Comparison of ThinPrep Integrated Imager-Assisted Screening versus Manual Screening of ThinPrep Liquid-Based Cytology Specimens.

OBJECTIVE: The aim of this study was to find out whether ThinPrep Integrated Imager (Hologic Inc.) screening is non-inferior to manual screening in the detection of cervical lesion. STUDY DESIGN: For a total of 4,011 ThinPrep Pap test specimens stained by ThinPrep staining, manual screening (Manual arm) and ThinPrep Integrated Imager screening (Imager arm) were performed so as not to be screened by the same cytotechnologist, and the sensitivity and specificity in the detection of cervical lesion were compared using McNemar's test. RESULTS: The sensitivity to detect CIN1 or more squamous cell abnormalities or glandular abnormalities was 91.67% (= 374/408, 95% confidence interval [CI]: 88.44-94.08%) for the Manual arm and 92.40% (= 377/408, 95% CI: 89.28-94.70%) for the Imager arm, and the specificity was 88.87% (= 3,113/3,503, 95% CI: 87.77-89.88%) for the Manual arm and 89.55% (= 3,137/3,503, 95% CI: 88.48-90.54%) for the Imager arm. The differences in sensitivity and in specificity, respectively, were 0.74% (95% CI: -3.14-4.61%, McNemar's test, p = 0.8041) and 0.69% (95% CI: -0.13-1.50%, McNemar's test, p = 0.1125). About the equality of sensitivity and specificity between the 2 methods, 95% CIs of the difference between sensitivity and specificity are in the clinical equivalence range of ±5%, so the Imager arm is non-inferior to the Manual arm. CONCLUSION: The Imager arm was confirmed to have an equivalent and non-inferior capacity in the detection of cervical lesions compared with the Manual arm, suggesting that its practical application in cervical cytology tests is highly possible.

Colon Metastasis From Microscopic Serous Carcinoma of the Fallopian Tube Fimbria Mimicking a Primary Colon Cancer.

Metastatic diseases rarely develop in the colorectum, and diagnosing colorectal metastasis by biopsy without history of a malignant tumor or clinical information of a primary tumor is challenging. A 65-year-old woman with a 6-month history of constipation and diarrhea was admitted to our hospital and diagnosed with rectosigmoid colonic micropapillary carcinoma. Low anterior resection was performed after neoadjuvant chemotherapy. Because the lipoleiomyoma in the uterus obstructed the operator's vision, total hysterectomy and bilateral salpingo-oophorectomy were performed. Examination of the colon and adnexa, together with immunohistochemical studies, revealed that the colonic tumor was actually serous carcinoma that had metastasized from the left fimbria of the fallopian tube. Retrospective immunohistochemical examination of the colon biopsy specimen suggested carcinoma with a Müllerian immunophenotype. When a colon biopsy reveals carcinoma with an invasive micropapillary pattern without a component of conventional tubular adenocarcinoma, immunohistochemical examination should be performed to rule out the possibility of metastasis.

Pulmonary Metastasis of Undifferentiated Uterine Sarcoma Forming Fluid-Containing Cyst.

Undifferentiated uterine sarcoma (UUS) is a high-grade sarcoma with no specific differentiation; however, it exhibits variable positivity for CD10 as an immunohistochemical marker of endometrial stroma, suggesting immunohistochemical differentiation into endometrial stroma. It has been reported that some low-grade endometrial stromal sarcoma pulmonary metastatic foci show cystic changes; however, whether pulmonary metastatic UUS foci are solid or cystic remains undescribed. A 63-year-old woman underwent a hysterectomy. The subsequent pathologic diagnosis was UUS. After the operation, she was treated with chemotherapy; however, pulmonary solitary shadow was radiologically detected. Eight months after the gynecologic operation, her pulmonary lesion was surgically resected. Pathologically, the lesion consisted of a cyst containing serous fluid with thick whitish wall composed of tumor cells, which led to the diagnosis of metastatsis of UUS. The cyst seemed to be formed via secondary degeneration. She remains healthy without recurrence 28 months after her first visit to our hospital.

Ultrasound-based logistic regression model LR2 versus magnetic resonance imaging for discriminating between benign and malignant adnexal masses: a prospective study.

