Acquired Angioedema in Selected Neoplastic Diseases.

Background and Objectives. Acquired angioedema is a relatively common revelation accompanying some diseases such as autoimmune or cancer. The study aimed to assess the incidence of one subtype of angioedema-C1-INH-AAE (acquired angioedema with C1 inhibitor deficiency). Material and methods. The study was retrospective and based on 1 312 patients with a final diagnosis of breast cancer, colorectal cancer, or lung cancer: 723 women and 589 men with a mean age of 58.2 ± 13.5 years. The cancer diagnosis according to the ICD (International Classification of Diseases)-10 code, medical history including TNM (Tumour, Node, Metastasis) staging, histopathology, and assessment of the occurrence of C1-INH-AAE angioedema were analysed. Results. C1-INH-AAE occurred more often in patients with cancer than in the control group, as follows: 327 (29%) vs. 53 (6%) for p < 0.05. C1-INH-AAEs were observed most often in the group of patients diagnosed with breast cancer compared to colorectal and lung groups: 197 (37%) vs. 108 (26%) vs. 22 (16%) (p < 0.05). A higher incidence of C1-INH-AAE was observed in the early stages of breast cancer. However, there was no relationship between the occurrence of C1-INH-AAE and the BRCA1 (Breast Cancer gene 1)/BRCA2 (Breast Cancer gene 2) mutation or histopathological types of breast cancer. Conclusion. Angioedema type C1-INH-AAE occurs more often in patients with selected neoplastic diseases, especially in the early stages of breast cancer.

A novel GNAS-mutated human induced pluripotent stem cell model for understanding GNAS-mutated tumors.

A missense mutation of the guanine nucleotide binding protein alpha stimulating activity polypeptide 1 (GNAS) gene, typically Arg201Cys or Arg201His (R201H/R201C), leads to constitutive activation of the Gsα-cyclic AMP (cAMP) signaling pathway that causes several diseases. However, no germline mutations of GNAS have been identified to date, likely due to their lethality, and no robust human cell models have been generated. Therefore, the aim of this study was to generate GNAS-mutated disease-specific induced pluripotent stem cells as a model for these diseases. We then analyzed the functionality of this induced pluripotent stem cell model and differentiated epithelial cells. We generated disease-specific induced pluripotent stem cells by introducing a mutation in GNAS with the clustered regularly interspaced short palindromic repeats (CRISPR) nickase method, which has lower off-target effects than the conventional CRISPR/Cas9 method. We designed the target vector to contain the R201H mutation in GNAS, which was transfected into human control induced pluripotent stem cells (Nips-B2) by electroporation. We confirmed the establishment of GNASR201H-mutated (GNASR201H/+) induced pluripotent stem cells that exhibited a pluripotent stem cell phenotype. We analyzed the effect of the mutation on cAMP production, and further generated teratomas for immunohistochemical analysis of the luminal epithelial structure. GNAS-mutated induced pluripotent stem cells showed significantly higher levels of intracellular cAMP, which remained elevated state for a long time upon hormonal stimulation with parathyroid hormone or adrenocorticotropic hormone. Immunohistochemical analysis revealed that several mucins, including MUC1, 2, and MUC5AC, are expressed in cytokeratin 18 (CK18)-positive epithelial cells. However, we found few CK18-positive cells in mutated induced pluripotent stem cell-derived teratoma tissues, and reduced MUCINs expression in mutated epithelial cells. There was no difference in CDX2 expression; however, mutated epithelial cells were positive for CEA and CA19-9 expression. GNASR201H-mutated induced pluripotent stem cells and GNASR201H-mutated epithelial cells have distinct phenotypic and differentiation characteristics. We successfully established GNASR201H-mutated human induced pluripotent stem cells with increased cAMP production. Considering the differentiation potential of induced pluripotent stem cells, these cells will be useful as a model for elucidating the pathological mechanisms of GNAS-mutated diseases.

Monoexponential, Biexponential, and stretched-exponential models using diffusion-weighted imaging: A quantitative differentiation of breast lesions at 3.0T.

