Histopathological and Immunohistochemical Mechanisms of Bone Marrow-Derived Mesenchymal Stem Cells in Reversion of Gastric Precancerous Lesions.

BACKGROUND: Gastric cancer (GC) stands as one of the most prevalent cancer types worldwide, holding the position of the second leading cause of cancer-related deaths. Gastric lesions represent pathological alterations to the gastric mucosa, with an elevated propensity to advance to gastric cancer. Limited research has explored the potential of stem cells in the treatment of gastric lesions. METHODS: This study aimed to explore the potential of intravenous transplantation of labeled bone marrow-derived mesenchymal stem cells (BMMSCs) to inhibit the progression of precancerous gastric lesions. RESULTS: In the gastric lesion disease model group, the rat tissue exhibited noteworthy mucosal atrophy, intestinal metaplasia, dysplasia, and inflammatory cell infiltration. Following the infusion of BMMSCs, a notable decrease in gastric lesions was found, with atrophic gastritis being the sole remaining lesion, which was confirmed by morphological and histological examinations. BMMSCs that were colonized at gastric lesions could differentiate into epithelial and stromal cells, as determined by the expression of pan-keratin or vimentin. The expression of vascular endothelial growth factor was significantly elevated following BMMSC transplantation. BMMSCs could also upregulate the production of humoral immune response cytokines, including interleukin (IL)-4 and IL-10, and downregulate the production of IL-17 and interferon-gamma, which could be highly associated with the cellular immune response and inflammation severity of the lesions. CONCLUSIONS: BMMSC transplantation significantly reduced inflammation and reversed gastric lesion progression.

Medical management determinants of the maxillofacial precancerous and benign diseases malignancy.

OBJECTIVE: Aim: To identify the medical management determinants of the maxillofacial precancerous and benign diseases malignancy. PATIENTS AND METHODS: Materials and Methods: 150 people with maxillofacial cancer and 100 people with precancerous and benign diseases of the same localization were interviewed. RESULTS: Results: There were revealed: a low percentage of detection during check-up (10.2-15.8%), more than a third of cases (35.8-37.4%) are diagnosed by chance; not all patients undergo histological verification of the diagnosis (25.7% in cancerous and 43.2% in precancerous and benign diseases); not all are under follow up observation (24.7-27.7%). The risk of precancerous and benign diseases malignancy is the highest at 40-59 years of age (OR=4.4; 95% CI: 1.9-10.5), andalso increases with the duration of the disease for more than 5 years (2.2; 1.2-4.10 ), in patients who didn't undergo histological verification (2.2; 1.3-3.8), don't follow doctors' recommendation on visits and treatment (2.4; 1.4-4.1), don't trust doctors and are dissatisfied with medical care (2.1; 1.3-3.6). The risk groups of the maxillofacial oncological, precancerous and benign diseases are men, who are 1.5 times more likely to suffer from them than women and are characterized by lower medical care activity. The risk factors of the maxillofacial precancerous and benign diseases malignancy are low financial (4.6; 1.7-12.4) and territorial (3.3; 1.1-10.3) accessibility of medical care, including dental care (2.8; 1.6-4.8). CONCLUSION: Conclusions: It is necessary to improve the prevention and medical care in order to advance the early detection of maxillofacial cancer, taking into account the established medical management determinants of malignancy.

Future Directions for Research on Anal Precancerous Lesion Treatment.

ABSTRACT: The benefit of treating anal precancerous lesions to reduce anal cancer progression was recently shown in people living with HIV. This will certainly impact the future development of recommendations on anal cancer prevention by including anal precancerous lesions screening and treatment for people living with HIV. However, by bringing this topic to the spotlight, it has also uncovered data that are still missing in this field and that need to be addressed by research.This article will discuss the many unanswered questions about treatment of anal precancerous lesions and future directions for research.

American Association of Oral and Maxillofacial Surgeon's Position Paper on Oral Mucosal Dysplasia.

Oral potentially malignant disorders (OPMDs) of the oral mucosa include leukoplakia, erythroplakia, erythroleukoplakia, lichen planus, and oral lichenoid lesions, each with varying incidences of dysplastic disease at the time of presentation and each with observed incidences of malignant transformation over time. The primary goal of the management of dysplasia, therefore, includes their early detection and treatment prior to malignant transformation. The recognition and management of these OPMDs and an understanding of their potential progression to oral squamous cell carcinoma will reduce the morbidity and mortality associated with these lesions with expedient and properly executed treatment strategies that will have a positive effect on patient survival. It is the purpose of this position paper to discuss oral mucosal dysplasia in terms of its nomenclature, epidemiology, types, natural history, and treatment to acquaint clinicians regarding the timing of biopsy, type of biopsy, and follow-up of patients with these lesions of the oral mucosa. This position paper represents a synthesis of existing literature on this topic with the intention of closing gaps in our understanding of oral mucosal dysplasia while also stimulating new thinking to guide clinicians in the proper diagnosis and management of OPMDs. The fifth edition of the World Health Organization classification of head and neck tumors published in 2022 represents new information regarding this topic and a construct for this position paper.

