Cáncer oral: etiología, lesiones precancerosas y tratamiento / Oral cancer: etiology, precancerous lesions and treatment

Introducción: el cáncer oral es una de las neoplasias malignas más comunes en el mundo, sin embargo, a pesar de las herramientas diagnósticas actuales, existe un alto grado de morbilidad y mortalidad debido al diagnóstico tardío y a la falta de conciencia por parte de la población sobre el consumo de tabaco, alcohol, entre otras sustancias. Objetivo: el objetivo de la presente revisión es brindar información actual sobre las lesiones precancerosas, etiología, diagnóstico y tratamiento del cáncer oral. Material y métodos: se realizó una búsqueda bibliográfica en cinco bases de datos digitales sobre artículos revisados por pares desde el 2015 hasta la actualidad. Conclusión: el cáncer oral es una patología frecuente que causa graves consecuencias y secuelas en las personas que lo padecen, un conocimiento amplio de las lesiones premalignas junto con el diagnóstico temprano por parte del profesional y una mayor conciencia sobre los factores de riesgo, juegan un papel fundamental para prevenir la presencia y desarrollo de esta patología (AU)

Introduction: oral cancer is one of the most common malignant neoplasms in the world, despite the current diagnostic tools, there is a high degree of morbidity and mortality due to late diagnosis and lack of awareness of the population on the consumption of tobacco, alcohol, among other substances. Objective: the objective of this review is to provide present information of the precancerous lesions, etiology, diagnosis and treatment of oral cancer. Material and methods: a bibliographic search was carried out in five digital databases on peerreviewed articles from 2015 to the present. Conclusion: oral cancer is a frequent pathology that can cause serious consequences and sequelae in people who suffer it, an extensive knowledge of premalignant lesions among with an early diagnosis by the professional and a greater awareness of risk factors, play a fundamental role to prevent the establishment and/or progression of this pathology (AU)

Detección e integración del virus del papiloma humano de alto riesgo en lesiones pre-neoplásicas en mujeres del sur de Chile: un estudio transversal / High-risk human papillomavirus detection and integration in preneoplastic lesions among women in Southern Chile: a cross-sectional study

INTRODUCCIÓN: El virus del papiloma humano de alto riesgo (VPH-AR) es responsable del cáncer de cuello uterino y sus lesiones preneoplásicas. Los genotipos VPH16 y VPH18 son los más frecuentes en este cáncer. La integración del VPH-AR en el genoma de la célula hospedera es crucial en la carcinogénesis cervical, pero la etapa en que ocurre en la población chilena es incierta. OBJETIVO: Evaluar la integración de VPH16 y VPH18 en lesiones pre-neoplásicas de cuello uterino. MÉTODOS: Se analizaron 108 muestras de raspados cervicales. El VPH se genotipificó mediante reacción de polimerasa en cadena (RPC) e hibridación no radiactiva. La integración de VPH16 y VPH18 se determinó por presencia del gen E2 mediante RPC. RESULTADOS: VPH16 y VPH18 se detectaron en 36,1% y 12,0% de las muestras, respectivamente. El VPH16 se integró en 23,1% de los casos de VPH16, mientras que VPH18 se integró en 100% de las muestras positivas para este genotipo. CONCLUSIONES: La integración VPH-AR es un evento temprano en la carcinogénesis cervical que ocurre en casi la mitad de las lesiones pre-neoplásicas y es más frecuente en VPH18 que en VPH16. La evaluación de la integración VPH-AR puede ser una herramienta útil para detectar el virus en la población chilena.

BACKGROUND: High-risk Human Papillomaviruses (HR-HPVs) are the etiological agents of cervical cancer and its preneoplastic lesions. HPV16 and 18 are the most frequent HR-HPV genotypes detected in cervical cancer. HR-HPV genome integration into the host cell is an important event in the carcinogenic process. However, it remains uncertain which stage of cervical carcinogenesis HPV16 and 18 integration occurs in the Chilean population. AIM: The goal of this study was to evaluate HPV16 and HPV18 integration in preneoplastic lesions of the cervix. METHODS: DNA was extracted from 108 cervical scrape samples with preneoplastic lesions. HPV was genotyped using PCR and non-radioactive hybridization. The integration status of HPV16 and HPV 18 was determined by evaluating the E2 gene presence through PCR. RESULTS: HPV16 and HPV18 tested positive in 36.1% and 12.0% of samples, respectively. HPV16 was found integrated in 23.1% of HPV 16 cases, while HPV 18 in 100% of samples positive for this viral genotype. CONCLUSIONS: HR-HPV integration is an early event in cervical carcinogenesis, occurring in nearly half of preneoplastic lesions and being more frequent in HPV18 than in HPV16. The evaluation of HR-HPV integration can be utilized as a complementary tool for detecting HPV in the Chilean population.

Esófago de Barrett: Actualización en el diagnóstico y tratamiento / Barrett's Esophagus: Update on the Diagnosis and Treatment. Review

El esófago de Barrett (EB) se define como la condición en la cual una mucosa columnar metaplásica predispuesta a neoplasia reemplaza la mucosa escamosa del esófago distal. La guías actuales recomiendan que el diagnóstico requiere el hallazgo de metaplasia intestinal (MI) con células caliciformes de al menos 1 cm de longitud. El EB afecta aproximadamente al 1% de la población general y hasta en 14% de los pacientes con enfermedad por reflujo gastroesofágico (ERGE). El EB es precursor del adenocarcinoma esofágico (ACE), neoplasia en aumento en países occidentales. Los principales factores de riesgo descritos para ACE asociado a EB son: sexo masculino, edad > 50 años, obesidad central y tabaquismo. El riesgo anual de ACE en EB sin displasia, displasia de bajo (DBG) y alto grado es 0,1-0,3%, 0,5% y 5-8%, respectivamente. El tratamiento del EB no displásico consiste en un cambio de estilo de vida saludable, quimioprevención mediante inhibidores de la bomba de protones y vigilancia endoscópica cada 3 a 5 años. Se recomienda que a partir de la presencia de DBG los pacientes sean referidos a un centro experto para la confirmación del diagnóstico, estadio y así definir su manejo. En pacientes con EB y displasia o cáncer incipiente, el tratamiento endoscópico consiste en la resección y ablación, con un éxito cercano al 90%. El principal evento adverso es la estenosis esofágica que es manejada endoscópicamente.

