Cases Of Low-grade Dysplasia Research Articles

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.

Tumor heterogeneity and carcinoma in resected specimens of gastric low-grade dysplasia: A retrospective single center study.

Lesions diagnosed as gastric low-grade dysplasia (LGD) may be pathologically upgraded to early gastric cancer (EGC) or high-grade dysplasia (HGD) after endoscopic resection (ER). In this study, we investigated the risk factors for pathological upgrades after ER and assessed the reason for these upgrades by retrospectively analyzing ER data between January 1999 and December 2019. We enrolled patients with LGD confirmed by forceps biopsy; the patients were classified into pathologically concordant (LGD) and upgraded (HGD and EGC) groups according to the pathology of their resected specimen. To determine the risk factors for upgrade, we compared the endoscopic findings of the concordant and upgraded groups via 1:1 matched case-control design. To find the reasons for discordance, all upgraded cases were pathologically re-evaluated. Among 1,643 cases of LGD, pathological upgrades were observed in 423 (25.7%) resected specimens and EGC was found in 111 (6.7%) lesions. After matching the upgraded and concordant cases, lesion sizes exceeding 1.5 cm (odds ratio (OR): 1.8; 95% CI: 1.1-3.0), mucosal nodularity (OR: 10.8; 95% CI: 5.6-21.0), heterogeneous color (OR: 3.0; 95% CI: 1.7-5.3), presence of erosion (OR: 2.7; 95% CI: 1.8-5.3), and open-type gastric atrophy (OR: 2.9; 95% CI: 1.7-4.9) were noted to be significantly associated with upgraded pathology to EGC. Among the EGC cases, 99 (89.2%) were found to have pre-existing dysplasia. In conclusion, endoscopic evaluations should be performed because of possible pathological upgrades and co-existence of carcinomas in LGDs, especially when they exhibit surface nodularity, erosion, heterogeneous color, and large size.

Conventional Adenomatous Polyps: Study of Histomorphological Features Using a Novel Scoring System

Introduction: Conventional adenomatous polyps are dysplastic proliferations that arise from the surface of the mucosa and grow in a top-down fashion. Dysplasia is graded as low-grade and high-grade using a two-tiered grading system. Aim: To grade the dysplasia in conventional adenomatous polyps by applying a novel scoring system. Materials and Methods: This cross-sectional study was conducted in the Department of Pathology, ESIC Medical College and Post Graduate Institute of Medical Science and Research (PGIMSR), Rajajinagar, Bengaluru, Karnataka, India. A total of 46 cases reported as conventional adenomatous polyps were reviewed from January 2020 to June 2022. A cytological grading system was applied, evaluating eight parameters consisting of architectural and cytological features. Each parameter was scored, resulting in a total score ranging from 8 to 24. The final diagnosis was determined based on the histological pattern and the total cytological score. The results were tabulated in an excel sheet and analysed using mean, standard deviation, percentage, and frequency tables. The relationship between the independent variables was evaluated using the Chi-square test. A p-value of less than 0.05 was considered significant. Results: Out of the 46 cases, most presented in the 4th decade of life 12 (32.61%) cases. The mean age of presentation was 54.56±11.91 years (mean±SD) with a male to female ratio of 1.4:1. The most common site was the sigmoid colon 17 (36.96%) cases. There were 26 cases of low-grade dysplasia with a mean score of 9.1 and 20 cases of high-grade dysplasia with a mean score of 15.2. The most common type was tubular adenoma with low-grade dysplasia 24 (52.17%) cases and a mean cytological score of 9. The high-grade dysplasia in tubular adenomas 7 (15.22%) cases, tubulovillous adenomas 11 (23.19%) cases, and villous adenomas 2 (4.35%) cases had mean scores of 13.3, 15.2, and 18, respectively. Conclusion: Dysplasia in adenomatous polyps is an independent risk factor for malignancy. The cytological scoring system helps in accurately diagnosing the grade of dysplasia and simplifies the process. The present study emphasizes the need for objective criteria, paving the way for implementing relevant surveillance and clinical protocols.

