Prognostic nomogram for overall survival in stage IIB-IVA cervical cancer patients treated with concurrent chemoradiotherapy.

OBJECTIVE: On the basis of outcome data from concurrent chemoradiotherapy (CCRT) for locally advanced cervical squamous cell carcinoma, the authors developed a nomogram for predicting survival outcome. STUDY DESIGN: Two hundred fifty-one eligible patients with International Federation of Gynecology and Obstetrics stage IIB-IVA squamous cell carcinoma of the uterine cervix who underwent CCRT were included for the construction of the nomogram. Predictor variables included age, serum squamous cell carcinoma antigen, tumor size, parametrium invasion, hydronephrosis, bladder/rectum invasion, and lymph node metastases. Internal validation of the nomogram was performed. RESULTS: A nomogram for predicting the 5 year overall survival for these patients was constructed on the basis of a Cox regression model from 7 parameters. The concordance index was 0.69. CONCLUSION: This nomogram is a predictive tool, upon external validation, that can be used to counsel patients in predicting outcomes. The discriminatory ability of the nomogram indicates that this population should not be considered homogeneous with respect to risk of death.

Physiology and potential application of NKT cells: a minireview.

CD1d-restricted T (NKT) cells are potent regulators of autoimmunity, tumor immunity, and transplantation-related immunity. NKT cells are a subset of innate lymphocytes that recognize endogenous or exogenous glycolipids in the context of CD1d molecules. Recent progress in the research of NKT cells has proved that NKT cells function as a bridge between innate and adaptive immunity in anticancer immunity. Furthermore, NKT cells also function as a bridge to tolerance or rejection of grafts in organ transplantation. Harnessing the function of NKT cells, and trying to put it into clinical application in the treatment of autoimmune disease, anticancer cell immunotherapy, and organ transplantation are the dreams of immunologists. This minireview will focus on the physiology of NKT cells and potential clinical application.

Importance of delivered cycles and nomogram for intraperitoneal chemotherapy in ovarian cancer.

OBJECTIVE: Intraperitoneal (IP) chemotherapy has gained enthusiasm in the treatment of ovarian cancer. Despite having a better survival advantage than intravenous (IV) chemotherapy, IP chemotherapy still poses significant morbidity and complications. Identifying the subset of patients who could best benefit from IP chemotherapy, and those who would least benefit from this treatment, thus avoiding potential complications, is critical. METHODS: Between January 2001 and December 2007, 367 patients with stage III epithelial ovarian cancer underwent randomized trial for IP/IV chemotherapy were recruited to construct a nomogram, which is a graphical representation of Cox proportional hazards model adopting six weighted risk factors including age, CA125, IP/IV delivery, stage, histology, and upper abdominal metastases. The nomogram was internally validated for discrimination and calibration. The concordance index was used for quantifying the predictive ability of overall survival with bootstrapping to correct for bias. RESULTS: The cycles of completed IP chemotherapy had an impact on overall survival (> or =5 vs. < or =4 cycles, P=0.02). A nomogram for predicting median survival and 5-year survival probability was constructed with a concordance index of 0.72. Upper abdominal tumor metastases (P<0.001) and colon resection (P=0.02) predicted increased chances for early discontinuation of IP chemotherapy. CONCLUSIONS: At least five IP cycles are needed to achieve better survival. Nomogram can help to identify the subset of patients who can least benefit from IP chemotherapy, thus avoiding potential IP complications and help to facilitate discussion between patient and physician, risk stratification, and help to guide clinical care.

Estimating the long-term clinical impact of cervical cancer vaccination in Taiwan.

The high burden of human papillomavirus (HPV) infection and subsequent cervical cancer in the presence of screening in Taiwan suggests the need for further prevention strategies. Epidemiology and screening practices vary considerably between countries, and specific analyses are required to estimate the impact of HPV vaccination. This study adapted a computer-based health economic model to Taiwan to project the clinical impact of the introduction of a prophylactic vaccine against persistent HPV 16/18 infection on cervical disease. A Markov model based on the natural history of HPV and cervical cancer was developed to simulate transitions between health states (normal, HPV, cervical intraepithelial neoplasia [CIN] stages I to III, cervical cancer stages I to IV, and death) in the presence of screening. The model was calibrated to Taiwan epidemiological end points including age-specific HPV prevalence, prevalence of CIN lesions, and predicted cervical cancer incidence and mortality. Taiwanese screening and treatment practices were modeled, and published clinical trial data were used to estimate vaccine efficacy. With 100% vaccine coverage in a 13-year-old cohort of females, there is estimated to be a 71% reduction in cervical cancer cases and deaths due to all HPV types and substantial reductions in the prevalence of precancerous lesions and screening outcomes. Removing the risk of HPV infection of a large proportion of Taiwanese females, with a high underlying cervical cancer incidence rate, would be expected to have dramatic effects on the health care system and mortality in Taiwan.

Regulatory T cells: potential target in anticancer immunotherapy.

