Low-grade Intraepithelial Neoplasia Research Articles

Aerobic Vaginitis: is Enterococcus faecalis Another Risk Factor in the Progression of Cervical Intraepithelial Neoplasia to Cervical Cancer—Literature Review

Objective: The aim of our review article is to show Enterococcus faecalis (E. faecalis) as a risk factor of cervical cancer. Mechanism: Aerobic vaginitis (AV) is the absence of a balance of vaginal flora containing aerobic and intestinal pathogens, varying degrees of vaginal inflammation and immature epithelial cells. The causes of AV responsible for inflammatory changes are: E. faecalis, Esherichia coli, group B streptococcus and Staphylococcus aureus. The pathogenic effect of aerobic microorganisms such as E. faecalis shows that it causes spontaneous abortion, premature birth, puerperal sepsis, abscesses, and urinary tract infections. Findings in Brief: AV caused by E. faecalis is more common in low-grade and high-grade cervical intraepithelial neoplasia (CIN) than in women with a normal Pap test and is thought to contribute to the progression of cervical cancer. E. faecalis produces hydrogen superoxide which causes chromosomal instability in intestinal epithelial cell infection, which is considered a key factor in the carcinogenic process. The presence of the Human papilloma virus (HPV) 16 gene and genome in E. faecalis in cervical cancer biopsy material leads to a specific link that may be a risk factor in the progression of CIN toward cancer. The presence of HPV in this bacteria can lead to persistent HPV infection, CIN development and progression to cervical cancer. Conclusions: Increased vaginal pH, lactobacilli deficiency, and the ability of E. faecalis to contain HPV-16 in episomal form in E. faecalis-induced AV could be key promoters of persistence and proliferation of cervical HPV as a risk factor in development of CIN and cervical cancer.

Endoscopic or Follow-up Treatment for Gastric Indeterminate Tumors Is the Preferred Method of Management.

BackgroundEndoscopic forceps biopsy (EFB) lacks precision in diagnosing indeterminate tumors. When the presence of early gastric cancer (EGC) is macroscopically suspected, but biopsy pathology fails to give a diagnosis of neoplasia, it causes problems in clinical management. The purpose of this study was to discuss the outcome of gastric indeterminate tumors and the clinical factors associated with predicting EGC.MethodsThe medical records of 209 patients diagnosed with gastric indeterminate neoplasia by biopsy forceps were retrospectively studied. Initial endoscopic findings were analyzed and predictors of EGC were evaluated.ResultsThe final pathological diagnosis in 209 patients included adenocarcinoma (n = 7), high-grade intraepithelial neoplasia (n = 11), low-grade intraepithelial neoplasia (n = 21), and non-neoplastic lesion (n = 170). Multivariate analysis showed that older age (OR = 1.78; 95% CI = 1.17–2.71; p = 0.008), patients undergoing narrow band imaging (NBI) (OR = 3.40; 95% CI = 1.37–8.43; p = 0.008), and surface erosion (OR = 3.53; 95% CI = 1.41–8.84; p = 0.007) were associated with the upgraded group, and were significantly associated with risk. Univariate logistic regression analysis showed that among patients with NBI, the presence of demarcation line (DL) (OR = 24.00; 95% CI = 4.99–115.36; p < 0.0001), microvascular (MV) pattern irregularity (OR = 9.129; 95% CI = 2.36–35.34; p = 0.001), and the presence of white opaque substance (WOS) (OR = 10.77; 95% CI = 1.14–101.72; p = 0.038) were significant risk factors.ConclusionsFor gastric indeterminate tumors, older patient age, lesion surface with erosion, clear DL visible under NBI observation, presence of WOS, and irregular MV pattern are suggestive of the high possibility of neoplasia and need to be focused on and may benefit more from endoscopic resection treatment as opposed to simple endoscopic follow-up.

The Potential Value of Gastric Histopathology for Predicting Colorectal Adenomatous Polyps Among the Chinese Population: A Retrospective Cross-Sectional Study.

