Mucosal microbial microenvironment in early gastric neoplasia and non-neoplastic gastric disease.

BACKGROUND AND AIM: The biological characterization of microbial environment in early gastric cancer (EGC), other than Helicobacter pylori, is limited. This study aimed to explore the microbial microenvironment in chronic gastritis (CG), fundic gland polyps (FGPs), low-grade intraepithelial neoplasia (LGIN), and EGC. METHODS: 16S-rRNA gene sequencing and bioinformatic analysis were performed on 63 individuals with 252 mucosal biopsies or endoscopic submucosal dissection margin samples from endoscopy. RESULTS: The microbiota in gastric LGIN functions analogously to EGC in terms of functional prediction. Neoplastic lesions showed a significant difference to CG or FGPs in beta diversity of the microbiota. Bacteria genera including Paracoccus, Blautia, Barnesiella, Lactobacillus, Thauera, Collinsella were significantly enriched in gastric neoplastic mucosa (LGIN and EGC) compared with non-neoplastic tissues (CG and FGPs). While Pseudomonas and Kingella were depleted in neoplastic tissues. FGPs showed a distinctive microbial network system that negatively interacted with Helicobacter. CONCLUSIONS: In terms of the mucosal microbial microenvironment, gastric LGIN and EGC showed no significant difference as early neoplastic lesions. We observed a coordinated microbial microenvironment that correlated negatively with Helicobacter.

Establishment and validation of a model to determine the progression risk of low grade intraepithelial neoplasia.

OBJECTIVE: To establish and validate a model to determine the progression risk of gastric low-grade intraepithelial neoplasia (LGIN). METHODS: A total of 705 patients with gastric LGIN at the endoscopy center of Jiangsu Provincial People's Hospital during January 2010 and August 2017 were retrospectively reviewed. Basic clinical and pathological information were recorded. According to the time sequence of the initial examination, the first 605 patients were enrolled in the derivation group, and the remaining 100 patients were used in the validation group. SPSS 19 software was used as statistical analysis to determine independent risk factors for progression of LGIN of the stomach and to establish a risk model. The ROC was used to verify the application value of the predictive model. RESULTS: Univariate and multivariate analysis suggested that sex, multiple location, congestion, ulceration and form were independent risk factors for prolonged or advanced progression in patients with LGIN. Based on this, a predictive model is constructed: P = ex/(1 + ex) X = - 10.399 + 0.922 × Sex + 1.934 × Multiple Location + 1.382 × Congestion + 0.797 × Ulceration + 0.525 × Form. The higher of the P value means the higher risk of progression. The AUC of the derivation group and validation group were 0.784 and 0.766, respectively. CONCLUSION: Sex, multi-site, hyperemia, ulcer and morphology are independent risk factors for the prolongation or progression of patients with gastric LGIN. These factors are objective and easy to obtain data. Based on this, a predictive model is constructed, which can be used in management of patients. The model can be used to identify high-risk groups in patients with LGIN that may progress to gastric cancer. Strengthening follow-up or endoscopic treatment to improve the detection rate of early cancer or reduce the incidence of gastric cancer can provide a reliable basis for the treatment of LGIN.

Endoscopic acanthosis nigricans appearance: A novel specific marker for diagnosis of low-grade intraepithelial neoplasia.

BACKGROUND AND AIM: At present, there is no recognized diagnostic criteria for gastric low-grade intraepithelial neoplasia (LGIN). The purpose of this study was to determine whether an "endoscopic acanthosis nigricans appearance (EANA)" could be a useful endoscopic marker for distinguishing LGIN lesions from peripheral non-neoplastic tissues. METHODS: A retrospective study was conducted on 638 cases of suspected superficial lesions with endoscopic images from white light endoscopy and magnifying endoscopy combined with narrow band imaging. According to the pathological results of accurate biopsies, those lesions were divided into three groups: a control group, an LGIN group, and an early gastric cancer (EGC) group. RESULTS: According to the presence of EANAs, the sensitivity, specificity, positive predictive value, and negative predictive value for differentiating between the LGIN and control groups were 24.8%, 97.3%, 78.3%, and 76.6%, respectively. The sensitivity (84.1%) and negative predictive value (92.4%) were significantly improved by combining EANA with types IV-VI pit pattern. The intervening part and mean gray value of glands, representing microsurface features and microvascular variation, were significantly larger or higher in EANA lesions than in the surrounding non-neoplastic mucosa. LGIN with EANA was more likely to be present in lesions of type 0-IIa. In addition, the prevalence of EANAs in EGC was 16.7%. CONCLUSION: An EANA could be used as an auxiliary indicator for a diagnosis of LGIN in suspected lesions. It could also play a potential assistive role in the diagnosis of EGC lesions.

