Characteristics and risk factor analyses of high-grade intraepithelial neoplasia in older patients with colorectal polyps

BACKGROUND According to the degree of intradermal neoplasia in the colorectal exhalation,it can be divided into two grades:Low-grade intraepithelial neoplasia(LGIN)and high-grade intraepithelial neoplasia(HGIN).Currently,it is difficult to accurately diagnose LGIN and HGIN through imaging,and clinical diagnosis depends on postoperative histopathological diagnosis.A more accurate method for evaluating HGIN preoperatively is urgently needed in the surgical treatment and nursing intervention of colorectal polyps.AIM To explore the characteristics and risk factors of HGIN in older patients with colorectal polyps.METHODS We selected 84 older patients diagnosed with HGIN as the HGIN group(n=95 colonic polyps)and 112 older patients diagnosed with LGIN as the LGIN group(n=132 colonic polyps)from Shandong Provincial Hospital Affiliated to Shandong First Medical University.The endoscopic features,demographic characteristics,and clinical manifestations of the two patient groups were compared,and a logistic regression model was used to analyze the risk factors for HGIN in these patients.RESULTS The HGIN group was older and had a higher number of sigmoid colon polyps,rectal polyps,pedunculated polyps,polyps≥1.0 cm in size,polyps with surface congestion,polyps with surface depression,and polyps with villous/tubular adenomas,a higher proportion of patients with diabetes and a family history of colorectal cancer,patients who experienced rectal bleeding or occult blood,patients with elevated carcinoembryonic antigen(CEA)and cancer antigen 199(CA199),and lower nutritional levels and higher frailty levels.The polyp location(in the sigmoid colon or rectum),polyp diameter(≥1.0 cm),pathological diagnosis of(villous/tubular adenoma),family history of colorectal cancer,rectal bleeding or occult blood,elevated serum CEA and CA199 levels,lower nutritional levels and higher frailty levels also are independent risk factors for HGIN.CONCLUSION The occurrence of high-grade neoplastic transformation in colorectal polyps is closely associated with their location,size,villous/tubular characteristics,family history,elevated levels of tumor markers,and lower nutritional levels and higher frailty levels.

C634Y mutation in RET-induced multiple endocrine neoplasia type 2A:A case report

BACKGROUND Multiple endocrine neoplasia type 2(MEN2)is a rare,autosomal dominant endocrine disease.Currently,the RET proto-oncogene is the only gene implicated in MEN2A pathogenesis.Once an RET carrier is detected,family members should be screened to enable early detection of medullary thyroid carcinoma,pheochromocytoma,and hyperparatitity.Among these,medullary thyroid carcinoma is the main factor responsible for patient mortality.Accordingly,delineating strategies to inform clinical follow-up and treatment plans based on genes is paramount for clinical practitioners.CASE SUMMARY Herein,we present RET proto-oncogene mutations,clinical characteristics,and treatment strategies in a family with MEN2A.A family study was conducted on patients diagnosed with MEN2A.DNA was extracted from the peripheral blood of family members,and first-generation exon sequencing of the RET protooncogene was conducted.The C634Y mutation was identified in three family members spanning three generations.Two patients were sequentially diagnosed with pheochromocytomas and bilateral medullary thyroid carcinomas.A 9-yearold child harboring the gene mutation was diagnosed with medullary thyroid carcinoma.Surgical resection of the tumors was performed.All family members were advised to undergo complete genetic testing related to the C634Y mutation,and the corresponding treatments administered based on test results and associated clinical guidelines.CONCLUSION Advancements in MEN2A research are important for familial management,assessment of medullary thyroid cancer invasive risk,and deciding surgical timing.

Early detection of multiple endocrine neoplasia type 1: A case report

BACKGROUND Multiple endocrine neoplasias(MENs)are a group of hereditary diseases invol-ving multiple endocrine glands,and their prevalence is low.MEN type 1(MEN1)has diverse clinical manifestations,mainly involving the parathyroid glands,gastrointestinal tract,pancreas and pituitary gland,making it easy to miss the clinical diagnosis.CASE SUMMARY We present the case of a patient in whom MEN1 was detected early.A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hos-pital.Blood tests at admission revealed hypercalcemia and hypophosphatemia,and emission computed tomography of the parathyroid glands revealed a hy-perfunctioning parathyroid lesion.Gastroscopy findings suggested a duodenal bulge and ulceration.Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb.Further blood tests revealed elevated levels of serum gastrin.Surgery was performed,and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy.The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year.CONCLUSION For patients who present with gastrointestinal symptoms accompanied by hyper-calcemia and hypophosphatemia,clinicians need to be alert to the possibility of MEN1.

