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This systematic review aimed to investigate complications related to initial trocar insertion among 3 different laparoscopic techniques: Veress needle (VN) entry, direct trocar entry (DTE), and open entry (OE). A literature search was completed, and complications were assessed. Major vessel injury, gastrointestinal injury, and solid organ injury were defined as major complications. Minor complications were defined as subcutaneous emphysema, extraperitoneal insufflation, omental emphysema, trocar site bleeding, and trocar site infection. Arm-based network meta-analyses were performed to identify the differences in complications among the 3 techniques. Seventeen studies were included in the quantitative analysis. DTE resulted in fewer major complications when compared with VN entry although the difference was not significant (p = .23) as well as significantly fewer minor complications (p < .001). There were no significant differences in minor complications when comparing OE and DTE (p = .74). Fewer major complications were observed with OE compared with VN entry although the difference was not significant (p = .31). There were significantly fewer minor complications for patients who underwent OE (p = .01). DTE patients experienced the least number of minor complications followed by VN entry and OE. In conclusion, major complications are extremely rare, and all 3 insertion methods can be performed without mortality.

INTRODUCTION Although various perinatal complications have been reported to be increased in the pregnant patients with adenomyosis, it is not clear what type of patients with adenomyosis is more likely to cause obstetric complications. In this study, we focused on the positional relationship between the placenta and adenomyosis lesion in evaluating perinatal prognosis of pregnant patients with adenomyosis. MATERIAL AND METHODS This retrospective cohort study was carried out between 1 January 2005 and 31 December 2019 in a single institution. Adenomyosis was diagnosed by magnetic resonance imaging (MRI) and/or transvaginal ultrasonography (TVUS). To evaluate the influence of adenomyosis on perinatal outcomes, we classified the positional relationship between the placenta and the adenomyosis lesion into two groups and examined the perinatal prognosis of the patients with adenomyosis by analyzing their clinical records. Group I (n = 9) was defined when the placenta was not overlaid on adenomyosis lesion. Group II (n = 11) was defined when a part of the placenta was overlaid on adenomyosis lesion. RESULTS Twenty pregnant patients with adenomyosis were analyzed. There were no differences in clinical backgrounds between group I and group II. There was a significant increase in the obstetric morbidity in group II than that of Group I(group I: 6.3%, 4/63 vs group II: 18.6%, 26/77; P < 0.001). In group II, fetal growth restriction (FGR) was more frequent (0%, 0/9 vs 45.5%, 5/11; P = 0.042) and the birth weight was significantly lower than that in group I (2951.1 g ± 326.5 g vs 2318.9 ± 656.1 g; P = 0.037). There was a trend of lighter weight of the placenta in group II (550.6 ± 66.5 g vs 437.5 ± 117.8 g; P = 0.063) and the volume of bleeding during delivery was a higher trend in group II than that in group I (845.1 ± 367.1 g vs 1356 ± 604.8 g; P = 0.083). Group II was furtherly subdivided into group IIa (less than half the major axis of the placenta overlaid on adenomyosis lesion) and group IIb (more than half the major axis of placenta overlaid on adenomyosis lesion). The obstetric morbidity tended to be higher in group IIb than in group IIa (group IIa: 22.9%, 8/35 vs group IIb: 42.9%, 18/42); P = 0.09). In group IIb, the frequency of FGR was significantly higher (group IIa: 0%, 0/5 vs IIb: 83.3%, 5/6; P = 0.020) and the birth weight was significantly lower than those in group IIa (2656.8 ± 231.9 g vs 2037 ± 780.1 g; P = 0.040). All cases of FGR, hypertensive disorder of pregnancy (HDP), and oligohydramnios were observed in group IIb. CONCLUSION Placental localization near adenomyosis may increase the risk of perinatal complications.