[Risk Factors for Missed Diagnosis of Esophageal Low-grade Intraepithelial Neoplasia in Endoscopic Forceps Biopsy Compared with Endoscopic Submucosal Dissection].

OBJECTIVE: To investigate the risk factors for pathological upgrading after endoscopic treatment of esophageal lesions which confirmed to be low-grade intraepithelial neoplasia (LGIN) by preoperative biopsy. METHODS: A total of 148 patients who were confirmed to be LGIN in preoperative forceps underwent further endoscopic resection between November 2013 and July 2018. According to the final pathological results after endoscopic treatment, they were divided into pathological upgrading group and pathological non-upgrading group, and their clinicopathological characteristics were analyzed and compared through univariate and multivariate analysis. RESULTS: The average age of the patients was (59.95±7.75) years old and the percent of male patients was 67.57% (100/148). Most lesions were located in the middle esophagus (99 cases) and lower esophagus (38 cases). Endoscopic gross type was mainly depressed type (72 cases). The en-bloc resection rate was 99.32% (147/148). Among the patients (77, 52.03%) who had pathological upgrading, 33 (22.3%) cases were HGIN, 25 (16.9%) cases were in-situ cancer, and 19 (12.8%) cases were superficial esophageal squamous cell carcinoma. Univariate analysis showed that circumferential extent (≥1/2), longitudinal diameter (≥3 cm), submucosa involvement found by endoscopic ultrasongraphy, depressed gross type and redness of lesion mucosa were risk factors for postoperative pathological upgrading. Multivariate analysis indicated that the redness of the lesion mucosa and longitudinal diameter (≥3 cm) of the lesion were independent risk factors for pathological upgrading. CONCLUSIONS: For esophageal lesions diagnosed by biopsy as LGIN, clinicians should be highly alert to the pathological underestimate if the lesion surface is reddened and its longitudinal diameter is greater than 3 cm.

Application of clip traction in endoscopic submucosal dissection to the treatment of early esophageal carcinoma and precancerous lesions.

BACKGROUND AND AIM: It is usually difficult to obtain a good view of the dissection plane during esophageal endoscopic submucosal dissection (ESD). Therefore, the aim of this study was to investigate the efficacy and safety of clip traction in ESD for the treatment of early esophageal carcinoma (EEC) or precancerous lesions. METHODS: This is a case-matched comparative study. We selected 100 EEC patients who had undergone ESD. Fifty cases underwent ESD without clip traction (non-clip group), and 50 cases underwent ESD with clip traction (clip group). The patient-related variables, dissection time, data regarding muscularis propria injury, etc. were statistically analyzed. RESULTS: ESD was successful in all cases without complication. There were no significant differences between the two groups with respect to age, gender, the longitudinal diameter of the lesions, etc. Wide visual field exposure of the submucosal tissue below the lesion was obtained by applying clip traction. The dissection time of ESD was shorter in the clip group than in the non-clip group [22.02 (6.77) min vs 26.48 (12.56); P = 0.018] when the extent of lesion was less than half of the circumference of the esophagus; otherwise, there was no difference between the two groups (P = 0.252). Moreover, the muscularis propria injuries in the clip group were obviously less than the non-clip group (10 vs 30 %, P = 0.007). CONCLUSION: Clip traction can decrease the rate of muscularis propria injury and shorten the dissection time. It is recommended as a safe and effective auxiliary procedure for the treatment of esophageal ESD.

Quality of life and fear of cancer recurrence after endoscopic treatment for early Barrett's neoplasia: a prospective study.

