CDYL loss promotes cervical cancer aggression by increasing PD-L1 expression via the suppression of IRF2BP2 transcription.

BACKGROUND: Recurrent or metastatic cervical cancer have an extremely low 5-year survival rates about 17% due to limited therapeutic options. CDYL plays a critical role in multiple cancer development, as an oncogene or tumor suppressor in a context-dependent manner. However, the role of CDYL in cervical carcinogenesis has not yet been explored. METHODS: CDYL expression was examined in cervical cancer and cell lines. The effect of CDYL/IRF2BP2/PD-L1 axis on malignant phenotypes of cervical cancer cells were tested with gain-of-function experiments. A mouse model of cervical cancer was developed to validate the in vitro results. RESULTS: Clinical data analysis revealed that CDYL was downregulated and associated with a poor prognosis in cervical cancer patients. CDYL overexpression suppressed cervical cancer cells proliferation and invasion in vitro and vivo assays and enhanced the immune response by decreasing PD-L1 expression and reversing the tumor immunosuppressing microenvironment. Mechanistically, CDYL inhibited the PD-L1 expression through transcriptionally suppressing IRF2BP2 in cervical cancer cells. CONCLUSIONS: Taken together, our findings established the crucial role of CDYL in cervical carcinogenesis and sensitivity for immune checkpoint blockade therapy, and supported the hypothesis that CDYL could be a potential novel immunotherapy response predictive biomarker for cervical cancer patients.

Role of immunophenotypic characterisation in prognostic subtyping of intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (iCCA) is classified by the 5th WHO classification of tumours of the digestive system as large duct type (LDT) and small duct type (SDT), based on the anatomical location, morphological appearances, immunophenotype, and gene events. We evaluated the subtyping system using real-world data and established a supplementary method using immunohistochemical (IHC) detection. We retrospectively investigated 190 cases of surgically resected iCCA and classified them according to histological evaluations and gene detection. The prognostic value of the IHC markers were evaluated according to the relapse-free survival (RFS) and overall survival (OS). Basic histological classification was insufficient, with 61 cases classified as uncertain. This method showed no prognostic value for RFS or OS. The four-marker IHC detection, including EMA, S100P, N-cadherin, and CRP, which classified 68 cases as LDT, 108 cases as SDT, and 14 cases as uncertain, was highly efficient in subtyping and prognosis. The seven-marker method, including CD56, MUC5AC and MUC6, was consistent with the four-marker method. FGFR2 gene fusion was exclusively detected in 20 cases of SDT iCCA, according to the four- and seven-marker IHC detection. This novel method of iCCA classification exhibited diagnostic, prognostic and therapeutic value in clinical practice.

Lymphocyte-to-monocyte ratio after primary surgery is an independent prognostic factor for patients with epithelial ovarian cancer: A propensity score matching analysis.

Background: The aim of this study was to elucidate the prognostic value of preoperative lymphocyte-to-monocyte ratio (LMR) after primary surgery in epithelial ovarian cancer (EOC) patients using a propensity score matching (PSM) analysis. Methods: We retrospectively reviewed consecutive EOC patients who underwent primary surgery between January 2008 and December 2019. Patients were divided into two groups according to the optimal cutoff value of preoperative LMR. PSM (1:1) was conducted to eliminate confounding factors. A Cox proportional hazards model and the Kaplan-Meier estimator were employed to investigate the potential prognostic factors. Results: A total of 368 EOC patients were included in this study. The optimal cutoff value of LMR was identified as 4.65. Low preoperative LMR was significantly correlated with low albumin, high CA125 level, more blood loss, a high likelihood of ascites, advanced FIGO stage, and poor differentiation (all p < 0.05). After matching, Kaplan-Meier curves showed that the group with LMR < 4.65 experienced significantly shorter OS (p = 0.015). Multivariate Cox analysis revealed that low LMR (HR = 1.49, p = 0.041), advanced FIGO stage (HR = 5.25, p < 0.001), and undefined residual disease (HR = 3.77, p = 0.002) were independent factors in predicting poor OS. A forest plot revealed that LMR had better prognostic value in younger EOC patients, patients with BMI ≥ 25 kg/m2 and albumin ≥ 35 g/L, CA125 ≥ 35 U/L, patients who had undergone optimal surgery, and those who had completed chemotherapy. Additionally, low-LMR patients who had undergone incomplete chemotherapy had a shorter median OS compared with those who completed chemotherapy treatment (48.5 vs. 105.9 months, p = 0.026). Conclusions: LMR could be used as an independent prognostic factor for EOC patients after primary surgery; a noticeable negative effect of LMR was observed among EOC patients with age < 65, good preoperative nutritional status, and more aggressive tumor biology, and among those who underwent optimal surgery. Completing adjuvant chemotherapy is essential to improve survival outcomes among EOC patients with LMR < 4.65 after surgery.