Molecular diagnostic approaches in detecting rearranged during transfection oncogene mutations in multiple endocrine neoplasia type 2

Different types of neuroendocrine cancer,including medullary thyroid cancer(MTC)and thyroid C-cell hyperplasia,are part of multiple endocrine neoplasia type 2(MEN2).A proto-oncogene mutation of the rearranged during transfection(RET)gene changes the way that receptor tyrosine kinases work.Multiple endocrine neoplasia,a pathological condition,involves these kinases.When the RET protooncogene changes,it can cause endocrine adenomas and hyperplasia to happen at the same time or one after the other.Pheochromocytoma,medullary thyroid carcinoma,and hyperparathyroidism,alone or in combination,are present in MEN2A patients.Some patients may also have skin lichen amyloidosis or Hirschsprung's disease.Patients with MEN2A often present with MTC.MTC is aggressive and has the worst prognosis,as most patients exhibit lymph node metastasis.MTC is one of the important causes of death in patients with MEN2A.RET mutation analysis aids in identifying MEN2A symptoms and monitoring levels of calcium,thyroid hormones,calcitonin,normetanephrine,fractionated metanephrines,and parathyroid hormone.The earlier diagnosis of MTC significantly improves survival and prompts better management of MEN2A.In this editorial,we will discuss the significance of molecular diagnostic approaches in detecting RET oncogene mutations in MEN2A.

Adverse Pregnancy Outcomes Following Cryotherapy, Thermal Ablation and Loop Electrosurgical Excision Procedure for Cervical Intraepithelial Neoplasia Treatment: A Pilot Study among Zambian Women

Background: Cervical Intraepithelial neoplasia treatments have become essential interventions to manage cervical lesions. Majority of the recipients of these treatments are women within the reproductive age group, who according to literature may be at risk of adverse pregnancy outcomes. This pilot study is part of a study investigating adverse pregnancy outcomes among women who received Cryotherapy, Thermal ablation and Loop Electrosurgical Excision Procedure compared to the untreated women in Zambia. Materials and Methods: This descriptive study analyzed records of 886 (n = 443 treated and n = 443 untreated) women aged 15 - 49 years. The women were either screened with Visual Inspection with Acetic Acid or treated for Cervical Intraepithelial neoplasia at the Adult Infectious Disease Centre between January 2010 and December 2020. Women meeting the criteria were identified using the Visual Inspection with Acetic Acid screening records and telephone interviews to obtain the adverse pregnancy outcome experienced. Data were analysed using STATA version 16 to determine the prevalence and obtain frequency distribution of outcomes of interest. Univariate and multivariable binary logistic regression estimated odds of adverse pregnancy outcomes across the three treatments. Results: The respondents were aged 15 to 49 years. Adverse pregnancy outcomes were observed to be more prevalent in the treatment group (18.5%) compared to the untreated group (5.4%). Normal pregnancy outcomes were lower in the treated (46.3%;n = 443) than the untreated (53.7%;n = 443). The treated group accounted for the majority of abortions (85.2%), prolonged labour (85.7%) and low birth weight (80%), whereas, the untreated accounted for the majority of still births (72.7%). Women treated with cryotherapy (aOR = 2.43, 95% CI = 1.32 - 4.49, p = 0.004), thermal ablation (aOR = 6.37, 95% CI = 0.99 - 41.2, p = 0.052) and Loop Electrosurgical Excision Procedure (aOR = 9.67, 95% CI = 2.17 - 43.1, p = 0.003) had two-, six- and ten-times higher odds of adverse pregnancy outcomes respectively, relative to women who required no treatment. Conclusion: Adverse pregnancy outcomes are prevalent among women who have received treatment in Zambia. The findings indicate that treating Cervical Intraepithelial Neoplasia has been linked to higher chances of experiencing abortion, delivering low birth weight babies and enduring prolonged labor that may result in a caesarean section delivery. Cervical neoplasia treatments, particularly Loop Electrosurgical Excision Procedure, are associated with significantly increased odds of adverse pregnancy outcomes. It is essential to include information about prior Cervical Intraepithelial neoplasia treatment outcomes in obstetric care.

