High-grade neuroendocrine head and neck cancer: Case series and review of the literature.

BACKGROUND: High-grade neuroendocrine cancers (NEC) of the head and neck (HN) are rare and aggressive, accounting for ≤1 % of all HN cancers, with a 5-year overall survival (OS) of ≤20 %. This case series examines clinical characteristics, treatments, and outcomes of patients diagnosed at a regional UK HN cancer centre over the last 23 years. METHODS: A retrospective review of medical records was conducted for all patients diagnosed with NEC HN from 1st January 2000 until 1st March 2023 at Velindre Cancer Centre. RESULTS: During the study period, 19 cases of NEC HN were identified, primarily affecting males (n = 15, 79 %). Median age of 67 years (range: 44-86). At diagnosis, 32 % of patients (n = 6) were smokers. The most common primary tumour sites were larynx (n = 5, 26.3 %) and sinonasal (n = 5, 26.3 %). Most patients presented with advanced loco-regional disease or distant metastasis, with stage IVA (n = 6, 32 %) and stage IVC (n = 6, 32 %) being the most common. The key pathology marker was synaptophysin, present in 100 % of the tested patients (n = 15). In the study, of the 12 patients with non-metastatic disease, 10 received a combination of treatments that included radiotherapy (RT). Some of these patients also received chemotherapy (CT) at the same time as their radiotherapy. Surgery alone was used in two patients with stage II disease. Seven subjects had complete responses, and one achieved a partial response. Among the seven metastatic patients, three received CT, and one underwent palliative RT, all achieving a partial response. In all cases, the CT used was carboplatin and etoposide. After a median follow-up of 11 months (range: 1-96), the median OS was 27 months for the overall population, 51 months for those treated radically, and three months for metastatic patients with palliative treatment. The 1-year OS for all patients was 54.3 %, the 2-year OS was 46.5 %, and the 5-year OS was 23.3 %. Among patients treated radically, these rates were 65.3 %, 52.2 %, and 26.1 %, respectively. For patients treated palliatively, the 1-year OS was 33.3 %. CONCLUSION: This case series contributes preliminary observations on the characteristics and management of non-metastatic NEC HN, suggesting potential benefits from multimodality treatment strategies. Given the small cohort size, these observations should be interpreted cautiously and seen as a foundation for further research.

Achieving complete metabolic response in stage IV lung adenocarcinoma with chemotherapy, nivolumab, ipilimumab, and salvage SBRT: A case report.

Oncogene-negative, PDL1-negative metastatic non-small cell lung cancer (NSCLC) presents significant treatment challenges due to its complexity and resistance to conventional therapies. The case report presented addresses a 55-year-old male patient with oncogene-negative, PDL1-negative stage IV lung adenocarcinoma, showcasing an exceptional complete metabolic response to a multimodality treatment combining double immune checkpoint inhibition (ICI) and chemotherapy, followed by salvage stereotactic body radiotherapy (SBRT). The patient underwent a treatment regimen incorporating two cycles of carboplatin, pemetrexed, nivolumab, and ipilimumab followed by nivolumab, and ipilimumab maintenance. After a partial response, SBRT was applied to persistent lesions, achieving a complete metabolic response. This case highlights the potential of combining dual ICI with chemotherapy and SBRT in treating oncogene-negative, PDL1-negative NSCLC underscoring the importance of multimodality treatment strategies.

Global Stage Distribution of Breast Cancer at Diagnosis: A Systematic Review and Meta-Analysis.

