Prognostic factors and adjuvant therapy on survival in early-stage cervical adenocarcinoma/adenosquamous carcinoma after primary radical surgery: A Taiwanese Gynecologic Oncology Group (TGOG) study.

OBJECTIVE: We aimed to identify prognostic factors of early-stage cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC) treated with primary radical surgery, and to evaluate the impact of postoperative adjuvant therapy on outcome. METHODS: The clinical-pathological data of all patients (n = 1132) with stages I-II cervical AC/ASC treated with primary radical surgery at the member hospitals of the Taiwanese Gynecologic Oncology Group were retrospectively reviewed. RESULTS: In multivariate analysis, stage II, deep stromal invasion (DSI), lymphovascular space invasion (LVSI), positive pelvic lymph node (PLN), and parametrial involvement (PI) were significant factors for recurrence-free survival (RFS), while only DSI, PI, and positive PLN were independent factors for cancer-specific survival (CSS). Low- and high-risk groups were defined by prognostic scores derived from the four factors (DSI, LVSI, positive PLN, PI) selected by internal validation. Postoperative adjuvant therapy significantly improved outcome for PLN-positive patients (RFS, p = 0.014; CSS, p = 0.016), but not for PLN-negative high-risk group because of higher mean prognostic score (p = 0.028) of adjuvant+ than adjuvant- patients. CONCLUSIONS: PLN metastasis, PI, DSI, and LVSI were independent prognostic factors. Prospective studies of postoperative adjuvant therapy with prognostic score and nodal status stratification for cervical AC/ASC are necessary.

Correlation of chitinase 3-like 1 single nucleotide polymorphisms and haplotypes with uterine cervical cancer in Taiwanese women.

BACKGROUND: This study aimed to investigate the relationships of chitinase 3-like 1 (CHI3L1) single nucleotide polymorphisms (SNPs) and haplotypes with the development of uterine cervical cancer in Taiwanese women. The SNPs frequencies and haplotypes were also correlated with the clinicopathologic variables of cervical cancer, cancer recurrence, and patient survival. METHODOLOGY AND PRINCIPAL FINDINGS: Ninety-nine patients with invasive cancer and 61 with pre-cancerous lesions of the uterine cervix were compared to 310 healthy control subjects. Three SNPs rs6691378 (-1371, G/A), rs10399805 (-247, G/A) and rs4950928 (-131, C/G) in the promoter region, and one SNP rs880633 (+2950, T/C) in exon 5 were analyzed by real time polymerase chain reaction and genotyping. The results showed that the mutant homozygous genotype AA of CHI3L1 SNP rs6691378 and AA of rs10399805, and haplotypes AACC and AACT increased the risk of developing pre-cancerous lesions and invasive cancer. The patients with these risk haplotypes had higher than stage I tumors, larger tumors, and vaginal invasion. In logistic regression model, they also tended to have poor survival event [p = 0.078; odds ratio (OR): 2.99, 95% confidence interval (CI): 0.89-10.08] and a higher probability of recurrence event (p = 0.081; OR: 3.07, 95% CI: 0.87-10.81). There was a significant association between the CHI3L1 risk haplotypes and probability of recurrence (p = 0.002; hazard ratio: 6.21, 95% CI: 1.90-20.41), and a marginal association between the risk haplotypes and overall survival (p = 0.051; hazard ratio: 3.76, 95% CI: 0.99-14.29) in the patients with SCC, using Cox proportional hazard model. CONCLUSION: The CHI3L1 SNPs rs6691378 and rs10399805 and CHI3L1 haplotypes all correlated with the development of cervical pre-cancerous lesions and invasive cancer. The cervical cancer patients with the CHI3L1 haplotypes AACC or AACT had poor clinicopathologic characteristics and poor recurrence and survival events. These risk haplotypes were associated with higher recurrence, especially in the patients with SCC.

Primary treatment and prognostic factors of carcinosarcoma of the ovary, fallopian tube, and peritoneum: a Taiwanese Gynecologic Oncology Group Study.

