Acceptability of bariatric surgery in people with endometrial cancer and atypical hyperplasia: A qualitative study.

OBJECTIVE: In young individuals with obesity, infertility, and endometrial cancer, significant, sustained weight loss through bariatric surgery may result in a durable oncologic and reproductive response. However, it is not known whether bariatric surgery is acceptable to this patient population. We performed a qualitative study to understand the acceptability of bariatric surgery in young individuals with obesity and endometrial cancer or atypical hyperplasia. STUDY DESIGN: All participants were of reproductive age with body mass index [BMI] ≥ 35 and grade 1 endometrial cancer or atypical hyperplasia. Semi-structured interviews were used to explore participant perception of their weight, fertility, and the possibility of bariatric surgery as part of the treatment strategy for their endometrial cancer/atypical hyperplasia. Thematic saturation was reached after 14 interviews. RESULTS: Fourteen participants with a median age of 34 years (range 27-38) and BMI of 42 (33-64) were interviewed. Participants were reluctant to accept bariatric surgery as a treatment option due to 1) lack of knowledge about the procedure, 2) stigma attached to bariatric surgery, and 3) fear of the risks associated with bariatric surgery. Their perception towards their weight, fertility, and cancer diagnosis was characterized by concepts of 'helplessness', 'isolation', 'frustration', and 'guilt'. We observed a significant gap in participant understanding of the complex interplay between their cancer, infertility, and obesity. CONCLUSIONS: More support and resources are required, with patient-oriented counseling focused on the implication of their weight on their cancer diagnosis and fertility, before presenting bariatric surgery as a treatment option.

2022 European guideline for the management of balanoposthitis.

BACKGROUND: This guideline is an update to the 2014 edition of the European guideline for the management of balanoposthitis. Balanoposthitis describes inflammation of the glans penis and prepuce and is caused by a range of disparate conditions including infection, dermatoses and premalignancy. OBJECTIVE: The main objectives of this guideline are to aid recognition of the symptoms and signs and complications of penile skin conditions and to offer recommendations on the diagnostic tests and treatment for a selected group of these conditions. METHODS: The previous guideline was updated following a literature review and priority was given to randomized controlled trial and systematic review evidence. RESULTS: The updated guideline includes amended management for infective balanitis to provide clear guidance for Group A streptococcal infections, management of on going Lichen sclerosus (to include circumcision and supportive management to reduce the recurrence of genital herpes and warts), additional regimens for Zoonoid change, use of calcineurin inhibitors in management and risk of premalignancy and change of nomenclaturefrom Premalignant conditions to Penile Intraepithelial neoplasia (PeIN). CONCLUSION: Balanoposthitis has a widerange of causes high quality evidence specific to the management of penile disease is not available for all the conditions described.

Presence of Candida and its associated factors in participants attending oral cancer screening in the lower northeastern area of Thailand.

BACKGROUND: Certain evidence indicated high prevalence of Candida in oral potentially malignant disorders (OPMDs) and oral cancer (OC). This study was aimed to investigate the presence of Candida and its associated factors in participants who attended the oral cancer screening program in the lower northeastern districts of Thailand. METHODS: Convenient participants residing in the lower northeastern districts of Thailand who attended the oral cancer screening were enrolled. A questionnaire retrieving demographic characteristics, risk factors of oral cancer, and risk of having Candida was completed. Oral examination was performed by oral medicine specialists or oral surgeons. The participants were categorized into 4 groups according to their clinical diagnosis, namely normal oral mucosa (NOM), OPMDs/OC, non-OPMDs/OC and clinically suspected oral candidiasis (CSOC). Stimulated saliva flow rate was measured. Dip-slide test was performed in each participant to evaluate the presence of Candida. The levels of Candida were categorized into high and low levels according to the score received from the dip-slide test. Factors associated with high levels of Candida were identified using multivariate logistic regression analysis. RESULTS: A total of 577 participants were recruited. High levels of Candida were found in 31.3%, 24.7%, 25.9% and 18.1% in the OPMDs/OC, the non-OPMDs/OC, the CSOC and the NOM groups, respectively. According to multivariate logistic regression analysis, age above 60 years, female gender, betel quid chewing habit, use of denture, hyposalivation, and being in the CSOC group were found to be significantly associated with high levels of Candida. CONCLUSION: Higher number of participants in the OPMDs/OC group was found to have high levels of Candida. Increasing age, female gender, betel quid chewing habit, use of denture, hyposalivation and having CSOC lesions were associated with high levels of Candida.