Endoscopic therapy is the treatment of choice for high grade intraepithelial neoplasia (HGIN) or early cancer (≤T1sm1) in Barrett's esophagus (BE). We prospectively evaluated the effect of endoscopic treatment on quality of life (QOL) and fear of cancer (recurrence) and compared this with the effect of Barrett's surveillance or surgery. Patients treated endoscopically for early Barrett's neoplasia (n = 42, HGIN - T1sm1N0M0) were compared with three groups: patients with non-dysplastic BE undergoing surveillance (n = 44); patients treated surgically for early BE neoplasia (HGIN - T2N0M0, n = 21); patients treated surgically for advanced BE cancer (T1N1M0 - T3N1M0, n = 19). QOL (SF-36; EORTC-QLQ-C30; EORTC-QLQ-OES18) and fear of cancer recurrence (Worry of Cancer Scale [WOCS] and the Hospital Anxiety and Depression Scale [HADS]) were measured at baseline, 2 and 6 months after treatment. The endoscopic treatment group reported significantly better QOL in both physical and mental scales of SF-36 and EORTC-QLQ-C30 and less esophageal cancer related symptoms compared to both surgical groups. The endoscopic treatment group reported significant more worry for cancer recurrence (WOCS) compared to the early surgical group. Their scores on the WOCS were comparable with the scores of the advanced surgical group. Endoscopic treatment of early esophageal cancer has less negative impact on QOL and esophageal cancer symptoms than surgery. However, endoscopically treated patients worry as much about cancer recurrence as patients treated surgically for advanced cancer.

Molecular evolution of intestinal-type early gastric cancer according to Correa cascade.

Early screening is crucial for the prevention of intestinal-type gastric cancer. The objective of the current study was to ascertain molecular evolution of intestinal-type gastric cancer according to the Correa cascade for the precise gastric cancer screening. We collected sequential lesions of the Correa cascade in the formalin-fixed and paraffin-embedded endoscopic submucosal dissection-resected specimens from 14 Chinese patients by microdissection, and subsequently determined the profiles of somatic aberrations during gastric carcinogenesis using the whole exome sequencing, identifying multiple variants at different Correa stages. The results showed that TP53, PCLO, and PRKDC were the most frequently mutated genes in the early gastric cancer (EGC). A high frequency of TP53 alterations was found in low-grade intraepithelial neoplasia (LGIN), which further increased in high-grade intraepithelial neoplasia (HGIN) and EGC. Intestinal metaplasia (IM) had no significant correlation with EGC in terms of mutational spectra, whereas both LGIN and HGIN showed higher genomic similarities to EGC, compared with IM. Based on Jaccard similarity coefficients, three evolutionary models were further constructed, and most patients showed linear progression from LGIN to HGIN, ultimately resulting in EGC. The ECM-receptor interaction pathway was revealed to be involved in the linear evolution. Additionally, the retrospective validation study of 39 patients diagnosed with LGIN indicated that PRKDC mutations, in addition to TP53 mutations, may drive LGIN progression to HGIN or EGC. In conclusion, the current study unveils the genomic evolution across the Correa cascade of intestinal-type gastric cancer, elucidates the underlying molecular mechanisms of gastric carcinogenesis, and provides some evidence for potential personalized gastric cancer surveillance.

Successful treatment by a chlorin e6 derivative mediated photodynamic therapy combined holmium laser for cervical and vaginal giant condyloma acuminata and low-grade intraepithelial neoplasia:A case report.

Photodynamic therapy (PDT) is proved effective for treating low-grade squamous intraepithelial lesions (LSIL) and condylomata acuminata (CA). 5-Aminolevulinicacid (5-ALA) is the most common applied photosensitizer, but high rate of unbearable pain and relative long incubation time were reported. Here, we report a 27-year-old woman suffering from cervical and vaginal giant CA with LSIL involving the whole right vaginal fornix, cervical surface, and vaginal wall. Holmium yttrium aluminum garnet (Ho: YAG) laser was first applied to remove the giant CA lesions. STBF, a derivative of chlorin e6 (Ce6) was then applied on suspicious lesions as a new photosensitizer for 1 h. Lesions were exposed to LED illumination with a wavelength of 630 nm and light dose of 200-284 J/cm2 for cervical canal and the vaginal surfaces, 100-150 J/cm2 for cervix surface. Vaginal giant CA and LSIL lesions got complete remission at 6-month follow-up. Mild tolerable adverse reactions were observed after STBF-PDT and relieved in 24 h. Thus, the combination of Ho: YAG laser and STBF-PDT may be a novel option for cervical and vaginal giant CA and LSIL, especially for special vaginal fornix areas.

