Anti-tumor activity of histone deacetylase inhibitors and the effect on ATP-binding cassette in ovarian carcinoma cells.

INTRODUCTION: Ovarian cancer is of worldwide importance, and has a significantly high mortality rate due to therapy failure. Drug resistance might be one of most importance factors. Histone deacetylase inhibitors (HDACi) have been reported to be a new class of promising anti-tumor agents, thus this study aimed to investigate the effect of HDAC on the chemo-resistance genes of human ovarian carcinoma cell lines. METHODS: The expressions of ATP binding cassette (ABC) transporter genes, multidrug-resistant protein (MDR1) and multidrug resistance-associated proteins (MRP1 and 2) of ovarian cancer cell lines OC-109 and SK-OV-3 after HDACi treatment were determined. RESULTS: HDACi, including sodium butyrate (NaB), suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) reduced ovarian cancer cell viability from 4.4% to 68.8%, in both dose- and time-dependent manners. The effect of HDACi on MDR1, MRP1, and MRP2 showed induced expression of MDR1 mRNA, but reduced mRNA expression of MRP1 and MRP2. CONCLUSIONS: The effect of HDACi on the reduced viability of ovarian cancer cell lines, concomitant with the induced expression of MDR1 and reduced expression of MRP1 and 2, might provide additional benefits in the management of ovarian cancers in the future.

Whole-body positron emission tomography with 18F-fluorodeoxyglucose is an effective method to detect extra-pelvic recurrence in uterine sarcomas.

PURPOSE OF INVESTIGATION: To assess the clinical use of F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in the post-therapy surveillance of uterine sarcoma. METHODS: Eight whole-body FDG-PET studies were performed in seven women with previously treated uterine sarcoma. Conventional image studies (computed tomography) and physical examinations were performed for follow-up. All FDG-PET studies were indicated to localize suspected recurrences noted by conventional methods. RESULTS: The per case sensitivity of the FDG-PET studies and CT scans was 85.7% (6/7) and 100% (7/7), respectively (p = 0.174). FDG-PET was able to detect seven extrapelvic metastastic sites below the diaphragm (7/7, sensitivity: 100%), including the liver, spleen, paraaortic lymph node, spine and paracolic gutter, as well as pulmonary lesions in five patients, while the CT scan detected only three lesions (3/7, sensitivity: 42.9%; p = 0.070). FDG-PET detected only four recurrent pelvic lesions (4/6) and CT scan detected six (6/6) recurrent pelvic lesions (66.7% vs 100%, p = 0.455). CONCLUSIONS: The FDG-PET showed a better detection rate than the abdominal CT scan for extrapelvic metastatic lesions and a similar detection rate as well as abdominal CT scan. FDG-PET can serve as a useful detection tool for patients with uterine sarcomas because nearly 80% of recurrence involve an extrapelvic site.

Adenomyosis and risk of preterm delivery.

OBJECTIVE: To evaluate the risk of preterm delivery in patients with adenomyosis. DESIGN: A 1:2 nested case-control study. SETTING: Tertiary-care institution. POPULATION: A base cohort population of 2138 pregnant women who attended routine prenatal check-up between July 1999 and June 2005. METHODS: From this base cohort population, gravid women with singleton pregnancy who delivered prior to the completion of 37 weeks of gestation were identified and formed the study group. Singleton gravid women who had term delivery and who matched with age, body mass index, smoking, and status of previous preterm delivery were recruited concurrently and served as control group. Preterm delivery cases were further divided into spontaneous preterm delivery and preterm premature rupture of membranes (PPROM) cases. MAIN OUTCOME MEASURES: Risk analysis of preterm delivery between gravid women with and without adenomyosis. RESULTS: One-hundred and four preterm delivery case subjects and 208 control subjects were assessed. Overall, gravid women with adenomyosis were associated with significantly increased risk of preterm delivery (adjusted odds ratio 1.96, 95% CI 1.23-4.47, P=0.022). For subgroup analysis, gravid women with adenomyosis had an adjusted 1.84-fold risk of spontaneous preterm delivery (95% CI 1.32-4.31, P=0.012) and an adjusted 1.98-fold risk of PPROM (95% CI 1.39-3.15, P=0.017). CONCLUSIONS: Gravid women with adenomyosis were associated with increased risk of both spontaneous preterm delivery and PPROM. A common pathophysiological pathway may exist in these two disorders. Further in-depth biochemical and molecular studies are necessary to explore this phenomenon.

