Diet and lifestyle in relation to small intestinal cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC).

PURPOSE: The incidence of small intestinal cancer (SIC) is increasing, however, its aetiology remains unclear due to a lack of data from large-scale prospective cohorts. We examined modifiable risk factors in relation to SIC overall and by histological subtype. METHODS: We analysed 450,107 participants enrolled in the European Prospective Investigation into Cancer and Nutrition cohort. Cox proportional hazards models were used to estimate univariable and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During an average of 14.1 years of follow-up, 160 incident SICs (62 carcinoids, 51 adenocarcinomas) were identified. Whilst univariable models revealed a positive association for current versus never smokers and SIC (HR, 95% CI: 1.77, 1.21-2.60), this association attenuated in multivariable models. In energy-adjusted models, there was an inverse association across vegetable intake tertiles for SIC overall (HRT3vsT1, 95% CI: 0.48, 0.32-0.71, p-trend: < 0.001) and for carcinoids (HRT3vsT1, 95% CI: 0.44, 0.24-0.82, p-trend: 0.01); however, these attenuated in multivariable models. Total fat was also inversely associated with total SIC and both subtypes but only in the second tertile (SIC univariable HRT2vsT1, 95% CI: 0.57, 0.38-0.84; SIC multivariable HRT2vsT1, 95% CI: 0.55, 0.37-0.81). Physical activity, intake of alcohol, red or processed meat, dairy products, or fibre were not associated with SIC. CONCLUSION: These exploratory analyses found limited evidence for a role of modifiable risk factors in SIC aetiology. However, sample size was limited, particularly for histologic subtypes; therefore, larger studies are needed to delineate these associations and robustly identify risk factors for SIC.

Contributions of Adenocarcinoma and Carcinoid Tumors to Early-Onset Colorectal Cancer Incidence Rates in the United States.

BACKGROUND: Early-onset colorectal cancer (EOCRC) incidence rates (IRs) are rising, according to previous cancer registry analyses. However, analysis of histologic subtypes, including adenocarcinoma (the focus of CRC screening and diagnostic testing) and carcinoid tumors (which are classified as "colorectal cancer" in SEER [Surveillance, Epidemiology, and End Results] databases but have a distinct pathogenesis and are managed differently from adenocarcinoma), has not been reported. OBJECTIVE: To assess EOCRC IRs and changes in IRs over time, stratified by histology. DESIGN: Retrospective analysis. SETTING: Yearly IRs according to SEER 18 data from 2000 to 2016 on age-specific colon-only, rectal-only, and combined-site CRC cases, stratified by histology ("overall" CRC [all histologic subtypes], adenocarcinoma, and carcinoid tumors) and age. PATIENTS: 119 624 patients with CRC. MEASUREMENTS: IRs per 100 000 population, changes in 3-year average annual IRs (pooled IRs from 2000 to 2002 vs. those from 2014 to 2016), and annual percentage change (APC) in persons aged 20 to 29, 30 to 39, 40 to 49, and 50 to 54 years. RESULTS: The steepest changes in adenocarcinoma 3-year average annual IRs were for rectal-only cases in persons aged 20 to 29 years (+39% [0.33 to 0.46 per 100 000]; P < 0.050) and 30 to 39 years (+39% [1.92 to 2.66 per 100 000]; P < 0.050) and colon-only cases in those aged 30 to 39 years (+20% [3.30 to 3.97 per 100 000]; P < 0.050). Corresponding APCs were 1.6% (P < 0.050), 2.2% (P < 0.050), and 1.2% (P < 0.050), respectively. In persons aged 40 to 49 years, 3-year average annual IRs increased in both colon-only (+13% [12.21 to 13.85 per 100 000]; P < 0.050) and rectal-only (+16% [7.50 to 8.72 per 100 000]; P < 0.050) subsites. Carcinoid tumors were common, representing approximately 4% to 20% of all colorectal and 8% to 34% of all rectal cancer cases, depending on age group and calendar year. Colon-only carcinoid tumors were rare. Colorectal carcinoid tumor IRs increased more steeply than adenocarcinoma in all age groups, thus affecting the contribution of carcinoid tumors to overall cancer cases over time. These changes were driven by rectal subsites and were most pronounced in persons aged 50 to 54 years, in whom rectal carcinoid tumors increased by 159% (2.36 to 6.10 per 100 000) between 2000 to 2002 and 2014 to 2016, compared with 10% for adenocarcinoma (18.07 to 19.84 per 100 000), ultimately accounting for 22.6% of all rectal cancer cases. LIMITATION: Population-based data. CONCLUSION: These findings underscore the importance of assessing histologic CRC subtypes independently. Doing so may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of outcomes from efforts to reduce adenocarcinoma risk, and can guide future research. PRIMARY FUNDING SOURCE: None.

