Complicaciones, clínica y tratamiento de pacientes con hepatocarcinoma, posterior a quimioembolización en dos hospitales de Quito / Complications, symptoms and treatment of patients with hepatocellular carcinoma, after chemoembolization in two hospitals in Quito

INTRODUCCIÓN. La quimioembolización transarterial ha demostrado mejorar la tasa de sobrevida en los pacientes con hepatocarcinoma, se ha descrito como tratamiento paliativo; es útil, efectivo y bien tolerado. Esta terapéutica tiene el objetivo de disminuir el volumen tumoral. OBJETIVO. Determinar las complicaciones que presentan los pacientes con diagnóstico de hepatocarcinoma, posterior a la realización de quimioembolización transarterial del servicio de Gastroenterología del Hospital de Especialidades Carlos Andrade Marín y Hospital de Especialidades Eugenio Espejo, durante el período enero 2015 - enero 2020. MATERIALES Y MÉTODOS. Es un estudio retrospectivo observacional transversal; se diseñó un formulario de recolección de información, utilizando media y desvío estándar para variables cuantitativas; frecuencia y porcentaje para cualitativas; en las variables con distribución no paramétrico se recurrió a la mediana, rango intercuartil y sus intervalos, además se utilizó Chi Cuadrado, Índice de Yates y test de U Mann Whitney. Se trabajó en el paquete estadístico SPSS versión 26. RESULTADOS. Se analizaron 97 pacientes, el 60,8% fue de sexo masculino de los cuales el 56.7% presentó alguna comorbilidad; la mayoría de los pacientes no tuvieron complicaciones, sin embargo, la hipertensión arterial se presentó como manifestación clínica post quimioembolización transarterial (10,3%); el choque, el síndrome ascítico ­ edematoso y el dolor abdominal fueron las complicaciones de mayor frecuencia. Los datos estadísticamente significativos fueron los siguientes: los pacientes con hepatocarcinoma y cirrosis hepática con severidad Child Pugh B, tuvieron un porcentaje mayor de complicaciones valor p = 0,01; un tamaño más grande del tumor sobre el número de lesiones, se relacionó con presentar alguna complicación postquimioembolización transarterial valor p = 0,001, lo que significó un aumento en la estancia hospitalaria valor p = 0,006; los pacientes que presentaron complicaciones mayores y menores tuvieron un tiempo de hospitalización más prolongado valor p < 0,05; la asociación entre la mortalidad y las complicaciones post quimioembolización en hospitalización y en UCI tuvieron una tasa general de 3,2% valor p = 0,001. CONCLUSIÓN. Las complicaciones mayores como el síndrome ascítico edematoso y el estado de choque, se mantuvieron sobre la media general. Con una tasa de mortalidad esperada según la tendencia internacional.

INTRODUCTION: Transarterial chemoembolization has been shown to improve the survival rate in patients with hepatocarcinoma, it has been described as palliative treatment; it is useful, effective and well tolerated. This therapy aims to reduce tumor volume, due to its embolic, vascular and cytotoxic effects. OBJECTIVE: To determine the complications presented by patients diagnosed with hepatocarcinoma, after performing transarterial chemoembolization of the Gastroenterology service of the Carlos Andrade Marín Specialty Hospital and Eugenio Espejo Specialty Hospital, during the period January 2015 - January 2020. METHODOLOGY: This cross-sectional observational study was conducted in patients with hepatocarcinoma who underwent transarterial chemoembolization. A form was designed for the collection of information, through a pseudonymized database, which was analyzed using the statistical package SPSS version 26. RESULTS: 97 patients were analyzed, 60.8% were male, of which 56.7% presented some comorbidity; Most of the patients had no complications, however, arterial hypertension presented as a clinical manifestation after transarterial chemoembolization in 10.3%; shock, ascites edema decompensation and abdominal pain were the most frequent complications. The statistically significant data were the following: patients with hepatocellular carcinoma and liver cirrhosis with Child Pugh B severity had a higher percentage of complications valor p = 0,01; a larger tumor size compared to the number of lesions was related to presenting some post-transarterial chemoembolization complication valor p = 0,001, which meant an increase in hospital stay valor p = 0,006; patients who presented major and minor complications had a longer hospitalization time valor p < 0,05, the association between mortality and post chemoembolization complications in hospitalization and in the ICU had an overall rate of 3.2% valor p = 0,001. CONCLUSION. Major complications, such as edematous ascitic syndrome and shock, remained above the general average. With an expected mortality rate according to the international trend.

The Variation of the Fetal Esophageal Mucosa at the End of Gestation may be a Possible Etiopathogenic Factor for Barrett's Esophagus / La Variación de la Mucosa Esofágica Identificada al Final de la Gestación Puede ser un Posible Factor Etiopatogénico para el Esófago de Barrett

SUMMARY: Barrett's esophagus is a condition where the distal third of the esophagus changes its epithelial lining from non- keratinized stratified squamous to simple columnar. This cross-sectional descriptive study was conducted to characterize the esophageal mucosa in the third trimester of pregnancy and determine possible variants in its development and was carried out in the Morphology Laboratory of the Health Faculty of the Industrial University of Santander, Colombia, with 45 human fetuses in the third trimester of gestation (weeks 25-40). A section of the distal esophagus and the first portion of the cardial region of the stomach were obtained, and the histological sections were subjected to a fixation process with 5 % formaldehyde solution. The sections were stained with hematoxylin and eosin and were evaluated for the presence of epithelial change or glands in the esophageal lamina propria. The change from non- keratinized stratified squamous epithelium to simple columnar epithelium was observed in the esophageal mucosa in five fetuses (11.1 %). In 15 cases (33.3 %), the presence of mucous glands underlying the epithelium was determined. In two fetuses, simple columnar epithelium was observed in the esophageal mucosa and underlying submucosal glands (4.4 %). The lack of replacement of the columnar epithelium by squamous epithelium in the distal third of the esophagus and the presence of mucous glands in the last third of gestation may suggest the presentation of Barret's esophagus in adulthood and thus, a predisposition to develop esophageal adenocarcinoma.

