Nora Manoukian Forones

Background: Colorectal cancer (CRC) is the third more common cancer with around 1.9 million people diagnosed in 2020. Age is an important risk factor for CRC development and older patients have the lowest survival rates which has been associated with age-related comorbidities and less aggressive treatment. Older individuals present a systemic low-level of chronic inflammation (inflammageing) and, at the same time, they develop a less efficient adaptive immune response, in addition to the changes in innate immunity with an overall negative impact in the immune response (immunosenescence). These processes contribute for tumor cell evasion of the immune surveillance and development of a tumor microenvironment (TME) favorable for metastatic spread. Objective: T or B cell signature related to the patient outcome after therapy could be a very useful tool to anticipate the treatment of disease relapse or metastasis. Methods: We evaluated 24 patients with CRC in a follow-up of at least 24 months and correlated with T and B cells subsets. Results: We found that patients with disease relapse (n=2) presented the highest levels of double negative B cells (B DN). Other patients with high levels of B DN were classified as CRC 2 group and presented also lower IgM memory and higher switched memory B cells. Conclusion: Our findings suggest a possible exploratory association between alterations in B-cell subsets and clinical outcomes. A higher number of patients and further characterization of DN B cells are fundamental to use these cells as prognostic biomarker in CRC.

Background: Cancer is a malignant disease characterized by the accumulation of genetic alterations with uncontrolled cell growth. In 2022, approximately 20 million new cancer cases and nearly 10 million deaths occurred globally. Cancer patients are at high risk for malnutrition due to the disease and treatment. Sarcopenia can negatively affect clinical outcomes and is associated with a higher likelihood of adverse results, including falls, fractures, low physical performance, and mortality. Objective: The aim of this study was to determine whether ultrasound of the gastrocnemius muscle can be a method for detecting the risk or presence of sarcopenia in patients with digestive system cancer. Methods: This is a cross-sectional study conducted with patients diagnosed with digestive system cancer, aged 18 years or older, undergoing treatment. The 2018 EWGSOP algorithm was used to evaluate sarcopenia, and participants were classified into two groups: one group at risk for sarcopenia or sarcopenic and another group as non-sarcopenic. A portable ultrasound (BodyMetrix™ BX2000 ultrasound) was used to measure the thickness of the gastrocnemius muscle. Results: The diagnostic performance of ultrasound (US) and calf circumference (CC) in detecting sarcopenia was evaluated by the area under the ROC curve. The area under the curve for US was 0.940, with 80% sensitivity and 100% specificity, and for CC, it was 0.889, with 72% sensitivity and 95% specificity. We found a negative correlation between the measure of the gastrocnemius muscle by ultrasound (US) and Sarc-CalF, and a positive correlation between the US and calf circumference (CC). Conclusion: The evaluated method shows potential for clinical application, suggesting it could be a fast and sensitive clinical tool. However, further studies are needed to establish robust evidence base and achieve a more accurate sarcopenia diagnosis for early multidisciplinary intervention.

Background: Chemotherapy-induced diarrhea is a common and distressing side effect experienced by patients undergoing cancer treatment, particularly those with gastrointestinal cancer. It can lead to significant health complications, including dehydration, electrolyte imbalances, and treatment interruptions. Recent studies have shown that the gut microbiome plays an important role in the development and severity of chemotherapy-induced diarrhea. Modulating the gut microbiome with probiotics has emerged as a potential strategy for preventing and managing chemotherapy-induced diarrhea.

SciELO Preprints Collection is an integral part of SciELO, an international cooperation program aiming at the development of open access scientific communication covering all areas of knowledge. It operates as a collection of non-peer-reviewed manuscripts within the SciELO Network of national and thematic collection of journals. Background: Pancreatic exocrine insufficiency (PEI) is a condition characterized by reduced exocrine secretion, leading to decreased food digestion, and digestive tract surgeries can be a cause. Postoperative de novo PEI is defined as the onset of digestive symptoms following surgeries, which show significant improvement after the initiation of pancreatic enzyme replacement therapy (PERT). The diagnosis of postoperative PEI may be delayed due to mild or nonspecific symptoms, both in pancreatic surgeries and in upper abdominal surgeries. Aims: The aim of this study was to conduct a systematic review on the diagnosis and treatment of de novo PEI related to digestive surgeries, in collaboration with the development of a consensus among the main surgical societies in Brazil. Methods: The steering committee developed 10 questions related to two areas of interest: diagnosis and treatment. A systematic review was conducted for each of the domains. The evidence was assessed for quality using the GRADEpro tool. Recommendations were formulated for each of the questions. The final report was reviewed by representatives of the surgical societies for the consolidation and approval of the recommendations through a modified Delphi system. Results: De novo PEI should be considered in case of the onset of postoperative digestive symptoms. Diagnostic methods vary in complexity of execution, with varying sensitivity and specificity in the postoperative condition. Fecal Elastase-1 (FE-1) has limited value in diagnosing PEI in the postoperative setting. PERT can be initiated based on clinical suspicion, and there is no difference in approach regarding the type of surgery performed. PERT should be started at the appropriate dose for the intensity of symptoms and adjusted up or down according to symptom control. Proper treatment of PEI leads to symptom improvement and an increase in quality of life. PERT should be maintained as long as patients have a favorable clinical response. Conclusions: The recommendations encompass the diagnosis and treatment of de novo EPI and can serve as a basis for the establishment of educational programs led by the participating surgical societies.

