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Background: Gallbladder cancer is rare but associated with significant morbidity and mortality necessitating the early identification of premalignant and malignant lesions to improve overall prognosis. Despite limited evidence regarding the effectiveness of transabdominal ultrasound (US) in the detection of gallbladder polyps, it plays a key role in current European guidelines. The aim of this study was to investigate gallbladder polyp prevalence in a western European population and assess the diagnostic accuracy of transabdominal US., Methods: Data from patients who underwent cholecystectomy for US detected gallbladder polypoid lesions at four hospitals in Ireland and the United Kingdom between 2010 and 2018 were retrospectively collected. Patient demographics, ultrasonographic, and histopathologic findings were analyzed., Results: A total of 134 patients underwent cholecystectomy for US-detected gallbladder polyps. After histopathologic examination, pseudopolyps were found in 75 (56%) specimens with dysplastic or malignant polyps seen in only six (4.5%) specimens. Mean size for neoplastic polyps was 33 mm. The positive predictive value for US in detecting neoplastic polyps in this study was 4.5%, which is significantly lower than the 10%-15% reported previously., Conclusions: Although the prevalence of neoplastic polyps in this study is higher than in the previous literature, the distribution of pseudopolyps and true polyps is as expected. With all malignant polyps being >10 mm in diameter, these findings support the current size thresholds stated in European guidelines. The poor diagnostic accuracy of US demonstrated may have led to significant number of patients undergoing unnecessary surgical intervention, further supporting the argument for improved strategies for the investigation of gallbladder polyps., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Background: Barrett's oesophagus is one of the most common pre-malignant lesions in the world. Currently the mainstay of therapy is surgical management of advanced cancer but this has improved the five-year survival very little since the 1980s. As a consequence, improved survival relies on early detection through endoscopic surveillance programmes. Success of this strategy relies on the fact that late-stage pre-malignant lesions or very early cancers can be cured by intervention. Currently there is considerable controversy over which method is best: that is conventional open surgery or endotherapy (techniques involving endoscopy)., Objectives: We used data from randomised controlled trials (RCTs) to examine the effectiveness of endotherapies compared with surgery in people with Barrett's oesophagus, those with early neoplasias (defined as high-grade dysplasia (HGD) and those with early cancer (defined as carcinoma in-situ, superficially invasive, early cancer or superficial cancer T-1m (T1-a) and T-1sm (T1-b))., Search Methods: We used the Cochrane highly sensitive search strategy to identify RCTs in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, EBMR, Controlled Trials mRCT and ISRCTN, and LILACS, in July and August 2008. The searches were updated in 2009 and again in April 2012., Selection Criteria: Types of studies: RCTs comparing endotherapies with surgery in the treatment of high-grade dysplasia or early cancer. All cellular types of cancer were included (i.e. adenocarcinomas, squamous cell carcinomas and more unusual types) but will be discussed separately., Types of Participants: patients of any age and either gender with a histologically confirmed diagnosis of early neoplasia (HGD and early cancer) in Barrett's or squamous lined oesophagus. Types of interventions; endotherapies (the intervention) compared with surgery (the control), all with curative intent., Data Collection and Analysis: Reports of studies that meet the inclusion criteria for this review would have been analysed using the methods detailed in Appendix 9., Main Results: We did not identify any studies that met the inclusion criteria. In total we excluded 13 studies that were not RCTs but that compared surgery and endotherapies., Authors' Conclusions: This Cochrane review has indicated that there are no RCTs to compare management options in this vital area, therefore trials should be undertaken as a matter of urgency. The problems with such randomised methods are standardising surgery and endotherapies in all sites, standardising histopathology in all centres, assessing which patients are fit or unfit for surgery and making sure there are relevant outcomes for the study (i.e. long-term survival (over five or more years)) and no progression of HGD., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

In recent years, the serrated neoplasia pathway where serrated polyps arise as a colorectal cancer has gained considerable attention as a new carcinogenic pathway. Colorectal serrated polyps are histopathologically classified into hyperplastic polyps (HPs), sessile serrated lesions, and traditional serrated adenomas; in the serrated neoplasia pathway, the latter two are considered to be premalignant. In western countries, all colorectal polyps, including serrated polyps, apart from diminutive rectosigmoid HPs are removed. However, in Asian countries, the treatment strategy for colorectal serrated polyps has remained unestablished. Therefore, in this review, we described the clinicopathological features of colorectal serrated polyps and proposed to remove HPs and sessile serrated lesions ≥ 6 mm in size, and traditional serrated adenomas of any size., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Gallbladder polyps (GBPs) are gallbladder lesions which can progress to gallbladder malignancy. The incidence has been estimated as high as 12.1% of all cholecystectomy patients. Gallbladder malignancy typically presents late, and therefore carries a poor prognosis. By identifying potential GBPs early, it would be possible to treat polyps before they undergo malignant change. The current gold standard for GBP identification is with histological examination which is performed after cholecystectomy. This study sought to assess whether radiological imaging could reliably identify GBPs and therefore guide management., Methods: 1000 consecutive patients already undergoing cholecystectomy were sampled from two UK hospitals. Patients who underwent ultrasonography and had histological analysis of their gallbladders were selected. Overall 905 patients were included in the study., Results: There were 12 histologically confirmed GBPs in the cohort (1.33%). US correctly detected 1 GBP, with a sensitivity of 8.3% (95% CI 0.2-38.5%) and specificity of 96.0% (95% CI 94.5-97.2%). The overall accuracy was 94.8 (95% CI 93.2-96.2%)., Conclusion: These data show that US is an ineffective tool for GBP identification. The lack of prior operator exposure, imprecise nature of US and possible obstruction of images from underlying gallstone disease delivered a high rate of false positives., Implications for Practice: Surgical or oncological decisions regarding GBPs should not be based upon US findings alone as this would lead to unnecessary interventions. MRI should be investigated as an alternative imaging modality for GBP identification, as its differentiation of soft tissues could guide surgical management., Competing Interests: Conflict of interest statement The authors confirm they have no conflicts of interest to declare., (Copyright © 2019 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.)

Purpose: To predict the histologic invasiveness of pure GGNs using the maximum CT value., Patients and Methods: One hundred eighty patients underwent a resection of pure GGNs. On preoperative CT imaging studies, we selected the axial section that showed the densest component of each GGN. The CT value was measured using a DICOM (Digital Imaging and Communication in Medicine) viewer, excluding portions of vessels and bronchi. The correlation between the CT value and GGN histologic diagnosis was analyzed., Results: The numbers of patients with atypical adenomatous hyperplasia, adenocarcinoma-in-situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IAC) were 9, 108, 56, and 7, respectively. One of the IAC tumors exhibited lymphatic invasion, and there were no cases of vascular invasion. In comparison to preinvasive lesions (atypical adenomatous hyperplasia and AIS), invasive lesions (MIA and IAC) were correlated with a higher maximum CT value (-404 ± 113 Hounsfield units [HU] vs. -216 ± 125 HU, P < .01). The cutoff point of maximum CT value was determined at -300 HU using receiver operating characteristic curve analysis, and exhibited sensitivity and specificity of 83% and 88%, respectively. Multivariate analysis revealed that maximum CT value was an independent predictor of histologic invasiveness (odds ratio 39, P < .01). The interobserver reliability was satisfactory (intraclass correlation coefficient, 0.738; unweighted kappa-values, 0.722)., Conclusion: IAC and MIA accounted for 4% and 31% of the pure GGN lesions, respectively. Higher maximum CT value (≥ -300 HU) was a useful predictor of histologic invasiveness., (Copyright © 2020 Elsevier Inc. All rights reserved.)

