Implementation of visual inspection with acetic acid and Lugol's iodine for cervical cancer screening in rural China.

OBJECTIVE: To address the value of visual inspection where HPV-based screening is not yet available, we evaluated the real-world effectiveness of visual inspection with acetic acid (VIA) and with Lugol's iodine (VILI) as a primary screening method for cervical cancer in rural China. METHODS: A total of 206 133 women aged 30-59 years received two rounds of VIA/VILI screening for cervical cancer in 2006-2010. Women with positive screening results underwent colposcopy and direct biopsy, and were treated if cervical intraepithelial neoplasia grade 2 or worse (CIN2+) was diagnosed. Clinical effectiveness of VIA/VILI was evaluated by process and outcome measures. RESULTS: The VIA/VILI positivity rate, biopsy rate and detection rate of CIN2+ in the second round were significantly lower than in the first round. The 2-year cumulative detection rate of CIN2+ varied from 0.53% to 0.90% among the four cohorts initiated in 2006, 2007, 2008, and 2009. The first round of screening detected 60%-83% of CIN2, 70%-86% of CIN3, and 88%-100% of cervical cancer. Over 92% of CIN2+ were found at the early stage. CONCLUSION: Multiple rounds of visual inspection with continuous training and quality assurance could act as a temporary substitutional screening method for cervical cancer in resource-restricted settings.

Claustrum modulates behavioral sensitivity and EEG activity of propofol anesthesia.

AIMS: The claustrum has long been regarded as a vital center for conscious control. Electrical stimulation or damage to the claustrum can result in decreased awareness or loss of consciousness, suggesting that the claustrum may be a target for the action of general anesthetics. This study aimed to determine the role of the claustrum in propofol anesthesia. METHODS: We first applied a fiber photometry calcium signal recording system to record the claustral neuronal activity during the entire process of propofol anesthesia. Chemogenetic activation of claustral neurones was then performed to verify their role in anesthesia. Finally, muscimol (GABAa receptor agonist) and gabazine (GABAa receptor antagonist) were microinjected into the claustrum to determine whether their GABAa receptors were involved in modulating propofol anesthesia. EEG and behavioral indicators, such as anesthetic sensitivity and efficacy, were recorded and analyzed. RESULTS: An evident anesthesia-related change in claustrum neuronal activity was suppressed during propofol-induced unconsciousness and restored following recovery from anesthesia. Chemogenetic activation of claustrum neurons results in attenuated propofol sensitivity, a shorter anesthesia duration, and an EEG shift toward wakefulness. Manipulation of GABAa receptors in the claustrum showed bidirectional control of propofol sensitivity, as activation decreases anesthesia efficiency while inactivation augments it. Additionally, inhibiting claustrum GABAa receptors increases cortical EEG slow waves. CONCLUSIONS: Claustrum neurones and their GABAa receptors are implicated in the modulation of propofol anesthesia in both behavioral and EEG assessments. Our findings create scope to reveal the brain targets of anesthetic action further and add to the existing evidence on the consciousness-modulating role of the claustrum.

ALOX12B promotes carcinogenesis in cervical cancer by regulating the PI3K/ERK1 signaling pathway.

Cervical cancer is a malignant disease and a threat to women's health worldwide. Surgical resection followed by radiotherapy or chemotherapy is the main treatment strategy for cervical cancer; however, patients with cervical cancer, especially those with late-stage disease, may not benefit from these traditional therapies, which results in poor clinical outcome. ALOX12B is a gene encoding lipoxygenase, and a mutation in ALOX12B was detected in lung and breast cancer. Furthermore, ALOX12B is essential to the proliferation of epidermoid carcinoma cells; however, the role of ALOX12B in cervical cancer has not been studied thus far, to the best of our knowledge. In the present study, the expression levels of ALOX12B were reduced in cervical cancer cells by lentiviral transfection, and it was found that both cell proliferation and clone formation ability were significantly reduced, and the cell cycle was blocked at G1 phase. Tumor growth was also suppressed in vivo in a xenograft tumor model, but the migration of tumor cells was not affected by ALOX12B. Subsequently, using western blotting, it was demonstrated that knockdown of ALOX12B decreased the expression levels of PI3K, MEK1, ERK1, C-fos and cdc25. Meanwhile, overexpression of ALOX12B increased the expression levels of these five molecules. Conclusively, ALOX12B promoted cell proliferation in cervical cancer via regulation of the PI3K/ERK1 signaling pathway. The present study may improve our understanding of the molecular mechanisms underlying the function of ALOX12B in cervical cancer and inform new therapeutic strategies.

