Low-grade Dysplasia Lesions Research Articles

Low coverage whole genome sequencing of low-grade dysplasia strongly predicts colorectal cancer risk in ulcerative colitis.

Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC), and this risk increases dramatically in those who develop low-grade dysplasia (LGD). However, there is currently no accurate way to risk-stratify patients with LGD, leading to both over- and under-treatment of cancer risk. Here we show that the burden of somatic copy number alterations (CNAs) within resected LGD lesions strongly predicts future cancer development. We performed a retrospective multi-centre validated case-control study of n=122 patients (40 progressors, 82 non-progressors, 270 LGD regions). Low coverage whole genome sequencing revealed CNA burden was significantly higher in progressors than non-progressors (p=2×10-6 in discovery cohort) and was a very significant predictor of CRC risk in univariate analysis (odds ratio = 36; p=9×10-7), outperforming existing clinical risk factors such as lesion size, shape and focality. Optimal risk prediction was achieved with a multivariate model combining CNA burden with the known clinical risk factor of incomplete LGD resection. The measurement of CNAs in LGD lesions is a robust, low-cost and rapidly translatable predictor of CRC risk in IBD that can be used to direct management and so prevent CRC in high-risk individuals whilst sparing those at low-risk from unnecessary intervention.

The Natural Disease Course of Pancreatic Cyst–Associated Neoplasia, Dysplasia, and Ductal Adenocarcinoma: Results of a Microsimulation Model

Estimates on the progression of precursor lesions to pancreatic cancer (PC) are scarce. We used microsimulation modeling to gain insight into the natural disease course of PC and its precursors. This information is pivotal to explore the efficacy of PC screening. A Microsimulation Screening Analysis model was developed in which pancreatic intraepithelial neoplasms and cysts can evolve from low-grade dysplasia (LGD) to high-grade dysplasia (HGD) to PC. The model was calibrated to Dutch PC incidence data and Japanese precursor prevalence data (autopsy cases without PC) and provides estimates of PC progression (precursor lesion onset and stage duration). Mean LGD state durations of cysts and pancreatic intraepithelial neoplasms were 15.8 years and 17.1 years, respectively. Mean HGD state duration was 5.8 years. For lesions that progress to PC, the mean duration was 4.8-4.9 years for LGD lesions and 4.0-4.1 years for HGD lesions. In 13.7% of individuals who developed PC, the HGD state lasted less than 1 year. The probability that an individual at age 50 years developed PC in the next 20 years was estimated to be 1.8% in the presence of any cyst and 6.1% in case of an LGD mucinous cyst. This 20-year PC risk was estimated to be 5.1% for individuals with an LGD pancreatic intraepithelial neoplasm. Mean duration of HGD lesions before development of PC was estimated to be 4.0 years. This implies a window of opportunity for screening, presuming the availability of a reliable diagnostic test. The probability that an LGD cyst will progress to cancer was predicted to be low.

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

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

The Adaptive Immune Landscape of the Colorectal Adenoma-Carcinoma Sequence.

Background. The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma–carcinoma sequence (ACS). Methods. We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic). Results. The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones. Conclusions. The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment.

Usefulness of the Japan narrow-band imaging expert team classification system for the diagnosis of sessile serrated lesion with dysplasia/carcinoma.