Appendiceal Carcinoids in Children-Prevalence, Treatment and Outcome in a Large Nationwide Pediatric Cohort.

Background and Objectives: Appendiceal carcinoids are rare neuroendocrine tumors and mainly found incidentally during histopathological examination following appendectomy. This observational cohort study was performed to determine the prevalence, treatment modalities and outcomes in children diagnosed with an appendiceal carcinoid tumor. Materials and Methods: Data from the largest German statutory health insurance "Techniker Krankenkasse" were analyzed within an 8-year period: January 2010 to December 2012 and January 2016 to December 2020. Patient characteristics, surgical technique, type of surgical department, diagnostic management, and postoperative morbidity were analyzed. Results: Out of 40.499 patients following appendectomy, appendiceal carcinoids were found in 44 children, resulting in a prevalence of 0.11%. Mean age at appendectomy was 14.7 (±2.6) years. Laparoscopic approach was performed in 40 (91%) cases. Right-sided hemicolectomy was performed in 8 (18%) patients. Additional diagnostic work-up (CT and MRI) was recorded in 5 (11%) children. Conclusions: This large nationwide pediatric study shows that 1 in 1000 patients was found to have a neuroendocrine tumor of the appendix (prevalence 0.11%), emphasizing its low prevalence in the pediatric age group. The majority of patients were treated with appendectomy only. However, treatment modalities are still variable. Longer follow-up analyses are needed to evaluate published guidelines and recommendations to aim for a limited surgical approach.

Risk of Small Bowel Adenocarcinoma, Adenomas, and Carcinoids in a Nationwide Cohort of Individuals With Celiac Disease.

BACKGROUND & AIMS: The incidence of small bowel cancers is increasing. Associations have been made between celiac disease (CD) and small bowel cancers, but there have been no detailed studies of large cohorts. METHODS: Through the nationwide Epidemiology Strengthened by Histopathology Reports in Sweden cohort study, we retrieved data from Sweden's 28 pathology departments on all individuals who received a diagnosis of CD from 1965 through 2017. Individuals with CD, defined as duodenal or jejunal villous atrophy (stage 3 Marsh score), were matched with as many as 5 randomly selected reference individuals from the general population. We used stratified Cox regression to calculate hazard ratios (HRs) for small bowel adenocarcinoma, adenomas, and carcinoids. RESULTS: During a median follow-up of 11 years, we identified 48,119 individuals with CD (patients) and 239,249 reference individuals. Beginning at 1 year after a diagnosis of CD, 29 patients (0.06%) received a diagnosis of small bowel adenocarcinoma vs 45 reference individuals (0.02%), 7 patients received a diagnosis of carcinoids vs 31 reference individuals, and 48 patients received a diagnosis of adenomas vs 50 reference individuals. Corresponding HRs were small bowel adenocarcinoma 3.05 (95% confidence interval [CI], 1.86-4.99), carcinoids 0.59 (95% CI, 0.16-2.10), and adenomas 5.73 (95% CI, 3.70-8.88). HRs were independent of sex and age. Overall, there was 1 extra case of small bowel adenocarcinoma in every 2944 patients with CD followed for 10 years. There was an inverse association between mucosal healing risk of future small bowel adenocarcinoma (HR, 0.18; 95% CI, 0.02-1.61), although the HR failed to attain statistical significance. CONCLUSIONS: In an analysis of a nationwide pathology database in Sweden, we found the absolute risk of small bowel adenocarcinoma is low in individuals with CD. However, risks of small bowel adenocarcinoma and adenomas (but not carcinoids) are significantly increased in people with CD compared to people without this disease.