Dental hygienists and dentists as providers of brush biopsies for oral mucosa screening.

BACKGROUND: Oral cancer is a severe and potentially fatal disease usually starting in the squamous epithelium lining the oral cavity. Together with oropharyngeal carcinoma, it is the fifth to sixth most common malignancy worldwide. To limit the increase in the global oral cancer incidence over the past two decades, the World Health Assembly adopted a resolution urging member states to integrate preventive measures such as engagement and training of dental personnel in screening, early diagnosis, and treatment into their national cancer control programs. AIM: The aim of this study was to investigate if dental hygienists (DHs) and dentists (Ds) in general dental practice care can be entrusted to perform brush sampling of oral potentially malignant disorders (OPMDs), and to evaluate their level of comfort in performing brush biopsies. METHODS: Participants were five DHs and five Ds who received one day of theoretical and clinical training in oral pathology to identify OPMDs (leukoplakia [LP], erythroplakia [EP], and oral lichen planus [OLP]), and perform brush sampling for PAP cytology and high-risk human papillomavirus (hrHPV) analysis. RESULTS: Out of 222 collected samples, 215 were adequate for morphological assessment and hrHPV analysis. All the participants agreed that sample collection can be incorporated in DHs and Ds routine clinical duties, and most of them reported that sample collection and processing was easy/quite easy. CONCLUSION: Dentists and DHs are capable of collecting satisfactory material for cytology and hrHPV analysis. All the participating DHs and Ds were of the opinion that brush sampling could be handled routinely by DHs and Ds in GDP.

The cost of diagnosing endometrial cancer: Quantifying the healthcare cost of an abnormal uterine bleeding workup.

OBJECTIVE: The evaluation of women with perimenopausal abnormal uterine bleeding (AUB) and postmenopausal bleeding (PMB) to detect endometrial cancer (EC) and its precursors is not standardized and can vary widely. Consequently, costs associated with the workup and management undoubtedly vary. This study aimed to quantify costs of AUB/PMB evaluation to understand the healthcare burden associated with securing a pathologic diagnosis. METHODS: Women ≥45 years of age presenting to a single institution gynecology clinic with AUB/PMB for diagnostic workup were prospectively enrolled February 2013-October 2017 for a lower genital tract biospecimen research study. Clinical workup of AUB/PMB was determined by individual provider discretion. Costs of care were collected from administrative billing systems from enrollment to 90 days post enrollment. Costs were standardized and inflation-adjusted to 2017 US Dollars (USD). RESULTS: In total, there were 1017 women enrolled with 5.6% diagnosed with atypical hyperplasia or endometrial cancer (EC). Within the full cohort, 90-day median cost for AUB/PMB workup and management was $2279 (IQR $512-4828). Among patients with a diagnostic biopsy, median 90-day costs ranged from $2203 (IQR $499-3604) for benign or disordered proliferative endometrium (DPE) diagnosis to $21,039 (IQR $19,084-24,536) for a diagnosis of EC. CONCLUSIONS: The costs for diagnostic evaluation of perimenopausal AUB and PMB vary greatly according to ultimate tissue-based diagnosis. Even reassuring benign findings that do not require further intervention-the most common in this study's cohort-yield substantial costs. The development of sensitive, specific, and more cost-effective diagnostic strategies is warranted.

Clinical applicability of a new scoring system for population-based screening and risk factors of gastric cancer in the Wannan region.