After endoscopic resection (ER) of gastric dysplasia, metachronous gastric neoplasm (MGN) appears to have an incidence rate similar to that detected after ER of early gastric cancer (EGC). We investigated whether the risk of MGN after ER for gastric dysplasia is different between patients with low-grade dysplasia (LGD) and high-grade dysplasia (HGD). Between March 2011 and December 2016, 198 patients with LGD (LGD group) and 46 patients with HGD (HGD group) who underwent ER were included in the study. During a median follow-up of 2.5 years, MGNs developed in 21 patients (10.6%) in the LGD group and in 6 patients (13.0%) in the HGD group. Hazard ratios (HRs) for MGNs (HR, 1.45; P = 0.425) and for metachronous HGD or gastric cancer (HR, 2.41; P = 0.214) in the HGD group were not different than those of the LGD group. However, considering patients without Helicobacter pylori infection, those in the HGD group had a significantly increased risk of metachronous HGD or gastric cancer compared to those in the LGD group (HR in HGD-group, 5.23; P = 0.044). These results indicate that meticulous surveillance endoscopy is needed to detect MGNs after ER of gastric dysplasia, especially in patients with HGD, including those without H. pylori infection.

Background: Endoscopic eradication therapy of dysplastic Barrett's esophagus (BE) and early esophageal neoplasia has emerged as an effective treatment option. Data for the role of spray cryotherapy (SCT) in this setting is relatively limited., Objective: To evaluate the safety and long-term outcomes of SCT-based multimodal therapy in the management of dysplastic BE and early esophageal neoplasia., Design: Single-center, retrospective, cohort study., Setting: Academic, tertiary care center between August 2008 and February 2019., Methods: A retrospective chart review was conducted of the prospectively maintained endoscopic cryotherapy database at our center. Fifty-seven patients were identified who underwent SCT treatment for dysplastic BE and esophageal or Gastro-esophageal (GE) junction adenocarcinoma during the study period. Primary outcome was complete eradication of intestinal metaplasia (CE-IM); secondary outcome was complete eradication of dysplasia (CE-D)., Results: A total of 171 SCT procedures were performed in 57 patients. The majority of patients were male (89.5%) with long-segment BE (93%; mean segment length 6.2 cm). Complete follow-up data was available for 56 of these 57 patients. 43.9% (25/57) of patients underwent radiofrequency ablation (RFA) during the course of treatment (e.g. after initiating SCT). 33.3% of patients (19/57) were RFA failures prior to SCT. Additionally, 68.4% (39/57) of patients underwent endoscopic resection (EMR) prior to SCT as part of our multimodal approach to treatment of BE dysplasia/neoplasia. Four patients (7%) are currently undergoing active ablation and/or EMR treatment. CE-IM was achieved in 75% (39/52) of patients, and CE-D in 98.1% (51/52). Mean duration of overall follow-up was 4.8 years, with mean CE-IM durability of 2.6 years., Limitations: Single-center only, retrospective study design., Conclusion: SCT-based multimodal endoscopic therapy can achieve very high CE-IM (75%) and CE-D (>98%) rates in a high-risk population with esophageal dysplasia and/or neoplasia., (© The Author(s) 2020. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue samples were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 samples (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer samples, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings., Competing Interests: Competing interest statement: Waters Corporation provided supplies and maintenance for the mass spectrometry equipment used. Z.T. serves as a paid consultant for Waters Corporation. J.B. is employed by Waters Corporation., (Copyright © 2020 the Author(s). Published by PNAS.)

Objectives: Healing of gastric endoscopic submucosal dissection (ESD)-induced ulcer is critical for patient recovery. During ESD treatment, submucosal incisions are made with an electrosurgical knife to accomplish en bloc resections of superficial lesions. Nevertheless, excess electrocoagulation may decrease the blood supply of ESD-induced ulcer and delay the ulcer healing. The aim of this retrospective study was to evaluate the effectiveness of conservative electrocoagulation followed by porcine fibrin sealant (FS) as a wound microvessels-protective hemostatic technique in promoting the healing of ESD-induced ulcer., Methods: A total of 332 patients with early gastric cancer (EGCs), or gastric precancerous lesion and gastric adenoma were retrospectively analyzed. Propensity score matching was used to compensate for the differences in age, gender, tumor location, resected specimen area, and pathology. One-month ulcer healing rates and delayed bleeding were compared between two matched groups (combined hemostats group and electrocautery group)., Results: A total of 115 matched pairs were created after propensity score matching. There was no difference in tumor location, specimen surface area, tumor differentiation and invasion depth between groups. The completed healing rate 1 month after ESD was 44.3% in combined hemostats group and 30.4% in electrocautery group (P = 0.004). There was no difference in delayed massive bleeding rate between two groups (P = 0.300). In addition, based on the multivariate regression analysis for ulcer healing rate, the use of FS (OR, 0.348, 95% CI 0.196 - 0.617, P = 0.000) and larger specimen size (OR, 2.640, 95% CI 2.015-3.458, P = 0.000) were associated with nonhealing ulcer 1 month after ESD., Conclusion: Applying conservative electrocoagulation followed by porcine FS as a wound microvessels-protective hemostatic technique can promote ESD-induced ulcer healing without increasing delayed bleeding.