Pregnancy and Obstetrical Outcomes Following Treatment for Cervical Intra-Epithelial Neoplasia (CIN) in Two Hospitals of a Low-Resource Country

Objective: In Cameroon, more than 80% of women suffering from cervical intraepithelial neoplasia (CIN) are within the reproductive age. This study intended to analyze the pregnancy outcomes following cervical treatment in Cameroon. Methods: This was a cohort study with two years retrospective data collection involving 82 women who underwent cervical treatment for CIN in two Cameroonian hospitals from January 2015 to December 2017. Data were collected from CIN treatment to end of pregnancy where applicable. Data analysis was done using Epi Info software version 3.5.4. Results: We collected data from 82 patients aged 27 to 48 years, with a mean age of 36.5 (SD: 5.3) years. During the study period, 33 out of 82 participants became pregnant 40.2 [29.56 - 51.66]%. The factor associated with pregnancy occurrence after treatment was age less than 35 years (Odds ratio = 4.37 [1.7 - 11.2]. From the 33 pregnancies recorded, 17 (51.5%) ended in a delivery, amongst which 15 (88.2%) were vaginal. Conclusion: Pregnancy frequency over two years following cervical treatment for CIN was relatively good, and younger women (age 35 years) were significantly more like to have conceived compared to their older counterparts. Post-treatment delivery outcomes seem to be similar to those in the general population.

SGK3 overexpression correlates with a poor prognosis in endoscopically resected superficial esophageal squamous cell neoplasia:A long-term study

BACKGROUND The expression status of serum and glucocorticoid-induced protein kinase 3(SGK3)in superficial esophageal squamous cell neoplasia(ESCN)remains unknown.AIM To evaluate the SGK3 overexpression rate in ESCN and its influence on the prognosis and outcomes of patients with endoscopic resection.METHODS A total of 92 patients who had undergone endoscopic resection for ESCN with more than 8 years of follow-up were enrolled.Immunohistochemistry was used to evaluate SGK3 expression.RESULTS SGK3 was overexpressed in 55(59.8%)patients with ESCN.SGK3 overexpression showed a significant correlation with death(P=0.031).Overall survival and disease-free survival rates were higher in the normal SGK3 expression group than in the SGK3 overexpression group(P=0.013 and P=0.004,respectively).Cox regression analysis models demonstrated that SGK3 overexpression was an independent predictor of poor prognosis in ESCN patients(hazard ratio 4.729;95% confidence interval:1.042-21.458).CONCLUSION SGK3 overexpression was detected in the majority of patients with endoscopically resected ESCN and was significantly associated with shortened survival.Thus,it might be a new prognostic factor for ESCN.

Distribution of High-Risk Human Papillomavirus Genotypes among Women with Colposcopic Diagnosis of Cervical Intraepithelial Neoplasia in Bangladesh

Background: The incidence of cervical cancer is high in Bangladesh and there is a high prevalence of preinvasive lower genital tract disease among women of reproductive age. Persistent high-risk Human Papilloma Virus (HPV) infection is the main underlying cause of cervical cancer and its precursor, cervical intraepithelial neoplasia (CIN). Objective: The aim of the study was to identify the subtypes of high-risk HPV infection among women with the colposcopic diagnosis of cervical intraepithelial neoplasia in Bangladesh. Methods: This cross-sectional observational study was conducted in the colposcopy clinic of Dhaka Medical College Hospital over a six-month period. A total of 100 participants were enrolled. Married women, between 30 - 60 years of age with colposcopically diagnosed cervical intra epithelial neoplasia were enrolled. Women with chronic illness, pregnancy, and women unable to consent were excluded from this study. After counselling, colposcopically directed punch biopsies were taken from each CIN case concurrently with high-risk HPV testing by polymerase chain reaction (PCR). Results: The mean age of the patients was 38.69 (SD ±7.76) years. CIN 1 was diagnosed in 57% of participants, while 24% had CIN II and 19% had CIN III lesions. High-risk HPV was present in 52 patients. HPV 16 was the most common identified in 28 (53.84%) and HPV 18 was the second most common with 20 (38.46%) either singly or in combination with other high-risk subtypes. The other HPV strains, HPV 31, 33, 35, 52, 56 and 58, were also detected either as mono or co-infections. Out of the 52 HPV positive cases, 29 (55.8%) had mono infection and 23 (44.2%) had co-infection with several subtypes. The highest incidence (50%) of oncogenic HPV infections was present among women aged 35 - 45 years. Risk factors associated with HPV positive cases were high parity (P 0.05), early age at marriage (P = 0.754) and early age of first child. Conclusion: This study identified a high prevalence of HPV 16 and 18 genotypes. HPV vaccination with the current 9-valent HPV vaccine, which contains HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58. Will be an effective public health measure to eradicate cervical cancer in Bangladesh.

