Risk of advanced neoplasia after removal of colorectal adenomas with high-grade dysplasia.

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.

Hepatic Duct Adenoma Identified Using Direct Cholangioscopy.

Bile duct adenomas (BDAs) are rare benign tumors that can arise in the intra-hepatic or extra-hepatic biliary tree. We present a case of a 46-year-old female who presented with symptoms suggestive of choledocholithiasis. Direct cholangioscopy identified a 15 mm polypoid lesion in the common hepatic duct (CHD). Biopsy revealed a BDA. We present this case to highlight the role of direct cholangioscopy in the diagnosis and management of BDAs.

The Outcome of Local Excision of Rectal Adenomas with High-Grade Dysplasia by Transanal Endoscopic Microsurgery: A Single-Center Experience.

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.

Can we manage the melanocytic lesions with peripheral globules according to the grade of dysplasia?

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.

Familial pancreatic cancer: a long fruitful journey.

In the early years of my GI fellowship, a healthy 40-year-old man came to my clinic and announced that he was going to die of pancreatic cancer. His brothers, father and uncles had all died of the disease; he felt his fate was inescapable. I asked whether his family members had seen doctors or had any tests. His answer was yes to both. Even so, doctors could not diagnose the pancreatic cancer at early stages. CT scans were always negative. I thought to myself, in order to help this patient-CT scans may not be reliable for early detection. Perhaps other methods of imaging the pancreas might be of more benefit. This patient opened a door that led to a 30-year journey of trying to detect pancreatic cancer at earlier stages when it is curable.

Differential diagnosis of gastric low- and high grade dysplasia using C6orf15 protein.

OBJECTIVE: To investigate the expression of C6orf15 protein in gastric endoscopic biopsy specimens and its usage as an ancillary diagnostic biomarker in determining the grade of gastric dysplasia. METHODS: We selected 102 patients with gastric endoscopic biopsy specimens from Jinling Hospital. These were divided into four groups: 22 cases of gastric mucosal benign lesions, 28 with low-grade dysplasia (LGD, intestinal-type: 21 cases，foveolar-type: 7cases), 28 with high-grade dysplasia (HGD, intestinal-type: 20 cases，foveolar-type: 8 cases), and 24 cases of gastric adenocarcinoma. We examined the expressions of C6orf15, P53, and Ki67 in 102 gastric endoscopic biopsy specimens, including 47 cases with accompanying endoscopic submucosal dissection (ESD) specimens, using immunohistochemistry. RESULTS: In gastric HGD and gastric adenocarcinoma, the c6orf15 protein exhibits diffuse and strong cytoplasmic expression in tumor cells. Conversely, in gastric LGD and benign gastric mucosal lesions, the c6orf15 protein shows negative or faint yellow cytoplasmic staining. The expression rate of C6orf15 in high-grade gastric dysplasia (HGD, 93 %) and gastric adenocarcinoma (100 %) was significantly higher than in the gastric mucosal benign lesion group (0 %) and the low-grade dysplasia (LGD, 7 %) group (P < 0.001). CONCLUSION: The detection of C6orf15 protein expression could serve as a valuable adjunctive diagnostic tool for distinguishing between gastric HGD, LGD, and benign lesions. The combined assessment of C6orf15, P53, and Ki67 expressions may be beneficial in determining the grade of gastric dysplasia and evaluating the risk of progression in gastric mucosal lesions in clinical practice.

Intraductal papillary mucinous neoplasms of the pancreas: Cytologic-histologic correlation study and evaluation of the cytologic accuracy in identifying high-grade dysplasia/invasive adenocarcinoma.

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.

The absolute number of small and diminutive adenomas with high-grade dysplasia is substantially higher compared with large adenomas: a retrospective pooled study.

