A nationwide birth year-by-year analysis of effectiveness of HPV vaccine in Japan.

In Japan, the age-adjusted incidence of cervical cancer has been increasing constantly and rapidly among younger women. We set out to accurately confirm the effectiveness of the HPV vaccine in Japan. Data were collected for women born in the fiscal year (FY) 1990 to 1997, who became eligible for their 20-y-old cervical cancer screening between the FY 2010 to 2017. The adjusted incidence of cervical intraepithelial neoplasia (CIN)1+ in women born in FY 1990 to 1993, that is those who reached the national vaccination target age prior to the introduction of publicly subsidized HPV vaccinations, referred here after as "the pre-introduction generation", was 1.42% (242/17 040). The incidence in the "vaccination generation" (women born in FY 1994 to 1997, that is those who were heavily vaccinated as a group when they were of the nationally targeted age of 13-16) was 1.66% (135/8020). There was no significant difference between these incidence rates. However, our FY birth year-by-year analysis revealed that the incidence of CIN1+ was obviously lower than that predicted based on just the trend for CIN1+ seen in the pre-introduction generation. Our analysis revealed that the incidence of CIN3+ was obviously lower in the vaccination generation than in the pre-introduction generation (P = .0008). The incidence of CIN was already tending to increase in both the pre-introduction and vaccination generations. The changes in CIN incidence by individual birth FY must be examined to accurately determine the actual effects of the HPV vaccine for reducing mild cervical lesions.

Ergonomic and sustainable posture for gynecological laparoscopic surgeons determined based on images analyzed using artificial intelligence.

Studies have reported the emergence of work-related musculoskeletal disorders (WMSD) due to surgery. In fact, the usfige of long-shafted instruments has been suspected to induce WMSD in laparoscopic surgery. The present study therefore investigated whether differences in the range of motion of the face and neck, and the shoulder, elbow and hand on the dominant hand side, existed when using short- and long-shafted laparoscopic coagulation shears (LCS) during a gynecological laparoscopic surgery, based on images analyzed using artificial intelligence. After identifying the corresponding body parts in the video, the range of motion was illustrated graphically for each joint coordinate, followed by statistical analysis for changes in the position of each part. The range of motion for the face and neck did not significantly differ, whereas those for the shoulder, elbow and hand became noticeably broader when using the 36-cm long-shafted LCS than when using the 20-cm short-shafted LCS. Overall, the shorter LCS promoted a narrower range of motion compared with the 36-cm LCS, suggesting its potential for reducing the physical strain placed on the surgeon's body during gynecological laparoscopic surgery.

Impact of histological subtype on survival of patients with surgically-treated stage IA2-IIB cervical cancer: adenocarcinoma versus squamous cell carcinoma.

OBJECTIVES: To evaluate the significance of adenocarcinoma (AC) compared with squamous cell carcinoma (SCC) with regard to the survival of surgically-treated early stage cervical cancer patients. METHODS: We retrospectively reviewed the medical records of 520 patients with FIGO stage IA2-IIB cervical cancer who were treated with radical hysterectomy with or without adjuvant radiotherapy between January 1998 and December 2008. The patients were classified according to (i) pathological risk factors (low-, intermediate-, or high-risk group) and (ii) adjuvant radiotherapy (concurrent chemoradiotherapy [CCRT group] or radiotherapy alone [RT group]). Survival outcomes were examined by Kaplan-Meier method and compared with Log-rank test. Multivariate analysis for disease-specific survival (DSS) was performed using Cox proportional hazards regression model to investigate the prognostic significance of histological subtype. RESULTS: AC histology was associated with significantly decreased DSS compared with SCC histology in the intermediate- and high-risk groups (hazard ratio: 3.06 and 2.88, respectively, both P<0.05) while there was no survival difference in the low-risk group (P=0.1). Among patients who received any types of adjuvant radiotherapy, DSS of AC histology patients were significantly poorer than SCC histology. Multivariate analysis demonstrated AC histology to be an independent predictor of decreased DSS in both CCRT and RT groups. Moreover, pelvic nodal metastasis significantly predicted the poor survival of patients with AC histology who received CCRT in multivariate analysis CONCLUSIONS: Adenocarcinoma is an independent prognostic indicator of poor survival in early stage cervical cancer patients with intermediate- and high-risk factors, regardless of the type of adjuvant radiotherapy after radical hysterectomy.