Sessile serrated lesion (SSL) is a colorectal polyp that has malignant potential. However, the dysplastic components within an SSL can be difficult to diagnose with conventional endoscopy, because most SSLs with dysplasia/carcinoma have subtle mucosal features. Many studies have indicated that narrow-band imaging (NBI) observations of colorectal polyps are very useful, accurate predictors of histology. We aimed to verify the usefulness of the Japan NBI Expert Team (JNET) classification system for the diagnosis of SSLs with dysplasia/carcinoma. We examined 709 endoscopically or surgically resected lesions that were pathologically diagnosed as SSL, including 647 with no dysplasia, 37 with low-grade dysplasia, 15 with high-grade dysplasia, and 10 with submucosal invasive carcinoma. We retrospectively evaluated their clinicopathologic characteristics and conventional endoscopic and magnifying NBI endoscopic findings using the JNET system. Cases in all groups were more frequently located in the proximal colon. Submucosal invasive carcinomas were significantly larger than no dysplasia and low-grade dysplasia lesions. Almost all studied lesions (96.3%) were covered with a mucus cap. Five hundred and eighty (81.8%) lesions exhibited dark spots inside the crypts, which are NBI findings' characteristic of SSL. As for the JNET classification of magnifying NBI endoscopic findings, all 709 lesions showed Type 1. Six hundred and eighteen (95.5%) SSLs with no dysplasia lesions exhibited Type 1 only, whereas 52 (83.9%) SSLs with dysplasia/carcinoma had a combination of Type 1 and Type 2A, 2B, or 3, corresponding to SSL and dysplasia/carcinoma, respectively. The JNET classification had high sensitivity (83.9%), specificity (95.5%), and overall diagnostic accuracy (94.5%) for diagnosing SSLs with dysplasia/carcinoma. Use of magnifying NBI endoscopy with the JNET classification might be useful for diagnosing SSLs with dysplasia/carcinoma. This increased awareness may also improve the recognition of SSLs with dysplasia/carcinoma.

Incidence Rate of Gastric Cancer Adenocarcinoma in Patients With Gastric Dysplasia: A Systematic Review and Meta-Analysis.

Several studies have reported the risk of progression to gastric adenocarcinoma (GAC) in patients with gastric dysplasia (GD); however, the findings are controversial. We performed a systematic review and meta-analysis to study the incidence rate of GAC among patients with GD. Using a comprehensive search strategy, we systematically searched online databases including PubMed, Scopus, EMBASE, Cochrane Library, and Web of Science databases for identifying all relevant original articles through inception until July 2018. Cochran Q and I tests were used to assess heterogeneities between included studies. The incidence rates of GAC and their corresponding 95% confidence intervals (CIs) were pooled using random-effect or fixed-effect models. Of the 1980 retrieved records, 30 eligible articles (61 studies) were included. The overall pooled incidence rate of GAC was 40.36 (95% CI, 27.08-55.71; I, 96.0%) cases per 1000 person-years in patients with GD. Subgroup analysis according to the type of GD indicated the highest incidence rate of GAC was 186.40 (95% CI, 106.63-285.60; I, 94.6%) per 1000 person-years among patients with high-grade dysplasia (HGD) lesions. Although the incidence rates of GAC in low-grade dysplasia (LGD) lesions and in nonclassified lesions were 11.25 (95% CI, 3.91-21.22; I, 89.3%), and 1.40 (95% CI, 0.00-9.71; I, 78.8%), respectively. Compared with patients with LGD lesions, progression rate from GD to GAC was roughly 16 times greater in patients with HGD lesions. As the majority of patients with GAC are diagnosed in an advanced stage our study suggests strict management of HGD lesions to prevent GAC.

136 Usefulness of Magnifying Narrow-Band Imaging Endoscopy for the Diagnosis of Sessile Serrated Adenoma/Polyp With Dysplasia/Carcinoma