Background Although there have been a number of reports on urinary voiding symptoms associated with surgical interventions for gynecologic cancer and post-voiding symptoms, there have been few reports on urinary storage symptoms such as urinary incontinence (UI) and overactive bladder (OAB). The purpose of this study was to examine the rates and impact on quality of life (QOL) of urinary storage symptoms after gynecologic cancer surgery. Methods A questionnaire survey, including Japanese-language versions of the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), Overactive Bladder Symptom Score (OABSS), and Incontinence Impact Questionnaire-7 (IIQ-7), was distributed to gynecologic cancer patients who underwent hysterectomy between 2008 and 2013. Results Of the 145 patients analyzed, 49 (33.8%) had UI pre-surgery, and 76 (52.4%) had UI post-surgery, including 34 (35.4%) first-time UI patients, with a significant difference between pre- and post-surgery. Of the 49 subjects with UI pre-surgery, 43 (87.7%) had stress incontinence, while of the 76 patients with UI post-surgery, 44 (57.1%) had stress incontinence, and 24 (31.2%) had mixed incontinence. Seven (4.8%) subjects had OAB pre-surgery, whereas 19 (13.1%) had OAB symptoms post-surgery (including 15 first-time OAB patients), with a significant difference between pre- and post-surgery. IIQ-7 scores were markedly higher for patients with mixed incontinence post-surgery than for those with stress incontinence, indicating a lower QOL. Logistic regression analysis identified the number of Cesarean sections and days of urinary bladder catheterization as risk factors for postoperative UI. Conclusions UI and OAB rates were higher after gynecologic cancer surgery than in the general female population. The mixed incontinence rate was markedly higher post-surgery; QOL was low for such patients due to the combination of urge and stress incontinence. Multiple Cesarean sections and urinary bladder catheterization post-surgery were risk factors for post-surgical UI.

Aim It is commonly thought that laparoscopic surgery leads to faster postoperative recovery for its low invasiveness. We evaluated postoperative quality of life (QOL) after laparoscopic myomectomy (LM) by using the Euro-QOL 5 dimension (EQ-5D) score and analyzed its relationship to surgical factors. Methods Between 2014 and 2016, 541 patients underwent LM at our institution. We included 86 patients in the final analysis (16% response rate) who replied to the EQ-5D questionnaire, in order to investigate postoperative QOL. We evaluated patients' EQ-5D score before the operation and on the 3rd, 7th, 14th, 21st and 28th postoperative day (POD). We investigated the degree of correlation between the EQ-5D score and four surgical characteristics (operation time, intraoperative bleeding, number of resected myomas and weight of specimen). We examined correlation between EQ-5D scores and chief complaints such as hypermenorrhea, dysmenorrhea, other pain, myoma enlargement, palpable tumor and desire for childbearing. We also examined correlation between EQ-5D scores and other factors such as patient's age, infertility, history of abdominal surgery, marriage and body mass index. Results Full recovery, defined as an EQ-5D score of 1.0, was reported 2.3% of patients by POD3, 18.6% by POD7, 58.1% by POD14, 73.3% by POD21 and 86.0% by POD28. Longer duration of operation correlated weakly with poor recovery on POD3. Intraoperative bleeding, number of resected myomas and weight of the specimen did not significantly influence EQ-5D score. There was no correlation between chief complaints or other factors mentioned above and EQ-5D score. Conclusions More than a half of the patients undergoing LM included in our study reported full recovery of QOL after 2 weeks. The time to recover QOL was slightly influenced by the operation time. However, when LM was finished without any complications, postoperative QOL eventually seemed to improve regardless of the surgical characteristics such as operation time, intraoperative bleeding, number of resected myomas and weight of specimen.