Investigating the relative efficacies of combination chemotherapy of paclitaxel/carboplatin, with or without anthracycline, for endometrial carcinoma.

PURPOSE: Recently a combination of paclitaxel and carboplatin (TC) (without an anthracycline) has begun to be used as an adjuvant or remission induction therapy, without any critical supportive evidence of its efficacy relative to a combination chemotherapy of taxane, platinum and anthracycline such as TEC (paclitaxel, epirubicin and carboplatin). The aim of our present study was to conduct the required clinical evaluations of the relative effectiveness of TC compared to TEC. METHODS: A retrospective comparison between the efficacy of TEC and TC regimens used for endometrial carcinoma at the Osaka University Hospital and the Osaka Medical Center for Cancer and Cardiovascular Diseases in Osaka, Japan, respectively, from 1999 to 2009 was performed. The clinical characteristics of the patients who received either TEC or TC were not significantly different, and TEC and TC therapies were initiated based on similar indications for chemotherapy. TEC regimen was paclitaxel (150 mg/m(2)), epirubicin (50 mg/m(2)) and carboplatin (AUC 4). TC regimen consisted of paclitaxel (175 mg/m(2)) and carboplatin (AUC 5). RESULTS: TEC was demonstrated to provide significantly better survival than TC as an adjuvant therapy for resected Stage III/IV diseases (p = 0.017 for progression-free survival and p = 0.014 for overall survival, by the log-rank test). However, in recurrent or more advanced cases, TC and TEC demonstrated similar effects on survival (p = 0.55 for progression-free survival and p = 0.63 for overall survival). CONCLUSIONS: TEC should be offered as an adjuvant therapy to Stage III/IV patients. TC may be considered for recurrent or unresectable cases as a remission induction therapy.

Prediction, based on resection margins, of long-term outcome of cervical intraepithelial neoplasia 3 treated by Shimodaira-Taniguchi conization.

PURPOSE: The aim of the present study was to analyze the long-term outcome of cervical intraepithelial neoplasia 3 (CIN 3) after treatment with the Shimodaira-Taniguchi conization procedure, based on the status of the resection margins. METHODS: In the Osaka University Hospital, conization using the Shimodaira-Taniguchi procedure has been routinely performed for CIN 3. Medical records of patients during the period from 2001 to 2008, whose post-conization diagnosis was CIN 3, were retrospectively analyzed for outcome versus margin status. RESULTS: During the median follow-up period of 565 days (range 34-3,013), CIN disease was again detected in 14 of 243 patients; it was found in 7 patients among 198 margin-negative cases, and in 7 patients among 45 margin-positive cases. There was a significant difference in the reappearance rate demonstrated between the cases with positive and negative margins (p = 0.0018). Among the patients whose first follow-up post-conization cytology was normal, recurrence-free probability was significantly higher in margin-negative cases than in margin-positive ones (hazard ratio, 5.19; 95% CI, 1.175-22.994; p = 0.0041). CONCLUSION: For the first time, we demonstrate that after treatment of CIN 3 lesions by Shimodaira-Taniguchi conization the status of the resection margin was a significant predictor for long-term outcome.

Intraoperative frozen section assessment of myometrial invasion and histology of endometrial cancer using the revised FIGO staging system.

