Hyperthermic intrathoracic chemotherapy with cisplatin for ovarian cancer with pleural metastasis

Intrathoracic metastasis of ovarian cancer has poor prognosis regardless of treatment modality. Recent development of surgical techniques and the new concept of direct infusion of chemotherapeutic agents with hyperthermia could help with the treatment of disseminated diseases in ovarian cancer. Using video-assisted thoracoscopic surgery and intracavitary chemotherapy with hyperthermia, we tried hyperthermic intrathoracic chemotherapy for a case of stage IV high-grade serous ovarian cancer with pleural metastasis. There was no high-grade complication related to the procedure. The patient is alive without disease at 32 months after initial treatment.

Survival benefit of laparoscopic surgical staging-guided radiation therapy in locally advanced cervical cancer / 부인종양

OBJECTIVE: This study was designed to evaluate the survival benefit of laparoscopic surgical staging (LSS)-guided tailored radiation therapy (RT) in locally advanced cervical cancer (LACC). METHODS: We retrospectively reviewed 89 LACC patients' medical records who primarily received non-surgical treatment, of which pretreatment LSS was performed in 20 (LSS group) and primary chemoradiation therapy (CCRT) without LSS (CCRT group) was carried out in 69 from January 2000 to January 2006. We analyzed clinical characteristics, pretreatment imaging study results and survival outcomes including disease free survival (DFS) and overall survival (OS) to compare them between the two groups. RESULTS: There were as many as eight cases (40%) of LSS related complications. The mean time interval between LSS and RT or CCRT was 26.6 days (+/-18.8 days). Six out of twenty (30%) in LSS group and 10 out of 69 (14.5%) in CCRT group received extended field RT when paraaortic lymph nodes (LNs) were positive based on the pathologic findings after LSS and the results of imaging studies, respectively. Three-year DFS and OS were both better in 33 imaging-negative CCRT group patients than those in 4 imaging-negative/pathology-positive (false negative) patients after LSS (3-year DFS, 50% vs. 87%, p=0.022; 3-year OS, 50% vs. 84%, p=0.033). The 5-year DFS rates were 52% and 55% in LSS group and in CCRT group, respectively (p=0.28). The 5-year OS rates were 68% in LSS group and 62% in CCRT group without significant difference between the two groups (p=0.79). CONCLUSION: We found that LSS-based RT tailoring did not show survival benefit in LACC despite inaccuracy of imaging-based RT tailoring. Further studies are required to find new method to overcome this inaccuracy and improve survival outcomes.

The prevalence of endometriosis in cases of total hysterectomy / 대한산부인과학회지

OBJECTIVE: We investigated whether surgical methods, age, parity and obesity were correlated to endometriosis in patients who had hysterectomy. METHODS: This research was surveyed and reviewed of patients who underwent total abdominal hysterectomy, laparoscopic hysterectomy and vaginal hysterectomy in Kyungpook National University Hospital from 1999 to 2006, based on clinical recordings and pathologic reports. Based on these data, we investigated whether age, parity, obesity and pathologic diagnosis were correlated to prevalence rate of endometriosis. Also we investigated the correlations with anatomic lesion of endometriosis and surgical methods. SPSS version 12.0 chi- square test was conducted as the statistical data. RESULTS: The total 4,830 cases of hysterectomy were undergone. Out of these, endometriosis was found at 125 cases (2.5%). Among them, 76 cases of endometriosis were found at 2,260 cases of abdominal hysterectomy (3.3%). 31 cases of endometriosis were found at 1,589 cases of vaginal hysterectomy (1.95%), and 18 cases of endometriosis were found at 981 cases of laparoscopic hysterectomy (1.83%). The correlation with laparoscopic hysterectomy and endometriosis had the statistically significant high rate (P0.05). CONCLUSION: Even the prevalence of endometriosis was low (2.5%) in total cases of hysterectomy, laparoscopic hysterectomy had more prevalence rate of endometriosis than other types of hysterectomy. because suspicious lesions were inspected carefully, Magnified laparoscopic view make us to identify suspicious endometriotic lesion more clearly than other type of hysterectomy.

