Epithelial Ovarian Carcinoma Associated with Metastases to Central Nervous System: Two Case Reports.

We experienced two rare cases of metastases to the central nervous system (cerebral and leptomeningeal metastases) from primary epithelial ovarian carcinoma. The first case was a 55-year-old woman who developed carcinomatous meningitis while on chemotherapy for ovarian cancer stage IIIC. Cytological analysis confirmed carcinomatous cells of ovarian origin in the cerebrospinal fluid. Magnetic resonance imaging demonstrated abnormal hyperintensity in the cerebral sulci on fluid attenuated inversion recovery (FLAIR) sequence with enhanced gadolinium indicating leptomeningeal metastases. Her consciousness rapidly declined and she died 42 days after diagnosis. The second case was a 63-year-old woman who underwent surgery for ovarian cancer and who was diagnosed as stage IA. Thirty-eight months after surgery, she developed weakness of the left hand and headaches. A CT scan revealed metastases to the right cerebrum and she was treated with surgical resection followed by radiotherapy. Five months after resection, she developed ileus caused by multiple relapses in the pelvis. Despite chemotherapy, her performance status declined and she died nine months after the resection. Both cases were rare because the first case was isolated leptomeningeal metastases, and the second case was confirmed relapse site in the cerebrum due to neurological symptoms despite her early clinical stage.

HPV genotyping for triage of women with abnormal cervical cancer screening results: a multicenter prospective study.

BACKGROUND: In cervical cancer screening programs, women with abnormal cytology are referred for colposcopy for histological evaluation. We examined whether a human papillomavirus (HPV) genotyping assay could be used to identify women who do not need immediate colposcopy and biopsy because of low risk of cervical intraepithelial neoplasia grade 3 or worse (CIN3+). METHODS: We prospectively evaluated test performance for 2 carcinogenic HPV genotypes (HPV16/18), for 8 types (HPV16/18/31/33/35/45/52/58), and for 13 types (HPV16/18/31/33/35/45/51/52/56/58/59/68) for prediction of histological CIN3+ results among 427 screen-positive women referred for colposcopy. The study subjects consisted of 214 women with low-grade squamous intraepithelial lesion (LSIL), 184 with high-grade squamous intraepithelial lesion (HSIL), and 29 with atypical squamous cells, cannot exclude HSIL (ASC-H). RESULTS: Among women with LSIL cytology, HPV16/18 positivity was 29.4 % and increased to 58.9 % for 8 types and to 74.8 % for 13 types (P < 0.001). The risk of CIN3+ biopsy results was still 7.9 % for women testing negative for HPV16/18, but decreased to 0.0 % for those testing negative for at least eight types of HPV (HPV16/18/31/33/35/45/52/58). Although HPV genotyping results enabled additional risk stratification among women with HSIL/ASC-H cytology, the risk of histological CIN3+ diagnosis among women testing negative for eight types or more was still sufficiently high (>35 %) to warrant immediate colposcopy referral. CONCLUSIONS: Of women with LSIL cytology, those testing negative for at least eight of the highest-risk types of HPV (HPV16/18/31/33/35/45/52/58) may not need immediate colposcopy and biopsy. This would reduce the number of colposcopy referrals by approximately 40 %. However, the HPV genotyping assay is not likely to alter the clinical management of women with HSIL/ASC-H.

Optimizing biopsy procedures during colposcopy for women with abnormal cervical cancer screening results: a multicenter prospective study.

BACKGROUND: In cervical cancer screening programs, women with abnormal cytology results are referred to colposcopy for histological diagnosis. This study was designed to evaluate the sensitivity of colposcopic procedures for detecting cervical cancer and its precursor, cervical intraepithelial neoplasia (CIN). METHODS: Women referred to colposcopy for abnormal cytology were enrolled from four hospitals. Gynecologists were required to take a colposcopy-guided biopsy from the worst of the abnormal-looking areas as a first biopsy. They were also asked to take ≥ 3 cervical specimens including by endocervical curettage (ECC). Random biopsies were performed at the gynecologist's discretion. We analyzed 827 biopsy results from 255 women who were diagnosed by central pathologists as having histology of CIN or cancer. RESULTS: In this study, 78.1% of diagnoses of CIN grade 2 or worse (CIN2+) (the threshold that would trigger intensive management) were obtained from a first colposcopy-guided biopsy. The additional diagnostic utility of second and third colposcopy-guided biopsies was 16.4 and 1.8%, respectively. The combined sensitivity of two colposcopy-directed biopsies for CIN2+ detection was >90%, regardless of the colposcopist. Random biopsies and ECC increased the diagnostic yield of CIN2+ lesions otherwise missed by colposcopy-guided biopsies alone, but only by 1.2 and 2.4%, respectively. Random biopsies were more useful for women referred after low-grade abnormal cytology (P = 0.01). The utility of ECC was greatest among women with unsatisfactory colposcopy (P = 0.03) or aged ≥ 40 years (P = 0.02). CONCLUSIONS: Our data suggest that at least two colposcopy-directed biopsies should be taken for histological diagnosis. Random biopsies and ECC are recommended for special populations.