Prognostic significance of lymphovascular invasion in patients with pT1b esophageal squamous cell carcinoma.

BACKGROUND: Lymphovascular invasion (LVI) is a crucial predictor of lymph node metastasis (LNM). However, few studies have investigated the LVI positivity rate and its clinical significance in pT1b esophageal squamous cell carcinoma (ESCC) using immunohistochemistry and elastin staining. METHODS: We collected data from158 patients with pT1b ESCC who had undergone radical esophagectomy. All paraffin blocks of invasive carcinoma from each patient were subjected to HE staining, elastin staining + CK (AE1/AE3) immunohistochemistry (E&IHC), and CD31/D2-40 + CK (AE1/AE3) double immunohistochemistry (D-IHC). The LVI was classified into types, i.e., vascular invasion (VI) and lymphatic vessel invasion (LI), and its location, quantity, and clinical significance were explored. RESULTS: The positivity rates of VI by E&IHC (E-VI), VI by CD31D-IHC (CD31-VI), and LI by D2-40 D-IHC (D2-40-LI) were significantly higher than those obtained by HE staining (P < 0.001, respectively). CD31-VI and E-VI were independent adverse prognostic factors for recurrence-free survival (RFS), and they were significantly associated with poor distant metastasis-free survival and overall survival in pT1b ESCC. Intratumoral LVI was also crucial in pT1b ESCC, and L2 (the count of D2-40-LI was 5 or more) was the strongest predictor for LNM and RFS in pT1b ESCC. CONCLUSION: E&IHC and D-IHC can dramatically improve the detection rate of LVI in pT1b ESCC, and the classification and grading of LVI can help to improve the prediction of LNM and prognosis.

Differences in Treatment Modalities and Prognosis of Elderly Patients with Ovarian Cancer: A Two-Center Propensity Score-Matched Study.

Background: The prognosis of older patients with ovarian cancer is poor. We evaluated the effect of chronological age and different treatment characteristics on the prognosis of older patients with ovarian cancer; Methods: The study retrospectively analyzed patients aged over 60 years who underwent cytoreduction followed by platinum-based adjuvant chemotherapy between January 2011 and December 2019 in two national centers in China. Propensity score matching (PSM, 1:1) was performed to stratify the comorbidity- and treatment-related factors. The Kaplan−Meier method was employed to estimate progression-free survival (PFS) in the original cohort and the cohort after PSM; Results: A total of 324 patients were evaluated. The Age ≥ 70 group often received more neoadjuvant chemotherapy (62.3% vs. 31.2%, p < 0.001), more discontinuation of adjuvant chemotherapy (31.2% vs. 10.8%, p < 0.001), and had more severe chemotherapy-related toxicity (45.6% vs. 34.2%, p = 0.040) than the Age < 70 group. After matching, the PFS of the Age < 70 group was not significantly different from the Age ≥ 70 group (median PFS = 12.4 and 11.9 months, respectively, p = 0.850). Furthermore, the advanced FIGO stage, non-R0 cytoreduction, and discontinuation of adjuvant chemotherapy were all found to be poor prognostic factors. Serum albumin level <40 g/L (HR = 2.441, p = 0.018) and age ≥ 70 years (HR = 2.639, p = 0.008) led to more severe chemotherapy-related toxicity. Additionally, poor renal function (HR = 5.128, p = 0.002) was in association with discontinuation of adjuvant chemotherapy; Conclusions: The chronological age of older patients cannot be seen as a poor prognostic factor. Older patients may benefit most from R0 cytoreduction followed by the completion of chemotherapy. Postoperative poor renal function and serum albumin level <40 g/L may help predict the discontinuation of adjuvant chemotherapy.