[Application of transvaginal external fascia trachelectomy in the treatment of CIN and micro-invasive cervical cancer].

OBJECTIVE: To explore the feasibility and safety of transvaginal external fascia trachelectomy to conservatively treat patients with stage Ia1 squamous carcinoma of the uterine cervix (SCC) and cervical intraepithelial neoplasia (CIN) III, who are not suitable to take cold knife conization (CKC). METHODS: From July 2002 to September 2010, those patients who had a strong desire to preserve the uterus or fertility but also are confronted with following situations received transvaginal external fascia trachelectomy: CIN III with large area lesion (colposcopically observed lesion area was larger than 3/4 of the cervix), or patients with CIN II-III suffered recurrence or had persistent lesion or positive margin after CKC or LEEP, or patients with CIN II-III upgraded into stage Ia1 SCC through LEEP and pathological confirmation (except for those with lymphovascular space invasion), or CIN III patients complicated with upper vaginal intraepithelial neoplasia (VAIN). Their clinical information and data were reviewed and analyzed. RESULTS: Among the 79 cases, who underwent transvaginal external fascia trachelectomy, six were stage Ia1 SCC, 61 were CIN III with a large area lesion (23 cases had glandular involvement), three were CIN III complicated with VAIN, six were CIN III with persistent lesion after LEEP, two were CIN III with positive margins after LEEP, and one case had recurrence after conization. The median age of these patients was 33 years old, ranging from 23 to 40 years old. The mean operation time was 39 min (rang 20-60 min), the average amount of bleeding was 40 ml (rang 1-300 ml) and the mean hospital stay was 10 d ( rang 6-17 d). The CIN III patients complicated with VAIN received this surgery with resection of the adjacent vaginal mucosa more than 2 cm in 3.8% (3/79). The median follow-up time was 49 months (8-85 months) and none of these patients had ureteral injury or large amount of intraoperative or postoperative bleeding or post-operative recurrence. No patient complained any effect on their sexual life. Among the five patients with reproductive desire, one was at her 22 w gestation after one induced abortion and one spontaneous abortion, four patients experienced term birth in which three were cesarean section and one was natural labour. CONCLUSIONS: Transvaginal external fascia trachelectomy is a safe and effective conservative treatment for stage Ia1 SCC, CIN III with large area lesion, CIN III complicated with VAIN and CIN II-III suffering recurrence, persistent lesion or positive margins after CKC and others that are not suitable to take CKC.

Prevalence of human papillomavirus and cervical intraepithelial neoplasia in China: a pooled analysis of 17 population-based studies.

High-risk (HR) human papillomavirus (HPV) prevalence has been shown to correlate well with cervical cancer incidence rates. Our study aimed to estimate the prevalence of HR-HPV and cervical intraepithelial neoplasia (CIN) in China and indirectly informs on the cervical cancer burden in the country. A total of 30,207 women from 17 population-based studies throughout China were included. All women received HPV DNA testing (HC2, Qiagen, Gaithersburg, MD), visual inspection with acetic acid and liquid-based cytology. Women positive for any test received colposcopy-directed or four-quadrant biopsies. A total of 29,579 women had HR-HPV testing results, of whom 28,761 had biopsy confirmed (9,019, 31.4%) or assumed (19,742, 68.6%) final diagnosis. Overall crude HR-HPV prevalence was 17.7%. HR-HPV prevalence was similar in rural and urban areas but showed dips in different age groups: at age 25-29 (11.3%) in rural and at age 35-39 (11.3%) in urban women. In rural and urban women, age-standardized CIN2 prevalence was 1.5% [95% confidence interval (CI): 1.4-1.6%] and 0.7% (95% CI: 0.7-0.8%) and CIN3+ prevalence was 1.2% (95% CI: 1.2-1.3%) and 0.6% (95% CI: 0.5-0.7%), respectively. Prevalence of CIN3+ as a percentage of either all women or HR-HPV-positive women steadily increased with age, peaking in 45- to 49-year-old women. High prevalence of HR-HPV and CIN3+ was detected in both rural and urban China. The steady rise of CIN3+ up to the age group of 45-49 is attributable to lack of lesion removal through screening. Our findings document the inadequacy of current screening in China while indirectly raising the possibility that the cervical cancer burden in China is underreported.

