Glucosamine and Chondroitin Supplements and Risk of Colorectal Adenoma and Serrated Polyp.

BACKGROUND: Studies have shown an inverse association between use of glucosamine and chondroitin supplements and colorectal cancer risk. However, the association with the precursor lesion, colorectal adenoma and serrated polyp, has not been examined. METHODS: Analyses include 43,163 persons from the Nurses' Health Study (NHS), Health Professionals Follow-up Study (HPFS), and NHS2 who reported on glucosamine/chondroitin use in 2002 and who subsequently underwent ≥1 lower gastrointestinal endoscopy. By 2012, 5,715 conventional (2,016 high-risk) adenomas were detected, as were 4,954 serrated polyps. Multivariable logistic regression for clustered data was used to calculate OR and 95% confidence intervals (CI). RESULTS: Glucosamine/chondroitin use was inversely associated with high risk and any conventional adenoma in NHS and HPFS: in the pooled multivariable-adjusted model, glucosamine + chondroitin use at baseline was associated with a 26% (OR = 0.74; 95% CI, 0.60-0.90; P heterogeneity = 0.23) and a 10% (OR = 0.90; 95% CI, 0.81-0.99; P heterogeneity = 0.36) lower risk of high-risk adenoma and overall conventional adenoma, respectively. However, no association was observed in NHS2, a study of younger women (high-risk adenoma: OR = 1.09; 95% CI, 0.82-1.45; overall conventional adenoma: OR = 1.00; 95% CI, 0.86-1.17), and effect estimates pooled across all three studies were not significant (high-risk: OR = 0.83; 95% CI, 0.63-1.10; P heterogeneity = 0.03; overall conventional adenoma: OR = 0.93; 95% CI, 0.85-1.02; P heterogeneity = 0.31). No associations were observed for serrated polyps. CONCLUSIONS: Glucosamine/chondroitin use was associated with lower risks of high-risk and overall conventional adenoma in older adults; however, this association did not hold in younger women, or for serrated polyps. IMPACT: Our study suggests that glucosamine and chondroitin may act on early colorectal carcinogenesis in older adults.

Pólipos de glândulas fúndicas: a histologia pode ser utilizada para prever uso de inibidores de bomba de próton? / Gastric fundic gland polyps: can histology be useful to predict proton pump inhibitors use?

ABSTRACT BACKGROUND: Fundic gland polyps allegedly increased in frequency in recent decades, and had attracted great attention due to possible association with prolonged proton pump inhibitor therapy. Prolonged use of this drug could cause parietal cell hyperplasia, obstruction of glandular lumen and cystic dilation of the gland. OBJECTIVE: This study aims to analyze clinical and pathological features of fundic gland polyps in patients with and without proton pump inhibitor therapy in a selected population from Brazil. METHODS: It was selected a sample of 101 Brazilian patients (78 females and 23 males), from a five years retrospective search of the files from a private pathology laboratory. The patients had an average age of 57 years and we included patients with a histological diagnosis of fundic gland polyp. The clinical data were obtained from their files and all histological slides were reviewed and examined with hematoxylin and eosin (HE) and Giemsa. RESULTS: Information about the use or non-use of proton pump inhibitors (PPI) was obtained in 84 patient files. In 17 cases we could not determine if PPI were used or not. Among those in which the information was available, a positive history of anti-acid therapy was observed in 63 (75.0%) patients. Parietal cell hypertrophy/hyperplasia and parietal cell protrusions were detected in most slides. Histological findings were identical in PPI users and PPI negative patients. Helicobacter pylori infection was detected in just two samples. Epithelial dysplasia or adenocarcinoma were not observed in our cases. Histopathological analysis of fundic gland polyps could not distinguish between PPI and non-PPI related cases. Parietal cell cytoplasmic protrusions, an alleged marker of prolonged acid suppression therapy, was detected in both groups. CONCLUSION: Histological features could not discriminate anti-acid therapy related fundic glands polyps in our patients.