Conventional papillary thyroid carcinoma with intraglandular lymphatic dissemination shows more aggressive features.

OBJECTIVE: To investigate the invasive capability and other clinicopathological features of conventional papillary thyroid carcinoma (CVPTC) with intraglandular lymphatic dissemination. METHODS: Seventy-three conventional papillary thyroid carcinoma patients receiving total thyroidectomy were analyzed in this study. The expression of BRAF-V600E, D2-40 and CD31 in all thyroid samples was detected by immunohistochemical staining. The results were evaluated by two pathologists and were statistically analyzed. The rate of positive BRAF-V600E expression and the clinical invasiveness of CVPTC with intraglandular dissemination, multifocal non-intraglandular dissemination-CVPTC and single focus-CVPTC were evaluated. The correlation between BRAF-V600E expression, lymphatic vessel density, microvessel density and the clinicopathological characteristics of conventional papillary thyroid carcinoma were assessed. RESULTS: Twenty-five intraglandular dissemination-CVPTC, 17 multifocal non-intraglandular dissemination-CVPTC and 31 single focus-CVPTC cases were included in this study. The results showed that BRAF-V600E expression was independently correlated with intraglandular dissemination, age and pN staging (P < 0.05). The lymphatic vessel density in the intraglandular dissemination-CVPTC group was higher than that in the non-intraglandular dissemination-CVPTC group (P < 0.05). Compared with cases without intraglandular dissemination, intraglandular dissemination-CVPTC was associated with a younger age, higher lymph node metastasis rate, pN staging, the expression of BRAF-V600E and increased Capsule invasion and lymphovascular tumor thrombus (P < 0.05). During the follow-up of 30 months (median 15 months), two patients in the intraglandular dissemination-CVPTC group had cervical lymph node metastasis after the first operation. CONCLUSIONS: Intraglandular dissemination-CVPTC shows more aggressive features, and intraglandular lymphatic dissemination may be a potential biological indicator of poor prognosis.

Sporadic foveolar-type adenoma in gastric body/antrum junction with gastritis cystica profunda.

BACKGROUND: Sporadic gastric foveolar-type adenomas are extremely rare and are usually small, flat or slightly raised lesions that occur in the oxyntic mucosa. CASE PRESENTATION: We reported here a case of a 70-year-old female with a sporadic gastric foveolar-type adenoma occurring in the mucosa at the junction of the gastric body/antrum. The adenoma was a protruding lesion of 2 × 1.8 cm sized, causing symptoms of upper gastrointestinal bleeding, and the basal and surrounding mucosa showed pseudopyloric gland metaplasia without atrophy, intestinal metaplasia, H. pylori infection, or active inflammation. It had somatic mutations in both APC and KRAS genes. CONCLUSIONS: This is the first reported case of a large sporadic gastric foveolar-type adenoma that occurred in the mucosa of pseudopyloric gland metaplasia and with Gastritis Cystica Profunda, which modify our understanding of the morphological features and molecular underpinnings of this type of lesion.

Overexpression of NDRG2 promotes the therapeutic effect of pazopanib on ovarian cancer.

