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Background Methods Results Conclusion Intraductal papillary mucinous tumour (IPMN) of pancreas is increasingly recognized to have malignant potential. Fukuoka guidelines are commonly used to select patients with IPMN for resection due to high chance of malignancy, which includes high‐grade dysplasia (HGD) or invasive carcinoma (IC).A retrospective study on consecutive patients who have undergone pancreatectomy with IPMN as the final pathology was performed. Operative and survival outcomes were analysed. The positive predictive values (PPV) of high‐risk stigmata (HRS) and worrisome features (WF) of Fukuoka guidelines for HGD/IC were determined.Between August 2011 and September 2020, various types of pancreatectomy were performed for 36 patients with histologically proven IPMN. They included 26 pancreaticoduodenectomy, 7 distal pancreatectomy, 2 central pancreatectomy, and 1 total pancreatectomy. There were 30 branch duct type IPMN, 5 main duct type, and 1 mixed type. There was no 30‐day mortality. Overall complications and pancreatic fistula occurred in 44.4% and 5.6% of patients, respectively. Patients without HGD/IC had 100% survival at 5 years with no recurrent disease. There were 13 patients with HGD/IC, their 1‐, 3‐, 5‐year overall and disease‐free survival were 84.6%, 76.9%, 67.3% and 84.6%, 68.4%, 58.6%, respectively, both significantly shorter than non‐HGD/IC group (P = 0.002 and 0.001, respectively). The PPV of HRS and WF for HGD/IC were 33.3% and 23.5%, respectively. The combined PPV of HRS and WF for HGD/IC was 38.0%.Survival after pancreatectomy for IPMN was favourable, but was significantly worse in the presence of HGD/IC. Fukuoka guidelines were useful in predicting malignant IPMN. [ABSTRACT FROM AUTHOR]

Gastric cardia adenocarcinoma (GCA) and esophageal squamous cell carcinoma (ESCC) present significant health challenges in China, often diagnosed at advanced stages with poor prognoses. However, effective biomarkers for early detection remain elusive. This study aimed to integrate methylome and transcriptome data to identify DNA methylation markers for the early detection of GCA and ESCC. In the discovery stage, we conducted Infinium MethylationEPIC array analysis on 36 paired GCA and non-tumor adjacent tissues (NAT), identifying differentially methylated CpG sites (DMCs) between GCA/ESCC and NAT through combined analyses of in-house and publicly available data. In the validation stage, targeted pyrosequencing and quantitative real-time RT-PCR were performed on paired tumor and NAT samples from 50 GCA and 50 ESCC patients. In the application stage, an independent set of 438 samples, including GCA, ESCC, high- and low-grade dysplasia (HGD/LGD), and normal controls, was tested for selected DMCs using pyrosequencing. Our analysis validated three GCA-specific, two ESCC-specific, and one tumor-shared DMCs, exhibiting significant hypermethylation and decreased expression of target genes in tumor samples compared with NAT. Leveraging these DMCs, we developed a GCA-specific 4-marker panel (cg27284428, cg11798358, cg07880787, and cg00585116) with an area under the receiver operating characteristic curve (AUC) of 0.917, effectively distinguishing between cardia HGD/GCA patients and cardia LGD/normal controls. Similarly, an ESCC-specific 3-marker panel (cg14633892, cg04415798, and cg00585116) achieved an AUC of 0.865 in distinguishing esophageal HGD/ESCC cases. Furthermore, integrating cg00585116, age, and alcohol consumption yielded a tumor-shared logistic model with good discrimination for two cancer/HGD (AUC, 0.767; 95% confidence interval, 0.720–0.813). The mean AUC of the model after 5-fold cross-validation was 0.764. In summary, our study identifies novel DNA methylation markers capable of accurately distinguishing GCA/ESCC and HGD from LGD and normal controls. These findings offer promising prospects for targeted DNA methylation assays in future minimally invasive cancer screening methods. [ABSTRACT FROM AUTHOR]

Background Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer. Methods Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated. Results We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC. Conclusion UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.

Screening colonoscopy and polypectomy are the cornerstone in decreasing the incidence and mortality of colorectal cancer. Despite the low incidence of colorectal cancer in India, there has been a rising trend in the incidence of colonic polyps and cancer over the last decade. It is, hence, imperative that we are well equipped in the management of colonic polyps. Adequate training in the detection and characterization of polyps to aid in their management is necessary. Detection of polyps can be increased by adhering to the standards of colonoscopy, including good bowel preparation, cecal intubation rate, adequate withdrawal time and use of distal attachment devices. A detected polyp needs optimal characterization to predict histology in real time and decide on the management strategies. Characterization of the polyps requires high-definition-white light endoscopy and/or image-enhanced endoscopy (dye based or digital). Various factors that help in predicting histology include size, location and morphology of the polyp and the pit pattern, vascular and surface pattern of the polyp. Polyps can be differentiated as neoplastic or non-neoplastic with reasonable accuracy with the above features. Prediction of advanced pathology including high-grade dysplasia and deep sub-mucosal invasion is essential, as it helps in deciding if the lesion is amenable to endotherapy and the technique of endoscopic resection. Adequate training in image-enhanced endoscopy is necessary to assess advanced pathology in polyps. Technology pertaining to image-enhanced endoscopy includes narrow banding imaging and blue laser imaging; newer variations are being introduced every few years making it necessary to be abreast with growing information. The recent advances in gastrointestinal (GI) endoscopy with the advent of endocytoscopy and artificial intelligence seem promising and are predicted to be the future of GI endoscopy. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) outcomes in terms of incidence and mortality are significantly worse in African Americans than other Americans. While differences in primary preventions for neoplasia (diet, obesity remediation, aspirin prophylaxis) are being elucidated, genetic mutations affecting premalignant lesions and immune response mechanisms may possibly also explain the increased incidence and mortality, particularly from right-sided disease. Objective: Our team therefore examined colonic segments seeking to test the hypothesis that the immune response and somatic genetic profiles of the colonic anatomic segments may vary and thus account for variations in neoplasia risk among the various colonic segments revealing an antigenic relationship with precancerous lesions. The p87 antigenic field effect is recognized via Adnab-9 antibody immunohistochemistry to be significantly less in the right colon in African Americans, particularly in the cecum. Method: Since small high-grade dysplastic adenomas (SHiGDA) likely missed by CRC screening may progress to cancer, we used Ion Torrent™ sequencing of DNA extracted from four normal colonic segments (two left-sided and two right) of patients with SHiGDAs. We also contrasted unique mutational fields in one patient with a large HiGDA (APC with unique mutations) and one patient who prospectively developed a SHiGDA (JAK3). Result: The SHiGDA (small high-grade dysplastic polyp) patient was p87 negative for any extracted stool, saliva, or colonic effluent via ELISA (enzyme linked immunoadsorbant assay). Furthermore, mean values of expression in segments from the right colon were reduced with respect to the means obtained from the left segments in 233 patients evaluated for a p87 field effect. This has recently been shown to be the case in a large cohort of AA and Caucasian 2294 patients, possibly explaining the right-sided CRC disparity in African Americans and the subsequent increase in mortality. This field effect disparity is also true for two cancers contracted by the SHiGDa patient (lung and prostate). Conclusion: Thus, this pilot study suggests that the reduction in p87 in the right colon is possibly correlated with JAK3 mutations. If confirmed, JAK3 mutations, known to be associated with immune aberrations, may provide a mechanistic explanation for the lack of a p87 (protein 87 kilodaltons) field in some patients with HGD polyps who might benefit from possible intervention such as more intensive screening. Limited microbiome studies were also performed on two patients with familial cancer syndromes and these compared favorably with controls available from the literature.