OBJECTIVES: The objective of this study was to assess the value of intraoperative frozen section (IFS) diagnosis for myometrial invasion and histology of endometrial cancer using the revised International Federation of Gynecology and Obstetrics (FIGO) staging system. METHODS: The medical records of 303 patients with endometrial cancer who underwent surgery with intraoperative diagnosis at the Osaka University Hospital between January 1999 and December 2008 were reviewed. Intraoperative frozen section diagnosis was retrospectively analyzed for the accuracy rates of myometrial invasion and histology compared with the final diagnosis and with preoperative prediction by magnetic resonance imaging (MRI) and endometrial curettage. RESULTS: When using the previous FIGO staging system, the accuracy rate of IFS for the diagnosis of myometrial invasion was 77%, whereas the accuracy rate of preoperative prediction by MRI was 54%. However, using the newly revised FIGO staging system for myometrial invasion, the accuracy rate of IFS was 87% and the preoperative prediction by MRI was 82%. The accuracy rate of IFS for the diagnosis of histology was 71%, whereas the accuracy rate of preoperative prediction by endometrial curettage was 68%. CONCLUSION: Although under the previous FIGO staging system IFS diagnosis was significantly more accurate than preoperative prediction by MRI, when using the newly revised FIGO staging system, there are no significant differences between the values of preoperative and intraoperative diagnoses. The accuracy of IFS, however, trends to be slightly better than the preoperative procedures of MRI and endometrial surface biopsy. Thus, IFS diagnosis is still useful for directing primary operative management.

Metastatic mucinous adenocarcinoma of the ovary is characterized by advanced patient age, small tumor size, and elevated serum CA125.

BACKGROUND/AIMS: An intraoperative diagnosis in cases with primary and metastatic ovarian carcinomas is important for adequate treatment. The aim of the present study was to find a reliable method to discriminate primary from metastatic mucinous adenocarcinomas (MACs) of the ovary intraoperatively. METHODS: Clinical features of all primary and metastatic mucinous ovarian carcinomas diagnosed from 1994 to 2008 at the Osaka University and Osaka Rosai Hospitals, Osaka, Japan, were reviewed retrospectively. RESULTS: Among the 73 MACs, 51 (70%) and 22 cases (30%) were diagnosed as primary and metastatic ovarian carcinomas, respectively. The distributions of tumor size, patient age, and serum CA125 level were significantly different between primary and metastatic cases. Our algorithm that categorizes patients ≥50 years whose tumor size was <10 cm into metastatic cases, and patients <50 years, or the ones whose tumor size was ≥10 cm, into primary tumors, provided an 84% accuracy in our population. CONCLUSIONS: A more reliable method to discriminate primary from metastatic MACs of the ovary by patient age and serum tumor markers was derived from our study population.

Usefulness of computed tomography in predicting cytoreductive surgical outcomes for ovarian cancer.

PURPOSE: The objective of this study was to identify features of preoperative computed tomography (CT) scans that can best predict outcomes of primary cytoreductive surgery in ovarian cancer patients. METHODS: Preoperative CT scans of 98 patients were evaluated retrospectively. Multiple logistic regression analysis was used to develop two models. RESULTS: Although optimal surgical reduction was attempted in 98 patients, 12 had suboptimal results. Having tumor implants on the small or large bowel mesenteries (any size) or at other sites (cutoff index: ≥ 1 cm) was found to be significant (p < 0.001) for predicting a suboptimal cytoreduction outcome. Two predictive models were created using multiple logistic regression analysis; both consider diffuse peritoneal thickening (DPT), infrarenal para-aortic or pelvic lymph node involvement, a bowel encasement tumor (≥ 2 cm), and any tumor implants in the cul-de-sac as significant. Model 1 adds consideration to any tumors in the pelvic or retroperitoneum and has an accuracy of 90.8% for predicting a suboptimal surgery. Model 2 (accuracy of 93.9%) adds to the core of predictors the presence of tumor implants on the bowel mesenteries (≥ 2 cm), omental caking (≥ 2 cm), and ascites fluid. CONCLUSION: Using specific CT findings from patients with ovarian cancer, we have devised two predictive models that have an accuracy of greater than 90% for predicting whether cytoreductive surgery will completely remove all tumor tissue, which should greatly aid in the differential decision-making as to whether to attempt cytoreductive surgery first, or to advance directly to neoadjuvant chemotherapy.

Early reduction of glucose uptake after cisplatin treatment is a marker of cisplatin sensitivity in ovarian cancer.