BACKGROUND: We aimed to evaluate the clinical applicability of a new scoring system that comprises the variables age, sex, pepsinogen ratio (PGR), gastrin-17 (G-17), and Helicobacter pylori (Hp) infection for gastric cancer (GC) screening in the Wannan region, China. We also explored the risk factors of GC in the Wannan region. METHODS: We prospectively enrolled asymptomatic participants from January 1, 2019 to June 30, 2021 at the First Affiliated Hospital of Wannan Medical College. We used a receiver operating characteristic (ROC) curve to estimate the screening value of combined measurements of pepsinogen I, PGII, PGR, G-17, and Hp. Univariate analysis and multivariate analysis were used to explore the independent risk factors of GC. RESULTS: A total of 25,194 asymptomatic patients were eventually screened. The area under the ROC curve (AUC) of combined measurements was 0.817 (95% confidence interval [CI] 0.721-0.913), the sensitivity was 81.5%, and the specificity was 77.8%. The detection rate of this new scoring system for GC screening in low-, medium-, and high-risk groups was 0%, 1.63%, and 9%, respectively (P < 0.001). Multivariate analysis showed that age (odds ratio [OR], 5.934; 95% CI 3.695-9.529; P < 0.001), sex (OR 5.721; 95% CI 2.579-12.695; P < 0.001), Hp infection (OR 1.992; 95% CI 1.255-3.163; P = 0.003), a history of smoking (OR 2.028; 95% CI 1.213-3.392; P = 0.007), consuming a high-salt diet (OR 2.877; 95% CI 1.807-4.580; P < 0.001), frequently eating pickled foods (OR 1.873; 95% CI 1.125-3.120; P = 0.016), and frequently eating fried foods (OR 2.459; 95% CI 1.384-4.369; P = 0.002) were independent risk factors for GC and precancerous lesions. However, frequent consumption of green vegetables (OR 0.388; 95% CI 0.242-0.620; P < 0.001) was an independent protective factor against GC and precancerous lesions. CONCLUSION: The new scoring system for GC screening was feasible in the Wannan region, especially in high-risk populations. Frequent consumption of green vegetables was an independent protective factor against GC and precancerous lesions.

Gastric Antral Mucosal Changes in Children With Intestinal Metaplasia.

Objectives: The gastric mucosal change accompanying gastric antral intestinal metaplasia (IM) in the pediatric population and its clinical implications remain unclear. Methods: We retrieved all patients younger than 18 years who had upper GI endoscopy with a pathology diagnosis of antral IM between 2009 and 2020. Each biopsy was evaluated for the presence of dysplasia, Helicobacter pylori, gastritis, and other pathologic changes. Results: A total of 134 patients with antral IM were identified; 72 (53.7%) with coexisting pathology including chronic gastritis (n = 22), reactive gastropathy (n = 16), focal mild chronic inflammation (n = 13), gastric eosinophilia (n = 9), chronic active gastritis associated with (n = 2) and without Helicobacter infection (n = 3), and others (n = 7). The remaining 62 (46.3%) showed isolated IM. Gastric IM increased with age, and was often accompanied by other pathologic changes, especially in female children. Twenty-seven patients had follow up biopsies; 11 of the 27 patients (40.7%) showed persistent IM in at least one repeat biopsies. None demonstrated dysplasia. Conclusions: In children, antral IM increases with age and often coexists with other pathologic changes. Gastric IM could persist for at least months to years in a significant subset of patients with chronic gastritis and gastric eosinophilia.

The Risk of Endometrial Malignancy and Other Endometrial Pathology in Women with Abnormal Uterine Bleeding: An Ultrasound-Based Model Development Study by the IETA Group.

OBJECTIVES: The aim of this study was to develop a model that can discriminate between different etiologies of abnormal uterine bleeding. DESIGN: The International Endometrial Tumor Analysis 1 study is a multicenter observational diagnostic study in 18 bleeding clinics in 9 countries. Consecutive women with abnormal vaginal bleeding presenting for ultrasound examination (n = 2,417) were recruited. The histology was obtained from endometrial sampling, D&C, hysteroscopic resection, hysterectomy, or ultrasound follow-up for >1 year. METHODS: A model was developed using multinomial regression based on age, body mass index, and ultrasound predictors to distinguish between: (1) endometrial atrophy, (2) endometrial polyp or intracavitary myoma, (3) endometrial malignancy or atypical hyperplasia, (4) proliferative/secretory changes, endometritis, or hyperplasia without atypia and validated using leave-center-out cross-validation and bootstrapping. The main outcomes are the model's ability to discriminate between the four outcomes and the calibration of risk estimates. RESULTS: The median age in 2,417 women was 50 (interquartile range 43-57). 414 (17%) women had endometrial atrophy; 996 (41%) had a polyp or myoma; 155 (6%) had an endometrial malignancy or atypical hyperplasia; and 852 (35%) had proliferative/secretory changes, endometritis, or hyperplasia without atypia. The model distinguished well between malignant and benign histology (c-statistic 0.88 95% CI: 0.85-0.91) and between all benign histologies. The probabilities for each of the four outcomes were over- or underestimated depending on the centers. LIMITATIONS: Not all patients had a diagnosis based on histology. The model over- or underestimated the risk for certain outcomes in some centers, indicating local recalibration is advisable. CONCLUSIONS: The proposed model reliably distinguishes between four histological outcomes. This is the first model to discriminate between several outcomes and is the only model applicable when menopausal status is uncertain. The model could be useful for patient management and counseling, and aid in the interpretation of ultrasound findings. Future research is needed to externally validate and locally recalibrate the model.