Background: Many studies reported the presence of adenomas with high-grade dysplasia (HGD) at index colonoscopy increased the incidence of advanced neoplasia (AN) and colorectal cancer (CRC) following. However, the conclusion remains obscure due to lack of studies on the specific population of adenomas with HGD. This study aimed to assess the long-term risk of AN and CRC after removal of adenomas with HGD. Methods: A total of 814 patients who underwent adenomas with HGD removal between 2010 and 2019 were retrospectively analyzed. The outcomes were the incidences of AN and CRC during surveillance colonoscopy. Cox proportional hazards models were utilized to identify risk factors associated with AN and CRC. Results: During more than 2000 person-years of follow-up, we found that AN and CRC incidence densities were 44.3 and 4.4 per 1000 person-years, respectively. The 10-year cumulative incidence of AN and CRC were 39.1% and 5.5%, respectively. In the multivariate model, synchronous low-risk polyps (HR 1.80, 95% CI 1.10–2.93) and synchronous high-risk polyps (HR 3.99, 95% CI 2.37–6.72) were risk factors for AN, whereas participation in surveillance colonoscopy visits (HR 0.56, 95% CI 0.36–0.88 for 1 visit; HR 0.10, 95% CI 0.06–0.19 for ≥ 2 visits) were associated with decreased AN incidence. Additionally, elevated baseline carcinoembryonic antigen (CEA) level (HR 10.19, 95% CI 1.77–58.59) was a risk factor for CRC, while participation in ≥ 2 surveillance colonoscopy visits (HR 0.11, 95% CI 0.02–0.56) were associated with decreased CRC incidence. Interestingly, for 11 patients who developed CRC after removal of adenomas with HGD, immunohistochemistry revealed that 8 cases (73%) were deficient mismatch repair CRCs. Conclusions: Patients who have undergone adenoma with HGD removal are at higher risk of developing AN and CRC, while surveillance colonoscopy can reduce the risk. Patients with synchronous polyps, or with elevated baseline CEA level are considered high-risk populations and require more frequent surveillance. [ABSTRACT FROM AUTHOR]

Background/Objectives: Although excision of melanocytic nevi with high‐grade dysplasia is recommended by the World Health Organization (WHO), clinical studies investigating the approach based on the grading dysplasia of melanocytic lesions with peripheral globules (PGs) are lacking. We investigated the grades of dysplasia and their distinguishable dermoscopic and clinical features to provide accurate data for managing these lesions. Methods: We retrospectively classified histologically confirmed melanocytic lesions with PGs according to the 2018 WHO Classification of Skin Tumours criteria in a university hospital in Turkey. Dermoscopic features, lesions, and patient characteristics were recorded. Results: Sixty‐six lesions of 56 patients were included. After classification, 9.1% (n: 6) of lesions were melanomas, 39.4% (n: 26) were high‐grade dysplastic nevi, and 50% (n: 33) were low‐grade dysplastic nevi (n: 33, 50%). There was one nevus with no dysplasia (n: 1, 1.5%). Univariate analysis revealed that ≥31 years of age, irregular shape of peripheral globules, black colour, total colour count, and maximum diameter of the lesion were associated with high‐grade dysplasia and melanoma. In the multivariate analyses, ≥31 years of age (OR = 3.80, 95% CI, 1.17–12.37), irregular shape of peripheral globules (OR = 3.90, 95% CI, 1.15–13.2), and total colour count (OR = 3.21, 95% CI, 1.2–8.5) were significant predictive factors for the lesions with high‐grade dysplasia and melanomas. Conclusions: To avoid the underdiagnosis of both melanomas and high‐grade dysplastic nevi with PGs, the irregular shape of peripheral globules and multiple colours after the third decade may be useful in making an excision decision. The risk increases every 1‐year increase in age. Excision is suggested for all melanocytic lesions with PGs for patients 60 years or older because of the high risk of melanoma and melanocytic nevus with high‐grade dysplasia. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) outcomes in terms of incidence and mortality are significantly worse in African Americans than other Americans. While differences in primary preventions for neoplasia (diet, obesity remediation, aspirin prophylaxis) are being elucidated, genetic mutations affecting premalignant lesions and immune response mechanisms may possibly also explain the increased incidence and mortality, particularly from right-sided disease. Objective: Our team therefore examined colonic segments seeking to test the hypothesis that the immune response and somatic genetic profiles of the colonic anatomic segments may vary and thus account for variations in neoplasia risk among the various colonic segments revealing an antigenic relationship with precancerous lesions. The p87 antigenic field effect is recognized via Adnab-9 antibody immunohistochemistry to be significantly less in the right colon in African Americans, particularly in the cecum. Method: Since small high-grade dysplastic adenomas (SHiGDA) likely missed by CRC screening may progress to cancer, we used Ion Torrent™ sequencing of DNA extracted from four normal colonic segments (two left-sided and two right) of patients with SHiGDAs. We also contrasted unique mutational fields in one patient with a large HiGDA (APC with unique mutations) and one patient who prospectively developed a SHiGDA (JAK3). Result: The SHiGDA (small high-grade dysplastic polyp) patient was p87 negative for any extracted stool, saliva, or colonic effluent via ELISA (enzyme linked immunoadsorbant assay). Furthermore, mean values of expression in segments from the right colon were reduced with respect to the means obtained from the left segments in 233 patients evaluated for a p87 field effect. This has recently been shown to be the case in a large cohort of AA and Caucasian 2294 patients, possibly explaining the right-sided CRC disparity in African Americans and the subsequent increase in mortality. This field effect disparity is also true for two cancers contracted by the SHiGDa patient (lung and prostate). Conclusion: Thus, this pilot study suggests that the reduction in p87 in the right colon is possibly correlated with JAK3 mutations. If confirmed, JAK3 mutations, known to be associated with immune aberrations, may provide a mechanistic explanation for the lack of a p87 (protein 87 kilodaltons) field in some patients with HGD polyps who might benefit from possible intervention such as more intensive screening. Limited microbiome studies were also performed on two patients with familial cancer syndromes and these compared favorably with controls available from the literature. [ABSTRACT FROM AUTHOR]

Background: Local excision by transanal endoscopic microsurgery (TEM) is considered an acceptable treatment for rectal adenomas with high-grade dysplasia (HGD). This study aims to assess the likelihood of harboring an invasive carcinoma in preoperatively diagnosed HGD polyps and evaluate the risk factors for tumor recurrence in patients with final HGD pathology. Methods: Data from patients who underwent TEM procedures for adenomatous lesions with HGD from 2005 to 2018 at the Rabin Medical Center, Hasharon Hospital, were analyzed. Collected data included patient demographics, preoperative workup, tumor characteristics and postoperative results. Follow-up data including recurrence assessment and further treatments were reviewed. The analysis included two subsets: preoperative pathology of HGD (sub-group 1) and postoperative final pathology of HGD (sub-group 2) patients. Results: Forty-five patients were included in the study. Thirty-six patients had a preoperative diagnosis of HGD, with thirteen (36%) showing postoperative invasive carcinoma. Thirty-two patients had a final pathology of HGD, and three (9.4%) experienced tumor recurrence. Large tumor size (>5 cm) was significantly associated with recurrence (p = 0.03). Conclusions: HGD rectal polyps are associated with a significant risk of invasive cancer. Tumor size was a significant factor in predicting tumor recurrence in patients with postoperative HGD pathology. The TEM procedure is an effective first-line treatment for such lesions. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this scoping review is to understand the extent, type of evidence, and overall findings in relation to the impact of endoscopic treatment (ET) on health-related quality of life (HR-QoL) in patients with Barrett's dysplasia and early oesophageal cancer. Methods: A comprehensive search was conducted for literature between 2001 and 2022 in computerised databases (PubMed, Embase, Cochrane Library, and CINAHL Complete). Additionally, sources of unpublished literature were searched in Google Advanced Search. After title and abstract checking, full-text papers were retrieved. Data were extracted, synthesised, key information tabulated, and a narrative synthesis completed. Results: Six studies were included in the final analysis. Twelve different survey tools were utilised across all studies. Study designs included three randomised controlled studies, two prospective observational studies, and a single retrospective observational study. The average age of study participants ranged from 60.3 to 71.0 years. Two studies evaluated HR-QoL as primary outcome measures, but most research evaluated HR-QoL as a secondary outcome. Health domains evaluated in the studies focussed on the biophysical and psychosocial aspects of quality of life. Conclusion: A small number of research studies have been conducted in this area. Due to the heterogeneity and small number of included studies, it was difficult to draw conclusions about the impact of specific ET types on HR-QoL. Overall, there were perceived psychological benefits while undergoing ET. Future research could target specific ET subtypes and measure HR-QoL at baseline and post-procedures in the short and long term. [ABSTRACT FROM AUTHOR]

