Villous Size Research Articles

Prediction of metachronous advanced colorectal neoplasia by KRAS mutation in polyps.

The potential of molecular markers in the removed polys as reliable predictors of metachronous lesions is still uncertain. Our aim was to evaluate the role of somatic mutations in KRAS in polyps of patients with high-risk adenomas to predict the risk of advanced polyps or colorectal cancer (CRC) within 3 years. A total of 518 patients were prospectively enrolled. The included patients had adenomas ≥10mm, high-grade dysplasia, villous component or ≥3 more adenomas at baseline and were scheduled to undergo surveillance colonoscopy at 3years±6months. Somatic KRAS mutation was performed on 1189 polyps collected from these patients. At surveillance, advanced lesions were defined as adenomas with a size of ≥10mm. High-grade dysplasia or villous component, serrated polyps ≥10mm or with dysplasia or CRC. At baseline, 81 patients (15.6%) had KRAS mutations in at least one polyp. Patients with KRAS mutated polyps had more frequent villous histological lesions and size ≥20mm. In the multivariate analysis, adjusted for age and sex, only age (odds ratios [OR], 1.06; 95% confidence interval [CI], 1.02-1.09; p<0.001), ≥5 adenomas (OR, 3.92; 95% CI, 1.96-7.82), and KRAS mutation (OR, 2.54; 95% CI, 1.48-4.34; p<0.01) were independently associated with the development of advanced lesions at surveillance. Our results show that, in patients with high-risk adenomas, the presence of somatic mutations in KRAS is an independent risk factor for the development of advanced metachronous polyps.

Diandric triploid partial mole versus digynic nonmolar triploidy: is morphological assessment sufficient for the diagnostic distinction?

Diagnostic separation of diandric triploid gestation, i.e. partial mole from digynic triploid gestation, is clinically relevant, as the former may progress to postmolar gestational trophoblastic neoplasia. The aim of the study was to investigate if the combination of abnormal histology combined with ploidy analysis-based triploidy is sufficient to accurately diagnose partial mole. A genotype-phenotype correlation study was undertaken to reappraise histological parameters among 20 diandric triploid gestations and 22 digynic triploid gestations of comparable patient age, gestational weeks, and clinical presentations. Two villous populations, irregular villous contours, pseudoinclusions, and syncytiotrophoblast knuckles, were common in both groups. Villous size ≥2.5 mm, cistern formation, trophoblastic hyperplasia, and syncytiotrophoblast lacunae were significantly more common in the partial hydatidiform mole. Cistern formation had the highest positive predictive value (PPV) (93%) and highest specificity (96%) for diandric triploid gestation, although the sensitivity was 70%. Cistern formation combined with villous size ≥2.5 mm or trophoblast hyperplasia or syncytiotrophoblast lacunae had 100% specificity and PPV, but a marginal sensitivity of 60%-65%. A moderate interobserver agreement (Kappa = 0.57, Gwet's AC1 = 0.59) was achieved among four observers who assigned diagnosis of diandric triploid gestation or digynic triploidy solely based on histology. None of histological parameters are unique to either diandric triploid gestation or digynic triploid gestation. Cistern formation is the most powerful discriminator, with 93% PPV and 70% sensitivity for diandric triploid gestation. While cistern formation combined with either trophoblastic hyperplasia or villous size ≥2.5 mm or syncytiotrophoblast lacunae has 100% PPV and specificity for diandric triploid gestation, the sensitivity is only 60% to 65%. Therefore, in the presence of triploidy, histological assessment is unable to precisely classify 35% to 40% of diandric triploid gestations or partial moles.

Small intestinal resident eosinophils maintain gut homeostasis following microbial colonization

The intestine harbors a large population of resident eosinophils, yet the function of intestinal eosinophils has not been explored. Flow cytometry and whole-mount imaging identified eosinophils residing in the lamina propria along the length of the intestine prior to postnatal microbial colonization. Microscopy, transcriptomic analysis, and mass spectrometry of intestinal tissue revealed villus blunting, altered extracellular matrix, decreased epithelial cell turnover, increased gastrointestinal motility, and decreased lipid absorption in eosinophil-deficient mice. Mechanistically, intestinal epithelial cells released IL-33 in a microbiota-dependent manner, which led to eosinophil activation. The colonization of germ-free mice demonstrated that eosinophil activation in response to microbes regulated villous size alterations, macrophage maturation, epithelial barrier integrity, and intestinal transit. Collectively, our findings demonstrate a critical role for eosinophils in facilitating the mutualistic interactions between the host and microbiota and provide a rationale for the functional significance of their early life recruitment in the small intestine.

