Risk factors that affect the treatment of interstitial cystitis using intravesical therapy with a dimethyl sulfoxide cocktail.

INTRODUCTION AND HYPOTHESIS: Dimethyl sulfoxide (DMSO) bladder instillation is a standard therapy for interstitial cystitis (IC); however, there are varying degrees of success. We hypothesize that first-line intravesical therapy with a DMSO cocktail will optimize treatment outcome. METHODS: Ninety women with newly diagnosed IC were enrolled consecutively for the treatment. The IC symptom and problem index was used as an outcome measure. RESULTS: Six (6.7%) patients dropped out of the treatment due to intolerable bladder irritation. Fifty-five (65.5%) of the remaining 84 patients, who completed the treatment, experienced ≧50% symptomatic improvement. After a regression analysis, three clinical variables were found to affect treatment adversely, i.e., the presence of advanced cystoscopic glomerulations, microscopic hematuria, and urodynamic detrusor underactivity, respectively. CONCLUSIONS: Our results suggest bladder instillation with a DMSO cocktail may well be considered as first-line therapy for IC patients. However, there exists a subgroup of nonresponders who may have severe disease.

Genetic polymorphism of the plasminogen activator inhibitor-1 is associated with an increased risk of endometrial cancer.

BACKGROUND AND OBJECTIVES: To investigate the association of uPA system genes, including uPA, uPA receptor (uPAR), and plasminogen activator inhibitor (PAI)-1 gene polymorphisms, with risk of endometrial cancer. METHODS: In the present case control study, we enrolled a total of 134 patients with endometrial cancer confirmed by histopathology and 302 unrelated healthy individuals. Genetic polymorphisms of uPA system genes, including uPA rs4065 C/T SNP, uPAR rs344781 T/C SNP, and PAI-1 rs1799889 4G/5G SNP were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping analysis. RESULTS: Frequency of PAI-1 rs1799889 4G/4G genotype and 4G allele differed significantly between patients with endometrial cancer (36.6% and 61.6%, respectively) and healthy individuals (25.5% and 52.2%, respectively). Individuals with PAI-1 rs1799889 4G/4G genotype were at higher risk of endometrial cancer (OR = 2.26; 95% CI: 1.20-4.27). Stratification analysis showed individuals with PAI-1 rs1799889 4G/4G genotype were at elevated risk for endometrioid type (OR = 2.49; 95% CI 1.27-4.88), low stage (stages I-II) endometrial cancer (OR = 2.34; 95% CI 1.21-4.52). However, no significant differences in uPA C/T SNP, uPAR T/C SNP genotypes were observed between endometrial carcinoma cases and controls. CONCLUSIONS: Individuals with PAI-1 rs1799889 4G/4G genotype were at significantly higher risk of endometrial cancer in this study.

Clinical parameters associated with unsatisfactory specimens of conventional cervical smears.

Although The Bethesda System 2001 attempted to standardize the criteria for specimen adequacy, much confusion still exists, which includes the significance of unsatisfactory smears, the causes and clinical conditions related to unsatisfactory smears, and the appropriate management of unsatisfactory smears. The aim of this study is to find out the clinical factors associated with unsatisfactory cervical smears. We reviewed the medical charts of patients who received conventional Pap smears between March 2006 and August 2006 in a tertiary care center. After excluding 378 cases with incomplete demographic data, the clinical data of 7,059 cases were processed for analysis. Clinical parameters retrieved included: history of pelvic malignancy, pelvic irradiation, conization, hysterectomy, pregnancy status, within 3-months postpartum. Vaginal bleeding, abnormal vaginal discharge, intrauterine device, and cervical polyps found during pelvic examinations were also documented. The 1,397 cases with history of pelvic irradiation, pelvic malignancy, and hysterectomy were excluded. Finally, 5,662 cases were enrolled for data analysis. The relationship between clinical parameters and unsatisfactory smears were analyzed by Pearson's chi-square test with Yates' continuity correction and multivariate binary logistic regression test. The incidence of unsatisfactory smears was 4.5% (252/5,662). Clinical parameters correlated with unsatisfactory smears were postpartum status (OR = 1.92, 95% CI = 1.23-3.01, P = 0.004), vaginal bleeding (OR = 2.02, 95% CI = 1.30-3.16, P = 0.002), and endocervical polyps (OR = 2.62, 95% CI = 1.39-4.947, P = 0.003). In conclusion, if any of these parameters are noted prior to obtaining a Pap smear, optimal collecting devices, better sampling techniques, and liquid-based cytology should be considered to decrease the incidence of unsatisfactory smears.