BACKGROUND: Diffusion-weighted imaging (DWI) plays an important role in the differentiation of malignant and benign breast lesions. PURPOSE: To investigate the utility of various diffusion parameters obtained from monoexponential, biexponential, and stretched-exponential DWI models in the differential diagnosis of breast lesions. STUDY TYPE: Prospective. POPULATION: Sixty-one patients (age range: 25-68 years old; mean age: 46 years old) with 31 malignant lesions, 42 benign lesions, and 28 normal breast tissues diagnosed initially by clinical palpation, ultrasonography, or conventional mammography were enrolled in the study from January to September 2016. FIELD STRENGTH: 3.0T MR scanner, T1 WI, T2 WI, DWI (conventional and multi-b values), dynamic contrast-enhanced. ASSESSMENT: The apparent diffusion coefficient (ADC) was calculated by monoexponential analysis. The diffusion coefficient (ADCslow ), pseudodiffusion coefficient (ADCfast ), and perfusion fraction (f) were calculated using the biexponential model. The distributed diffusion coefficient (DDC) and water molecular diffusion heterogeneity index (α) were obtained using a stretched-exponential model. All parameters were compared for malignant tumors, benign tumors, and normal breast tissues. A receiver operating characteristic curve was used to compare the ability of these parameters, in order to differentiate benign and malignant breast lesions. STATISTICAL TESTS: All statistical analyses were performed using statistical software (SPSS). RESULTS: ADC, ADCslow , f, DDC, and α values were significantly lower in malignant tumors when compared with normal breast tissues and benign tumors (P < 0.05). However, ADC and f had higher area under the receiver operating characteristic curve (AUC) values (0.889 and 0.919, respectively). DATA CONCLUSION: The parameters derived from the biexponential and stretched-exponential DWI could provide additional information for differentiating between benign and malignant breast tumors when compared with conventional diffusion parameters. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2019;50:1461-1467.

[Cytologic diagnosis of adenoid cystic carcinoma of salivary glands and distinction from basal cell adenoma].

Objective: To describe the cytologic features of adenoid cystic carcinoma (ADCC) of salivary glands, and to identify distinguishing cytologic features of ADCC and basal cell adenoma (BCA). Methods: A retrospective review of cytology smears of 30 cases of ADCC and 12 cases of BCA of salivary glands were performed. All cases were collected from Beijing Tongren Hospital, Capital Medical University from January 2010 to January 2017. Except for 2 aspirate smears of ADCC, all were touch imprint smears. All cases had further histological confirmation. Results: Neoplastic ductal cells of ADCC were arranged in three-dimensional clusters, sheets and singles. Hyaline globules were found in most cases (20/30, 66.7%). The nuclei were round to oval, showing varying degrees of nuclear atypia. These included (1) the nuclei were hyperchromatic, demonstrating coarse or slightly coarse, irregularly distributed chromatin; (2) the nuclei were slightly large and vary in size; (3) appearance of the nuclei had a different degree of irregularity (often mild). Nucleoli were common seen (21/30, 70.0%), and were prominent in some cases. Mitosis and necrosis were rare. Cytologically, BCA showed cell arrangements and nuclear features overlapped with those of ADCC. The cytologic difference between these two tumors included: (1) the tumor cells presented rarely in singles; (2) hyaline globules were very uncommon (1/12) in BCA; (3) nuclei of BCA were hypochromatic or slightly hyperchromatic, homogeneous and uniform in appearance and size, overall without nuclear atypia and they were smaller and slender then those of ADCC and (4) individual cells of BCA showed relatively abundant cytoplasm. Conclusions: The cytologic features of ADCC and BCA both overlap and different from each other. Most cases can be diagnosed by cytologic examination. The presence of hyaline globules is an important diagnostic clue of ADCC, although not pathognomonic. Nuclear atypia of neoplastic ductal cells is an essential cytological feature in the diagnosis of ADCC, and is the most reliable point for differential diagnosis of ADCC and BCA.

Population pharmacokinetics of thrombomodulin alfa in pediatric patients with hematological malignancy and disseminated intravascular coagulation.

