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Thrombotic microangiopathy (TMA) is an anatomopathological lesion mediated by endothelial dysfunction and characterized by the creation of microthrombi in small vessels. In patients with cancer, it may be due to toxicity secondary to chemotherapy, tumor embolization, or hematopoietic progenitor transplantation. Cancer-associated TMA is an underestimated entity that generally appears in the final stages of the disease, although it may also be the initial manifestation of an underlying cancer. Support treatment is necessary in all cases and, depending on the cause, different targeted therapies may be used. The prognosis is very poor. In this article we present a comprehensive review of the existing literature on the physiological mechanisms of cancer-associated TMA. Afterwards, five clinical cases will be presented of patients who developed TMA and were diagnosed in our Department in 2023. We present a discussion of the different causes that triggered the condition, the possible reasons behind the underestimation of this pathology, and the measures that may be adopted. [ABSTRACT FROM AUTHOR]

A 81-year-old woman with a history of mild chronic heart failure and invasive lobular breast carcinoma pT2N0M0 diagnosed in 2009 and treated by mastectomy, chemotherapy, radiotherapy and adjuvant endocrine therapy with letrozole until 2016. Since then the patient has been disease-free. She presented to the Emergency Room in April 2023 due to severe postprandial epigastric pain and a 7 kg weight loss in the last 3 months. Abdominal computed tomography was performed showing thickening of the gastric antrum and proximal duodenum walls, peritoneal implants and ascites that suggested primary gastric tumor or lymphoma as the first possibility. An endoscopic ultrasound was schedule, performing a biopsy of the gastric lesion and placing a Hot-Axios® stent. The sample showed infiltration by lobular breast carcinoma CK7 (+), CK20 (-), CDX2 (-), GATA3 (+) GCDFP15 (+) RE (+) RP (-) HER2 (-). Treatment with capecitabine was started, with which it continues currently.

Introduction: Breast cancer is among the most frequently diagnosed cancers worldwide, with 2.3 million new cases reported annually. The condition causes a social and economic impact known as financial toxicity of cancer. The study aims to explore the extra expenses borne by patients and their families on being diagnosed with breast cancer., Methodology: An observational, descriptive, cross-sectional study was conducted. The data was collected between November 2021 and March 2022 at the Medical Oncology Service in Complejo Asistencial Universitario de Salamanca, Spain. The variables under investigation were additional economic costs, physical disability (as measured by the Barthel Index), instrumental activities of daily living (as measured by the Lawton-Brody Scale), and caregiver burden (measured using the ZARIT scale)., Results: The final sample size was N  = 107. The study yielded the following outcomes: the median age was 55 years old and the majority of participants were female, with a proportion of 99.1%. The incidence rates for stage I and II were 31.8 and 35.5%, respectively. The median Barthel score was 100 points, while the Lawton and Brody score were 8 points and the ECOG score was 2 points. The analysis of primary caregiver burden resulted in a median ZARIT score of 15 points. The expenses related solely to the cancer diagnosis totaled 1511.22 euros per year (316.82 euros for pharmaceuticals; 487.85 euros for orthopedic equipment; 140.19 euros for home help; and 566.36 euros for housing adaptation or transfer to a hospital). The average annual income before diagnosis was 19962.62 euros. However, after being diagnosed with breast cancer, there is a significant income decrease of 15.91%, resulting in a reduced average annual income of 16785.98 euros. Additionally, a significant correlation was found between total expenditure and the level of dependency ( p = 0.032) and functional status ( p = 0.045)., Conclusion: These findings indicate that breast cancer patients experience a considerable economic burden, which worsens as their functional status deteriorates. Therefore, we believe policies should be implemented to help control this economic deterioration resulting from a serious health condition., 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 © 2024 Fernandez-Rodriguez, Taboada-Taboada, Garcia-Martin, Sanchez-Gomez, Saez-Gutierrez, Rihuete-Galve and Fonseca-Sánchez.)