Cisplatin is an effective chemotherapeutic agent for ovarian cancer, but the sensitivity of cancers differs in individual cases. Because cisplatin is reported to suppress glucose uptake, we investigated the correlation between glucose uptake and sensitivity to the drug. A fluorescent derivative of D-glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diaxol-4-yl) amino]-2-deoxyglucose), was used to evaluate glucose uptake. Two ovarian cancer cell lines, SKOV-3 as a relatively resistant line and OVCAR-3 as a relatively sensitive line, were analyzed. Both cell lines had a decreased number of cells accompanied by cell death 24 h after cisplatin treatment, but not at 3 h. In contrast, glucose uptake was decreased 3 h after high-dose cisplatin treatment, which correlated with the sensitivity to the drug at 24 h. The protein levels of glucose transporter 1 (GLUT1) did not change with cisplatin treatment. In contrast, the membrane localization of GLUT1 disappeared after cisplatin treatment. Other cisplatin-resistant cell lines did not show an early decrease in glucose uptake after cisplatin treatment. The early decrease in glucose uptake and later cell death also correlated in cultured cancer cells from ovarian cancer patients. Thus, the decrease in glucose uptake at an early time point after high dose cisplatin treatment reflected cisplatin chemosensitivity in ovarian cancer cells. Measuring glucose uptake might be useful as a rapid evaluation of cisplatin chemosensitivity in ovarian cancer patients.

Endometrial carcinoma with extra-abdominal metastasis: improved prognosis following cytoreductive surgery.

BACKGROUND: Incidence of endometrial carcinoma, the most common malignancy of the female pelvis, has been steadily increasing during the last three decades. The prognosis for stage IVb cases with extra-abdominal metastases is extremely poor, with no current consensus regarding treatment. The aim of the present study was to examine the benefits of cytoreductive surgery for such cases. METHODS: Clinicopathological features of 33 stage IVb cases of endometrial carcinoma diagnosed during the 1991-2008 study period were retrospectively reviewed utilizing clinical records. Cytoreduction was conducted in 30 cases. RESULTS: The median progression-free survival (PFS) and overall survival (OS) of those patients with optimal cytoreduction of their disease (with residual masses < or =2 cm), were significantly better than those with suboptimal reduction (with residual masses > 2 cm), not only among the 15 stage IVb patients with only intra-abdominal metastasis (group I) (P = 0.0003 and 0.0007) but also among the 15 cases with extra-abdominal metastasis (group E) (P = 0.013 and 0.016). Multivariate Cox proportional-hazards analysis demonstrated that the adjusted hazard ratio (HR) for the maximum size of residual disease (>2 vs. < or =2 cm) was 10.4 [95% confidence interval (CI), 1.27-84.70, P = 0.030] in group I and 16.92 (95% CI, 1.41-203.09, P = 0.026) in group E. CONCLUSIONS: This is the first demonstration that aggressive cytoreductive surgery for stage IVb endometrial carcinoma with extra-abdominal metastasis has a beneficial role. However, further investigation is still required to establish better standard therapy for stage IVb endometrial cancer.

Endometrial carcinoma: better prognosis for asymptomatic recurrences than for symptomatic cases found by routine follow-up.

BACKGROUND: The aim of this study was to determine if there is a prognostic value for the presence of symptoms at the time of recurrence detection in surgically resected endometrial carcinoma patients. METHODS: During the study period of 2000-2006, complete surgical removal of endometrial carcinoma was achieved in 271 stage I-IV endometrial cancer cases at the Department of Obstetrics and Gynecology of Osaka University Hospital, Osaka, Japan. A subsequent recurrence was detected in 29 (11%) of these cases. Patient characteristics and clinicopathological features were retrospectively reviewed utilizing their clinical records. RESULTS: Among the 29 cases with a recurrence, 13 (45%) had symptoms, whereas in the other 16 cases (55%) the recurrent disease was found only during routine follow-up procedures. Although the time to detection of recurrence was similar for both asymptomatic and symptomatic cases, progression-free survival after detection in the 16 asymptomatic patients was significantly longer than for the 13 symptomatic patients (P = 0.017); this was found to be especially true in those who underwent chemotherapy as their adjuvant therapy (P = 0.023). CONCLUSIONS: A better prognosis after recurrence was demonstrated in cases that were asymptomatic at the time of recurrence detection than in those in which the tumor was symptomatic. This finding implies that, after the initial surgical resection, intensive follow-up intervention looking for asymptomatic recurrences may significantly improve the prognosis of endometrial carcinoma patients. A further in-depth prospective study is required to establish a standard strategy of follow-up care for endometrial cancer patients.

