LINE-1 hypomethylation level as a potential prognostic factor for epithelial ovarian cancer.

A genome-wide hypomethylation is a common and crucial event in cancer. This study was to evaluate common epithelial ovarian cancer (EOC) if long interspersed element-1 (LINE-1) repetitive sequences methylation levels are progressively decreased during multistage carcinogenesis and there are the correlation between LINE-1 methylation levels and clinicopathologic characteristics. A total of 59 pairs of microdissected EOC tissues obtained from patients with EOC were examined for the methylation levels of LINE-1 repetitive sequences by a COBRALINE-1 (combined bisulfite restriction analysis of LINE-1) PCR protocol. The methylation levels were correlated with clinicopathologic parameters to determine the potential role of global hypomethylation as a prognostic marker for EOC. The LINE-1 methylation levels of 59 EOCs, 34.87 +/- 7.39%, were lower than in representative normal ovarian tissues (46.89 +/- 8.31%; 95% CI: 9.42-14.62; P < 0.001, paired-two-tailed t test). A decrease in the LINE-1 level of methylation was correlated with histological subtypes, higher FIGO and advanced tumor grade. Patients with greater hypomethylation (i.e., a methylation level

Angiogenesis in cervical intraepithelial neoplasia and early-staged uterine cervical squamous cell carcinoma: clinical significance.

The objective of this study is to evaluate angiogenesis in cervical intraepithelial neoplasia (CIN), microinvasive squamous cell carcinoma (MIC), and early-staged squamous cell carcinoma (SCC), stage IB-IIA of the cervix. Microvessel density (MVD) was evaluated and correlated with other pathologic prognostic factors and disease outcomes. Four hundred seventy-four cervical specimens were studied. Among these, 100 were designated normal cervix, 30 CIN1, 32 CIN2, 178 CIN3, 74 MIC, and 60 early-staged SCC. MVD per high-power field (x400) of early-staged SCC, MIC, and CIN3 were significantly higher in comparison to CIN2, CIN1, and control subjects (P<0.05). There was no statistically significant difference in MVD between control group, CIN1, and CIN2. In early-staged SCC, no correlation between MVD and pelvic lymph node status, parametrial involvement, depth of stromal invasion, and lymphovascular space invasion was found. Patients with bad outcomes (recurrence or death) showed no statistically different MVD from the ones who had unremarkable clinical courses.

Neoadjuvant gemcitabine and cisplatin followed by radical surgery in (bulky) squamous cell carcinoma of cervix stage IB2.

OBJECTIVES: This study aimed to evaluate the efficacy and toxicity of gemcitabine in combination with cisplatin as neoadjuvant therapy in patients with cervical carcinoma stage IB2. PATIENTS AND METHODS: Chemotherapy-naive patients with histologic diagnosis of squamous cell cervical carcinoma staged as IB2 were treated with 2 cycles of cisplatin (70 mg/m(2) on day 1) and gemcitabine (1000 mg/m(2) on days 1 and 8), given every 21 days. After chemotherapy, patients underwent radical hysterectomy and pelvic lymphadenectomy. Patients judged to have a non-resectable disease were treated with standard pelvic radiation. RESULTS: Between September 2000 to March 2004, 28 patients were enrolled in the study, of which 27 were evaluable for efficacy and toxicity. The mean age was 39 years (30-55). The overall clinical response rate was 88.9% (24/27), with complete response (CR) in 9/27 patients (33.3%) and partial response in 15/27 patients (55.5%). Three patients (11.1%) did not respond and nobody progressed. A pathological CR was noted in 2 of 24 patients who underwent radical surgery. The 3 non-responding patients were subsequently treated with radiation and achieved CR. Grades 3 or 4 neutropenia, anemia, or thrombocytopenia was observed in 18.5%, 7.4%, and 3.7% patients respectively. Non-hematological toxicity was mild except grade 3 nausea/vomiting in 18.5% patients. At median follow-up time of 36.7 months (range 7-51 months), the 3-year survival was 88.9%. CONCLUSION: Neoadjuvant treatment with gemcitabine/cisplatin combination for patients with cervical cancer (stage IB2) appears encouraging, with manageable and acceptable toxicity profile.

Results of radiation therapy in stage 1B cervical carcinoma at King Chulalongkorn Memorial Hospital: fifteen-year experience.

