High-grade pancreatic intraepithelial neoplasia diagnosed based on changes in magnetic resonance cholangiopancreatography findings:A case report

BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination modalities.However,it can be diagnosed by pancreatic juice cytology from indirect findings.Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct(MPD)and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography(ERCP).We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range,but without caudal MPD dilatation on magnetic resonance cholangiopancreatography(MRCP).CASE SUMMARY A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision,which revealed pancreatic cysts.MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation.Thus,course observation was performed.After 24 mo,MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst.We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination.We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN.Pancreatic parenchyma invasion was not observed,and curative resection was achieved.CONCLUSION High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.

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.

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.

Estimation of economic burden throughout course of cervical squamous intraepithelial lesion and cervical cancer in China:A nationwide multicenter cross-sectional study

Objective: Cervical squamous intraepithelial lesion(SIL) and cervical cancer are major threats to females' health and life in China, and we aimed to estimate the economic burden associated with their diagnosis and treatment.Methods: A nationwide multicenter, cross-sectional, hospital-based survey was conducted in 26 qualified hospitals across seven administrative regions of China. We investigated females who had been pathologically diagnosed with SIL and cervical cancer, and included five disease courses(“diagnosis”, “initial treatment”,“chemoradiotherapy”, “follow-up” and “recurrence/progression/metastasis”) to estimate the total costs. The median and interquartile range(IQR) of total costs(including direct medical, direct non-medical, and indirect costs), reimbursement rate by medical insurance, and catastrophic health expenditures in every clinical stage were calculated.Results: A total of 3,471 patients in different clinical stages were analyzed, including low-grade SIL(LSIL)(n=549), high-grade SIL(HSIL)(n=803), cervical cancer stage ⅠA(n=226), ⅠB(n=610), ⅡA(n=487), ⅡB(n=282), Ⅲ(n=452) and Ⅳ(n=62). In urban areas, the estimated total costs of LSIL and HSIL were $1,637.7(IQR:$956.4-$2,669.2) and $2,467.1(IQR:$1,579.1-$3,762.3), while in rural areas the costs were $459.0(IQR:$167.7-$1,330.3) and $1,230.5(IQR:$560.6-$2,104.5), respectively. For patients with cervical cancer stage ⅠA,ⅠB, ⅡA, ⅡB, and Ⅲ-Ⅳ, the total costs were $15,034.9(IQR:$11,083.4-$21,632.4), $19,438.6(IQR:$14,060.0-$26,505.9), $22,968.8(IQR:$16,068.8-$34,615.9), $26,936.0(IQR:$18,176.6-$41,386.0) and $27,332.6(IQR:$17,538.7-$44,897.0), respectively. Medical insurance covered 43%-55% of direct medical costs for cervical cancer patients, while the coverage for SIL patients was 19%-43%. For most cervical cancer patients, the expense was catastrophic, and the extent of catastrophic health expenditure was about twice large for rural patients than that for urban patients in each stage.Conclusions: The economic burden of SIL and cervical cancer in China is substantial, with a significant proportion of the costs being avoidable for patients with LSIL. Even for those with medical insurance, catastrophic health expenditures are also a major concern for patients with cervical cancer, particularly for those living in rural areas.

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.

Extramammary Paget’s Disease Manifested by Intraepithelial Adenocarcinoma of the Vulva and Anus Combined with Invasive Adenocarcinoma of the Ampullary Part of the Rectum

The Object of the Study: The author of the given paper describes an unusual combination of two diseases: extramammary Paget’s disease manifested by intraepithelial adenocarcinoma of the vulva and anus combined with invasive adenocarcinoma of the ampullary part of the rectum and describes the atypical manifestations of these diseases. The Content: The content of this research paper includes a description of the patient, an analysis of the clinical picture, diagnostic methods and therapeutic interventions used, a report of the following disease, and the result of the presented case. The Result of the Research Work: The result of the research work is the analysis of a clinical case with two different tumors, where such a combination of tumors is rarely described in the literature. Moreover, no large specific sample with this combination of diseases is available. Patient Characteristics: The given case report describes a patient of the Palliative Care Unit of the Gerontology Clinic with a primary diagnosis of C20-rectal adenocarcinoma in the background of the anal canal, perineal skin Paget’s disease, stage IV. The presented complications of the patient’s primary diagnosis are multiple metastases in the liver;status post palliative chemotherapy;hepatomegaly;metastases to abdominal lymph nodes, inguinal lymph nodes;metastases at Th12, L4 level;pain syndrome. The presented above combination of diagnosed diseases is very rare. Applied Diagnostics: In October 2021, it was performed diagnostic manipulation: biopsy and the pathologist have provided a microscopic description. The first tissue fragment had a pronounced electrothermal lesion and the epithelial structures were not valuable. The second skin tissue fragment was covered with hyperplastic and acanthotic epithelium;its basal and middle layers contained multiple large cells proliferates extending into the medial epidermis, and the cytoplasm of these cells reacted positively with PAS (Periodic Acid Schiff reaction). It needs to be noted that the patient had previously had several years of biopsies from the perineal and anal epidermis, where Paget’s disease had also been diagnosed. The performed immunohistochemistry showed these cells to be CK20 positive, CK7 rare positive and p16 negative. The following pathohistological findings were made: morphological and immunohistochemical picture is consistent with Paget’s disease. According to the ICD-10, the patient was diagnosed with C51 malignant neoplasm of the female external genitalia. Using imaging diagnostics, it became clear that the patient’s rectal adenocarcinoma had progressed to metastatic stage with distant liver metastases in the background of anal canal, perineal skin Paget’s disease. Therapeutic Plan of the Patient: Based on the patient’s main diagnoses, the complications of the principal diagnosis, the patient’s overall severe condition, pain syndrome, age and comorbidities, palliative chemotherapy was approved as a therapeutic option in council of doctors. Monitoring and Outcome of the Patient: The patient’s general condition was becoming worse over time, and she was diagnosed with exitus latalis in December 2022. At that time, the patient was discharged from hospital and was on palliative care at home under the control of her family physician.

