Clinical Application of the Next Generation Sequencing for Molecular Classification in Endometrial Carcinomas / 中山大学学报(医学科学版)

ObjectiveTo explore the clinical application of molecular classification in endometrial cancers with the next generation sequencing （NGS）. MethodsTotally 112 cases of endometrial carcinoma diagnosed by pathology in The Sun Yat-sen University Cancer Center were collected. All of them were tested by hybridized-capture second-generation sequencing based on 1，021 gene panel. The molecular variation spectrum of each subtype and its relationship between the clinicopathological features were analyzed. ResultsThe cases were distributed as follows： 8 （7.1%） POLE mutation， 34 （30.4%） mismatch repair deficient， 26 （23.2%） TP53 mutation， 44 （39.3%） non-specific molecular profile. The median tumor mutation burden was respectively 252.0， 38.4， 5.8 and 5.4 Muts/Mb. There were no significantly differences among four subtypes in clinicopathological features such as age， histological grade， lymph node metastasis and clinical stage. PTEN （75.5%）， PIK3CA （66.7%）， ARID1A （55.9%）， TP53 （40.2%）， NF1 （29.4%） were the most common mutations in endometrial cancers. ConclusionsThe utilization of NGS in endometrial cancers can simultaneously identify molecular subgroups， screen Lynch syndrome and obtain molecular variation spectrum， which can provide guidance for immunotherapy and targeted therapy， contribute to further accumulation and exploration of molecular genetic characteristics.

Clinical and morphological features of large-cell neuroendocrine carcinomas and small-cell lung carcinomas expressing the DLL3 and ASCL1 oncoproteins

Abstract Intratumoral similarities and differences between large-cell neuroendocrine carcinomas (LCNECs) and small-cell lung carcinomas (SCLCs) are determined partially by the Notch signaling pathway, which controls the switch from neuroendocrine to slight/non-neuroendocrine cell fate. LCNECs are divided into two subgroups according to genomic alterations: type I LCNECs exhibit a neuroendocrine profile characterized by achaete‐scute homolog 1 (ASCL1)high/delta-like protein 3 (DLL3)high/NOTCHlow and type II LCNECs show the pattern ASCL1low/DLL3low/NOTCHhigh. Here, we used immunohistochemistry, transmission electron microscopy, and digital analysis to examine the role of the Notch ligand DLL3 as an immunomarker of the neuroendocrine state and ASCL1 as a regulator of cell-cell interactions in SCLCs and LCNECs. High DLL3 and ASCL1 expression was associated with atypical submicroscopic characteristics involving nuclear size, chromatin arrangement, Golgi apparatus, and endoplasmic reticulum, and was characteristic of type I LCNECs with similarity to SCLCs, whereas low DLL3 and ASCL1 expression was found in both SCLCs and type II LCNECs. In patients diagnosed at an early stage who did not have metastasis and who underwent chemotherapy, DLL3high and ASCL1high SCLCs and type I LCNECs were associated with a better prognosis and a lower risk of death. The present findings suggested that DLL3/ASCL1 are potential therapeutic targets and prognostic indicators in patients with SCLCs or LCNECs.

Immunoexpression of PTEN, HER2/neu, and Ki-67 in endoscopic gastric carcinoma biopsies; their correlation with histological subtypes and one-year survival

Background: Gastric carcinoma is a major cause of cancer-related morbidity and mortality worldwide. Gastric neoplasms arise from genetic and epigenetic changes in various genes. Present study evaluates the immunoexpression of PTEN, HER2/neu, and Ki-67 in endoscopic gastric carcinoma biopsies and correlates the expression of these proteins with clinicopathological features. Material and Methods: Adequate endoscopic biopsies of 27 cases of gastric carcinoma were evaluated for World Health Organization (WHO) and Lauren's classification subtypes along with HER2/neu, PTEN, and Ki-67 immunoexpression. HER2/neu immunostaining was scored as proposed in the Trastuzumab for gastric cancer (ToGA) trial while PTEN staining and downregulation were assessed using an immunoreactive score. The cut-off for Ki-67 expression was taken as 90th percentile of the values in adjacent non-neoplastic tissue. All statistical analysis was done at 5% level of significance with SPSS v22 statistical software. Results: Tubular adenocarcinoma was the commonest WHO histological subtype and 56% of cases were of intestinal type as per Lauren's classification. 55.6% of cases showed a complete loss of PTEN expression in neoplastic tissue. 17 of the 19 cases with adjacent non-neoplastic tissue showed PTEN downregulation in neoplastic tissue. 81.5% of cases had a high Ki-67 index and HER2/neu overexpression was noted in 36% of cases. All the four cases who died had high Ki-67 proliferation indices; 3 patients had loss of PTEN expression and HER2/neu overexpression. Conclusion: We conclude that these immunomarkers can play important role in the behavior of gastric carcinomas and can be targeted for new therapies.