RESUMO CONTEXTO: Os pólipos das glândulas fúndicas do estômago supostamente aumentaram em frequência nas últimas décadas e atraíram grande atenção devido à possível associação com a terapia prolongada com inibidores da bomba de prótons. O uso prolongado deste fármaco pode causar hiperplasia das células parietais, obstrução do lúmen glandular e dilatação cística da glândula. OBJETIVO: Este estudo tem como objetivo analisar os aspectos clínicos e patológicos dos pólipos das glândulas fúndicas em pacientes com e sem terapia com inibidores da bomba de prótons em uma população selecionada do Brasil. MÉTODOS: Foi selecionada uma amostra de 101 pacientes brasileiros (78 do sexo feminino e 23 do sexo masculino), a partir de uma pesquisa retrospectiva de cinco anos dos arquivos de um laboratório privado de patologia. Os pacientes tinham uma idade média de 57 anos e foram incluídos pacientes com diagnóstico histológico de pólipo das glândulas fúndicas. Os dados clínicos foram obtidos a partir de seus prontuários e todas as lâminas histológicas foram revisadas e examinadas com hematoxilina e eosina (HE) e Giemsa. RESULTADOS: Informações sobre o uso ou não uso de inibidores da bomba de próton (IBP) foram obtidas em 84 prontuários de pacientes. Em 17 casos, não foi possível determinar se o IBP foi usado ou não. Entre aqueles em que a informação estava disponível, observou-se uma história positiva de terapia com IBP em 63 (75,0%) pacientes. A hipertrofia das células parietais/hiperplasia e protrusões das células parietais foram detectadas na maioria das lâminas. Os achados histológicos foram idênticos em usuários de IBP e pacientes não usuários. A infecção por Helicobacter pylori foi detectada em apenas duas amostras. A displasia epitelial ou o adenocarcinoma não foram observados em nossos casos. A análise histopatológica dos pólipos das glândulas fúndicas não pôde distinguir entre os casos IBP e não relacionados ao IBP. As protuberâncias citoplasmáticas das células parietais, um suposto marcador de terapia prolongada de supressão de ácido, foram detectadas em ambos os grupos. CONCLUSÃO: Características histológicas não podem discriminar os pólipos das glândulas fúndicas relacionados à terapia anti-secretora em nossos pacientes.

Doenças imunomediadas em pacientes com doença celíaca e em seus familiares: um estudo comparativo entre idade e sexo / Immune mediated diseases in patients with celiac disease and their relatives: a comparative study of age and sex

ABSTRACT BACKGROUND: Up to 15% of other immune-mediated diseases (IMDs) can occur in patients with CD throughout their lives and are associated with multiple factors, including sex and sex hormone levels. Moreover, sex is associated with differences in clinical presentation, onset, progression, and outcomes of disorders. OBJECTIVE: To investigate the prevalence of IMDs at diagnosis in patients with celiac disease (CD) and their first-degree relatives and to compare the findings between female and male patients of different age. METHODS: A retrospective study including Brazilian patients with CD who visited the same doctor during January 2012 to January 2017 was performed. Demographic and medical history data were collected through self-administered questionnaires and medical charts of the patients. In total, 213 patients were examined at diagnosis: 52 males (mean age, 40.0 years) and 161 females (mean age, 41.4 years). The patients were divided into two groups according to sex and age. RESULTS: IMDs were observed in 60.2% of the female (97/161) and 42.3% of the male patients (22/52; P=0.22). However, the frequency of IMDs was significantly higher in females aged 51-60 years than in males with same age (P=0.0002). Dermatitis herpetiformis (DH) was significantly more prevalent in males (P=0.02), whereas atopy was more prevalent in females (P=0.02). IMDs observed in first-degree relatives were similar to those observed in patients (70.9%; P<0.001), with a higher number observed in female relatives. CONCLUSION: The frequency of IMDs in CD patients was similar in all age groups and both sexes, except women diagnosed with CD after 51 years of age presented with an increased frequency of IMDs compared with males. Dermatitis herpetiformis was more prevalent in males, whereas atopy was more prevalent in females. No difference was observed in the type of IMDs between the first-degree relatives of both sexes.