Rising incidence of appendiceal neoplasms over time: Does pathological handling of appendectomy specimens play a role?

BACKGROUND: Appendectomy is the most common emergent surgical procedure. Primary appendiceal neoplasms are rare entities that are usually detected incidentally in less than 2% of all appendectomies. The increase in the incidence rates of appendiceal neoplasms over time raises the question whether there is an actual change in the disease occurrence or is it a matter of increased recognition and reporting of what would have been previously missed and undiagnosed. OBJECTIVES: In our study, we aimed to review the archived tissue specimens of patients who were diagnosed with appendiceal neoplasms during the past decade at our institution and compare our clinical experience with published data to identify possible reasons that contribute to the increase in incidence rates of such neoplasms over the past few years. METHODS: Using a pathological database of surgical specimens from patients who underwent appendectomies between January 01, 2010 and September 30, 2020 at a large academic medical center, a single-center retrospective cohort analysis was performed, and medical charts of patients were reviewed. RESULTS: Of the total 1568 patients included, 102 (6.5%) had appendiceal neoplasms divided between primary (79.4%) and secondary/metastatic (20.6%) neoplasms. Annual incidence of appendiceal neoplasms over the past 10 years in our institution demonstrated an increasing trend from 5.6% in 2010 to 12.7% in 2020, which we hypothesize might be attributed to submitting more representative sections of the appendix for pathological examination than we had previously. Our results also showed that 2.8% of patients initially presenting with a typical clinical picture of acute appendicitis had appendiceal neoplasms as a truly incidental finding, while 20.3% of patients who underwent elective appendectomies for a suspicious appendiceal mass were found to be neoplastic. Interestingly, among the 80 cases of epithelial neoplasms, more non-carcinoid neoplasms were detected than carcinoid tumors. CONCLUSION: Based on our results and what has been published recently, we confirm an additional increase in incidental appendiceal neoplasms found in appendectomies performed for a clinical picture of acute appendicitis, which may be related to more thorough specimen assessment. Whether this is clinically impactful remains to be determined. However, these data support a modification in the way appendectomy specimens are handled in pathology labs post-operatively.

Primary malignant ovarian carcinoid; management and outcomes.

OBJECTIVE: To investigate the clinicopathological characteristics and survival of patients with malignant ovarian carcinoid tumor (OC). MATERIALS AND METHODS: The National Cancer Database was accessed and patients diagnosed between 2004 and 2015 with a OC who did not have a personal history of a tumor at another site were selected. Overall survival (OS) was assessed for patients who had ≥1 month of follow-up. OS rates were estimated following generation of Kaplan-Meier curves and compared with the log-rank test. RESULTS: A total of 588 patients with a median age of 51.5 years were identified. The majority were White (71.6%), had unilateral tumors (94.2%) with a median size of 3.8 cm that were confined to the ovary (88%). Patients with early stage disease (n = 431) had excellent OS compared to those with advanced stage (II-IV) disease (n = 51), p < 0.001; 5-yr OS rates were 95.4% and 53.1% respectively. For patients with stage I disease, there was no difference in OS between those who did (n = 211) and did not (n = 175) have hysterectomy, p = 0.92. For patients with advanced stage disease, administration of adjuvant chemotherapy was not associated with better survival, p = 0.093. CONCLUSIONS: OCs are typically small, unilateral tumors confined to the ovary arising in perimenopausal patients. Survival outcomes are excellent for patients with early stage disease and unilateral salpingo-oophorectomy appears to be curative.

Changing Disparity of Gastric Cancer Incidence by Histological Types in US Race-Specific Populations.

