Predictors of trimodality therapy in patients with muscle-invasive bladder cancer and effect on survival

Background Due to its unique advantages over radical cystectomy (RC), trimodality therapy (TMT) is increasingly being utilized by patients diagnosed with muscle-invasive bladder cancer (MIBC) who are not suitable for or refuse RC. However, achieving a satisfactory oncological outcome with TMT requires strict patient selection criteria, and the comparative oncological outcomes of TMT versus RC remain controversial. Methods Patients diagnosed with non-metastatic MIBC who underwent TMT or RC were identified from the SEER database during 2004–2015. Before one-to-one propensity score matching (PSM), logistic regression was utilized to identify predictors of TMT. After matching, K-M curves were generated to estimate cancer-specific survival (CSS) and overall survival (OS) with log-rank to test the significance. Finally, we conducted univariate and multivariate Cox analyses to identify independent prognostic factors for CSS and OS. Results The RC and TMT groups included 5812 and 1260 patients, respectively, and the TMT patients were significantly older than the RC patients. Patients with advanced age, separated, divorced, or widowed (SDW) or unmarried marital status (married as reference), and larger tumor size (< 40 mm as reference) were more likely to be treated with TMT. After PSM, TMT was found to be associated with worse CSS and OS, and it was identified as an independent risk factor for both CSS and OS. Conclusion MIBC patients may not be carefully evaluated prior to TMT, and some non-ideal candidates underwent TMT. TMT resulted in worse CSS and OS in the contemporary era, but these results may be biased. Strict TMT candidate criteria and TMT treatment modality should be required (AU)

Neoadjuvant chemotherapy with dose-dense MVAC in muscle-invasive bladder cancer: a tertiary center experience

Purpose Neoadjuvant chemotherapy in muscle-invasive bladder cancer (MIBC) patients has proven beneficial in overall survival. However, the optimal regimen is still a matter of debate. Materials and method In this retrospective analysis, we evaluate the results obtained in 42 patients treated in our center with 4 cycles of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) followed by radical cystectomy from August 2015 to October 2020. All patients had cT2 or higher non-metastatic MIBC. Clinical and pathological outcomes are reported. Results Of the 42 patients, 90.5% were men (n = 38) and the mean age was 65 years. All of them had ECOG 0–1 at diagnosis and most tumors had an initial clinical stage T2N0 (76%). Thirty-six patients (85.7%) completed 4 cycles of neoadjuvant treatment, and 21.4% required a dose reduction. The most frequent adverse event (AE) was grade 1–2 asthenia (81%), while neutropenia was the most frequent grade 3 or higher AE (38%). Complete pathological response (ypT0, ypN0) was achieved in 50% of patients (n = 21), and down-staging was observed in 57.1% (n = 24). Only one patient presented radiological progressive disease during neoadjuvant treatment (2.4%), and after a mean follow-up time of 31.5 months, 33.3% of patients experienced disease recurrence. Conclusions Neoadjuvant chemotherapy with 4 cycles of dd-MVAC is an effective regimen with high rates of pathological complete responses and down-staging along with an acceptable toxicity profile. DD-MVAC should be considered as an alternative to cisplatin and gemcitabine in patients with good clinical performance status (AU)

CISD2 promotes lung squamous carcinoma cell migration and invasion via the TGF-B1-induced Smad2/3 signaling pathway

Background Although aberrant expression of CDGSH iron sulfur domain 2 (CISD2) contributes to the tumorigenesis and progression of numerous human cancers, the biological function of CISD2 and its specific prognostic value in lung squamous cell carcinoma (LUSC) have yet to be comprehensively explored. The current study aimed to elucidate the role of CISD2 in LUSC as well as the underlying molecular mechanisms. Methods Immunohistochemistry was conducted to detect the protein expression of CISD2 and analyze whether high expression of CISD2 affects the overall survival (OS) of LUSC patients. Cell proliferation, colony formation, wound healing and Transwell invasion assays were performed to clarify whether CISD2 contributes to LUSC cell proliferation and disease progression. Quantitative real-time reverse transcription-PCR and western blot assays were used to detect the levels of transcription factors and key epithelial-mesenchymal transition (EMT)-related markers in LUSC cells after CISD2 knockdown and overexpression to determine whether CISD2 regulates transforming growth factor-beta (TGF-β)-induced EMT in LUSC. Results Immunohistochemistry of human tissue microarrays containing 90 pairs of adjacent and cancerous tissues revealed that CISD2 is considerably overexpressed in LUSC and strongly linked to poor OS. Functional experiments suggested that silencing endogenous CISD2 inhibited the growth, colony formation, migration, and invasion of H2170 and H226 cell lines. Exogenous overexpression of CISD2 facilitated these phenotypes in SK-MES-1 and H2170 cells. Furthermore, CISD2 promoted EMT progression by increasing the expression of mesenchymal markers (N-cadherin, vimentin, Snail, and Slug) as well as SMAD2/3 and reducing the expression of the epithelial marker E-cadherin. Mechanistically, our studies provide the first evidence that CISD2 can promote EMT by enhancing TGF-β1-induced Smad2/3 expression in LUSC cells (AU)