OBJECTIVE: This study aimed to determine the clinical prognostic factors involved in carcinosarcoma of the ovary, fallopian tube, and peritoneum. MATERIALS AND METHODS: This retrospective study was undertaken by the Taiwanese Gynecologic Oncology Group. The retrieved clinical data included demographic characteristics, medical disease, tumor status, extent of surgery, and adjuvant chemotherapy. RESULTS: In total, 63 patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum were identified. Sixty-one patients with complete data were enrolled for further data analysis. The mean follow-up period was 1.0 year, and the mean overall survival was 15.4 months. By log-rank tests, age, menopausal status, parity, hypertension, diabetes, primary tumor size, para-aortic lymph node metastasis, pretreatment CA-125, preceding diagnostic surgery, hysterectomy, lymphadenectomy, other surgeries, and paclitaxel use were not predictive of overall survival.Omentectomy, no gross residual implants after surgery, platinum treatment, and no pelvic lymph node metastasis had a trend toward better survival. Early diagnosis at stage I and cisplatin/ifosfamide regimen were significant associated with a better overall survival in log-rank and simple Cox regression tests. Bilateral ovarian tumors and metastatic tumors larger than 2 cm were significantly associated with a poorer overall survival. CONCLUSIONS: Early diagnosis at stage I, unilateral ovarian tumor, metastatic tumors less than 2 cm, and cisplatin/ifosfamide regimen were predictive of a better survival.Omentectomy and complete debulking surgery also showed a trend toward better survival. Thus, these treatment strategies should be applied in patients with carcinosarcoma of the ovary, fallopian tube, and peritoneum.

Interleukin-6 as an early chronic inflammatory marker in polycystic ovary syndrome with insulin receptor substrate-2 polymorphism.

PROBLEM: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder. This study was to evaluate whether insulin receptor substrate (IRS)-2 Gly1057Asp polymorphism influences chronic inflammatory parameters in Taiwanese patients with PCOS. METHOD OF STUDY: DNA was extracted from whole blood samples for genotyping and detection of IRS-2 Gly1057Asp polymorphism in 129 PCOS women and 109 control women. Ninety-seven PCOS women accepted metformin treatment for 3 months, and low-grade chronic inflammatory markers were assessed. RESULTS: The levels of IL-6 were significantly elevated in PCOS women compared with normal women. Among allelic variant of IRS-2, concentrations of IL-6 were greater in IRS-2 homozygous Asp population. Treatment with metformin significantly reduced IL-6, especially in PCOS patients with IRS-2 homozygous Asp variant. CONCLUSION: The results showed that IL-6 may be an early low-grade chronic inflammatory marker among PCOS patients with IRS-2 polymorphism in Taiwanese population. This pharmacologic study in IRS-2 polymorphism may provide more information for preventing long-term complications in PCOS.

Chromosomal imbalances in lung adenocarcinomas with or without mutations in the epidermal growth factor receptor gene.

BACKGROUND AND OBJECTIVE: Epidermal growth factor receptor (EGFR) mutations are common in lung adenocarcinomas of Asian patients, implying a good response to treatment with the EGFR tyrosine kinase inhibitors, gefitinib and erlotinib. However, the distinct chromosomal imbalances between lung adenocarcinomas with and those without EGFR mutations have not been fully elucidated. METHODS: Seventy-seven patients of surgically resected lung adenocarcinoma were analysed for the EGFR exon 19 deletion and the L858R mutation, using mutant-enriched PCR, and for chromosomal imbalance alterations using comparative genomic hybridization. RESULTS: EGFR mutations were detected in 42 (54.5%) patients, including 22 with the exon 19 deletion and 20 with the L858R mutation. The mean number of chromosomal arms with imbalance alterations was significantly higher in tumours with EGFR mutations than in those lacking these two mutations. The minimal regions with gain on 1q23-q31, 6p12-p21.1 and 7q11.2, and loss on 3p21, 8p22-p23, 9q33, 10q25 and 13q13, differed significantly between lung adenocarcinomas with or without EGFR mutations. However, neither EGFR mutations, nor any of the common chromosomal imbalance alterations alone, exhibited significant associations with tumour stage or disease-specific survival of the patients. CONCLUSIONS: These results indicate that imbalance alterations at several chromosomal regions occur significantly more frequently in lung adenocarcinomas with EGFR mutations than in those without such mutations. Tumour growth-related genes in these chromosomal regions should be further investigated to improve our understanding of the common genetic alterations in lung adenocarcinomas with EGFR mutations.

