Analysis of therapeutic mechanism of Liushen Wan against colitis-associated colorectal cancer based on network pharmacology and validation in mice / 南方医科大学学报

OBJECTIVE@#To explore the therapeutic mechanism of Liushen Wan (LSW) against colitis-associated colorectal cancer (CAC) by network pharmacology.@*METHODS@#TCMSP, BATMAN-TCM, CNKI, PubMed, Genecards, OMIM, and TTD databases were used to obtain the related targets of LSW and CAC. The common targets of LSW and CAC were obtained using Venny online website. The PPI network was constructed using Cytoscape 3.8.2 to screen the core targets of LSW in the treatment of CAC. GO and KEGG enrichment analysis were conducted using DAVID database. The therapeutic effect of LSW on CAC was evaluated in a C57BL/6J mouse model of AOM/DSS-induced CAC by observing the changes in body weight, disease activity index, colon length, and size and number of the tumor. HE staining and RT-qPCR were used to analyze the effect of LSW on inflammatory mediators. Immunohistochemistry and TUNEL staining were used to evaluate the effect of LSW on the proliferation and apoptosis of AOM/DSS-treated colon tumor cells. Immunohistochemistry and Western blotting were used to detect the effects of LSW on the expression of TLR4 proteins in CAC mice.@*RESULTS@#Network pharmacology analysis identified 69 common targets of LSW and CAC, and 33 hub targets were screened in the PPI network. KEGG pathway enrichment analysis suggested that the effect of LSW on CAC was mediated by the Toll-like receptor signaling pathway. In the mouse model of AOM/DSS-induced CAC, LSW significantly inhibited colitis-associated tumorigenesis, reduced tumor number and tumor load (P < 0.05), obviously improved histopathological changes in the colon, downregulated the mRNA levels of proinflammatory cytokines, and inhibited the proliferation (P < 0.01) and promoted apoptosis of colon tumor cells (P < 0.001). LSW also significantly decreased TLR4 protein expression in the colon tissue (P < 0.05).@*CONCLUSION@#LSW can inhibit CAC in mice possibly by regulating the expression of TLR4 to reduce intestinal inflammation, inhibit colon tumor cell proliferation and promote their apoptosis.

Recognition of the membrane anatomy-based laparoscopic assisted right hemicolectomy / 中华胃肠外科杂志

Although it has become a consensus in the field of colorectal surgery to perform radical tumor treatment and functional protection under the minimally invasive concept, there exist many controversies during clinical practice, including the concept of embryonic development of abdominal organs and membrane anatomy, the principle of membrane anatomy related to right hemicolectomy, D3 resection, and identification of the inner boundary. In this paper, we analyzed recently reported literature with high-level evidence and clinical data from the author's hospital to recognize and review the membrane anatomy-based laparoscopic assisted right hemicolectomy for right colon cancer, emphasizing the importance of priority of surgical dissection planes, vascular orientation, and full understanding of the fascial space, and proposing that the surgical planes should be dissected in the parietal-prerenal fascial space, and the incision should be 1 cm from the descending and horizontal part of the duodenum. The surgery should be performed according to a standard procedure with strict quality control. To identify the resection range of D3 dissection, it is necessary to establish a clinical, imaging, and pathological evaluation model for multiple factors or to apply indocyanine green and nano-carbon lymphatic tracer intraoperatively to guide precise lymph node dissection. We expect more high-level evidence of evidence-based medicine to prove the inner boundary of laparoscopic assisted radical right colectomy and a more rigorous consensus to be established.

Neoadjuvant immunotherapy for colorectal cancer / 中华胃肠外科杂志

Immunotherapy has been one of the hot topics in the field of colorectal cancer research in recent years. Patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) are the main beneficiaries of immunotherapy. The response rate of patients with dMMR/MSI-H colorectal cancer receiving neoadjuvant immunotherapy is nearly 100%, of which the pathological complete response rate approximately accounts for 60%-67%. The prospect of neoadjuvant immunotherapy in dMMR or MSI-H colorectal cancer patients, especially in the rectal cancer patients, lies in achieving sustainable clinical complete response so as to achieve organ preservation and avoid adverse effects on reproductive, sexual, bowel and bladder function after surgery and radiotherapy. Studies have shown that part of the colorectal cancer patients of microsatellite stability (MSS) or mismatch repair proficient (pMMR) can respond to neoadjuvant immunotherapy in combination with other treatment methods such as radiotherapy and chemotherapy. In pMMR or MSS colorectal cancer, optimizing neoadjuvant immunotherapy regimens and finding effective efficacy prediction biomarkers are important research directions. In neoadjuvant immunotherapy, overcoming primary and secondary resistance and identifying the pseudoprogression and hyperprogression of neoadjuvant immunotherapy are clinical challenges that require attention. This paper comprehensively reviews the research progress, controversies,challenges and future research directions of neoadjuvant immunotherapy (mainly immune checkpoint inhibitors) in colorectal cancer.