Importance: Stage at diagnosis is a key prognostic factor for cancer survival. Objective: To assess the global distribution of breast cancer stage by country, age group, calendar period, and socioeconomic status using population-based data. Data Sources: A systematic search of MEDLINE and Web of Science databases and registry websites and gray literature was conducted for articles or reports published between January 1, 2000, and June 20, 2022. Study Selection: Reports on stage at diagnosis for individuals with primary breast cancer (C50) from a population-based cancer registry were included. Data Extraction and Synthesis: Study characteristics and results of eligible studies were independently extracted by 2 pairs of reviewers (J.D.B.F., A.D.A., A.M., R.S., and F.G.). Stage-specific proportions were extracted and cancer registry data quality and risk of bias were assessed. National pooled estimates were calculated for subnational or annual data sets using a hierarchical rule of the most relevant and high-quality data to avoid duplicates. Main Outcomes and Measures: The proportion of women with breast cancer by (TNM Classification of Malignant Tumors or the Surveillance, Epidemiology, and End Results Program [SEER]) stage group. Results: Data were available for 2.4 million women with breast cancer from 81 countries. Globally, the proportion of cases with distant metastatic breast cancer at diagnosis was high in sub-Saharan Africa, ranging from 5.6% to 30.6% and low in North America ranging from 0.0% to 6.0%. The proportion of patients diagnosed with distant metastatic disease decreased over the past 2 decades from around 3.8% to 35.8% (early 2000s) to 3.2% to 11.6% (2015 onwards), yet stabilization or slight increases were also observed. Older age and lower socioeconomic status had the largest proportion of cases diagnosed with distant metastatic stage ranging from 2.0% to 15.7% among the younger to 4.1% to 33.9% among the oldest age group, and from 1.7% to 8.3% in the least disadvantaged groups to 2.8% to 11.4% in the most disadvantaged groups. Conclusions and Relevance: Effective policy and interventions have resulted in decreased proportions of women diagnosed with metastatic breast cancer at diagnosis in high-income countries, yet inequality persists, which needs to be addressed through increased awareness of breast cancer symptoms and early detection. Improving global coverage and quality of population-based cancer registries, including the collection of standardized stage data, is key to monitoring progress.

Clinical Experience with Abemaciclib in Patients Previously Treated with Another CDK 4/6 Inhibitor in a Tertiary Hospital: A Case Series Study.

The three approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, including abemaciclib, have shown differences in their preclinical, pharmacological, and clinical data. Abemaciclib stands out for its broader target range and more rapid and intense activity. It has demonstrated efficacy as a monotherapy or in combination with tamoxifen in endocrine-refractory metastatic breast cancer (MBC) patients with prior chemotherapy. However, the clinical data on abemaciclib after exposure to previous CDK4/6 inhibitors are limited. In this single-center retrospective case series, we identified all patients who received abemaciclib until February 2022 after experiencing documented progression on palbociclib or ribociclib. The safety profile and clinical outcomes of abemaciclib treatment in this specific patient cohort were evaluated. Eleven patients were included in this retrospective case series, nine receiving abemaciclib with tamoxifen. Eight patients had visceral involvement, and the median age was 69 (ranging from 42 to 84). The median time from the end of prior CDK4/6 inhibitor treatment to abemaciclib initiation was 17.5 months (ranging from 3 to 41 months). Patients had undergone a median of three prior therapies (ranging from 1 to 7), including chemotherapy in 54.5% of cases. The median follow-up time was six months (ranging from 1 to 22 months). The median progression-free survival (PFS) was 8 months (95% CI 3.9-12). Five patients continued abemaciclib treatment, and one patient with liver metastases achieved a complete hepatic response. The most common adverse events were diarrhea (72.7%, no grade ≥ 3) and asthenia (27.3%, no grade ≥ 3). Our preliminary findings suggest that abemaciclib could be an effective and safe treatment option for MBC patients who have previously received palbociclib or ribociclib.

Prognostic value of human leukocyte antigen G expression in solid tumors: a systematic review and meta-analysis.

Introduction: Identification of modulators of the immune response with inhibitory properties that could be susceptible for therapeutic intervention is a key goal in cancer research. An example is the human leukocyte antigen G (HLA-G), a nonclassical major histocompatibility complex (MHC) class I molecule, involved in cancer progression. Methods: In this article we performed a systematic review and meta-analysis on the association between HLA-G expression and outcome in solid tumors. This study was performed in accordance with PRISMA guidelines and registered in PROSPERO. Results: A total of 25 studies met the inclusion criteria. These studies comprised data from 4871 patients reporting overall survival (OS), and 961 patients, reporting disease free survival (DFS). HLA-G expression was associated with worse OS (HR 2.09, 95% CI = 1.67 to 2.63; P < .001), that was higher in gastric (HR = 3.40; 95% CI = 1.64 to 7.03), pancreatic (HR = 1.72; 95% CI = 0.79 to 3.74) and colorectal (HR = 1.55; 95% CI = 1.16 to 2.07) cancer. No significant differences were observed between the most commonly utilized antibody (4H84) and other methods of detection. HLA-G expression was associated with DFS which approached but did not meet statistical significance. Discussion: In summary, we describe the first meta-analysis associating HLA-G expression and worse survival in a variety of solid tumors. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022311973.