Possibility of molecular targeting therapy for the treatment of cancer of unknown primary origin by analysis of intracellular signaling molecules.

Recently, antibody-mediated epidermal growth factor receptor (EGFR) blockade has become a major research focus, and a number of clinical studies on this new treatment have been started in the field of clinical oncology. This retrospective study investigated the role of KRAS gene mutations and clinical features for possibilities for new therapies in patients with cancer of unknown primary (CUP). We investigated the role of KRAS, PIK3CA and BRAF gene mutations and clinical features for possibilities for new therapies in patients with CUP. Nine patients with metastases from an unknown primary tumor were included in this retrospective study. The KRAS, BRAF and PI3KCA mutational analyses were carried out by means of PCR using genomic DNA for each PCR reaction. The mutation rate in CUP for codon 12 or 13 of the KRAS gene and for PIK3CA was lower than that in colorectal cancer, while the same mutation rate for BRAF was almost the same in the two; this means that the EGFR antibodies can possibly treat CUP.

Huge pedunculated angiomyofibroblastoma of the vulva.

We present the case of a huge pedunculated benign mesenchymal myxoid tumor that developed on the right labia majora of a 48-year-old-woman. The excised mass weighed 4534 g and was 23 cm in diameter; the cut surface was yellowish and elastic. Microscopic examination revealed spindle and plump oval tumor cells arranged with abundant capillary vessels in an edematous stroma. Immunohistochemical staining showed that the tumor cells were positive for vimentin, desmin, estrogen receptor, and progesterone receptor, but negative for alpha-smooth muscle actin, CD34, CD45, CD68, and S-100. Based on these features, the pathological diagnosis was angiomyofibroblastoma. A pedunculated angiomyofibroblastoma is extremely rare and, to the best of our knowledge, this is the biggest such tumor in terms of size and weight reported to date. It is especially important in such a huge mass greater than 10 cm that angiomyofibroblastoma is differentiated from aggressive angiomyxoma, which is a deeply invasive and recurrent neoplasm.

Adsorption of irinotecan onto oral adsorbent AST-120 (Kremezin) for preventing delayed diarrhea.

PURPOSE: One of the significant dose-limiting toxicities of irinotecan hydrochloride (CPT-11) is severe diarrhea due to impairment of the intestinal membrane induced by the excreted CPT-11 and its metabolites. AST-120 (Kremezin) is a prominent oral adsorbent that consists of porous spherical carbonic particles. To evaluate whether Kremezin can prevent the diarrhea induced by CPT-11, we investigated the adsorption characteristics of CPT-11 and its metabolites onto Kremezin in vitro and in vivo. METHODS: For in vitro studies, Kremezin was added to each solution containing one of the camptothecin drugs (CPT-11, SN-38, and SN-38-glucuronide), and adsorption activities were determined under various conditions. For in vivo studies, CPT-11 was consecutively administered, and the occurrence of diarrhea was compared between Kremezin-treated and non-treated rats. RESULTS: Kremezin drastically adsorbed the camptothecin drugs in vitro, and the adsorption percentages of the camptothecin drugs for 60 min were more than 85%. In addition, the frequency of diarrhea in Kremezin-treated rats decreased by approximately half of that in the non-treated rats. CONCLUSION: Kremezin showed potent adsorption capacities for the camptothecin drugs and mitigated the symptoms of diarrhea in rats. These results suggest that Kremezin is useful to prevent the diarrhea in clinical CPT-11 chemotherapy.

Single vaginal ectopic ureter of fetal metanephric duct origin, ipsilateral kidney agenesis, and ipsilateral rudimentary uterine horn of the bicornuate uterus.

BACKGROUND: Congenital anomalies arising from the urogenital tracts are common. We experienced two cases of specific urogenital anomalies. CASE: Two Japanese women had a single ectopic ureter opening in the central wall of the vagina, ipsilateral kidney agenesis, and ipsilateral rudimentary uterine horn of the bicornuate uterus. One had squamous cell carcinoma of the uterine cervix, and the other had adenocarcinoma of the vagina arising from the ectopic ureter meatus, which was histologically confirmed as fetal metanephric duct remnant. One had vesico-vaginal fistula postoperatively, resulting from separating the ureter-like duct from the bladder. CONCLUSION: Concomitant occurrence of anomalies suggests the common genetic backgrounds, which are not well known. Clinically, the ectopic vaginal ureter is important as a possible background of vaginal adenocarcinoma, and information on the ureter-like duct course is required during surgery.