Background: Neutrophilia is an increase in the number of neutrophils over 7.5×103/µL. An increase in leukocytes over 50×103/µL is called a leukemoid reaction; and when it is associated with a solid tumor, it is considered a paraneoplastic syndrome called paraneoplastic leukemoid reaction (PLR). It is a very rare clinical condition and it is very unusual for it to be associated with carcinosarcoma. We present two cases of a leukemoid reaction observed in the Medical Oncology Department of the University Hospital of Salamanca between May and September 2023. The main objectives of our article are to describe the unusual appearance of paraneoplastic leukocytosis at the diagnosis of carcinosarcoma carcinosarcoma, explain in a detailed way its diagnostic procedure and to show the poor prognosis to which it is associated., Case Description: In our presentation, we describe two similar cases: first of all, a 60-year-old woman without relevant medical history. She was referred by her primary physician to the Department of Internal Medicine in August 2023 with asthenia, lumbar pain, and weight loss of 12 kg of 3 months of evolution. The physical examination revealed a palpable hypogastric mass. An abdominal, pelvic, and thoracic computed tomography (CT) scan revealed a heterogenous solid mass with necrotic areas originating in the uterus. The anatomopathological diagnosis was carcinosarcoma. The patient showed a progressive worsening in her renal function associated with hyperviscosity secondary to hyperleukocytosis caused by 170×103/µL neutrophils. In the second case we describe the diagnosis of a PLR secondary to a kidney carcinosarcoma. When the patient started chemotherapy, he presented 55.08×103/µL leukocytes, 53.16×103/µL neutrophils. Eight days after receiving chemotherapy, the patient was admitted as an emergency with oligoanuria and decreased consciousness. He presented creatinine 6.25 mg/dL, phosphate 12.4 mg/dL, leukocytes 1.05×103/µL, and neutrophils 0.71×103/µL. The clinical diagnosis was acute exacerbation of multifactorial mixed (renal and prerenal) chronic kidney disease associated with tumor lysis syndrome and grade 3 neutropenia. The patient presented a poor evolution, dying after 2 months., Conclusions: PLR is a severe paraneoplastic syndrome associated with different types of solid tumors. Its appearance at the time of diagnosis of a tumor implies a poor vital prognosis.

Hepatoid gastric adenocarcinoma (HGA) is a rare subtype of gastric cancer. It usually presents with non-specific digestive tract symptoms and is usually diagnosed in advanced stages. It has radiological and histological similarities to hepatocarcinoma (HCC), and serum elevation of alpha-fetoprotein (AFP) is characteristic, as is positive staining for this marker on immunohistochemistry. Given the low incidence and poor prognosis of this type of tumour, it is essential to make a correct differential diagnosis and to initiate early surgical treatment in localised stages and systemic treatment in those where the disease is disseminated. In this context, we present the case of a GHA diagnosed this year in our centre.

Sodium-glucose cotransporter-2 (iSGLT2) inhibitors, which include dapagliflozin, canagliflozin and empagliflozin, are a class of drugs initially used in the oral treatment of diabetes, heart failure and renal failure. They target the reabsorption of glucose in the kidney. Although they bring benefit to patients with these conditions and in general produce few adverse effects, in some cases, iSGLT2 can cause serious adverse effects such as metabolic acidosis, and fungal or bacterial urinary infections. Oncology patients, who in general have a weak immune system and are usually treated with chemotherapy and/or immunotherapy, are more susceptible to this type of adverse events than other patients. For this reason, it is necessary to adequately select the patients eligible to receive this type of drug and evaluate the potential benefits for them. In this series of five cases, we present two cases of metabolic acidosis, two cases of bacterial urinary sepsis, and one case of fungal urinary sepsis that occurred in patients admitted to the Medical Oncology Department of the University Hospital of Salamanca in 2023., Learning Points: Adverse events associated with iSGLT2 can lead to serious complications in immunocompromised patients. There have been cases of prolonged admissions with high morbidity and mortality due to bacterial or fungal infections and metabolic acidosis, all of which are side effects derived from their use.In oncology patients, an adequate evaluation of the risk-benefit balance must be conducted before the introduction of new drugs.Studies should be conducted to assess the risk of serious adverse effects in oncology patients undergoing treatment with chemotherapy or immunotherapy., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2024.)