A case in which laparoscopic right salpingo-oophorectomy was performed in a patient with a lumboperitoneal shunt.

INTRODUCTION: Ventriculoperitoneal (VP shunts) and lumboperitoneal shunts (LP shunts) are used to treat hydrocephalus. The effectiveness of LP shunts has recently been demonstrated. Due to population aging, the number of patients with LP shunts is expected to increase. PRESENTATION OF CASE: A 51-year-old female, in whom an LP shunt had been inserted to treat hydrocephalus after a subarachnoid hemorrhage, underwent laparoscopic right salpingo-oophorectomy for a right endometriotic cyst. We consulted a neurosurgeon and confirmed the route of the shunt. We started a normal laparoscopic procedure. The head of the shunt tube was located in Douglas' pouch and was an obstacle to the procedure. We moved the head of the shunt tube to the vesicouterine pouch and successfully conducted the standard operation. We report the case together with a literature review. DISCUSSION: There have been several reports about gynecological laparoscopic surgery being performed in patients with VP shunts. On the other hand, we did not find any English literature about gynecological laparoscopic surgery being conducted in patients with LP shunts during a PubMed search. CONCLUSION: This is the first report about gynecological laparoscopic surgery being performed in a patient with an LP shunt.

Fathers' participation in the HPV vaccination decision-making process doesn't increase parents' intention to make daughters get the vaccine.

INTRODUCTION: The HPV vaccination rate in Japan has been dismally low. Our previous survey work found that mothers in Japan, who have a strong influence over their daughters, often are receptive to the fathers' participation in the family's decision-making process about getting their daughter HPV vaccinated. METHODS: We conducted a survey to investigate the nature of the influence of fathers' participation on the mother's decision-making process. From an internet survey panel, we selected a pool of 1,499 eligible mothers who had 12-18 years old daughters. The mothers were randomized into three Groups. To the mothers in Group A, we gave an educational leaflet regarding HPV vaccination and a second leaflet which recommended that they talk with their husbands about the vaccination. To Group B, we gave only the educational leaflet. No leaflets were sent to Group C. A structured survey questionnaire was then distributed through the internet to the mothers. RESULTS: In Groups A, B, and C, their intention to have their daughter receive the HPV vaccine was 21.6%, 20.7% and 8.2%, respectively. The percent of Group A mothers who thought their husband's opinion was important for when they made the decision was significantly higher (70%) than in Group B (56.6%) or Group C (47.1%). CONCLUSIONS: The fathers' participation in the mothers' decision-making does not increase the likelihood of HPV vaccination for their daughters. On the other hand, the educational leaflet proved to be effective for this cause.

Japanese Mothers' Intention to HPV Vaccinate Their Daughters: How Has It Changed over Time Because of the Prolonged Suspension of the Governmental Recommendation?

The trend for cervical cancer in younger women has been increasing recently in Japan. However, as a result of the suspension of governmental recommendation, Japan's HPV (human papillomavirus) vaccination rate for girls born since 2000 has dropped sharply. We conducted an internet survey in December of 2019, 76 months after the suspension of recommendation, to verify the intention of mothers to inoculate their daughter under current circumstances and compared with our previous surveys and leaflet intervention effect. The rates of mothers who replied that they would "inoculate" were significantly higher at 9 and 23 months, but by 32 months after the suspension the rate was significantly lower (p < 0.05, p < 0.05, p < 0.05, respectively). The rates of the mothers who replied they would not inoculate were significantly lower at 9 months and 23 months, but at 76 months was significantly higher (p < 0.05, p < 0.05, p < 0.05, respectively). We found that intervention with a leaflet that could be used under the current suspension of the governmental recommendation did not increase the mothers' intention to inoculate their daughters. A leaflet that actively encourages vaccination may increase the intent of vaccination. It is strongly recommended that the MHLW promptly resume its recommendations for HPV vaccination.

Enhanced expression of Annexin A4 in clear cell carcinoma of the ovary and its association with chemoresistance to carboplatin.

