What's new about the tumor microenvironment of urothelial carcinoma?

Urothelial carcinoma is a significant global health concern that accounts for a substantial part of cancer diagnoses and deaths worldwide. The tumor microenvironment is a complex ecosystem composed of stromal cells, soluble factors, and altered extracellular matrix, that mutually interact in a highly immunomodulated environment, with a prominent role in tumor development, progression, and treatment resistance. This article reviews the current state of knowledge of the different cell populations that compose the tumor microenvironment of urothelial carcinoma, its main functions, and distinct interactions with other cellular and non-cellular components, molecular alterations and aberrant signaling pathways already identified. It also focuses on the clinical implications of these findings, and its potential to translate into improved quality of life and overall survival. Determining new targets or defining prognostic signatures for urothelial carcinoma is an ongoing challenge that could be accelerated through a deeper understanding of the tumor microenvironment.

Orthostatic hypotension as an unusual presentation of spinal calcium pyrophosphate deposition disease: case report and review of literature.

Calcium pyrophosphate crystal deposition disease (CPPD), also known as pseudogout, with spinal involvement, is associated with clinical manifestations of acute nerve compression or chronic spinal stenosis. Precipitation of crystals of calcium pyrophosphate dihydrate in connective tissues can lead to acute inflammatory arthritis, degenerative chronic arthropathies, and radiographic evidence of cartilage calcification. We present a case of an 87-year-old woman, with unstudied chronic polyarthralgia and symptomatic orthostatic hypotension. It were documented acute calcium pyrophosphate deposition wrist arthritis, and cervical CT and MRI was suggestive of spinal involvement of CPPD. Workup excluded other causes of OH. Surgical approach could be indicated to minimize the symptoms, but it was contra-indicated due to the patient's performance status, so histological diagnosis was not possible. Muscle atrophy played an important part in the rapid progression of this insidious chronic disease. Conservative and symptomatic treatment achieve scarce short-term clinical improvement. Spinal involvement of CPPD was thought to be rare but recent studies show a higher prevalence than expected. We call for attention to the extent of structural changes that may occur when not early diagnosed nor treated. High clinical suspicion is required and this is, to our knowledge, the first report of orthostatic hypotension as a presentation of CPPD.

A Rare Case of Mediastinal Mass: Thymoma and Thymic Tumor.

Thymomas and thymic carcinomas are rare mediastinal neoplasms arising from thymic epithelial cells, and the presence of synchronous or metachronous primary thymic neoplasms in a single patient is an extremely rare event. Thymoma patients appear to have an inherent predisposition toward developing additional neoplasms. This additionally presents a diagnostic challenge, revealing the importance of multidisciplinary expertise to the management of these patients. This is a case report of a patient with a thymoma and thymic carcinoma, submitted to surgical resection and postoperative radiotherapy.

Impact of Immune-Related Adverse Events on Immune Checkpoint Inhibitors Treated Cancer Patients' Survival: Single Center Experience and Literature Review.

Immune-related adverse events have emerged as a new challenge and its correlation with survival remains unclear. The goal of our study was to investigate the effect of irAE on survival outcomes in solid tumor patients receiving ICI treatment. This was a retrospective, single-center study at a university hospital involving patients with malignancy who received immune checkpoint inhibitors. Chart review was performed on each patient, noting any irAE, including new events or worsening of previous autoimmune condition after starting treatment with ICI. A total of 155 patients were included, 118 (76.1%) were male, with median age of 64 years. Median follow up time was 36 months. Seventy patients (45.2%) had at least one irAE. Of all irAE, nine (8.1%) were classified as grade 3 or higher according to the CTCAE version 5.0. There was one death secondary to pneumonitis. Median ICI cycles until first irAE onset was 4 (range: 2-99). The objective response rate was higher for patients who developed irAE (18.7% vs. 9.0%; p = 0.001), as was median overall survival (18 months (95% CI, 8.67-27.32) vs. 10 (95% CI, 3.48-16.52) months; p < 0.016) and progression free survival (10 months (95% CI, 5.44-14.56) vs. 3 months (95% CI, 1.94-4.05); p = 0.000). The risk of death in patients with irAE was 33% lower when compared to patients without such events (hazard ratio (HR): 0.67; 95% CI, 0.46-0.99; p = 0.043). Development of irAE predicted better outcomes, including OS in patients with advanced solid tumors treated with ICI. Further prospective studies are needed to explore and validate this prognostic value.

Best Supportive Care of the Patient with Oesophageal Cancer.

