Epidemiological and experimental studies have established that specific human papillo-mavirus(HPV) types are strongly associated with cervical cancer. In understanding the role of HPV in the development of cervical cancer, more accurate and efficient detection method of various HPV types is warranted. Currently polymerase chain reaction(PCR)-based methods are the most commonly used one. Recently developed PCR systems, mainly, amplify a region of the L1 or E1 genes of HPVs which may not be integrated into host chromosome and more likely to produce false negative results. In this paper we describe the design and use of a simplified PCR system with high sensitivity in which all primers are multiplexed in the same PCR mixture. The full genomic sequence of HPV types were obtained from the HPV Sequence Database(http://hpv-web.lanl.gov). Matrix, homology and alignment analyses were carried out by using computer programs such as CLUSTAL V, DNASIS(TM) and Amplify. To determine the detection sensitivity of our PCR system, we have performed experiments using cloned HPV DNAs of type 16 and 18 serially diluted(10-fold dilutions from 10 picogram to 0.01 femtogram per assay) and in a cocktail. By alignment and comparing the sequences we located regions of outer and inner primer sequences based on the E6, E7 and E1 open reading frames which is usually integrated into host chromosome. Amplimer size were determined in order to be below than 400 base pair. The sensitivity of our PCR system ranged from the 1 copy per cell for HPV 16 and 10 copies per cell for HPV 18. This sensitivity was maintained when cloned HPV 16 and 18 DNAs were applied both individually and in a cocktail with variable mixing ratio. Our PCR system shows high sensitivity and specificity with minimal competitive inhibition between primers. This multiplex nested PCR system may be efficiently used for simultaneous detection and typing of HPV 16 and 18 in paraffin-embedded sections or rapid prepared samples.
Base Pairing ; Clone Cells ; DNA ; Human papillomavirus 16 ; Human papillomavirus 18 ; Humans* ; Open Reading Frames ; Polymerase Chain Reaction* ; Sensitivity and Specificity ; Uterine Cervical Neoplasms

OBJECTIVE: This study was performed to identify the prognostic factor for survival of patients with recurrent cervical cancer. METHODS: Sixty-eight patients were diagnosed as recurrent cervical cancer at the Seoul National University Hospital from January, 1988 to December, 1998. Recurrence was defined as new evidence of tumor after 6 months of disease free survival. Retrospective analysis was done in terms of clinical features and the Cox proportional hazard model was used to identify independent variables associated with an improved survival rate. Histopathologic types were distributed as follows; squamous cell carcinoma in 70.6%, adenocarcinoma in 11.8%, adenosquamous cell carcinoma in 11.8%, and small cell carcinoma in 1.5%. Distribution of FIGO stage was as follows; stage I in 25.0%, stage II in 66.2%, and stage III in 4.4%. Sites of recurrence were as follows; central pelvic recurrence in 44.1%, pelvic side wall recurrence in 11.8%, and distant metastasis in 44.1% and the most common site of distant recurrence was extrapelvic lymph nodes (29.4%). 29.4% of recurrences were observed within the first 12 months after initial therapy, 50.0% within 2 years and 64.7% within 3 years. RESULTS: Positive rate of SCC-Ag at initial diagnosis was 45.2% with cutoff value of 2.0 ng/ml. Positive rate of SCC-Ag at the diagnosis of recurrence was 60.0%. Overall response rate to the treatment was 29.1%. Complete response rate was higher in central pelvic recurrrence than pelvic side wall recurrence and distant metastasis (P = 0.002) and also higher in normal SCC-Ag level (< or = 2.0 ng/ml) at the diagnosis of recurrence than elevated level (P = 0.032). Cumulative survival rates of 1 year after recurrence was 66.8%, 2 year 36.7%, and 5 year 18.7%. Central recurrence showed higher cumulative survival rate than pelvic side wall or distant recurrence (P = 0.029). The patients with elevated SCC-Ag level at the time of diagnosis of recurrence showed lower cumulative survival rate than those with normal SCC-Ag level (P < 0.001). Cox proportional hazard model showed that SCC-Ag elevation at the time of diagnosis of recurrence retained significant values in predicting survival(OR = 2.56; 95% CI = [1.22-5.39]; P = 0.01). CONCLUSION: SCC-Ag elevation at the diagnosis of the recurrence is a strong independent prognostic indicator for survival of patients with recurrent cervical cancer.
Adenocarcinoma ; Carcinoma, Small Cell ; Carcinoma, Squamous Cell ; Diagnosis ; Disease-Free Survival ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Proportional Hazards Models ; Recurrence ; Retrospective Studies ; Seoul ; Survival Rate ; Uterine Cervical Neoplasms*