El esófago de Barrett es una afección en la que el tercio distal del esófago cambia su revestimiento epitelial de escamoso estratificado no queratinizado a columnar simple. Este estudio descriptivo de corte transversal tiene como objetivo caracterizar la mucosa esofágica en el tercer trimestre del embarazo y determinar posibles variantes en su desarrollo y se realizó en el laboratorio de Morfología de la Facultad de Salud de la Universidad Industrial de Santander-Colombia, con 45 fetos humanos en el tercer trimestre de gestación (semanas 25-40). Se obtuvo una sección del esófago distal y la primera porción de la región cardial del estómago y las secciones histológicas se sometieron a un proceso de fijación con solución de formaldehído al 5 %. Los cortes se tiñeron con hematoxilina y eosina y se evaluaron determinando la presencia de cambio epitelial y glándulas en la lámina propia del esófago. El cambio de epitelio escamoso estratificado no queratinizado a epitelio cilíndrico simple se observó en la mucosa esofágica en cinco fetos (11,1 %). En 15 casos (33,3 %) se determinó la presencia de glándulas mucosas subyacentes al epitelio. En dos fetos se observó epitelio cilíndrico simple en la mucosa esofágica y glándulas submucosas subyacentes (4,4 %). La falta de reemplazo del epitelio cilíndrico por epitelio escamoso en el tercio distal del esófago y la presencia de glándulas mucosas en el último tercio de la gestación pueden sugerir la presentación de esófago de Barrett en la edad adulta y una predisposición a desarrollar adenocarcinoma de esófago.

CLCA1 is Poorly Expressed in Stomach Adenocarcinoma and Correlates with Immune Infiltration / CLCA1 se Expresa Deficientemente en el Adenocarcinoma de Estómago y se Correlaciona con la Infiltración Inmune

SUMMARY: Calcium-activated chloride channel regulator 1 (CLCA1) is associated with cancer progression. The expression and immunologic function of CLCA1 in stomach adenocarcinoma (STAD) remain unclear. In this investigation, the expression of CLCA1 in STAD tissues and its involvement in the progression and immune response of STAD were examined using databases such as cBioPortal, TISIDB, and UALCAN. In order to validate the expression level of CLCA1 protein in gastric adenocarcinoma, thirty clinical tissue specimens were gathered for immunohistochemical staining. The findings indicated a downregulation of CLCA1 in STAD patients, which was correlated with race, age, cancer grade, Helicobacter pylori infection, and molecular subtype. Through the examination of survival analysis, it was identified that diminished levels of CLCA1 within gastric cancer cases were linked to decreased periods of post-progression survival (PPS), overall survival (OS), and first progression (FP) (P<0.05). The CLCA1 mutation rate was lower in STAD, but the survival rate was higher in the variant group. The correlation between the expression level of CLCA1 and the levels of immune infiltrating cells in STAD, as well as the immune activating molecules, immunosuppressive molecules, MHC molecules, chemokines, and their receptor molecules, was observed. Gene enrichment analysis revealed that CLCA1 may be involved in STAD progression through systemic lupus erythematosus (SLE), proteasome, cell cycle, pancreatic secretion, and PPAR signaling pathways. In summary, CLCA1 is anticipated to function as a prognostic marker for patients with STAD and is linked to the immunization of STAD.

El regulador 1 del canal de cloruro activado por calcio (CLCA1) está asociado con la progresión del cáncer. La expresión y la función inmunológica de CLCA1 en el adenocarcinoma de estómago (STAD) aún no están claras. En esta investigación, se examinó la expresión de CLCA1 en tejidos STAD y su participación en la progresión y respuesta inmune de STAD utilizando bases de datos como cBioPortal, TISIDB y UALCAN. Para validar el nivel de expresión de la proteína CLCA1 en el adenocarcinoma gástrico, se recolectaron treinta muestras de tejido clínico para tinción inmunohistoquímica. Los hallazgos indicaron una regulación negativa de CLCA1 en pacientes con STAD, que se correlacionó con la raza, la edad, el grado del cáncer, la infección por Helicobacter pylori y el subtipo molecular. Mediante el examen del análisis de supervivencia, se identificó que los niveles reducidos de CLCA1 en los casos de cáncer gástrico estaban relacionados con períodos reducidos de supervivencia posterior a la progresión (PPS), supervivencia general (OS) y primera progresión (FP) (P <0,05). La tasa de mutación CLCA1 fue menor en STAD, pero la tasa de supervivencia fue mayor en el grupo variante. Se observó la correlación entre el nivel de expresión de CLCA1 y los niveles de células inmunes infiltrantes en STAD, así como las moléculas activadoras inmunes, moléculas inmunosupresoras, moléculas MHC, quimiocinas y sus moléculas receptoras. El análisis de enriquecimiento genético reveló que CLCA1 puede estar involucrado en la progresión de STAD a través del lupus eritematoso sistémico (LES), el proteasoma, el ciclo celular, la secreción pancreática y las vías de señalización de PPAR. En resumen, se prevé que CLCA1 funcione como un marcador de pronóstico para pacientes con STAD y está vinculado a la inmunización de STAD.

