Histologic Dysplasia Research Articles

Esophageal cancers missed at upper endoscopy in Central Norway 2004 to 2021 – A population-based study

IntroductionThe incidence of esophageal cancers is increasing in many Western countries and the rate of missed esophageal cancers (MEC) at upper endoscopy is of concern. We aimed to calculate the MEC rate and identify factors associated with MEC.MethodsThis was a retrospective population-based cohort study including 613 patients diagnosed with esophageal cancer in Central Norway 2004–2021. MEC was defined as esophageal cancer diagnosed 6–36 months after a non-diagnostic upper endoscopy. Patient characteristics, tumor localization, histological type and cTNM stage were recorded. Symptoms, endoscopic findings, use of sedation and endoscopists experience at the endoscopy prior to esophageal cancer diagnosis and at the time of diagnosis were recorded. The association between these factors and MEC was assessed.ResultsForty-nine (8.0%) of 613 cancers were MEC. There was a significant increase in annual numbers of esophageal cancer (p < 0.001) as well as of MEC (p = 0.009), but MEC rate did not change significantly (p = 0.382). The median time from prior upper endoscopy to MEC diagnosis was 22.9 (12.1–28.6) months. MEC patients were older and were diagnosed with disease with a lower cTNM stage and cT category than non-missed cancers, whereas tumor localization and histological type were similar between the groups. The use of sedation or endoscopist experience did not differ between the endoscopy prior to esophageal cancer diagnosis and at the time of diagnosis. High proportions of MEC patients had Barrett’s esophagus (n = 25, 51.0%), hiatus hernia (n = 26, 53.1%), esophagitis (n = 10, 20.4%) or ulceration (n = 4, 8.2%). Significant proportions of MECs were diagnosed after inappropriate follow-up of endoscopic Barrett’s esophagus, histological dysplasia or ulcerations.ConclusionsThe annual number of MEC increased during the study period, while the MEC rate remained unchanged. Endoscopic findings related to gastroesophageal reflux disease such as esophagitis and Barrett’s esophagus were identified in a high proportion of patients with subsequent MECs. Cautious follow-up of these patients could potentially reduce MEC-rate.

Manilkara zapota (L.) P. Royen Leaf Mitigates Colitis-Associated Colon Cancer through Anti-inflammatory Modulation in BALB/C Mice.

Colitis-associated colon cancer (CAC) arises from prolonged inflammation of the inner colon lining. An alternative approach to treating or preventing CAC involves the use of natural products such as Manilkara zapota (L.) P. Royen or M. zapota, which has been studied for its medicinal and pharmacological properties. Previous research has demonstrated the anticancer effects of M. zapota leaf aqueous extract (MZLAE) on colon cancer cells. However, no animal study has investigated the effects of MZLAE on CAC. Therefore, this study aimed to assess the potential anti-inflammatory effects of MZLAE on CAC in mice. In the present study, CAC was induced using azoxymethane (AOM) and dextran sodium sulphate (DSS). The mice were randomly assigned into five groups: (a) normal, (b) AOM/DSS, (c) AOM/DSS + 50 mg/kg MZLAE, (d) AOM/DSS + 100 mg/kg MZLAE, and (e) AOM/DSS + 200 mg/kg MZLAE. Various parameters including disease activity index (DAI), colon length and weight, reactive oxygen species (ROS), superoxide, superoxide dismutase (SOD), histopathological assessment, and proinflammatory cytokines expression were analysed. The results indicated that MZLAE improved DAI scores, colon length, colon histological dysplasia and inflammation scores, and SOD level, while also reducing ROS production and expression of proinflammatory cytokines (tumour necrosis factor-alpha (TNF- α) and interleukin 6 (IL-6)). In conclusion, this study suggests that MZLAE may serve as a promising source of antioxidants and anti-inflammatory agents for alleviating CAC.

Integrated Molecular Characterization of Intraductal Papillary Mucinous Neoplasms: An NCI Cancer Moonshot Precancer Atlas Pilot Project.