Diagnosis of gastric intraepithelial neoplasia by narrow-band imaging and confocal laser endomicroscopy

AIM:To evaluate the diagnosis of different differentiated gastric intraepithelial neoplasia (IN) by magnifica-tion endoscopy combined with narrow-band imaging (ME-NBI) and confocal laser endomicroscopy (CLE). METHODS:Eligible patients with suspected gastric IN lesions previously diagnosed by endoscopy in secondary hospitals and scheduled for further diagnosis and tratment were recruited for this study. Excluded from the study were patients who had liver cirrhosis, impaired renal function, acute gastrointestinal (GI) bleeding, coagulopathy, esophageal varices, jaundice, and GI post-surgery. Also excluded were those who were pregnant, breastfeeding, were younger than 18 years old, or were unable to provide informed consent. All patients had all mucus and bile cleared from their stom-achs. They then received upper GI endoscopy. When a mucosal lesion is found during observation with whitelight imaging, the lesion is visualized using maximal magnification, employing gradual movement of the tip of the endoscope to bring the image into focus. Saved images are analyzed. Confocal images were evaluated by two endoscopists (Huang J and Li MY), who were familiar with CLE, blinded to the related information about the lesions, and asked to classify each lesion as either a low grade dysplasia (LGD) or high grade dysplasia (HGD) according to given criteria. The results were compared with the final histopathologic diagnosis. ME-NBI images were evaluated by two endoscopists (Lu ZS and Ling-Hu EQ) who were familiar with NBI, blinded to the related information about the lesions and CLE images, and were asked to classify each lesion as a LGD or HGD according to the "microvascular pattern and surface pattern" classification system. The results were compared with the final histopathologic diagnosis. RESULTS: The study included 32 pathology-proven low grade gastric IN and 26 pathology-proven high grade gastric IN that were detected with any of the modalities. CLE and ME-NBI enabled clear visualization of the vascular microsurface patterns and microvascular structures of the gastric mucosa. The accuracy of the CLE and the ME-NBI diagnosis was 88% (95% CI:78%-98%) and 81% (95% CI: 69%-93%), respectively. The kappa coefficient of agreement between the histopathology and the in vivo CLE imaging was 0.755; between the histopathology and the in vivo CLE imaging was 0.615. McNemar's test (binomial distribution used) indicated that the agreement was significant (P < 0.05). When patients were diagnosed by MENBI with CLE, the overall accuracy of the diagnosis was 86.21% (95% CI:73%-96%), and the kappa coefficient of agreement was 0.713, according to McNemar's test (P < 0.05). CONCLUSION:Higher diagnostic accuracy, sensitivityand specificity of CLE over ME-NBI indicate the feasibility of these two techniques for the efficacious diagnostic classification of gastric IN.

High-grade pancreatic intraepithelial lesions： prevalence and implications in pancreatic neoplasia

BACKGROUND： High-grade pancreatic intraepithelial neoplasia（Pan IN-3）, a precursor of pancreatic ductal adenocarcinoma（PDAC）, is not universally detected in resected pancreatic neoplasms. We sought to determine the prevalence and prognostic relevance of Pan IN-3 lesions in primary surgical resections of PDACs and intraductal papillary mucinous neoplasms（IPMNs）.METHODS： A retrospective review of a tertiary care center pathology database（1/2000-6/2014） was performed. Demographics, imaging, pathology, disease-recurrence, and survival data were reviewed.RESULTS： A total of 458 patients who underwent primary pancreatic resection were included. “Pan IN-3” lesions were found in 74（16.2%） patients who either had PDAC（n=67） or main duct（MD）-IPMN（n=7）. Among IPMN-MDs, Pan IN-3 lesions were exclusively found in those with pathological evidence of chronic pancreatitis. For PDACs, the median overall survival（OS） for pancreata with Pan IN-3 lesions was significantly better than those without（OS 1.12 years, interquartile range [IQR] 0.72, 2.05 years vs OS 0.86 years, IQR 0.64,1.60 years respectively; P=0.04）. Multivariate Cox regression analysis demonstrated that the presence of Pan IN-3 lesions was associated with a reduced risk of death（HR=0.43; 95% CI： 0.23-0.82; P=0.01）.CONCLUSIONS： Following primary resection of pancreatic adenocarcinoma, the lower survival observed in patients without Pan IN-3 lesions might suggest a state of complete or accelerated transformation. Further investigations are necessary to validate these findings that might impact disease prognosis and management.