Discovery of inverted discordant p57 expression in random clusters of dysmorphic chorionic villi of third trimester placentas suggests a more common occurrence of such phenomenon than initially described

IntroductionInverted discordant p57 expression in chorionic villi, characterized by a loss of nuclear staining in cytotrophoblast with retained staining in villous stromal cells, is rarely described. Following an incidental finding of such peculiar staining pattern in rare clusters of dysmorphic chorionic villi (DCV) in a perinatal autopsy case, we reviewed our archived cases of third trimester placentas with DCV to systematically analyze these curious foci. MethodsHistopathological features and p57 expression of 26 placentas with DCV were carefully studied by light microscopy and p57 immunohistochemistry. p57 pattern of expression was correlated with a comprehensive list of maternal, fetal, and placental features to reveal potential associations. ResultsInverted discordant p57 expression was observed in 17/26 (65.4%) cases, encompassing all cases with aberrant p57 immunostaining in this series. Among the many features investigated, only the focality (occurring as a single focus) of DCV (Fisher's exact test, p = 0.008) and small cluster size of ≤30 villi (Fisher's exact test, p = 0.034) correlated significantly with inverted discordant p57 staining. Other common features of DCV with inverted discordant p57 expression include larger villous size compared with surrounding tertiary villi (13/17, 76.4%), prominent but not hyperplastic and focally to moderately hyperplastic syncytiotrophoblast (17/21, 80.9%), abnormal shapes/irregular contours (17/22, 77.3%), and markedly hypovascular villous stroma (11/17, 64.7%). No distinctive maternal or fetal features were observed. DiscussionInverted discordant p57 expression in DCV of third trimester placentas is likely underreported, and might not be an unusual occurrence outside of suspected molar specimens.

May the morphological findings in the first-trimester abortion materials be indicative of inherited thrombophilia?

İnherited thrombophilia is associated with severe pregnancy complications including recurrent spontaneous abortion. In the light of this strong association, the impact of thrombophilic mutations on the placenta and their morphological reflections has aroused attention of both clinicians and pathologists. In the present study, we aimed to show the association between placental abnormalities with thrombophilia by examining the morphological findings in a wide range of first-trimester chorionic villi. We performed a histological examination on the abortion specimens obtained from 129 patients with recurrent pregnancy losses that were evaluated with respect to inherited thrombophilia based on the presence of Factor V Leiden (G1691A), Prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations detected by genetic analysis. Abortion materials either with and without thrombophilia were evaluated in terms of the morphological parameters such as hydropic change, vascularity, fibrosis, fibrinoid degeneration, Hofbauer macrophage, syncytiotrophoblast knotting, villitis, calcification, villous contour and villous size, hemorrhage, thrombus, proliferation of trophoblasts, villous stromal or villous vascular karyorrhexis. No statistically significant difference was found between the patient groups with and without thrombophilia in terms of morphological findings except vascularity of chorionic villi. The avascular chorionic villi (<3 vessels per villus) were found in 62.9% and 16.9% obtained from the women with and without thrombophilic mutation, respectively. This difference was statistically significant (P < 0.001). As a conclusion, it could be stated that the analysis of morphological findings in the abortion specimen is not a time-wasting process. Particularly, data related with vascularity of chorionic villi would be precious and beneficial. We suggest that highlighting the presence of avascular villi in the pathology report as a parameter would be guiding for clinicians regarding the impact of the thrombophilic gene mutations.

