Clinical efficacy of photodynamic therapy.

OBJECTIVE: The management of cervical intraepithelial neoplasia (CIN) and early invasive cancer of the uterine cervix is very difficult to approach, especially in case of young woman who wants to preserve her fertility. Conization of the cervix may have various kinds of disadvantage. The objective of this clinical retrospective study is to investigate the therapeutic effects and clinical efficacy of photodynamic therapy (PDT) including combined chemo-photodynamic therapy in patients with pre-malignant CIN and malignant invasive cervical cancer. METHODS: Total number of PDT trial case was 50 cases and total number of patient was 22 patients who registered to PDT clinic. We used photogem sensitizer and 632 nm diode laser in early two cases. After then we performed PDT using photofrin sensitizer and 630 nm diode laser in other cases. We used flat-cut, microlens, cylindrical diffuser, and interstitial type optic fibers in order to irradiate the lesions. 240 J/cm2 energy was irradiated to the lesions. RESULTS: CIN 2 were 4 cases (18.2%) and CIN 3 were 15 (68.2%) and invasive cervical cancer were 3 (13.6%). Complete remission (CR) was found in 20 patients (91%). One case of 19 patients with CIN lesion recurred at 18 months after PDT treatment. CR was found in 18 cases in the patients with CIN lesions (95%). CR was found in 2 cases in the patients with invasive cervical cancer (67%). CONCLUSION: Our data showed that CR rate was fantastic in CIN group (95%). This study suggests that PDT can be recommended as new optimistic management modality on the patients with pre-malignant CIN lesions including carcinoma in situ and relatively early invasive cancer of the uterine cervix. Combined chemo-photodynamic therapy is essential in case of invasive cervical cancer. For the young age group who desperately want to preserve their fertility and have a healthy baby, PDT can be a beacon of hope.

Uterine arteriovenous malformation with positive serum beta-human chorionic gonadotropin: Embolization of both uterine arteries and extra-uterine feeding arteries.

The incidence of uterine arteriovenous malformation (AVM) is rare. However, it is clinically significant in that it can cause life-threatening vaginal bleeding. We report a case of a large uterine AVM with positive serum beta-human chorionic gonadotropin. A presumptive diagnosis was made; a uterine AVM accompanied by, early pregnancy or retained product of conception. Because this uterine AVM was extensive, transcatheter arterial embolization of both uterine arteries and extra-uterine feeding arteries was performed. Three months after undergoing transcatheter arterial embolization, complete resolution of the uterine AVM was confirmed without major complication.

Struma ovarii and peritoneal strumosis with thyrotoxicosis.

BACKGROUND: Struma ovarii is a highly specialized form of mature ovarian teratoma consisting of thyroid tissue and exhibiting all the histological features of the thyroid gland. Malignant transformation of thyroid tissue in struma ovarii and metastasis are extremely uncommon. In rare cases, benign thyroid tissue may spread to the peritoneal cavity, and pathologic examination of the peritoneal implants shows multiple nodules of varying sizes of mature thyroid tissue similar to struma ovarii. This condition is termed "peritoneal strumosis." SUMMARY: We report a 49-year-old woman with struma ovarii complicated by peritoneal strumosis with thyrotoxicosis. After surgical resection of the struma ovarii and peritoneal strumosis the patient became euthyroid. CONCLUSION: To the best of our knowledge this is the first report of a patient with peritoneal strumosis complicated by thyrotoxicosis. The relative contribution to circulating thyroid hormones by the patient's struma ovarii as compared to the peritoneal strumosis is not known.

Polymerase chain reaction-based fluorescent Luminex assay to detect the presence of human papillomavirus types.

Becuase 40% of human papillomavirus (HPV) infections are mixed infections, the accurate identification of high-risk HPV genotypes in mixed infections is important for defining a woman's risk for progression to cervical cancer. Thus, advanced Luminex-based HPV genotyping has been developed to simultaneously detect the presence of multiple HPV types. Here, we describe the development of a Luminex-based HPV genotyping that combines polymerase chain reaction amplification with hybridization to fluorescence-labeled polystyrene bead microarrays (Luminex suspension array technology). New HPV type-specific oligonucleotide probes and YBT L1/GP6-1 primers were used to detect the HPV types in 132 clinical samples. We simultaneously evaluated the usefulness of this technique on clinical samples. We detected 15 specific HPV types (6, 16, 18, 31, 35, 42, 51, 52, 55, 56, 58, 59, 66, 67 and 68) examined with specificity without known cross-reaction to other HPV types. The detection limit for the different HPV types was above 500 plasmids. We compared the performance of the Luminex-based assay to the established HPV DNA microarray chip for polymerase chain reaction products derived from 53 clinical samples. The evaluation showed excellent agreement. The Luminex-based HPV genotyping was a sensitive, reproducible technique for the simultaneous genotyping of all clinically relevant genital HPV types. This assay system may be used to provide critical clinical information for early detection of HPV, especially in cases where the HPV copy numbers are low and the latency period of HPV infection is prolonged.

