¿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.

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.

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.

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.

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.

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.

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.

Cervical precancerous lesions at the Tchibanga Regional Hospital and the University Hospital in Gabon in 2018: smartphone as a screening tool for diagnosis

Background: Cervical precancerous lesions are disorders that can induce discoloration changes. Their detection is difficult in remote areas in the absence of adequate equipment. The objectives were to evaluate Smartphone performance in diagnosing cervical precancerous lesions in Tchibanga, Gabon. Methods: It was an interventional cross-sectional study to evaluate the validity and reliability of the smartphone as a tool for diagnosing atypical changes in the cervix. Study period was between July 1, 2017, to February 28, 2018, at the Tchibanga Regional Hospital (CHRT) and the University Hospital (CHU). The variability between examiners was determined according to Cohen's Kappa formula. The Gold standard test was the cytology. Results: Compared to the examiner -1, the examiner - 2 found a high percentage of inflammations as atypical transformations: 15.3% versus 9%. With regard to smartphonic impressions, the examiner-1 found the normal impressions almost equal to that of the examiner-2, 72.9% versus 72.2%. The concordance between positive smartphonic impressions was 93.8% and 95.5% between negative smartphonic impressions, with k = 0.86. Conclusion: In view of the above, the concordance between positive and negative smart phonic impressions was 93.8 and 95.5% with k = 0.86. The performance parameters being good, there is a need to use the smartphone as a tool for the diagnosis of precancerous lesions

Barriers to cyotherapy treatment services for precancerous cervical lesions among women in Western Kenya

BACKGROUND Cervical cancer is the fourth most fatal and common disease globally among women of reproductive age in Kenya; it ranks the second most frequent type of cancer after breast cancer. Due to the high burden, cryotherapy treatment services, which are effective for the treatment of precancerous lesions are available in selected health facilities in Kenya, however, barriers to the treatment services are poorly understood. Nonetheless, understanding these barriers is critical for enhanced service delivery. MATERIALS AND METHODS :A descriptive facility-based cross-sectional study design was carried out to determine the barriers to cryotherapy treatment services among 60 women of reproductive age on a one-year therapy at Migosi Sub County Hospital in Western Kenya. The participants were selected purposively and interviewed via telephone calls using pre-coded semi-structured questionnaires. However, data from 5 nurses working in the cryotherapy section were collected through face-to-face interviews at the health facility. Data were entered in an excel sheet and then exported to SPSS version 23.0 for analysis. Both descriptive and inferential statistics (Chi-square) were used and data were presented in form of tables. RESULTS :Overall, 52 (85.4%) respondents adhered to post-care treatment instructions and reported no adverse reactions. However, 28 (46.7%) experienced unavailability of cryotherapy services at the time of the appointment and got the services later, 24 (40%) got the services at the time of the appointment but waited for a long time before being served, 37 (61.7%) did not know why they were being treated and 46 (76.7%) had misconceptions and myths about the therapy. In addition, there was a statistically significant association between knowing both the benefits of screening and cryotherapy [X 2 (1, N = 60) = 5.90, p = .02]. Also, the knowledge of the benefits of cryotherapy did not influence one's decision to wait for cryotherapy treatment services, [X 2(1, N = 60) = 3.98, p = .46]. CONCLUSION : The study shows very good adherence to post-treatment instruction but inadequate availability of cryotherapy treatment services. Also, the misconceptions and myths about cryotherapy are public health concerns. Therefore, the study recommends improved awareness campaigns and service delivery for the enhanced uptake of cryotherapy treatment services.

Cervical cancer in the Hauts-Bassins region of Burkina Faso: Results of a screening campaign by visual inspection with acetic acid (VIA screening in Burkina Faso)

This study was conducted to describe the distribution of precancerous and cancerous lesions of the cervix uteri, enumerated during a mass screening in Burkina Faso. We conducted a cross-sectional study involving 577 women aged 18 to 60 years, carried out from November 23 to December 19, 2013, in the city of Bobo-Dioulasso and in the rural commune of Bama. Regarding the screening results, 89 participants (15.4%) were positive for pre-malignant cervical lesions. Chi-square testing and logistic regression analyses were conducted to identify the likelihood of cervical pre-cancer lesion in the women. Participants less than 29 years old were approximately 3 times more likely to have cervical lesions than participants >39 years. Participants who were parous (1-3 deliveries) and multiparous (four or more deliveries) were approximately 4 times more likely to present with cervical lesions than nulliparous women. Access to screening services is low in the Bobo-Dioulasso region. Further research should be conducted to understand the incidence and distribution of cervical precancerous and cancerous lesions in Burkina Faso. (Afr J Reprod Health 2022; 26[6]:97-103).