BACKGROUND: The incidence pattern of gastric cancer by histological types across major race/ethnic groups is unknown. METHODS: Age-standardized rates from 1992-2016 by race/ethnicity were calculated using data from Surveillance, Epidemiology, and End Results Program (SEER). Annual percent changes (APCs) in rates and corresponding 95% confidence intervals (CIs) were calculated and pairwise comparison of rates between race/ethnic groups was performed using the Joinpoint Regression Program. Calendar periods of incidence rates of gastric cardia and non-cardia cancer by histological types across race/ethnicity groups were shown by figures. RESULTS: The White population has the highest incidence of gastric cardia adenocarcinoma and the incidence is keeping constant from 1992 through 2016 except the decreasing in the Asian population (AAPC = -1.4, 95%CI (-2.1, -0.8)). Although the incidence of non-cardia adenocarcinoma is decreasing in each group, the descending trend in the Asian population is the quickest (AAPC = -3.8, 95%CI (-4.0, -3.5)). Gastric carcinoids were observed to have statistically significant increasing trends in all race/ethnicity groups, especially in Hispanic women from 0.4 per 100,000 to 1.6 per 100,000 persons. The incidence of gastrointestinal stromal tumors (GISTs) is rising, with Non-Hispanic blacks having the highest incidence. CONCLUSION: This study demonstrated disparities in the incidence of gastric cancer by histological types among different race/ethnic groups. Further investigations are warranted to understand the changing incidence patterns by race/ethnicity.

Elevated prevalence of nodal positivity in carcinoid tumours of the appendix smaller than 2 cm has a negative impact on overall survival.

AIM: The current standard of care for clinically node-negative carcinoid tumours of the appendix < 2.0 cm in size is appendectomy alone. The aim of this analysis was to evaluate the prevalence of pathological nodal positivity in clinically node-negative appendiceal tumour specimens < 2.0 cm and quantify the impact of occult pathological nodal positivity on overall survival following resection. METHOD: A retrospective database review of the 2019 US National Cancer Database for appendiceal cancer identified 2007 cases of clinically node-negative appendiceal carcinoid tumours based on SEER histology codes 8240, 8241, 8242, 8243, 8243, 8244, 8245, 8246 and 8249. Kaplan-Meier with log-rank testing and multivariate Cox regression analysis evaluated the impact of occult nodal positivity on overall survival following resection for clinically node-negative appendiceal carcinoma. RESULTS: The prevalence of occult nodal positivity increased from 1.9% for sub-centimetre tumours to 7% for tumours between 1.0 and 1.5 cm, 16.5% for tumours between 1.5 and 2.0 cm and to >29.5% for tumours > 2.0 cm. Rates of metastatic spread were similar for tumours < 2.0 cm but increased for larger tumours. Over two-thirds of patients received a segmental colectomy as definitive surgical therapy. After controlling for differences in cohorts, multivariate analysis showed an increased hazard ratio for mortality of 162% (HR 2.62, CI 1.884-3.541) for patients with pathological node-positive disease. CONCLUSION: Clinically node-negative carcinoid tumours of the appendix bigger than 1.5 cm have an increased rate of occult nodal spread which has a negative impact on overall survival.

Epidemiology of Large Bowel Carcinoid Tumors in the USA: A Population-Based National Study.

BACKGROUND AND AIMS: Prior studies have shown that about 90% of all carcinoid tumors occur in the GI tract. However, epidemiological studies of these tumors have been limited by small sample size. Our aim was to obtain a more robust epidemiologic survey of large bowel carcinoids (LBC), using population-based data in order to more accurately identify risk factors for these tumors. METHODS: We used a commercial database (Explorys Inc, Cleveland, OH) which includes electronic health record data from 26 major integrated US healthcare systems. We identified all patients aged 18 and older who were diagnosed with LBC, excluding appendiceal carcinoids, between 1999 and 2018 based on Systematized Nomenclature Of Medicine-Clinical Terms (SNOMED-CT) and evaluated the prevalence of LBC. We also performed univariate analysis to describe age-, race-, and gender-based distributions and to identify potential risk factors. RESULTS: Of the 62,817,650 individuals in the database, 4530 were identified to have LBC with an overall prevalence of 7.21/100,000. Individuals with LBC were more likely to be elderly (age > 65) [OR 2.17, CI 2.05-2.31, p < 0.0001], smokers [OR 3.25; 95% CI 3.00-3.53, p < 0.0001], have a history of alcohol use [OR 3.75; 95% CI 3.52-3.99, p < 0.0001], diabetes mellitus (DM) [OR 4.42; 95% CI 4.14-4.72, p < 0.0001], obesity [OR 1.58; 95% CI 1.43-1.74, p < 0.0001], family history of cancer [OR 8.06; 95% CI 7.47-8.71, p < 0.0001], and personal history of ulcerative colitis [OR 6.93; 95% CI 5.55-8.64, p < 0.0001] or Crohn's disease [OR 6.45; 95% CI 5.24-7.95, p < 0.0001]. The prevalence of LBC was less among Caucasians compared to African-Americans [OR 0.57; 95% CI 0.53-0.61, p < 0.0001]. There was no statistically significant gender-based difference; men versus women [OR 1.02; 95% CI 0.96-1.08, p = 0.47]. The most common presenting symptoms included flushing, diarrhea, nausea, weight loss, and abdominal pain, while the most common GI associations included perforation, obstruction, hemorrhage, intussusception, and volvulus. CONCLUSION: This is the largest epidemiological study evaluating the prevalence of LBC. We estimated the prevalence rate of LBC to be 7.21/100,000. The presence of significant risk factors with the clinical picture suspicious for a LBC should warrant thorough evaluation as these tumors can lead to life-threatening complications. Further studies are needed to better understand the mechanism of association between these risk factors and LBC.

