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Introduction: Hemorrhagic cystitis (HC) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT), characterized by inflammation and bleeding of the bladder. Hyperbaric oxygen therapy (HBOT) has been shown to be effective in the treatment of radiation-induced HC. However, the optimal treatment for HC after allogeneic HSCT has not yet been established. Furthermore, limited research has been conducted on the use of HBOT in this setting. This study aimed to evaluate the effectiveness and safety of HBOT in patients with late-onset HC after allogeneic HSCT., Methods: Twenty-five-year (1998-2022) retrospective analysis performed in all consecutive patients with confirmed late-onset HC after allogeneic HSCT treated with HBOT at two centers in Portugal. Medical records were reviewed for clinical and laboratory features, primary indications for allogeneic HSCT, conditioning regimen, and treatment strategies for HC. Patients received 100% oxygen at 2.1-2.5 atmosphere absolute pressure (ATA) for 70-90-minute periods, once daily, five times per week. Complete clinical response was defined as the absence of macroscopic hematuria sustained for at least 2 weeks, and partial response was described as a downgrading in the severity of HC. Statistical significance was considered for values of p < 0.05., Results: The sample included 61 patients with a mean age of 28.0 (SD 14.2) years, 33 males. Complete response was achieved in 72.1% (n = 44) of patients and partial response in 14.8% (n = 9). Concerning patients with a complete response, the median number of HBOT sessions was 15.5 sessions (IQR 10.0-26.8). Patients treated with 10 or more sessions of HBOT had a higher rate of complete or partial response (OR 12.5, 95%CI 1.9-83.2, p-value < 0.05). There was no response in 8 (13.1%) patients, and 6 interrupted the treatments early. Only 2 patients suspended the HBOT due to a lack of clinical benefit., Conclusion: Our study supports using of HBOT as an adjunctive treatment for late-onset HC after allogeneic HSCT. Furthermore, 10 or more HBOT sessions delivered seem to impact the rate of HC resolution. Prospective, randomized, and well-controlled trials are needed to establish HBOT's definitive efficacy and safety., (© 2024. The Author(s).)

Neuroblastoma is the most frequently diagnosed cancer during the first year of life. This neoplasm originates from neural crest cells derived from the sympathetic nervous system, adrenal medulla, or paraspinal ganglia. The clinical presentation can vary from an asymptomatic mass to symptoms resulting from local invasion and/or spread of distant disease spread. The natural history of neuroblastoma is highly variable, ranging from relatively indolent biological behavior to a high-risk clinical phenotype with a dismal prognosis. Age, stage, and biological features are important prognostic risk stratification and treatment assignment prognostic factors. The multimodal therapy approach includes myeloablative chemotherapy, radiotherapy, immunotherapy, and aggressive surgical resection. Hyperbaric oxygen therapy (HBOT) has been proposed as a complementary measure to overcome tumor hypoxia, which is considered one of the hallmarks of this cancer treatment resistance. This article aims to review the relevant literature on the neuroblastoma pathophysiology, clinical presentation, and different biological and genetic profiles, and to discuss its management, focusing on HBOT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alpuim Costa, Gonçalves-Nobre, Sampaio-Alves, Guerra, Arana Ribeiro and Espiney Amaro.)

Introduction: Despite modern radiotherapy (RT) techniques, radiation-induced proctitis (RIP) remains a significant complication of RT for pelvic organ malignancies. Over the last decades, an enormous therapeutic armamentarium has been considered in RIP, including hyperbaric oxygen therapy (HBOT). However, the evidence regarding the impact of HBOT on RIP is conflicting. This study aims to evaluate the effectiveness and safety of HBOT in the treatment of RIP., Methods: Ten-year (2013-2023) retrospective analysis of all consecutive patients with RIP treated with HBOT at Centro de Medicina Subaquática e Hiperbárica (CMSH) (Armed Forces Hospital - Lisbon, Portugal). Patients were exposed to 100% oxygen at 2.5 ATA, in a multiplace first-class hyperbaric chamber, for 70-min periods, once daily, five times per week. Fisher's exact test was performed using SPSS (version 23.0); p<0.05 was accepted as statistically significant., Results: Of a total of 151 patients with RIP, 88 were included in the final analysis, of whom 38.6% evidenced other concurrent radiation-induced soft tissue lesions. The most reported primary pelvic tumor treated with RT was prostate cancer (77.3%), followed by cervical cancer (10.2%). Hematochezia was the most observed clinical manifestation (86.4%). After a median of 60 HBOT sessions (interquartile range [IQR]: 40-87.5), 62.5% and 31.8% of patients achieved a clinical complete and partial response, respectively, with a hematochezia resolution rate of 93.7% (complete or partial). While partial and complete responses require fewer than 70 sessions of HBOT in terms of overall RIP symptoms (p=0.069), isolated hematochezia tends to require at least 70 sessions (p=0.075). Individuals with at least two concurrent late radiation tissue injuries were associated with a complete response to HBOT (p=0.029). Only about 5.7% of patients did not respond to the treatment. Eighteen patients (20.5%) developed reversible ear barotrauma. The number of HBOT sessions was a predictor of HBOT side effects (odds ratio: 1.010; 95% confidence interval, 1.000-1.020; p=0.047)., Conclusion: The HBOT proved to be an effective and safe treatment for RIP refractory to medical and/or endoscopic treatments. This real-world evidence study adds value to published data on the management of RIP with HBOT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Moreira Monteiro, Alpuim Costa, Mareco and Espiney Amaro.)