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.

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.

Associations between cancer family history and esophageal cancer and precancerous lesions in high-risk areas of China / 中华医学杂志(英文版)

BACKGROUND@#Family clustering of esophageal cancer (EC) has been found in high-risk areas of China. However, the relationships between cancer family history and esophageal cancer and precancerous lesions (ECPL) have not been comprehensively reported in recent years. This study aimed to provide evidence for identification of high-risk populations.@*METHODS@#This study was conducted in five high-risk areas in China from 2017 to 2019, based on the National Cohort of Esophageal Cancer. The permanent residents aged 40 to 69 years were examined by endoscopy, and pathological examination was performed for suspicious lesions. Information on demographic characteristics, environmental factors, and cancer family history was collected. Unconditional logistic regression was applied to evaluate odds ratios between family history related factors and ECPL.@*RESULTS@#Among 33,008 participants, 6143 (18.61%) reported positive family history of EC. The proportion of positive family history varied significantly among high-risk areas. After adjusting for risk factors, participants with a family history of positive cancer, gastric and esophageal cancer or EC had 1.49-fold (95% confidence interval [CI]: 1.36-1.62), 1.52-fold (95% CI: 1.38-1.67), or 1.66-fold (95% CI: 1.50-1.84) higher risks of ECPL, respectively. Participants with single or multiple first-degree relatives (FDR) of positive EC history had 1.65-fold (95% CI: 1.47-1.84) or 1.93-fold (95% CI: 1.46-2.54) higher risks of ECPL. Participants with FDRs who developed EC before 35, 45, and 50 years of age had 4.05-fold (95% CI: 1.30-12.65), 2.11-fold (95% CI: 1.37-3.25), and 1.91-fold (95% CI: 1.44-2.54) higher risks of ECPL, respectively.@*CONCLUSIONS@#Participants with positive family history of EC had significantly higher risk of ECPL. This risk increased with the number of EC positive FDRs and EC family history of early onset. Distinctive genetic risk factors of the population in high-risk areas of China require further investigation.@*TRIAL REGISTRATION@#ChiCTR-EOC-17010553.

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.

Clinical research progress and implications of therapeutic vaccines for cervical cancer and precancerous lesions: a qualitative systematic review / 中华肿瘤杂志

Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.

Academy of Medicine, Singapore clinical guideline on endoscopic surveillance and management of gastric premalignant lesions

Gastric cancer (GC) has a good prognosis, if detected at an early stage. The intestinal subtype of GC follows a stepwise progression to carcinoma, which is treatable with early detection and intervention using high-quality endoscopy. Premalignant lesions and gastric epithelial polyps are commonly encountered in clinical practice. Surveillance of patients with premalignant gastric lesions may aid in early diagnosis of GC, and thus improve chances of survival. An expert professional workgroup was formed to summarise the current evidence and provide recommendations on the management of patients with gastric premalignant lesions in Singapore. Twenty-five recommendations were made to address screening and surveillance, strategies for detection and management of gastric premalignant lesions, management of gastric epithelial polyps, and pathological reporting of gastric premalignant lesions.

Análise do perfil microbiano de lesões orais potencialmente malignas / The microbial profile of potentially malignant oral disorders