Potential role of preoperative serum CA125 for the differential diagnosis between uterine leiomyoma and uterine leiomyosarcoma.

PURPOSE: Most comparisons between uterine leiomyoma and uterine leiomyosarcoma have been based on postoperative pathological or molecular analyses. Very few reports have investigated preoperative differentiation between uterine leiomyoma and uterine leiomyosarcoma. METHODS: Between January 1990 and December 2003, 42 consecutive patients with uterine leiomyosarcoma treated at index hospitals were analyzed. Meanwhile, 84 patients with uterine leiomyomas were used as controls. The diagnostic performance of preoperative serum CA125 for the differential diagnosis between uterine leiomyoma and uterine leiomyosarcoma using receiver operating characteristic (ROC) curves was evaluated. Data presentations were categorized into premenopausal and postmenopausal groups. Diagnostic efficiency was calculated as the sensitivity multiplied by the specificity. RESULTS: Values of preoperative serum CA125 were significantly higher in the uterine leiomyosarcoma group than those in the uterine leiomyoma group. There was significant overlapping of preoperative serum CA125 between the uterine leiomyoma group and early-stage uterine leiomyosarcoma. For both the premenopausal and postmenopausal group, there was a significant difference in the distribution of preoperative serum CA125 in early-stage and advanced-stage uterine leiomyosarcoma. The optimal cutoff values of serum CA125 for the premenopausal group and postmenopausal group was 162 U/mL and 75 U/mL, respectively. CONCLUSION: These findings demonstrated that preoperative serum CA125 had a potential role in the differential diagnosis between early-stage and advanced-stage uterine leiomyosarcoma. Further investigation with a larger sample size at adequate power is necessary to verify the current study.

Radical hysterectomy: past, present, and future.

After an analysis of 3,441 radical hysterectomies performed in our department, we found, after modification of the operative technique in 1983, the more lateral the excision the less the recurrence rate. The recurrence rate for Stage 1b-2a and Stage 2b patients comparing the years before 1983 to the years after decreased to 12.4% from 15.7% (158/1,006 vs 268/2,163; p = 0.009) in Stage 1b-2a and 24.6% from 55.8% (38/68 vs 47/191; p = 0.0007) in Stage 2b, respectively. With the modern trend of aspiring for an easier lifestyle, most physicians practice earlier. Therefore only very few physicians study radical hysterectomy. As the skill of surgery needs a longer period of education and training, it may only interest physicians who work with medical professionals as part of a team at a medical center. In the future, we should provide gynecological residents not only with a training program using the classic textbooks, but also with different points of view on changes and developments in radical hysterectomy. We hope to promote an attitude of offering patients access to different choices and opportunities of therapy. Radical hysterectomy is in fact a treatment option for patients with bulky cervical lesions and Stage 2b in particular.

Improved early detection of cervical intraepithelial lesions by combination of conventional Pap smear and speculoscopy.

PURPOSE: To evaluate the efficacy of the addition of speculoscopy to a Pap smear in cervical cancer screening. METHODS: All women were screened using the Pap smear plus speculoscopy (PapSure) and colposcopy in the multicenter trial. The final diagnosis of each patient was based on a histological evaluation of the colposcopic target biopsy. Results were analyzed using a proportional compare test, sensitivity, specificity and predictive value with significant value determined at less than 0.05. RESULTS: Of 1,717 eligible cases, 26 cases had LGSIL and 16 cases had HGSIL. Of the Pap smears, five cases had LSIL and 14 cases had HGSIL. Of the combination of the PapSure, 23 cases had LGSIL and 16 cases had HGSIL. The sensitivity of the Pap smear to that of PapSure was calculated at 45.2% and 92.9%, respectively (p < 0.001). The estimated cost to detect a cervical lesion using PapSure is less than that of the Pap smear. CONCLUSION: The addition of speculoscopy along with a Pap smear screening results in early detection of cervical lesions in comparison to the Pap smear alone. This screening combination is also more cost-effective and requires fewer visits to the clinic in comparison to a Pap smear screening alone.