A case of massive serous ascites following radical hysterectomy with bilateral pelvic lymphadenectomy for cervical adenocarcinoma stage IB2 / 부인종양

Ascites following radical hysterectomy with retroperitoneal lymphadenectomy for invasive cervical cancer has been reported previously. Most of these reports described chylous ascites. The chylous ascitic fluid is milky; further, chylous ascites leads to nutritional problems. Authors present the case of a patient who developed serous ascites following radical hysterectomy with bilateral pelvic lymphadenectomy. The amount of ascites was approximately 18,000 ml over 52 days. The patient had no nutritional problems or complications. Although the etiology could not be determined, Authors surmise that the ascites may have been due to massive drainage from injured lymphatic channels below the cisterna chyli. Authors could not found any literatures which described massive serous ascites following surgery in gynecologic malignancy and reports this case with review of literatures.

A differential gene expression profiles by cDNA microarrays in endometrioid endometrial carcinoma: a preliminary study / 부인종양

OBJECTIVE: Endometrial carcinoma is the most common gynecological malignant disease in industrialized countries. However, the molecular bases for endometrial tumoriogenesis are not clearly elucidated. Our hypothesis is that there may be some difference in gene expression patterns between normal endometrium and endometrial cancer lesion. In this study, we analyzed the difference of gene expression profile with cDNA microarray. METHODS: Normal endometrial tissues and cancer lesions were gathered from three patient with endometrioid endometrial cancer. cDNA microarray technique (KNU 4.8K chip) was applied to screen the different gene expression profiles. RESULTS: Many genes such as interleukin-1 receptor-associated kinase 1 (IRAK1), bifunctional apoptosis regulator (BFAR), paraneoplastic antigen MA2 (PNMA2), zinc finger protein 257 (ZNF257), ras homolog gene family, member F (in filopodia) (ARHF), cell division cycle 27 (CDC27) were over-expressed in the endometrial cancer tissue. The genes were down-regulated in the endometrial cancer samples included fibronectin 1 (FN1), meiotic checkpoint regulator (MCPR), transforming growth factor beta-stimulated protein TSC-22 (TSC22), programmed cell death 4 (neoplastic transformation inhibitor) (PDCD4), transcript variant 2, matrix metalloproteinase 2 (MMP2), insulin-like growth factor binding protein 4 (IGFBP4), retinoblastoma binding protein 7 (RBBP7), insulin-like growth factor binding protein 3 (IGFBP3), downregulated in ovarian cancer 1 (DOC1). CONCLUSION: The result of this analysis supports the hypothesis that the endometrial cancer tissue has distinct gene expression profile from normal endometium. But, the vaildation of gene expression with RT-PCR and the further study are needed.

Trocar-site metastasis after laparoscopic gynecologic oncologic surgery / 대한산부인과학회지

OBJECTIVE: The purpose of this study was to evaluate the incidence of abdominal-wall tumor implantation after laparoscopic procedure in patients with gynecologic malignancies. METHODS: The records of 184 patients who had a laparoscopic operations or laparotomy after laparoscopic diagnostic procedures from Aug. 1994 to Aug. 2003 in our hospital were reviewed. The presence of metastasis at trocar site of laparoscopic surgery and incision site of laparotomy was examined. RESULTS: Abdominal-wall tumor implantations were developed at two port site in one patient. This result showed an incidence of 0.24% (2/819), as 2 ones in 819 abdominal trocar sites and 0.5% (1/184), as 1 in 184 procedures. This patient had a FIGO stage III a, grade2 adenocarcinoma of endometrium and underwent laparoscopic modified radical hysterectomy with both pelvic lymphadenectomy. In addition, tumor implantation was occurred at laparotomy skin incision site in one patient, a incidence of 2.2% (1/45), as 1 in 45 laparotomy procedures. This patient had a stage II, squamous cell carcinoma of the vagina, who had received second courses of Ifosfamide-Cisplantin neoadjuvant chemotherapy and open laparotomy with radical hysterectomy with upper vaginectomy was followed by laparoscopic pelvic lymphadenectomy due to fixed grossly metastatic nodes. CONCLUSION: Recently, the use of laparoscopic procedure in oncology was increased, the new complication such as abdominal-wall implantation at trocar site was introduced. The abdominal-wall implantation at trocar site could be prevented by patients selection, intraperitoneal and port-site lavage, surgical modification. And all patients should have careful follow up with special attention to the trocar sites. Port site implantation was rare, but could be occurred in the incidence of 0.5% per procedure.