Diagnosis of advanced disease in cases of colorectal cancer in a developing country

Objectives Colorectal cancer (CRC) is the second leading cause of cancer death in the world, with survival correlated with the extension of the disease at diagnosis. In many low-/middle-income countries, the incidence of CRC is increasing rapidly, while decreasing rates are observed in high-income countries. We evaluated the anatomopathological profile of 390 patients diagnosed with CRC who underwent surgical resection, over a six-year period, in the state of Paraíba, northeastern Brazil. Results Adenocarcinomas accounted for 98% of the cases of primary colorectal tumors, and 53.8% occurred in female patients. The average age of the sample was 63.5 years, with 81.8% of individuals older than 50 years of age and 6.4% under 40 years of age. The most frequent location was the distal colon; pT3 status was found in 71% of patients, and pT4 status, in 14.4%. Angiolymphatic and lymph-node involvements were found in 48.7% and 46.9% of the cases respectively. Distant metastasis was observed in 9.2% of the patients. Advanced disease was diagnosed in almost half of the patients (48.1%). The women in the sample had poorly-differentiated adenocarcinomas (p=0.043). Patients under 60 years of age had a higher rate of lymph-node metastasis (p=0.044). Tumor budding was present in 27.2% of the cases, and it was associated with the female gender, themucinous histological type, and the depth of invasion (pT3 and pT4). Conclusions We conclude that the diagnosis of advanced disease in CRC is still a reality, with a high occurrence of aggressive prognostic factors, which results in a worse prognosis. (AU)

Exactitud diagnóstica de la tomografía computarizada en la estadificación del cáncer de colon / Diagnostic accuracy of computed tomography in colon cancer staging

Resumen Introducción: Una terapia emergente para el cáncer de colon es la neoadyuvancia, en casos seleccionados. Dicha selección se basa en el análisis preoperatorio de imágenes mediante tomografía computada. Objetivo: Nuestro objetivo es determinar la exactitud diagnóstica del examen para estadificar el cáncer de colon y su correlación entre radiólogos expertos. Materiales y Método: Estudio de exactitud diagnóstica. Previo cálculo muestral se seleccionaron aleatoriamente 47 pacientes con adenocarcinoma colónico resecado con intención curativa e imágenes hasta 60 días previo cirugía. Se evaluó profundidad de invasión tumoral e invasión linfonodal por 2 radiólogos expertos y ciegos entre sí. Las diferencias fueron auditadas por un tercer radiólogo experto. Se compararon resultados con la biopsia, calculando la sensibilidad, especificidad, valor predictivo negativo, valor predictivo positivo y exactitud diagnóstica del examen. Se calculó la concordancia entre radiólogos mediante el índice de kappa. Resultados: La exactitud para diferenciar tumores T3-T4 de T1-T2 fue del 89,4%. En cambio, la capacidad para diferenciar tumores T4 de los T3 fue de un 65,9%. La exactitud para determinar un N (+) fue de un 66%. La concordancia entre radiólogos fue de 0,929 para identificar tumores T1-2, de 0,602 para T3, de 0,584 para T4. Para determinar un N (+), la concordancia fue de 0,521. Conclusión: La exactitud diagnóstica de la tomografía computada en cáncer de colon es adecuada para distinguir tumores avanzados. Sin embargo, su capacidad para discriminar entre T3 y T4, los N (+) y la baja concordancia entre radiólogos, sugiere la necesidad de buscar técnicas imagenológicas complementarias.

Introduction: Neoadjuvant therapy is an emerging treatment for selected cases of colon cancer. The decision is based on the analysis of preoperative images taken by computed tomography. However, its ability to discriminate those who could benefit from this therapy is unknown. Aim: Our objective is to determine the diagnostic accuracy of computed tomography to evaluate the colon cancer stage and its correlation among expert radiologists. Materials and Method: Diagnostic accuracy study. After sample size calculation, we randomly selected 47 patients who underwent a colonic adenocarcinoma resection with curative intent and had available images up to 60 days after surgery. The depth of tumor and lymph nodal invasion were evaluated by two expert radiologists, blinded to each other. The differences between radiologists were audited by a third one. The results were correlated with biopsy as the gold standard. We calculated sensitivity, specificity, negative predictive value, positive predictive value, and diagnostic accuracy of computed tomography. The agreement between radiologists was calculated using the kappa index. Results: The accuracy to differentiate T3-T4 tumors from T1-T2 was 89.4%. In contrast, ability to differentiate T4 tumors from T3 tumors was 65.9%. The accuracy to determine an N (+) was 66%. Agreement between radiologists was 0.929 to identify T1-2, 0.602 for T3, 0.584 for T4 tumors. To determine an N (+), the concordance was 0.521. Conclusion: Diagnostic computed tomography accuracy in colon cancer is adequate to differentiate advanced tumors. However, its ability to discriminate between T3 and T4, N (+) and the low agreement between radiologists suggests the need for complementary imaging techniques.

Progress in pulmonary enteric adenocarcinoma / 中华肿瘤杂志

Pulmonary enteric adenocarcinoma (PEAC), as a rare histologic subtype of primary lung adenocarcinoma, is defined as an adenocarcinoma in which the enteric component exceeds 50%. It is named after its shared morphological and immunohistochemical features with colorectal cancer. While with such similarity, the differential diagnosis of PEAC and lung metastatic colorectal cancer is a great challenge in the clinic. PEAC may originate from the intestinal metaplasia of respiratory basal cells stimulated by risk factors such as smoking. Current studies have found that KRAS is a relatively high-frequency mutation gene, and other driver gene mutations are rare. In terms of immunohistochemistry, in pulmonary enteric adenocarcinoma, the positive rate was 88.2% (149/169) for CK7, 78.1% (132/169) for CDX2, 48.2% (82/170) for CK20 and 38.8% (66/170) for TTF1. As for clinical features, the average age of onset for pulmonary enteric adenocarcinoma was 62 years, male patients accounted for 56.5% (35/62), smokers accounted for 78.8% (41/52), and 41.4% (24/58) of the primary lesion was located in the upper lobe of the right lung. In terms of treatment, conventional non-small cell lung cancer (NSCLC) regimens rather than colorectal cancer regimens are now recommended. There is still an urgent need for more basic and clinical research, in-depth exploration of its molecular feature and pathogenesis from the level of omics and other aspects, to help diagnosis and differential diagnosis, and find the optimal chemotherapy regimen, possibly effective targeted therapy and even immunotherapy.