Patients with inflammatory bowel disease (IBD) have an increased risk of colorectal carcinoma. The significance of serrated lesions resembling traditional serrated adenoma (TSA) in IBD patients is unclear. In this retrospective study, we analyzed 52 TSA-like lesions arising in 30 IBD patients and diagnosed in colectomy or endoscopic specimens. The 27 colectomy lesions presented predominantly as ill-defined areas with granular appearance, with a median size of 15 mm, located throughout the large bowel and associated with synchronous advanced colorectal lesions in 58%. Low-grade serrated dysplasia was present in 56%, high-grade serrated dysplasia in 37%, and TSA-type cytology in 7%. Increased Ki-67 immunostaining and abnormal p53 expression were identified in 96% and 48%, respectively; 74% had a KRAS mutation, and 4% had a BRAF mutation. Endoscopically resectable TSA-like lesions were all discrete polypoid lesions, smaller in size (median 9 mm), predominantly in the distal large bowel, with an adjacent precursor polyp in 24%, and associated with synchronous and metachronous advanced colorectal lesions in 6%. Most (92%) show TSA-type cytology. p53 overexpression was present in 4%, KRAS mutation in 41%, and BRAF mutation in 32%. None of the 52 TSA-like lesions demonstrated loss of MLH1 or SATB2 expression by immunohistochemistry. On follow-up, 4 patients were diagnosed with colorectal carcinoma or high-grade adenomatous IBD-associated dysplasia. None of the patients with lesions showing TSA-type cytology only developed an advanced lesion. Our findings suggest that some TSA-like lesions, essentially from colectomy, may represent a form of IBD-associated dysplasia associated with an increased risk of advanced neoplasia., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Study Objective: Because postmenopausal bleeding (PMB) is associated with up to 10% of endometrial neoplasia and office endometrial sampling fails in approximately 10% and is inadequate in 30% of cases, the objective was to determine the role of hysteroscopic endometrial resection (HER) for the diagnosis and treatment of women with PMB., Design: A retrospective cohort., Setting: A university-affiliated teaching hospital., Patients: One hundred fifty-one women with PMB (September 1990-December 2010)., Intervention: HER in the operating room., Measurements and Main Results: The median (range) age and body mass index were 58 (50-87) years and 29 (21-52) kg/m 2 , respectively. Office endometrial biopsy failed in 30 (19.8%), was inadequate in 20 (13.2%), identified nonatypical endometrial hyperplasia (NAH) in 21 (14%), atypical hyperplasia (AH) in 4 (2.6%), and endometrial cancer (EC) in 2 (1.3%) women. HER in 151 women identified 7 new cases of AH (3 from failed/inadequate office biopsy and 4 from NAH) and 9 EC (5 from failed/inadequate office biopsy, 1 from proliferative endometrium, 2 from NAH, and 1 from AH). All 27 women with NAH were treated by HER alone. Of 8 women with AH, 6 were treated with HER and 2 with hysterectomy; no residual endometrium was found in hysterectomy specimens. Of the 11 women with EC, 2 refused hysterectomy and are well 10 and 15 years after HER. Hysterectomy was performed for 9 of 11 EC cases, 2 of 8 AH cases, and 1 for abnormal uterine bleeding. Six women had repeat HER for persistent abnormal uterine bleeding, and 10 were lost to follow-up. At a median follow-up of 11.5 years (range, 7-20 years), 132 (12 hysterectomies + 10 lost) of 151 (87.4%) women were satisfied with no further bleeding., Conclusion: In women with PMB, hysteroscopic endometrial resection concomitantly with resection of intrauterine pathology by experienced surgeons is feasible, safe, and effective for diagnosis in all cases and treatment of the majority of intrauterine pathology including NAH and selected cases of AH and EC., (Copyright © 2019 AAGL. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Endoscopic screening reduces incidence and mortality of colorectal cancer (CRC) because precursor lesions, such as conventional adenomas or serrated polyps, are removed. Individuals with polypectomies are advised to undergo colonoscopy surveillance to prevent CRC. However, guidelines for surveillance intervals after diagnosis of a precursor lesion, particularly for individuals with serrated polyps, vary widely, and lack sufficient supporting evidence. Consequently, some high-risk patients do not receive enough surveillance and lower-risk subjects receive excessive surveillance., Methods: We examined the association between findings from first endoscopy and CRC risk among 122,899 participants who underwent flexible sigmoidoscopy or colonoscopy in the Nurses' Health Study 1 (1990-2012), Nurses' Health Study 2 (1989-2013), or the Health Professionals Follow-up Study (1990-2012). Endoscopic findings were categorized as no polyp, conventional adenoma, or serrated polyp (hyperplastic polyp, traditional serrated adenoma, or sessile serrated adenoma, with or without cytological dysplasia). Conventional adenomas were classified as advanced (≥10 mm, high-grade dysplasia, or tubulovillous or villous histology) or nonadvanced, and serrated polyps were assigned to categories of large (≥10 mm) or small (<10 mm). We used a Cox proportional hazards regression model to calculate the hazard ratios (HRs) of CRC incidence, after adjusting for various potential risk factors., Results: After a median follow-up period of 10 years, we documented 491 incident cases of CRC: 51 occurred in 6161 participants with conventional adenomas, 24 in 5918 participants with serrated polyps, and 427 in 112,107 participants with no polyp. Compared with participants with no polyp detected during initial endoscopy, the multivariable HR for incident CRC in individuals with an advanced adenoma was 4.07 (95% confidence interval [CI] 2.89-5.72) and the HR for CRC in individuals with a large serrated polyp was 3.35 (95% CI 1.37-8.15). In contrast, there was no significant increase in risk of CRC in patients with nonadvanced adenomas (HR 1.21; 95% CI 0.68-2.16, P = .52) or small serrated polyps (HR 1.25; 95% CI 0.76-2.08; P = .38)., Conclusions: These findings provide support for guidelines that recommend repeat lower endoscopy within 3 years of a diagnosis of advanced adenoma and large serrated polyps. In contrast, patients with nonadvanced adenoma or small serrated polyps may not require more intensive surveillance than patients without polyps., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Pancreatic cysts are increasingly diagnosed, mainly during abdominal imaging performed for other reasons. Between pancreatic cystic neoplasm, intraductal papillary mucinous neoplasms are the most common pre-malignant entities. Intraductal papillary mucinous neoplasms involving side branches overall harbor a low risk of malignancy, and in the recent past, a progressively more conservative approach has been consolidated. Purpose of this report is to summarize the evidence supporting the current practice for the management of branch duct intraductal papillary mucinous neoplasm and to offer a useful practical guide from first observation to post-operative follow-up., Materials and Methods: Review of the most important scientific literature on intraductal papillary mucinous neoplasms was made. In this review article, we also report the experience of a high volume center in managing Pancreatic cystic neoplasms., Results: The correct management during surveillance still is a matter of debate, since many guidelines have been published suggesting different clinical approaches. Recently, follow-up discontinuation has also been proposed in selected cases., Conclusion: Despite significant improvements made by the increase of evidence, selecting surgical candidates because of an increased risk of malignant progression remains an unsolved issue and a hot topic for pancreatologists.

Background: The importance of ACF is not fully explained, however, their number may be a good predictor of synchronous and metachronic adenoma or other polyps whose removal reduces the risk of CRC. Due to the epidemiological and genetic association of ACF with pre-cancer lesions, they may be a potential CRC biomarker. The aim of our study was to show that the number and type of rectal ACF may be a good predictive factor for the presence of polyps located proximally from the splenic flexure and that the type and number of ACF can correlate with the number and specific types of polyps in the large intestine., Methods: The study included 131 patients who underwent colonoscopy combined with rectal mucosa staining with 0.25% methylene blue. The number of rectal ACF was determined and bioptats were sampled for histopathological examination to assess the type of ACF. Endoscopic ACF assessment criteria given by L. Roncucci were used. The obtained material was subjected to statistical analysis using probability distribution, U-test, t-student test, and chi 2 as well as the Statistica 7.1 software package., Results: The study population was divided into three subgroups according to the number of ACF observed, i.e. ACF < 5, 5-10 and > 10. ACF < 5 were found in 35 patients (29.41%), 5-10 ACF in 70 (58.82%) and ACF > 10 in 14 individuals (11.76%). The study revealed the presence of normal ACF (p = 0.49), hyperplastic ACF (p = 0.34), dysplastic ACF (p = 0.11), and mixed ACF (p = 0.06). A single type of ACF was most commonly observed (n = 88, p = 0.74). In the researched group a larger number of ACF is concurrent with adenomas and hyperplastic polyps. The number of ACF clearly correlates with the dysplasia advancement in the adenoma and the number of polyps found., Conclusions: Rectal ACF are a useful marker for the presence of cancerous lesions in the proximal and distal sections of the large intestine.

Background: Basaloid salivary gland neoplasms (BSNs), which include benign primary tumors and primary or metastatic malignancies, show overlapping morphology in fine-needle aspiration (FNA). The Milan system recommends assigning a grade (low or high) to malignant salivary neoplasms because of the impact on surgical planning. This study investigated cytomorphologic features of BSNs on FNA that would help to favor a high-grade malignancy over a low-grade malignancy or a benign tumor., Methods: Two pathologists performed a double-blinded cytologic evaluation of FNA cases diagnosed as BSNs that had corresponding surgical resections. The diagnosis made with the Milan system was correlated with the final surgical diagnosis and grade. Cytologic sensitivity, specificity, and predictive values were calculated., Results: There were 132 BSN FNA cases; cytology slides were available for 77 of 87 patients who had undergone resection. The risk of malignancy for the benign neoplasm (BN), salivary gland neoplasm of uncertain malignant potential (SUMP), suspicious for malignancy (SFM), and malignant categories were 13.6%, 22%, 100%, and 100%, respectively. The sensitivity of the malignant/SFM category was 51.7%; another 37.9% of confirmed malignancies were diagnosed as SUMP. The specificity of the BN category was 86%. Favoring a high-grade malignancy on FNA had 100% accuracy (5 of 5). Favoring a low-grade malignancy on FNA had 75% accuracy (6 of 8). The most specific cytomorphologic clues for a high-grade malignancy were necrotic/apoptotic debris, mitoses, discohesion, and anisonucleosis., Conclusions: BSNs encompass a broad spectrum of primary and metastatic tumors. Necrotic/apoptotic debris, mitotic activity, discohesion, and significant anisonucleosis, alone or especially in combination, should make a cytopathologist suspect a high-grade malignancy., (© 2019 American Cancer Society.)

OBJECTIVE. Atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) are among high-risk lesions that have been previously recommended for surgical excision when diagnosed on core needle biopsy. Recent studies have examined whether imaging surveillance is a reasonable alternative to surgical management for these lesions. This article synthesizes the evidence regarding management of atypical hyperplasia and LCIS diagnosed on core needle biopsy and clinical implications of these diagnoses on future breast cancer risk as well as highlights areas of further research needed to improve practice guidelines for these high-risk lesions. CONCLUSION. Although surgical excision is still recommended after diagnosis of ADH on core needle biopsy, in specific circumstances ALH and LCIS can safely be managed by imaging surveillance.