Induction of perineural invasion in salivary adenoid cystic carcinoma by circular RNA RNF111

Objective Local recurrence, distant metastasis, and perineural invasion (PNI) viciously occur in salivary adenoid cystic carcinoma (SACC), resulting in a poor prognosis. This study aimed to explore the mechanism by which circular RNA RNF111 (circ-RNF111) regulates PNI in SACC by targeting the miR-361-5p/high mobility group box 2 (HMGB2) axis. Method Circ-RNF111 and HMGB2 were highly expressed in SACC specimens, while miR-361-5p was underexpressed. Functional experiments showed that ablating circ-RNF111 or promoting miR-361-5p hindered the biological functions and PNI of SACC-LM cells. Results HMGB2 overexpression induced the reversal of SACC-LM cell biological functions and PNI caused by circ-RNF111 knockout. Furthermore, reduction of circ-RNF111 suppressed PNI in a SACC xenograft model. Circ-RNF111 regulated HMGB2 expression through targeted modulation of miR-361-5p. Conclusion Taken together, circ-RNF111 stimulates PNI in SACC by miR-361-5p/HMGB2 axis and may serve as a potential therapeutic target for SACC (AU)

Perineural invasion predicts poor survival and cervical lymph node metastasis in oral squamous cell carcinoma

Background: Oral squamous cell carcinoma (OSCC) usually invades peripheral nerves through a process known as perineural invasion (PNI), recognized as an adverse factor considered for the administration of postoperative adjuvant therapy. The aim of this study was to assess the impact of PNI on survival and cervical lymph node metastasis in a cohort of OSCC patients. Material and methods: Presence, location and extension of PNI were assessed in a cohort of 57 paraffin-embedded OSCC resections. Clinico-pathological variables were obtained from each case. Five-year overall survival (OS) and 5-year disease-specific survival (DSS) curves were constructed according to the Kaplan-Meier method and compared with log-rank test. The Cox proportional hazard model was used to assess the role of PNI as an independent risk factor related to poor survival, and a binary logistic regression was performed to estimate the predictive value of PNI for regional lymph node metastasis. Results: PNI was observed in 49.1% of the cases, affecting only small nerves. Peritumoral PNI was the most common location, and multifocal PNI the most frequent extent. Most PNI positive cases had cervical metastasis (p=0.001), and PNI was more frequent in stages III-IV than in I-II (p=0.02). The five-year OS and the 5-year DSS decreased in PNI positive and peritumoral PNI cases. PNI was an independent risk factor for poor 5-year OS and poor 5-year DSS. The odds for cervical lymph node metastasis were of 6.076 (p=0.006) and 10.257 (p=0.007) for PNI and Tumor budding (TB) positive cases, respectively. Conclusions: PNI is a frequent finding in OSCC and an independent risk factor for poor OS and DSS. PNI and TB are both risk factors associated to an increased likelihood for the development of lymph node metastasis. Therefore, we suggest further investigations to test the combined PNI-TB scoring system in risk stratification models for OSCC. (AU)

La presencia de infiltración linfovascular y de un alto número de mitosis se asocia a un mayor riesgo de recidiva en sarcoma pleomórfico dérmico / Lymphovascular Invasion and High Mitotic Count Are Associated With Increased Risk of Recurrence in Pleomorphic Dermal Sarcoma