Protein Expression Profile using Two-Dimensional Gel Analysis in Squamous Cervical Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Screening in cervical cancer is now progressing to discover candidate genes and proteins that may serve as biological markers and that play a role in tumor progression. We examined the protein expression patterns of the squamous cell carcinoma (SCC) tissues from Korean women with using two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometer. MATERIALS AND METHODS: Normal cervix and SCC tissues were solubilized and 2-DE was performed using pH 3~10 linear IPG strips of 17 cm length. The protein expression was evaluated using PDQuest 2-D software(TM). The differentially expressed protein spots were identified with a MALDI-TOF mass spectrometer, and the peptide mass spectra identifications were performed using the Mascot program and by searching the Swiss-prot or NCBInr databases. RESULTS: A total of 35 proteins were detected in SCC. 17 proteins were up-regulated and 18 proteins weredown-regulated. Among the proteins that were identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, alpha-enolase, squamous cell carcinoma antigen 1 and 2, glutathione S-transferase and apolipoprotein a1) were protein previously known to be involved in tumor, and 21 proteins were newly identified in this study. CONCLUSION: 2-DE offers the total protein expression profiles of SCC tissues; further characterization of these differentially expressed proteins will give a chance to identify the badly needed tumor-specific diagnostic markers for SCC.

Adenosine 5'-triphosphate induced NF-kappa B and intracellular calcium mobilization in cervical cancer cells / 대한산부인과학회지

OBJECTIVE: To know the effect of adenosine 5'-triphosphate (ATP) on intracellular calcium level and cell proliferation in cervical cancer cells. METHODS: Study design: Four different human cervical cancer cell lines (Caski, C33A, HeLaS3 and SiHa) were used in this study. The change of intracellular calcium level, cell proliferation and the activity of proliferation- and calcium-related transcription factors by extracellular ATP were examined in these cell lines. RESULTS: Extracellular ATP induced calcium mobilization, cell proliferation and the activation of NF-kappa B in all cell lines used. CONCLUSION: These results suggest that calcium mobilization and NF-kappa B dependent signaling pathway play an important role in the cell proliferation by ATP in cervical cancer.

Genetic Alteration of p16INKA4A Promoter Region in Endometrial Carcinoma / 부인종양

OBJECTIVE: This study was performed to evaluate the status of p16 tumor suppressor gene in 25 endometrial carcinomas (ECs) and to correlate the loss of heterozygosity (LOH) at p16 locus, the presence of inactivating mutations, the methylation status of the promotor, and the expression of p16 protein with clinicopathological parameters. METHODS: Methylation-specific PCR (MSP) distinguishes unmethylated from methylated alleles in a given gene on sequence changes produced after bisulfite treatment of DNA. Allelic losses were determined at two polymorphic dinucleotide repeat microsatellite markers of the p16 gene on chromosome 9p21 that included D9S974 and D9S1748 at CDKN2A. Mutations were analyzed by exons 1 and 2 of p16 PCR-SSCP. Immunohistochemical staining for p16 protein was performed. The associations between genetic alterations of the p16 and the clinicopathological parameters of ECs were evaluated by chi-squared or Fisher's extraction tests. RESULTS: The median age of the 25 cases was 52 years, ranging from 32 to 72. The median tumor size was 3.6 cm, ranging from 0.8 to 9.5 cm. Histologically, the ECs were 21 endometrioid, 2 adenosquamous, 1 secretory and 1 papillary serous types. Nine cases of p16 protein staining were negative or minimal positive in 25 ECs (36%). Allelic losses were found in 6 loci (66.7%) of 5 ECs without p16 protein expression (Fisher's extraction test, p=0.0029), In this study, only 2 of 25 ECs (8%) disclosed mutations. Non-endometrioid (secretory and adenosquamous) carcinomas showed more frequent mutation and methylation than endometrioid carcinomas (p=0.043) and high grades (G3, p=0.018) showed more frequent mutation and methylation than low grade ECs. CONCLUSION: This study suggests that methylation of p16 promoter region seems not to be common (only 9.5% in our present series) and not to be associated with loss of nuclear p16 protein expression. Loss of p16 protein indicates a higher frequency of LOH, which contributes to the development of high grade or aggressive ECs. The mechanism of p16 inactivation is not clear, so other genetic or nongenetic mechanisms for inactivation should be further studied.