The indication for surgical resection of intraductal papillary mucinous neoplasms (IPMNs) is defined by imaging features, such as mural nodules. Although carbohydrate antigen (CA) 19-9 was selected as a parameter for worrisome features, no serum biomarkers were considered when deciding on surgical indications in the latest international consensus guideline. In this study, we assessed whether clinical factors, imaging findings, and serum biomarkers are useful in predicting malignant IPMNs. A total of 234 resected IPMN cases in Chiba University Hospital from July 2005 to December 2021 were retrospectively analyzed. Among the 234 patients with resected IPMNs diagnosed by preoperative imaging, 117 were diagnosed with malignant pathologies (high-grade dysplasia and invasive IPMNs) according to the histological classification. In the multivariate analysis, cyst diameter ≥30 mm; p = 0.035), enhancing mural nodules on multidetector computed tomography (≥5 mm; p = 0.018), and high serum elastase-1 (≥230 ng/dl; p = 0.0007) were identified as independent malignant predictors, while CA19-9 was not. Furthermore, based on the receiver operator characteristic curve analyses, elastase-1 was superior to CA19-9 for predicting malignant IPMNs. Additionally, high serum elastase-1 levels (≥230 ng/dl; p = 0.0093) were identified as independent predictors of malignant IPMNs in patients without mural nodules on multidetector computed tomography (MDCT) in multivariate analysis. The serum elastase-1 level was found to be a potentially useful biomarker for predicting malignant IPMNs. [ABSTRACT FROM AUTHOR]

Objective: Intraductal papillary mucinous neoplasms (IPMNs) may be associated with invasive adenocarcinoma, low-grade dysplasia (LGD), or high-grade dysplasia (HGD). We aimed to review the cytologic-histologic correlation of cases with a histologic diagnosis of IPMN. Material and Methods: A database search (January 2010--January 2021) was performed for resected IPMNs with preceding endoscopic ultrasound-guided fine-needle aspiration (FNA). Cytology slides were reviewed for the presence of benign, atypical, or malignant cells, and necrosis. Histologically, IPMNs were classified as benign (LGD) or malignant (HGD or adenocarcinoma). Results: There were 41 patients with IPMN; 24 malignant and 17 benign. Sixteen of the 24 malignant IPMNs were accurately classified as malignant on cytology. There were eight false negatives and one false positive. Cytology yielded a sensitivity of 67% and a specificity of 94%. Among the 16 true positives with FNA diagnosis of adenocarcinoma, seven were IPMNs with HGD, and nine had invasive adenocarcinomas on histology. Cellular morphology and absence or presence of necrosis did not help distinguish HGD from adenocarcinoma on cytology (P > 0.5). Sampling errors and interpretative errors resulted in false-negative cases. Cytology yielded diagnoses related to IPMN in 73% of cases (30/41) and lack of identification of mucinous cells/mucinous background resulted in interpretative errors (9). Conclusion: This study shows that there is a good correlation between cytopathology and surgical pathology diagnoses of IPMNs and that cytology is mostly able to recognize IPMN with HGD/adenocarcinoma. However, heterogeneity in areas of IPMN with HGD/adenocarcinoma may result in sampling errors yielding false-negative cases. Mucinous cells/background should raise the suspicion of IPMN on cytology, even when no neoplastic epithelium is present for the evaluation of dysplasia. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Low-grade dysplasia (LGD) in Barrett's esophagus (BE) is associated with an increased risk of progression to high-grade dysplasia or esophageal adenocarcinoma. However, because of substantial interobserver variability in the diagnosis of LGD, a patient's management plan and health outcome depend largely on which pathologist reviews their case. This study evaluated the ability of a tissue systems pathology test that objectively risk stratifies patients with BE (TissueCypher, TSP-9) to standardize management in a manner consistent with improved health outcomes for patients with BE. METHODS: A total of 154 patients with BE with community-based LGD from the prospectively followed screening cohort of the SURF trial were studied. Management decisions were simulated 500 times with varying generalist (n516) and expert (n514) pathology reviewers to determine the most likely care plan with or without use of the TSP-9 test for guidance. The percentage of patients receiving appropriate management based on the known progression/nonprogression outcomes was calculated. RESULTS: The percentage of patients with 100% of simulations resulting in appropriate management significantly increased from 9.1% for pathology alone, to 58.4% when TSP-9 results were used with pathology, and further increased to 77.3%of patients receiving appropriate management when only TSP-9 results were used. Use of the test results also significantly increased the consistency of management decisions for patients when their slides were reviewed by different pathologists (P < 0.0001). DISCUSSION: Management guided by the TSP-9 test can standardize care plans by increasing the early detection of progressors who can receive therapeutic interventions, while also increasing the percentage of nonprogressors who can avoid unnecessary therapy and be managed by surveillance alone. [ABSTRACT FROM AUTHOR]

Simple Summary: For hilar cholangiocarcinoma (HCCA), margin positivity after hilar resection for bile duct cancer is commonly observed due to its longitudinal spread along the subepithelial plane; however, we cannot draw conclusions regarding the prognostic effects of margins with high-grade dysplasia (HGD) or carcinoma. This study aimed to investigate the significance of positive bile duct margins and indications for extended resection in patients with middle bile duct cancer and to analyze the incidence of the R1 HGD margin and its clinical significance. We found that overall survival and disease-free survival in the R1 HGD–CIS margin were comparable with the R0 margin and significantly better than the R1 carcinoma. Extended resection should be considered in patients with R1 carcinoma-positive margins; however, extended resection in cases of R1 HGD-positive margins may not be necessary. Margin positivity after hilar resection (HR) for bile duct cancer is commonly observed due to its longitudinal spread along the subepithelial plane; nevertheless, we cannot draw conclusions regarding the prognostic effects of margins with high-grade dysplasia (HGD) or carcinoma. We aimed to investigate the oncologic effect according to the margin status after HR, particularly between the R1 HGD and the R1 carcinoma. From 2008 to 2017, 149 patients diagnosed with mid-bile duct cancer in Samsung Medical Center, South Korea, were divided according to margin status after HR and retrospectively analyzed. Recurrence patterns were also analyzed between the groups. There were 126 patients with R0 margins, nine with R1 HGD, and 14 with R1 carcinoma. The mean age of the patients was 68.3 (±8.1); most patients were male. The mean age was higher in R1 carcinoma patients than in R1 HGD and R0 patients (p = 0.014). The R1 HGD and R1 carcinoma groups had more patients with a higher T-stage than R0 (p = 0.079). In univariate analysis, the prognostic factors affecting overall survival were age, T- and N-stage, CA19-9, and margin status. The survival rate of R0 was comparable to that of R1 HGD, but the survival rate of R0 was significantly better compared to R1 carcinoma (R0 vs. R1 HGD, p = 0.215, R0 vs. R1 carcinoma, p = 0.042, respectively). The recurrence pattern between the margin groups did not differ significantly (p = 0.604). Extended surgery should be considered for R1 carcinoma; however, in R1 HGD, extended operation may not be necessary, as it may achieve oncologic outcomes similar to R0 margins with HR. [ABSTRACT FROM AUTHOR]