INTRODUCTION: Sessile serrated adenoma/polyp (SSA/P) is an early precursor lesion in the serrated neoplasia pathway, which results in BRAF-mutated colorectal carcinomas with high levels of microsatellite instability. Therefore, accurate diagnosis of SSA/P and its dysplastic components is endoscopically important. However, the usefulness of magnifying narrow-band imaging (NBI) endoscopy for SSA/Ps with dysplastic change has not yet been fully elucidated. The aim of this study was to verify the usefulness of magnifying NBI endoscopy for the diagnosis of SSA/P with dysplasia/carcinoma. METHODS: Among 939 endoscopically or surgically resected lesions pathologically diagnosed as SSA/P with or without dysplasia/carcinoma at Juntendo University Hospital (Tokyo, Japan) between 2011 and 2018, a total of 709 lesions had images available. These SSA/P lesions included 647 with no dysplasia (ND), 37 with low-grade dysplasia (LGD), 15 with high-grade dysplasia (HGD), and 10 with submucosal invasive carcinoma (SIC). We retrospectively evaluated magnifying NBI endoscopic findings using the Japan NBI Expert Team (JNET) system. RESULTS: The clinicopathological and endoscopic characteristics of the studied lesions are summarized in Table 1. The HGD and SIC lesions were associated with advanced age. All the lesions were more frequently located in the proximal colon. The SIC lesions were significantly larger than the ND and LGD lesions. All the lesions frequently exhibited endoscopic findings characteristic of SSA/P, such as mucus cap and Type II-Open pit pattern. As for the JNET classification of magnifying NBI endoscopy findings, all 709 lesions were type 1. Six hundred and eighteen (96%) ND lesions exhibited type 1 only, whereas 52 (84%) SSA/P with dysplasia/carcinoma lesions had a combination of type 1 and types 2A, 2B, or 3, corresponding to SSA/P and dysplasia/carcinoma, respectively (Figures 1 and 2). Furthermore, the JNET classification had high sensitivity (84%) and specificity (96%) for diagnosing SSA/P with dysplasia/carcinoma. CONCLUSION: Recently, the JNET was established and has proposed a universal NBI magnifying endoscopic classification of colorectal tumors. Our findings suggest that the use of magnifying NBI endoscopy using the JNET classification might be useful for the diagnosis of not only conventional colorectal tumors, but also SSA/P with dysplasia/carcinoma. This increased awareness may also improve the recognition of SSA/Ps with dysplasia or invasive carcinoma.

Multi-target stool DNA test in the surveillance of inflammatory bowel disease: a cross-sectional cohort study

Background and aim: Colonoscopic surveillance is recommended in patients with longstanding inflammatory bowel disease (IBD) as they are at increased risk of colorectal cancer (CRC). Non-invasive surveillance may improve compliance and access. Multi-target stool DNA (MT-sDNA) has been validated for screening of sporadic CRC but has not been assessed in IBD. Our aim was to assess the performance of a MT-sDNA test in a real-life surveillance setting of patients with longstanding IBD.Material and methods: A total of 192 IBD patients enrolled from two prospective cohorts submitted an EDTA buffered stool sample and underwent chromo- or white light colonoscopy. Stools were assayed for methylated BMP3 & NDRG4, mutant KRAS and β-actin by a laboratory blinded to clinical data.Results: The multitarget-sDNA panel was positive in 2/2 CRC and 5/15 low-grade dysplasia (LGD) < 1 cm in diameter. Sensitivities were 100% (95% CI 16–100%) for CRC and 33% (95% CI 13–61%) for LGD lesions <1 cm, with specificities of 87% (95% CI 81–91%) and 93% (95% CI 88–96%), respectively. The estimated number of patients needed to screen to detect a single CRC was 96 (95% CI 93–99%) and was 28 (95% CI 22–34%) to detect any colorectal neoplasia (CRN).Conclusion: The MT-sDNA panel detected CRC in IBD. Sensitivity for sub-centimeter colorectal neoplasms in IBD patients appears similar to that observed in the general population. The test may be a valuable tool for detection of malignancy during structured surveillance of long-term IBD in a first line hospital setting.

Integrated expression analysis identifies transcription networks in mouse and human gastric neoplasia.

Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. The Tff1 knockout (KO) mouse model develops gastric lesions that include low-grade dysplasia (LGD), high-grade dysplasia (HGD), and adenocarcinomas. In this study, we used Affymetrix microarrays gene expression platforms for analysis of molecular signatures in the mouse stomach [Tff1-KO (LGD) and Tff1 wild-type (normal)] and human gastric cancer tissues and their adjacent normal tissue samples. Combined integrated bioinformatics analysis of mouse and human datasets indicated that 172 genes were consistently deregulated in both human gastric cancer samples and Tff1-KO LGD lesions (P < .05). Using Ingenuity pathway analysis, these genes mapped to important transcription networks that include MYC, STAT3, β-catenin, RELA, NFATC2, HIF1A, and ETS1 in both human and mouse. Further analysis demonstrated activation of FOXM1 and inhibition of TP53 transcription networks in human gastric cancers but not in Tff1-KO LGD lesions. Using real-time RT-PCR, we validated the deregulated expression of several genes (VCAM1, BGN, CLDN2, COL1A1, COL1A2, COL3A1, EpCAM, IFITM1, MMP9, MMP12, MMP14, PDGFRB, PLAU, and TIMP1) that map to altered transcription networks in both mouse and human gastric neoplasia. Our study demonstrates significant similarities in deregulated transcription networks in human gastric cancer and gastric tumorigenesis in the Tff1-KO mouse model. The data also suggest that activation of MYC, STAT3, RELA, and β-catenin transcription networks could be an early molecular step in gastric carcinogenesis.

Clinical implications of low grade dysplasia found during inflammatory bowel disease surveillance: a retrospective study comparing chromoendoscopy and white-light endoscopy.

Background and study aims Current guidelines recommend the use of pancolonic chromoendoscopy for surveillance of patients with inflammatory bowel disease (IBD). It is currently unknown whether low grade dysplasia (LGD) found using chromoendoscopy carries a similar risk of high grade dysplasia (HGD) or colorectal cancer (CRC) compared with LGD detected using white-light endoscopy (WLE). The aim of this study was to compare the risk of advanced neoplasia, a combined endpoint of HGD and CRC, during follow-up after detection of lesions containing LGD identified with either chromoendoscopy or WLE. Patients and methods A retrospective cohort was established to identify patients who underwent IBD surveillance for ulcerative colitis or colonic Crohn's disease between 2000 and 2014. Subgroups were identified, based on the endoscopic technique (standard definition resolution WLE, high definition resolution WLE or chromoendoscopy). LGD detected in random biopsies was considered invisible LGD. Patients were followed until detection of advanced neoplasia, colectomy, death, or the last known surveillance colonoscopy. Results Of 1065 patients undergoing IBD surveillance, 159 patients underwent follow-up for LGD, which was visible in 133 cases and invisible in 26 cases. On follow-up, five cases of HGD and five cases of CRC were detected. The overall incidence rate of advanced neoplasia was 1.34 per 100 patient-years with a median follow-up of 4.7 years and a median time to advanced neoplasia of 3.3 years. There were no significant differences in the incidence of advanced neoplasia between chromoendoscopy-detected and WLE-detected LGD. Conclusion Advanced neoplasia was found to develop infrequently after detection of LGD in patients undergoing endoscopic surveillance for IBD. LGD lesions detected with either chromoendoscopy or WLE carry similar risks of advanced neoplasia over time.

Ectopic Gastric and Intestinal Phenotypes, Neuroendocrine Cell Differentiation, and SOX2 Expression Correlated With Early Tumor Progression in Colorectal Laterally Spreading Tumors

IntroductionThe significance of the ectopic gastric phenotype remains unclear in patients with colorectal laterally spreading tumors (LSTs). We investigated clinicopathologic differences among LST subtypes, aiming to identify factors indicative of malignant transformation and invasion that are linked to ectopic gastric phenotype and tumor progression. Materials and MethodsWe analyzed the morphologic characteristics of 105 colorectal LSTs resected by endoscopic submucosal dissection. LSTs were classified into 2 subtypes: granular (G-LST) and nongranular (NG-LST). Resected LSTs were analyzed histologically and were immunohistochemically stained for MUC5AC, MUC6, chromogranin A, CD10, and SOX2. ResultsThe 105 LSTs included 60 G-LSTs and 45 NG-LSTs. By histology, G-LSTs comprised 5 adenomas with low-grade dysplasia (LAs), 45 adenomas with high-grade dysplasia (HAs), and 10 adenocarcinomas invading the submucosa (SMs). NG-LSTs comprised 8 LAs, 25 HAs, and 12 SMs. MUC5AC positivity was significantly higher in G-LSTs compared to NG-LSTs (P = .002), and MUC5AC positivity in HA lesions was significantly higher than in LA lesions (P = .01). MUC6 and SOX2 positivity in SM G-LSTs, and chromogranin A positivity in SM NG-LSTs were significantly higher than in HAs (P = .01, .01, and .03, respectively). CD10 positivity in SM NG-LSTs was significantly higher than in HAs and LAs (P = .02 and .01, respectively). ConclusionEctopic gastric and intestinal phenotypes, neuroendocrine cell differentiation, and SOX2 expression differ according to tumor grade in colorectal LSTs, and these markers are correlated with early tumor progression in each LST subtype.