Histopathological and risk factor analyses of oral potentially malignant disorders and oral cancer in a proactive screening in northeastern Thailand.

BACKGROUND: Lip and oral cavity cancer has been reported as the 10th most common cancer in Thailand. Recently, a screening program for oral potentially malignant disorders (OPMDs) and oral cancer was conducted in the northeastern Thailand which took into consideration a total of 371,911 people who resided in the provinces of Buriram, Chaiyaphum, Nakhon Ratchasima, and Surin. METHODS: A total of 330,914 subjects were consecutively screened for risk factors of oral cancer by village health volunteers (VHVs) using a questionnaire (S1). Then, 186,710 subjects with one or more risk factors for oral cancer were referred for oral screening by dental auxiliaries or dentists at sub-district level hospitals (S2) where 86,941 subjects were subsequently screened. Afterwards, 1576 subjects with suspicious oral lesions for OPMDs or oral cancer attended local hospitals for further investigation and treatment. Oral medicine specialists, oral surgeons, and local dentists at the district level hospitals performed biopsies and the samples were sent for histopathological analysis. The objectives of the study were to report the histopathology findings from the biopsies obtained from these subjects and the associated risk factors. RESULTS: Out of 427 subjects who received biopsies, complete diagnostic results were obtained from 409 patients (462 specimens). The 5 most common histopathological results from these specimens were mild epithelial dysplasia (27.3%), fibroepithelial hyperplasia (14.5%), oral lichen planus/oral lichenoid reactions (11.5%), moderate epithelial dysplasia (8%), and acanthosis with or without hyperkeratosis (5%). Oral squamous cell carcinoma was detected in 14 subjects and 11 other forms of oral cancer were revealed. Among the analyzed risk factors, habitual betel quid chewing was established as a statistically significant risk factor associated with OPMDs and oral cancer. CONCLUSION: The most frequently observed histopathological results of clinically suspected oral cancer and OPMDs included mild epithelial dysplasia, fibroepithelial hyperplasia, oral lichen planus/oral lichenoid reactions, moderate epithelial dysplasia, and acanthosis with or without hyperkeratosis. Betel quid chewing habit was found to be associated with OPMDs and oral cancer.

Differential Expression of α-Enolase in Clinical Gastric Tissues and Cultured Normal/Cancer Cells in Response to Helicobacter pylori Infection and cagA Transfection.

Background and Objectives: The role of α-enolase (ENO1) in Helicobacter pylori-related gastric lesions might be a critical factor in the pathogenesis, but remains undefined. Materials and Methods: This study investigated the differential expression of α-enolase in clinical gastric specimens and cultured normal/cancer cells in response to H. pylori (cagA+) infection and cagA transfection using qPCR, Western blots and histochemical methods. Results: A total of 172 gastric specimens were collected from 142 patients, the former comprising chronic superficial gastritis (CSG), precancerous diseases (PCDs, including atrophic gastritis, intestinal metaplasia and dysplasia) and gastric cancer (GC) cases. Among the CSG and PCD cases, the H. pylori-infected group had significantly elevated ENO1 mRNA levels compared with the uninfected group. In the GC cases, differential ENO1 expressions were detected between the cancer tissues and the paracancerous tissues. Notably, significant difference was first detected between the GC cell (AGS) and the normal cell (GES-1) as a response of ENO1 to H. pylori infection and cagA transfection. Conclusions: This report reveals that ENO1 expression is associated with H. pylori infection, cagA transfection, co-culture duration, multiplicity of infection, gastric normal/cancerous cell lines and cellular differentiation. The findings may be crucial bases for further ascertaining H. pylori pathogenic mechanism and formulating novel therapeutic and diagnostic strategies.

Non-conventional types of dysplastic changes in gastrointestinal tract mucosa - review of morphological features of individual subtypes.