Background: Non-small cell lung cancer (NSCLC) has undergone a major change in the last decade in terms of survival and prognosis due to the introduction of new drugs in the last 10 years. One of the drugs with the most promising preliminary results in NSCLC are PARP inhibitors (iPARPs), whose clinical trials have very heterogeneous results. The use of iPARPs in NSCLC may lead to increased survival in several selected patients, and their use may become a standard in the coming years. However, there is currently controversy about the efficacy and safety of these drugs in NSCLC. Therefore, future studies are needed to evaluate their role in these tumours. The aim of this review is to evaluate the efficacy and safety of iPARPs in the treatment of NSCLC., Methods: We performed a systematic review with meta-analysis using the different clinical trials (PubMed, COCHRANE, Science Direct, EMBASE and the clinical trial registry) that evaluated the efficacy and safety of iPARP in NSCLC by PRISMA criteria. The primary endpoint was to evaluate the efficacy of iPARPs in the treatment of NSCLC through overall and progression-free survival (OS and PFS). Two authors independently reviewed the articles and abstracts (A.O.H. and J.R.R.), with subsequent confirmation by a third independent reviewer (E.B.M.). The heterogeneity of the included studies in the meta-analysis was assessed by using the I2 statistic., Results: A total of 14 articles were included for analysis (2,651 patients). A total of 1,503 patients were randomised in iPARP arms and 1,148 patients were included in control arms. Three clinical trials were conducted in localised or locally advanced NSCLC and 11 in advanced or metastatic stages. The global OS of the meta-analysis showed a hazard ratio (HR) of 0.85 [95% confidence interval (CI): 0.74-0.97] with a heterogeneity (I2) of 0% (P=0.84). PFS showed a HR of 0.93 (95% CI: 0.74-1.17) with an I2=51% (P=0.07). The overall adverse event rate (grade 1-5) was similar in both iPARP and placebo arms., Conclusions: iPARPs are a future promising in the treatment of NSCLC in terms of efficacy and safety. Proper patient selection [homologous recombination deficiency (HRD) positive] is key for future clinical trials. The studies conducted to date open a new approach for a novel treatment modality in NSCLC.

Background: The introduction of immunotherapy in the treatment of non-small cell lung cancer (NSCLC) has resulted in a radical change in patients' treatment responses and survival rates. The increased percentage of long survivors, improved toxicity profiles compared to chemotherapy, and the possible applications for different NSCLC scenarios, have led to immune checkpoint inhibitors (ICIs) becoming the cornerstone of NSCLC treatment. Therefore, the objective of this review is to describe the current and future perspectives of NSCLC treatment., Methods: A systematic review according to the PRISMA criteria has been performed based on clinical trials with immunotherapy in NSCLC from the start of these treatments until June 2022., Results: The use of ICIs is widespread across both first- and second-line treatments with anti-PD-1, anti-PD-L1, and anti-CTLA-4 drugs. New indications for immunotherapy in NSCLC have focused on adjuvant (atezolizumab) and neoadjuvant (nivolumab), with ICIs now present in all stages of NSCLC treatment. Given the promising results seen in clinical trials, new ICIs [anti- lymphocyte activation gene-3 (LAG-3) or IDO1] currently under development, will soon be used as standard treatment for NSCLC., Conclusions: Immunotherapy is the mainstay of NSCLC treatment in all stages, including adjuvant, neoadjuvant and advanced tumors. The development of new molecules will revolutionize the treatment of NSCLC in the coming years., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-4218/coif). JPMG serves as an unpaid editorial board member of Annals of Translational Medicine from June 2022 to May 2024. The other authors have no conflicts of interest to declare., (2023 Annals of Translational Medicine. All rights reserved.)

