Multiplicity of Advanced T Category–Tumors Is a Risk Factor for Survival in Patients with Colorectal Carcinoma

Background Previous studies on synchronous colorectal carcinoma (SCRC) have reported inconsistent results about its clinicopathologic and molecular features and prognostic significance. Methods Forty-six patients with multiple advanced tumors (T2 or higher category) who did not receive neoadjuvant chemotherapy and/or radiotherapy and who are not associated with familial adenomatous polyposis were selected and 99 tumors from them were subjected to clinicopathologic and molecular analysis. Ninety-two cases of solitary colorectal carcinoma (CRC) were selected as a control considering the distributions of types of surgeries performed on patients with SCRC and T categories of individual tumors from SCRC. Results SCRC with multiple advanced tumors was significantly associated with more frequent nodal metastasis (p = .003) and distant metastasis (p = .001) than solitary CRC. KRAS mutation, microsatellite instability, and CpG island methylator phenotype statuses were not different between SCRC and solitary CRC groups. In univariate survival analysis, overall and recurrence-free survival were significantly lower in patients with SCRC than in patients with solitary CRC, even after adjusting for the extensiveness of surgical procedure, adjuvant chemotherapy, or staging. Multivariate Cox regression analysis revealed that tumor multiplicity was an independent prognostic factor for overall survival (hazard ratio, 4.618; 95% confidence interval, 2.126 to 10.030; p < .001), but not for recurrence-free survival (p = .151). Conclusions Findings suggested that multiplicity of advanced T category–tumors might be associated with an increased risk of nodal metastasis and a risk factor for poor survival, which raises a concern about the guideline of American Joint Committee on Cancer’s tumor-node-metastasis staging that T staging of an index tumor determines T staging of SCRC

Synchronous mucosal Schwann-cell hamartomas in a young adult suggestive of mucosal Schwann-cell harmatomatosis: a case report

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Mucosal Schwann-cell hamartoma is a rare mesenchymal polyp that presents in the intestine. Despite lacking ganglion cells, it resembles a gastrointestinal ganglioneuroma. Case presentation We report a case of synchronous mucosal Schwann-cell hamartomas in a young male patient, who presented with a single discrete polyp in the mid-rectum and multiple polypoid mucosal lesions in the distal rectum. Conclusion To the best of our knowledge, this is the first report of a case of multiple mucosal Schwann-cell hamartomas

Importância dos Saca-Rabos (Herpestes Ichneumon) como Reservatório de Mycobacterium avium subsp. paratuberculosis. Deteção por Técnicas Tradicionais e Moleculares

Poster apresentado nas IV Jornadas de Genética, realizadas na UTAD, Vila Real, nos dias 1,2 e 3 de Março de 2012.Os saca-rabos (Herpestes ichneumon) também conhecidos por mangustos, são carnívoros diurnos selvagens que juntamente com a geneta (Genetta genetta) representam os exemplares da família Viverridae em Portugal. É uma espécie cinegética de caça menor que se alimenta de coelhos, roedores, aves, cobras, insectos e ovos. Neste estudo colheram-se amostras de 8 animais mortos por atropelamento e em ações de controlo de predadores, durante os anos de 2010 e 2011, nos concelhos de Idanha-a-Nova e Penamacor do distrito de Castelo Branco. As amostras colhidas foram fígado, pulmão, baço, intestino, rim, gânglio mesentérico, retrofaríngeo, mediastínico, amígdalas e fezes. As amostras foram submetidas à técnica de PCR e a cultura microbiológica em meios específicos. Em três saca-rabos (37,5%) detectou-se Mycobacterium avium subsp. paratuberculosis (Map) através da técnica de biologia molecular. Dois eram machos e um era fêmea. Map foi confirmado também em cultura nos dois machos. Sete saca-rabos (87,5%) apresentaram bactérias álcool-ácido resistentes compatíveis com Map em esfregaços de diferentes tecidos, quando corados pelo método de Ziehl-Neelsen. Estes resultados preliminares confirmam os saca-rabos como reservatório de Map no nosso país. Atualmente, estão a ser desenvolvidos mais estudos para a avaliação dos saca-rabos na dinâmica da infeção de Map em mamíferos selvagens

Composite scoring system and optimal tumor budding cut-off number for estimating lymph node metastasis in submucosal colorectal cancer

Background Tumor budding is associated with lymph node (LN) metastasis in submucosal colorectal cancer (CRC). However, the rate of LN metastasis associated with the number of tumor buds is unknown. Here, we determined the optimal tumor budding cut-off number and developed a composite scoring system (CSS) for estimating LN metastasis of submucosal CRC. Methods In total, 395 patients with histologically confirmed T1N0–2M0 CRC were evaluated. The clinicopathological characteristics were subjected to univariate and multivariate analyses. The Akaike information criterion (AIC) values of the multivariate models were evaluated to identify the optimal cut-off number. A CSS for LN metastasis was developed using independent risk factors. Results The prevalence of LN metastasis was 13.2%. Histological differentiation, lymphatic or venous invasion, and tumor budding were associated with LN metastasis in univariate analyses. In multivariate models adjusted for histological differentiation and lymphatic or venous invasion, the AIC value was lowest for five tumor buds. Unfavorable differentiation (odds ratio [OR], 8.16; 95% confidence interval [CI], 1.80–36.89), lymphatic or venous invasion (OR, 5.91; 95% CI, 2.91–11.97), and five or more tumor buds (OR, 3.01; 95% CI, 1.21–7.69) were independent risk factors. In a CSS using these three risk factors, the rates of LN metastasis were 5.6%, 15.5%, 31.0%, and 52.4% for total composite scores of 0, 1, 2, and ≥ 3, respectively. Conclusions For the estimation of LN metastasis in submucosal CRC, the optimal tumor budding cut-off number was five. Our CSS can be utilized to estimate LN metastasis.This work was supported by the Korean government (MSIT) Grant No. 2021R1F1A1063000 from the National Research Foundation of Korea (NRF)