Introduction: The risk that a large polyp (≥10 mm) evolves into high-grade dysplasia (HGD) is relatively high compared with that of a small/diminutive polyp (<10 mm). Recently, the detection of small and diminutive polyps has been substantially improved with the advancement of endoscopy. However, further research is needed on the role of the incidence of HGD caused by the co-occurrence of small and diminutive polyps in the progression of HGD. In this study, we aim to investigate whether and how the small and diminutive polyps correlate with the incidence of HGD in the population. Methods: The pooled data were deeply analyzed from four published randomized controlled trials (RCTs) regarding colon polyp detection. All polyps detected were examined and confirmed by pathologists. The primary outcome was the composition ratio of the HGD polyps in each polyp size category. Results: Among a total of 3,179 patients with 2,730 polyps identified, there were 83 HGD polyps confirmed, and 68 patients had at least one polyp with HGD. The risk of development of HGD was lower for a single small and diminutive polyp than for one large polyp (2.18% vs. 22.22%, P < 0.0001). On the contrary, the composition ratio for HGD from small and diminutive polyps was significantly higher than that from the large ones (68.67% vs. 31.33%, P < 0.0001). The combined number of HGD presented a trend negatively correlated to size. Conclusions: Our data demonstrated that the absolute number of HGD significantly derives more from small and diminutive polyps than from the large ones, and the collective number of small and diminutive polyps per patient is indicative of his/her HGD exposure. These findings positively provide novel perspectives on the management of polyps and may further optimize the prevention of colorectal cancer. Systematic Review Registration: http://www.chictr.org.cn, identifier ChiCTR1900025235, ChiCTR1800017675, ChiCTR1800018058, and ChiCTR1900023086.

Advanced endoscopic imaging for detection of Barrett's esophagus.

Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC), and is caused by chronic gastroesophageal reflux. BE can progress over time from metaplasia to dysplasia, and eventually to EAC. EAC is associated with a poor prognosis, often due to advanced disease at the time of diagnosis. However, if BE is diagnosed early, pharmacologic and endoscopic treatments can prevent progression to EAC. The current standard of care for BE surveillance utilizes the Seattle protocol. Unfortunately, a sizable proportion of early EAC and BE-related high-grade dysplasia (HGD) are missed due to poor adherence to the Seattle protocol and sampling errors. New modalities using artificial intelligence (AI) have been proposed to improve the detection of early EAC and BE-related HGD. This review will focus on AI technology and its application to various endoscopic modalities such as high-definition white light endoscopy, narrow-band imaging, and volumetric laser endomicroscopy.

The impact of endoscopic treatment on health-related quality of life in patients with Barrett's neoplasia: a scoping review.

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.

Serum elastase-1 predicts malignancy in intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND: 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. METHODS: A total of 234 resected IPMN cases in Chiba University Hospital from July 2005 to December 2021 were retrospectively analyzed. RESULTS: 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. CONCLUSION: The serum elastase-1 level was found to be a potentially useful biomarker for predicting malignant IPMNs.

Acute pancreatitis in intraductal papillary mucinous neoplasm: a single-center retrospective cohort study with systematic review and meta-analysis.

BACKGROUND: Intraductal papillary mucinous neoplasm (IPMN) is a cystic tumor of the pancreas arising from abnormal papillary proliferation of ductal epithelial cells, and is a precancerous lesion of pancreatic malignancy. This study aimed to evaluate associations between acute pancreatitis (AP) and histologic subtypes of IPMN. METHODS: In the clinical study, patients with IPMN confirmed by surgical resection specimens at our institute between 2009 and 2021 were eligible for inclusion. Associations and predictive accuracy of AP on the presence of HGD were determined by logistic regressions. In addition, a systematic review and meta-analysis was conducted through literatures upon search in PubMed, Embase, CENTRAL, China National Knowledge Infrastructure (CKNI), and Wanfang database, up to June, 2023. Pooled effects of the associations between AP and HGD and intestinal epithelial subtype subtype, shown as odds ratios (ORs) with 95% confidence intervals (CIs), were calculated using random effects model. RESULTS: The retrospective cohort study included 47 patients (32 males, 15 females) diagnosed with IPMN at our center between 2009 and 2021, including 11 cases with AP (median 62 years) and 36 cases (median 64.5 years) without. Accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of AP in predicting HGD were 78.7%, 57.1%, 82.5%, 36.4%, and 91.7%, respectively. Univariate logistic regression analysis showed that AP group had greater odds of presence of HGD (OR: 6.29,95% CI: 1.14-34.57) than non-AP group. Meta-analysis of five case-control studies in the literature included 930 patients and showed that AP-IPMN patients had higher odds for HGD (OR: 2.13, 95% CI 1.38-3.29) and intestinal epithelial subtype (OR: 5.38, 95% CI: 3.50-8.27) compared to non-AP IPMN. CONCLUSIONS: AP is predictive of malignancy in patients with IPMN.

Application of convolutional neural network-based endoscopic imaging in esophageal cancer or high-grade dysplasia: A systematic review and meta-analysis.