Characteristics and risk factor analyses of high-grade intraepithelial neoplasia in older patients with colorectal polyps.

BACKGROUND: According to the degree of intradermal neoplasia in the colorectal exhalation, it can be divided into two grades: Low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN). Currently, it is difficult to accurately diagnose LGIN and HGIN through imaging, and clinical diagnosis depends on postoperative histopathological diagnosis. A more accurate method for evaluating HGIN preoperatively is urgently needed in the surgical treatment and nursing intervention of colorectal polyps. AIM: To explore the characteristics and risk factors of HGIN in older patients with colorectal polyps. METHODS: We selected 84 older patients diagnosed with HGIN as the HGIN group (n = 95 colonic polyps) and 112 older patients diagnosed with LGIN as the LGIN group (n = 132 colonic polyps) from Shandong Provincial Hospital Affiliated to Shandong First Medical University. The endoscopic features, demographic characteristics, and clinical manifestations of the two patient groups were compared, and a logistic regression model was used to analyze the risk factors for HGIN in these patients. RESULTS: The HGIN group was older and had a higher number of sigmoid colon polyps, rectal polyps, pedunculated polyps, polyps ≥ 1.0 cm in size, polyps with surface congestion, polyps with surface depression, and polyps with villous/tubular adenomas, a higher proportion of patients with diabetes and a family history of colorectal cancer, patients who experienced rectal bleeding or occult blood, patients with elevated carcinoembryonic antigen (CEA) and cancer antigen 199 (CA199), and lower nutritional levels and higher frailty levels. The polyp location (in the sigmoid colon or rectum), polyp diameter (≥ 1.0 cm), pathological diagnosis of (villous/tubular adenoma), family history of colorectal cancer, rectal bleeding or occult blood, elevated serum CEA and CA199 levels, lower nutritional levels and higher frailty levels also are independent risk factors for HGIN. CONCLUSION: The occurrence of high-grade neoplastic transformation in colorectal polyps is closely associated with their location, size, villous/tubular characteristics, family history, elevated levels of tumor markers, and lower nutritional levels and higher frailty levels.

A new, simplified endoscopic scoring system for predicting clinical outcome in gastric low-grade intraepithelial neoplasia: the "e-cout system".

BACKGROUND AND OBJECTIVES: The clinical outcomes of gastric low-grade intraepithelial neoplasia (LGIN) exhibit significant diversity, and the current reliance on endoscopic biopsy for diagnosis poses limitations in devising appropriate treatment strategies for this disease. This study aims to establish a prognostic prediction scoring system (e-Cout system) for gastric LGIN, offering a theoretical foundation for solving this clinical challenge. METHODS: Retrospectively selecting 1013 cases meeting the inclusion and exclusion criteria from over 300,000 cases of upper gastrointestinal endoscopy performed at the Digestive Endoscopy Center of our hospital between 2000 and 2022, the cohort included 484 cases as development cohort and 529 cases for validation. Employing relevant statistical analysis, we used development cohort data to establish the e-Cout system for gastric LGIN, and further used validation cohort data to for internal validation. RESULTS: In the developmental stage, based on accordant regression coefficients, we assigned point values to six risk factors for poor prognosis: 4 points for microvessel (MV) distortion, 3 points for MV thickening, 2 points for ulcer, and 1 point each for lesion size > 2cm, disease duration > 1 year, and hyperemia and redness on the lesion surface. Patients were then categorized into four risk levels: low risk (0-1 point), medium risk (2-3), high risk (4-6), and very high risk (≥7). During the validation stage, significant differences in the three different outcomes of gastric LGIN were observed across all risk levels. The probability of reversal and progression showed a significant decrease and increase, respectively, with escalating of risk levels, and these differences were statistically significant (P< 0.001). CONCLUSIONS: The proposed e-Cout system holds promise in aiding clinicians to predict the probability and risk levels of different clinical outcomes in patients with gastric LGIN. This system is expected to provide an improved foundation and guidance for the selection of clinical strategies for this disease.

Identification of Immune Infiltrating Cell-Related Biomarkers in Early Gastric Cancer Progression.