RESUMO CONTEXTO: Até 15% das outras doenças imunomediadas (DIMs) podem ocorrer em pacientes com doença celíaca ao longo de suas vidas e estão associados a múltiplos fatores, incluindo sexo e níveis de hormônios sexuais. Além disso, o sexo está associado a diferenças na apresentação, início, progressão e desfecho das doenças. OBJETIVO: Investigar a prevalência de DIMs ao diagnóstico de doença celíaca e em seus familiares de primeiro grau e comparar os resultados entre sexo feminino e masculino em diferentes idades. MÉTODOS: Estudo retrospectivo incluindo pacientes brasileiros com diagnóstico de doença celíaca que realizaram acompanhamento com o mesmo médico no período de janeiro 2012 a janeiro de 2017. Dados demográficos e histórico médico foram coletados através de um questionário auto administrado e prontuários médicos dos pacientes envolvidos. No total, 213 pacientes eram portadores de doença celíaca, dos quais 52 do sexo masculino (idade média 40,0 anos) e 161 do sexo feminino (idade média 41,4 anos). Os pacientes foram divididos em dois grupos de acordo com o sexo e idade. RESULTADOS: DIMs foram observadas em 60,2% das pacientes femininas (97/161) e 42,4% dos pacientes masculinos (22/52; P=0,22). Entretanto, a frequência de DIMs foi significantemente maior em pacientes do sexo feminino com idade entre 51-60 anos que em pacientes masculinos da mesma idade (P=0,0002). Dermatite herpetiforme apresentou maior prevalência no sexo masculino (P=0,02), enquanto atopia obteve maior prevalência nas pacientes do sexo feminino (P=0,02). DIMs observadas em familiares de primeiro grau foram similares as encontradas nos pacientes (70,9%; P<0,001), com um maior número observado em familiares femininos. CONCLUSÃO: A frequência de DIMs em pacientes com doença celíaca foi similar nos grupos etários e ambos sexos, exceto as mulheres com diagnóstico de doença celíaca após a idade de 51 anos, as quais apresentaram um aumento na frequência de DIMs em comparação com os pacientes do sexo masculino. Dermatite herpetiforme apresentou maior prevalência em pacientes do sexo masculino, enquanto que atopia foi mais prevalente no sexo feminino. Em relação ao sexo, não foi observada diferença no tipo de DIMs observada entre os familiares de primeiro grau.

GASTRIC FUNDIC GLAND POLYPS: CAN HISTOLOGY BE USEFUL TO PREDICT PROTON PUMP INHIBITORS USE?

BACKGROUND: Fundic gland polyps allegedly increased in frequency in recent decades, and had attracted great attention due to possible association with prolonged proton pump inhibitor therapy. Prolonged use of this drug could cause parietal cell hyperplasia, obstruction of glandular lumen and cystic dilation of the gland. OBJECTIVE: This study aims to analyze clinical and pathological features of fundic gland polyps in patients with and without proton pump inhibitor therapy in a selected population from Brazil. METHODS: It was selected a sample of 101 Brazilian patients (78 females and 23 males), from a five years retrospective search of the files from a private pathology laboratory. The patients had an average age of 57 years and we included patients with a histological diagnosis of fundic gland polyp. The clinical data were obtained from their files and all histological slides were reviewed and examined with hematoxylin and eosin (HE) and Giemsa. RESULTS: Information about the use or non-use of proton pump inhibitors (PPI) was obtained in 84 patient files. In 17 cases we could not determine if PPI were used or not. Among those in which the information was available, a positive history of anti-acid therapy was observed in 63 (75.0%) patients. Parietal cell hypertrophy/hyperplasia and parietal cell protrusions were detected in most slides. Histological findings were identical in PPI users and PPI negative patients. Helicobacter pylori infection was detected in just two samples. Epithelial dysplasia or adenocarcinoma were not observed in our cases. Histopathological analysis of fundic gland polyps could not distinguish between PPI and non-PPI related cases. Parietal cell cytoplasmic protrusions, an alleged marker of prolonged acid suppression therapy, was detected in both groups. CONCLUSION: Histological features could not discriminate anti-acid therapy related fundic glands polyps in our patients.

BRAF inhibitor treatment of melanoma causing colonic polyps: An alternative hypothesis.