Clinicopathological features of gastric alpha-fetoprotein-producing adenocarcinoma with SWI/SNF complex deletion / 中华病理学杂志

Objective: To investigate the clinicopathological features and treatment of gastric alpha-fetoprotein (AFP)-producing adenocarcinoma with SWI/SNF complex deletion. Methods: Four cases of gastric AFP-producing adenocarcinoma with SWI/SNF complex deletion diagnosed in Zhongshan Hospital of Fudan University from January 2021 to December 2022 were collected, and their histomorphological characteristics, immunohistochemical (IHC), in situ hybridization of Epstein-Barr virus-encoded RNA (EBER), next-generation sequencing results, clinicopathological features and treatment were summarized, and literature review was conducted. Results: Among the 4 patients, there were three males and one female. They presented with abdominal pain, belching and melena. Serum AFP was significantly elevated in three patients, and endoscopy showed ulcerative lesions. Microscopically, the tumor cells showed mainly diffuse flaky or nest-like growth and typical characteristics of hepatoid adenocarcinoma. In two cases there were adenoid growth, and the tumor cells in these areas possessed clear cytoplasm, suggesting enteroblastic differentiation. The tumor cell nuclei were pleomorphic with large nucleoli and brisk mitoses. The IHC results showed that the tumor cells expressed AFP, GPC3 and SALL4, and there was retained expression of broad-spectrum keratin (CKpan) and E-cadherin. IHC detection of SWI/SNF complex subunits, namely INI1 (SMARCB1), BRG1 (SMARCA4), BRM (SMARCA2), ARID1A protein was performed. In all four cases the hepatoid adenocarcinoma region and enteroblastic differentiation region showed SMARCA2 deletion, and one case with enteroblastic differentiation also showed ARID1A deletion. SMARCB1 and SMARCA4 deletions were not seen. All the four cases were diffusely positive for p53 protein, and the Ki-67 proliferation index was 80%-90%. There were no mismatch repair deletion detected; one cases showed HER2 was strongly positive (3+), and EBER was negative. None of the four cases had mutations in the SWI/SNF complex-related subunits detected by next-generation sequencing. Among the four patients, two underwent palliative surgery due to distant metastasis at the time of surgery, two underwent radical resection. Postoperative adjuvant chemotherapy was given to three patients. Conclusions: AFP-producing adenocarcinoma is a rare subtype of gastric cancer, which can be combined with SWI/SNF complex deletion, and the pathomorphological manifestations are different from the classical SWI/SNF complex deletion of undifferentiated carcinoma with rhabdoid phenotype.

Mass spectrometry analysis of intact protein N-glycosylation signatures of cells and sera in pancreatic adenocarcinomas / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Perianal Paget's disease metachronically associated with adenocarcinoma

Introduction: This article describes an unusual case of perianal Paget's Disease in a 42-year-old man, highlighting distinct characteristics about more typical cases. Case report: 42-year-old male patient with persistent perianal lesion, recurrent abscesses, and discomfort. Magnetic resonance imaging indicated a possible fistulous path. Biopsy revealed secondary anal Paget's disease and adenocarcinoma. Chemotherapy and radiotherapy treatment demonstrated a positive response. Discussion: Perianal Paget's Disease is a rare condition of the anal canal that is part of the Extramammary Paget's Disease (EMPD) group. Symptoms include itching, pain, perianal bleeding, and skin lesions. Diagnosis can be challenging and usually involves performing a histopathological biopsy associated with an immunohistochemical study. Treatment varies and may involve surgery, radiotherapy, and chemotherapy. Due to the rarity of the disease, the best therapeutic approach is not yet well defined, and follow-up is essential due to the risk of recurrence. Conclusion: Perianal Paget's Disease is rare and requires differentiation from other conditions. Early detection is essential to prevent malignancy. (AU)

Effects of rosmarinic acid and doxorubicine on an ovarian adenocarsinoma cell line (OVCAR3) via the EGFR pathway

Purpose: We aimed to reveal the effects of rosmarinic acid (RA), which has come to the forefront with its antitumor and antioxidant properties in many studies recently in the ovarian adenocarcinoma cell line, on the epidermal growth factor receptor (EFGR) signaling pathway in the presence of doxorubicin (DOX). Methods: Ovarian adenocarcinoma cell line (OVCAR3) and human skin keratinocyte cell line human skin keratinocyte cell line (HaCaT) were used as control. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was applied to determine the effect of RA and DOX on the proliferation of OVCAR3 and HaCaT cells. Bcl2 expression and epidermal growth factor receptor (EGFR) and western blot analysis were performed to determine the expression levels of the markers. Results: It was determined that RA (IC50 = 437.6 µM) and DOX (IC50 = 0.08 µM) have the ability to inhibit the proliferation of OVCAR3 cells and induce apoptosis in a 72-hour time and dose-dependent manner. Western blot showed that the expression level of Bcl-2 and EGFR in OVCAR3 cells was down-regulated by RA and DOX. Conclusions: Apoptosis in OVCAR3 cells can potentially be induced by RA via the EGFR pathway, and RA may be a potent agent for cancer therapy.

Vigilancia activa en cáncer de próstata en un grupo de pacientes asistidos en el Centro Docente Asociado de Oncología Médica Rivera: Cooperativa Médica de Rivera (COMERI) / Active surveillance in prostate cancer in a group of patients assisted at the Rivera Associated Teaching Center for Medical Oncology: Rivera Medical Cooperative (COMERI) / Vigilância ativa do câncer de próstata em um grupo de pacientes atendidos no Rivera Associated Teaching Center for Medical Oncology: Rivera Medical Cooperative (COMERI)

Introducción: En Uruguay el cáncer de próstata ocupa el primer lugar en incidencia y el tercer lugar en mortalidad en el hombre. La mayoría de estos cánceres se diagnostican en estadios precoces. Hoy en día, para pacientes con adenocarcinoma de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, la vigilancia activa es una opción adecuada. Objetivos: Describir una población de pacientes con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, en vigilancia activa en COMERI. Material y métodos: Estudio descriptivo, observacional, retrospectivo. Se incluyeron pacientes con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, tratados entre 2010 y 2018 en COMERI. Se recopilaron datos en el sistema de registro clínico electrónico. Resultados: Se incluyeron 33 pacientes, la mediana de edad al diagnóstico fue de 74 años. Todos los pacientes fueron sometidos a controles clínicos y determinación de PSA cada 3 meses. El tacto rectal se realizó en forma anual. El tiempo mediano de vigilancia activa fue de 33 meses. Durante el seguimiento, se observaron pocas variaciones en los valores de PSA. El 21% de los pacientes fue sometido a una nueva biopsia durante el seguimiento activo, y en todos los casos, el Gleason se mantuvo incambiado. Ningún paciente abandonó la modalidad de vigilancia activa. Conclusión: En nuestro entorno, la vigilancia activa se considera una opción terapéutica válida para pacientes altamente seleccionados con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, y es bien aceptada por ellos.