Chromosomal gain of 3q and loss of 11q often associated with nodal metastasis in early stage cervical squamous cell carcinoma.

BACKGROUND/PURPOSE: Cervical cancer remains a health problem among women worldwide. Delineation of genetic changes is critical to understanding the molecular basis of tumor progression, as well as for identifying genetic markers for early identification of patients at high risk for a poor outcome. METHODS: To provide comparative genomic hybridization data for cervical squamous cell carcinoma in Taiwan, and to gain further insight into genetic markers associated with lymph node metastasis of this disease, we performed comparative genomic hybridization analysis of 30 consecutive cases of cervical squamous cell carcinoma (24 stage IB and 6 stage IIB). RESULTS: The results disclosed that higher staged tumors or those with lymph node metastasis had more chromosomal imbalances. The commonly recurrent chromosomal imbalances were gains of 3q (46.7%), 1q (36.7%) and 8q (20.0%) and losses of 11q (36.7%), 3p (33.3%), 6q (23.3%), and 2q (20.0%). The frequencies of these chromosomal imbalances in stage IB and IIB tumors did not differ significantly. However, when compared with tumors without lymph node metastasis, the loss of 11q14-q22 (5/9 vs. 3/21, p = 0.019) and gains of 3q11-q22 and 3q26-qter (6/9 vs. 5/21, p = 0.026) were significantly more prevalent in tumors with lymph node metastasis. CONCLUSION: The results suggest that certain tumor-associated genes residing on 3q and 11q warrant further investigation to elucidate their role in the progression of this disease.

Major complications of operative gynecologic laparoscopy in southern Taiwan: a follow-up study.

STUDY OBJECTIVES: This follow-up study examined the major complications among 4307 operative gynecologic laparoscopies. The overall complication rate and each individual category were compared with those of our previous study period. The clinical outcome and salvage procedures were correlated with the time of recognition and the severity of initial procedures in the individual injury type. DESIGN: Retrospective, comparative study based on medical record reviewing (Canadian Task Force classification II-3). SETTING: Tertiary teaching hospital, Chi Mei Foundation Hospital in southern Taiwan. PATIENTS: Records of women (n = 4307) aged 40.5 +/- 11.7 years (mean +/- SD [95% CI 40.1-40.5]) who underwent operative gynecologic laparoscopies from January 2000 through February 2006 were reviewed in this study. The complications were compared with those of our previous study based on 1507 laparoscopies performed between December 1992 and November 1999 for follow-up comparison. INTERVENTIONS: Gynecologic laparoscopic surgeries. MEASUREMENTS AND MAIN RESULTS: Thirty-four complications occurred in 31 patients requiring repair procedures, 3 of whom had multiple complications, with an overall complication rate of 0.72% (31/4307). There were 13 bladder injuries (0.30%), 7 bowel injuries (0.16%), 3 cases of internal bleeding (0.07%), 4 vaginal stump hematomas or abscesses (0.09%), 3 ureteral injuries (0.07%), 3 major vessel injuries (0.07%), and 1 trocar site hematoma (0.02%). In addition, there were 125 (2.88%) postoperative blood transfusions without additional operative intervention. The major complication rate decreased compared with that of the previous study (0.72% [95% CI 0.51%-1.02%] vs 1.59% [95% CI 1.07%-2.36%]; p = .005). The overall complication rates were not significantly different between laparoscopic hysterectomy (LH) group and non-LH group. However, bladder injury happened more frequently in the LH group, whereas bowel injury was more common in the non-LH group. In addition, the severity of the original injury, timing of recognition, and accompanying salvage procedures correlated with the clinical outcomes. CONCLUSION: The significantly decreased major complication rate, as compared with that of our previous study period, confirms the importance of experience accumulation and use of preventive maneuvers in reducing the complication rate. There were no significant differences among the individual injury category during these 2 study periods. The manifestations of bowel injury were highly variable and individualized. The accumulation of surgical experience with the aid of preventive maneuvers is helpful to reduce the complication rate significantly.