Should adequacy criteria in cervicovaginal cytology be modified after radiotherapy, chemotherapy, or hysterectomy?

BACKGROUND: The general criterion of an unsatisfactory Papanicolaou (Pap) test in the 2001 version of the Bethesda system is not applicable to patients after treatment with radiotherapy, chemotherapy, or hysterectomy. The current study was performed to determine whether specimen adequacy criteria for Pap tests should be modified for these conditions. METHODS: Consecutive patients who underwent conventional Pap tests between March and August 2006 were reviewed. The original reports were done according to the 2001 Bethesda system, with cellularity criteria modified in patients with a history of radiotherapy, chemotherapy, or hysterectomy. The slides of these patients were reviewed again. The degrees of cellularity, obscuring red blood cells, and inflammation were recorded. RESULTS: The final analyses included 7033 patients for which there were complete data. The original interpretation was unsatisfactory in 4.4% of all samples. When the 1337 slides obtained from patients with a history of radiotherapy, chemotherapy, and/or hysterectomy were reviewed using the general satisfactory threshold of >8000 squamous cells/slide and <75% of the epithelium obscured, the incidence of unsatisfactory Pap tests increased from 4.3% to 13.2% (176 of 1337 slides). The odds ratios for unsatisfactory Pap tests for a history of radiotherapy, chemotherapy, and age >50 years were 2.70, 2.51, and 1.39, respectively. The majority of unsatisfactory Pap tests were because of low cellularity. The lower limits of adequate cellularity after radiotherapy or chemotherapy can be set at 2000 cells/slide, which can lower the unsatisfactory rate while at the same time resulting in no increase in the false-negative rate. Hysterectomy alone was not found to be associated with unsatisfactory Pap tests. CONCLUSIONS: In patients who received pelvic radiotherapy or chemotherapy, the incidence of low-cellularity Pap tests was unacceptably high. A lower cellularity (estimated 2000 cell/slide) could be used as a satisfactory threshold.

Temporary cross-clamping of the infrarenal abdominal aorta during cesarean hysterectomy to control operative blood loss in placenta previa increta/percreta.

OBJECTIVE: To evaluate the efficacy and safety of temporary cross-clamping of the infrarenal abdominal aorta for controlling operative blood loss during cesarean hysterectomy in severe invasive placentation. CASE REPORT: A 35-year-old woman with a significant risk factor of four previous cesarean sections and placenta previa was referred to Taichung Veterans General Hospital with suspected abnormal placentation at 37 weeks of gestation. Obstetric ultrasonography and magnetic resonance imaging showed a bulky inhomogeneous placenta with extensive uterine serosa-bladder interface hypervascularity and suspicious focal bladder invasion. Cesarean hysterectomy was performed with the use of temporary cross-clamping of the infrarenal abdominal aorta. The duration of aortic cross-clamping was 1 hour, and the estimated blood loss was 2,000 mL. The patient was discharged home on postoperative day 11 with no postoperative sequelae. CONCLUSION: With this limited experience, we are encouraged by the apparent reduction in operative blood loss after the use of temporary cross-clamping of the infrarenal abdominal aorta during cesarean hysterectomy. Further investigation is needed to determine the efficacy and safety of this procedure.

Tissue-engineered fascia from vaginal fibroblasts for patients needing reconstructive pelvic surgery.

INTRODUCTION AND HYPOTHESIS: Mesh-augmented reconstructive surgery for pelvic organ prolapse (POP) does not meet clinical expectations. A tissue-engineered fascia equivalent needs to be developed. METHODS: Human vaginal fibroblasts (HVFs) from 10 patients were characterized in vitro. Eligible HVFs and a biodegradable scaffold were used to fabricate a fascia equivalent, which was then transplanted in vivo. RESULTS: The cultured HVFs were divided into high (n = 6) or low (n = 4) collagen I/III ratio groups. Cells of the high-ratio group exhibited significantly higher proliferation potential than those of the low-ratio group (P < 0.05). A fascia equivalent was made with HVFs of the high-ratio group. In the subsequent animal study, a well-organized neo-fascia formation containing HVFs could be traced up to 12 weeks after transplantation. CONCLUSIONS: Our results suggest that a tissue-engineered fascia could be developed from HVFs in vitro and in vivo, which might be an effective treatment for POP in the future.

Matrix metalloproteinase-7 (MMP-7) polymorphism is a risk factor for endometrial cancer susceptibility.