The concept of regulatory T cells was first described in the early 1970s, and regulatory T cells were called suppressive T cells at that time. Studies that followed have demonstrated that these suppressive T cells negatively regulated tumor immunity and contributed to tumor growth in mice. Despite the importance of these studies, there was extensive skepticism about the existence of these cells, and the concept of suppressive T cells left the center stage of immunologic research for decades. Interleukin-2 receptor alpha-chain, CD25, was first demonstrated in 1995 to serve as a phenotypic marker for CD4+ regulatory cells. Henceforth, research of regulatory T cells boomed. Regulatory T cells are involved in the pathogenesis of cancer, autoimmune disease, transplantation immunology, and immune tolerance in pregnancy. Recent evidence has demonstrated that regulatory T cell-mediated immunosuppression is one of the crucial tumor immune evasion mechanisms and the main obstacle of successful cancer immunotherapy. The mechanism and the potential clinical application of regulatory T cells in cancer immunotherapy are discussed.

Laparoscopic uterosacral nerve ablation with and without presacral neurectomy in the treatment of primary dysmenorrhea: a prospective efficacy analysis.

OBJECTIVE: To evaluate the efficacy of laparoscopic uterosacral nerve (LUNA) alone vs. LUNA plus presacral neurectomy (PN) in the treatment of primary dysmenorrhea. STUDY DESIGN: Seventy-four patients were randomly allocated to LUNA alone or LUNA plus PN. Evaluation of severity of menstrual pain was based on multidimensional scoring. RESULTS: Sixty-seven patients were eligible for analysis (35 LUNA alone, 32 LUNA plus PN). Baseline demographic features were comparable between the 2 groups. There was no difference between them in the proportion of improvement in dysmenorrhea at 3 months of follow-up (69% for LUNA vs. 73% for LUNA plus PN, p = 0.923), and the results were maintained at 6 and 12 months of follow-up. More surgical complications were found in the LUNA plus PN group. CONCLUSION: For patients with primary dysmenorrhea, LUNA plus PN has no additive therapeutic advantage over LUNA alone, and more surgical complications may be encountered.

Efficacy analysis of trans-obturator tension-free vaginal tape (TVT-O) plus modified Ingelman-Sundberg procedure versus TVT-O alone in the treatment of mixed urinary incontinence: a randomized study.

OBJECTIVE: The treatment of women with mixed urinary incontinence still poses a great challenge. This study evaluated surgical outcomes of combined trans-obturator tension-free vaginal tape (TVT-O) and modified Ingelman-Sundberg (IS) procedure for the treatment of mixed urinary incontinence. METHODS: A randomized controlled trial was conducted. Ninety-six women diagnosed with mixed incontinence were randomized, with 49 allocated to TVT-O plus IS and 47 to TVT-O alone. A baseline urodynamic study and evaluation of quality of life (QOL) was conducted. The primary outcome measure was objective assessment of surgical outcomes, and the secondary outcome measure was warning time. RESULTS: Objective surgical response rate was significantly higher in the TVT-O plus IS group than in the TVT-O alone group (84.8% vs. 62.8%; p=0.019). Furthermore, a significant increase in warning time was observed in the TVT-O plus IS group (from 3.9 to 9.4 min; p=0.006), but the increase in warning time within the TVT-O alone group was not statistically significant (from 4.3 to 4.5 min; p=0.695). Postoperative complications were similar in the two study groups with respect to pelvic hematoma, nerve injury, sepsis, mesh erosion, and fistula formation. However, fever occurred more frequently in the TVT-O plus IS group (30.4% vs. 20.9%; p=0.026). CONCLUSIONS: Mixed urinary incontinence can potentially be treated with a one-step combined surgery using trans-obturator sling plus modified IS procedure. Although surgical time and blood loss were significantly increased in the TVT-O plus IS group, overall morbidity was not significantly increased.

Primary dysmenorrhea and risk of preterm delivery.

Little is known about the mechanism and biochemical pathway of preterm delivery. Some drugs used to treat preterm labor are also useful for the treatment of primary dysmenorrhea. This study attempted to evaluate the association between primary dysmenorrhea and preterm delivery from an epidemiological perspective. A nested case-control study was conducted; 329 singleton preterm delivery cases were investigated, in aggregate and in subgroups (spontaneous preterm labor and preterm premature rupture of membranes). Concurrently, 329 singleton gravid women with term delivery served as controls. Medical charts and records provided information about the maternal history of dysmenorrhea, index pregnancy outcome, and demographic characteristics. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using the multiple logistic regression method. Gravid women with a history of primary dysmenorrhea had no more risk of preterm delivery than those without a history of primary dysmenorrhea (adjusted OR, 1.16; 95% CI, 0.95 to 2.19; p=0.37). However, for subgroup analysis, gravid women with severe primary dysmenorrhea were associated with an adjusted 2.73-fold risk of spontaneous preterm delivery (95% CI, 1.49 to 4.95; p=0.02), and with an adjusted 1.51-fold risk of preterm premature rupture of membranes (95% CI, 0.68 to 3.22; p=0.31). Severe primary dysmenorrhea is associated with an increased risk of spontaneous preterm delivery. A common pathophysiologic pathway may exist between these two disorders. Further in-depth biochemical and molecular studies are necessary to explore this phenomenon.