BackgroundIt remains unknown whether gastric histopathology is associated with the occurrence of colonic neoplasms. We aimed to clarify the association between gastric histopathology and different types of colorectal polyps (CP) and colorectal cancer (CRC), and whether various gastric histopathologies are risk factors for different types of CP and CRC.MethodsA retrospective cross-sectional study was conducted on 5,986 patients who underwent gastroscopy and colonoscopy simultaneously at Shaoxing People’s Hospital from August 1, 2019, to May 31, 2020. The Pearson χ2 test was used to analyze the occurrence of various gastric histopathologies in different types of CP and CRC, and logistic regression was used to determine whether various gastric histopathologies were risk factors for different types of CP and CRC.ResultsFor the Chinese population, male sex (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.41–1.97, P < 0.001) and old age (OR 1.03, 95% CI 1.02–1.04, P < 0.001) were risk factors for non-adenomatous polyps (NAP), but Helicobacter pylori (H. pylori) and various gastric histopathologies were not significant in the NAP compared with the normal group. Nevertheless, it is noteworthy that, similar to male sex and old age, H. pylori (OR 1.22, 95% CI 1.08–1.38, P = 0.002), low-grade intraepithelial neoplasia (LGIN) (OR 1.79, 95% CI 1.21–2.66, P = 0.004), gastric fundus gland polyps (FGPs) (OR 1.44, 95% CI 1.11–1.87, P = 0.007), hyperplastic/inflammatory gastric polyps (GHP or GIP) (OR 1.50, 95% CI 1.06–2.12, P = 0.022), and atrophy/intestinal metaplasia (AG or IM) (OR 1.27, 95% CI 1.13–1.43, P < 0.001) were all risk factors for colorectal adenomatous polyps (AP). However, the results of CRC showed that old age (OR 1.13, 95% CI 1.10–1.16, P < 0.001) and H. pylori (OR 1.67, 95% CI 0.99–2.75, P < 0.05) were risk factors for CRC (OR 1.67, 95% CI 0.99–2.75, P < 0.05), but not sex and various gastric histopathologies (P > 0.05).ConclusionGastric histopathology, such as AG or IM, LGIN, FGP, and GHP or GIP, were risk factors for AP, but not for NAP and CRC, indicating that gastric histopathology has potential predictive value for AP in the Chinese population.

Cytology-based Screening for Anal Intraepithelial Neoplasia in Immunocompetent Brazilian Women with a History of High-Grade Cervical Intraepithelial Neoplasia or Cancer.

To determine the prevalence and possible variables associated with anal intraepithelial neoplasia and anal cancer in immunocompetent women with high-grade cervical intraepithelial neoplasia. A cross-sectional study involving immunocompetent women with a histological diagnosis of high-grade cervical intraepithelial neoplasia and cervical cancer, conducted between January 2016 and September 2020. All women underwent anal cytology and answered a questionnaire on characterization and potential risk factors. Women with altered cytology were submitted to anoscopy and biopsy. A total of 69 women were included in the study. Of these, 7 (10.1%) had abnormal anal cytology results: (high-grade lesion, atypical squamous cells of undetermined significance, and atypical squamous cells, cannot exclude high-grade lesions: 28,5% each; low grade lesion: 14,3%). Of the anoscopies, 3 (42.8%) showed alterations. Of the 2 (28,5% of all abnormal cytology results) biopsies performed, only 1 showed low-grade anal intraepithelial neoplasia. The average number of pregnancies, vaginal deliveries, and abortions was associated with abnormal anal cytology. However, the highest mean regarding the cesarean sections was associated with normal cytology. The prevalence of anal intraepithelial neoplasia was compatible with data from recent studies, especially those conducted in Brazil. Opportunistic screening for anal intraepithelial neoplasia in this high-risk population should be considered. Anal cytology is suitable for this purpose, due to its low cost and feasibility in public health services.

A Single-Center Follow-Up Study of Low-Grade Gastric Intraepithelial Neoplasia and the Screening of Key Genes of Precancerous Lesions.

ObjectiveThe study aimed to summarize the morphological characteristics of low-grade gastric intraepithelial neoplasia (LGIN) and explore its outcomes and risk factors. Additionally, it aimed to screen the core different expression genes (DEGs) of high-grade gastric intraepithelial neoplasia (HGIN) using bioinformatics methods to identify biomarkers for early gastric cancer outcomes.MethodsThe clinical and pathological data of 449 patients with LGIN in the endoscopy center of the Second Hospital of Hebei Medical University from June 2013 to September 2018 were collected for retrospective analysis. The GSE130823 and GSE55696 data sets were selected from the Gene Expression Omnibus database, and the GEO2R tool was used to screen DEGs in HGIN and chronic gastritis tissue types. A DEG functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery. The STRING database was utilized to create a protein–protein interaction network, and the CytoHubba plug-in was used to screen the key genes of HGIN.ResultsThe incidence of LGIN increased with age, and most of the patients were aged between 45–59 years (P = 0.048). Lesions were found mainly in the cardia, mostly in people aged 60 (P < 0.05). Progression occurred in 42 of 449 patients, with a 9.4% rate of cancer development. Foci larger than 10 mm, ulcerative lesions, and an Helicobacter pylori-positive result were factors affecting the outcome of LGIN (P < 0.05). Seven core genes of HGIN were screened, including MYC, SOX2, CDX2, TBX3, KRT7, CDKN2A, and MUC5AC.ConclusionThe patients with LGIN reflected the potential for developing cancer. A magnifying gastroscope can contribute to the detection of early gastric cancer. Additionally, the MYC, CDX2, and TBX3 genes may act as specific biomarkers of HGIN.