Colonic polyps may arise from BRAF inhibitor treatment of melanoma, possibly due to paradoxical activation of the mitogen-activated protein (MAP)-kinase pathway. In an alternative evidence based scenario, tubular colonic adenomas with APC gene mutations have also been identified in the context of BRAF inhibitor treatment, in the absence of mutations of MAPK genes. A minority of colorectal cancers develop by an alternative "serrated polyp pathway". This article postulates a novel hypothesis, that the established phenotypic and molecular characteristics of serrated colonic polyps/CRC offer an intriguing insight into the pathobiology of BRAF inhibitor induced colonic polyps. Serrated polyps are characterized by a CpG island methylation phenotype, MLH1 silencing and cellular senescence. They also have BRAF mutations. The contention is that BRAF inhibitor induced polyps mimic the afore-described histology and molecular features of serrated polyps with the exception that instead of the presence of BRAF mutations they induce C-RAF homodimers and B-RAF: C-RAF heterodimers.

Three Pathways of Colonic Carcinogenesis in Rats.

BACKGROUND: Colorectal cancer (CRC) is one of the more intensively studied human malignancies. For many years, the general view has been that the vast majority of CRCs in humans evolve from conventional (tubular or villous) adenomas via the adenoma-carcinoma pathway. More recently, serrated colorectal polyps (hyperplastic polyps, sessile serrated polyps and traditional serrated adenomas) have emerged as an alternative pathway of colorectal carcinogenesis in humans. Archival sections from early experiments in Sprague-Dawley (SD) rats injected with dimethylhydrazine (DMH) were reviewed and the histology of colonic neoplasias was re-evaluated. Out of 215 colonic neoplasias, 9% were serrated adenomas and 6% serrated carcinomas, 11% conventional adenomas, 39% highly differentiated carcinomas, 21% gut-associated lymphoid tissue (GALT) carcinomas, 13% signet-ring cell carcinomas, and 1% villous carcinomas. In a more recent review of archived sections from DMH-treated rats with colonic GALT follicles, dysplastic crypts exhibiting asymmetrical bifurcations in GALT mucosa were found in 49% and colonic GALT carcinomas in 53% of 276 DMH-treated rats. Histology of the 146 colonic GALT-carcinomas revealed highly differentiated carcinoma in 75%, signet-ring cell carcinoma in 20%, mucinous carcinomas in 3% and mixed in the remaining 2%. Highly differentiated carcinomas were seen to evolve from dysplastic crypts with asymmetric bifurcations and from adenomas and signet-ring cell carcinomas, and from non-dysplastic crypts having goblet cells with marked anisocytosis. It is apparent that DMH treatment in SD rats induced conventional adenomas, conventional carcinomas, serrated adenomas, serrated carcinomas and GALT carcinomas. The paradigm permits to monitor in detail the early histological steps that epitomize the three alternative pathways of colonic carcinogenesis in SD rats. This model might be useful for analyzing different molecular aberrations evolving during the conventional adenoma-carcinoma pathway, the serrated carcinoma pathway, and the GALT carcinoma pathway of colonic carcinogenesis, under standard laboratory conditions.

Black Spot, a Novel Gastric Finding Potentially Induced by Proton Pump Inhibitors.

Objective We have recently discovered new gastric lesions with black spots. There have been no reports about black spots and their clinicopathological features. We therefore report the clinicopathological features of black spots and assess their causes and mechanisms. Methods Sixty-four patients with black spots among 26,620 Japanese patients that underwent endoscopy between May 2012 and October 2014 were enrolled. Endoscopic findings of black spots were defined as black pigmentations in the gastric mucosa by conventional endoscopy. We investigated the clinicopathological characteristics, including gender, age, underlying diseases and medications, endoscopic and pathologic findings of patients with black spots. Results The prevalence of patients with black spots was 0.24%. Of sixty-four cases, 44 (68.8%) were taking proton pump inhibitors (PPIs). Eight (12.5%) were taking corticosteroids. There were 10 cases (15.6%) with decreased renal function. All black spots were identified only in the fundic gland region. Forty-one (64.1%) patients had multiple (more than ten) black spots. There were two different types: black spots on the flat mucosa and black spots on fundic gland polyps. Pathologically, parietal cell protrusions, fundic gland cysts and brownish pigmentation in fundic gland cysts were seen in 26 (76.5%), 23 (67.6%) and 6 (17.6%) patients, respectively. Conclusion We herein describe gastric black spots as a new gastric mucosal finding that arises only in the fundic gland region. The black spots are pathologically brownish pigmentations in fundic gland cysts. Adverse events of PPIs and parietal cell protrusion caused by PPI use are strongly considered to be one of the etiologies of black spots.