Expression of LIN28A/B and Let-7 miRNAs in canine mammary carcinomas / Expressão de LIN28A/B e Let-7 miRNAs em carcinomas mamários caninos

LIN28 is a RNA-binding protein including two highly conserved homologous, LIN28A and LIN28B. Proto-oncogenes such as LIN28A and LIN28B are generally targeted by the let-7 miRNAs in different types of human cancers. Here, we determined the expression of LIN28A in canine mammary tumor samples and the LIN28/let-7 pathway in canine mammary cell lines. In those cell lines, we identified a functional LIN28/let-7 pathway which exhibited high expression of let-7 members and low expression of its targets, including LIN28A and LIN28B. However, the mammary carcinoma tissue samples showed a frequent expression of LIN28A being expressed mainly in the epithelial cells. No association was observed between LIN28A expression and histopathological classification and grade, TNM and survival time. Our results suggested a possible role of the LIN28A protein in the development of canine mammary carcinomas due to the high frequency observed in the tumor samples (28 of 32). The in vitro experiments suggested that the LIN28/let-7 pathway is active in the tumor cells evaluated. However, more studies are necessary to elucidate the exact role of LIN28/let-7 pathway in canine mammary carcinomas.

LIN28 é uma proteína de ligação ao RNA, com duas formas homólogas altamente conservadas, LIN28A e LIN28B. Os proto-oncogenes LIN28A e LIN28B são regulados pela família de miRNAs let-7 em diferentes tipos de cânceres em humanos. No presente trabalho, o objetivo foi determinar a expressão de LIN28A em amostras de tumor mamário de cadelas e a via LIN28/let-7 em linhagens celulares mamárias caninas. Nestas linhagens, através das técnicas de qPCR e RNAseq, foi identificado que a via LIN28/let-7 apresenta-se funcional, com alta expressão dos membros da família let-7 e baixa expressão de seus alvos, entre eles LIN28A e LIN28B. No entanto, as amostras de tecidos de carcinomas mamários caninos demonstraram expressão frequente de LIN28A, sendo observada principalmente em células epiteliais. Não foram observadas associações entre expressão de LIN28A com classificação e gradação histopatológicas, TNM e tempo de sobrevida. Nossos resultados sugerem uma possível relação da proteína LIN28A no desenvolvimento de carcinomas mamários caninos devido à alta frequência observada nas amostras tumorais (28 de 32). Os experimentos in vitro sugerem que a via LIN28/let-7 é ativa nas linhagens celulares caninas avaliadas. Entretanto, estudos funcionais ainda são necessários para elucidar a função exata da via LIN28/let-7 nos carcinomas mamários caninos.

Tumor-promoting role of Porphyromonas gingivalis fimbrillin in progression of esophageal squamous cell cancer / 中华微生物学和免疫学杂志

Objective:To investigate the effects of Porphyromonas gingivalis ( P. gingivalis) fimbrillin (FimA) on the progression of esophageal squamous cell carcinoma (ESCC). Methods:Wild-type P. gingivalis and fimA gene-deleted P. gingivalis ( fimA-/-P. gingivalis) were used to infect ESCC cells after morphology and PCR identification. Immunofluorescence, CCK-8 and Transwell chamber were used to detect the effects of FimA on the infectivity of P. gingivalis and it influences on cell invasion, proliferation and migration. Western blot was used to detect pSmad2/3 changes. The growth of tumor was detected in a nude mouse model bearing subcutaneous tumor. Results:Deletion of FimA might reduce the interbacterial adhesion of P. gingivalis. Compared with wild-type P. gingivalis, less fimA-/-P. gingivalis could infect NE6-T cells. Moreover, the proliferation, migration and invasion of NE6-T and KYSE30 cells as well as the activation of pSmad2/3 induced by P. gingivalis were inhibited after deletion of FimA. The growth of KYSE30 infected by fimA-/-P. gingivalis in nude mice was significantly slower than that of the wild-type P. gingivalis group. Conclusions:FimA mediated the effects of P. gingivalis on promoting the evolution of ESCC and was a potential target molecule to block the tumor-promoting effect of P. gingivalis.