A retrospective study was performed on 131 patients with stage 1B cervical carcinoma who were referred and treated with external beam radiation and intracavitary brachytherapy at the Division of Radiation Therapy, Department of Radiology, King Chulalongkorn Memorial Hospital between February 1985 and February 2000. Primary outcomes were overall survival rate, progression free survival rate, recurrence, and treatment-related complications. The treatment results from different sources of intracavitary radiation therapy were secondary endpoints. The number of patients treated with Ra-226, Cs-137, and Ir-192 intracavitary irradiation were 12, 84, and 35 patients respectively. The median follow-up times were 69, 59, and 21 months for Ra-226, Cs-137, and Ir-192, respectively. Actuarial 5-year overall survival rate was 89 per cent. The 5-year progression free survival rate was 80 per cent. Actuarial 5-year survival and progression free survival rate were comparable among different sources of intracavitary brachytherapy (p = 0.553 and p=0.793, respectively). The overall recurrent rate was 16.8 per cent. Of the recurrence; 40.9 per cent was locoregional, 54.6 per cent was distant failure, and 4.5 per cent was combined locoregional and distant failure. The overall complication rate was 25.95 per cent. The severe complication rates (Grade III-V) from treatment occurred in the urinary bladder (0.76%) and in the small bowel (0.76%.) These results suggest that radiation therapy alone is an effective treatment for stage 1B cervical carcinoma. Additionally, all types of intracavitary brachytherapy provide comparable clinical results.

Unilateral deep vein thrombosis associated with a large myoma uteri. A case report.

BACKGROUND: Deep vein thrombosis is a rare complication of myoma uteri. There have been few reports on this association. CASE: A 42-year-old woman presented with a myoma uteri, 24 weeks in size, that had compressed the pelvic veins and caused unilateral deep vein thrombosis of the left leg. After anticoagulation therapy, a total abdominal hysterectomy was performed, with an uneventful recovery. CONCLUSION: Although deep vein thrombosis associated with myoma uteri is a rare event, it can be managed successfully with anticoagulants and hysterectomy. Myoma uteri with deep vein thrombosis is an indication for hysterectomy.

Double uterus with unilaterally obstructed hemivagina and ipsilateral renal agenesis: a variety presentation and a 10-year review of the literature.

A double uterus with a unilaterally obstructed hemivagina is a rare condition, usually associated with ipsilateral renal agenesis. Herein, we report two cases, the first case presenting with abdominal pain and pelvic mass. Hemihysterectomy was performed leaving the contralateral uterus intact. The second case presented with chronic foul smelling vaginal discharge. The diagnosis was a double uterus and pyocolpos of the left vagina. Excision of the left vaginal septum and drainage were performed. The postoperative course of both cases was uneventful and the patients were well at the six-week follow-up. An accurate diagnosis, appropriate management and the prevention of future fertility problems are discussed.

Acute and follow-up results of laser angioplasty: single center experience.

Excimer laser angioplasty was used to treat total occluded coronary arteries and instent restenosis lesions with high success rate. To assess immediate and long-term results of patients treated with excimer laser, we analyzed demographic information and the immediate results of 44 patients who underwent ELCA. The patients were followed up and assessed for clinical restenosis. The initial success rate of ELCA was 86.4 per cent which is comparable to plain balloon angioplasty performed during the same period. Clinical restenosis was 29 per cent. In conclusion, ELCA for patients with coronary artery disease can be performed with initial high success rate and reasonable long-term restenosis.

Phase II study of high-dose paclitaxel in platinum-refractory epithelial ovarian cancer.

The purposes of this study were to determine the efficacy of paclitaxel, using a dose of 200 mg/m2 intravenous continuous infusion over 24 hours every three weeks in the treatement of platinum-refractory epithelial ovarian cancer (EOC) and to evaluate the toxicities. Eligibility criteria included: histologically proven EOC, platinum resistance, measurable disease, Zubrod performance status grade 0-2, expected survival of > 3 months and adequate hematological function. Response was assessed at three-cycle intervals or earlier if required. Twenty-one patients were recruited in this study. The response rate was 52% (2 CR, 9 PR) with a median duration of response of six months. The median progression-free interval was eight months and the median survival was 12 months. Leukopenia was the predominant toxic effect. Eighty-six percent of patients required granulocyte-colony stimulation factor (G-CSF). All patients had alopecia grade 3. In conclusion, high-dose paclitaxel is active in platinum-refractory EOC with manageable toxicities.

Telomerase assay for differentiating between malignancy-related and nonmalignant ascites.