Expression patterns of the DAZ-associated protein DAZAP1 in rat and human ovaries.

OBJECTIVE: To evaluate the expression of DAZAP1 (deleted in azoospermia-associated protein 1) in rat and human ovaries. DESIGN: Experimental study. SETTING: University hospital. PATIENT(S): Twelve corpus luteum (CL) specimens were collected during operation, either by laparoscopic surgery for CL rupture or by laparotomy for benign gynecologic conditions. INTERVENTION(S): Surgical excision of 12 human CL. MAIN OUTCOME MEASURE(S): Proteins analyzed by immunohistochemical staining, Western blotting, and co-immunoprecipitation experiments. RESULT(S): DAZAP1 is expressed in rat and human luteal cells. Expression of DAZAP1 decreases with advancing stages of CL. Co-immunoprecipitation experiments show in vivo interaction of DAZ-like (DAZL) protein with DAZAP1 in the ovarian tissues. CONCLUSION(S): The expression patterns of DAZAP1 and DAZL are identical within rat and human ovaries. In mammalian species, DAZAP1 may be involved in diverse reproductive functions, ranging from cell cycle regulation and maturation of oocytes to differentiation of luteal cells.

Molecular cytogenetics of ovarian granulosa cell tumors by comparative genomic hybridization.

OBJECTIVE: Patients with stage I granulosa cell tumors (GCTs) may occasionally develop metastasis, which is hard to predict using pathologic criteria. It is interesting to elucidate whether certain chromosomal imbalances (CIs), detected by comparative genomic hybridization (CGH), could be useful prognostic markers. METHODS: CGH was used to identify CI(s) in 37 adult-type GCTs from 36 women. Nonrandom CIs were compared with clinical and pathological features to evaluate their significance as a prognostic marker. RESULTS: Twenty-two (61%) of the 36 primary tumors had CIs. One woman's tumor showed identical CIs to another tumor that occurred in contralateral ovary 2 years later, supporting a metastatic nature. The nonrandom CIs included losses of 22q (31%), 1p33-p36 (6%), 16p13.1 (6%), and 16q (6%) and gains of 14 (25%), 12 (14%), and 7p15-p21 (6%). No tumor exhibited high-level amplification. The associations between each CI and pathological features, including the growth pattern, tumor size, and mitotic activity, were not evident. The only CI repeatedly detected in tumors with metastasis was monosomy 22, which presented in 2 of the 4 cases with metastasis but also in 2 of the 5 cases without recurrence for more than 5 years. CONCLUSIONS: Monosomy 22 was the most common CI in GCTs, which often coexisted with trisomy 14 (in 55% cases). Deletion of 22q seems to be, albeit not very specific, associated with the risk of early metastases of stage I disease. The role of loss-of-function mutation(s) of certain putative tumor suppressor gene(s) on 22q is worthy of further investigations.

Effects of laparoscopic ovarian drilling on young adult women with polycystic ovarian syndrome.