As lesões orais potencialmente malignas são alterações que exibem maior risco de transformação maligna em comparação com a mucosa saudável. Apesar de sua relevância, a literatura ainda não definiu o papel da microbiota na etiologia e no processo de malignização dessas lesões. Assim, neste trabalho, realizamos um estudo do tipo caso controle de caráter longitudinal, prospectivo e quantitativo onde avaliamos as populações bacterianas do microbioma oral em pacientes com lesões orais potencialmente malignas. Para isso, utilizamos um questionário estruturado e coletamos swabs orais em pacientes portadores de leucoplasia, eritroplasia, líquen plano, lesão liquenóide oral e também controles saudáveis. Participaram do estudo 60 indivíduos, no período de coleta de 2018 à 2020,sendo 39 do grupo caso e 21 do grupo controle. A maioria dos pacientes era do sexo feminino (42/60; 70%) com média de idade de 57 anos, e mais da metade dos indivíduos eram não fumantes (35/60; 58,3%) e etilistas (36/60; 60%). Dentre os diagnósticos, observamos a maioria dos indivíduos com líquen plano oral/lesão liquenóide oral (13/39), seguidos de leucoplasia homogênea (10/39), eritroleucoplasia (8/39), leucoplasia verrucosa proliferativa (6/39) ou eritroplasia (2/39). A borda da língua foi o local mais comumente acometido, com a maioria apresentando múltiplos sítios (21/39). A displasia epitelial foi avaliada nas lesões, exceto líquen plano e lesões liquenóides, e 18 pacientes tiveram algum grau de displasia. Um total de 73 amostras tiveram a região V3-V4 do gene 16S rRNA amplificada e sequenciada, sendo 60 amostras referentes à primeira coleta e 13 ao segundo momento de coleta dos participantes do grupo caso, sendo que 3/13 desses indivíduos vieram a ter um diagnóstico de carcinoma espinocelular oral. Identificamos maior quantidade de genomas bacterianos por genomas humanos nas amostras do grupo caso, no entanto, a diversidade e composição bacteriana foram semelhantes entre casos e controles. No total, identificamos 9 filos, 15 classes, 24 ordens, 47 famílias e 67 gêneros bacterianos. O gênero mais abundante foi Streptococcus em ambos os grupos, com menor frequência nos casos. Encontramos ainda alta abundância dos gêneros Granulicatella e Blautia nos indivíduos com lesões orais e menor abundância de Methylobacterium, Lautropia e Oribacterium. Observamos também que a abundância de Granulicatella e Bergeyella foi maior nas lesões com displasia epitelial. A transformação maligna em carcinoma espinocelular oral ocorreu em 10/39 (25,6%) dos casos, onde a presença de displasia epitelial aparentou ser um fator de risco relevante. A diversidade bacteriana foi semelhante entre os indivíduos do grupo caso que sofreram ou não malignização, porém, a abundância dos gêneros Capnocytophaga, Finegoldia, Prevotella e Prevotella 2 foi maior nas amostras que sofreram malignização, mesmo antes do processo acontecer. Não encontramos diferenças na composição bacteriana entre os dois tempos de coleta, ao diagnóstico e após aproximadamente um ano, e também não observamos diferenças significativas na quantidade de DNA bacteriano e humano. Ao inferirmos as vias metabólicas derivadas das bactérias identificadas nas amostras, observamos também similaridade entre os grupos caso e controle, e apenas duas vias preditas apresentaram abundância com diferenças estatisticamente significativas entre ambos. Dessa maneira, nossos resultados sugerem que distúrbios orais potencialmente malignos podem estar associados a uma disbiose do microbioma oral, e que alguns gêneros bacterianos podem ser potenciais biomarcadores ou agentes importantes neste processo biológico.