The differential diagnosis between malignancy-related ascites (MRAs) and nonmalignant ascites (NMAs) has remained an essential problem in clinical practice. Our purpose was to determine the diagnostic value of ascitic fluid telomerase activity in discriminating these two categories compared with that of cytological examination. Twenty-five MRAs and 47 NMAs as the control group were enrolled in our study. In the MRA group, telomerase activity was detected in 13 of 16 (81.3%) cases of peritoneal carcinomatosis and in 6 of 9 (66.7%) cases of hepatocellular carcinoma (HCC)-associated ascites. Contrasting that, cytological examination was positive in only 9 of 16 (56.3%) and 1 of 9 (11.1%) cases, respectively. In the NMA group, telomerase-positive ascitic fluid samples were found in 2 of 47 (4.3%) cases, all belonging to subgroups that contained large numbers of lymphocytes in the ascites. In our study, the telomerase activity and cytological examination exhibited a sensitivity of 76% and 40% and a specificity of 95.7% and 100%, respectively. Regarding subgroups of MRAs, the telomerase activity and cytological examination demonstrated a sensitivity of 81.3% and 56.3%, respectively, in peritoneal carcinomatosis and a sensitivity of 66.7% and 11.1%, respectively, in HCC-associated ascites. In conclusion, telomerase activity is a more sensitive marker than cytological examination for differentiating between MRAs and NMAs. It may also serve as a useful indicator for detecting early i.p. metastasis in HCC-associated ascites.

Telomerase activity and human papillomavirus in malignant, premalignant and benign cervical lesions.

The purpose of this study was to define a correlation between telomerase activity and human papillomavirus (HPV) in normal control tissue and in benign, premalignant and malignant cervical lesions. Telomerase activity was detectable in 33 out of 34 cases of squamous-cell carcinoma, five out of six cases of microinvasive carcinoma, 8 out of 20 cases and two out of six cases of high- and low-grade squamous intraepithelial lesions (SILs) respectively. The higher frequency of positive telomerase in invasive carcinoma compared with SILs was observed in both HPV-associated and non-associated groups. Whereas 92.6% of HPV-positive and 100% of HPV-negative invasive lesions expressed telomerase, only 50% of HPV-positive and 25% of HPV-negative SILs did. Interestingly, telomerase activity was also detectable in 13 out of 28 cases of benign lesions regardless of the presence of HPV. In conclusion, there may be two roles of telomerase in the cervix. The first one would present in benign lesions; the second is associated with cancer development and activated during the late stage of multistep carcinogenesis in both HPV-positive and -negative groups.

Micro stent I, initial results, and six months follow-up by quantitative coronary angiography.

The Micro stent (MS) is a balloon expandable stent that allows the treatment of stenoses in distal and tortuous coronary arteries. This prospective study was performed to evaluate initial and late results of MS implantations. A total of 127 MS (101 in native coronary arteries and 26 in saphenous vein grafts) were implanted in 85 patients (1.5 stents/pt, 65 male, and 20 female, age 62, +/-10 yr) with angina pectoris class II-III: 21 (25%), angina pectoris class IV: 41(48%), and acute myocardial infarction: 23 (27%). Indications per segment treated (n=93): elective: 49 (53%); suboptimal balloon angioplasty (PTCA) result: 33 (35%); bailout: 11 (12%). The patients were discharged with 100 mg of aspirin daily unless other indications for oral anticoagulants were present. Procedural success (diameter stenosis of 30% without the occurrence of clinical events within 3 wk) was 85%. Early clinical events (<3 wk included: death:1%; subacute closure: 5%; coronary artery bypass surgery (CABG): 1%; vascular complications: 4%. Late clinical events (3 wk-6 mo) included: acute myocardial infarction:3%, PTCA 5%, CABG 3%, angina class Ill-IV: 4%. Quantitative angiographic results were: the minimum lumen diameter increased from 0.90+/-0.72 before to 3.05+/-0.48 mm ( 50% at FU) was 13%. This study demonstrates high procedural and late success rates of Micro stent implantations.

13-cis-retinoic acid and interferon-alpha 2a therapy in locally advanced squamous cell carcinoma of the cervix: p53 alteration, proliferating cell nuclear antigen expression and angiogenesis response.