Introduction We investigated whether temporary bilateral laparoscopic uterine artery clipping with hysteroscopic transcervical resection (LUA clipping-TCR) is an effective minimally invasive treatment for the management of cervical pregnancy. Materials and methods : This study is a retrospective clinical case series conducted at Teine Keijinkai Hospital from January 2014 to June 2019. Nine cervical pregnancies among 164 ectopic pregnancies were retrospectively examined. The intervention involved performing LUA clipping-TCR on villous tissue. Information on patient characteristics, clinical data, and surgical details was collected from medical records and surgical videos. Results The mean (range) age of the patients was 33 years (29–41 years); and mean gestational sac diameter, 12.8 mm (5–24 mm). Five patients had a history of intrauterine procedures. Three patients had a positive fetal heartbeat. The mean (range) preoperative serum hCG level (mIU/mL), surgical time (min), uterine artery blocking time (min), and amount of surgical blood loss (ml) were 14,040 (2880–41,367), 82 (62–120), 42 (21–68), and 57 (10–200), respectively. The mean decrease in serum hCG level (second postoperative day) and duration until resumption of menstruation were 79.7 % (70–86.7 %) and 46 days (35–80 days), respectively. The hospitalization period was 2–3 days, with no evidence of persistent ectopic pregnancy. Live birth was achieved in four cases. Discussion Our results confirm previous findings and provide new evidence that LUA clipping-TCR is effective for cervical pregnancy management and fertility preservation, respectively. Future large-scale prospective studies to compare different cervical pregnancy management methods are required.

Purpose To examine the rates, causes, and impact on quality of life (QOL) of urinary storage symptoms after gynecologic cancer surgery. Methods A questionnaire survey, including Japanese-language versions of the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), Overactive Bladder Symptom Score (OABSS), and Incontinence Impact Questionnaire-7 (IIQ-7), was distributed to gynecologic cancer patients who underwent hysterectomy between 2008 and 2013. Results Of the 145 patients analyzed, 49 (33.8%) had urinary incontinence (UI) pre-surgery and 76 (52.4%) had UI post-surgery, including 34 (35.4%) first-time UI patients, with a significant difference between pre- and post-surgery. Of the 49 subjects with UI pre-surgery, 43 (87.7%) had stress incontinence, while of the 76 patients with UI post-surgery, 44 (57.1%) had stress incontinence, and 24 (31.2%) had mixed incontinence. Seven (4.8%) subjects had overactive bladder (OAB) pre-surgery, whereas 19 (13.1%) had OAB symptoms post-surgery (including 15 first-time OAB patients), with a significant difference between pre- and post-surgery. IIQ-7 scores were markedly higher for patients with mixed incontinence post-surgery than for those with stress incontinence, indicating a lower QOL. Logistic regression analysis identified the number of Cesarean sections and days of urinary bladder catheterization as risk factors for postoperative UI. Conclusions UI and OAB rates were higher after gynecologic cancer surgery than in the general female population. The mixed incontinence rate was markedly higher post-surgery; QOL was low for such patients due to the combination of urgency and stress incontinence. Multiple Cesarean sections and urinary bladder catheterization post-surgery were risk factors for post-surgical UI.

Aim Postlaparoscopic shoulder pain (SP), mainly caused by pneumoperitoneum with CO2 , sometimes suffers patients. This study was aimed to analyze the backgrounds of SP after gynecologic laparoscopy to clarify the risk of SP. Methods We analyzed answers of questionnaire about the degree of SP from 696 patients undergoing gynecologic laparoscopic surgery since 2014-2018. The questionnaire asks the degree of SP with numeric rating scale from 0 to 10, before and 3 days after operation. We defined cases in which postoperative score elevated more than three compared to preoperative score as SP(+). Analyzed backgrounds were age, parity, body mass index, operative method, operative duration and amount of hemorrhage. Statistics was performed by Fisher exact analysis as univariate analysis, and with logistic regression as multivariate analysis. All laparoscopic surgeries were performed under 10-12 mmHg in pressure of pneumoperitoneum with CO2 . Results Univariate analysis revealed categories 'less than 50 years old', and 'over 2 h' and 'over 3 h' in operative duration resulted significant high rate of SP(+). For these three factors, multivariate analysis resulted that "less than 50 years old' and 'over 3 h in operative duration' were significantly high. Conclusion This study suggests that 'less than 50 years' old and 'over 3 h in operative duration' were risk factors of postlaparoscopic SP. To protect from SP after laparoscopy, some countermeasures should be necessary especially for these patients.