Barrett's esophagus (BE) is the condition in which a metaplastic columnar mucosa predisposed to neoplasia replaces the squamous mucosa of the distal esophagus. The current guidelines recommends that diagnosis requires the finding of intestinal metaplasia (IM) with goblet cells of at least 1 cm in length. BE affects approximately 1% of the general population and up to 14% of patients with gastroesophageal reflux disease (GERD). BE is a precursor of esophageal adenocarcinoma (EAC), which has increased in western countries. The main risk factors described for EAC associated with BE are male sex, age > 50 years, central obesity and tobacco use. Annual risk of EAC in patients with BE without dysplasia, low grade (LGD) and high-grade dysplasia is 0,1-0,3%, 0,5% y 5-8%, respectively. Treatment of non-dysplastic BE consists mainly of a healthy lifestyle change, chemoprevention with proton pump inhibitors and surveillance endoscopy every 3 to 5 years. It is recommended that from the presence of LGD patients are referred to an expert center for confirmation of the diagnosis, stage and thus define their management. In patients with BE and dysplasia or early-stage cancer, endoscopic therapy with resection and ablation is successful in about 90% of the patients. The main adverse event is esophageal stricture, which is managed endoscopically.

¿Está la virtud en el punto medio? La incertidumbre del CIN2 y el papel del VPH / Is virtue at the midpoint? The uncertainty of CIN2 and the role of HPV

Objetivo: La biopsia guiada por colposcopia (BGC) marca el manejo de la neoplasia intraepitelial cervical. El objetivo de este estudio fue evaluar la concordancia de los resultados entre la BGC y la escisión amplia de la zona de transformación (LLETZ, large loop excision of the transformation zone), y la utilidad del genotipado del virus del papiloma humano (VPH) para seleccionar a las pacientes con riesgo de lesión intraepitelial escamosa de alto grado/neoplasia intraepitelial cervical 3 (HSIL/CIN3). Método: Se compararon los resultados de la BGC y de la LLETZ, siendo esta última el método de referencia. Se evaluó la relación del genotipo del VPH con el diagnóstico final de HSIL/CIN3. Resultados: La precisión de la biopsia comparada con LLETZ fue del 61,4%. La tasa de concordancia fue del 64,4% para CIN1, del 31,4% para CIN2 y del 77,4% para CIN3. La tasa global de sobrediagnóstico fue del 18,68% y la de subdiagnóstico del 19,89%. En mujeres menores de 30 años, la concordancia fue del 62,79% (CIN1 65%, CIN2 39,58% y CIN3 73,08%), la tasa de sobrediagnóstico del 22,67% y la tasa de subdiagnóstico del 15,11%. La infección por VPH16 tuvo una odds ratio de 3,86 para el diagnóstico final de HSIL/CIN3+. Conclusiones: El diagnóstico de CIN2 por BGC parece insuficiente para seleccionar a las pacientes para tratamiento escisional, principalmente en mujeres jóvenes. El hallazgo de VPH16 es un factor de riesgo de HSIL/CIN3+ independientemente del resultado de la biopsia.

Objective: Colposcopy-guided biopsy (CGB) is a basic tool for the management of cervical intraepithelial neoplasia. The aim of this study is to evaluate the concordance of results between CGB and large loop excision of the transformation zone (LLETZ), and the usefulness of human papillomavirus (HPV) genotyping to select patients at risk of H-SIL/CIN3. Method: The results of colposcopy-guided biopsy and LLETZ were compared, with LLETZ being the gold standard. The relationship of HPV genotype to the final diagnosis of CIN3 was assessed. Results: The accuracy of CGB compared to LLETZ was 61.4%. The concordance rate was 64.4% for CIN1, 31.4% for CIN2 and 77.4% for CIN3. The overall overdiagnosis rate was 18.68% and underdiagnosis rate was 19.89%. In women under 30 years of age the concordance rate was 62.79% (CIN1 65%, CIN2 39.58% and CIN3 73.08%), and the rate of overdiagnosis and underdiagnosis was 22.67% and 15.11%, respectively. HPV16 infection had an odds ratio of 3.86 for the final diagnosis of CIN3+ and the result was significant regardless of the biopsy result. Conclusions: The CGB result as CIN2 is inaccurate and seems insufficient to select patients for excisional treatment, mainly in young women. HPV16 infection is a risk factor for CIN3+ regardless of the colposcopy-guided biopsy result.

Aspectos histológicos, genéticos y moleculares de las lesiones preneoplásicas de la mucosa gástrica / Histological, genetic and molecular aspects of preneoplastic lesions of the gastric mucosa

Siendo el cáncer gástrico la 3ª causa de muerte por cáncer en Chile, y existiendo estrategias de tamizaje consistentes en pesquisa de lesiones preneoplásicas de la mucosa gástrica, es relevante conocer los aspectos genéticos y moleculares que puedan ser aplicados, en la optimización de dichas estrategias a grupos de mayor riesgo. El objetivo de este manuscrito fue revisar la evidencia actual en los aspectos señalados, y de la inmunohistoquímica de 4 marcadores (p53, CDX2, MUC2 y S100A9) en la mucosa gástrica normal y en las lesiones preneoplásicas de la misma.

