High-grade Neoplasia Research Articles

Retrospective study on endoscopic treatment of recurrent esophageal cancer patients after radiotherapy.

Esophageal cancer poses a significant health burden globally. Endoscopic treatment has emerged as a viable option for patient ineligible for surgery or experiencing disease recurrence post-radiotherapy. Patients visiting the Department of Endoscopy at the Cancer Hospital of China Academy of Medical Sciences between March 2009 and March 2024 were retrospectively analyzed. Inclusion criteria encompassed patients with histologically confirmed esophageal cancer who had not undergone surgery, but received radiotherapy or CRT, and subsequently opted for endoscopic treatment. Data on demographics, treatment modalities, recurrence patterns, histopathological characteristics, and outcomes were collected. Statistical analysis was conducted using SPSS 27.0, employing Kolmogorov-Smirnov tests for data normality assessment. Out of 25 included patients, the mean age was 60.29years, with a predominance of males (88%). Most patients (64%) received chemoradiotherapy (CRT), while the rest underwent radiotherapy alone. The median follow-up duration was 50.92months, with a median recurrence time of 38.92months. Majority (56%) presented with a solitary lesion and 76% had negative margins. Histopathological analysis revealed various stages of cancer, with the most common being high-grade squamous epithelial neoplasia (64%). Survival analysis indicated a 72% overall survival rate, with 16% surviving beyond 5-year post-treatment. Approximately, 20% succumbed during the study, primarily due to non-esophageal causes (16%). Endoscopic treatment shows promise as a therapeutic option for selected esophageal cancer patients, offering favorable outcomes in terms of survival and disease control. Further prospective studies are warranted to validate these findings and optimize patient selection criteria for endoscopic interventions in esophageal cancer management.

The significance of extensive HPV genotyping for cervical high-grade neoplasia among women with atypical glandular cells.

To examine the associated risk of cervical intraepithelial neoplasm grade 3+ (CIN3+) lesions in patients with AGC and extensive human papillomavirus (HPV) genotyping. Cases with atypical glandular cell (AGC) interpretation on a Papanicolaou (Pap) test were identified along with associated extensive HPV genotyping and histologic follow-up results. Within this cohort of 469,694 Pap tests, 0.4% were diagnosed as AGCs. In total, 1267 cases had concurrent high-risk HPV (hrHPV) genotyping, and 40.3% were hrHPV positive. The percentage of AGC cases with cervical CIN3+ on histologic follow-up was 52.2% when hrHPV was positive, whereas it was 4.9% with a negative hrHPV result. The top 5 hrHPV genotypes associated with cervical CIN3+ in this cohort were HPV16, HPV18, HPV58, HPV52, and HPV33. Indeed, 92.8% of the hrHPV-associated CIN3+ lesions identified in this cohort were positive for at least one of these HPV genotypes. The sensitivity of detecting cervical CIN3+ lesions was 85.6% with the top 5 hrHPV genotypes (HPV16/18/58/52/33) and only increased to 89.0% when the additional 12 genotypes were included. In patients with an AGC Pap, the risk of having a cervical CIN3+ lesion is greatly increased by positivity for hrHPV types 16, 18, 58, 52, and/or 33. Incorporating comprehensive HPV genotyping into AGC cytology allows for refined risk stratification and more tailored management strategies.

Should we perform sigmoidoscopy for colorectal cancer screening in people under 45 years?

The strategy for preventing colorectal cancer is screening by colonoscopy, which offers a direct way for detection and removal of adenomatous polyps (APs). American College of Gastroenterology guidelines recommend that people aged ≥ 45 years should undergo colonoscopy; however, how to deal with people aged ≤ 45 years is still unknown. To compare the prevalence of APs and high-grade neoplasia between the left and right colon in patients ≤ 45 years. A retrospective observational study was conducted at a single tertiary III hospital in China. This study included patients aged 18-45 years with undergoing initial colonoscopy dissection and pathological diagnosis AP or high-grade neoplasia between February 2014 and January 2021. The number of APs in the entire colon while screening and post-polypectomy surveillance in following 1-3 years were evaluated. A total of 3053 cases were included. The prevalence of APs in the left and right colon was 55.0% and 41.6%, respectively (OR 1.7, 95%CI 1.6-2.4; P < 0.05). For APs with high-grade neoplasia, the prevalence was 2.7% and 0.9%, respectively (OR 3.0, 95%CI 2.0-4.6; P < 0.05). Therefore, the prevalence of APs and high-grade neoplasia in the left colon was significantly higher than in the right colon in patients aged ≤ 45 years. There were 327 patients who voluntarily participated in post-polypectomy surveillance in following 1-3 years, and APs were found in 216 cases (66.1%); 170 cases had 1-3 polyps (52.0%) and 46 cases had > 3 polyps (14.1%; OR 0.3, 95%CI 0.1-0.6; P < 0.05). This study suggests that flexible sigmoidoscopy would be an optimal approach for initial screening in people aged ≤ 45 years and would be a more cost-effective and safe strategy.