Clinical variation in surveillance and management of Barrett’s esophagus: A cross-sectional study of gastroenterologists and gastrointestinal surgeons

Appropriate surveillance and treatment of Barrett's esophagus (BE) is vital to prevent disease progression and decrease esophageal adenocarcinoma (EAC)-related mortality. We sought to determine the variation in BE care and identify improvement opportunities. 275 physicians (113 general gastroenterologists, 128 interventional gastroenterologists, 34 gastrointestinal surgeons) cared for 3 simulated patients, one each from 3 BE clinical scenarios: non-dysplastic BE (NDBE), BE indefinite for dysplasia (IND), and BE with low grade dysplasia (LGD), and care scores were measured against societal guidelines. Overall quality-of-care scores ranged from 17% to 85% with mean of 47.9% ± 11.8% for NDBE, 50.8% ± 11.7% for IND, and 52.7% ± 12.2% for LGD. Participants appropriately determined risk of progression 20.3% of the time: 14.4% for NDBE cases, 19.9% for LGD cases, and 26.8% for IND cases (P = .001). Treatment and follow-up care scores averaged 12.9% ± 17.5% overall. For the LGD cases, guideline-recommended twice-daily PPI treatment was ordered only 24.7% of the time. Guideline-based follow-up endoscopic surveillance was done in only 27.7% of NDBE cases and 32.7% of IND cases. For the LGD cases, 45.4% ordered endoscopic eradication therapy while 25.1% chose annual endoscopic surveillance. Finally, participants provided counseling on lifestyle modifications in just 20% of cases. Overall care of patients diagnosed with BE varied widely and showed room for improvement. Specific opportunities for improvement were adherence to guideline recommended surveillance intervals, patient counseling, and treatment selection for LGD. Physicians would potentially benefit from additional BE education, endoscopic advances, and better methods for risk stratification.

Risk of progression in Barrett’s esophagus based on diagnoses of general and gastrointestinal pathologists. A retrospective case-control study from Northern and Central Finland

Background Esophageal adenocarcinoma (EAC) is the sixth leading cause of cancer-related death worldwide. It develops through Barrett’s metaplasia – dysplasia sequence. However, the effectiveness of endoscopic surveillance is limited, since diagnosis of low-grade dysplasia (LGD) is known to be challenging for pathologists. Our aim was to compare the risk of Barrett’s progression based on diagnoses of general and expert gastrointestinal (GI) pathologists in a population-based cohort. Methods A total of 60 patients with non-dysplastic metaplasia (BE) or LGD progressing to high grade dysplasia (HGD) or EAC during follow-up could be identified in the population. For comparison, series representing non-progressive BE (n = 56) and LGD cases (n = 54), matched for age, gender, and length of follow-up were collected. All available original HE stained slides (n = 292) were blindly re-evaluated by two experienced GI pathologists and patient groups of progressive non-progressive BE and LGD were formed according to revised diagnoses. Results Original diagnosis for each sample was changed in 25% of BE, 59% of LGD, and 33% of HGD diagnoses. Of the original LGD diagnoses, 53% were downgraded to BE or indefinite for dysplasia (ID). Of LGD diagnoses made by an expert GI pathologist, 61% were in the progressive LGD group, whereas only 42% of general pathologists’ LGD diagnoses were in the progressive LGD group. Conclusion Based on this retrospective case-control study, LGD is strongly over-diagnosed among general pathologists. LGD diagnosed by expert GI pathologists predicts progressive disease. Recommendation for consensus diagnosis by expert GI pathologists is justified also in the Finnish population-based setting.

Spindle cell type squamous dysplasia of the esophagus: a clinicopathological analysis

Objective: To investigate the clinicopathological features and significance of spindle cell type squamous dysplasia of the esophagus. Methods: The clinicopathological data of 37 cases of spindle cell type squamous dysplasia of esophagus were collected retrospectively at People's Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), Pingdingshan, China, from 2009 to 2019. The histological and immunohistochemical characteristics were analyzed, with a literature review. Results: The median age of the 37 patients was 65 years (range 47-81 years), while the ratio of men to women was 1.5∶1.0. There were 4 cases in the upper esophagus, 31 in the middle esophagus and 2 in the lower esophagus. The median diameter of the lesions was 14 mm (range 3-40 mm). According to the Paris classification, 11 cases were 0-Ⅱa, 14 cases were 0-Ⅱb, 3 cases were 0-Ⅱb and 0-Ⅱa, and 9 cases were 0-Ⅱc. Under endoscope, the lesional mucosa was reddish. The micro-vessels were dilated, with various shapes and density. Histologically, tumor cells and nuclei were spindle shaped or elongated spindle shaped, with considerable homogeneity, dark nuclei and delicate or slightly thickened chromatin. The mitosis was conspicuous, and atypic mitoses were seen; the cytoplasm was acidophilic, and the intercellular bridge was obvious. The cells were dense and often lost polarity, but still arranged in parallel, mostly perpendicular to the basement membrane. Spindle cells often involved the whole layer of epithelium, with no gradient maturation and differentiation of normal squamous epithelium. The tumor was well demarcated. The spindle cells often invaded lamina propria. There were 15 cases with focal high-grade dysplasia and superficial invasive squamous cell carcinoma. Immunohistochemical staining showed that the mutation rate of p53 was 41.4% (12/29), the median of Ki-67 labeling index was 40% (range 20%-80%), and the abnormal distribution pattern of Ki-67 was 29 (100%). According to the initial pathological diagnosis, there were 6 cases of low-grade dysplasia, 4 cases of atypical epithelial cells and 27 cases of high-grade dysplasia and superficial invasive squamous cell carcinoma. Conclusions: Spindle tumor cells have moderate to severe atypia, and some tumors show invasive pattern. P53 mutation and Ki-67 abnormal distribution pattern indicate that they are high-grade dysplasia of esophageal squamous epithelium. The unique characteristics of spindle tumor cells suggest that they may represent a spindle cell subtype in the morphological spectrum of esophageal squamous dysplasia. When the knowledge of the lesion is insufficient, it can be easily misdiagnosed or missed.