Introduction: In Uruguay, prostate cancer ranks first in incidence and third in mortality among men. The majority of these cancers are diagnosed at early stages. Nowadays, active surveillance is an appropriate option for patients with adenocarcinoma of very low risk, low risk, or favorable intermediate risk. Objectives: To describe a population of patients with prostate cancer of very low risk, low risk, or favorable intermediate risk under active surveillance at COMERI. Materials and Methods: Descriptive, observational, retrospective study. Patients with prostate cancer of very low risk, low risk, or favorable intermediate risk treated between 2010 and 2018 at COMERI were included. Data were collected from the electronic clinical registry system. Results: Thirty-three patients were included, with a median age at diagnosis of 74 years. All patients underwent clinical monitoring and PSA determination every 3 months. Digital rectal examination was performed annually. The median time of active surveillance was 33 months. During follow-up, there were few variations in PSA values. 21% of patients underwent a repeat biopsy during active surveillance, and in all cases, the Gleason score remained unchanged. No patient discontinued active surveillance. Conclusion: In our setting, active surveillance is considered a valid therapeutic option for highly selected patients with prostate cancer of very low risk, low risk, or favorable intermediate risk, and it is well accepted by them.

Introdução: No Uruguai, o câncer de próstata ocupa o primeiro lugar em incidência e o terceiro lugar em mortalidade entre os homens. A maioria desses cânceres é diagnosticada em estágios precoces. Atualmente, para pacientes com adenocarcinoma de risco muito baixo, baixo risco ou risco intermediário favorável, a vigilância ativa é uma opção adequada. Objetivos: Descrever uma população de pacientes com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável sob vigilância ativa em COMERI. Material e métodos: Estudo descritivo, observacional, retrospectivo. Foram incluídos pacientes com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável, tratados entre 2010 e 2018 em COMERI. Os dados foram coletados no sistema de registro clínico eletrônico. Resultados: Foram incluídos 33 pacientes, com mediana de idade no diagnóstico de 74 anos. Todos os pacientes foram submetidos a controles clínicos e determinação de PSA a cada 3 meses. O toque retal foi realizado anualmente. O tempo médio de vigilância ativa foi de 33 meses. Durante o acompanhamento, houve poucas variações nos valores de PSA. 21% dos pacientes foram submetidos a uma nova biópsia durante a vigilância ativa, e em todos os casos, o Gleason permaneceu inalterado. Nenhum paciente abandonou a modalidade de vigilância ativa. Conclusão: Em nosso ambiente, a vigilância ativa é considerada uma opção terapêutica válida para pacientes altamente selecionados com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável, e é bem aceita por eles.

Factores pronósticos y la influencia en la supervivencia de operados de cáncer de pulmón en el Hospital Universitario General Calixto García / Prognostic Factors and their Influence of Patients Operated on for Lung Cancer at Hospital Universitario General Calixto García

Introducción: El cáncer de pulmón ocupa el primer lugar entre las causas de mortalidad por cáncer a nivel mundial y solamente el 15,6 por ciento de los que padecen esta enfermedad sobreviven los 5 años. Objetivo: Evaluar la influencia de los factores pronósticos en la supervivencia de operados por cáncer de pulmón. Métodos: Estudio observacional descriptivo, tipo serie de casos de 107 enfermos operados en el Hospital Universitario General Calixto García en el período 2015-2020. Se utilizaron las variables tipo histológico, estadio clínico, estado físico e intervención quirúrgica. Resultados: Predominó el sexo masculino en edades entre 60-69 años, con antecedentes de hipertensión arterial y tabaquismo. Los síntomas que predominaron fueron la disnea, la tos y el dolor torácico. Las etapas clínicas más frecuentes fueron en orden: IIIA, IIB, IIA y las variantes histopatológicas adenocarcinoma y epidermoide. La técnica quirúrgica más empleada fue la lobectomía. Conclusiones: Los factores pronósticos de mayor significación estadística son la comorbilidad, la presencia de síntomas y el diagnóstico tardío. Los factores pronósticos relacionados con el tumor y el tratamiento quirúrgico con adyuvancia tienen una alta repercusión en la supervivencia(AU)

Introduction: Lung cancer ranks first among the causes of cancer mortality worldwide and only 15.6 percent of those with this disease survive the 5 years. Objective: To assess the influence of prognostic factors on the survival of patients operated on for lung cancer. Methods: A descriptive observational study of case series was carried out with 107 patients operated on at Hospital Universitario General Calixto García in the period 2015-2020. The variables histological type, clinical stage, physical condition and surgical intervention were used. Results: There was a predominance of the male sex, aged 60-69 years, with a history of arterial hypertension and smoking. The predominant symptoms were dyspnea, cough and chest pain. The most frequent clinical stages were IIIA, IIB, IIA, in that order; and the predominant histopathological variants were adenocarcinoma and epidermoid. The most commonly used surgical technique was lobectomy. Conclusions: The prognostic factors of greatest statistical significance are comorbidity, presence of symptoms and late diagnosis. Prognostic factors related to the tumor or the adjuvant surgical treatment have a high impact on survival(AU)

Comprehensive Analysis of CLCA1 Expression, Immune Infiltration and Immune Checkpoints in Colon Adenocarcinoma / Análisis Completo de la Expresión de CLCA1, Infiltración Inmune y Puntos de Control Inmunológico en Colonadenocarcinoma