Fabrication of hydroxyl group modified monodispersed hybrid silica particles and the h-SiO(2)/TiO(2) core/shell microspheres as high performance photocatalyst for dye degradation.

The monodisperse hybrid silica particles (h-SiO(2)) were firstly prepared by a modified sol-gel process and the surface was modified in situ with double bonds, then abundant carboxyl moieties were introduced onto the surface of the silica core via thiol-ene click reaction. Afterward, the h-SiO(2)/TiO(2) core/shell microspheres were prepared by hydrolysis of titanium tetrabutoxide (TBOT) via sol-gel process in mixed ethanol/acetonitrile solvent, in which the activity of TBOT could be easily controlled. The carboxyl groups on the surface of silica particles promote the formation of a dense and smooth titania layer under well control, and the layer thickness of titania could be tuned from 12 to 100nm. The well-defined h-SiO(2)/TiO(2) core/shell structures have been confirmed by electron microscopy and X-ray photoelectron spectroscopy studies. After calcination at 500°C for 2h, the amorphous TiO(2) layer turned into anatase titania. These anatase titania-coated silica particles showed good photocatalytic performance in degradation of methyl orange aqueous solution under UV light.

Human papillomavirus testing and cervical cytology in primary screening for cervical cancer among women in rural China: comparison of sensitivity, specificity, and frequency of referral.

The causal relationship between persistent high-risk human papillomavirus infection and cervical cancer is widely accepted. HR-HPV DNA testing, alone or in combination with Pap smear testing, may have a role in primary screening. The screening results (VIA, VILI, Pap, and HR-HPV DNA) of 9,057 women in rural China were analyzed to determine the screening performance for the detection of CIN3+. All screening strategies had comparable AUCs (0.9). Cotesting strategies had the overall highest sensitivity for CIN3+ (99.4%), followed by HR-HPV DNA testing alone (96.3%), Pap alone (80.2%), and reflex testing (75.4%). Reflex testing had the highest specificity (96.7%), followed by Pap alone (93.3%), HR-HPV DNA testing alone (85.5%), and both cotesting strategies (LSIL: 84.8%, HSIL: 84.8%). Of the single-test strategies, HR-HPV DNA testing had a higher sensitivity (96.3% vs. 80.2%) compared with Pap testing. The specificity of the Pap test was higher (93.3% vs. 85.5%) and it had a lower percent referred for colposcopy (7.8% vs. 15.8%) than HR-HPV DNA testing. HR-HPV DNA testing with a 10.0 cutoff point (relative light units/cutoff ratio) had a sensitivity (85.2%) and specificity (90.6%) estimate comparable to Pap testing. A single-test primary screening strategy with adequate performance would permit less frequent screening and be most appropriate. Of the primary screening strategies investigated in this setting in China, the performance of HR-HPV DNA testing with an increased cutoff-point might best meet these criteria.

[Efficacy of complications of different surgical treatments in cervical intraepithelial neoplasia III].

OBJECTIVE: To compare the rate of surgical complications and surgical failure of different surgical treatments in cervical intraepithelial neoplasia (CIN) III. METHODS: From Jan 2002 to Jun 2007, 1256 patients with CIN III confirmed by histopathologic punch biopsy and excision biopsy of cervical specimens were analyzed retrospectively. Among them, 74 patients accepted loop electrosurgical excision procedure (LEEP), 869 patients adopted cold knife conization (CKC), 49 patients received vaginal enlarged amputation of cervix, as well as 264 patients accepted external fascia hysterectomy, Chi-square test was used to compare the rate of surgical efficacy and complications of different surgical treatments. RESULTS: The surgical failure incidence of LEEP, CKC, vaginal enlarged amputation of cervix and external fascia hysterectomy were 4.1% (3/74), 0.2% (2/869), 0 and 0.4% (1/264) respectively, which was significantly higher in LEEP than that in CKC (P = 0.004) and external fascia hysterectomy (P = 0.034), while there was no statistical difference between CKC and external fascia hysterectomy (P = 0.549). The rate of surgical complications of LEEP, CKC, vaginal enlarged amputation of cervix and external fascia hysterectomy were 8.1% (6/74), 6.2% (54/869), 6.1% (3/49) and 2.3% (6/264) respectively, which were not statistically significant (P = 0.067) among them. CONCLUSION: LEEP, CKC, vaginal enlarged amputation of cervix and external fascia hysterectomy are all secure and effective procedures for patients with CIN III, who can take the individual choice depending on their different conditions.