Detection of HPV infection by analyzing the changes in structure of peripheral blood lymphocytes specifically induced by HPV E7 antigen.

PURPOSE: Detection of human papilloma virus (HPV) infection in clinical practice was examined based on the observation that peripheral blood lymphocytes exposed in vitro to antigenic or mitogenic stimulation change their intracellular structures as measured by polarization of fluorescent light emitted by labeled cells. MATERIALS AND METHODS: A total of 47 women were enrolled in this study. They were classified into four groups based on the results of HPV-DNA detection in cervical tissues by the Hybrid Capture II kit (Digene, Gaithersburg, MD, USA) and pathological examination. Ten women with no HPV-DNA detection were used as a normal control group. Fifteen women without pathological diagnosis in the cervical tissues had HPV-DNA detection. Ten women with CIN lesions had 80% HPV-DNA detection. Twelve women with invasive squamous cell carcinoma had 100% HPV detection. Peripheral blood lymphocytes derived from all women were collected and then exposed to HPV-E7 antigen and PHA mitogen. RESULTS: The positive response rate of HPV-E7 antigen was ten percent (1/10) in the normal control group, 73.3% (11/15) in the HPV infectious women, 50% (5/10) in the CIN women, and 91.7% (11/12) in the cervical cancer patients. The overall sensitivity rate of blood tests was 77.1% and the specificity rate was 57.8% when the Hybrid Capture II HPV Test kit was used as the standard detection method for cervical tissue. CONCLUSIONS: The results showed that peripheral blood lymphocytes derived from patients with cervical lesions might be another choice to be used as a screening method to detect HPV infection compared with conventional methods.

Parametrial tumor spreading patterns in cervix cancer patients treated by radical hysterectomy.

OBJECTIVES: To evaluate tumor-spreading patterns in the parametrium. METHODS: We conducted a prospective clinical trial between January 1998 and December 2000 to define a new method for parametrium evaluation. The parametrium was divided into three areas, paracorpus, paracervix, and paravagina. A total of 284 consecutive patients with FIGO stage IB to IIA cervical cancer who had undergone radical hysterectomy were considered for the study. RESULTS: Of the 262 patients who were found eligible for evaluation, 135 had histopathologic analysis performed according to the new method and 127 with the traditional method. The detection of rate of parametrial invasion was 36 (26.7%) with the new and 13 (10.2%) with the traditional method (P=0.0014). The frequency of pelvic lymph node metastasis was 66.7% in patients who had tested positive for invasion of the paracorpus, 57.7% in those who had tested positive for invasion of the paracervix, and 71.4% in those who had tested positive for invasion of the paravagina. The frequency of pelvic lymph node metastasis in patients who had tested negative for invasion of the paracorpus, paracervix, or paravagina was 4.0%. Tumor cells tend to spread laterally and inferiorly in the parametrium. CONCLUSIONS: Using our classification of three parametrium areas for histologic examination can increase the detection rates of parametrial tumor invasion and help prevent failure of local treatment by allowing to implement appropriate adjuvant therapy.

Intraperitoneal cancer spread after laparoscopic cystectomy for mature teratoma with malignant transformation.

Laparoscopic surgery for ovarian dermoid cysts has been accepted. However, its potential limitations should be considered, including technique difficulty, intraoperative tumor spillage and malignant transformation. We report a case of ovarian dermoid cysts with malignant transformation that was initially treated using laparoscopic cystectomy, but was complicated by intraperitoneal tumor dissemination.

Extramammary Paget's disease found by abnormal vulvar brush sampling.

