FLOX (5-fluorouracil + leucovorin + oxaliplatin) chemotherapy for colorectal cancer leads to long-term orofacial neurotoxicity: a STROBE-guided longitudinal prospective study.

BACKGROUND: Colorectal carcinoma (CRC) is widely treated by chemotherapy based on an intensely neurotoxic drug: oxaliplatin (OXL). We objective to evaluate prospectively the orofacial neurotoxicity during FLOX (fluorouracil + leucovorin + OXL) chemotherapy. METHODS: So, 46 patients with CRC were prospectively evaluated during FLOX chemotherapy by 3 cycles (C) of 6 weeks (W) each. We weekly applied the orofacial section of the Acute and Chronic Neuropathy Questionnaire of Common Toxicity Criteria for Adverse Events of the National Cancer Institute of the United States of America (Oxaliplatin-specific neurotoxicity scale). Patients were asked the following concerning the severity (scores 0-5) of orofacial symptoms: jaw pain, eyelids drooping, throat discomfort, ear pain, tingling in mouth, difficulty with speech, burning or discomfort of the eyes, loss of any vision, feeling shock/pain down back and problems breathing. We summed the scores (0-50) and evaluated the clinicopathological data. Friedman/Dunn, Chi square and multinomial regression logistic tests were used (SPSS 20.0, p < 0.05). RESULTS: There was a significant increase in sum of orofacial neurotoxicity from baseline to C1.W3, C2.W1 and C3.W5 (p < 0.001) due increase in scores of jaw pain (p < 0.001), eyelids drooping (p = 0.034), throat discomfort (p < 0.001), ear pain (p = 0.034), tingling in mouth (p = 0.015), burning/discomfort of your eyes (p < 0.001), loss of any vision (p < 0.001), feeling shock/pain down back (p < 0.001), problems with breathing (p = 0.045), but not difficulty with speech (p = 0.087). Women (p = 0.021) and young patients (p = 0.027) had significant higher prevalence of orofacial neurotoxicity. CONCLUSIONS: FLOX-related orofacial neurotoxicity begins acutely and remains long term with increased incidence in women and younger patients.

Molecular epidemiology of Clostridium difficile infection in a Brazilian cancer hospital.

Clostridium difficile is a Gram-positive spore forming anaerobic bacterium and the main cause of healthcare-associated diarrhea. This study aimed to perform the phenotypic characterization and molecular typing of Clostridium difficile isolates among patients at a cancer hospital in Brazil. During 18 months, 48 diarrheic fecal samples were collected, of these 48% were positive in either one or both of the performed tests: detection of toxins A/B and culture. Clostridium difficile was recovered from four samples (17%). All strains carried toxin A and B genes, and the isolates belonged to PCR-ribotype 014/020, PGFE-type NAP4 and toxinotype XVIII. On the other hand, one isolate belonged to a novel PCR-ribotype, and PFGE-type, likewise to toxinotype IXb. The isolates showed susceptibility to metronidazole, vancomycin and moxifloxacin, and were resistant to ciprofloxacin. Finally, the findings indicate high positivity between the samples tested, suggesting an expressive importance of this infection, including detection of a novel ribotype/PFGE-type of Clostridium difficile, and show for the first time the detection of community-associated Clostridium difficile infection (CA-CDI) in these patients in Northeast Brazil. These data emphasize the importance to a better understanding of the epidemiological situation of this infection in Brazilian hospitals.

Hereditary Breast Cancer in the Brazilian State of Ceará (The CHANCE Cohort): Higher-Than-Expected Prevalence of Recurrent Germline Pathogenic Variants.

Purpose: There is a significant lack of epidemiological data on hereditary cancer in Northeast Brazil. This is the largest study on the prevalence and mutational spectrum of cancer predisposition genes conducted in this region and the first in the State of Ceará. Methods: Patients ≥18 years of age that were referred to CHANCE (Grupo de Câncer Hereditário do Ceará) from March 2014 to December 2020 with testing criteria for breast cancer susceptibility genes according to NCCN v.1.2021 were eligible to participate. The inclusion of patients was limited to one individual per family and to those born in the State of Ceará. All patients underwent a hereditary cancer panel testing with at least 30 genes. Results: A total of 355 patients were included, and 97 (27.3%) carried a P/LP germline variant in 18 different genes. Among the 97 P/LP carriers, BRCA1 (31, 31.9%) and BRCA2 (25, 25.7%) were the most frequently mutated genes, followed by PALB2 (10, 10.3%), CHEK2 (7, 7.2%) and ATM (4, 4.1%). A small number of recurrent variants (detected in three or more individuals) in BRCA1, BRCA2, CHEK2 and ATM represented the majority of the P/LP variants described in this cohort. Conclusion: In this cohort, the prevalence of L/PL was high, particularly involving the BRCA1, BRCA2, PALB2, CHEK2 and ATM genes and, to a lesser extent than expected, the TP53 gene. A high frequency of recurrent variants was also observed, for which further and larger analyses should clarify the presence of any possible founder effect. Characterizing the mutational profile of cancer predisposition genes in diverse populations may contribute to cancer prevention and therapeutic management.

