 (76.1%) follow-ups were performed virtually. All consultation visits returned to in-person assessment by 2022, while 67.0% and 41.4% follow-ups remained virtual in 2022 and 2023, respectively. The year of follow-up, sex, employment and Charlston comorbidity index were associated with virtual follow-up use in the multivariable analysis. DISCUSSION: Virtual care remained a predominant method of GEP-NET patient assessment in the peri-pandemic period. These results highlight an opportunity to improve access to subspecialty neuroendocrine cancer care through the continued use of virtual care.

Somatostatin receptor 2 (SSTR2) expression is associated with better clinical outcome and prognosis in rectal neuroendocrine tumors.

Somatostatin analogues have recently been used as therapeutic targets for metastatic or surgically unresectable gastroenteropancreatic (GEP) neuroendocrine tumors (NETs), and associated somatostatin receptor (SSTR) expression has been well demonstrated in most GEP NETs, with the exception of rectal NETs. SSTR2 immunohistochemical expressions were evaluated in 350 surgically or endoscopically resected rectal NETs and compared to clinicopathologic factors. SSTR2 expression was observed in 234 (66.9%) rectal NET cases and associated tumors with smaller size (p = 0.001), low pT classification (p = 0.030), low AJCC tumor stage (p = 0.012), and absence of chromogranin expression (p = 0.009). Patients with rectal NET and SSTR2 expression had significantly better overall survival than those without SSTR2 expression both by univariable (p = 0.006) and multivariable (p = 0.014) analyses. In summary, approximately two-thirds of rectal NETs expressed SSTR2. SSTR2 expression was significantly associated with favorable behavior and good overall survival in patients with rectal NETs. Furthermore, SSTR2 expression can be used as prognostic factors. When metastatic disease occurs, SSTR2 expression can be used a possible target for somatostatin analogues.

Peptide Receptor Radionuclide Therapy Using 177Lu-DOTATATE: Nursing Roles in Managing Patients With Gastroenteropancreatic Neuroendocrine Tumors.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a diverse family of cancers that occur within the gastrointestinal tract and pancreas. Peptide receptor radionuclide therapy (PRRT) via 177Lu-DOTATATE is a newer therapeutic option for certain patients with somatostatin receptor-positive GEP-NETs. OBJECTIVES: This review informs on how oncology nurses treating patients with GEP-NETs receiving PRRT using 177Lu-DOTATATE can facilitate care. METHODS: Guidance on the monitoring, management, and care of patients undergoing PRRT for GEP-NETs was developed based on published literature and the nursing experience of the authors. A case study is summarized to highlight key concepts. FINDINGS: Oncology nurses provide assessment, education, direct care, and emotional support when caring for patients with GEP-NETs receiving PRRT with 177Lu-DOTATATE. As the treatment landscape evolves, so too will these roles and responsibilities.

Gastroenteropancreatic neuroendocrine carcinoma in children and adolescents: a population-based study.

PURPOSE: Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC) in children is an exceptionally rare and aggressive form of cancer. We aimed to conduct a population-based cohort study to predict overall survival (OS) in pediatric patients with GEP-NEC. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was employed to identify all pediatric patients with GEP-NEC diagnosed between 2000 and 2019. To create survival curves based on various criteria, Kaplane-Meier estimations were utilized. The log-rank test was used to compare survival curves. The variables associated with OS were determined using Cox proportional-hazards regression. Furthermore, we developed a nomogram to predict overall survival in pediatric GEP-NEC patients. RESULTS: A total of 103 pediatric GEP-NEC patients were identified. The tumors primarily affected females (62.2%). The majority of GEP-NEC was found in the appendix (63.1%), followed by the pancreas (23.3%) and the intestinal tract (13.6%). The highest rates of localized stage (76.9%) and surgery (98.5%) were found in the NEC of appendix origin. However, pancreatic origins had the largest proportion of distant disease (66.7%) but the lowest percentage of surgery (37.5%). Overall 1-year, 3-year, and 5-year survival rates for all patients were 94.4%, 85.4%, and 85.4%, respectively. Tumors of pancreatic origin had the worst survival compared with those of the appendix and intestinal tract. The Cox proportional hazard regression revealed that only site was an important independent predictor of survival. CONCLUSIONS: Our study revealed that only the primary site was found to be the most important predictor of the OS in pediatric GEP-NEC. It's important to work closely with a multidisciplinary team, including oncologists, surgeons, and other specialists, to determine the most appropriate treatment plan for pediatric GEP-NEC.

ASO Practice Guidelines Series: Surgical Management of Gastrointestinal (Midgut) Neuroendocrine Neoplasms.

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.