Prognostic significance of CKS2 and CD47 expression in patients with gastric cancer who underwent radical gastrectomy.

To investigate the protein expression levels of cyclin-dependent kinase subunit 2 (CKS2) and the cluster of differentiation (CD) 47 in gastric cancer (GC) and their clinical significance. A total of 126 GC patients who underwent radical resection were selected as study subjects. Additionally, 32 patients with benign gastric tumour, 42 patients with low-grade intraepithelial neoplasia (LGIEN), and 49 patients with high-grade intraepithelial neoplasia (HGIEN) who underwent surgery were selected as the control groups. Immunohistochemistry was used to detect the expression of CKS2 and CD47 in surgical specimens. We statistically analysed the clinical significance of the expression of the two factors. (1) The positivity rates for CKS2 in benign gastric tumour tissue, LGIEN tissue, HGIEN tissue, and GC tissue gradually increased, that is, 6.3% (2/32), 30.9% (13/42), 38.8% (19/49), and 60.3% (76/126), respectively, and the positivity rates for CD47 were 18.8% (6/32), 38.1% (16/42), 46.9% (23/49), and 65.9% (83/126), respectively. (2) High expression of CKS2 and CD47 were associated with tumour diameter, Lauren classification, number of lymph node metastases, and TNM stage. In addition, the immunohistochemical scores for CKS2 and CD47 were positively correlated (r=.625, P=.000). (3) The median follow-up time of 126 patients was 46.5months, and the overall survival (OS) rate was 40.5% (51/126). Survival analysis showed that compared with that in the CKS2 (-) group, the OS rate for patients in the CKS2 (+) group was significantly worse and that compared with the CD47 (-) group, the CD47 (+) group had significantly worse OS (30.1% vs 60.5%, χ2 =15.67, P=.000). (4) The OS rates of CKS2 (+) CD47 (+) group, CKS2 (+) CD47 (-) group, CKS2 (-) CD47 (+) group, and CKS2 (-) CD47 (-) group were 20.0% (13/65), 58.3% (7/12), 57.1% (8/14), 65.7% (23/35), respectively, the prognosis of patients in CKS2 (+) CD47 (+) group was significantly poor. High expression levels of CKS2 and CD47 were closely related to the occurrence of GC and can be used as independent risk factors to assess the prognosis of patients.

Comparison of Endoscopic Radiofrequency Ablation and Argon Plasma Coagulation in Patients with Gastric Low-Grade Intraepithelial Neoplasia: A Large-Scale Retrospective Study.

Background Gastric low-grade intraepithelial neoplasia (LGIN) is a precancerous lesion of gastric cancer. Endoscopic therapies represented by radiofrequency ablation (RFA) and argon plasma coagulation (APC) have been applied to treat gastric LGIN in recent years. However, no comparative study examining the effectiveness and safety profiles of RFA and APC has been reported. Methods A single-center, large-scale, retrospective study, including 73 and 50 patients treated with RFA and APC, respectively, was conducted in the First Medical Center of Chinese PLA General Hospital from October 2015 to October 2020, with a two-year follow-up. Effectiveness, complications, operative factors, and other data were assessed. Results At 2 years of follow-up, cure, relapse, recurrence, and progression rates were 90.4%, 9.6%, 9.6%, and 2.7% in the RFA group, respectively, versus 90%, 10%, 12%, and 4% in the APC group, respectively, with no statistically significant differences between the two groups (all p > 0.05). However, the mean lesion size was significantly larger in the RFA group (2.6 ± 1.0 cm) than in the APC group (1.5 ± 0.6 cm) (p < 0.001); there was also a significant difference in the composition ratio of large lesions between the two groups (p < 0.001). No serious postoperative complications showed in either group, and the abdominal pain was the most common symptom in the short term after surgery. Conclusions RFA and APC are both safe and effective destructive therapies for gastric LGIN. RFA is more suitable for flat and large lesions, while APC is more suitable for small lesions, especially those with slight local uplift or depression. An intraoperative submucosal injection is expected to be an effective method for relieving postoperative abdominal pain.

