Genomic profiling in GIST: Implications in clinical outcome and future challenges.

Gastrointestinal Stromal Tumors (GIST) are the most frequent mesenchymal neoplasia of the digestive tract. Genomic alterations in KIT, PDFGRA, SDH, and BRAF genes are essential in GIST oncogenesis. Therefore, the mutations in these genes have demonstrated clinical implications. Tumors with deletions in KIT-exon 11 or duplications in exon 9 are associated with a worse prognosis. In contrast, KIT-exon 11 substitutions and duplications are associated with a better clinical outcome. Moreover, mutations in Kit exon 9 and 11 are actionable, due to their response to imatinib, while mutations in PDGFRA respond to sunitinib and/or avapritinib. Although, molecular testing on tissue samples is effective; it is invasive, requires adequate amounts of tissue, and a long experimental process is needed for results. In contrast, liquid biopsy has been proposed as a simple and non-invasive method to test biomarkers in cancer. The most common molecule analyzed by liquid biopsy is circulating tumor DNA (ctDNA). GISTs ctDNA testing has been demonstrated to be effective in identifying known and novel KIT mutations that were not detected using traditional tissue DNA testing and have been useful in determining progression risk and response to TKI therapy. This allows the clinician to have an accurate picture of the genetic changes of the tumor over time. In this work, we aimed to discuss the implications of mutational testing in clinical outcomes, the methods to test ctDNA and the future challenges in the establishment of alternatives of personalized medicine.

Latin American young patients with gastric adenocarcinoma: worst prognosis and outcomes.

Background: Incidence of young patients (aged 40 years or younger) diagnosed with gastric carcinoma has increased worldwide. Young GC diagnosis, have clinicopathological features that differ from elderly, and is correlated with bad prognosis factors. The purpose of this work is to describe the prevalence, clinic-pathological features, and prognosis of overall survival (OS) of young Latin-American patients with GC. Methods: Retrospective, observational study. Included patients treated at the National Cancer Institute [2004-2020]. Statistical analysis: χ2 and t-test, Kaplan-Meier, Log-Rank and Cox-Regression. Statistical significance differences were assessed when P was bilaterally <0.05. Results: A total of 2,543 patients fulfilled the inclusion criteria. Young-patients were predominantly female (54%), with diffuse-type adenocarcinoma (68%), signet-ring-cell (72%), poor-differentiation (90%), and metastatic (79%). In OS analysis, patients with metastatic disease, showed differences regarding age, young patients reported a median-OS of 8 versus 13 months for elderly patients (P=0.001). Among young patients, differences were also observed regarding gender, young-female patients had a median-OS of 5 versus 11 months for young-man (P=0.001). Conclusions: This is one of the pioneer studies correlating age with gender and the prognostic features of bad prognosis in Latin-American population. Besides, supports the idea that a global effort is required to improve awareness, prevention, and early diagnosis of GC.

Impact of ileostomy in the adjuvant treatment and outcome of colon cancer.

BACKGROUND: After tumor resection, a preventive diverting loop ileostomy creation is a routine surgical procedure to prevent anastomotic leakage and infections and to preclude secondary surgeries. Despite its benefits, several studies have proposed potential complications that extend the disease course by impairing the feasibility of adjuvant chemotherapy and adherence. PURPOSE: The aim of this study was to evaluate the impact of ileostomy complications on the adherence to adjuvant treatment and overall survival (OS) of colon cancer (CC) patients. METHODS: Retrospective, observational study. Patients diagnosed with colon adenocarcinoma were treated between January 2010 and December 2020 at the National Cancer Institute in Mexico. STATISTICAL ANALYSIS: χ2 and t-test, Kaplan-Meier, log-rank, and Cox regression. Statistical significance differences were assessed when p was bilaterally < 0.05. RESULTS: The most frequent complications of loop-derived ileostomy were hydro-electrolytic dehydration (50%), acute kidney injury (AKI) (26%), grade 1-2 diarrhea (28%), and grade 3-4 diarrhea (21%) (p = 0.001). Patients with complete chemotherapy did not reach the median OS. In contrast, the median OS for patients with non-complete chemotherapy was 56 months (p = 0.023). Additionally, 5-year OS reached to 100% in the early restitution group, 85% in the late restitution group, and 60% in the non-restitution group (p = 0.016). Finally, AKI (p = 0.029; 95% confidence interval (CI) 3.348 [1.133-9.895]), complete chemotherapy (p = 0.028; 95% CI 0.376 [0.105-0.940]), and reversed ileostomy (p = 0.001; 95% CI 0.125 [0.038-0.407]) remained as predictors of overall survival for patients with CC treated with a loop ileostomy. CONCLUSIONS: Our results emphasize the early stoma reversal restitution as a safe and feasible alternative to prevent severe complications related to ileostomies which improve chemotherapy adherence and overall survival of colon cancer patients. This is one of the pioneer studies analyzing the impact of ileostomy on treatment adherence and outcome of Latin American patients with colon cancer. TRIAL REGISTRATION: Retrospective study No. 2021/045, in April 2021.