OBJECTIVES: Ovarian cancer is the second commonly seen cancer in the US, patients with ovarian cancer are commonly diagnosed in the advanced stage. Pazopanib is an inhibitor of multiple tyrosine kinases and has been approved in treatment for carcinoma by FDA. N-myc downstream-regulated gene 2 (NDRG2) has been regarded as a cancer suppressor gene and presented an inhibition effect in cancer proliferation, invasion, and migration.Design: NDRG2 was overexpressed or inhibited in SKOV-3 cells, then experiments were performed to detect the apoptosis of cells. The expression or secretion of pro-cancer molecules was detected. And the expression of apoptosis-related proteins and the ASK1/JNK1 signaling pathway was detected. METHODS: The NDRG2 overexpression and inhibition model was firstly constructed in SKOV-3 cells, the apoptotic cells were detected using flow cytometry. The expression of cellular metastasis genes was detected using the qPCR method. The angiogenesis factors was detected using the ELISA method. Expression of each target protein was detected using western blotting analysis. RESULTS: NDRG2 overexpression and inhibition model were constructed in the SKOV-3 cell line, overexpression of NDRG2 enhanced the effect of pazopanib on inhibition of the expression of metastasis-related molecules and angiogenesis-related factors. The apoptosis process of cells was also enhanced after overexpression of NDRG2, and these effects were regulated by the activation of the ASK1/JNK1 signaling pathway.Limitations: The effect of NDRG2 in animal models and more cell lines needs to be explored in further study. CONCLUSIONS: NDRG2 might be a therapeutic target in treatment for ovarian cancer.

CASC11 Overexpression Predicts Poor Prognosis and Regulates Cell Proliferation and Apoptosis in Ovarian Carcinoma.

INTRODUCTION: It is known that CASC11 can promote colorectal cancer. However, the function of CASC11 in ovarian carcinoma (OC) remains elusive. METHODS: In this study, we measured the expression levels of CASC11 and miR-182 in both OC and healthy control samples by performing qPCR. The interaction between CASC11 and miR-182 was analyzed by the overexpression experiment and qPCR. Cell apoptosis was analyzed by cell apoptosis assay, and the prognostic value of CASC11 for OC was analyzed by survival curve analysis. RESULTS: We found that CASC11 and microRNA-182 (miRNA-182) were upregulated in OC. Plasma CASC11 was upregulated in OC patients and predicted early-stage OC. Follow-up study revealed that high plasma levels of CASC11 were closely correlated with poor survival conditions of OC patients. CASC11 and miRNA-182 were positively correlated in OC. Overexpression of CASC11 mediated the upregulation of miRNA-182 in cells of OC cell lines, while miRNA-182 overexpression did not significantly affect CASC11 expression. Overexpression of CASC11 and miRNA-182 promoted cancer cell proliferation and inhibited cancer cell apoptosis. CONCLUSION: Therefore, CASC11 overexpression predicts poor prognosis and CASC11 regulates cell proliferation and apoptosis as well as microRNA-182 expression in ovarian carcinoma.

Soil acidification amendments change the rhizosphere bacterial community of tobacco in a bacterial wilt affected field.

Application of soil amendments has been wildly used to increase soil pH and control bacterial wilt. However, little is known about causal shifts in the rhizosphere microbial community of crops, especially when the field naturally harbors the disease of bacterial wilt to tobacco for many years due to long-term continuous cropping and soil acidification. In this study, biochar (CP), lime (LM), oyster shell powder (OS) and no soil amendment additions (Control; CK) were assessed for their abilities to improve the soil acidification, change the composition of rhizosphere soil bacterial communities and thus control tobacco bacterial wilt. The results showed that oyster shell powder significantly increased soil pH by 0.77 and reduced the incidence of tobacco bacterial wilt by 36.67% compared to the control. The Illumina sequencing -based community analysis showed that soil amendment applications affected the composition of rhizosphere bacterial community and increased the richness and diversity. In contrast, the richness and diversity correlated negatively to disease incidence. Using LEfSe analyses, 11 taxa were found to be closely related with disease suppression, in which Saccharibacteria, Aeromicrobium, and Pseudoxanthomonas could be potential indicators of disease suppression. Our results suggested that the suppression of bacterial wilt after the application of soil amendments (especially oyster shell powder) was attributed to the improved soil pH and increased bacterial richness and diversity.