BACKGROUND: The diagnostic performances of the International Ovarian Tumor Analysis (IOTA) ultrasound-based logistic regression model (LR2) and magnetic resonance imaging (MRI) in discriminating between benign and malignant adnexal masses have not been directly compared in a single study. METHODS: Using the IOTA LR2 model and subjective interpretation of MRI findings by experienced radiologists, 265 consecutive patients with adnexal masses were preoperatively evaluated in two hospitals between February 2014 and December 2015. Definitive histological diagnosis of excised tissues was used as a gold standard. RESULTS: From the 265 study subjects, 54 (20.4%) tumors were histologically diagnosed as malignant (including 11 borderline and 3 metastatic tumors). Preoperative diagnoses of malignant tumors showed 91.7% total agreement between IOTA LR2 and MRI, with a kappa value of 0.77 [95% confidence interval (CI), 0.68-0.86]. Sensitivity of IOTA LR2 (0.94, 95% CI, 0.85-0.98) for predicting malignant tumors was similar to that of MRI (0.96, 95% CI, 0.87-0.99; P = 0.99), whereas specificity of IOTA LR2 (0.98, 95% CI, 0.95-0.99) was significantly higher than that of MRI (0.91, 95% CI, 0.87-0.95; P = 0.002). Combined IOTA LR2 and MRI results gave the greatest sensitivity (1.00, 95% CI, 0.93-1.00) and had similar specificity (0.91, 95% CI, 0.86-0.94) to MRI. CONCLUSIONS: The IOTA LR2 model had a similar sensitivity to MRI for discriminating between benign and malignant tumors and a higher specificity compared with MRI. Our findings suggest that the IOTA LR2 model, either alone or in conjunction with MRI, should be included in preoperative evaluation of adnexal masses.

Intravenous injection of umbilical cord-derived mesenchymal stromal cells attenuates reactive gliosis and hypomyelination in a neonatal intraventricular hemorrhage model.

Intraventricular hemorrhage (IVH) is a frequent complication of preterm newborns, resulting in cerebral palsy and cognitive handicap as well as hypoxic ischemic encephalopathy and periventricular leukomalacia. In this study, we investigated the restorative effect on neonatal IVH by umbilical cord-derived mesenchymal stromal cells (UC-MSCs) cultured in serum-free medium (RM medium) for clinical application. UC-MSCs were cultured with αMEM medium supplemented with FBS or RM. A neonatal IVH mouse model at postnatal day 5 was generated by intraventricular injection of autologous blood, and mice were intravenously administered 1×105 UC-MSCs two days after IVH. Brain magnetic resonance imaging was performed at postnatal day 15, 22 and neurological behavioral measurements were performed at postnatal day 23, accompanied by histopathological analysis and cytokine bead assays in serum after IVH with or without UC-MSCs. Both UC-MSCs cultured with αMEM and RM met the criteria of MSCs and improved behavioral outcome of IVH mice. Moreover the RM group exhibited significant behavioral improvement compared to the control group. Histopathological analysis revealed UC-MSCs cultured with RM significantly attenuated periventricular reactive gliosis, hypomyelination, and periventricular cell death observed after IVH. Furthermore, human brain-derived neurotrophic factor and hepatocyte growth factor were elevated in the serum, cerebrospinal fluid and brain tissue of neonatal IVH model mice 24h after UC-MSCs administration. These results suggest UC-MSCs attenuate neonatal IVH by protecting gliosis and apoptosis of the injured brain, and intravenous injection of UC-MSCs cultured in RM may be feasible for neonatal IVH in clinic.

Two cases of adenocarcinoma in situ arising in lobular endocervical glandular hyperplasia indicating localization of mucin on the cluster surface as an early cytological finding of malignant transformation.

