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Objective: To preliminarily investigate the clinical outcomes of secondary loop electrosurgical excision procedure (LEEP) combined with transcervical resection of endocervical tissue (i.e., second combined surgeries) in patients with positive endocervical margins following the initial LEEP for high-grade squamous intraepithelial lesion (HSIL) or adenocarcinoma in situ (AIS) of the cervix. Methods: Patients who underwent second combined surgeries due to positive endocervical margins after the initial LEEP for cervical HSIL or AIS at Obstetrics and Gynecology Hospital, Fudan University between August 2015 and September 2023 were included. Postoperative cytological examinations, high-risk human papillomavirus (HR-HPV) testing, colposcopic biopsy results, and cervical canal length were followed up to evaluate the clinical efficacy of second combined surgeries. Results: (1) General clinical data: a total of 67 patients were enrolled, including 34 with cervical HSIL (HSIL group) and 33 with AIS (AIS group). In the HSIL group before the time of initial LEEP, the mean age was (41.3±5.3) years, with all patients positive for HR-HPV preoperatively. Preoperative cytology results revealed ≤low-grade squamous intraepithelial lesion (LSIL) in 13 cases and ≥HSIL in 21 cases. The preoperative cervical canal length was (3.71±0.17) cm. Patients in the AIS group before their the first LEEP were at an average age of (39.1±8.7) years old, with preoperative HR-HPV positive. Among them, 16 cases showed preoperative cytological results of ≤LSIL, while 17 cases showed ≥HSIL. The preoperative cervical canal length was (3.64±0.21) cm. (2) Pathological findings and postoperative follow-up of the HSIL group following second combined surgeries:in the HSIL group, the residual rate of HSIL in the endocervical canal tissue (ECT) was 24% (8/34). Out of the 34 HSIL patients, 10 cases (29%, 10/34) remained with positive endocervical margins post-second combined surgeries. Among these 10 patients, 5 cases (5/10) had no lesion detected in ECT, while the remaining 5 cases (5/10) exhibited HSIL in their ECT. Conversely, 24 patients (71%, 24/34) had negative endocervical margins after second combined surgeries. Of these 24 patients, 3 cases (12%, 3/24) were found to have HSIL in ECT, and 21 cases (88%, 21/24) had no lesion in ECT. During follow-ups conducted at 6 and 12 months post-second combined surgeries, the clearance rates of HR-HPV were 91% (31/34) and 100% (34/34), respectively. Notably, among the 29 patients (85%, 29/34) who were followed up for a period of 2 years or longer, all cases maintained a consistently negative HR-HPV status, highlighting the effectiveness of second combined surgeries in achieving long-term HR-HPV clearance (100%, 29/29). (3) Pathological findings and postoperative follow-up of the AIS group following second combined surgeries: the residual rate of AIS in the ECT following second combined surgeries among AIS patients was 15% (5/33). Out of the 33 AIS patients, 11 cases (33%, 11/33) had positive endocervical margins post-operation, among whom AIS was detected in the ECT of 2 cases (2/11), while 1 case (1/11) was diagnosed with adenocarcinoma in the cervical canal tissue (subsequently underwent radical surgery and was excluded from this study). In contrast, 22 patients (67%, 22/33) had negative endocervical margins post-operation, with AIS found in the ECT of 2 cases (9%, 2/22) and no lesions detected in the remaining 20 cases (91%, 20/22). Follow-up evaluations conducted at 6 and 12 months postoperatively revealed HR-HPV clearance rates of 91% (29/32) and 97% (31/32), respectively. All 32 (100%, 32/32) AIS patients were followed up for a duration of ≥2 years post-second combined surgeries, during which HR-HPV remained consistently negative. (4) Complications and cervical length following second combined surgeries: neither the HSIL group nor the AIS group experienced significant complications such as hemorrhage, infection or cervical canal adhesion. At the 6-month follow-up, the cervical length of both HSIL and AIS patients exceeded 3 cm. By the 12-month follow-up, the cervical length had recovered to 96.5% and 97.5% when compared to the original length, respectively, for the HSIL and AIS groups. Conclusions: For patients with HSIL or AIS who exhibit positive endocervical margins following the initial LEEP procedure, undergoing second combined surgeries presents as an optimal choice. This surgical intervention guarantees thorough excision of the lesion, and subsequent colposcopic follow-up evaluations consistently demonstrate an absence of residual disease or recurrence. Moreover, it augments the rate of sustained HR-HPV negativity, thereby contributing to more favorable clinical outcomes.

Objective: Submucosal infiltration of less than 200 μm is considered an indication for endoscopic surgery in cases of superficial esophageal cancer and precancerous lesions. This study aims to identify the risk factors associated with submucosal infiltration exceeding 200 micrometers in early esophageal cancer and precancerous lesions, as well as to establish and validate an accompanying predictive model., Methods: Risk factors were identified through least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. Various machine learning (ML) classification models were tested to develop and evaluate the most effective predictive model, with Shapley Additive Explanations (SHAP) employed for model visualization., Results: Predictive factors for early esophageal invasion into the submucosa included endoscopic ultrasonography or magnifying endoscopy> SM1(P<0.001,OR = 3.972,95%CI 2.161-7.478), esophageal wall thickening(P<0.001,OR = 12.924,95%CI,5.299-33.96), intake of pickled foods(P=0.04,OR = 1.837,95%CI,1.03-3.307), platelet-lymphocyte ratio(P<0.001,OR = 0.284,95%CI,0.137-0.556), tumor size(P<0.027,OR = 2.369,95%CI,1.128-5.267), the percentage of circumferential mucosal defect(P<0.001,OR = 5.286,95%CI,2.671-10.723), and preoperative pathological type(P<0.001,OR = 4.079,95%CI,2.254-7.476). The logistic regression model constructed from the identified risk factors was found to be the optimal model, demonstrating high efficacy with an area under the curve (AUC) of 0.922 in the training set, 0.899 in the validation set, and 0.850 in the test set., Conclusion: A logistic regression model complemented by SHAP visualizations effectively identifies early esophageal cancer reaching 200 micrometers into the submucosa., (© 2024. The Author(s).)

Objective: To describe the prevalence of incidental malignant pathology following a hysterectomy performed for benign reasons., Method: A descriptive cross-sectional study based on hospital records. Women who underwent hysterectomy for benign reasons at a general referral hospital between 2013 and 2021 were included. Women with obstetric hysterectomy were excluded. Measured variables: age, route of hysterectomy, type of hysterectomy, histopathological diagnosis of premalignant lesion or invasive cancer, type of cancer. Analysis: Descriptive, the prevalence of preneoplastic and neoplastic conditions was estimated for the overall period., Results: Of 816 clinical records, 674 cases (87 %) met the inclusion criteria and were analyzed. The premenopausal population predominated. Twentysix cases of unexpected malignant disease were identified, yielding a prevalence of 3.8 %, and 13 cases of premalignant pathology (1.9 %). The most common origin was the cervix (40 %), followed by the ovary (33 %)., Conclusions: Patients undergoing hysterectomy for benign conditions should be informed about the risk of unexpected injury. The importance of performing, in our context an adequate preoperative approach to rule out cervix uteri and ovarian cancer is emphasized. Follow-up studies of patients with unanticipated cancer are required to determine their treatment and prognosis in the region.

Background: Endoscopic submucosal dissection (ESD) is widely used as a standard treatment regimen for early gastric cancers (EGCs). However, such an approach is time consuming and has a high risk of perforation and bleeding in some corner-site lesions because of the obscured view and difficulty in submucosal lifting. The newly developed pocket-creation method (PCM) provides a clearer view and better traction of the submucosal layer than conventional ESD (c-ESD). Nevertheless, no prospective randomized study has evaluated the efficacy of the PCM in EGCs and precancerous lesions., Methods: This was a prospective randomized controlled trial. Patients with superficial gastric neoplastic lesions ≥ 20 mm were randomly assigned to the PCM-ESD group or c-ESD group. The primary outcome was dissection speed., Results: There were 28 patients in the PCM-ESD group and 27 in the c-ESD group. The median dissection speed was significantly higher in the PCM-ESD group than in the c-ESD group (21.5 mm 2 /min vs 14.3 mm 2 /min, P < .001). Meanwhile, the operation time in the PCM-ESD group was significantly shorter than that in the c-ESD group (30 vs 40 min, P = .047). In multiple linear regression analysis, the treatment method was independently associated with the resection speed of ESD., Conclusion: PCM-ESD was an effective and safe treatment for EGCs and precancerous lesions., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Disclosure The author disclosed no financial relationships.