Cancer of the vulva accounts for approximately 0.5% of all gynecologic malignancies. At diagnosis, one-third of these cases is detected in an advanced stage (FIGO stages III, IV), and local extension of primary vulvar cancer may involve adjacent midline structures such as the clitoris, urethra, vagina, and anus. Initial surgical therapy of such locally advanced primary cancers may compromise the functional integrity of midline structures, necessitating ultraradical surgery including pelvic exenteration. In view of the relatively elderly age of the patients and the morbidity of this ultraradical dissection, concomitant chemoradiation therapy - that the efficacy had been proven in head and neck cancer, anal cancer has approached for patients with locally advanced vulvar cancer. We experienced a case of stage III vulvar cancer patient, who underwent concomitant chemoradiation therapy with 5-fluorouracil(FU) and cisplatin and who showed complete response. So, we report this case with brief review of the literatures.
Aged ; Anal Canal ; Anus Neoplasms ; Cisplatin ; Clitoris ; Diagnosis ; Female ; Head and Neck Neoplasms ; Humans ; Pelvic Exenteration ; Urethra ; Vagina ; Vulvar Neoplasms*

This phase II study aimed to assess the clinical activity and toxicity of ifosfamide based regimen in patients with epithelial ovarian cancer, relapsed or refractory to cisplatin-containing combination chemotherapy. From July 1991 to June 1993, 18 patients with epithelial ovarian cancer, relapsed or refractory to cisplatin were treated as follows. Relapsed cases were treated with IP(ifosfamide 4,0g/m2 intravenously and cisplatin 60mg/m2 intravenously on day 1) regimen every 3-4 weeks. The regimen used in refractory cases was Et-I(etoposide 100mg/m2 intravenously on days 1 to 3 and ifosfamide 1.0g/m2 intravenously on days 1 to 5) regimen every 3 or 4 weeks. The uroprotectant mesna was concomitantly used. Responses and toxicities were evaluated according to the WHO Criteria. The overall response rate was 27.8%(5/18), including 2 complete response and 3 partial response. There were four episodes(22.2%) of grade 3, 4 myelosuppression, but no other grade 3, 4 non-hematologic toxicity. Salvage therapy with ifosfamide based regimen is a useful and well tolerated treatment strategy in selected patients with relapsed ovarian cancer.
Cisplatin ; Drug Therapy, Combination ; Humans ; Ifosfamide ; Mesna ; Ovarian Neoplasms* ; Recurrence ; Salvage Therapy

Under certain pathophysiological conditions, such as inflammation and ischemia, the concentration of H+ ion in the tissue surrounding neurons is changed. Variations in H+ concentration are known to alter the conduction and/of the gating properties of several types of ion channels. Several types of K+ channels are modulated by pH. In this study, the whole cell configuration of the patch clamp technique has been applied to the recording of the responses of change of external pH on the delayed rectifier K+ current of cultured DRG neurons of rat. Outward K+ currents were examined in DRG cells, and the Charybdotoxin and Mn2+ could eliminate Ca2+-dependent K+ currents from outward K+ currents. This outward K+ current was activated around -60 mV by step depolarizing pulses from holding potential -70 mV. Outward K+ currents were decreased by low external pH. Activation and steady-state inactivation curve were shifted to the right by acidification, while there was small change by alkalization. These results suggest that H+ could be alter the sensory modality by changing and modifying voltage-dependent K+ currents, which participated in repolarization.
Animals ; Charybdotoxin ; Diagnosis-Related Groups ; Ganglia, Spinal* ; Hydrogen-Ion Concentration* ; Inflammation ; Ion Channels ; Ischemia ; Neurons ; Rats* ; Spinal Nerve Roots*