STUDY OBJECTIVE: To assess changes in serum hormone levels and ovarian stromal blood flow after laparoscopic ovarian drilling (LOD) in young adult women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, nonrandomized study (Canadian Task Force classification II-1). SETTING: Tertiary care, major teaching hospitals. PATIENTS: Anovulatory young women with PCOS who were resistant to clomiphene citrate. INTERVENTION: Laparoscopic ovarian drilling. MEASUREMENTS AND MAIN RESULTS: To evaluate the endocrinological effects of LOD, serum leptin, insulin-like growth factor-1, estrone (E1), and estradiol were measured before and after ovarian drilling in the early follicular phase. Three-dimensional transabdominal power Doppler examinations were performed to determine the effects of LOD. Serum leptin was correlated with body mass index (BMI) before LOD. Levels of BMI, fasting blood sugar, and leptin were higher and LH, LH/FSH, and the sugar/insulin ratio were lower in the obese group. There were significant decreases in the free androgen index, and total testosterone, luteinizing hormone (LH), and LH/follicle-stimulating hormone (FSH) levels, and a significant increase in sex hormonebinding globulin (SHBG) concentration in the 3 months after the operation. The vascularization index and vascularization flow index of the intraovarian stroma significantly decreased after treatment. Reversed correlations between leptin and LH, LH/FSH, E1, thyroid-stimulating hormone, and SHBG were noted 3 months after the operation compared with levels obtained before the operation. CONCLUSIONS: Treatment of young adult women with PCOS using LOD did not influence leptin levels but changed the ovarian stromal blood flow dynamics during short-term follow-up. The surgical procedure may be beneficial both to endocrine profiles and to intraovarian stromal flow in patients with PCOS.

New helical incision for removal of large uteri during laparoscopic-assisted vaginal hysterectomy.

The objective of our study was to evaluate the feasibility of a new incision technique for vaginal removal of large uteri during laparoscopic-assisted vaginal hysterectomy (LAVH). The helical uterine incision with uterine arteries preligation was performed during LAVH. The medical records for 522 women with uterine tumors who underwent LAVH from January 2001 through November 2003 were studied retrospectively. The mean uterine weight of all 522 patients was 325 +/- 213 g (range 32-1350 g), and the mean operation duration was 73 +/- 21 minutes. The patients were divided into three subgroups: patients with uteri weighing less than 300 g (group A), patients with uteri weighing between 300 and 500 g (group B), and patients with uteri weighing more than 500 g (group C). The mean uterine weight was 172 +/- 69 g, 374 +/- 56 g, and 678 +/- 181 g for groups A, B, and C, respectively; and the mean operation duration was 67 +/- 17 minutes, 73 +/- 19 minutes, and 90 +/- 24 minutes for groups A, B, and C, respectively. No linear relationship between uterine weight and operation duration was noted in the regression analysis and analysis of variance testing in group B. Uteri weighing between 300 and 500 g were extracted vaginally without difficulty using the new helical uterine incision technique. Use of the helical incision technique reduced operation duration, and restoration of the uterine anatomy for pathologic examination was made easily. The complication rate was 0.8%, which is relatively low compared with our previous report (1.38%) in 580 LAVH procedures. In conclusion, the helical transvaginal uterine incision proved to be an efficient and safe procedure for removal of large uteri during LAVH.

Preliminary results of laparoscopic modified radical hysterectomy in early invasive cervical cancer.

STUDY OBJECTIVE: To compare laparoscopic modified radical hysterectomy (LMRH) with traditional modified radical hysterectomy (MRH) in women with early invasive cervical cancer. DESIGN: Prospective, nonrandomized study (Canadian Task Force classification II-1). SETTING: Chi Mei Foundation Medical Center, Tainan, Taiwan. PATIENTS: Ten women with cervical cancer stage Ia2 to Ib1 (

Laparoscopic surgery for omental pregnancy.

A 16-year-old girl underwent emergency laparoscopic surgery for what was thought to be hematoperitoneum secondary to extrauterine pregnancy. During the operation, omental pregnancy was diagnosed and treated by laparoscopy. According to Studiford's criterion, this case can be classified as a primary omental pregnancy. When performing laparoscopy for suspected tubal pregnancy with no visible pathologic changes on either tube, careful evaluation of the whole abdominal cavity is necessary so as not to overlook an abdominal pregnancy.