Background: Cervical cancer continues to disproportionately burden women in low/middle-income countries like Ghana. We examined treatment patterns and histopathological outcomes among women screened using visual inspection with acetic acid (VIA) and/or mobile colposcopy who subsequently underwent thermal ablation, large loop excision of the transformation zone (LLETZ), or cold knife conization at the Cervical Cancer Prevention and Training Centre, Battor. We also assessed the prevalence of cervical intraepithelial neoplasia 2+ (CIN2+) or micro-invasive disease and their associated factors for women who underwent excisional treatments. The treatment choices for cervical precancerous lesions suitable for resource-limited settings have also been described from the perspective of a center that manages a heterogenous population., Methods: We conducted an analysis of secondary data collected between June 2016 and June 2023 among women with positive findings on VIA or mobile colposcopy who subsequently underwent thermal ablation or large loop excision of the transformation zone (LLETZ). The prevalence of histopathology outcomes, including no dysplasia, CIN1 - 3, and micro-invasive disease, were estimated with 95% confidence intervals (CIs). Factors associated with histopathological findings were modeled using multinomial logistic regression., Results: For the study period, 14 (10.6%) of the total 132 participants underwent cervical lesion treatment at outreach locations, all via thermal ablation. The remaining 118 (89.4%) were treated at the Catholic Hospital, Battor using LLETZ (n = 66, 55.9%), thermal ablation (n = 51, 43.2%), and cold knife conization (n = 1, 0.9%). Among 65 women with histopathology reports, the most frequent histopathological finding was no dysplasia (47.7%; 95% CI, 35.1 - 60.5), followed by CIN2 and CIN3 (20.0%; 95% CI, 11.1 - 31.8 each), CIN1 (7.7%; 95% CI, 2.5 - 17.0) and micro-invasion (4.6%; 95% CI, 1.0 - 12.9). Those with micro-invasive disease were significantly older than those with CIN1, CIN2, and CIN3 (p = 0.036, 0.022, 0.009, respectively), but not significantly older than those who showed no dysplasia (p = 0.088). For each unit increase in age, the likelihood of CIN3 was relatively significantly reduced compared to no dysplasia (crude relative risk ratio [RRR] = 0.93; 95% CI, 0.86 - 0.99). This association was neither observed with the remaining histopathological groups nor for parity and persisted after controlling for parity (adjusted RRR = 0.92; 95% CI, 0.85 - 0.99; p = 0.025)., Conclusion: This paper largely demonstrates treatment options available to women and practitioners in LMICs. The high combined prevalence of high-grade precancerous lesions and micro-invasive disease underscores the need to increase cervical cancer awareness that would enhance screening attendance and hasten efforts at moving from opportunistic to organized screening in Ghana. This will enhance early cervical lesion detection and treatment, while simultaneously re-evaluating and cutting down on unnecessary treatment., (© 2024. The Author(s).)

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of laparoscopic or robot-assisted pancreatoduodenectomy versus open pancreatoduodenectomy for people with benign, premalignant, and malignant disease., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Competing Interests: Disclosure The author disclosed no financial relationships. Commentary In this case, the author describes the use of a novel AI program for the detection of gastric dysplasia before embarking on ESD in a patient with known “high-grade dysplasia” on a “random” antral biopsy. The most annoying scenario for any endoscopist is the inability to find a biopsy-proven dysplastic lesion during endoscopy! Light chromoendoscopy is an excellent tool for categorizing and localizing lesions within the colon. However, the sensitivity of such a modality in upper GI tract lesions, especially within the stomach, is very limited. Early gastric dysplastic lesions can present only as subtle elevations or depressions with faint erythema, fine focal mucosal granularity, or small clusters of erosions. The above-mentioned subtle presentations usually affect the accurate endoscopic identification of precancerous lesions and hinder border definition before planned ESD. Often, dye-enhanced chromoendoscopy is the standard method of identification of these subtle lesions. However, this can be time consuming and not highly specific. There has been growing interest in the past few years in integrating AI with endoscopy for enhanced detection of cancerous and precancerous lesions of the stomach and esophagus, with promising results. In this case, using AI resulted in proper lesion detection and clear border definition of the lesion. Consequently, it was not necessary to preform wide field resection, which increases the procedural time and rate of adverse events. In the near future, AI will be an integral part of endoscopic surveillance approaches for gastric intestinal metaplasia, eliminating the need for extensive biopsies! Tara Keihanian, MD, MPH, Assistant Professor, Division of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA Mohamed O. Othman, MD, GIE Senior Associate Editor

Objective: To investigate the risk factors for delayed postoperative bleeding after endoscopic submucosal dissection (ESD) in patients with gastric precancerous lesions and to construct a risk prediction model., Methods: This retrospective analysis included clinical data from patients with gastric precancerous lesions who underwent ESD at Wuhan University People's Hospital between November 2016 and June 2022. An XGBoost model was built to predict delayed bleeding after ESD using risk factors identified by univariable and multivariate logistic regression analysis. The model was evaluated using receiver operating characteristic curves (ROC), and SHapely Additive exPlanations (SHAP) analysis was used to interpret the model., Results: Seven factors were statistically associated with delayed postoperative bleeding in gastric precancerous lesions after ESD: age, low-grade intraepithelial neoplasia, hypertension, lesion size ≥ 40 mm, operative time ≥ 120 min, female, and nonuse of hemoclips. A risk prediction model was established. In the training cohort, the model achieved an AUC of 0.97 (0.96-0.98), a sensitivity of 0.90, a specificity of 0.94, and an F1 score of 0.91. In the validation cohort, the AUC was 0.94(0.90-0.98), with a sensitivity of 0.85, a specificity of 0.89, and an F1 score of 0.85. In the test cohort, the AUC was 0.94 (0.89-0.99), the sensitivity was 0.80, the specificity was 0.92, and the F1 score was 0.84, indicating strong predictive capability., Conclusion: In this study, an XGBoost prediction model for assessing the risk of delayed postoperative bleeding after ESD in patients with gastric precancerous lesions was developed and validated. This model can be applied in clinical practice to effectively predict the risk of post-ESD bleeding for individual patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Results of initial endoscopic biopsy of gastric lesions often differ from those of the final pathological diagnosis. We evaluated whether an artificial intelligence-based gastric lesion detection and diagnostic system, ENdoscopy as AI-powered Device Computer Aided Diagnosis for Gastroscopy (ENAD CAD-G), could reduce this discrepancy., Materials and Methods: We retrospectively collected 24,948 endoscopic images of early gastric cancers (EGCs), dysplasia, and benign lesions from 9,892 patients who underwent esophagogastroduodenoscopy between 2011 and 2021. The diagnostic performance of ENAD CAD-G was evaluated using the following real-world datasets: patients referred from community clinics with initial biopsy results of atypia (n=154), participants who underwent endoscopic resection for neoplasms (Internal video set, n=140), and participants who underwent endoscopy for screening or suspicion of gastric neoplasm referred from community clinics (External video set, n=296)., Results: ENAD CAD-G classified the referred gastric lesions of atypia into EGC (accuracy, 82.47%; 95% confidence interval [CI], 76.46%-88.47%), dysplasia (88.31%; 83.24%-93.39%), and benign lesions (83.12%; 77.20%-89.03%). In the Internal video set, ENAD CAD-G identified dysplasia and EGC with diagnostic accuracies of 88.57% (95% CI, 83.30%-93.84%) and 91.43% (86.79%-96.07%), respectively, compared with an accuracy of 60.71% (52.62%-68.80%) for the initial biopsy results (P<0.001). In the External video set, ENAD CAD-G classified EGC, dysplasia, and benign lesions with diagnostic accuracies of 87.50% (83.73%-91.27%), 90.54% (87.21%-93.87%), and 88.85% (85.27%-92.44%), respectively., Conclusions: ENAD CAD-G is superior to initial biopsy for the detection and diagnosis of gastric lesions that require endoscopic resection. ENAD CAD-G can assist community endoscopists in identifying gastric lesions that require endoscopic resection., Competing Interests: Jinbae Park and Jiwoon Jeon are employees of Ainex Co., LTD. The other authors have no conflict of interest or financial arrangement that could potentially influence the presented research., (Copyright © 2024. Korean Gastric Cancer Association.)

Currently, the most frequently used surgical treatment for symptomatic, benign, premalignant cystic and neuroendocrine neoplasms of the pancreatic head is the Whipple procedure or pylorus-preserving pancreatoduodenectomy (PD). However, when performed for treatment of benign tumors, PD is a multiorgan resection involving loss of pancreatic and extrapancreatic tissue and functions. PD for benign neoplasm is associated with the risk of considerable early postoperative complications and an in-hospital mortality of up to 5%. Following the Whipple procedure a new onset of diabetes mellitus is observed in 14-20% and new exocrine insufficiency in 25-45%, leading to metabolic dysfunction and impairment of quality of life persisting after resection of benign tumors. Symptomatic neoplasms are indication for surgery. Patients with asymptomatic pancreatic tumors are treated according to the criteria of surveillance protocols. The goal of surgical treatment for asymptomatic patients is, according to the guideline criteria, interruption of the surveillance program before the development of an advanced stage cancer associated with the neoplasm. Tumor enucleation and duodenum-preserving pancreatic head resection, either total or partial, are parenchyma-sparing resections for benign neoplasms of the pancreatic head. The first choice for small tumors is enucleation; however, enucleation is associated with an increased risk of pancreatic fistula B + C following pancreatic main duct injury. Duodenum-preserving total or partial pancreatic head resection has the advantage of low postoperative surgery-related complications, a mortality of < 0.5% and maintenance of the endocrine and exocrine pancreatic functions. Parenchyma-sparing pancreatic head resections should replace classical Whipple procedures for neoplasms of the pancreatic head., (© 2024. The Author(s).)

