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.

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.

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.

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)

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.

Selective photodynamic effects on cervical adenocarcinoma cells provided by F127 Pluronic®-based micelles modulating hypericin delivery

Abstract Cervical cancer is a leading cause of death among women. The endocervical adenocarcinoma (ECA) represents an aggressive and metastatic type of cancer with no effective treatment options currently available. We evaluated the antitumoral and anti-migratory effects of hypericin (HYP) encapsulated on Pluronic F127 (F127/HYP) photodynamic therapy (PDT) against a human cell line derived from invasive cervical adenocarcinoma (HeLa) compared to a human epithelial cell line (HaCaT). The phototoxicity and cytotoxicity of F127/HYP were evaluated by the following assays: colorimetric assay, MTT, cellular morphological changes by microscopy and long-term cytotoxicity by clonogenic assay. In addition, we performed fluorescence microscopy to analyze cell uptake and subcellular distribution of F127/HYP, cell death pathway and reactive oxygen species (ROS) production. The PDT mechanism was determined with sodium azide and D-mannitol and cell migration by wound-healing assay. The treatment with F127/HYP promoted a phototoxic result in the HeLa cells in a dose-dependent and selective form. Internalization of F127/HYP was observed mainly in the mitochondria, causing cell death by necrosis and ROS production especially by the type II PDT mechanism. Furthermore, F127/HYP reduced the long-term proliferation and migration capacity of HeLa cells. Overall, our results indicate a potentially application of F127/HYP micelles as a novel approach for PDT with HYP delivery to more specifically treat ECA.

Primer caso de escisión mesorrectal total transanal (TaTME) para el tratamiento del cáncer de recto medio en un centro docente universitario: descripción de la técnica / First case of transanal total mesorectal excision (TaTME) for middle rectal cancer in a teaching tertiary center: technical aspects / Primeiro caso de excisão total do mesorreto transanal (TaTME) para tratamento de câncer de reto meio em um centro universitário de ensino: aspectos tecnicos

La escisión mesorrectal transanal (TaTME: transanal total mesorectal escision) es la última de una larga lista de desarrollos técnicos y tecnológicos para el tratamiento del cáncer de recto medio y bajo. Incluso para los cirujanos colorrectales experimentados, lograr una escisión mesorrectal total (emt) de calidad en cirugía oncológica no siempre es sencillo, por la dificultad de obtener un adecuado acceso a la pelvis. Los estudios realizados han mostrado resultados comparables al abordaje laparoscópico, con tasas elevadas de escisiones mesorrectales completas y bajo porcentaje de margen circunferencial radial (CRM: circumferential radial margin) y distal positivos, con un adecuado número de ganglios resecados. Como toda técnica nueva, su implementación puede traer consecuencias no intencionales. La complejidad del abordaje, la dificultad en la identificación de nuevos repères y planos anatómicos, ha llevado a complicaciones graves como la lesión uretral o la siembra tumoral pelviana. Por ello, la comunidad quirúrgica ha retrasado la implementación masiva de la técnica y desarrollado estrategias de enseñanza y monitorización de este procedimiento para su realización en centros de alto volumen. El objetivo de esta publicación es presentar el primer caso de TaTME en un centro docente universitario y difundir en nuestra comunidad científica el fundamento de la técnica, sus indicaciones, describir los principales pasos técnicos, complicaciones, resultados oncológicos y funcionales.

Transanal total mesorectal excision (TaTME) is the last of a long list of technical and technological developments for treatment of middle and low rectal cancer. Even for skilled colorectal surgeons, achieving a good quality total mesorectal excision (TME) in oncology surgery is not always simple, due to the difficulty of obtaining optimal access to the pelvis. So far, studies have shown similar results to laparoscopic surgery, with high rates of complete mesorectal excisions and low rate of circumferential radial margin (CRM) and distal margin with an appropriate number of resected lymph nodes. Like every new technique, its implementation can bring unwanted consequences. The complexity of the approach, the difficulty in the identification of new landmarks and anatomic planes, has led to serious complications such as urethral injury or tumoral seeding. This has made slowdown the massive implementation of the technique among the surgical community, addressing the need of developing training programs and mentoring of this procedure that belongs to high volume centers. The aim of this publication is to present the first case of TaTME in a teaching tertiary center and spread, in our scientific community, the principles of the technique, its indications, main technical steps, complications and functional and oncologic results.