Integrated molecular analysis of genomic and transcriptomic alterations in the multistep progression of IPMNs, which are bona fide precursors of pancreatic cancer, identifies features associated with progression of low-risk lesions to high-risk lesions and cancer, which might enable patient stratification and cancer interception strategies.

Molecular biomarkers of progression from Barrett’s esophagus to esophageal adenocarcinoma

IntroductionBarrett’s esophagus (BO) is a pre-malignant condition for esophageal adenocarcinoma (OAC), the incidence rate of which has risen dramatically over the last four decades in the Western world. The 5-year survival rate of OAC is poor, and one of the ways to improve it would be by focusing on identifying high-risk Barrett’s patients through a surveillance program. Currently, histologic dysplasia is the only recognized marker of progression to OAC. Molecular biomarkers found in tissue samples that predict which patients have a higher risk of progression to OAC may act as a reliable tool for the stratification of patients with BO.AimTo determine whether molecular biomarkers have a potential use in predicting which patients with BO have a higher risk of progression to OAC.MethodsImmunohistochemistry was performed on 25 tissue samples obtained from the endoscopic biopsies of 19 patients with confirmed BO. Hematoxylin and eosin (H&amp;amp;E) staining was used to confirm the presence of BO and dysplasia. Staining was performed in an external independent laboratory. Statistical analysis using the Mann–Whitney U test was performed using R Studio® statistical software.ResultsOf the 19 patients sampled, three had low-grade dysplasia (LGD), and all had confirmed metaplasia diagnostic of BO. Expression of cyclin D1 was noted to be elevated in patients with LGD compared with those with metaplasia only (p = 0.042). Expression of Sox2 was elevated in metaplastic BO cells compared with normal squamous cells within the same stain (p = 0.046). Of all eight biomarkers tested, β-catenin had the greatest overall expression (p &amp;lt; 0.004).ConclusionsIsolating elevated cyclin D1 in patients with LGD highlights its potential use as a biomarker in identifying BO patients at risk of developing dysplasia, and, in turn, their possible progression to OAC. Elevated levels of both Sox2 and β-catenin may also serve as markers for disease progression when overexpressed in BO patients. Both conclusions, however, would need long-term follow-up to fully establish their prognostic usefulness, as at the time of writing no patients in this study had gone on to develop OAC. Although only a small sample size was present for this study, and follow-up was limited, it serves as a strong pilot for further research into the use of novel biomarkers in predicting which BO patients are at high risk of developing dysplasia and progressing to OAC.

Appendiceal lesions in serrated polyposis patients are easily overlooked but only seldomly lead to colorectal cancer.

Serrated polyposis syndrome (SPS) is the most prevalent colonic polyposis syndrome and is associated with an increased colorectal cancer risk. A recent study in resected appendices of SPS patients reported that 6/23 (26.1 %) of identified serrated polyps had histological dysplasia. We evaluated the prevalence and clinical relevance of appendiceal lesions in a large SPS cohort. Prospective data from 2007 to 2020 for a cohort of 199 SPS patients were analyzed. Data were retrieved from endoscopy and pathology reports. Patients who underwent (pre)clearance colonoscopies, surveillance colonoscopies, or colorectal surgery including the appendix were separately evaluated for the presence of appendiceal lesions. The primary outcome was the prevalence of adenocarcinomas and serrated polyps/adenomas with advanced histology in the surgery group. 171 patients were included, of whom 110 received endoscopic surveillance and 34 underwent surgery. Appendiceal lesion prevalence in the surgery group was 14 /34 (41.2 %, 95 %CI 24.7 %-59.3 %); none were advanced on histology. Detection rates in the (pre)clearance group were 1 /171 (0.6 %, 95 %CI 0.01 %-3.2 %) for advanced and 3 /171 (1.8 %, 95 %CI 0.04 %-5.0 %) for nonadvanced appendiceal lesions, all of which were sessile serrated lesions. During 522 patient-years of surveillance, no advanced appendiceal lesions were detected at endoscopy, and in 1 /110 patients (0.9 %, 95 %CI 0.02 %-5.0 %) was a nonadvanced lesion detected. Appendiceal lesions are common in SPS patients. The discrepancy between the endoscopic detection rate of appendiceal lesions and the reported prevalence in surgically resected appendices suggests a substantial miss-rate of appendiceal lesions during colonoscopy. Advanced appendiceal lesions are however rare and no appendiceal adenocarcinomas occurred, implying limited clinical relevance of these lesions.