Clear cell carcinoma (CCC) of the ovary is known to be highly resistant to platinum-based chemotherapy. The purpose of our study was to identify a candidate protein that is associated with chemoresistance of CCC and to investigate the specific mechanism of chemoresistance conferred by the identified protein. Enhanced expression of Annexin A4 (Anx A4) was identified in ovarian CCC cells using 2-D differential gel electrophoresis (2D-DIGE) and mass spectrometry. Anx A4 levels were elevated in CCC cells compared with non-CCC cells as determined by real-time RT-PCR and Western blot analysis. Immunohistochemical analysis of Anx A4 was performed in 126 epithelial ovarian cancer tissue samples and demonstrated significantly elevated levels of Anx A4 protein levels in ovarian CCC tumors compared with ovarian serous and endometrioid tumors (p < 0.01). Anx A4-transfected ovarian non-CCC cells were more resistant to carboplatin (IC50 = 42 microM) compared with control cells (IC50 = 23 microM) as determined by modified MTT assay. Intracellular platinum levels were significantly lower in Anx A4-transfected cells compared with control cells after carboplatin treatment (p = 0.0020) and after an additional 360 min of carboplatin-free incubation (p = 0.0004), as measured by atomic absorption spectrophotometry. Expression of Anx A4 is elevated in ovarian CCC tumors and is associated with chemoresistance in cultured ovarian cancer cells. These results demonstrate that Anx A4 confers chemoresistance in ovarian cancer cells in part by enhancing drug efflux. Thus, Anx A4 may represent a novel therapeutic target of chemoresistance in patients with ovarian CCC.

PIK3CA gene mutations and amplifications in uterine cancers, identified by methods that avoid confounding by PIK3CA pseudogene sequences.

PIK3CA codes for a Class IA p110-alpha catalytic subunit of the PI3Ks (phosphatidylinositol 3-kinases) that regulate various signaling pathways important for neoplasia, including cell proliferation, motility, adhesion, and survival. Pro-oncogenic mutations in exons 9 and 20 of the PIK3CA gene have been frequently observed in numerous types of human malignancies. Amplification of the PIK3CA gene has been reported in uterine cervical cancers. In this study, we have done in depth analysis of uterine cervical and endometrial cancers for PIK3CA gene mutations and amplifications. In uterine cervical cancers, PIK3CA mutations were found in 3 of 22 cases (14%), all of them in exon 9. In endometrial cancers, a similar incidence of mutations was found, in 3 of 29 cases (10%), however they were all within exon 20. Amplification of the PIK3CA gene was also detected in 2 out of 22 (9%) cervical cancers and 3 out of 29 (10%) endometrial cancers. In this study, we were unable to find a clear association between PIK3CA mutations and gene amplifications, nor with tumor histological subtypes or staging. Mutations and amplifications of the PIK3CA gene are relatively infrequent in human cervical and endometrial cancers; however, PIK3CA gene alteration may still play a role in some subset of uterine cancers.

Clonality and HPV infection analysis of concurrent glandular and squamous lesions and adenosquamous carcinomas of the uterine cervix.

We analyzed the clonality and human papillomavirus (HPV) infection status of concurrent glandular and squamous lesions and adenosquamous carcinomas of the uterine cervix to clarify their histogenesis. The glandular and squamous components were clonally different from each other in 7 informative concurrent lesions. HPV was episomal in 2 polyclonal glandular dysplasias (GDs). HPV was in a mixed integrated-episomal form in a monoclonal GD, an adenocarcinoma in situ, and an adenocarcinoma. Both tumor components were monoclonal in origin in 6 adenosquamous carcinomas, with identical patterns of X-chromosomal inactivation and types and physical status of HPV. These results imply that the concurrent glandular and squamous lesions are formed separately, whereas adenosquamous carcinoma is more likely to be a combination tumor of monoclonal origin, and that integration of HPV has an important role in the progression from polyclonal GD through monoclonal expansion to adenocarcinoma in situ and adenocarcinoma.

Frequent inactivation of RUNX3 in endometrial carcinoma.