A excisão mesorretal transanal (TaTME: transanal total mesorectal escision) é o mais recente de uma longa linha de desenvolvimentos técnicos e tecnológicos para o tratamento do câncer retal inferior e médio. Mesmo para cirurgiões colorretais experientes, nem sempre é fácil obter uma excisão total do mesorreto (EMT) de qualidade em cirurgia de câncer, devido à dificuldade de obter acesso adequado à pelve. Os estudos realizados mostraram resultados comparáveis ​​à abordagem laparoscópica, com altas taxas de excisões completas do mesorreto e baixo percentual de margem radial circunferencial positiva (CRM: circumferential radial margin) e distal, com número adequado de linfonodos ressecados. Como qualquer nova técnica, sua implementação pode ter consequências não intencionais. A complexidade da abordagem, a dificuldade em identificar novos repères e planos anatômicos, levou a complicações graves, como lesão uretral ou semeadura de tumor pélvico. Por esse motivo, a comunidade cirúrgica atrasou a implementação massiva da técnica e desenvolveu estratégias de ensino e acompanhamento desse procedimento para sua realização em centros de alto volume. O objetivo desta publicação é apresentar o primeiro caso de TaTME em um centro de ensino universitário e divulgar em nossa comunidade científica as bases da técnica, suas indicações, descrever as principais etapas técnicas, complicações, resultados oncológicos e funcionais.

Perfil Clínico-Epidemiológico do Câncer Colorretal na Região Oeste do Paraná, Brasil, 2016-2018 / Clinical and Epidemiological Profile of Colorectal Cancer in Paraná's Western Region, Brazil, 2016-2018 / Perfil Clínico-Epidemiológico de lo Cáncer Colorrectal en la Región Oeste de Paraná, Brasil, 2016-2018

Introdução: O câncer colorretal é a neoplasia mais frequente do trato gastrointestinal, sendo a segunda principal causa de morte por câncer no mundo. Objetivo: Traçar um perfil clínico-epidemiológico do câncer colorretal na Região Oeste do Paraná (Brasil), entre 2016 e 2018. Método: Estudo observacional analítico do tipo transversal, construído a partir da análise de resultados de exames anatomopatológicos, realizados entre 2016 a 2018. Realizaram-se análises por estatística descritiva, teste de associação qui-quadrado e U de Mann-Whitney. Adotou-se nível de significância de 5%. Resultados: A análise de 509 laudos positivos para câncer colorretal permitiu identificar o predomínio de pacientes do sexo masculino e a idade média de diagnóstico de 62 anos. A malignidade mostrou-se mais incidente na faixa etária de 61 a 70 anos (29,9%), e considerável número de casos ocorreu em pacientes abaixo de 50 anos (19,6%). Houve predomínio em cólon esquerdo e do tipo histológico adenocarcinoma infiltrativo moderadamente diferenciado. Verificou-se associação entre topografia da doença e sexo, com maior predominância do sexo feminino para tumores do cólon direito e do sexo masculino para tumores do cólon esquerdo (p=0,0081). Conclusão: A partir deste estudo, delineia-se um perfil clínico-epidemiológico do câncer colorretal na Região Oeste do Paraná, com maior incidência da doença em homens, sexagenários, além de predomínio de tumores em cólon esquerdo e do tipo adenocarcinoma infiltrativo moderadamente diferenciado. Tais achados são relevantes considerando a possibilidade de aplicação assertiva de protocolos internacionais de rastreio do câncer nessa população