Correlation of adenoassociated virus type 2 and high-risk human papillomavirus type 16 and 18 infection in the cervix of Korean women / 대한산부인과학회지

OBJECTIVE: Previous studies were showed that adenoassocited virus (AAV) infection was had negative effects on human papillomavirus (HPV) infection and that the cervical cancer cell growth is inhibited by AAV infection. We detected of AAV 2 and high-risk HPV infection and researched correlation with AAV 2 and HPV in cervical cell. METHODS: Cell of normal cervix (49 persons), infected HPV cervix (45 persons), cervical intraepithelial neoplasm (CIN) I (31 persons), II (20 persons), III (35 persons), and invasive cancer (30 persons) were investigated by PCR using AAV-2 and HPV type 16 and 18 specific primers. RESULTS: AAV 2 was detected in 8 out of 49 normal cervix (16.3%), 2 out of 45 infected HPV cervix (4.4%), 3 out of 31 CIN I (9.7%), 4 out of 20 CIN II (20%), 8 out of 35 CIN III (22.8%), and 3 out of 30 invasive cervical cancer cases (30%). However, HPV 16 was detected in 5 out of 49 normal cervix (10.2%), 20 out of 45 infected HPV cervix (44.4%), 13 out of 31 CIN I (42%), 11 out of 20 CIN II (55%), 19 out of 35 CIN III (54.3%), and 21 out of 30 invasive cervical cancer cases (70%). HPV 18 was detected in 6 out of 49 normal cervix (12.2%), 18 out of 45 infected HPV cervix (40%), 16 out of 31 CIN I (51.6%), 10 out of 20 CIN II (50%), 22 out of 35 CIN III (62.8%), and 13 out of 30 invasive cervical cancer cases (43.3%). CONCLUSION: AAV 2 was detected in normal and infected HPV cervix, CIN (I, II, III) and invasive cervical cancer. As compared to normal, CIN I and CIN II, suggesting significant correlation between AAV 2 and HPV type 16. Further, researches continue to be done relationship to AAV 2 and HPV infection in cervix.

Search for Gene Expression in Cervical Squamous Cell Carcinoma using GeneFishing(TM) DEG PCR Technique / 대한산부인과학회지

OBJECTIVE: The aim of this study was to investigate the gene expression profiles using GeneFishing(TM) DEG kit in Korean women with cervical squamous cell carcinoma. METHODS: Cervical cancer biopsies were obtained from patients at the Department of Obstetrics and Gynecology, St. Mary's hodpital. In this study, we used a common reference that was mixed with an equal amount of RNA extracted from non-cervical cancer patients. The profiles of expression genes between cervical normal and squamous cell carcinoma tissue were identified using GeneFishing(TM) DEG Kit and screened by BLAST search. RESULTS: Almost 100 differential expressed genes were identified in universal control and cervical squamous cell carcinoma, 53 of differential expressed genes, up-regulated expression of 32 and 21 down-regulated expression was sequenced. Up-regulated genes were calcylin, calgranulin A, TRK oncogene, HLC5, fibrillarin, collagene type I alpha1 etc. and down-regulated genes were galectin 1, PRP8 pre-mRNA precessing factor 8 homology, clusterin etc. CONCLUSION: We identified gene expression profile in cervical squamous cell carcinoma using GeneFishing(TM) Kit in Korean women. The functional genomics of these genes should be further studied.

Degradation of the Retinoblastoma Tumor Suppressor Protein by the Human Papillomavirus-16 E7 Variants

Human papillomavirus type 16 (HPV-16) plays an etiological role in benign and malignant epithelial tumors. A critical event in HPV transformation of human cells is the inactivation of retinoblastoma protein (pRB) by the E7 protein. The metabolic half-life of pRB is decreased in cells that express high-risk HPV E7 proteins. The present study investigated the frequency of HPV-16 E7 variants in Korean women and compared the pRB degradation activity of E7 variant proteins. Of the 40 HPV-positive specimens from a total of 91 tissue specimens, 21 HPV-16 positive specimens were studied by sequencing analysis to determine the variation of E7 gene. The most frequent E7 variant was N29S (57%). The HPV-16 E7 variant was more prevalent in invasive cervical cancer tissue specimens than in those from low grade clinical stage. The degradation of pRB in HaCaT cells by HPV-16 E7 variant proteins was investigated by western blot analysis. There was no significant difference in pRB degradation activity between the HPV-16 E7 prototype protein and E7 variant proteins. The pRB degradation activity did not differ among HPV-16 E7 variants. These results suggest that the E7-induced degradation of pRB is important in cervical tumorigenesis; however, there was no relation between the pRB degradation activity and the variations in HPV-16 E7 protein among Korean women.