Introducción y objetivo El fibroxantoma atípico (FXA) y el sarcoma pleomórfico dérmico (SPD) son neoplasias de origen mesenquimal poco frecuentes. Debido a la baja incidencia del SPD y a una nomenclatura históricamente confusa existe poca información acerca de la verdadera agresividad de este tumor. Realizamos el presente estudio con el objetivo de identificar qué características clínicas y/o histológicas del SPD son predictoras de riesgo de recidiva. Material y método Se diseñó un estudio bicéntrico observacional retrospectivo de 31 casos de SPD diagnosticados y tratados en el Hospital Clínico Universitario de Valencia y el Instituto Valenciano de Oncología, entre los años 2005 y 2020. Se realizó un análisis descriptivo de las características clínicas e histológicas, un análisis inferencial univariado y un análisis multivariado mediante la regresión de Cox. Resultados En el análisis univariado, la recidiva tumoral (p<0,001), la necrosis (p=0,020), la infiltración linfovascular (p=0,037), la infiltración perineural (p=0,041) y el número de mitosis (categorizado en categorizado en <18 y ≥18 por 10 campos de gran aumento) (p=0,093), se asociaron a una menor supervivencia libre de enfermedad. En el análisis multivariado, el número de mitosis (categorizado en <18 y ≥18) y la infiltración linfovascular (p<0,05) se asociaron a una menor supervivencia libre de enfermedad. Conclusión El SPD es un tumor agresivo, en el que la presencia de un alto recuento mitótico (≥18) y/o invasión linfovascular se asocian a un mayor riesgo de recidiva y a una peor supervivencia libre de enfermedad. La necrosis y la infiltración perineural, también son hallazgos que probablemente se asocien a una mayor agresividad tumoral (AU)

Background and objective Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are rare mesenchymal tumors. Due to the low incidence of PDS and a historically confusing nomenclature, little is known about the true aggressiveness of this tumor. The aim of this study was to investigate clinical and histologic risk factors for recurrence in PDS. Material and methods Retrospective, observational, bicentric study of 31 PDSs diagnosed and treated at Hospital Clínico Universitario de Valencia and Instituto Valenciano de Oncología in Valencia, Spain, between 2005 and 2020. We described the clinical and histologic features of these tumors and performed univariate analysis and multivariate Cox regression analysis. Results In the univariate analysis, tumor recurrence (P<.001), necrosis (P=.020), lymphovascular invasion (P=.037), perineural invasion (P=.041), and mitotic count (<18 vs ≥18 mitoses per 10 high-power fields) (P=.093) were associated with worse disease-free survival. In the multivariate Cox regression analysis, mitotic count and lymphovascular invasion retained their significance as predictors of worse disease-free survival (P<.05). Conclusions PDS is an aggressive tumor in which a high mitotic count (≥18) and lymphovascular invasion are associated with a higher risk of recurrence and worse disease-free survival. Necrosis and perineural invasion are also probably linked to increased tumor aggressiveness (AU)

[Translated article] Lymphovascular Invasion and High Mitotic Count Are Associated With Increased Risk of Recurrence in Pleomorphic Dermal Sarcoma / La presencia de infiltración linfovascular y de un alto número de mitosis se asocia a un mayor riesgo de recidiva en el sarcoma pleomórfico dérmico

Background and objective Atypical fibroxanthoma and pleomorphic dermal sarcoma (PDS) are rare mesenchymal tumors. Due to the low incidence of PDS and a historically confusing nomenclature, little is known about the true aggressiveness of this tumor. The aim of this study was to investigate clinical and histologic risk factors for recurrence in PDS. Material and methods Retrospective, observational, bicentric study of 31 PDSs diagnosed and treated at Hospital Clínico Universitario de Valencia and Instituto Valenciano de Oncología in Valencia, Spain, between 2005 and 2020. We described the clinical and histologic features of these tumors and performed univariate analysis and multivariate Cox regression analysis. Results In the univariate analysis, tumor recurrence (P<.001), necrosis (P=.020), lymphovascular invasion (P=.037), perineural invasion (P=.041), and mitotic count (<18 vs ≥18 mitoses per 10 high-power fields) (P=.093) were associated with worse disease-free survival. In the multivariate Cox regression analysis, mitotic count and lymphovascular invasion retained their significance as predictors of worse disease-free survival (P<.05). Conclusions PDS is an aggressive tumor in which a high mitotic count (≥18) and lymphovascular invasion are associated with a higher risk of recurrence and worse disease-free survival. Necrosis and perineural invasion are also probably linked to increased tumor aggressiveness (AU)