Background: Mild cellular atypia of esophageal squamous epithelial dysplasia has a risk of progressing to cancer that poses great confusion for pathological diagnosis. There is no research on the diagnosis and differential diagnosis of esophageal squamous dysplasia by the expression of immunohistochemical (IHC) p53. The study aims to conduct a graded diagnosis of esophageal squamous epithelial hyperplasia by combining p53 expressions and microscopic histomorphological characteristics. Methods: The study was conducted from January 2021 to January 2022 and included a total of 208 cases including 262 specimens with atypical hyperplasia or dysplasia of squamous epithelia discovered by esophageal mucosal biopsy. HE staining was used to grade the epithelial hyperplasia degree, and all cases underwent p53 IHC evaluation. Results: Benign lesions: we did not find any p53 IHC mutant-phenotype (0/12 cases) in 12 cases of esophagitis. We found 10 cases (10/80 cases) of p53 IHC mutant-phenotype in 80 cases of low-grade dysplasia, and 158 cases (158/170 cases) of p53 IHC mutant-phenotype of high-grade lesions in 170 cases of high-grade dysplasia and early cancer based on the χ2 test results. We found statistically significant differences in p53 IHC mutant-phenotype between the high-grade squamous epithelial lesions and benign lesions. The sensitivity and specificity of p53 in detecting high-grade squamous epithelial lesions were 92.9% and 89.1%, respectively. The positive predictive value was 94.0%, and the negative predictive value was 87.2%. Conclusion: In this study, we found that p53 IHC had high sensitivity and specificity in detecting high-grade esophageal squamous epithelial lesions. Therefore, it has potential to be used as a routine item in pathological detection for auxiliary risk stratification of esophageal squamous epithelial lesions. [ABSTRACT FROM AUTHOR]

Background: Sessile serrated adenomas are important precursors to colorectal cancers and account for 30% of colorectal cancers. The United States Multi-Society Task Force recommends that patients with sessile serrated adenomas undergo surveillance similar to tubular adenomas. However, the risk of metachronous neoplasia when the high-risk adenoma co-exists with sessile serrated adenomas is poorly defined. Objective: To examine the risk of metachronous neoplasia in the presence of high-risk adenoma and synchronous sessile serrated adenomas compared with isolated high-risk adenoma. Data sources: PubMed, Embase, Scopus, Cochrane Library. Study selection: A literature search for studies evaluating the risk of metachronous neoplasia in patients with high-risk adenoma alone and those with synchronous high-risk adenoma and sessile serrated adenomas during surveillance colonoscopy was conducted on online databases. Main outcome measures: The primary outcome of interest was the presence of metachronous neoplasia. Results: Of the 1164 records reviewed, six (four retrospective and two prospective) studies met inclusion criteria with 2490 patients (1607 males, mean age 59.98 ± 3.23 years). Average follow-up was 47.5 ± 12.5 months. There were 2068 patients with high-risk adenoma on index colonoscopy and 422 patients with high-risk adenoma and synchronous sessile serrated adenomas. Pooled estimates showed a significantly elevated risk for metachronous neoplasia in patients with high-risk adenoma and synchronous sessile serrated adenomas (pooled odds ratio 2.21; 95% confidence intervals 1.65–2.96; p < 0.01). There was low heterogeneity (I2 = 11%) among the studies. Sensitivity analysis of the prospective studies alone also showed elevated risk of metachronous neoplasm (pooled odds ratio 2.56; 95%, confidence intervals 1.05–6.23; p = 0.04). Limitations: Inclusion of a small number of retrospective studies. Conclusions: The presence of high-risk adenomas and synchronous sessile serrated adenomas is associated with an increased risk of metachronous neoplasia. Therefore, shorter surveillance intervals may be considered in patients with high-risk adenoma and synchronous sessile serrated adenomas compared to those with high-risk adenoma alone. [ABSTRACT FROM AUTHOR]

BACKGROUND: Anal high-grade squamous intraepithelial lesions (HSILs) ablation may reduce the incidence of invasive cancer, but few data exist on treatment efficacy and natural regression without treatment. METHODS: An open-label, randomized, multisite clinical trial of human immunodeficiency virus (HIV)-infected adults aged ≥27 years with 1-3 biopsy-proven anal HSILs (index HSILs) without prior history of HSIL treatment with infrared coagulation (IRC). Participants were randomized 1:1 to HSIL ablation with IRC (treatment) or no treatment (active monitoring [AM]). Participants were followed every 3 months with high-resolution anoscopy. Treatment participants underwent anal biopsies of suspected new or recurrent HSILs. The AM participants underwent biopsies only at month 12. The primary end point was complete clearance of index HSIL at month 12. RESULTS: We randomized 120 participants. Complete index HSIL clearance occurred more frequently in the treatment group than in the AM (62% vs 30%; risk difference, 32%; 95% confidence interval [CI], 13%-48%; P < .001). Complete or partial clearance (clearance of ≥1 index HSIL) occurred more commonly in the treatment group (82% vs 47%; risk difference, 35%; 95% CI, 16%-50%; P < .001). Having a single index lesion, compared with having 2-3 lesions, was significantly associated with complete clearance (relative risk, 1.96; 95% CI, 1.22-3.10). The most common adverse events related to treatment were mild or moderate anal pain and bleeding. No serious adverse events were deemed related to treatment or study participation. CONCLUSION: IRC ablation of anal HSILs results in more clearance of HSILs than observation alone.

Over the last two decades, endoscopic eradication therapy has been established as the therapeutic strategy of choice for patients with Barrett's oesophagus-related dysplasia and early oesophageal adenocarcinoma. With a multimodal approach, ablative therapies have been highly effective in achieving remarkable eradication rates of metaplastic epithelium with an acceptable adverse event rate. Among ablative techniques, radiofrequency ablation is currently considered as the first-line option as its efficacy and safety are strongly supported by relevant data. Nevertheless, radiofrequency ablation is costly, and not universally available, or applicable to every situation. Moreover, primary failure and recurrence rates are not negligible. In the last few years, cryotherapy techniques and hybrid argon plasma coagulation have been increasingly assessed as potential novel ablative therapies. Preliminary data have been promising and suggest that they may even have a role as first-line options, alternatively to radiofrequency ablation. The aim of this review is to provide a practical guide for the ablation of Barrett's oesophagus, with emphasis on the different ablative options. [ABSTRACT FROM AUTHOR]