BACKGROUND: Esophageal cancer is the seventh-most common cancer type worldwide, accounting for 5% of death from malignancy. Development of novel diagnostic techniques has facilitated screening, early detection, and improved prognosis. Convolutional neural network (CNN)-based image analysis promises great potential for diagnosing and determining the prognosis of esophageal cancer, enabling even early detection of dysplasia. AIM: To conduct a meta-analysis of the diagnostic accuracy of CNN models for the diagnosis of esophageal cancer and high-grade dysplasia (HGD). METHODS: PubMed, EMBASE, Web of Science and Cochrane Library databases were searched for articles published up to November 30, 2022. We evaluated the diagnostic accuracy of using the CNN model with still image-based analysis and with video-based analysis for esophageal cancer or HGD, as well as for the invasion depth of esophageal cancer. The pooled sensitivity, pooled specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the curve (AUC) were estimated, together with the 95% confidence intervals (CI). A bivariate method and hierarchical summary receiver operating characteristic method were used to calculate the diagnostic test accuracy of the CNN model. Meta-regression and subgroup analyses were used to identify sources of heterogeneity. RESULTS: A total of 28 studies were included in this systematic review and meta-analysis. Using still image-based analysis for the diagnosis of esophageal cancer or HGD provided a pooled sensitivity of 0.95 (95%CI: 0.92-0.97), pooled specificity of 0.92 (0.89-0.94), PLR of 11.5 (8.3-16.0), NLR of 0.06 (0.04-0.09), DOR of 205 (115-365), and AUC of 0.98 (0.96-0.99). When video-based analysis was used, a pooled sensitivity of 0.85 (0.77-0.91), pooled specificity of 0.73 (0.59-0.83), PLR of 3.1 (1.9-5.0), NLR of 0.20 (0.12-0.34), DOR of 15 (6-38) and AUC of 0.87 (0.84-0.90) were found. Prediction of invasion depth resulted in a pooled sensitivity of 0.90 (0.87-0.92), pooled specificity of 0.83 (95%CI: 0.76-0.88), PLR of 7.8 (1.9-32.0), NLR of 0.10 (0.41-0.25), DOR of 118 (11-1305), and AUC of 0.95 (0.92-0.96). CONCLUSION: CNN-based image analysis in diagnosing esophageal cancer and HGD is an excellent diagnostic method with high sensitivity and specificity that merits further investigation in large, multicenter clinical trials.

Endoscopic resection of early gastric cancer.

Endoscopic resection (ER) is an effective treatment for early gastric cancer (EGC) without metastases. Existing endoscopic mucosal resection (EMR) is easy to perform, has few complications, and can be applied when the lesion size is small. However, en bloc and complete resection rates vary depending on the size and severity of the lesion. EMR using the cap-mounted panendoscopic method and EMR after circumferential preamputation of the lesion are useful in the treatment of EGC. However, completely oversized lesions (≥2 cm) and lesions associated with ulcers or submucosal fibrosis are more likely to fail resection. Endoscopic submucosal dissection has been widely used to resect tumors larger than 2 cm in diameter and has a higher acceptable complication rate and en bloc and complete resection rates than EMR. ER for EGC is superior to surgical resection in terms of improving patient quality of life. Additionally, compared to surgery, emergency rooms have a lower rate of treatment-related complications, shorter hospital stays, and lower costs. Accordingly, the indications for ER are expanding in the field of therapeutic endoscopy. Long-term outcomes regarding recurrence are excellent in both absolute and extended criteria for ER in EGC. Close surveillance should be performed after ER to detect early metachronous gastric cancer and precancerous lesions that can be treated with ER. Follow-up gastroscopy and abdominopelvic computed tomography scans every 6 to 12 months are recommended for patients who undergo curative ER for EGC on absolute or extended criteria.

Different Oncologic Outcomes According to Margin Status (High-Grade Dysplasia vs. Carcinoma) in Patients Who Underwent Hilar Resection for Mid-Bile Duct Cancer.

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.

Colloid Carcinoma Arising in an Intestinal-Type Intraductal Papillary Mucinous Neoplasm with High-Grade Dysplasia Appearing as Signet-Ring Cells of the Pancreas by Serial Pancreatic Juice Aspiration Cytology: A Case Report.

