BACKGROUND: Neuroendocrine neoplasms (NENs) are increasing in incidence globally. Previous analysis of the UK cancer database (National Cancer Registration and Analysis Service (NCRAS)) showed a notable female survival advantage in most tumour sites. This study aims to compare NCRAS to the Surveillance, Epidemiology, and End Results Program (SEER) to validate these results using the same statistical methods.
METHODS: A total of 14,834 and 108,399 patients with NENs were extracted from NCRAS and SEER, respectively. Sixty-months survival for both males and females for each anatomical site of NENs were calculated using restricted mean survival time (RMST) and Kaplan-Meier Survival estimates. The sixty-month RMST female survival advantage (FSA) was calculated.
RESULTS: FSA was similar in NCRAS and SEER. The highest FSA occurred in lung and stomach NENs.
CONCLUSIONS: The data from SEER confirm the findings published by NCRAS. Female survival advantage remains unexplained.

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Several inflammation scores have shown association with survival outcomes for patients with neuroendocrine tumours (NET) treated with peptide receptor radionuclide therapy (PRRT). However, whether these scores add value to established prognostic factors remains unknown. In this retrospective, cohort study of 557 NET patients undergoing PRRT in a tertiary referral centre from 2005 to 2015, we examined inflammatory markers and scores previously associated with cancer outcomes, using Cox proportional hazard models and Akaike\'s information criterion. Lower albumin (hazard ratio [95% confidence interval], .91 [.87-.95] per unit), as well as higher C-reactive protein (CRP; 1.02 [1.01-1.02]), Glasgow Prognostic Score (GPS; 1 vs. 0: 1.67 [1.14-2.44], 2 vs. 0 3.60 [2.24-5.79]), CRP/albumin ratio (1.84 [1.43-2.37]) and platelet count (Plt) × CRP, but not white blood cell, neutrophil and thrombocyte counts or derived neutrophil to lymphocyte ratio (dNLR), were associated with shorter median overall survival (OS) in an adjusted analysis. The addition of parameters based on albumin and CRP, but not dNLR, to a base model including age, chromogranin A, the cell proliferation marker Ki-67, performance status, tumour site and previous treatments improved the predictive accuracy of the base model. In an exploratory analysis of patients with available erythrocyte sedimentation rate (ESR) and CRP, ESR emerged as the most powerful predictor. When added to a prognostic model for OS in NET patients treated with PRRT, most inflammation scores further improved the model. Albumin was the single marker adding most value to the set of established prognostic markers, whereas dNLR did not seem to improve the model\'s prognostic ability.

Introduction Acute appendicitis is one of the common causes of acute abdomen in adults, which is managed widely with appendicectomy. Neuroendocrine tumours are the most common appendiceal tumours diagnosed incidentally on appendicectomy specimens.  Methods  Demographic data, presenting complaints, indications for appendicectomy, and the histology findings based on histopathological reports of the patients who have undergone appendicectomy for appendicitis at surgical units of Teaching Hospital, Jaffna, from 1st of January 2019 to 31st of December 2022 were retrospectively analyzed.  Results Of the 1341 histopathology reports, 0.2% (n=3) were neuroendocrine tumours (NET). The mean age of the patients with NET was 48.6, and 66.6% of them were females. All three NETs identified in appendicectomy specimens were well differentiated and smaller than 2 cm. All three had negative resection margins and were managed only with appendicectomy.  Conclusion  NETs of the appendix are the commonest appendiceal neoplasms. The majority of them are diagnosed incidentally in appendicectomy specimens. Surgical management of the tumours is either by appendicectomy or hemicolectomy, which depends mainly on tumor size. Surgical decisions should be tailor-made to the patients based on multi-disciplinary team decisions.