Enhancing upper tract urothelial carcinoma diagnosis: Utility of cytokeratin 17 and CK20/CD44/p53 immunohistochemical panel

Upper tract urothelial carcinoma (UTUC) presents diagnostic challenges due to small biopsy specimen size, poor orientation, and technical obstacles that can yield equivocal diagnoses. This uncertainty often mandates repeated biopsies to evaluate the necessity of nephroureterectomy. Prior studies have suggested cytokeratin 17 (CK17) immunostain as an adjunctive tool for diagnosing bladder urothelial neoplasia in both urine cytology and tissue biopsy specimens. We evaluated the utility of CK17 in differentiating UTUC from benign urothelium and its ability to stratify low-grade from high-grade neoplasia. Our study involved a cohort of previously diagnosed cytology (n = 29) and tissue specimens from biopsies and resections (n = 85). We evaluated CK17 staining percentage in cytology and tissue samples and localization patterns in biopsy/resection samples. Our findings showed a statistically significant distinction (p < 0.05) between UTUC and benign tissue specimens based on full thickness localization pattern (odds ratio 8.8 [95% CI 1.53–67.4]). The percentage of CK17 staining failed to significantly differentiate neoplastic from non-neoplastic cases in cytology or tissue samples. Additionally, based on prior research showing the efficacy of CK20/CD44/p53 triple panel in bladder urothelial neoplasia, we utilized tissue microarrays to evaluate if these markers could distinguish UTUC from benign urothelium. We found that CK20/CD44/p53, individually or in combination, could not distinguish urothelial neoplasia from non-neoplasia. Full thickness CK17 urothelial localization by immunohistochemistry was highly reproducible with excellent interobserver agreement and may play a supplementary role in distinguishing upper tract urothelial neoplasia from benign urothelium.

Abstract 4166: TSPO-targeted near-infrared optical probe for early identification and localization of high-risk premalignant pancreatic lesions

Abstract Background: Pancreatic cancer is the third most prevalent cause of cancer death in the U.S. with a ~10% survival rate. Surgery represents one of the best opportunities for extending survival and potential cures. Fluorescence-guided surgery (FGS) employing near-infrared (NIR) fluorescence-based targeting agents improves resection margins, allowing removal of small lesions not visible under white light. We previously reported a targeted NIR tracer (V-1520) of translocator protein (TSPO) expression that demonstrated proof-of-principle utility in high-grade pancreatic lesions arising in Ptf1a-Cre; LSL-KrasG12D/+; Smad4flox/flox (KCS) of pancreatic cancer. The purpose of the present study is to evaluate the utility of V-1520 to identify low-grade, premalignant yet high risk lesions in KCS mice; in this scenario we attempted to model use of V-1520 to remove lesions likely to manifest as future recurrence. We compared the uptake of the tracer in these mice from weaning to adulthood to systematically evaluate the efficacy of FGS as a function of lesion grade. Experimental: The tracer, V-1520, was synthesized and KCS mice were generated as reported.1 Mice were injected with 30μg of V-1520 intravenously 24 hours before imaging. Images were acquired using the 800nm channel. KCS and WT mice were imaged as a function of from 4 to 11 weeks age. After imaging, tumor tissues and major organs were harvested for ex-vivo imaging, histopathology and Cryo-Fluorescent Tomography (CFT). Summary: We found, V-1520 prominently localized in low-grade, premalignant PanIN cystic lesions with malignancy potential, as well as pancreatic tumors with and without local invasion. In contrast, V-1520 did not accumulate in healthy pancreata of KCS or WT mice. Mice as young as 4 weeks exhibited localized accumulation of the tracer with low grade PanIN and early dysplasia. The fluorescence intensity was further enhanced in mice with higher grade disease, whereby the pathology was characterized by high-grade cyst formation, increased nuclear/cytoplasm ratio, acinar to ductal metaplasia and invasion. Low and high-grade neoplasia was characterized by high TSPO immunoreactivity, consistent with in-vivo imaging. Confocal microscopy was used to colocalize V-1520 accumulation and TSPO immunoreactivity; V-1520 was found to prominently localized to premalignant epithelia pancreatic cancer cells. CFT illustrated that the primary localization of V-1520 included the liver, kidneys, and pancreatic diseases. Conclusion: These studies suggest the utility of V-1520 to identify high-risk pancreatic lesions that could be removed with surgery. Encouragingly, the V-1520 was capable of differentiating tumors from surrounding non-tumor tissue at an early stage, which could lead to better resections and delay and/or prevent recurrence in the future. 1. Clinical Cancer Research 26(22), 15 Nov. 2020 5914-5925 Citation Format: Shilpa Sharma, Denise Hernandez, Xiaoxia Wen, Jianbo Wang, Cong-Dat Pham, Beibei Huang, Henry Charles Manning. TSPO-targeted near-infrared optical probe for early identification and localization of high-risk premalignant pancreatic lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4166.