BACKGROUND: Thrombomodulin alfa (TM-α) is a new class of anticoagulant drug for patients with disseminated intravascular coagulation (DIC). This study aimed to determine the pharmacokinetics of TM-α and determine the optimal dose in pediatric patients with hematological malignancy and DIC. PROCEDURE: Pediatric patients with hematological malignancy and DIC were administered TM-α at a dose of 0.06 mg/kg (380 U/kg) over 30 min every 24 hr. Blood samples were taken at steady state before the start, immediately after the end, and 24 hr after the start of the sixth administration. Population pharmacokinetic analysis was performed using sparse samples with the nonlinear mixed-effect modeling program NONMEM® , version 7.3. RESULTS: The actual and predicted plasma concentrations of TM-α based on the final population pharmacokinetic model showed a good linear correlation. Clearance and volume of distribution of TM-α were affected by body weight. The clearance of TM-α in pediatric patients with hematological malignancy and DIC was higher than that in adults as previously reported. Six of eight patients did not achieve the target trough concentration at steady state. Furthermore, the pharmacokinetic simulation based on the estimated pharmacokinetic parameters from the final model demonstrated that TM-α administered at a dose of 0.06 mg/kg every 24 hr also failed to achieve the target trough concentration at steady state in the majority of pediatric patients. CONCLUSIONS: Our study shows that further dose adjustment of TM-α is necessary considering the higher clearance per body weight in pediatric patients with hematological malignancy and DIC.

Diagnostic imaging and endoscopic finding in dogs and cats with gastric tumors: a review.

Medical imaging is an essential part of the diagnostic workup of many gastrointestinal disorders. This paper reviews imaging and endoscopy of gastric tumors in dogs and cats and the techniques used. The appearance of the normal as well as the various aspects of gastric tumors are described for these different modalities. Plain radiography is widely available but has limited diagnostic value. Contrast radiography has higher sensitivity but is laborious and time-consuming. Ultrasonography (if an adequate acoustic window is available), endosonography and endoscopy are the most appropriate modalities for diagnosing gastric tumors. They are especially useful when obtaining samples for cytologic or histopathologic examination, because the imaging modalities do not always differentiate between inflammatory or infectious conditions and neoplastic disorders. Hydro-helical CT was found helpful for evaluating the location and local invasiveness of the lesion. Ultrasonography and endoscopy are useful modalities for taking adequate biopsies.

L'imagerie diagnostique est un élément important du diagnostic de nombreuses affections gastro-intestinales. Cet article donne un aperçu des diverses techniques d'imagerie qui peuvent être utilisées pour identifier des tumeurs gastriques chez le chien et le chat. On décrit aussi bien les aspects physiologiques que les altérations pathologiques. Des clichés radiographiques sont en général facilement disponibles, ils n'ont toutefois qu'une valeur diagnostique limitée. Les études utilisant des moyens de contraste ont une meilleure valeur diagnostique mais nécessitent du temps et de travail. L'échographie (pour autant qu'on dispose d'une fenêtre acoustique adéquate), l'endosonographie et l'endoscopie sont les techniques diagnostiques les plus sûres pour identifier les tumeurs gastriques. Comme les techniques d'imagerie ne permettent pas toujours de différencier entre inflammation et tumeur, elles sont particulièrement utiles pour prélever des échantillons pour la cytologie ou l'histopathologie. Le scanner hydro-hélical est utile pour définir la localisation et l'extension d'une lésion, alors que l'échographie et l'endoscopie servent avant tout à effectuer des biopsies adéquates.

[Surgical aspects of intraductal papillary mucinous neoplasm of the pancreas]. / A pancreas intraductalis papillaris mucinosus neoplasmájának sebészi vonatkozásai.

Intraductal papillary mucinous neoplasms (IPMN) have a distinguished role amongst the exocrine pancreatic tumours. Although IPMN is less than 1% of all pancreatic neoplasms, cystic tumours, which has got in the spotlight recently, belong to this histopathological subtype up to 20% to 30%. IPMN originate from the main- and accessory pancreatic ducts. Rate of malignancy, prognosis and, therefore, the operative indications can be quite different. Although the prognosis of ductal carcinoma developed on the basis of IPMN is similar to classic adenocarcinoma - 10% 5-year survival - the overall prognosis of IPMN is much more favourable with over 70% survival rate in case of non-invasive cancers. Hence, it is important the timely diagnosis and surgical resection of IPMN to prevent development of invasive cancer.