BACKGROUND: The goal of our study was to evaluate the influence of genetic polymorphisms of matrix metalloproteinases (MMP)-2, MMP-3 and MMP-7 on susceptibility to endometrial cancer. METHODS: In the present study, we enrolled a total of 118 patients with endometrial cancer confirmed by histopathology, and 229 unrelated healthy individuals. Polymorphism for the MMP-2 (rs2285053), MMP-3 (rs3025058) and MMP-7 (rs11568818) genes was genotyped by polymerase chain reaction-restriction enzyme length polymorphism. RESULTS: The frequencies of MMP-7 -181 G/G and A/G genotypes were found to be significantly higher in cancer patients compared with healthy controls (p = 0.017). Stratification showed that individuals with MMP-7 -181 G allele were at increased risk for endometrial cancer when >50 years of age [odds ratios (OR) = 2.03; 95% confidence interval (CI) 1.21-3.39], endometrioid (OR = 1.80; 95% CI 1.11-2.92), low (stage I-II) (OR = 1.73; 95% CI 1.05-2.83) or high stage (stage III-IV) (OR = 2.69; 95% CI 1.16-6.24). Compared with the A/A genotype, the A/G + G/G genotype modified the risk of developing endometrial carcinoma and significance was detected in patients over 50 years old, and those with endometrioid type and high stage endometrial cancer. However, no significant difference in MMP-2 (-735 C/T) and MMP-3 (6A/5A) genotypes was observed between endometrial carcinoma cases and controls. CONCLUSIONS: This is the first report on the association of MMP-2, MMP-3 and MMP-7 gene polymorphisms in endometrial cancer. Our results suggest that individuals with the MMP-7 -181 G/G and A/G genotype may have an increased risk of developing endometrial cancer.

Genetic polymorphism of the tissue inhibitor of metalloproteinase-1 is associated with an increased risk of endometrial cancer.

BACKGROUND: Tissue inhibitors of metalloproteinases (TIMPs) are a family of multifunctional proteins known to possess a broad range of biological activities involved in tumorgenesis and mRNA expression of TIMP family members has been shown to be upregulated in numerous cancers and correlates with clinical outcomes. We investigated the association of TIMP-1 and TIMP-2 gene polymorphism with risk of endometrial cancer. METHODS: In the present case-control study, we enrolled a total of 118 endometrial cancer patients confirmed by histopathology and 229 unrelated healthy individuals. Polymorphism for TIMP-1 (_372C>T) and TIMP-2 (_418G>C and _303C>T) genes was genotyped by PCR-RFLP. RESULTS: Frequency of TIMP-1_372C/C genotype and 372-C allele differed significantly between patients with endometrial cancer (38.1% and 56.4% respectively) and healthy individuals (22.7% and 44.1% respectively). Individuals with TIMP-1_372 C/C genotype were at higher risk of endometrial cancer (OR=2.37; 95%CI: 1.33-4.22). Stratification analysis showed that individuals with TIMP-1_372 C/C genotype were at increased risk for endometrioid (OR=2.46; 95% CI 1.34-4.53) and low stage (stages I-II) endometrial cancer (OR=3.24; 95% CI 1.22-4.13). However, no significant differences in TIMP-2_418G>C and TIMP-2_303C>T genotypes were observed between endometrial carcinoma cases and controls. CONCLUSION: Individuals with TIMP-1_372C/C genotype were at significantly higher risk of endometrial cancer.

Prenatal detection of bladder wall involvement in invasive placentation with sequential two-dimensional and adjunctive three-dimensional ultrasonography.

OBJECTIVE: The purpose of this study was to determine the diagnostic capability of sequential two-dimensional (2D) and adjunctive three-dimensional (3D) ultrasonography (US) in identifying the location and extent of placental invasion of the bladder. MATERIALS AND METHODS: Forty-five patients at risk of placenta previa were examined sequentially with 2D US and then with a targeted scan of the region of interest with adjunctive 3D US to determine whether those patients suspected of having advanced invasive placentation by conventional ultrasonographic evidence had placental invasion of the bladder. The images were coded as positive, negative or indeterminate (equivocal) for bladder invasion. Follow-up postoperative outcomes were obtained. RESULTS: Seven of the 45 patients exhibited characteristic ultrasonographic findings for placenta increta/percreta. Among these seven patients with advanced invasive placentation, a targeted scan with adjunctive 3D US correctly provided additional corroborative information to the 2D US indeterminate diagnosis in patients who were found with variable degrees of bladder wall involvement at surgery. CONCLUSION: 3D US may be a useful adjunctive tool in refining 2D ultrasonographic techniques to identify the extent and degree of placental invasion of the bladder. The advantages of 3D US are: (1) a multiplanar image display allows viewing of sections from sagittal, coronal and axial planes at the same time, thereby more accurately determining the location and extent of placental invasion; (2) the viewing planes of the spatial angioarchitecture network can be arbitrarily manipulated to better delineate the aberrant vessels protruding into the bladder; (3) 3D reconstruction images can be clearly displayed by live 3D in a rotation mode for a better illustrative effect.