Características clínico-patológicas de las lesiones malignas del tracto urinario inferior / Clinicopathological features of malignant lesions of the lower urinary tract / Características clínico-patológicas de lesões malignas do trato urinário inferior

RESUMEN Introducción: El cáncer de vejiga es un tumor mucho más frecuente de lo que a veces nos transmiten las estadísticas o los medios de comunicación. Ocupa el noveno lugar en cuanto al número de diagnósticos de cáncer a nivel mundial y se reporta aproximadamente cinco veces más frecuente en varones que en mujeres. Objetivo: Describir las características clínico-patológicas de los tumores malignos del tracto urinario inferior. Método: Se realizó un estudio descriptivo y transversal de 186 pacientes con tumores malignas del tracto urinario inferior diagnosticados anatomo-patológicamente en el Hospital Provincial Clínico Quirúrgico Docente "Saturnino Lora Torres", de Santiago de Cuba, entre los años 2017 al 2020. Una vez recopilados los datos se procesaron mediante el sistema estadístico SPSS, en su versión 21.0. Resultados: En la serie la mayoría de los afectados fueron hombres entre los 60 y 79 años de edad, siendo más frecuente en el sexo masculino. Predominaron los carcinomas uroteliales con el 96,4 % del total en su variedad papilar y de alto grado de malignidad. Conclusiones: Los tumores malignos del tracto urinario inferior son un problema de salud de baja frecuencia cuya trascendencia es la afectación individual a quien lo padece, y su comportamiento clínico patológico, en sentido general, fue similar a lo reportado por la literatura nacional e internacional, salvo pequeñas y puntuales diferencias relativo a los síntomas, el diagnóstico histológico, en parte, y el grado de malignidad de las lesiones.

ABSTRACT Introduction: Bladder cancer is a more common tumor that sometimes the statistics database or media conveyed to us. It ranks ninth concerning cancer diagnoses worldwide and it is reported to be approximately five times more frequent in males than in females. Objective: To describe the clinicopathologic features of malignant lower urinary tract tumors. Method: A descriptive and cross-sectional study involving a total of 186 patients was conducted. Anatomical and pathological diagnoses were carried out to all patients with malignant lower urinary tract tumor at the Hospital Provincial Clínico Quirúrgico Docente "Saturnino Lora Torres" in Santiago de Cuba, from 2017 throughout 2020. Once the data were collected, they were processed using the SPSS statistical system, version 21.0. Results: Most affected patients with lower urinary tract tumor had an average age of 60 to 70, arising most frequently in males. The 96.4 % of the total of the patients were diagnosed with urothelial carcinomas (predominant), described in its papillary variety and the high degree of malignant transformation. Conclusions: Malignant lower urinary tract tumors are health problems labeled as the low frequency which differ in their transformation according to the patient. The clinical pathological behavior of the tumor, in a general sense, was similar to that reported in the national and international literature, except for small and pointed differences regarding symptoms, histological diagnosis, and the degree of the lesions´ malignant transformation.

RESUMO Introdução: O câncer de bexiga é um tumor mais comum do que às vezes o banco de dados de estatísticas ou a mídia veiculada por nós. Ele ocupa o nono lugar em diagnósticos de câncer em todo o mundo e é relatado ser aproximadamente cinco vezes mais frequente em homens do que em mulheres. Objetivo: Descrever as características clínico-patológicas dos tumores malignos do trato urinário inferior. Método: Foi realizado um estudo descritivo e transversal envolvendo um total de 186 pacientes. Os diagnósticos anatômicos e patológicos foram realizados a todos os pacientes com tumor maligno do trato urinário inferior no Hospital Provincial Clínico Quirúrgico Docente "Saturnino Lora Torres" em Santiago de Cuba, de 2017 a 2020. Uma vez coletados os dados, eles foram processados ​​no SPSS sistema estatístico, versão 21.0. Resultados: A maioria dos pacientes afetados com tumor do trato urinário inferior tinha uma idade média de 60 a 70 anos, surgindo mais frequentemente no sexo masculino. 96,4% do total dos pacientes foram diagnosticados com carcinomas uroteliais (predominantes), descritos em sua variedade papilar e alto grau de transformação maligna. Conclusões: Os tumores malignos do trato urinário inferior são problemas de saúde rotulados como de baixa frequência e que diferem em sua transformação de acordo com o paciente. O comportamento clínico-patológico do tumor, de um modo geral, foi semelhante ao relatado na literatura nacional e internacional, exceto por pequenas e pontuadas diferenças quanto à sintomatologia, ao diagnóstico histológico e ao grau de transformação maligna das lesões.

Caffeic acid and protocatechuic acid modulate Nrf2 and inhibit Ehrlich ascites carcinomas in mice

Objective: To assess the nuclear factor-erythroid 2-related factor-2 (Nrf2) modulatory effect of caffeic acid and protocatechuic acid and determine the anti-tumor activity of these phenolic compounds against Ehrlich ascites carcinoma growth in mice. Methods: Antioxidant activity of protocatechuic acid and caffeic acid was assessed using ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH). Nrf2 activation potential of phenolic compounds was tested by quantitative realtime polymerase chain reaction, and luciferase complementation reporter assays. In vivo efficacy was tested using the Ehrlich ascites carcinoma model. Results: FRAP and DPPH radical scavenging assays showed that caffeic acid and protocatechuic acid were more potent compared with cinnamic acid and benzoic acid. Luciferase complementation reporter assays identified caffeic acid and protocatechuic acid as the activators of Nrf2. Both caffeic acid and protocatechuic acid upregulated the expression of Nrf2 target genes heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC), and glutamate-cysteine ligase modifier subunit (GCLM) and the activity of NAD(P)H:quinone oxidoreductase 1 (NQO1) when tested on HCT-116 cells using a cell-based assay system at 9 h. In addition, intraperitoneal administration of caffeic acid and protocatechuic acid to Ehrlich ascites carcinoma bearing mice suppressed tumor growth and angiogenesis. Conclusions: Caffeic acid and protocatechuic acid can modulate Nrf2 and inhibit Ehrlich ascites carcinoma cells.