Abstract 2155: PMR-116, a novel inhibitor of ribosome biogenesis with antitumor activity in preclinical models of prostate cancer

Abstract Advanced prostate cancer is characterised by mutations and amplifications of genes involved in regulating protein synthesis. PTEN-loss stimulates activity of the mTOR pathway, while amplification of MYC leads to increased ribosome biogenesis and elevated mRNA translation rate. Our previous work has demonstrated the efficacy of co-targeting ribosome biogenesis, via inhibition of RNA Pol I activity, and 4E-BP1 phosphorylation to suppress prostate cancer growth in vivo in GEMM of PCa and in patient-derived xenografts (Rebello et al., Clinical Cancer Research, 2016; Lawrence et al., European Urology, 2018). In a collaboration with Pimera Inc., we investigated the efficacy of their new lead RNA Pol I inhibitor PMR-116 in models of prostate cancer. PMR-116 is well tolerated in vivo in mice and can be given at 300mg/kg weekly. Using the Hi-MYC mouse model of PCa we show that dosing 6 month old mice once weekly for 4 weeks can decrease the incidence of invasive lesions by up to 85% compared to vehicle control while reverting glands to patterns of low grade intraepithelial neoplasia. PMR-116 rapidly inhibits proliferation in the Hi-MYC model with a 50% decrease in Ki67 observed 12 hours after oral administration. Conversely, PMR-116 showed minimal anti-tumour efficacy in the PTEN-null model of PCa suggesting that elevated MYC signalling may be required for optimal response. To further validate our promising GEMM results in more clinically relevant human-derived models, we used patient-derived xenografts lines we established from multidrug-resistant, metastatic PCa (Lawrence et al, European Urology, 2018). PMR-116 treatment decreased tumour volume in all PDX tested including complete response in a line in which tumour volume decreased by ~90% compared to baseline. We believe this new RNA Pol I inhibitor shows promising results in a wide range of preclinical models and may exert higher efficacy in tumours expressing high levels of MYC. PMR-116 is currently in Phase I dose escalation trial in patient with solid tumours (ACTRN12620001146987). Citation Format: Alisee Huglo, Richard Rebello, Mitchell Lawrence, Gail Risbridger, Denis Drygin, Mustapha Haddach, Katherine Hannan, Ross Hannan, Luc Furic. PMR-116, a novel inhibitor of ribosome biogenesis with antitumor activity in preclinical models of prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2155.

Potential Factors Predicting Histopathologically Upgrade Discrepancies between Endoscopic Forceps Biopsy of the Colorectal Low-Grade Intraepithelial Neoplasia and Endoscopic Resection Specimens.

Background It was gradually accepted that endoscopic fragment biopsy (EFB) diagnosis cannot accurately guarantee the absence of higher-grade neoplasms within the lesion of the digestive tract. There are no well-established predictors for histopathologically upgrade discrepancies between EFB diagnosing colorectal low-grade intraepithelial neoplasia (LGIN) and endoscopic resection (ER) specimens. Methods A total of 918 colorectal LGINs was histopathologically diagnosed by EFB, including 162 cases with upgrade discrepancy and 756 concordant cases. We compared clinicopathological data of EFB and ER specimens between these two groups. Multivariate analysis was performed to identify predictors for this upgrade histopathology. Results The predominant upgrade discrepancy of LGINs diagnosed by EFB was upgrades to high-grade dysplasia (114/918, 12.4%), followed by upgrades to intramucosal carcinoma (33/918, 3.6%), submucosal adenocarcinoma (10/918, 1.1%), and advanced adenocarcinoma (5/918, 0.5%). NSAID history (OR 4.83; 95% CI, 2.27-10.27; p < 0.001), insufficient EFB number (OR 2.99; 95% CI, 1.91-4.68; p < 0.001), maximum diameter ≥ 1.0 cm (OR 6.18; 95% CI, 1.32-28.99; p = 0.021), lobulated shape (OR 2.68; 95% CI, 1.65-4.36; p < 0.001), erythema (OR 2.42; 95% CI, 1.50-3.91; p < 0.001), erosion (OR 7.12; 95% CI, 3.91-12.94; p < 0.001), surface unevenness (OR 2.31; 95% CI, 1.33-4.01; p = 0.003), and distal location of the target adenoma (OR 3.29; 95% CI, 1.68-6.41; p < 0.001) were associated with the histologically upgrade discrepancies. Conclusion NSAID history, insufficient EFB number, adenoma size and location, and abnormal macroscopic patterns are potential predictors for upgrade histopathology of LGINs diagnosed by EFBs. The standardization of EFB number and advanced imaging techniques could minimize the risk of neglecting the potential of this upgrade histopathology.