Mucosa color and size may indicate malignant transformation of chicken skin mucosa-positive colorectal neoplastic polyps.

Lipid metabolism reprogramming is suspected to exist in pre-cancerous lesions, including colorectal adenoma. Screening colonoscopy frequently reveals chicken skin mucosa (CSM; white or yellow-white speckled mucosa) surrounding colorectal polyps, caused by macrophages engulfing and accumulating the lipids decomposed by colon cells or adjacent tumors. CSM-positive colorectal polyps are associated with various diseases; however, their prognosis varies greatly. Cold snare polypectomy is commonly used to resect lesions up to 10 to 15 mm in diameter without signs of submucosal invasion but is controversial for CSM-positive colorectal polyps. Improved imaging is required to diagnose and treat CSM-positive colorectal polyps. To highlight the clinical significance of CSM surrounding colorectal polyps and clarify the associated treatment for endoscopists. This retrospective cohort study included 177 patients with CSM-positive colorectal polyps diagnosed using endoscopy. All patient-related information was extracted from the Goldisc soft-clinic DICOM system or electronic medical record system. Based on the pathological results, patients were classified as non-neoplastic polyps (five juvenile polyps), neoplastic polyps, non-invasive high-grade neoplasia (NHGN), or submucosal invasive carcinoma (SM stage cancer). We analyzed and compared the clinical features, suspected risk factors for malignant transformation of neoplastic polyps, and early infiltration of submucosal carcinoma. The diameters of NHGN and SM polyps were much smaller than those of neoplastic polyps. Most NHGN polyps had a deeper red mucosal color. On logistic regression analyses, diameter and deeper red mucosal color were independent risk factors for malignant transformation of neoplastic polyps. Type 1 CSM was more common in high-grade intraepithelial neoplasia and SM; type 2 CSM was more common in neoplastic polyps. Logistic regression analyses revealed no significant differences in the malignant transformation of neoplastic polyps or early submucosal invasion of CSM-positive colorectal cancer. Changes in the CSM mucosa surrounding neoplastic polyps and submucosal invasion of colorectal cancer disappeared within 12 months. No tumor recurrence was found during either partial or complete endoscopic resection of the CSM. CSM-positive colorectal polyps > 1 cm in diameter or with deeper red mucosa may be related to NHGN. Resection of CSM surrounding colorectal adenomas did not affect tumor recurrence.

Margin status after loop electrosurgical excision procedure (LEEP) and laser excision in patients with high-grade cervical neoplasia

IntroductionEarly management of high-grade cervical intraepithelial neoplasia is one of the key steps in cervical cancer prevention after vaccination and screening. It relies on lesion removal by surgical excision, and the French National Cancer Institute (INCa) in 2016 recommend using a loop electro excision procedure (LEEP). However, the laser excision method seems to be as effective with similar rates of negative excision margins and postoperative clearance of HPV. ObjectiveThe main objective of our study was to compare the laser excision method to LEEP by evaluating the quality of the surgical margins. We also studied factors associated with the status of the margins and the depth of cones. MethodsWe conducted a retrospective unicentric study between 2009 and 2017. ResultsTwo hundred and thirty-one patients were included: 154 laser excisions and 77 LEEP. Negative surgical margin was achieved in 69.5 % of laser excisions and 72.7 % of LEEP (p = 0.649). Concerning factors predicting margin status, only a greater cone depth was associated with negative margins (OR: 0.91 (95 %CI: 0.84, 0.89); p = 0.02). The surgical technique was not found to be associated with the status of the margins (OR: 0.85 (95 %CI: 0.46,1.56); p = 0.61). Concerning factors predicting cone depth, only the LEEP was associated with a shorter cone depth (OR: 0.24 (95 %CI: 0.08, 0.69); p 0.008). Significant results are based on univariate analysis. ConclusionNo difference was found between the two technics concerning the rate of negative margins. However, LEEP seems to be associated with shorter cone depth in this study.