Clinicopathological features of basal cell type dysplasia of esophagus

Objective: To investigate the clinicpathological features of basal cell type dysplasia of the esophagus. Methods: The clinicopathological data of 71 cases of basal cell type dysplasia of esophagus were collected at the People's Liberation Army Joint Logistics Support Force 989 Hospital, from 2009 to 2019, and the histomorphologic characteristics and immunophenotype were evaluated. The relevant literature was reviewed. Results: The ratio of male to female patients was 1.6∶1.0, and the median age was 65 years (range 48-81 years). The tumors were located in the upper segment of the esophagus in four cases (5.6%), the middle segment in 54 cases (76.1%), and the lower segment in 13 cases (18.3%).The median maximal tumor diameter was 12.0 mm (range 3-42 mm). According to Paris Classification, 0-Ⅱb accounted for 42.3% (30/71) of the cases. Under endoscope, the lesions were reddish with abnormal mucosal microvessels. Histologically, the neoplastic cells were small, with a high nuclear-cytoplasmic ratio, similar to basal cells, and uniform in morphology. The structural atypia was characterized by dense and disordered tumor cells, loss of basal cell polarity, and absence of normal squamous differentiation gradient. In 10 cases, the tumors were confined to the lower part of the epithelium. The tumor cells were smaller and more uniform in shape, and extend to the superficial lamina propria. Sixty-one tumors involved at least the entire layer of the upper cortex. There were 31 cases of neoplasms with superficial invasive carcinoma. The types of neoplasms included typical squamous cell carcinoma, basaloid squamous cell carcinoma, small cell neuroendocrine carcinoma, squamous cell carcinoma with sebaceous adenoid carcinoma, and differentiation of glandular/ductal epithelioid carcinoma. Immunohistochemical staining showed that the mutant expression rate of p53 protein was 41.5% (17/41). All 41 cases (100.0%) showed abnormal distribution pattern of Ki-67. According to the initial pathologic diagnosis, there were 18 cases of low grade dysplasia, 12 cases of atypical epithelial cells, and 41 cases of high grade dysplasia and superficially invasive carcinoma. Conclusions: Basal cell type dysplasia has unique morphologic characteristics and represents a tumor subtype in the morphologic lineage of esophageal squamous dysplasia. Tumor cells of basal cell type dysplasia, especially those distributed only in the lower part of the stratified squamous epithelium, may be tumor stem cells at the earliest stage of esophageal carcinogenesis and have multidirectional differentiation potential. When the tumor is confined to the lower part of the stratified squamous epithelium, it does not meet the diagnostic criteria for esophageal squamous dysplasia as defined by the current WHO classification.

Comparative analysis of differences between preoperative endoscopic biopsy and postoperative pathological examination for diagnosis of gastric intraepithelial neoplasia.

ObjectiveThis study was performed to compare the differences between preoperative endoscopic biopsy (PEB) and postoperative pathological examination (PPE) for diagnosis of gastric intraepithelial neoplasia (GIN).MethodsFrom September 2016 to July 2019, 188 consecutive patients with GIN at Yuyao People’s Hospital were retrospectively analyzed. The 188 patients had 218 GIN lesions. All patients underwent PEB and either endoscopic submucosal dissection or surgical treatment. PPE was performed on pathological tissues that had been surgically removed.ResultsAmong 138 cases of low-grade dysplasia (LGD) diagnosed by PEB, 46 were upgraded to high-grade dysplasia (HGD), 20 were upgraded to early gastric cancer (EGC), and 2 were downgraded to inflammation after PPE. Among 42 cases of HGD, 23 were upgraded to EGC, 2 were downgraded to LGD, and 2 were downgraded to inflammation after PPE. Among 38 cases of EGC, 1 was downgraded to HGD and 2 were downgraded to LGD after PPE. The original diagnosis was maintained after the operation in 120 cases of GIN.ConclusionBiopsy did not fully reflect the lesions of GIN. Biopsy review should be actively performed, and the lesions should be clarified by endoscopic submucosal dissection or surgery.