Introducción y objetivo El fibroxantoma atípico (FXA) y el sarcoma pleomórfico dérmico (SPD) son neoplasias de origen mesenquimal poco frecuentes. Debido a la baja incidencia del SPD y a una nomenclatura históricamente confusa existe poca información acerca de la verdadera agresividad de este tumor. Realizamos el presente estudio con el objetivo de identificar qué características clínicas y/o histológicas del SPD son predictoras de riesgo de recidiva. Material y método Se diseñó un estudio bicéntrico observacional retrospectivo de 31 casos de SPD diagnosticados y tratados en el Hospital Clínico Universitario de Valencia y el Instituto Valenciano de Oncología, entre los años 2005 y 2020. Se realizó un análisis descriptivo de las características clínicas e histológicas, un análisis inferencial univariado y un análisis multivariado mediante la regresión de Cox. Resultados En el análisis univariado, la recidiva tumoral (p<0,001), la necrosis (p=0,020), la infiltración linfovascular (p=0,037), la infiltración perineural (p=0,041) y el número de mitosis (categorizado en categorizado en <18 y ≥18 por 10 campos de gran aumento) (p=0,093), se asociaron a una menor supervivencia libre de enfermedad. En el análisis multivariado, el número de mitosis (categorizado en <18 y ≥18) y la infiltración linfovascular (p<0,05) se asociaron a una menor supervivencia libre de enfermedad. Conclusión El SPD es un tumor agresivo, en el que la presencia de un alto recuento mitótico (≥18) y/o invasión linfovascular se asocian a un mayor riesgo de recidiva y a una peor supervivencia libre de enfermedad. La necrosis y la infiltración perineural, también son hallazgos que probablemente se asocien a una mayor agresividad tumoral (AU)

New thoughts and findings on invasion and metastasis of pancreatic ductal adenocarcinoma (PDAC) from comparative proteomics: multi-target therapy

As one of the most aggressive malignant tumors, pancreatic ductal adenocarcinoma (PDAC) ranks as the fourth cancer-related mortality in the world. The extremely low survival rate is closely related to early invasion and distant metastasis. However, effective target therapy for weakening its malignant behavior remains limited. Over the past decades, many proteins correlating with invasion and metastasis of PDAC have been discovered using proteomics. The discovery of these proteins gives us a deeper understanding of the invasive and migratory processes of PDAC. This review is a systemic integration of these proteomics findings over the past 10 years. The discovered proteins were typically associated with the glycolytic process, hypoxic microenvironment, post-translational modification, extracellular matrix, exosomes, cancer stem cells, and immune escape. Some proteins were found to have multiple functions, and, cooperation between different proteins in the invasive and metastatic processes was found. This cooperation, and not just single protein function, may play a more significant role in the poor prognosis of PDAC. Therefore, multi-target therapy against these cooperative networks should be a primary choice in the future (AU)

ZEB1-activated Notch1 promotes circulating tumor cell migration and invasion in lung squamous cell carcinoma

Background Lung squamous cell carcinoma (LUSC) is recognized as the major subtypes of non-small cell lung cancer (NSCLC). Circulating tumor cells (CTCs) are critical players in tumor metastasis. A molecular profiling of CTCs has previously identified notch receptor 1 (Notch1) as an important mediator in NSCLC. Therefore, we investigate Notch1 roles in LUSC and its related mechanisms. Methods The serum levels of Notch1 were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The CTCs isolated from blood samples were characterized via an immunofluorescence method. Cell motion was determined using Transwell chambers. The regulatory relationship between Notch1 and zinc finger E-box-binding homeobox 1 (ZEB1) was verified by chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The protein levels were detected by western blotting. Results Higher Notch1 expression in patients with LUSC than that in normal controls was observed. Notch1 knockdown inhibited cell motion and epithelial–mesenchymal transition (EMT). ZEB1 transcriptionally activated Notch1. ZEB1 upregulation exacerbated the malignant phenotypes of CTCs. Conclusion ZEB1-activated Notch1 promotes malignant phenotypes of CTCs in LUSC and indicates poor prognosis (AU)

Elaboración de un índice pronóstico inmunonutricional en pacientes con cáncer de vejiga músculo-infiltrante candidatos a cistectomía radical / Development of an immune-nutritional prognostic index in patients with muscle-infiltrating bladder cancer candidates for radical cystectomy