Esophageal adenocarcinoma (EAC) develops in a step-wise manner, from low-grade dysplasia (LGD) to high-grade dysplasia (HGD), and ultimately to invasive EAC. However, there remains diagnostic uncertainty about LGD and its risk of progression to HGD/EAC. The aim is to investigate the role of Ki-67, immune-histochemical marker of proliferation, surface expression in patients with confirmed LGD, and risk stratify progression to HGD/EAC. A retrospective cohort study was conducted. Patients with confirmed LGD and indefinite for dysplasia (IND), with a mean follow-up of ≥1 year, were included. Pathology specimens were stained for Ki-67 and analyzed for evidence of surface expression. Our results reveal that 29% of patients with confirmed LGD who stained positive with Ki-67 progressed to HGD/EAC as opposed to none (0%) of the patients who stained negative, a statistically significant result (P  = 0.003). Similarly, specimens from patients with IND were stained and analyzed revealing a nonsignificant trend toward a higher rate of progression for Ki-67 positive cases versus Ki-67 negative, 30% versus 21%, respectively. Ki-67 expression by itself can identify patients with LGD at a high risk of progression. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the role of immunohistochemical (IHC) expression of p53 and other potential clinical parameters as prognostic markers for predicting neoplastic progression in Barrett oesophagus (BE) patients diagnosed as indefinite for dysplasia (IND). The study included patients with established BE of any extent who had a diagnosis of IND accompanied by concurrent p53 immunohistochemistry (IHC) stain at the index endoscopic procedure and at least one follow‐up examination between 2000 and 2021. Correlation between disease progression from IND to higher‐grade dysplasia [low‐grade dysplasia (LGD), high‐grade dysplasia (HGD) and oesophageal adenocarcinoma (EAC)] and clinicopathological parameters were analysed. A total of 149 patients (99 males; mean age 63.3 ± 10.0 years, range = 35–89) were included in the final analysis. Median follow‐up was 37.1 months [interquartile range (IQR) = 20.5–59.1 months]. Progression rates from IND to LGD and HGD were 12.1% (18 of 149) and 2.7% (four of 149), respectively. On multivariate analysis, the number of IND diagnoses was significantly associated with progression to both LGD and HGD (P = 0.016 and P < 0.001, respectively). Cox regression analysis showed that aberrant p53 expression was significantly associated with progression to LGD [hazard ratio (HR) = 4.87, 95% confidence interval (CI) = 1.91–12.45, P = 0.001] and HGD (HR = 21.81, 95% CI = 1.88–253.70, P = 0.014). Kaplan–Meier survival analysis also demonstrated that aberrant p53 expression was significantly associated with progression to LGD (P < 0.001) and HGD (P = 0.001). Our results suggest that frequency of IND diagnoses and status of p53 expression can help to stratify risk of neoplastic progression in BE patients with IND. [ABSTRACT FROM AUTHOR]

In a case of long-segment Barrett's esophagus with multifocal high-grade dysplasia with multiple comorbidities, circumferential endoscopic submucosal dissection was performed. Following the procedure, the esophageal stricture was also managed.

Endoscopic resection (ER) is feasible for treating well-circumscribed dysplasia in patients with ulcerative colitis (UC). However, long-term prognosis of ER for high-grade dysplasia (HGD) in patients with UC remains unclear. We aimed to evaluate the long-term prognoses of ER for HGD compared with low-grade dysplasia (LGD) and verify the feasibility of ER and follow-up with surveillance colonoscopy for HGD. An observational, single-center retrospective study included 38 and 22 patients with LGD and HGD who were followed-up with surveillance colonoscopy after ER. We evaluated the cumulative incidence rate of metachronous HGD or colorectal cancer (CRC) and identified the characteristics of metachronous dysplasia. The median follow-up period was 56 months, and surveillance colonoscopies were performed 3.6 times (mean). The 5-year cumulative incidence rate of HGD/CRC was relatively high in HGD (24.6%) than in LGD (13.7%), but the difference was not significant (p =.16). In HGD cases, six metachronous dysplasia lesions (two LGD and four HGD) were detected 11.6–40.5 months after ER. However, these patients did not progress to CRC. All metachronous lesions were well-circumscribed and with no invisible dysplasia surrounding them; they were 'endoscopically resectable' lesions. Two of the four metachronous HGD lesions were treated endoscopically and two, by colectomy. No synchronous HGD or CRC was detected in the colectomy specimens. Our results suggest that ER and follow-up with surveillance colonoscopy is feasible in patients with HGD when histological complete resection is achieved. [ABSTRACT FROM AUTHOR]

Background: In patients with BD-IPMN, surgical indications have been focused on finding malignant lesions (HGD, high-grade dysplasia/IC, invasive carcinoma). The aim of this study was to compare the preoperative factors that distinguish HGD from LGD (low-grade dysplasia) and HGD from IC to find the optimal pathologic target for surgery according to individuals, considering surgical risks and outcomes. Methods: We retrospectively analyzed 232 patients with BD-IPMN diagnosed based on pathology after surgery and preoperative images. The primary outcome was identifying preoperative factors distinguishing HGD from LGD, and HGD from IC. Results: In patients with LGD/HGD, a solid component or an enhancing mural nodule ≥ 5 mm (OR = 9.29; 95% CI: 3.3–54.12; p < 0.000) and thickened/enhancing cyst walls (OR = 6.95; 95% CI: 1.68–33.13; p = 0.008) were associated with HGD. In patients with malignant lesions (HGD/IC), increased serum CA 19-9 (OR = 12.59; 95% CI: 1.81–87.44; p = 0.006) was associated with IC. Conclusions: The predictive factors for HGD were the presence of a solid component or an enhancing mural nodule ≥ 5 mm and thickened/enhancing cyst walls compared with LGD, and if accompanied by increased CA 19-9, it might be necessary to urgently evaluate the lesion due to the possibility of progression to IC. Based on this finding, we need to find HGD as the optimal pathologic target for surgery to improve survival in low-surgical-risk patients, and IC could be assumed to be the optimal pathologic target for surgery in high-surgical-risk patients because of high morbidity and mortality associated with surgery. [ABSTRACT FROM AUTHOR]

Background/Aim: Although the link between diverticular disease (DD) of the colon and colon polyp is known, the relationship between colon adenocarcinoma is not clear. This study evaluated the association between DD and adenomatous polyp or colon adenocarcinoma. Methods: Patients who underwent colonoscopy for the first time in 2020-2021 were evaluated and included in this retrospective cohort study. Patients with a previous history of cancer diagnosis, colon surgery, DD, and inflammatory bowel disease were excluded from the study. Age, gender, colonoscopy indications, colonoscopy diagnoses, presence of DD, characteristics of polyps (pathology, diameter, number, localization), and presence of adenocarcinoma were recorded. Obtained data were analyzed between DD and non-DD groups. Results: A total of 2633 patients were included in the study. The prevalence of DD was 16.4%. Colon adenocarcinoma was detected in 4.7%. The adenomatous polyp rate was 14.1%. A significantly higher rate of adenomatous polyps was detected in the DD group compared to the non-DD group (19.7% vs. 12.9%; P = 0.001). Higher rates of high-grade dysplasia (3.0 vs. 1.1%; P = 0.002) and colon adenocarcinoma (7.2% vs. 4.2%; P = 0.008) were observed in the DD group also. In logistic regression analyses, it was observed that the presence of concomitant DD increases the risk of adenomatous polyps (OR: 1.469, 95% CI: 1.158-1.865), the risk of adenomatous polyps with positive villous component (OR: 2.378, 95% CI: 1.437-3.934), the risk of adenomatous polyps with high-grade dysplasia (OR: 2.822, 95% CI: 1.426-5.582), and the risk of colon adenocarcinoma (OR: 2.953, 95% CI: 1.445-6.533). Conclusion: DD is associated with precancerous lesions of the colon (adenomatous polyp, villous adenoma, high-grade dysplasia) and colon adenocarcinoma. Further studies are needed to investigate its association with colon carcinogenesis and its role and value in cancer screening. [ABSTRACT FROM AUTHOR]