Introduction: The colorectal cancer is the most frequent neoplasm of the gastrointestinal tract and the second cause of cancer related death. Objective: To design a clinical and epidemiological profile of the colorectal cancer at the Western Region of the Paraná State from 2016 to 2018. Method: Analytical cross-sectional observational study based on the evaluation of the results of anatomopathological exams, between 2016 and 2018, at a regional specialized center. Analyses were performed using descriptive statistics, chi-square test for association and Mann-Whitney U test. A significance level of 5% was adopted. Results: The analysis of 509 positive anatomopathological reports of colorectal cancer allowed to identify the predominance of male patients and mean age at diagnosis of 62 years. The malignancy was more incident in patients between 61 and 70 years of age (29.9%). A considerable number of cases was found in patients younger than 50 years (19.6%). The disease was predominant at the left colon, of the type moderately differentiated infiltrating adenocarcinoma according to the histological classification. Association between the tumor topography and sex was found, with predominance of females for the right colon and males for the left colon (p=0.0081). Conclusion: This study designed the colorectal cancer clinical and epidemiological profile at Paraná's Western Region. The disease affects more males, older than 60 years of age, mostly with moderately differentiated infiltrative adenocarcinoma at the left colon. These findings are relevant considering the possibility of applying international cancer screening protocols in this population.

Introducción: El cáncer colorrectal es la neoplasia más frecuente del tracto gastrointestinal y la segunda causa de muerte por cáncer a nivel mundial. Objetivo: Trazar un perfil clínico-epidemiológico del cáncer colorrectal en el Oeste de Paraná (Brasil), entre 2016 y 2018. Método: Estudio observacional analítico transversal realizado con los análisis de resultados de exámenes anatomopatológicos entre 2016 a 2018. Se realizaron análisis mediante estadísticas descriptivas, prueba de asociación chi-cuadrado y U de MannWhitney. Se adoptó nivel de significación del 5%. Resultados: Entre los 509 informes positivos para cáncer colorrectal, el 52,8% de los pacientes eran del sexo masculino y tenían promedio de edad de diagnóstico de 62 años. El cáncer fue más frecuente en el grupo de 61 a 70 años (29,9%) y un número significativo de casos se presentó en pacientes menores de 50 años (19,6%). Predominó la enfermedad de colon izquierdo y del tipo histológico de adenocarcinoma infiltrante moderadamente diferenciado. Fue encontrado asociación entre la topografía y el sexo, con mayor predominio del sexo femenino para los tumores de colon derecho y del sexo masculino para los tumores de colon izquierdo (p=0,0081). Conclusión: Se elabora un perfil clínico-epidemiológico del cáncer colorrectal en la región Oeste de Paraná, con mayor incidencia en el sexo masculino, edad de 60 años, predominio de tumores en el colon izquierdo y del tipo adenocarcinoma infiltrante moderadamente diferenciado. Estos puntos son relevantes considerando la posibilidad de aplicación asertiva de protocolos internacionales de rastreo del cáncer en esta población.

Réplica à Carta às Editoras de Autoria de Pablo Salomón Montes-Arcón / Reply to the Letter to the Editors by Pablo Salomón Montes-Arcón / Respuesta a la Carta a las Editoras por Autoria de Pablo Salomón Montes-Arcón

Réplica à Carta às Editoras de Autoria de Pablo Salomón Montes-Arcón.

Importancia de la Estadificación del Cáncer Colorrectal para Pacientes y Profesionales de la Salud / Importance of Staging of Colorectal Cancer for Patients and Health Professionals / Importância do Estadiamento do Câncer Colorretal para Pacientes e Profissionais de Saúde

Carta às editoras com considerações referentes à importância do estadiamento no câncer colorretal para pacientes e profissionais de saúde sobre o artigo "Perfil Clínico-epidemiológico do Câncer Colorretal na Região Oeste do Paraná, Brasil, 2016-2018", publicado na Revista Brasileira de Cancerologia 2023; 69 (1): e-174215.

