Case report: Primary CDK4/6 inhibitor and endocrine therapy in locally advanced breast cancer and its effect on gut and intratumoral microbiota.

Locally advanced breast cancer poses significant challenges to the multidisciplinary team, in particular with hormone receptor (HR) positive, HER2-negative tumors that classically yield lower pathological complete responses with chemotherapy. The increasingly significant use of CDK 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) in different breast cancer settings has led to clinical trials focusing on this strategy as a primary treatment, with promising results. The impact of the microbiota on cancer, and vice-versa, is an emerging topic in oncology. The authors report a clinical case of a postmenopausal female patient with an invasive breast carcinoma of the right breast, Luminal B-like, staged as cT4cN3M0 (IIIB). Since the lesion was considered primarily inoperable, the patient started letrozole and ribociclib. Following 6 months of systemic therapy, the clinical response was significant, and surgery with curative intent was performed. The final staging was ypT3ypN2aM0, R1, and the patient started adjuvant letrozole and radiotherapy. This case provides important insights on primary CDK4/6i plus ET in locally advanced unresectable HR+/HER2- breast cancer and its potential implications in disease management further ahead. The patient's gut microbiota was analyzed throughout the disease course and therapeutic approach, evidencing a shift in gut microbial dominance from Firmicutes to Bacteroidetes and a loss of microbial diversity following 6 months of systemic therapy. The analysis of the intratumoral microbiota from the surgical specimen revealed high microbial dissimilarity between the residual tumor and respective margins.

Successful management of bilateral orbital metastases from invasive lobular breast cancer with abemaciclib and letrozole: a case report and literature review.

Breast cancer is a significant global health concern, contributing to substantial morbidity and mortality among women. Hormone receptor-positive (HR+)/HER2-negative (HER2-) breast cancer constitutes a considerable proportion of cases, and significant advancements have been made in its management. CDK4/6 inhibitors (CDK4/6is) are a new targeted therapy that has demonstrated efficacy in adjuvant, advanced and metastatic settings. The propensity of lobular breast carcinomas for estrogen-rich sites, such as periocular tissues and orbital fat, may explain their tendency for orbital metastases. Current treatment strategies for these cases are predominantly palliative, and the prognosis remains poor. This article presents a unique case of a 51-year-old female with progressive right periorbital edema, pain, and limited ocular motility. An imaging work-up showed bilateral intra and extraconal orbital infiltration, which was biopsied. The histopathologic analysis disclosed mild chronic inflammatory infiltrate with thickened fibrous tissue and moderately differentiated lobular carcinoma cells, positive for GATA3 and CK7 markers, with 100% of tumor nuclei expressing estrogen receptors (ER+). A systemic evaluation showed a multicentric nodular formation in both breasts. Further diagnostic assessments unveiled an HR+/HER2- bilateral lobular breast carcinoma with synchronous bilateral orbital metastases. Systemic treatment was initiated with abemaciclib 150mg twice daily and letrozole 2.5mg once a day. However, this regimen was interrupted due to toxicity. After two weeks, treatment was resumed with a reduced abemaciclib dose (100mg twice daily) alongside letrozole, with a reasonable tolerance. Nearly two years after the initial diagnosis of inoperable metastatic cancer, the patient remains on the same systemic treatment regimen with no signs of invasive disease. This case report is the first of a patient presenting with bilateral orbital metastases from bilateral lobular breast cancer, showing an impressive and sustained response to a first-line treatment regimen combining abemaciclib and letrozole. A literature review on bilateral orbital metastases from breast cancer is also presented.

Hyperbaric oxygen therapy as a complementary treatment in neuroblastoma - a narrative review.

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.

Communication preferences and perceptions of cancer patient during their first medical oncology appointment.