Evaluation of the dysplastic changes evolving in mucosa of various segments of gastrointestinal tract is a part of routine practice. Morphologically different or non-conventional types of dysplastic changes are described in the mucosa of gastrointestinal tract besides the most common conventional type of dysplasia. Non-conventional dysplasias can arise de-novo or they can be found in association with chronic gastrointestinal conditions, such as Barretts esophagus, chronic atrophic gastritis, and inflammatory bowel disease. Non-conventional types of dysplasia include serrated, crypt base of foveolar dysplasia and lesions as pyloric or oxyntic gland adenoma. Non-conventional types of dysplasia arising in inflammatory bowel disease represent specific category with broad morphological spectrum of changes. The aim of this work is to present a comprehensive review of morphological characteristics of individual subtypes of non-conventional dysplastic changes with focus on differences and specificity in particular parts of gastrointestinal tract and provide a functional handout for daily diagnostic practice.

Proteomics signature of autoimmune atrophic gastritis: towards a link with gastric cancer.

BACKGROUND: Autoimmune atrophic gastritis (AAG) is a chronic disease that can progress to gastric cancer (GC). To better understand AAG pathology, this proteomics study investigated gastric proteins whose expression levels are altered in this disease and also in GC. METHODS: Using two-dimensional difference gel electrophoresis (2D-DIGE), we compared protein maps of gastric corpus biopsies from AAG patients and controls. Differentially abundant spots (|fold change|≥ 1.5, P < 0.01) were selected and identified by LC-MS/MS. The spots were further assessed in gastric antrum biopsies from AAG patients (without and with Helicobacter pylori infection) and from GC patients and unaffected first-degree relatives of GC patients. RESULTS: 2D-DIGE identified 67 differentially abundant spots, with 28 more and 39 less abundant in AAG-corpus than controls. LC-MS/MS identified these as 53 distinct proteins. The most significant (adjusted P < 0.01) biological process associated with the less abundant proteins was "tricarboxylic acid cycle". Of the 67 spots, 57 were similarly differentially abundant in AAG-antrum biopsies irrespective of H. pylori infection status. The differential abundance was also observed in GC biopsies for 14 of 28 more abundant and 35 of 39 less abundant spots, and in normal gastric biopsies of relatives of GC patients for 6 and 25 spots, respectively. Immunoblotting confirmed the different expression levels of two more abundant proteins (PDIA3, GSTP gene products) and four less abundant proteins (ATP5F1A, PGA3, SDHB, PGC). CONCLUSION: This study identified a proteomics signature of AAG. Many differential proteins were shared by GC and may be involved in the progression of AAG to GC.

Atypical endometrial polyps and the incidence of endometrial cancer: a retrospective cohort study.

OBJECTIVE: The aim of this study was to evaluate the incidence of endometrial carcinoma, proven after hysterectomy, in patients diagnosed with atypical endometrial hyperplasia confined to a polyp. A secondary aim was to establish factors associated with (pre-)malignant alterations in a polyp. DESIGN: A retrospective cohort study. SETTING: Maastricht University Medical Centre (MUMC+) and Máxima Medical Centre in Eindhoven/Veldhoven (Máxima MC). POPULATION: Women who underwent a hysteroscopic polyp resection between 2008 and 2016. METHODS: Patient characteristics and histopathology results of the polyp and, in the case of a hysterectomy, uterus were collected from patients' charts. RESULTS: A total of 1445 complete hysteroscopic polyp resections were included. Of those, 1390 polyps showed benign histopathology results, 39 polyps contained atypical hyperplasia and 16 polyps contained endometrial carcinoma. A hysterectomy was performed in 35 women who were diagnosed with atypical hyperplasia confined to a polyp after hysteroscopic polyp resection. Histopathological assessment showed no additional (pre-)malignant changes of the endometrium in 12 women (30.8%), atypical hyperplasia in 11 women (28.2%) and endometrial carcinoma in 12 women (30.8%). None of the prognostic factors under consideration were significantly associated with (pre-)malignant changes in a polyp. CONCLUSION: The incidence of endometrial carcinoma in the surrounding endometrium after complete resection of a polyp with atypical hyperplasia is 30.8% in this study. This supports the current advice to perform a hysterectomy and bilateral salpingo-oophorectomy. No prognostic factor for (pre-)malignant changes in a polyp was established. TWEETABLE ABSTRACT: The incidence of endometrial carcinoma after complete resection of a polyp with atypical hyperplasia is high.