Establishment and clinical validation of an artificial intelligence YOLOv51 model for the detection of precancerous lesions and superficial esophageal cancer in endoscopic procedure

Objective: To construct the diagnostic model of superficial esophageal squamous cell carcinoma (ESCC) and precancerous lesions in endoscopic images based on the YOLOv5l model by using deep learning method of artificial intelligence to improve the diagnosis of early ESCC and precancerous lesions under endoscopy. Methods: 13, 009 endoscopic esophageal images of white light imaging (WLI), narrow band imaging (NBI) and lugol chromoendoscopy (LCE) were collected from June 2019 to July 2021 from 1, 126 patients at the Cancer Hospital, Chinese Academy of Medical Sciences, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, ESCC limited to the mucosal layer, benign esophageal lesions and normal esophagus. By computerized random function method, the images were divided into a training set (11, 547 images from 1, 025 patients) and a validation set (1, 462 images from 101 patients). The YOLOv5l model was trained and constructed with the training set, and the model was validated with the validation set, while the validation set was diagnosed by two senior and two junior endoscopists, respectively, to compare the diagnostic results of YOLOv5l model and those of the endoscopists. Results: In the validation set, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the YOLOv5l model in diagnosing early ESCC and precancerous lesions in the WLI, NBI and LCE modes were 96.9%, 87.9%, 98.3%, 88.8%, 98.1%, and 98.6%, 89.3%, 99.5%, 94.4%, 98.2%, and 93.0%, 77.5%, 98.0%, 92.6%, 93.1%, respectively. The accuracy in the NBI model was higher than that in the WLI model (P<0.05) and lower than that in the LCE model (P<0.05). The diagnostic accuracies of YOLOv5l model in the WLI, NBI and LCE modes for the early ESCC and precancerous lesions were similar to those of the 2 senior endoscopists (96.9%, 98.8%, 94.3%, and 97.5%, 99.6%, 91.9%, respectively; P>0.05), but significantly higher than those of the 2 junior endoscopists (84.7%, 92.9%, 81.6% and 88.3%, 91.9%, 81.2%, respectively; P<0.05). Conclusion: The constructed YOLOv5l model has high accuracy in diagnosing early ESCC and precancerous lesions in endoscopic WLI, NBI and LCE modes, which can assist junior endoscopists to improve diagnosis and reduce missed diagnoses.

Health-Related Quality of Life and Utility Scores of Posttreatment Patients with Gastric Cancer at Different Pathological Stages: A Cross-Sectional Study.

Background Health-related quality of life (HRQoL) is a key variable in the evaluation of health economics. We aimed to evaluate the HRQoL and utility scores of patients with gastric cancer and related precancerous lesions by assessing their quality of life using a single standardized health measurement instrument. Methods A cross-sectional study was conducted in six counties in Shangdong Province from November 2019 to March 2020. Subjects with precancerous lesions and gastric cancer (cardia and noncardia) were included and surveyed. Patients were divided into four groups: low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), early gastric cancer (EGC), and advanced gastric cancer (AGC). All patients, except those with LGIN, received treatment. The five-level EQ-5D was used to assess HRQoL and generate utility scores using the Chinese-specific tariff published in 2017. Results The study included 566 respondents. The average utility was 0.927 for precancerous lesions (LGIN: 0.930; HGIN: 0.926), 0.906 for early gastric cancer (EGC), and 0.756 for advanced gastric cancer (AGC). Visual analogue scale (VAS) means were 76.82 (LGIN: 78.08; HGIN: 74.81), 72.26, and 69.16 for precancerous lesions, EGC, and AGC, respectively. HRQoL was lower in women with AGC than in men (0.612 vs. 0.792, P = 0.035). AGC patients were more likely to report problems across all five dimensions than patients in other stages. The proportion of patients reporting pain/discomfort problems was highest across all gastric cancer stages (LGIN, 35.6%; HGIN, 34.4%; EGC, 35.6%; and AGC, 55.7%), followed by anxiety/depression (LGIN, 17.5%; HGIN, 18%; EGC, 22.8%; and AGC, 47.7%). Conclusions HRQoL declined as cancer progressed, with the most dramatic decline observed in patients with AGC. A more advanced pathological stage was associated with a greater decrease in health utility. The obtained utilities for different pathological stages of gastric cancer were significant parameters for researchers to perform further cost-utility analysis. Pain/discomfort and anxiety/depression were problems that seriously affected the patients in all groups.

Immunological substantiation of complex therapy in patients with mild HPV-associated cervical intraepithelial neoplasia