Proteomic analyses of cervical cancer tissues by two-dimensional gel electrophoresis and mass spectrometry / 대한산부인과학회지

OBJECTIVE: Comparison of protein expressions by two-dimensional gel electrophoresis (2-DE) in normal cervix and squamous cell carcinoma tissues in Korean women. METHODS: Normal cervix and squamous cell carcinoma tissues were solubilized with 2-DE buffer and the first dimension of PROTEAN IEF CELL, isoelectric focusing (IEF), was performed using pH3-10 linear IPG strips of 17 cm. And then running 12% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and sliver stain. Scanned image was analyzed using PDQuest 2-D softwareTM. Protein spot spectrum was identified by assisted laser desorption/ionization-time of fighting (MALDI-TOF) and the protein mass spectrum identifications were performed by searching protein databases of Swiss-prot/TrEMBL, Mascot and MS-FIT. RESULTS: We found 9 up-regulation proteins (Alpha enolase, Keratin 19 type I, Keratin 20 type I, Keratin 13 type I, beta-actin, Aflatoxin B1 aldehyde reductase 1, Annexin A2, Squamous cell carcinoma antigen 2, unknown), 7 down-reguation proteins (Annexin 1, Myosin regulatory light chain 2, 14-3-3 protein epsilon, Heat shock 27 kDa protein, Hypothetical protein (DKFZP434C1715), Tumor necrosis factor receptor superfamily member 13B, Smoth muscle protein 22-alpha) and 6 up and down-regulation proteins (Tropomyosin 1, Tropomyosin 2, Tropomyosin 3, Serine (or cysteine) proteinase inhibitor, Phosphatidylinositol transfer protein alpha isoform, Src homology 3 domain-containing protein HIP-55) between normal cervix and squamous cell carcinoma cell tissues. CONCLUSION: 2-DE offers total protein expressions between normal cervix and squamous cell carcinoma cell tissues, and searching of differently expressed protein for the diagnostic markers of squamous cell carcinoma tissue.

cDNA Microarray Analysis of Gene Expression Profiles Associated with Cervical Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The molecular pathology of cervical cancers associated with human papillomavirus infection is presently unclear. In an effort to clarify this issue, the gene expression profiles and pathogenic cellular processes of cervical cancer lesions were investigated. MATERIALS AND METHODS: Cervical cancer biopsies were obtained from patients at the Department of Obstetrics and Gynecology, The Catholic University of Korea. The disease status was assigned according to the International Federation of Gynecology and Obstetrics. The tissue samples of 11 patients (invasive cancer stage Ib- IIIa) were investigated by a cDNA microarray of 4, 700 genes, hierarchical clustering and the Gene Ontology (GO). Total RNA from cervical cancer and non-lesional tissues were labeled with Cy5 and Cy3. The HaCaT human epithelial keratinocyte cell line was used as a negative control cell. The stages of invasive cancer were Ib to IIIb. All specimens were obtained by punch-biopsies and frozen in liquid nitrogen until required. RESULTS: 74 genes, showing more than a 2 fold difference in their expressions, were identified in at least 8 of the 11 patients. Of these genes, 33 were up-regulated and 41 were down-regulated. The gene expression profiles were classified into 345 mutually dependent function sets, resulting in 611 cellular processes according to their GO. The GO analysis showed that cervical carcinogenesis underwent complete down-regulation of cell death, protein biosynthesis and nucleic acid metabolism. The genes related to nucleic acid binding and structural molecule activity were also significantly down-regulated. In contrast, significant up-regulation was shown in the skeletal development, immune response and extracellular activity. CONCLUSION: These data are suggestive of potentially significant pathogenetic cellular processes, and showed that the down-regulated functional profiling has an important impact on the discovery of pathogenic pathways in cervical carcinogenesis. GO analysis can also overcome the complexity of the expression profiles of the cDNA microarray via a cellular process level approach. Thereby, a valuable prognostic candidate gene, with real relevance to disease-specific pathogenesis, can be found at the cellular process levels.