Human papillomavirus type-distribution in cervical cancer in China: the importance of HPV 16 and 18.

Prophylactic vaccination against HPV 16 and 18 has the potential for effective prevention of high-grade precancer (cervical intraepithelial neoplasia [CIN)] 2/3) and ICC caused by these viruses (globally 50 and 70%, respectively) when employed in women prior to starting sexual activity. To provide data for decisions on HPV vaccination in China, we determined HPV type-distribution in ICC and CIN 2/3 from women of different regions within China. A multicenter study was conducted by randomized sampling of paraffin blocks of 664 ICC (630 squamous cell carcinoma [SCC]; 34 adenocarcinoma [ADC]), 569 CIN 2/3 cases from seven regions of China. Histological diagnosis was confirmed in 1,233 cases by consensus review. HPV DNA was detected using the SPF10 LiPA25 version 1 assay. HPV prevalence was 97.6% in SCC, 85.3% in adenocarcinoma, and 98.9% in CIN 2/3. HPV 16 (76.7%) and HPV 18 (7.8%) were the most common, together accounting for 84.5% of SCC, followed by HPV 31 (3.2%), HPV 52 (2.2%), and HPV 58 (2.2%). HPV positivity in SCC did not differ notably by region. However, SCC cases from women

[Analysis of 4223 hospitalized patients with cervical cancer during 1990-2007].

OBJECTIVE: To analyze the changes in epidemiology and treatment of hospitalized patients with cervical cancer during 1990-2007. METHODS: Overall, 4648 patients with cervical cancer were diagnosed in our hospital from Jan 1990 to Nov 2007, but only 4223 patients with initial treatment in our hospital were studied retrospectively. Pearson Chi-square test was used to compare the age, stage, histopathologic type and treatment methods between different times. RESULTS: (1) The mean age of cervical cancer patients gradually decreased over the past 18 years, from 54.4 years during 1990-1999 to 47.2 years during 2000-2007; the proportion of young patients aged < or = 35 years increased from 4.77% (89/1865) during 1990-1999 to 11.75% (277/2358) during 2000-2007. (2) The proportion of patients with cervical cancer (stage I a-II a) increased from 14. 32% (267/1865) during 1990-1999 to 40.75% (961/2358) during 2000-2007, whereas the proportion of patients with cervical cancer (stage II b-IV) decreased from 85.68% (1598/1865) during 1990-1999 to 59.25% (1397/2358) during 2000-2007. (3) There was no significant change in histopathologic type of cervical cancer, and squamous cell carcinoma of cervix remained the main type of cervical cancer. (4) The treatment pattern of cervical cancer changed significantly: radiotherapy was the main method (75.28%) for cervical cancer during 1990-1999, but during 2000-2007, it was replaced by concurrent chemoradiotherapy (35.79%). CONCLUSIONS: The proportion of young women with cervical cancer was increased during 1990-2007, and at the same period early stage cervical cancer increased, but late stage cervical cancer decreased. It is obvious that chemotherapy has become the important therapy in cervical cancer.

[Study of the risk factors for ovarian metastasis in patients with endometrial carcinoma].