The Variable Characteristics of Human Papillomavirus in Squamous Cell Carcinoma and Adenocarcinoma of Cervix in China.

OBJECTIVE: A hospital-based multicenter, retrospective study was conducted to compare the distribution of human papillomavirus (HPV) in squamous cell carcinoma (SCC) and cervical adenocarcinoma (CADC) in China. METHODS: Paraffin-embedded tissue blocks diagnosed as SCC and CADC across China were collected, as well as the total number of diagnosed invasive cervical cancer of the 9 selected centers. DNA enzyme immunoassay, reverse hybridization, and multiplex type-specific polymerase chain reaction were used for HPV genotyping. RESULTS: The ratios of CADC to SCC were increasing from 2005 to 2010, in parallel with HPV prevalence in CADC. In 630 patients with SCC (mean ± SD age, 45.40 ± 10.30) and 718 patients with CADC (mean ± SD age, 46.09 ± 10.59) recruited, HPV prevalence rates were 97.6% and 74.5%, respectively. Human papillomavirus viral load for SCC is significantly higher than that for CADC. Most common HPV types distributed in SCC and CADC were HPV-16 (78.5%, 75.1%-81.6%; 47.1%, 42.9%-51.3%), HPV-18 (8.0%, 6.1%-10.4%; 41.1%, 37.0%-45.3%), HPV-52 (2.3%, 1.4%-3.8%; 5.6%, 4.0%-7.9%), and HPV-45 (1.1%, 0.6%-2.3%; 3.9%, 2.6%-5.9%). Different diagnostic mean ± SD age for HPV-16/HPV-18 versus other high-risk HPV types were observed: SCC (44.5 ± 9.94 vs 51.0 ± 10.83, p < .05) and CADC (44.1 ± 9.44 vs 47.4 ± 10.41, p = .006). For HPV-negative cases, mean ± SD age was 46.1 ± 10.73 in SCC and 50.3 ± 11.85 in CADC, which were older than the positive (45.4 ± 10.31, 44.5 ± 9.64). HPV-16 and HPV-18 were the most frequent HPV types in both histological types, and HPV-18 was more frequent in CADC than in SCC. CONCLUSIONS: Human papillomavirus infection was identified more often in SCC than in CADC. Women with HPV-associated cancers, especially HPV-16/HPV-18, were of a younger age at diagnosis when compared with non-HPV-associated cancers.

Long non-coding RNA UCA1 modulates the glycolysis of cervical cancer cells by miR-493-5p/HK2.

Long noncoding RNAs (lncRNAs) are associated with tumor development and progression. LncRNA UCA1 (UCA1) recently has been reported to take part in cancer cell proliferation. However, the expression and underlying molecular mechanism of UCA1 in cervical cancer cell glycolysis is unclear. This study aimed to investigate the role of UCA1 in cervical cancer. In order to explore the role of UCA1 in cervical cancer, first, the expression levels of UCA1 in cervical cancer tissues were measured, and the results showed that UCA1 levels were higher in cancer tissues compared to matched adjacent normal tissues. The inhibition of UCA1 expression suppressed human cervical cancer cell proliferation and glycolysis. Additionally, our experimental results indicated that UCA1 could directly bind to miR-493-5p and regulate miR-493-5p expression in an inverse manner. Namely, UCA1 could reverse the inhibitory effect of miR-493-5p on cervical cancer cells' proliferation and glycolysis. Moreover, we revealed that HK2 is a target gene of miR-493-5p through a Targetscan prediction. It was verified that miR-493-5p downregulated HK2 mRNA and protein levels using real time RT-PCR and Western blotting. In a summary, this study demonstrated that UCA1 functioned as an oncogene by UCA1/miR-493-5p/HK2 axis in cervical cancer.