Dysplastic Lesions of the Larynx.

There have been many advancements in the clinical and histologic diagnosis of laryngeal dysplasia (LD), but diagnosis still necessitates invasive histologic evaluation. Furthermore, despite improved histologic identification of dysplastic lesions, the exact details of pathophysiologic progression and the risk of malignant transformation is still uncertain. These unknowns create a barrier to establishing an ideal grading and classification system, which prevents the establishment of a precise and consistent treatment paradigm. Identifying these gaps in knowledge serves to highlight where further studies are warranted, ideally focusing on a better understanding of the biological behavior of LD. This would ultimately allow for the creation of a reliable grading and classification system and for the formalization of management and treatment guidelines for LD.

Vaccinating women previously treated for human papillomavirus-related cervical precancerous lesions is highly cost-effective in China.

Background: The 2021 Chinese Expert Consensus on the Clinical Application of the Human Papillomavirus (HPV) Vaccine recommended vaccination for women who previously received ablative or excisional treatment for high-grade squamous intraepithelial lesion (HSIL). This study evaluates the cost-effectiveness of HPV vaccination in women previously treated for cervical precancerous lesions. Methods: We used a Markov model to simulate the disease progression of both low- and high-risk HPV subtypes. We followed a cohort of 100,000 women aged 18-45 years who received treatment for cervical precancerous lesions for a lifetime (80 years). We used the Incremental Cost-Effectiveness Ratios (ICER) with a 5% discount rate to measure the cost-effectiveness of nine vaccination strategies, including a combination of HPV bivalent (HPV-2), quadrivalent (HPV-4) and nonavalent vaccine (HPV-9), each with three vaccination doses (one-, two- and three-dose). We conducted one-way sensitivity analysis and probabilistic sensitivity analysis. We followed the CHEERS 2022 guidelines. Results: Compared to the status quo, the nine vaccination strategies would result in $3.057-33.124 million incremental cost and 94-1,211 incremental quality-adjusted life-years (QALYs) in 100,000 women previously treated for cervical precancerous lesions. Three vaccination strategies were identified on the cost-effectiveness frontier. In particular, ICER for one-dose HPV-4 vaccination was US$10,025/QALY compared to the status quo (no vaccination); ICER for two-dose HPV-4 vaccination was US$17,641//QALY gained compared to one-dose HPV-4 vaccination; ICER for three-dose HPV-4 vaccination was US$27,785/QALY gained compared with two-dose HPV-4 vaccination. With a willingness-to-pay of three times gross domestic product per capita (US$37655), three-dose HPV-4 vaccination was the most cost-effective vaccination strategy compared with the lower-cost non-dominated strategy on the cost-effectiveness frontier. A probabilistic sensitivity analysis confirmed a 99.1% probability of being cost-effective. If the cost of the HPV-9 is reduced to 50% of the current price, three-dose HPV-9 vaccination would become the most cost-effective strategy. Discussion: Three-dose HPV-4 vaccination is the most cost-effective vaccination strategy for women treated for precancerous cervical lesions in the Chinese setting.

Extramammary Paget's Disease of the Vulva and Concomitant Premalignant/Malignant Vulvar Lesions: A Potential Challenge in Diagnosis and Treatment.

The aim of the present study was to evaluate the incidence of concomitant vulvar cancers or premalignant lesions in women surgically treated for extramammary Paget's disease of the vulva (EMPDV) through a multicenter case series. The medical records of all women diagnosed with and treated for EMPDV from January 2010 to December 2020 were retrospectively analyzed. Women with EMPDV and synchronous vulvar cancer, vulvar intraepithelial neoplasia (VIN) and/or lichen sclerosus (LS) at the histology report were included in the study. A total of 69 women eligible for the present study were considered. Concomitant vulvar lesions occurred in 22 cases (31.9%). A total of 11 cases of synchronous VIN (50%) and 14 cases (63.6%) of concomitant LS were observed. One patient (4.5%) had synchronous vulvar SCC (FIGO stage 1B). Women with EMPDV and concomitant premalignant/malignant vulvar lesions had a significantly higher rate of invasive EMPDV and wider lesions with an extravulvar involvement. The specific meaning of the association between EMPDV, VIN, SCC and LS remains unclear. The potential overlapping features between different vulvar lesions highlight the importance of dedicated gynecologists and pathologists in referral centers.