OBJECTIVES: Gastric cancer (GC) is one of the most prevalent malignancies worldwide, and early detection is crucial for improving patient survival rates. We aimed to identify immune infiltrating cell-related biomarkers in early gastric cancer (EGC) progression. METHODS: The GSE55696 and GSE130823 datasets with low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and EGC samples were downloaded from the Gene Expression Omnibus database to perform an observational study. Immune infiltration analysis was performed by single sample gene set enrichment analysis and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data. Weighted gene co-expression network analysis was used to explore the co-expression modules and genes, and further enrichment analysis was performed on these genes. A protein-protein interaction (PPI) network of these genes was constructed to identify biomarkers associated with EGC progression. Screened hub genes were validated by the rank sum test and reverse transcription quantitative polymerase chain reaction. RESULTS: Immune scores were significantly elevated in EGC samples compared to LGIN and HGIN samples. The green-yellow module exhibited the strongest correlation with both immune score and disease progression. The 87 genes within this module were associated with the chemokine signaling pathways, the PI3K-Akt signaling pathways, leukocyte transendothelial migration, and Ras signaling pathways. Through PPI network analysis, the hub genes identified were protein tyrosine phosphatase receptor-type C (PTPRC), pleckstrin, CD53, CD48, lymphocyte cytosolic protein 1 (LCP1), hematopoietic cell-specific Lyn substrate 1, IKAROS Family Zinc Finger 1, Bruton tyrosine kinase, and Vav guanine nucleotide exchange factor 1. Notably, CD48, LCP1, and PTPRC showed high expression levels in EGC samples, with the remaining hub genes demonstrating a similar expression trend. CONCLUSION: This study identified 9 immune cell-related biomarkers that may be actively involved in the progression of EGC and serve as potential targets for GC diagnosis and treatment.

Esophageal low-grade intraepithelial neoplasia overlying multiple leiomyomas: A case report and review of the literature.

Background: Esophageal leiomyoma is the most common benign submucosal mesenchymal tumor. Esophageal intraepithelial neoplasia includes low-grade and high-grade intraepithelial neoplasia. The coexistence of epithelial lesions and the subepithelial lesion is rare. We recorded a case of esophageal low-grade intraepithelial neoplasia (LGIN) overlying multiple esophageal leiomyomas and followed with a review of the literature. Case presentation: A 49-year-old female patient came for the treatment of esophageal lesions. The submucosal eminences were observed in the right posterior wall and the left anterior wall of the esophagus by Esophagogastroduodenoscopy (EGD). Additionally, we noticed the mucosa of the right wall with brown background color and the dilated, tortuous vessels by narrow-band imaging (NBI). Then we ensured that the submucosal lesions originated from the esophageal mucosal muscle by endoscopic ultrasonography (EUS) and enhanced CT. Subsequently, the submucosal eminence of the right posterior wall and the overlying mucosal lesion were removed together by endoscopic submucosal dissection (ESD). Postoperative pathological diagnosed esophageal submucosal leiomyoma with focal LGIN. Review EGD showed white scars on the right wall of the upper esophagus three months later, while pathological biopsy showed slight squamous epithelial hyperplasia in the left wall. We decided that the left submucosal lesion can be resected at a selective-time operation, and we continue to follow up as planned. Conclusions: The case of intraepithelial neoplasia overlying the submucosal tumor is rare. Either missed diagnosis or overdiagnosis should be avoided through EGD and pathological biopsy.

Clinical efficacy and prognostic risk factors of endoscopic radiofrequency ablation for gastric low-grade intraepithelial neoplasia.

