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Current clinical trials of combined EGFR-tyrosine kinase inhibitors (TKI) and immune checkpoint blockade (ICB) therapies show no additional effect. This raises questions regarding whether EGFR-TKIs attenuate ICB-enhanced CD8+ T lymphocyte function. Here we show that the EGFR-TKI afatinib suppresses CD8+ T lymphocyte proliferation, and we identify CAD, a key enzyme of de novo pyrimidine biosynthesis, to be a novel afatinib target. Afatinib reduced tumor-infiltrating lymphocyte numbers in Lewis lung carcinoma (LLC)–bearing mice. Early afatinib treatment inhibited CD8+ T lymphocyte proliferation in patients with non–small cell lung cancer, but their proliferation unexpectedly rebounded following long-term treatment. This suggests a transient immunomodulatory effect of afatinib on CD8+ T lymphocytes. Sequential treatment of afatinib with anti-PD1 immunotherapy substantially enhanced therapeutic efficacy in MC38 and LLC-bearing mice, while simultaneous combination therapy showed only marginal improvement over each single treatment. These results suggest that afatinib can suppress CD8+ T lymphocyte proliferation by targeting CAD, proposing a timing window for combined therapy that may prevent the dampening of ICB efficacy by EGFR-TKIs.Significance:This study elucidates a mechanism of afatinib-mediated immunosuppression and provides new insights into treatment timing for combined targeted therapy and immunotherapy.

It includes supplementary material and method, one table, and figure and figure legend

Background and Aims Intrapapillary capillary loops (IPCLs) are microvascular structures that correlate with the invasion depth of early squamous cell neoplasia and allow accurate prediction of histology. Artificial intelligence may improve human recognition of IPCL patterns and prediction of histology to allow prompt access to endoscopic therapy for early squamous cell neoplasia where appropriate. Methods One hundred fifteen patients were recruited at 2 academic Taiwanese hospitals. Magnification endoscopy narrow-band imaging videos of squamous mucosa were labeled as dysplastic or normal according to their histology, and IPCL patterns were classified by consensus of 3 experienced clinicians. A convolutional neural network (CNN) was trained to classify IPCLs, using 67,742 high-quality magnification endoscopy narrow-band images by 5-fold cross validation. Performance measures were calculated to give an average F1 score, accuracy, sensitivity, and specificity. A panel of 5 Asian and 4 European experts predicted the histology of a random selection of 158 images using the Japanese Endoscopic Society IPCL classification; accuracy, sensitivity, specificity, positive and negative predictive values were calculated. Results Expert European Union (EU) and Asian endoscopists attained F1 scores (a measure of binary classification accuracy) of 97.0% and 98%, respectively. Sensitivity and accuracy of the EU and Asian clinicians were 97%, 98% and 96.9%, 97.1%, respectively. The CNN average F1 score was 94%, sensitivity 93.7%, and accuracy 91.7%. Our CNN operates at video rate and generates class activation maps that can be used to visually validate CNN predictions. Conclusions We report a clinically interpretable CNN developed to predict histology based on IPCL patterns, in real time, using the largest reported dataset of images for this purpose. Our CNN achieved diagnostic performance comparable with an expert panel of endoscopists.

Background Endoscopic submucosal dissection (ESD) is gradually turning into the standard treatment for superficial esophageal squamous cell carcinoma (SESCC), however, the long-term outcomes have hardly ever been reported outside Japan. Method We consecutively recruited patients with SESCC who had received ESD treatment at E-Da Hospital. The demographics, pathological characteristics, and Lugol staining background pattern (type A or B: none or 10 small or multiform LVLs) were collected, and then correlated to outcomes and survival. Results Total of 229 lesions were enrolled and the mean lesion size was 3.28 ± 1.69 (range 1–10) cm. 72% of the lesions had a type C-D Lugol staining background pattern. After ESD, the en bloc and R0 resection rates were 93.9% and 83.5%, respectively. Forty-nine subjects developed complications, including six (2.6%) with major bleeding, two (0.9%) with perforation, and 41 (17.9%) with strictures. Pathological staging showed that 19 cases had deep submucosal cancer invasion and subsequently received adjuvant therapies. During a mean follow-up period of 52.6 (range 3–146) months, 41 patients developed metachronous recurrence. The patients with a type C-D Lugol staining background pattern were associated with a higher risk of recurrence than those with few LVLs (log-rank P = 0.019). The 10-year survival rate was more than 90%, and only eight patients died of ESCC. Conclusion ESD has excellent long-term outcomes but a high risk of metachronous recurrence. The Lugol staining pattern over the background mucosa could offer the risk stratification of metachronous recurrence.