Fulvestrant en la práctica clínica: análisis de efectividad en pacientes uruguayas con cáncer de mama HR+/HER2. / Fulvestrant in clinical practice: Effectiveness analysis in Uruguayan patients with HR+/HER2- breast cancer.

Introduction: Fulvestrant demonstrated benefits in overall survival and progression-free survival in patients with advanced breast cancer, who are hormone receptor-positive and human epidermal growth factor receptor 2 negative. The characteristics, evolution, and survival of patients with hormone receptor-positive, HER2-negative breast cancer treated with fulvestrant were evaluated according to the national treatment coverage protocols of the National Resources Fund, with the aim of understanding the efficacy of fulvestrant in patients treated in usual clinical practice and comparing our results with those from pivotal studies. Methods: A database from the National Resources Fund covering the period from 2009 to 2022 was used. Survival curves were assessed using the Kaplan-Meier method, and differences were analyzed using the Log-Rank test. Results: A total of 1085 patients with an average age of 63,66 years were included. Following a follow-up of 14 months, the median overall survival was 16 months, and the median progression-free survival was 6 months. The presence of liver and bone metastases was associated with a shorter overall survival. Patients from the public sector and those with a better performance status experienced longer overall survival. Conclusions: Our findings provide a valuable perspective for treatment management in a context of limited resources. Overall survival and progression-free survival were somewhat lower than those reported in pivotal clinical trials. The presence of liver and bone metastases was associated with worse prognosis and survival; additionally, patients with worse performance status had shorter overall survival. These findings underscore the need for personalized therapies, opening new lines of future research.

Introducción: Fulvestrant demostró beneficio en sobrevida global y sobrevida libre de progresión en pacientes con cáncer de mama avanzado, con receptores hormonales positivos y receptor de factor de crecimiento epidérmico humano 2 negativo. Se evaluaron las características, la evolución y la sobrevida de pacientes con cáncer de mama receptor hormonal positivo, HER2 negativo, tratadas con fulvestrant, de acuerdo con los protocolos nacionales de cobertura de tratamiento del Fondo Nacional de Recursos. Su objetivo fue conocer la eficacia de fulvestrant en pacientes tratados en la práctica clínica habitual. Se compararon los resultados obtenidos en el presente trabajo con los resultados de los estudios pivotales. Métodos: Se utilizó la base de datos del Fondo Nacional de Recursos, que abarca el período de 2009 a 2022. La evaluación de las curvas de sobrevida se realizó mediante el método Kaplan-Meier y las diferencias se analizaron utilizando el test de Log-Rank. Resultados: Se incluyeron 1085 pacientes con una edad media de 63,66 años. Tras un seguimiento de 14 meses, la mediana de la sobrevida global fue de 16 meses y la de la sobrevida libre de progresión de 6 meses. La presencia de metástasis hepáticas y óseas se asoció con una menor sobrevida global. Los pacientes del sector público y aquellos con una mejor escala de estado funcional experimentaron una mayor sobrevida global. Conclusiones: Los resultados obtenidos ofrecen una perspectiva valiosa para la gestión de tratamientos en un contexto de recursos limitados. La sobrevida global y la sobrevida libre de progresión fueron algo inferiores a los reportados en los ensayos clínicos pivotales. La presencia de metástasis hepáticas y óseas se asoció a un peor pronóstico y una peor sobrevida. Además, los pacientes con peor escala de estado funcional tuvieron una menor sobrevida global. Estos hallazgos subrayan la necesidad de terapias personalizadas, abriendo nuevas líneas de investigación futura.

Ochratoxin A and Its Role in Cancer Development: A Comprehensive Review.