Prenatal diagnosis of extrastructurally abnormal chromosomes: clinical experience and literature review.

BACKGROUND: To evaluate the clinical association of extrastructurally abnormal chromosomes (ESACs) with pregnancy outcome based on the cytogenetic characteristics of the ESACs. METHODS: We retrospectively reviewed 12 ESAC cases identified from 12,991 cases who received genetic amniocentesis between January 1983 and March 2008. Prenatal ultrasound findings, characteristics of ESACs (karyotypes, special features, origin, inheritance) and pregnancy outcomes were recorded. RESULTS: The prenatal prevalence of ESACs was 0.092% (12/12,991). Of the 12 ESAC cases, all were de novo. Seven (58.3%) originated from nonacrocentric chromosomes and the other 5 (41.7%) were from acrocentric chromosomes, with 3 originating from chromosome 15. Six of the 12 cases (50%) were large ESACs; however, the other 6 (50%) were medium to small ESACs. All acrocentric ESACs contained dicentric and bisatellite characteristics. Using FISH and SKY techniques, the origins of 2 cases (patients 10 and 12) were clearly identified to be from chromosomes 15 and 10, respectively. Five of the 12 ESAC cases (41.7%) had congenital anomalies found by prenatal ultrasound. All were nonacrocentric in origin that were medium (1/5) to large (4/5) in size. After prenatal genetic counseling, 8 of the 12 (66.7%) couples opted to terminate the pregnancy. The other 4 (33.3%) continued the pregnancy and their babies were delivered at term normally and were followed-up, with normal development ranging from 2 to 17 years. CONCLUSION: With sophisticated cytogenetic characterization and ultrasound examination, it is possible to precisely categorize most fetuses with ESACs as being either at high risk of abnormality or at a relatively low risk.

Mitochondria transfer can enhance the murine embryo development.

PURPOSE: To evaluate the effect of mitochondrial transfer on embryonic development. MATERIALS AND METHODS: Mitochondria concentrates were collected from murine hepatocytes and fertilized murine zygotes from young and older mice in the 2PN stage were subjected to mitochondrial transfer and cultured in vitro to evaluate the embryonic development. RESULTS: After extended in vitro culture, 37.65% and 20.91% embryos from the young mice developed to the blastocyst stage in the injected and control groups respectively, which is statistically significant. There was no difference in terms of hatching rates (1.76% and 1.82% respectively). Zygotes from the older mice (>20 weeks old) that received mitochondrial transfer also had a better developmental outcome than the control group (54.35% and 18.92% developed to morula stage, 43.48% and 8.11% developed to the blastocyst stage respectively), which is statistically significant. CONCLUSIONS: Our results for the murine model provide direct scientific evidence that mitochondrial transfer improves embryonic development. However, potential risks such as mitochondrial heteroplasmy, nuclear-mitochondrial interaction and epigenetic aspects all deserve further evaluation before mitochondrial transfer is applied clinically.

Prenatal diagnosis and perinatal management of maternal-fetal congenital parvovirus B19 infection.

OBJECTIVE: In nonimmune pregnant woman, the primary infection with parvovirus B19 may lead to transplacental transmission to the fetus with variable outcomes, including congenital anemia, hydrops fetalis, fetal death or spontaneous resolution. CASE REPORT: The first case was of a 28-year-old woman, gravida 2, para 1, whose fetus was found to have left-sided pleural effusion on a sonogram at 29 weeks of gestation. A sample of aspirated pleural fluid was positive for parvovirus B19 by polymerase chain reaction. Cordocentesis showed fetal hemoglobin level of 5.0 g/dL. Intraperitoneal transfusion (IPT) was performed, because access to the fetal circulation was difficult. Thirty milliliters of group O, Rh-positive packed red cells were transfused into the peritoneal cavity. A non-hydropic baby weighing 2,680 g was delivered at 33 weeks of gestation. The neonates complete blood count examination showed a hemoglobin level of 16.3 g/dL. The newborn baby was discharged in stable condition. The second case was of a 31-year-old woman, gravida 2, para 1, whose fetus was found to have ascites, hypertrophic cardiomyopathy, and placentomegaly on a sonogram at 23 weeks of gestation. An amniotic fluid sample was positive for parvovirus B19 DNA by polymerase chain reaction. Fetal ascites and hypertrophic cardiomyopathy gradually resolved after maternal iron supplementation and 2 weeks of intrauterine digitalization therapy. A healthy infant weighing 3,198 g was delivered at 37 weeks of gestation. The neonates complete blood count examination showed a hemoglobin level of 10.3 g/dL. CONCLUSION: Termination of pregnancy is rarely indicated, because B19 virus is not teratogenic. Although intravascular transfusion offers obvious theoretical advantages, in some cases in which access to the fetal circulation is difficult or impossible, IPT should be performed combined with appropriate medical treatment. Thus, there is still a place for IPT in modern management of the severely anemic fetus, and this technique should not be neglected.