Levofloxacin-based therapy or bismuth-based quadruple therapy are the recommended second-line regimens for Helicobacter pylori eradication after failure of clarithromycin-based therapy. However, resistance to levofloxacin has increased in the past decade. Furthermore, little is known about the long-term effects of H pylori eradication on the antibiotic resistome. In this study, we compared these second-line eradication therapies for efficacy, tolerability, and short-term and long-term effects on the gut microbiota, antibiotic resistome, and metabolic parameters.We did a multicentre, open-label, parallel group, randomised controlled trial at eight hospitals in Taiwan. Adult patients (age ≥20 years) with persistent H pylori infection after first-line clarithromycin-based therapy were randomly assigned (1:1, permuted block sizes of four) to receive levofloxacin-based sequential quadruple therapy for 14 days (EAML14; esomeprazole 40 mg and amoxicillin 1 g for 7 days, followed by esomeprazole 40 mg, metronidazole 500 mg, and levofloxacin 250 mg for 7 days, all twice-daily) or bismuth-based quadruple therapy for 10 days (BQ10; esomeprazole 40 mg twice daily, bismuth tripotassium dicitrate 300 mg four times a day, tetracycline 500 mg four times a day, and metronidazole 500 mg three times a day). All investigators were masked to the randomisation sequence. The primary endpoint was H pylori eradication rate measured byBetween Feb 25, 2015, and Dec 11, 2020, 560 patients were randomly assigned to receive EAML14 or BQ10 (n=280 per group; 261 [47%] men and 299 [53%] women). Mean age was 55·9 years (SD 12·7) in the EAML14 group and 54·9 years (12·3) in the BQ10 group. Eradication of H pylori was achieved in 246 (88%) of 280 participants in the EAML14 group and 245 (88%) of 280 in the BQ10 group according to ITT analysis (risk difference -0·4%, 95% CI -5·8 to 5·1; p=0·90). In the per-protocol analysis, 246 (90%) of 273 participants in the EAML14 group and 245 (93%) of 264 participants in the BQ10 group achieved H pylori eradication (risk difference 2·7%, 95% CI -0·2 to 7·4; p=0·27). Transient perturbation of faecal microbiota diversity at week 2 was largely restored to basal state 1 year after EAML14 or BQ10. Diversity recovery was slower with BQ10, and recovery in species abundance was partial after both therapies. On shotgun sequencing, we observed significant increases in total resistome after EAML14 (p=0·0002) and BQ10 (p=4·3 × 10We found no evidence of superiority between levofloxacin-based quadruple therapy and bismuth-based quadruple therapy in the second-line treatment of H pylori infection. The transient increase in the antibiotic resistome and perturbation of faecal microbiota diversity were largely restored to pretreatment state from 2 months to 1 year after eradication therapy.The Ministry of Science and Technology of Taiwan, the Ministry of Health and Welfare of Taiwan, National Taiwan University Hospital, Taipei Veteran General Hospital, and the Australian Federal Government through the St George and Sutherland Medical Research Foundation.For the Chinese translation of the abstract see Supplementary Materials section.

Colorectal endoscopic submucosal dissection is technically demanding, and the traction offered by gravity, cap, or clip-with-line during conventional endoscopic submucosal dissection remains unsatisfactory. Robotic systems are still under development and are expensive. We proposed double-scope endoscopic submucosal dissection with strong and adjustable traction offered by snaring the lesion with additional scope.This study aimed to test the novel double-scope endoscopic submucosal dissection with snare-based traction.This was a retrospective study that reviewed double-scope endoscopic submucosal dissection compared with matched conventional endoscopic submucosal dissection, and size, location, morphology, and pathology between groups were compared.This study was conducted in a referral endoscopy center in a local hospital.This study included patients with colorectal lesions receiving double-scope endoscopic submucosal dissection and matched conventional endoscopic submucosal dissection.The pathological completeness, procedure time, and complications were analyzed.Fifteen double-scope endoscopic submucosal dissection procedures, with 11 lesions located in the proximal colon with a median size of 40 mm, were performed. The median procedure time of double-scope endoscopic submucosal dissection was 32.45 (interquartile range, 16.03-38.20) minutes. The time required for second scope insertion was 2.57 (interquartile range, 0.95-6.75) minutes; for snaring, 3.03 (interquartile range, 2.12-6.62) minutes; and for actual endoscopic submucosal dissection, 28.23 (interquartile range, 7.90-37.00) minutes. All lesions were resected completely. No major complication was encountered. The procedure time was significantly shorter than that of 14 matched conventional endoscopic submucosal dissections (54.61 [interquartile range, 33.11-97.25] min; p = 0.021).This was a single-center, single-operator, retrospective case-controlled study with limited cases.This study confirmed the feasibility of double-scope endoscopic submucosal dissection with snare-based traction to shorten procedure time and to simplify endoscopic submucosal dissection. Additional trials are required.