Background: Endometrial intraepithelial neoplasia, also known as complex atypical hyperplasia, is a precancerous lesion of the endometrium associated with a 40% risk of concurrent endometrial cancer at the time of hysterectomy. Although a majority of endometrial cancers diagnosed at the time of hysterectomy for endometrial intraepithelial neoplasia are low risk and low stage, approximately 10% of patients ultimately diagnosed with endometrial cancers will have high-risk disease that would warrant lymph node assessment to guide adjuvant therapy decisions. Given these risks, some physicians choose to refer patients to a gynecologic oncologist for definitive management. Currently, few data exist regarding preoperative factors that can predict the presence of concurrent endometrial cancer in patients with endometrial intraepithelial neoplasia. Identification of these factors may assist in the preoperative triaging of patients to general gynecology or gynecologic oncology., Objective: To determine whether preoperative factors can predict the presence of concurrent endometrial cancer at the time of hysterectomy in patients with endometrial intraepithelial neoplasia; and to describe the ability of preoperative characteristics to predict which patients may be at a higher risk for lymph node involvement requiring lymph node assessment at the time of hysterectomy., Materials and Methods: We conducted a retrospective cohort study of women undergoing hysterectomy for pathologically confirmed endometrial intraepithelial neoplasia from January 2004 to December 2015. Patient demographics, imaging, pathology, and outcomes were recorded. The "Mayo criteria" were used to determine patients requiring lymphadenectomy. Unadjusted associations between covariates and progression to endometrial cancer were estimated by 2-sample t-tests for continuous covariates and by logistic regression for categorical covariates. A multivariable model for endometrial cancer at the time of hysterectomy was developed using logistic regression with 5-fold cross-validation., Results: Of the 1055 charts reviewed, 169 patients were eligible and included. Of these patients, 87 (51.5%) had a final diagnosis of endometrial intraepithelial neoplasia/other benign disease, whereas 82 (48.5%) were ultimately diagnosed with endometrial cancer. No medical comorbidities were found to be strongly associated with concurrent endometrial cancer. Patients with endometrial cancer had a thicker average endometrial stripe compared to the patients with no endometrial cancer at the time of hysterectomy (15.7 mm; standard deviation, 9.5) versus 12.5 mm; standard deviation, 6.4; P = .01). An endometrial stripe of ≥2 cm was associated with 4.0 times the odds of concurrent endometrial cancer (95% confidence interval, 1.5-10.0), controlling for age. In all, 87% of endometrial cancer cases were stage T1a (Nx or N0). Approximately 44% of patients diagnosed with endometrial cancer and an endometrial stripe of ≥2 cm met the "Mayo criteria" for indicated lymphadenectomy compared to 22% of endometrial cancer patients with an endometrial stripe of <2 cm., Conclusion: Endometrial stripe thickness and age were the strongest predictors of concurrent endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia. Referral to a gynecologic oncologist may be especially warranted in endometrial intraepithelial neoplasia patients with an endometrial stripe of ≥2 cm given the increased rate of concurrent cancer and potential need for lymph node assessment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Surveillance of gastric precancerous lesions (GPL) is recommended, but the data on their clinical and endoscopic management in a "real-life" practice are limited. Our aim was to study the modalities of endoscopic management of patients with GPL in France., Design: All the patients diagnosed with GPL in our center between 2000 and 2015 were grouped and analyzed according to the most severe GPL found, in the following order: atrophic gastritis only (AG), intestinal metaplasia (IM), low grade dysplasia (LGD), high grade dysplasia (HGD)., Results: Out of 16,764 patients having undergone upper endoscopy with gastric biopsies, 507 were identified with GPL (detection rate 3.2%). Overall, Helicobacter pylori infection was found in 41% of patients. IM was by far the most frequently found lesion (79%), followed by LGD (17%), HGD (2%), and AG only (2%). H. pylori infection rate was decreasing, while the age of the patients was increasing, together with the increasing severity of GPL (p = 0.005). Only 28% of the patients had at least one follow-up endoscopy. No correlation was found between the endoscopist's appreciation of the mucosa and histological results., Conclusion: In France, GPL can be expected in about 3% of patients undergoing upper endoscopy with gastric biopsies for any reason. The correlation between the endoscopic evaluation and histology is poor. Spreading of published guidelines should improve the management of patients with GPL in the future., (© 2019 S. Karger AG, Basel.)

Purpose: To evaluate the individual and combined ability of videostroboscopy (VS), high-speed digital imaging (HSDI), enhanced endoscopy (EE) and saline infusion (SI) to predict neoplasia, defined as glottic precursor lesion (GPL) or T1a glottic cancer, in patients suspected for glottic neoplasia., Methods: A nationwide prospective cohort study of patients treated by cordectomy for suspected GPL or T1a glottic cancer from August 1st 2016 to October 31st 2018 was conducted in the five Danish University Departments of Head and Neck surgery. Sensitivity, specificity, negative and positive predictive values, and area under Receiver Operating Curves (AUC-ROC) were calculated with 95% confidence intervals with respect to the histological diagnosis. Logistic regression with an imputation model for missing data was applied., Results: 261 patients aged 34-91 years participated; 79 (30.3%) with non-neoplasia (i.e., inflammation, papilloma, hyperkeratosis) and 182 (69.7%) neoplasia, hereof 95 (36.4%) with GPL and 87 (33.3%) with T1a glottic cancer. Data from 188 VS, 60 HSDI, 100 preoperative EE, 209 intraoperative EE, and 234 SI were analyzed. In the complete case analysis the AUC-ROC of each diagnostic test was low, but increased when the tests were combined and especially if the combination included EE. However, multinomial logistic regression with imputation showed significant association (p < 0.05) only between age, male gender, and perpendicular vasculature in intraoperative EE, and the endpoint neoplasia., Conclusions: Intraoperative EE was the most accurate diagnostic method in detecting neoplasia. The prediction ability of methods applied preoperatively was more limited, but improved when test modalities were combined.

Purpose: The malignant upgrade rate of flat epithelial atypia (FEA) diagnosed on core needle biopsy varies between 0 and 30%. Excision versus observation with radiological follow-up for these lesions remains controversial. We hypothesize that the local rate of FEA is low and that close radiological surveillance is a reasonable treatment option for patients diagnosed with pure FEA on breast needle core needle biopsy., Methods: This study was a retrospective review of a prospectively collated provincial pathology database. Patients diagnosed with FEA alone on needle core biopsy between 2006 and 2016 were included in our analysis. Patients who had FEA present together with either in situ or invasive carcinoma within the same biopsy cores were excluded. Along with patient demographics, the size of the lesion on preoperative imaging, the method of extraction, and the presence of co-existing benign and malignant pathology on final excision biopsy were analyzed. An independent pathological review was performed to confirm our results and help reduce inter-observer bias., Results: The local rate of malignant upgrade when pure FEA is diagnosed on a breast needle core biopsy is 12%. Age at time of diagnosis, size of original lesion on mammogram, presence of atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia on core needle biopsy, the use of vacuum-assisted biopsy (VAB), or concordant imaging did not significantly correlate with malignant upgrade risk. None of the patients who were managed with radiological follow-up had malignant upgrade during follow-up. Patients undergoing radiological follow-up alone were more likely to have a VAB, concordant imaging, and no concurrent ADH., Conclusion: Our local malignant upgrade rate is consistent with published literature. We suggest radiological follow-up is a safe alternative in patients with pure flat epithelial atypia and concordant imaging, particularly those patients with small lesions in which microcalcifications can be removed completely with vacuum-assisted biopsy.

Background/aims: To evaluate gastric early differentiate-type carcinogenesis, we attempted to identify clinicopathological and biological differences in differentiated-type minute intramucosal neoplasia (MIMN), which was defined as a tumor with a diameter of < 5 mm., Methods: We examined clinicopathological findings and biological factors, including TP53 overexpression, mucin phenotype, Ki-67-positive rate, MLH1, intranuclear accumulation of β-catenin, and DNA methylation status (low methylation epigenotype [LME], intermediate methylation epigenotype, and high methylation epigenotype [HME]) in MIMNs. In addition, non-MIMNs were also analyzed. In the present study, MIMN and non-MIMN were also examined based on low-grade dysplasia, high-grade dysplasia, and intramucosal cancer (IMC)., Results: In clinicopathological findings, there were significant differences in sex ratios and tumor locations between MIMNs and non-MIMNs. Among the examined biological factors, no significant differences in the frequencies of biological factors were observed between the 2 intramucosal neoplasia types. However, the frequency of intranuclear accumulation of β-catenin was higher in non-MIMNs than in MIMNs. Finally, although the frequency of HME was significantly lower in MIMNs than in non-MIMNs, the opposite was observed for LME., Conclusions: The current finding suggested that DNA methylation and accumulation of β-catenin were closely associated with tumor development from MIMN to non-MIMN., (© 2019 S. Karger AG, Basel.)