METTL27 is a prognostic biomarker of colon cancer and associated with immune invasion / 南方医科大学学报

OBJECTIVE@#To investigate the expression and gene function of methyltransferase-like protein 27 (METTL27) in colon cancer, its association with immune infiltration and its prognostic significance.@*METHODS@#We analyzed the expression levels of METTL27 in 33 cancers using R language and identified METTL27 as a differential gene in colon cancer. The related signaling pathways of METTL27 were analyzed by gene functional annotation and enrichment. SsGSEA algorithm was used to analyze immune infiltration, and logistic analysis was used to evaluate the correlation between METTL27 expression and clinicopathological features of the patients. Kaplan-meier analysis, univariate and multivariate Cox regression analysis were performed to construct a nomogram for evaluating the correlation between METTL27 expression and clinical prognosis. The expression level of METTL27 was further verified in colorectal cancer cell lines and 16 clinical specimens of colorectal cancer tissues using qPCR and Western blotting.@*RESULTS@#METTL27 was highly expressed in 21 cancers, and its expression was significantly higher in colon cancer than in adjacent tissues (P < 0.001). METTL27-related genes were identified by differential analysis, and functional annotation revealed that METTL27 was significantly enriched in transmembrane transport and lipid metabolism, and 5 related signaling pathways were identified by GSEA. METTL27 expression was negatively correlated with different T helper cells and central memory T cells (P < 0.001). The patients with a high METTL27 mRNA expression had a poor survival outcome. Cox regression analysis showed that METTL27 expression was an independent prognostic factor of the overall survival. The expression level of METTL27 was significantly higher in the colorectal cancer cell line than in normal cells (P < 0.05).@*CONCLUSION@#METTL27 is overexpressed in colon cancer and is associated with a poor prognosis of the patients. A high expression of METTL27 showed is associated less T cell immune infiltration, suggesting the potential of METTL27 as a prognostic marker of colon cancer.

Understanding and Targeting the Colon Cancer Pathogenesis: A Molecular Perspective

Abstract Colorectal cancer (CRC) one of the leading cause of cancer-related deaths worldwide. With the presently available knowledge on CRC, it is understood that the underlying is a complex process. The complexity of CRC lies in aberrant activation of several cellular signaling pathways that lead to activation and progression of CRC. In this context, recent studies have pointed towards the role of developmental pathways like; hedgehog (HH), wingless-related integration site (WNT/ß-catenin) and Notch pathways that play a crucial role in maintenance and homeostasis of colon epithelium. Moreover, the deregulation of these signaling pathways has also been associated with the pathogenesis of CRC. Therefore, in the search for better therapeutic options, these pathways have emerged as potential targets. The present review attempts to highlight the role of HH, WNT/ß-catenin and Notch pathways in colon carcinogenesis

Selective Cytotoxic effect of Probiotic, Paraprobiotic and Postbiotics of L. casei strains against Colorectal Cancer Cells: Invitro studies

Abstract This study highlights the cytotoxic effect of three L. casei strains on colorectal cell lines in invitro conditions. Different concentrations of live, heat killed (HK) and cell free supernatant (CFS) of three L.casei strains were subjected to CaCo2 and MRC5 cell lines. The viability of the treated and untreated cells was determined after 72 hrs by MTT assay, and IC50 estimated. Apoptosis was evaluated by Annexin V-propidium iodide method using flow cytometry. The live, HK and CFS of the L. casei strains showed cytotoxic effects on colorectal cell lines with significant differences. The cytotoxicity effects of live cells on CaCo2 cells were significantly higher (p˂0.01) than the HK cells. A dose dependent response was observed, as higher concentrations resulted in enhanced cytotoxicity effects. Live L.casei 1296-2cells inhibited 91% of CaCo2 cell growth, with IC50 of less than 108 cfu/ml. MRS medium and concentrations of CFS at above 20% v/v, were cytotoxic to the normal cell lines. Flow cytometry analyses of L. casei 1296-2 indicated that cytotoxicity effects on CaCo2 cells is related to apoptotic induction. Invitro studies indicate that Live and CFS of L. casei 1296-2 might be promising candidate for the control of colorectal cancers

Innovative pharmaceutical strategies for niclosamide repositioning / Estratégias farmacêuticas inovadoras para o reposicionamento da niclosamida