13 páginas, 7 figuras, Current clinical trials of combined EGFR-tyrosine kinase inhibitors (TKI) and immune checkpoint blockade (ICB) therapies show no additional effect. This raises questions regarding whether EGFR-TKIs attenuate ICB-enhanced CD8+ T lymphocyte function. Here we show that the EGFR-TKI afatinib suppresses CD8+ T lymphocyte proliferation, and we identify CAD, a key enzyme of de novo pyrimidine biosynthesis, to be a novel afatinib target. Afatinib reduced tumor-infiltrating lymphocyte numbers in Lewis lung carcinoma (LLC)-bearing mice. Early afatinib treatment inhibited CD8+ T lymphocyte proliferation in patients with non-small cell lung cancer, but their proliferation unexpectedly rebounded following long-term treatment. This suggests a transient immunomodulatory effect of afatinib on CD8+ T lymphocytes. Sequential treatment of afatinib with anti-PD1 immunotherapy substantially enhanced therapeutic efficacy in MC38 and LLC-bearing mice, while simultaneous combination therapy showed only marginal improvement over each single treatment. These results suggest that afatinib can suppress CD8+ T lymphocyte proliferation by targeting CAD, proposing a timing window for combined therapy that may prevent the dampening of ICB efficacy by EGFR-TKIs. SIGNIFICANCE: This study elucidates a mechanism of afatinib-mediated immunosuppression and provides new insights into treatment timing for combined targeted therapy and immunotherapy. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/12/3270/F1.large.jpg., This study was supported by Taiwan Ministry of Science and Technology grants MOST 104-2320-B-002-044-MY3, MOST 106-2320-B-002-046-MY3, and MOST 108-2320-B-002-024-MY3, National Health Research Institutes grants NHRI-EX106-10401BI and NHRI-EX109-10725BI, National Taiwan University grants NTU107L890504 and NTU110L893503 to M.-S. Lee, and National Taiwan University Hospital grants 106-003451, 107-003849, 108-004269, and 109-004720 to C.-C. Ho. This work was also supported by MINECO grants BFU2016-80570-R and RTI2018-098084-B-I00 (AEI/FEDER, UE). The authors would like to thank the Laboratory Animal Core Facility at the College of Medicine, National Taiwan University for their services

Diabetes mellitus (DM) is a risk factor for pancreatic cancer but its prognostic impact remains controversial. We aimed to investigate the association between long-standing DM and the risk of mortality.This population-based cohort study analyzed data from the national healthcare database in Taiwan. We identified all patients diagnosed with pancreatic cancer and excluded those who were diagnosed with DM with-in 2 years of the cancer diagnosis. Eligible patients were grouped into long-standing DM (2 years) and nondiabetic controls, and were compared for overall survival using a Cox proportional hazard model. Sensitivity tests stratified by cancer stages (as indicated by specific treatment) were performed.Patients with long-standing DM were significantly older (mean age, 71.38 years versus 66.0 years; P.0001) and had a higher Charlson comorbidity index (9.53 versus 6.78; P.0001) and diabetes comorbidity severity index (2.38 versus 0.82; P.0001) compared with the non-DM controls. Although the unadjusted analysis showed a higher risk of mortality in the patients with long-term DM (crude hazard ratiolsqb;HR], 1.26; 95% confidence intervallsqb;CI], 1.20 to 1.33; P.0001), the association became insignificant after adjustment for age, sex, and comorbidity index (adjusted HR, 1.01; 95% CI, 0.95 to 1.06, P = .84). Subgroup analyses also showed no association between long-term DM and mortality in various subgroups stratified by cancer treatment.After adjusting for associated comorbidities and complications, long-standing DM per se was not an independent prognostic factor for overall survival in this nationwide population-based cohort with pancreatic cancer.CCI = Charlson Comorbidity Index; CI = confidence interval; DCSI = Diabetes Complication Severity Index; DM = diabetes mellitus; HR = hazard ratio; ICD = International Classification of Diseases; NHIRD = National Health Insurance Research Database; RCIPD = Registry for Catastrophic Illness Patient Database.