Background: Gastric polyposis is common in familial adenomatous polyposis (FAP) syndrome. However, the incidence and risk factors for gastric cancer (GC) are unclear. We aimed to evaluate the incidence of GC and associated risk factors in a large FAP population., Methods: Retrospective review of patients with FAP undergoing upper endoscopy at Mayo Clinic from 1989 to 2023. Cumulative incidence of GC (95% CIs) were calculated using Kaplan-Meier survival approaches. Associations of clinical characteristics with development of GC were examined using Cox proportional hazards regression., Results: A total of 337 patients underwent 2502 endoscopies with a median of 10.4 years (IQR, 3.9-17.2) of endoscopic surveillance. At any time during surveillance, 294 patients (87%) had gastric polyps; 200 (59%), fundic gland polyps; 116 (34%), low-grade dysplasia (LGD); and 11 (3.3%), high-grade dysplasia (HGD). Among these, only 6 patients (2%) developed GC-5 with HGD (3 [50%] on previous endoscopy and 2 [33%] at the time of cancer diagnosis) and 1 (16%) with LGD on previous endoscopy. The 10-year cumulative incidence of GC is 0% with no polyps, 1% with polyps, 6% with LGD, 11% with polyps ≥2 cm, and 20% with HGD. Both HGD and polyps ≥2 cm had a strong association with the development of GC (P < .001)., Conclusion: Although the overall risk of GC in FAP is low, outcomes remain poor. GC can be predicted by endoscopic findings and specific GC surveillance guidelines are imperative to improve detection rates and guide timely intervention., (Copyright © 2024 Society for Surgery of the Alimentary Tract. Published by Elsevier Inc. All rights reserved.)

The aim of the study was to evaluate the diagnostic accuracy of p16/Ki-67 dual immunostaining (p16/ Ki-67 DS) in cervical cytology and the number of positive p16/Ki-67 cells to diagnose high grade cervical intraepithelial neoplasia (CIN2+) in colposcopy population.

Objectives: Specimen adequacy is an important quality assurance component of a cervical Papanicolaou test. Although consensus exists on minimal acceptable cellularity for cervical Papanicolaou tests, no such criteria exist for endocervical curettage (ECC) specimens. We sought to identify minimum acceptable cellularity for accurate diagnosis of high-grade dysplasia (HGD) on ECC.Methods: All patients with HGD diagnosed in a loop electrosurgical excision procedure (LEEP) from May 8, 2018, to December 18, 2019, and an ECC in the preceding 6 months at our institution were included (n = 51). All ECCs performed before the LEEP were evaluated for cellularity of squamous cells using Aperio eSlide Manager (Leica Biosystems). Biopsy results concurrent with the ECC were noted. We compared the number of squamous cells in positive and negative ECC specimens using a t-test. The proportion of ECC specimens and concurrent biopsies undergoing immunohistochemical (IHC) staining for p16 were compared using the χ2 test. P < .05 was considered significant.Results: Endocervical curettage specimens positive for HGD have increased cellularity compared with negative ECC specimens (mean cellularity, 10,165 vs 1,055; P < .05). Further, IHC staining for p16 was more likely to be performed on an ECC specimen positive for HGD than on a negative ECC specimen (50% vs 3%; P < .05). Biopsies performed concurrently with a negative ECC finding were more likely to undergo p16 IHC than biopsies performed concurrently with a positive ECC finding (51% vs 7%; P < .05). Finally, we observed no difference in the proportion of biopsies undergoing IHC staining for p16 when comparing biopsies positive for HGD with negative biopsies (37% vs 46%; P = .33).Conclusions: We find cellularity of approximately 10,000 cells adequate to diagnose HGD in an ECC specimen and cellularity of approximately 1,000 cells to be inadequate. Further, we find p16 IHC commonly used as a "rule-in" test on ECC specimens at our institution. Biopsies accompanying an ECC specimen negative for HGD are more likely to undergo p16 IHC than those accompanying an ECC specimen positive for HGD, but there is no difference in the proportion of biopsies undergoing p16 IHC when comparing positive and negative results in the biopsies themselves. These findings further support the need for adequate cellularity for diagnosis in ECC, especially when a biopsy is technically difficult. Further areas for exploration include investigating laboratory procedures to maximize the cellularity of ECC specimens. [ABSTRACT FROM AUTHOR]

Background: Colonoscopy surveillance guidelines set the surveillance schedule based on polyp characteristics. Polyps with high-grade dysplasia (HGD) require 3 years of follow-up regardless of size. However, it is unclear whether patients with diminutive polyps (≤5 mm) with HGD have a higher risk. We evaluated the effect of diminutive adenoma with HGD on adenoma occurrence. Methods: From January 2015 to December 2017, patients who underwent index and surveillance colonoscopy were retrospectively screened. The patients were grouped into no adenoma group, low-risk (patients with ≤2 low-grade dysplasia [LGD]), diminutive HGD, and high-risk (HGD >5 mm, ≥3 adenomas) groups according to the index colonoscopy results. Each group was analyzed using logistic analysis. Results: The mean follow-up period was 22.47 months. Altogether, 610 (50.45%) patients had LGD and 152 (12.5%) had HGD. Among them, 61 (5.0%) patients had a diminutive polyp with HGD. Analysis of the risks of developing advanced adenoma in the surveillance colonoscopy showed that compared to the no adenoma group, the diminutive HGD group did not show a significant risk (odds ratio [OR] = 1.503 [0.449–5.027], p = 0.509), while the high-risk group showed a significant risk (OR = 2.044 [1.015–4.114], p = 0.045). Conclusions: Diminutive adenoma with HGD increased the risk of adenoma on surveillance colonoscopy, and in the case of advanced adenoma, the risk was increased, but it was not statistically significant. [ABSTRACT FROM AUTHOR]

Background/Aims: Some cases of gastric low-grade dysplasia (LGD) and high-grade dysplasia (HGD) on forceps biopsy (FB) are diagnosed as gastric cancer (GC) after endoscopic resection (ER). This study aims to evaluate the clinical outcomes of ER for gastric LGD and HGD on pretreatment FB and to identify the factors that predict pathologic upstaging to GC. Methods: Patients who underwent ER for LGD and HGD on pretreatment FB from March 2005 to February 2018 in 14 hospitals in South Korea were enrolled, and the patients’ medical records were reviewed retrospectively. Results: This study included 2,150 cases of LGD and 1,534 cases of HGD diagnosed by pretreatment FB. In total, 589 of 2,150 LGDs (27.4%) were diagnosed as GC after ER. Helicobacter pylori infection, smoking history, tumor location in the lower third of the stomach, tumor size >10 mm, depressed lesion, and ulceration significantly predicted GC. A total of 1,115 out of 1,534 HGDs (72.7%) were diagnosed with GC after ER. Previous history of GC, H. pylori infection, smoking history, tumor location in the lower third of the stomach, tumor size >10 mm, depressed lesion, and ulceration were significantly associated with GC. As the number of risk factors predicting GC increased in both LGD and HGD on pretreatment FB, the rate of upstaging to GC after ER increased. Conclusions: A substantial proportion of LGDs and HGDs on pretreatment FB were diagnosed as GC after ER. Accurate ER procedures such as endoscopic submucosal dissection should be recommended in cases of LGD and HGD with factors predicting pathologic upstaging to GC.