Our experience in the short-term diagnostic-therapeutic management of the patient with anal dysplasia

IntroductionAnal intraepithelial neoplasia (AIN) is a premalignant lesion of anal squamous cell carcinoma. HIV-positive males who have sex with males, are the most affected at-risk population. Cytology and anuscopy are the best accepted methods for its diagnosis, although it is controversial which patients should complete it with a biopsy. Neither which patients should undergo treatment nor which is the best treatment is not well established. With this study, we would like to present our experience in the diagnostic-therapeutic management of AIN in the short term. MethodsRetrospective observational study of patients at risk of AIN with altered anal cytology who underwent high-resolution anuscopy with biopsy. After histological confirmation of dysplasia, they started treatment with trichloroacetic acid. Its effectiveness was verified by subsequent cytology. The demographic variables of the sample and the results of both diagnostic and treatment tests were analyzed. ResultsThe majority were HIV-positive males (104/115) and 50% had sexual relations with other men. We included 115 patients with altered anal cytology, of whom 92% had dysplasia on biopsy. 97% with atypia of uncertain significance on cytology had histological dysplasia. Cytology normalized after treatment in 60% of patients. ConclusionEarly detection of AIN should be routinely considered in known at-risk populations. Any cytological abnormality should be biopsied. Tricholoroacetic acid can be an effective treatment achieving a high percentage of regression, although currently, the information we have is of low level of evidence.

Prognostic Role of the Initial Grade of Dysplasia on Premalignant Vocal Fold Lesions

The main objective of this study was to analyze the prognostic role of the initial grade of dysplasia on the progression to SCC. Retrospective cohort. This study was performed in the Otorhinolaryngology Department of a tertiary hospital center from January 2010 to December 2020. Every patient submitted to a microlaryngoscopy during this period with a histology of dysplasia on the first biopsy was included. A total of 112 patients were included and median follow-up was 24 months (range 1-120 months). Mean age at diagnosis was 59.71 (+/- 12.03) and 88 patients were male (78.6%). Initial grade of dysplasia was mild on 60 patients (53.6%), moderate on 24 (21.4%), severe on 18 (16.1%), and carcinoma in situ in 10 (8.9%). Overall, 25 patients (21.4%) developed invasive squamous cell carcinoma (SCC) and 15 (13.4%) died during follow-up. On an adjusted 5 year's progression free survival analysis, considering gender, age, dysplasia grade, tobacco and alcohol consumption, the initial grade of dysplasia was the only factor significantly associated with progression to carcinoma (P=.047). When compared to mild dysplasia, moderate dysplasia had a Hazard Ratio (HR) of 0.81 (95%CI 0.21-3.22); severe dysplasia had a HR of 1.76 (95%CI 0.59-5.30) and carcinoma in situ had a HR of 4.25 (95%CI 1.44-12.59). The initial dysplasia grade seems to be the most important prognostic factor regarding progression to SCC in patients with premalignant vocal fold disease.

Clinical Endoscopic and Histologic Findings of a Long-Term Follow-Up (10.7 Years) After Roux-en-Y Laparoscopic Gastric Bypass: a Prospective Study.