Specific Cellular and Humoral Immune Responses to the Neoantigen RBD of SARS-CoV-2 in Patients with Primary and Secondary Immunodeficiency and Healthy Donors.

Patients with antibody deficiency disorders, such as primary immunodeficiency (PID) or secondary immunodeficiency (SID) to B-cell lymphoproliferative disorder (B-CLPD), are two groups vulnerable to developing the severe or chronic form of coronavirus disease caused by SARS-CoV-2 (COVID-19). The data on adaptive immune responses against SARS-CoV-2 are well described in healthy donors, but still limited in patients with antibody deficiency of a different cause. Herein, we analyzed spike-specific IFN-γ and anti-spike IgG antibody responses at 3 to 6 months after exposure to SARS-CoV-2 derived from vaccination and/or infection in two cohorts of immunodeficient patients (PID vs. SID) compared to healthy controls (HCs). Pre-vaccine anti-SARS-CoV-2 cellular responses before vaccine administration were measured in 10 PID patients. Baseline cellular responses were detectable in 4 out of 10 PID patients who had COVID-19 prior to vaccination, perceiving an increase in cellular responses after two-dose vaccination (p < 0.001). Adequate specific cellular responses were observed in 18 out of 20 (90%) PID patients, in 14 out of 20 (70%) SID patients and in 74 out of 81 (96%) HCs after vaccination (and natural infection in some cases). Specific IFN-γ response was significantly higher in HC with respect to PID (1908.5 mUI/mL vs. 1694.1 mUI/mL; p = 0.005). Whereas all SID and HC patients mounted a specific humoral immune response, only 80% of PID patients showed positive anti-SARS-CoV-2 IgG. The titer of anti-SARS-CoV-2 IgG was significantly lower in SID compared with HC patients (p = 0.040), without significant differences between PID and HC patients (p = 0.123) and between PID and SID patients (p =0.683). High proportions of PID and SID patients showed adequate specific cellular responses to receptor binding domain (RBD) neoantigen, with a divergence between the two arms of the adaptive immune response in PID and SID patients. We also focused on the correlation of protection of positive SARS-CoV-2 cellular response to omicron exposure: 27 out of 81 (33.3%) HCs referred COVID-19 detected by PCR or antigen test, 24 with a mild course, 1 with moderate symptoms and the remaining 2 with bilateral pneumonia that were treated in an outpatient basis. Our results might support the relevance of these immunological studies to determine the correlation of protection with severe disease and for deciding the need for additional boosters on a personalized basis. Follow-up studies are required to evaluate the duration and variability in the immune response to COVID-19 vaccination or infection.

Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck.

Neuroendocrine carcinomas (NECs) of the head and neck (HN) account for <1% of HN cancers (HNCs), with a 5-year overall survival (OS) <20%. This is a retrospective study of HN NECs diagnosed at our institution between 2005 and 2022. Immunohistochemistry and next-generation sequencing (NGS) were used to evaluate neuroendocrine markers, tumor mutational burden (TMB), mutational profiles and T-cell receptor repertoires. Eleven patients with high-grade HN NECs were identified (male:female ratio 6:5; median age 61 (Min-Max: 31-86)): nasoethmoidal (3), parotid gland (3), submaxillary gland (1), larynx (3) and base of tongue (1). Among n = 8 stage II/IVA/B, all received (chemo)radiotherapy with/without prior surgery or induction chemotherapy, with complete response in 7/8 (87.5%). Among n = 6 recurrent/metastatic patients, three received anti-PD1 (nivolumab (2), pembrolizumab (1)): two achieved partial responses lasting 24 and 10 months. After a median follow-up of 30 and 23.5 months since diagnosis and since recurrent/metastatic, median OS was not reached. Median TMB (n = 7) was 6.72 Mut/Mb. The most common pathogenic variants were TP53, HNF1A, SMARCB1, CDKN2A, PIK3CA, RB1 and MYC. There were 224 median TCR clones (n = 5 pts). In one patient, TCR clones increased from 59 to 1446 after nivolumab. HN NECs may achieve long-lasting survival with multimodality treatment. They harbor moderate-high TMBs and large TCR repertoires, which may explain responses to anti-PD1 agents in two patients and justify the study of immunotherapy in this disease.