Study Objective To evaluate a new magnetic resonance imaging (MRI) grading system for preoperative differentiation between benign and variant-type uterine leiomyomas including smooth muscle tumors of uncertain malignant potential (STUMPs). Design Retrospective analysis (Canadian Task Force classification III). Setting Teaching hospital (Teine Keijinkai Hospital). Patients Three-hundred thirteen patient medical records were retrospectively reviewed if treated for uterine myomas and diagnosed with variant type leiomyomas or STUMPs (n = 27) or benign, typical leiomyomas (n = 286) and treated between January 2012 and December 2014. Intervention Uterine myoma classifications using MRI findings according to a 5-grade system (grades I–V) based on 3 elements. Measurements and Main Results Uterine myoma MRI classifications were based on 3 elements: T2-weighted imaging (high or low), diffusion-weighted imaging (high or low), and apparent diffusion coefficient values (high or low; apparent diffusion coefficient Conclusion This novel MRI grading system for uterine myomas may be beneficial in differentiating benign leiomyomas from STUMPs or variant type leiomyomas and could be a future effective presurgical assessment tool.

Objective: To evaluated the utility and safety of the Cavitron ultrasonic surgical aspirator (CUSA) for laparoscopic paraaortic lymphadenectomy in gynecologic malignancies.Methods: Between January 2007 and January 2008, we performed laparoscopic treatment of gynecologic cancer in 22 patients. In all patients, laparoscopic lymphadenectomy was included in the surgical procedures. In 10 of 22 patients, CUSA was used for the dissection of the left-sided para-aortic lymph nodes. The range of lymphadenectomy was up to the renal vein for patients with endometrial and ovarian cancers, and up to the inframesentric artery for patients with cervical cancer. We analyzed the number of removed lymph nodes and the time needed for the procedure. The results in the group with CUSA and those without CUSA were compared.Result: The number of lymph nodes removed was equivalent between the groups, irrespective of the range of lymphadenectomy. However, the operative time was shortened in the group with CUSA. We had no particular complications in either group.Conclusion: We safely performed laparoscopic lymphadenectomy using CUSA. There is a possibility that by using CUSA, the time required for laparoscopic lymphadenectomy may be shortened.

We investigated the relationships between tumor necrosis factor (TNF) gene polymorphism, circulating TNF-alpha (TNF-alpha) concentrations, and bone mineral density (BMD) in the lumbar spine. TNF gene polymorphisms studied were the Nco I polymorphism within the first intron of TNF-beta (TNF-beta) and three single nucleotide polymorphisms in the promoter region of the TNF-alpha gene, at positions -857, -863, and -1031. Allelic variants of the TNF gene were identified using restriction fragment length polymorphism (RFLP) analysis in 177 postmenopausal Japanese women within 10 years after menopause, aged 56.4 +/- 4.5 years (mean +/- SD). A significantly higher prevalence of the alleles TNF-alpha-863A (20.3% versus 9.9%) and TNF-alpha-1031C (21.3% versus 12.4%) was seen in the low BMD group (Z-score0, n = 91) than in the high BMD group (0Z-score, n = 86). In genotype analysis, although difference did not reach a significant level, women with the rarest allelic variants, i.e., homozygous TNFbl, TNF-alpha-863A, and TNF-alpha-1031C, showed the lowest BMD Z-scores. Women with another rarest allelic variant, TNF-alpha-857T/T had significantly lower BMD Z-scores than did women with TNF-alpha-857C/T or -857C/C. The BMD Z-score decreased significantly with an increase in the total number of such rare alleles. Serum concentrations of TNF-alpha did not differ significantly among groups divided by genotypes. Multiple linear regression analysis revealed that the total number of rare alleles, in addition to the body mass index and the number of years since menopause, was an independent predictor of the BMD. These presumptive functional polymorphisms of the TNF gene may be associated with the lumbar spine BMD in early postmenopausal Japanese women.