Two Cases of Malignant Melanoma in Vulva / 대한산부인과학회잡지

Vulvar melanomas are account for 4-10% of all malignant tumors of the vulva and are the second most common cause of the vulvar malignancy with the highest frequency in the sixth and seventh decades and rare with incidence of 0.1 to 0.19 per 100,000 women. The most common presentation is a vulvar mass, although pruritis and bleeding also are frequent. In some cases, the melanoma has arisen from a pre-existing benign or atypical pigmented lesion. Vulvar melanomas appear to behavior as other cutaneous melanomas. Both the level of invasion of a malignant melanoma and its thickness have prognostic significance. Vascular space invasion and tumor necrosis also are associated with a poorer prognosis. Recently the radical vulvectomy dose not appear to improve survival when compared to wide local excision with bilateral inguinofemoral lymphadenectomy. We had 2 cases of vulvar melanoma treated with wide local excision and laparoscopic inguinofemoral lymphadenectomy.

Comparison of Embryonic Developmental Capacity by different Co-culture Time of Oocytes in IVF-ET Cycles / 대한불임학회지

OBJECTIVE: To evaluate whether co-culture of oocytes on vero cell monolayers from Day 0 (Day 0 group) after egg retrieval results in an increase in developmental capacity such as fertilization rate, embryo quality, blastulation and clinical pregnancy rate compared with co-culture of oocytes from Day 1 (Day 1 group). METHODS: Sperms were treated with Hams F-10 supplemented with 10% human follicular fluid (hFF). Vero cells for co-culture were prepared in TCM-199 with 10% FBS. Oocytes were co-cultured from Day 0 and fertilized oocytes were co-cultured from Day 1 on vero cell monolayers in DMEM with 10% and 20% hFF, respectively after egg retrieval. On day 1, 2 and 5, fertilization rate and grade of embryos and blastocysts were evaluated. Results (fertilization rate, cleavage rate, grade of embryos and blastocysts and pregnancy rate) were considered statistically significant when p value was less than 0.05 using t-test and ci2. RESULTS: In sibling oocytes of same cycles, no differences were found in fertilization rate (94.6 vs. 91.4%), cleavage rates (94.6 vs. 91.4%), embryo grade (on day 2 and 3) and blastulation (65.6 vs. 57.0%) and their grade. In different oocytes of different cycles (patients), no differences were found in fertilization (79.8 vs. 78.3%), cleavage rates (77.7 vs. 76.4%) and blastulation (56.0 vs. 45.3%), but pregnancy rate was higher in the Day 0 group than in the Day 1 group (60.0 vs. 42.9%). CONCLUSIONS: This study revealed that the embryonic development capacities were not affected by the different co-culture time in the sibling oocytes of same cycles. Although no statistical significance, because of small size of study, there was a trend for higher pregnancy rates in Day 0 group compared to Day 1 group in different oocytes of different cycles.

Genomic Analysis of Human Papillomavirus Type 16 in Cervical Cancer

To study the correlation of human papillomavirus (HPV) infection with clinical stage in cervical abnormalities, 17 cases of normal cervical tissue and 69 cases of abnormal cervical tissue (cervical intraepithelial neoplasia and invasive cervical cancer) was examined by PCR with HPV-specific consensus primers. One case (5.9%) of normal cervical tissue and 42 cases (60.9%) of abnormal cervical tissues harbored HPV. To investigate the integration of HPV genome in 24 cases of HPV 16 positive cervical cancer, E2 gene of HPV 16 was amplified. Integration of HPV 16 was found in 7 cases (29.2%) with E2 disruption. All samples with E2 disruption were from invasive cervical cancer. A multiplex PCR for the mapping of integrated HPV 16 genome with an anchor primer and indicator primers showed that 11 cases (45.8%) were disrupted somewhere in HPV genome but E6, E7, and LCR regions were conserved in all cases. Seven types of integrated HPV genome from long- (7,062 bp) to short-conserved type (3,204 bp) with various deletions were detected by the multiplex PCR. These results show that integration can be detected more accurately by multiplex PCR than by E2 PCR, and E2 disruption is not a critical event of integration

Clinicopathologic Variables Related to Residual Neoplasia after Cervical Conization / 대한산부인과학회잡지