Abstract An endoscope system using 5‐color light‐emitting diodes (LEDs) (EVIS X1: CV‐1500, Olympus Co., Tokyo, Japan) was released worldwide in July 2020. In addition to the improvement of narrow band imaging (NBI), this system enables texture and color enhancement imaging (TXI). TXI makes the lesion reddish and supports better visibility of colorectal lesions in comparison to white light imaging for improving lesion detection. On the other hand, another 4‐color LED endoscope system (ELUXEO: BL‐7000; Fujifilm, Tokyo, Japan) has been on the market in the West since 2017. This system enables blue light imaging (BLI) and linked color imaging (LCI). Generally, the accurate comparison between two images obtained by two different endoscope systems is difficult. To resolve this problem, we developed a method named the tablet‐image comparison (TIC) method. TIC is a simple, easy, and paperless method to get images under similar conditions of two endoscope systems for an accurate comparison. We herein report two colorectal lesions in which accurate comparisons of images between TXI and LCI and between improved NBI and BLI obtained in the EVIS X1 and ELUXEO systems were performed using the TIC method. One was IIa 30 mm (high‐grade dysplasia) and the other was IIa 25 mm (low‐grade adenoma). A detailed comparison between TXI and LCI could be performed by TIC. In these two cases, with a distant view, TXI showed greater redness than LCI. LCI showed slightly higher brightness than TXI. In magnified TXI and LCI, the irregularities observed were similar to NBI and BLI, respectively.

Background: Sessile serrated adenomas are important precursors to colorectal cancers and account for 30% of colorectal cancers. The United States Multi-Society Task Force recommends that patients with sessile serrated adenomas undergo surveillance similar to tubular adenomas. However, the risk of metachronous neoplasia when the high-risk adenoma co-exists with sessile serrated adenomas is poorly defined. Objective: To examine the risk of metachronous neoplasia in the presence of high-risk adenoma and synchronous sessile serrated adenomas compared with isolated high-risk adenoma. Data sources: PubMed, Embase, Scopus, Cochrane Library. Study selection: A literature search for studies evaluating the risk of metachronous neoplasia in patients with high-risk adenoma alone and those with synchronous high-risk adenoma and sessile serrated adenomas during surveillance colonoscopy was conducted on online databases. Main outcome measures: The primary outcome of interest was the presence of metachronous neoplasia. Results: Of the 1164 records reviewed, six (four retrospective and two prospective) studies met inclusion criteria with 2490 patients (1607 males, mean age 59.98 ± 3.23 years). Average follow-up was 47.5 ± 12.5 months. There were 2068 patients with high-risk adenoma on index colonoscopy and 422 patients with high-risk adenoma and synchronous sessile serrated adenomas. Pooled estimates showed a significantly elevated risk for metachronous neoplasia in patients with high-risk adenoma and synchronous sessile serrated adenomas (pooled odds ratio 2.21; 95% confidence intervals 1.65–2.96; p < 0.01). There was low heterogeneity (I2 = 11%) among the studies. Sensitivity analysis of the prospective studies alone also showed elevated risk of metachronous neoplasm (pooled odds ratio 2.56; 95%, confidence intervals 1.05–6.23; p = 0.04). Limitations: Inclusion of a small number of retrospective studies. Conclusions: The presence of high-risk adenomas and synchronous sessile serrated adenomas is associated with an increased risk of metachronous neoplasia. Therefore, shorter surveillance intervals may be considered in patients with high-risk adenoma and synchronous sessile serrated adenomas compared to those with high-risk adenoma alone.

Uterine ichthyosis is a rare condition characterized by the extensive replacement of the endometrial surface with keratinized squamous epithelium. While generally benign, it can be associated with premalignant or malignant lesions, making its management critical. Here, we present a case of a 66-year-old patient diagnosed with uterine ichthyosis, highlighting the presence of high-grade dysplasia within the metaplastic squamous epithelium. This finding emphasizes the necessity for careful evaluation and appropriate surgical treatment to rule out potential associated neoplasms. Given the rarity of uterine ichthyosis and its implications for patient management, further research is warranted to establish clear guidelines for diagnosis and treatment. This case underscores the importance of ongoing clinical vigilance and interdisciplinary collaboration in managing patients with this condition., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Maltauro et al.)

Background: Ubiquitin C-terminal hydrolase L1 (UCHL1), which encodes thiol protease that hydrolyzes a peptide bond at the C-terminal glycine residue of ubiquitin, regulates cell differentiation, proliferation, transcriptional regulation, and numerous other biological processes and may be involved in lung cancer progression. UCHL1 is mainly expressed in the brain and plays a tumor-promoting role in a few cancer types; however, there are limited reports regarding its role in lung cancer., Methods: Single-cell RNA (scRNA) sequencing using 10X chromium v3 was performed on a paired normal-appearing and tumor tissue from surgical specimens of a patient who showed unusually rapid progression. To validate clinical implication of the identified biomarkers, immunohistochemical (IHC) analysis was performed on 48 non-small cell lung cancer (NSCLC) tissue specimens, and the correlation with clinical parameters was evaluated., Results: We identified 500 genes overexpressed in tumor tissue compared to those in normal tissue. Among them, UCHL1, brain expressed X-linked 3 (BEX3), and midkine (MDK), which are associated with tumor growth and progression, exhibited a 1.5-fold increase in expression compared to that in normal tissue. IHC analysis of NSCLC tissues showed that only UCHL1 was specifically overexpressed. Additionally, in 48 NSCLC specimens, UCHL1 was specifically upregulated in the cytoplasm and nuclear membrane of tumor cells. Multivariable logistic analysis identified several factors, including smoking, tumor size, and high-grade dysplasia, to be typically associated with UCHL1 overexpression. Survival analyses using The Cancer Genome Atlas (TCGA) datasets revealed that UCHL1 overexpression is substantially associated with poor survival outcomes. Furthermore, a strong association was observed between UCHL1 expression and the clinicopathological features of patients with NSCLC., Conclusion: UCHL1 overexpression was associated with smoking, tumor size, and high-grade dysplasia, which are typically associated with a poor prognosis and survival outcome. These findings suggest that UCHL1 may serve as an effective biomarker of NSCLC.

In a case of long-segment Barrett's esophagus with multifocal high-grade dysplasia with multiple comorbidities, circumferential endoscopic submucosal dissection was performed. Following the procedure, the esophageal stricture was also managed. [ABSTRACT FROM AUTHOR]

Purpose: This study has two aims: determine the prevalence of CIN3 + in patients with discordant cotesting, defined as negative cytology and positive human papillomavirus (HPV) testing, and identify factors (including HPV strain) associated with CIN3 + , defined as cervical intraepithelial neoplasia (CIN) 3 or cancer within this population. Methods: We conducted a retrospective chart review of women age 30–65 with intact cervices who had discordant cotesting results between January 1, 2013 and September 1, 2018, at an academic medical center. We used the t test for continuous variables and the Chi-square test for categorical variables to compare women with and without CIN3 +. To identify factors associated with CIN3 + , we performed univariate and multivariate logistic regression. Results: The primary outcome was the prevalence of CIN3 + based on pathologic diagnosis following biopsy or excisional procedure. Among 375 patients with discordant co-testing, the mean age was 43.8 years, 58.4% were parous, and 84.8% were white. Overall, 43/375 (12.0%) had CIN3 + and 7/375 (1.9%) had AIS. On logistic regression, only parity ≥ 1 (p = 0.04, adjusted OR = 2.23, CI = 1.06–4.68) was significantly associated with CIN3 +. HPV-18 was less likely to be associated with CIN3 + (p = 0.02, adjusted OR 0.08, CI 0.01–0.65) but was present in 43% of AIS cases. HPV16 and other HR-HPV strains were highly associated with CIN3 +. Conclusion: Women with discordant cotesting are at significant risk for CIN3 +. We recommend that biopsy be performed at the time of indicated colposcopy for all patients with discordant cotesting to assess for high-grade dysplasia. [ABSTRACT FROM AUTHOR]