Bariatric surgery, with laparoscopic Roux-en-Y gastric bypass (LYGB), is one of the most effective treatments for long-term weight loss. However, there are few publications concerning endoscopic evaluations at late control. The purpose was to evaluate the macroscopic and histological findings at the distal esophagus, gastric pouch, jejunal limb and the evolution of Barrett's esophagus (BE) in the long term. Cohort of 110 patients with obesity underwent LYGB in a university hospital. Several clinical, endoscopic and histological evaluations were performed after surgery. Exclusion criteria were previous bariatric procedure, hiatal hernia > 4cm, BE with histological dysplasia and body mass index (BMI) > 50kg/m2. Average age was 38.7 ± 9years with 70% females. BMI averaged 39.6 ± 6kg/m2. Follow-up was 10.7 ± 2years, and 18 patients (16.4%) were lost. The total weight loss was 23.4 ± 7kg. Erosive esophagitis, present in 33% of patients, decreased to 5%. After surgery, intestinal metaplasia regressed to cardial mucosa in 5 of 8 patients. One patient developed a short-segment BE. The level of control to gastroesophageal reflux disease (GERD) symptom control was 87% to responders (Visick I-II) and 13% to non-responders (Visick III-IV). An increase in dilated cardia type III was observed (p < 0.001). The length of the gastric pouch increased significantly after surgery (p < 0.001). Anastomotic ulcers healed at 6months with proton pump inhibitor (PPI) use, without recurrence. LYGB is a very effective surgical procedure to control symptoms of GERD and/or endoscopic erosive esophagitis. Besides, regression of Barrett's mucosa to carditis occurred in 62%.

Nuestra experiencia en el manejo diagnóstico-terapéutico a corto plazo del paciente con displasia anal

IntroductionAnal intraepithelial neoplasia (AIN) is a premalignant lesion of anal squamous cell carcinoma. HIV-positive males who have sex with males, are the most affected at-risk population. Cytology and anuscopy are the best accepted methods for its diagnosis, although it is controversial which patients should complete it with a biopsy. Neither which patients should undergo treatment nor which is the best treatment is not well established. With this study, we would like to present our experience in the diagnostic-therapeutic management of AIN in the short term. MethodsRetrospective observational study of patients at risk of AIN with altered anal cytology who underwent high-resolution anuscopy with biopsy. After histological confirmation of dysplasia, they started treatment with trichloroacetic acid. Its effectiveness was verified by subsequent cytology. The demographic variables of the sample and the results of both diagnostic and treatment tests were analyzed. ResultsThe majority were HIV-positive males (104/115) and 50% had sexual relations with other men. We included 115 patients with altered anal cytology, of whom 92% had dysplasia on biopsy. 97% with atypia of uncertain significance on cytology had histological dysplasia. Cytology normalized after treatment in 60% of patients. ConclusionEarly detection of AIN should be routinely considered in known at-risk populations. Any cytological abnormality should be biopsied. Tricholoroacetic acid can be an effective treatment achieving a high percentage of regression, although currently, the information we have is of low level of evidence.

Sporadic non-ampullary duodenal adenoma with low-grade dysplasia: Natural history and clinical management.

Background and study aims Management strategies for sporadic non-ampullary duodenal adenoma with low-grade dysplasia (LGD) are not well established. This study aimed to analyze progression factors and determine suitable treatment strategies for LGD lesions. Patients and methods We retrospectively analyzed consecutive LGD lesions (n = 125) in patients followed up for ≥ 6 months (median, 45 months) and evaluated the changes in clinicopathological features during follow-up. All LGD lesions were classified into two groups: stable LGD (no increase or < 5 mm increase in tumor size, with unchanged histological dysplasia grade) and progressive LGD (≥ 5 mm increase in tumor size and/or progression to high-grade dysplasia or adenocarcinoma). Results Eighty-six LGD were classified as stable and 39 as progressive. Location on the oral side of the papilla of Vater, large initial tumor size ( ≥ 10 mm), macroscopically complex type, red color, and nodularity were significantly frequent in progressive LGD than in stable LGD. In multivariate analysis, large initial tumor size (odds ratio [OR], 10.2; 95 % confidence interval [CI], 3.3–32.1; P < 0.001) and location on the oral side of the papilla of Vater (OR: 1.8, 95 % CI: 1.4–12.5; P = 0.012) were significant factors for progression. Moreover, initial tumor size < 5 mm rarely progressed (0%–3.9 %); however, initial tumor size ≥ 20 mm and 10–19 mm located on the oral side of the papilla of Vater had a high-risk progression rate (75.0–85.7 %). Conclusions According to the risk stratification of progression factors by initial tumor size and location, we can determine suitable treatment indications for LGD lesions.