[Multidisciplinary experts consensus on diagnosis and treatment of precancerous lesions of hepatocellular carcinoma (2023 version)].

According to the latest statistical data, the incidence and mortality rate of hepatocellular carcinoma in China are still on the rise, posing a major threat to the health of the Chinese population. The occurrence is closely related to the formation of precancerous lesions in the liver. The clinical and basic research on precancerous lesions of hepatocellular carcinoma has developed rapidly, and the concepts and specific techniques for diagnosis and treatment have also undergone new changes and advancements. Therefore, based on the first version in 2020, this consensus has organized multidisciplinary experts to compile and improve a new version by integrating the latest progress in their respective professional fields at home and abroad. It aims to enhance clinicians' understanding of precancerous lesions of hepatocellular carcinoma standardize the pathology, imaging, and molecular diagnostic criteria, broaden early screening methods, formulate scientifically rational treatment plans, and help promote the advancement of diagnosis and treatment strategies and to enhance the overall 5-year survival rate of patients with hepatocellular carcinoma.

[Endoscopic diagnosis and treatment of early colorectal cancer and precancerous lesions: current status and future prospects].

Early detection of colorectal cancer and precursor lesions under colonoscopy, and timely and optimal treatment remain the crucial means for reducing colorectal cancer-related deaths. In this article, we focused on the hot spots in recent years, reviewed the progress of endoscopic diagnosis and treatment of serrated lesions and inflammatory bowel disease (IBD)-related dysplasia, the application of endocytoscopy and the management of early colorectal cancer/precancerous lesions, and provided new prospects for future studies.

Consensus guidelines on management of oral potentially malignant disorders.

Oral cancer is usually preceded by oral potentially malignant disorders (OPMDs) and early detection can downstage the disease. The majority of OPMDs are asymptomatic in early stages and can be detected on routine oral examination. Though only a proportion of OPMDs may transform to oral squamous cell carcinoma (OSCC), they may serve as a surrogate clinical lesion to identify individuals at risk of developing OSCC. Currently, there is a scarcity of scientific evidence on specific interventions and management of OPMDs and there is no consensus regarding their management. A consensus meeting with a panel of experts was convened to frame guidelines for clinical practices and recommendations for management strategies for OPMDs. A review of literature from medical databases was conducted to provide the best possible evidence and provide recommendations in management of OPMDs.

The Recurrence of Cervical Precancerous Lesion Among HIV Positive and Negative Ethiopian Women After Cryotherapy: A Retrospective Cohort Study.

BACKGROUND: Early testing and treatment is among the successful strategies for the prevention and control of cervical precancerous and invasive cancer, and a paramount for women with HIV. In Ethiopia, visual inspection with acetic acid for screening and cryotherapy treatment is commonly practiced, though the recurrence of the precancerous lesion after treatment has not been well documented. OBJECTIVE: This study was aimed to estimate the association of HIV status and the recurrence of cervical precancerous lesion after cryotherapy among Ethiopian women. METHODS: We conducted a retrospective cohort study from January to April 2021. The time to the incidence of recurrence was compared between HIV positive and HIV negative women. Cox regression models were used to adjust the analyses for potential confounders, and only women treated with cryotherapy after a positive Visual Inspection with Acetic acid (VIA) screening test were included. RESULTS: A total of 140 eligible patient cards were included in the analysis with the median follow-up of 15.5 months. The overall recurrence rate was 15.7% (22/140), with a greater proportion among HIV negative women, 19.0% (4/21) than HIV positive 15.1% (18/119). Prolonged use of corticosteroid and higher age were the major significant predictors of a higher likelihood of recurrence. The recurrence of screening positive lesion was higher among women aged above 39 years (hazard ratio (HR) of 11.94 (95% CI, 1.07-133.04; P = .04), and women with prolonged use of corticosteroid (HR = 7.82, 95% CI = 1.04-58.75; P = .046) than their counterparts. CONCLUSION: The recurrence of cervical precancerous lesion after cryotherapy was higher than the expert panel report by WHO with a higher proportion among women of old age and prolonged corticosteroid use. Cryotherapy showed a satisfying performance against the recurrence of cervical disease diagnosed through VIA. To substantiate, our findings, further prospective cohort study is also recommended.