Legacy effects of continuous chloropicrin-fumigation for 3-years on soil microbial community composition and metabolic activity.

Chloropicrin is widely used to control ginger wilt in China, which have an enormous impact on soil microbial diversity. However, little is known on the possible legacy effects on soil microbial community composition with continuous fumigation over different years. In this report, we used high throughput Illumina sequencing and Biolog ECO microplates to determine the bacterial community and microbial metabolic activity in ginger harvest fields of non-fumigation (NF), chloropicrin-fumigation for 1 year (F_1) and continuous chloropicrin-fumigation for 3 years (F_3). The results showed that microbial richness and diversity in F_3 were the lowest, while the metabolic activity had no significant difference. With the increase of fumigation years, the incidence of bacterial wilt was decreased, the relative abundance of Actinobacteria and Saccharibacteria were gradually increased. Using LEfSe analyses, we found that Saccharibacteria was the most prominent biomarker in F_3. Eight genera associated with antibiotic production in F_3 were screened out, of which seven belonged to Actinobacteria, and one belonged to Bacteroidetes. The study indicated that with the increase of fumigation years, soil antibacterial capacity may be increased (possible reason for reduced the incidence of bacterial wilt), and Saccharibacteria played a potential role in evaluating the biological effects of continuous fumigation.

PIK3CA mutations and downstream effector p-mTOR expression: implication for prognostic factors and therapeutic targets in triple negative breast cancer.

Although PIK3CA mutations and phosphorylated mTOR (p-mTOR) expression are two main events on PI3K/Akt/mTOR pathway, limited data has reported their roles in triple negative breast cancer (TNBC). Thus, we evaluated the associations of these two biomarkers and clinicopathological characteristics and prognosis in large Chinese TNBC patients. Immunohistochemistry (IHC) analysis was used to assess p-mTOR expression level in 218 TNBC patients. Direct sequencing was applied to detect the most important hotspot regions in exons 9 and 20 of PIK3CA gene. In the TNBC cohort, mutations were identified in 11.5% cases which were associated with basal-like subtype. The somatic point mutations were independently associated with worse overall survival (HR=0.400, 95% CI: 0.193-0.830, P=0.014). As for p-mTOR expression, 47.7% of the tumors were positive and the staining was shown in cytoplasm, nuclear and perinuclear areas. There were significant differences observed in tumor size, lymph node status, and clinical stage between p-mTOR positive and p-mTOR negative cases. Notably, we found a significant association between p-mTOR expression and PIK3CA mutations. Patients with p-mTOR staining also demonstrated shorter overall survival (HR=0.710, 95% CI: 0.514-0.980, P=0.037). Therefore, PIK3CA mutations and its downstream effector p-mTOR expression were two important regulators for activating the PI3K/Akt/mTOR pathway. Both of them could be served as adverse prognostic biomarkers and may contribute to the targeted therapy for TNBC patients with poor outcome.

Using community analysis to explore bacterial indicators for disease suppression of tobacco bacterial wilt.

Although bacterial communities play important roles in the suppression of pathogenic diseases and crop production, little is known about the bacterial communities associated with bacterial wilt. Based on 16S rRNA gene sequencing, statistical analyses of microbial communities in disease-suppressive and disease-conducive soils from three districts during the vegetation period of tobacco showed that Proteobacteria was the dominant phylum, followed by Acidobacteria. Only samples from September were significantly correlated to disease factors. Fifteen indicators from taxa found in September (1 class, 2 orders, 3 families and 9 genera) were identified in the screen as being associated with disease suppression, and 10 of those were verified for potential disease suppression in March. Kaistobacter appeared to be the genus with the most potential for disease suppression. Elucidating microbially mediated natural disease suppression is fundamental to understanding microecosystem responses to sustainable farming and provides a possible approach for modeling disease-suppressive indicators. Here, using cluster analysis, MRPP testing, LEfSe and specific filters for a Venn diagram, we provide insight into identifying possible indicators of disease suppression of tobacco bacterial wilt.