SUMMARY: Colon adenocarcinoma (COAD) is a prevalent disease worldwide, known for its high mortality and morbidity rates. Despite this, the extent of investigation concerning the correlation between COAD's CLCA1 expression and immune cell infiltration remains insufficient. This study seeks to examine the expression and prognosis of CLCA1 in COAD, along with its relationship to the tumor immune microenvironment. These findings will offer valuable insights for clinical practitioners and contribute to the existing knowledge in the field. In order to evaluate the prognostic significance of CLCA1 in individuals diagnosed with colorectal cancers, we conducted a comprehensive analysis using univariate and multivariate Cox regression models along with receiver operating characteristic curve (ROC) analysis. This study was performed on the patient data of COAD obtained from The Cancer Genome Atlas (TCGA) database. Nomograms were developed to anticipate CLCA1 prognostic influence. Furthermore, the CLCA1 association with tumor immune infiltration, immune checkpoints, immune checkpoint blockade (ICB) response, interaction network, and functional analysis of CLCA1-related genes was analyzed. We found that Colon adenocarcinoma tissues significantly had decreased CLCA1 expression compared to healthy tissues. Furthermore, the study revealed that the group with high expression of CLCA1 demonstrated a significantly higher overall survival rate (OS) as compared to the group with low expression. Multivariate and Univariate Cox regression analysis revealed the potential of CLCA1 as a standalone risk factor for COAD. These results were confirmed using nomograms and ROC curves. In addition, protein-protein interaction (PPI) network analysis and functional gene enrichment showed that CLCA1 may be associated with functional activities such as pancreatic secretion, estrogen signaling and cAMP signaling, as well as with specific immune cell infiltration. Therefor, as a new independent predictor and potential biomarker of COAD, CLCA1 plays a crucial role in the advancement of colon cancer.

El adenocarcinoma de colon (COAD) es una enfermedad prevalente a nivel mundial, conocida por sus altas tasas de mortalidad y morbilidad. Sin embargo, el alcance de la investigación sobre la correlación entre la expresión de CLCA1 de COAD y la infiltración de células inmunes sigue siendo insuficiente. Este estudio busca examinar la expresión y el pronóstico de CLCA1 en COAD, junto con su relación con el microambiente inmunológico del tumor. Estos hallazgos ofrecerán conocimientos valiosos para los profesionales clínicos y contribuirán al conocimiento existente en el campo. Para evaluar la importancia de pronóstico de CLCA1 en personas diagnosticadas con cáncer colorrectal, realizamos un análisis exhaustivo utilizando modelos de regresión de Cox univariados y multivariados junto con un análisis de la curva característica operativa del receptor (ROC). Este estudio se realizó con los datos de pacientes de COAD obtenidos de la base de datos The Cancer Genome Atlas (TCGA). Se desarrollaron nomogramas para anticipar la influencia pronóstica de CLCA1. Además, se analizó la asociación de CLCA1 con la infiltración inmunitaria tumoral, los puntos de control inmunitarios, la respuesta de bloqueo de los puntos de control inmunitarios (ICB), la red de interacción y el análisis funcional de genes relacionados con CLCA1. Descubrimos que los tejidos de adenocarcinoma de colon tenían una expresión significativamente menor de CLCA1 en comparación con los tejidos sanos. Además, el estudio reveló que el grupo con alta expresión de CLCA1 demostró una tasa de supervivencia general (SG) significativamente mayor en comparación con el grupo con baja expresión. El análisis de regresión de Cox multivariado y univariado reveló el potencial de CLCA1 como factor de riesgo independiente de COAD. Estos resultados se confirmaron mediante nomogramas y curvas ROC. Además, el análisis de la red de interacción proteína- proteína (PPI) y el enriquecimiento de genes funcionales mostraron que CLCA1 puede estar asociado con actividades funcionales como la secreción pancreática, la señalización de estrógenos y la señalización de AMPc, así como con la infiltración de células inmunes específicas. Por lo tanto, como nuevo predictor independiente y biomarcador potencial de COAD, CLCA1 desempeña un papel crucial en el avance del cáncer de colon.

Esófago de Barrett: Actualización en el diagnóstico y tratamiento / Barrett's Esophagus: Update on the Diagnosis and Treatment. Review

El esófago de Barrett (EB) se define como la condición en la cual una mucosa columnar metaplásica predispuesta a neoplasia reemplaza la mucosa escamosa del esófago distal. La guías actuales recomiendan que el diagnóstico requiere el hallazgo de metaplasia intestinal (MI) con células caliciformes de al menos 1 cm de longitud. El EB afecta aproximadamente al 1% de la población general y hasta en 14% de los pacientes con enfermedad por reflujo gastroesofágico (ERGE). El EB es precursor del adenocarcinoma esofágico (ACE), neoplasia en aumento en países occidentales. Los principales factores de riesgo descritos para ACE asociado a EB son: sexo masculino, edad > 50 años, obesidad central y tabaquismo. El riesgo anual de ACE en EB sin displasia, displasia de bajo (DBG) y alto grado es 0,1-0,3%, 0,5% y 5-8%, respectivamente. El tratamiento del EB no displásico consiste en un cambio de estilo de vida saludable, quimioprevención mediante inhibidores de la bomba de protones y vigilancia endoscópica cada 3 a 5 años. Se recomienda que a partir de la presencia de DBG los pacientes sean referidos a un centro experto para la confirmación del diagnóstico, estadio y así definir su manejo. En pacientes con EB y displasia o cáncer incipiente, el tratamiento endoscópico consiste en la resección y ablación, con un éxito cercano al 90%. El principal evento adverso es la estenosis esofágica que es manejada endoscópicamente.

Barrett's esophagus (BE) is the condition in which a metaplastic columnar mucosa predisposed to neoplasia replaces the squamous mucosa of the distal esophagus. The current guidelines recommends that diagnosis requires the finding of intestinal metaplasia (IM) with goblet cells of at least 1 cm in length. BE affects approximately 1% of the general population and up to 14% of patients with gastroesophageal reflux disease (GERD). BE is a precursor of esophageal adenocarcinoma (EAC), which has increased in western countries. The main risk factors described for EAC associated with BE are male sex, age > 50 years, central obesity and tobacco use. Annual risk of EAC in patients with BE without dysplasia, low grade (LGD) and high-grade dysplasia is 0,1-0,3%, 0,5% y 5-8%, respectively. Treatment of non-dysplastic BE consists mainly of a healthy lifestyle change, chemoprevention with proton pump inhibitors and surveillance endoscopy every 3 to 5 years. It is recommended that from the presence of LGD patients are referred to an expert center for confirmation of the diagnosis, stage and thus define their management. In patients with BE and dysplasia or early-stage cancer, endoscopic therapy with resection and ablation is successful in about 90% of the patients. The main adverse event is esophageal stricture, which is managed endoscopically.