Introduction. As is known, the development of invasive cervical cancer is preceded by cervical intraepithelial neoplasia of varying severity, which is a pathological process in which cells with varying degrees of atypia and impaired differentiation appear in the thickness of the stratified squamous epithelium of the cervix.Objective. To study the effect of complex therapy in patients with mild HPV-associated cervical intraepithelial neoplasia on the dynamics of local cytokine status and autoimmunity parameters.Materials and methods. The study included 86 patients aged 35 to 40 years with morphologically verified mild cervical intraepithelial neoplasia. The main group consisted of 52 patients who, along with radio wave destruction of the cervix, were prescribed an immunostimulating drug with antiviral activity “Groprinosin-Richter” 1000 mg 3 times a day for 10 days 10–14 days before destruction and similar 2 courses after 10–14 days after it. The comparison group included 34 patients who underwent only radio wave destruction of the cervix.Results. An analysis of the outcomes of low-grade squamous intraepithelial lesions after 6 months showed that in the main group, CIN I regression was observed in 92.3% of patients, persistence – in 7.7% of cases, while in the comparison group, CIN I regression was noted in 73,5% of cases, persistence – in 26.5% of patients.Conclusions. Conducting complex therapy, including radio wave destruction and the use of a drug with immunostimulating and antiviral activity “Groprinosin-Richter” in patients with low-grade HPV-associated cervical intraepithelial neoplasia, leads to the elimination of the initial imbalance of cytokines and normalization of autoantibody levels, helping to reduce the likelihood of HPV persistence and CIN progression to invasive cervical cancer uterus.

Estrogen receptor expression is modulated in human and mouse prostate epithelial cells during cancer progression

Substantial data posit estrogen receptors (ERs) as promising targets for prostate cancer (PCa) therapeutics. However, the trials on assessing the chemo-preventive or therapeutic potential of ER targeting drugs or selective estrogen receptor modulators (SERMs) have not yet established their clinical benefits. This could be ascribed to a possible modulation in the ER expression during PCa progression. Further it is warranted to test various ER targeting drugs in appropriate preclinical models that simulate human ER expression pattern during PCa progression. The study was undertaken to revisit the existing data on the epithelial ER expression pattern in human cancerous prostates and experimentally determine whether these patterns are replicated in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice, a model for human PCa. Estradiol (E2) binding to the plasma membrane of the epithelial cells and its modulation during the PCa progression in TRAMP were also investigated.A reassessment of the existing data revealed a trend towards downregulation in the epithelial expression of wild-type ESR1 transcripts in high-grade PCa, compared to non-cancerous prostate in humans. Next, epithelial cell-enriched populations from TRAMP prostates (TP) displaying low-grade prostatic intraepithelial neoplasia (LGPIN), high-grade PIN (HGPIN), HGPIN with well-differentiated carcinoma (PIN + WDC), WDC (equivalent to grade 2/3 human PCa), and poorly-differentiated carcinoma (PDC-equivalent to grade 4/5 human PCa) revealed significantly higher Esr1 and Esr2 levels in HGPIN and significantly reduced levels in WDC, compared to respective age-matched control prostates. These patterns for the nuclear ERs were similar to the trend shown by E2 binding to the plasma membrane of the epithelial cells during PCa progression in TRAMP. E2 binding to epithelial cells (EpCAM+), though significantly higher in TPs displaying LGPIN, decreased significantly as the disease progressed to WDC. The study highlights a reduction in the epithelial ESR level with the PCa progression and this pattern was evident in both humans and TRAMP. These observations may have major implications in refining PCa therapeutics targeting ER.

A nested case-control study on the relationship between red blood cell folate and the prognosis of low-grade cervical intraepithelial neoplasia

Objective: To evaluate the relationship between red blood cell folate (RBC folate) and the prognosis of low-grade cervical intraepithelial neoplasia (CIN 1). Methods: In the married women cohort established in 2014, 564 women with CIN 1 diagnosed by pathology were recruited. The demographic characteristics and factors of cervical intraepithelial neoplasia were collected. Meanwhile, the infection status of human papillomavirus (HPV) was detected by molecular diversion hybridization, and the level of RBC folate was measured by chemical photoimmunoassay. After 24 months of follow-up, pathological examination was performed again to observe the prognosis of participants. The women with reversal were taken as the control group,and those with continuous and progressive CIN 1 were taken as the case group respectively. The relationship between RBC folate and CIN 1 outcome was evaluated by logistic regression model. Results: 453 women completed the follow-up, aged (49.72±6.84) years old. CIN 1 was reversed in 342 women, continued in 58 cases and progressed in 53 cases. The RBC folate level M (Q1,Q3) were 399.01 (307.10, 538.97) ng/ml, 316.98 (184.74, 428.49) ng/ml and 247.14 (170.54, 348.97) ng/ml, respectively. With the decrease of RBC folate, the risk of continuous and progressive CIN 1 increased (all P<0.001), while the risk of reversal CIN 1 decreased gradually (P<0.001). Combined with high-risk human papillomavirus (HR-HPV) infection status, low level of RBC folate could increase the risk of CIN 1 progression regardless of HR-HPV infection (HR-HPV infection: OR=21.34, 95%CI: 3.98-114.54; HR-HPV uninfection: OR=11.15, 95%CI: 2.34-53.13). Conclusion: Low level of RBC folate could increase the risk of CIN 1 persistence and progression regardless of HR-HPV infection.