The antiparasitic niclosamide has shown promising anticancer activity in preclinical studies against several types of cancer, such as colorectal and prostate. Thus, the objective of this work was to develop innovative formulations for the repositioning of niclosamide as an anticancer agent. In chapter I, a critical review of the literature on the physicochemical properties of the drug was carried out, in addition the results of clinical studies against colorectal and prostate cancer. Besides, a review was carried out on studies that developed formulations containing this drug, as well as hypotheses to improve the biopharmaceutical performance of this molecule. In chapter II, the development of solid amorphous dispersion containing niclosamide was carried out. Drug/polymer solutions were acoustic levitated and characterized by synchrotron X-ray light. This set allowed fast, high quality measurements, as well as the identification of niclosamide recrystallization. Plasdone® and Soluplus® demonstrated better properties to form amorphous dispersions, with the latter showing superior solubility enhancement. The study showed that the developed formulation increased the apparent saturation solubility of niclosamide in water by two times. In chapter III the objective was the development, physicochemical characterization and in vitro anticancer activity of a niclosamide nanoemulsion, having HCT-116 cells as a cellular model. Preliminary results indicated Capmul® MCM C8 as the best liquid lipid for the system, but the first nanoemulsions containing this lipid were not stable to justify its usage. On the other hand, Miglyol® 812 indicated to be a suitable liquid lipid for the system. The niclosamide nanoemulsion (~200 nm) with Miglyol® 812 and poloxamer 188 was stable for 56 days, with a monomodal particle size distribution. Cell viability assay against HCT-116 cells demonstrated that niclosamide cytotoxicity is time and concentration dependent. Results herein obtained encourage further research to understand and optimize niclosamide performance as an anticancer drug substance

O antiparasitário niclosamida tem apresentado promissora atividade anticâncer em estudos pré- clínicos contra diversos tipos de câncer, como coloretal e próstata. Assim, o objetivo deste trabalho foi desenvolver formulações inovadoras para o reposicionamento da niclosamida como agente anticâncer. No capítulo I foi realizada revisão crítica da literatura sobre as propriedades físico-químicas do fármaco, além de resultados de estudos clínicos da niclosamida contra câncer de coloretal e de próstata. Além disso, foi feita revisão sobre estudos que desenvolveram formulações contendo esse fármaco, bem como hipóteses para melhorar o desempenho biofarmacêutico dessa molécula. No capítulo II foi realizado o desenvolvimento de dispersão solida amorfa contendo niclosamida. Soluções de fármaco/polímero foram levitadas em levitador acústico e caracterizadas por raios-X de luz síncrotron. Este conjunto permitiu medições rápidas e de alta qualidade, bem como identificação de recristalização da niclosamida. Plasdone® e Soluplus® demonstraram melhores propriedades para formar as dispersões amorfas, com o último apresentando aumento de solubilidade superior. O estudo mostrou que a formulação desenvolvida aumentou em duas vezes a solubilidade aparente de saturação da niclosamida em água. No capítulo III o objetivo foi o desenvolvimento, a caracterização físicoquímica e atividade anticâncer in vitro de uma nanoemulsão de niclosamida, tendo células HCT-116 como modelo celular. Resultados preliminares indicaram o Capmul® MCM C8 como o melhor lipídio líquido para o sistema, mas as primeiras nanoemulsões contendo este lipídio não foram estáveis para justificar seu uso. Por outro lado, Miglyol® 812 indicou ser um lipídio líquido adequado para o sistema. A nanoemulsão de niclosamida (~200 nm) com Miglyol® 812 e poloxâmero 188 foi estável por 56 dias, com distribuição monomodal do tamanho de partícula. O ensaio de viabilidade celular contra células HCT-116 demonstrou que a citoxicidade da niclosamida é dependente do tempo e da concentração. Os resultados aqui obtidos encorajam mais pesquisas para entender e otimizar o desempenho da niclosamida como uma substância anticancerígena

Tumor de colon como hallazgo incidental en un paciente con endocarditis por Streptococcus gallolyticus: experiencia desde la práctica clínica / Colon tumor as an incidental finding in a patient with endocarditis due to Streptococcus gallolyticus: experience from clinical practice

El Streptococcus gallolyticus del colon. La fisiopatología que explica este fenómeno implica el aumento local de niveles de lactato puede presentarse como el germen causal de la endocarditis infecciosa en pacientes con lesiones premalignas y malignas, colágeno, fibrinógeno y fibronectina secundario a la hiperactividad metabólica tumoral que genera un ambiente adecuado para el crecimiento y adhesión bacteriana a la pared intestinal y posterior translocación al torrente sanguíneo. Simultáneamente, se establece la presencia de infecciones secundarias por la formación de biofilms, tanto a nivel colorrectal como en válvulas cardíacas. El objetivo del manuscrito es un mapeo en la literatura médica disponible sobre la correlación entre la endocarditis por Streptococcus gallolyticus y las lesiones premalignas y malignas de colon. Simultáneamente, exponer la experiencia clínica de un hombre de 82 años con diagnóstico de endocarditis por Streptococcus gallolyticus y el hallazgo incidental de pólipos adenomatosos del colon(AU)

Streptococcus gallolyticus can present as the causative germ of infective endocarditis in patients with premalignant and malignant lesions of the colon. The pathophysiology that explains this phenomenon involves the local increase in lactate that can be presented as the causal germ of infective endocarditis in patients with premalignant and malignant lesions, collagen, fibrinogen, and fibronectin levels secondary to tumor metabolic hyperactivity, which generates a suitable environment for bacterial growth and adhesion to the intestinal wall and subsequent translocation to the bloodstream. Simultaneously, the presence of secondary infections is established due to the formation of biofilms, both at the colorectal level and in the heart valves. The objective of the manuscript is a mapping in the available medical literature on the correlation between Streptococcus gallolyticus endocarditis and premalignant and malignant colonic lesions. Simultaneously, to present the clinical experience of an 82-year-old man diagnosed with Streptococcus gallolyticus endocarditis and the incidental finding of adenomatous polyps of the colon(AU)