OBJECTIVE: To evaluate the clinicopathologic variables that are important for predicting residual disease after cervical conization in hysterectomy specimens. METHODS: We performed retrospective review of 125 patients who had undergone cervical conization and endocervical curettage followed by subsequent hysterectomy. Pathologic findings of the cone margins, endocervical curettage samples, and residual lesions in the postcone hysterectomy specimens were recorded for analysis. RESULTS: The prevalence rates of positive cone margins increased with higher severity of cervical neoplasia. There was a statistically significant difference in the prevalence of residual disease in hysterectomy specimens between patients with positive endocervical margins on cone biopsy(67.3%) and those with negative margins(11.8%) (p<0.01). Most residual lesions in the postcone hysterectomy specimens were similar to cone pathology, however the possibility of more advanced lesions in the uterus was present in patients with positive cone margins. Residual disease was significantly more frequently found in patients with positive endocervical curettage(82.4%)(p<0.01). Especially, when both the endocervical margin and endocervical curettage were positive, residual disease was present in 25 of 28 (89.3%) hysterectomy specimens. CONCLUSIONS: From these results, we concluded that the status of endocervical margin and endocervical curettage have significant predictive value with respect to the presence or absence of residual disease, and final decision in regard to subsequent management should be based on histologic finding of the cone margins and endocervical curettage as well as the patient's age and desire to retain reproductive capability.

Peritoneal Fluid levels of various Cytokines in Patients with Ovarian Lesions / 대한산부인과학회잡지

OBJECTIVE: Recent studies have shown that multifunctional cytokines have been implicated in the pathogenesis and pathophysiology of various ovarian lesions including ovarian cancer and endometriosis. This study was performed to determine the possibility of the clinical usefulness of peritoneal cytokines in patients with various ovarian lesions. METHODS: Peritoneal fluid was obtained from patients with benign cystic adenoma(n=11), benign cystic teratoma(n=10), endometriosis(n=23), malignant ovarian tumor(n=11), and women without evidence of any pathology(n=7) at the time of laparotomy or operative laparoscopic surgery and were examined for the levels of IFN-gamma, IL-1beta, IL-5, IL-6, IL-10 and TNF-alpha using enzyme-linked immunosorbent assay(ELISA). Statistical analysis was performed with the one way ANOVA, Scheffe test or Mann-Whitney test. RESULTS: The mean concentration of IL-6 and IL-10 was significantly higher in peritoneal fluid specimens with ovarian cancer than other benign pathology(p<0.05). Both IL-6 and IL-10 levels in peritoneal fluid specimens with endometriosis tended to be higher than normal, and the levels of IL-6 and IL-10 were significantly higher in peritoneal fluid of women with severe endometriosis compaired to women with mild endometriosis (p<0.05). CONCLUSION: This study supports the concept that regional immunologic dysfunction might be involved in the disease process of various ovarian pathology such as ovarian cancer and endometriosis. A larger study would help in evaluating the potential use of local peritoneal cytokines in differentiating ovarian cancer from other benign pathology, and demonstrating any association between concentrations of cytokines and severity of endometriosis.

Pathologic Changes in Uterine Leiomyomas Treated by GnRH Agonist Goserelin / 대한산부인과학회잡지

OBJECTIVE: To define the pathologic changes underlying the mechanism of shrinkage of uterine leimyoma in patients treated with goserelin. METHODS: Retrospective evaluation of pathologic changes seen in leiomyoma removed by hysterectomy or myomectomy in treated and untreated patients was done. Microscopic review of all cases was performed without knowledge of the therapeutic history. Each leiomyoma was assessed for hyalinization, hydropic change, lymphocytic infiltrate, nuclear atypia, and hypercellularity. RESULTS: Hyaline degeneration and hydropic changes were found significantly more frequent in patient treated with goserelin (P<0.05). The differences between treated and untreated groups in lymphocytic infiltrate, nuclear atypia, and hypercellularity were not statistically significant. The ultrastructural features of variable numbers of the treated muscle cells showed large vacuole, marked swelling of mitochondria, and compound lysosomal structures presumed to have been formed from damaged intracellular organelles. CONCLUSION: It appears that the rapid decrease in size of the leiomyoma treated with goserein occurs as the smooth muscle tissue undergoes hydropic change and hyaline degeneration. It seems that other cellular degenerative changes may be involved in the mechanism shrinkage of uterine leiomyoma.