Background: The prevalence of undefined pancreatic cystic neoplasms (PCNs) is high in the general population, increasing with patient age. PCNs account for different biological entities with different potential for malignant transformation. The clinician must balance his or her practice between the risk of surgical overtreatment and the error of keeping a malignant lesion under surveillance., Methods: We review and discuss the clinical management of PCNs. Specifically, we analyze the main features of PCNs from the surgeon's point of view, as they present in the outpatient clinic. We also review the different consensus guidelines, address recent controversies in the literature, and present the current clinical practice at 4 different European Centers for pancreatic surgery., Results: The main features of PCNs were analyzed from the surgeon's point of view as they present in the outpatient clinic. All aspects of surgical management were discussed, from indications for surgery to intraoperative management and surveillance strategies., Conclusions: Management of PCNs requires a selective approach with the aim of minimizing clinically relevant diagnostic mistakes. Through the evaluation of clinical and radiological features of a PCN, the surgeon can elaborate on a diagnostic hypothesis and assess malignancy risk, but the final decision should be tailored to the individual patient's need., (© 2019 S. Karger AG, Basel.)

Background: Risk stratification is a critical element for the successful implementation of cytopathology reporting systems. To the authors' knowledge, there are limited prior studies regarding risk stratification for The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSCPC). In the current study, the authors reported on a single-institution experience on 3-year prospective PSCPC regarding risk of malignancy (ROM) and the overall risk of malignancy (OROM)., Methods: A computerized search was performed from August 2014 to December 2017 for all pancreatic fine-needle aspiration (FNA) samples. Pathology from surgical resections and biopsies and relevant radiologic and clinical follow-up data were collected. The ROM and the OROM were calculated. The OROM was based on the total number of FNA samples in each category., Results: A total of 1017 pancreatic FNA cases were identified, with surgical and/or clinical follow-up data available for 548 cases. The cytopathologic diagnoses included 242 nondiagnostic (category I), 162 benign (category II), 142 atypical (category III), 20 neoplastic-benign (category IV: benign), 133 neoplastic-other (category IV: other), 28 suspicious (category V), and 290 malignant (category VI) cases. A total of 364 malignancies were documented in 11 cases, 4 cases, 36 cases, 0 cases, 36 cases, 21 cases, and 255 cases, respectively, from categories I, II, III, IV: benign, IV:other, V, and VI. The ROM was 25%, 17.4%, 41.8%, 0%, 34.3% (95.2%), 95.5%, and 99.6%, respectively, and the OROM was 4.5%, 2.5%, 25.3%, 0%, 27.1% (83.3%), 75%, and 87.9%, respectively, for categories I, II, III, IV: benign, IV: other (with high-grade dysplasia), V, and VI., Conclusions: The true ROM for PSCPC is likely between the ROM and OROM for the benign and indeterminate categories. In the neoplastic-other category (category IV: other), identifying high-grade dysplasia is important for its association with malignancy and a higher ROM., (© 2019 American Cancer Society.)

Background: Increasing evidence suggests the involvement of cancer stem cells (CSCs) in both oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Among the various CSC markers, aldehyde dehydrogenase (ALDH) 1, B cell-specific Moloney murine leukaemia virus integration site 1 (Bmi1), and octamer-binding protein 4 (OCT4) have been noted to increase in OSCC. The aim of the study was to analyze ALDH1, Bmi1, and OCT4 expression in OED and OSCC with clinicopathologic correlation and survival analysis., Methods: A total of 40 cases each of OED and OSCC were retrieved from departmental archives. Expression of ALDH1, Bmi1, and OCT4 was analyzed using immunohistochemistry and was correlated with clinicopathological parameters. A follow-up ranging from 6 to 52 months was considered for Kaplan-Meier survival analysis. The log-rank test was performed to analyze significant difference in survival rates., Results: The expression levels of ALDH1, Bmi1, and OCT4 increased significantly from OED through OSCC ( P < .05). The expression of ALDH1 and OCT4 showed a significant correlation with lymph node metastasis. Positive cases of ALDH1 showed a significantly reduced survival rate compared to cases showing negative expression. Kaplan-Meier survival analysis showed a significant reduction of survival rate ( P = .00) in patients showing a positive expression for all the 3 markers., Conclusion: ALDH1 and OCT4 could be used as individual prognostic markers for assessing prognosis. ALDH1, Bmi1, and OCT4 could be used as a collective panel of markers to enable surgeons in predicting the prognosis of patients and thereby carry out prompt follow-up for such cases.

Objective: To study the incidence of gallbladder polyps and the possibilities of modern methods of diagnosis and surgical treatment of this disease., Material and Methods: There were 42 laparoscopic cholecystectomies in patients with diagnosed gallbladder polyps. The polyps were diagnosed preoperatively. Intraoperative diagnosis during surgery for gallstone disease was observed in 3 cases. A comparative analysis of preoperative examination did not reveal any advantages of certain diagnostic approach., Results: Hyperplastic polyp was the most common type ( n =20, 47.6%), adenomatous polyps occurred in 19 (45.3%) cases, cholesteric polyps - in 3 (7.1%) patients. All patients had signs of chronic inflammation of the gallbladder wall with its infiltration by lymphocytes and histiocytes., Conclusion: Further studies with clear criteria for the diagnosis of gallbladder polyps including ones for determining true polyps, precancerous and malignant polyps are required.

The aim of our study was to determine the prevalence of endometrial premalignant and malignant lesions in women undergoing hysteroscopy and to identify anthropologic factors related to the presence of malignancy. Data on 3470 women with submucosal myomas or endometrial polyps suspected on ultrasound were retrospectively analyzed. Hysteroscopy was performed in all these women in order to make a more precise diagnosis. Histologic analysis of endometrial samples obtained during hysteroscopy was used to confirm the diagnosis. Statistical analysis was performed using the SPSS 20.0.0 software. The mean age of study women was 49.1±13.3 years. The number of procedures performed due to the referral diagnosis of endometrial or submucosal myoma significantly increased over the 16-year study period. A significantly higher number of women had a benign histopathologic diagnosis. Histologic analysis revealed malignancy in 67 women. The youngest woman and oldest woman with malignant findings was aged 32 and 75, respectively. A significantly higher number of women with atypical hyperplasia and malignancy were in menopause. A comparable number of women with different histologic findings lived in urban and rural areas. There were a significantly larger proportion of widows among women with the histologic diagnosis of atypical hyperplasia or malignancy. The prevalence rate of malignancy in women having undergone hysteroscopy for polyps and myoma found by ultrasound was 1.93%. Postmenopausal status and older age were associated with an increased risk of malignancies, but premalignant changes and malignancies were also found in young and premenopausal women. Therefore, diagnostic hysteroscopy can be recommended in women of all age groups.

Background: Appendiceal diverticular disease (ADD) is a rare pathology which is associated with an increased mortality risk due to rapid perforation and high rates of neoplasm. In our study, we aimed to evaluate the clinical and histopathological characteristics of ADD with differences from acute appendicitis (AA) diagnosis and to determine the association with neoformative processes., Methods: The 4279 patients who underwent appendectomy were evaluated retrospectively. ADD patients histopathologically classified into four groups. Patients' demographic characteristics, imaging and preoperative laboratory findings, additionally postoperative histopathology results were compared between groups., Results: The prevalence of ADD was 2.29% (n = 98). In addition, the male/female ratio was 2.37 in ADD patients who were found to be significantly older than those with AA patients. Type III was the most frequently (62.2%) identified sub-group of ADD. The incidence of neoplasms, plastrone, and Littre's hernia was found statistically higher in ADD group than AA group. Mucinous adenomas (10.2%) was the most common neoplasm while the carcinoid tumor (1%) and precancerous serrated adenomas (4.1%) were also reported., Conclusions: As a result, high neoplasm in ADD patients can be shown with incidence of perforation and plastron, and in order to avoid possible neoplasm or major complications, it is necessary to carry out new studies for the right diagnosis of ADD whether the diagnosis is done preoperatively or ıntraoperatively. We recommend surgical resection of the ADD, which may even be incidentally detected during any surgical procedure, due to its high risk of neoplasm and rapid perforation.