A large upper abdominal mass in an adolescent with high Ca 19.9: a case report

Mucinous cystic neoplasms of the liver are uncommon cystic lesions of the liver, most commonly seen in women in the fifth decade of life. We present a case of a 16-year-old girl with an incidentally discovered abdominal mass while undergoing a tonsillectomy. Investigation revealed a multiloculated, septated 17 × 17 × 11 cm cystic lesion arising from the left lobe of the liver, with displacement of the remaining upper abdominal viscera. Serum Ca19.9 was significantly elevated at 2256 U/ml (range 0–37), but other bloods including liver function tests, alphafoetoprotein and carcinoembryonic antigen were within normal limits. We proceeded to open formal left hemi-hepatectomy. Histology was consistent with a diagnosis of mucinous cystic neoplasm with low-grade intra-epithelial neoplasia.

Autophagy Blockage Reduces the Incidence of Pancreatic Ductal Adenocarcinoma in the Context of Mutant Trp53.

Macroautophagy (hereafter referred to as autophagy) is a homeostatic process that preserves cellular integrity. In mice, autophagy regulates pancreatic ductal adenocarcinoma (PDAC) development in a manner dependent on the status of the tumor suppressor gene Trp53. Studies published so far have investigated the impact of autophagy blockage in tumors arising from Trp53-hemizygous or -homozygous tissue. In contrast, in human PDACs the tumor suppressor gene TP53 is mutated rather than allelically lost, and TP53 mutants retain pathobiological functions that differ from complete allelic loss. In order to better represent the patient situation, we have investigated PDAC development in a well-characterized genetically engineered mouse model (GEMM) of PDAC with mutant Trp53 (Trp53 R172H ) and deletion of the essential autophagy gene Atg7. Autophagy blockage reduced PDAC incidence but had no impact on survival time in the subset of animals that formed a tumor. In the absence of Atg7, non-tumor-bearing mice reached a similar age as animals with malignant disease. However, the architecture of autophagy-deficient, tumor-free pancreata was effaced, normal acinar tissue was largely replaced with low-grade pancreatic intraepithelial neoplasias (PanINs) and insulin expressing islet β-cells were reduced. Our data add further complexity to the interplay between Atg7 inhibition and Trp53 status in tumorigenesis.

Clinical efficacy and prognostic risk factors of endoscopic radiofrequency ablation for gastric low-grade intraepithelial neoplasia.

BACKGROUNDThe use of radiofrequency ablation (RFA) has been reported in the treatment of gastric low-grade intraepithelial neoplasia (LGIN). However, its efficacy and prognostic risk factors have not been well analyzed.AIMTo explore the efficacy and prognostic risk factors of RFA for gastric LGIN in a large, long-term follow-up clinical study.METHODSThe clinical data of 271 consecutive cases from 198 patients who received RFA for treatment of gastric LGIN at the Chinese PLA General Hospital from October 2014 to October 2020 were reviewed in this retrospective study. Data on operative parameters, complications, and follow-up outcomes including curative rates were recorded and analyzed.RESULTSThe curative rates of endoscopic RFA for gastric LGIN at 3 mo, 6 mo, and 1-5 years after the operation were 93.3%, 92.8%, 91.5%, 90.3%, 88.5%, 85.7%, and 83.3%, respectively. Multivariate analyses revealed that Helicobacter pylori (H. pylori) infection and disease duration > 1 year had a significant effect on the curative rate (P < 0.001 and P = 0.013, respectively). None of patients had bleeding, perforation, infection, or other serious complications after RFA, and the main discomfort was postoperative abdominal pain.CONCLUSIONRFA was safe and effective for gastric LGIN during long-term follow-up. H. pylori infection and disease course > 1 year may be the main risk factors for relapse of LGIN after RFA.

Beneficial effects of endoscopic screening on gastric cancer and optimal screening interval: a population-based study.