TUMOR FIBROSO SOLITARIO CEREBRAL: A PROPÓSITO DE UN CASO

Introduction: Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms that, although typically develop in the visceral pleura, occasionally occur in the intracranial cavity. Furthermore, they are characterized by high rates of metastasis and recurrence. Case Report: We present the case of a 59-year-old male patient with a 3-month history of headache and bradyphrenia. Computed tomography revealed a neoformative tumor infiltrating the nasal cavity, ethmoid sinuses, and anterior cranial fossa, involving the left frontal lobe. The patient underwent two exploratory craniectomies, during which diagnoses suggestive of high-grade glial neoplasia and SFT were made. For precise diagnosis, immunohistochemistry was performed, which was consistent with solitary fibrous tumor. The case is analyzed, focusing particularly on histopathological aspects, the unusual location of this tumor, and its variable clinical manifestations.

An Alternative to Cytology in Triaging Cisgender Men and Transgender Women With HIV for High-Resolution Anoscopy.

To evaluate high-risk human papillomavirus testing (hrHPV) as an alternative for anal cytology in screening for high-grade anal neoplasia (AIN2-3) among males with HIV. To identify predictive risk factors for AIN2-3 and develop a clinical tool to triage males with HIV for high-resolution anoscopy (HRA) without cytology. Retrospective cohort study of 199 adult cisgender men and transgender women with HIV referred to an anal neoplasia clinic in the Southeastern United States between January 2018 and March 2021. Each subject underwent cytology, hrHPV, and HRA. Clinical and sociodemographic risk factors were collected for each subject. Significant risk factors for AIN2-3 were identified using logistic regression, and a triage tool incorporating these factors was developed. Screening test characteristics were calculated for cytology with and without adjunct hrHPV, hrHPV alone, and the triage tool. In multivariate analysis, significant predictors of AIN2-3 were hrHPV positivity (odds ratio [OR] = 11.98, CI = 5.58-25.69) and low CD4 count (OR = 2.70, CI = 1.20-6.11). There was no significant difference in positive or negative predictive values among the tool, stand-alone hrHPV, and anal cytology with adjunct hrHPV. Sensitivity and specificity were not significantly different for stand-alone or adjunctive hrHPV testing. Compared with cytology, stand-alone hrHPV and the novel triage tool reduced unnecessary HRA referrals by 65% and 30%, respectively. Stand-alone hrHPV would have missed 11 of 74 AIN2-3 and generated 74 fewer unnecessary HRAs than current cytology-based screening patterns, which led to 115 unnecessary HRAs in our cohort. We propose triaging those with low CD4 count, hrHPV positivity, and/or smoking history for HRA.

Colonoscopy Combined with Me-Nbi to Observe the Canceration Characteristics of Colon Polyps and the Correlation of RHOC Protein Expression.

The current study was carried out to analyze the characteristics of colon polyps canceration observed by colonoscopy combined with ME-NBI (Magnifying Endoscopy combined with Narrow-Band Imaging) and its correlation with RhoC (Ras homolog gene family, member C) protein expression. For this purpose, A total of 300 patients with colorectal polyps and cancerous lesions (192 colorectal polyps and 200 cancerous lesions) who were treated in the digestive endoscopy room of the hospital and underwent colonoscopy were selected, and they were divided into polyp group and malignant lesion according to the diagnosis results. groups, 150 cases in each group. There were 75 patients with non-adenomatous polyps and 75 patients with adenomatous polyps in the polyp group; 75 patients with high-grade neoplasia and cancerous changes in the malignant group. The microvascular structure and surface structure of the lesions were observed by colonoscopy, and the correlation between microvascular morphological characteristics and RhoC protein expression was analyzed. Results showed that the probability of positive RhoC protein expression in the polyp group was significantly lower than that in the malignant transformation group, and the difference was statistically significant (P<0.05). In the malignant transformation group, the positive rate of RhoC expression in mucosal and submucosal superficial infiltration of 150 patients with colon polyp carcinoma was lower than that in submucosal deep infiltration, and the difference was statistically significant (P<0.05). NICE (National Institute for Clinical Excellence) type 2 was diagnosed as colorectal superficial submucosal The sensitivity, specificity, and accuracy of colorectal submucosal invasion were 73.1%, 84.6%, and 83.2%, respectively; the sensitivity, specificity, and accuracy of NICE type 3 in diagnosing colorectal submucosal invasion were 74.6%, 96.8%, and 92.7%, respectively. . Type 2 and type 3 lesions with cancerous features in NICE classification were correlated with the expression of RhoC protein (P<0.05). In conclusion, NICE classification under colonoscopy combined with magnifying colonoscopy has a good effect on colorectal lesions. Differential diagnostic value, RhoC protein is highly expressed in colon cancer and is closely related to the occurrence of colon cancer and the depth of lesion invasion. With the progression of colorectal adenomas, the expression of RhoC protein in the lesions gradually increased.