Introducción El tumor vesical músculo-infiltrante (TVMI) tiene una supervivencia libre de recidiva (SLR) del 50% a los cinco años, la quimioterapia neoadyuvante (QTN) ha aumentado la misma un 8%, pero no está claro qué pacientes se pueden beneficiar en mayor grado de la misma. Objetivo Evaluar el valor pronóstico del estado inmunológico-nutricional en los pacientes con TVMI candidatos a cistectomía, y desarrollar un score que permita identificar precistectomía a los pacientes con peor pronóstico (pT3-4 y/o pN0-1). Material y método Se realizó un análisis retrospectivo de 284 pacientes con TVMI tratados con cistectomía radical. Se revisó la analítica preoperatoria y se calcularon índices inmunonutricionales. El método de Kaplan-Meier se utilizó para el cálculo de la SLR. Para el análisis multivariante se utilizó la regresión de Cox. Resultados Mediante análisis univariante se observó una relación estadísticamente significativa con el índice leucocito/linfocito (p = 0,0001), el índice neutrófilo/linfocito (p = 0,02) el índice pronóstico nutricional (p = 0,002), y el ratio plaqueta/linfocito (p = 0,002). En análisis multivariante, el ratio leucocito/linfocito (p = 0,002) y el IPN (p = 0,04) se comportaron como factores pronósticos independientes de disminución de SLR, y se elaboró con ello un score pronóstico que divide a los pacientes en tres grupos pronósticos. El 80% de los pacientes con tumores pT3-4 y/o pN0-1 se encontraban en los grupos de pronóstico medio-malo. Conclusión La incorporación en la práctica clínica de un score inmunonutricional precistectomía ayudaría a seleccionar a un grupo de pacientes con estadio patológico más desfavorable y peor SLR. Creemos que estos pacientes podrían beneficiarse en mayor medida de una QTN (AU)

Introduction Muscle-infiltrating bladder tumor (MIBT) has a recurrence-free survival (RFS) of 50% at 5 years. Although neoadjuvant chemotherapy (NCT) has increased it by 8%, which group of patients benefits the most from this treatment remains unclear. Objective Evaluate the prognostic value of immune-nutritional status in patients with MIBT who are candidates for cystectomy, and to develop a score that allows identifying patients with a worse prognosis (pT3-4 and/or pN0-1). Material and methods A retrospective analysis was carried out on 284 patients with MIBT treated with radical cystectomy. Preoperative laboratory tests were analyzed and immune-nutritional indices were calculated. The Kaplan–Meier method was used to calculate the PFS. Cox regression was used for multivariate analysis. Results Univariate analysis showed a statistically significant relationship with leukocyte/lymphocyte index (p = 0.0001), neutrophil/lymphocyte index (p = 0.02), prognostic nutritional index (p = 0.002), and platelet/lymphocyte ratio (p = 0.002). In multivariate analysis, the leukocyte/lymphocyte ratio (p = 0.002) and PNI (p = 0.04) behaved as independent prognostic factors of decreased RFS. Based on these, a prognostic score was developed to classify patients into 3 prognostic groups. Eighty percent of patients with pT3-4 and/or pN0-1 tumors were in the intermediate–poor prognostic groups. Conclusion The implementation of a precystectomy immune-nutritional score in clinical practice would help in the selection of a group of patients with a more unfavorable pathologic stage and worse PFS. We believe that these patients could benefit more from a NACT (AU)

Estudio inicial sobre la comparación del rendimiento diagnóstico de la PET/RM con [18F]FDG y la PET/TC con [18F]FDG para la estadificación torácica del cáncer de pulmón de células no pequeñas: enfoque en la invasión pleural / An initial study on the comparison of diagnostic performance of 18F-FDG PET/MR and 18F-FDG PET/CT for thoracic staging of non-small cell lung cancer: Focus on pleural invasion

Objetivo Comparar el rendimiento diagnóstico de la PET/RM con [18F]FDG y la PET/TC de forma preliminar en relación con la estadificación torácica del cáncer de pulmón de células no pequeñas (CPCNP) con un enfoque especial en la evaluación de la invasión pleural. Métodos Se incluyeron 52 pacientes con CPCNP con confirmación histopatológica y sometidos a seguimiento durante un año más. Se realizó una PET/TC con [18F]FDG de cuerpo entero y a continuación una PET/RM torácica para la estadificación torácica inicial. Las imágenes de PET/RM torácica se adquirieron simultáneamente e incluyeron secuencias potenciadas en T2, con y sin saturación grasa, en T1 y de difusión. Dos radiólogos evaluaron de forma independiente la estadificación T, N torácica y la afectación pleural. Se utilizó la prueba de Chi-cuadrado de McNemar para comparar las diferencias entre PET/TC y PET/RM en los criterios de evaluación. Se realizó análisis ROC de eficacia diagnóstica con calculó del área bajo la curva (AUC) para el estudio de la invasión pleural. Resultados La PET/RM mostró una mayor sensibilidad y especificidad en la detección de invasión pleural respecto a la PET/TC; 82 vs. 64% (p=0,625), 98 vs. 95% (p=1.000). Los resultados del análisis ROC de la PET/TC vs. la PET/RM respecto a la invasión pleural fueron los siguientes: AUCPET/TC=0,79, AUCPET/RM=0,90, p=0,21. Los resultados de la estadificación T y N fueron casi idénticos en la PET/TC y la PET/RM. Las diferencias existentes entre la PET/TC y la PET/RM para la estadificación T y N y la precisión de la invasión pleural no fueron estadísticamente significativas (p>0,05 en cada una). Conclusión La PET/RM y la PET/TC demostraron un rendimiento equivalente en la evaluación de la estadificación torácica preoperatoria de los pacientes con CPCNP (AU)