OBJECTIVE: Our objective was to determine whether RUNX3 tumor suppressor is inactivated in endometrial carcinoma. METHODS: We have investigated 24 endometrial carcinomas, 3 endometrial carcinoma cell lines, and 9 normal endometria for genetic and epigenetic alterations of RUNX3. Reverse-transcription PCR (RT-PCR), methylation-specific PCR (MS-PCR) analysis, and loss of heterozygosity (LOH) analysis were performed. We also tested RUNX3 protein expression by immunohistochemistry. RESULTS: Using RT-PCR technique, we observed a significant loss of RUNX3 mRNA expression in nine of 24 endometrial carcinomas (38%) and in all 3-cell lines (100%). In contrast, all nine of the normal endometria showed an abundant expression of RUNX3 mRNA. Methylation-specific PCR (MS-PCR) analysis of the CpG islands of RUNX3 showed the promoter region to be hypermethylated in 18 of 21 analyzed carcinomas (86%), whereas only two of nine normal endometria (22%) were methylated (p<0.01). By using two polymorphic microsatellite markers, D1S199 and D1S1676, we detected 1p36 LOH in 7 of 21 carcinomas (33%). We observed a significant relationship between the loss of RUNX3 mRNA expression and this regional LOH (p<0.01). Immunohistochemical staining showed that RUNX3 protein expression was lost in 12 of 21 endometrial carcinomas (57%). We observed a significantly more frequent loss of RUNX3 protein expression in the histologically higher-grade tumors (Grade 3) than in Grade 1 or 2 tumors (p<0.01). CONCLUSION: These findings indicate that RUNX3 inactivation may play an important role in carcinogenesis of the endometrium, especially in high-grade endometrial carcinoma.

Overexpression of LAMP3/TSC403/DC-LAMP promotes metastasis in uterine cervical cancer.

LAMP3 (DC-LAMP, TSC403, CD208) was originally isolated as a gene specifically expressed in lung tissues. LAMP3 is located on a chromosome 3q segment that is frequently amplified in some human cancers, including uterine cervical cancer. Because two other members of the LAMP family of lysosomal membrane glycoproteins, LAMP1 and LAMP2, were previously implicated in potentially modulating the interaction of vascular endothelial and cancer cells, we hypothesized that LAMP3 might also play an important part in metastasis. To clarify the metastatic potential of LAMP3 in cervical cancers, we transfected a LAMP3 expression vector into a human uterine cervical cancer cell line, TCS. In an in vitro invasion assay, the migration of LAMP3-overexpressing TCS cells was significantly higher than in control TCS cells. In an in vivo metastasis assay, distant metastasis was detected in 9 of 11 LAMP3-overexpressing TCS cell-injected mice and in only 1 of 11 control mice. Histologic study showed that LAMP3-overexpressing cells readily invaded into the lymph-vascular space. In clinical samples, quantitative real-time reverse transcription-PCR (RT-PCR) analyses showed that LAMP3 mRNA was significantly up-regulated in 47 of 47 (100%) cervical cancers and in 2 of 15 (13%) cervical intraepithelial neoplasias, compared with a low level of LAMP3 mRNA expressed in normal uterine cervixes. Interestingly, high LAMP3 expression was significantly correlated with the overall survival of patients with stage I/II cervical cancers. These findings indicate that LAMP3 overexpression is associated with an enhanced metastatic potential and may be a prognostic factor for cervical cancer.

Rare hydrosalpinx in a sexually inactive adolescent successfully treated with laparoscopy.

The majority of cases of symptomatic hydrosalpinx needing treatment are caused by sexually transmitted diseases. However, here, we present a rare case of a hydrosalpinx occurring in a sexually-inactive adolescent girl successfully treated with laparoscopy. A 17-year-old girl presenting with lower abdominai symptoms had a surgical history for an inguinal hernia at infancy. Transabdominal ultrasonography revealed a multicystic lesion in the pelvis, and magnetic resonance imaging suggested hydrosalpinx. Due to the abdominal pain and a suspicion of torsion, laparoscopic surgery was performed. After aspiration and resection of a cystic tumor, we confirmed that the left ovary was normal and that the tumor involved the left fallopian tube, which was twisted at the isthmus. Although relatively rare in postmenarchal sexually inactive adolescents, clinicians and surgeons must still consider hydrosalpinx as a possible diagnosis when encountering an adolescent patient with lower abdominal pain.