The Missed Opportunity: HIV, Hepatitis C Virus (HCV), and Hepatitis B Virus (HBV) Positive Patients in Neoadjuvant and Perioperative Immunotherapy Clinical Trials for Lung Cancer.

This editorial addresses a critical oversight in recent clinical trials on neoadjuvant or perioperative immunotherapy for lung cancer, the exclusion of patients with human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV). The ethical implications of this exclusion are highlighted, demonstrating how it undermines principles of inclusivity and equity in clinical research. We emphasize the necessity to include these patients to enhance the generalizability of trial findings. We suggest that trial eligibility criteria be revised, and collaborations with patient advocacy groups be initiated to ensure more inclusive future trials. This approach aims to uphold ethical research practices, yielding robust, representative data, and ultimately improving patient care in oncology.

Perforation of the Nasal Septum in a Colorectal Cancer Patient Treated With Aflibercept: A Case Report.

Aflibercept is an antiangiogenic agent used in patients with metastatic colorectal cancer who have progressed to a first-line oxaliplatin-based regimen. The main adverse effects (AEs) of antiangiogenic agents are fatigue, asthenia, anorexia, hypertension, proteinuria, urinary tract infection, diarrhea, and neutropenia. Other AEs, such as hemorrhage, thromboembolic events, and gastrointestinal perforation, are much less frequent. Nasal septal perforation caused by antiangiogenic agents is even rarer. The published literature on this subject is scarce. Here, we report the case of a 54-year-old male with metastatic colorectal cancer undergoing treatment with leucovorin, fluorouracil (5-FU), irinotecan, and aflibercept who presented with epistaxis and nasal congestion. An otolaryngologist performed a rhinoscopy that revealed a perforation of the nasal septum. Aflibercept was withdrawn first, and local treatment was applied with lubricant and antibacterial lotions. It was considered a non-life-threatening side effect, and given the high risk of not continuing treatment in this patient with a recent recurrence, aflibercept was reintroduced in combination with leucovorin, 5-FU, and irinotecan. The patient continued local treatment and follow-up with medical oncology and otolaryngology with gradual improvement of symptoms. Follow-up was discontinued due to disease progression and death after 16 months of the event.

Case Report: Bocavirus Infection Radiologically Resembling a Congestive Heart Failure in a Patient with Metastatic Castration-Resistant Prostate Cancer.

Background: Human bocavirus (HBoV) is a viral pathogen from the genus Bocaparvovirus (family Parvoviridae, subfamily Parvovirinae) discovered in 2005. Most of available literature is about HBoV in children and adults with hematological malignancies and in otherwise healthy children with respiratory infections. Information regarding infection in the adult population with solid tumors is scarce. Case Report: We report the case of a 51-year-old male with metastatic castration resistant prostate cancer undergoing chemotherapy treatment who presented with fever, dyspnea, dry cough, and pleuritic pain. Imaging techniques showed signs of congestive heart failure. Symptoms, laboratory tests and echocardiography revealed a more probable infectious etiology. Antibiotic therapy was started. A polymerase chain reaction (PCR) test of nasopharyngeal exudate for respiratory viruses was positive for HBoV. The rest of the microbiological tests were negative. Bronchoalveolar lavage (BAL) was performed. Bacterial culture of BAL was negative while respiratory virus PCR confirmed positivity for HBoV. Antibiotic therapy was discontinued. The patient gradually recovered. Conclusions: Emerging infectious diseases are a notorious threat for immunocompromised populations such as solid tumor patients. This case is unique because to our knowledge this is the first case report article of HBoV in a solid tumor patient and because imaging techniques exhibited signs of congestive heart failure that did not correlate with the rest of the tests. It shows that unusual pathogens should be considered when managing serious clinical complications with uncommon presentations in cancer patients. Notable diagnostic efforts should be made to reach a diagnosis in these cases.

Evidence of exhausted lymphocytes after the third anti-SARS-CoV-2 vaccine dose in cancer patients.