Tissue Systems Pathology Test Objectively Risk Stratifies Barrett's Esophagus Patients With Low-Grade Dysplasia.

Low-grade dysplasia (LGD) is the best predictor of neoplastic progression in Barrett's esophagus (BE). Most LGD cases are downstaged to nondysplastic (ND) BE on expert pathologist review, which is prone to interobserver variation and not widely available. Recent studies indicate that a risk prediction assay (TissueCypher) risk stratifies patients with NDBE for neoplastic progression. We aimed to investigate whether this risk prediction assay predicts neoplastic progression in BE patients with LGD. A blinded, retrospective cohort study was derived from the screening cohort of a randomized controlled trial of SURveillance vs RadioFrequency ablation for BE patients with LGD. Hematoxylin and eosin and p53 immunohistochemistry slides from the first endoscopy with LGD were independently reviewed by 3 expert pathologists and tested by the risk prediction assay. Revision diagnoses of NDBE were considered low risk, although indefinite for dysplasia, and LGD were considered high risk for progression. A total of 155 BE patients (123 men), mean age 61 ± 10 years, were analyzed. Thirty-four patients (22%) progressed to high-grade dysplasia/esophageal adenocarcinoma (median time 2.4 years) and 121 did not progress (median high-grade dysplasia/esophageal adenocarcinoma-free surveillance 7.9 years). The risk prediction assay sensitivity was 68% vs 76% for the 3 pathologists, and specificity was 79% vs 64%-77.0% for the pathologists. The assay detected 50%-56% of progressors that were downstaged to NDBE by the pathologists. The risk prediction assay provided significant risk stratification in BE patients with LGD and identified progressors that the experts downstaged to NDBE. This objective assay provides an effective solution to the lack of standardization of expert pathology review of LGD.

Invasive and Noninvasive Progression After Resection of Noninvasive Intraductal Papillary Mucinous Neoplasms.

To define frequencies, pattern of progression (invasive vs noninvasive), and risk factors of progression of resected noninvasive intraductal papillary mucinous neoplasms (IPMNs). There is a risk of progression in the remnant pancreas after resection of IPMNs. Four hundred forty-nine consecutive patients with resected IPMNs from 1995 to 2018 were included to the study. Patients with invasive carcinoma or with follow-up <6 months were excluded. Noninvasive progression was defined as a new IPMN, increased main pancreatic duct size, and increased size of an existing lesion (5 mm compared with preoperative imaging). Invasive progression was defined as development of invasive cancer in the remnant pancreas or metastatic disease. With a median follow-up of 48.9 months, progression was identified in 124 patients (27.6%); 108(24.1%) with noninvasive and 16(3.6%) with invasive progression. Median progression follow-up was longer for invasive progression (85.4 vs 55.9 months; P = 0.001). Five-and 10-year estimates for a cumulative incidence of invasive progression were 6.4% and 12.9% versus 26.9% and 41.5% for noninvasive progression. After risk adjustment, multifocality (HR 4.53, 95% CI 1.34-15.26; P = 0.02) and high-grade dysplasia (HGD) in the original resection (HR 3.60, 95% CI 1.13-11.48; P = 0.03) were associated with invasive progression. Progression to invasive carcinoma can occur years after the surgical resection of a noninvasive IPMN. HGD in the original resection is a risk factor for invasive progression but some cases of low-grade dysplasia also progressed to cancer. Patients with high-risk features such as HGD and multifocal cysts should be considered for more intensive surveillance and represent an important cohort for future trials such as anti-inflammatory or prophylactic immunotherapy.

Length of Barrett\u2019s esophagus in the presence of low-grade dysplasia, high-grade dysplasia, and adenocarcinoma