Background/Aims: Esophageal cancer is not an uncommon cancer in Korea, however, the prognosis still remains very poor with a 5 year survival rate bemg less than l0% mainly becauae of the delayed diagnosis. Although chromoscopy with lugol solution has been received to diagnose the esophageal cancer in an early stage without difficulty, its clinical use has not been popular yet in Korea. This study was performed prospectively to evaluate the usefulness of the chromoscopy for the detection of superficial esophageal cancer in risk patients for esophageal cancer. Methods: Ninety-five patients were selected among persons who received gasiroscopy at Asan Medical Center between Jan. 1996 and May 1996 and were prospectively included for chromoscopy. Inclusion criteria for the chromoscopy were patients older than 60 years of age with smoking history of more than 30 packyears, and/or past or family history of cancers. After conventional endoscopic examination, lugol solution was sprayed to stain the glycogen granules in the epithelial cells. The size of unstained lesion was measured and stainability was classified into 5 grades. All lesions unstained were biopsied for histological diagnosis.(continue...)
Chungcheongnam-do ; Delayed Diagnosis ; Epithelial Cells ; Esophageal Neoplasms* ; Glycogen ; Humans ; Korea ; Prognosis ; Prospective Studies ; Smoke ; Smoking ; Survival Rate

Even though malignant potential of vaginal intraepithelial neoplasia(VaIN) may be low, the prevalence is increasing and the mean age at diagnosis is decreasing. Various treatment options have been used for the eradication of ValN, but most effective standard protocol is not present because it is a rare disease. Laser vaporization was used to treat 7 patients with VaIN diagnosed at Department of Obstetrics and Gynecology, Seoul National University Hospital between 1992 to 1996. The patients were from 40 to 70 years of age with a mean 57 of years. All patients had a history of radical or simple hysterectomy, and final pathologic diagnosis were as follows : cervical cancer(n=5), cervical intraepithelial neoplasia(n=l), leiomyoma(n=l). Vaginal intrae-pithelial neoplasia(VaIN) was identified between 4 months and 8 years after first operation. All lesions were unifocal disease and found at the upper one third of the vagina. Treatment was performed with a CO2 laser unit and colposcope. Four(57%) out of seven patients had general anesthesia for the purpose of treatment. Patients were followed up for an average of 16.8 months with regular cytologic evaluation, colposcopy and biopsy. Failure of therapy was defined as evidence of intraepithelial neoplasia in any one of these three parameters. Only one patients showed persistent disease and the others remain free of disease. The success rate of therapy was 85.7%(6/7). (continue)
Anesthesia, General ; Biopsy ; Colposcopes ; Colposcopy ; Diagnosis ; Gynecology ; Humans ; Hysterectomy ; Laser Therapy ; Lasers, Gas* ; Obstetrics ; Prevalence ; Rare Diseases ; Seoul ; Vagina ; Volatilization*

Most men referred for breast imaging have palpable lumps. Most lesions that are evaluated are benign, and malignancy is less common. Although there are characteristic imaging features of malignancy, substantial overlap is presented between benign and malignancy. Therefore, other imaging modalities are increasingly being used for accurate evaluation. We report on various male breast lesions using ultrasonography, mammography, computed tomography, and positron emission tomography-computed tomography. Pathognomonic histologic findings of each case are also provided.
Breast* ; Electrons ; Humans ; Male ; Mammography ; Ultrasonography