Systematic review with meta-analysis: fundic gland polyps and proton pump inhibitors.

BACKGROUND: A causal association between proton pump inhibitor (PPI) use and fundic gland polyps has been suggested, but the data are conflicting. AIM: To clarify the relationship through a meta-analysis of the existing data. METHODS: A systematic retrieval and selection of records was performed. The main inclusion criteria were original studies reporting the prevalence of fundic gland polyps in PPI users or the reverse, compared to controls. Key outcomes were the odds ratios (OR) for fundic gland polyp prevalence in association with PPI use, prevalence of PPI use amongst subjects with fundic gland polyps and fundic gland polyp prevalence among PPI users. Statistical analysis was performed using Mix 2.0 Pro. RESULTS: The initial search using electronic databases and manual searching retrieved 339 peer-reviewed articles and abstracts. Twenty articles met all inclusion and exclusion criteria, with a total of 40 218 subjects included. The meta-analysis of 12 studies revealed an increase in fundic gland polyps amongst PPI users compared to controls (OR 2.46, 95% CI 1.42-4.27, P = 0.001), particularly among individuals taking PPIs for at least 6 months (OR: 4.71, 95% CI 2.22-9.99, P < 0.001) or 12 months (OR: 5.32, 95% CI 2.58-10.99, P < 0.001). CONCLUSIONS: Proton pump inhibitor usage is associated with a significantly increased prevalence of fundic gland polyps, and there is a trend for this to increase with longer length of PPI exposure. However, the meta-analysis is limited mainly to cohort studies.

A hypermorphic epithelial ß-catenin mutation facilitates intestinal tumorigenesis in mice in response to compounding WNT-pathway mutations.

Activation of the Wnt/ß-catenin pathway occurs in the vast majority of colorectal cancers. However, the outcome of the disease varies markedly from individual to individual, even within the same tumor stage. This heterogeneity is governed to a great extent by the genetic make-up of individual tumors and the combination of oncogenic mutations. In order to express throughout the intestinal epithelium a degradation-resistant ß-catenin (Ctnnb1), which lacks the first 131 amino acids, we inserted an epitope-tagged ΔN(1-131)-ß-catenin-encoding cDNA as a knock-in transgene into the endogenous gpA33 gene locus in mice. The resulting gpA33(ΔN-Bcat) mice showed an increase in the constitutive Wnt/ß-catenin pathway activation that shifts the cell fate towards the Paneth cell lineage in pre-malignant intestinal epithelium. Furthermore, 19% of all heterozygous and 37% of all homozygous gpA33(ΔN-Bcat) mice spontaneously developed aberrant crypt foci and adenomatous polyps, at frequencies and latencies akin to those observed in sporadic colon cancer in humans. Consistent with this, the Wnt target genes, MMP7 and Tenascin-C, which are most highly expressed in benign human adenomas and early tumor stages, were upregulated in pre-malignant tissue of gpA33(ΔN-Bcat) mice, but those Wnt target genes associated with excessive proliferation (i.e. Cdnn1, myc) were not. We also detected diminished expression of membrane-associated α-catenin and increased intestinal permeability in gpA33(ΔN-Bcat) mice in challenge conditions, providing a potential explanation for the observed mild chronic intestinal inflammation and increased susceptibility to azoxymethane and mutant Apc-dependent tumorigenesis. Collectively, our data indicate that epithelial expression of ΔN(1-131)-ß-catenin in the intestine creates an inflammatory microenvironment and co-operates with other mutations in the Wnt/ß-catenin pathway to facilitate and promote tumorigenesis.