INTRODUCTION: Doctors are usually reluctant to perform a vulvar biopsy on a patient with non-specific chronic vulvitis--especially because of the rarity of vulvar malignancy in young women--until the lesion is suspected of being malignant. Therefore, most cases of extramammary Paget's disease (EMPD) were originally misdiagnosed as chronic and recurrent vulvar lesions. Late diagnosis of invasive lesions occurring in elderly females have resulted in cases of death. CASE: A 37-year-old patient showed an extended lesion on the vulva and perineum. In addition, abnormal cells were found from a vulvar scrape smear, and a following punch biopsy was used to diagnose and determine the extension of the disease. CONCLUSION: Diagnosis and demarcation of EMPD remain difficult due to the multifocal lesions and subtle nature of the disease. Brush sampling taken from suspicious areas can be a guide for multiple biopsies to demarcate the lesion before major surgery. A brush biopsy is presented as a first-step method to detect vulvar malignancy.

Incarcerated hernia in a 5-mm cannula wound.

Laparoscopic suturing and repairing of the fascial opening at 10- to 12-mm cannula puncture sites is well established; however, closing a 5-mm cannula wound is not well documented. We often leave the wound open without suture and cover it with gauze after removing the surgical drainage tube. An unusual early postoperative complication of laparoscopic surgery was an incarcerated hernia in a 5-mm cannula site. The 9-year-old girl underwent laparoscopic surgery due to an 8-cm ovarian mature teratoma. After 7 days, she came to our hospital because of a protruding mass in the left cannula wound. The mass was excised, and incarcerated fallopian tube torsion with necrotic change was diagnosed.

Preoperative staging of cervical carcinoma with MR imaging: a reappraisal of diagnostic accuracy and pitfalls.

The purpose of this study was to assess the diagnostic accuracy and pitfalls of MR imaging in preoperative staging of cervical cancer. Magnetic resonance imaging was performed to determine the tumor staging for 41 patients with cervical carcinoma emphasizing tumor size, parametrial invasion, vaginal invasion, and lymph node metastases. According to the correlation of MR findings with surgical-pathological features, there was less than 5 mm discrepancy in the size in 29 of 34 tumors (85.3%) that were larger than 1 cm. In assessing parametrial invasion, vaginal invasion and lymph node metastases, MR imaging had an accuracy of 95, 83, and 86%, respectively. In determining stage of disease and differentiating operable (< or =stage IIA) from advanced disease (> or =stage IIB), MR imaging had an accuracy of 82.9 and 93%. Pitfalls leading to staging errors included difficulties in differentiating cancer foci from surrounding tissue edema and detecting microscopic tumor extension. Magnetic resonance imaging is accurate in the evaluation of parametrial invasion and differentiation of operable from advanced disease. The ability of MR imaging to detect microscopic extra-cervical tumor extension and differentiate cancer foci from surrounding tissue edema is not as reliable.

Primary epithelial ovarian carcinoma in Taiwanese women.

PURPOSE OF INVESTIGATION: Primary epithelial ovarian carcinoma is common in industrial countries but rare in the Orient. In fact, it is still a rare disease in Taiwan. In this article, we report the general data of Taiwanese patients with primary epithelial ovarian carcinoma. METHODS: In this retrospective study we used univariate and multivariate analysis models to analyze the prognosis of patients with surgically confirmed primary epithelial ovarian carcinoma. One hundred and ninety-four patients from 1990 to 1996 were identified and enrolled in this study. RESULTS: The mean follow-up time was 44.7 months with an interval between 15.1 months and 105.9 months. Univariate analysis showed postmenopausal status, advanced stage, presence of lymph node metastasis, poor differentiation, and suboptimal surgery as risk factors for disease recurrence and subsequent deaths. Multivariate analysis demonstrated stage as the most important factor correlated with recurrent disease (risk ratio: 7.303 and 5.409, respectively), followed by optimal surgery (RR: 2.447), and cellular differentiation (RR: 1.677). CONCLUSIONS: Our data on the Taiwan population were consistent with other reports of different races. Early detection for primary epithelial ovarian cancer is of great importance because stage is still the most important predictor in disease-free survival and disease-related deaths. Application of the most reliable and acceptable methods of screening is our goal in the next century after weighing benefits over costs.