A microRNA panel that regulates proinflammatory cytokines as diagnostic and prognosis biomarkers in colon cancer.

Colon cancer (CC) is the third most common neoplasm and the fourth cause of cancer-related death worldwide in both sexes. It has been established that inflammation plays a critical role in tumorigenesis and progression of CC. Immune, stromal and tumor cells supply the tumor microenvironment with pro-inflammatory cytokines such as interleukin 1ß, TNFα, IL-6 and IL-11, to hyperactivate signaling pathways linked to cancerous processes. Recent findings suggest a putative role of microRNAs (miRNAs) in the progression and management of the inflammatory response in intestinal diseases. Moreover, miRNAs are able to regulate expression of molecular mediators that are linking inflammation and cancer. In this work a miRNA panel differentially expressed between healthy, inflammatory bowel disease (IBD) and CC tissue was established. Identified miRNAs regulate signaling pathways related to inflammation and cancer progression. An inflammation associated-miRNA panel composed of 11-miRNAs was found to be overexpressed in CC but not in inflamed or normal tissues (miR-21-5p, miR-304-5p, miR-577, miR-335-5p, miR-21-3p, miR-27b-5p, miR-335-3p, miR-215-5p, miR-30b-5p, miR-192-5p, miR-3065-5p). The association of top hit miRNAs, miR-3065-5p and miR-30b-5p expression with overall survival of CC patients was demonstrated using Kaplan-Meier tests. Finally, differential miRNA expression was validated using an inflammation-associated CC model induced by Azoxymethane/Dextran Sodium Sulfate (AOM/DSS) to compare miRNA expression in normal and inflamed tissue versus CC tissues. Based on these findings we propose the identified inflammatory miRNA panel as a potent diagnostic tool for CC determination.

Cociente ganglionar como factor pronóstico de recurrencia tumoral en pacientes con carcinoma escamoso de cavidad oral.

BACKGROUND: The lymph node ratio (LNR) is a recent tool, but its predictive value for recurrence is uncertain. OBJECTIVE: To evaluate LNR as a prognostic factor for disease-free survival (DFS) in patients with oral squamous cell carcinoma. METHOD: Retrospective observational study. Patients with oral squamous cell carcinoma undergoing resection and lymph node dissection. Chi squared, Kaplan-Meier, log rank and Cox regression tests were run; bilateral p ≤ 0.05 determined statistical significance. RESULTS: 88 patients were included, 45% (n = 40) men and 54% (n = 48) women, mean age of 60.42 (± 14.28) years. Main tumor location in tongue (75%); 61% in clinical stage I-III and 39% in clinical stage IV. Population was divided into LNR < 0.06 (58%) and LNR ≥ 0.06 (42%). The median DFS was not reached for both groups (p = 0.018). Predictors of DFS were the LNR (p = 0.024; hazard ratio [HR]: 2.20; confidence interval of 95% [95% CI]: 1.11-4.39) and the clinical stage (p = 0.004; HR: 1.76; 95% CI: 1.19-2.59). In the multivariate analysis, predictors were not maintained (p = 0.227 and 0.191, respectively). CONCLUSIONS: Significant differences were observed in the DFS analysis, however, they were not predictive of local recurrence in the multivariate analysis.

ANTECEDENTES: El cociente ganglionar (LNR) es una herramienta reciente, pero su valor predictivo de recurrencia es incierto. OBJETIVO: Evaluar el LNR como factor pronóstico de supervivencia libre de enfermedad (SLE) en pacientes con carcinoma oral de células escamosas. MÉTODO: Estudio retrospectivo observacional. Pacientes con carcinoma oral de células escamosas sometidos a resección y disección ganglionar. Se aplicaroon las pruebas de ji al cuadrado, Kaplan-Meier, log rank y regresión de Cox; se consideró estadísticamente significativo p ≤ 0.05 bilateral. RESULTADOS: Fueron incluidos 88 pacientes, el 45% (n = 40) hombres y el 54% (n = 48) mujeres, con una edad media de 60.42 (± 14.28) años. La principal localización tumoral fue la lengua (75%); el 61% en etapa I-III y el 39% en etapa IV. Se dividió en LNR < 0.06 (58%) y LNR ≥ 0.06 (42%). La mediana de SLE no fue alcanzada para ambos grupos (p = 0.018). Resultaron predictores de SLE el LNR (p = 0.024; hazard ratio [HR]: 2.20; intervalo de confianza del 95% [IC95%]: 1.11-4.39) y la etapa clínica (p = 0.004; HR: 1.76; IC95%: 1.19-2.59). En el análisis multivariado no se mantuvieron predictores (p = 0.227 y p = 0.191, respectivamente). CONCLUSIONES: Se observaron diferencias significativas en el análisis de SLE, pero no se mantuvieron como predictoras de recurrencia local en el análisis multivariado.