Expression analysis of p16 and TOP2A protein biomarkers in cervical cancer lesions and their correlation with clinico-histopathological characteristics in a referral hospital, Tanzania.

Biomarkers yield important information for early diagnosis of cervical cancer. However, they are rarely applied for prognosis of cervical cancer in Tanzania, where visual inspection assay with acetic acid or Lugol's iodine and Pap test are being used as the standard screening/ diagnostic methods. This was a retrospective hospital-based cross-sectional study that was conducted to assess cyclin-dependent kinase inhibitor (p16) and topoisomerase II-alpha (TOP2A) proteins expression among women seeking cervical cancer care at Kilimanjaro Christian Medical Centre, Tanzania between May 1, 2017 and May 10, 2018. Immunohistochemistry technique was used to detect the expressions of p16 and TOP2A proteins from the retrieved formalin-fixed and paraffin-embedded (FFPE) cervical biopsies. A total of 145 patients, with a mean age of 52.1 ± 12.9 years, were included in this study. Upon immunohistochemistry staining, 103 (71.0%) and 90 (62.1%) were p16 and TOP2A positive respectively. There was a strong association between histopathological class and p16/TOP2A expression levels (Fisher's exact test, p<0.001). Moreover, there was a strong positive correlation between p16/TOP2A and cancerous cervical lesions (Spearman's rank correlation coefficients = 0.833 and 0.687, p = 0.006 and 0.005, respectively). The age-adjusted odds ratio for predicting cervical cancer lesions were independently significant for p16/TOP2A biomarkers in FFPE cervical tissues [p16: OR = 1.142 (95% CI: 1.059-1.232, p<0.001) and TOP2A: OR = 1.046 (95% CI: 1.008-1.085, p = 0.015)]. Importantly, the diagnostic performance of p16 was higher than that of TOP2A in the diagnosis of cancerous lesions from non-cancerous cervical lesions (sensitivity: 97.2% versus 77.6%, accuracy: 92.8% versus 87.8%, respectively). Our study has highlighted that over-expression of TOP2A is related to the grade of cervical intraepithelial neoplasia but does not predict prognosis in cervical cancer. Similarly, expression of p16 is related to degree of histological dysplasia and malignancy, suggesting its prognostic and predictive value in the management of cervical cancers. Further bigger studies are needed to validate their applications in the early diagnosis of cervical cancer.

Comparison of Estimation Method in Diagnostic Meta-Analysis: An Application in Dentistry

In this study, the objective was to compare different estimation methods in diagnostic meta-analysis. In this scope, DerSimonian and Laird (DL), Restricted Maximum Likelihood (REML), Sidik and Jonkman (SJ), Hedges and Olkin (HO), Maximum Likelihood (ML), Paule and Mandel (PM) estimation methods were examined. In the implementation part, effectiveness of Clinical Oral Examination (COE) in predicting the diagnosis of histological dysplasia or Oral Squamous Cell Carcinoma (OSCC) was studied.

Outcomes of sinonasal oncocytic papilloma by endoscopic approach in 69 patients

ObjectiveSinonasal oncocytic papilloma (SOP) is a rare subtype of sinonasal papilloma. There are currently few reports on its clinical features and outcomes after endoscopic surgical resection. This study aims to explore the clinical characteristics of SOP and potential factors predicting tumor recurrence through a single-center retrospective case series analysis. MethodsWe conducted a retrospective analysis of 69 patients who underwent endoscopic surgery of SOP from June 2012 to April 2019. The data of patients’ demographics, clinical features, follow-up period, and treatment outcomes were collected. ResultsThe series includes 43 males and 26 females with an average age of 60.2 years. The tumor commonly involved the nasal cavity (n = 59; 89.4%), followed by maxillary sinus (n = 31; 44.9%), ethmoid sinus (n = 28; 40.6%), frontal sinus (n = 6; 8.7%) and sphenoid sinus (n = 6; 8.7%). The follow-up period ranged from 3 months to 96 months (mean, 34.6 months) and nine patients (13%) developed tumor recurrence during the follow-up period. Univariate analysis found that the recurrence of SOP was significantly related to tumor attachment site, Oikawa tumor stage, and histological dysplasia (p<0.05). Multivariate COX regression analysis found that Oikawa staging system (p = 0.024) and presence of dysplasia (p = 0.04) were significantly related to tumor recurrence. ConclusionSOP had low recurrence rate which was comparable to sinonasal inverted papilloma in the endoscopic era. Our findings also demonstrated that presence of dysplasia is an independent prognostic factor for recurrence free survival.