Lobular endocervical glandular hyperplasia (LEGH) is an endocervical glandular hyperplastic lesion containing pyloric gland-like mucin, and has recently been recognized as a precursor lesion of malignant glandular lesions of the endocervix. The pyloric gland-like mucin contained in LEGH and gastric-type adenocarcinoma is observed as golden-yellowish by Papanicolaou staining. However, to our knowledge, the chronological course of the endocervical cytology of LEGH, eventually resulting in malignancy, has never been demonstrated to date. Here, we report two cases of gastric-type adenocarcinoma in situ (AIS) arising in LEGH, together with an analysis of their cytological course. In both cases, localization of mucin on the surface of glandular cell clusters was observed prior to nuclear atypia in endocervical cytology. In addition, the diagnosis of gastric-type AIS arising in LEGH was confirmed by pathological diagnosis of hysterectomy specimens in both cases. Histologically, all glandular cells of the LEGH without nuclear atypia contained a large amount of PAS-positive mucin. On the other hand, in atypical glandular cells, localization of the mucin on the luminal surface was observed, although mucin was abundant throughout the cytoplasm in some areas. Our cases show the course of acquirement of cytological atypia of LEGH, and indicate the significance of localization of mucin on the surface of glandular cell clusters as an early finding of the malignant transformation of LEGH in endocervical cytology. Our results indicate that the distribution of mucin in glandular cells should be analyzed together with nuclear atypia in the endocervical cytology of suspected cases of LEGH.

Neurosphere formation enhances the neurogenic differentiation potential and migratory ability of umbilical cord-mesenchymal stromal cells.

BACKGROUND AIMS: The human umbilical cord (UC) is a rich source of mesenchymal stromal cells (MSCs), which have been reported to have multi-lineage potential. The objectives of this study were to investigate the characteristics and capacity of UC-MSC neurosphere formation and whether this event enhances the propensity of UC-MSCs to undergo neural differentiation. METHODS: UC-MSCs were collected by the improved explant method. UC-MSCs and neurosphere-forming UC-MSCs (UC-MSC-neurospheres) were induced to undergo neurogenic differentiation, the latter of which were induced by suspension culturing in the presence of epidermal growth factor and basic fibroblast growth factor. The differentiation and migratory capacities of the individual cultures were then compared on the basis of the expression of neural markers, as measured by immunocytochemistry, immunoblotting and quantitative real-time polymerase chain reaction and transwell assays, respectively. RESULTS: Both UC-MSCs and UC-MSC-neurospheres were capable of differentiating into neurogenic cells when cultured in neurogenic differentiation medium. However, pre-conditioned UC-MSC-neurospheres exhibited significantly higher expression of neural markers--including microtubule-associated protein (MAP2), MUSASHI1, glial fibrillary acidic protein (GFAP), and NESTIN--compared with those derived from UC-MSCs directly. Moreover, UC-MSC-neurospheres expressed significantly higher levels of the stemness markers NANOG, KLF4 and OCT4 than did UC-MSCs. Migration assays also revealed that both UC-MSCs and UC-MSC-neurospheres actively migrate toward glucose-depleted cells. CONCLUSIONS: Neurogenic differentiation potential probably is greater in UC-MSC-neurospheres than in UC-MSCs. Thus, UC-MSC-neurospheres may serve as a better source of cells for neurogenic regenerative medicine.

A case of simultaneous bilateral spontaneous pneumothorax after the Nuss procedure.

We present a case of simultaneous bilateral spontaneous pneumothorax caused by a pleuro-pleural communication formed from Nuss procedure for pectus excavatum. A 17-year-old man with a history of Nuss operation complained chest pain and dyspnea. A chest roentgenogram demonstrated a tiny bilateral pneumothorax and two metallic bars inserted at the Nuss procedure. Computed tomography revealed furthermore a bulla in the apex of the left lung. The bilateral pneumothorax critically deteriorated after 4 days from onset and urgent bilateral chest drainages were performed. Nevertheless the drainages the full expansion of both lungs was not obtained and air leakage only from left side was continued. A video-assisted left bullectomy was performed 9 days after the tube insertion. The two bars penetrating anterior mediastinal pleura were thought to be a cause of the simultaneous bilateral spontaneous pneumothorax.

Immunosuppressive properties of Wharton's jelly-derived mesenchymal stromal cells in vitro.