Introduction: Immunotherapy represents a key pillar of cancer treatments, with high response rates and long survival. Its use is increasing, mainly at the expense of the geriatric population due to the ageing of this population. However, despite its benefit, its safety in certain areas such as cardiotoxicity is largely unknown. The aim of this study is to assess the safety of immunotherapy in elderly patients using real-world data., Methods: This is an ambispective study of patients ≥ 70 years old with solid tumours who were treated with immunotherapy at the University Hospital of Salamanca. Cardiotoxicity was assessed using the CTCAEv5.0 criteria., Results: In total, 195 patients were included (76.9% male and 23.1% female), with a mean age of 75 years [70-93]. The percentage of patients with cardiotoxicity was 1.54%; 1.35% of patients with previous heart disease were diagnosed with cardiotoxicity, and 1.65% of those without previous heart disease were diagnosed with cardiotoxicity. The median time from the initiation of treatment until the cardiac event was 45 days [14-96]. The most frequent toxicity was myocarditis in 66.7% of patients, followed by arrhythmias in 33.3% of patients., Conclusions: Immunotherapy is shown to be a safe treatment in elderly cancer patients in terms of cardiotoxicity. The event rate shows no difference between patients with or without cardiac comorbidity.

A 73-year-old male with a history of chronic obstructive pulmonary disease and stage IV lung adenocarcinoma, being treated with the PD-1 inhibitor nivolumab, presented to the Emergency Room with a two-day history of coffee ground emesis and melena. On examination, he was tachycardic (130 per minute) and hypotensive (95/55 mmHg). Laboratory studies revealed anemia (6.9 g/dl), leukocytosis and hyper-lactatemia (lactate 6.3 mmol/l). Esophagogastroduodenoscopy was performed which showed diffuse circumferential blackish, necrotic-appearing mucosa of the first third of the esophagus. These findings were consistent with a diagnosis of acute esophageal necrosis (AEN). A biopsy of the esophageal mucosa demonstrated fragments of necrotic tissue with predominant lymphocyte infiltration. He was managed with a strict restriction of oral intake, total parenteral nutrition, double-dose proton pump inhibitors and broad-spectrum antibiotics (piperacillin/tazobactam). Despite the measures adopted, the patient presented a progressive clinical deterioration and died of multiple organ failure 12 days after admission.

The relationship between viral infections and cancer is well known and has been established for decades. Multiple tumours are generated from alterations secondary to viral infections 2 resulting from a dysregulation of the immune system in many cases. Certain causal relationships, such as that between the Epstein-Barr virus (EBV) in nasopharyngeal cancer or hepatitis C and B viruses in hepatocarcinoma, have been clearly established, and their implications for the prognosis and treatment of solid tumours are currently unknown. Multiple studies have evaluated the role that these infections may have in the treatment of solid tumours using immunotherapy. A possible relationship between viral infections and an increased response to immune checkpoint inhibitors (ICIs) has been established at a theoretical level in solid neoplasms, such as EBV-positive cavum cancer and human papillomavirus (HPV)-positive and oropharyngeal cancer. These could yield a greater response associated with the activation of the immune system secondary to viral infection, the consequence of which is an increase in survival in these patients. That is why the objective of this review is to assess the different studies or clinical trials carried out in patients with solid tumours secondary to viral infections and their relationship to the response to ICIs.