UNLABELLED: OBJECTIVE To investigate the risk factors for ovarian metastasis and the possibility of ovarian preservation in patients with endometrial carcinoma. METHODS: The clinicopathological features of endometrial carcinoma patients who were diagnosed and treated initially with a surgical staging procedure from Jan 1997 to Dec 2006 in our hospital were retrospectively reviewed. RESULTS: Of the 638 cases reviewed, 36 (5.6%, 36/638) had ovarian metastasis. Univariate analysis revealed that histological type and grade, myometrial invasion, positive peritoneal fluid cytology, pelvic lymph node metastasis, invasion of parauterine, para-aortic node metastasis and invasion of uterine serosa were significantly associated with ovarian metastasis (P < 0.05); while age, lymph-vascular invasion and cervical invasion were not significantly associated with ovarian metastasis (P > 0.05). Factors predictive of ovarian metastasis by multivariate analysis were ranked as follows according to risk intensity: pelvic lymph node metastasis, positive peritoneal cytology, and histological grade. CONCLUSION: In young patients with grade 1 endometrioid carcinoma, with no pelvic lymph node metastasis, no para-aortic lymph node metastasis, no myometrial invasion and with negative peritoneal fluid cytology, ovarian preservation could be considered.

[Concurrent chemoradiotherapy versus radiotherapy in advanced cervical carcinoma].

BACKGROUND & OBJECTIVE: Cisplatin-based concurrent chemoradiotherapy has become the standard treatment modality for locally advanced cervical cancer. However, the optimal chemotherapy regimen combined with radiotherapy remains controversial. This study was to compare the therapeutic efficacy and toxicity of concurrent chemoradiotherapy with those of radiotherapy, and those among different regimens of concurrent chemoradiotherapy for stage IIB-IIIB cervical cancer. METHODS: From Jan. 2003 to Dec. 2004, 285 patients with stage IIB-IIIB cervical cancer treated in Maternal and Child Health Hospital of Jiangxi Province were randomly assigned to receive radiotherapy alone or concurrent chemoradiotherapy. According to different chemotherapy regimens, patients in the concurrent chemoradiotheapy group were randomly chosen to receive radiotherapy with chemotherapy of bleomycin and cisplatin (RT+BP), radiotherapy with chemotherapy of taxol and carboplatin (RT+TP), and radiotherapy with chemotherapy of 5-fluorouracil and cisplatin (RT+FP). The 3-year survival rates and toxicity of different groups were compared. RESULTS: After a median follow-up of 42 months, the 3-year survival was higher in the concurrent chemoradiotheray group (75%) than in the radiotherapy group (65%) (P=0.042). Acute treatment-related toxicity (grade III and IV) was higher in the concurrent chemoradiotherapy group than in the radiotherapy group (P<0.001); while the delayed treatment-related toxicity was similar in the two groups (P=0.613). The 3-year survival rates of BP, TP and FP chemoradiotherapy groups were 74%, 80% and 71%, without significant differences (P=0.792). Acute toxicities (grade III and IV) and delayed toxicities were similar among the three groups. CONCLUSIONS: Concurrent chemoradiotherapy significantly improves the survival for patients with stage IIB-IIIB cervical cancer compared to radiotherapy alone. Among the three chemoradiotherapy regimens, radiotherapy combined with taxol and carboplatin exerts a slightly higher 3-year survival than the other two regimens with tolerable toxicity.

[Clinical analysis of 48 patients with vaginal enlarged amputation of cervix].

OBJECTIVE: To evaluate the feasibility and safety of vaginal enlarged amputation of cervix to treat patients with cervical cancer of stage Ia1 and cervical intraepithelial neoplasia grade III (CIN III) who were unfit for conization surgery. METHODS: From July 2002 to May 2007, patients with cervical cancer at stage Ia1, diagnosed by pathology after loop electrosurgical excision procedure (LEEP), large area CIN III (the area of lesion>or=3/4 on colposcopy), CIN III coexisted with vaginal intraepithelial neoplasia (VAIN) in the superior segment of vagina, CIN II-III recurrence or with residual lesion, positive margin after conization of cervix, who wanted to preserve fertility and (or) corpus uteri were selected to receive vaginal enlarged amputation of cervix. RESULTS: Forty-eight cases including 5 with cervical cancer in stage Ia1, 38 with large area CIN III (9 with gland involvement), 2 with residual lesion and 2 with positive margin after LEEP, 1 recurrence after cold knife conization, received the procedure successfully. The median age was 34 years (range 27-40), median operation time was 60 minutes (range 30-100), median blood loss was 40 ml (range 5-300), and median hospital stay was 10 days (range 7-17). After follow-up 1-39 months, no patient had postoperative complications and recurrence, and all patients resumed normal menstrual cycle and sexual life. CONCLUSION: Vaginal enlarged amputation of cervix appears to be a safe and feasible procedure for patients with cervical cancer at stage Ia1 and CIN III who are unfit for conization surgery.