Objective To compare the diagnostic performance of 18F-FDG PET/MR and PET/CT preliminarily for the thoracic staging of non-small cell lung cancer (NSCLC) with a special focus on pleural invasion evaluation. Methods Fifty-two patients with pathologically confirmed NSCLC were included and followed for another year. Whole-body 18F-FDG PET/CT and subsequent thoracic PET/MR were performed for initial thoracic staging. Thoracic (simultaneous) PET/MR acquired PET images and MRI sequences including T2 weighted imaging, with and without fat saturation, T1 weighted imaging, and diffusion weighted imaging. Two radiologists independently assessed the thoracic T, N staging and pleural involvement. The McNemar Chi-square test was used to compare the differences between PET/CT and PET/MR in the criteria. The area under the receiver-operating-characteristic curves (AUC) was calculated. Result Compared to PET/CT, PET/MR exhibited higher sensitivity, specificity in the detection of pleural invasion; 82% vs. 64% (P=.625), 98% vs. 95% (P=1.000), PET/MR to PET/CT, respectively. The receiver-operating-characteristic analysis results of PET/CT vs. PET/MR for the pleural invasion were as follow: AUCPET/CT=0.79, AUCPET/MR=0.90, P=.21. Both T staging results and N staging results were approximately identical in PET/CT and PET/MR. Differences between PET/CT and PET/MR in T staging, N staging as well as pleural invasion accuracy were not statistically significant (P>.05, each). Conclusion PET/MR and PET/CT demonstrated equivalent performance about the evaluation of preoperative thoracic staging of NSCLC patients. PET/MR may have greater potential in pleural invasion evaluation for NSCLC, especially for solid nodules, crucial to clinical decision-making, though our results did not demonstrate statistical significance (AU)

Adenocarcinoma gástrico: revisión del TNM y de las vías de diseminación / Gastric adenocarcinoma: A review of the TNM classification system and ways of spreading

El cáncer gástrico es el quinto cáncer más frecuente en el mundo. El subtipo histológico más frecuente es el adenocarcinoma. Para su estadificación se utiliza la 8.ª edición de la clasificación TNM de la American Joint Comittee on Cancer. Los ligamentos perigástricos, el mesenterio, el omento y los espacios potenciales entre los revestimientos peritoneales parietal y visceral, son estructuras con gran implicación en la estadificación. La diseminación de la enfermedad se ve afectada por la localización del tumor en el estómago, así como por la anatomía ligamentaria y linfática. La tomografía computarizada es la modalidad de imagen de elección para la estadificación clínica preoperatoria del cáncer gástrico, y es esencial para la planificación del tratamiento. Existen múltiples vías de diseminación en el cáncer gástrico que se deben conocer para poder realizar una correcta valoración radiológica: linfática, subperitoneal, invasión directa, transperitoneal, hematógena e invasión venosa extramural. (AU)

Gastric cancer is the fifth most common cancer in the world. The most common histologic subtype is adenocarcinoma. Gastric adenocarcinomas are staged using the American Joint Committee on Cancer's 8th TNM classification. The perigastric ligaments, mesentery, omentum, and potential spaces between the parietal and visceral peritoneal linings are important structures for staging. The spread of disease is influenced by the location of the tumor within the stomach, as well as by the anatomy related to the ligaments and lymph vessels. CT is the imaging modality of choice for the preoperative clinical staging of gastric cancer, and it is essential for planning treatment. To be able to do an adequate imaging workup, radiologists need to know the different pathways through which gastric cancer can spread: lymphatic, subperitoneal, direct invasion, transperitoneal, hematogenous, and extramural venous invasion. (AU)