Clinical efficacy of primary human papillomavirus (HPV) screening with partial genotyping for HPV-16 and HPV-18 subtypes in women from 25 years old.

Cervical screening programmes differ in the age of women recommended for primary human papillomavirus (HPV) testing. This study aims to determine the clinical efficacy and impact of 14-high-risk HPV DNA testing for women from 25 years old. This was a retrospective analysis of data collected prospectively from women 25 years or older who attended hospital-based gynaecology clinics for cervical screening. Women with history of cervical neoplasia or abnormal cytology were excluded. High-risk HPV DNA testing with partial genotyping for HPV-16 and HPV-18 were performed on cobas 4800 System (Roche Diagnostics International AG, Rotkreuz, Switzerland). Women tested positive for the 12 other high-risk HPV subtypes (HPV-12 other) had a reflex cytology test. Positive screening included positive for HPV-16 and/or HPV-18, HPV-12 other with cytology abnormalities equal to or greater than atypical squamous cells of undetermined significance, and repeated positive HPV at 12 months. HPV detection and colposcopy referral rates, and detection of high-grade neoplasia were determined. Of 10,967 women studied, 822 (7.50%) were HPV DNA positive. The overall discharge rate to routine screening according to screening protocol was 93.1%. Colposcopy referral rate was 4.4%. The screening detected 41 cervical intraepithelial neoplasia grade 2+ (CIN2+) (0.37%) and 31 (0.28%) CIN3+. The number of colposcopies needed per case of CIN2+ was 9.5, similar for women below and above 30 years old. The number of colposcopies needed per case of CIN3+ for HPV-16 positivity was 8.5, compared to 17.0 for other categories (P=0.040). Colposcopy efficacy was similar for HPV-18 and HPV-12 other positivity with abnormal cytology. Taking CIN2+ detection and colposcopy referral rate as endpoints, HPV testing in Singapore can be extended to include women from 25 years old.

Diagnostic value of high-risk HPV other than type 16/18 in high-grade cervical neoplasia among cytology-negative women: A multicenter retrospective study.

Human papillomavirus (HPV) is a necessary cause of cervical cancer, and a tool more sensitive than cytology for the early screening of cervical precancers. The two most carcinogenic genotypes HPV 16/18 have been reported in the majority of studies. High-risk HPVs other than HPV 16/18 (non-16/18-hrHPVs) cause approximately a quarter of cervical cancers, and we aimed to analyze the genotype-specific prevalence, risk and diagnostic efficiency of non-16/18-hrHPVs in cervical carcinogenesis among Chinese cytology-negative women. A total of 7043 females who had abnormal cervical testing results from January 2018 to October 2021 were enrolled, among them 3091 were cytology-negative. Descriptive statistics was used to estimate the HPV genotype-specific prevalence, and multivariable logistic regression was used to estimate the genotype-specific non-16/18 hrHPVs risk of cervical carcinogenesis. The evaluation of diagnostic value among HPV genotypes included the possibility of predicting cervical intraepithelial neoplasia grade 2/3 or worse (CIN2+/CIN3+) and the diagnostic efficiency measured by increased referral rate and referral numbers of colposcopies per additional CIN2+/CIN3+ detected. Among HPV-positive cytology-negative women, the five dominant genotypes for CIN2+/CIN3+ were HPV 31/33/35/52/58. HPV 52/58/33 had comparatively high sensitivity and specificity in predicting CIN2+/CIN3+, while the referral strategy of multiple HPV58 required 26 colposcopies to detect 1 CIN3+, compared with 14, 12, and 8 required by multiple HPV52, 31, and 33, respectively. HPV31/33/35/52/58 infections are significant risk factors for cervical lesions, and multiple HPV 31/33/52 infections should be included in the previously recommended HPV16/18 genotyping triage for colposcopy in China, as the benefits of disease prevention may outweigh the disadvantages of increasing requirements for colposcopy services.

Narrow band imaging versus lugol chromoendoscopy in screening for esophageal squamous neoplasia: a randomized trial.