Gastric Cancer: Emerging Trends in Prevention, Diagnosis, and Treatment.

Gastric adenocarcinoma (GC) is the fourth leading cause of global cancer mortality, and the leading infection-associated cancer. Helicobacter pylori is the dominant risk factor for GC and classified as an IARC class I carcinogen. Surveillance of gastric premalignant conditions is now indicated in high-risk patients. Upper endoscopy is the gold standard for GC diagnosis, and image-enhanced endoscopy increases the detection of gastric premalignant conditions and early gastric cancer (EGC). Clinical staging is crucial for treatment approach, defining early gastric cancer, operable locoregional disease, and advanced GC. Endoscopic submucosal dissection is the treatment of choice for most EGC. Targeted therapies are rapidly evolving, based on biomarkers including MSI/dMMR, HER2, and PD-L1. These advancements in surveillance, diagnostic and therapeutic strategies are expected to improve GC survival rates in the near term.

Microenvironment in Oral Potentially Malignant Disorders: Multi-Dimensional Characteristics and Mechanisms of Carcinogenesis.

Oral potentially malignant disorders (OPMDs) are a group of diseases involving the oral mucosa and that have a risk of carcinogenesis. The microenvironment is closely related to carcinogenesis and cancer progression by regulating the immune response, cell metabolic activities, and mechanical characteristics. Meanwhile, there are extensive interactions between the microenvironments that remodel and provide favorable conditions for cancer initiation. However, the changes, exact roles, and interactions of microenvironments during the carcinogenesis of OPMDs have not been fully elucidated. Here, we present an updated landscape of the microenvironments in OPMDs, emphasizing the changes in the immune microenvironment, metabolic microenvironment, mechanical microenvironment, and neural microenvironment during carcinogenesis and their carcinogenic mechanisms. We then propose an immuno-metabolic-mechanical-neural interaction network to describe their close relationships. Lastly, we summarize the therapeutic strategies for targeting microenvironments, and provide an outlook on future research directions and clinical applications. This review depicts a vivid microenvironment landscape and sheds light on new strategies to prevent the carcinogenesis of OPMDs.

Academy of Medicine, Singapore clinical guideline on endoscopic surveillance and management of gastric premalignant lesions.

Gastric cancer (GC) has a good prognosis, if detected at an early stage. The intestinal subtype of GC follows a stepwise progression to carcinoma, which is treatable with early detection and intervention using high-quality endoscopy. Premalignant lesions and gastric epithelial polyps are commonly encountered in clinical practice. Surveillance of patients with premalignant gastric lesions may aid in early diagnosis of GC, and thus improve chances of survival. An expert professional workgroup was formed to summarise the current evidence and provide recommendations on the management of patients with gastric premalignant lesions in Singapore. Twenty-five recommendations were made to address screening and surveillance, strategies for detection and management of gastric premalignant lesions, management of gastric epithelial polyps, and pathological reporting of gastric premalignant lesions.

[Clinical research progress and implications of therapeutic vaccines for cervical cancer and precancerous lesions: a qualitative systematic review].

Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.

Treatment of Anal High-Grade Squamous Intraepithelial Lesions to Prevent Anal Cancer.

BACKGROUND: The incidence of anal cancer is substantially higher among persons living with the human immunodeficiency virus (HIV) than in the general population. Similar to cervical cancer, anal cancer is preceded by high-grade squamous intraepithelial lesions (HSILs). Treatment for cervical HSIL reduces progression to cervical cancer; however, data from prospective studies of treatment for anal HSIL to prevent anal cancer are lacking. METHODS: We conducted a phase 3 trial at 25 U.S. sites. Persons living with HIV who were 35 years of age or older and who had biopsy-proven anal HSIL were randomly assigned, in a 1:1 ratio, to receive either HSIL treatment or active monitoring without treatment. Treatment included office-based ablative procedures, ablation or excision under anesthesia, or the administration of topical fluorouracil or imiquimod. The primary outcome was progression to anal cancer in a time-to-event analysis. Participants in the treatment group were treated until HSIL was completely resolved. All the participants underwent high-resolution anoscopy at least every 6 months; biopsy was also performed for suspected ongoing HSIL in the treatment group, annually in the active-monitoring group, or any time there was concern for cancer. RESULTS: Of 4459 participants who underwent randomization, 4446 (99.7%) were included in the analysis of the time to progression to cancer. With a median follow-up of 25.8 months, 9 cases were diagnosed in the treatment group (173 per 100,000 person-years; 95% confidence interval [CI], 90 to 332) and 21 cases in the active-monitoring group (402 per 100,000 person-years; 95% CI, 262 to 616). The rate of progression to anal cancer was lower in the treatment group than in the active-monitoring group by 57% (95% CI, 6 to 80; P = 0.03 by log-rank test). CONCLUSIONS: Among participants with biopsy-proven anal HSIL, the risk of anal cancer was significantly lower with treatment for anal HSIL than with active monitoring. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02135419.).