Background: Brain metastasis (BM) is a major clinical problem in metastatic breast cancer (MBC), occurring in 50% of patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. Historically omitted from clinical trials, recent studies of novel HER2-targeted agents have focused on HER2+ BM patients, addressing stable but also progressing BM and leptomeningeal carcinomatosis (LMC)., Summary: This review aimed to summarize the most relevant data on treating patients with HER2+ BM and LMC., Key Messages: The treatment paradigm for patients with HER2+ MBC has changed. Local therapies play an important role, but accumulating evidence on the intracranial activity and clinical benefit of anti-HER2 targeting therapies might lead to a shift in the paradigm on treating BM in the next few years towards more widespread use of systemic therapy., Competing Interests: Marta Filipa Freire Vaz Batista: consulting/advisory board: AstraZeneca; speaker/conferences: Daiichi-Sankyo and Nutricia; travel fees: AstraZeneca, Daiichi-Sankyo, Pfizer, and GSK. Inês Eiriz: speaker/sonferences: Novartis; travel fees: Gilead, Novartis, and Pierre Fabre. Amanda Fitzpatrick: no conflict of interest to declare. Fanny Le Du: consulting/advisory board: Daiichi-Sankyo, Lilly, Seagen Inc., Novartis, Pfizer, Roche, and Sandoz; speaker/conferences: Amgen, Lilly, Novartis, and Pierre Fabre; travel fees: Daiichi-Sankyo, Lilly, Novartis, Pierre Fabre, and Pfizer. Sofia Braga: consulting/advisory board: Daiichi-Sankyo, AstraZeneca, Novartis, and Roche; speaker/conferences: Daiichi-Sankyo, AstraZeneca, Novartis, and Roche; travel fees: Daiichi-Sankyo, AstraZeneca, Novartis, and Roche. Diogo Alpuim Costa has received honoraria from the Portuguese Navy, CUF Oncologia, and NTT DATA and has served as a speaker, advisory board member, or has received research or education funding from AstraZeneca, CUF Oncologia, Daiichi-Sankyo, Gilead, Hoffmann-La Roche, Merck KGaA, Merck Sharp & Dohme, Nestlé, Novartis, Pfizer, Nanobiotix, Puma Biotechnology Inc., Sanofi, Seagen Inc., and Uriage., (Copyright © 2022 by S. Karger AG, Basel.)

Germline pathogenic variants in the Breast Cancer Genes 1 ( BRCA1 ) and 2 ( BRCA2 ) are responsible for Hereditary Breast and Ovarian Cancer (HBOC) syndrome. Genetic susceptibility to breast cancer accounts for 5-10% of all cases, phenotypically presenting with characteristics such as an autosomal dominant inheritance pattern, earlier age of onset, bilateral tumours, male breast cancer, and ovarian tumours, among others. BRCA2 pathogenic variant is usually associated with other cancers such as melanoma, prostate, and pancreatic cancers. Many rearrangements of different mutations were found in both genes, with some ethnic groups having higher frequencies of specific mutations due to founder effects. Despite the heterogeneity of germline BRCA1/BRCA2 mutations in Portuguese breast or/and ovarian cancer families, the first described founder mutation in the BRCA2 gene (c.156&#95;157insAlu) and two other variants in the BRCA1 gene (c.3331&#95;3334del and c.2037delinsCC) contribute to about 50% of all pathogenic mutations. Furthermore, the families with the BRCA1 c.3331&#95;3334del or the c.2037delinsCC mutations share a common haplotype, suggesting that these may also be founder mutations in the Portuguese population. Identifying specific and recurrent/founder mutations plays an important role in increasing the efficiency of genetic testing since it allows the use of more specific, cheaper and faster strategies to screen HBOC families. Therefore, this review aims to describe the mutational rearrangements of founder mutations and evaluate their impact on the genetic testing criteria for HBOC families of Portuguese ancestry.