Random biopsy in colposcopy-negative quadrant is not effective in women with positive colposcopy in practice.

AIM: To assess the efficacy of random biopsy in diagnosing those high-grade squamous intraepithelial lesions or carcinomas (HSIL+) missed by colposcopy-directed biopsy, and to identify the scenarios of cervical cancer screening when random biopsy is necessary. PATIENTS/INTERVENTIONS: Data from 1997 women who participated in the Shanxi Province Cervical Cancer Screening Study I (SPOCCS I) were reviewed. Each woman received human papillomavirus (HPV) testing with the second-generation hybrid capture, liquid-based cytology, four-quadrant biopsy and endocervical curettage. The final diagnosis was based on the most severe pathological result obtained. The efficacy of random biopsy and colposcopy-directed biopsy was evaluated on the basis of the final pathological results. RESULTS: For women with severe cytological abnormalities (HSIL+) and negative colposcopy, the yield of HSIL+ diagnosed by random biopsy was 25%. On the other hand, the yield of HSIL+ diagnosed by random biopsies in the negative quadrant was no more than 4% when the colposcopy was positive, regardless of the cytological findings. For women with negative HPV, no HSIL+ was found by random biopsy. For women with severe cytological abnormalities (HSIL+) and positive HPV, the yield of HSIL+ diagnosed by random biopsy was 35% when colposcopy was negative. For women with low-grade intraepithelial lesion (LSIL) and positive HPV, the yield of HSIL+ diagnosed by random biopsy was 12.5% when colposcopy was negative. CONCLUSION: Random biopsy is not effective in the negative quadrant in women with positive colposcopy, but should be performed in women with cytological HSIL+ but negative colposcopy, or in those with cytological LSIL or HGSL+ and positive HPV but negative colposcopy.

[Value of 4-quadrant biopsies under colposcopy for detecting precancerous lesions in cervical cancer screening].

OBJECTIVE: To evaluate the value of colposcopical 4-quadrant biopsies for detecting precancerous lesion in cervical cancer screening. METHODS: We used the data of a cross-sectional screening study in 1999, in which 1,997 women received cervical cancer screening in Xiang Yuan County, Shanxi province. The sensitivity, specificity and accuracy of both 4-quadrant biopsy and colposcopy directed biopsy to detect high-grade or more severe squamous intraepithelial lesions (HSIL+) were calculated. RESULTS: 1,784(89.3%) women who received 4-quadrant biopsies and endocervical curettage were negative. 127(6.4%) women were diagnosed as LSIL, 74(3.7%) women as HSIL and 12(0.6%) cases of squamous cell carcinoma. 1,478(74.0%) women who received biopsies in the sites of abnormal lesions were negative, 463(23.2%) cases of LSIL, 41(2.1%) cases of HSIL, 15(0.8%) cases of squamous cell carcinoma. The positive rate was 26.0%(519/1,997) for colposcopy, and the coincidence rate was 73.7% with pathological diagnosis. Sensitivity and specificity were 81.4% and 76.5% of colposcopy for HSIL+. In total of 519 women were found to be with any abnormal colposcopic appearance. The consistency rate between 4-quadrant biopsies and suspicious lesion-directed biopsies was 96.3%. By suspicious lesion-directed biopsy alone, 14.8% cervical lesions were miss-diagnosed, of which 8.6%(5/58) cases of total HSIL and 24.1%(14/58) cases of all LSIL. CONCLUSIONS: 4-quadrant biopsy can detect more HSIL+ lesions and is more accurate than suspicious lesion biopsy alone. As an important triage technique to detect cervical precancerous lesions, it can improve the detection rate of HSIL+ lesions in cervical cancer screening.