BACKGROUND: The use of radiofrequency ablation (RFA) has been reported in the treatment of gastric low-grade intraepithelial neoplasia (LGIN). However, its efficacy and prognostic risk factors have not been well analyzed. AIM: To explore the efficacy and prognostic risk factors of RFA for gastric LGIN in a large, long-term follow-up clinical study. METHODS: The clinical data of 271 consecutive cases from 198 patients who received RFA for treatment of gastric LGIN at the Chinese PLA General Hospital from October 2014 to October 2020 were reviewed in this retrospective study. Data on operative parameters, complications, and follow-up outcomes including curative rates were recorded and analyzed. RESULTS: The curative rates of endoscopic RFA for gastric LGIN at 3 mo, 6 mo, and 1-5 years after the operation were 93.3%, 92.8%, 91.5%, 90.3%, 88.5%, 85.7%, and 83.3%, respectively. Multivariate analyses revealed that Helicobacter pylori (H. pylori) infection and disease duration > 1 year had a significant effect on the curative rate (P < 0.001 and P = 0.013, respectively). None of patients had bleeding, perforation, infection, or other serious complications after RFA, and the main discomfort was postoperative abdominal pain. CONCLUSION: RFA was safe and effective for gastric LGIN during long-term follow-up. H. pylori infection and disease course > 1 year may be the main risk factors for relapse of LGIN after RFA.

ITIH4 is a novel serum biomarker for early gastric cancer diagnosis.

BACKGROUND: Gastric cancer (GC) is one of the most lethal forms of cancer due to the absence of tools for its early detection. Here, we explored critical biomarkers for early diagnosis. MATERIALS AND METHODS: Key biomarkers in serum from patients with early gastric cancer (EGC) and healthy controls (HCs) were identified via mass spectrometry and the expression of inter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) was evaluated using several methods. Furthermore, ITIH4 expression in sera and exosomes from patients with EGC, advanced GC (AGC), low grade intraepithelial neoplasia (LGN), chronic superficial gastritis with Helicobacter pylori infection (Hpi), other systemic malignant tumors (OSTs), and healthy controls was also evaluated. RESULTS: ITIH4 was identified as a key biomarker in patients with EGC. Its expression level in serum from the EGC group, which showed the highest specificity (94.44%), was significantly higher than those in sera from other GC groups as well as the control. Western blot analysis, immunohistochemical staining, and exosome analysis also confirmed ITIH4 expression in sera from patients with GC, but not in those from healthy individual. CONCLUSION: ITIH4 is a key biomarker in serum from patients with EGC and has potential as a high value diagnostic marker for EGC.

Sporadic adenoma or ulcerative colitis associated neoplasia? The endoscopist's information has an impact on diagnosis and patient management.

BACKGROUND: Diagnosing low grade intraepithelial neoplasia (LGIN) in patients with ulcerative colitis (UC) is difficult. Distinguishing between sporadic adenoma (SA) and UC associated LGIN is even more challenging but has clinical impact. We aimed to examine, if the morphological distinction between both entities is reliably possible, how it influences patient's outcome and the role of the endoscopist in this decision with respect to current endoscopy classification schemes. METHODS: Seven pathologists retrospectively reevaluated 425 cases of LGIN in UC patients, diagnosed between 2009 and 2017 with preceding expert consensus and follow up in two separate readings, based on published morphological differentiation criteria. In the first evaluation, the observers were blinded to any clinical data. In the second evaluation, they knew patients' age as well as endoscopic features. They also rated their subjective diagnostic certainty. RESULTS: Diagnostic correctness improved significantly in the second assessment as did the pathologists' confidence in their diagnoses (p < 0.001 - p = 0.019). Knowledge of clinical and endoscopical data led to a higher percentage of SA (71.8% vs. 85.6%). UC associated LGIN showed significant earlier LGIN relapse as well as more high grade intraepithelial neoplasia and carcinoma during follow up (p < 0.001, p < 0.001, p = 0.005). CONCLUSIONS: Distinction between SA and UC associated LGIN is important as it has an impact on patients' follow up and treatment. Morphological distinction remains difficult with moderate interobserver variability. Adequate clinical information significantly improves pathologists' diagnoses as well as their confidence in their diagnoses.

Endoscopic Submucosal Dissection for the Treatment of Superficial Epithelial Gastric Neoplasia in a Portuguese Centre.