Purpose: The primary aim was to analyze the current practices on the use of operative hysteroscopy for preserving fertility in patients diagnosed with endometrial cancer and premalignancies. Our secondary objectives included investigating medical therapy and analyzing reported pregnancy-related outcomes subsequent to fertility preservation procedures., Methods: We performed a semi-systematic literature review on PubMed, employing pertinent terms related to hysteroscopy, fertility preservation, and endometrial cancer and premalignancies. Patients undergoing operative hysteroscopy with or without following medical treatment were included. We adhered to the PRISMA 2020 statement and utilized Covidence software to manage our systematic review. We performed a pooled analysis on various outcomes., Results: Our final analysis included 15 studies evaluating 458 patients, where 238 (52.0%) were diagnosed with endometrial cancer, and 220 (48.0%) had endometrial premalignancies. With 146 pregnancies in our study, the overall pregnancy rate was 31.9%. Among these, 97 resulted in live births, accounting for 66.4% of the reported pregnancies. In terms of medical treatment, various forms of progestins were reported. Complications or adverse effects related to operative hysteroscopy were not reported in more than half of the studies. Among those studies that did report them, no complications nor adverse effects were documented. After hysteroscopic resection, complete response to medical treatment has been reported in 65.5% of the overall cases., Conclusion: Our review sheds light on the contemporary landscape of operative hysteroscopy for fertility preservation in endometrial cancer and premalignancies. Future studies should include the integration of molecular classification into fertility-preserving management of endometrial malignancies to offer a more personalized and precise strategy., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Low grade intraepithelial neoplasia (LGIN) and high grade intraepithelial neoplasia (HGIN) are potential precancerous lesion of gastric neoplasms. Endoscopic submucosal dissection (ESD) is the first option for the treatment of precancerous lesion and early gastric cancer (EGC). Traction is an effective method to improve efficiency, and reduce complications during ESD. In this study, we shared a useful traction method using the clip-and-snare method with a pre-looping technique (CSM-PLT) for precancerous lesion and EGC., Methods: We retrospectively analyzed patients received ESD combined with CSM-PLT or conventional ESD from June 2018 to December 2021 in Shenzhen People's hospital. The primary outcome was resection speed., Results: Forty-two patients were enrolled in ESD combined with CSM-PLT group and sixty-five patients in conventional ESD group respectively. Baseline characteristics were comparable among two groups (P>0.05). There were no significant differences in terms of R0 resection rate, en bloc resection rate (97.6% vs. 98.5%, P = 1.000 and 97.6% vs. 96.9%, P = 1.000, respectively), operation costs (933.7 (644.1-1102.4) dollars vs. 814.7 (614.6-988.3) dollars, P = 0.107), and hospital stays (8.0 ± 3.1 days vs. 7.3 ± 3.2 days, P = 0.236). In addition, no significant difference was observed with respect to complications (P>0.05). However, the resection speed of ESD combined with CSM-PLT was faster than that of conventional ESD (11.3 (9.4-14.9) mm 2 /min vs. 8.0 (5.8-10.9) mm 2 /min, P < 0.001), particularly lesions located in anterior wall and lesser curvature. In addition, the association between ESD combined with CSM-PLT and resection speed was still supported after propensity matching scores (PMS)., Conclusions: CSM-PLT can help to improve ESD efficiency without reducing the en bloc resection rate or increasing the incidence of complications., (© 2024. The Author(s).)

Gastric cystica profunda (GCP) is an uncommon but underestimated gastric lesion. Its precancerous potential determines its significance. In addition to previous mucosa injury due to operations, biopsy or polypectomy, chronic active and atrophic gastritis may also lead to the development of GCPs. By carefully examining the stomach and taking biopsy samples from the susceptible regions, the stage of atrophy can be determined. Chronic atrophic gastritis is a risk factor for cancer evolvement and it can also contribute to GCPs formation. GCPs frequently occur close to early gastric cancers (EGCs) or EGC can arise from the cystic glands. Endoscopic resection is an effective and minimally invasive treatment in GCP., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Objective: Barrett's esophagus (BE) is a precancerous condition that has the potential to develop into esophageal cancer (EC). Currently, there is a wide range of management options available for individuals at different pathological stages in Barrett's esophagus (BE). However, there is currently a lack of knowledge regarding their comparative efficacy. To address this gap, we conducted a network meta-analysis of published randomized controlled trials to examine the comparative effectiveness of all regimens., Methods: Data extracted from eligible randomized controlled trials were utilized in a Bayesian network meta-analysis to examine the relative effectiveness of BE's treatment regimens and determine their ranking in terms of efficacy. The ranking probability for each regimen was assessed using the surfaces under cumulative ranking values. The outcomes under investigation were complete ablation of BE, neoplastic progression of BE, and complete eradication of dysplasia., Results: We identified twenty-three RCT studies with a total of 1675 participants, and ten different interventions. Regarding complete ablation of non-dysplastic BE, the comparative effectiveness ranking indicated that argon plasma coagulation (APC) was the most effective regimen, with the highest SUCRA value, while surveillance and PPI/H2RA were found to be the least efficacious regimens. For complete ablation of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, photodynamic therapy (PDT) had the highest SUCRA value of 94.1%, indicating it as the best regimen. Additionally, for complete eradication of dysplasia, SUCRA plots showed a trend in ranking PDT as the highest with a SUCRA value of 91.2%. Finally, for neoplastic progression, radiofrequency ablation (RFA) and surgery were found to perform significantly better than surveillance. The risk of bias assessment revealed that 6 studies had an overall high risk of bias. However, meta-regression with risk of bias as a covariate did not indicate any influence on the model. In terms of the Confidence in Network Meta-Analysis evaluation, a high level of confidence was found for all treatment comparisons., Conclusion: Endoscopic surveillance alone or PPI/H2RA alone may not be sufficient for managing BE, even in cases of non-dysplastic BE. However, APC has shown excellent efficacy in treating non-dysplastic BE. For cases of BE with low-grade dysplasia, high-grade dysplasia, or esophageal cancer, PDT may be the optimal intervention as it can induce regression of BE metaplasia and prevent future progression of BE to dysplasia and EC., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The primary benefit of post-colorectal cancer (CRC) colonoscopic surveillance is to detect and remove premalignant lesions to prevent metachronous CRC. Current guidelines for long-term colonoscopic surveillance post early age onset CRC (EOCRC) resection are based on limited evidence. The aims of this study were to assess the diagnostic yield of colonoscopic surveillance post-EOCRC resection and identify molecular and clinicopathological risk factors associated with advanced neoplasia., Methodology: A retrospective cohort study of prospectively collected data was conducted at St Mark's hospital, London, United Kingdom, for patients diagnosed with EOCRC who underwent at least one episode of post-CRC colonoscopic surveillance between 1978 and 2022. We collected clinicopathological data including tumour molecular status and neoplasia detection rates., Results: In total, 908 colonoscopic surveillance procedures were performed in 195 patients over 2581.3 person-years of follow-up. The diagnostic yields of metachronous CRC, advanced adenomas and non-advanced adenomas were 1.76%, 3.41% and 22.69% respectively. Sixteen patients (8.21%) developed metachronous CRC, and the majority (87.5%) were detected more than 3 years post index EOCRC diagnosis. Detection of advanced neoplasia was significantly higher in EOCRC patients with Lynch syndrome (26.15%) compared with those in whom Lynch syndrome was excluded (13.13%) (OR, 2.343; 95% CI, 1.014-5.256; p = 0.0349)., Conclusions: During colonoscopic surveillance post-EOCRC resection, the long-term risk of developing metachronous advanced neoplasia remains high in the context of Lynch syndrome, but this trend is not as clearly evident when Lynch syndrome has been excluded., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Today, endoscopy plays a decisive role not only in the detection of colorectal adenomas and carcinomas, but also in the treatment of precancerous lesions, in particular flat adenomas and early carcinomas. In recent years, endoscopic submucosal dissection (ESD) has become increasingly important alongside classic polypectomy and mucosal resection after saline injection using a snare (EMR). Using ESD the lesion is marked, injected submucosally using viscous substances and the mucosa incised and tunneled with a transparent cap and a fine diathermy knife. Particularly in the case of widespread and high-risk lesions ESD enables a quasi-surgical "en bloc" resection almost regardless of size, with a histological R0 resection rate of far over 90% in specialized centers. ESD enables an excellent histopathological evaluation and has a low recurrence risk of 1-3%. Endoscopic full-thickness resection using a dedicated device (FTRD system) represents another addition to the armamentarium. It can be used for circumscribed submucosal, suspicious or scarred changes up to 2 cm in the middle and upper rectum. Endoscopic intermuscular dissection (EID) enables histopathological analysis of the complete submucosa beyond the mucosa and upper submucosal layer by including the circular inner muscle layer within the resection specimen. It reduces basal R1 situations and offers a new perspective for T1 carcinomas through curative, organ-preserving endoscopic therapy, especially in the case of deep submucosal infiltration alone, without other risk factors for metastases. Indications, the procedure itself and significance of the various techniques for premalignant and early malignant lesions in the rectum are presented., Competing Interests: Es besteht kein primärer Interessenskonflikt in Bezug auf den Beitrag. Forschungsunterstützung: Erbe, Tübingen: Fujifilm Europe, Ratingen; Medtronic, Meerbusch; Ovesco, Tübingen. Honorare für Vorträge: Falk Foundation, Freiburg; Fujifilm Europe, Ratingen; Ovesco, Tübingen., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: The single-visit strategy, also known as the "screen-and-treat" approach, is widely used to screen for cervical cancer in low- and middle-income countries. The screen-and-treat approach leads to unnecessary or inadequate treatment. Thus, a study was conducted to determine the histopathological patterns of aceto-white lesions on visual inspection with acetic acid (VIA) in patients who underwent a Loop Electrosurgical Excision Procedure (LEEP) at Bugando Medical Centre between January 2016 and December 2020., Method: A 5-year retrospective cross-sectional case record review was conducted on 329 women who had LEEP at Bugando Medical Centre following a positive VIA cervical screening test. A standard data abstraction form was used to collect patient information. Missing client information records and LEEP without histopathological results were exclusion criteria. For statistical analysis, STATA version 15 was used; in descriptive statistics, frequency, mean, and standard deviation were used. The Chi 2 and Fisher's exact tests were used to investigate the relationship between patient characteristics and histopathological patterns, and a P-value of 0.05 was considered statistically significant in multinomial models., Results: This study looked at 329 patients who had LEEP following a VIA positive but were not eligible for cryotherapy. Our study participants had a mean age of 40 ± 8.2 SD. There were 203 (61.7%) patients with benign lesions, including 4 with schistosomiasis and 2 with cervical tuberculosis. The precancerous lesions were discovered in 100 cases (30.4%), and 26 (7.9%) already had invasive cervical cancer. Out of 100 patients with precancerous lesions, 58 (17.6%) and 42 (12.8%) have high- and low-grade squamous intraepithelial (HSIL and LSIL) lesions, respectively. The presence of a precancerous lesion was found to be associated with age 31-40 years (P-value 0.042) and HIV positivity (P-value 0.004)., Conclusion: Most patients in this study had benign cervical lesions, which do not require LEEP treatment. Nonetheless, a considerable percentage of invasive cervical malignancies and rare benign diseases such as schistosomiasis and cervical tuberculosis were identified. A screen-and-treat approach within well-equipped tertiary hospitals like Bugando Medical Centre should explore alternative options instead of relying solely on straight LEEP., (© 2024. The Author(s).)