The esophageal gland duct may serve as a pathway for the spread of early esophageal squamous cell neoplasia (ESCN) to a deeper layer. Deep intraductal tumor spreading cannot be completely eradicated by ablation therapy. However, the risk factors of ductal involvement (DI) in patients with ESCNs have yet to be investigated. We consecutively enrolled 160 early ESCNs, which were treated with endoscopic submucosal dissection. The resected specimens were reviewed for the number, morphology, resected margin, distribution and extension level of DI, which were then correlated to clinical factors. A total of 317 DIs (median:3, range 1–40 per-lesion) in 61 lesions (38.1%) were identified. Of these lesions, 14 have DIs maximally extended to the level of lamina propria mucosa, 17 to muscularis mucosae, and 30 to the submucosa. Multivariate logistic regression analysis showed that tumors located in the upper esophagus (OR = 2.93, 95% CI, 1.02–8.42), large tumor circumferential extension (OR = 5.39, 95% CI, 1.06–27.47), deep tumor invasion depth (OR = 4.12, 95% CI, 1.81–9.33) and numerous Lugol-voiding lesions in background esophageal mucosa (OR = 2.65, 95% CI, 1.10–6.37) were risk factors for DI. The maximally extended level of ducts involved were significantly correlated with the cancer invasion depth (P

Endoscopic submucosal dissection (ESD) has become the standard treatment for superficial esophageal squamous cell neoplasia (SESCN); however, local recurrence still occurs occasionally even in patients who meet the current curative criteria. Esophageal ducts of the submucosal gland may serve as a pathway for the spread of SESCN to a deeper layer. However, the clinical impact of ductal involvement (DI) in patients undergoing ESD has yet to be investigated.We consecutively enrolled patients with SESCN who were treated with ESD. The resected specimens were meticulously reviewed in multiple section slices for the presence and resected margins of DI, and their correlations with clinical factors were evaluated.A total of 210 lesions were analyzed, of which 78 (37.1%) presented with DI. The presence of submucosal invasion, lymphovascular invasion (LVI), and DI were indicators of worse prognosis (P .05). Deep extended DIs were misdiagnosed as deep submucosal invasive cancer in 4 cases (2%). Of the 185 patients who met the criteria for curative ESD (ie, R0 resection and no deep submucosal invasion or LVI), 11 (5.9%) developed local recurrence/metastasis during a mean follow-up of 55.2 months (range, 6 to 140) months. Compared with patients with without DI, patients with DI had worse recurrence-free survival (P = .008, log-rank test) and a higher local risk of recurrence (12.7% vs 2.5%) after curative ESD (hazard ratio, 4.20; P = .038).A precise histological assessment of DI in SESCN is crucial after ESD, given that DI is common and associated with worse outcome. Whether total removal of esophageal glands/ducts can improve outcome requires future study.

Aim: The aim of this study was to investigate the long-term outcomes of endoscopic submucosal dissection (ESD) for superficial esophageal squamous cancer. Methods: A literature search was conducted using PubMed, ProQuest and Cochrane Library databases. Primary outcomes were overall survival, disease-specific survival and recurrence-free survival at 5 years. Secondary outcomes included adverse events, recurrence and metastasis. Hazard ratios were calculated based on time to events for survival analysis, and odds radios were used to compare discrete variables. Results: A total of 3796 patients in 21 retrospective studies, including 5 comparative studies for ESD and esophagectomy were enrolled. The invasion depth was 52.0% for M1–M2, 43.2% for M3–SM1 and 4.7% for SM2 or deeper. The 5-year survival rate was: overall survival 87.3%, disease-specific survival 97.7%, and recurrence-free survival 85.1%, respectively. Pooled local recurrence of ESD was 1.8% and metastasis was 3.3%. In terms of the comparison between ESD and esophagectomy, there was no difference in the overall survival (86.4% versus 81.8%, hazard ratio = 0.66, 95% CI = 0.39–1.11) as well as disease-specific and recurrence-free survival. In addition, ESD was associated with fewer adverse events (19.8 % versus 44.0%, odds ratio = 0.3, 95% CI = 0.23–0.39). Conclusions: For superficial esophageal squamous cancer, ESD may be considered as the primary treatment of for mucosal lesions, and additional treatment should be available for submucosal invasive cancers.