Nasopharyngeal carcinoma during pregnancy.

OBJECTIVE: Nasopharyngeal carcinoma, particularly during pregnancy, rarely comes to medical attention before it spreads to the regional lymph nodes. CASE REPORT: We report a 26-year-old Taiwanese woman who suffered from persistent headache and purulent nasal discharge during mid-pregnancy. Magnetic resonance imaging examination showed a large soft tissue mass measuring 3 x 2 x 2 cm in the left nasopharynx at 31 weeks of gestation. Punch biopsy of the tumor was done, and the histopathologic report revealed poorly differentiated, non-keratinizing type of squamous cell carcinoma (T4N2M0). A female infant weighing 1,790 g was delivered by cesarean section at 33 weeks of gestation with Apgar scores of 5 and 8 at 1 and 5 minutes, respectively. The patient received chemotherapy and radiation therapy after delivery. She was disease-free for 3 years. Subsequently, the patient delivered a second healthy infant weighing 3,084 g in a consecutive pregnancy, with a 3-year birth interval. Her first and second child showed normal psychomotor development at 3 years and 6 months of age, respectively. CONCLUSION: The possibility of rare nasopharyngeal carcinoma should be considered in any pregnant woman with presenting symptoms of persistent headache and abnormal nasal discharge, and a detailed thorough investigation is indicated. Successful pregnancy outcome can be achieved after tailored use of a combination of chemotherapy and radiotherapy.

Transitional cell carcinoma of the ovary.

OBJECTIVE: Transitional cell carcinoma (TCC) of the ovary is a rare, recently recognized, subtype of ovarian surface epithelial cancer. We present a case of TCC of the ovary, managed by staging operation and followed by postoperative chemotherapy with carboplatin and cyclophosphamide. CASE REPORT: A 67-year-old postmenopausal woman presented with a 2-year history of progressive enlargement of an abdominal mass. Pelvic sonography and abdominal computed tomography showed a pelvic mass measuring 210 x 165 x 203 mm. The serum CA-125 titer was also elevated (65.01 U/mL). A staging operation with total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy and pelvic lymph node dissection was performed. After surgery, the pathologic report of the left ovarian tumor was TCC, grade 2-3, stage IA. The patient then underwent four cycles of postoperative chemotherapy with carboplatin and cyclophosphamide. CA-125 levels declined to within the normal range after the first cycle of chemotherapy. CONCLUSION: TCC of the ovary is a rare subtype of epithelial ovarian cancer. It differs from malignant Brenner tumor by the absence of a benign or borderline Brenner component. Surgical resection is the primary therapeutic approach, and patient outcomes after chemotherapy are better than for other types of common epithelial ovarian cancers.

Cardiotocographic and Doppler ultrasonographic findings in a fetus with brain death syndrome.

OBJECTIVE: The diagnosis of brain death syndrome by cardiotocography (CTG) and Doppler ultrasonography (US) is reported in a fetus at 35 weeks of gestation. CASE REPORT: A 23-year-old, gravida 2, para 0, woman was referred to our hospital because of the absence of fetal movements. CTG showed fixed fetal heart rate (FHR) pattern. A detailed Doppler US examination of the fetus showed extensive cystic lesions of both cerebral hemispheres, polyhydramnios, total absence of neuromuscular parameters of biophysical profile (BPP) and the cessation of cerebral blood flow. Umbilical cord artery blood gas analysis showed pH 7.3, PaO2 30 mmHg and PaCO2 35 mmHg. A floppy male infant weighing 2,450 g was delivered vaginally at 36 weeks of gestation and the Apgar scores were 1 and 1 at 5 and 10 minutes, respectively. The neonate died 2 days after delivery. Postmortem examination of the brain showed diffuse, anoxic changes with multicystic encephalomalacia in both hemispheres and the brain stem. No other maternal or placental abnormalities were seen. CONCLUSION: The possibility of intrauterine brain death should be considered in all cases of prolonged fixed FHR pattern, accompanied by absence of neuromuscular parameters of BPP, polyhydramnios and demonstrated cessation of cerebral blood flow by Doppler US. Increased awareness of this event may prevent unnecessary emergency cesarean section.