Natural progression of menstrual pain in nulliparous women at reproductive age: an observational study.

BACKGROUND: Menstrual pain can be alleviated after childbirth. The purpose of this observational study was to evaluate the natural progression of menstrual pain among nulliparous women at their reproductive age. METHODS: A questionnaire-based study of perimenopausal women with a history of primary dysmenorrhea was performed. The study subjects were recruited between July 1, 2001 and June 30, 2005. Severity of menstrual pain was graded using a multidimensional scoring system. RESULTS: A total of 247 nulliparous women with primary dysmenorrhea were enrolled, and of these, 218 patients were eligible for analysis. Patients who had more frequent intercourse (p = 0.016), fewer associated systemic symptoms (p = 0.028), and use of oral contraceptive pills (p = 0.039) tended to have a higher chance of an improvement in dysmenorrhea after age 40. Multidimensional scoring distribution over chronologic age revealed that patients had significantly improved menstrual pain after 40 years of age. CONCLUSION: For nulliparous women with primary dysmenorrhea, the severity of menstrual pain decreased significantly after age 40. More studies are needed to explore this phenomenon from a biochemical or molecular basis.

Treatment of primary deep dyspareunia with laparoscopic uterosacral nerve ablation procedure: a pilot study.

BACKGROUND: This pilot study was undertaken to evaluate the effect of laparoscopic uterosacral nerve ablation (LUNA) for treatment of primary deep dyspareunia. METHODS: Between July 2002 and June 2003, 12 consecutive patients diagnosed with primary deep dyspareunia were treated with the LUNA procedure. The evaluation scoring system included the Hospital Anxiety and Depression Scale and the revised Sabbatsberg Sexual Rating Scale, done at baseline and 3, 6, and 12 months after LUNA. RESULTS: At the initial 3-month follow-up period, 3 patients were very satisfied with their treatment, 5 were satisfied, 2 uncertain, 1 dissatisfied, and 1 very dissatisfied. The corresponding figures at the 12-month follow-up visit were 2, 4, 4, 1, and 1, respectively. Overall, 8 (66.7%) patients in this trial were very satisfied or satisfied at the initial postoperative evaluation and 6 of them (50.0%) remained satisfied at the final evaluation. CONCLUSION: Over half of the study patients felt satisfied with the results of treatment with LUNA. Further prospective controlled clinical trials are mandatory to validate its effectiveness.

Impact of pregnancy on primary dysmenorrhea.

OBJECTIVE: Because it has been observed that dysmenorrhea can improve after childbirth, this investigation was intended to quantify the impact of both gestational length and mode of delivery on primary dysmenorrhea. METHODS: This is an 8-year prospective observational study. Patients with a history of dysmenorrhea who later gave birth were evaluated for improvement on the severity of dysmenorrhea, with use of visual analogue scale (VAS), and Likert-type scale. RESULT: Final analysis involved 3694 patients. Women who had spontaneous delivery would have significantly more improvement than women with cesarean delivery per VAS (term delivery, 51 vs. 33, P<0.001; preterm delivery, 17 vs. 10, P<0.001). For first delivery, patients in the spontaneous delivery subgroup were the most likely to have improvement in severity of dysmenorrhea. For second delivery, only patients in the spontaneous delivery subgroup had statistically significant improvement. CONCLUSION: Both length of gestation and mode of delivery have an impact on primary dysmenorrhea. The most significant improvement occurred after the first delivery.

Successful treatment of deep dyspareunia and primary dysmenorrhea with laparoscopic uterosacral nerve ablation (LUNA) procedure.

Deep dyspareunia, often described as pain resulting from pelvic thrusting during sexual intercourse, is relatively common and has many causes. To date, feasible surgical interventions for deep dyspareunia are very rare. The two procedures which have been mentioned in the literature for the treatment of deep dyspareunia were laparoscopic uterosacral ligament ablation (LUNA) and uterine ventrosuspension. We report the case of a young female patient, aged 32, gravida 3, parity 2, presenting with deep dyspareunia and primary dysmenorrhea for 4 years. She had both subjective and objective improvements for dyspareunia and primary dysmenorrhea following LUNA operation. Further large-scaled randomized controlled trial is mandatory to verify the surgical effect of LUNA operation for patients with deep dyspareunia.

Combined diverticulectomy and anti-incontinence surgery for patients with urethral diverticulum and stress urinary incontinence: is anti-incontinence surgery really necessary?

OBJECTIVE: Urethral diverticulum has been identified in 0.6-6% of women and is diagnosed most frequently in the third to fifth decades. Combined diverticulectomy and anti-incontinence surgery are usually undertaken for patients with urethral diverticulum who present with symptoms of stress urinary incontinence. However, this approach may not always be necessary. CASE REPORT: We report two cases with urethral diverticulum and stress urinary incontinence successfully treated with diverticulectomy only. CONCLUSION: This clinical approach could avoid the potential complications of anti-incontinence surgery.