[Study on the value assessment of various screening programs regarding cervical cancer screening strategy in the rural areas of China].

OBJECTIVE: To evaluate the application value and feasibility of various cervical screening methods and to explore a rapid and efficient cervical cancer screening program for the women in the rural areas of China. METHODS: We sequentially conducted human papillomavirus (HPV) DNA test by hybrid capture-2 (hc2) with cervical cells, liquid-based thinprep cytology test (TCT), visual inspection with acetic acid (VIA), visual inspection with iodine (VILI), colposcopy respectively for the 2499 married women between 30 and 49 years from Xiushui county of Jiangxi province. All the detection methods were performed independently under double-blind design. Women who were diagnosed positive for having any VIA,VILI and colposcopy inspection or for those women who were diagnosed negative for VIA, VILI and colposcopy but with positive result of HPV or TCT test underwent cervical biopsy directly and endocervical curettage (ECC)when necessary. We performed cervical biopsy endocervical curettage within two weeks to observe the sensitive (SE), specificity (SP), negative predict value (NPV) and positive predict value (PPV) of these detection methods when used alone or combined each other, including HPV test, TCT inspection, VIA, VILI, and colposcopy, the pathological diagnosises of cervical tissue were confirmed by IARC (International Agency for Research on Cancer) while the cytological findings were underegone through the updated program of TBS (The Bethesda System) in 2001. RESULTS: A total of 2499 women underwent the screening and found 443 women who were diagnosed as HPV positive, 337 women with abnormal cervical cytology and 27 women with ASC-H, 157 cases with ASCUS; 103 cases with HSIL, 49 cases with LSIL and 1 cervical cancer. According to the pathological findings. There were 181 women diagnosed as cervical intraepithelial neoplasia (CIN) or cervical cancer, including 81 cases with CIN1 37 cases with CIN2,60 case cervical cancer. The sensitivity rates of HPV, TCT, HPV+ TCT, VIA, VILI, VIA+VILI and colposcopy were 96.67%, 89.47%, 97.98%, 56.57%, 36.36%, 63.64% and 39.39%, and the specificity rates were 85.00%, 96.91%, 86.97%, 94.60%, 96.23%, 92.97% and 98.14% respectively. CONCLUSION: HPV + TCT seemed to be more sensitive than other screening methods in the cervical cancer screening program.

[The usefulness of p16INK4a in cytological screening of cervical carcinoma].

OBJECTIVE: To evaluate the value of p16INK4a immuncytochemical examination in cytological screening of cervical carcinoma and precancerous lesions. METHODS: p16JNK4a immuncytochemical detection was performed on 220 specimens remaining from liquid-based cytology, followed up by biopsy histology , and compared with the results of high-risk human papillomavirus ( HR - HPV ) DNA tests . Results In patients with cytological diagnosis of squamous cell carcinoma( SCC) , high-grade squamous intraepithelial lesion (HSIL) , low-grade squamous intraepithelial lesion (LSIL) , atypical squamous cells-cannot exclude HSIL (ASC-H) , and atypical squamous cells of undetermined significance (ASC-US) , the positive rates of p16INK4a were 100.0% (7/7), 92. 2% (107/116) , 24. 3% (17/70) , 100. 0% (14/14) and 36.4% (4/ 11) , respectively. In 111 of the 150 p6INK4a positive cases, we found 97 (87.4% ) cases which had biopsy diagnosises of > or =CIN2, but none in 18 of 70 p16INK4a negative cases was. The difference in the positive rates for p16INK4a between cervical intraepithelial neoplasia (CIN) 1 and > or =CIN2 lesions had statistical significance (P < 0. 01) , whereas for HR-HPV DNA test it was not. CONCLUSION: p16LNK4a is over-expressed in a HSIL, and it may be useful in cytological screening of high risk patients.