Assessing the Impact of Metformin Use on Colonic Polyp Behavior

Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide. Age-appropriate CRC screening with colonoscopy provides two benefits: (1) early cancer detection; and (2) resection of premalignant colonic polyps. The principle of cancer chemoprophylaxis has been proposed as a possible synergistic approach to endoscopic colon cancer prevention. Patients with diabetes mellitus (DM) are at increased risk of CRC, compared to non-diabetics. Metformin, one of the most commonly used therapeutic agents used to treat type 2 DM has previously been studied as a potential chemoprophylactic agent against CRC, however, the results have been mixed. We investigate the impact of metformin use on the behavior of colonic polyp generation in a veteran population. Methods: We performed a retrospective observational study. Included were average-risk patients with at least two documented screening colonoscopies between 1997 and 2013 at the Veterans Affairs New York Harbor Healthcare System. Exclusion criteria were: family history of CRC; personal history of IBD; personal or family history of polyposis syndromes. Patient demographics (age, sex, race, ethnicity, body mass index) and colon polyp-specific data (number, histology, largest size) were collected via chart review. Comparative statistics were performed. Results: 1,344 patients were included in our analyses (190 had prescription for metformin prior to their index colonoscopy, 1,154 were non-users). Mean follow-up was 6.9 vs. 7.2 years, respectively. Baseline demographic characteristics are summarized in Table 1. At index colonoscopy, metformin users had fewer adenomatous polyps compared to non-users 1.16 vs. 1.68 (p = 0.0046). In follow-up, however, metformin users had a statistically significant a higher per-annum rate of adenoma generation 0.36 vs. 0.25 as well as higher per-annum rates of high-risk adenoma generation (defined as villous histology, high-grade dysplasia, and/or size > 1 cm). Conclusion: While metformin appeared to be protective against adenomatous polyps at time of index colonoscopy, metformin users demonstrated higher rates of per-annum adenoma generation, including high-risk adenomas. There were no differences in sessile serrated polyp generation at baseline or in follow-up. The effect of metformin use on colon polyp behavior should be further investigated with specific aim of assessing impact of timing of drug exposure on colon cancer chemoprophylaxis.248_A Figure 1 No Caption available.248_B Figure 2 No Caption available.

Automated image analysis of placental villi and syncytial knots in histological sections

IntroductionDelayed villous maturation and accelerated villous maturation diagnosed in histologic sections are morphologic manifestations of pathophysiological conditions. The inter-observer agreement among pathologists in assessing these conditions is moderate at best. We investigated whether automated image analysis of placental villi and syncytial knots could improve standardization in diagnosing these conditions. MethodsPlacentas of antepartum fetal death at or near term were diagnosed as normal, delayed or accelerated villous maturation. Histologic sections of 5 cases per group were photographed at ×10 magnification. Automated image analysis of villi and syncytial knots was performed, using ImageJ public domain software. Analysis of hundreds of histologic images was carried out within minutes on a personal computer, using macro commands. ResultsCompared to normal placentas, villi from delayed maturation were larger and fewer, with fewer and smaller syncytial knots. Villi from accelerated maturation were smaller. The data were further analyzed according to horizontal placental zones and groups of villous size. DiscussionNormal placentas can be discriminated from placentas of delayed or accelerated villous maturation using automated image analysis. Automated image analysis of villi and syncytial knots is not equivalent to interpretation by the human eye. Each method has advantages and disadvantages in assessing the 2-dimensional histologic sections representing the complex, 3-dimensional villous tree. Image analysis of placentas provides quantitative data that might help in standardizing and grading of placentas for diagnostic and research purposes.

Abstract B85: Racial differences in the risk of serrated polyps and conventional adenomas in a younger aged, uninsured population in South Carolina