McKittrick Wheelock syndrome secondary to adenocarcinoma of the rectum: case report and diagnostic considerations

Introduction: McKittrick-Wheelock syndrome is a rare entity characterized by chronic diarrhea, acute kidney injury, and hydroelectrolytic imbalance associated with a large rectal tumor, frequently a villous adenoma. Case report: A 69-year-old male with chronic diarrhea with mucus. He underwent a colonoscopy with biopsies, reporting adenocarcinoma of the rectum in situ, and underwent a robot assisted intersphincteric resection with colo-anal anastomosis and a protecitive ileostomy. Discussion: Described in 1954, this syndrome is manifested by electrolyte imbalance and acute renal injury secondary to diarrhea associated with a rectal villous adenoma, often with long lasting symptoms. The most frequent symptom being watery diarrhea with mucus. The definitive treatment consists of surgical resection. Conclusion: Although this is a rare pathology, it should be considered as a differential diagnosis in cases of chronic diarrhea associated with water and electrolyte disorders. (AU)

Study of long non-coding RNA Tug 1 expression in Egyptian colorectal adenocarcinoma patients

Purpose: Colorectal cancer (CRC) is one of the most fatal tumors worldwide. In Egypt, most CRC cases occur in individuals > 40 years old. TUG1 has been proved to be disrupted in different malignancies and may have a critical role in tumor progression, invasion, and metastasis. However, its role in CRC has not been adequately studied. Materials / Methods: Quantitative real-time polymerase chain reaction (PCR) was used to evaluate the expression levels of long non-coding RNA (LncRNA) taurine upregulated gene 1 (TUG1), in nonmetastatic and metastatic CRC tissues and adjacent noncancerous tissues as control. Results: LncRNA TUG1 expression was significantly upregulated in both nonmetastatic and metastatic CRC tissues, in comparison with the adjacent noncancerous tissue. It was found that TUG1 could have a possible prognostic role in CRC, by comparing the sensitivity and specificity of TUG1 with those of CEA and CA19-9. Conclusion: The results of the current study suggest that the LncRNA TUG1 participates in the malignant behaviors of CRC cells. (AU)

Adenocarcinoma de vesícula biliar: un caso de presentación temprana / Gallbladder adenocarcinoma: an early-stage case

El cáncer de la vesícula biliar es una enfermedad rara, con una incidencia mundial de 2 casos por cada 100 000 individuos con un pronóstico desfavorable. Con el aumento de colecistectomías por causas benignas, se ha incrementado la detección incidental de neoplasias vesiculares en las piezas quirúrgicas, siendo este el método diagnóstico más frecuente, generando retrasos en el manejo y requiriendo reintervenciones extensas. Debido a lo anterior, se resalta la importancia de un diagnóstico temprano preoperatorio, con el objetivo de ofrecer un tratamiento quirúrgico potencialmente curativo. Se presenta el caso de un paciente masculino de 72 años con un cuadro intermitente de dolor abdominal y pérdida de peso de un año de evolución, el cual fue diagnosticado con cáncer vesicular en etapa temprana y sometido a una colecistectomía laparoscópica extendida con linfadenectomía y hepatectomía parcial con una evolución a 6 meses sin complicaciones y bajo un protocolo de vigilancia periódica.

Gallbladder cancer is a rare disease, accounting a global incidence of 2 cases per 100 000 individuals with an unfavorable prognosis. The rise in cholecystectomies for benign causes has increased an incidental detection of vesicular neoplasms in the surgical specimens, being the main diagnostic method, therefore it generated delay in the management, requiring extensive re-interventions. It is important to improve early preoperative diagnosis, with the aim of offering a potentially curative surgical treatment. We present a case of a 72-year-old male with intermittent abdominal pain and weight loss of one year of evolution, who was diagnosed with early stage gallbladder cancer and underwent an extended laparoscopic cholecystectomy with lymphadenectomy and partial hepatectomy with a 6 months evolution without complications and under a periodic surveillance protocol.

Escisión meso-rectal total por vía trans anal (TaTME). Experiencia institucional / Trans anal total meso-rectal excision (TaTME). Institutional experience

Introducción. La cirugía es la base del tratamiento curativo del cáncer de recto. La escisión meso-rectal total ha permitido mejorar los desenlaces oncológicos, disminuyendo las tasas de recurrencia locorregional e impactando en la supervivencia global. El empleo de esta técnica en los tumores de recto medio o distal es un reto quirúrgico, en el que la vía trans anal, permite superar las dificultades técnicas. Método. Se realizó un estudio observacional retrospectivo, recolectando la información de los pacientes con cáncer de recto medio y distal llevados a cirugía con esta técnica, en dos instituciones de cuarto nivel en Medellín, Colombia, entre enero de 2017 y marzo de 2022. Se analizaron sus características demográficas, la morbilidad perioperatoria y la pieza quirúrgica. Resultados. Se incluyeron 28 pacientes sometidos al procedimiento trans anal y laparoscópico de forma simultánea; al 57 % se les realizó una ileostomía de protección. Hubo complicaciones en el 60,7 % de los pacientes; ocurrieron cuatro casos de fuga anastomótica. No se presentó ninguna mortalidad perioperatoria. Conclusiones. La tasa de morbilidad perioperatoria es acorde con lo reportado en la literatura. Se resalta la importancia de la curva de aprendizaje quirúrgica y de incluir la calificación de la integridad meso-rectal dentro del informe patológico. Se requiere seguimiento a largo plazo para determinar el impacto en desenlaces oncológicos, calidad de vida y morbilidad