Progress of Intramural Metastasis of Esophageal Squamous Cell Carcinoma / 肿瘤防治研究

Intramural metastasis (IM) is defined as metastatic tumor from the primary tumor to the digestive tracts through the intramural lymphatic system. It can occur in esophageal, gastric and colorectal carcinomas, especially in esophageal squamous cell carcinoma. The combination of histological morphological evaluation and molecular pathology can assist in the identification of IM and multiple primary carcinomas (MPCs). IM is usually associated with a poor prognosis and also affects the treatment. This article reviews the anatomical and histological basis, clinicopathological characteristics, treatment and prognosis of IM in ESCC, the identification of IM and MPCs and how to improve the detection rate of IM, to guide accurate diagnosis and treatment.

A pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) (NET and undifferentiated carcinoma of the pancreas with osteoclast-like giant cells) with metastatic neuroendocrine component to the liver

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells (UCOGCs) is an extremely rare morphologically and clinically distinct variant of pancreatic ductal adenocarcinoma (PDAC), exhibiting a characteristic component of reactive osteoclast-like giant cells admixed with neoplastic mononuclear cells. Sommers and Meissner first described it in 1954 as an "unusual carcinoma of the pancreas". Later it acquired many different names. In 2010, the WHO classified these tumors as a variant of PDAC under the heading of "undifferentiated carcinoma with osteoclast-like giant cells". Here we describe the first case of pancreatic mixed neuroendocrine-non-neuroendocrine neoplasms (MiNEN) composed of UCOGC and pancreatic neuroendocrine tumor (NET), which occurred in a 78-year-old man with biliary colic and pancreatitis. The mass did not respond to the chemotherapy, and he soon developed liver metastasis from the NET component, and unfortunately, the patient passed away 10 months later. Since UCOGC is extremely rare, and its association with NET has not been reported yet, our case expands the knowledge regarding its unusual presentation and poor prognosis.

Study of malignant tumours of the uterine corpus: histopathology and immunohistochemistry

Background: The uterine corpus represents the second most common site for malignancy in the female genital tract. This study was performed to ascertain the profile of malignant tumours of the uterine corpus reported at our centre.Methods: A retrospective analysis of cases retrieved from the archives of the department of pathology from January 2014 to December 2016. Clinical information of the patients was collected from the hospital records.  Classification and grading of the tumours were done according to the current WHO classification.Results: Nineteen cases were studied. There were ten cases of endometrial adenocarcinoma, five cases of leiomyosarcoma, three cases of endometrial stromal sarcoma and one case of carcinosarcoma(malignant mixed mullerian tumour). The age range of endometrial adenocarcinoma was 55 to 85 years and presented with post menopausal bleeding, whereas endometrial stromal sarcomas occurred in women above 45 years of age. Leiomyosarcomas had age range from 26 to 65 years. All leiomyosarcomas were clinically diagnosed as fibroid. Majority of endometrial adenocarcinomas were well differentiated endometroid type. Out of the three endometrial stromal sarcomas two were high grade, one with metastasis. All leiomyosarcomas showed mitotic rate above 10/10hpf.Conclusions: Endometrial carcinomas form the majority of malignant tumours of uterine corpus and occur in older age group followed by leiomyosarcomas. Endometrial stromal sarcomas are less common and occur in middle aged and older patients. Leiomyosarcomas and stromal sarcomas are usually misdiagnosed as fibroids clinically unless metastases are present.

Síndrome de Gorlin-Goltz. Diagnóstico molecular, nuevos tratamientos / Gorlin-Goltz syndrome. Molecular diagnosis, new treatments

Introducción: El síndrome de Gorlin-Goltz o síndrome de carcinoma de nevo basocelular es un desorden hereditario autosómico dominante que predispone principalmente a la proliferación de múltiples carcinomas basocelulares, queratoquistes odontogénicos y defectos del desarrollo, causados por la mutación del gen Patched localizado en el cromosoma 9. Presentación del caso: Se reporta un paciente con características de este síndrome, en la clínica de COMF de la UNAM. El diagnóstico fue basado en los estudios clínicos, imagenológicos y moleculares. Conclusiones: El conocimiento de esta enfermedad puede orientarnos a la sospecha diagnóstica de lesión quística o premaligna en forma oportuna, lo que permite prevenir complicaciones y brindar un tratamiento integral para así mejorar la calidad de vida de este tipo de pacientes (AU)