Background: Ochratoxin A (OTA) is widely recognized for its broad spectrum of toxic effects and is classified as a potential human carcinogen, placed in group 2B by the International Agency for Research on Cancer (IARC). Its presence in food and beverages poses a significant health hazard. Extensive research has documented the efficient absorption and distribution of OTA throughout the body via the bloodstream and tissues, underscoring the associated health risk. Additionally, ongoing studies aim to clarify the link between OTA exposure and carcinogenesis. The obtained results indicate a strong correlation between OTA and renal cell carcinoma (RCC), with potential associations with other malignancies, including hepatocellular carcinoma (HCC), gallbladder cancer (GBC), and squamous cell carcinoma (SCC). OTA is implicated in oxidative stress, lipid peroxidation, apoptosis, DNA damage, adduct formation, miRNA deregulation, and distributions in the cell cycle, all of which may contribute to carcinogenesis. Conclusions: Despite significant research efforts, the topic remains inexhaustible and requires further investigation. The obtained results do not yield definitive conclusions, potentially due to species-specific differences in the animal models used and challenges in extrapolating these results to humans. In our review, we delve deeper into the potential mechanisms underlying OTA-induced carcinogenesis and discuss existing limitations, providing directions for future research.

ERK inhibitor: A candidate enhancing therapeutic effects of conventional chemo-radiotherapy in esophageal squamous cell carcinoma.

For patients with esophageal squamous cell carcinoma (ESCC), standard therapeutic methods (cisplatin and radiotherapy) have been found to be ineffective and severely toxic. Targeted therapy emerges as a promising solution for this dilemma. It has been reported that targeted therapies are applied alone or in combination with standard conventional therapies for the treatment of a variety of cancers. To the best of our knowledge, in patients with ESCC, the combinational methods containing standard therapy and ERK-targeted therapy have yet to be explored. To analyze the prognostic role of p-ERK in ESCC patients, the Kaplan-Meier analysis and Cox regression model were used. To assess the effects of ERK-targeted therapy (GDC0994) on ESCC cells, in vitro studies including CCK-8 assay, colony formation assay, and scratch wound healing assay were conducted. In addition, the changes in cell cycle distribution and apoptosis were analyzed by flow cytometry. Besides, to assess the efficacy of different therapies in vivo, the xenograft tumor models were established by subcutaneously inoculating tumor cells into the flank/leg of mice. In patients with ESCC, a strong correlation between the high expression level of p-ERK and the poor prognosis (p < 0.01, Log-Rank test) has been identified. By analyzing the results from CCK-8 and scratch wound healing assays, we demonstrated that the ERK inhibitor repressed the viability and migration of ESCC cells. In addition, following the treatment of GDC0994, the volumes of xenograft tumors significantly decreased (p < 0.001, one-way ANOVA). Furthermore, blocking the mitogen-activated protein kinase (MAPK/ERK) pathway enhanced the therapeutic efficacy of both cisplatin and radiotherapy (p < 0.05). These findings imply the role of p-ERK in the prognosis of ESCC patients and the therapeutic value of ERK inhibitors in ESCC.

Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: a multisite U.S. study.

BACKGROUND: Tumor mutational burden (TMB) is a potential biomarker to predict tumor response to immuno-oncology agents in patients with metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A multi-site cohort study evaluated patients diagnosed with stage IV NSCLC between 2012 and 2019 who had received comprehensive genomic profiling (CGP) and any NSCLC-related treatment at 9 U.S. cancer centers. Baseline characteristics and clinical outcomes were compared between patients with TMB <10 and TMB ≥10. RESULTS: Among the 667 patients with CGP results, most patients received CGP from Foundation Medicine (64%) or Caris (20%). Patients with TMB ≥10 (vs. TMB <10) were associated with a positive smoking history. TMB was associated with ALK (p = 0.01), EGFR (p < 0.01), and TP53 (p < 0.05) alterations. TMB >10 showed a significant association towards longer overall survival (OS) (HR: 0.43, 95% CI: 0.21-0.88, p = 0.02) and progression-free survival (PFS) (HR: 0.43, 95% CI: 0.21-0.85, p = 0.02) in patients treated with first-line immunotherapy and tested by Foundation Medicine or Caris at treatment initiation. CONCLUSIONS: TMB levels greater than or equal to 10 mut/Mb, when tested by Foundation Medicine or Caris at treatment initiation, were significantly associated with improved OS and PFS among patients treated with first-line immunotherapy-containing regimens. Additional prospective research is warranted to validate this biomarker along with PD-L1 expression.