From left to right. para-aortic lymph nodes sampling during pancreatoduodenectomy for pancreatic cancer / Da esquerda para a direita. ressecção de linfonodos para-aórticos durante duodenopancreatectomia para câncer pancreático

ABSTRACT BACKGROUND: Para-aortic lymph nodes involvement in pancreatic head cancer has been described as an independent adverse prognostic factor. To avoid futile pancreatic resection, we systematically perform para-aortic lymphadenectomy as a first step. AIMS: To describe our technique for para-aortic lymphadenectomy. METHODS: A 77-year-old female patient, with jaundice and resectable pancreatic head adenocarcinoma, underwent pancreaticoduodenectomy associated with infracolic lymphadenectomy. RESULTS: The infracolic anterior technique has two main advantages. It is faster and prevents the formation of postoperative adhesions, which can make subsequent surgical interventions more difficult. CONCLUSIONS: We recommend systematic para-aortic lymphadenectomy as the first step of pancreaticoduodenectomy for pancreatic head adenocarcinoma by this approach.

RESUMO RACIONAL: O envolvimento dos gânglios linfáticos para-aórticos no câncer da cabeça do pâncreas tem sido descrito como um fator prognóstico adverso independente. Para evitar a ressecção pancreática inútil, realizamos sistematicamente linfadenectomia para-aórtica. OBJETIVOS: Descrever a técnica de linfadenectomia para-aórtica. MÉTODOS: Paciente do sexo feminino, 77 anos, com quadro de icterícia e adenocarcinoma da cabeça do pâncreas ressecável, submetida à duodenopancreatectomia associada à linfadenectomia infracólica. RESULTADOS: Esta técnica anterior infracólica tem duas vantagens principais: é mais rápida e evita a formação de aderências pós-operatórias, o que pode dificultar as intervenções cirúrgicas subsequentes. CONCLUSÕES: Recomendamos a linfadenectomia para-aórtica sistemática como o primeiro passo da duodenopancreatectomia para o adenocarcinoma da cabeça do pâncreas por esta abordagem.

Relación localización-tipo histológico del adenocarcinoma gástrico en pacientes del IAHULA Mérida Venezuela. Repercusiones quirúrgicas / Relation between location and histology in adenocarcinoma gastric patients at IAHULA Mérida Venezuela. Surgical implications

El cáncer gástrico es una neoplasia común en el mundo, su patrón anatómico cambió, con diferencias entre grupos poblacionales. Es importante establecer la relación entre la localización de la lesión y su histología, planteando exigencias quirúrgicas diferentes. Objetivo: describir el comportamiento de la patología en Mérida Venezuela y los procedimientos quirúrgicos empleados en su manejo. Método : investigación observacional transversal en pacientes del IAHULA con adenocarcinoma gástrico, durante el periodo enero 2016 hasta diciembre 2020,Resultados : en relación a su localización anatómica la distribución fue: 47 antro pilórico, 33 cardias y el resto en el cuerpo gástrico. Las lesiones difusas o con células en anillo de sello predominaron en las 3 ubicaciones del estómago, pero con cifras similares para aquellas en el cardias/fundus, a diferencia de las lesiones de la región de antro/píloro donde hubo 36 de tipo difuso y 11 de tipo intestinal. Las lesiones antro pilóricas se asociaron con la resección oncológica mediante gastrectomía subtotal (p 0,000). No se detectó asociación entre la localización de la lesión y la clasificación propuesta por Laurent (p 0,073).Conclusión : a pesar de la importancia de la ubicación de la lesión y el tipo histológico para fines quirúrgicos, no se encontró la referida relación, lo que resalta la heterogeneidad en la presentación del adenocarcinoma gástrico en la localidad(AU)