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.

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 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.

Treatment strategy for gastric non-invasive intraepithelial neoplasia diagnosed by endoscopic biopsy

Treatment strategies,whether as follow-up or"total incisional biopsy"for gastric noninvasive intraepithelial neoplasia diagnosed by examination of an endoscopic forceps biopsy specimen,are controversial due to problems associated with the diagnostic accuracy of endoscopic forceps biopsy and questions about the safety and efficacy of endoscopic treatment.Based on the histological findings of the biopsy specimen,it is difficult to differentiate between reactive or regenerative changes,inflammation and neoplastic changes,intraepithelial and invasive tumors.Therefore,gastric neoplasia diagnosed as noninvasive intraepithelial often develop into invasive carcinoma during follow-up.Recent advances in endoscopic modalities and treatment devices,such as image-enhanced endoscopy and highfrequency generators,may make endoscopic treatment,such as endoscopic submucosal dissection(ESD),a therapeutic option for gastric intraepithelial neoplasia,including low-grade neoplasms.Future studies are required to evaluate whether ESD is a valid strategy for gastric intraepithelial neoplasm with regard to safety and cost effectiveness.

Proteomic analysis of pancreatic intraepithelial neoplasia and pancreatic carcinoma in rat models

AIM:To detect the proteomic variabilities of pancreatic intraepithelial neoplasia(PanIN)and pancreatic carcinoma(PC)induced by 7,12-dimethylbenzanthracene(DMBA) in rat models and to identify potential biomarkers.METHODS:Sixty adult male Sprague Dawley rats were randomized into three groups.The rats had DMBA implanted into their pancreas for one(n=20)or two months(n=20)or assigned to the normal group(n =20).The rats were killed after one or two months,and were evaluated histopathologically.Three tissue samples from each group of rats with either normal pancreas,PanIN(PanIN-2)or PC were examined by 2D-DIGE.The different expression spot features were analyzed by matrix-assisted laser desorption/ionizationtime of flight/time of flight(MALDI-TOF/TOF)tandem mass spectrometry.The expression of enolase 1,a differentially expressed protein,was identified by immu-nohistochemistry.RESULTS:There was significant difference in the proportions of neoplastic changes between the 1-and 2-mogroups(P=0.0488).There was an increase in the frequency of adenocarcinomas in the 2-mo group compared with the 1-mo group(P=0.0309).No neoplastic changes were observed in any of the animals in the normal group.Enolase 1,pancreatic ELA3B,necdin,Hbp23,CHD3,hnRNP A2/B1,Rap80,and Gnb2l1 were up-regulated in the PanIN and PC tissues,and CEL,TPT1,NME2,PCK2,an unnamed protein product,and glycine C-acetyltransferase were down-regulated in the PanIN and PC tissues.The immunohistochemical results showed that enolase 1 expression was up-regulated in the pancreatic cancer tissues of rats and humans.CONCLUSION:The pancreatic protein expression changes induced by DMBA suggest potential molecular targets for the early diagnosis and treatment of PC.

Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota-Key players in the pathogenesis of celiac disease

Celiac disease(CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens(HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive(specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiotahomeostasis, epithelial layer integrity, and the gutassociated lymphoid tissue with its intraepithelial lymphocytes(IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.

Differential gene expression profiling of gastric intraepithelial neoplasia and early-stage adenocarcinoma

AIM: To investigate the differentiated whole genome expression profiling of gastric high- and low-grade intraepithelial neoplasia and early-stage adenocarcinoma.