Introduction: Evidence is scant regarding the long-term humoral and cellular responses Q7 triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in cancer patients after repeated booster doses. The possibility of T-cell exhaustion following these booster doses in this population has not yet been fully studied and remains uncertain. Methods: In this single-center prospective observational study, we explored the specific humoral and cellular response to S1 antigen in 36 patients with solid malignancies at baseline, and after the second and third doses of the mRNA-1273 vaccine. Results: A dual behavior was observed: 24 (66.7%) patients showed partial specific IFN-γ response after the second dose that was further enhanced after the third dose; and 11 (30.5%) already showed an optimal response after the second dose and experienced a marked fall-off of specific IFN-γ production after the third (4 patients negativization), which might suggest T cell exhaustion due to repetitive priming to the same antigen. One (2.8%) patient had persistently negative responses after all three doses. Seroconversion occurred in all patients after the second dose. We then studied circulating exhausted CD8+ T-cells in 4 patients from each of the two response patterns, those with increase and those with decrease in cellular response after the third booster. The patients with decreased cellular response after the booster had a higher expression of PD1+CD8+ and CD57+PD1+CD8+ exhausted T cells compared with those with an increased cellular response both in vivo and in vitro. The proportion of PD1+CD8+ and CD57+PD1+CD8+ exhausted T cells inversely correlated with IFN-γ production. Discussion: Our preliminary data show that the two-dose SARS-CoV-2 vaccine regimen was beneficial in all cancer patients of our study. An additional booster seems to be beneficial in suboptimal vaccine seroconverters, in contrast to maximal responders that might develop exhaustion. Our data should be interpreted with caution given the small sample size and highlight the urgent need to validate our results in other independent and larger cohorts. Altogether, our data support the relevance of immunological functional studies to personalize preventive and treatment decisions in cancer patients.

Adverse drug reactions to the three doses of the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) mRNA-1273 vaccine in a cohort of cancer patients under active treatment of a tertiary hospital in Madrid, Spain.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines efficacy and safety have been tested in phase 3 studies in which cancer patients were not included or were underrepresented. Methods: The objective of this study is to evaluate the safety profile of the mRNA-1273 vaccine across cancer patients and its relationship to patients' demographics. This retrospective cohort study included patients 18-years or older with solid malignancies receiving active treatment in our hospital who had received the three-dose schedule of the mRNA9 1273 vaccine and whose side effects after each dose were recorded. Patient electronic medical records were reviewed retrospectively to collect data between April 19, 2021, and December 31, 2021. Patients with documented previous infection by SARS-Cov-2 were excluded from the study. Results: A total of 93 patients met the inclusion criteria. Local adverse drug reactions (ADRs) were reported more frequently after the first and second dose than after the third (41.9%, 43% and 31.1% of the patients respectively), while systemic ADRs followed the opposite pattern (16.1%, 34.4% and 52.6% of the patients respectively). We found a statistically significant association between sex and systemic ADRs after the third dose. Cochran-Armitage test showed a statistically significant linear trend, p = 0.012, with a higher Eastern Cooperative Oncology Group (ECOG) score associated with a lower proportion of patients suffering from systemic side effects. A logistic regression showed that women had 5.79 times higher odds to exhibit systemic ADRs after the third dose (p=0.01) compared to males. Increasing age was associated with a decreased likelihood of exhibiting ADRs (p=0.016). Conclusion: The mRNA-1273 vaccine shows a tolerable safety profile. The likelihood of ADRs appears to be associated with gender and age. Its association with ECOG scores is less evident. Further studies are needed to elucidate this data in cancer patients.

A propósito de un caso: divertículo de Kommerell / About a case: Kommerell's diverticulum

La presencia de sibilantes refractarios y localizados en una sola área de auscultación en los adultos, sobre todo si están acompañados de anormalidades espirométricas y radiológicas, son a menudo la expresión clínica de una condición que requiere un proceso diagnóstico más profundo, más allá del facilista diagnóstico de asma. Entre estas anomalías se encuentran los anillos vasculares como el divertículo de Kommerel, que es una variante con una prevalencia muy baja y se caracteriza por la presencia de un arco aórtico derecho con una salida de la arteria subclavia izquierda aberrante y que provoca síntomas por la compresión de las estructuras adyacentes a estas. Aportamos en este caso clínico, el proceso diagnóstico de uno de estos hallazgos incidentales: la presencia de sibilantes localizados en una paciente joven, asintomática con una espirometría alterada que podría hacernos sospechar la presencia de broncomalacia, una aspiración de cuerpo extraño, un proceso infeccioso, tumoral o un anillo vascular que pasó desapercibido hasta la edad adulta.