Interleukin-5 inhibition of biliary cell chloride currents and bile flow.

Recent studies have detected significant elevations of interleukin (IL)-5 mRNA in the liver parenchyma of patients with both primary biliary cirrhosis and acute rejection after liver transplantation. In both of these disorders, intrahepatic biliary epithelial cells (BECs) are the targets of injury. We hypothesized that BECs may themselves express IL-5 receptors that may modulate key biliary functions. RNAs coding for IL-5alpha and -beta receptors were amplified by RT/PCR from a biliary cell line derived from a human cholangiocarcinoma (Mz-ChA-1) and verified by DNA sequencing. IL-5 receptor distribution was detected immunocytochemically on Mz-ChA-1 cells, immortalized murine BEC, bile duct-ligated rat liver, and isolated cholangiocytes. Patch-clamp studies on Mz-ChA-1 cells showed that IL-5 inhibits 5'-N-ethylcarboxamidoadenosine-stimulated chloride currents. Additional functional studies showed that IL-5 inhibits secretin-induced bile flow. We conclude that BECs express IL-5 receptors and that IL-5 modulates BEC chloride currents and fluid secretion. Since IL-5 has previously been associated with cholestatic liver disease, we speculate that IL-5 may contribute to liver injury through its effects on biliary secretion.

Intraperitoneal cisplatin-based chemotherapy vs. intravenous cisplatin-based chemotherapy for stage III optimally cytoreduced epithelial ovarian cancer.

OBJECTIVE: To compare the survival between intraperitoneal cisplatin-based chemotherapy (IPCT) and intravenous cisplatin-based chemotherapy (IVCT) in stage III epithelial ovarian cancer with minimal residual disease (<1 cm) after primary debulking surgery. METHOD: One hundred and thirty-two patients with stage III epithelial ovarian cancer after optimal primary debulking surgery with minimal residual disease between April 1990 and March 1995 were entered into a randomized clinical trial in which IPCT or IVCT was administered at 3-week intervals. Patients in the IPCT arm received cisplatin-based (100 mg/m(2)) intraperitoneal chemotherapy. Patients in the IVCT arm received cisplatin-based (50 mg/m(2)) intravenous chemotherapy. The tumor response was assessed every 3 months. The hematological toxicity using the South West Oncology Group (SWOG) toxicity criteria was assessed. Catheter complications associated with intraperitoneal chemotherapy were also analyzed. RESULT: The estimated median survival in the IPCT group was 43 months (95% confidence interval, 34-54) and IVCT group was 48 months (95% confidence interval, 37-59). The hazard ratio of death was not statistically significant between IPCT and IVCT (hazard ratio, 1.13; 95% CI, 0.69-1.86; P=0.317). The frequencies of hematological toxic effects were significantly lower in the IPCT group than in the IVCT group. CONCLUSION: Intravenous and intraperitoneal chemotherapy are associated with equivalent survival in patients with minimal residual stage III epithelial ovarian cancer after optimal cytoreductive surgery.

Identifying local tumor variables for operable node-negative, margin-free patients with bulky cervical carcinoma of FIGO stage IB, IIA and IIB without adjuvant therapies.