OBJECTIVE: To evaluate prognostic importance of p53, PCNA and vascularization alteration in patients with locally advanced cervical squamous cell carcinoma (SCC) after combination therapy with 13-cis-retinoic acid (13cRA) and interferon-alpha 2a (IFN-alpha 2a). METHODS: 13cRA and IFN-alpha 2a were administered to patients with locally advanced cervical SCC. Formalin fixed, paraffin embedded tissues sections obtained at pre- and post-therapy, respectively, were stained immunohistochemically with anti-p53, anti-PCNA and anti CD31. RESULTS: p53 alteration was demonstrated in 5/10 patients and 3/10 patients pre- and post-therapy, respectively. There was no correlation between p53 alteration and prognosis. After therapy, two patients with complete response had lower PCNA expression whereas the non-responders demonstrated the opposite result. The vascularization showed a correlation with PCNA and prognosis. In the response group, patients had lower microvessel count while the metastatic group exhibited higher count. CONCLUSIONS: The present study suggests that p53 alteration is neither related to the prognosis of cervical SCC nor is it influenced by the combination therapy while PCNA expression and vascularization might be constitute potential markers for tumorigenesis, prognosis and responsiveness to this novel regimen.

A phase II and pharmacokinetic study of enloplatin in patients with platinum refractory advanced ovarian carcinoma.

This was a study of enloplatin in 18 evaluable patients with platinum refractory ovarian cancer. They received an i.v. infusion of enloplatin over 1.5 h without prehydration every 21 days. One patient had a partial response (6%; 95% CI 0-26%) lasting 2.8 months. The median survival was 9.4 months (95%; CI 5.1-19.7%). Neutropenia was the dose-limiting toxicity. Nephrotoxicity was manageable. Enloplatin is the major form of the free drug in plasma. However, 13.5 h after initiation of treatment, 85% of the drug in plasma is protein bound. Elimination of the drug is mainly renal. Enloplatin pharmacokinetics is similar to that of carboplatin. Thus, the plasma pharmacokinetics of enloplatin is dictated by the cyclobutanedicarboxylato (CBDCA) ligand and not the novel amino ligand.

Perforation of interventricular septum in acute myocardial infarction.

Eight cases of ruptured interventricular septum associated with myocardial infarction were diagnosed at Siriraj Hospital between 1985-1995. Clinical congestive heart failure and holosystolic murmur were found in all. Diagnosis was confirmed by echocardiogram and right heart catheterization in all patients. Two patients died from congestive heart failure preoperatively and the third case died from organ failure and sepsis postoperatively. Another five cases underwent successful ventricular septal defect closure and coronary artery bypass with good results.

Experience of the first 60 cases of intracoronary stent placement.

In conclusion, elective stent placement, compared to angioplasty, has a higher clinical success rate. However, in our early experience major complications did occur.

Immediate angioplasty results of total coronary artery occlusion in Thai population.

Attempted angioplasty of totally occluded vessels may be done. However, a lower success rate is expected compared to those with subtotal occlusion. The complication rate is comparable to that of partial occlusion in experienced hands.

Leuprolide acetate for treating refractory or persistent ovarian granulosa cell tumor.

OBJECTIVE: To evaluate leuprolide acetate for treating refractory or persistent ovarian granulosa cell tumor (GCT). STUDY DESIGN: We treated six patients who had recurrent or persistent ovarian GCT with monthly intramuscular injections of a depot formulation of leuprolide acetate, 7.5 mg. Four patients had received prior cisplatin-based chemotherapy. Initially these patients' tumors had responded to the cisplatin, but then the disease had progressed in all cases. One of these four patients also had received prior therapy with tamoxifen that had resulted in three months of stable disease. Two patients had received no prior chemotherapy. RESULTS: Responses could be evaluated in five of the six patients; in the sixth patient, only survival was evaluable. Among the five evaluable patients, two achieved partial responses lasting 3 and 11 months, with disease progression-free intervals of 4 and 12 months. The other three patients (60%; 95% confidence interval [CI], 20-95%), including two whose disease had progressed on chemotherapy, had stable disease with disease progression-free intervals of 3+, 3+ and 13+ months. The objective response rate was 40% (two of five patients; 95% CI, 10-90%). Cessation of disease progression was noted in all five of the evaluable patients (100%; 95% CI, 40-100%). The sixth patient, whose disease could not be evaluated, was treated with leuprolide acetate for 24 months and at this writing had no clinical evidence of disease. The therapy was convenient to administer, and no major side effects were noted. Leuprolide acetate thus appears to have activity in patients with refractory GCT, and it may prolong the disease progression-free interval. Further trials of this relatively nontoxic and convenient therapy are warranted.

Micro stent, quantitative coronary angiography, and procedural results.