BACKGROUND : The effectiveness of endoscopic screening on gastric cancer has not been widely investigated in China and the screening interval of repeated screening has not been determined. METHODS : In a population-based prospective study, we included 375,800 individuals, 14,670 of whom underwent endoscopic screening (2012-2018). We assessed the associations between endoscopic screening and risk of incident gastric cancer and gastric cancer-specific mortality, and examined changes in overall survival and disease-specific survival following screening. The optimal screening interval for repeated endoscopy for early detection of gastric cancer was explored. RESULTS : Ever receiving endoscopic screening significantly decreased the risk of invasive gastric cancer (age- and sex-adjusted relative risk [RR] 0.69, 95 % confidence interval [CI] 0.52-0.92) and gastric cancer-specific mortality (RR 0.33, 95 %CI 0.20-0.56), particularly for noncardia gastric cancer. Repeated screening strengthened the beneficial effect on invasive gastric cancer-specific mortality of one-time screening. Among invasive gastric cancers, screening-detected individuals had significantly better overall survival (RR 0.18, 95 %CI 0.13-0.25) and disease-specific survival (RR 0.18, 95 %CI 0.13-0.25) than unscreened individuals, particularly for those receiving repeated endoscopy. For individuals with intestinal metaplasia or low grade intraepithelial neoplasia, repeated endoscopy at an interval of < 2 years, particularly within 1 year, significantly enhanced the detection of early gastric cancer, compared with repeated screening after 2 years (P-trend = 0.02). CONCLUSION : Endoscopic screening prevented gastric cancer occurrence and death, and improved its prognosis in a population-based study. Repeated endoscopy enhanced the effectiveness. Screening interval should be based on gastric lesion severity.

Characteristics and potential malignancy of colorectal juvenile polyps in adults: a single-center retrospective study in China

BackgroundColorectal juvenile polyps are rare and generally considered benign in adults. Carcinogenesis or neoplastic changes are rarely mentioned in the literature. We systematically evaluated the characteristics and potential malignancy of colorectal juvenile polyps in adults.MethodsWe retrospectively reviewed the medical records of 103 adults diagnosed with colorectal juvenile polyps from September 2007 to May 2020 at our hospital. The characteristics, endoscopic findings, occurrence of intraepithelial neoplasia, carcinogenesis and diagnostic value of chicken skin mucosa (CSM) were analyzed.ResultsThe average age of patients with juvenile polyps was 43.2 years (range, 19 to 78 years). A total of 101 patients (101/103, 98.1%) had a single juvenile polyp, and two patients had multiple polyps (107 polyps in total). Polyp sizes ranged from 0.5 to 5 cm. One (1/107, 0.9%) juvenile polyp was cancerous, and 7 (7/107, 6.5%) developed low-grade intraepithelial neoplasia. Neoplasia and cancerization did not appear in the two patients with multiple polyps. A 27-year-old female had a 2-cm polyp with well-differentiated adenocarcinoma in the mucosa in the sigmoid colon with erosion on the surface. CSM was observed adjacent to 17 polyps, which were all located in the rectum and sigmoid colon, and one polyp showed low-grade intraepithelial neoplasia.ConclusionsColorectal juvenile polyps occur in a wide range of locations and in variable sizes and numbers. These polyps are solitary in most patients and have neoplastic potential. CSM is not a tumorigenic marker in colorectal juvenile polyps and usually occurs in the distant colorectum. Colorectal juvenile polyps in adults may progress from low-grade intraepithelial neoplasia to high-grade intraepithelial neoplasia and then to carcinoma and should be treated when discovered and regularly followed as colorectal adenomas.

Clinicopathological Features and Long-Term Outcomes of Intraductal Papillary Neoplasms of the Bile Duct of the Liver: Single-Institution Experience with 146 Patients

BackgroundIntraductal papillary neoplasm of the bile duct (IPNB) has a wide range of histopathology and intra- and extrahepatic tumor locations. MethodsThis retrospective single-center study evaluated the clinicopathological features and long-term outcomes of 146 patients with IPNB of the liver (IPNB-L) who underwent hepatic resection between January 2002 and June 2019. ResultsThe 146 patients included 97 (66.4%) men and 49 (33.6%) women, of mean age 64.3±8.0 years. Seventy-two (49.3%) patients were incidentally diagnosed, with no specific symptoms, and 18 (12.3%) were found to have hepatolithiasis. Sixty-one (41.8%) and two (1.4%) patients underwent concurrent bile duct resection and pancreaticoduodenectomy, respectively, and 130 (89.0%) underwent R0 resection. Low-grade and high-grade intraepithelial neoplasia, and invasive carcinoma were identified in 26 (17.8%), 50 (34.2%), and 70 (47.9%) patients, respectively. Five-year tumor recurrence and patient survival rates were 8.4% and 93.9%, respectively, in patients with high-grade neoplasia; and 41.5% and 72.3%, respectively, in patients with invasive carcinoma. CA19-9>37 U/mL and R1 resection were independent risk factors for tumor recurrence and reduced survival in patients with carcinoma. The combination of hypermetabolic fluorodeoxy-glucose-positron emission tomography (FDG-PET) or elevated CA19-9 showed a sensitivity of 91.8% and a specificity of 61.9% for the prediction of IPNB-L with high-grade neoplasia and carcinoma. ConclusionsIPNB-L is a rare type of intrahepatic biliary neoplasm that can range histologically from benign disease to invasive carcinoma. Surgical curability is the most important prognostic factor, thus aggressive resection is highly recommended to achieve R0 resection.