Aims: The diagnosis of radial scars/complex sclerosing lesions (RSs/CSLs) onpercutaneous biopsy carries a risk of histological underestimation. Consequently, surgical excision is often performed in order to exclude a possible associated malignancy. The aim of this study was to assess the rate of 'upgrade to carcinoma' upon subsequent surgical excision of RS/CSL cases diagnosed on vacuum-assisted large-core biopsy (VALCB). We also analysed the risk factors for upgrade in order to determine a subset of patients who could avoid surgery and benefit from conservative management with clinical and imaging follow-up., Methods and Results: This was a retrospective observational single-centre study on 174 consecutive RS/CSL cases diagnosed on VALCB from May 2008 to October 2015. Univariate analysis was performed to identify clinical, radiological and histological risk factors for upgrade. Surgical excision was performed following VALCB diagnosis of 88 RS/CSL cases with or without associated atypia. The overall rate of surgical upgrade to carcinoma was 9.1% (8/88). None of the benign biopsies without atypia was surgically upgraded. Additional to atypia, risk factors for upgrade were non-incidental finding of the RS/CSL, the mammographic appearance, and the number of fragments obtained during the biopsy procedure (P < 0.05)., Conclusion: We demonstrate that VALCB revealing an RS/CSL is reliable for excluding malignancy when there is no associated atypia and when radiological and histological findings are concordant. In such cases, surgery can be avoided in favour of clinical and imaging follow-up. When an RS/CSL is associated with atypia, the decision to perform surgical excision depends on other associated risk factors., (© 2019 John Wiley & Sons Ltd.)

Background: HER2 is an oncoprotein which is overexpressed in several cancers including breast and stomach. Several studies have shown that HER2 is overexpressed in gallbladder cancer and in precancerous lesions. The present study was undertaken to assess pattern and level of expression of HER2 in metaplasia, dysplasia, and different stages of gallbladder carcinoma, which would determine its suitability as a prognostic biomarker in neoplastic transformation of gallbladder epithelium. The study was also aimed at to find the significance of Ki-67 index in these lesions., Methods and Materials: One hundred and twenty-eight patients who underwent cholecystectomy comprised the study group. Among them, 108 (84.4%) specimens showing metaplasia, dysplasia, and carcinoma on routine histopathology were considered as cases and 20 (15.6%) specimens of chronic cholecystitis having non-metaplastic mucosa were considered as control. Immunohistochemistry (IHC) was performed for HER2 and Ki-67. For HER2 interpretation ASCO/CAP guideline for breast cancer was followed. Chi-square test was used to find out the significance of HER2 expression in dysplasia/metaplasia/carcinoma. The ANOVA and Tukey-Kramer Multiple Comparisons Test were used for determining the association of Ki-67 with malignant transformation., Results and Conclusions: Overexpression of HER2 was observed in 48% (n = 12) of adenocarcinomas, 58% (n = 7) of high-grade dysplasia, 47% (n = 8) of low-grade dysplasia, and 74% (n = 25) of intestinal metaplasia. Ki-67 index increases in a non-linear fashion as the precursor lesions progress toward malignancy. In the future, these markers might be used as a prognostic biomarker for gallbladder carcinoma and its precursor lesions and it might become a valid indication for targeted therapies for gallbladder cancer.

Background: The effectiveness of multiband mucosectomy (MBM) for early esophageal cancer and precancerous lesions is still in uncertainty. We aimed to evaluate the efficacy and safety of this procedure and to compare it with cap-assisted endoscopic resection (EMR-cap)., Methods: A systematic search of both English and Chinese databases was performed from inception to April 30, 2019. Complete resection rate, local recurrence rate, and procedure time were considered the primary outcome measures. Prevalence of complications was considered the secondary outcome measure. All data analyses were performed using Review Manager Software., Results: Two randomized controlled trials (RCTs) and 3 non-RCTs were included in the final meta-analysis. When compared with the EMR-cap technique, MBM had a similar complete resection rate [odds ratio (OR)=2.09, 95% confidence interval (CI): 0.78-5.60, P=0.14], a similar local recurrence rate (OR=0.50, 95% CI: 0.09-2.67, P=0.42), a shorter resection time (mean difference: -9.08, 95% CI: -13.86 to -4.30, P=0.0002), a shorter procedure time (mean difference: -13.36, 95% CI: -17.85 to -8.86, P<0.00001), a lower bleeding rate (OR=0.45, 95% CI: 0.24-0.83, P=0.01), a similar perforation rate (OR=0.55, 95% CI: 0.15-2.06, P=0.37), and a similar stricture rate (OR=0.77, 95% CI: 0.10-5.84, P=0.80). The results of non-RCTs were consistent with those of RCTs., Conclusions: MBM is similar to EMR-cap in terms of efficacy and safety for endoscopic resection of early cancer and precancerous lesions of the esophagus. However, MBM is less time-consuming.

Retrieval of lesions after endoscopic polypectomy enables histopathologic analysis and guides future surgical management and endoscopic surveillance intervals. Various techniques and devices have been described with distinct advantages and disadvantages to accomplish retrieval. Appropriate histopathologic analysis depends on lesion handling and preparation. How lesions are handled further depends on size, endoscopic appearance, and removal technique. Endoscopic marking or tattooing is a well-described process that uses dye mediums to leave longstanding marks in the colon. Techniques, dye mediums, and locations within the colon influence tattoo approach., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Diminutive colorectal lesions are polyps and flat lesions 1 to 5 mm in size, and small are 6 to 9 mm in size. The best resection method is the cold snare. Cold forceps are acceptable for 1- to 3-mm lesions, but should not be used to piecemeal polyps. Cold snaring has few complications and is more effective than cold forceps for 4- to 5-mm polyps and as effective and more efficient than hot snaring for 6- to 9-mm polyps., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate the predictive value of preoperative peripheral inflammatory markers in patients with vocal fold leukoplakia., Methods: A retrospective study was performed of the patients diagnosed with vocal fold leukoplakia and who accepted carbon dioxide (CO 2 ) laser resection in our center in the last 10 years. We calculated the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) after collecting and analyzing the clinical, histopathological and laboratory data. The potential relation between blood indexes and clinical events as recurrence or canceration was evaluated., Results: A total of 589 patients were involved, including 300 cases without recurrence (group A), 198 with recurrence but not canceration (group B) and 91 transformed into squamous cancer (group C). Baseline analysis of NLR, PLR, and MLR showed no difference among the three groups before the first surgery. But all the indexes significantly elevated in groups B (P < 0.001, < 0.001, 0.023, respectively) and C (P = 0.009, 0.004, 0.007, respectively) in the last operation. The receiver-operating curve (ROC) analysis showed NLR as a potential marker of canceration of leukoplakia (AUC = 0.837) and the cutoff value was 2.505. When regrouping with pathological outcomes, severe dysplasia and squamous cell carcinoma (SCC) groups both revealed a higher level of NLR, PLR, and MLR comparing to the no dysplasia, mild dysplasia, and moderate dysplasia groups. NLR, PLR, and MLR in high-risk group (moderate, severe dysplasia and carcinoma) also elevated comparing to low-risk group (no dysplasia, mild dysplasia) (P = 0.039, 0.011, 0.007, respectively)., Conclusions: The peripheral inflammatory markers NLR, PLR, and MLR are closely connected with the development of vocal fold leukoplakia. NLR may be a potential marker to predict the poor outcomes (recurrence or canceration) of patients in first surgery.

Microglandular adenosis (MGA) of the breast is exceedingly rare, with only a few case reports and series published to date. Previous studies have elegantly demonstrated the progression of benign MGA to atypical MGA to MGA-in situ carcinoma to invasive carcinoma and therefore suggest MGA as a possible non-obligate precursor lesion to a subset of breast carcinomas. Immunohistochemically, MGA is negative for estrogen receptor (ER), progesterone receptor (PR), and HER2-neu oncoprotein expression, and carcinomas arising in the setting of MGA are often reported to be triple negative. In this article, we present a unique case of an ER+/PR+/HER2- invasive carcinoma associated with MGA and atypical MGA. Our case highlights the diagnostic pitfall of MGA and suggests that MGA is a heterogeneous group of lesions with potential for either luminal-type or basal-type differentiation during progression to breast carcinoma.