Oral potentially malignant disorders have a higher risk of becoming cancer than healthy mucosal tissues. However, up until now, the literature did not define the role of the microbiota in the origin and development of malignancy in these lesions. Thus, here we conducted a longitudinal, prospective, and quantitative case-control study where we evaluated the bacterial composition of the oral microbiome in patients with potentially malignant lesions. Therefore, we used a structured questionnaire and performed oral swabs on patients with leukoplakia, erythroplakia, lichen planus, oral lichenoid lesion, and healthy controls. A total of 60 individuals, collected between 2018 to 2020, were enrolled in the study, of which 39 were cases and 21 were controls. The majority of patients were female (42/60; 70%) with a mean age of 57 years and over half of the individuals were non-smokers (35/60; 58.3%) and alcoholics (36/60; 60%). Among the diagnoses, there were oral lichen planus/oral lichenoid lesion (13/39), homogeneous leukoplakia (10/39), erythroleukoplakia (8/39), proliferative verrucous leukoplakia (6/39) and erythroplakia (2/39). The tongue edge was the most common location affected, with the majority having multiple sites (21/39). Epithelial dysplasia was assessed in the lesions, except for lichen planus and lichenoid lesions, and 18 patients had some degree of dysplasia. A total of 73 samples had the V3-V4 region of the 16S rRNA gene amplified and sequenced, in which 60 samples were collected at diagnosis (first collection point) and 13 samples were collected after approximately a year (second moment of collection). At least 03/13 of these patients were later diagnosed with oral squamous cell carcinoma. We identified a higher amount of bacterial per human genomes in the samples of the case group, however, the bacterial diversity and composition were similar between cases and controls. We identified 9 phyla, 15 classes, 24 orders, 47 families, and 67 bacterial genera. The most abundant genus was Streptococcus in both groups, with lower relative frequency in the individuals with potentially malignant lesions. We found a higher abundance of the genera Granulicatella and Blautia in the cases and lower abundance of Methylobacterium, Lautropia, and Oribacterium. We also observed that the abundance of Granulicatella and Bergeyella increased in the lesions with epithelial dysplasia. Malignant transformation into oral squamous cell carcinoma occurred in 10/39 (25.6%) of the cases patients, where the presence of epithelial dysplasia was a relevant risk factor. The bacterial diversity was similar between the individuals in the case group regardless if they malignized or not, however, the abundance of the genera Capnocytophaga, Finegoldia, Prevotella, and Prevotella 2 was higher in the samples that underwent malignization, even before this process took place. We did not find significant differences in the bacterial composition between the two collection points and we also did not observe significant differences in their amount of bacterial and human DNA. When inferring the metabolic pathways derived from the bacteria identified in the samples, we also observed similarity between the case and control groups, and only two predicted pathways showed abundance with statistically significant differences between them. Thus, our results suggest that potentially malignant oral disorders may be associated with a dysbiosis of the oral microbiome, and that some bacterial genera may be potential biomarkers or important agents in this biological process.

Inmunoexpresión de p53 y su relación con el grado de severidad en displasia epitelial oral / Immunoexpression of p53 and its relationship with the degree of severity in oral epithelial dysplasia

Introducción: La displasia epitelial oral (DEO) es la presencia de alteraciones celulares y tisulares, lo que puede significar una etapa anterior al desarrollo del cáncer. Múltiples marcadores han sido considerados para estimar su potencial neoplásico y evolución a carcinoma, incluyendo a la molécula p53, se considera como participe de diversos fenómenos de la homeostasis celular. Objetivo: Determinar la relación entre la inmunoexpresión de p53 DO-7 y PAb 240 con el grado de severidad de la displasia epitelial oral. Material y métodos: Se analizaron nueve muestras de DEO (tres para cada grado de severidad). La inmunoexpresión de p53 tipo silvestre (DO-7) y forma mutada (PAb 240), fue determinada a través de ensayo de inmunohistoquímica por peroxidasa. Se obtuvieron la media y desviación estándar y se realizó la prueba χ2 (p < 0.05). Resultados: La edad media fue de 65.7 ± 11.4 años, la zona anatómica con mayor presencia de DEO es el borde lateral de la lengua. Ocho de nueve muestras fueron positivas para DO-7 y solo dos para PAb 240. Conclusiones: Nuestros resultados indican que, aunque la expresión de p53 DO-7 podría estar relacionada parcialmente con la patogénesis de la displasia epitelial, no todas las displasias presentaron la forma mutada de p53 (PAb 240). Lo cual coincide con el comportamiento biológico incierto de las displasias al poder permanecer sin cambios, involucionar o transformarse

Introduction: Oral epithelial dysplasia (OED) is the presence of cellular and tissue alterations, which may mean a stage prior to the development of cancer. Multiple markers have been considered to estimate its pathogenic potential and evolution to neoplasms, including the p53 molecule, considered as participating in various phenomena of cellular homeostasis. Objective: To determine the relationship between the immunoexpression of p53 DO-7 and PAb 240 with the degree of severity of oral epithelial dysplasia. Material and methods: Nine OED samples were analyzed (three for each degree of severity). The immunoexpression of wild-type p53 (DO-7) and mutated form (PAb 240) was determined through a peroxidase immunohistochemical assay. The mean and standard deviation were obtained, and χ2 test (p < 0.05) were performed. Results: The mean age was 65.7 ± 11.4 years, with a greater presence of OED in the anatomical area of the lateral side of the tongue. Eight out of nine samples were positive for DO-7 and only two for PAb 240. Conclusions: Our results indicate that, although the expression of p53 DO-7 could be partially related to the pathogenesis of epithelial dysplasia, not all dysplasias presented the mutated form of p53 (PAb 240), which coincides that not all dysplasias have a potential for malignant transformation and that could be related to other oncogenic mechanisms (AU)