The incidence and patterns of colorectal cancers in Sri Lanka from 2001 to 2010: Analysis of national cancer registry data.

OBJECTIVES: The incidence of colorectal cancer (CRC) has been increasing in many Asian countries. This study aims to analyse trends in CRC incidence and histological patterns in Sri Lanka. METHODS: All newly diagnosed patients with CRC in Sri Lanka during 2001-2010 included in the National Cancer Registry were analysed for trends in incidence using Joinpoint regression software. RESULTS: A total of 7,694 CRC (male:female = 1.02:1, mean age = 58.7 years) were analysed. The incidence of CRC in Sri Lanka has increased from a WHO age-standardised rate of 2.9/100,000 in 2001 (95%-confidence interval [95%-CI]: 2.64-3.16) to 6.08/100,000 in 2010 (95%-CI: 5.71-6.44). This is an estimated annual percentage change (EAPC) of 8.9 (95%-CI: 7.5-10.4). The proportional increase in incidence was observed to be greater for females (2.8 to 5.6, EAPC: 9.4 (95%-CI: 7.7-11.2), p < .05) than males (3.02 to 6.62, EAPC: 8.5 (95%-CI: 6.9-10.2), p < .05). CONCLUSIONS: Similar to other Asian countries, a significant increase in the incidence of CRC was observed in Sri Lanka. Rate of the increase may have been artificially inflated due to better case reporting and diagnostic scrutiny. Future studies focussing on trends in tumour stage and fatality will help shed light on changing patterns in the burden of CRC in Sri Lanka.

Proton Pump Inhibitor Use, Hypergastrinemia, and Gastric Carcinoids-What Is the Relationship?

Neuroendocrine tumors (NETs) throughout the body are the focus of much current interest. Most occur in the gastrointestinal tract and have shown a major increase in incidence over the past 30 years, roughly paralleling the world-wide increase in the use of proton pump inhibitor (PPI) drugs. The greatest rise has occurred in gastric carcinoids (g-NETs) arising from enterochromaffin-like (ECL) cells. These tumors are long known to occur in auto-immune chronic atrophic gastritis (CAG) and Zollinger-Ellison syndrome (ZES), with or without multiple endocrine neoplasia type-1 (MEN-1), but the incidences of these conditions do not appear to have increased over the same time period. Common to these disease states is persistent hypergastrinemia, generally accepted as causing g-NETs in CAG and ZES, and postulated as having similar tumorigenic effects in PPI users. In efforts to study the increase in their occurrence, g-NETs have been classified in a number of discussed ways into different grades that differ in their incidence and apparent pathogenesis. Based on a large amount of experimental data, tumorigenesis is mediated by gastrin's effects on the CCK2R-receptor on ECL-cells that in turn leads to hyperplasia, dysplasia, and finally neoplasia. However, in all three conditions, the extent of response of ECL-cells to gastrin is modified by a number of genetic influences and other underlying risk factors, and by the duration of exposure to the hormonal influence. Data relating to trophic effects of hypergastrinemia due to PPI use in humans are reviewed and, in an attached Appendix A, all 11 reports of g-NETs that occurred in long-term PPI users in the absence of CAG or ZES are summarized. Mention of additional suspected cases reported elsewhere are also listed. Furthermore, the risk in humans may be affected by the presence of underlying conditions or genetic factors, including their PPI-metabolizer phenotype, with slow metabolizers likely at increased risk. Other problems in estimating the true incidence of g-NETs are discussed, relating to non-reporting of small tumors and failure of the Surveillance, Epidemiology, and End Results Program (SEER) and other databases, to capture small tumors or those not accorded a T1 rating. Overall, it appears likely that the true incidence of g-NETs may be seriously underestimated: the possibility that hypergastrinemia also affects tumorigenesis in additional gastrointestinal sites or in tumors in other organ systems is briefly examined. Overall, the risk of developing a g-NET appears greatest in patients who are more than 10 years on drug and on higher doses: those affected by chronic H. pylori gastritis and/or consequent gastric atrophy may also be at increased risk. While the overall risk of g-NETs induced by PPI therapy is undoubtedly low, it is real: this necessitates caution in using PPI therapy for long periods of time, particularly when initiated in young subjects.