Introduction. Surgery is the pillar of curative treatment for rectal cancer. Total meso-rectal excision has improved oncological outcomes, decreasing locoregional recurrence rates and impacting overall survival. The use of this technique in tumors of the middle or distal rectum is a surgical challenge, in which the trans anal route allows overcoming technical difficulties. Method. A retrospective observational study was carried out, collecting information from patients with middle and distal rectal cancer undergoing surgery with this technique, in two level 4 institutions in Medellín, Colombia, between January 2017 and March 2022. Results. Twenty-eight patients were included; their demographic characteristics, perioperative morbidity, and surgical specimen were analyzed. All patients underwent the trans anal and laparoscopic procedures simultaneously; 57% underwent a protective ileostomy. There was no perioperative mortality. Complications occurred in 60.7% of the patients. Only four cases of anastomotic leak occurred. Conclusions. The perioperative morbidity rate is consistent with that reported in the literature; the importance of the surgical curve and to include the qualification of the meso-rectal integrity within the pathological report is highlighted. Long-term follow-up is required to determine the impact on oncological outcomes, quality of life, and morbidity

Fulminant endogenous panophthalmitis caused by Clostridium septicum infection / Panoftalmite endógena fulminante por infecção por Clostridium septicum

ABSTRACT We report an unusual case of fulminant endogenous Clostridium septicum panophthalmitis. A 74-year-old male patient presented with sudden amaurosis in the right eye, which in a few hours, evolved into an orbital cellulitis, endophthalmitis, anterior segment ischemia, and secondary perforation of the eye. A complete diagnostic study, which included cranial and orbital contrast-enhanced computed tomography scan, contrast-enhanced magnetic resonance imaging, blood cultures, and complete blood work, were performed. No causal agent was identified. Clostridium septicum infection caused fulminant gaseous panophthalmitis. Despite broad-spectrum antibiotic treatment, evisceration of the eyeball was necessary. The extension study showed a colon adenocarcinoma as the origin of the infection. Clostridium septicum panophthalmitis is a rare but aggressive orbital infection. This infection warrants the identification of a neoplastic process in the gastrointestinal tract in many cases not previously described.

RESUMO Este é o relato de um caso incomum de panoftalmite endógena fulminante por Clostridium septicum. Um paciente do sexo masculino, 74 anos, apresentou amaurose súbita no olho direito, que em poucas horas evoluiu para celulite orbitária, endoftalmite, isquemia do segmento anterior e perfuração secundária do olho. Foi realizado um estudo diagnóstico completo, que incluiu uma tomografia computadorizada com contraste cranial e orbital, um exame de ressonância magnética, hemocultura e hemograma completo. Nenhum agente causal foi identificado. A infecção por Clostridium septicum causou uma panoftalmite gasosa fulminante. Apesar do tratamento com antibióticos de amplo espectro, foi necessário eviscerar o globo ocular. O estudo de seguimento mostrou um adenocarcinoma de cólon como a origem da infecção. A panoftalmite por Clostridium septicum é um tipo raro, mas muito agressivo de infecção orbitária. Essa infecção deve sugerir a busca por um processo neoplásico no trato gastrointestinal, em muitos casos não diagnosticado anteriormente.

Identification of antarctic soil bacteria exhibiting antiproliferative activity against a colon cancer cell line / Identificación de bacterias de suelo antártico que presentan actividad antiproliferativa sobre una línea celular de cáncer de colon

SUMMARY: Cancer is the second leading cause of death in the world and colorectal cancer is the only cancer that has shown a sustained increase in mortality in the last decade. In the search for new chemotherapeutic agents against cancer, extremophilic microorganisms have shown to be a potential source to obtain molecules of natural origin and with selective cytotoxic action towards cancer cells. In this work we analyzed the ability of a collection of Antarctic soil bacteria, isolated on Collins Glacier from the rhizosphere of Deschampsia antarctica Desv plant, to secrete molecules capable of inhibiting cell proliferation of a colorectal cancer tumor line. Our results demonstrated that culture supernatants from the Antarctic bacteria K2I17 and MI12 decreased the viability of LoVo cells, a colorectal adenocarcinoma cell line. Phenotypic and genotypic characterization of the Antarctic bacteria showed that they were taxonomically related and nucleotide identity analysis based on the 16S rRNA gene sequence identified the bacterium K2I17 as a species belonging to the genus Bacillus.

El cáncer es la segunda causa de muerte en el mundo y el cáncer colorrectal es el único que presenta un aumento sostenido de la mortalidad en la última década. En la búsqueda de nuevos agentes quimioterapeúticos contra el cáncer, se ha propuesto a los microorganismos extremófilos como una fuente potencial para obtener moléculas de origen natural y con acción citotóxica selectiva hacia las células cancerígenas. En este trabajo analizamos la capacidad de una colección de bacterias de suelo antártico, aisladas en el glaciar Collins desde rizosfera de la planta de Deschampsia antarctica Desv, de secretar moléculas capaces de inhibir la proliferación celular de una línea tumoral de cáncer colorrectal. Nuestros resultados demostraron que los sobrenadantes de cultivo de las bacterias antárticas K2I17 y MI12 disminuyeron la viabilidad de la línea celular de adenocarcinoma colorrectal LoVo, en un ensayo de reducción metabólica de MTT. La caracterización fenotípica y genotípica de las bacterias antárticas, demostró que estaban relacionadas taxonómicamente y el análisis de la identidad nucleotídica en base a la secuencia del gen ARNr 16S identificó a la bacteria K2I17 como una especie perteneciente al género Bacillus.