SUMMARY: Since gastric cancer is the 3rd leading cause of death from cancer in Chile, and there are screening strategies consisting of screening for preneoplastic lesions of the gastric mucosa, it is important to know certain genetic and molecular aspects that can be applied in optimizing these strategies for higher risk groups. The aim of this manuscript was to review the current evidence on the aforementioned aspects, and on the immunohistochemistry of 4 markers (p53, CDX2, MUC2 and S100A9) in normal gastric mucosa and in its preneoplastic lesions.

Avaliação do conhecimento e da percepção de cirurgiões-dentistas e estudantes de odontologia acerca de desordens potencialmente malignas / Knowledge assessment and perception among dentists and dental students about potentially malignant disorders

Introdução: As desordens potencialmente malignas (DPM) são condições da cavidade oral que apresentam risco significativo para o desenvolvimento do câncer. Desse modo, o diagnóstico precoce torna-se essencial no prognóstico de lesões orais. Para isso, analisar o perfil de conhecimento acerca dessas desordens é fundamental ao identificar lacunas na educação e promover alternativas para melhorar a qualidade no diagnóstico. Objetivo: Avaliar a percepção de cirurgiões-dentistas (CDs) e estudantes de Odontologia brasileiros acerca de seu conhecimento e capacidade de identificar DPM. Métodos: Foi realizado um estudo transversal através de aplicação de questionário online. Foram aplicados dois questionários com 24 questões, um para estudantes e outro para CDs, divididos em três seções: dados demográficos e acadêmicos, treinamento, atitudes e autopercepção sobre DPM e conhecimento de DPM. A análise estatística envolveu os testes de Pearson, Mann-Whitney e Kruskal-Wallis. Resultados: O estudo foi composto por 209 participantes, 76 CDs e 133 estudantes de odontologia. A maioria dos participantes nunca realizou curso que envolvia o diagnóstico de desordens potencialmente malignas. A pontuação sobre o conhecimento de DPM variou de 0 a 10 pontos, sendo a média entre estudantes de 6,29±1,77 e entre CDs de 7,01±1,82. A maior taxa de acertos foi para as questões que discutiam a conduta clínica e a definição das desordens. Já as questões com menor taxa de acertos foram sobre lesões que não são consideradas potencialmente malignas, potencial de malignização e definição de Carcinoma in Situ. Conclusão: Há lacunas no conhecimento de estudantes de odontologia e CDs na identificação das desordens potencialmente malignas. Logo, essa deficiência reforça a necessidade de mais treinamentos e investimentos em educação, bem como de acompanhamento periódico de pacientes com tais desordens, a fim de prevenir potenciais transformações malignas.

Introduction: Potentially malignant disorders (PMD) are conditions of the oral cavity that present a significant risk for the development of cancer. Thus, early diagnosis becomes essential in the prognosis of oral lesions. Therefore, assessing the knowledge profile of these disorders is essential to identify gaps in education and to promote alternatives to improve the quality of their diagnosis. Objective: Evaluate the perception of brazilian dentists and dental students about their knowledge and ability to identify PMD. Methods: A cross-sectional study was carried out using an online questionnaire. Two questionnaires with 24 questions were applied, one for students and other for dentists, divided into three sections: demographic and academic data, training, attitudes and self-perception about potentially malignant disorders and knowledge of potentially malignant disorders. Statistical analysis involved Pearson, Mann-Whitney and Kruskal-Wallis tests. Results: The study consisted of 209 participants, 76 dentists and 133 dentistry students. Most participants never attended a course that involved the diagnosis of potentially malignant disorders. The score of knowledge about potentially malignant disorders ranged from 0 to 10 points, with a mean of 6.29±1.77 among students and 7.01±1.82 among dentists. The highest rate of correct answers was for questions that discussed clinical management and the definition of disorders. The questions with the lowest rate of correct answers were about lesions that are not considered potentially malignant, malignancy potential and the definition of Carcinoma in Situ. Conclusion: There are gaps in the knowledge of dental students and dentists in the identification of potentially malignant disorders. Therefore, this deficit reinforces the needed of more training and investments in education, as well as more training and investments in education and periodic follow-up of patients with such disorders are needed in order to prevent potential malignant transformations.

Pathological evaluation of endoscopic submucosal dissection for early gastric cancer and precancerous lesion in 411 cases / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the pathological characteristics of endoscopic submucosal dissection (ESD) specimens for early gastric cancer and precancerous lesions, accumulating experience for clinical management and pathological analysis.@*METHODS@#A total of 411 cases of early gastric cancer or precancerous lesions underwent ESD. According to the Japanese guidelines for ESD treatment of early gastric cancer and classification of gastric carcinoma, the clinicopathological data, pathologic evaluation, concordance rate of pathological diagnosis between preoperative endoscopic forceps biopsies and their ESD specimens (in 400 cases), as well as the risk factors of non-curative resection of early gastric cancer, were analyzed retrospectively.@*RESULTS@#23.4% (96/411) of the 411 cases were adenoma/low-grade dysplasia and 76.6% (315/411) were early gastric cancer. The latter included 28.0% (115/411) non-invasive carcinoma/high-grade dysplasia and 48.7% (200/411) invasive carcinoma. The concordance rate of pathological diagnosis between endoscopic forceps biopsies and ESD specimens was 66.0% (264/400), correlating with pathological diagnosis and lesion location (P < 0.01). The rate of upgraded diagnosis and downgraded diagnosis after ESD was 29.8% (119/400) and 4.2% (17/400), respectively. Among the 315 cases of early gastric cancer, there were 277 cases (87.9%) of differentiated type and 38 cases (12.1%) of undifferentiated type. In the study, 262 cases (83.2%) met with absolute indication, while 53 cases (16.8%) met relative indication. En bloc and curative resection rates were 98.1% and 82.9%, respectively. Risk factors for non-curative resection included a long diameter >20 mm (OR=3.631, 95%CI: 1.170-11.270, P=0.026), tumor infiltration into submucosa (OR=69.761, 95%CI: 21.033-231.376, P < 0.001)and undifferentiated tumor histology (OR=16.950, 95%CI: 4.585-62.664, P < 0.001).@*CONCLUSION@#Several subjective and objective factors, such as the limitations of biopsy samples, the characteristics and distribution of the lesions, different pathological understanding, and the endoscopic sampling and observation, can lead to the differences between the preoperative and postoperative pathological diagnosis of ESD. In particular, the pathological upgrade of postoperative diagnosis was more significant and should receive more attention by endoscopists and pathologists. The curative resection rate of early gastric cancer in ESD was high. Non-curative resection was related to the long diameter, the depth of tumor invasion and histological classification. ESD can also be performed in undifferentiated early gastric cancer if meeting the indication criteria. The comprehensive and standardized pathological analysis of ESD specimens is clinically important to evaluate the curative effect of ESD operation and patient outcomes.

Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion / 中华肿瘤杂志

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

Comparison of in vivo plasma pharmacokinetics and urine excretion of main components in Xihuang Formula in rats with precancerous lesions of breast cancer / 中国中药杂志

The UPLC-MS/MS was established for the determination of acetyl-11-keto-beta-boswellic acid(AKBA) and β-boswellic acid(β-BA), the main active components of Olibanum and Myrrha extracts in Xihuang Formula, in rat plasma and urine. The effects of compatibility on the pharmacokinetic behaviors of AKBA and β-BA in rats were investigated, and the differences in pharmacokinetic behaviors between healthy rats and rats with precancerous lesions of breast cancer were compared. The results showed that compared with RM-NH and RM-SH groups, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05 or P<0.01), T_(max) decreased(P<0.05 or P<0.01), and C_(max) increased(P<0.01) after compatibility. The trends of AKBA and β-BA were the same. Compared with RM-SH group, the T_(max) decreased(P<0.05), C_(max) increased(P<0.01), and the absorption rate increased in the normal group of Xihuang Formula. The results of urinary excretion showed that there was a decreasing trend in the urinary excretion rate and total urinary excretion of β-BA and AKBA after compatibility, but there was no statistical difference. Compared with normal group of Xihuang Formula, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05), T_(max) increased(P<0.05), and the clearance rate decreased in the breast precancerous lesion group. AUC_(0-t) and AUC_(0-∞) of AKBA showed an increasing trend, the in vivo retention time was prolonged, and the clearance rate was reduced, but there was no significant difference compared with the normal group. The cumulative urinary excretion and urinary excretion rate of β-BA and AKBA decreased under pathological conditions, indicating that pathological conditions could affect the in vivo process of β-BA and AKBA, and reduce their excretion in the form of prototype drugs, showing different pharmacokine-tic characteristics from normal physiological conditions. In this study, UPLC-MS/MS analysis method was established, which was sui-table for in vivo pharmacokinetic analysis of β-BA and AKBA. This study laid a foundation for the development of new dosage forms of Xihuang Formula.

Effect and mechanism of Xihuang Pills on rats with precancerous lesions of breast / 中国中药杂志

The purpose of this study was to explore the effect and mechanism of Xihuang Pills on rats with precancerous lesions of the breast. Of 48 healthy female rats, 8 were randomly selected as blank group, and the other 40 were treated with 7,12-dimethylbenzanthracene(DMBA) combined with estrogen and progestin to establish a model of precancerous lesions of the breast. The successfully modeled rats were randomly divided into a model group, a tamoxifen group(1.8 mg·kg~(-1)·d~(-1)), a Xihuang Pills low-dose group(0.3 g·kg~(-1)·d~(-1)), a medium-dose group(0.6 g·kg~(-1)·d~(-1)) and a high-dose group(1.2 g·kg~(-1)·d~(-1)). After 30 days of admi-nistration, the histopathological changes of viscera and breast were observed by haematoxylin and eosin(HE) staining, and the visceral index was calculated. Enzyme linked immunosorbent assay(ELISA) was used to detect the contents of estradiol(E_2) and progesterone(P) in serum. The protein expressions of vascular endothelial growth factor(VEGF) and fibroblast growth factor 2(FGF2) were detected by immunohistochemistry. The protein expressions of VEGF, vascular endothelial growth factor receptor 2(VEGFR2), phosphorylated-vascular endothelial growth factor receptor 2(p-VEGFR2), B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were detected by Western blot and the mRNA expressions of VEGF, FGF2, CXC-chemokine receptor 4(CXCR4), cysteine aspartic acid-specific protease(caspase-3), and stromal cell-derived factor 1(SDF-1) were detected by real-time polymerase chain reaction(RT-PCR). HE staining revealed that the model group had some liver and kidney damages and severe hyperplastic mammary tissue, while the Xihuang Pills high-dose group had mild hyperplasia. Compared with the model group, the Xihuang Pills groups had lo-wer ovarian coefficient(P<0.05 or P<0.01) and Xihuang Pills high-dose group had lower uterine coefficient(P<0.01). ELISA results showed that compared with the model group, expressions of E_2 and P in Xihuang Pills high-dose group were significantly decreased(P<0.05 or P<0.01). Immunohistochemistry, Western blot and RT-PCR indicated that compared with the conditions in the model group, the protein and mRNA expressions of VEGF and FGF2 in the Xihuang Pills groups were down-regulated(P<0.05 or P<0.01), and the protein expression of Bcl-2 was lowered(P<0.01); there was a decrease in the protein expressions of VEGFR2 and p-VEGFR2(P<0.01), a down-regulation in the mRNA expressions of CXCR4 and SDF-1(P<0.01), while an increase in the mRNA expression of caspase-3(P<0.01) in both Xihuang Pills medium-dose and high-dose groups; the protein expression of Bax in Xihuang Pills high-dose group was increased(P<0.01). The above results indicated that Xihuang Pills can effectively intervene in precance-rous lesions of the breast, and the mechanism may be related to the regulation of E_2 and P secretion as well as the inhibition of angiogenesis and chemokine receptor expression, thus controlling the occurrence of precancerous lesions of the breast in rats.

Risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery, and to provide a reasonable basis for preoperative evaluation and postoperative follow-up. Methods:This study retrospective analyzed the relationship between clinicopathological factors and clinical outcome（recurrence, canceration, recurrence-free survival, and canceration-free survival） in 148 patients undergoing surgical treatment in Chongqing General Hospital from 2014 to 2017. Results:The five-year overall recurrence rate was 14.86% and the overall recurrence rate was 8.78%. Univariate analysis showed that smoking index, laryngopharyngeal reflux and lesion range were significantly associated with recurrence（P<0.05）, and smoking index and lesion range were significantly associated with canceration（P<0.05）. Multivariate logistic regression analysis showed that smoking index ≥600 and laryngopharyngeal reflux were independent risk factors for recurrence（P<0.05）, and smoking index ≥600 and lesion range ≥1/2 vocal cord were independent risk factors for canceration（P<0.05）. The mean carcinogenesis interval for the postoperative smoking cessation group was significantly longer（P<0.05）. Conclusion:Excessive smoking, laryngopharyngeal reflux and a wide range of lesions may be related to postoperative recurrence or malignant progression of precancerous lesions in the vocal cord, and further large-scale multi-center prospective randomized controlled studies are needed to clarify the effects of the above factors on recurrence and malignant changes in the future.

Multidisciplinary experts consensus on diagnosis and treatment of precancerous lesions of hepatocellular carcinoma (2023 version) / 中华肝脏病杂志

According to the latest statistical data, the incidence and mortality rate of hepatocellular carcinoma in China are still on the rise, posing a major threat to the health of the Chinese population. The occurrence is closely related to the formation of precancerous lesions in the liver. The clinical and basic research on precancerous lesions of hepatocellular carcinoma has developed rapidly, and the concepts and specific techniques for diagnosis and treatment have also undergone new changes and advancements. Therefore, based on the first version in 2020, this consensus has organized multidisciplinary experts to compile and improve a new version by integrating the latest progress in their respective professional fields at home and abroad. It aims to enhance clinicians' understanding of precancerous lesions of hepatocellular carcinoma standardize the pathology, imaging, and molecular diagnostic criteria, broaden early screening methods, formulate scientifically rational treatment plans, and help promote the advancement of diagnosis and treatment strategies and to enhance the overall 5-year survival rate of patients with hepatocellular carcinoma.

Fertility-preserving treatment outcomes in endometrial cancer and atypical hyperplasia patients with different molecular profiles / 中华妇产科杂志

Objective: To investigate the impact of molecular classification and key oncogenes on the oncologic outcomes in patients with endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) receiving fertility-preserving treatment. Methods: Patients with EC and AEH undergoing progestin-based fertility-preserving treatment and receiving molecular classification as well as key oncogenes test at Obstetrics and Gynecology Hospital, Fudan University from January 2021 to March 2023 were reviewed. Hysteroscopic lesion resection and endometrial biopsy were performed before initiating hormone therapy and every 3 months during the treatment to evaluate the efficacy. The risk factors which had impact on the treatment outcomes in EC and AEH patients were further analyzed. Results: Of the 171 patients analyzed, the median age was 32 years, including 86 patients with EC and 85 patients with AEH. The distribution of molecular classification was as follows: 157 cases (91.8%) were classified as having no specific molecular profile (NSMP); 9 cases (5.3%), mismatch repair deficient (MMR-d); 3 cases (1.8%), POLE-mutated; 2 cases (1.2%), p53 abnormal. No difference was found in the cumulative 40-week complete response (CR) rate between the patients having NSMP or MMR-d (61.6% vs 60.0%; P=0.593), while the patients having MMR-d had increased risk than those having NSMP to have recurrence after CR (50.0% vs 14.4%; P=0.005). Multi-variant analysis showed PTEN gene multi-loci mutation (HR=0.413, 95%CI: 0.259-0.658; P<0.001) and PIK3CA gene mutation (HR=0.499, 95%CI: 0.310-0.804; P=0.004) were associated with a lower cumulative 40-week CR rate, and progestin-insensitivity (HR=3.825, 95%CI: 1.570-9.317; P=0.003) and MMR-d (HR=9.014, 95%CI: 1.734-46.873; P=0.009) were independent risk factors of recurrence in EC and AEH patients. Conclusions: No difference in cumulative 40-week CR rate is found in the patients having NSMP or MMR-d who received progestin-based fertility-preserving treatment, where the use of hysteroscopy during the treatment might be the reason, while those having MMR-d have a higher risk of recurrence after CR. Oncogene mutation of PTEN or PIK3CA gene might be associated with a lower response to progestin treatment. The molecular profiles help predict the fertility-preserving treatment outcomes in EC and AEH patients.