Recent studies have reported that mesenchymal stromal cells (MSCs) migrate to areas of inflammation and suppress adverse immune reactions. Bone marrow (BM)-derived MSCs have been successfully used in patients with acute graft versus host disease (GVHD), but the harvesting of BM carries certain risks for the donor. To circumvent these, we obtained MSCs from Wharton's jelly (WJ) derived from umbilical cord and investigated their potential for immunosuppression. In a mixed lymphocyte reaction (MLR), responder T cell proliferation triggered by allogeneic dendritic cells was inhibited efficiently by WJ-MSCs derived from the same donor of responder cells or those from a third party donor. These inhibitory effects were reversed in a dose-dependent manner in the presence of 1-methyl-DL-tryptophan, an inhibitor of the soluble factor indoleamine 2, 3-dioxygenase (IDO). Immunosuppression by WJ-MSCs was also attenuated by blocking cell-cell contact between WJ-MSCs and responder T cells using a Transwell chamber. Moreover, IDO gene expression was induced in both WJ- and BM-MSCs by inflammatory cytokine IFN-γ, but HLA-DR was expressed in BM-MSCs and not in WJ-MSCs upon stimulation by a relatively low concentration of IFN-γ. These results indicate that WJ-MSCs exert their immunosuppressive effects by cell-cell contact with activated T cells and in part through IDO, and suggest the need for cells rather than soluble factors secreted from MSCs to achieve immunosuppressive therapy in severe cases of GVHD.

[A Patient with Recurrent Ovarian Cancer Who Was Hypersensitive to Carboplatin Exhibited Complete Response to Gemcitabine and Nedaplatin].

A 57-year-old multiparous woman with FIGO stage IV ovarian cancer underwent primary surgery and was administered postoperative chemotherapy consisting of paclitaxel and carboplatin (TC). Complete response was confirmed on computed tomography. After a 20-month platinum free interval (PFI), an elevated serum CA125 level and recurrence in the peritoneum were confirmed, and she was retreated with TC as second-line chemotherapy. A hypersensitivity reaction occurred after administering the second dose of carboplatin; therefore, carboplatin was changed to nedaplatin. Complete response was confirmed on computed tomography, and the serum CA125 level returned to normal. After an 8-month PFI, an elevated serum CA125 level and recurrence in the peritoneum and liver were confirmed, and she was treated with 6 cycles of combination chemotherapy consisting of gemcitabine (1,000 mg/m2: day 1 and 8 q3 weeks)and nedaplatin (80 mg/m2: day 1 q3 weeks). Only cytopenia (grade 2: CTCAE v4.0) was noted as a complication during chemotherapy. Complete response was confirmed on computed tomography. This report presents the case of a patient with recurrent ovarian cancer who was platinum sensitive and successfully treated with gemcitabine and nedaplatin after showing a hypersensitivity reaction to carboplatin.

Serum- and xeno-free cryopreservation of human umbilical cord tissue as mesenchymal stromal cell source.

BACKGROUND AIMS: Human umbilical cord (UC) has become a notable source for mesenchymal stromal cells (MSCs) that can migrate to areas of inflammation and damaged tissue and can suppress excess immune reactions and to repair, respectively. Although UC is a solid tissue, there are several advantages, including repeatable uses from the same donor sample when needed and the possibility of future explorations for cells with unknown potential, if we could cryopreserve the UC as a living tissue material. However, because the cryoprotectants in the previous reports included animal- or allogeneic human-derived serum or no serum, the frozen-thawed UC-MSCs were inferior to fresh UC-MSCs in cell proliferation. The objective of this study was to find a suitable cryopreservation method of UC for clinical use. METHODS: The UC was cut in cross-section and incised longitudinally, immersed in the cryoprotectant and frozen slowly. Later, it was thawed and minced rapidly, and the fragments of UC were cultured by improved explant method. RESULTS: The highest yield of cells was obtained from frozen-thawed UC with serum- and xeno-free cryoprotectant, STEM-CELLBANKER, when compared with others. The cells derived from frozen-thawed UC stored in STEM-CELLBANKER expressed the phenotypes of MSCs, retained the immunosuppressive properties in allogeneic mixed lymphocyte reactions and the differentiation potentials (into adipocyte and chondrocytes) comparable to those derived from fresh UC. CONCLUSIONS: UC can be cryopreserved in serum- and xeno-free cryoprotectant as a living tissue while keeping its growth and functions equivalent to fresh UC. Our method is simple and feasible for clinical use.