Abstract Compared to European Americans (EA), African Americans (AA) have higher colorectal cancer (CRC) incidence and are diagnosed with CRC at younger ages. The reasons for these disparities are poorly understood, but one contributing factor could be reduced access to high-quality preventative care. To address CRC disparities, this study assessed whether a racial difference in risk of large bowel polyps (precursors to most CRC) persists within a younger-aged, uninsured population in South Carolina (SC) undergoing screening colonscopy. We analyzed data from a multi-site statewide CRC screening program in SC to explore the risk of large bowel polyps among AA and EA. Eligible patients were uninsured, asymptomatic, had no personal history of colorectal neoplasia, and were between the ages 45-64 years (AA) or 50-64 years (EA). Using generalized linear regression, we estimated risk ratios and 95% confidence intervals (CI) as measures of the association between race and risk for one or more conventional adenomas or serrated polyps adjusting for age, sex, family history of CRC, and clinical site. Serrated polyps (SP) were defined as one or more hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, and mixed adenomatous polyps. SP were first classified in a single category since not all project pathologists used up-to-date pathologic terminology and there was a high-level of variability among clinical sites in use of newer SP categories (i.e., sessile, traditional adenomas). Serrated adenomas included any SP with serrated adenomatous features (sessile, traditional, or mixed). Advanced SP were defined as SP with large size (an estimated ≥ 1 cm). Conventional adenomas (CA) were defined as tubular, tubulovillous, or villous polyps. Advanced CA were defined as adenomas with at least 25% villous component (TVA), high-grade dysplasia (HGD), or large size. We also stratified polyps separately according to colonic region (proximal or distal colorectum), large size, and advanced CA histology (TVA, HGD). Of the 237 subjects enrolled (127 AA, 91 EA, 19 other), 233 had a complete exam (i.e., to the cecum). Our results suggested a lower risk of SP among AA compared to EA: any SP (RR 0.50 (95% CI 0.30-0.84)), any serrated adenoma (RR 0.35 (95% CI 0.11-1.14)), and any large SP (RR 0.27 (95% CI 0.09-0.85)). Although not always statistically significant, the trend in the results indicate that the risk of CA was higher in AA compared to EA: any CA 1.17 (95% CI 0.77-1.79), large CA 2.16 (95% CI 0.70-6.66), proximal large CA 4.24 (95% CI 1.0-18.01), and any advanced CA 1.38 (95% CI 0.55-3.42). In patients under 55 years of age (median age), AA compared to EA had higher risk of advanced CA histology lesions RR 4.11 (95% 1.05 -16.11), but otherwise risks were similar in the age groups. Overall, our findings suggest that it is important to consider type of polyp and age when assessing risk in different racial groups. Our results in this unique study population are consistent with an earlier study showing that AA have a lower risk of metachronous SP and among younger patients, an increased risk of conventional adenomas, especially advanced lesions. The persistence of these observations within a study population comprised of all medically underserved individuals implies that the unique features of the epidemiology of colorectal neoplasia in AA cannot be completely attributed to access to care barriers. Citation Format: Kristin Wallace, Anthony Alberg, Bridgette Blankenship, Heather Brandt, Renay Caldwell, James Dunn, Patricia Hegedus, Brenda Hoffman, Courtney Marsh, March Seabrook, Marylou Stinson, Annie Thibault, Franklin Berger. Racial differences in the risk of serrated polyps and conventional adenomas in a younger aged, uninsured population in South Carolina. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B85.

Usefulness of white-light imaging–guided narrow-band imaging for the differential diagnosis of small ampullary lesions

Small ampullary tumors and inflammatory lesions have similar endoscopic findings and are difficult to differentiate. Narrow-band imaging (NBI) can visualize microvessels and mucosal microstructure clearly and is widely used to diagnose early gastric and colon cancer. To evaluate the usefulness of NBI for differentiating ampullary tumors from benign diseases. Retrospective cohort study. Tertiary-care hospital. All 45 patients who had suspicious ampullary lesions (enlarged or protruded morphology) during duodenoscopy and underwent NBI between March 2010 and January2011. NBI. NBI images were assessed for irregular villous arrangement, irregular villous size, ridge disappearance, demarcation with normal villi, and abnormal microvasculature. Histology of NBI-guided lesion biopsy specimens provided the final diagnoses. Agreement between NBI images and histologic findings was analyzed. Of the 60 ampullary lesions, 11, 26, and 23 were adenocarcinomas, adenomas, and benign inflammatory diseases, respectively. Irregular villous arrangement, irregular villous size, ridge disappearance, demarcation with normal villi, and abnormal microvasculature were observed in 45%, 63%, 50%, 48%, and 58% of the lesions, respectively. Multivariate analysis revealed that irregular villous arrangement (odds ratio [OR] 15.76; 95% confidence interval [CI], 3.38-64.12; P< .001) and abnormal microvasculature (OR 86.63; 95% CI, 14.56-515.41; P< .001) were significant independent factors for identifying ampullary adenomas and adenocarcinoma. All tumors had at least one abnormal NBI feature. Retrospective design. The NBI findings of irregular villous arrangement and/or abnormal microvasculature were useful for differentially diagnosing ampullary tumors. NBI may complement the accurate diagnosis of ampullary lesions by white-light imaging.