IntroductionThe identification and follow-up of ultra-short Barrett’s esophagus (BE) is controversial. BE surveillance guidelines emphasize mainly on long-segment BE. However, in practice a substantial proportion of esophageal adenocarcinoma (EAC) are found close to the gastro-esophageal junction (GEJ). Our study aims to chart the length of BE when low-grade dysplasia (LGD), high-grade dysplasia (HGD) and EAC arise in BE.MethodsEndoscopic findings from all cases with a diagnosis of LGD and HGD in BE between June 2014 and June 2019, and 100 consecutive cases of EAC diagnosed between June 2018 and August 2019, were reviewed. Additionally, 438 consecutive gastroscopies were reviewed to identify 100 cases of non-dysplastic BE.Results99 cases of LGD and 61 cases of HGD were reviewed. LGD and HGD when diagnosed, was located in BE ≤ 1 cm in 20% and 18% cases, respectively. LGD and HGD when diagnosed, was located in BE ≤ 3 cm in 48.5% and 40.9% cases, respectively. LGD and HGD when diagnosed in BE ≤ 3 cm was found at index endoscopy in 67% and 42% cases, respectively. Of the 100 cases of EAC, only 23 had concurrent visible BE, with BE higher than the level of EAC in seven. EAC when found, had its proximal extent ≤ 1 cm from GEJ in 22% and ≤ 3 cm from GEJ in 40% cases. Of the 100 non-dysplastic BE, 53% were ≤ 1 cm and 78% were ≤ 3 cm long.ConclusionAlmost 20% of all dysplasia in BE occurs in BE < 1 cm. Over 40% occurs in BE < 3 cm. Similarly, 20% of EAC occurs within 1 cm of GEJ and 40% occur within 3 cm. A majority of dysplasia diagnosed within 3 cm of the GEJ is found on index endoscopy. We propose that all lengths of columnar lined epithelium above the GEJ are recognized as BE and subjected to a thorough biopsy protocol.

Clinical Outcomes of Endoscopic Resection for Low-Grade Dysplasia and High-Grade Dysplasia on Gastric Pretreatment Biopsy: Korea ESD Study Group.

Background/AimsSome 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.MethodsPatients 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.ResultsThis 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.ConclusionsA 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.

Microvascular density and hypoxia-inducible factor in intraepithelial vocal fold lesions

ObjectiveThe promotion of neovascularisation is a crucial aspect of carcinogenesis. The study evaluates the microvascular density (MVD) and expression of hypoxia-induced factor (HIF-1α) in hypertrophic vocal fold (VF) lesions of different histopathological states including non-dysplastic, low-grade, high-grade dysplasia and invasive glottic cancer.Materials and methodsHistological specimens collected from patients diagnosed and treated in a single centre with different histological grades were immunohistochemically stained with CD31, CD34 and HIF-1α. Of the total number of 77 analysed VF specimens, 20 were non-dysplastic, 20 had low-grade dysplasia, 17 high-grade dysplasia and 20 were invasive cancers.ResultsThe highest mean value for MVD evaluated with expression of CD31 (MVD CD31) was 21.23 ± 14.46 and identified in the low-grade dysplasia group. The average MVD CD31 was 13.74 ± 5.56 and 20.11 ± 9.28 in the high-grade dysplasia and invasive cancer group, respectively. The highest MVD evaluated with CD34 (MVD CD34) was revealed for invasive cancer 35.64 ± 17.21. The MVD CD34 was higher for low-grade than in high-grade dysplasia (25.87 ± 12.30 vs 24.65 ± 15.92, respectively). The expression of HIF-1α was strong or very strong in 60% of non-dysplastic lesions, 100% of low-grade dysplasia cases, 53% of high-grade dysplasia cases and 50% of invasive cancer cases. The comparison of MVD CD31 with MVD CD34 revealed a strong positive correlation (ρ value 0.727). The comparison of both MVD CD31 and MVD CD34 with HIF-1α resulted in no linear relationship (ρ value of 0.143 and 0.165, respectively).ConclusionThe stage of low-grade dysplasia in intraepithelial vocal fold lesions is related to significant advancement of angiogenesis together with the highest hypoxia level.

Evaluation of MUC-1, MUC-4, CDX-2 and OCT-1 expression profiles in gastric carcinomas and precancerous lesions

Aim: We investigated the diagnostic and prognostic utility of MUC-1, MUC-4, CDX2 and OCT-1 expression profiles in high-mortality gastric carcinomas and their precancerous lesions.Material and Methods: Areas in proximity of dysplasias and gastric carcinomas that were suspected of having intestinal metaplasia were stained with PAS / Alcian Blue at pH 2.5 and pH 0.5; Giemsa staining was applied for evaluation of presence of H. Pylori.Results: Presence of MUC-1 expression may exclude the diagnosis of low-grade dysplasia. MUC-1 and MUC-4 overexpression may be used for determination of groups at high risk of development of carcinomas, primarily in cases of high-grade dysplasia, while overexpression of MUC-1 in gastric carcinomas may be used as a favorable prognostic factor. Presence of CDX2 expression in various histological types of carcinomas gives rise to a suggestion that intestinal differentiation occurs in all histological types at least to some degree. OCT-1 plays a role in CDX2-mediated carcinogenesis and its regulation. Conclusion: In cases of dysplasia occurring with intestinal metaplasia, CDX2 was found to be expressed at a significantly higher degree (95.5%, p=0.011). Expression of CDX2 and OCT-1 was observed in all high-grade dysplasia cases, and was significantly higher in comparison to low-grade dysplasia cases (p=0.042; p=0.006, respectively). MUC-1 and MUC-4 expression significantly increased with each progressing stage of precancerous lesions in all lesions following low-grade dysplasia (p=0.0001; p=0.027, respectively). MUC-1 expression was the lowest (53.6%) in weak cohesive type carcinomas. Positive immunoreactivity with MUC-1 and CDX2 was higher in cases with a smaller number of metastatic lymph nodes compared to the cases with a larger number thereof.