Simultaneous resection for colon cancer and synchronous liver metastases: case series with follow-up / Resección simultánea por cáncer de colon y metástasis hepáticas sincrónicas: serie de casos con seguimiento

SUMMARY: Treatment of colonic cancer (CC) and synchronic liver metastasis (SLM) is still controversial in relation to how to act. The aim of this study was to analyze initial single center experience in simultaneous surgical approach of patients with CC and SLM, in terms of overall survival (OS) and disease-free survival (DFS). Retrospective case series of patients with CC and SLM undergoing simultaneous surgery, consecutively, at Clínica RedSalud Mayor Temuco, between 2007 and 2021. Outcome variables were OS and DFS. Other variables of interest were postoperative morbidity (POM), surgical time, hospital stay and mortality. Descriptive statistics was used (measures of central tendency and dispersion), and survival analysis was estimated applying Kaplan Meier curves. Sixteen patients (10 female and 6 male) were operated, with a median age of 61 years. The most frequent localization was cecum and right colon (37.5 %). In all patients some type of liver resection was added (parenchymal-sparing hepatectomy or anatomical resection). Median surgical time and hospital stay were 150 min and 5 days respectively. POM was 31.2 % (5 cases), mainly Clavien & Dindo I and II (12.5 % of patients required a re-intervention). With a median follow-up of 52 months 1, 3 and 5-year OS were 100 %, 62.5 %, and 50.0 % respectively. On the other hand, DFS rates of 1, 3 and 5-year were 75.0 %, 43.8 %, and 25.0 % respectively. The series had no mortality. OS, DFS, POM and mortality, were like other series. Simultaneous resection of CC and SLM is an aggressive approach, but not compromise oncological outcomes.

RESUMEN: El tratamiento del cáncer de colon (CC) con metástasis hepática sincrónica (MHS), tiene un tratamiento controvertido aún. El objetivo de este estudio fue analizar la experiencia unicéntrica en el tratamiento de pacientes con CC y MHS simultáneo, en términos de supervivencia global (SG) y supervivencia libre de enfermedad (SLE). Serie de casos retrospectiva consecutiva, de pacientes con CC y MHS sometidos a cirugía simultánea, en Clínica RedSalud Mayor Temuco, entre 2007 y 2021. Las variables de resultado fueron SG y SLE. Otras variables de interés fueron la morbilidad postoperatoria (MPO), tiempo quirúrgico, estancia hospitalaria y mortalidad. Se utilizó estadística descriptiva (medidas de tendencia central y dispersión) y se estimó supervivencia aplicando curvas de Kaplan Meier. Se operaron 16 pacientes (10 mujeres y 6 hombres), con mediana de edad de 61 años. La localización más frecuente fue ciego-colon derecho (37,5 %). En todos los casos se practicó algún tipo de resección hepática (hepatectomía conservadora o resección anatómica). La mediana del tiempo quirúrgico y la estancia hospitalaria fueron de 150 min y 5 días respectivamente. La MPO fue del 31,2 % (5 casos), principalmente Clavien & Dindo I y II (hubo 12,5 % de reintervenciones). Con una mediana de seguimiento de 52 meses. La SG a 1, 3 y 5 años fue 100 %, 62,5 % y 50,0 %, respectivamente. Por otro lado, la SLE a 1, 3 y 5 años fue 75,0 %, 43,8 % y 25,0 %, respectivamente. La serie no tuvo mortalidad. La SG, SLE, MPO y la mortalidad fueron similares a otras series. La resección simultánea de CC y SLM es agresiva, pero no compromete los resultados oncológicos.

Chemical composition, antiproliferative and antioxidant attributes of ethanolic extract of resinous sediment from Etlingera elatior (Jack. ) inflorescence

The ethanolic extract of resinous sediment (EERS) of Etlingera elatior young inflorescence was examined for its anticancer effect and potential antioxidant activity. The anticancer effect of the EERS was evaluated on four human cancer cell lines, HCT 116, HT-29, Hela, and MCF-7, using the MTT assay. GC-MS analysis showed that the main components found in the EERS were nonyl cyclopropane (4.44%), 1-tetradecane (3.66%), cyclotetradecane (2.41%), cyclododecane (1.92%), and 1-decene (1.72%). The antioxidant activity was determined through different methods. High amounts of TPC and TFC in the EERS were found. Moderate antioxidant capacity of the EERS was detected by DPPH and ABTS assays, with EC50 values of 44.19 and 56.61 µg/mL and a high FRAP value of 281.79 nmol Fe+2 equivalent/mg extract. In the MTT assay, the EERS showed potent anticancer activity, with IC50 values of 19.82, 37.001, 50.49, and 53.29 µg/mL against HT-29, HCT 116, Hela, and MCF-7 tumour cell lines, respectively. Moreover, the results were comparable to or less potent than the standard reference drug, 5-fluorouracil. The results showed that the EERS of Etlingera elatior inflorescence contained a high amount of polyphenols and flavonoids, which may to the selective antiproliferative effects towards colon cancer in vitro