A morphometric and histological study of placental malaria shows significant changes to villous architecture in both Plasmodium falciparum and Plasmodium vivax infection

BackgroundMalaria in pregnancy remains a major health problem. Placental malaria infection may cause pathophysiological changes in pregnancy and result in morphological changes to placental villi. Quantitative histomorphological image analysis of placental biopsies was performed to compare placental villous architecture between active or treated placental malaria cases and controls.MethodsA total of 67 placentas were studied from three clinical groups: control patients who did not have malaria (n = 27), active (n = 14) and treated (n=26) malaria cases, including both Plasmodium falciparum and Plasmodium vivax infections. Image analysis of histological placental sections was performed using ImageJ software to measure the number and size (area) of terminal villi, perimeter measurement per villus and total perimeter per unit area, and number of capillaries per villus (vascularity). Histological features of placental malaria were scored and these results were correlated with malaria status and clinical outcomes.ResultsVillous size correlated with vascularity (p <0.0001) but was inversely correlated with observed villi per unit area, (p = 0.0001). Significantly greater villous area and vascularity was observed in UK controls. Indices of histological malaria infection were significantly greater in active versus treated malaria cases. Active placental malaria cases showed significantly smaller villous area (p <0.0084), vascularity (p <0.0139) and perimeter (p <0.0006) than treated malaria cases or controls, but significantly more villi per unit area (p <0.0001). Villous size in treated malaria cases was significantly larger than active placental malaria cases (p <0.001) and similar to controls. There was a significant relationship between villous number and anaemia at the time of infection (p <0.0034), but not placental weight, birth weight or gestational age at delivery. No differences were found between histology or villous morphology comparing infections with P. falciparum or P. vivax.ConclusionsThese results imply that villous size, perimeter and vascularity are acutely decreased during active placental malaria, decreasing the surface area available for gas exchange per villus. However the increased number of villi per unit area offsets this change and persists after treatment. Histopathological and villous architectural changes may be reversed by early detection and appropriate anti-malarial treatment.

Partial Hydatidiform Mole

Histologic diagnosis of partial hydatidiform mole (PHM) continues to be problematic, and DNA genotyping has recently become cost-effective for precise separation of PHM from its mimics. We performed a comprehensive reevaluation of histologic parameters of PHM in correlation with DNA genotyping. A total of 143 early abortion specimens were subjected to genotyping as part of the routine workup, resulting in 60 cases of PHM, 52 cases of various chromosomal trisomies, and 31 cases of nonmolar diploid gestations. All available hematoxylin and eosin slides were reviewed retrospectively by 2 gynecologic pathologists blinded to the genotyping results. Significant histologic overlaps were present among genetically confirmed PHM, hydropic abortions, and chromosomal trisomy syndromes. The following morphologic parameters emerged with diagnostic significance for PHM: villus size, presence of 2 villous populations, round or oval pseudoinclusions, at least moderate villous hydrops, cistern formation, and trophoblastic hyperplasia. The most sensitive morphologic features for PHM included villous hydrops (86% sensitivity) or the presence of at least 1 of the following 3 parameters: 2 villous populations, round or oval pseudoinclusions, and cisterns (84% sensitivity). The presence of cisterns and villous size ≥2.5 mm had the highest positive predictive value (90%) for PHM. In conclusion, no single or combined morphologic features are sufficient for definitive diagnosis of PHM. The presence of any one of the following histologic findings should prompt DNA genotyping workup to rule out PHM: round or oval pseudoincludions, cistern formation, 2 populations of villi, and a villous size of ≥2.5 mm.

Intrauterine growth restriction reduces intestinal structure and modifies the response to colostrum in preterm and term piglets

We investigated some consequences of intrauterine growth restriction (IUGR) on weight and structural and functional parameters of the intestine at birth and after 2 days of colostrum feeding. IUGR altered intestinal morphology, leading to a longer and thinner small intestine in piglets born both preterm and at full term, together with reduced villous size in term IUGR piglets. Preterm IUGR piglets displayed an improved ability to adapt to colostrum intake by rapid intestinal catch-up growth, relative to other groups of pigs. In contrast, intestinal nutrient absorption surface was impaired by IUGR during the first days of life in term piglets. The postnatal effects of IUGR may have long term consequences for developing piglets, and these effects may depend on gestational age at birth, preterm or term.