Fibronectin-1: A Predictive Immunotherapy Response Biomarker for Muscle Invasive Bladder Cancer

Background: Muscle-invasive bladder cancer (MIBC) is characterized as bladder tumors that infiltrate into the muscle layer, along with multiple metastasis and poor prognosis. Numerous research studies have been performed to identify the underlying clinical and pathological alterations that occur. However, few studies have revealed the molecular mechanism of its progression based upon the immunotherapy response. Our present study was designed to identify biomarkers which may predict the immunotherapy response by investigating the tumor microenvironment (TME) in MIBC. Methods: The transcriptome and clinical data of MIBC patients were obtained and analyzed with R version 4.0.3 (POSIT Software, Boston, MA, USA) ESTIMATE package. Differentially expressed immune-related genes (DEIRGs) were identified and further analyzed via the protein-protein interaction network (PPI). Meanwhile, univariate Cox analysis was utilized to screen out the prognostic DEIRGs (PDEIRGs). Then, the PPI core gene was matched with PDEIRGs to obtain the target gene-fibronectin-1 (FN1). Human MIBC and control tissues were collected and FN1 was measured with Quantitative Reverse Transcription PCR (qRT-PCR) and Western-Blot. Finally, the relationship between FN1 expression level and MIBC was validated through survival, univariate Cox, multivariate Cox, Gene Set Enrichment Analysis (GSEA) and correlation analysis of tumor infiltrating immune cells. Results: TME DEIRGs were identified and the target gene FN1 was obtained. The higher expression of FN1 was confirmed in MIBC tissues via bioinformatics analysis, qRT-PCR and Western-Blot. Moreover, higher FN1 expression correlated with reduced survival time and FN1 expression was further favorably correlated with clinic-pathological features (grade, TNM stage, invasion, lymphatic and distant metastasis) (AU)

Cirugía endoscópica vs. cirugía abierta en pacientes con neoplasias nasosinusales malignas con invasión cerebral. Estudio de serie de casos / Endoscopic versus open surgery in patients with malignant sinonasal tumors and brain invasion. A case series study

Objetivos: Evaluar la efectividad, la seguridad y los costos perioperatorios del abordaje endonasal endoscópico en pacientes con tumores nasosinusales malignos con invasión cerebral. Pacientes y método: Se realizó un estudio observacional de serie de casos. Se compararon 30 pacientes con tumores nasosinusales malignos e invasión cerebral operados (2015-2017) mediante abordaje endoscópico con una serie histórica de 53 casos operados (2010-2015) mediante cirugía abierta. Se utilizó el método de emparejamiento por puntaje de propensión para controlar el efecto de factores pronósticos. Las variables de respuesta primaria fueron el control local y la supervivencia global a los tres años. Se analizaron variables de costo perioperatorio. Resultados: Después del emparejamiento se identificaron 50 pacientes (25 en cada grupo terapéutico) con edad promedio de 55 años, 62% de sexo masculino. Predominó el carcinoma de células escamosas y la invasión cerebral grado II. El control local de la enfermedad a los tres años, la supervivencia global y libre de progresión fueron superiores en el abordaje endoscópico. El abordaje endoscópico redujo el tiempo quirúrgico en 1 hora y 20 minutos y la estadía hospitalaria en 19 días en comparación con la cirugía abierta. El abordaje endoscópico mejoró la independencia funcional y redujo las complicaciones. El ahorro promedio estimado con el abordaje endoscópico fue de aproximadamente $7.355,18 por paciente. Conclusiones: El abordaje endonasal endoscópico constituye un procedimiento seguro, efectivo y más económico en los pacientes con neoplasias nasosinusales malignas e invasión cerebral (AU)

Objectives: To determine the safety, effectiveness and perioperative costs of endonasal endoscopic approach in brain invasive malignant sinonsal tumors patients. Materials and methods: This was a case series bidirectional study; that included 30 brain invasive malignant sinonsal tumors patients treated by endonasal endoscopic approach (2015-2017) and 53 by open surgery (2010-2015). Propensity score matching was used to compensate the prognostic factors; in a sample of 50 patients (25 per group). Primary response variables was local control and 3-years overall survival. Perioperative cost variables were analyzed. Results: A number of 50 patients were included after matching (25 in each therapeutic group). The age average was 55 years and male proportion was 62%. Squamous cell carcinoma and grade II lesions were the most represented in the sample. Endonasal endoscopic approach reduced surgical time in 1 hour 20 minutes, transfusion needs in 5.5 fold and hospitalization in 19 days; in comparison with open technique. Oncologic control based on surgical free margins, local control, overall survival and progression free survival after three years was higher when the resection was performed endoscopically. Functional status was enhanced and complications diminished by using endoscopic approach. Saving was estimated in $7 355.18 per patient. Conclusions: Endonasal endoscopic approach represents a safe, effective and economic procedure in selected patients with malignant sinonasal tumors and brain invasion (AU)