Gene mutations in stool from gastric and colorectal neoplasia patients by next-generation sequencing

AIM To study cancer hotspot mutations by next-generation sequencing(NGS) in stool DNA from patients with different gastrointestinal tract(GIT) neoplasms. METHODS Stool samples were collected from 87 Finnish patients diagnosed with various gastric and colorectal neoplasms, including benign tumors, and from 14 healthy controls. DNA was isolated from stools by usingthe PSP~? Spin Stool DNA Plus Kit. For each sample, 20 ng of DNA was used to construct sequencing libraries using the Ion AmpliS eq Cancer Hotspot Panel v2 or Ion AmpliS eq Colon and Lung Cancer panel v2. Sequencing was performed on Ion PGM. Torrent Suite Software v.5.2.2 was used for variant calling and data analysis.RESULTS NGS was successful in assaying 72 GIT samples and 13 healthy controls, with success rates of the assay being78% for stomach neoplasia and 87% for colorectal tumors. In stool specimens from patients with gastric neoplasia, five hotspot mutations were found in APC,CDKN2 A and EGFR genes, in addition to seven novel mutations. From colorectal patients, 20 mutations were detected in AKT1, APC, ERBB2, FBXW7, KIT, KRAS,NRAS, SMARCB1, SMO, STK11 and TP53. Healthy controls did not exhibit any hotspot mutations, except for two novel ones. APC and TP53 were the most frequently mutated genes in colorectal neoplasms, with five mutations, followed by KRAS with two mutations.APC was the most commonly mutated gene in stools of patients with premalignant/benign GIT lesions.CONCLUSION Our results show that in addition to colorectal neoplasms,mutations can also be assayed from stool specimens of patients with gastric neoplasms.

Thedual pathogenesisofpenileneoplasia: The heterogeneous morphology of human papillomavirus-relatedtumors

Objective:Penile neoplasia,usually of squamous histogenesis,is currently classfied into human papillomavirus(HPV)-related or-dependent and non-HPV-related or-indepen dent.There are distinct morphological differences among the two groups.New research studies on penile cancer from Northern countries showed that the presence of HPV is corre lated with a better prognosis than virus negative people,while studies in Southern countries had not confirmed,perhaps due to differences in staging or treatment.Methods:We focused on the description of the HPV.related carcinomas of the penis.The approach was to describe common clinical features followed by the pathological features of each entity or subtype stressing the characteristics for differential diagnosis,HPV genotypes,and prognostic features of the invasive carcinomas.Similar structure was followed for penile intraepithelial neoplasia,except for prognosis because of the scant evidence available.Results:Most of HPV-related lesions can be straightforwardly recognized by routine hematoxylin and eosin stains,but in some cases surrogate p16 immunohistochemical staining or molecular methods such as in situ hybridization or polymerase chain reaction can be utilized.Currently,there are eight tumor invasive variants associated with HPV,as follows:basaloid,warty,warty-basaloid,papillary basaloid,clear cell,medullary,lymphoepithelioma-like,and giant condylomas with malignant transformation.Conclusion:This review presents and describes the heterogeneous clinical,morphological,and genatypic features of the HPV-related subtypes of invasive and non-invasive penile neoplasia.