Introduction: Thanks to mammographic screening and the improvement of breast cancer diagnostics, the detection of precancers is also increasing. They are defined as morphological changes of the mammary gland which are more likely to cause cancer. The evaluated precancers are atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS) and radial scar., Methodology: In the period 1. 1. 2018-31. 12. 2022, we performed 1,302 planned operations for breast disease at the Surgical Clinic of Teaching Hospital Plzeň, of which 30 (2%) were precancer operations. ADH was confirmed 11×, LCIS 8×, and a radical scar 11×. The average age of the patients in all three groups was 56 years (27-85). Precancer was diagnosed 8× only by sonography, 3× by mammography and 19× by a combination of both methods. Subsequently, a puncture biopsy was always completed. We performed 28 tumor excisions with intraoperative biopsy and 2 mastectomies., Results: In the case of ADH from puncture biopsy, ADH was confirmed intraoperatively 8×, DCIS was diagnosed 2×, and mucinous carcinoma 1×. In LCIS, no tumor was found by intraoperative biopsy 4×, LCIS was confirmed 1×, lobular invasive carcinoma was diagnosed 1×, mastectomy was performed 2× without intraoperative biopsy. In the radial scar, ADH was diagnosed 3×, sclerosing adenosis 6×, DCIS 1×, invasive carcinoma 1×. After the final histological processing of the samples, there was an increase in diagnosed carcinomas. In ADH, DCIS was confirmed 3×, DIC 2×, and mucinous carcinoma 1×. In LCIS, LIC was diagnosed 3×. In the radial scar, DCIS was confirmed 1×, and invasive carcinoma remain 1×. Thus, carcinoma was diagnosed in 11 patients (37%) thanks to the surgical solution. No patient underwent axillary node surgery. All 11 patients subsequently underwent oncological treatment, always a combination of radiotherapy and hormone therapy. All patients are alive, 10 patients are in complete remission of the disease, one with DCIS experienced a local recurrence after 4 years., Conclusion: Surgical treatment of precancers of the breast makes sense, DCIS or even invasive cancer is often hidden in addition to precancer. Thanks to the surgical solution, the cancer was detected in time.

Aim: Esophageal cancer is a disease with high morbidity and mortality, exploring effective treatment methods is the key to the treatment of this disease. This study aims to compare the clinical efficacy and safety of multi-band mucosectomy (MBM) and endoscopic submucosal dissection (ESD) in the treatment of single early esophageal cancer (EEC) and precancerous lesions, and whether MBM can achieve better clinical effect as an effective treatment method., Methods: The clinical data of 70 patients with EEC and precancerous lesions who were treated with MBM and ESD in the Fourth Affiliated Hospital of China Medical University from May 2021 to May 2023 and could be followed up were retrospectively analyzed. They were divided into two groups according to different treatment methods: MBM group (31 cases) and ESD group (39 cases). The general data, perioperative conditions, endoscopic treatment effect and pathological results of the two groups were compared., Results: The duration of endoscopic treatment in MBM group was shorter than that in ESD group [36 (25~39) min vs 46 (41~57) min, p < 0.05], and there was no significant difference in the intraoperative bleeding rate between the two groups (12.90% vs 7.69%, p > 0.05). There was no significant difference in the rate of intraoperative perforation between the two groups (3.23% vs 7.69%, p > 0.05), and the hospitalization time in MBM group was shorter than that in ESD group [5 (4~7) days vs 8 (7~12) days, p < 0.05]. The hospitalization cost was less [2535 (2423~2786) dollars vs 4485 (3858~5794) dollars, p < 0.05]. No postoperative bleeding occurred in both groups. There was no statistically significant difference in postoperative stenosis rate between MBM group and ESD group (3.23% vs 12.82%, p > 0.05), and no statistically significant difference in postoperative local recurrence rate (12.90% vs 5.13%, p > 0.05). There was no significant difference in the rate of additional surgery (9.68% vs 2.56%, p > 0.05). The en bloc resection rate of MBM group was lower than that of ESD group (77.42% vs 97.44%, p < 0.05), but there was no significant difference in the complete resection rate between the two groups (87.10% vs 97.44%, p > 0.05). The postoperative pathological results of MBM group showed 13 cases of low-grade intraepithelial neoplasia (LGIN), 11 cases of high-grade intraepithelial neoplasia (HGIN), and 7 cases of canceration, while the postoperative pathological results of ESD group showed 10 cases of LGIN, 14 cases of HGIN, and 15 cases of canceration, with no statistical significance (p > 0.05)., Conclusions: MBM and ESD are effective methods for the treatment of EEC and precancerous lesions. MBM has the advantages of short hospital stay, quick recovery and low cost. However, compared with MBM, ESD can improve the complete resection rate of the lesion, avoid the occurrence of positive incisal margin, and reduce the risk of secondary treatment and additional surgery.