Should We Screen Gastric Cancer in an Intermediate Gastric Cancer Risk Country?: International Award

Introduction: Gastric cancer is the fifth most common cancer and the third most common cause of cancer—related death worldwide. In high risk gastric cancer countries, gastric cancer screening is implemented but in intermediate risk countries it is debatable. The aims of this study were to evaluate the prevalence of active infection of Helicobacter Pylori as well as the presence of gastric cancer and gastric cancer precursors in an asymptomatic population submitted to colon cancer screening. Methods: We made a prospective study in an intermediate risk country of gastric cancer of patients undergoing colorectal cancer screening colonoscopy with general anesthesia and performed at the same time the upper endoscopy with blind biopsies from the gastric body and antrum, according to Sydney protocol. Results: We included 1364 Caucasian patients, 54.4% female, with mean age of 57.1±11.1 years. There was gastric cancer family history in 1.7% of the patients. Helicobacter Pylori infection was present in 41% in the gastric body and in 41.1% in the antrum. We found an incidence of gastric atrophy in both locations (gastric body and antrum) in 5.1% and intestinal metaplasia in 13.3%. There were 4 cases of low grade dysplasia and we diagnosed 12 gastric cancers (0.9%). Conclusion: The prevalence of Helicobacter Pylori was 41% and we found 12 gastric cancer in an asymptomatic population (0.9% incidence). As an intermediate risk gastric cancer country, we would recommend gastric cancer screening at the same time of colon cancer screening, followed by a structured surveillance program in case of intestinal metaplasia, dysplasia or gastric cancer.

Malignant and Nonmalignant Complications of the Rectal Stump in Patients with Inflammatory Bowel Disease.

Patients with refractory inflammatory bowel disease (IBD) might require a subtotal colectomy with construction of an ileostomy. Due to the risk of nerve damage and pelvic sepsis, the diverted rectum is often left in situ. Evidence on long-term complications of this rectal stump is limited, particularly in patients with Crohn's disease (CD). In addition to the risk of development of neoplasia, diversion proctitis is a frequently reported rectal stump associated complication. Surprisingly, clear recommendations concerning rectal stump surveillance and timing of proctectomy are lacking. Through the use of a pathology database and a review of medical records, we established a cohort of IBD patients with a diverted rectum. Among these patients, long-term complications of the rectal stump were identified. Main endpoint was advanced neoplasia (carcinoma or high-grade dysplasia [HGD]) in the rectal stump. Risk factors for advanced neoplasia were identified using Cox regression modeling. In the second, prospective part of the study, a questionnaire was sent out to 165 patients with either a rectal stump in situ or who had undergone a proctectomy, in order to identify differences in patient-reported outcome measures associated with the excision of the rectal stump. From 530 patients with IBD and a (temporal) diversion of the rectum, we included 250 patients in whom the rectal stump was left in situ for more than 12 months. The majority of patients was female (61%) and had Crohn's disease (67%). On follow-up (median 8 years), 8 carcinomas, 2 cases of high-grade dysplasia, and 7 cases of low-grade dysplasia were found with incidence rates of 3.9 and 8.5 per 1000 patient-years of follow-up for cancer and all neoplasia, respectively. The 8 cases of rectal stump cancer (RSC) were diagnosed after a median of 15 years after colectomy. A history of colorectal neoplasia was associated with advanced rectal stump neoplasia. Out of 191 patients with endoscopic follow-up, rectal stump inflammation occurred in 161 (88.5%) patients. Results of the questionnaire did not show a significant difference in quality of life between patients with and patients without a rectal stump, although the latter group reported significantly more sexual and urinary symptoms than patients with a rectal stump in situ. The majority of rectal stump patients reported rectal blood loss, but 65.5% of them were not or barely limited in daily life by their rectal stumprelated problems. Rectal stump cancer has a low incidence rate, with patients with a history of colonic neoplasia carrying the highest risk of developing this severe complication. We observed no significant differences in quality of life between rectal stump and postproctectomy patients, but proctectomy surgery is associated with sexual and urinary complications.