The tumour microenvironment (TME) comprises a complex ecosystem of different cell types, including immune cells, cells of the vasculature and lymphatic system, cancer-associated fibroblasts, pericytes, and adipocytes. Cancer proliferation, invasion, metastasis, drug resistance and immune escape are all influenced by the dynamic interaction between cancer cells and TME. Microbes, such as bacteria, fungi, viruses, archaea and protists, found within tumour tissues, constitute the intratumour microbiota, which is tumour type-specific and distinct among patients with different clinical outcomes. Growing evidence reveals a significant relevance of local microbiota in the colon, liver, breast, lung, oral cavity and pancreas carcinogenesis. Moreover, there is a growing interest in the tumour immune microenvironment (TIME) pointed out in several cross-sectional studies on the correlation between microbiota and TME. It is now known that microorganisms have the capacity to change the density and function of anticancer and suppressive immune cells, enabling the promotion of an inflammatory environment. As immunotherapy (such as immune checkpoint inhibitors) is becoming a promising therapy using TIME as a therapeutic target, the analysis and comprehension of local microbiota and its modulating strategies can help improve cancer treatments.

Introduction: Cancer care providers have faced many challenges in delivering safe care for patients during the COVID-19 pandemic. This cross-sectional survey-based study investigated the impact of the pandemic on clinical practices of Portuguese medical oncologists caring for patients with breast cancer., Methods: An anonymous online survey comprising 42 questions gathered information regarding COVID-19 testing, treatment in (neo)adjuvant and metastatic settings, and other aspects of breast cancer management. Practices before and during the pandemic were compared, and potential differences in outcomes according to respondents' regions, case volumes, and practice type were explored., Results: Of 129 respondents, 108 worked in the public health system, giving a representative national picture of the impact of the COVID-19 pandemic on breast cancer management. Seventy-one percent of respondents reported a reduction in visits for new cases of breast cancer, and there was a shift towards increased use of telemedicine. Clinical decision-making was largely unaffected in the most aggressive indications (i.e., triple-negative, HER2-positive, visceral crisis). The use of neoadjuvant therapy increased when access to surgery was difficult, whereas dose-dense regimens decreased, and cyclin-dependent kinase 4/6 inhibitor treatment decreased for less aggressive disease and increased for more aggressive disease. The use of oral formulations and metronomic chemotherapy regimens increased, and clinical trial participation decreased. Some differences by respondents' region and case volume were noted., Conclusion: Medical oncologists in Portugal implemented many changes during the COVID-19 pandemic, most of which were logical and reasonable responses to the current healthcare emergency; however, the true impact on patient outcomes remains unknown., (© 2022. The Author(s).)

Breast cancer (BC) is the most common malignancy and the second cause of cancer-specific death in women from high-income countries. Infectious agents are the third most important risk factor for cancer incidence after tobacco and obesity. Dysbiosis emerged as a key player that may influence cancer development, treatment, and prognosis through diverse biological processes. Metastatic BC has a highly variable clinical course, and more recently, immune checkpoint inhibitors (ICIs) have become an emerging therapy in BC. Even with standardised treatment protocols, patients do not respond similarly, reflecting each individual´s heterogeneity, unique BC features, and tumour microenvironment. However, there is insufficient data regarding predictive factors of response to available treatments for BC. The microbiota could be a crucial piece of the puzzle to anticipate better individual BC risk and prognosis, pharmacokinetics, pharmacodynamics, and clinical efficacy. In recent years, it has been shown that gut microbiota may modulate cancer treatments' efficacy and adverse effects, and it is also apparent that both cancer itself and anticancer therapies interact with gut microbiota bidirectionally. Moreover, it has been proposed that certain gut microbes may protect the host against inappropriate inflammation and modulate the immune response. Future clinical research will determine if microbiota may be a prognostic and predictive factor of response to ICI and/or its side effects. Also, modulation of microbiota can be used to improve outcomes in BC patients. In this review, we discuss the potential implications of metabolomics and pharmacomicrobiomics that might impact BC immunotherapy treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Vitorino, Baptista de Almeida, Alpuim Costa, Faria, Calhau and Azambuja Braga.)