Fertility drugs and the risk of breast and gynecologic cancers.

The evaluation of cancer risk among patients treated for infertility is complex, given the need to consider indications for use, treatment details, and the effects of other factors (including parity status) that independently affect cancer risk. Many studies have had methodologic limitations. Recent studies that have overcome some of these limitations have not confirmed a link between drug use and invasive ovarian cancers, although there is still a lingering question as to whether borderline tumors might be increased. It is unclear whether this merely reflects increased surveillance. Investigations regarding breast cancer risk have produced inconsistent results. In contrast, an increasing number of studies suggest that fertility drugs may have a special predisposition for the development of uterine cancers, of interest given that these tumors are recognized as particularly hormonally responsive. Additional studies are needed to clarify the effects on cancer risk of fertility drugs, especially those used in conjunction with in vitro fertilization. Because many women who have received such treatments are still relatively young, further monitoring should be pursued in large well-designed studies that enable assessment of effects within a variety of subgroups defined by both patient and disease characteristics.

Lack of efficacy of blueberry in nutritional prevention of azoxymethane-initiated cancers of rat small intestine and colon.

BACKGROUND: Blueberries may lower relative risk for cancers of the gastrointestinal tract. Previous work indicated an inhibitory effect of consumed blueberry (BB) on formation of aberrant crypt foci (ACF) in colons of male Fisher F344 rats (inbred strain). However, effects of BB on colon tumors and in both genders are unknown. METHODS: We examined efficacy of BB in inhibition of azoxymethane (AOM)-induced colon ACF and intestine tumors in male and female Sprague-Dawley rats (outbred strain). Pregnant rats were fed a diet with or without 10% BB powder; progeny were weaned to the same diet as their dam and received AOM as young adults. RESULTS: Male and female rats on control diet had similar numbers of ACF at 6 weeks after AOM administration. BB increased (P < 0.05) ACF numbers within the distal colon of female but not male rats. There was a significant (P < 0.05) diet by gender interaction with respect to total colon ACF number. Colon and duodenum tumor incidences were less in females than males at 17 weeks after AOM. BB tended (0.1 > P > 0.05) to reduce overall gastrointestinal tract tumor incidence in males, however, tumor incidence in females was unaffected (P > 0.1) by BB. There was a tendency (0.1 > P > 0.05) for fewer adenocarcinomas (relative to total of adenomatous polyps plus adenocarcinomas) in colons of female than male tumor-bearing rats; in small intestine, this gender difference was significant (P < 0.05). BB favored (P < 0.05) fewer adenocarcinomas and more adenomatous polyps (as a proportion of total tumor number) in female rat small intestine. CONCLUSION: Results did not indicate robust cancer-preventive effects of BB. Blueberry influenced ACF occurrence in distal colon and tumor progression in duodenum, in gender-specific fashion. Data indicate the potential for slowing tumor progression (adenomatous polyp to adenocarcinoma) by BB.

Meat and meat-mutagen intake, doneness preference and the risk of colorectal polyps: the Tennessee Colorectal Polyp Study.

Although meat intake has been fairly consistently linked to the risk of colorectal cancer, only a few studies have evaluated meat intake by doneness level and the heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) produced by high temperature cooking of meat in relation to colorectal adenomatous and hyperplastic polyps. We evaluated these associations in a large colonoscopy-based case-control study. Included in this study were participants with adenomatous polyp only (n = 573), hyperplastic polyp only (n = 256), or both adenomatous and hyperplastic polyps (n = 199), and 1,544 polyp-free controls. In addition to information related to demographic and other lifestyle factors, meat intake by cooking method and doneness preference were obtained through telephone interviews. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals for the association between exposures and colorectal polyp risks. Presence of hyperplastic polyp was found to be positively associated with high consumption of total meat (p(trend) = 0.076) or red meat (p(trend) = 0.060), with an approximate 50-60% elevated risk observed in the highest vs. the lowest intake group. High intake of 2-amino-I-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo [4,5]quinoxaline (DiMeIQx) were associated with increased risk for hyperplastic polyp (p(trend) = 0.036 and 0.038, respectively). With a possible exception of the intake of total well-done meats (p(trend) = 0.055) or well-done red meats (p(trend) = 0.074) with the risk of large adenomas, no other positive association was found specifically for the risk of adenomas with any of the exposure variables aforementioned. This study provides additional support for a positive association of high intake of red meat with colorectal adenomas, and suggests that high intake of meats and meat carcinogens may also be associated with hyperplastic polyps.