Supplemental material, Supp for Long-term outcomes of endoscopic submucosal dissection and comparison to surgery for superficial esophageal squamous cancer: a systematic review and meta-analysis by Jen-Hao Yeh, Ru-Yi Huang, Ching-Tai Lee, Chih-Wen Lin, Ming-Hung Hsu, Tsung-Chin Wu, Po-Jen Hsiao and Wen-Lun Wang in Therapeutic Advances in Gastroenterology

Background & Aims We aimed to compare the efficacy of genotypic resistance–guided therapy vs empirical therapy for eradication of refractory Helicobacter pylori infection in randomized controlled trials. Methods We performed 2 multicenter, open-label trials of patients with H pylori infection (20 years or older) failed by 2 or more previous treatment regimens, from October 2012 through September 2017 in Taiwan. The patients were randomly assigned to groups given genotypic resistance–guided therapy for 14 days (n = 21 in trial 1, n = 205 in trial 2) or empirical therapy according to medication history for 14 days (n = 20 in trial 1, n = 205 in trial 2). Patients received sequential therapy containing esomeprazole and amoxicillin for the first 7 days, followed by esomeprazole and metronidazole, with levofloxacin, clarithromycin, or tetracycline (doxycycline in trial 1, tetracycline in trial 2) for another 7 days (all given twice daily) based on genotype markers of resistance determined from gastric biopsy specimens (group A) or empirical therapy according to medication history. Resistance-associated mutations in 23S ribosomal RNA or gyrase A were identified by polymerase chain reaction with direct sequencing. Eradication status was determined by 13C-urea breath test. The primary outcome was eradication rate. Results H pylori infection was eradicated in 17 of 21 (81%) patients receiving genotype resistance–guided therapy and 12 of 20 (60%) patients receiving empirical therapy (P = .181) in trial 1. This trial was terminated ahead of schedule due to the low rate of eradication in patients given doxycycline sequential therapy (15 of 26 [57.7%]). In trial 2, H pylori infection was eradicated in 160 of 205 (78%) patients receiving genotype resistance–guided therapy and 148 of 205 (72.2%) patients receiving empirical therapy (P = .170), according to intent to treat analysis. The frequencies of adverse effects and compliance did not differ significantly between groups. Conclusions Properly designed empirical therapy, based on medication history, is an acceptable alternative to genotypic resistance–guided therapy for eradication of refractory H pylori infection after consideration of accessibility, cost, and patient preference. ClinicalTrials.gov ID: NCT01725906.

BACKGROUND AND AIM Optimal staging of the invasion depth of superficial esophageal squamous cell carcinoma is vital before endoscopic treatment. A new simplified magnified narrow-band imaging (M-NBI) classification system based on vascular architecture has recently been developed by the Japan Esophageal Society; however, its validity remains uncertain. METHODS A total of 11 experienced and 11 inexperienced endoscopists were invited to join an endoscopic training program, which was composed of pretest, educational section, and post-test. The pretest and post-test sections included a set of endoscopic photos from 40 subjects with superficial esophageal squamous cell carcinoma with various invasion depths. Each subject appeared twice in the test, one with white-light imaging (WLI) only and the other with both WLI and M-NBI. The educational section included lectures and video demonstrations. RESULTS The accuracy of WLI alone and combined with M-NBI at baseline were 0.53, 0.57 and 0.43, 0.41 for the experienced and inexperienced endoscopists, respectively, which then improved to 0.57, 0.63 and 0.49, 0.52 after training. Inter-observer agreement (k-value) of WLI alone and combined WLI and M-NBI for the experienced and inexperienced endoscopists also improved from 0.61, 0.61, and 0.61, 0.53 to 0.68, 0.71, and 0.71, 0.59, respectively. Multivariate analysis revealed that the educational course but not experience in endoscopy, NBI, or magnification significantly improved the diagnostic accuracy. M-NBI had a significant additional benefit to WLI, with an improvement in accuracy from 36% to 56% for the cases with m3/sm1 cancers (P