The Clinicopathological and Prognostic Value of NLR, PLR and MLR in Non-Muscular Invasive Bladder Cancer

Background: The clinicopathological and prognostic relevance of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and monocyte/lymphocyte ratio (MLR) in non-muscular invasive bladder cancer (NMIBC) was investigated. Methods: All patients who underwent transurethral resection of bladder tumor (TURBT) and postoperative intravesical chemotherapy had their peripheral blood levels of NLR, PLR, and MLR quantified. The preoperative peripheral blood levels of NLR, PLR, and MLR were analyzed in patients with G1, G2, and G3 NMIBC. A total of 208 patients was divided into poor prognosis (PP, with recurrence, n=51) and good prognosis (GP, no recurrence, n=157) groups, according to whether the recurrence of NMIBC was observed at 1-year follow-up after treatment. Univariate and multivariate logistic regression analyses were performed to evaluate the prognostic factors in NMIBC. In addition, receiver operating characteristic (ROC) curves were used to analyze the prognostic performance of NLR, PLR, and MLR in NMIBC. Results: The preoperative peripheral blood level of PLR was significantly increased in patients with G3 NMIBC compared with that in patients with G1 (p < 0.05) and G2 NMIBC (p < 0.05). The results of univariate and multivariate logistic regression analyses showed that the tumor diameter, differentiation grade, and preoperative peripheral blood levels of NLR, PLR, and MLR were independent prognostic factors for NMIBC recurrence (p < 0.05). Compared with the NMIBC patients without recurrence, 3.490%, 177.575% and 3.175% were determined as the optimum prognostic cutoffs for NLR, PLR, and MLR, respectively. ROC curve was used to evaluate the sensitivity, specificity, and area under the curve (AUC) of NLR, PLR, MLR, and combinations. In contrast to NLR, PLR, or MLR, the combination of NLR, PLR, and MLR (AUC 0.758, sensitivity 66.70%, specificity 89.80%,Youden index 0.565) (AU)

Carcinoma basocelular histológicamente agresivo con especial atención a la infiltración galeal del cuero cabelludo / Histologically Agressive Basal Cell Carcinoma With Particular Emphasis On Galeal Infiltration Of The Scalp

En el manejo del carcinoma basocelular (CBC) es fundamental conocer los factores de riesgo que predicen un comportamiento más agresivo. Estos factores de riesgo se dividen esencialmente en factores clínicos y en factores histopatológicos. En este trabajo revisamos e ilustramos los hallazgos histopatológicos predictivos de agresividad en el CBC. Dichos factores histopatológicos predictivos de agresividad incluyen las variedades histológicas clásicas de CBC «agresivas»: la morfeiforme, la infiltrativa, la micronodular, la metatípica, la basoescamosa y el CBC con diferenciación sarcomatoide. Pero, aparte de las variedades referidas, existen también 2hallazgos histopatológicos asociados a CBC agresivos, uno bien conocido y reflejado en la literatura, que es la infiltración perineural de filetes nerviosos de más de 0,1mm de diámetro o subdérmicos, y el otro es la extensión subgaleal. La infiltración galeal no está bien reconocida como tal en literatura, pero es un factor predictivo de agresividad importante en el CBC y queremos llamar la atención sobre él (AU)

Familiarity with predictors of more aggressive behavior is crucial to the management of basal cell carcinoma (BCC). Risk factors for aggressive BCC are essentially divided into clinical and histopathologic factors. In this review we examine histopathologic features predictive of aggressiveness in BCC. The morpheaform, infiltrative, micronodular, metatypical, and basosquamous subtypes and BCC with sarcomatoid differentiation are classically considered predictive of aggressive behavior. However, 2 other features associated with aggressive BCC are perineural invasion (invasion of nerves below the dermis or nerves larger than 0.1mm in caliber) and subgaleal extension. While the former is well known and widely described in the literature, the latter is not generally recognized as a risk factor, even though it is predictive of highly aggressive behavior. In this review, we draw attention to its importance (AU)