Clinicopathological features of patients with RET fusion-positive non-small cell lung cancer / 中华病理学杂志

Objective: To investigate the clinicopathological features, treatment and prognosis of patients with RET fusion positive non-small cell lung cancer (NSCLC). Methods: A total of 1 089 NSCLCs were retrieved at Affiliated Hospital of Jiangnan University from August 2018 to April 2020. In all cases, multiple gene fusion detection kits (fluorescent PCR method) were used to detect the gene status of RET, EGFR, ALK, ROS1, KRAS, BRAF and HER2; and immunohistochemical method was used to detect the expression of PD-L1 and mismatch repair related proteins. The correlation between RET-fusion and patients' age, gender, smoking history, tumor stage, grade, pathologic type, and PD-L1, mismatch repair related protein expression was analyzed. Results: There were 22 cases (2.02%) detected with RET fusion-positive in 1 089 NSCLC patients, in which 11 males and 11 females; and the median age was 63.5 years. There were 20 adenocarcinomas, including 11 acinar predominant adenocarcinoma (APA), five solid predominant adenocarcinoma (SPA) and four lepidic predominant adenocarcinoma (LPA); There were one case each of squamous cell carcinoma (non-keratinizing type) and sarcomatoid carcinoma (pleomorphic carcinoma). There were 6 and 16 patients with RET fusion-positive who were in stage Ⅰ-Ⅱ and Ⅲ-Ⅳ respectively, and 16 cases with lymph node metastasis, 11 cases with distant metastasis. Among RET fusion-positive cases, one was detected with HER2 co-mutation. The tumor proportion score of PD-L1≥1% in patients with RET fusion positive lung cancer was 54.5% (12/22). Defects in mismatch repair protein expression were not found in patients with RET fusion positive NSCLC. Four patients with RET fusions positive (two cases of APA and two cases of SPA) received pratinib-targeted therapy, and two showed benefits from this targeted therapy. Conclusions: The histological subtypes of RET fusions positive NSCLC are more likely to be APA or SPA. RET fusion-positive NSCLC patients are associated with advanced clinical stage, lymph node metastases, and they may benefit from targeted therapy with RET-specific inhibitors.

Application of the WHO Classification of Thoracic Tumors (2021) grading system in invasive pulmonary adenocarcinoma and its correlation with the targeted genes' variations / 中华病理学杂志

Objective: To investigate the applicability of the 2021 WHO classification of thoracic tumors' new grading system for invasive pulmonary adenocarcinoma (IPA) with different clinical stages and its correlation with the characteristics of targeted genes' variation. Methods: A total of 2 467 patients with surgically resected primary IPA in Shanghai Pulmonary Hospital, Shanghai, China from September to December 2020 were retrospectively analyzed. Eligible cases were graded using the new grading system of IPA of the 2021 WHO classification of thoracic tumors. The clinicopathological data and targeted-gene abnormality were collected. The utility of new grading system of IPA in different clinical stages was investigated. The correlation of clinicopathological features and targeted-gene abnormality in different grades of IPA were compared. Results: All 2 311 cases of IPA were included. There were 2 046 cases of stage Ⅰ IPA (88.5%), 169 cases of stage Ⅱ (7.3%), and 96 cases of stage Ⅲ (4.2%). According to the new classification system of IPA, 186 cases (9.1%), 1 413 cases (69.1%) and 447 cases (21.8%) of stage-Ⅰ adenocarcinoma were classified as Grade 1, Grade 2 and Grade 3, respectively. However, there were no Grade 1 adenocarcinomas in stages Ⅱ and Ⅲ cases. Among stage-Ⅱ and Ⅲ IPA cases, there were 38 Grade 2 cases (22.5%) and 131 Grade 3 cases (77.5%), and 3 Grade 2 cases (3.1%) and 93 Grade 3 cases (96.9%), respectively. In stage-Ⅰ cases, no tumor cells spreading through airspace (STAS), vascular invasion or pleural invasion was found in Grade 1 of IPA, while the positive rates of STAS in Grade 2 and 3 IPA cases were 11.3% (159/1 413) and 73.2% (327/447), respectively. There was a significant difference among the three grades (P<0.01). Similarly, the rates of vascular and pleural invasion in Grade 3 IPA cases were 21.3% (95/447) and 75.8% (339/447), respectively, which were significantly higher than those of 1.3% (19/1 413) and 3.0% (42/1 413) in Grade 2 (P<0.01). EGFR mutational rates in Grades 1, 2 and 3 IPA were 65.7% (94/143), 76.4% (984/1 288) and 51.3% (216/421), respectively. The differences among the three grades were statistically significant (P<0.01). No fusion genes were detected in Grade 1 IPA, while the positive rates of ROS1 and ALK fusion genes in Grade 3 were 2.4% (10/421) and 8.3% (35/421), respectively, which were significantly higher than that of 0.5% (7/1 288) and 1.6% (20/1 288) in Grade 2 (P<0.01). In stage-Ⅱ cases, only EGFR mutation rate in Grade 2 adenocarcinoma (31/37, 83.8%) was higher than that in Grade 3 adenocarcinoma (71/123, 57.7%; P<0.01). However, the correlation between the new grade system of IPA and the distribution characteristics of targeted-gene variation cannot be evaluated in stage Ⅲ cases. Conclusions: The new grading system for IPA is mainly applicable to clinical stage-Ⅰ patients. Tumor grades of IPA are strongly correlated with the high-risk factors of prognosis and the distribution features of therapeutic targets. It is of great significance and clinical value to manage postoperative patients with early-stage IPA.

Advances in the Study of Invasive Non-mucinous Adenocarcinoma with Different Pathological Subtypes / 中国肺癌杂志

Lung cancer is the leading cause of cancer death in the world today, and adenocarcinoma is the most common histopathological type of lung cancer. In May 2021, World Health Organization (WHO) released the 5th edition of the WHO classification of thoracic tumors, which classifies invasive non-mucinous adenocarcinoma (INMA) into lepidic adenocarcinoma, acinar adenocarcinoma, papillary adenocarcinoma, solid adenocarcinoma, and micropapillary adenocarcinoma based on its histological characteristics. These five pathological subtypes differ in clinical features, treatment and prognosis. A complete understanding of the characteristics of these subtypes is essential for the clinical diagnosis, treatment options, and prognosis predictions of patients with lung adenocarcinoma, including recurrence and progression. This article will review the grading system, morphology, imaging prediction, lymph node metastasis, surgery, chemotherapy, targeted therapy and immunotherapy of different pathological subtypes of INMA.
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