[Fertility-sparing treatment for gynecologic cancer].

Japanese women bear children at a later age. Thus, fertility-sparing treatment for gynecologic cancer is very important. Per the Japanese treatment guidelines for cervical cancer, the uterus can be preserved by performing cervical conization alone in patients with stage I A1 disease. Radical trachelectomy (RT) is not yet recommended for patients with stage I A2 or I B 1 disease in Japan. Further, RT will not be popular in Japan because cervical cancer can be prevented with HPV vaccine. The efficacy of fertility-sparing treatment with a high-dose of medroxyprogesterone acetate for grade 1 endometrial cancer was proven in a Japan clinical oncology group (JCOG) phase II study. Japanese multi-institutional retrospective investigation data confirm that fertility-sparing surgery is safe for patients with stage I A disease with non-clear cell histology grade 1 or 2. These data suggest that patients with stage I A disease with clear cell histology and those with stage I C disease with non-clear cell histology grade 1 or 2 can be candidates for fertility sparing surgery followed by adjuvant chemotherapy.

Stratifying the risk of lymph node metastasis in undifferentiated-type early gastric cancer.

AIM: To study how lymph node metastasis (LNM) risk is stratified in undifferentiated-type early gastric cancer (undiff-EGC) dependent on combinations of risk factors. METHODS: Five hundred and sixty-seven cases with undiff-EGC undergoing gastrectomy with lymphadenectomy were examined retrospectively. Using clinicopathological factors of patient age, location, size, an endoscopic macroscopic tumor form, ulceration, depth, histology, lymphatic involvement (LI) and venous involvement (VI), LNM risk was examined and stratified by conventional statistical analysis and data-mining analysis. RESULTS: LNM was positive in 44 of 567 cases (7.8%). Univariate analysis revealed > 2 cm, protrusion, submucosal (sm), mixed type, LI and VI as significant prognostic factors and > 2 cm and LI-positive were independent factors by multivariate analysis. In preoperatively evaluable factors excluding LVI, sm and > 2 cm were independent factors. According to the depth and size, cases were categorized into the low-risk group [m and ≤ 2 cm, 0% (LNM incidence)], the moderate-risk group (m and > 2 cm, 5.6%; and sm and ≤ 2 cm, 6.0%), and the high-risk group (sm and > 2 cm, 19.3%). On the other hand, LNM occurred in 1.4% in all LI-negative cases, greatly lower than 28.2% in all LI-positive cases, and LNM incidence was low in LI-negative cases even in the moderate- and high-risk groups. CONCLUSION: LNM-related factors in undiff-EGC were depth and size preoperatively while those were LI and size postoperatively. Among these factors, LI was the most significantly correlated factor.

Improved explant method to isolate umbilical cord-derived mesenchymal stem cells and their immunosuppressive properties.

The umbilical cord (UC) has become one of the major sources of mesenchymal stem cells (MSCs). The common explant method of isolating UC-derived MSCs (UC-MSCs) involves mincing the UCs into small fragments, which are then attached to a culture dish bottom from which the MSCs migrate. However, the fragments frequently float up from the bottom of the dish, thereby reducing the cell recovery rate. To overcome this problem, we demonstrate an improved explant method for UC-MSC isolation, which involves the use of a stainless steel mesh (Cellamigo(®); Tsubakimoto Chain Co.), to protect the tissue from floating after the minced fragments are aligned at regular intervals in culture dishes. The culture medium was refreshed every 3 days and the adherent cells and tissue fragments were harvested using trypsin. The number of UC-MSCs isolated from 1 g of UC using the explant method with Cellamigo was 2.9 ± 1.4 × 10(6)/g, which was significantly higher than that obtained without Cellamigo (0.66 ± 0.53 × 10(6)/g) (n = 6, p < 0.01) when cells reached 80-90% confluence. In addition, the processing and incubation time required to reach 80-90% confluence was reduced in the improved explant method compared with the conventional method. The UC-MSCs isolated using the improved method were positive for CD105, CD73, CD90, and HLA class I expression and negative for CD45 and HLA class II expression. The isolated UC-MSCs efficiently inhibited the responder T cells induced by allogeneic dendritic cells in a mixed lymphocyte reaction. Conclusively, we demonstrated that the use of Cellamigo improves the explant method for isolating UC-MSCs.