Composite monoclonal B-cell lymphocytosis and MYD88 L265P-positive lymphoplasmacytic lymphoma in a patient with IgM light chain amyloidosis: Case report.

Monoclonal B-cell lymphocytosis (MBL) is an early or precursor asymptomatic proliferation of chronic lymphocytic lymphoma (CLL)-like B-cells. Lymphoplasmacytic lymphoma (LPL), often clinically associated with Waldenström macroglobulinemia, is a B-cell neoplasm characterized by frequent MYD88 L265P mutation. Here, we report a rare composite MBL and LPL in a patient with IgM light chain (AL) amyloidosis. A 74-year-old male with a known IgM monoclonal protein developed proteinuria. No lymphocytosis was detected. Renal biopsy showed deposition of AL λ amyloid in the glomeruli and vessels. Subsequent bone marrow biopsy revealed nodular atypical CLL-like small B-cell proliferation and scattered peripheral LPL. Immunohistochemistry and/or flow cytometry revealed that the atypical CLL-like population expressed CD19, CD20, CD5, weak CD23, LEF-1 and diminished surface Igκ. The LPL was positive for CD19, CD20 and surface Igλ. Using laser-capture microdissection and allele-specific polymerase chain reaction, we confirmed that MYD88 L265P was detectable in the LPL but not in the atypical CLL-like population. Thus, we demonstrated that these two populations were clonally independent, and made the diagnosis of composite MBL and LPL. An integrated clinical, pathological, immunophenotypic and genetic assessment is essential in such complicated cases, and especially 'clone-specific' MYD88 genotyping may facilitate the differential diagnoses of low-grade B-cell lymphomas.

Anal Cancer Precursor Lesions in HIV-Infected Persons: Tissue Human Papillomavirus Type Distribution and Impact on Treatment Response.

BACKGROUND: Data on tissue distribution of human papillomavirus types in anal high-grade squamous intraepithelial lesions are limited and the impact on treatment outcomes poorly understood. OBJECTIVE: We aimed to investigate potential predictors of treatment failure after electrocautery ablation, including human papillomavirus type(s) isolated from index lesions. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a tertiary academic referral center in New York City. PATIENTS: Seventy-nine HIV-infected patients with a diagnosis of anal high-grade squamous intraepithelial lesions between January 2009 and December 2012 were included, and genomic DNA was extracted from biopsy tissue. MAIN OUTCOME MEASURES: The prevalence of human papillomavirus types in index lesions and surveillance biopsies after electrocautery ablation were analyzed to evaluate treatment response. RESULTS: Of 79 anal high-grade squamous intraepithelial lesions, 71 (90%) tested positive for ≥1 human papillomavirus type; 8 (10%) had no human papillomavirus detected. The most common type was 16 (39%), followed by 33 (15%). Human papillomavirus type 18 was seen in 3%. Sixty-one patients (77%) underwent electrocautery ablation and had subsequent surveillance biopsies. Surveillance biopsies yielded benign findings or low-grade squamous intraepithelial lesions in 31 (51%) of 61 and recurrent high-grade squamous intraepithelial lesions in 30 (49%) of 61 patients (mean follow-up: 35 mo). Ablation response did not differ significantly based on baseline demographics, smoking history, history of anogenital warts, mean CD4 T-cell count, antiretroviral-therapy use, and HIV viral load (<50 copies/mL). The recurrence of high-grade lesions was not significantly associated with high-risk human papillomavirus types detected in index lesions. LIMITATIONS: Human papillomavirus genotyping in surveillance biopsies was not performed. CONCLUSIONS: Anal high-grade squamous intraepithelial lesions in HIV-infected patients contain a wide range of human papillomavirus types, and individual lesions commonly harbor multiple types concomitantly. Recurrence of anal high-grade squamous intraepithelial lesions after electrocautery ablation occurs frequently and is not affected by high-risk human papillomavirus types. See Video Abstract at http://links.lww.com/DCR/A833.

Novel Screening Tests for Barrett's Esophagus.