Prevalence of Small Intestine Carcinoid Tumors: A US Population-Based Study 2012-2017.

BACKGROUND AND AIMS: Most carcinoid tumors of the gastrointestinal tract are located in the small bowel (SB). Epidemiological studies of these tumors have been limited by small sample sizes. Our aim was to evaluate the epidemiology of SB carcinoids (SBCs) using a large database. METHODS: We queried a commercial database (Explorys), an aggregate of electronic health data from 26 US healthcare systems. We identified patients with SBCs between 2012 and 2017. We evaluated the epidemiology of SBC and identified possible risk factors. RESULTS: Of the 35,798,290 individuals in the database between 2012 and 2017, we identified 3280 patients with SBCs, with a prevalence of 9.2/100,000. Prevalence was higher in men [odds ratio (OR) 1.23, 95% confidence interval (CI) 1.153-1.322, p < 0.0001], whites [OR 2.031, 95% CI 1.872-2.203, p < 0.0001], and elderly (aged > 65) [OR 4.856, 95% CI 4.533-5.203, p < 0.0001]. Patients with SBCs were more likely to have a history of smoking [OR 2.749, 95% CI 2.549-2.970, p < 0.0001], alcohol use [OR 2.031, 95% CI 1.864-2.21, p < 0.0001], obesity (BMI > 30) [OR 3.476, 95% CI 3.213-3.761, p < 0.0001], diabetes mellitus [OR 4.198, 95% CI 3.900-4.519, p < 0.0001], and a family history of cancer [OR 5.902, 95% CI 5.396-6.456, p < 0.0001]. CONCLUSIONS: This is one of the largest studies done on the prevalence of SBC. The prevalence of 9.2/100,000 individuals is higher than previously reported. Further genetic and environmental studies are needed to understand the potential mechanisms for the risk factors identified in this study.

Incidence of composite intestinal adenoma-microcarcinoid in 158 surgically resected polyps and its association with squamous morule.

Composite intestinal adenoma-microcarcinoid (CIAM) is a rare colorectal lesion consisting of adenoma and small well-differentiated neuroendocrine cell clusters at its base. Its incidence is unknown. Benign squamous morule may demonstrate a neuroendocrine phenotype by immunohistochemistry. We investigated the incidence and clinicopathologic features of CIAM in endoscopically unresectable, surgically removed colorectal adenomas and evaluated its association with squamous morule. Archived pathology materials from 158 surgically resected colorectal adenomas were reviewed. 139 (88%) polyps were entirely submitted for microscopic examination. All lymph nodes were negative for adenocarcinoma and neuroendocrine tumor. CIAM was identified in 6 (3.8%) cases. The microcarcinoid (MC) was distributed over a mean of 5.8 mm (range < 1 to 12 mm), and was multifocal in 5 cases. The MC component was positive for synaptophysin in 6, CK5/6 in 4, and ß-catenin in 3 cases. Two of 6 (33.3%) CIAM showed concurrent squamous morule, compared to 4.0% (6 of 152) of adenomas without MC (p < 0.05). At the end of the mean follow-up of 53 months, 4 were free of disease and one patient with previous history of pulmonary large cell neuroendocrine carcinoma (NEC) had a recurrence of NEC. One patient died of an unrelated disease. The incidence of CIAM in surgically removed colorectal adenomas is 3.8%, with an indolent clinical course. Frequent co-expression of CK5/6 and ß-catenin in MC combined with common co-existence of squamous morule in the same polyp suggests shared pathogenesis of MC in CIAM and squamous morule, likely representing altered Wnt/ß-catenin signaling pathway.