Mutation analysis of K-ras protooncogene in colorectal adenocarcinomas and polyps in Russian patients

To estimate diagnostic value of K-ras mutations during cancer risk group formation, they were studied in the samples of sporadic carcinomas (n = 33) and malignant (n = 13) polyps of large intestine obtained during surgery or polypectomy. Using PCR analysis, restriction analysis, SSCP analysis and automated sequencing, eight various point mutations were revealed. Six of them were located in codon 12 and two, in codon 13 of the K-ras gene. Mutation frequency in carcinomas, benign and malignant polyps was 43, 49, and 69%, respectively. In the healthy tissue of the large intestine, no changes in codons 12 and 13 in the K-ras gene were observed. Mutations in the groups of Russian patients examined partially overlapped. In patients with colorectal carcinoma the mutation frequency in the K-ras gene was not associated with disease onset age, location, and the extent of tumor differentiation while it was associated with the stage of tumor process. The maximum mutation frequency was revealed in polyps of patients over 70 years of age as well as in the adenomas of villous histology and large size ((1 cm). No correlation between the K-ras mutation frequency and the extent of polyp dysplasia was observed.

Colostrum--more than just an immunoglobulin supplier.

The adaptation of neonates to various environmental factors is critical and usually associated with the highest morbidity and mortality rates in the lifespan of farm animals. Adaptability is basically hampered by immaturity of organ functions and controlling systems. Thus, the growth hormone - insulin-like growth factor (IGF) axis, which is of primary importance for postnatal growth regulation, is not fully functioning. Some changes are primarily of constitutional nature. Thus, in young calves plasma nitrate and creatinine concentrations decrease from high concentrations at birth during the first week of life to the values seen in older cattle and can not be influenced by nutrition. Major changes occur with respect to nutrition because the primarily parenteral supply of nutrients changes to an exclusively enteral supply. The proper functioning of the gastrointestinal tract (GIT) is therefore of primary importance and characterized by exquisite developmental and functional changes. The intake of colostrum (C) by newborn calves not only influences the immune status, but also the development of the GIT and of other organs, metabolism and endocrine systems. C contains high amounts of cells (leucocytes), nutrients (carbohydrates, especially lactose; fatty acids and lipids; amino acids and proteins; minerals; vitamins), bioactive substances (hormones, growth factors and cytokines, such as insulin-like growth factors, epidermal growth factor, insulin, prolactin and tumor necrosis factor-α; enzymes; nucleotides; polyamines). The greatest mass of these nutrient and nonnutrient substances - with the major exception of casein and lactose - is available to newborns with the first C. Ingestion of C is essential for all farm animals. C intake (as shown in calves) stimulates the proliferation of the small intestine, increases villous size and absorptive capacity, an effect which is likely associated with reduced apoptosis. As shown in calves, there are specific receptors for several of the ingested hormones and growth factors (such as insulin, IGFs) localized in the mucosa of the small intestine and colon. The receptor number is exhibiting ontogenetical changes and/or is influenced by early postnatal nutrition and it can basically be expected that the ingested hormones and growth factors influence GIT development upon receptor interaction. Feeding IGF-I alone to calves did, however, not influence small intestinal epithelial proliferation and villous size, but feeding an extract derived from first-milked bovine C (which contained high amounts of IGFs, insulin, lactoferrin and various other growth factors) to a formula containing nearly no bioactive substances stimulated small intestinal epithelial proliferation and villous size. The intestinal absorption of immunoglobulins and of some other proteins and peptides is possible only during a short period after birth (length depending on species) and there is indication that (at least in calves) the status of non-esterified fatty acids, triglycerides, phospholipids, essential fatty acids, s-carotin, retinol and tocopherol depends, too, on early postnatal C ingestion. In addition, the plasma amino acid profile and especially the glutamine/glutamate ratio (in calves) depends on whether C is ingested immediately after birth or not. Even though the intake of lactose is smaller than if mature milk is ingested, early C intake is also important for longer-lasting glucose homeostasis, likely due to enhanced gluconeogenesis. Time-point

Inter‐endoscopist variation in polyp and neoplasia pick‐up rates in flexible sigmoidoscopy screening for colorectal cancer