The Micro stent (MS) is a radiopaque stainless steel balloon expandable intracoronary stent. The stent is mounted on a rapid-exchange delivery system. From August 1994-March 1995, 127 MS were implanted in 85 patients (pts, 1.5 stents/pt, 85 in native vessels and 42 in bypass vein grafts, 61 males and 24 female, age 33-77 yr, mean age 61 +/- 10 yr). Pts studied were scheduled for either elective PTCA (n = 62, 73%) or PTCA for acute myocardial infarction (n = 23, 27%). Elective stent implantation was performed in 45 pts (53%). An MS was implanted because of a suboptimal balloon angioplasty result in 26 pts (31%). The stent was implanted because of threatened or acute vessel closure after balloon angioplasty in 14 pts (16%). During the procedure, 500 mg aspirin and 2 x 7,500 units of heparin were administered intravenously, followed by systemic heparinization for 48 hr. Pts were discharged with 100 mg aspirin daily (n = 50, 59%), or anticoagulant drugs and 100 mg aspirin daily (n = 19, 22%), or anticoagulant drugs only (n = 16, 19%). Angiographic results were analyzed with computer-assisted quantitative coronary arteriography. Angiographic success (defined as a residual stenosis of < 30%) was achieved in 124 of 127 attempts (98%). The mean minimal luminal diameter of the target lesions increased from 0.88 +/- 0.79 mm before stent implantation to 3.08 +/- 0.56 mm (P < 0.001). The percentage of diameter stenosis was reduced from 77.9 +/- 20.9% before to 13.3 +/- 10.5% (P < 0.001) after stent implantation. The average initial gain was 2.53 +/- 1.37 mm. The procedural success rate (defined as a residual stenosis of < 30% without occurrence of major clinical events within 3 wk after procedure) was 84%. Major clinical events included: death 1 pt (1%); cerebrovascular accident, 1 pt (1%); subacute stent closure, 5 pts (6%); coronary artery bypass grafting, 3 pts (4%); false femoral aneurysm, 2 pts (2%). The initial results of Micro stent implantation are promising. No anticoagulant therapy was given to most of the patients (59%). Few vascular and bleeding complications were observed. However, at this stage, no data about the restenosis rate after implantation of a Micro stent are available.

Non-invasive diagnostic approaches of the dissection of the aorta: transesophageal echocardiography vs computed tomography.

The accuracy of non-invasive diagnosis of aortic dissection between transesophageal echocardiography (TEE) and computed tomography (CT) was studied in 21 patients. All patients had both diagnostic procedures. With TEE examination, De Bakey's type I was found in 9 patients, type II in 1 and type III in 10 while CT imaging revealed aortic dissection in 19 out of 21 patients. If the dissection found by both diagnostic procedures was considered definitive then both examinations were similarly sensitive. TEE is a preferred choice of non invasive work up for aortic dissection. Medical and surgical therapy in appropriate cases evaluated by TEE give rise to good results in the majority of patients.

Phase II study of intravenous topotecan as a 5-day infusion for refractory epithelial ovarian carcinoma.

PURPOSE: To determine the efficacy and toxicity of topotecan administered as a 5-day intravenous infusion in patients with advanced ovarian cancer refractory to cisplatin-based chemotherapy. PATIENTS AND METHODS: Thirty patients with advanced epithelial ovarian cancer refractory to cisplatin-based chemotherapy received intravenous infusions of topotecan 1.5 mg/m2 delivered over 30 minutes each day for 5 days. A course was repeated every 21 days. The patient eligibility requirements included age > or = 18 years, Zubrod score < or = 2, measurable disease, adequate hepatic and renal function, neutrophil count > or = 1,500/microL, platelet count > or = 100,000/microL, and anticipated survival > or = 3 months. RESULTS: Twenty eight patients were assessable for response and toxicity. All patients were assessable for survival. The major toxicity from administration of topotecan at this dose schedule was myelosuppression; 21 patients required dose reductions. Four patients had neutropenic fever that required hospitalization, and seven patients required platelet transfusions. Maculopapular pruritic exanthema occurred in 20% of patients; gastrointestinal side effects were mild. No deaths were reported on the study. At dose levels of 1.5, 1.25, and 1.0 mg/m2, 61%, 31%, and 25% of patients, respectively, required dose reductions. Of 28 assessable patients, four (14%; 95% confidence interval [CI], 4% to 34%) achieved a partial response (PR) at a median of 1.4 months and lasting 8.9 months, and 17 had stable disease (SD). The overall median survival time was 10.0 months (95% CI, 8.1 to 13.5). CONCLUSION: Topotecan shows modest clinical activity against cisplatin-refractory ovarian cancer, although the dose-intensity is compromised by the depth of the granulocyte nadir and the duration of granulocytopenia. Further studies of topotecan may necessitate a reevaluation of optimal dose schedule, with the possible incorporation of multilineage cytokines, and its activity in taxane-resistant tumors.