BACKGROUND: The first medical oncology appointment serves as a platform for patients to comprehend their diagnosis and prognostic implications of cancer. This study aimed to determine patients' communication preferences during their first medical oncology appointment and to assess the disparities between patients' preferences and perceptions. METHODS: A total of 169 cancer patients participated by completing the Communication in First Medical Oncology Appointment Questionnaire (C-FAQ), a two-section questionnaire designed to assess patients' preferences and perceptions regarding Content (information provided and its extent), Facilitation (timing and location of information delivery), and Support (emotional support) during their first medical oncology appointment. A comparative analysis was conducted to assess the variations between preferences and perceptions. RESULTS: Content emerged as the most significant dimension compared to Facilitation and Support. The physician's knowledge, honesty, and ability to provide clear information were considered the most important attributes. Patients evaluated most of their preferences as "very important". Patients' perception of the communication dimensions present during their appointment was below preferences for 11 items, indicating significant discrepancies in clinical practice. CONCLUSIONS: Patients highly valued their preferences concerning Content, Facilitation, and Support dimensions of communication. However, patient preferences were more prominently oriented towards the Content dimension. The discrepancies between preferences and perceptions should be viewed as an opportunity for enhancing communication skills through training.

The effectiveness of hyperbaric oxygen therapy for managing radiation-induced proctitis - results of a 10-year retrospective cohort study.

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.

Mutation Patterns in Portuguese Families with Hereditary Breast and Ovarian Cancer Syndrome.

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_157insAlu) and two other variants in the BRCA1 gene (c.3331_3334del and c.2037delinsCC) contribute to about 50% of all pathogenic mutations. Furthermore, the families with the BRCA1 c.3331_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.

Local Breast Microbiota: A "New" Player on the Block.

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.

Hyperbaric Oxygen Therapy as a Complementary Treatment in Glioblastoma-A Scoping Review.

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. The mainstay of management for GBM is surgical resection, radiation (RT), and chemotherapy (CT). Even with optimized multimodal treatment, GBM has a high recurrence and poor survival rates ranging from 12 to 24 months in most patients. Recently, relevant advances in understanding GBM pathophysiology have opened new avenues for therapies for recurrent and newly diagnosed diseases. GBM's hypoxic microenvironment has been shown to be highly associated with aggressive biology and resistance to RT and CT. Hyperbaric oxygen therapy (HBOT) may increase anticancer therapy sensitivity by increasing oxygen tension within the hypoxic regions of the neoplastic tissue. Previous data have investigated HBOT in combination with cytostatic compounds, with an improvement of neoplastic tissue oxygenation, inhibition of HIF-1α activity, and a significant reduction in the proliferation of GBM cells. The biological effect of ionizing radiation has been reported to be higher when it is delivered under well-oxygenated rather than anoxic conditions. Several hypoxia-targeting strategies reported that HBOT showed the most significant effect that could potentially improve RT outcomes, with higher response rates and survival and no serious adverse events. However, further prospective and randomized studies are necessary to validate HBOT's effectiveness in the 'real world' GBM clinical practice.

Impact of the COVID-19 Pandemic on Breast Cancer Management in Portugal: A Cross-Sectional Survey-Based Study of Medical Oncologists.

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.

This study was an online survey of Portuguese medical oncologists to determine how they managed patients with breast cancer during the COVID-19 pandemic. Forty-two questions covered topics such as how COVID testing was done, the types of cancer treatments used, and how this compared to before the pandemic. It also examined whether the geographic region, the number of patients each doctor was responsible for (caseload), and the type of medical institution influenced how patients with breast cancer were managed. One hundred and twenty-nine oncologists completed the survey, of whom 108 worked in the public health system, making this survey representative of breast cancer management during the COVID-19 pandemic across Portugal. Most (71%) said there were fewer visits for new cases of breast cancer during lockdown. The use of telemedicine increased, as did the use of pre-surgery hormone therapy or chemotherapy when access to surgery was difficult, and the use of anticancer medications taken orally or metronomically (low doses given frequently over a long time period). Chemotherapy given very frequently (dose-dense) was used less often, and fewer patients participated in clinical trials. Treatment decisions for patients with aggressive breast cancer types (e.g., triple-negative breast cancer) were largely unchanged, except for greater use of cyclin-dependent kinase 4/6 inhibitors­drugs targeting the cell cycle and cell division control. Geographic region and caseload influenced treatment decisions. All of these changes in breast cancer treatment during the COVID-19 pandemic were logical and reasonable for the circumstances, but their long-term impact is not yet known.