Context: Memorial Symptom Assessment Scale (MSAS) is a multidimensional tool developed to evaluate frequency, severity, and distress of common symptoms present in cancer patients., Objective: To translate the original English version of MSAS and prove the reliability and validity of the Spanish version., Methods: MSAS scale was translated into Spanish and administered to 246 cancer patients aged between 18 and 85 years. They attended the Day Hospital to receive chemotherapy. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 and Rotterdam Symptom Checklist were used to test criterion validity., Results: TOTAL MSAS, Physical Symptom Subscale (PHYS), Psychological Symptom Subscale (PSYCH), and Global Distress Index (GDI) reported high internal consistency: 0.891, 0.801, 0.825, 0.813, respectively. Exploratory factor analysis identified two-factors structure and confirmatory factor analysis showed good adjustment rates. The emotional functioning subscale of European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 highly correlated with PSYCH (r = -0.868; P < 0.001) and GDI (r = -0.810; P < 0.001), whereas social functioning subscale correlated with PSYCH (r = -0.704; P < 0.001) and GDI (r = -0.624; P < 0.001). The PHYS of Rotterdam Symptom Checklist correlated with PHYS (r = 0.876; P < 0.001) and the PSYCH with PSYCH (r = 0.872; P < 0.001)., Conclusion: The Spanish version of MSAS was determined to be a valid and reliable scale in cancer patients., (Copyright © 2016 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: Study the loss or reduction of the cellular adhesion mediated for E-cadherin in oral leukoplakias, oral squamous cell carcinomas and metastatic nodules. Study the loss of continuity of the laminin and collagen IV expression in the epithelial basal membrane from the biological development of the oral leukoplakias and oral carcinomas., Material and Method: we have studied 124 samples of patient pays leukoplakias and oral carcinomas with diverse diagnosis that embrace from normal epithelium (13 samples), mild dysplasias (2), moderate dysplasias (12), in situ carcinomas (13), microinvasive carcinomas (11) oral squamous cell carcinomas (64 samples) and metastatic nodules (9). 7 blocks of tissue microarrays were built with needle of 2mm and was carried out a study by means of immunohistochemical technique for E-cadherin (clone 36, Biogenex), Laminin (078P, Biogenex) and Collagen IV (PHM12, Biogenex)., Results: In Mild and Moderate Dysplasias the results present loss of E-cadherin, Laminin, and Collagen IV (20%) expression. in situ and microinvasive carcinomas, the results presented loss of E-cadherin expression (73%), and loss in Laminin and Collagen IV expression (57%). In the squamous cell carcinomas , we find E-cadherin underexpression (90%) and discontinuity in the Basal Membrane. (70%). All the metastatic nodules presented loss of E-cadherin expression and discontinuity in Laminin and Collagen IV expression., Conclusions: The loss of E-cadherin expression is increased when increasing the dysplasia grade of lesions. The loss of continuity in the laminin and Collagen IV expression follow a parallel evolution from dysplasias to metastatic nodules. The underexpression of the three markers has been significant in the evolution of the oral lesions.

Objectives: We intend to know the protein expression of genetic alterations that take place in the early stages in the field cancerization of oral cavity in our means as well as to study the cellular proliferation by means of Ki-67 and the protein product expression of p53 to value if the alterations in the protein products expression of these markers happen in a sequential pathway through the different stages in the field cancerization of oral cavity., Materials and Methods: A study was made by immunohistochemistry on 53 patients that presented lesions of oral leukoplaquia, assisted by the ENT service at University Hospital of Salamanca, from 1.990 up to 2000. 11 samples of normal epithelium, 15 mild to moderate dysplasias, 15 in situ carcinomas and 12 microinvasive carcinomas are included in the study., Results: we find an increased cellular proliferation and p53 over-expression as we advance in the grade of severity histopathologic of these lesions. The most early alterations are a significant increase of cell proliferation in mild and moderate dysplasias and an increased p53 over-expression., Conclusions: Oral leukoplaquia is a precancerous stage that constitutes a cancerisable lesion due to the genetic alterations that mediate in the evolution of lesion. Routine Immunohistochemical and molecular study of these lesions allow us to know the protein expression of genetic alterations that can help in the early diagnosis and treatment of this pathology, having special relevance the study of Ki-67 in early stages and p53 in advanced lesions.

A retrospective study was made of 29 patients with cervical metastasis of an unknown primary tumor. Sixteen patients received local treatment with surgery and radiotherapy (group A) and 13 patients were treated with induction chemotherapy, surgery and radiotherapy (group B). All patients responded. Local recurrence occurred in 21.4% of group A and 20% of group B. The frequency of distant metastases was similar (18.8% vs 15.4%). The mean survival time of 68 months in group A was longer than the 40 months of group B, and the a 2-year survival rate was 81% in group A and 67% in group B. The 5-year survival was better in group B (56% vs 40%). The primary tumor was identified twice as often in the patients who received only local treatment (group A 37.5% and group B 15.4%). Detection of the primary tumor was the only factor that significantly influenced patient survival.