Quality evaluation of the literature on clinical randomized controlled trials of traditional Chinese medicine for treatment of gastric precancerous lesions in the past 20 years / 浙江大学学报·医学版

OBJECTIVES@#To evaluate the methodological quality of randomized controlled trials (RCTs) of traditional Chinese medicines for the treatment of gastric precancerous lesions in the past 20 years.@*METHODS@#The RCTs on traditional Chinese medicines for gastric precancerous lesions were searched from the CNKI, Wanfang database, VIP, PubMed, and Embase from January 2001 to December 2021. The retrieved articles were screened, extracted and evaluated based on the 2010 edition of CONSORT statement, Cochrane Risk of Bias Assessment Scale and additional evaluation indicators.@*RESULTS@#A total of 840 papers were included. According to the Cochrane Risk of Bias Assessment Scale, the high risk of bias in the application of randomized methods was 5.95%; the risk of uncertainty for the allocation scheme concealment was 98.93%; the risk of uncertainty for blinding of patients or testers was 98.69%; the risk of uncertainty for blinding of the outcome assessor was 100.00%; the risk of bias for completeness of the outcome data was 2.86%; and the risk of uncertainty for selective reporting was 98.45%. The CONSORT statement evaluating the quality of reporting showed that 100.00% of the RCT articles reported the 8 entries; 36.79% of the literature mentioned the method of randomized sequence generation, but only 27.62% of the literature mentioned who implemented the randomized program, 1.07% of the literature hid the randomized program and 1.31% of the studies were blinded; 36.67% of the literature reported adverse reactions; no literature reported sample size prediction methods. Additional evaluation indicators showed that 17.02% of the studies had ethical approval; 43.81% of the literature specified Chinese medicine evidence; 16.55% of the studies excluded severe heterotrophic hyperplasia; 7.26% of the studies conducted follow-up; and 65.12% of the literature used composite efficacy indicators; 46.67% of the literature applied pathological histological evaluation; 2.62% of the literature applied quality of life evaluation.@*CONCLUSIONS@#The overall risk of bias in RCTs of traditional Chinese medicines for gastric precancerous lesions is high, and the quality of most of the study reports needs to be improved. In the future, it is necessary to strengthen the study design of RCTs and refer to appropriate traditional Chinese medicines evidence grading standards, select study protocols according to different purposes, provide objective and strong evidence for clinical studies on traditional Chinese medicines, and carry out clinical study design and result reporting suitable for traditional Chinese medicines according to the CONSORT principle.

Efectividad de la crioterapia suministrada por enfermeras para lesiones preneoplásicas del cuello uterino / Effectiveness of cryotherapy delivered by nurses for treatment of cervical preneoplasic lesions

Introducción. El cáncer de cuello uterino es un problema de salud pública relevante en países de ingresos medios y bajos. El seguimiento de mujeres con tamización positiva y el acceso a tratamiento para neoplasia intraepitelial cervical (NIC) son retos mayores en estos países. Objetivo. Evaluar la efectividad de la crioterapia suministrada por enfermeras en casos de neoplasia intraepitelial de cérvix. Materiales y métodos. Se hizo la inspección visual directa con ácido acético y solución yodada (VIA-VILI), y se practicó colposcopia con biopsia, a mujeres entre los 25 y los 59 años, residentes en zonas de bajos ingresos de Bogotá. Profesionales de enfermería entrenados ofrecieron tratamiento inmediato con crioterapia a mujeres positivas en la inspección visual. Se les practicó colposcopia con biopsia antes del tratamiento y en un control a los 12 meses. Se evaluó la efectividad mediante tasas de curación (resultado: sin lesión) y regresión de NIC2/3 (resultado: ≤NIC1), por verificación colposcópica e histológica. Resultados. Se tamizaron 4.957 mujeres. En total, 499 fueron positivas y 472 aceptaron el tratamiento inmediato. Recibieron crioterapia por enfermería 365 mujeres (11 NIC2/3). La tasa de curación fue del 72 % (IC95%: 39-94 %) por verificación colposcópica, y del 40 % (IC95%: 22-85 %) por histología. Las tasas de regresión fueron del 100 y el 60 %, respectivamente. Se reportaron dos eventos adversos no graves relacionados. Conclusiones. Las tasas de curación y regresión por verificación colposcópica son similares a las reportadas con crioterapia administrada por médicos. El tamaño de la muestra con NIC2/3 dificulta la comparación por tipo de verificación. Los hallazgos apoyan la implementación de estrategias de "ver y tratar" por parte de enfermería en poblaciones con acceso limitado a servicios de salud.

Introduction. Cervical cancer is a relevant public health problem for low- and middle-income countries. Follow-up of positive-screened women and compliance with treatment of precancerous lesions are major challenges for these settings. Objective. To evaluate the efficacy of cryotherapy delivered by nurses for cervical intraepithelial neoplasia (CIN). Materials and methods. Direct visual inspection with acetic acid and lugol iodine (VIA-VILI), and colposcopy/biopsy were performed on women 25 to 59 years old, residents of low-income areas in Bogotá, Colombia. Trained nurses offered immediate cryotherapy to every woman with positive visual inspection. Colposcopy/biopsy was performed before treatment and at a 12-month follow-up. The effectiveness was measured as cure (outcome: no-lesion) and regression (outcome: CIN1) rates of CIN2/3 using colposcopic and histological verification. Results. A group of 4.957 women with VIA/VILI was valuated. In total, 499 were screen positive and 472 accepted immediate treatment. A total of 365 women (11 CIN2/3) received cryotherapy by nurses. Cure rate was 72% (95%CI: 39%-94%) and 40% (95%CI: 22%-85%) by colposcopic and histological verification, respectively. Regression rates were 100% and 60%. There were two related non-serious adverse events. Conclusions. Cure and regression rates by colposcopic verification are like those reported for cryotherapy delivered by doctors. The sample size (CIN2/3) hinders comparisons by type of verification. Our findings support the implementation of screen-and-treat algorithms by nurses among populations with limited access to health services.