Sobrevida de pacientes com câncer colorretal em um Cancer Center / Survival of patients with colorectal cancer in a cancer center

ABSTRACT BACKGROUND: Hospital-based studies recently have shown increases in colorectal cancer survival, and better survival for women, young people, and patients diagnosed at an early disease stage. OBJECTIVE: To describe the overall survival and analyze the prognostic factors of patients treated for colorectal cancer at an oncology center. METHODS: The analysis included patients diagnosed with colon and rectal adenocarcinoma between 2000 and 2013 and identified in the Hospital Cancer Registry at A.C.Camargo Cancer Center. Overall 5-year survival was estimated using the Kaplan-Meier method, and prognostic factors were evaluated in a Cox regression model. Hazard ratios (HR) are reported with 95% confidence intervals (CI). RESULTS: Of 2,279 colorectal cancer cases analyzed, 58.4% were in the colon. The 5-year overall survival rate for colorectal cancer patients was 63.5% (65.6% and 60.6% for colonic and rectal malignancies, respectively). The risk of death was elevated for patients in the 50-74-year (HR=1.24, 95%CI =1.02-1.51) and ≥75-year (HR=3.02, 95%CI =2.42-3.78) age groups, for patients with rectal cancer (HR=1.37, 95%CI =1.11-1.69) and for those whose treatment was started >60 days after diagnosis (HR=1.22, 95%CI =1.04-1.43). The risk decreased for patients diagnosed in recent time periods (2005-2009 HR=0.76, 95%CI =0.63-0.91; 2010-2013 HR=0.69, 95%CI =0.57-0.83). CONCLUSION: Better survival of patients with colorectal cancer improves with early stage and started treatment within 60 days of diagnosis. Age over 70 years old was an independent factor predictive of a poor prognosis. The overall survival increased to all patients treated in the period 2000-2004 to 2010-2013.

RESUMO CONTEXTO: Estudos hospitalares recentes têm demonstrado aumento da sobrevida do câncer colorretal e melhor sobrevida para mulheres, jovens e pacientes diagnosticados em estágio precoce da doença. OBJETIVO: Descrever a sobrevida global e analisar os fatores prognósticos de pacientes tratados para câncer colorretal em um centro de oncologia. MÉTODOS: Foram incluídos pacientes com diagnóstico de adenocarcinoma de cólon e reto entre 2000 e 2013, identificados no Registro Hospitalar de Câncer do A.C.Camargo Cancer Center. A sobrevida global aos 5 anos foi estimada pelo método de Kaplan-Meier e os fatores prognósticos foram avaliados pelo modelo de Cox. As razões de risco (HR) são relatadas com intervalos de confiança (IC) de 95%. RESULTADOS: Dos 2.279 casos de câncer colorretal analisados, 58,4% eram de cólon. A taxa de sobrevida global aos 5 anos para pacientes com câncer colorretal foi de 63,5% (65,6% e 60,6% para câncer de cólon e retal, respectivamente). O risco de óbito foi elevado para pacientes na faixa etária de 50-74 anos (HR=1,24; IC95% =1,02-1,51) e ≥75 anos (HR=3,02; IC95% =2,42-3,78), para pacientes com câncer retal (HR=1,37; IC95% =1,11-1,69) e para aqueles cujo tratamento foi iniciado >60 dias após o diagnóstico (HR=1,22; IC95% =1,04-1,43). O risco diminuiu para pacientes diagnosticados em períodos recentes (2005-2009 HR=0,76; IC95% =0,63-0,91; 2010-2013 HR=0,69; IC95% =0,57-0,83). CONCLUSÃO: A sobrevida dos pacientes com câncer colorretal é maior naqueles em estágio inicial e com início do tratamento antes dos 60 dias.. Idade acima de 70 anos foi fator independente preditivo de mau prognóstico. A sobrevida global aumentou para todos os pacientes tratados no período de 2000-2004 a 2010-2013.

Development, in vitro biocompatibility, and antitumor efficacy of acetic acid-modified Cordyceps sinensis polysaccharide nanoparticle drug delivery system

Docetaxel-loaded acetic acid conjugated Cordyceps sinensis polysaccharide (DTX-AA-CSP) nanoparticles were prepared through dialysis and their release rates in vitro, particle sizes, zeta potentials, drug loading capacities, and encapsulation efficiencies were characterized for the synthesis of AA-modified CSPs from traditional Chinese medicine Cordyceps sinensis (Berk.) Sacc. Then, the AA-modified CSPs were characterized by 1H-NMR and FT-IR. Furthermore, the biocompatibility of the delivery carrier (AA-CSP nanoparticles) was assessed on human umbilical vein endothelial cells. In vitro antitumor activity studies on DTX-AA-CSP nanoparticles were conducted on the human liver (HepG2) and colon cancer cells (SW480). The DTX-AA-CSP nanoparticles were spherical and had an average size of 98.91±0.29 nm and zeta potential within the −19.75±1.13 mV. The encapsulation efficiency and loading capacity were 80.95%±0.43% and 8.09%±0.04%, respectively. In vitro, DTX from the DTX-AA-CSP nanoparticles exhibited a sustained release, and the anticancer activities of DTX-AA-CSP nanoparticles against SW480 and HepG2 were significantly higher than those of marketed docetaxel injection (Taxotere®) in nearly all the tested concentrations. The AA-CSP nanoparticles showed good biocompatibility. This study provided a promising biocompatible delivery system for carrying antitumor drugs for cancer therapy