Protective Immunity Against Challenge Infection with Trichinella spiralis in the Rat

Protective immunity and immune response were studied in rats after primarily infection with Trichinella spiralis. The parameters measured include serum antibody isotype responses, mesenteric lymph node (MLN) cell and spleen cell proliferation responses in vitro, and the levels of interferon (IFN)-γ, interleukin (IL)-2, IL-4 and IL-10 as markers of the T-helper (Th) subset. Protective immunity was assessed by the degree of expulsion of adult worms from the rat intestine. Protective immunity against adult worms after challenge infection was 99.80%. Although IFN-γ, IL-2, IL-4 and IL-10 in both the MLNs and spleen were detected, IFN-γ and IL-2 levels were higher in the spleen than in the MLNs, and IL-4 and an increased amount of IL-10 was released in the MLNs as compared to the spleen. The levels of the specific immunoglobulins (Ig) G, IgM, IgG1 and IgG2a on week 6 after primary infection, and on day 7 after challenge infection, were higher as compared to levels in uninfected rats that only received a challenge infection (P ? 0.001), whereas the antibody level of IgG1 was significantly elevated from that of IgG2a (P ? 0.001). These results demonstrate that Th1 type responses predominated. In addition, as Th2 type cytokines were also produced, it is proposed that the protective immunity by primary infection was also related to the Th1 type responses

Association of pathway mutation with survival after recurrence in colorectal cancer patients treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapy

Background Although the prognostic biomarkers associated with colorectal cancer (CRC) survival are well known, there are limited data on the association between the molecular characteristics and survival after recurrence (SAR). The purpose of this study was to assess the association between pathway mutations and SAR. Methods Of the 516 patients with stage III or high risk stage II CRC patients treated with surgery and adjuvant chemotherapy, 87 who had distant recurrence were included in the present study. We analyzed the association between SAR and mutations of 40 genes included in the five critical pathways of CRC (WNT, P53, RTK-RAS, TGF-β, and PI3K). Results Mutation of genes within the WNT, P53, RTK-RAS, TGF-β, and PI3K pathways were shown in 69(79.3%), 60(69.0%), 57(65.5%), 21(24.1%), and 19(21.8%) patients, respectively. Patients with TGF-β pathway mutation were younger and had higher incidence of mucinous adenocarcinoma (MAC) histology and microsatellite instability-high. TGF-β pathway mutation (median SAR of 21.6 vs. 44.4 months, p = 0.021) and MAC (20.0 vs. 44.4 months, p = 0.003) were associated with poor SAR, and receiving curative resection after recurrence was associated with favorable SAR (Not reached vs. 23.6 months, p <  0.001). Mutations in genes within other critical pathways were not associated with SAR. When MAC was excluded as a covariate, multivariate analysis revealed TGF-β pathway mutation and curative resection after distant recurrence as an independent prognostic factor for SAR. The impact of TGF-β pathway mutations were predicted using the PROVEAN, SIFT, and PolyPhen-2. Among 25 mutations, 23(92.0%)-24(96.0%) mutations were predicted to be damaging mutation. Conclusions Mutation in genes within TGF-β pathway may have negative prognostic role for SAR in CRC. Other pathway mutations were not associated with SAR.This research was supported by the Seoul National University Hospital (SNUH) Research Fund (03–2014-0440) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1277 and HI13C2163). The funding bodies had no influence on the design of the study and collection, analysis, and interpretation of data and in writing the manuscript

Blood-testis barrier integrity depends on Pin1 expression in Sertoli cells

The conformation and function of a subset of serine and threonine-phosphorylated proteins are regulated by the prolyl isomerase Pin1 through isomerization of phosphorylated Ser/Thr-Pro bonds. Pin1 is intensely expressed in Sertoli cells, but its function in this post mitotic cell remains unclear. Our aim was to investigate the role of Pin1 in the Sertoli cells. Lack of Pin1 caused disruption of the blood-testis barrier. We next investigated if the activin pathways in the Sertoli cells were affected by lack of Pin1 through immunostaining for Smad3 protein in testis tissue. Indeed, lack of Pin1 caused reduced Smad3 expression in the testis tissue, as well as a reduction in the level of N-Cadherin, a known target of Smad3. Pin1&minus;/&minus; testes express Sertoli cell marker mRNAs in a pattern similar to that seen in Smad3+/&minus; mice, except for an increase in Wt1 expression. The resulting dysregulation of N-Cadherin, connexin 43, and Wt1 targets caused by lack of Pin1 might affect the mesenchymal&ndash;epithelial balance in the Sertoli cells and perturb the blood-testis barrier. The effect of Pin1 dosage in Sertoli cells might be useful in the study of toxicant-mediated infertility, gonadal cancer, and for designing male contraceptives