BACKGROUND: The programmed death 1 inhibitor toripalimab plus the angio-immuno kinase inhibitor surufatinib revealed a tolerable safety profile and preliminary efficacy in patients with advanced solid tumours in a phase I study.
METHODS: This was an open-label, single-arm, multi-cohort phase II study in China. Patients with advanced neuroendocrine tumours (NETs) or neuroendocrine carcinomas (NECs) or mixed neuroendocrine non-neuroendocrine neoplasms (MiNENs) who had failed or were intolerable of standard treatment were given surufatinib (250 mg orally, once daily) plus toripalimab (240 mg intravenously, once every 3 weeks). Primary end-point was investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end-points included duration of response (DoR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety.
RESULTS: Forty patients were enrolled into two cohorts by tumour types (NET, n = 19; NEC-MiNEN, n = 21). ORRs (95% CIs) were 21.1% (6.1-45.6) and 23.8% (8.2-47.2) in the NET and NEC-MiNEN cohorts, respectively. Median DoR was 7.1 months (6.9-not evaluable [NE]) and 4.1 months (3.0-NE), respectively. Median PFS was 9.6 months (4.1-NE) and 4.1 months (1.5-5.5); median OS was 27.3 (15.3-NE) and 10.9 months (9.1-14.6), respectively. Overall, grade ≥ 3 treatment-related adverse events occurred in 18 (45.0%) patients.
CONCLUSIONS: Surufatinib plus toripalimab showed antitumour activity and a tolerable safety profile in patients with previously treated NETs/NECs/MiNENs. Further study of this combination regimen is ongoing for advanced NECs, for which current therapeutic options remain limited.
RESULTS: gov: NCT04169672.

BACKGROUND: Claudin 18.2-targeted therapy has shown significant efficacy in treating claudin 18.2-positive cancers. However, limited systematic studies have investigated characteristics of claudin 18.2 expression in neuroendocrine neoplasms (NENs).
METHODS: Data and specimens from 403 cases of digestive NENs were retrospectively collected, and claudin 18.2 expression was detected using immunochemical staining.
RESULTS: Claudin 18.2 was positive in 19.6% (79/403) of the digestive NENs. The highest positive rate of claudin 18.2 was observed in gastric NENs (72/259, 27.8%), accounting for 91.1% (72/79) of all positive cases. The positivity rate was significantly higher in gastric NENs compared to pancreatic (2/78, 2.6%) or colorectal NENs (2/38, 5.3%; p < 0.05). For digestive NENs, claudin 18.2 positivity was significantly higher in neuroendocrine carcinomas (NECs) (37/144, 25.7%) than in neuroendocrine tumours (NETs; 14/160, 8.8%; p < 0.001), but no significant difference was found between gastric NECs (59/213, 27.7%) and gastric NETs (13/46, 28.3%; p > 0.05). The positivity was significantly higher in large-cell NECs (LCNECs; 28/79, 35.4%) and MiNEN (mixed neuroendocrine-non- neuroendocrine neoplasms)-LCNECs (23/66, 34.8%) compared to small-cell NECs (SCNECs; 9/65, 13.8%) and MiNEN-SCNECs (5/33, 15.2%; p < 0.05). Claudin 18.2 expression was more prevalent in gastric NENs than in pancreatic (12.5 ×; p = 0.001) and colorectal NENs (5.9 ×; p = 0.021). Claudin 18.2 staining was a useful method for identify the gastric origins of NETs, with a sensitivity of 28.3% and a specificity of 99.1%.
CONCLUSIONS: The expression characteristics of claudin 18.2 in NENs were characterized, which may provide a clinicopathological reference for targeted therapies in patients with NENs.

OBJECTIVE: Peptide receptor radionuclide therapy (PRRT) using [177Lu]Lu-DOTATATE has been shown to effectively prolong progression free survival in grade 1-2 gastroenteropancreatic neuroendocrine tumours (GEP-NET), but is less efficacious in patients with extensive liver metastases. The aim was to investigate whether tumour uptake in liver metastases can be enhanced by intra-arterial administration of [177Lu]Lu-DOTATATE into the hepatic artery, in order to improve tumour response without increasing toxicity.
METHODS: Twenty-seven patients with grade 1-2 GEP-NET, and bi-lobar liver metastases were randomized to receive intra-arterial PRRT in the left or right liver lobe for four consecutive cycles. The contralateral liver lobe and extrahepatic disease were treated via a \"second-pass\" effect and the contralateral lobe was used as the control lobe. Up to three metastases (> 3 cm) per liver lobe were identified as target lesions at baseline on contrast-enhanced CT. The primary endpoint was the tumour-to-non-tumour (T/N) uptake ratio on the 24 h post-treatment [177Lu]Lu-SPECT/CT after the first cycle. This was calculated for each target lesion in both lobes using the mean uptake. T/N ratios in both lobes were compared using paired-samples t-test.
RESULTS: After the first cycle, a non-significant difference in T/N uptake ratio was observed: T/NIA = 17·4 vs. T/Ncontrol = 16·2 (p = 0·299). The mean increase in T/N was 17% (1·17; 95% CI [1·00; 1·37]). Of all patients, 67% (18/27) showed any increase in T/N ratio after the first cycle.
CONCLUSIONS: Intra-arterial [177Lu]Lu-DOTATATE is safe, but does not lead to a clinically significant increase in tumour uptake.