Gastric cancer is a common cancer worldwide; his anatomic pattern did change with differences between populations. It is important to know the relation between localization and histology, because of different surgical exigencies.Objective: in order to determinate the behavior of gastric cancer in Merida, Venezuela. Methods: transversal and observational study, with IAHULA gastric adenocarcinoma patients between January 2016 to December 2020. Results : the anatomical localization distribution was: 47 antro pyloric, 33 at cardias and the other cases at the gastric body. Histological distribution: Diffuses or signet ring cells adenocarcinomas were most common in every gastric localization but similar numbers to the proximal location were placed, different results at antro/pyloric with 36 diffuses and 11 intestinal according the Laurent classification. The antro/pyloric cases had significant relation with resection of subtotal gastrectomy (p 0,000). There was not association between the gastric location and the Laurent classification (p 0,073).Conclusion : no matter the importance described to the initial anatomical location and the histology type talking about surgical implications, there was no relation between both factors, so there is a big heterogeneity in gastric adenocarcinoma in Merida, Venezuela(AU)

Adenocarcinoma de vesícula biliar: una entidad poco frecuente y mortal. A propósito de un caso / Gallbladder adenocarcinoma: a rare and fatal entity. A case report

Introducción: El adenocarcinoma de vesícula biliar es de las neoplasias digestivas con peor pronóstico; es poco común, y está asociado a una alta mortalidad. La mayoría de los diagnósticos son incidentales cuando se realiza exploración quirúrgica por sospecha de colelitiasis; encontrando malignidad en el 1 a 2% de estos casos. Produce síntomas inespecíficos, llevando a diagnósticos tardíos, empeorando así el pronóstico. Las características de esta neoplasia y el diagnóstico tardío hacen que muchas veces la resección curativa no sea posible. Caso Clínico : Paciente femenino de 45 años, quien refiere inicio de enfermedad actual (IEA) en diciembre de 2021 cuando posterior a ingesta de comida presenta dolor de aparición súbita, opresivo, de fuerte intensidad en epigastrio, intermitente. Ultrasonido abdominal (USA) reporta LOE vesicular. Se decide resolución mediante colecistectomía abierta extendida, donde se encuentra vesícula biliar (VB), con tumor en su interior que ocupa 30% de la luz, se realiza biopsia intraoperatoria, diagnosticándose ADC de vesícula. La paciente evolucionó satisfactoriamente y es egresada. En controles periódicos no hay evidencia de recidiva de la enfermedad. Conclusión : El cáncer de vesícula biliar (CVB) es una patología poco común, de difícil diagnóstico y asociado a una alta tasa de mortalidad, que produce síntomas inespecíficos por lo que es necesario un alto índice de sospecha para su diagnóstico. El manejo y conducta terapéutica depende de la extensión y el estadiaje del tumor. Es necesaria la realización de más estudios para determinar y estandarizar el manejo de esta infrecuente neoplasia(AU)

Introduction: Gallbladder adenocarcinoma is one of the digestive neoplasms with the worst prognosis; it is uncommon and is associated with high mortality. Most diagnoses are incidental when surgical exploration is performed due to suspected cholelithiasis, with malignancy found in 1 to 2% of these cases. It produces nonspecific symptoms, leading to late diagnoses, thereby worsening the prognosis. The characteristics of this neoplasm and the late diagnosis often make curative resection impossible.Clinical Case : A 45-year-old female patient who reported the onset of the current illness in December 2021. After a meal, she experienced sudden, intense, and intermittent epigastric pain. Abdominal ultrasound (US) reported gallbladder wall thickening. It was decided to perform an extended open cholecystectomy, and a tumor was found inside the gallbladder, occupying 30% of its lumen. An intraoperative biopsy was performed, diagnosing gallbladder adenocarcinoma. The patient recovered satisfactorily and was discharged. Subsequent follow-up visits have shown no evidence of disease recurrence.Conclusion : Gallbladder cancer (GBC) is a rare condition with a challenging diagnosis and a high mortality rate. It produces nonspecific symptoms, so a high index of suspicion is necessary for its diagnosis. The management and therapeutic approach depend on the tumor's extent and staging. Further studies are needed to determine and standardize the management of this uncommon neoplasm(AU)