Missed diagnosis of early gastric cancer or high-grade intraepithelial neoplasia

AIM: To investigate the causes of missed diagnosis of early gastric cancer (EGC) or high-grade intraepithelial neoplasia (HGIN) in Chongqing, China. METHODS: The present study summarizes 103 cases of EGC/HGIN detected by esophagogastroduodenos-copy (EGD) and pathological analysis from January 2010 to December 2011. Dimethyl silicone oil was administrated orally 15 min before the EGD procedures. The stomach was cleaned by repeated washing with saline when the gastroscope entered the stomach cavity. Suspected EGC lesions were subject to conventional biopsy sampling and pathological examinations. The correlation between lesion locations, endoscopic morphology of cancerous sites, training level of the examiners, pathological biopsies, and missed diagnosis was analyzed. RESULTS: Twenty-three cases were missed among the 103 cases (22.23%) of EGC/HGIN. The rate of missed EGC in the gastroesophageal junction (8/19, 42.1%) was significantly higher than at other sites (15/84, 17.86%) (χ2 = 5.253, P = 0.022). In contrast, the rate of missed EGC in the lower stomach body (2/14, 14.29%) was lower than at other sites (21/89,23.6%), but there were no significant differences (χ2 = 0.289, P = 0.591). The rate of missed EGC in the gastric antrum (5/33, 15.15%) was lower than at other sites (18/70, 25.71%), but there were no significant differences (χ2 = 1.443, P = 0.230). Endoscopists from less prestigious hospitals were more prone to not diagnosing EGC than those from more prestigious hospitals (χ2 = 4.261, P = 0.039). When the number of biopsies was < 4, the rate of missed diagnosis was higher (20/23, 89.96%) than for when there were > 4 biopsies (3/23, 13.04%) (P < 0.001). In addition, there was no significant difference in the rate of missed diagnosis in patients with 1-3 biopsy specimens (χ2 = 0.141, P = 0.932). CONCLUSION: Endoscopists should have a clear understanding of the anatomical characteristics of the esophagus/stomach, and endoscopic identification of early lesions increases with the number of biopsies.

Endoscopic resection techniques for colorectal neoplasia:Current developments

Endoscopic polypectomy and endoscopic mucosal resection(EMR) are the established treatment standards for colorectal polyps. Current research aims at the reduction of both complication and recurrence rates as well as on shortening procedure times. Cold snare resection is the emerging standard for the treatment of smaller(< 5 mm) polyps and is possibly also suitable for the removal of noncancerous polyps up to 9 mm. The method avoids thermal damage, has reduced procedure times and probably also a lower risk for delayed bleeding. On the other end of the treatment spectrum, endoscopic submucosal dissection(ESD)offers en bloc resection of larger flat or sessile lesions. The technique has obvious advantages in the treatment of high-grade dysplasia and early cancer. Due to its minimal recurrence rate, it may also be an alternative to fractionated EMR of larger flat or sessile lesions. However, ESD is technically demanding and burdened by longer procedure times and higher costs. It should therefore be restricted to lesions suspicious for high-grade dysplasia or early invasive cancer.The latest addition to endoscopic resection techniques is endoscopic fullthickness resection with specifically developed devices for flexible endoscopy.This method is very useful for the treatment of smaller difficult-to-resect lesions,e.g., recurrence with scar formation after previous endoscopic resections.

Prevalence of HPV Infection And Cervical Intraepithelial Neoplasia And Attitudes towards HPV Vaccination among Chinese Women Aged 18-25 in Jiangsu Province

Objective：Few data are available on the epidemiology of HPV and cervical cancer among Chinese women younger than 25 years old.This study aimed to estimate the HPV infection rate and the prevalence of cervical intraepithelial neoplasia（CIN） in women aged 18-25,as well as their knowledge of and attitudes towards HPV vaccination.Methods：A population-based cervical cancer screening study was conducted on women aged 18-25 in Jiangsu province in 2008.Participants provided socio-demographic,reproductive and behavioral information and completed a survey about their knowledge of and attitudes towards HPV vaccination.Women then underwent a gynecologic exam to provide two cervical exfoliated cell samples for high risk HPV DNA testing and liquid-based cytology（LBC） as well as visual inspection with acetic acid（VIA）.Women testing positive for any test were referred to colposcopy and biopsy.The gold standard for diagnosis of cervical lesions was directed or random biopsies.Results：Within the sample of 316 women,3.4% of them were diagnosed with CIN grade 2 or worse lesions and 17.1% were found to be positive for HPV DNA.Among these young women,extra-marital sexual behavior of them（OR=2.0,95%CI：1.1-3.8） or their husbands（OR=2.6,95%：1.4-4.7） were associated with an increased risk of HPV positivity.Although overall HPV awareness was low,after a brief educational intervention,98.4% reported they would electively receive HPV vaccination and would also recommend that their daughters be vaccinated.However,most urban and rural women reported their ideal maximum out-of-pocket contribution for HPV vaccination to be less than 500 RMB and 50-100 RMB,respectively.Conclusion：Our study indicates cervical disease burden is relatively high among sampled Chinese women aged 18-25.Appropriate educational interventions for female adolescents and strategies to subsidize vaccine costs are definitely needed to ensure the effectiveness of vaccination campaigns in China.