The presence of refractory and localized wheezing in a single area of auscultation in adults, especially if they are accompanied by spirometric and radiological abnormalities, are often the clinical expression of a condition that requires a deeper diagnostic process, beyond the easy diagnosis of asthma. Among these abnormalities are vascular rings such as Kommerell¨s diverticulum, which is a very low prevalence variant and it is characterized by the presence of a right aortic arch with an aberrant exit from the left subclavian artery and that causes symptoms due to compression of the adjacent structures. In this clinical case, we provide the diagnosis process of one of these incidental findings, such as the presence of localized wheezing in a young asyntomatic patient with altered spirometry that could lead us to suspect the presence of bronchomalacia, foreign body aspiration, an infection, tumor or vascular ring that went unnoticed until adulthood.

Clinical-radiological approach for the diagnosis of cleidocranial dysplasia in adults: A familial cases series.

Cleidocranial dysplasia is a rare disease with an autosomal-dominant inheritance that mainly affects the bones of the axial skeleton. In this report, we discuss the clinical and radiological signs of a case series comprising three sisters and the son of one of the sisters, all with suspected bone dysplasia.

Pain assessment in Spanish rheumatology outpatient clinics: EVADOR Study. / Evaluación del dolor en consultas de reumatología españolas: Estudio EVADOR.

INTRODUCTION: rheumatic diseases are the most frequent cause of non-malignant chronic pain. In recent years, pain and its management have become more important in rheumatology. OBJECTIVES: to estimate the prevalence and characteristics of pain associated with rheumatic pathology treated in rheumatology clinics in Spain, as well as their treatment and response to it. METHODS: Multicentre observational study with two phases (cross-sectional and prospective). Variables were collected from the doctor, patient, pain and its management, comorbidities, therapeutic response and related psychosocial aspects. The differences between de novo (NP) vs follow-up (FP) patients were analyzed. RESULTS: 34 centres and 1084 patients were included, 32% NP and 68% FP. Pain was present in 86%, was chronic in 81% and neuropathic in 12% of the surveyed population. Fifty percent of the patients would regard their pain as tolerable if its intensity according to the visual numeric scale (VNS) was≤2. Among the FP it was more frequent to have the perception of controlled pain (65.5% vs 49.4%) and to be satisfied with the treatment (53.3% vs. 35.6%). Of these patients, 23.5% had been treated with opioids in the previous month. CONCLUSIONS: In the last decade, the prevalence of pain in rheumatology in Spain remains high, although it has diminished. The use of opioids, on the other hand, has increased.

Hepatitis B surface antigen loss after discontinuing nucleos(t)ide analogue for treatment of chronic hepatitis B patients is persistent in White patients.

OBJECTIVE: The objective of this study was to determine the long-term clinical outcome and persistence of hepatitis B surface antigen (HBsAg) loss after discontinuation of treatment. BACKGROUND: The prognosis of patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs) who discontinue treatment after loss of HBsAg remains largely unknown, particularly in White patients. PATIENTS AND METHODS: We analysed a cohort of patients with CHB who discontinued NA treatment after loss of HBsAg. A total of 69 patients with hepatitis-B-e antigen-positive or hepatitis-B-e antigen-negative CHB with undetectable HBsAg during NA treatment were included after discontinuation of treatment, and followed up for a median period of 37.8 months (interquartile range: 23.8-54.6 months). RESULTS: At the end of follow-up, none of the patients showed spontaneous reappearance of HBsAg and only one patient had detectable hepatitis B virus DNA (22 IU/ml). Another patient negative for HBsAg and anti-HBs developed hepatitis B virus reactivation without elevated transaminases after treatment with corticosteroids and vincristine for dendritic cell neoplasm, 38 months after withdrawal of the antiviral treatment. Regarding clinical outcome, a patient with cirrhosis developed hepatocellular carcinoma, 6.6 years after discontinuing treatment. None of the patients had hepatic decompensation or underwent liver transplantation. CONCLUSION: HBsAg clearance after discontinuing NAs in patients with CHB is persistent and associated with good prognosis. The risk for developing hepatocellular carcinoma persists among patients with cirrhosis.