An optimal method for endoscopic detection of esophageal squamous cell neoplasia in high-risk individuals is not yet established. We aimed to compare the narrow-band imaging (NBI) and Lugol chromoendoscopy in screening for esophageal neoplasia among patients after treatment for head and neck squamous cell cancers (HNSCC). We randomly assigned 300 patients ≥1 year after curative treatment of HNSCC in a 2:1 ratio to NBI or Lugol endoscopy. Following white-light examination of the esophagus, one of the assigned imaging modality was performed and biopsies were taken from any suspicious lesion identified with NBI or Lugol chromoendoscopy. The primary endpoint was positive predictive value (PPV) of biopsied lesion for diagnosis of esophageal neoplasia (high-grade intraephitelial neoplasia (HG-IEN) and invasive squamous cell esophageal carcinoma, ESCC). The secondary endpoints included number of biopsied lesions, time of esophagus examination, and endoscopy tolerance. In 294 patients (204NBI: 90Lugol) 3 ESCC(1.02%) and 2 HG-IEN (0.68%) were diagnosed. The PPV of NBI and Lugol in per-lesion analysis were 7.69% (95% CI, 0.94%-25.1%) and 8.11% (95% CI, 1.70%-21.9%), respectively (P = 1.0). The NBI outperformed Lugol in the rate of patients requiring biopsy (12.75% vs. 41.11%, P = 0.003), esophagus examination time (3.50 min. vs. 5.15 min., P <0.001) and endoscopy tolerance (25.0 mm vs. 36.5mm, P = 0.002). With a comparable PPV, but lower number of biopsies required, shorter examination time and better patient tolerance, NBI could be considered primary screening method for ESCC in patients with HNSCC.

Real-world effectiveness of HPV vaccination against cervical neoplasia among birth cohorts ineligible for routine vaccination.

Human papillomavirus (HPV) vaccine effectiveness may differ between settings. Here we present the first real-world effectiveness study of HPV vaccination on high-grade cervical lesions from Norway, among women who received HPV vaccine outside the routine program. We performed an observational study of all Norwegian women born 1975 to 1996 and retrieved individual data from nationwide registries on HPV vaccination status and incidence of histologically verified high-grade cervical neoplasia during 2006 to 2016. We estimated the incidence rate ratio (IRR) and 95% confidence intervals (CI) for vaccination vs no vaccination by Poisson regression stratified by age at vaccination <20 years and ≥20 years. The cohort consisted of 832 732 women, of which 46 381 (5.6%) received at least one dose of HPV vaccine by the end of 2016. The incidence rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) increased with age regardless of vaccination status and was highest at age 25 to 29, at 637/100 000 among unvaccinated women, 487/100 000 among women vaccinated before age 20 and 831/100 000 among women vaccinated at age 20 or older. The adjusted IRR of CIN2+ between vaccinated and unvaccinated women was 0.62 (95% CI: 0.46-0.84) for women vaccinated below age 20, and 1.22 (95% CI: 1.03-1.43) for women vaccinated at age 20 or older. These findings indicate that HPV vaccination among women too old to be eligible for routine HPV vaccination is effective among women who are vaccinated below age 20 but may not have the desired impact among women who are vaccinated at age 20 or older.

A158 FINDINGS FROM A MULTIDISCIPLINARY DATABASE FOR PATIENTS WITH BARRETT'S ESOPHAGUS AND EARLY ESOPHAGEAL ADENOCARCINOMA