RELATIONSHIP BETWEEN CYCLIN G1 AND HUMAN PAPILLOMA VIRUS INFECTION IN CERVICAL INTRAEPITHELIAL NEOPLASIA AND CERVICAL CARCINOMA

Objective To evaluate the overexpression of cyclin G1 in cervical intraepithelial neoplasia （CIN） and cervical carcinoma, and the correlation between cyclin G1 and high-risk human papilloma virus （HPV） infection. Methods All of the specimens were obtained from the Department of Pathology of China-Japan Friendship Hospital from January 2000 to August 2004. We detected the expression of cyclin G1 with immunohistochemistry, HPV16/18 infection with in situ hybridization, and high-risk HPV infection with Hybrid capture system Ⅱ （HC-Ⅱ） in normal group （25 cases）, CIN Ⅰ （48 cases）, CIN Ⅱ （56 cases）, CIN Ⅲ（54 cases）, and invasive cervical squamous-cell carcinoma （SCC, 31 cases）. Results The positive rates of cyclin G1 expression in CIN（77.85% ）and SCC cervical tissues （87. 10% ） were significantly higher than normal （ 8.00%, P 〈 0. 01 ）, and the intensities of cyclin G1 expression in CIN（40. 60% ） and SCC cervical tissues （61.51%） were significantly higher than normal （2. 72%, P 〈0.05）. The positive rates and intensities of cyclin G1 expression increased gradually with the grade of cervical lesions. High-risk HPV infection rates were higher in CIN and SCC than normal groups （P 〈 0.05 ）. There was a positive correlation between cyclin G1 expression and high-risk HPV infection detected with HC-Ⅱ （Kendall＇s tau-b =0. 316, 0. 269, 0. 352, and 0. 474 in CIN Ⅰ, CIN Ⅱ, CIN Ⅲ, and SCC, respectively, P 〈 0. 05 ）. Conclusions Cyclin G1 is overexpressed in CIN and SCC. Cyclin G1 may be a biomarker for detecting CIN and SCC. Cyclin G1 may play an important role in the oncogenesis of CIN and SCC by high-risk HPV infection.

Pancreatic intraepithelial neoplasia arising from an ectopic pancreas in the small bowel

BACKGROUND： Ectopic pancreatic tissue is relatively uncommon, and is characterized as pancreatic tissue with no contact with the normal pancreas, and with its own ductal system and blood supply. It is usually asymptomatic, and can be incidentally diagnosed by conventional imaging studies. METHOD： A 69-year-old woman with a prior history of bilateral breast carcinoma presented with ectopic pancreatic intraepithelial neoplasia （PanIN） that was identified incidentally in the small bowel during an oncological resection of a synchronous primary pancreatic adenocarcinoma, and renal cell carcinoma. RESULTS： The patient underwent subtotal pancreatectomy with splenectomy, regional lymphadenectomy, radical left nephrectomy, and small bowel resection with primary anastomosis of ectopic PanlN-2. She had an uneventful hospitalization and was discharged home on postoperative day 7. CONCLUSIONS： The occurrence of ectopic PanIN is extremely unusual with only few cases previously reported in the literature. The need for negative margins after surgical resection of ectopic PanIN lesions remains controversial.

Diagnostic and Therapeutic Cold Knife Conization for Cervical Intraepithelial Neoplasia

OBJECTIVE of using cold （CIN）. METHODS To evaluate the diagnostic and therapeutic efficacy knife conization for cervical intraepithelial neoplasia We retrospectively analyzed 186 cases with CIN diagnosed and treated in our hospital; compared the histologic diagnoses from cervical conization and from colposcopic multiple punch biopsies, and then evaluated their postoperative histologic findings and clinical outcomes. RESULTS Of the 186 cases, there was a correlation in histologic findings between cervical conization and colposcopic multiple punch biopsies in 138 cases （74.2%）, and there was no correlation in the other 48 cases （25.8%）. Incomplete excision was performed in 8 cases （4.3%）, but the failure rate was only 1.1%; the cure rate was 98.9%. Five cases with early invasive cancer were found. Eleven patients underwent subsequent hysterectomy. The main complications associated with conization were hemorrhage and cervical stenosis. Bleeding occurred in 8 （4.3%） of the patients, and cervical stenosis occurred in 3 （1.6%）. CONCLUSION Cervical intraepithelial neoplasia was diagnosed more accurately using conization than by colposcopic multiple punch biopsies. Conization can also play an important role in the treatment for CIN. If properly performed, the procedure has a low risk of complications. It can provide an accurate histologic representation of the disease process, and be curative in most cases.