Introduction: Gorlin-Goltz syndrome or cell-based nevus carcinoma syndrome is an autosomal dominant inherited disorder that predisposes mainly to the proliferation of multiple basal cell carcinomas, maxillary keratocysts and developmental defects, caused by the mutation of the Patched gene located on chromosome 9. Case presentation: A patient with specific characteristics compatible with this syndrome was reported in the COMF Department of the UNAM. The diagnosis was based on clinical studies, radiology and genetic studies. Conclusions: Knowledge of this problem can guide us to the diagnostic suspicion in a timely manner, thus preventing complications, and to provide an improved integral treatment of the quality of life of this type of patients (AU)

Osteopontin expression and its relationship with prognostic biomarkers in canine mammary carcinomas / Expressão de osteopontina e sua relação com biomarcadores prognóstico nos carcinomas mamários caninos

Osteopontin is a glycophosphoprotein implicated in different physiologic and pathologic processes and is known to be involved in progression and metastasis of various cancers in humans, but this relation is still little explored in the veterinary. The aim was to evaluate the expression of osteopontin in canine mammary carcinomas and its relation with well-established canine mammary tumor biomarkers. For that, expression of OPN, EGFR, HER2, and c-Kit were evaluated along with Ki67 rate in 43 mammary carcinomas. Osteopontin was demonstrated to be expressed by neoplastic epithelial cells in all carcinomas as well as in stromal cells from the tumor microenvironment. Relation between high osteopontin expression and EGFR positivity (P<0.001) and HER2 overexpression (P=0.012) was demonstrated. In conclusion, high OPN expression seems to be related to poor prognosis and MAPK pathway activation, given the association with EGFR and HER2, members of the MAPK signaling pathway.(AU)

A osteopontina é uma glicofosfoproteina implicada em diferentes processos fisiológicos e patológicos, sendo conhecida por estar envolvida na progressão e metástase de vários cânceres nos humanos, no entanto, essa relação é ainda pouco explorada na veterinária. O objetivo deste trabalho foi avaliar a expressão da osteopontina nos carcinomas mamários caninos e sua relação com biomarcadores bem estabelecidos para esta neoplasia. Para isto, foi avaliada a expressão de OPN, EGRH, HER2 e c-Kit juntamente com a taxa de Ki67 em 43 carcinomas mamários. A osteopontina foi expressa pelas células epiteliais neoplásicas em todos os carcinomas, assim como, nas células estromais do microambiente tumoral. Foi demonstrada uma relação entre uma alta expressão de osteopontina e positividade para EGFR (P<0.001) e superexpressão de HER2 (P=0.012). Em conclusão, alta expressão de OPN parece estar relacionada com mau prognóstico e ativação da via MAPK, devido a sua associação com EGRF e HER2, os quais são membros desta via de sinalização.(AU)

Prognostic factors in thyroid carcinomas: a 17-year outcome study

ABSTRACT Objectives The aim of our study was to evaluate the survival rate of all thyroid carcinomas (TCs) diagnosed in the 1999-2015 period in the Republic of North Macedonia and to analyze the prognostic influence of several characteristics on development of distant metastases, as well as to analyze the prognostic effect of seven clinical and constitutional features on mortality. Material and methods A retrospective analysis of medical data from all TCs diagnosed in 1999-2015 was performed. The survival rate of all types of TCs was estimated using the Kaplan Meier method. Univariate and multivariate logistic regression analysis was applied for evaluation of the predictive role of seven clinical and constitutional characteristics for development of distant metastases, and the univariate Cox-proportional model was applied for evaluation of the predictors for mortality. Results A total of 422 TC cases were diagnosed in the 17-year period, with an average survival time of 212.99 months. Results of the univariate regression analysis showed that dimension at initial ultrasound and histopathological type of tumor were significantly predictive variables for distant metastases. Multifocal tumors vs. unifocal tumors < 15 mm significantly increased the probability of distant metastases by 7.401 (p = 0.005, 95% CI = 1.817-30.190) times. Age, initial lymph node involvement, number of radioiodine therapies, and histopathology of the tumor were selected as independent significant predictors for mortality. Conclusion Our results showed an excellent overall prognosis of thyroid tumors in the Macedonian population. The dimension of the tumor, multifocality, and histopathological type were the most relevant prognostic predictive features for development of distant metastases.