How Commonly Is the Diagnosis of Gastric Low Grade Dysplasia Upgraded following Endoscopic Resection? A Meta-Analysis.

Gastric dysplasia is a well-known precancerous lesion. Though the diagnosis of gastric low grade dysplasia (LGD) is generally made from endoscopic forceps biopsy (EFB), the accuracy is doubtful after numerous EFB-proven gastric LGD were upgraded to gastric high grade dysplasia (HGD) or even carcinoma (CA) by further diagnostic test with the procedure of endoscopic resection (ER). We aimed to evaluate the upgraded diagnosis rate (UDR) and the risk factors by ER in EFB-proven gastric LGD lesions. Two investigators independently searched studies reporting the UDR by ER in EFB-proven gastric LGD lesions from databases and analyzed the overall UDR, HGD-UDR and CA-UDR. The pooled UDR by ER in EFB-proven gastric LGD lesions was 25.0% (95% CI, 20.2%-29.8%), made up of HGD-UDR and CA-UDR by rates of 16.7% (95% CI, 12.8%-20.6%) and 6.9% (95% CI, 4.2%-9.6%) respectively. Lesion size larger than 2 cm, surface with depression and nodularity under endoscopic examinations were the major risk factors associated with UDR. In conclusion, one quarter of EFB-proven gastric LGD lesions will be diagnosed as advanced lesions, including gastric HGD (16.7%) and gastric CA (6.9%) by ER. The diagnosis of those LGD lesions with an endoscopic diameter larger than 2cm, and depressed or nodular surface are more likely to be upgraded after ER.

Clinical features of pharyngeal intraepithelial neoplasias and outcomes of treatment by endoscopic submucosal dissection

Endoscopic detection of superficial squamous epithelial lesions of the pharynx has increased. To clarify the association between macroscopic and histologic characteristics of intraepithelial pharyngeal neoplasias, and to evaluate the effectiveness of endoscopic submucosal dissection (ESD) for their treatment. Retrospective analysis of the features of high-grade dysplasia or carcinoma in situ (HGD/CIS) versus low-grade dysplasia (LGD) and of ESD-based outcomes. Endoscopy department at a university hospital. Fifty-one patients with 66 lesions treated by ESD from November 2007 to March 2011. Primary hypopharyngeal lesions were significantly more frequent in HGD/CIS than in LGD (54.1% vs 20.7%, P = .011), and oropharyngeal lesions were significantly less frequent in HGD/CIS (45.9% vs 79.3%, P = .011). HGD/CIS lesions were significantly larger than LGD lesions (median 8 mm vs 4 mm, P < .01). Morphologically, type 0-IIa was significantly more frequent in HGD/CIS lesions than in LGD lesions (37.8% vs 3.4%, P < .001), and type 0-IIb was significantly less frequent in HGD/CIS lesions (59.5% vs 96.6%, P < .001). The type IV intraepithelial papillary capillary loop pattern was significantly less frequent in HGD/CIS lesions than in LGD lesions (27.0% vs 55.2%, P = .025), and type V-2 was significantly more frequent in HGD/CIS lesions (18.9% vs 0%, P = .015). The en bloc resection rate was 97%. No serious complications occurred. There were no recurrent or metachronous tumors in the 41 patients followed for more than 1 year (median follow-up 27 months). Retrospective design and single-center study. HGD/CIS and LGD differ in various clinical features. ESD appears to be an effective treatment for pharyngeal intraepithelial neoplasias.