PURPOSE OF REVIEW: There has been an exponential increase in the incidence of esophageal adenocarcinoma (EAC) over the last half century. Barrett's esophagus (BE) is the only known precursor lesion of EAC. Screening for BE in high-risk populations has been advocated with the aim of identifying BE, followed by endoscopic surveillance to detect dysplasia and early stage cancer, with the intent that treatment can improve outcomes. We aimed to review BE screening methodologies currently recommended and in development. RECENT FINDINGS: Unsedated transnasal endoscopy allows for visualization of the distal esophagus, with potential for biopsy acquisition, and can be done in the office setting. Non-endoscopic screening methods being developed couple the use of swallowable esophageal cell sampling devices with BE specific biomarkers, as well as trefoil factor 3, methylated DNA markers, and microRNAs. This approach has promising accuracy. Circulating and exhaled volatile organic compounds and the foregut microbiome are also being explored as means of detecting EAC and BE in a non-invasive manner. Non-invasive diagnostic techniques have shown promise in the detection of BE and may be effective methods of screening high-risk patients.

Distribution of high-risk α-genus human papillomavirus genotypes impacts cutaneous neoplasms.

BACKGROUND: High-risk α-genus human papillomaviruses (α-HPVs) are linked to cervical and genital carcinomas; however, their correlation with cutaneous squamous cell carcinoma (cuSCC) or premalignant skin lesions remains controversial. OBJECTIVE: We evaluated the contribution of high-risk α-HPV to the occurrence of cuSCC, Bowen's disease and actinic keratosis (AK), and the distribution of high-risk α-HPV genotypes in these cutaneous tumours. METHODS: HPV genotypes were determined using a commercial PCR-based microarray on skin tissue samples collected from 76 [38 young (<60 years) and 38 elderly (>60 years)] cuSCC, 34 Bowen's disease, 48 AK patients and 10 young controls. Associations between α-HPV prevalence and relevant risk factors were analysed. RESULTS: High-risk α-HPV was more frequently detected in cuSCC patients (57.9%) than in the patients with Bowen's disease (38.2%), AK (0.0%) and control patients (10.0%). The high-risk α-HPV prevalence was higher in young than in elderly cuSCC patients (65.8% vs. 50.0%, P = 0.031). The most common HPV type was 16, present in 90.9% of all HPV-carrying cuSCC patients. Multiple infections with different high-risk α-HPV types were found in 20.5% of HPV-related cuSCC, whereas only single infection with type 16 was found in Bowen's disease. Although sun exposure is known as a major risk factor for cuSCC, high-risk α-HPVs were more frequently found in non-exposed sites rather than in sun-exposed sites of cuSCC. CONCLUSION: Multiple infections, as well as single infection with high-risk α-HPV may link to cuSCC. In spite of the involvement of high-risk α-HPV at high levels in cuSCC and Bowen's disease, no high-risk α-HPV was detected in AK patients, suggesting that Bowen's disease rather than AK might be involved in the development of HPV-related cuSCC as a precursor.

Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro- and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations.

Are There Any Predictors of Endometrial Premalignancy/Malignancy within Endometrial Polyps in Infertile Patients?

BACKGROUND: In the literature, there is no detailed analysis on the prediction factors for premalignancy/malignancy within endometrial polyps (EPs) in infertile patients. In this study, we aimed to determine the frequency of endometrial premalignancy/malignancy within EPs in infertile patients undergoing office hysteroscopic polypectomy and identify the factors that can potentially predict an endometrial premalignancy/malignancy within EPs. METHOD: A total of 957 infertile patients undergoing office hysteroscopy were diagnosed with EPs between February 2011 and August 2018. Patients were divided into 2 groups according to the pathological examination of EPs as benign (Group 1; n = 939) and premalignant/malignant (Group 2; n = 18). The medical records of all patients included in the study were reviewed retrospectively. RESULTS: In this cohort, prevalence of endometrial premalignancy/malignancy within EPs was 18/957 (1.88%). On univariate analysis, age, polyp size, diabetes, hypertension, and causes of infertility did not differ between the 2 groups. On multivariate analysis, diffuse polypoid appearance of the endometrial cavity on office hysteroscopy (hazard ratio [HR] 4.1; 95% CI 1.576-10.785), duration of infertility, (HR 4; 95% CI 1.279-12.562), and body mass index (HR 7.9; 95% CI 2.591-24.258) were found to be independent predictors of endometrial premalignancy/malignancy within polyps in infertile patients. CONCLUSION: When diffuse polypoid appearance of the endometrial cavity is detected in an infertile patient during office hysteroscopy, hysteroscopy-guided resection and endometrial curettage should be performed. The pathological specimen should be sent for histopathological evaluation to diagnose possible endometrial premalignancy/malignancy within polyps.