Effect of microvascular invasion on long-term prognosis of liver resection for multiple hepatocellular carcinomas / 医学研究生学报

ObjectiveOnly few studies have been published of the effect of microvascular invasion (MVI) on long-term prognosis of liver resection (LR) for multiple hepatocellular carcinomas (mHCCs). Therefore, we investigate the efficacy of MVI on long-term prognosis of the patients undergoing LR formHCCs.MethodsThe clinical data of 505 patients undergoing LR for mHCCs in the Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University between March 2009 and March 2015 were retrospectively analyzed. Patients were divided into the MVI(+) group （n=279）and MVI (-) group (n=226), and146 patients in MVI (+) group and 124 patients in MVI (-) group received adjuvant transarterial chemoembolization (TACE). The Kaplan-Meier approach was used for survival analysis and the Cox proportional-hazards regression model was used forthe risk factors of long-term survival rate.ResultsThe early recurrence rate of MVI (+) group was significantly higher than that of MVI (-) group (60.4% vs 40.5%, P<0.01), and the 1-, 3-, 5-year overall survival rate of MVI (+) group was significantly lower than those in MVI (-) group (70.5%, 47.4%, 33.4% vs 86.6%, 66.8%, 50.1%, P<0.05). Among MVI (+) patients, the early recurrence rate and 1-, 3-, 5-year overall survival rate in the adjuvant TACE group were better than those in the control group (early recurrence rate 41.3% vs 39.3%, P<0.05; 1, 3, 5 year overall survival rate 92.8%, 72.5%, 53.1% vs 78.6%, 59.5%, 47.3%, P<0.05). Multivariate Cox model indicated that the Alpha-foetoprotein (AFP) level, maximum tumor diameter/minimum tumor diameter, MVI and adjuvant TACE were independent risk factors for early recurrence (HR=1.48, 1.51, 1.34, 0.76, P<0.05); maximum tumor diameter, intraoperative blood transfusion, MVI and adjuvant TACE were independent risk factors for postoperative overall survival (HR=1.75, 1.75, 1.36, 0.68, P<0.05).ConclusionMVI is a risk factor for early recurrence and poor long-term prognosis after LR for mHCCs. For mHCCs with MVI, adjuvant TACE after LR could reduce the early recurrence rate and improve the long-term survival rate.

Influence of interleukins on prognosis of patients with oral squamous cells carcinoma / Influência de interleucinas no prognóstico de pacientes portadores de carcinoma de células escamosas intraoral

ABSTRACT Squamous cell carcinoma is a malignant neoplasm that affects the structures and tissues of the oral cavity. Interleukins (IL) synthesized from a tumor modulate a cascade reaction that may influence the prognosis of the disease. We aim to investigate in the literature whether interleukins are mediators that negatively or positively influence the prognosis of patients with oral squamous cell carcinoma. A systematic review study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) instructions. PubMed (including MedLine), Scopus, Web of Science, SciELO and Latin American and Caribbean Health Sciences (LILACS) databases were used as the primary sources for the study; OpenGrey and OpenThesis were used to search for "gray literature". The search conducted in seven general databases resulted in a set of 858 studies, while the search conducted in two databases for gray literature resulted in 82 studies, totaling 940 studies. From these, 15 studies were selected for this systematic review (eight studies presented low bias risk; four studies presented moderate bias risk; and three studies presented high risk of bias). Although they may act on the anti-tumor immune response pathways, the IL evaluated in the present systematic review (IL-4, IL-6, IL-8, IL-10, IL-12 and IL-13) tend to present a response associated with the intensification of carcinogenesis and poor prognosis in patients with oral squamous cell carcinoma.

RESUMEN El carcinoma de células escamosas es una neoplasia maligna que afecta las estructuras y los tejidos de la cavidad oral. Interleucinas (IL) sintetizadas a partir de un tumor modulan una cascada de reacciones que puede influenciar el pronóstico de la enfermedad. Nuestro objetivo es investigar en la literatura si las IL son mediadoras que influyen negativamente o positivamente en el pronóstico de pacientes con carcinoma oral de células escamosas. Un estudio de revisión sistemática fue realizado bajo las instrucciones del Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Las bases de datos PubMed (incluyendo MedLine), Scopus, Web of Science, SciELO y Latin American and Caribbean Health Sciences (LILACS) fueron usadas como fuentes primarias de estudio; OpenGrey y OpenThesis, para pesquisar la literatura gris. La búsqueda realizada en siete bases de datos generales resultó en un conjunto de 858 estudios, mientras la búsqueda realizada en dos bases de datos para literatura gris resultó en 82 estudios, totalizando 940 investigaciones. Entre ellas, 15 fueron elegidas para la presente revisión sistemática (ocho estudios presentaron bajo riesgo de sesgo; cuatro, riesgo moderado; tres, riesgo alto). A pesar de poder actuar en vías de respuesta inmune antitumoral, las IL evaluadas en esta revisión (IL-4, IL-6, IL-8, IL-10, IL-12, y IL-13) suelen presentar una respuesta asociada a la intensificación del proceso de carcinogénesis y al pronóstico desfavorable en pacientes portadores de carcinoma oral de células escamosas.