[p16 and PR immunoreactivity and human papillomavirus infection in endocervical adenocarcinoma].

OBJECTIVE: The aim of this study was to investigate the characteristics of p16 and PR immunoreactivity and HPV infection in endocervical adenocarcinoma. METHODS: Paraffin blocks of 62 patients with endocervical adnocarcinoma treated in the Cancer Institute and Hospital, Chinese Academy of Medical Sciences from year 2005 to year 2010 were collected. p16 and PR immunostaining and HPV detecting by SPF-10 PCR were conducted on all cases. RESULTS: HPV infection rate of the 62 endocervical adnocarcinoma cases was 74.2% with four cases combined with CIN3. Among the 46 HPV-positive cases, there were 22 cases of HPV18 infection (47.8%), 14 cases of HPV16 infection (30.4%), one case of HPV59 infection (2.2%). and nine multiple HPV infection cases (19.6%). The mean age of the 16 HPV-negative cases was (49.6 ± 10.5)year, while the mean age of the 46 HPV-positive cases was (42.8 ± 9.7)year, showing a significant difference between the two subgroups (P = 0.022). The positive rate of p16 infection was 80.6%. Association analysis showed that the results of p16 and HPV test were independent to each other (P = 0.077). The positive rate of PR was 3.2%. Among the 62 cases, there were 24 cases containing normal cervical glands, with 19 cases PR-positive in the normal cervical glands and the positive rate was 79.2%. The difference of PR positivity between neoplastic glands and normal glands was statistically significant by Chi-square test (P < 0.01) . CONCLUSIONS: The HPV infection rate of endocervical adnocarcinoma is 74.2%, and the major subtypes were HPV16 and HPV18 infection. p16 immunoreactivity in endocervical adenocarcinoma maybe not the proof of high-risk HPV-related neoplasm. PR staining can be used as a reference designator to differentiate between neoplastic and normal cervical glands.

[Modified approach to difficult vaginal hysterectomy].

OBJECTIVE: To explore the advantage, feasibility and safety of modified approach to difficult vaginal hysterectomy and provide scientific rationales for expanding its indications. METHODS: A retrospective study was conducted for 237 patients undergoing hysterectomy for benign disease of uterus (without prolapse) from January 2009 to July 2012. Both modified approach to difficult vaginal hysterectomy (TVH, n = 167) and abdominal hysterectomy (TAH, n = 70) were performed. Two groups were compared for epidemiological, clinical characteristics, operative duration, intraoperative blood loss volume, perioperative and postoperative complications, hospitalization duration, inflammatory response and follow-up outcomes. TVH was divided into 3 subgroups of enlarged uterus (n = 100), prior pelvic surgeries/endometriosis history (n = 25) and complicated cases with multiple factors (n = 42). Then the surgical outcome parameters were compared for each group. RESULTS: The operative duration, intraoperative blood loss volume and blood transfusion amount were significantly less in the TVH group than those in the TAH group (P < 0.05). No major perioperative complications occurred in either group. There was no conversion from TVH into TAH. Inflammatory response, gastrointestinal recovery and hospitalization duration for the TVH group were significantly shorter than those of the TAH group (P < 0.05). The hospitalization expense was almost the same in two groups (P > 0.05). Postoperative complications and the quality of sexual health were not statistically different between two groups at 1 month and 6 months post-operation (P > 0.05). The data of three TVH subgroups were collected. The complicated cases with multiple factors group had longer hospitalization duration than the enlarged uterus and the prior pelvic surgeries/endometriosis history groups (P < 0.05). Similarly the volume of blood loss in the complicated cases with multiple factors group was significantly more than those of other two groups (P < 0.05). CONCLUSION: As one kind of mini-invasive surgery with less complications, higher safety and feasibility, modified approach to difficult vaginal hysterectomy offers shorter operative duration, less volume of blood loss and faster recovery.