BACKGROUND: Oesophageal cancer patients have poor survival, and most are unfit for curative or systemic palliative treatment. This article aims to review the best supportive care for oesophageal cancer, focusing on the management of its most frequent or distinctive symptoms and complications. METHODS: Evidence-based review on palliative supportive care of oesophageal cancer, based on Pubmed search for relevant clinical practice guidelines, reviews and original articles, with additional records collected from related articles suggestions, references and societies recommendations. RESULTS: We identified 1075 records, from which we screened 138 records that were related to oesophageal cancer supportive care, complemented with 48 additional records, finally including 60 records. This review summarizes the management of oesophageal cancer-related main problems, including dysphagia, malnutrition, pain, nausea and vomiting, fistula and bleeding. In recent years, several treatments have been developed, while optimal management is not yet standardized. CONCLUSION: This review contributes toward improving supportive care and decision making for oesophageal cancer patients, presenting updated summary recommendations for each of their main symptoms. A robust body of evidence is still lacking, and the best supportive care decisions should be individualized and shared.

[Chronic Pain After Outpatient Inguinal Hernioplasty: Retrospective Cohort Study]. / Dor Crónica Pós-Hernioplastia Inguinal em Regime de Ambulatório: Estudo de Coorte Retrospetivo.

INTRODUCTION: Chronic postoperative pain is the most frequent late complication of inguinal hernia repair surgery. The aim of this study is to evaluate the incidence of chronic post-hernioplasty pain in outpatient care at Centro Hospitalar do Porto, describe it, analyse its relation with other variables defined in the literature and study its functional interference. MATERIAL AND METHODS: We performed a retrospective cohort study between February and May 2016, using a structured telephone interview composed of questions from the authors and sections of published questionnaires, two of which are validated for the Portuguese language and culture. We included men who underwent ambulatory inguinal hernioplasty, by laparotomy or laparoscopy, at Centro Hospitalar do Porto, between January 2011 and October 2015. RESULTS: In a final sample of 829 surgeries, the incidence of chronic post-hernioplasty pain was 24.0% [confidence interval: 21.2 - 27.1]. The development of chronic post-hernioplasty pain was higher in patients with pre-surgical pain and younger age and was related with the presence of pain during the first month after surgery. No relationship was found between surgical technique and the development of chronic post-hernioplasty pain. Of the individuals with chronic pain, 65.0% mentioned moderate-severe 'pain on the average' and 37.7% presented descriptors suggestive of neuropathic pain. The only parameter evaluated with which chronic post-hernioplasty pain 'did not interfere completely' was sleep. DISCUSSION: The prevalence found for chronic posthernioplasty pain with significant functional interference is in line with data retrieved from literature. The predictive potential of pre-surgical pain and young age for the development of chronic posthernioplasty pain is also in agreement with previous studies. Limitations were found to this study given its retrospective nature. CONCLUSION: The high prevalence of chronic post-hernioplasty pain raises the urgent need for raising awareness regarding this issue among health care professionals. The main areas for improvement are diagnosis, follow-up and treatment of pain.

Introdução: A dor crónica pós-cirúrgica é a complicação tardia mais frequente da cirurgia de reparação de hérnia inguinal. Este trabalho visa determinar a incidência de dor crónica pós-hernioplastia inguinal em ambulatório no Centro Hospitalar do Porto, estudar a sua relação com determinadas variáveis descritas na literatura, avaliar as suas características e interferência funcional.Material e Métodos: Realizámos um estudo de coorte retrospetivo, entre fevereiro e maio de 2016, por entrevista telefónica estruturada composta por perguntas dos autores e secções de três questionários publicados, dois dos quais validados para a língua e cultura portuguesas. Incluímos os homens submetidos a hernioplastia inguinal, por laparotomia ou laparoscopia, em ambulatório, no Centro Hospitalar do Porto, entre janeiro de 2011 e outubro de 2015.Resultados: Na amostra final de 829 hernioplastias, a incidência de dor crónica pós-hernioplastia foi de 24,0% [intervalo de confiança: 21,2 - 27,1]. O desenvolvimento de dor crónica foi superior nos doentes com dor pré-cirúrgica, nos doentes mais jovens e relacionou-se com o momento de início da dor pós-cirúrgica. Não encontrámos relação com a via de abordagem, clássica ou laparoscópica. Dos indivíduos com dor crónica, 65,0% apresentaram dor 'em média' moderada ou forte e 37,7% apresentavam descritores sugestivos de dor de origem neuropática. A dor crónica pós-hernioplastia do ponto de vista funcional apenas 'não interferiu completamente' com o sono.Discussão: A prevalência encontrada de dor crónica pós-hernioplastia, com interferência funcional importante, é congruente com os dados disponíveis na literatura. O potencial preditor da presença de dor pré-cirúrgica e idade jovem do doente para o desenvolvimento de dor crónica pós-hernioplastia é também corroborado pela literatura. Tratando-se de um estudo de coorte retrospetivo, o estudo apresenta as limitações inerentes.Conclusão: A elevada prevalência de dor crónica pós-hernioplastia encontrada apontam para a urgência na sensibilização dos profissionais de saúde para esta problemática e otimização do follow-up, diagnóstico e tratamento da dor.