Management of pediatric appendiceal carcinoid: a single institution experience from 5000 appendectomies.

AIM OF THE STUDY: Appendiceal carcinoid (neuroendocrine tumor or NET) is a rare neuroendocrine neoplasm often found incidentally following appendectomy for appendicitis. Surgery for appendicitis is currently under scrutiny and children are increasingly managed conservatively with antibiotics alone. Herein, we aimed to review our experience with the management of appendiceal carcinoids at our institution. METHODS: Following ethical approval, we reviewed the charts of all patients who underwent appendectomy for appendicitis at our institution between 2000 and 2018. The pathology registry was consulted to identify children diagnosed with appendiceal carcinoid. Outcome measures included incidence, demographics, and management. MAIN RESULTS: During the study period, 32 children (23 female) had an appendiceal carcinoid confirmed at pathology. Of these, 13 were initially treated with appendectomy (total of 5,059 appendectomies: 0.3% incidence). The other 19 had an appendectomy elsewhere by an adult general surgeon and were referred to our institution for further management. Overall, the mean age at diagnosis was 13 ± 2.7 years and all patient had a preoperative diagnosis of appendicitis, none of suspected carcinoid. Most children (75%) had acute non-perforated appendicitis. The overall mean size of the lesion was 1 ± 0.9 cm, with a > 2 cm lesion in 3 patients. Following diagnosis, 12 children (38%) underwent an ileocolic resection, due to carcinoid size, invasiveness, and margin clearance. CONCLUSIONS: In our cohort, the incidence of appendiceal carcinoid among children with appendicitis is very low. Most carcinoids are small, located at the tip, associated with non-perforated appendicitis, and present in girls. Most were treated with appendectomy alone, with more extensive surgery performed in one third of children.

Natural History of Localized and Locally Advanced Atypical Lung Carcinoids after Complete Resection: A Joined French-Italian Retrospective Multicenter Study.

BACKGROUND: The natural history and the best modality of follow-up of atypical lung carcinoids (AC) remain ill defined. The aim of this study was to analyze recurrence-free survival (RFS) after complete resection (R0) of stage I-III pulmonary AC. Secondary objectives were prognostic parameters, the location of recurrences, and the modality of follow-up. METHODS: A retrospective review of 540 charts of AC patients treated between 1998 and 2008 at 10 French and Italian centers with experience in lung neuroendocrine tumor management was undertaken. The exclusion criteria were MEN1-related tumor, history of another cancer, referral after tumor relapse, and being lost to follow-up. A central pathological review was performed in each country. RESULTS: Sixty-two patients were included. After a median follow-up time of 91 months (mean 85, range 6-165), 35% of the patients experienced recurrence: 16% were regional recurrences and 19% were distant metastases. Median RFS was not reached. The 1-, 3-, and 5-year RFS rate was 90, 79, and 68%, respectively. In univariate analysis, lymph node involvement (p = 0.0001), stage (p = 0.0001), mitotic count (p = 0.004), and type of surgery (p = 0.043) were significantly associated with RFS. In multivariate analysis, lymph node involvement was significantly associated with RFS (HR 95% CI: 0.000-0.151; p = 0.004). During follow-up, somatostatin receptor scintigraphy, fibroscopy, and abdominal examination results were available for 22, 12, and 25 patients, respectively. The median time interval for imaging follow-up was 10 months. CONCLUSIONS: After complete resection of AC, recurrences were observed mostly within the first 5 years of follow-up, within bronchi, mediastinal nodes, the liver, and bones. In R0 patients, lymph node involvement could help to stratify follow-up intervals. Suboptimal imaging is evidenced.