Clinicopathological features of minute pharyngeal lesions diagnosed by narrow-band imaging endoscopy and biopsy

To evaluate the utility of magnified narrow-band imaging (NBI) endoscopy for diagnosing and treating minute pharyngeal neoplasia. Magnified NBI gastrointestinal examinations were performed by the first author. A magnification hood was attached to the tip of the endoscope for quick focusing. Most of the examinations were performed under sedation. Magnified NBI examinations were performed for all of the pharyngeal lesions that had noticeable brownish areas under unmagnified NBI observation, and an intrapapillary capillary loop (IPCL) classification was made. A total of 93 consecutive pharyngeal lesions were diagnosed as IPCL type IV and were suspected to represent dysplasia. Sixty-two lesions of approximately 1 mm in diameter were biopsied in the clinic, and 17 lesions with larger diameters were resected by endoscopic submucosal dissection (ESD) at the Hiroshima University Hospital. In addition to the histological diagnoses, the lesion diameters were microscopically measured in 45 of the 62 biopsies. Thirty-four of the 62 biopsied patients received endoscopic follow up. Minute pharyngeal lesions were diagnosed in 93 of approximately 3000 patients receiving magnified NBI examinations at the clinic. Of the 93 patients with IPCL type IV lesions, 80 were men, and 13 were women. Fifty-six were drinkers, and 57 were smokers. Two had esophageal cancer. Twenty-one lesions were located on the posterior hypopharyngeal wall, and 72 lesions were located on the posterior oropharyngeal wall. All 93 lesions were flat and showed similar findings in the magnified and unmagnified NBI examinations. Although almost all of the IPCL type IV lesions showed faint redness when examined under white light, it was difficult to diagnose the lesions using only this technique because the contrast was weaker than that achieved in the NBI examinations. Of the 93 lesions, only 3 had diameters greater than 2.1 mm. Sixty-two lesions of approximately 1 mm were biopsied in the clinic, whereas 17 larger lesions were treated by ESD at the Hiroshima University Hospital. Of the 79 pharyngeal lesions that were biopsied or resected by ESD, 5 were histologically diagnosed as high-grade dysplasia, 39 were diagnosed as low-grade dysplasia, and 39 were determined to be non-dysplastic lesions. There were no cancerous lesions. Histologically, abnormal cell size variations and increased nuclear size were observed in all of the high-grade dysplasia lesions, while the incidence of these findings in the low-grade dysplasia lesions was low. Of the 62 biopsied lesions, 45 were microscopically measurable. The measured diameters ranged from 0.1 to 2.0 mm. The dysplasia ratios increased with the diameters. A follow-up endoscopic examination of the 34 biopsied patients found the rate of complete resection by biopsy to be 79%. The largest lesion in which complete resection was expected was a low-grade dysplasia of 1.9 mm in diameter. Minute pharyngeal lesions suspected to be dysplasia that are identified by NBI magnifying endoscopy should be biopsied to determine the diagnosis and further treatment.

Clinical parameters including serum pepsinogen level and management strategy in patients with premalignant gastric dysplasia