A case of adenomyomatous polyp of the uterus associated with tamoxifen therapy.

A case of adenomyomatous polyp of the uterine endometrium is reported. The patient was 64-year-old woman treated with tamoxifen. Ultrasonography demonstrated a heterogeneous hyperechoic mass with small cystic spaces in the uterus. On magnetic resonance imaging (MRI), a thick stalk with many thin restiform branches within a large solid and cystic endometrial mass showed dendriform low intensity on T2-weighted images and intense enhancement on contrast-enhanced T1-weighted images. The prominent dendriform central fibrous core on MRI reflected a thick stalk originating from the myometrium with numerous branches containing abundant smooth muscle fibers, and may represent the pathologic feature of adenomyomatous polyp.

[Risk of chronic stomach diseases and cancer in occupational exposure to monocyclic aromatic carbohydrates (benzol and its homologs)]. / Risk razvitiia khronicheskikh zabolevanii i raka zheludka u lits, kontaktirovavshikh v usloviiakh proizvodstva s monotsiklicheskimi aromaticheskimi uglevodorodami (benzolom i ego gomologami).

A statistically significant rise in the frequency of chronic atrophic gastritis, a precursor of cancer, has been identified in subjects exposed to monocyclic aromatic carbohydrates.

Evolution of alachlor-induced nasal neoplasms in the Long-Evans rat.

The chloracetanilide herbicide alachlor (2-chloro-2',6-diethyl-N-(methoxymethyl)-acetanilide) induces nasal neoplasms in rats following chronic dietary exposure. The present study sought to identify the cellular origin and mechanisms of tumor induction and progression. Male Long-Evans rats were fed alachlor (0 or 126 mg/kg/day) beginning at 6 weeks of age. Following 1 month of alachlor ingestion, neither histological abnormalities nor enhanced cell division (assessed by BrdU incorporation) occurred in any region of the nasal cavity. Six months of alachlor exposure resulted in proliferation of basal and nonbasal cells in the olfactory mucosa while inducing nasal masses in 7 of 15 animals. Tumors ranged from dysplastic plaques to polypoid adenomas and originated in the olfactory regions of the nasal cavity. Neoplasms were associated with regions of respiratory metaplasia and were often covered with a low cuboidal, poorly ciliated epithelium. Tumor cells did not express characteristics of the olfactory mucosa, including olfactory marker protein (OMP, for neurons) and NMa (antibody recognizing cytochrome P450 [CYP] 2A3, found in Bowman's glands). Sites of plaque and tumor development coincided with regions of NMa immunoreactivity. These data suggest that local metabolism is important in alachlor-induced olfactory tumors and support the concept that metaplastic respiratory epithelial cells give rise to the observed neoplasms.

High grade, synchronous colon cancers after renal transplantation: were immunosuppressive drugs to blame?

Recipients of renal transplants are known to have an increased incidence of cancer, which is believed to be related to the use of immunosuppressive drugs used to prevent rejection. Although the risks of lymphoma and Kaposi's sarcoma are clearly increased in this setting, the association with colon cancer is controversial. We report a 44-yr-old woman, 20 yr post-renal transplant, and with no family history of colorectal cancer or polyps, who was found to have synchronous, poorly differentiated colon cancers associated with extensive abdominal lymph node, bone marrow, and bone (skull) metastasis. The long term immunosuppressive drugs that she had received may have been an important factor in her tumor development and/or progression. Our case and literature review suggest a possible mild, increased risk of colon cancer development in patients after renal transplantation.

Phenolphthalein-containing laxative use in relation to adenomatous colorectal polyps in three studies.