Carcinoma epidermoide puro-combinado de vesícula biliar / Gallbladder epidermoid carcinoma

Background: Gallbladder epidermoid carcinoma is rare and more common in women over 55 years of age. Aim: To report the features of 15 patients with gallbladder epidermoid carcinoma. Material and Methods: Review of medical records of patients with gallbladder cancer in an oncology service. Results: Of 207 patients with gallbladder cancer, 15patients aged 53-72years, 93% women had an epidermoid component in their cancer. Forty percent were diabetic and 33% had cholelithiasis. All had locoregional extension of the tumor. A cholecystectomy was done in nine patients (using open surgery in six). In six patients, only a biopsy was done. Median survival was 4.2 months. Conclusions: Gallbladder epidermoid carcinoma is uncommon and has a bad prognosis.

Carcinoma epidermoide primario del estómago: reporte de tres casos / Primary squamous cell carcinoma of the stomach: report of three cases

Gastric squamous cell carcinoma (SCC) is a rare type of cancer. We report three patients with the tumor. A 65 years old male presenting with weight los and heartburn. An upper gastrointestinal endoscopy revealed an ulcerated tumor whose biopsy disclosed a gastric epidermoid carcinoma. The patient was operated and chemotherapy was attempted, but he died five months later. A 39 years old male with an antral tumor corresponding to an epidermoid carcinoma. He was operated and received chemotherapy and radiotherapy and died one year later. A 79 years old female with a distal antral tumor corresponding to a undifferentiated epidermoid carcinoma. She received palliative therapy and died two months later.

Effects of Dietary Components During and After Concomitant Chemoradiotherapy, Radiotherapy, or Sequential Chemoradiotherapy to the Abdominopelvic Area.

Radiotherapy is a fundamental part of the treatment of pelvic neoplasms. Up to 90% of patients develop gastrointestinal symptoms as a result of acute injury to the small and large intestine, particularly in the mucosa. Radiotherapy leads to atrophy of the intestinal epithelium, acute crypt inflammation, inflammatory infiltration of the epithelium, malabsorption of lactose, and biliary salts as well as alterations in pancreatic enzymes and biliary salts, resulting in the malabsorption syndrome and dysbiosis. The most commonly reported symptoms of pelvic radiation disease include changes in bowel habits (94%), decreased fecal consistency (80%), frequency of bowel movements (74%), bowel urgency (39%), and fecal incontinence (37%). Although nutritional interventions with dietary modifications have been reported to prevent and treat gastrointestinal symptoms, the evidence remains inconclusive.

[Primary squamous cell carcinoma of the stomach. Report of three cases]. / Carcinoma epidermoide primario del estómago. Reporte de tres casos.

Gastric squamous cell carcinoma (SCC) is a rare type of cancer. We report three patients with the tumor. A 65 years old male presenting with weight los and heartburn. An upper gastrointestinal endoscopy revealed an ulcerated tumor whose biopsy disclosed a gastric epidermoid carcinoma. The patient was operated and chemotherapy was attempted, but he died five months later. A 39 years old male with an antral tumor corresponding to an epidermoid carcinoma. He was operated and received chemotherapy and radiotherapy and died one year later. A 79 years old female with a distal antral tumor corresponding to a undifferentiated epidermoid carcinoma. She received palliative therapy and died two months later.

[Gallbladder epidermoid carcinoma]. / Carcinoma epidermoide puro-combinado de vesícula biliar.

BACKGROUND: Gallbladder epidermoid carcinoma is rare and more common in women over 55 years of age. AIM: To report the features of 15 patients with gallbladder epidermoid carcinoma. MATERIAL AND METHODS: Review of medical records of patients with gallbladder cancer in an oncology service. RESULTS: Of 207 patients with gallbladder cancer, 15patients aged 53-72years, 93% women had an epidermoid component in their cancer. Forty percent were diabetic and 33% had cholelithiasis. All had locoregional extension of the tumor. A cholecystectomy was done in nine patients (using open surgery in six). In six patients, only a biopsy was done. Median survival was 4.2 months. CONCLUSIONS: Gallbladder epidermoid carcinoma is uncommon and has a bad prognosis.