Inter-Observer and Intra-Observer Variations in the Assessment of Epithelial Dysplasia in Oral Lichenoid Diseases.

Oral lichen planus (OLP) and oral lichenoid lesions (OLL) can both present with histological dysplasia. Despite the presence of WHO-defined criteria for the evaluation of epithelial dysplasia, its assessment is frequently subjective (inter-observer variability). The lack of reproducibility in the evaluation of dysplasia is even more complex in the presence of a lichenoid inflammation. We evaluated dysplasia in 112 oral biopsies with lichenoid inflammation in order to study the inter-observer and the intra-observer variability.

Large prolapse-related lesions of the sigmoid colon.

Large prolapse-related lesions (LPRL) of the sigmoid colon have been documented histologically but may not be readily recognized endoscopically. Colonic lesions referred for endoscopic mucosal resection (EMR) were enrolled prospectively. Endoscopic features were carefully documented prior to resection. Final diagnosis was made based on established histologic criteria, including vascular congestion, hemosiderin deposition, fibromuscular hyperplasia, and crypt distortion. Of 134 large ( ≥ 20 mm) sigmoid lesions, 12 (9.0 %) had histologic features consistent with mucosal prolapse. Distinct endoscopic features were: broad-based morphology; vascular pattern obscured by dusky hyperemia; blurred crypts of varying size and shape; and irregular spacing of sparse crypts. Focal histologic dysplasia was identified in 6 of 12 lesions (50.0 %). LPRL of the sigmoid colon exhibit a distinct endoscopic profile. Although generally non-neoplastic, dysplasia may be present, warranting consideration of EMR.

Aneuploidy in targeted endoscopic biopsies outperforms other tissue biomarkers in the prediction of histologic progression of Barrett's oesophagus: A multi-centre prospective cohort study.

BackgroundThe cancer risk in Barrett's oesophagus (BO) is difficult to estimate. Histologic dysplasia has strong predictive power, but can be missed by random biopsies. Other clinical parameters have limited utility for risk stratification. We aimed to assess whether a molecular biomarker panel on targeted biopsies can predict neoplastic progression of BO.Methods203 patients with BO were tested at index endoscopy for 9 biomarkers (p53 and cyclin A expression; aneuploidy and tetraploidy; CDKN2A (p16), RUNX3 and HPP1 hypermethylation; 9p and 17p loss of heterozygosity) on autofluorescence-targeted biopsies and followed-up prospectively. Data comparing progressors to non-progressors were evaluated by univariate and multivariate analyses using survival curves, Cox-proportional hazards and logistic regression models.Findings127 patients without high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) at index endoscopy were included, of which 42 had evidence of any histologic progression over time. Aneuploidy was the only predictor of progression from non-dysplastic BO (NDBO) to any grade of neoplasia (p = 0.013) and HGD/OAC (p = 0.002). Aberrant p53 expression correlated with risk of short-term progression within 12 months, with an odds ratio of 6.0 (95% CI: 3.1–11.2). A panel comprising aneuploidy and p53 had an area under the receiving operator characteristics curve of 0.68 (95% CI: 0.59–0.77) for prediction of any progression.InterpretationAneuploidy is the only biomarker that predicts neoplastic progression of NDBO. Aberrant p53 expression suggests prevalent dysplasia, which might have been missed by random biopsies, and warrants early follow up.