Photodynamic therapy-generated tumor cell lysates with CpG-oligodeoxynucleotide enhance immunotherapy efficacy in human papillomavirus 16 (E6/E7) immortalized tumor cells.

Immunotherapy with photodynamic therapy (PDT) offers great promise as a new alternative for cancer treatment; however, its use remains experimental. In this study, we examined the immunotherapeutic significance of human papillomavirus (HPV)-immortalized tumor cell lysates induced by PDT with CpG-oligodeoxynucleotide (ODN). PDT-cell lysates were generated by irradiating Radachlorin (5 microg/mL) preloaded TC-1 cells carrying HPV 16 E7. PDT-cell lysates plus ODN coinjection for protection against E7-expressing tumors as well as specific immune responses were evaluated with the following tests: heat shock protein 70 (HSP70) enzyme-linked immunosorbent assay, in vitro and in vivo tumor growth inhibition, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) assay, cytotoxic T-lymphocyte assay, and fluorescence activated cell sorting (FACS) analysis. PDT-cell lysates plus ODN coinjection showed a significant suppression of tumor growth at both prophylactic and therapeutic levels, compared to PDT (or F/T)-cell lysates or ODN alone. In addition, we evaluated the level of the immune response with the coinjection. HSP70, an important regulator of inflammatory and immune response, was observed in abundance in the PDT-cell lysates. IFN-gamma production and cytotoxic T lymphocytes (CTL) responses were induced by PDT-cell lysates plus ODN injection. The coinjection resulted in PDT-cell lysate-specific antibodies (IgG1, IgG2a, IgG2b, and IgG3) and T-helper cell responses significantly higher than PDT-cell lysates alone. Moreover, IFN-gamma production and CTL responses were significantly induced in the PDT-cell lysate plus ODN immunized groups. These enhanced immune responses appeared to be mediated by CD8+ T cells only. These data suggest that PDT-cell lysates plus ODN injection may be an effective approach to induce CTL immune responses as a possible immunotherapeutic strategy for cancer therapy.

Protein expression profile using two-dimensional gel analysis in squamous cervical cancer patients.

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 approximately 10 linear IPG strips of 17 cm length. The protein expression was evaluated using PDQuest 2-D software. 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 were down-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.

Speculoscopy as Pap Smear Adjunct.

PURPOSE: Speculoscopy, or magnified chemiluminescent examination (MCE), is a new visual method for the detection of cervical neoplasia. It utilizes low magnification and a special "blue-white" chemiluminescent light. The purpose of this study was to evaluate the screening effectiveness of speculoscopy combined with the conventional Papanicolaou smear, as compared with the latter alone, through a clinical trial in Korea. MATERIALS AND METHODS: This prospective, randomized, university hospital-based clinical study was performed in the outpatient clinic of the Department of Obstetrics and Gynecology at Dankook University Medical Center from December 1, 2001 to June 30, 2002. Of the 113 patients aged 19~74 years who had undergone both conventional Papanicolaou cervical cytologic test and speculoscopy, 38 cases underwent histologic diagnoses by colposcopy- directed biopsy. RESULTS: Of the 113 patients, there were 87 (77.0%) spe-culoscopy diagnoses of negative, 9 (8.0%) of suspicious, and 17 (15.0%) of positive. Of the 38 histologic diagnoses, there were 19 (50.0%) diagnoses of negative, 7 (18.4%) of LSIL, 1 (2.6%) of HSIL, 10 (26.3%) of SCC, and 1 (2.6%) of ACC. Pap smear showed sensitivity of 77.8% and specificity of 81.3%, whereas speculoscopy showed 94.1% and 100.0%, respectively, and Pap smear combined with speculoscopy showed 100.0% and 81.3%, respectively. CONCLUSION: Speculoscopy showed a higher sensitivity rate than Pap smear as a screening test, although the sample size was small. Speculoscopy combined with Pap smear is thought to be a very effective method for detecting cervical neoplasia.