Diagnosis and therapies for gastric non-invasive neoplasia

There has been a great discrepancy of pathological diagnosis for gastric non-invasive neoplasia/dysplasia between Japanese and western pathologists. In Japan, lesions that most western pathologists diagnose as dysplasia are often considered adenocarcinoma based on nuclear and structural atypia regardless of the presence of invasion. In the Vienna classification, gastric non-invasive intraepithelial neoplasia(NIN) weredivided into low grade and high grade(including intramucosal cancer of Japanese criteria). The diagnosis by both endoscopy and pathology of biopsy specimen is difficult. Recent advances of diagnostic modality such as magnified endoscopy and imaged enhanced endoscopy is expected to improve the diagnostic yield for NIN. There are two treatment strategies for NIN, observation and diagnostic therapy by endoscopic resection(ER). ER is acceptable because of its less invasiveness and high local control rate, on the other hand, cancer-developing rate of low-grade NIN is reported to be low. Therefore there is controversy for the treatment of gastric NIN. Prospective study based on unified pathological definition is required in the future.

How significant is the association between metabolic syndrome and prevalence of colorectal neoplasia?

The incidence and prevalence of metabolic syndrome(MS) and colorectal cancer(CRC) has been rising in developed countries. The association between these two diseases has been widely studied and reported. Less evidence is available about the relationship between MS and CRC precancerous lesions(adenomatous polyps, adenomas). The aim of this paper is to present an overview of our scientific understanding of that topic and its implication in clinical practice. One of the principal goals of current CRC secondary prevention efforts is to detect and remove the precancerous lesions in individuals with an average CRC risk to prevent the development of invasive cancer. MS is not currently considered a high-risk CRC factor and is therefore not included in the guidelines of organized screening programs. However, in light of growing scientific evidence, the approach to patients with MS should be changed. Metabolic risk factors for the development of adenomas and cancers are the same- obesity, impaired glucose tolerance, dyslipidemia, hypertension, cardiovascular diseases and diabetes mellitus type 2. Therefore, the key issue in the near future is the development of a simple scoring system, easy to use in clinical practice, which would identify individuals with high metabolic risk of colorectal neoplasia and would be used for individual CRC secondary prevention strategies. Currently, such scoring systems have been published based on Asian(Asia-Pacific Colorectal Screening Score; APCS) and Polish populations.

Pink-color sign in esophageal squamous neoplasia, and speculation regarding the underlying mechanism

AIM:To investigate the reasons for the occurrence of the pink-color sign of iodine-unstained lesions. METHODS:In chromoendoscopy, the pink-color sign of iodine-unstained lesions is recognized as useful for the diagnosis of esophageal squamous cell carcinoma. Patients with superficial esophageal neoplasms treated by endoscopic resection were included in the study. Areas of mucosa with and without the pink-color sign were evaluated histologically. The following histologic features that were possibly associated with the pinkcolor sign were evaluated. The keratinous layer and basal cell layer were classified as present or absent. Cellular atypia was classified as high grade, moderate grade or low grade, based on nuclear irregularity, mitotic figures, loss of polarity, chromatin pattern and nuclear/cytoplasmic ratio. Vascular change was assessed based on dilatation, tortuosity, caliber change and variability in shape. Vessels with these four findings were classified as positive for vascular change. Endoscopic images of the lesions were captured immediately after iodine staining, 2-3 min after iodine staining and after complete fading of iodine staining. Quantitative analysis of color changes after iodine staining was also performed. RESULTS:A total of 61 superficial esophageal neoplasms in 54 patients were included in the study. The lesions were located in the cervical esophagus in one case, the upper thoracic esophagus in 10 cases, the mid-thoracic esophagus in 33 cases, and the lower thoracic esophagus in 17 cases. The median diameter of the lesions was 20 mm (range:2-74 mm). Of the 61 lesions, 28 were classified as pink-color sign positive and 33 as pink-color sign negative. The histologic diagnosis was high-grade intraepithelial neoplasia (HGIN) or cancer invading into the lamina propria in 26 of the 28 pink-color sign positive lesions. There was a significant association between pink-color sign positive epithelium and HGIN or invasive cancer (P = 0.0001). Univariate analyses found that absence of the keratinous layer and cellular atypia were significantly associated with the pink-color sign. After Bonferroni correction, there were no significant associations between the pink-color sign and presence of the basal membrane or vascular change. Multivariate analyses found that only absence of the keratinous layer was independently associated with the pink-color sign (OR = 58.8, 95%CI:5.5-632).Quantitative analysis was performed on 10 superficial esophageal neoplasms with both pink-color sign positive and negative areas in 10 patients. Pink-color sign positive mucosa had a lower mean color value in the late phase (pinkish color) than in the early phase (yellowish color), and had similar mean color values in the late and final phases. These findings suggest that pinkcolor positive mucosa underwent color fading from the color of the iodine (yellow) to the color of the mucosa (pink) within 2-3 min after iodine staining. Pink-color sign negative mucosa had similar mean color values in the late and early phases (yellowish color), and had a lower mean color value in the final phase (pinkish color) than in the late phase. These findings suggest that pink-color sign negative mucosa did not undergo color fading during the 2-3 min after iodine staining, and underwent color fading only after spraying of sodium thiosulfate. CONCLUSION:The pink-color sign was associated with absence of the keratinous layer. This sign may be caused by early fading of iodine staining.