Aneuploidy in Targeted Endoscopic Biopsies Outperforms Other Tissue Biomarkers in the Prediction of Histologic Progression of Barrett's Oesophagus: A Multi-Centre Prospective Cohort Study

Introduction: The cancer risk in Barrett’s oesophagus (BO) is difficult to estimate. Confirmed histologic dysplasia has strong predictive power, but can be missed by random biopsies, while other clinical parameters have limited utility for risk stratification. We aimed to assess the utility of a large panel of molecular biomarkers on targeted biopsies to predict neoplastic progression of BO. Methods: In a prospective study in three tertiary centres, 203 patients with BO were tested for 9 biomarkers (p53 and cyclin A expression; aneuploidy and tetraploidy; CDKN2A (encoding for p16), RUNX3 and HPP1 hypermethylation; 9p and 17p loss of heterozygosity) on autofluorescence-targeted biopsies taken at index endoscopy and followed-up as per clinical standard. Data comparing progressors to non-progressors were evaluated by univariate and multivariate analyses using survival curves, Cox-proportional hazards and logistic regression models. Findings: 127 patients with no high-grade dysplasia (HGD) or early oesophageal adenocarcinoma (OAC) were included, of which 42 had evidence of any histologic progression over time. Aneuploidy was the only predictor of progression from non-dysplastic BO (NDBO) to any grade of neoplasia (p=0.013) and HGD/OAC (p=0.002). Aberrant p53 expression correlated with the risk of short-term progression within 12 months, with an odds ratio for histologically missed dysplasia of 6.0 (95% CI: 3.1-11.2). A biomarker panel comprising aneuploidy and p53 had an area under the ROC curve of 0.68 (95% CI: 0.59-0.77) for prediction of any histologic progression. Interpretation: In our study, aneuploidy is the only biomarker that predicts neoplastic progression of NDBO. Aberrant p53 expression suggests prevalent dysplasia, which might have been missed by random biopsies, and warrants early follow up. Funding Statement: This study was funded by a Medical Research Council Program Grant to RCF and by a Lister Institute for Preventive Medicine prize to RCF, with additional clinical research infrastructure support from the Experimental Cancer Medicine Centre and the Cambridge Biomedical Research Centre. Declaration of Interests: KR reports grants, personal fees and non-financial support from Olympus, outside the submitted work. JJGHMB reports grants from Olympus Endoscopy, outside the submitted work. Other authors declare no conflicts of interest. Ethics Approval Statement: This was a prospective study approved by the Cambridgeshire 2 Research Ethics Committee (09/H0308/118) and the Amsterdam University Medical Centre (AUMC) Medical Ethics Committee (MEC 09/073). This was a National Institute of Health research (NIHR) portfolio study (UKCRN ID 7561).

Metachronous colorectal pathology among survivors of young-onset colorectal cancer: Implications for postresection colonoscopic surveillance.

64 Background: Patients with sporadic young-onset colorectal cancer (CRC) are postulated to have a more biologically active colorectum prone to malignant transformation earlier in life. It is unknown whether there is elevated risk for metachronous colorectal pathology after the index cancer. We aimed to define this risk, to inform their post-resection endoscopic surveillance. Methods: Consecutive CRC patients (aged 18-50, n = 728) were prospectively followed after surgical resection between 2009 and 2017. Patients presenting with hereditary CRC, recurrent disease, or without endoscopy follow-up were excluded. All endoscopy records were subjected to natural language processing and further reviewed. Metachronous colorectal pathology of interest included: high-risk adenoma (≥1cm in size, &gt; 3 in number, or tubulovillious/high-grade dysplasia histology), second CRC, and endoscopically detectable local recurrence. Results: During a 48-month (median) follow-up, 457 patients underwent 1,192 person-years of colonoscopic follow-up. The median age at CRC diagnosis was 44 years. Disease arose from the proximal colon in 9.4%, distal colon in 23.0% and rectum in 67.6%, and was stages I/II in 191 (41.8%), III in 185 (40.4%), and IV in 81 (17.7%). The majority (95.8%) underwent segmental resection, while the remainder had extended resections for synchronous pathology not amendable to preoperative endoscopic clearance. The overall incidence of metachronous pathology was 32 per 1000 person-years: 31 patients developed high-risk adenomas (6.8%), 1 had a second CRC (0.2%), and 7 had luminal recurrences (1.5%). The median time to metachronous pathology was 13.9 (IQR: 11.8-33.1) months, with 21 (53.8%) detected between 12 and 48 months post-resection. Conclusions: For young-onset CRC survivors, the incidence of metachronous colorectal pathology was 32 per 1000 person-years of follow-up. Given the time pattern of detection, adding an interval colonoscopy between the current recommended post-resection surveillance at 12 and 48 months may be beneficial. [Table: see text]