OBJECTIVE: Cervical carcinoma can be adequately treated when diagnosed in early stage. However, the progsnosis of recurrent cervical carcinoma remains poor. The objective of this study is to analyze the prognostic factors affecting survial of recurrent cervical carcinoma patients. METHODS: The clinical characteristics of eighty-three patients who were diagnosed as recurrent cervical carcinoma from Jan 1988 to Apr 1999 were retrospecively analyzed, The initial FIGO stage of II (67.5%) was the most predominant. There were 9.6% of adenocarcinoma, 9.6% of adenosquamous carcinoma, and 1.2% of small cell carcinoma other than squamous cell carcinoma (77.1%). Diagnosis of recurrence was made by histopathologic examination, CT/MRI, Chest X-ray, intravenous pyelography. The recurrence was detected on routine follow-up in 41.0%. Comparison of Kaplan-Meyer survival curve was made with log-rank test, P-value less than 0.05 was regarded as statistically significant. RESULTS: Overall 2-year survival rate was 37.3% and median survival was 17 [13-21, 95%CI] months. Four patients survived more than 5 years. There was no significant difference among survival rates of histopathologic types, Survival rates of patients with central recurrence were significantly higher than those of lateral and distant recurrence (P= 0.009). 13 patients who did not receive any treatment after recurrence survived only for 9 [7-11] months and the survival of those were significantly lower than the survival of patients who received treatment of any kind (P<0.001). The treatment modalities after recurrence did not affect survival. CONCLUSION: We conclude that regular follow-up of cervical carcinoma patients is very important in detecting recurrence and that treatment after recurrence does affect survival of patients.
Adenocarcinoma ; Carcinoma, Adenosquamous ; Carcinoma, Small Cell ; Carcinoma, Squamous Cell ; Diagnosis ; Follow-Up Studies ; Humans ; Recurrence ; Survival Rate ; Thorax ; Urography

OBJECTIVE: Large loop excision of transformation zone(LLETZ) is gaining popularity as an alternative to other ablative or cone methods for the treatment of cervical intraepithelial neoplasia(CIN). The optimal management of CIN after LLETZ, however, remains controversial and the reliable predictors of residual disease after LLETZ have not been consistently identified. This study was performed to identify factors to predict residual disease after LLETZ. METHODS: From August 1993 to July 1995, 133 patients who received subsequent hysterectomy after LLETZ in Department of Obstetrics and Gynecology at Seoul National University Hospital were retrospectively reviewed. Residual disease was defined as positive findings of CIN or further advanced findings in hysterectomy specimen. The age of patients, the severity of disease and the status of resection margin(RM) were analyzed for predictive values of residual disease. The Chi-square test, Fisher's exact test and Student t-test were used for statistical analysis. RESULTS: The residual disease after hysterectomy was negative in 85.7%(114/133) and positive in 14.3%(19/133). Among 19 cases with positive residual disease, 3 cases were revealed to be microinvasive cervical cancer. The mean age of patients with no residual disease was 42.5 years(range; 27-71) and that of patients with residual disease was 49.1 years(range; 33-72). Nine out of 94 cases(9.6%) with negative RM and 10 out of 39 cases(25.6%) with positive RM in LLETZ had residual disease. Two out of 14 cases(14.3%) with CIN II and 17 out of 119 cases(14.3%) with CIN III in LLETZ had residual disease. The success of LLETZ which means no residual disease was influenced by the age of patients(p=0.005) and the status of resection margin of LLETZ(p=0.032). CONCLUSION: The negative resection margin in LLETZ does not always guarantee that there is no residual disease. Close preoperative workup and more aggressive treatment plan(wide conization or hysterectomy) should be considered in patients who has higher possibility of positive residual disease such as old age and positive resection margin in LLETZ.
Cervical Intraepithelial Neoplasia* ; Conization ; Gynecology ; Humans ; Hysterectomy ; Obstetrics ; Retrospective Studies ; Seoul ; Uterine Cervical Neoplasms