Radiotherapy (RT) is the backbone of multimodality treatment of more than half of cancer cases. Despite new modern RT techniques, late complications may occur such as radiation proctitis (RP). The natural history of RP is unpredictable. Minor symptoms may resolve spontaneously or require conservative treatment. On the other hand, for similar and uncomplicated clinical contexts, symptoms may persist and can even be refractory to the progressive increase in treatment measures. Over the last decades, an enormous therapeutic armamentarium has been considered in RP, including hyperbaric oxygen therapy (HBOT). Currently, the evidence regarding the impact of HBOT on RP and its benefits is conflicting. Additional prospective and randomised studies are necessary to validate HBOT's effectiveness in the 'real world' clinical practice. This article reviewed the relevant literature on pathophysiology, clinical presentation, different classifications and discuss RP management including a proposal for a therapeutic algorithm with a focus on HBOT., Competing Interests: Conflict-of-interest statement: Nothing to declare., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Breast cancer (BC) is the most common malignancy and the second cause of cancer-specific death in women from high-income countries. Recently, gut microbiota dysbiosis emerged as a key player that may directly and/or indirectly influence development, treatment, and prognosis of BC through diverse biological processes: host cell proliferation and death, immune system function, chronic inflammation, oncogenic signalling, hormonal and detoxification pathways. Gut colonisation occurs during the prenatal period and is later diversified over distinct phases throughout life. In newly diagnosed postmenopausal BC patients, an altered faecal microbiota composition has been observed compared with healthy controls. Particularly, β-glucuronidase bacteria seem to modulate the enterohepatic circulation of oestrogens and their resorption, increasing the risk of hormone-dependent BC. Moreover, active phytoestrogens, short-chain fatty acids, lithocholic acid, and cadaverine have been identified as bacterial metabolites influencing the risk and prognosis of BC. As in gut, links are also being made with local microbiota of tumoural and healthy breast tissues. In breast microbiota, different microbial signatures have been reported, with distinct patterns per stage and biological subtype. Total bacterial DNA load was lower in tumour tissue and advanced-stage BC when compared with healthy tissue and early stage BC, respectively. Hypothetically, these findings reflect local dysbiosis, potentially creating an environment that favours breast tumour carcinogenesis (oncogenic trigger), or the natural selection of microorganisms adapted to a specific microenvironment. In this review, we discuss the origin, composition, and dynamic evolution of human microbiota, the links between gut/breast microbiota and BC, and explore the potential implications of metabolomics and pharmacomicrobiomics that might impact BC development and treatment choices toward a more personalised medicine. Finally, we put in perspective the potential limitations and biases regarding the current microbiota research and provide new horizons for stronger accurate translational and clinical studies that are needed to better elucidate the complex network of interactions between host, microorganisms, and drugs in the field of BC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Alpuim Costa, Nobre, Batista, Ribeiro, Calle, Cortes, Marhold, Negreiros, Borralho, Brito, Cortes, Braga and Costa.)

Pneumatosis cystoides intestinalis (PCI) is characterized by gas-filled cysts within gastrointestinal tract wall from esophagus to rectum, with preferential involvement of large and small intestine. PCI is rare with an estimated incidence of 0.03 to 0-2% in general population. PCI can be distinguished into idiopathic (15%) or secondary (85%) and the clinical picture ranges from completely asymptomatic to life-threatening intraabdominal complications. Although etiology of PCI appears to be multifactorial, the exact pathophysiology is poorly understood and two main theories have been proposed (mechanical and bacterial). Over the last decades, an enormous therapeutic armamentarium was considered in PCI's management, including hyperbaric oxygen therapy (HBOT). Treatment comprises conservative treatment in mild cases to surgery in highly symptomatic and complicated PCI. In the late 70s, HBOT started to be used in selected cases of PCI not responding to conservative measures. Since then, several case reports, case series, and reviews have been published in the literature with variable outcomes. The overall response rate and complete response were 92.1% ( n = 82/89) and 65.2% ( n = 58/89), respectively, with a median follow-up of 7 months. Furthermore, HBOT is extremely safe, with few reported complications in the literature when used for PCI. Nevertheless, a randomized, controlled, and double-blind clinical trial is unlikely to occur given the rarity of PCI, logistical issues of HBOT, and methodological considerations related to adequate blinding with a sham-controlled group. HBOT in combination with personalized diet and antibiotics may be beneficial for moderate to severe PCI in patients with no indication for emergency exploratory laparotomy. The purpose of this article is to synthesize the existing data, analyse results of previous studies, identify gaps in knowledge, and discuss PCI' management, including the proposal of an algorithm, with a special focus on HBOT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Alpuim Costa, Modas Daniel and Vieira Branco.)