Background: Management of breast lesions of uncertain malignant potential diagnosed at core needle biopsy (CNB) is controversial due to variable upstage rate (UR) with surgical excision (SE)., Methods: We performed an IRB-approved retrospective analysis of adult women who underwent CNB demonstrating atypical ductal hyperplasia (ADH), flat epithelial atypia, radial scar, or intraductal papilloma then SE between 2010 and 2022. We evaluated CNB pathology for combination diagnoses (CD), defined as multiple primary lesions or primary with lobular neoplasia (LN), and surgical pathology for upstage., Results: 719 patients were included. UR was 12.2% (88/719). CD experienced higher UR than pure (17.7% (45/254) vs. 9.2% (43/465), p ​= ​0.001). ADH/LN had the highest UR of all CD (34.6% (9/26), p ​= ​0.001). Increased size (15.6 vs. 10.5 ​mm, p ​< ​0.001), distance from nipple (79 vs. 66 ​mm, p ​< ​0.001), and personal history of breast cancer (p ​= ​0.04) were associated with UR., Conclusions: CD was associated with increased UR. ADH/LN had the highest UR., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: Vulval cancer accounts for around 4% of all gynaecological malignancies and most tumours ( > 90%) are of a squamous cell histotype. Most lesions arise on a background of differentiated VIN (dVIN) or lichen sclerosus (LS). Surgical treatment has undergone a paradigm shift with less radical surgery being attempted to preserve vulval structure and function, without compromising oncological outcome., Material and Methods: In this single site retrospective analysis, we consider the data from a tertiary oncology unit, to assess progression-free survival based on the presence of a precursor lesion at the margin of resection.123 patients with FIGO stage 1 vulvar SCC (n = 33 1A, n = 90 1B) were included., Results: One Hundred Five patients (85%) had an associated precursor lesion (dVIN and/or LS). Within the follow-up period, 33 patients (26.8%) had invasive recurrence, of which 24 (72.7%) had surgical resection margins which were positive for a precursor lesion. In patients with an acceptable microscopically clear invasive resection margin of > 2 mm the presence of a precursor lesion at the margin conveyed a higher risk of malignant recurrence when compared to those with completely clear margins (HR = 2.42; 95% CI 1.14-5.16)., Conclusions: This study adds to the available literature emphasising the clinical significance of dVIN or LS at the surgical margin of optimally resected disease. In those who have marginal involvement of a precancerous lesion, increased surveillance should be considered. Future work should explore the need for additional adjuvant therapy in this cohort.

Objective: To assess the impact of a multicomponent intervention in women with cervical dysplasia who were treated with loop electrosurgical excision procedure (LEEP), as well as the time between colposcopy and treatment., Design: Retrospective cohort study., Intervention: Clinic participation in a multicomponent cervical cancer prevention program that included community outreach, patient in-reach, and navigation, as well as provider capacity building with in-person training and ongoing telementoring through Project ECHO., Main Outcome Measures: Medical records were reviewed to evaluate women with cervical dysplasia undergoing treatment with LEEP within 90 days of colposcopy, as well as time between colposcopy and treatment. Baseline data from year 1 were compared with each subsequent year of implementation. Additional variables examined included patient's age, history of abnormal screening results, and percentage of families living below poverty line based on county of residence, parity, and clinic site. We performed logistic regression and multiple linear regression analyses to assess the programmatic impact in the outcomes of interest by year of program implementation., Results: A total of 290 women were included in the study. The proportion of women undergoing treatment within 90 days of colposcopy increased from 76.2% at baseline to 91.3% in year 3 and 92.9% in year 4 of program implementation. The odds of undergoing treatment within 90 days were 5.11 times higher in year 4 of program implementation than at baseline. The mean time between colposcopy and LEEP decreased from 62 days at baseline to 45 days by year 4 of program implementation., Conclusions: Implementation of our multicomponent cervical cancer prevention program increased the proportion of women undergoing LEEP within 90 days of colposcopy and decreased the time between colposcopy and LEEP. This program has the potential to support cervical cancer prevention efforts and could be implemented in other low-resource settings., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: Oral potentially malignant disorders, including oral epithelial dysplasia (OED), are a group of conditions with an increased risk of progression to oral cancer. Clinical management of OED is challenging and usually involves monitoring with repeated incisional biopsies or complete surgical excision., Objective: To determine if complete surgical excision of OED impacts malignant transformation or improves survival outcomes in lesions that progress to malignancy., Design: A retrospective review of all patients diagnosed with OED between 2009 and 2016 was completed, and patients were followed until January 2022 for disease course and outcomes., Results: Hundred and fifty-five cases of OED met the inclusion criteria. Among the 61 lesions managed by observation, 15 progressed to cancer. Among the 94 lesions managed by surgical excision, 27 progressed to cancer. The overall malignant transformation rate was 27%, with an annual rate of 6.4%. Surgical excision with or without histologically negative margins did not decrease malignant transformation but was associated with lower oncologic staging at the time of diagnosis and improved survival., Conclusions and Relevance: Surgical excision of OED with or without negative margins did not reduce the rate of transformation to oral cancer but resulted in lower oncologic staging at diagnosis, leading to improved patient outcomes. Our results support the implementation of more extensive tissue sampling to improve cancer diagnosis and patient outcomes., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: An important cervical cancer prevention strategy in low- and middle-income countries (LMICs) has been single-visit screen-and-treat (SV-SAT) approach, using visual inspection with acetic acid (VIA) and ablative treatment with cryotherapy to manage precancerous lesions. While SV-SAT with VIA and cryotherapy have established efficacy, its population level coverage and impact on reducing cervical cancer burden remains low. In Kenya, the estimated cervical cancer screening uptake among women aged 30-49 is 16% and up to 70% of screen-positive women do not receive treatment. Thermal ablation for treatment of precancerous lesions of the cervix is recommended by the World Health Organization and has the potential to overcome logistical challenges associated with cryotherapy and facilitate implementation of SV-SAT approach and increase treatment rates of screen-positive women. In this 5-year prospective, stepped-wedge randomized trial, we plan to implement and evaluate the SV-SAT approach using VIA and thermal ablation in ten reproductive health clinics in central Kenya., Methods: The study aims to develop and evaluate implementation strategies to inform the national scale-up of SV-SAT approach with VIA and thermal ablation through three aims: (1) develop locally tailored implementation strategies using multi-level participatory method with key stakeholders (patient, provider, system-level), (2) implement SV-SAT approach with VIA and thermal ablation and evaluate clinical and implementation outcomes, and (3) assess the budget impact of SV-SAT approach with VIA and thermal ablation compared to single-visit, screen-and-treat method using cryotherapy., Discussion: Our findings will inform national scale-up of the SV-SAT approach with VIA and thermal ablation. We anticipate that this intervention, along with tailored implementation strategies will enhance the adoption and sustainability of cervical cancer screening and treatment compared to the standard of care using cryotherapy., Trial Registration: NCT05472311., (© 2023. The Author(s).)