We report a case of colloid carcinoma (CC) arising from an intestinal-type intraductal papillary mucinous neoplasm with high-grade dysplasia (IPMNHGD) of the pancreas, diagnosed with serial pancreatic juice aspiration cytological examination (SPACE). A rapidly growing intraductal papillary mucinous neoplasm (IPMN) in a 71-year-old Japanese man accelerated his hospitalization in our institute. Clinically, a large, ruptured pancreatic cyst was suspected. Cytologically, several mucin-positive signet-ring cells were scattered in the inflammatory, necrotic, or mucinous background. Signet-ring cells in cell block specimens were immunoreactive for MUC2, MUC5AC, maspin, S100P, and claudin-18. The final cytologic diagnosis was CC arising in an intestinal-type IPMNHGD with intraperitoneal penetration. The patient died two months after an explorative laparotomy. The cytologic diagnosis was achieved through SPACE, and the presence of signet-ring cells was characteristic. Anti-claudin-18.2-specific monoclonal antibody therapy will likely be used to treat patients with IPMNHGD in the future. This case highlights the diagnostic utility of SPACE, with particular emphasis on the characteristic presence of signet-ring cells. Furthermore, it anticipates the potential use of anti-claudin-18.2- specific monoclonal antibody therapy in the management of IPMNHGD patients.

The Tissue Systems Pathology Test Outperforms Pathology Review in Risk Stratifying Patients With Low-Grade Dysplasia.

BACKGROUND & AIMS: Low-grade dysplasia (LGD) is associated with an increased risk of progression in Barrett's esophagus (BE); however, the diagnosis of LGD is limited by substantial interobserver variability. Multiple studies have shown that an objective tissue systems pathology test (TissueCypher Barrett's Esophagus Test, TSP-9), can effectively predict neoplastic progression in patients with BE. This study aimed to compare the risk stratification performance of the TSP-9 test vs benchmarks of generalist and expert pathology. METHODS: A blinded cohort study was conducted in the screening cohort of a randomized controlled trial of patients with BE with community-based LGD. Biopsies from the first endoscopy with LGD were assessed by the TSP-9 test and independently reviewed by 30 pathologists from 5 countries per standard practice. The accuracy of the test and the diagnoses in predicting high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) were compared. RESULTS: A total of 154 patients with BE (122 men), mean age 60.9 ± 9.8 years were studied. Twenty-four patients progressed to HGD/EAC within 5 years (median time of 1.7 years) and 130 did not progress to HGD/EAC within 5 years (median 7.8 years follow-up). The TSP-9 test demonstrated higher sensitivity (71% vs mean 63%, range 33%-88% across 30 pathologists), than the pathology review in detecting patients who progressed (P = .01186). CONCLUSIONS: The TSP-9 test outperformed the pathologists in risk stratifying patients with BE with LGD. Care guided by the test can provide an effective solution to variable pathology review of LGD, improving health outcomes by upstaging care to therapeutic intervention for patients at high risk for progression, while reducing unnecessary interventions in low-risk patients.

Use of Immunohistochemical p53 Mutant-Phenotype in Diagnosis of High-Grade Dysplasia of Esophageal Squamous Epithelia.

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.

Risk of Metachronous Neoplasia with High-Risk Adenoma and Synchronous Sessile Serrated Adenoma: A Systematic Review and Meta-Analysis.

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.

Comparison of the AmpFire® Multiplex HPV Assay to the Xpert® HPV Assay for detection of human papillomavirus and cervical disease in women with human immunodeficiency virus: a pragmatic performance evaluation.

BACKGROUND: Low- and middle-income countries (LMICs) account for nearly 85% of the global cervical cancer burden, yet have the least access to high-performance screening. International guidelines recommend human papillomavirus testing (HPV) as primary screening, yet implementation is inhibited by the cost of HPV testing. Atila AmpFire® HPV Assay (AmpFire) is both affordable and easy to use, and offers individual genotyping. The objective of this study was to compare the performance of the AmpFire HPV assay to the Xpert® HPV assay in detection of both HPV and clinically significant cervical disease. METHODS: We utilized stored cervical specimens from a prospective cohort study of women living with human immunodeficiency virus (HIV) in Botswana conducted from May to July 2018. Positive and negative percent agreement was calculated for the AmpFire and Xpert assays, as was detection of high-grade cervical dysplasia. RESULTS: 63 stored cervical specimens had detectable DNA after thawing and were included in the analysis. The positive percent agreement was 91.2% (95%CI 76.3-98.1) and negative percent agreement was 79.3% (95% CI 60.3-92.0). Six cases positive by AmpFire but negative by Xpert were HPV genotypes 35, 52 (n = 2), 58, 68, and co-infection with HPV 45 and 68. Both Xpert and AmpFire assays detected HPV in all 10 samples of women who had high-grade cervical dysplasia. CONCLUSIONS: The AmpFire HPV assay demonstrated excellent analytic performance in both detection of HPV and clinically significant cervical disease. AmpFire HPV is a promising option to increase access to affordable, type-specific HPV screening for cervical cancer in LMICs.