BACKGROUND: The emergence of endoscopic submucosal dissection (ESD) made possible en bloc resection of neoplastic gastric lesions, regardless of lesion size, with reduced rates of complications and recurrence. This technique has become the preferred method for curative resection, instead of conventional endoscopic mucosal resection and surgery, when distant metastases have negligible risk. In Western countries experience with this technique has evolved quickly, with an increasing number of case series reported in the literature. This study aims to report the short- and long-term outcomes of ESD in gastric epithelial neoplastic lesions by a single operator in a Portuguese centre. METHODS: A retrospective analysis of all gastric ESDs in a tertiary specialised unit during a 5-year period, between May 2012 and September 2017, was performed. RESULTS: A total of 114 ESDs of gastric epithelial lesions were performed during this period; 96.5% of them were removed en bloc and 87.6% with R0 resection. A curative treatment was achieved in 83.2% of the cases. Complications occurred in 13.2% of the procedures, including early and delayed bleeding in 12 patients (10.5%) and one perforation (0.9%). With a median follow-up period of 12 months (interquartile range [IQR] = 18), 6 cases of recurrence at the previous ESD site were diagnosed: 4 residual lesions and 2 local recurrences in previous R0 resections. Residual lesions occurred more often in patients with larger lesions (median = 40.0 mm, IQR = 26 vs. median = 20.0 mm, IQR = 15, p = 0.008) and with positive horizontal margins (HMs) after resection (50.0 vs. 0.0%, Fisher exact test, p < 0.001). The cumulative incidence of metachronous gastric lesions at 34 months was 16.1%. All new lesions were effectively treated using an endoscopic technique. The disease-specific survival at 12 months was 100%. CONCLUSION: This study showed that ESD is an effective resection technique for gastric lesions with a good safety profile, confirming other European series. Regardless, high en bloc resection positive HM is still a problem in some specimens resected by ESD. Endoscopic surveillance can detect local recurrence and new lesions during early stages, potentially treatable by endoscopy.

INTRODUÇÃO: O aparecimento da dissecção endoscópica da submucosa (ESD) tornou possível a resseção em bloco de lesões neoplásicas superficiais do estômago, independentemente da sua dimensão, com reduzidas taxas de complicações e recorrência. Esta técnica tem evoluído como método preferencial face á mucosectomia convencional e cirurgia, quando a metastização á distância tem risco negligenciável. No mundo ocidental a experiência nesta técnica tem evoluído de forma rápida surgindo um número crescente de séries na literatura. Este estudo tem como objetivo reportar os resultados a curto e longo prazo da ESD de lesões epiteliais gástricas realizadas por um único operador num centro Português. MÉTODOS: Análise retrospetiva unicêntrica dos casos de ESD de lesões epiteliais gástricas, realizadas durante um período de 5 anos, entre maio de 2012 e setembro de 2017. RESULTADOS: Foram realizadas 114 ESDs de neoplasias epiteliais gástricas durante o período em estudo, com uma taxa de resseção em bloco de 96.5% e R0 de 87.6%. A resseção curativa confirmou-se em 83.2% dos casos. Ocorreram complicações em 13.2% dos procedimentos, incluindo hemorragia em 12 doentes (10.5%) e 1 perfuração (0.9%). Com uma mediana de follow-up de 12 meses (variação interquartil [IQR] 18), verificaram-se 6 casos de recorrência local: 4 lesões residuais e 2 recorrências em resseções R0 prévias. Observaram-se mais frequentemente lesões residuais de ESD de lesões de maiores dimensões (mediana = 40.0 mm, IQR = 26 vs. mediana = 20.0 mm, IQR = 15, p = 0.008) e com margens horizontais (HM) positivas após a resseção (50.0% vs. 0.0%, Teste exato de Fisher, p < 0.001). A incidência cumulativa de lesões gástricas metácronas aos 34 meses foi de 16.1%. Todas as novas lesões foram eficazmente tratadas por endoscopia. A sobrevivência específica aos 12 meses de follow-up foi de 100%. Conclusão: Este estudo mostra que a ESD gástrica é uma técnica eficaz e segura para o tratamento de lesões neoplásicas precoces confirmando a maioria das séries europeias. Embora a ESD permita geralmente uma resseção em bloco as HM positivas continuam a ser um problema em alguns doentes. A vigilância endoscópica pode detetar recorrência local e novas lesões, em estádios precoces, potencialmente tratáveis por endoscopia.

Differential gene expression profiling of gastric intraepithelial neoplasia and early-stage adenocarcinoma.