Ineffective polypectomy technique may lead to incomplete polyp resection, high complication rates, interval colorectal cancer, and costly referral to surgery. Despite its central importance to endoscopy, training in polypectomy is not standardized nor has the most effective training approach been defined. Polypectomy competence is rarely reported and quality metrics for this skill are lacking. Use of tools and measurements to assess polypectomy outcomes is low. There is a need for standardization of training and remediation in polypectomy; defining standards of competent polypectomy and how it is feasibly measured; and integration of polypectomy quality metrics into training programs and the accreditation process., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Colonoscopic polypectomy is fundamental to effective prevention of colorectal cancer. Polypectomy reduces colorectal cancer incidence and mortality by altering the natural history and progression of precancerous precursor polyps. Epidemiologic data from the United States, where colorectal cancer rates have been steadily declining in parallel with screening efforts, provide indisputable evidence about the effectiveness of polypectomy. Randomized controlled trials of fecal occult blood tests and flexible sigmoidoscopy, and observational colonoscopy studies, provide additional support. Longitudinal studies have shown variable levels of protection after polypectomy, highlighting the central importance of high quality and adequate surveillance of higher-risk patients., (Published by Elsevier Inc.)

Objective: Endoscopic submucosal dissection (ESD) is a technique for en bloc resection of neoplastic lesions of the digestive tract. Endoscopic submucosal dissection was developed in Asia, and data from Western countries are scarce. Our study aimed to assess the efficacy and safety of ESD for resection of superficial premalignant and malignant epithelial neoplasms in a tertiary center in Italy., Patients and Methods: All patients with gastrointestinal lesions who underwent ESD between January 2013 and December 2018 in our center were retrospectively evaluated. Technical success, en bloc, R0, curative resection, and complication rates were assessed., Results: A total of 107 lesions (stomach, no.=41; rectum, no.=32; colon, no.=28; esophagus, no.=5; duodenum, no.=1) were resected by ESD in 93 patients. Endoscopic submucosal dissection was technically successful in 99.1% (106/107) of lesions. Among the 90 superficial premalignant and malignant epithelial neoplasms, en bloc, and R0 resection rates were 97.8% (no.=88) and 75.6% (no.=68), respectively. Major complications occurred in 9.3% (10/107) of cases: 4 (3.7%) were perforations and 6 (5.6%) were major bleedings. All complications, but two which needed surgery, were managed endoscopically., Conclusions: Our study shows that ESD is a feasible, effective, and safe technique in a Western country.

Early-stage (T1) esophagogastric junction cancer continues to represent 2-3% of all cases. Adenocarcinoma is the most frequent and important type, the main risk factors for which are gastroesophageal reflux and Barrett's esophagus with dysplasia. Patients with mucosal (T1a) or submucosal (T1b) involvement initially require a thorough digestive endoscopy, and narrow-band imaging can improve visualization. Endoscopic treatment of these lesions includes endoscopic mucosal resection, radiofrequency ablation and endoscopic submucosal dissection. Accurate staging is necessary in order to provide optimal treatment. The most precise staging technique in these cases is endoscopic ultrasound. The suspicion of deep invasion of the submucosa, presence of unfavorable anatomopathological characteristics or impossibility to perform endoscopic resection make it necessary to consider surgical resection., (Copyright © 2019 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.)

Gastric adenocarcinoma carries a poor prognosis, in part due to the late stage of diagnosis. Risk factors include Helicobacter pylori infection, family history of gastric cancer-in particular, hereditary diffuse gastric cancer and pernicious anaemia. The stages in the progression to cancer include chronic gastritis, gastric atrophy (GA), gastric intestinal metaplasia (GIM) and dysplasia. The key to early detection of cancer and improved survival is to non-invasively identify those at risk before endoscopy. However, although biomarkers may help in the detection of patients with chronic atrophic gastritis, there is insufficient evidence to support their use for population screening. High-quality endoscopy with full mucosal visualisation is an important part of improving early detection. Image-enhanced endoscopy combined with biopsy sampling for histopathology is the best approach to detect and accurately risk-stratify GA and GIM. Biopsies following the Sydney protocol from the antrum, incisura, lesser and greater curvature allow both diagnostic confirmation and risk stratification for progression to cancer. Ideally biopsies should be directed to areas of GA or GIM visualised by high-quality endoscopy. There is insufficient evidence to support screening in a low-risk population (undergoing routine diagnostic oesophagogastroduodenoscopy) such as the UK, but endoscopic surveillance every 3 years should be offered to patients with extensive GA or GIM. Endoscopic mucosal resection or endoscopic submucosal dissection of visible gastric dysplasia and early cancer has been shown to be efficacious with a high success rate and low rate of recurrence, providing that specific quality criteria are met., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Endoscopic submucosal dissection (ESD) is an effective, minimally invasive, surgery-sparing technique for the treatment of early gastric cancer (EGC). It is not well established whether EGC within the Japanese expanded criteria can be safely and effectively treated using ESD in the West. We describe the outcomes of ESD for endoscopically suspected, biopsy specimen-confirmed EGC and its adenomatous precursor lesions (pEGC) using the Vienna classification of dysplasia in a Western cohort., Methods: Prospective data were collected on all pEGCs undergoing ESD at a single expert endoscopy center. Outcomes were compared among pEGC, satisfying the Japanese absolute and expanded criteria, those outside criteria, and those specimens that contained low-grade dysplasia (LGD) only. Specialist GI pathologists reviewed and classified all ESD specimens. Patients were followed up at 6 and 12 months., Results: Over 71 months, 135 pEGCs in 121 patients (mean age, 72.0 years; 61.2% men) underwent ESD. Median pEGC size was 20 mm (interquartile range, 15-30), and 62 (45.9%) satisfied the expanded clinical criteria. Perforation occurred in 1.5% and postprocedural bleeding in 5.2%. Forty-two pEGCs (31.1%) contained LGD only. Rates of en bloc and R0 resection were 94.8% and 86.7%, respectively. One hundred seven pEGCs (79.2%) met the absolute or expanded criteria for endoscopic cure. Two pEGCs recurred during follow-up. Ten of 26 patients with pEGC (38.5%) outside criteria for cure underwent surgery after ESD with residual tumor detected in 3 specimens. Fifteen patients with outside criteria for pEGCs did not undergo surgery because of frailty or their expressed wish. Eleven of 15 patients have so far undergone first surveillance with 1 of 11 experiencing endoscopic and histologic recurrence., Conclusions: ESD is a safe and effective treatment for pEGCs in a Western context. Patients who either decline or are too frail for surgery, with outside criteria resections, may benefit from ESD for local disease control. Large Western studies of ESD for pEGCs are required to define long-term patient outcomes and surveillance guidelines, particularly where pathology shows LGD or high-grade dysplasia only. (Clinical trial registration number: NCT02306707.)., (Copyright © 2019. Published by Elsevier Inc.)

Background: Endometrial cancer and atypical hyperplasia are rare in young women but create a dilemma between desire for pregnancy and oncologic outcomes., Objective: To identify remission rates and associated prognostic factors in patients undergoing fertility-sparing management for endometrial cancer and atypical hyperplasia., Search Strategy: MEDLINE was searched for studies published between January 1, 1950 and July 31, 2017 using various search terms., Selection Criteria: Studies evaluating fertility-sparing management in patients aged between 19 and 44 years with atypical hyperplasia or stage I endometrial cancer., Data Collection and Analysis: Use of PRISMA guidelines to conduct a meta-analysis of the proportion of patients in remission and meta-regression analysis to test the effect of possible prognostic factors for remission., Main Results: A total of 3673 studies were screened; 65 studies including 1604 patients met the inclusion criteria. The remission rate was 0.75 (95% CI, 0.73-0.77). Operative hysteroscopy for endometrial sampling was associated with higher remission rates (OR 2.31; 95% CI, 1.10-4.84; P=0.03). Studies with higher ratios of infertile women were associated with higher remission rates (OR 4.21; 95% CI, 1.44-12.33; P<0.01)., Conclusion: Operative hysteroscopy is the preferred endometrial sampling method for patients with atypical hyperplasia or endometrial cancer undergoing fertility-sparing management., (© 2019 International Federation of Gynecology and Obstetrics.)