RESUMO O carcinoma de células escamosas é uma neoplasia maligna que afeta as estruturas e os tecidos da cavidade oral. Interleucinas (IL) sintetizadas a partir de um tumor modulam uma cascata de reações que poderá influenciar o prognóstico da doença. Objetiva-se investigar na literatura se as interleucinas são mediadores que influenciam negativamente ou positivamente o prognóstico de pacientes com carcinoma de células escamosas intraoral. Um estudo de revisão sistemática foi realizado segundo as instruções do Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). As bases de dados PubMed (incluindo MedLine), Scopus, Web of Science, SciELO e Latin American and Caribbean Health Sciences (LILACS) foram utilizadas como fontes de estudo primárias; OpenGrey e OpenThesis, utilizadas para pesquisar a "literatura cinzenta". A busca realizada em sete bases de dados gerais resultou em um conjunto de 858 estudos, enquanto a realizada em duas bases de dados para literatura cinza, em 82 estudos, totalizando 940 pesquisas. Destas, 15 foram selecionadas para a presente revisão sistemática (oito estudos apresentaram baixo risco de viés; quatro, moderado risco de viés; e três, alto risco de viés). Apesar de poderem atuar nas vias de resposta imune antitumoral, as IL avaliadas nesta revisão (IL-4, IL-6, IL-8, IL-10, IL-12 e IL-13) tendem a apresentar uma resposta associada à intensificação do processo de carcinogênese e ao prognóstico desfavorável em pacientes portadores do carcinoma de células escamosas intraoral.

Cutaneous inflammation as a marker of malignant transformation in a patient with linear unilateral basaloid follicular hamartoma

Basaloid follicular hamartoma is a rare, benign and superficial malformation of hair follicles, characterized histologically by epithelial proliferation of basaloid cells with radial disposition. It can be mistaken for basal cell carcinoma. Even though these hamartomas are considered benign lesions, malignant transformation has rarely been reported. We report the case of a 45-year-old healthy woman, with linear, unilateral basaloid follicular hamartoma which developed inflamed papules histologically suggestive of basal cell carcinoma. We believe that identification of local inflammation could be a clinical clue to guide us towards a malignant transformation of basaloid follicular hamartoma.

Carcinoma buccal mucosa with left axillary lymph node metastasis: First reported case and review of the literature

Head-and-neck squamous cell carcinomas are tumors with propensity mostly for locoregional spread. The most frequent sites of metastasis include lung, bone, liver, adrenal, heart, and kidney. Distant metastasis to axillary lymph nodes from buccal mucosa cancer is extremely rare. To the authors' knowledge, this is the first case reported where a gentleman who was treated for carcinoma right buccal mucosa developed left axillary lymph node metastasis at 6th year of follow-up.

Assessment of fatigability, depression, and self-esteem among head-and-neck carcinoma patients in a tertiary care hospital in South India

Background: Head and Neck Carcinoma (HNCs) are the most common form of cancer in India. Patients with head-and-neck carcinomas often suffer from various distressing symptoms. The exact cause of these symptoms, as to whether disease or treatment or other factor induced, needs to be established. Objectives: This study was done to assess fatigability, depression, and self-esteem among HNC study group before start, during, and in postradiation period and to find out the determinants of these parameters. Materials and Methods: Seventy newly diagnosed HNC patients and equivalent number of age- and gender-matched controls were interviewed using standardized questionnaires, before start of concurrent chemoradiotherapy (CCRT). The study group patients were interviewed again in the 4th week and postcompletion of CCRT in the 7th week. Results: Mean age of the study group was 55.1 ± 11.3 years. Three-fourth of them (52 [74.3%]) were males. Majority of them (26 [37.1%]) had oral carcinomas. Baseline fatigue (P < 0.001) and depression scores (P < 0.001) were significantly more, while self-esteem scores (P = 0.004) were significantly less among the study group compared to controls before the onset of radiation. Mean fatigue and depression scores were found to significantly increase (P < 0.001), while self-esteem scores were found to significantly deteriorate (P < 0.001) over the course of CCRT among these patients. There was significant positive correlation (P < 0.001) between fatigue and depression scores and negative correlation (P < 0.001) of these parameters with self-esteem scores before, during, and after CCRT. There was no association between age and gender of the study group with any of these parameters. Multivariate analysis showed that baseline fatigue was significant (P < 0.001) and, depression after completion of the entire course of CCRT was significantly influenced by baseline depression levels (P = 0.011). Conclusions: Fatigue and depression need to be periodically screened among HNC study group on CCRT so as to initiate prompt remedial measures for its alleviation

Sequential Therapy with Induction Chemotherapy Followed by Concurrent Chemoradiation in Locally Advanced Squamous Cell Carcinomas of the Head and Neck