Human papillomavirus genotype distribution in cervical intraepithelial neoplasia grade 2/3 and invasive cervical cancer in Japanese women.

OBJECTIVE: Human papillomavirus vaccines are being introduced worldwide and are expected to reduce the incidence of cervical cancer. Here we report a cross-sectional study using a validated human papillomavirus genotyping method to reveal the human papillomavirus prevalence and genotype distribution in Japanese women with cervical intraepithelial neoplasia Grade 2/3 and invasive cervical cancer. METHODS: Cervical exfoliated cells were collected from 647 patients with abnormal cervical histology (cervical intraepithelial neoplasia Grade 2, n = 164; cervical intraepithelial neoplasia Grade 3, n = 334; and invasive cervical cancer, n = 149), and subjected to the PGMY-PCR-based genotyping assay. The association between human papillomavirus infection and lesion severity was calculated using a prevalence ratio. RESULTS: Overall, the prevalence of human papillomavirus deoxyribonucleic acid was 96.3% in cervical intraepithelial neoplasia Grade 2, 98.8% in cervical intraepithelial neoplasia Grade 3 and 88.0% in invasive cervical cancer (97.8% in squamous cell carcinoma and 71.4% in adenocarcinoma). The three most prevalent types were as follows: human papillomavirus 16 (29.3%), human papillomavirus 52 (27.4%) and human papillomavirus 58 (22.0%) in cervical intraepithelial neoplasia Grade 2; human papillomavirus 16 (44.9%), human papillomavirus 52 (26.0%) and human papillomavirus 58 (17.4%) in cervical intraepithelial neoplasia Grade 3; and human papillomavirus 16 (47.7%), human papillomavirus 18 (23.5%) and human papillomavirus 52 (8.7%) in invasive cervical cancer. The prevalence ratio of human papillomavirus 16 was significantly higher in cervical intraepithelial neoplasia Grade 3 compared with cervical intraepithelial neoplasia Grade 2 (prevalence ratio, 1.62; 95% confidence interval, 1.26-2.13) and in squamous cell carcinoma compared with cervical intraepithelial neoplasia Grade 3 (prevalence ratio, 1.55; 95% confidence interval, 1.25-1.87). Multiple infections decreased from cervical intraepithelial neoplasia Grade 2/3 (38.4/29.6%) to invasive cervical cancer (14.1%), whereas co-infections with human papillomavirus 16/52/58 were found in cervical intraepithelial neoplasia Grade 2/3. CONCLUSIONS: The results of this study provide pre-vaccination era baseline data on human papillomavirus type distribution in Japanese women and serve as a reliable basis for monitoring the future impact of human papillomavirus vaccination in Japan.

Stage-specific embryonic antigen 4 in Wharton's jelly-derived mesenchymal stem cells is not a marker for proliferation and multipotency.

BACKGROUND: Umbilical cord Wharton's jelly (WJ) is a rich source of mesenchymal stem cells (MSCs) similar to bone marrow (BM) and adipose tissues. Stage-specific embryonic antigen (SSEA)4 has been reported as a stem cell marker in BM-derived MSCs, but whether SSEA4(+) cells have growth and differentiation advantages over SSEA4(-) cells remains controversial. To gain insight into the role of SSEA4, we studied SSEA4(+) cells in WJ-derived MSCs (WJ-MSCs). METHODS: WJ-MSCs were collected by the explant (WJe-MSCs) or collagenase methods (WJc-MSCs) and analyzed by flow cytometry and reverse-transcription polymerase chain reaction (RT-PCR). To evaluate whether culture conditions influenced the SSEA4 expression, WJe-MSCs were cultured in the medium supplemented with different fetal bovine serum (FBS) concentrations. RESULTS: SSEA4 was expressed for a long-term culture. In contrast, SSEA3(+) disappeared rapidly in early passages of the culture. The incidence of SSEA4(+) and SSEA3(+) cells was similar between WJe-MSCs and WJc-MSCs at passages P0-P9, except for transient depletion of SSEA4 expression in early passages of WJe-MSCs. These were CD73(+)CD105(+) cells that express embryonic stem cell markers detected by RT-PCR. No differences in growth and differentiation ability of osteocytes and adipocytes were observed between the sorted SSEA4(+) cells and SSEA4(-) cells. Further, SSEA4 expression in WJe-MSCs was significantly correlated with FBS concentration in the culture medium. DISCUSSION: SSEA4, which may display altered expression profiles in response to culture conditions, may not be an essential marker of WJ-MSC multipotency.