Sarcopenia como factor predictivo de dehiscencia de anastomosis en pacientes operados de cáncer de colon / Predictive value of sarcopenia for anastomotic dehiscense in colon cancer surgery

Resumen Introducción: Una complicación importante de la cirugía colorrectal es la dehiscencia de anastomosis (DA). El estado nutricional es uno de los factores importantes en la DA. Una forma objetiva para evaluar nutricionalmente a los pacientes es medir la sarcopenia, definida como disminución de masa muscular esquelética, que puede ser objetivada por análisis de Unidades Hounsfield (UH) y área muscular (AM) por medio de Tomografía Computarizada de Abdomen y Pelvis (TCAP). Objetivo: Evaluar si existe relación entre la DA y la presencia de sarcopenia detectada por medición de UH y AM en TCAP en pacientes sometidos a colectomía por cáncer. Materiales y Método: Estudio de casos y controles con estadística analítica. Se eligen de manera aleatoria 21 pacientes con DA y 40 sin DA. Se incluyen > 18 años, con colectomía por cáncer y anastomosis primaria. Fueron excluidos pacientes ostomizados, que no tuvieran TCAP preoperatoria o que éste no permitiera medir UH y AM. La evaluación imagenológica fue realizada por radiólogo experto. Resultados: La comparación entre grupos evidencia que son homogéneos con respecto al sexo (predomino hombres), edad (promedio 60 años) y localización. Se evidencia signos imagenológicos sugerentes de sarcopenia en el grupo de DA, puesto que existe disminución en UH con valores estadísticamente significativos y tendencia a presentar valores menores en el AM. Conclusiones: La presencia de sarcopenia evaluada por alteración de UH en estudio radiológico se correlaciona con DA, pudiendo ser un predictor de riesgo. La importancia de este hallazgo es que es un factor de riesgo potencialmente corregible.

Introduction: An important complication of colorectal surgery is anastomotic dehiscence (AD). Nutritional status is one of the important factors in AD. An objective way to evaluate the patients' nutritional status is to measure sarcopenia, which is the reduction of skeletal muscle mass. It is possible to standardize Sarcopenia using the analysis of the Hounsfield Units (HU) and the muscular area (MA) which consider Computed Tomography of Abdomen and Pelvis (CTAP). Aim: To evaluate whether there is a relationship between AD and the presence of sarcopenia detected by the measurement of HU and MA using CTAP. The situation considers patients undergoing colectomy for cancer. Materials and Method: Cases and controls were studied with analytical statistics. 21 patients with AD and 40 without AD were chosen randomly. They include > 18 years, with colectomy for cancer and primary anastomosis. Ostomized patients, who previous the surgery do not have CTAP or if it was not available to measure HU and MA, were excluded. The imaging evaluation was performed by an expert radiologist. Results: The comparison between groups shows that they are homogeneous with respect the sex (predominant men), age (average 60 years) and location. There are signs of imaging which suggest the presence of sarcopenia in the AD group. This is explained because there is an important statistical decrease in the HU values and a tendency to present lower MA values. Conclusions: The presence of sarcopenia due to alteration of HU in a radiological study is correlated with AD, and could be a predictor of risk. The importance of this finding is that this risk factor is potentially correctable.

Tumour sidedness and clinicopathological features of resected colon cancer in rural population of Northern Pakistan: single institutional analysis / Lateralidade tumoral e características clínico-patológicas do câncer de cólon ressecado na população rural do norte do Paquistão: análise em uma única instituição

ABSTRACT Objectives: Different clinicopathological and molecular features have been demonstrated between right and left sided colon cancers. We aimed to characterize colon cancer and sidedness among a North-Pakistani rural population diagnosed with colon cancer in our institution. Methods: Seventy patients were included in the study that received adjuvant chemotherapy at Bannu Institute of Nuclear Medicine Oncology and Radiotherapy) Bannu, Pakistan from January 2014 to December 2017. Chi-square test was used for significance of categorical variables. p-Values less than 0.05 were considered significant. Results: Mean age at diagnosis for right side colon cancer patients was 43.94 years and for left side colon cancer, it was 49.83 with no significant difference. Male patients were presented more with right (77% vs. 54%, p = 0.044) and females with predominantly left sided tumours i.e. (46% vs. 23%, p = 0.044). Right sided cancer tended to be more poorly differentiated (20% vs. 0%, p = 0.020). Mucinous adenocarcinoma was seen mostly in right sided colon cancer (37% vs. 3%, p ≤ 0.001). There were more locally advanced presentation of right side colon cancer with more node positive (83% vs. 60%, p = 0.025) and lymphovascular invasion (51% vs. 37%, p = 0.016). Sigmoid colon was the most common tumour subsite involved. Conclusion: Our study is the first report of colon cancer in a rural population in North-Pakistan. An earlier onset of tumours (44-50 years) was observed in comparison with global data.