Sistema OLGA (Operative Link on Gastritis Assessment) como marcador para cáncer gástrico y displasia en una población colombiana de alto riesgo: estudio multicéntrico / The Operative Link on Gastritis Assessment (OLGA) system as a marker for gastric cancer and dysplasia in a Colombian population at risk: A multicenter study

Introducción. En Asia y Europa, el sistema OLGA ha sido útil como marcador de riesgo de cáncer gástrico. Sin embargo, su utilidad en poblaciones de alto riesgo en Colombia aún se desconoce. Objetivo. Establecer si los estadios OLGA se asocian con un mayor riesgo de cáncer y displasia en una población de alto riesgo en Colombia y determinar la capacidad diagnóstica de la escala para evaluar dicho riesgo. Materiales y métodos. Se realizó un estudio multicéntrico con pacientes con cáncer gástrico y displasia (casos), y pacientes con atrofia y metaplasia intestinal (controles), provenientes de tres centros de una zona de alto riesgo de cáncer gástrico en Colombia. Se incluyeron 506 pacientes cuyo estudio endoscópico e histopatológico fue realizado mediante el sistema de Sydney y la estadificación de OLGA propuesta por Rugge. El efecto de cada variable de interés sobre la enfermedad (cáncer gástrico y displasia) se evaluó mediante modelos bivariados y multivariados. Un valor de p menor de 0,05 se consideró estadísticamente significativo. Resultados. Los estadios elevados del sistema OLGA (III-IV) se asociaron con un mayor riesgo de displasia y cáncer gástrico (OR ajustado = 8,71; IC95 % = 5,09-14,9; p=0,001) con una sensibilidad del 54,9 %, especificidad del 89,3 % y una razón de probabilidad positiva de 5,17. Conclusiones. El estadio OLGA es un marcador de riesgo de cáncer gástrico y displasia en la población de estudio. Se recomienda su implementación como estrategia para optimizar el diagnóstico oportuno y el seguimiento de pacientes con mayor riesgo.

Introduction. The OLGA system has been proved to be useful in Asia and Europe as a risk marker of gastric cancer. However, its usefulness in high-risk populations in Colombia is still unknown. Objective. To assess potential associations between the OLGA staging system and an increased risk of gastric cancer and dysplasia in a high-risk Colombian population and to establish diagnostic capacity of the scale to assess the risk. Materials and methods. We carried out a multicenter study including patients with cancer and dysplasia (cases) and patients with atrophy and intestinal metaplasia (controls). A total of 506 patients were recruited from three centers in an area with a high risk population in Colombia. The endoscopic and histopathologic studies were evaluated according to the Sydney system and the OLGA staging system proposed by Rugge. The effect of each variable on the disease (gastric cancer and dysplasia) was evaluated using bivariate and multivariate models. Statistical significance was set considering a p value inferior to 0.05. Results. Advanced stages of the OLGA system (III-IV) were associated with a higher risk of dysplasia and gastric cancer (adjusted OR = 8.71; CI95% = 5.09-14.9; p=0.001), sensitivity=54.9%, specificity=89.3% and positive likelihood ratio=5.17. Conclusions. The OLGA staging system is a risk marker for gastric cancer and dysplasia in the studied population. We recommend its implementation to improve the timely diagnosis and follow-up of patients with the highest cancer risk.

Guía de práctica clínica para la prevención primaria y secundaria y diagnóstico temprano de cáncer gástrico / Clinical practice guide for primary and secondary prevention and early diagnosis of gastric cancer

Resumen Objetivo: Generar recomendaciones basadas en la evidencia, para la prevención primaria y secundaria, el tratamiento de las lesiones preneoplásicas y el diagnóstico temprano del cáncer gástrico en población adulta, con el propósito de reducir la carga de la enfermedad. Materiales y métodos: El grupo desarrollador estuvo integrado por profesionales de la salud y tomadores de decisiones. Se construyeron preguntas clínicas contestables y se realizó la graduación de los desenlaces. Se elaboró la búsqueda de la información en MEDLINE; EMBASE y CENTRAL, siendo actualizada el 18 de octubre de 2018. La pesquisa también abarcó otras fuentes de información como la Revista Colombiana de Gastroenterología y la lectura en "bola de nieve" de las referencias incluidas. Se contactó a expertos en la materia con el objetivo de identificar estudios relevantes no publicados. Para la construcción de las recomendaciones, se realizó un consenso acorde con los lineamientos propuestos por la metodología GRADE, sopesando los beneficios, los efectos adversos derivados de la intervención, las preferencias de los pacientes y el potencial impacto de las intervenciones sobre los costos. Resultados: Se presenta la versión corta de la "Guía de práctica clínica para la prevención primaria, secundaria y diagnóstico temprano de cáncer gástrico", junto con su evidencia de soporte y respectivas recomendaciones. Conclusiones: Como recomendación central para la implementación, se recomienda erradicar la infección por H. pylori en los pacientes con o sin factores de riesgo, como estrategia de prevención de las condiciones precursoras de cáncer gástrico. La Guía deberá actualizarse en tres años.

