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.

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.

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.

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.

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)

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

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.

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 SULF1 as a Shared Gene in Idiopathic Pulmonary Fibrosis and Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer.@*METHODS@#Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases.@*RESULTS@#A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microenvironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts.@*CONCLUSIONS@#This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases.

Construction of Lung Adenocarcinoma Prognosis Model and Drug Sensitivity Analysis Based on Cuproptosis Related Genes / 中国肺癌杂志

BACKGROUND@#Lung cancer is one of the most common malignant tumors in the world, and the current lung cancer screening and treatment strategies are constantly improving, but its 5-year survival rate is still very low, which seriously endangers human health. Therefore, it is critical to explore new biomarkers to provide personalized treatment and improve the prognosis. Cuproptosis is a newly discovered type of cell death, which is due to the accumulation of excess copper ions in the cell, eventually leading to cell death, which has been suggested by studies to be closely related to the occurrence and development of lung adenocarcinoma (LUAD). Based on The Cancer Genome Atlas (TCGA) database, this study explored the association between cuproptosis-related genes (CRGs) and LUAD prognosis, established a prognostic risk model, and analyzed the interaction between CRGs and LUAD immune cell infiltration.@*METHODS@#The RNA-seq data of LUAD tissue and paracancerous or normal lung tissue were downloaded from the TCGA database; the RNA-seq data of normal lung tissue was downloaded from the Genotype-tissue Expression (GTEx) database, and the data of 462 lung adenocarcinoma cases were downloaded from the Gene Expression Omnibus repository (GEO) as verification. T the risk score model to assess prognosis was constructed by univariate Cox and Lasso-Cox regression analysis, and the predictive ability of the model was evaluated by receiver operating characteristic (ROC) curve and calibration curve. Immune-related and drug susceptibility analysis was further performed on high- and low-risk groups.@*RESULTS@#A total of 1656 CRGs and 1356 differentially expressed CRGs were obtained, and 13 CRGs were screened out based on univariate Cox and Lasso-Cox regression analysis to construct a prognostic risk model, and the area under the curves (AUCs) of ROC curves 1-, 3- and 5- year were 0.749, 0.740 and 0.689, respectively. Further study of immune-related functions and immune checkpoint differential analysis between high- and low-risk groups was done. High-risk groups were more sensitive to drugs such as Savolitinib, Palbociclib, and Cytarabine and were more likely to benefit from immunotherapy.@*CONCLUSIONS@#The risk model constructed based on 13 CRGs has good prognostic value, which can assist LUAD patients in individualized treatment, and provides an important theoretical basis for the treatment and prognosis of LUAD.

A case of pancreatic cancer treated with chemotherapy combined with immunotherapy and targeted therapy / 浙江大学学报·医学版

A 68-year-old male was admitted due to fatigue and poor appetite and diagnosed pathologically as pancreatic adenocarcinoma with liver metastasis. The tumor marker carbohydrate antigen 199 (CA199) level was 2003.4 U/mL. The patient received two cycles of modified FOLFIRINOX plus immune checkpoint inhibitor (penpulimab). However, the tumor did not shrink and CA199 level was even higher. Anlotinib was added from the 3rd cycle, and the size of primary tumor and metastatic lesions were significantly reduced. Laparoscopic distal pancreatectomy and splenectomy as well as liver metastasis resection was performed. Three cycles of combined therapy were adopted after surgery followed by maintenance therapy with anlotinib plus penpulimab. There was no evidence of tumor recurrence during the follow-up (nearly 19 months since diagnosis).

Identification of immune-related prognostic signature for colon adenocarcinoma based on weighted gene co-expression network analysis / 细胞与分子免疫学杂志

Objective To identify immune-related molecular markers in an attempt to predict prognosis of colon adenocarcinoma (COAD). Methods Immune related genes (IREGs) was analyzed based on the TCGA database. Weighted gene co-expression network analysis (WGCNA) and Cox regression analysis were used to establish risk models. According to the median risk score, COAD patients were divided into high risk and low risk groups. The prognostic difference were compared between the two groups. The function of the model was validated using GEO. Results A total of 1015 IREGs was obtained. The established model consisted of three genes: RAR related orphan receptor C (RORC), leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) and lectin galactoside-binding soluble galectin 4 (LGALS4). The high-risk group had significantly poorer prognosis than low-risk group in the GEO database, and it was validated using a GEO database. Further analysis via univariate and multivariate Cox regression analyses revealed that risk model could function as independent prognostic factor for COAD patients. Conclusion The risk model based on IREGs can predict the prognosis of patients with COAD.

Pathological Types,Expression of Mismatch Repair Protein,Human Epidermal Growth Factor Receptor 2,and Pan-TRK,and Eostein-Barr Virus Infection in Patients With Colorectal Cancer Resected in Tibet / 中国医学科学院学报