Abstract Background Previously, Barrett’s esophagus (BE) with high grade dysplasia (HGD) or neoplasia was treated with esophagectomy; however, recent guidelines support the use of endoscopic mucosal resection (EMR) for T1a esophageal adenocarcinoma (EAC) and potentially T1b EAC. Long term data for outcomes from EMR are lacking and these treatments are often provided with minimal collaboration between gastroenterologists and thoracic surgeons. Purpose Our primary aim was to describe the findings from our multidisciplinary database of patients with Barrett’s esophagus and EAC undergoing endoscopic treatment. Secondary aims were to compare the overall survival and recurrence-free survival of patients undergoing endoscopic resection to those undergoing esophagectomy. Method For the endoscopic resection cohort, a combined retrospective and prospective database was created containing demographic, clinical, and oncologic variables for patients undergoing endoscopic resection for early stage EAC from 2009 to 2021. For the esophagectomy cohort, a pre-existing retrospective database including patients undergoing esophagectomy for esophageal cancer from 2012 to 2018 at a single institution was used. A multivariate cox proportional hazards model was developed for recurrence-free survival and overall survival using a hypothesis driven approach. A kaplan-meier (KM) curve with associated log-rank test was created to evaluate recurrence-free survival and overall survival stratified by treatment modality. Result(s) A total of 108 patients were included in the analysis (73 EMR, 35 esophagectomy). Baseline characteristics including age, sex, and co-morbidities were similar among the two groups. KM curves stratified by treatment modality are provided in Figure 1. Esophagectomy was associated with greater DFS on univariate log-rank test (p = 0.0127), but no difference in OS (p = 0.9306). There was no significant difference between esophagectomy and endoscopic resection in the cox-model for OS (HR 1.03, 95% CI 0.45-2.32, p = 0.914). Endoscopic resection was associated with increased hazards of disease recurrence in the cox model for DFS (HR 2.56, 95% CI 1.1-6.0, p = 0.032). In the logistic regression model, high grade disease (OR 5.43, 95% CI 1.1 – 26.1, p = 0.035) and submucosal involvement (OR 7.8, 1.9-31.4, p = 0.004) were identified as significant predictors of positive margin necessitating esophagectomy after initial endoscopic resection. All patients who experienced a positive margin after endoscopic therapy were evaluated by a thoracic surgeon and proceeded to esophagectomy. Conclusion(s) In this largely retrospective analysis, our multidisciplinary approach was shown to be highly efficacious in the treatment of BE with EAC. Through optimizing collaboration between thoracic surgeons and gastroenterologists, patients receive the best therapeutic approach for their unique condition, taking into account oncologic factors and clinical comorbidities. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

The other colon cancer: a population-based cohort study of appendix tumour trends and prognosis.

Appendiceal neoplasms are rare subtypes of colorectal tumours that mainly affect younger patients some 20 years earlier than other colon tumours. The aim of this study was to gain more insight into the histological subtypes of this rare disease and include cases previously excluded, such as mucinous neoplasia. The cohort study included 1097 patients from the Munich Cancer Registry (MCR) diagnosed between 1998 and 2020. Joinpoint analysis was used to determine trend in incidence. Baseline demographic comparisons and survival analyses using competing risk and univariate/multivariate methods were conducted according to tumour histology: adenocarcinoma (ADENO), neuroendocrine neoplasia (NEN), mixed adeno-neuroendocrine carcinoma (MANEC), and low- (LAMN) and high-grade mucinous neoplasia (HAMN). Up to 2016 the number of cases increased significantly [annual per cent change (APC)=6.86, p< 0.001] followed by a decline in the following years (APC=-14.82, p= 0.014; average APC=2.5, p= 0.046). Comparison of all patients showed that NEN (48.4%) and mucinous neoplasms (11.6%) had a considerably better prognosis than ADENO (36.0%) and MANEC (3.0%, p< 0.0001). A multivariate analysis within the NEN and ADENO subgroups revealed that further histological classification was not prognostically relevant, while older age and regional tumour spread at diagnosis were associated with a poor prognosis. ADENO histology with high tumour grade and appendectomy only was also associated with poorer survival. Appendiceal neoplasms are histologically heterogeneous; however, this diversity becomes less relevant compared with the marked difference from cancers of the remaining colon. The previously observed increase in cases appears to be abating; fewer cases of appendicitis and/or appendectomies or changes in histopathological assessment may be behind this trend.

Artificial intelligence-guided discovery of gastric cancer continuum

BackgroundDetailed understanding of pre-, early and late neoplastic states in gastric cancer helps develop better models of risk of progression to gastric cancers (GCs) and medical treatment to intercept such progression.MethodsWe built a Boolean implication network of gastric cancer and deployed machine learning algorithms to develop predictive models of known pre-neoplastic states, e.g., atrophic gastritis, intestinal metaplasia (IM) and low- to high-grade intestinal neoplasia (L/HGIN), and GC. Our approach exploits the presence of asymmetric Boolean implication relationships that are likely to be invariant across almost all gastric cancer datasets. Invariant asymmetric Boolean implication relationships can decipher fundamental time-series underlying the biological data. Pursuing this method, we developed a healthy mucosa → GC continuum model based on this approach.ResultsOur model performed better against publicly available models for distinguishing healthy versus GC samples. Although not trained on IM and L/HGIN datasets, the model could identify the risk of progression to GC via the metaplasia → dysplasia → neoplasia cascade in patient samples. The model could rank all publicly available mouse models for their ability to best recapitulate the gene expression patterns during human GC initiation and progression.ConclusionsA Boolean implication network enabled the identification of hitherto undefined continuum states during GC initiation. The developed model could now serve as a starting point for rationalizing candidate therapeutic targets to intercept GC progression.