Human papillomavirus and human telomerase RNA component gene in cervical cancer progression

This study aimed to examine hTERC gene in different grades of cervical intraepithelial neoplasia (CIN) and cervical cancer, and the association between hTERC and high risk-human papillomavirus (HR-HPV) infection. Patients who underwent cervical cancer screening at the Second Affiliated Hospital of Kunming Medical University between October 2010 and December 2011 were enrolled. All patients underwent liquid-based cytology test and hybrid capture 2 (HC2) for HPV detection. hTERC was examined using fluorescence in situ hybridization (FISH). Cervical colposcopy biopsy was performed if any of the three results was positive. HC2, FISH, and pathology were compared. A total of 1200 women underwent screening, 150 patients underwent cervical biopsy: 32 in the normal group, 38 in the CIN1 group, 66 in the CIN2/3 group, and 14 in the invasive cervical cancer group. More patients had HR-HPV infection in the CIN2/3 group and ICC group compared with the CIN1 group. hTERC increased with increasing histological dysplasia. There was significant difference in hTERC positive rate between each of the three groups. More patients with hTERC gene amplification were observed in the positive HR-HPV group than in the HR-HPV negative group. In conclusion, hTERC is a potential marker for precancerous cervical cancer lesions. hTERC might be correlated with HR-HPV infection in cervical diseases.

HPV-based screening for cervical cancer among women 55-59 years of age

AimMany cervical cancers occurs among women over 65 and prevalence of HPV genotypes in this age cohort is sparingly studied. One aim of this study was to study the prevalence and distribution of HPV genotypes in women 55–59 years, with normal cytology when exiting the screening program. Secondly, HPV clearance as well as the value of HPV genotyping and/or liquid based cytology as triage tests for identifying histological dysplasia among women with persistent HPV was studied.MethodsWomen that exited the screening program with normal cytology, between the years 2012–2014, in Örebro County, Sweden, were invited to this study. A total of 2946 samples were analyzed with a broad-spectrum assay to detect both hrHPV and lrHPV in order to investigate the distribution of genotypes. In the consent group, women with a positive hrHPV test were offered a follow-up test and a cone biopsy for histological confirmation, and a follow up sample 6 months post cone.ResultsThe overall prevalence of hrHPV was 7.4% and 59% of them remained hrHPV positive in a follow-up test after 12 months. A total of 99 women had a cone biopsy done, where 19% showed histological dysplasia. HPV 53 was the most common genotype, and among women with histology confirmed LSIL or HSIL, HPV 31 was most common. A positive hrHPV result showed a PPV of 25% for LSIL+ and 12.5%for HSIL+. Using detection of HPV 16/18 genotypes as a triage test for hrHPV positive tests, indicated FNR for histological LSIL+ and HSIL+ of 94% and 87.5% respectively, whilst triage based on cervical cytology had a FNR of 69% for LSIL+ and 37.5% for HSIL+.ConclusionThe most common hrHPV genotypes among women 55–59 years of age were non HPV16/18 genotypes, and in this population, these genotypes represented most of the histological verified HSIL lesions. This result does not support the proposition of a HPV 16/18 triaging test after a positive hrHPV test as a marker of histological HSIL+ cervical lesions in women over 55 years of age. Similarly, cytological triage after a positive hrHPV showed no additional benefit in this population. Specific triaging tests should be validated to follow post-menopausal women with a positive hrHPV test.