[The impact of the first wave of the COVID-19 pandemic on oncological patients in a tertiary hospital]. / Impacto de la primera ola de la pandemia de COVID-19 en la atención a pacientes oncológicos en un hospital terciario.

BLACKGROUND: The COVID-19 pandemic has over-burdened the Spanish health service and, as a result, affected the treatment and management of oncological patients. The aim of this study is to make a descriptive analysis of the management of oncological patients and the functioning of the tumour committees in the University Hospital La Paz (Madrid) during the first wave of the pandemic. MATERIALS AND METHODS: A descriptive analysis was made, based on the results of a questionnaire given to all 18 adult tumour committees and 3 paediatric tumour committees in the University Hospital La Paz. Further information was obtained from all the hospital services involved in the diagnosis and treatment of oncological patients. RESULTS: During the first wave of the pandemic, there was a significant decrease in diagnostic tests. For many weeks, the majority of oncological surgical procedures were delayed or referred to other hospitals. Highly beneficial systemic and radiotherapeutic treatments were maintained and preoperative treatment was increased. The diagnosis and treatment of paediatric tumours was unaltered. Tumour committees were affected but each one adjusted in a different way. All the departments involved in the diagnosis and treatment of oncological patients made contingency plans to minimalize the effect on patients. CONCLUSION: This study shows how the management of oncological patients and the functioning of tumour committees was affected during the COVID-19 pandemic.

Appendiceal mucinous neoplasm, a rare diagnosis within gastrointestinal tumors. Case report.

Appendicular neoplasms are rare tumors, with an incidence of less than 0.05% among all gastrointestinal tumors. This work presents the case of a 52-year-old patient who manifested colicky pain in the right iliac fossa. Laboratory test results with bandemia and hyperbilirubinemia. Abdominal tomography with an acute appendicular inflammatory process, for which the patient was admitted for surgery. A dependent tumor of the cecum and appendicular region is observed, which compromises the ileocecal valve. The histopathological diagnosis was "low-grade appendiceal mucinous neoplasm." Appendiceal tumors are often incidental findings due to their low frequency; however, their possibility should not be dismissed.

Las neoplasias apendiculares son tumores raros, con una incidencia menor al 0.05% de todos los tumores gastrointestinales. Presentamos el caso de paciente de 52 años, quien acude por dolor cólico en fosa iliaca derecha. Estudios de laboratorio con bandemia e hiperbilirrubinemia. Tomografía abdominal con proceso inflamatorio apendicular agudo por lo que se ingresa a cirugía. Se observa tumoración dependiente de ciego y región apendicular que compromete válvula ileocecal. El diagnóstico histopatológico fue "neoplasia mucinosa apendicular de bajo grado. Los tumores de apéndice son a menudo hallazgos incidentales por su baja frecuencia, sin embargo, su posibilidad no debe descartarse.

[On the practice of therapy decision in locally limited prostate cancer: surgery vs. radiation-who benefits? : Allocation and results of a monocentric, cumulative long-term study]. / Zur Praxis der Therapieentscheidung beim lokal begrenzten Prostatakarzinom: Operation vs. Bestrahlung ­ wer profitiert? : Allokation und Ergebnisse einer unizentrischen, kumulativen Langzeitstudie.