Background High-grade dysplasia (HGD) and intramucosal carcinoma (IMC) in Barrett’s esophagus (BE) are now well-established indications for endoscopic resection (ER). Radiofrequency ablation (RFA) can be combined with ER in case of flat or long-segment BE ablation. We report here our experience of complementary RFA after widespread ER of neoplastic BE in daily practice. Method We retrospectively reviewed data of 89 patients, treated between 2006 and 2013 by ER alone (group 1) or by ER combined with RFA (group 2). Results Fifty-five patients in group 1 (7F/48M, mean age 68 years) underwent widespread ER with eradication of residual non-dysplastic BE. Complete eradication of HGD/IMC and intestinal metaplasia (IM) was achieved in 32/32 (100%) and 48/55 (87.3%) patients, respectively. Thirty-four patients in group 2 (3F/31M, mean age 67 years) had a multimodal treatment strategy, with widespread ER followed by RFA. Mean Prague classification of BE in this group was significantly longer (C4.4M6.6 vs. C2.7M4.5, P<0.001). Complete eradication of HGD/IMC and non-dysplastic BE was confirmed in 26/27 (96.3%) and 20/34 (58.8%) patients, respectively. There was no significant difference between groups concerning adverse events (16.4% vs. 23.5%, P=0.58) or recurrence rate of HGD/IMC (9.1% vs. 14.7%, P=0.42). The mismatch rate between preoperative and final histological diagnosis was high in both groups, at 45.5% and 26.5%. Conclusions A combination of ER and RFA can treat significantly longer neoplastic BE than ER alone, with the same efficiency and safety. Widespread ER, in contrast, is the only method of obtaining a reliable histological diagnosis. [ABSTRACT FROM AUTHOR]

Objective: To determine the value of neutrophil-lymphocyte ratio for predicting high-grade dysplasia among patients with neoplastic colorectal polyp. Method: We evaluated 30 patients with non-neoplastic polyp, 61 patients with neoplastic polyp (32 with high-grade dysplasia/29 without high-grade dysplasia), and 30 patients with normal colonoscopy as control group. Mean platelet volume, red cell distribution width, neutrophil and lymphocyte levels were recorded and neutrophil-lymphocyte ratio was calculated. Results: Mean neutrophil-lymphocyte ratio of patients with neoplastic polyp were higher than patients with non-neoplastic polyp and control group (2.56 ± 1.47, 1.77 ± 0.44, 1.76 ± 0.62, retrospectively) (p = 0.001). Mean platelet volume of patients with neoplastic polyp (8.76 ± 1.06) was lower than patients with non-neoplastic polyp (9.50 ± 1.27) and control group (10.96 ± 0.83) (p < 0.001). Mean neutrophil-lymphocyte ratio of patients with high-grade dysplasia (3.03 ± 1.88) was significantly higher than patients without high-grade dysplasia (2.14 ± 0.77) (p = 0.022). The cut-off value of neutrophil-lymphocyte ratio to predict the presence of highgrade dysplasia was 2.044 (sensitivity: 69%, specificity: 68%). Conclusion: Neutrophil-lymphocyte ratio, which is a simple non-invasive index can predict high-grade dysplasia and neoplastic polyp. Although mean platelet volume and red cell distribution width are not useful for identifying high-grade dysplasia in patients with colorectal polyp, mean platelet volume may be associated with neoplastic polyp. [ABSTRACT FROM AUTHOR]

Barrett's esophagus (BE) is an important risk factor for high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). The effect of proton pump inhibitors (PPIs) on the chemoprevention of HGD and/or EAC arising from BE remains controversial. PubMed, EMBASE, and Cochrane Library databases were systematically searched. Risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled by a random-effect model. Heterogeneity and its potential source were assessed. Fifteen studies with 26,291 BE patients were included. Meta-analysis of eight cohort studies showed that PPIs can significantly reduce the risk of HGD and/or EAC in BE patients (RR = 0.46; P < 0.001), but meta-analysis of six case-control studies showed no significant benefit of PPIs (OR = 0.64; P = 0.334). Heterogeneity was significant among both cohort and case-control studies, which might be attributed to the information sources of PPIs. There was no significant protective effect of high-dose PPIs on HGD and/or EAC in one RCT (RR = 0.84; P = 0.21), meta-analysis of two cohort studies (RR = 0.61; P = 0.28), or meta-analysis of two case-control studies (OR = 0.32; P = 0.08). Chemoprevention of HGD and/or EAC by PPIs may be considered in BE patients. However, there might not be further preventive effect of high-dose PPIs. [ABSTRACT FROM AUTHOR]

Background and Aim: High‐grade dysplasia (HGD) and T1 lesions are accidentally resected by cold snare polypectomy (CSP) and the characteristics, and follow‐up of them has not been reported. In this study, we analyzed the histopathological findings and recurrence of them. Methods: This was a multicenter retrospective‐cohort study. We collected HGD and T1 lesions of ≤ 10 mm resected by CSP among 15 520 patients receiving CSP from 2014 to 2019 at nine related institutions, and we extracted only cases receiving definite follow‐up colonoscopy after CSP of HGD and T1 lesions. We analyzed these tumor's characteristics and therapeutic results such as R0 resection and local recurrence and risk factors of recurrence. Results: We collected 103 patients (0.63%) and extracted 80 lesions in 74 patients receiving follow‐up colonoscopy for CSP scar. Mean age was 68.4 ± 12.0, and male rate was 68.9% (51/80). The mean tumor size (mm) was 6.6 ± 2.5, and the rate of polypoid morphology and rectum location was 77.5% and 25.0%. The rate of magnified observation was 53.8%. The rates of en bloc resection and R0 resection were 92.5% and 37.5%. The local recurrence rate was 6.3% (5/80, median follow‐up period: 24.0 months). The recurrence developed within 3 months after CSP for four out of five recurrent cases. Comparing five recurrent lesions to 75 non‐recurrent lesions, a positive horizontal margin was a significant risk factor (60.0% vs 10.7%, P < 0.001). Conclusions: High‐grade dysplasia and T1 resected by CSP were analyzed, and the local recurrence rate of them was substantially high. [ABSTRACT FROM AUTHOR]

Purpose: Previous research on the association between proton pump inhibitor (PPI) use and the risk of progression to high-grade dysplasia (HGD)/esophageal adenocarcinoma (EAC) in Barrett's Esophagus (BE) patients has generated inconsistent findings. This meta-analysis was performed to clarify the association. Methods: We performed a comprehensive search strategy to select relevant studies up to September 2020. Heterogeneity was assessed using the I-squared statistic. Odds ratios (OR) and 95% confidence intervals (CI) were calculated through either fixed-effects or random-effects model. Duration-response was also performed to assess the gain effects of different PPI intake duration. Sensitivity analysis, subgroup analyses, and tests for publication bias or other small-study effects were conducted. Results: Twelve studies with 155,769 subjects were included. The PPI use was associated with the reduced risk of BE progression to HGD/EAC (OR = 0.47, 95% CI = 0.32–0.71). In the duration–response analysis, the estimated OR for decreased risk of HGD/EAC with PPI intake duration of 12 months was 0.81 (95% CI = 0.71–0.91). Sensitivity analysis suggested the results of this meta-analysis were stable. No publication bias was detected. Conclusions: PPI use is associated with a decreased risk of HGD/EAC in patients with BE. For further investigation, that more well-designed studies are still needed to elucidate the protective effect of PPI usage on BE patients to prevent HGD/EAC. [ABSTRACT FROM AUTHOR]