Clinical characteristics of hepatocellular carcinoma in Spain. Comparison with the 2008-2009 period and analysis of the causes of diagnosis out of screening programs. Analysis of 686 cases in 73 centers. / Características clínicas del carcinoma hepatocelular en España. Comparación con el período 2008-2009 y análisis de las causas del diagnóstico fuera de cribado. Estudio de 686 casos en 73 centros.

BACKGROUND AND OBJECTIVE: In 2010 we published that 53% of cases of hepatocellular carcinoma (HCC) detected in Spain were diagnosed outside the context of standard screening programs, which consequently leads to lower survival rates. The aim of this study was to analyze the current situation and the causes of diagnosis out of screening programs. MATERIAL AND METHODS: Prospective registry of 73 second- and third-level Spanish healthcare centers carried out between October 1, 2014 and January 31, 2015. The baseline characteristics of the disease and the first treatment administered for the incidental primary liver tumors during such period were recorded. RESULTS: A total of 720 patients were included in the study: HCC (n=686), intrahepatic cholangiocarcinoma (n=29), hepatic cholangiocarcinoma (n=2), other (n=3). HCC characteristics: male 82%; mean age 67 years; cirrhosis 87%; main etiologies: alcohol 35%, HCV 30%, alcohol and HCV 15%, non-alcoholic fatty liver disease 6%; tumor stage: BCLC-0 11%, A 43%, B 19%, C 16% and D 11%; first treatment: transarterial chemoembolization (23%), percutaneous ablation (22%), symptomatic treatment (20%), resection (11%), sorafenib (11%). Three hundred and fifty-six patients (53%) were diagnosed outside of screening programs, mainly owing to the fact that they suffered from an undiagnosed liver disease (76%) and to the poor adherence to the screening program (18%). These patients were mainly male (P<.001), with an alcoholic etiology (P<.001) and active alcohol consumption (P<.001). Moreover, the disease was predominantly diagnosed at more advanced stages (P<.001) and was addressed with less radical treatments (P<.001). CONCLUSIONS: In Spain, the main cause of diagnosis of a HCC outside the context of a screening program is the absence of a prior diagnosis of a liver disease, particularly in alcohol-consuming men. Detecting a liver disease in asymptomatic populations and improving adherence to screening programs are the main areas that must be subject to improvement in order to improve the early detection of HCC.

Hernia diafragmática congénita de presentación tardía / Late-presenting congenital diaphragmatic hernia

La hernia diafragmática congénita de presentación tardía (HDCT) es una entidad infrecuente, representa del 5 a 20 % de todos los casos de hernia diafragmática congénita. La presentación clínica, diagnóstico y tratamiento difiere de la hernia de presentación neonatal, dada la ausencia de hipoplasia e hipertensión pulmonar. El amplio espectro clínico de la presentación tardía o su hallazgo radiológico incidental, pueden plantear un desafío diagnóstico; la demora en su detección y abordaje aumentan la morbimortalidad y ensombrecen el pronóstico. Presentamos el caso de una escolar de 8 años de edad a quien se le diagnostica una hernia diafragmática congénita izquierda y se hace revisión del diagnóstico, tratamiento y pronóstico de la enfermedad.

The late-presenting congenital diaphragmatic hernia is a rare entity that corresponds to the 5 - 20% of all congenital diaphragmatic hernia cases. The clinical manifestations ,diagnosis and treatment differ from the neonatal presentation in the absence of pulmonary hypoplasia and pulmonary hypertension. The wide clinical spectrum of the late-presenting diaphragmatic hernia or its incidental finding on radiological images can lead to a challenging diagnosis. The delay in the detection and approach increases the morbidity and mortality, and darkens the prognosis. We are presenting a case of an eighth year-old scholar who is diagnosed with a congenital left diaphragmatic hernia, as well as a review of the diagnosis, treatment and prognosis of this pathology.

Incidental bladder lipoma: a case report and review of the literature.

Conventional lipoma is the most common benign mesenchymal neoplasm in adults. However, bladder lipoma is a rare tumor. We report an incidental 0.5-cm, mucosal, bladder lipoma in a 75-year-old man, successfully treated with endoscopic excision. The tumor was found during the extension study of a high-grade urothelial carcinoma of the renal pelvis. A review of the published cases, including the present report, yielded a total of 16. Conclusions on this review are presented. The case is being reported because its rarity and to highlight the importance of complete workup to clarify associated disorders that may suggest extension of a malignant process.