AIM: The goal of this two-armed observational study was to map the clinical therapy effectiveness of radical prostatovesiculectomy (RPVE) and external beam radiation therapy (EBRT) in locally limited prostate cancer (PCA) in direct comparison over 20 years under clinical conditions. Retrospectively, the various variables and predictors for the individual therapy decision were identified, and the preference was to compared with studies on survival and recurrence characteristics. The presentation of toxicity was not the focus of this work. METHODOLOGY: In all, 743 patients from a single center were enrolled according to biopsy/staging chronologically in the sequence of the initial consultation after clarification and informed consent: 494 patients were in the RPVE arm and 249 patients in the EBRT arm. We used retrospective data analysis with univariate and multivariate comparisons in the alternative therapy arms. Multivariate logical regression models were developed to objectify the allocation process. Univariate processing of survival analyses, the comparison of tumor- and comorbidity-specific mortality rates was co-founded. RESULTS: Predictive variables for RPVE vs. EBRT therapy decision are significantly age, Gleason score, D'Amico index, Charlson index, prostate-specific antigen (PSA), and prostate volume. There was no significance level for the biopsy score. The age gap was in the median 67 (RPVE) and 73 (EBRT) years. Overall survival (n = 734, 20 years, all risks) in the RPVE arm was 56.8% (95% confidence interval [CI] 45.1-67.0%) and in the EBRT arm 19.2% (95%CI 9.2-31.8%). Comorbid risk was highly significantly (p < 0.0001) different (27.1% [95%CI 18.0-36.1%] in the RPVE arm, and 60.4% [95%CI 47.3-73.5%] in the EBRT arm). The risk of tumor-specific death at 16.2% (95%CI 8.1-24.4%) after RPVE and 20.5% (95%CI 11.7-29.3%) after EBRT was not significantly different (p = 0.2122, overlapping 95%CI). After stratification, a clear advantage can be demonstrated for the high-risk tumors after allocation to the RPVE arm. CONCLUSIONS: The complexity of the predictive variables of the PCA further complicates the individual therapy decision. According to our data, the higher D'Amico score, the rather low Charlson index, a high Gleason score and a higher organ volume speak for a valid therapy for RPVE.

Application of low anterior mediastinal tracheostomy for locally advanced cervicothoracic esophageal cancer undergoing total laryngopharyngoesophagectomy: a case report.

A sixty-six year-old woman came to hospital, complaining of dysphagia and weight loss. Esophagoscope showed a neoplasm between 15 and 20 cm from the incisors, biopsy revealed esophageal squamous cell carcinoma. Chest computed tomography (CT) showed that the cervical esophageal wall became thicker, the narrowing of the lumen extended downwards to the upper thoracic esophagus. Tumor invaded the membranous parts of the 5th to 12th rings of the trachea, and no swollen lymph nodes were observed in the mediastinum. The clinical stage was cT4N0M0 with borderline resectable possibility. The patient was assessed with stable disease after receiving two courses of neoadjuvant chemotherapy using DTX/CDDP/5-FU strategy. After a standard multidisciplinary treatment evaluation, total laryngopharyngoesophagectomy plus low anterior mediastinal tracheostomy (AMT) was performed. To ensure radical resection, we innovatively adopted the application of Double S-shaped myocutaneous flaps, which helps to extend the trachea and facilitate the stoma. Meanwhile, we removed the upper sternum, sternum stem, clavicle head and first and second costal cartilage to facilitate the tracheostomy and reduce the space around the stoma to avoid fluid accumulation. The pathological result showed pT4bN0M0 stage with partial response after neoadjuvant chemotherapy. This patient developed a minor anastomotic leakage which was effectively managed. Finally, she was discharged successfully 21 days after surgery.

PD-1/PD-L1 expression in pancreatic cancer and its implication in novel therapies.

Pancreatic cancer is the seventh leading cause of death in developed countries and it still has a poor prognosis despite intense research in the last 20 years. Immunotherapy is a relatively new strategy in cancer treatment. The aim of immunotherapy is to block the immunosuppressive effect of tumoral cells. The PD1/PD-L1 axis has an important role in the inhibition of effector T cells and the development of regulatory T cells (Tregs). Blocking these checkpoints, and also inhibitory signals, leads to apoptosis of Tregs and increased immune response of effector T cells against tumoral antigens. Unfortunately, pancreatic cancer is generally considered to be a non-immunogenic tumor. Thus PD-1/PD-L1 inhibitors demonstrated poor results in pancreatic cancer, excepting some patients with MSI/dMMR (microsatellite instability/deficient mismatch repair). Furthermore, pancreatic cancer has a particular microenvironment with a strong desmoplastic reaction, increased interstitial fluid pressure, hypoxic conditions, and acidic extracellular pH, which promote tumorigenesis and progression of the tumor. Mismatch repair deficiency (dMMR) is correlated with a high level of mutation-associated neoantigens, most recognized by immune cells which could predict a favorable response to anti-PD-1/PD-L1 therapy. PD-1/PD-L1 molecules could be also found as soluble forms (sPD-1, sPD-L1). These molecules have a potential role in the prognosis and treatment of pancreatic cancer.