Genotype distribution of human papillomaviruses in Japanese women with abnormal cervical cytology.

We report the prevalence and genotype distribution of human papillomaviruses (HPVs) among Japanese women with abnormal cervical cytology using the PGMY-CHUV assay, one of PGMY-PCR-based lineblot assays that was validated and shown to be suitable for the detection of multiple HPV types in a specimen with minimum bias. Total DNA was extracted from cervical exfoliated cells collected from 326 outpatients with abnormal Pap smears. Overall, 307 specimens (94%) were HPV-positive, 30% of which contained multiple genotypes. The prevalence of HPV DNA was 83% (49/59 samples) in atypical squamous cells of undetermined significance (ASC-US); 91% (20/22 samples) in atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H); 97% (130/134 samples) in low-grade squamous intraepithelial lesion (LSIL); and 99% (85/86 samples) in high-grade squamous intraepithelial lesion (HSIL). Three most frequent HPV types detected in HSIL were HPV16 (36%), HPV52 (24%), and HPV58 (14%). Our results suggest that multiple HPV infections are more prevalent in Japanese women than previously reported, and confirm that HPV52 and 58 are more dominant in their cervical precancerous lesions when compared to those reported in Western countries.

[A case of stage IVb vulvar cancer effectively treated by concurrent chemoradiotherapy with cisplatin].

A 72-year-old woman was hospitalized because of a 10 cm tumor in her right inguinal area. Furthermore, a 6 cm tumor mass was observed in her right vulva. Computed tomography revealed multiple swollen lymph nodes in the para-aortic and pelvic areas. On the basis of these findings, the patient was diagnosed with stage IVb squamous cell carcinoma of the vulva. Radiation therapy of 67.4 Gy/33 Fr was administered to the pelvis, inguinal area and vulva. Four courses of chemotherapy with cisplatin (40 mg/m(2)) were concurrently administered every week during radiation therapy. The response to chemoradiotherapy was assessed to be complete. The patient has been doing well without any recurrence for 24 months.

MRI of endometriotic cysts in association with ovarian carcinoma.

OBJECTIVE: Although mural nodules are considered to be the most important hallmark in the recognition of ovarian cancers accompanied with endometriotic cysts, benign neoplasms and even inflammatory diseases can show similar MRI findings. We sought to clarify the MRI characteristics of malignancy accompanied with endometriotic cysts of the ovary. MATERIALS AND METHODS: Contrast-enhanced MRI was performed and endometriosis was pathologically confirmed in 49 patients with endometriotic cysts displaying mural nodules. Malignancy was pathologically diagnosed in 33 patients and benignity, in 16. Clinical data including patient age and MRI findings in terms of the size of the endometriotic cysts, number of loculi, presence of shading of the cysts, size of the mural nodules, signal intensity of the mural nodules on T1- and T2-weighted images, and contrast enhancement of the mural nodules were retrospectively reviewed. Statistical analysis of each parameter used the Mann-Whitney U test. RESULTS: The mean age of the patients and mean size of the endometriotic cysts were significantly higher in patients with a malignant condition than in those with a benign condition. Contrast enhancement of the mural nodules was observed in 97% of malignant and 44% of benign tumors. The size of the mural nodules was significantly larger in patients with a malignant condition than in those with a benign condition. Differences in size between the bilateral diseases, multilocularity, existence of shading, and the signal intensities of mural nodules were not significantly different between the malignant and benign conditions. CONCLUSION: Endometriotic cysts with enhanced mural nodules are not always complicated with malignancy. In elderly patients, the presence of large enhanced nodules on large endometriotic cysts is more likely to indicate malignancy.