Background Endoscopic radiofrequency ablation (RFA) is a treatment option for early esophageal squamous cell neoplasia (ESCN); however, long-term follow-up studies are lacking. The risks of local recurrence and “buried cancer” are also uncertain. Methods Patients with flat-type ESCN who were treated with balloon-type ± focal-type RFA were consecutively enrolled. Follow-up endoscopy was performed at 1, 3, and 6 months, and then every 6 months thereafter. Endoscopic resection was performed for persistent and recurrent ESCN, and the histopathology of resected specimens was assessed. Results A total of 35 patients were treated with RFA, of whom 30 (86 %) achieved a complete response, three were lost to follow-up, and five (14 %) developed post-RFA stenosis. Two patients had persistent ESCN and received further endoscopic resection, in which the resected specimens all revealed superficial submucosal invasive cancer. Six of the 30 patients with successful RFA (20 %) developed a total of seven episodes of local recurrence (mean size 1.4 cm) during the follow-up period (mean 40.1 months), all of which were successfully resected endoscopically without adverse events. Histological analysis of the resected specimens revealed that six (86 %) had esophageal glandular ductal involvement, all of which extended deeper than the muscularis mucosae layer. Immunohistochemistry staining for P53 and Ki67 suggested a clonal relationship between the ductal involvement and epithelial cells. None of the tumors extended out of the ductal structure; no cases of cancer buried beneath the normal neosquamous epithelium were found. Conclusions Because ductal involvement is not uncommon and may be related to recurrence, the use of RFA should be conservative and may not be the preferred primary treatment for early ESCN.

INTRODUCTION: The incidence of early-onset colorectal cancer is increasing. This study explored the feasibility of fecal immunochemical test (FIT) and risk factors for predicting colorectal neoplasm in younger adults. METHODS: This single-center study included 6,457 participants who underwent health examination from 2013 to 2016 including index colonoscopy (3,307 individuals aged 30–49 years as the younger adult group and 3,150 aged ≥50 years as the average-risk group). Primary outcomes were adenoma detection rate (ADR) and advanced ADR (AADR). Findings of younger participants were stratified by the results of FIT and clinical risk factors and were compared with those of the average-risk group. RESULTS: Among participants aged 30–49 years, a positive FIT was associated with significantly higher ADR (28.5% vs 15.5, P < 0.001) and AADR (14.5% vs 3.7%, P < 0.001) than a negative FIT. Moreover, a positive FIT was associated with higher AADR in younger participants than in average-risk counterparts (14.5% vs 9.8%, P = 0.028). Although no single risk factor predicted FIT positivity in younger participants, nonalcoholic fatty liver disease was independently associated with higher ADR (odds ratio = 2.60, 95% confidence interval = 1.27–5.34, P = 0.001), and metabolic syndrome was independently predictive of higher AADR in younger participants than in average-risk participants (odds ratio = 3.46, 95% confidence interval = 1.66–7.21, P = 0.001). DISCUSSION: A positive FIT in people aged 30–49 years implies a higher risk of colorectal neoplasm, particularly among patients with nonalcoholic fatty liver disease and metabolic syndrome.

How long esophageal screening should be performed for, and on which sub-groups of head and neck cancer (HNC) survivors, remains uncertain. This retrospective study analyzed data from the Taiwan National Health Insurance Research Database from 1999 to 2013. A total of 68,131 newly- diagnosed HNC patients were enrolled. Subjects who received esophageal endoscopic screening within 6 months after their diagnosis date of index HNC were identified. The incidence trends of secondary primary EC were analyzed using a Cochran-Armitage trend test. Among the 9,707 patients who received index esophageal endoscopy screening, 101 (1.0%) cases of synchronous EC were diagnosed. The 5- and 10-year cumulative incidence rates of metachronous ECs were 1.4% and 2.7%, respectively in those with an initial negative index endoscopic finding. Patients with oropharynx or hypopharynx cancers were at significantly higher risk of developing metachronous ECs compared with those with oral or larynx cancers (10-year incidence rate: 3.3% vs. 0.9%, respectively; hazard ratio: 2.15; 95% confidence intervals: 1.57–2.96). Metachronous EC continues to develop in patients with HNC even at 10-years after treatment for primary HNC. HNC patients, especially those with oropharynx or hypopharynx cancer, may require long-term endoscopic surveillance.