What Is Most Important to the Endoscopist for Therapeutic Plan? Morphology versus Pathology: A Nationwide Multicenter Retrospective Study in Korea

Histologic discrepancy may sometimes occur between biopsy and endoscopic resection. We investigated the discrepancy rate between the biopsy and the resection lesion in the Korean population. From January 2010 to October 2016, 268 patients with gastric endoscopic mucosal resection/endoscopic submucosal dissection history from nationwide hospitals were enrolled retrospectively. We compared the histologic discrepancy rates from the biopsy and the resection. The mean age was 63.2 years. Gastric adenomas occurred most frequently in the antrum. The pathology of the resected specimens classified 25 lesions (9.3%) as gastritis/hyperplasia, 146 lesions (54.5%) as low-grade dysplasia, 76 lesions (28.4%) as high-grade dysplasia (HGD), and 21 lesions (7.8%) as adenocarcinoma. The discrepancy rate between biopsy and resection was 23.1 per cent. Among the 44 cases of gastritis/hyperplasia, two cases (4.5%) were diagnosed as HGD and 11 cases (25.0%) were diagnosed as cancer after resection. Among the 182 cases of low-grade dysplasia, 33 cases (18.1%) were diagnosed as HGD and nine cases (5.0%) were diagnosed as cancer after resection. Gastritis/hyperplasia, ulceration, and lesions in the lower body location were significant factors related to the discrepancies. Especially, discrepancy occurred most frequently in gastritis/hyperplasia lesions with ulcer in the lower body. There was considerable histologic discrepancy between biopsy and resection. Ulcerative-type tumor morphology and biopsy diagnosis of gastritis/hyperplasia are suggestive factors predictive of discrepancy between biopsy and resection in terms of malignancy. Therefore, although the results of biopsy are gastritis/hyperplasia, suspicious tumorous lesions with ulcer should be indicative of active endoscopic resection for diagnosis and treatment.

High infiltration of CD68+ macrophages is associated with poor prognoses of head and neck squamous cell carcinoma patients and is influenced by human papillomavirus.

Incidence of human papillomavirus (HPV)-related head and neck squamous cell carcinomas (HNSCCs) has increased over the last few decades. The reaction of the host immune system to these tumors remains biologically complex. Here, we investigated CD68+ macrophage numbers, reporting the prognostic value in comparison to other risk factors. We also examined CD68+ macrophage infiltration during disease progression regarding the impact of HPV infection, and we studied the role of HPV16-E6/E7 oncoproteins in CD68+ macrophage recruitment. CD68+ macrophage numbers were evaluated in 10 cases of tumor-free peri-tumoral epithelia, 43 cases of low-grade dysplasia, 45 cases of high-grade dysplasia and 110 cases of carcinoma. Our in vivo model was developed in 80 C3H/HeN mice orthotopically injected with HPV16-E6, -E7 or -E6/E7-transfected SCC-VII cell lines. High CD68+ macrophage numbers in the intra-tumoral compartment were associated with shorter patient survival (recurrence-free survival: p = 0.001; overall survival: p = 0.01). Multivariate analyses reported that CD68+ macrophage infiltration and tumor stage were strong and independent prognostic factors of HNSCC. CD68+ macrophage numbers increased during HNSCC progression both in intra-epithelial (p < 0.001) and stromal compartments (p < 0.001). A higher density of CD68+ macrophages was observed in advanced stages (p = 0.004). Patients with transcriptionally active HPV infections had higher CD68+ macrophage density than did HPV-negative patients (p = 0.003). CD68+ macrophage infiltration was higher in HPV-E7+ and −E6/E7+ mouse tumors than in -E6+ tumors (p = 0.029 and p < 0.001). In conclusion, the extent of CD68+ macrophage infiltration is a significant prognostic factor for HNSCC patients. The recruitment of macrophages increases during disease progression and is influenced by the HPV virus.

Use of DNA flow cytometry in the diagnosis, risk stratification, and management of gastric epithelial dysplasia