PURPOSE: To identify local risk factors for FIGO IB, IIA and IIB bulky cervical squamous cell carcinoma (tumor size > or = 4 cm) patients with node-negative, margin-free tumors treated by radical hysterectomy, pelvic lymph node and para-aortic lymph node dissections without adjuvant therapies. MATERIALS AND METHODS: Thirty-four patients were recruited between 1976 and 1989 because they all declined any postoperative adjuvant therapy. The pathology reports showed that all the specimen margins were free from cancer cells with no para-aortic or pelvic lymph node metastases. The survival interval was calculated starting from the time of surgical intervention to the time of death or the end of this study in the year 2000. RESULT: Tumor variables including cell differentiation, depth of stromal invasion, parametrial invasion, vaginal invasion, uterine body invasion, age, and FIGO stage were analyzed. Only vaginal invasion showed statistical significance for decreasing patient disease-free survival in both univariate and multivariate analyses with p values of 0.003 and 0.002, respectively. CONCLUSION: For node-negative and margin-free patients with bulky cervical squamous cell carcinoma with operable stage IB and IIB, surgical intervention alone could suffice when no vaginal invasion is noted plus an 85% survival rate could be achieved. A prospective pilot study should be initiated although this study showed an excellent survival rate which is perhaps due to the limited number of cases.

Power Doppler angiographic appearance and blood flow velocity waveforms in invasive cervical carcinoma.

OBJECTIVES: The aim of this study was to investigate the effectiveness of transvaginal power Doppler angiography in predicting cervical malignancy by detecting intratumoral blood flow and to understand the relationship between squamous cell carcinoma (SCC) serum levels and intratumoral blood flow analysis of invasive cervical carcinoma before treatment. METHODS: Thirty-eight patients with cervical carcinoma (35 with stages Ia to IVb invasive carcinoma, 3 with cervical carcinoma in situ) were enrolled for the evaluation of tumor flow using transvaginal ultrasound accompanied with power Doppler angiography before surgery. The pulsatility, resistance index, and vascular index of tumor flow were measured. Thirty patients with proven healthy cervices were used as the control group. Pretreatment SCC serum levels were obtained in 34 women with cervical carcinoma. RESULTS: The pulsatility index and resistance index were significantly lower in the study group than in the control group (P < 0.0001). The vascular index was also significantly lower in the study group than in the control group (P < 0.0001). There were no significant differences among patients with SCC type and non-SCC type cervical carcinoma (P > 0.05) among the six parameters. There was no significant correlation between the pretreatment SCC serum levels with any of the six parameters obtained from the intratumoral blood flow analysis in the SCC group. CONCLUSIONS: Transvaginal ultrasound with power Doppler angiography is a valuable diagnostic tool for differentiating benign tumors of the cervix from malignant ones. Intratumoral blood flow of the cervix supplied us with practical diagnostic information before surgery and may aid in early prediction and management of cervical carcinoma. The use of transvaginal ultrasound with power Doppler angiography in the grading of vascularity ratio within cervical masses provided more sonographic characteristics among the different subclassifications of cervical cancer and is more useful than color Doppler imaging in the visualization of sonographic morphology.

Dilemma in managing spontaneous pneumoperitoneum: a case report.

Pneumoperitoneum is often associated with an underlying severe life-threatening emergency. This emergency is always treated successfully by a surgical approach. When a patient situated in hopeless situation but is found with spontaneous pneumoperitoneum, it creates a dilemma. We deal with such a rare situation which occurred in a 58-year-old woman with recurrent cervical carcinoma. The patient received a radical hysterectomy, pelvic lymph node dissection and bilateral salpingo-oophorectomy 10 years ago. Recurrent retroperitoneal lymphadenopathy and inguinal lymphadenopathy were suspected by computed tomography and proven by excision biopsy of inguinal lymph node. She received a complete course of concurrent chemoradiation therapy; however, clinically persistent disease was suspected although it was very difficult to prove. Unfortunately, the case was complicated by severe radiation fibrosis over the whole abdominal wall, poor appetite and urinary tract infection. She was treated with supportive care treatment. Nevertheless, the patient was attacked by spontaneous pneumoperitoneum during hospitalization and died later and autopsy of the patient showed military carcinomatosis of the abdominal cavity and lower abdominal wall without any evidence of internal hollow organ perforation and intraabdominal infection. The cause of death might be related to her carcinomatosis with severe chacexia. Because pneumoperitoneum is always considered as a surgical emergency, we reviewed the possible causes of non-surgical pneumoperitoneum to avoid an unnecessary surgical approach.