Patients with esophageal squamous cell carcinomas (ESCCs) have poor survival and high recurrence rate, but lack a prognostic biomarker. Disabled-2 (DAB2) is a crucial tumor suppressor, but its roles in ESCCs are uncertain. We investigated whether low DAB2 expression in ESCCs could lead into tumor progression and poor prognosis. Our results found patients with low-DAB2 expression ESCCs had significantly larger tumor size, deeper tumor invasion depth, lymph node metastasis, worse survival, and higher recurrence rate (P

There is controversy over the best therapeutic approach for T1 colorectal cancer. We performed a systematic review and meta-analysis of long-term outcomes of endoscopic resection (ER) vs those of primary or additional surgery.We performed a systematic review of the PubMed, Embase, and Cochrane databases through October 2019 for studies that reported outcomes (overall survival, disease-specific survival, recurrence-free survival at 5 years, recurrence, and metastasis) of ER vs surgery in patients with colorectal neoplasms. Hazard ratios (HR) were calculated based on time to events.In total, 17 published studies with 19,979 patients were included. The median follow-up time among the studies was 36 months. The meta-analysis found no significant differences between primary ER and primary surgery in overall survival (79.6% vs 82.1%, HR, 1.10; 95% CI, 0.84-1.45), recurrence-free survival (96.0% vs 96.7%, HR, 1.28; 95% CI, 0.87-1.88), or disease-specific survival (94.8% vs 96.5%; HR, 1.09; 95% CI, 0.67-1.78). Additional surgery and primary surgery did not produce significant differences in recurrence-free survival (HR, 1.27; 95% CI, 0.85-1.89). A significantly lower proportion of patients who underwent primary ER had procedure-related adverse events (2.3%) than patients who underwent primary surgery (10.9%) (P.001). Lymphovascular invasion and rectal cancer, but not depth of submucosal invasion, were independently associated with recurrence for all T1 colorectal cancers.In a systematic review and meta-analysis, we found that ER should be considered as the first-line treatment for endoscopically resectable T1 colorectal cancers. In cases of noncurative resection, additional surgery can have comparable outcomes to primary surgery.

BACKGROUND AND AIM Simethicone is an anti-foaming agent commonly used during colonoscopy. Although several randomized trials have shown that oral simethicone in the bowel preparation regimen may improve bowel cleanness, whether it improves adenoma detection rate (ADR) or polyp detection rate remains undetermined. The aim of this study was to determine if oral simethicone in bowel preparation regimen before colonoscopy improves the ADR. METHODS A comprehensive literature review was conducted using PubMed, SDOL, Cochrane Library, and ProQuest databases through December 2017. Randomized controlled trials that compared bowel preparation regimens with simethicone versus those without it were included. Effect estimates from each study were extracted and underwent meta-analysis using appropriate models. The primary outcomes were ADR and polyp detection rate, and secondary outcomes included bowel preparation, bubble score, and withdrawal time. RESULTS Twelve published randomized controlled studies with 6003 participants were included for meta-analysis. There was no difference in the overall ADR (pooled risk ratio = 1.06, 95% confidence interval = 0.91-1.24) and right-side ADR (risk ratio = 1.50, 95% confidence interval = 0.82-2.75) between the groups with or without simethicone. However, the addition of simethicone improved adenoma detected per patient (2.20 ± 1.36 vs 1.63 ± 0.89) according to one of the included studies. Meta-regression revealed that the baseline ADR

Endoscopic radiofrequency ablation (RFA) is a rapidly evolving therapeutic modality for early flat esophageal squamous cell neoplasms (ESCNs). However, the in vivo tissue effects of RFA on the esophageal wall are uncertain.We prospectively enrolled eight patients with flat-type early ESCNs who were treated with balloon-based RFA. We evaluated the in vivo tissue effect on the esophagus using endoscopic ultrasound (EUS) and the histology of retrieved coagulum.The mean tumor length was 6.1 cm, and six of the eight patients achieved a complete response after primary RFA. Real-time evaluation of the tissue effect showed that the mucosa and submucosal layer were more edematous and thicker after RFA than before the procedure (mean 4.89 vs. 2.04 mm,Our findings suggest that the thermal effect of RFA may injure the submucosal layer and enable neoplastic epithelium to slough off without "burning."