Risk for gastric neoplasias in patients with chronic atrophic gastritis:A critical reappraisal

Chronic atrophic gastritis （CAG） is an inflammatory condition characterized by the loss of gastric glandular structures which are replaced by connective tissue （non-metaplastic atrophy） or by glandular structures inappropriate for location （metaplastic atrophy）. Epidemiological data suggest that CAG is associated with two different types of tumors： Intestinal-type gastric cancer （GC） and type I gastric carcinoid （T I GC）. The pathophysiological mechanisms which lead to the development of these gastric tumors are different, It is accepted that a multistep process initiating from Helico- bacterpylori-related chronic inflammation of the gastric mucosa progresses to CAG, intestinal metaplasia, dysplasia and, finally, leads to the development of GC. The T I GC is a gastrin-dependent tumor and the chronic elevation of gastrin, which is associated with CAG, stimulates the growth of enterochromaffin-like cells with their hyperplasia leading to the development of T I GC. Thus, several events occur in the gastric mucosa before the development of intestinatype GC and/ or T I GC and these take several years. Knowledge ofCAG incidence from superficial gastritis, its prevalence in different clinical settings and possible risk factors as- sociated with the progression of this condition to gastric neoplasias are important issues. This editorial intends to provide a brief review of the main studies regarding incidence and prevalence of CAG and risk factors for the development of gastric neoplasias.

Frequency, localization, and types of gastrointestinal stromal tumor-associated neoplasia

BACKGROUND In recent years,increasing evidence of second neoplasms associated with gastrointestinal stromal tumors(GIST)has been found.Numerous case reports,mostly retrospective studies and a few reviews,have been published.To our knowledge,however,no systematic review or meta-analysis of the existing data has been performed so far.AIM To prepare a compilation,as complete as possible,of all reported second tumor entities that have been described in association with GIST and to systematically analyze the published studies with regard to frequency,localization,and types of GIST-associated neoplasms.METHODS The MEDLINE and EBSCO databases were searched for a combination of the keywords GIST/secondary,synchronous,coincident/tumor,neoplasm,and relevant publications were selected by two independent authors.RESULTS Initially,3042 publications were found.After deletion of duplicates,1631 remained,and 130 papers were selected;22 of these were original studies with a minimum of 20 patients,and 108 were case reports.In the 22 selected studies,comprising a total number of 12050 patients,an overall rate of GIST-associated neoplasias of 20%could be calculated.Most second neoplasias were found in the gastrointestinal tract(32%)and in the male and female urogenital tract(30%).The specific risk scores of GISTs associated with other tumors were significantly lower than those without associated neoplasias.CONCLUSION In this first systematic review,we could confirm previously reported findings of a more than coincidental association between GIST and other neoplasias.The question whether there is an underlying causal association will need further investigation.Our data suggest that even GIST with a very low risk of disease progression should prompt screening for second neoplasia and subsequent frequent controls or extended staging.