Anal intraepithelial neoplasia: A review of diagnosis and management

Anal intraepithelial neoplasia(AIN) is a premalignant lesion of the anal mucosa that is a precursor to anal cancer. Although anal cancer is relatively uncommon, rates of this malignancy are steadily rising in the United States, and among certain high risk populations the incidence of anal cancer may exceed that of colon cancer. Risk factors for AIN and anal cancer consist of clinical factors and behaviors that are associated with the acquisition and persistence of human papilloma virus(HPV) infection. The strongest HPV-associated risk factors are HIV infection, receptive anal intercourse, and high risk sexual behavior. A history of HPVmediated genital cancer, which suggests infection with an oncogenic HPV strain, is another risk factor for AIN/anal cancer. Because progression of AIN to anal cancer is known to occur in some individuals over several years, screening for AIN and early anal cancer, as well as treatment of advanced AIN lesions, is reasonable in certain high-risk populations. Although randomized controlled trials evaluating screening and treatment outcomes are lacking, experts support routine screening for AIN in high risk populations. Screening is performed using anal cytological exams, similar to those performed in cervical cancer screening programs, along with direct tissue evaluation and biopsy via high resolution anoscopy. AIN can be treated using topical therapies such as imiquimod, 5-flurouracil, and trichloroacetic acid, as well as ablative therapies such as electrocautery and laser therapy. Reductions in AIN and anal cancer rates have been shown in studies where high-risk populations were vaccinated against the oncogenic strains of HPV. Currently, the CDC recommends both high-risk and average-risk populations be vaccinated against HPV infection using the quadrivalent or nonavalent vaccines. It is important for clinicians to be familiar with AIN and the role of HPV vaccination, particularly in high risk populations.

Duodenal intraepithelial T lymphocytes in patients with functional dyspepsia

AIM： To quantify the intraepithelial lymphocytes （IELs） and to document the membrane expression of CD4, CD8, TCRγδ and adhesion and/or activation-associated molecules （CD103, CD28, CD44, CD69, HLA-DR, CD95/ Fas） in the duodenal mucosa of patients with functional dyspepsia （FD） in order to provide arguments for an immunological process in FD. METHODS： Twenty-six FD patients according to Rome Ⅱ criteria （20 were H pylori negative） were studied and compared to 12 healthy adults. IELs were isolated from five duodenal biopsy samples, then quantified by microscopy and flow cytometry while the membrane phenotypes were determined by cytofluorometry. RESULTS： Duodenal histological examination was normal. In H pylori negative patients, the number of IELs was not different from that in healthy controls. Median percentage expression of CD4, CD8, or TCRy8 and CD103, CD44, CD28, CD69 on CD3＋ IELs, among the adhesion/activation associated molecules tested, was not different from that in healthy controls. In contrast, the median percentage expression of CD95/ Fas [22 （9-65） vs 45 （19-88）, P = 0.03] and HLADR expressing CD3＋ IELs [4 （0-30） vs 13 （4-42）, P = 0.04] was significantly lower in the H pylori negative FD group than in healthy controls, respectively. The number of IELs was significantly greater in H pylori positive FD patients than in healthy controls [median ratio for 100 enterocytes 27.5 （6.7-62.5） vs 10.8 （3-33.3）, P = 0.02] due to a higher number of CD8＋ CD3＋ IELs. CONCLUSION： In H pylori negative FD patients, the phenotypic characterization of IELs suggests that we cannot exclude a role of IELs in FD.

Clinical efficacy and prognostic risk factors of endoscopic radiofrequency ablation for gastric low-grade intraepithelial neoplasia

BACKGROUND The use of radiofrequency ablation(RFA)has been reported in the treatment of gastric low-grade intraepithelial neoplasia(LGIN).However,its efficacy and prognostic risk factors have not been well analyzed.AIM To explore the efficacy and prognostic risk factors of RFA for gastric LGIN in a large,long-term follow-up clinical study.METHODS The clinical data of 271 consecutive cases from 198 patients who received RFA for treatment of gastric LGIN at the Chinese PLA General Hospital from October 2014 to October 2020 were reviewed in this retrospective study.Data on operative parameters,complications,and follow-up outcomes including curative rates were recorded and analyzed.RESULTS The curative rates of endoscopic RFA for gastric LGIN at 3 mo,6 mo,and 1-5 years after the operation were 93.3%,92.8%,91.5%,90.3%,88.5%,85.7%,and 83.3%,respectively.Multivariate analyses revealed that Helicobacter pylori(H.pylori)infection and disease duration>1 year had a significant effect on the curative rate(P<0.001 and P=0.013,respectively).None of patients had bleeding,perforation,infection,or other serious complications after RFA,and the main discomfort was postoperative abdominal pain.CONCLUSION RFA was safe and effective for gastric LGIN during long-term follow-up.H.pylori infection and disease course>1 year may be the main risk factors for relapse of LGIN after RFA.

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.