Background: The Norwegian Colorectal Cancer Prevention study is an ongoing flexible sigmoidoscopy (FS) screening trial for colorectal cancer. Twenty‐one thousand average‐risk individuals, aged 50–64 years, living in two separate areas in Norway were randomly drawn from the Population Registry and invited to once‐only screening flexible sigmoidoscopy. Examinations were performed over 3 years, at 2 centres, by 8 different endoscopists, using the same type of equipment. The aim of the present study was to investigate possible differences between endoscopists in detecting individuals with polyps, adenomas and advanced lesions (adenomas with severe dysplasia and/or villous components and/or size larger than 9 mm and carcinoma) in flexible sigmoidoscopy screening. Methods: The present trial comprises data from 8822 individuals, aged 55–64 years, who have undergone a flexible sigmoidoscopy. In the study period, all lesions detected by the different endoscopists were registered. Tissue samples were taken from all lesions detected. Results: Detection rates varied significantly between endoscopists, ranging from 36.4% to 65.5% for individuals with any polyp, from 12.7% to 21.2% for any adenoma and from 2.9% to 5.0% for advanced lesions. In a multiple logistic regression model, the performing endoscopist was a strong independent predictor for detection of individuals with polyps (P < 0.001), adenomas (P < 0.001) and advanced lesions (P = 0.01). Conclusion: Detection rates for colorectal lesions vary significantly between endoscopists in colorectal cancer screening. Establishing systems for monitoring performance in screening programmes is important. Supervised training and re‐certification for endoscopists with poor performance should be considered.

Effect of Four Enteral Foods on the Small Bowel of Undernourished Rats after Midgut Resection

To describe the effects of new enteral foods on the adaptation of the gut mucosa after massive intestinal resection in rats. Laboratory experiment. Teaching hospital, Spain. 91 male Wistar rats, 69 of which were studied (5 were excluded and 17 died). Previously undernourished rats were subjected to either massive bowel resection (n = 30) or laparotomy (n = 26) and fed four enteral hypocaloric diets for 7 days: Alitraq (n = 7 in each group), Impact (n = 8 and 7), Enrich (n = 8 and 6), and Elemental (n = 7 and 6). The remainder were not operated on and fed chow (n = 7) or a diet containing no protein (n = 6). Two diets were high in protein (Alitraq and Impact) and two contained normal amounts (Enrich and Elemental). Bowel mucosal thickness and proliferation; disaccharidase activity; intestinal weight and length; body weight; and plasma somatostatin, IGF-1, and peptide YY concentrations. Enriched diets provided a higher body and intestinal weight, and increased length of jejunal and ileal villous size. Peptide concentrations were modified by resection but not by the diet given. Concentrations of somatostatin and insulin-like growth factor were reduced in all groups with the exception of somatostatin in the two diets high in protein in the sham-operated rats. Enriched diets all improve the intestinal adaptive response to massive bowel resection in rats, offering advantages over diets with normal amounts of protein.

Nutritional and intestinal effects of the novel immunosuppressive agents: Deoxyspergualin, rapamycin, and mycophenolate mofetil

Objectives: Transplantation of the small intestine would be an attractive therapeutic option for treatment of short bowel syndrome if effective, nontoxic immunosuppressive agents could be developed. This study examines the effect of three newly developed immunosuppressive agents: rapamycin, deoxyspergualin, and mycophenolate mofetil, on the nutritional status and intestinal function of normal juvenile rats. Design & Methods: Rapamycin (2 mg/kg every second day), deoxyspergualin (2 mg/kg every second day) and mycophenolate mofetil (MM) (25 mg/kg every second day) were injected subcutaneously for six weeks. Results: Rapamycin and deoxyspergualin caused significant reductions in weight gain without impairing feed intake. Both drugs caused small decreases in fat absorption; treatment with DSG induced an increase in permeability to 99Tc-DTPA. However, the permeability to other markers, such as mannitol and lactulose, was decreased in the rapamycin and mycophenolate mofetil-treated animals. Intestinal function in vitro was quantified using glucose flux (absorption). In the rapamycin group, there was a significant decrease in ileal uptake of glucose, with the net flux (absorption) being zero; there was an associated loss of villous size histologically. In the deoxyspergualin-treated groups, there was a decrease in the jejunal glucose flux. In the mycophenolate mofetil-treated animals, there was a decrease in jejunal with a compensatory increase in ileal glucose absorption. There were minor variations in intestinal morphology, but these were not consistent. Conclusions: Rapamycin and deoxyspergualin in these doses cause a significant reduction in weight gain in healthy juvenile animals, and all the drugs caused changes in the active transport characteristics of the intestine. Accordingly, the use of these drugs for intestinal transplantation should be evaluated carefully for their nutritional impact.