AIM: To investigate the differentiated whole genome expression profiling of gastric high- and low-grade intraepithelial neoplasia and early-stage adenocarcinoma. METHODS: Gastric specimens from an upper magnifying chromoendoscopic targeted biopsy were collected from March 2010 to May 2013. Whole genome expression profiling was performed on 19 low-grade intraepithelial neoplasia (LGIN), 20 high-grade intraepithelial neoplasia (HGIN), 19 early-stage adenocarcinoma (EGC), and 19 chronic gastritis tissue samples using Agilent 4 × 44K Whole Human Genome microarrays. Differentially expressed genes between different types of lesions were identified using an unpaired t-test and corrected with the Benjamini and Hochberg false discovery rate algorithm. A gene ontology (GO) enrichment analysis was performed using the GeneSpring software GX 12.6. The differentially expressed gene was verified using a real-time TaqMan® PCR assay with independent tissue samples, including 26 LGIN, 15 HGIN, 14 EGC, and 20 chronic gastritis. The expression of G0S2 were further validated by immunohistochemical staining (IHC) in 24 LGIN, 40 HGIN, 30 EGC and 61 chronic gastritis specimens. RESULTS: The gene expression patterns of LGIN and HGIN tissues were distinct. There were 2521 significantly differentially expressed transcripts in HGIN, with 951 upregulated and 1570 downregulated. A GO enrichment analysis demonstrated that the most striking overexpressed transcripts in HGIN compared with LGIN were in the category of metabolism, defense response, and nuclear factor κB (NF-κB) cascade. While the vast majority of transcripts had barely altered expression in HGIN and EGC tissues, only 38 transcripts were upregulated in EGC. A GO enrichment analysis revealed that the alterations of the immune response were most prominent in the progression from HGIN to EGC. It is worth noting that, compared with LGIN, 289 transcripts were expressed at higher levels both in HGIN and EGC. A characteristic gene, G0/G1 switch 2 (G0S2) was one of the 289 transcripts and related to metabolism, the immune response, and the NF-κB cascade, and its expression was validated in independent samples through real-time TaqMan® PCR and immunohistochemical staining. In real-time PCR analysis, the expression of G0S2 was elevated both in HGIN and EGC compared with that in LGIN (P < 0.01 and P < 0.001, respectively). In IHC analysis, G0S2 immunoreactivity was detected in the cytoplasmic of neoplastic cells, but was undetectable in chronic gastritis cells. The G0S2 expression in HGIN was higher than that of LGIN (P = 0.012, χ (2) = 6.28) and EGC (P = 0.008, χ (2) = 6.94). CONCLUSION: A clear biological distinction between gastric high- and low-grade intraepithelial neoplasia was identified, and provides molecular evidence for clinical application.

A case of branch duct type intraductal papillary neoplasm of the bile duct treated by open surgery after 11 years of follow-up.

The intraductal papillary neoplasm of the bile duct (IPNB) is a novel disease concept that was recently classified as a biliary cystic tumor by the revised World Health Organization classification. This is the case report of a 70-year-old female patient who experienced repeated episodes of obstructive jaundice and cholangitis since 2000, attributed to a mucus-producing hepatic tumor. Surgery was advised due to the repeated episodes; however, the patient refused. In May, 2011, the patient developed jaundice and fever and was treated with antibiotics. Since there was no improvement, the patient was admitted to the Tokyo Rosai Hospital. Abdominal computed tomography (CT) revealed a 50-mm cystic mass with an internal septum in the left hepatic lobe. Although the tumor size had remained almost unchanged compared to the initial CT scan performed in 2000, intra- and extra-hepatic bile duct dilation was more prominent on the second CT scan. Following admission, endoscopic retrograde cholangiopancreatography was performed and revealed an expanded papilla of Vater due to a mucous plug. A balloon catheter was inserted into the bile duct to remove the mucous plug, resulting in the drainage of copious amounts of mucus and infected bile. The patient finally consented to surgery and left hepatic lobectomy was performed. Consequently, the diagnosis of low-grade IPNB was made. Branch duct type IPNB, which is characterized by imaging appearance of a cystic mass and slow progression, is attracting increasing attention. In the present case, a cystic mass was identified in the left hepatic lobe, with no significant change in size after 11 years of follow-up, leading to the diagnosis of branch duct type IPNB. Considering the fact that IPNB is usually treated surgically at the time of diagnosis, the present case, due to the long-term follow-up, provides valuable insight into the natural history of the tumor.