The natural history of gastric epithelial dysplasia and the consequential surveillance strategies are not well defined in the West. To date, the diagnosis relies on morphology, and no reliable adjunct methods, either immunohistochemical or molecular, have reproducibly been able to confirm the diagnosis and/or risk stratify gastric epithelial dysplasia. Yet, such a tool would be useful in confirming the diagnosis, and developing objective and rational surveillance guidelines. DNA flow cytometry was performed using formalin-fixed paraffin-embedded gastric tissue from 23 cases of high-grade dysplasia and 38 cases of low-grade dysplasia. Twenty-four benign background mucosal samples from the same cohort (20 biopsies and 4 surgical resections from 16 low- and 8 high-grade dysplasia cases) were utilized as controls. The presence of DNA content abnormality (aneuploidy or elevated 4N fraction) correlated with increasing levels of dysplasia, as DNA content abnormality was detected in 18 (78%) of 23 high-grade dysplasia, 5 (13%) of 38 low-grade dysplasia, and none of 24 non-dysplastic samples. 1 and 4-year detection rates of high-grade dysplasia or gastric adenocarcinoma in low-grade dysplasia patients with DNA content abnormality were 80% (p = 0.003) and 100% (p = 0.005), respectively, whereas patients with low-grade dysplasia but with normal DNA content had 1, 4, and 12-year detection rates of 23, 32, and 54%, respectively. The univariate hazard ratio (HR) for subsequent detection of high-grade dysplasia or gastric adenocarcinoma in low-grade dysplasia patients with DNA content abnormality was 6.9 (p = 0.001). Older patients (HR = 1.1, p = 0.005) and those with familial adenomatous polyposis (HR = 9.7, p = 0.029) also had an increased risk for developing high-grade dysplasia or gastric adenocarcinoma in the univariate analysis, but only DNA content abnormality demonstrated a significantly elevated HR of 5.9 in the multivariate analysis (p = 0.005). While older age showed a minimally elevated risk (HR = 1.1, p = 0.013), no other potential risk factors, including male gender, ethnicity, polypoid endoscopic appearance, Helicobacter pylori infection, and intestinal metaplasia, were significantly associated with subsequent detection of high-grade dysplasia or gastric adenocarcinoma in the multivariate analysis. Among the 18 high-grade dysplasia cases with DNA content abnormality, 13 cases (72%) developed gastric adenocarcinoma within a mean follow-up time of 9 months, conferring a HR of 2.5; however, this did not reach statistical significance. In conclusion, the presence of DNA content abnormality can identify a subset of low-grade dysplasia patients who are at increased risk for subsequent detection of high-grade dysplasia or gastric adenocarcinoma. It can also provide confirmatory evidence to a morphologic impression or suspicion of high-grade dysplasia. The majority of gastric epithelial dysplasia patients with DNA content abnormality developed high-grade dysplasia or gastric adenocarcinoma within a year and thus may benefit from more thorough and rigorous endoscopic surveillance.

A Single Center Experience of Endoscopic Submucosal Dissection

Introduction: Endoscopic submucosal dissection (ESD) is an advanced endoscopic technique used for the resection of superficial gastrointestinal tumors with data showing high en bloc and curative resection rates in early gastric cancer. While it has been widely employed in East Asia, its adoption in the West has been slow due to the increased technical difficulty, higher rate of complications, longer procedure times and lower candidate populations. Methods: A retrospective review of the clinical and technical characteristics of ESD for superficial lesions of the gastrointestinal tract treated at Mount Sinai Beth Israel Medical Center, New York between May 2012 and December 2016. Results: We reviewed 59 cases of ESD - 46 gastric, 7 esophageal and 6 colorectal lesions. There were 21 cases of early malignancy, all in the upper GI tract (20 gastric, 1 esophageal). The overall en bloc resection rate was 70% (15/21) and R0 resection rate was 85% (18/21). Among the early gastric cancers, 7 were adenocarcinomas without invasion beyond the submucosa (T1), 3 were intramucosal carcinomas and 10 were cases of high grade dysplasia (HGD). There were 8 cases of low grade dysplasia with endoscopically-visible mucosal abnormalities, all of which were en bloc R0 resections. Eleven of the cases of gastric ESD were for submucosal tumors - 5 GISTs, 3 carcinoid tumors, 1 leiomyoma and 2 pancreatic rests. The seven esophageal lesions were 3 granular cell tumors, 2 dysplastic lesions in the setting of Barrett's esophagus, one case of HGD and one case of lymphoepithelioma-like carcinoma (curative R0 resection). Six of these cases were en bloc resections. Complete resection of 6 colorectal polyps were performed by ESD. Two of these polyps had previously undergone partial mucosal resection limiting en bloc resection. The average procedure time in the esophagus, stomach and colon was 76, 106 and 83 minutes respectively. The average resection sizes were 2, 3 and 2 cm respectively. There was one complication, in a patient who underwent ESD in the proximal stomach for a lesion with LGD, of delayed bleeding requiring hospitalization and endoscopic therapy. Conclusion: In this small single center series, ESD appears to be effective and safe with resection rates comparable to published data. With further experience, specialized training and development of dedicated instruments, ESD should become integrated into specialized endoscopic practice in the West for the treatment of GI tract neoplasms.