A flow cytometric study of 137 fresh hydropic placentas: correlation between types of hydatidiform moles and nuclear DNA ploidy.

Hydropic placentas may be classified by histopathology into hydropic abortus, partial hydatidiform mole, and complete hydatidiform mole. We studied 142 hydropic placentas: 39% were complete hydatidiform moles, 35% partial hydatidiform moles, and 26% hydropic abortuses. Villous vesicle size was predictive of histologic diagnosis. We determined DNA ploidy in 137 cases. Seventy-three percent of hydropic abortuses were diploid and 11% were triploid. Ninety percent of partial moles were triploid or near-triploid; one partial mole was haploid and one diploid. Of the complete moles, 50% were diploid, 43% were tetraploid, 3.6% polyploid, and 1.7% triploid. Partial moles had lower pre-evacuation beta-hCG levels than complete moles. Persistent tumor followed 33% of complete moles and 12% of partial moles. Although the numbers were small, no patient with a diploid, tetraploid, aneuploid, or haploid partial mole developed persistent disease. Among complete moles, the pre-evacuation beta-hCG level was not predictive of persistence (P = .15). Subdividing complete moles by ploidy, we found that tetraploid moles were associated with higher pre-evacuation beta-hCG levels than were diploid moles. However, tetraploidy was not associated with increased persistent tumor among complete moles. Although most partial moles were triploid and most complete moles were diploid or tetraploid, there was wider DNA heterogeneity among molar gestations than previously reported. In this series, DNA ploidy was not an independent predictor of persistence in complete moles.

The development of the placental villus during normal pregnancy: morphometric data base.

The morphological structures of the terminal villus of the normal human placenta were evaluated morphometrically throughout pregnancy. The Videoplan (Kontron) system was used to measure a total of 6000 villi. The cross-sectional surface and circumference of the villus decrease continuously until the 28th week and remain stable thereafter. The cross-sectional surface, number, and circumference of villous vessels only increase until the 20th week. The relative degree of vascularization, however, increases further until 28th week together with a continuous decrease in villous size. Epithelial plates start to appear in the 18th to 20th week, and their development is essentially completed by the 28th week. According to the data presented, the development and differentiation of the placental villus are completed by the 28th week of gestation. Any further increase in nutritional capacity can only be provided by an increase in the number of villi and not their individual maturation. These results represent a morphometric data base for the quantification of retarded placental development in placental insufficiency.

The Effects of Maternal Cigarette Smoking on Placental Morphology, Histomorphometry, and Biochemistry

We related cigarette smoking during pregnancy to the macroscopic and microscopic morphology, histomorphometry, and biochemistry of the placenta among participants in The Prenatal Project, a randomized, controlled trial of nutritional supplementation during pregnancy. The aim was to ascertain if the harmful effects of cigarette smoking on the fetus were reflected, and possibly mediated, by changes in the placenta, and whether such changes might be modified by the nutritional supplements, parallel to the nutritional reversal of birthweight depression among heavy smokers. Maternal smoking was associated with increased alkaline ribonuclease (RNase) levels, possibly resulting in disturbed protein synthesis. More smokers had placentas with villous hyperplasia on histologic examination. This was accompanied by biochemical evidence of significantly increased cellularity (increased DNA/gm of placental mass and decreased protein/DNA ratios) and (nonsignificant) trends to reduced syncytial villous cell size on histomorphometry. There were joint effects of cigarette smoking and use of either form of nutritional supplementation on the fibrin and stoma components of the villi, but such changes are not necessarily pathologic. The significant reduction in pathology of the stem villi among smokers was confined to those who were nutritionally supplemented, particularly heavy smokers. This change may thus have reflected the protective effects of supplementation on the birthweight of the offspring of these heavy smokers.