Background: The management of gastric cancer has become increasingly complex, highlighting the importance of clinical guidelines to ensure standardized care. The Second Brazilian Consensus on Gastric Cancer was developed to guide clinical practice across the country. Aims: The aim of this study was to evaluate the degree of implementation of the 2nd Brazilian Consensus recommendations in cancer reference centers in Brazil. Methods: This multicenter study involved 18 cancer centers that prospectively collected data over a one-year period. Notably, 21 key statements from the Consensus were assessed. Adherence was defined as following the recommendation in more than 80% of applicable cases. Results: Of the 21 statements, 11 (52.4%) met the predefined adherence threshold. The selective use of endoscopic ultrasound and PET-CT was consistent with the recommendations. However, diagnostic laparoscopy was underutilized, performed in only 24.7% of patients. Preoperative nutritional therapy, another key recommendation, was provided in just 42% of cases. D2 lymphadenectomy was performed in 79.8% of surgeries, but only 63.3% of specimens included ≥25 lymph nodes, the recommended minimum for adequate staging. Minimally invasive surgery (MIS) was performed in approximately 25% of early distal tumors but was rarely used in advanced proximal tumors. Despite not being recommended for early stage tumors, omentectomy and bursectomy were still performed in a significant number of T1/T2 cases. Preoperative chemotherapy was used in 35.4% of distal tumors ≥IB and 54.3% of proximal tumors, showing partial adherence to this recommendation. Conclusions: Just over half of the II Brazilian Consensus recommendations were implemented in routine practice. There was strong adherence to D2 lymphadenectomy and MIS for early distal tumors. However, there is still room for improvement in areas such as diagnostic laparoscopy, nutritional support, adequate lymph node retrieval, and using more neoadjuvant chemotherapy to enhance care and follow national guidelines.

Sarcopenia is a syndrome characterized by decreased strength, quantity and/or quality of skeletal muscle mass. When associated with cancer, it correlates with poorer clinical outcomes. Cancers of the gastrointestinal tract, prevalent globally and in Brazil, are associated with a greater nutritional risk. Early detection and intervention for nutritional risks are critical in this population. Recent studies on turmeric/curcumin have demonstrated beneficial effects in cancer patients. Specifically, curcumin have shown promise in reducing muscle depletion, oxidative stress, and improving strength and fatigue, factors related to sarcopenia. This review aims to elucidate sarcopenia and sarcopenia secondary to cancer, emphasizing nutritional management and the role of curcumin supplementation. Effective cancer management, whether with or without sarcopenia, demands comprehensive public health strategies and multimodal interventions within healthcare institutions. Nutrition is pivotal across the cancer care journey, encompassing screening, guidance, and provision of nutrients that support maintaining or recovering body composition. Curcumin supplementation emerges as a potential adjuvant to the standard cancer treatment and sarcopenia management. Nevertheless, further clinical studies are warranted to substantiate these findings.

Purpose: To identify the prognostic variables related to the survival of patients operated on for adenocarcinoma of the rectum who underwent preoperative radiochemotherapy (RCT).

Older individuals are more likely to develop solid cancers, but at the same time are more sensitive to the side effects of chemotherapy. In addition, older adults are more likely to present with chronic diseases (comorbidities) and immunosenescence that may decrease immunosurveillance against cancer. Clinical outcomes for the older patient with cancer are different from the younger patient and require different research and treatment approaches. Thus, alternative therapeutic approaches tailored specifically to the older patients are required. Colorectal cancer (CRC) has a high incidence in older individuals and is the third leading cause of cancer death globally. Anti-hypertensives are used by a large proportion of older patients and some studies have pointed to a positive impact of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) on CRC outcomes. As we have previously shown in a mouse model, lung metastases express ACE and contain many infiltrating myeloid-derived suppressor cells (MDSC); particularly high levels of MDSC are also present in the blood of older patients with CRC and other cancers, and are associated with disease severity. In this Commentary, we hypothesize that one mechanism responsible for the positive impact of ACEi or ARB on the outcome of CRC is the modulation of myeloid cells contributing to their maturation to non-suppressive neutrophils/monocytes and diverting them away from retaining an immature MDSC phenotype.

Background: Colorectal cancer is the third cause of cancer worldwide and a quarter of them are in the rectum. DEK oncogene is involved in several nuclear processes and can accelerate tumorigenesis. Objective: This study aims to evaluate the immunoexpression of DEK and Phospho-P38 proteins before neoadjuvant therapy in patients with rectum adenocarcinoma and correlate it with a clinical response and survival. Methods: Patients with adenocarcinoma of the middle and low rectum who underwent chemotherapy and radiotherapy followed by surgical tumor resection were included. The expression and quantification were studied by immunohistochemistry in the tumor biopsy tissues using a HScore system. Score ≥4 were considered positive and those with <4 negative. Results: 22 patients were included with a mean age of 63.55 years (SD: ±13.49). The clinical-stage before treatment was T3 on 72.7%, T4 on 18.2%, 31.8% were N1, 50% N0 and all M0. After chemo and radiotherapy, 54.6% were T3; 22.7% were classified as T2; 9.1% as T1, and 13.6% were T0. Among the tumors, 22.7% were positive for DEK and 63.6% positive for Phospho-P38. There was a positive correlation between DEK protein before treatment and pTNM stage (P=0.011). Phospho-P38 protein showed no correlation with these parameters. Patients with a negative HScore had a mean survival of 141.33 months (95%CI: 112.41-170.25) and those with a positive HSscore had a mean survival of 25.10 months (95%CI: 17.36-32.84; P<0.001). Conclusion: A higher expression of DEK was observed in advanced stages. Patients who presented DEK expression <4 had a higher survival, being a factor of worst prognosis.