Background and Aims: Treatment strategies for early cancers or precancerous lesions of the upper GI tract in patients with cirrhosis and esophagogastric varices (EGVs) are complicated and risky. The aim of this study was to assess the efficacy and safety of endoscopic submucosal dissection (ESD) in the treatment of such patients and explore optimal treatment strategies., Methods: We retrospectively enrolled 15 patients with cirrhosis and EGV who underwent ESD for early cancers or precancerous lesions of the upper GI tract from January 2012 to December 2021 at our center. Clinical features, endoscopic findings, treatment methods, adverse events, and follow-up data were analyzed., Results: Of the 15 patients, 1 had a platelet count <30 × 1000/mm 3 . Five were untreated for EGV, 1 was treated after ESD, 6 were treated before ESD, 1 was treated before and during ESD, and 2 were treated during ESD. The R0 resection rate was 100%. Of the 16 mucosal lesions, 15 were endoscopic resection bleeding (ERB)-0 or ERB-c1, and 1 was ERB-c2. No patient experienced deterioration in liver function. The only adverse events were fever in 2 patients and postoperative bleeding in 2 patients. During a median follow-up of 27 months, 1 patient's esophageal high-grade dysplasia recurred at 19 months. No death resulted from the ESD procedure, liver function injury, or GI tumor itself., Conclusions: ESD is an effective and safe treatment for early cancers or precancerous lesions of the upper GI tract in patients with cirrhosis and EGV. The incidence of severe adverse events is very low due to the development of individualized clinical treatment strategies., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: The natural course of gastric low-grade dysplasia (LGD) remains unclear, and there are inconsistent management recommendations among guidelines and consensus., Objective: This study aimed to investigate the incidence of advanced neoplasia in patients with gastric LGD and identify the related risk factors., Methods: Cases of biopsy demonstrated LGD (BD-LGD) at our center from 2010 to 2021 were reviewed retrospectively. Risk factors related to histological progression were identified, and outcomes of patients based on risk stratification were evaluated., Results: Ninety-seven (23.0%) of 421 included BD-LGD lesions were diagnosed as advanced neoplasia. Among 409 superficial BD-LGD lesions, lesion in the upper third of the stomach, H. pylori infection, larger size, and narrow band imaging (NBI)-positive findings were independent risk factors of progression. NBI-positive lesions and NBI-negative lesions with or without other risk factors had 44.7%, 1.7%, and 0.0% risk of advanced neoplasia, respectively. Invisible lesions, visible lesions (VLs) without a clear margin, and VLs with a clear margin and size ≤ 10 mm, or > 10 mm had 4.8%, 7.9%, 16.7%, and 55.7% risk of advanced neoplasia, respectively. In addition, endoscopic resection decreased the risk of cancer (P < 0.001) and advanced neoplasia (P < 0.001) in patients with NBI-positive lesions, but not in NBI-negative patients. Similar results were found in patients with VLs with clear margin and size > 10 mm. Moreover, NBI-positive lesions had higher sensitivity and lower specificity for predicting advanced neoplasia than VLs with a clear margin and size > 10 mm determined by white-light endoscopy (97.6% vs. 62.7%, P < 0.001; and 63.0% vs. 85.6%, P < 0.001, respectively)., Conclusion: Progression of superficial BD-LGD is associated with NBI-positive lesions, as well as with VLs with a clear margin (size > 10 mm) if NBI is unavailable, and selective resection of those lesions offers benefits for patients by decreasing the risk of advanced neoplasia., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Clinical guidelines recommend radiofrequency ablation (RFA) for eradication of Barrett esophagus in patients with low-grade dysplasia (LGD) and high-grade dysplasia (HGD), but evidence on whether RFA provides good value for money is still sparse. This study evaluates the cost-effectiveness of RFA in Italy., Methods: A Markov model was used to estimate lifelong costs and consequences of disease progression with different treatments. RFA was compared with esophagectomy in the HGD group or endoscopic surveillance in the LGD group. Clinical and quality-of-life parameters were derived from a review of the literature and expert opinions, whereas Italian national tariffs were used as a proxy for costs., Findings: RFA dominated esophagectomy in patients with HGD with a probability of 83%. For patients with LGD, RFA was more effective and more costly than active surveillance (incremental cost-effectiveness ratio, €6276 per quality-adjusted life-year). At a cost-effectiveness threshold of €15,272, the probability of RFA being the optimal strategy in this population was close to 100%. Model results were sensitive to the cost of the interventions and utility weights used in the different disease states., Implications: RFA is likely to be the optimal choice for patients with LGD and HGD in Italy. Italy is discussing the implementation of a national program for the health technology assessment of medical devices, requiring more studies to prove value for money of emerging technologies., Competing Interests: Declaration of Interest Mr Federici and Dr Callea reported that in past years CERGAS SDA Bocconi has received unconditional grants for projects related to the products of Medtronic Italy. In all these research projects, the company did not play a role in any of the phases of the work. Dr Testoni, Dr Costamagna, Dr Trentino, and Dr Repici have in the past received honoraria for lectures, presentations, speaker's bureaus, manuscript writing, and/or educational events. The authors have indicated that they have no other conflicts of interest regarding the content of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To investigate the clinical practices of diagnosing multicystic cervical lesions as a means to develop a more appropriate diagnostic algorithm for gastric-type adenocarcinoma (GAS) and its precursors., Methods: Clinical information for 159 surgically treated patients for multicystic disease of the uterine cervix was collected from 15 hospitals. We performed a central review of the MRI and pathological findings. The MRI findings were categorized into four types including two newly proposed imaging features based on the morphology and distribution of cysts, and the diagnosis accuracy was assessed. Among the four MRI types, types 1 and 2 were categorized as benign lesions that included LEGH; type 3 were precancerous lesions (with an assumption of atypical LEGH); and type 4 were malignant lesions., Results: The central pathological review identified 56 cases of LEGH, seven with GAS, four with another form of carcinoma, and 92 with benign disease. In clinical practice, over-diagnosis of malignancy (suspicion of MDA) occurred for 12/19 cases (63.2%) and under-diagnosis of malignancy occurred for 4/11 (36%). Among the 118 patients who had a preoperative MRI and underwent a hysterectomy, type 3 or 4 MRI findings in conjunction with abnormal cytology were positively indicative of premalignancy or malignancy, with a sensitivity and specificity of 61.1% and 96.7%, respectively., Conclusions: Although the correct preoperative diagnosis of cervical cancer with a multicystic lesion is challenging, the combination of cytology and MRI findings creates a more appropriate diagnostic algorithm that significantly improves the diagnostic accuracy for differentiating benign disease from premalignancy and malignancy., (© 2023. The Author(s).)

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history ( OR =3.090, 95% CI: 1.165-8.200; P <0.05), The AB type of intrapapillary capillary loop (IPCL) ( OR =11.215, 95% CI: 3.955-31.797; P <0.05) were the independent risk factors for the depth of invasion. The smoking history ( OR =5.824, 95% CI: 1.704-19.899; P <0.05), the presence of avascular area (AVA) ( OR =3.393, 95% CI: 1.285-12.072; P <0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

Objectives: This retrospective cohort study aimed to determine the prevalence of precancerous or malignant lesions of the cervix and/or endometrium among patients who underwent vaginal hysterectomy., Materials and Methods: Medical record of patients who had been diagnosed with pelvic organ prolapse (POP) and undergone vaginal hysterectomy from January 2009 to September 2018 in tertiary hospital was reviewed. The exclusion criteria included individuals who had previously received a diagnosis of gynecologic precancerous lesions or cancer, had abnormal preoperative findings, presented abnormal cervical cancer screening test results or abnormal results from preoperative endometrial biopsy, and had incomplete operative notes or pathological results., Results: The electronic medical records of 530 patients were reviewed and included in the analysis. Nine of the 530 patients (1.7%) had precancerous or malignant lesions of the cervix and/or endometrium. The prevalence of atypical endometrial hyperplasia and endometrial carcinoma were 0.19% and 0.57%, respectively. All of the patients with endometrial cancer subsequently underwent complete surgical staging. Precancerous cervical lesions were found in five patients (0.95%): CIN II 0.38% and CIN III 0.57%. No cases of cervical cancer were identified., Conclusions: It is possible to detect a minor prevalence of precancerous and malignant lesions following post-operative procedures in POP. The assessment of the elderly through the use of risk-based evaluation merits attention for the purpose of early identification. This study offers valuable insights that can be utilized in preoperative counseling and enhancing the preoperative evaluation process.

Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests.