Adenoid cystic carcinoma of the palpebral lobe of the lacrimal gland - case report and literature review.

Epithelial tumors of the lacrimal gland are rare and usually develop in the orbital lobe. We report the exceedingly rare occurrence of a primary adenoid cystic carcinoma in the palpebral lobe of the lacrimal gland. A 26-year-old female was referred for evaluation of a gradually enlarging mass in the lateral upper eyelid, previously diagnosed as a chalazion. Computed tomography revealed a heterogeneous round lesion anterior to the orbital rim. Excisional biopsy was compatible with an adenoid cystic carcinoma. After excluding distant metastasis, and as the patient refused adjuvant radiotherapy, a second surgical procedure, with wide local excision, was indicated. Follow-up showed no recurrence. This case highlights the importance of performing a thorough clinical examination when diagnosing any lateral upper eyelid mass. A high index of suspicion for malignant tumors of the lacrimal gland should always be maintained, and a complete excision with histological analysis should be preferred whenever possible.

Refining Therapy in Patients with HER2-Positive Breast Cancer with Central Nervous System Metastasis.

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.

Next-Generation Sequencing in Breast Cancer Management: A Case Report of Genomic Tumour Evolution over Time.

The clinicopathological breast cancer subtypes are used in clinical practice to better anticipate biological behaviour and guide systemic treatment strategy. In the adjuvant setting, genomic assay recurrence scores became widely available for luminal-like disease. Recently, next-generation sequencing (NGS) platforms have been used, essentially, in more advanced disease setting, in situations refractory to conventional treatment, or even in rare cancers for which there are no established treatment guidelines. Moreover, subpopulations of cancer cells with unique genomes within the same patient may exist across different regions of a tumour or evolve over time, which is called intratumoural heterogeneity. We herein report a case of a 38-year-old woman with breast cancer whose primary and metastatic disease exhibited discordant expression of hormone receptors, with the former being positive and the latter negative. Furthermore, the NGS analysis revealed slight and dynamic changes of mutational profiles between different metastatic lesions, potentially impacting breast cancer management and prognosis. These alterations may reflect tissular and temporal changes in tumour subclones and may also be due to the selective pressure caused by antineoplastic treatment. The use of genomic analyses in order to improve cancer treatment has been studied prospectively with encouraging results. The widespread use of NGS tests in clinical practice also creates new challenges. The most relevant may be to know which genomic alterations detected should be valued and how they should be targeted.

Hyperbaric oxygen therapy as a complementary treatment for radiation proctitis: Useless or useful? - A literature review.

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.

The Role of Hyperbaric Oxygen Therapy in Pneumatosis Cystoides Intestinalis-A Scoping Review.

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.

Human Microbiota and Breast Cancer-Is There Any Relevant Link?-A Literature Review and New Horizons Toward Personalised Medicine.

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, ß-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.

Human Microbiota and Immunotherapy in Breast Cancer - A Review of Recent Developments.

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.

A Potential Link Between Prolonged Cork Exposure and Intestinal-Type Sinonasal Adenocarcinoma - Special Findings of a Retrospective Cohort Analysis.

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.

Cancer During Pregnancy: How to Handle the Bioethical Dilemmas?-A Scoping Review With Paradigmatic Cases-Based Analysis.

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.

Stage III Kienböck's disease treated with hyperbaric oxygen: the role of an unusual approach to a rare condition.

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.