Mucosite e alterações de permeabilidade intestinal em pacientes portadores de câncer colorretal metastático tratados com 5-Fluorouracil (5-FU) e Irinotecano(CPT-11) / Gastrintestinal mucositis and permeability test abnormalities in metastatic colorectal cancer patients treated with 5-Fluoruracil (5-FU) and Irinotecan (CPT-11)

Introdução: A melhora da sobrevida dos pacientes com Câncer Colorretal (CCR)metastático proporciona a exposição por prolongados períodos aos agentes antineoplásicos disponíveis para o seu tratamento. A compreensão dos mecanismos envolvidos na mucosite gastrintestinal provocada por regimes com irinotecano, fluorouracil e ácido folínico (IFL) é necessária para que se trate com eficácia e segurança o maior número possível de doentes. No entanto, o relato das alterações intestinais associadas à mucosite é até hoje baseada apenas em escalas de sintomas(diarréia, dor abdominal, vômitos e náuseas) referidas pelos pacientes. Métodos: Utilizando o teste de permeabilidade intestinal pela recuperação urinária de lactulose e manitol, 25 pacientes de CCR metastático tratados com regime IFL em primeira linha foram submetidos à comparação da permeabilidade intestinal antes do início do tratamento e após 15 e 29 dias do primeiro ciclo do regime. Amostras do soro dos pacientes no momento antecedente ao início do tratamento e após 15 dias do seu início foram colhidas para comparação da dosagem de citocinas potencialmente envolvidas na mediação da mucosite gastrintestinal (TNFα, IL-1β, IL-6, IL-18, IL-18bp e IL-33). Resultados: Em comparação com o controle pré-tratamento, as alterações de permeabilidade intestinal foram significativas (p<0,05) nos dois momentos (D15 e D29) do primeiro ciclo de IFL, guardando correlação significativa com a intensidade de diarréia e dor abdominal reportada pelos pacientes. Não foi possível, entretanto, demonstrar alterações séricas significativas na dosagem dascitocinas testadas em comparação ao controle pré-tratamento. Conclusão: O teste de permeabilidade intestinal, portanto, foi capaz de detectar as alterações funcionais de permeabilidade intestinal secundárias à mucosite gastrintestinal provocada pelo regime IFL em pacientes portadores de CCR metastático.

Introduction: The improving survival of patients with metastatic colorectal cancer (CRC) promotes the increasing exposure of individuals with this disease to the effective systemic antineoplastic agents available. The comprehension of the mechanisms involved in the gastrointestinal mucositis associated with the bolus regimen with irinotecan, fluoruracil and folinic acid (IFL) is necessary to improve its efficacy and safety. Nevertheless, it is difficult to obtain a reliable measurement of the intestinal abnormalities caused by mucositis, as almost all the clinical dataavailable is reported on a patient reported symptoms-based scale analysis. Methods: With the lactulose/ mannitol intestinal permeability test as the experimental platform, 25 metastatic CRC patients treated with first line IFL were compared at the 15th and 29th day of the firs IFL cycle to each one’s pretreatment intestinal permeability performance. Blood samples of the same patients were obtained at the preceding moment of the treatment and at 15th day of the IFL first cycle to compare the serum levels of potentially involved cytokines (TNFα, IL-1β, IL-6, IL-18, IL-18bp e IL-33).Results: In contrast with the pretreatment controls, the permeability test was significantly (p<0,05) altered at the D15 and D29 in patients taking first cycle IFL.This abnormalities also reserve significant (p<0,05) correlation with the diarrhea and abdominal pain symptoms scale reported by the patients. Otherwise, it has not been possible to demonstrate serum levels differences of the addressed cytokines before and after the treatment. Conclusion: The lactulose/ mannitol permeability test is an detects functional intestinal abnormalities secondary to gastrointestinal mucositis caused by IFL to metastatic CRC patients.