Background: We evaluated the relationship between comorbidities associated with obesity, body mass index (BMI), and development of intestinal metaplasia (IM) after vertical sleeve gastrectomy (VSG)., Materials and Methods: All VSG specimens performed at an academic center between 2011 and 2018 were reviewed. All specimens underwent histopathologic assessment, while those with findings suspicious for IM underwent additional immunohistochemical work up. Baseline patient characteristics and demographic data were obtained from Iran National Obesity Surgery Database by retrospective review., Results: A total of 862 adult individuals underwent VSG during the study period and specimens were histopathologically examined. All patients had preoperative upper endoscopy. The most common histopathologic diagnosis was miscellaneous findings (57.8%) followed by no pathologic finding (36.7%). The minority of patients (5.5%) had IM. Although 40.5% of patients had positive Helicobacter pylori infection preoperatively, just 13.8% had still positive infection postoperatively. A significant association was found between IM and hypercholesterolemia (odds ratio: 1.95; 95% confidence interval: 1.1, 3.5)., Conclusion: This study found a correlation between histopathologic changes in patients with IM and hypercholesterolemia. Prospective research studies are recommended to further examine this correlation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To retrospectively analyze the preoperative endoscopic evaluation of the size, nature, and depth of lesions in endoscopic submucosal dissection (ESD) for early gastric cancer and precancerous lesions, determine whether the lesions can be completely resected, and reduce the risk of additional surgery after ESD., Methods: A total of 114 patients with high-grade intraepithelial neoplasia(HGIN) and early gastric cancer treated with ESD in Hebei General Hospital from January 2016 to April 2021 were enrolled in this study. The lesions were evaluated preoperatively according to the endoscopic findings of white light, magnifying endoscopy, endoscopic features of narrow band imaging, and preoperative pathology. Lesion size, positive resection margin, lesion depth, and vascular invasion of postoperative pathology were used as criteria., Results: There were 121lesions in 114 patients. The coincidence rates of preoperative and postoperative pathology were 87.21% (75/86) for HGIN and 92.1% (35/38) for adenocarcinoma. There was no significant difference in the coincidence rate between preoperative pathological evaluation and postoperative pathology among the 3 lesions (χ2 = 10.614, P = .005). The type and malignancy of the lesion were not related to its location or size. Magnifying endoscopy combined with narrow-band imaging showed that HGIN and early gastric cancer had clear borders, irregular microvessels, and irregular surface microarchitecture on endoscopic features. Lesions > 3 cm, surface ulcers and spontaneous bleeding may be risk factors for deeper lesions., Conclusion: ESD is not only a method for the treatment of early gastric cancer and precancerous lesions, but is also an important method for definite pathological diagnosis. Accurate preoperative assessment of lesion type, lesion extent and depth of invasion is helpful to improve the complete resection rate of ESD and reduce the risk of additional surgery., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Leukoplakia is common with a 1 % incidence in the population and may harbor preneoplastic changes. Diode lasers provide both precision and coagulation for excision of superficial lesions in clinical and operative settings with little damage to deeper tissue. We aim to determine the rate of oral and oropharyngeal hyperkeratosis and dysplasia recurrence after treatment with diode laser., Materials and Methods: Patients with oral or oropharyngeal hyperkeratotic or mild dysplastic lesions treated with pulsed diode laser between 2013 and 2020 at a tertiary academic institution were analyzed. The main outcome measure was recurrence of hyperkeratosis and dysplasia after treatment., Results: Fourteen patients received diode laser treatment for hyperkeratotic or mild dysplastic lesions of the oral cavity or oropharynx. Demographic features included 9 (64.3 %) females and mean age of 66.6 years. In these 14 patients, 18 distinct lesions were identified. Eleven (61.1 %) lesions were located on the oral tongue, 4 (22.2 %) on the buccal mucosa, 2 (11.1 %) on the hard palate, and 1 (5.6 %) on the soft palate. Average time from lesion clinical diagnosis to the first diode laser treatment was 8.3 months with an average number of 1.4 treatments per lesion. Three (16.7 %) lesions experienced recurrence after the most recent treatment. None of the lesions underwent malignant transformation. None of the patients experienced bleeding, tethering, or dysarthria after treatment. One patient developed pyogenic granuloma and reported chronic tongue pain., Conclusions: Pulsed diode laser treatment of leukoplakia was well tolerated with low complication rates and reasonable control of precancerous lesions., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The decision to undertake pancreaticoduodenectomy for benign and precancerous lesions has historically relied on outcomes data from operations for cancer. We aimed to describe risks for these specific patients and identify the highest risk groups., Methods: The ACS-NSQIP pancreatic targeted data was queried for pancreaticoduodenectomies for benign and pre-cancerous neoplasms from 2014 to 2018. Baseline characteristics, operative techniques and outcomes were examined. Multivariate regression was performed to identify predictors of major complications., Results: 748 patients underwent pancreaticoduodenectomy for (n = 541,72.3%) IPMN, (n = 87,11.6%) MCN, (n = 78,10.4%) serous cystadenoma, and (n = 42,5.6%) solid pseudopapillary neoplasm. Median LOS was 8 days. Major complications (n = 135,18.0%), non-home discharges (n = 83,11.1%) and readmissions (n = 153,20.5%) occurred frequently. In patients ≥ 80 years of age (n = 37), major complications (n = 11,29.7%) and non-home discharge (n = 9,24.3%) were quite common. 5-item modified frailty index ≥ 0.4 (OR 1.84,95%CI 1.06-3.19,p = 0.030), Male sex (OR 1.729,95%CI 1.152-2.595,p = 0.008), Age ≥ 65 (OR 1.63,95%CI 1.05-2.54,p = 0.29) and African-American race (OR 2.50,95%CI 1.22-5.16,p = 0.013) were independent predictors of major morbidity., Conclusions: Pancreaticoduodenectomies in this setting have high rates of major complications. Morbidity extends beyond the index hospitalization, with frequent readmission and non-home discharge. Patient specific factors, rather than technical or disease factors predicted outcomes. In certain patients, particularly those older than 80, the morbidity of this operation may exceed the cancer prevention benefits., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Although ovarian conservation at hysterectomy for benign gynecologic disease has demonstrated mortality benefit in young patients and this benefit may be sustained up to age 65 years, there is a scarcity of data regarding ovarian conservation in those with a diagnosis of endometrial hyperplasia, a premalignant uterine condition., Objective: This study aimed to examine patient, hospital, treatment, and histology characteristics related to ovarian conservation at the time of inpatient hysterectomy for endometrial hyperplasia., Study Design: The Healthcare Cost and Utilization Project's National Inpatient Sample was retrospectively queried to examine patients aged ≤65 years with endometrial hyperplasia who had inpatient hysterectomy from January 2016 to December 2019. The exclusion criteria included concurrent gynecologic malignancy, adnexal pathology, and lymphadenectomy. Cases were grouped by adnexal surgery status (ovarian conservation or oophorectomy). A multivariable binary logistic regression model was used to identify independent characteristics for ovarian conservation. A classification tree was constructed with recursive partitioning analysis to examine utilization patterns of ovarian conservation., Results: Overall, 3105 patients (31.1%) underwent ovarian conservation at hysterectomy among 9975 patients. The utilization of ovarian conservation decreased gradually until age 45 years and then markedly decreased by age 52 years (63.3%-15.3%; P<.001). In a multivariable analysis, younger age, non-White, urban nonteaching centers, and vaginal hysterectomy were associated with increased utilization of ovarian conservation, whereas endometrial hyperplasia with atypia, obesity, comorbidity, large bed capacity centers, and Midwest and South regions were associated with decreased utilization of ovarian conservation (all, P<.05). A classification tree identified 17 utilization patterns for ovarian conservation, ranging from 7.8% to 100.0% (absolute rate difference, 92.2%)., Conclusion: The utilization of ovarian conservation at the time of inpatient hysterectomy in patients undergoing surgical management for endometrial hyperplasia started decreasing in their mid-40s and seemed to occur earlier than in benign hysterectomy. There was substantial variability in ovarian conservation at the time of hysterectomy for endometrial hyperplasia based on patient, hospital, surgical, and histology factors, suggesting the possible benefit of clinical practice guidelines for ovarian conservation in this population., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Routine preoperative endoscopic evaluation for bariatric surgery is controversial; however, for patients undergoing endoscopy, some findings may alter surgical management. Gastric intestinal metaplasia (GIM) is found in up to 11.7% of the general population. When associated with determined risk factors, GIM has a risk of progressing to gastric cancer. The aim of our study was to assess the prevalence of GIM and possible associated factors in those undergoing bariatric surgery. We performed a retrospective chart review of patients who underwent primary sleeve gastrectomy or Roux-en-Y gastric bypass at our institution between January 1, 2016 and June 30, 2020. Baseline characteristics and preoperative endoscopic findings were obtained from all patients. Histopathologic analysis of sleeve gastrectomy specimens was reviewed. We identified 753 patients. Mean (SD) age and body mass index were 49.0 (13.1) years and 43.9 (7.1) kg/m 2 , respectively. Procedures consisted of 411 (54.6%) gastric bypasses and 342 (45.4%) sleeve gastrectomies. Esophagitis and Barrett esophagus were found in 18.1% and 5.0% of patients, respectively. Preoperative gastric biopsy identified Helicobacter pylori in 6.4% and GIM in 2.7%. Regression analysis found an association of Barrett esophagus (odds ratio 4.60; 95% CI 1.25-16.82) and age ≥ 60 years (odds ratio 2.67; 95% CI 1.04-6.90) with preoperative findings of GIM. Histopathologic analysis of sleeve gastrectomy specimens identified H. pylori in 1.8% and GIM in 0.9%. Older age and Barrett esophagus were associated with GIM in preoperative gastric biopsy. This association emphasizes the importance of a diligent examination during preoperative endoscopy., (© 2021. Italian Society of Surgery (SIC).)

The main clinical relevance of Barrett's esophagus (BE), a result of chronic exposure to gastroesophageal reflux, is its potential progression to esophageal adenocarcinoma (EAC). Although screening for BE is not recommended in the general population, after diagnosis of BE, a surveillance strategy for early detection of dysplasia or neoplasia is needed. The gold standard for diagnosis and surveillance is high-definition oral endoscopy with random biopsies. In addition, any visible lesion should be completely resected, which will be considered curative in the presence of low grade dysplasia (LGD), high-grade dysplasia (HGD) or EAC confined to the mucosa (T1a), followed by eradication of residual BE by endoscopic ablation. In the absence of a visible lesion, radiofrequency ablation should be performed to eradicate BE with LGD, HGD or intramucosal EAC., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

Background: Endoscopic treatment of precancerous lesions and early gastric cancer has been widely accepted in recent years. Endoscopic submucosal dissection (ESD), following established indication criteria, can lead to cure of the disease in more than 90% of cases., Objective: This study aimed to analyze the use of ESD in patients with early gastric cancer and precancerous lesions, as well as the results of the procedure, its complications and effectiveness in controlling the disease., Methods: This is a retrospective cohort study composed of 41 patients aged from 53 to 87 years (mean age: 65 years; 58.53% male) who were analyzed from 2008 to 2019. The variables collected from the medical records were: comorbidities, classification of the lesion regarding resection criteria, type of resection, histology, degree of invasion, resection margin, complications, disease recurrence. Statistical analysis was performed using the Kruskal-Wallis test, the McNemar's test, and the Mann-Whitney test, with 5% statistical significance (P<0.05)., Results: The most frequent site of the lesion was the gastric antrum and the predominant presentation by the Japanese or Paris classification was the one with depressed components in 56.09%. Adenocarcinoma occurred in 75.6% of the biopsies, and the remainder were adenomas without neoplasia. En-bloc resection occurred in 97.57% of cases, and compromise of the safety margin occurred in one patient. The main pre-existing comorbidity was liver cirrhosis in 29.26% of cases. There was a significant increase in post- ESD adenocarcinoma compared to pre-resection diagnosis. The mean follow-up time was 38.4 months, with one recurrence (2.43%) and two metachronous lesions (4.87%). Complications during and after the procedure occurred in three patients (7.31%), being due to bleeding (two cases) and perforation (one case). There was one death due to a cardiac event not directly related to the procedure., Conclusion: Endoscopic submucosal dissection proved to be a safe procedure, with a low complication and recurrence rate. Its recommendation must occur within the established criteria; however, it can be indicated for patients outside the criteria, if there is a high risk for surgical treatment.