Objective To study the pathological types,expression of mismatch repair protein,human epidermal growth factor receptor 2(HER2),and Pan-TRK,and Epstein-Barr virus(EBV)infection in patients with colorectal cancer resected in Tibet. Methods A total of 79 patients with colorectal cancer resected in Tibet Autonomous Region People's Hospital from December 2013 to July 2021 were enrolled in this study.The clinical and pathological data of the patients were collected.The expression of mismatch repair protein,HER2,and Pan-TRK was detected by immunohistochemical(IHC)staining,and detection of HER2 gene by fluorescence in situ hybridization(FISH)in the patients with HER2 IHC results of 2+ or above.EBV was detected by in situ hybridization with EBV-encoded small RNA. Results A total of 79 colorectal cancer patients were included in this study,with the male-to-female ratio of 1.26:1 and the mean age of(57.06±12.74)years(24-83 years).Among them,4 patients received preoperative neoadjuvant therapy.Colonic cancer and rectal cancer occurred in 57(57/79,72.15%,including 31 and 26 in the right colon and left colon,respectively)and 22(22/79,27.85%)patients,respectively.The maximum diameter of tumor varied within the range of 1-20 cm,with the mean of(6.61±3.33)cm.Among the 79 colorectal cancer patients,75(75/79,94.94%)patients showed adenocarcinoma.Lymph node metastasis occurred in 12(12/21,57.14%)out of the 21 patients with severe tumor budding,13(13/23,56.52%)out of the 23 patients with moderate tumor budding,and 2(2/31,6.45%)out of the 31 patients with mild tumor budding,respectively.The lymph node metastasis rate showed differences between the patients with severe/moderate tumor budding and the patients with mild tumor budding(all P<0.001).The IHC staining showed that mismatch repair protein was negative in 10(10/65,15.38%)patients,including 5 patients with both MSH2 and MSH6 negative,4 patients with both MLH1 and PMS2 negative,and 1 patient with MSH6 negative.Pan-TRK was negative in 65 patients.The IHC results of HER2 showed 0 or 1+ in 60 patients and 2+ in 5 patients.FISH showed no positive signal in the 5 patients with HER2 IHC results of 2+.The detection with EBV-encoded small RNA showed positive result in 1(1/65,1.54%)patient. Conclusions Non-specific adenocarcinoma of the right colon is the most common in the patients with colorectal cancer resected in Tibet,and 15% of the patients showed mismatch repair protein defects.EBV-associated colorectal carcer is rare,Pan-TRK expression and HER2 gene amplification are seldom.The colorectal cancer patients with moderate and severe tumor budding are more likely to have lymph node metastasis.

Nomogram-Based Prediction of Risk of Cervical Lymph Node Metastasis in Differentiated Thyroid Carcinoma / 中国医学科学院学报

Objective To establish a nomogram for predicting the risk of cervical lymph node metastasis in differentiated thyroid carcinoma (DTC). Methods The patients with complete clinical data of DTC and cervical lymph node ultrasound and diagnosed based on pathological evidence from January 2019 to December 2021 were assigned into a training group (n=444) and a validation group (n=125).Lasso regression was performed to screen the data with differences between groups,and multivariate Logistic regression to establish a prediction model with the factors screened out by Lasso regression.C-index and calibration chart were employed to evaluate the prediction performance of the established model. Results The predictive factors for establishing the model were lymph node short diameter≥0.5 cm,long-to-short-axis ratio<2,disappearance of lymph node hilum,cystic transformation,hyperechogenicity,calcification,and abnormal blood flow (all P<0.001).The established model demonstrated a good discriminative ability,with the C index of 0.938 (95%CI=0.926-0.961) in the training group. Conclusion The nomogram established based on the ultrasound image features of cervical lymph nodes in DTC can accurately predict the risk of cervical lymph node metastasis in DTC.

Persistent increase and improved survival of stage I lung cancer based on a large-scale real-world sample of 26,226 cases / 中华医学杂志(英文版)

BACKGROUND@#Lung cancer prevails and induces high mortality around the world. This study provided real-world information on the evolution of clinicopathological profiles and survival outcomes of lung cancer, and provided survival information within stage I subtypes.@*METHODS@#Patients pathologically confirmed with lung cancer between January 2009 and December 2018 were identified with complete clinicopathological information, molecular testing results, and follow-up data. Shifts in clinical characteristics were evaluated using χ2 tests. Overall survival (OS) was calculated through the Kaplan-Meier method.@*RESULTS@#A total of 26,226 eligible lung cancer patients were included, among whom 62.55% were male and 52.89% were smokers. Non-smokers and elderly patients took increasingly larger proportions in the whole patient population. The proportion of adenocarcinoma increased from 51.63% to 71.80%, while that of squamous carcinoma decreased from 28.43% to 17.60%. Gene mutations including EGFR (52.14%), KRAS (12.14%), and ALK (8.12%) were observed. Female, younger, non-smoking, adenocarcinoma patients and those with mutated EGFR had better survival prognoses. Importantly, this study validated that early detection of early-stage lung cancer patients had contributed to pronounced survival benefits during the decade. Patients with stage I lung cancer, accounted for an increasingly considerable proportion, increasing from 15.28% to 40.25%, coinciding with the surgery rate increasing from 38.14% to 54.25%. Overall, period survival analyses found that 42.69% of patients survived 5 years, and stage I patients had a 5-year OS of 84.20%. Compared with that in 2009-2013, the prognosis of stage I patients in 2014-2018 was dramatically better, with 5-year OS increasing from 73.26% to 87.68%. Regarding the specific survival benefits among stage I patients, the 5-year survival rates were 95.28%, 93.25%, 82.08%, and 74.50% for stage IA1, IA2, IA3, and IB, respectively, far more promising than previous reports.@*CONCLUSIONS@#Crucial clinical and pathological changes have been observed in the past decade. Notably, the increased incidence of stage I lung cancer coincided with an improved prognosis, indicating actual benefits of early detection and management of lung cancer.