Invasive ductal carcinoma detected within a fibroadenolipoma through digital breast tomosynthesis.

A 52-year-old patient referred to our hospital for a screening mammogram showed a suspicious new architectural distortion. Previously, a fibroadenolipoma within the right breast was diagnosed clinically and radiologically. Further work-up with tomosynthesis, magnetic resonance imaging, and magnetic resonance-guided biopsy showed an invasive ductal carcinoma within the fibroadenolipoma, which are usually benign breast lesions not associated with malignancy. This case report offers a review of the literature and a discussion of signs, which should alert the radiologist.

Low-grade appendiceal mucinous neoplasms with bowel obstruction.

BACKGROUND: Perforation of low-grade appendiceal mucinous neoplasms (LAMN) is characterized by its potential to spread mucin into peritoneal cavity, giving rise to pseudomyxoma peritonei, commonly treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.Symptoms of intestinal obstruction and appendiceal infection are rare at early stages of the disease, while abdominal distension are observed in the later stages due to mucin spread. METHODS: We report herein a case of LAMN with atypical symptoms in a 35-year-old woman with abdominal symptoms evoking an intestinal obstruction. RESULTS: An abdominal CT scan revealed an ileo-caecal intussusception. An exploratory laparotomy and examination of the peritoneal cavity ruled out an exteriorization of mucin and the bowel was resected. CONCLUSIONS: The pathology analysis confirmed the diagnostic of LAMN. This report aims to raise awareness among surgeons, of rare clinical presentations that LAMN may show, to adapt the surgical treatment to these patients and assign them to referral centers.

A Rare Primary Tumor of the Thyroid Gland: A New Case of Leiomyoma and Literature Review.

Primary leiomyomas of the thyroid are very rare. We here report a case of a 53-year-old woman with a painless mass at the right thyroid, revealed by physical examination. The patient underwent a lobectomy. Frozen sections showed a spindle cell tumor of the thyroid gland. The nuclei of some of the tumor cells were obviously enlarged and deeply stained. Pseudocapsule invasion was observed in small foci. Samples showed neither mitosis nor necrosis and the nature of the tumor was difficult to determine. Paraffin sections showed a well-circumscribed nodular composed of intersecting fascicles of spindled to slightly epithelioid cells with eosinophilic cytoplasm and blunt-ended, cigar-shaped nuclei. We observed no significant nuclear atypia, mitotsis, or necrosis. Immunohistochemical staining showed the tumor cells to be positive for α-smooth muscle actin and h-caldesmon but negative for TG, TTF1, PAX8, S-100, CT, CK, and CD34. The ki-67 index was very low (<1%). Primary thyroid leiomyoma is rare and difficult to diagnose using frozen sections. Diagnosis requires immunohistochemical staining. Leiomyoma may be mistaken for other thyroid tumors also characterized by spindle cells.

Hemangioma lobular capilar inusual en un paciente pediátrico. Reporte de caso y revisión de literatura / Unusual capillary lobular hemangioma in a pediatric patient. Case report and literature review

Lobular capillary hemangioma or pyogenic granuloma is a benign non-neoplastic lesion that is mainly presented as a tissue growth in response to irritation or trauma. It is located on the skin or on the mucous membrane, with the oral mucosa being the most frequent, with the gingiva standing out, but also appearing in other places such as the lips, buccal mucosa, palate and tongue, the latter being a very unusual location. This is a report of the case of a pediatric patient who underwent a surgical procedure of frenotomy, and who subsequently presented a lesion due to trauma possibly as a consequence of local anes-thesia, which forced an excisional biopsy, the histopathological diagnosis being capillary lobular hemangioma or pyogenic granuloma. Likewise, a literature review of this type of pathology is presented, with emphasis on its location in the tongue.