Introduction: Induction chemotherapy in locally advancedhead and neck cancers prior to local therapy has beendemonstrated to be non-inferior to concurrent chemoradiationin terms of overall survival (OS). Despite possible lack ofsurvival advantage, downsizing of tumours, allowing organpreservation along with the possible benefit of eradication ofmicrometastases earlier in the course of therapy makes thisa desirable approach for many heads and neck oncologistsworldwide. Study aimed to assess the immediate locoregionalresponse rates and to assess the toxicity profile of sequentialtherapy with three cycles of induction PFT followed byConcurrent Chemo-Radiation with weekly Cisplatin inLocally Advanced Head and Neck Cancers.Material and methods: 30 consecutive patients with locallyadvanced head and neck cancers attending the OPD at ourinstitute were included in the study. All patients were treatedwith 3 cycles of Induction chemotherapy with PFT regimen(Paclitaxel 175mg/m2 Day1, Cisplatin 100 mg/m² split to(Day 1-3), 5-FU 750 mg/m² Day 1 to 3) every 21 days. Thepatients were then taken up for concurrent chemoradiation(66 Gy RT along with weekly Cisplatin 40mg/sq.m.). Theimmediate locoregional response rates were assessed byclinical and radiological imaging. The toxicity profile of thetreatment was assessed with RTOG acute morbidity scoringcriteria and CTCAE Version 4.Results: 30 patients (3 female) were recruited for the study.Among them 3 were laryngeal cancer patients and thehypopharyngeal, oropharyngeal and the oral cavity cancerswere 9 each. 63% of them had complete response and 30%had partial response. The sub-sites of the hypopharynx andthe oropharynx had the best outcomes from this treatmentprotocol. 2 patients did not complete the planned treatment.11patients had grade 3 leukopenia and 2 patients had grade 4/febrile neutropenia. There was no grade 3 thrombocytopeniain the study group.Conclusion: Sequential therapy with three cycles of inductionPFT followed by concurrent chemoradiation is a feasiblealternative for moderately advanced and very advanced headand neck cancer. Patient selection and supportive care duringtreatment are very important for successful outcome.

Serum evaluation of leptin, IL-6, IGF-1 and estrogen in obese bitches with early stages of mammary carcinoma / Avaliação sérica de leptina, IL-6, IGF-1 e estrógeno em cadelas com excesso de peso e portadoras de carcinomas mamários em estágio inicial

The aim of this study was to relate the serum concentration IL-6, IGF-1, leptin and estrogen in non-castrated bitches with or without overweight and early stage mammary carcinomas. Forty-three bitches were divided into four groups, two groups without mammary carcinomas with and without overweight, and two groups with mammary carcinomas with and without overweight. Overweight bitches, with or without mammary carcinomas, were statistically different from bitches by ideal weight, in relation to ECC, IMCC and body fat percentages (P< 0.0001). There was a positive correlation between ECC and IMCC (P< 0.0001), ECC and % GC (P< 0.0001), and IMCC and % GC (P< 0.0001). A positive correlation was found between serum leptin and IL-6 (P= 0.0451) and leptin and IGF-1 (P= 0.05). A positive correlation (P= 0.0053) between ECC and leptin was found in the analysis of body evaluation methods and serum concentrations, and a negative correlation between ECC and IL-6 (P= 0.0435). Among the fat percentage and the leptin concentration, there was a positive correlation (P= 0.0016), as found between the IMCC and leptin (P= 0, 0209). In this study, no association was observed between excessive weight and the presence of early stage mammary carcinomas.(AU)

Este estudo teve por objetivo relacionar a concentração sérica de IL-6, IGF-1, leptina e estrógeno, em cadelas não castradas com ou sem excesso de peso, e carcinomas mamários em estágio inicial. Quarenta e três cadelas foram divididas em quatro grupos, sendo dois de cadelas sem carcinomas mamários, com e sem excesso de peso, e dois de cadelas com carcinomas mamários, com e sem excesso de peso. Cadelas com excesso de peso, com ou sem carcinomas mamários, foram estatisticamente diferentes de cadelas em peso ideal, em relação às avaliações corporais de ECC, IMCC e percentual de gordura corpórea (P<0,0001). Foi observada uma correlação positiva entre ECC e IMCC (P<0,0001), ECC e %GC (P<0,0001), e IMCC e %GC (P<0,0001). As análises de estrógeno, leptina, IL-6 e IGF-1 não apresentaram diferenças estatísticas entre os grupos. Demonstrou-se correlação positiva entre as concentrações séricas de leptina e IL-6 (P=0,0451) e leptina e IGF-1 (P=0,05). Encontrou-se correlação positiva entre ECC e leptina (P=0,0053) e negativa entre ECC e IL-6 (P=0,0435). Entre o percentual de gordura e leptina encontrou-se correlação positiva (P=0,0016), assim como entre IMCC e leptina (P=0,0209). Neste estudo, não se observou associação entre excesso de peso e a presença de carcinomas mamários em estadio inicial.(AU)