Phenolphthalein, the active ingredient in many laxatives, was recently found to be a carcinogen in animal models. Human data suggest a laxative-colon cancer association, but few data specifically address the effects of phenolthalein-containing laxatives. We examined use of phenolphtalein-containing laxatives in relation to occurrence of adenomatous colorectal polyps in data from three case-control studies. The study conducted in Los Angeles, California (1991-1993), and the two studies conducted in North Carolina (1988-1990 and 1992-1995) altogether included 866 cases and 1,066 controls. The prevalence of using phenolphthalein-containing laxatives at least once a week in the recent past, however, was less than 5% among these subjects. The multivariate-adjusted odds ratios associated with recent use of phenolphthalein-containing laxatives once a week or more were 1.8 -95% confidence interval (CI), 0.5-6.2] in Los Angeles, 1.0 (CI, 0.4-2.2) in North Carolina (1988-1990), and 1.1 (CI, 0.2-5.7) in North Carolina (1992-1995). For use of other types of laxatives, the corresponding odds ratios were 1.3 (CI, 0.9-1.9) in Los Angeles, 1.0 (CI, 0.5-1.7) in North Carolina (1988-1990), and 0.9 (CI, 0.4-1.8) in North Carolina (1992-1995). Although the low prevalence of frequent use made for relatively wide confidence intervals, overall these data suggest that use of phenolphthalein-containing laxatives does not increase risk of adenomatous colorectal polyps.

Evaluation of the potential carcinogenicity and genetic toxicity to humans of the herbicide acetochlor.

Comprehensive toxicological studies of the herbicide acetochlor are presented and discussed. Although it gave a negative profile of responses in the many toxicity tests conducted there were some findings that prompted further investigation. First, although non-mutagenic in the Salmonella assay, acetochlor was clastogenic to mammalian cells treated in vitro. This clastogenic potential was not expressed in vivo in four rodent cytogenetic assays (bone marrow and germ cells). Second, although acetochlor gave a negative response in rat liver UDS assays when tested at the acute MTD, gavage administration of a single, supra-MTD dose (2000 mg/kg) gave a weak positive assay response. This dose-level (2000 mg/kg) was necrotic to the liver, depressed hepatic glutathione levels by up to approximately 80%, altered the metabolism of acetochlor, and was associated with up to 33% lethality. In contrast, reference liver genotoxins such as DMN, DMH and 2AAF were shown to elicit UDS in the absence of such effects, and at approximately 400 x lower dose-levels. Finally, microscopic nasal polypoid adenomas were induced in the rat when acetochlor was administered for two years at the maximum tolerated dose (MTD). The tumours were not life-threatening, they did not metastasize, and no DNA damage was induced in the nasal cells of rats maintained on a diet containing the MTD of acetochlor for either 1 or 18 weeks (comet assay). In order to probe the mechanism of action of these high dose toxicities a series of chemical and genetic toxicity studies was conducted on acetochlor and a range of structural analogues. These revealed the chloroacetyl substructure to be the clastogenic species in vitro. Although relatively inert, this substituent is preferentially reactive to sulphydryl groupings, most evidently, to glutathione (GSH). Similar chemical reactivity and clastogenicity in vitro was observed for two related chemicals bearing a chloroacetyl group, both of which have been defined as non-carcinogens in studies reported by the US.NTP. These collective observations indicate that the source of the clastogenicity of acetochlor in vitro is also the source of its rapid detoxification in the rat in vivo, via reaction with GSH. Metabolic studies of acetochlor are described which reveal the formation of a series of GSH-associated biliary metabolites in the rat that were not produced in the mouse. The metabolism of acetochlor in the rat changes with increasing dose-levels, probably because of depletion of hepatic GSH. It is most likely that a rat-specific metabolite is responsible for the rat nasal tumours observed uniquely at elevated dose-levels. The absence of genetic toxicity to the nasal epithelium of rats exposed acutely or subchronically to acetochlor favours a non-genotoxic mechanism for the induction of these adenomas. The observation of a time- and dose-related increase in S-phase cells in the nasal epithelium is consistent with this conclusion. Despite some confusion caused by the early use of perilethal gavage administrations of acetochlor to rodents, and supra-MTD dietary concentrations in some of the chronic studies, the available MTD data are consistent with acetochlor not posing a genetic or carcinogenic hazard to humans.