Detection of high-grade cervical neoplasia using extended genotyping: Performance data from the longitudinal phase of the Onclarity trial

ObjectivesThe Onclarity cervical cancer screening trial was designed to establish the clinical validity of the Onclarity HPV assay for extended genotyping (xGT) during detection of high-grade cervical neoplasia grades 2 or 3 (≥CIN2 or ≥CIN3). Here, three-year follow up data is presented to evaluate the overall efficacy of these screening strategies, compared to the baseline data. MethodsAt baseline 29,513 women, ≥25 years, had evaluable cytology and valid high-risk HPV results. Women with atypical squamous cells-undetermined significance or worse cytology or a positive HPV test were referred for colposcopy/biopsy. Participants that did not reach the study end point (treatment for ≥CIN2) continued into the longitudinal phase that included the same protocol as baseline. ResultsThe three-year cumulative incident risk (CIR) for ≥CIN3 in HPV-negative women was 0.15% [95%CI: 0.06, 0.26] and for HPV- and cytology-negative women was 0.12% [95% CI: 0.03,0.23]. HPV16 carried the highest baseline and three-year ≥CIN3 CIR, followed by HPV31 and HPV18. At least one year of genotype-specific persistence increased ≥CIN3 risk for xGT results compared to genotype non-persistence, HPV clearance, or new infection over the same time period. Risk-based screening with immediate colposcopy for HPV16/18/31 and further xGT triage resulted in better ≥CIN3 sensitivity (79.2% versus 72.3%; relative difference of 6.9 [95%CI: 3.3, 10.4]) and a lower colposcopy/≥CIN3 ratio (9.2 versus 11.2; relative difference of −1.9 [95%CI: −2.6, −1.3]) when compared to primary HPV16/18-based screening. ConclusionsAn HPV-negative result offers the same assurance of no disease over three years of follow up as that offered by a negative co-testing result. xGT facilitates risk-based screening and persistence tracking and can help optimize disease detection during screening without excessive colposcopic procedures.

The risk of incident gastric cancer for populations with different precancerous gastric lesions: a prospective follow-up study

Objective: To provide evidence for optimizing the screening strategy for gastric cancer (GC), we evaluated the risk of incident GC for individuals with different precancerous gastric lesions in a prospective cohort study. Methods: Based on the National Upper Gastrointestinal Cancer Early Detection Program launched in Linqu, Shandong, a high-risk area of gastric cancer in China, we included a total of 14 087 subjects diagnosed with different gastric lesions stages by endoscopic screening from 2012 to 2018. Study subjects were prospectively followed up until December 31, 2019. The incidence of GC during the follow-up was ascertained by repeated endoscopic examinations, cancer, death registry reports, and active follow-up of study subjects and was confirmed by reviewing medical records extracted from the hospital information management system. The Poisson regression model was applied to calculate the relative risk (RR) and 95%CI for GC occurrence among subjects with different gastric lesions. Results: Among 14 087 subjects with different gastric lesions as determined by their first endoscopic examination in 2012-2018, 7 608 (54.00%) had a global diagnosis of superficial gastritis (SG), 2 848 (20.22%) had chronic atrophic gastritis (CAG), 3 103 (22.03%) had intestinal metaplasia (IM), and 520 (3.69%) had low-grade intestinal neoplasia (LGIN). During the follow-up, 109 subjects were diagnosed with GC, including 63 with high-grade intestinal neoplasia (HGIN) and 46 with invasive GC. Compared to subjects having normal gastric mucosa or SG, those with CAG (RR=3.85, 95%CI: 2.04-7.28), IM (RR=5.18, 95%CI: 2.79-9.60), and LGIN (RR=19.08, 95%CI: 9.97-36.53) had significantly increased risk of progression to GC. Individuals with these gastric lesions had an elevated risk of developing HGIN and invasive GC. For subjects with LGIN, the RR was 22.96 (95%CI: 9.71-54.27) for developing HGIN and 14.64 (95%CI: 5.37-39.93) for developing invasive GC. Subgroup analyses found that all age group subjects with LGIN diagnosed during the initial endoscopic examination had a significantly increased risk of developing the GC. Conclusions: Our large-scale prospective study on a high-risk area of GC showed that most residents aged 40-69 years had gastric lesions of different stages. Subjects with more advanced gastric lesions had a significantly increased risk of progression to GC.

The interventional direct peroral cholangioscopy toolbox for endoscopic snare resection of a high-grade biliary intraductal neoplasia

Video 1Demonstration of techniques for performing direct peroral cholangioscopy.