Ethical issues that arise during the care of a pregnant woman with cancer are challenging to physicians, policymakers, lawyers, and the bioethics community. The main purpose of this scoping review is to summarize existing literature regarding the bioethical dilemmas when a conflict arises in the maternal-fetus dyad, like the one related to cancer and pregnancy outcomes. Moreover, we illustrate the decision-making process of real-life case reports. Published data were searched through the PubMed and Google Scholar databases, as well as in grey literature, using appropriate controlled keywords in English and Portuguese. After identification, screening, eligibility and data extraction from the articles, a total of 50 was selected. There are several established ethical frameworks for conflict resolution and decision-making. Pragmatic theoretical approaches include case-based analysis, the ethics of care, feminist theory, and traditional ethical principlism that scrutinizes the framework of autonomy, justice, beneficence, and non-maleficence. In addition, society and practitioner values could mediate this complex ethical interplay. The physician must balance autonomy and beneficence-based obligations to the pregnant woman with cancer, along with beneficence-based obligations to the fetus. Ethical challenges have received less attention in the literature, particularly before the third trimester of pregnancy. Best, unbiased and balanced information must be granted both to the patient and to the family, regarding the benefits and harms for the woman herself as well as for the fetal outcome. Based on a previously validated method for analyzing and working up clinical ethical problems, we suggest an adaptation of an algorithm for biomedical decision-making in cancer during pregnancy, including recommendations that can facilitate counseling and help reduce the suffering of the patient and her family., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Alpuim Costa, Nobre, de Almeida, Ferreira, Gonçalves, Braga and Pais.)

Introduction: intestinal-type sinonasal adenocarcinoma (ITAC) is a rare epithelium tumor of the nasal cavities and paranasal sinuses. Exposure to wood and leather dusts is a strong etiological factor related to its development. Prolonged cork exposure has rarely been associated., Materials and Methods: thirty-seven-year (1981-2018) retrospective cohort analysis of all consecutive patients with sinonasal cancer (SNC) followed at our institution. Medical records were reviewed to determine patient demographics, occupational/environmental exposure, location and extent of the tumor, stage, histopathology findings, treatment strategies, and oncologic outcomes. Survival analysis was done using Kaplan-Meier method., Results: we evaluated 379 patients with SNC, including 39 (10.3%) ITAC. Patient median age was 73 years (range 49-87), 56% male and 69% with identified professional occupational exposure (54% for cork; 69.2% considering only those for which an agent has been identified). Seventy-two percent had locally advanced disease (stage III or IVA-B). The initial treatment was surgery in 77%, and 54% received adjuvant radiotherapy. The median time to progression, progression-free survival, and overall-survival was 2.36 years (95% CI 1.54-8.70), 1.96 years (95% CI 1.43-3.74), and 3.51 years (95% CI 2.33-10.02), respectively., Conclusion: ITAC is an uncommon malignancy that grows silently, which contributes to delayed diagnosis, advanced stage and low survival rates. In our cohort, we observed a high prevalence of cork occupational exposure. This finding may lead to the implementation of protection measures and suggest a potential link to be further studied., (Copyright © 2020 Alpuim Costa, Monteiro, André, Esteves, Sargento, Ferreira, Alexandre, Clara, Freire and Moreira.)

Kienböck's disease is a rare condition characterised by avascular necrosis of the lunate bone. Its natural history and aetiopathogenesis have not yet been clarified, nor are its triggering factors identified. We present a case of a 17-year-old male gymnast, without relevant medical/family history, with stage IIIA Kienböck's disease diagnosed in 2016. Initially, submitted to conservative treatment that proved to be insufficient. Consequently, surgical treatment was proposed, but refused. The patient instead underwent experimental treatment with hyperbaric oxygen (120 sessions, 100% oxygen at 2.5 atm, for 70 min periods, once daily, five times per week). In April 2018, a favourable clinical and radiological evolution was observed, with an improvement in the patterns of pain, motion and strength and an almost complete involution of the process of aseptic necrosis of the semilunar. To the best of our knowledge, this is the first report of Kienböck's disease treated with hyperbaric oxygen., Competing Interests: Competing interests: Coauthor NB is the father of the minor patient represented in the clinical case. He is a researcher in the area of Physics and Astronomy of the University of Bologna who encouraged and collaborated in all points concerning the accomplishment of the following article. The father and the patient signed the informed consent., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)