Abstract Objetive: Generate recommendations for primary and secondary prevention, treatment of gastric preneoplastic lesions, and early diagnosis of gastric cancer in the adult population, to increase the detection of gastric cancer in early stages. Material and methods: The developer group was made up of health professionals, decision-makers, and a representative of the patients. Answerable clinical questions were constructed and outcomes were graded. The search for information in MEDLINE was carried out; EMBASE and CENTRAL, being updated on October 18, 2018. The search also covered other sources of information such as the Colombian Journal of Gastroenterology and the "snowball" reading of the references included. Experts in the field were contacted to identify studies. For the construction of the recommendations, a consensus was made according to the guidelines proposed by the GRADE methodology, weighing the benefits, the adverse effects derived from the intervention, the preferences of the patients, and the potential impact of the interventions on costs. Results: The short version of the "Clinical practice guidelines for the primary, secondary, and early diagnosis of gastric cancer" is presented together with its supporting evidence and respective recommendations. Conclusions: As a central recommendation for implementation, it is recommended to eradicate H. pylori infection in patients with or without risk factors in whom it is detected to prevent gastric cancer precursor conditions. The Guide will need to be updated in three years.

A case of pseudomyogenic hemangioendothelioma misdiagnosed as low-grade malignant fibrous histiocytoma and review of literature / 中南大学学报(医学版)

Pseudomyogenic hemangioendothelioma (PHE) is a rare angiogenic tumor. Histologically, the morphological characteristics of neoplastic vessels and endothelial differentiation are not obvious, and it is easy to be confused with epithelioid sarcoma, epithelioid hemangioendothelioma and myogenic tumor. PHE usually occurs in arms and legs in young people and has a significant male predominance. The tumor has a predilection for the distal extremities and its typical manifestation is multiple center invasion of a single limb, which can involve all layers of skin and subcutaneous tissues,and is often accompanied by abvious pain. Histologically, PHE is characterized by infiltrative growth of tumor. Most tumor lesions are composed of sheets and loose fascicles of plump spindle or epithelioid cells within a background of variably prominent inflammatory infiltration, which was commonly composed of neutrophils. Some cells may resemble rhabdomyoblasts, and nuclear atypia and mitosis were rare. The tumor cells generally expressed positive cytokeratin (CK), ETS-related gene (ERG), Friend leukemia virus integration 1 (FLI1) and integrase interactor 1(INI1). In some cases, the tumor cells expressed CD31. A case of a young woman was reported in this paper, who presented with a subcutaneous mass with severe pain and was chronologically misdiagnosed with herpes zoster, low-grade malignant fibrous histiocytoma and epithelioid hemangioendothelioma. In this study, the clinical and pathological features, differential diagnosis and the latest progress in therapy of PHE were analyzed based on relevant literature.

A comprehensive update: gastrointestinal microflora, gastric cancer and gastric premalignant condition, and intervention by traditional Chinese medicine / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

With the recent upsurge of studies in the field of microbiology, we have learned more about the complexity of the gastrointestinal microecosystem. More than 30 genera and 1000 species of gastrointestinal microflora have been found. The structure of the normal microflora is relatively stable, and is in an interdependent and restricted dynamic equilibrium with the body. In recent years, studies have shown that there is a potential relationship between gastrointestinal microflora imbalance and gastric cancer (GC) and precancerous lesions. So, restoring the balance of gastrointestinal microflora is of great significance. Moreover, intervention in gastric premalignant condition (GPC), also known as precancerous lesion of gastric cancer (PLGC), has been the focus of current clinical studies. The holistic view of traditional Chinese medicine (TCM) is consistent with the microecology concept, and oral TCM can play a two-way regulatory role directly with the microflora in the digestive tract, restoring the homeostasis of gastrointestinal microflora to prevent canceration. However, large gaps in knowledge remain to be addressed. This review aims to provide new ideas and a reference for clinical practice.

Establishment and clinical validation of an artificial intelligence YOLOv51 model for the detection of precancerous lesions and superficial esophageal cancer in endoscopic procedure / 中华肿瘤杂志

Objective: To construct the diagnostic model of superficial esophageal squamous cell carcinoma (ESCC) and precancerous lesions in endoscopic images based on the YOLOv5l model by using deep learning method of artificial intelligence to improve the diagnosis of early ESCC and precancerous lesions under endoscopy. Methods: 13, 009 endoscopic esophageal images of white light imaging (WLI), narrow band imaging (NBI) and lugol chromoendoscopy (LCE) were collected from June 2019 to July 2021 from 1, 126 patients at the Cancer Hospital, Chinese Academy of Medical Sciences, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, ESCC limited to the mucosal layer, benign esophageal lesions and normal esophagus. By computerized random function method, the images were divided into a training set (11, 547 images from 1, 025 patients) and a validation set (1, 462 images from 101 patients). The YOLOv5l model was trained and constructed with the training set, and the model was validated with the validation set, while the validation set was diagnosed by two senior and two junior endoscopists, respectively, to compare the diagnostic results of YOLOv5l model and those of the endoscopists. Results: In the validation set, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the YOLOv5l model in diagnosing early ESCC and precancerous lesions in the WLI, NBI and LCE modes were 96.9%, 87.9%, 98.3%, 88.8%, 98.1%, and 98.6%, 89.3%, 99.5%, 94.4%, 98.2%, and 93.0%, 77.5%, 98.0%, 92.6%, 93.1%, respectively. The accuracy in the NBI model was higher than that in the WLI model (P<0.05) and lower than that in the LCE model (P<0.05). The diagnostic accuracies of YOLOv5l model in the WLI, NBI and LCE modes for the early ESCC and precancerous lesions were similar to those of the 2 senior endoscopists (96.9%, 98.8%, 94.3%, and 97.5%, 99.6%, 91.9%, respectively; P>0.05), but significantly higher than those of the 2 junior endoscopists (84.7%, 92.9%, 81.6% and 88.3%, 91.9%, 81.2%, respectively; P<0.05). Conclusion: The constructed YOLOv5l model has high accuracy in diagnosing early ESCC and precancerous lesions in endoscopic WLI, NBI and LCE modes, which can assist junior endoscopists to improve diagnosis and reduce missed diagnoses.