Patients with long-standing inflammatory bowel disease (IBD) involving at least 1/3 of the colon are at increased risk for colorectal cancer (CRC). Advancements in CRC screening and surveillance and improved treatment of IBD has reduced CRC incidence in patients with ulcerative colitis and Crohn's colitis. Most cases of CRC are thought to arise from dysplasia, and recent evidence suggests that the majority of dysplastic lesions in patients with IBD are visible, in part thanks to advancements in high definition colonoscopy and chromoendoscopy. Recent practice guidelines have supported the use of chromoendoscopy with targeted biopsies of visible lesions rather than traditional random biopsies. Endoscopists are encouraged to endoscopically resect visible dysplasia and only recommend surgery when a complete resection is not possible. New technologies such as virtual chromoendoscopy are emerging as potential tools in CRC screening. Patients with IBD at increased risk for developing CRC should undergo surveillance colonoscopy using new approaches and techniques., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript.

Lichen sclerosus (LSc) with penile cancer is found in about two thirds of specimens. It has been hypothesized that LSc represents a precancerous condition. To qualify as such, in addition to cytological atypia and similarity with the invasive tumor, a spatial correlation between LSc and neoplastic lesions needs to be demonstrated. The purpose of this study was to evaluate such a spatial relationship. Circumcision (28 cases) and penectomy (81 cases) specimens were evaluated. All cases had LSc, penile intraepithelial neoplasia (PeIN), and/or invasive squamous cell carcinomas. We examined LSc in relation to invasive carcinoma, PeIN, and normal epithelia. Invasive squamous cell carcinomas, classified according to the World Health Organization criteria as non-human papillomavirus (HPV)-related and HPV-related PeIN, were present in 100 cases. Non-HPV-related (differentiated) PeIN was the most common subtype associated with LSc (89%). There were 5 spatial patterns identified: (1) LSc adjacent to PeIN (23%), (2) LSc adjacent and comprising PeIN (42%), (3) LSc next to and within invasive carcinomas (8%), (4) LSc throughout the sequence PeIN-invasive carcinoma (24%), and (5) LSc was separate (with normal tissue between the lesions) from PeIN and/or invasive carcinomas in a minority of cases (3%). LSc within the cancer was not previously described. In this series, we found 35 cases with LSc within invasive carcinomas. The striking continuous spatial relationship among LSc, PeIN, and/or invasive carcinoma as shown in this study may be a necessary (but not sufficient) condition for the hypothesis postulating LSc as a penile precancerous lesion.

Background and aim: Clinical guidelines recommend endoscopy surveillance at given intervals or endoscopic therapy for Barrett's esophagus with low-grade dysplasia (LGD) and high-grade dysplasia (HGD). Whether these guidelines are followed in clinical practice is unknown and was assessed in this study. Methods: This nationwide Swedish cohort study included patients with Barrett's esophagus with histologically verified LGD or HGD from 50 centers in 2006-2013. These patients were followed up using nationwide registers. Adherence to clinical guidelines was explored. Eight potential risk factors for deviation from guidelines were assessed using multivariable logistic regression, providing adjusted odds ratios (OR) with 95% confidence intervals (95%CI). Results: Among 211 patients with Barrett's esophagus (mean age 67.0 years, standard deviation 9.7 years, 81% male), 71% had LGD and 29% had HGD. During median 3.9 years of follow-up, 84% underwent a follow-up endoscopy, 17% received endoscopic therapy and 8% underwent esophagectomy. The clinical management deviated from guidelines in 60% of all patients (69% in LGD and 39% in HGD), which was mainly due to under-surveillance (86%). Risk factors for deviation from guidelines were LGD compared to HGD (OR 3.4, 95%CI 1.7-6.8), longer Barrett's segment length (OR 2.0, 95%CI 1.0-3.9, comparing ≥3 cm with <3 cm), and treatment at gastroenterology compared to surgery departments (OR 2.3, 95%CI 1.2-4.4). Age, sex, calendar period and university hospital status were not associated with deviation from surveillance guidelines. Conclusions: Adherence to guidelines for dysplastic Barrett's esophagus is poor, particularly for LGD. Efforts to implement clinical guideline recommendations are needed.

Objective: To evaluate the short-term and long-term efficacy of endoscopic submucosal dissection (ESD) in the treatment of early low rectal cancer and precancerous lesions. Methods: Inclusion criteria: (1) Distance from the lower margin of tumor to the anal was ≤ 5 cm. (2) Early low rectal cancers were any size rectal epithelial tumors with infiltration depth limited to the mucosa and submucosa, which were diagnosed by postoperative pathology as high-grade intraepithelial neoplasia or adenocarcinoma of the rectum with infiltration depth of intramucosal or submucosal cancer (M or SM stage). (3) Precancerous lesions included adenoma and low-grade intraepithelial neoplasia of the rectum. (4) Patients received ESD treatment. Patients with tumor invasion depth over submucosa by pathology were excluded. From January 2008 to January 2018, 63 patients meeting the above criteria in Peking University First Hospital were enrolled in this descriptive cohort study. The disease characteristics, clinical manifestations, pathological types, treatment time, hospitalization time, en bloc resection rate (resection of the whole lesion), complete resection rate (both the horizontal and vertical incision margins were negative), postoperative complications and follow-up results were analyzed. Cummulative survival rate was calculated by Kaplan-Meier. Results: The diameter of the lesion was (29.0±23.4) mm and the distance from the lesion to the anus was (2.7±1.8) cm. The median operation time was 45.0 (range, 10.0 to 360.0) minutes, the median hospitalization time was 3.0 (range, 2.0 to 12.0) days, en bloc resection rate was 100%, complete resection rate was 96.8% (61/63), and 1 case (1.6%) had postoperative bleeding. The follow-up rate was 87.3% (55/63) and the median follow-up time was 57.9 (range, 15.6 to 121.1) months. No local recurrence was found during the follow-up period and the 5-year survival rate was 100%. Conclusion: Short- and long-term efficacy of ESD are quite good in the treatment of patients with early low rectal cancer and precancerous lesions.

Objectives: To study the inflammatory infiltrates associated with the different stages of laryngeal carcinogenesis., Design: Observational, matched case-control study of histopathologic specimens., Setting: An academic referral centre., Participants: A total of 45 patients who underwent removal of glottic lesions between 2008 and 2015. Patients were enrolled and categorised into three matched groups according to lesions' histopathologic diagnoses, 15 patients in each group: benign, pre-malignant and squamous cell carcinoma (SCC). Matching was based on age, gender and pack-years., Main Outcome Measures: Immunohistochemistry staining using monoclonal antibodies against CD4, CD8, CD68, CD20 and S100 representing T-helper cells, cytotoxic T cells, macrophages, B cells and dendritic cells, respectively. Cell counts and distributions were measured and compared between groups. Correlations between the different cells were examined., Results: The predominant cell type was CD8+, followed by CD68+ and CD4+. All inflammatory cells increased significantly in number in SCC (P-value < 0.001), with no significant difference between benign and pre-malignant groups. Strong correlations between the different cells were demonstrated only in the malignant group. S100+ cells correlated with both T-cell subsets, CD4+ (rho = 0.769, P-value = 0.001) and CD8+ (rho = 0.697, P-value = 0.0004). Infiltrates exhibited more extensive distribution in SCC compared to pre-malignant and benign; CD8+ and CD68+ cells were demonstrated in both intraepithelial and stromal regions in 93% of SCC lesions (P-value = 0.0001)., Conclusions: Laryngeal carcinoma demonstrates a unique pattern of inflammatory infiltrates, with significant changes in cell counts and distribution. Leucocyte infiltrates increased significantly in the transition from laryngeal pre-malignant lesion to malignancy while no significant differences were seen between benign and pre-malignant lesions., (© 2019 John Wiley & Sons Ltd.)