[Global guidelines for cervical cancer and precancerous lesions treatment: a systematic review].

Objective: To systematically summarize current status and recommendations of the global cervical cancer and precancerous lesions treatment guidelines. Methods: The retrieval for all the Chinese and English literature published before July 8, 2021 was conducted in PubMed, Embase, SinoMed Database, CNKI and Wanfang Database, supplemented by a search of health websites of countries worldwide, with"uterine cervical neoplasms""cervix cancer""cervical neoplasm""cervical precancerous lesions""treat*""guideline*""practice guideline*""consensus" "recommendation*""guidebook*"in English as well as"cervical precancerous lesions""cervical neoplasm""treatment""guideline*""consensus"in Chinese as search keywords. A total of 38 guidelines were included for data extraction and analysis. Results: Guidelines covered Asia, Europe, North America, South America and Oceania. Conservative observation was recommended for the CIN1 population. For the women with CIN2/CIN3, ablation or excision was recommended according to the specific situation and guidelines of developed countries give priority to the latter. In low and middle resource countries, given the availability of medical resources, ablative treatment was recommended as an alternative to excisional treatment if the women were eligible. For women with adenocarcinoma in situ (AIS), cervical conization or total hysterectomy was recommended depending on the patient's desire of fertility. For patients with cervical cancer, most guidelines recommended surgery for early disease and smaller lesions, otherwise concurrent chemoradiotherapy was usually the main treatment modality for advanced cancers. All guidelines recommended long-term follow-up to monitor disease recurrence after treatment. Follow-up methods included human papillomavirus (HPV) testing and/or cytology or colposcopy. Most guidelines recommended follow-up at 6 or 12 months after treatment for cervical precancerous lesions, and 3~4 months for cervical cancer. Conclusions: There are some differences in the treatment and management recommendations for cervical cancer and precancerous lesions issued by different countries and regions around the world. Based on the global treatment guidelines and medical resource of different regions, the treatment and management guidelines for cervical cancer and precancerous lesions suitable for different regions of China should be developed, so as to achieve effective treatment.

Laryngeal dysplasia: a 10-year review of rates of progression to invasive carcinoma and treatment-specific outcomes in a regional ENT department in Northern Ireland.

BACKGROUND: Laryngeal dysplasia represents a complex pre-malignant condition characterised by a spectrum of mucosal changes, with a reported malignant transformation rate from dysplasia to invasive carcinoma of 14.0 per cent. OBJECTIVE: To identify whether increasing glottic dysplasia severity is associated with higher local malignant transformation rates or adverse clinical outcomes. METHODS: This retrospective cohort study identified 125 patients with any histopathological grade of glottic dysplasia over a 10-year period who were followed up for a standardised 10-year period. RESULTS: The malignant transformation rate was 21.8 per cent over 10 years, demonstrating a statistically significant greater risk with increasing dysplasia severity. The mean time to transformation was 52 months, with time to transformation statistically associated with increasing dysplasia severity. Rapid progression to carcinoma within 12 months occurred in 40 per cent of cases, and 58 per cent of subsequently diagnosed laryngeal squamous cell carcinomas were tumour stage T1. CONCLUSION: Laryngeal dysplasia carries a significant malignant potential, appearing greatest within 12 months of diagnosis and with increasing severity of dysplasia.

Clonal hematopoiesis: Molecular and clinical implications.

Clonal hematopoiesis (CH) defines a population of hematopoietic cells with one or more somatic mutations/copy number alterations that can expand with time and under positive clonal selection pressures. The term CH of indeterminate potential (CHIP) operationally describes somatic mutations in leukemia-associated driver genes in hematopoietic stem cells with variant allele frequencies (VAF) of ≥ 2%, without evidence for an underlying hematological malignancy. Risk factors for CHIP include aging, inflammation, male sex, cigarette smoking, history of cancer and cancer treatments, germline predisposition states, among others. CHIP is a premalignant condition, with a low but definite risk of hematologic malignancies and is associated with increased all-cause mortality, largely due to cardiovascular disease and associated endothelial dysfunction. Here we review recent advances in CHIP, including diagnostic, prognostic, and potential therapeutic strategies.