RESUMO Objetivo: Características clínico-patológicas e moleculares distintas foram observadas em tumores de cólon no lado direito ou esquerdo. O presente estudo teve como objetivo caracterizar o câncer de cólon e sua lateralidade em uma população rural norte-paquistanesa diagnosticada com câncer de cólon nesta instituição. Métodos: O estudo incluiu 70 pacientes que foram submetidos a quimioterapia adjuvante no Instituto Bannu de Medicina Nuclear Radioterapia Oncológica (BINOR), Bannu, Paquistão, entre janeiro de 2014 e dezembro de 2017. O teste qui-quadrado foi utilizado para mensurar a significância das variáveis categóricas. Valores de p menores que 0,05 foram considerados significativos. Resultados: A média de idade ao diagnóstico entre pacientes com câncer de cólon no lado direito foi de 43,94 anos e entre aqueles com câncer de cólon no lado esquerdo, 49,83, sem diferença significativa. Os pacientes do sexo masculino apresentaram mais tumores no lado direito (77% vs. 54%, p = 0,044) e as pacientes do sexo feminino apresentaram mais tumores no lado esquerdo (46% vs. 23%, p = 0,044). Tumores mal diferenciados foram mais comumente observados no lado direito (20% vs. 0%, p = 0,020). Adenocarcinoma mucinoso foi observado principalmente em casos de tumores no lado direito (37% vs. 3%, p ≤ 0,001). A apresentação local estava mais avançada em tumores de cólon no lado direito, com mais linfonodos positivos (83% vs. 60%, p = 0,025) e invasão linfovascular (51% vs. 37%, p = 0,016). O cólon sigmoide foi o sublocal mais comum. Conclusão: O presente estudo é o primeiro relato de câncer de cólon em uma população rural no norte do Paquistão. Em comparação com dados globais, observou-se um surgimento mais precoce dos tumores (44-50 anos).

Metastasis esplénica de un adenocarcinoma de colon derecho / Splenic metastasis of a right colon adenocarcinoma

Introducción: Las metástasis únicas en bazo de origen colorrectal son extremadamente infrecuentes. Sin embargo, debido el control postoperatorio más estricto de la patología oncológica con estudios por imágenes modernos, la incidencia ha ido aumentando en los últimos años. Objetivo: Exponer el caso de una paciente con una metástasis esplénica de un tumor colónico primario. Caso clínico: Paciente de sexo femenino, de 85 años con antecedentes de colectomía derecha laparoscópica. La anatomía patológica informó: adenocarcinoma de colon T2 N0, sin requerir tratamiento quimioterápico adyuvante. En el seguimiento postoperatorio, durante el segundo año intercurrió con aumento del antígeno carcinoembrionario (CEA). Se realizó PET-TC que evidenció nódulo hipercaptante único de 3 cm. en bazo. Se programó la esplenectomía laparoscópica, evolucionando satisfactoriamente. La anatomía patológica definitiva informó adenocarcinoma metastásico de origen colónico. Conclusión: La metástasis esplénica de un tumor colónico es extremadamente infrecuente, existiendo solamente casos aislados en la literatura. En pacientes sin otro compromiso sistémico la esplenectomía debe recomendarse. (AU)

Introduction: Isolated splenic metastases are highly uncommon. The incidence has been increasing during the last years due to better medical imaging and long term follow up. Objective: We report a case of a patient who developed isolated splenic metastasis from right colon cancer. Case presentation: Female, 85 years old who underwent a laparoscopic right colectomy. The pathologic investigation confirmed: colon adenocarcinoma staged as T2 N0, without need of oncologic adjuvant therapy. In the postoperative follow up, during the second year, an increased serum carcinoembryonic antigen level was noticed. A PET TC was carried out and demonstrated a 3 cm focus of high radiotracer uptake in the spleen. Laparoscopic splenectomy was performed, postoperative course was uneventful. Pathologic exam demonstrated splenic parenquima invaded with adenocarcinoma originated in colon. Conclusion: Isolated splenic metastases is a very rare clinical entity. Only few case reports can be found in the literature. If they are no other sites of disease, splenectomy should be the optimal approach.

Aplicación de modelos paramétricos alternativos para el análisis de supervivencia de pacientes con cáncer / Application of alternative parametric models for the survival analysis of cancer patients

RESUMEN En el presente artículo se describe una metodología que permite tener un acercamiento a modelos probabilísticos alternativos para el análisis de supervivencia, con censura por la derecha, distintos a los que usualmente se estudian (distribución: exponencial, gamma, Weibull y log-normal), ya que es posible que los datos no se ajusten siempre con suficiente precisión por las distribuciones existentes. La metodología utilizada permite mayor flexibilidad de modelar observaciones extremas, ubicadas generalmente en la cola derecha de la distribución de los datos, lo cual admite que algunos eventos aún tengan la probabilidad de ocurrir, lo que no sucede con los modelos tradicionales y el estimador de Kaplan-Meier, el cual estima para los tiempos más prolongados, probabilidades de supervivencia aproximadamente iguales a cero. Para mostrar la utilidad de la propuesta metodológica, se consideró una aplicación con datos reales que relaciona tiempos de supervivencia de pacientes con cáncer de colon.

ABSTRACT This article describes a methodology that allows an approach to alternative right-censored probabilistic models for the analysis of survival, different to those usually studied (exponential, gamma, Weibull, and log-normal distribution) since it is possible that the data do not always fit with sufficient precision due to existing distributions. The methodology used allows for greater flexibility when modeling extreme observations, generally located in the right tail of data distribution, which admits that some events still have the probability of occurring, which is not the case with traditional models and the Kaplan-Meier estimator, which estimates for the longest times, survival probabilities approximately equal to zero. To show the usefulness of the methodological proposal, we considered an application with real data that relates survival times of patients with colon cancer (CC).