PD-1/PD-L1 Inhibitors Response in Triple-Negative Breast Cancer: Can Long Noncoding RNAs Be Associated?

As immune checkpoint inhibitors (ICI) emerge as a paradigm-shifting treatment option for patients with advanced or metastatic cancer, there is a growing demand for biomarkers that can distinguish which patients are likely to benefit. In the case of triple-negative breast cancer (TNBC), characterized by a lack of therapeutic targets, pembrolizumab approval for high-risk early-stage disease occurred regardless of PD-L1 status, which keeps the condition in a biomarker limbus. In this review, we highlight the participation of long non-coding RNAs (lncRNAs) in the regulation of the PD-1/PD-L1 pathway, as well as in the definition of prognostic immune-related signatures in many types of tumors, aiming to shed light on molecules that deserve further investigation for a potential role as biomarkers. We also conducted a bioinformatic analysis to investigate lncRNAs already investigated in PD-1/PDL-1 pathways in other cancer types, considering the TNBC molecular context. In this sense, from the generated data, we evidence here two lncRNAs, UCA1 and HCP5, which have not yet been identified in the context of the tumoral immune response in breast cancer. These candidates can be further explored to verify their use as biomarkers for ICI response. In this article, we present an updated review regarding the use of lncRNA as biomarkers of response to ICI, highlighting the versatility of using these molecules.

When guidelines face reality - Lynch syndrome screening in the setting of public health system in a developing country.

Lynch syndrome (LS) is the most common cause of hereditary colorectal cancer (CRC); however, it is still underrecognized and underdiagnosed. While international guidelines gravitate towards universal screening, the underuse of screening methods has been reported in real-world scenarios. This study aims to evaluate screening for LS among patients diagnosed with CRC in a public cancer center in Brazil and evaluate access to genetic counseling and testing for abnormal screens. For that purpose, all patients with CRC registered in our institution from July 2012 to December 2018 had their charts reviewed. Demographic and clinical characteristics were noted, as well as immunohistochemistry and microsatellite instability analysis results, when available. After applying exclusion criteria, a total of 1234 charts were reviewed. Among these, 257 patients were screened for LS, making up a 20.8% screening rate; when considering Jerusalem criteria, screening rate was 24.5%; for Bethesda criteria, it was 35.1%. Almost 80% of patients fulfilling Amsterdam criteria I/II were screened. There were 64 abnormal screens, from which 40 (62.5%) underwent genetic counseling and 12 (18.7%) underwent genetic testing. We concluded that overall screening rates for LS among CRC patients in a public cancer center in Brazil are low, and still very guided by stringent clinical criteria. Referral to genetic counseling and access to testing is limited, calling the whole process into question. Public policies aiming to raise awareness on hereditary cancer and include genetic testing in the public health system could help improve this scenario.

Clinical and Molecular Assessment of Patients with Lynch Syndrome and Sarcomas Underpinning the Association with MSH2 Germline Pathogenic Variants.

Lynch syndrome (LS) is a hereditary cancer-predisposing syndrome associated most frequently with epithelial tumors, particularly colorectal (CRC) and endometrial carcinomas (EC). The aim of this study was to investigate the relationship between sarcomas and LS by performing clinical and molecular characterization of patients presenting co-occurrence of sarcomas and tumors from the LS spectrum. We identified 27 patients diagnosed with CRC, EC, and other LS-associated tumors who had sarcomas in the same individuals or families. Germline genetic testing, mismatch repair (MMR) protein immunohistochemistry, microsatellite instability (MSI), and other molecular analyses were performed. Five LS patients presenting personal or family history of sarcomas were identified (3 MSH2 carriers and 2 MLH1), with 2 having Muir-Torre phenotypes. For two MSH2 carriers we confirmed the etiology of the sarcomas (one liposarcoma and two osteosarcomas) as LS-related, since the tumors were MSH2/MSH6-deficient, MSI-high, or presented a truncated MSH2 transcript. Additionally, we reviewed 43 previous reports of sarcomas in patients with LS, which revealed a high frequency (58%) of MSH2 alterations. In summary, sarcomas represent a rare clinical manifestation in patients with LS, especially in MSH2 carriers, and the analysis of tumor biological characteristics can be useful for definition of tumor etiology and novel therapeutic options.

[Laparoscopic cholecystectomy in transplant patients]. / Colecistectomia laparoscópica em transplantados.

OBJECTIVE: This study reviews our experience with laparoscopic cholecystectomy in the treatment of cholelithiasis in transplant patients. METHODS: Demographic data, medications used, and operative and postoperative data of all transplant recipients who were subjected to laparoscopic cholecystectomy for cholelithiasis at our hospital were obtained. RESULTS: A total of 15 transplant patients (13 renal transplantation and 2 bone marrow transplantation) underwent laparoscopic cholecystectomy. All patients were admitted to the hospital on the day of the operation. The immunosuppressive regimen was not modified during hospitalization. Clinical presentation of cholelithiasis was biliary colicky (n=12), acute cholecystitis (n=2), and jaundice (n=1). The operation was uneventful in all patients. Postoperative complications were nausea and vomiting in 2 patients, prolonged tracheal intubation in 1, wound infection in 1 and large superficial hematoma in 1 patient. CONCLUSION: Laparoscopic cholecystectomy is associated to a low morbidity and mortality and good postoperative outcome in transplant patients with uncomplicated cholecystitis.

Colecistectomia laparoscópica em transplantados / Laparoscopic cholecystectomy in transplant patients

OBJETIVO: Apresentar a nossa experiência com a colecistectomia laparoscópica no tratamento da colelitíase em transplantados. MÉTODOS: Dados demográficos, medicamentos utilizados e dados operatórios e pós-operatórios de todos transplantados que foram submetidos à colecistectomia laparoscópica por colelitíase no nosso hospital foram obtidos. Resultados: Quinze pacientes (13 transplantes renais e dois transplantes de medula óssea) foram submetidos à colecistectomia laparoscópica. Todos pacientes foram internados no hospital no dia da operação. O esquema imunossupressor não foi modificado durante a hospitalização. A apresentação clínica da colelitíase foi cólica biliar (n=12), colecistite aguda (n=2) e icterícia (n=1). A colecistectomia transcorreu sem intercorrências em todos pacientes. Complicações pós-operatórias foram náusea e vômitos em dois pacientes, intubação traqueal prolongada em um, infecção de ferida operatória em um e hematoma superficial grande em um paciente. CONCLUSÃO: Colecistectomia laparoscópica é associada à baixa morbidade e mortalidade e bom prognóstico pós-operatório em pacientes transplantados com colecistite não complicada.

OBJECTIVE: This study reviews our experience with laparoscopic cholecystectomy in the treatment of cholelithiasis in transplant patients. METHODS: Demographic data, medications used, and operative and postoperative data of all transplant recipients who were subjected to laparoscopic cholecystectomy for cholelithiasis at our hospital were obtained. RESULTS: A total of 15 transplant patients (13 renal transplantation and 2 bone marrow transplantation) underwent laparoscopic cholecystectomy. All patients were admitted to the hospital on the day of the operation. The immunosuppressive regimen was not modified during hospitalization. Clinical presentation of cholelithiasis was biliary colicky (n=12), acute cholecystitis (n=2), and jaundice (n=1). The operation was uneventful in all patients. Postoperative complications were nausea and vomiting in 2 patients, prolonged tracheal intubation in 1, wound infection in 1 and large superficial hematoma in 1 patient. CONCLUSION: Laparoscopic cholecystectomy is associated to a low morbidity and mortality and good postoperative outcome in transplant patients with uncomplicated cholecystitis.