Objective: To determine upgrade rates of lobular neoplasia (LN) to malignancy and evaluate factors that may predict upgrade., Methods: From 5/1/2003 to 12/30/2015, breast lesions diagnosed as LN (atypical lobular hyperplasia [ALH] or classic lobular carcinoma in-situ [LCIS]) on core biopsy that underwent surgical excision or at least 2 years imaging follow-up were identified. A subspecialty trained breast radiologist and pathologist reviewed imaging and pathology slides to confirm diagnosis and to determine if LN represented the target lesion, part of the target lesion, or an incidental finding. Imaging features, original BI-RADS final assessment category, biopsy method, biopsy device and final pathologic diagnosis were documented. Cases with both ALH and LCIS were classified as LCIS for analysis. Reason for biopsy of BI-RADS 2-3 was patient or referring physician preference. Upgrade rates to malignancy were determined for all cases., Results: In this study 73.7% (115/156) lesions were ALH and 26.3% (41/156) were LCIS+/-ALH. Surgical excision and imaging follow-up were performed in 71.2% (111/156) and 28.8% (45/156), respectively. Upgrade rates for ALH and LCIS were 0.0% (0/115) and 7.3% (3/41), respectively. Cancer developed at a site separate from core biopsy in 1.7% (2/115) ALH and 7.3% (3/41) LCIS cases. We found no association of upgrade rate with biopsy type, BI-RADS or target/part of target lesion versus incidental., Conclusion: Our study supports consideration of excision for LCIS, given 7.3% upgrade rate. Conversely, imaging surveillance might be appropriate following diagnosis of ALH alone., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the clinical importance of endometrial polyp size measured using saline infusion sonohysterography (SIS) before performing a hysteroscopic resection in predicting premalignant/malignant lesions., Methods: A retrospective observational study analysis was conducted of 365 patients, who underwent SIS, in a reference hospital. The longest plane of the polyp size was taken as base. Polyps were classified as benign, premalignant, or malignant., Results: The rates of premalignant and malignant lesions were 7.4% and 0.9%, respectively. The mean polyp size was 17.7 ± 0.5 mm in benign patients and 23.7 ± 1.8 mm in premalignant/malignant individuals (P < 0.001). In the group of polyps that were 0-10, 10-20, 20-30, and >30 mm, premalignancy/malignancy rates were 0.0%, 4.8%, 13.3%, and 18.8%, respectively. The cut-off value for polyp size to be able to predict lesions was calculated as 22.5 mm (sensitivity: 63%, specificity: 80%) on receiver operating characteristics curve analysis (P = 0.001, area under the curve 0.732). The power of the study was calculated as 90.86%., Conclusion: During the female reproductive years, endometrial polyps smaller than 10 mm, as measured in SIS, can be followed. However, when the polyp size is 22.5 mm or more, especially in postmenopausal women, treatment should be planned., (© 2021 International Federation of Gynecology and Obstetrics.)

Radiofrequency ablation (RFA) is the first-line treatment for flat Barrett's esophagus (BE) with dysplasia, however its role for persistent Barrett's esophagus (PBE) is unclear. PBE requires additional RFA sessions or application of cryotherapy to improve therapeutic response. We performed a retrospective cohort study evaluating cases of PBE treated by endoscopic eradication programs, with and without spray cryotherapy, and evaluated their safety and efficacy. We retrospectively identified patients with PBE, defined as ≤50% BE reduction or unchanged dysplasia after at least two RFA sessions. PBE was treated either by continued RFA (RFA Group) or converting to spray cryotherapy (CRYO Group), both followed by surveillance period. The rate of adverse events (AE), complete response of intestinal metaplasia (CRIM) and complete response of dysplasia (CRD) were recorded. A total of 46 patients, 23 per group, underwent 622 endoscopic therapies. Circumferential BE length was longer in the CRYO Group, but other baseline characteristics were similar, including maximal BE length. Esophageal strictures accounted for 14/16 total AE, 71% of which were RFA related, compared with 14% related to spray cryotherapy (P = 0.02). Overall CRIM/CRD rates in CRYO (83%) and RFA (96%) groups were not statistically different (P = 0.16), however cases in the CRYO Group required more treatment encounters (Median 19 vs. 12, P ≤ 0.01). Multimodal endotherapy is effective for eradicating PBE. Treatment programs incorporating spray cryotherapy are associated with less esophageal strictures but may require more treatment sessions to achieve eradication., (© The Author(s) 2021. 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.)

Penile intraepithelial neoplasia (PeIN) is a rare skin condition with potential to progress to invasive penile cancer. We performed a systematic review of treatment options and outcomes for PeIN. Topical agents showed response and recurrence rates of 40-100% and 20% for imiquimod, and 48-74% and 11% for 5-fluorouracil, respectively. Discontinuation of topical agents because of side effects was observed in 12% of cases. Response rates for laser therapies were 52-100%, with recurrence in 7-48% of cases and a change in penile sensitivity in 50%. Circumcision cleared preputial PeIN. Rates of recurrence after surgical treatment of glans PeIN were 25% for wide local excision, 4% for Mohs surgery, 5% for total glans resurfacing, and 10% for glansectomy. There are limited data on factors predictive of treatment response and on sequencing of treatment options. PATIENT SUMMARY: Several treatment options are available for men with precancerous lesions of the foreskin or glans. Close follow-up is necessary as lesions can recur or progress to invasive penile cancer., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Endoscopic Interventional Treatment of Precancerous Lesions and Early Carcinoma of the Esophagus - Criteria and Techniques of Local Ablation and Resection Abstract. Early carcinomas of the esophagus can safely be resected endoscopically and interventionally under very strict conditions (ER). In contrast to ablative procedures (radiofrequency ablation, cryo-ablation, argon plasma coagulation, photodynamic therapy), which can only be recommended for Barrett's or low-grade dysplasia, ER - which is called EMR (endoscopic mucosal resection in adenocarcinoma) or more in-depth ESD (endoscopic submucosa dissection in squamous cell carcinoma) - a defined, histologically examinable preparation. This is required starting with high-grade dysplasia, since 50% of patients with biopsy-confirmed high-grade dysplasia after ER already have an invasive carcinoma in the specimen. This diagnostic gap is thus also closed with an interventional ER. ER is therefore an option for high-grade dysplasia in Barrett's, carcinoma in situ (Cis) and conditionally in T1a (adeno- and squamous cell carcinoma) and early T1b tumors (adenocarcinoma).

Background: The World Health Organization recommends thermal ablation as an alternative to cryotherapy to treat women with precancerous lesions in low-resource settings. However, limited data are available on women's experience and adverse events (AEs) of the procedure in the context of Sub-Saharan Africa. The objective of this study was to evaluate the acceptability and safety of thermal ablation in women screened positive for precancerous cervical lesions., Methods: Asymptomatic women aged 30-49 years old living in the Dschang Health District were invited to participate in a cervical cancer screening campaign termed "3 T-Approach" (for Test-Triage and Treat). Recruited women were asked to perform HPV self-sampling followed by triage with visual assessment and treatment with thermal ablation if required. After treatment and 4-6 weeks later, interviews were conducted to assess women's experience on anxiety, discomfort, and pain during thermal ablation. AEs were recorded on pre-defined electronic forms 4-6 weeks after treatment to assess the procedure's safety., Results: Between September 2018 and December 2020, 399 HPV-positive women (18.7% of women screened) were recruited, 236 (59.1%) had a positive visual assessment, 234 were treated by thermal ablation and 198 (84.6%) received therapy in the same visit. Treatment was not considered as painful (score ≤ 4/10) by 209 (90.9%) patients while 5 (2.5%) reported high pain (score 8-10/10). During post-treatment interviews 4-6 weeks later, most reported AEs were graded mild or moderate (grade I-II). The most frequent symptoms reported as mild AEs (grade 1-2) were vaginal watery discharge (75.5%), vaginal bloody-stained discharge (21.5%) and malodourous discharge (14.5%). None of the participants experienced serious AEs (grade 3-4) or AEs requiring admission to hospital or emergency consultation. The vast majority of women (99.6%) would agree to repeat the procedure if necessary and (99.6%) would recommend it to friends or family., Conclusion: Thermal ablation is widely accepted by women and appears as a safe procedure. It may contribute to improving the link between screening and treatment in a single visit and to optimizing cervical cancer control in low-resource settings., Trial Registration: The study was registered on clinicaltrials.gov ( NCT03757299 ) in November 2018 (28/11/2018)., (© 2022. The Author(s).)