Pre-clinical studies have suggested sex hormone signalling pathways may influence tumorigenesis in neuroendocrine neoplasia (NEN). We conducted a retrospective, population-based study to compare overall survival (OS) between males and females with NEN. A total of 14,834 cases of NEN diagnosed between 2012 and 2018, recorded in England\'s National Cancer Registry and Analysis Service (NCRAS), were analysed. The primary outcome was OS with 5 years maximum follow-up. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Appendiceal, pulmonary and early-stage NEN were most commonly diagnosed in females; stomach, pancreatic, small intestinal, colonic, rectal and later-stage NEN were more often diagnosed in males. Females displayed increased survival irrespective of the stage, morphology or level of deprivation. On average, they survived 3.62 (95% CI 1.73-5.90) to 10.26 (6.6-14.45) months longer than males; this was statistically significant in NEN of the lung, pancreas, rectum and stomach (p < 0.001). The stage mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. The reasons underlying these differences are not yet understood. Overall, females diagnosed with NEN tend to survive longer than males, and the stage at presentation only partially explains this. Future research, as well as prognostication and treatment, should consider sex as an important factor.

Only limited information is available on the use of home parenteral nutrition (HPN) in patients with advanced neuroendocrine tumours (NETs) causing intestinal failure (IF). This study aims to report the outcomes of the explore the use of HPN in this patient cohort, in the largest case series to date.
A retrospective study in the United Kingdom and the Netherlands was performed, using the UK National British Artificial Nutrition Survey (BANS) and local databases in the Netherlands. Data regarding age, sex, NET grading, staging, treatment, HPN characteristics and survival outcomes were collected.
Data were collected on 41 patients (n = 18 males, 44%) with a median age of 65. Most primary tumours were in the small bowel (n = 35, 85%). The NETs were Grade 1 (n = 16, 39%), Grade 2 (n = 7, 17%), Grade 3 (n = 1, 2%). In 28 patients (n = 68%) there was stage IV disease with metastases located in the peritoneum, mesentery and or liver. There were two indications for HPN; short bowel syndrome (n = 27, 66%) and inoperable malignant bowel obstruction (n = 14, 34%). The median period on HPN was 11 months (interquartile range 4-25 months). 11 patients were still alive and receiving HPN treatment after 2 years, and 6 patients after 3 years. Six patients (22%) with short bowel syndrome (SBS) could be weaned from HPN. There was a statistically significant improved survival for patients with short bowel syndrome (median 24 months) compared to inoperable malignant bowel obstruction (median 7 months). The catheter-related bloodstream infection rate was comparable to other HPN patient cohorts at 1.0 per 1000 catheter days.
This study shows that HPN can be used safely in patients with NET and IF to increase survival beyond that reasonably expected in the context of either short bowel syndrome or inoperable malignant bowel obstruction. Patients with short bowel syndrome are most likely to benefit. Further prospective studies are necessary to validate survival benefits and to demonstrate the effect of HPN on quality of life.

UNASSIGNED: Neuroendocrine neoplasia (NEN) incidence is rising internationally. We aimed to evaluate the epidemiology of NEN in England and examine changes in survival over time.
UNASSIGNED: A retrospective, population-based study using nationally representative data between 1995 and 2018 from the National Cancer Registry and Analysis Service (NCRAS) in England was conducted on 63,949 tumours. Age-standardized incidence was calculated using Office for National Statistics (ONS) data. Overall survival (OS) was calculated using the Kaplan-Meier estimator. Multivariable analysis was performed using an accelerated failure time model.
UNASSIGNED: Of 63,949 cases, 50.5% (32,309) were female. Age-adjusted incidence increased 3.7-fold between 1995 and 2018 from 2.35 to 8.61 per 100,000. In 2018, highest incidence occurred in lung (1.47 per 100,000), small intestine (1.46 per 100,000), pancreas (1.00 per 100,000) and appendix (0.95 per 100,000). In multivariable analysis, age, sex, morphology, stage, site and deprivation were independent predictors of survival (p < 0.001). Survival of the entire cohort, and by primary site, is improving over time.
UNASSIGNED: NEN incidence continues to rise in England with survival improving over time. Relatively high survival compared to other cancers is an issue for long-term outcomes and funding of care.
UNASSIGNED: Data were extracted and transferred using a grant from Neuroendocrine cancer UK.