Surgical or endoscopic resection is recommended for the management of gastric high-grade dysplasia (HGD). However, there are no proper guidelines for the management of gastric low-grade dysplasia (LGD). We evaluated clinical parameters, histological results, and endoscopic follow-up to find a management strategy of LGD. A total of 590 patients with LGD, HGD, functional dyspepsia (FD), and early or advanced gastric cancer (EGC or AGC, respectively) were consecutively enrolled. We examined the association of clinical parameters including low serum pepsinogen (PG) I/II ratio of 3.0 or less with the disease phenotypes. Histological results between initial forceps biopsy and final endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) specimens were compared. Complications and recurrence were evaluated after EMR or ESD. The PG I/II ratio in FD was 4.2±1.7 (mean±SD), but was significantly lower in LGD (2.8±1.6, P<0.0001). The PG I/II ratio was not any lower in the HGD, EGC, and AGC groups. In patients with FD having a PG I/II ratio of 3.0 or less, multiple logistic regression analysis showed smoking habits and high salt intake were independent risk factors for gastric dysplasia or gastric cancer. About 11% (n=8/70) of LGD lesions were upgraded to HGD (6/70) or EGC (2/70) after EMR or ESD. Neither serious complications nor recurrence at the primary site after EMR or ESD were found in LGD. It is proposed that endoscopic resection followed by endoscopic surveillance might be a beneficial strategy for patients with LGD having a PG I/II ratio of 3.0 or less.

Clinical Parameters Including Serum Pepsinogen Level and Management Strategy in Patients with Gastric Low-Grade Dysplasia

Background/Aims: There are no proper guidelines for the management of gastric low-grade dysplasia (LGD). We evaluated clinical parameters, histological results and follow-up endoscopies to find a management strategy of LGD. Materials and Methods: A total of 590 patients with LGD, high-grade dysplasia (HGD), functional dyspepsia (FD), early or advanced gastric cancer (early gastric cancer [EGC] or advanced gastric cancer [AGC]) were consecutively enrolled. We examined the association of clinical parameters including low serum pepsinogen (PG) I/II ratio ≤3.0 with the disease phenotypes. Histological results between initial forceps-biopsy and endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) specimens were compared. Results: The PG I/II ratio in FD was 4.2±1.7, but was significantly low in LGD (2.8±1.6, P<0.0001). The ratio was not further decreased in the HGD, EGC, and AGC groups. In FD patients with the ratio of ≤3.0, smoking habits and high salt intake were independent risk factors for gastric dysplasia or gastric cancer. In about 11% (n=8/70) of LGD lesions, the pathologic diagnoses were upgraded to HGD or EGC after endoscopic resection. Neither serious complications nor recurrence at the primary site were found. Conclusions: It is proposed that endoscopic resection followed by endoscopic surveillance might be a beneficial strategy for patients with LGD having a PG I/II ratio of ≤3.0. (The Korean Journal of Helicobacter and Upper Gastrointestinal Research 2011;11:52-58)

Does Daily Alcohol and/or Cigarette Consumption Cause Low-grade Dysplasia, a Precursor of Esophageal Squamous Cell Carcinoma?

Cigarette smoking and alcohol consumption are well-known risk factors for esophageal squamous cell carcinoma (ESCC), which has a very poor prognosis. Successful screening strategies for precursor lesions that can be targets for early detection and treatment are required to prevent ESCC. This is a prospectively cross-sectional study. To clarify whether daily smoking and/or alcohol consumption are risk factors for dysplasia, which is the initial lesion leading to ESCC. Lugol chromoendoscopy was performed in 1,345 eligible individuals. Six hundred ninety individuals had daily smoking and/or alcohol consumption; 655 individuals did not smoke and drink alcohol. The effects of smoking and alcohol consumption among high-grade dysplasia (HGD), low-grade dysplasia (LGD), and controls without dysplasia were evaluated using multiple logistic regression analysis. Among 1,345 individuals, 17 HGD and 23 LGD lesions were confirmed histologically. The prevalence of both smoking and drinking consumption was significantly higher in HGD than in LGD individuals (age and sex adjusted odds ratio; 113.0, 95% confidence interval; 6.26), whereas no significant difference was seen in both consumption between LGD individuals and controls (odds ratio; 1.29, 95% confidence interval; 0.33-6.37). Approximately 70% of HGD individuals, but only 13% of LGD individuals, both smoked and consumed alcohol. Daily cigarette and alcohol consumption were not the risk factors for LGD, however, consumption of both were high-risk factors for HGD. We suggest that documenting the difference of risk factors for LGD and HGD can assist in the development of effective screening, early detection, and prevention strategies for ESCC.