[Diagnosis and treatment of the neuroendocrine tumors of the lung]. / A tüdõ neuroendokrin daganatainak diagnózisa és kezelése.

Lung neuroendocrine tumors comprise 20% of all pulmonary tumors. Their appearance and behavior are very heterogeneous. Histologically they are divided into four groups, well-differentiated and low-malignant typical carcinoid, poorly differentiated and worse prognosis atypical carcinoid, and highly malignant small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma. Of these, the most common is small cell lung cancer with an incidence of 15%, while those of large cell neuroendocrine tumors and lung carcinoids are 3% and 2%, respectively. The treatment and prognosis of carcinoids are very different from those of highly malignant small cell and large cell neuroendocrine carcinomas. The paper summarizes the characteristics of lung neuroendocrine tumors.

Causes, predictors and consequences of conversion from VATS to open lung lobectomy.

BACKGROUND: To analyze causes, predictors and consequences of conversions from intended VATS lobectomy to open surgery. METHODS: This is a retrospective analysis of a prospectively maintained database. RESULTS: From 2009 until December 2012, 232 patients were scheduled for anatomical VATS resection. Conversion to open surgery was necessary in 15 (6.5 %) patients. Reasons for conversion were bleeding in six, oncologic in five and technical in four patients (adhesions after pleuritis or radiotherapy for other tumors: 3; limited space: 1). In a univariable exact logistic regression analysis, conversion rate was significantly higher in patients after induction therapy (p = 0.019). There was also a statistical trend to a higher conversion rate in patients with larger tumor size (<3 vs. ≥3 cm, p = 0.117) and during the first half of our series (p = 0.107). Conversion rate was not influenced by patient age, nodal stage (pN0 vs. pN+), body mass index, the presence of chronic obstructive pulmonary disease, lung function (FEV1) or benign disease. In a multivariable exact logistic regression, induction treatment (p = 0.013) and tumor size (p = 0.04) were independent significant risk factors for conversion. Conversion did not translate into higher overall postoperative complication rate (33.3 vs. 29.5 %), longer chest drain duration (median, 5 vs. 5 days) or in-hospital mortality (0 vs. 1 %). However, length of hospital stay was significantly longer in the conversion group (median 11 vs. 9 days, p = 0.028). CONCLUSIONS: Induction therapy was an independent risk factor for conversion to thoracotomy in this VATS lobectomy series. Following induction therapy, patients should be carefully selected for a VATS approach. Conversion to thoracotomy did not increase the postoperative rate of complications or mortality, but significantly increased length of hospital stay.

Ovarian Teratoma in Routine Biopsy Material During a Five-Year Period.

Teratomas are tumors derived from germ cells, most frequently arising in the gonads. The aim of this study was to determine the number of ovarian teratomas diagnosed in the routine biopsy material at Ljudevit Jurak Clinical Department of Pathology, Sestre milosrdnice University Hospital Center during a 5-year period, as well as their clinical, gross and microscopic characteristics. Teratomas accounted for 48.6% (n=166) of primary ovarian tumors. The patient mean age was 34.74±12.37 years. Difference in the incidence of teratoma between the left and right ovary was not significant; bilateral teratoma was found in 13 patients. Teratomas were detected by ultrasonography in 115 (69.27%) cases and the rest were found during surgery performed for other indications. Most teratomas (n=161; 96.9%) were mature and cystic (dermoid cysts). Mature and solid teratomas were diagnosed in 5 (3.01%), ovarian struma in 2 (1.8%) cases and strumal carcinoid in 1 (1.2%) case. Mature cystic teratomas contained sebaceous material in 123 (76.8%) cases, and a total of 16 teeth were found; 157 (94.5%) teratomas measured <10 cm in largest diameter. Microscopically, mature cystic teratomas most frequently contained ectodermal (skin with appendages, mature glia and nerve ganglia) and mesodermal (fi brous, fat tissue, cartilage and bone) tissues. Frequently found tissues of endodermal origin were respiratory and intestinal epithelia. Small foci of thyroid tissue were found in 20 (12%) teratomas. Chronic granulomatous foreign body reaction in the wall of mature cystic teratomas was found in 11 (6.8%) tumors.