Background. The prognostic factors of adult granulosa cell tumor (AGCT) have not been well defined. Methods. In 27 AGCT patients, we examined clinical stage, microscopic patterns, mitotic index (MI), and lymph-vascular space invasion (LVSI) to determine whether these factors were related to disease-free survival (DFS) of patients with AGCT. We also performed immunohistochemical examination for p53. Results. Seventeen cases represented stage I tumors, four stage II, five stage III, and one stage IV. Patients with stage I disease had more favorable prognosis than those with stage II to IV disease ( p =0.034). There was no relation between the microscopic patterns and the DFS. The MI, which was categorized into 3/10high power field (HPF) and 4/10 HPF, was significantly related to patients DFS ( p

BACKGROUND Noncancerous cells simulating adenocarcinoma cells may interfere with the analysis of peritoneal cytology (PC) in patients with endometrial carcinoma. Immunocytochemistry (ICC) may improve the diagnosis of PC. METHODS PC slides from 115 patients with endometrial carcinoma were reviewed. Suspicious or positive cell clusters were recovered with a cell transfer method and were subjected to ICC for MOC-31, cytokeratin 5/6, and p53. Conventional Papanicolaou staining and ICC results were compared directly on the same cells. RESULTS By combined conventional and immunocytochemical PC (CONV-ICC-PC), cytodiagnosis was positive in 18 of 115 patients (15.7%) and suspicious in 3 of 115 patients (2.6%). According to a multivariate Cox regression analysis of patients with tumors confined to the uterus that included grade, myometrial invasion, cervical involvement, and CONV-ICC-PC, only CONV-ICC-PC was an independent prognostic factor (P < 0.05). A multivariate analysis for all of the patients studied that compared CONV-ICC-PC with staging variables revealed that only peritoneal metastasis (P < 0.0001) and lymph node metastasis (P < 0.01) were independent prognostic factors. When peritoneal metastases were excluded, CONV-ICC-PC (P < 0.01) and lymph node metastasis (P < 0.0025) were the independent prognostic factors. By cell transfer and p53 immunostaining in samples from 14 patients with malignant cells in their peritoneal washings, no deaths occurred among 5 patients with negative p53, whereas 5 of 9 patients with positive p53 died of disease at the time of data analysis. CONCLUSIONS MOC-31 immunostaining improves the diagnosis of PC in endometrial carcinoma. Positive PC is an important prognostic factor for patients with endometrial carcinoma confined to the uterus. The p53 positive cells in PC have possible prognostic significance. Cancer (Cancer Cytopathol) 2001;93:115–123. © 2001 American Cancer Society.

The prognostic significance of lymph node (LN) metastasis in clinically early-stage (pT1M0 or pT2M0) ovarian carcinoma has not yet been fully elucidated.From 1988 to 1997, 94 patients with ovarian carcinoma of pT1M0 (n = 78) or pT2M0 (n = 16) classification underwent surgery including systematic pelvic and paraaortic LN dissection. We investigated the prognostic factors of intraperitoneally determined early-stage ovarian carcinoma focusing on LN metastasis.LN metastasis was seen in 5.1% of pT1M0 and in 31.3% of pT2M0 tumors. Univariate analysis of grade, histology (clear cell vs others), size of primary tumor, peritoneal cytology, and LN metastasis revealed that histology (P0.01), size of tumor (P0.05), and LN metastasis (P0.0005) were related to patient survival of early-stage ovarian carcinoma. Peritoneal cytology (P = 0.053) and grade (P = 0.059) had marginal statistical significance. A multivariate Cox regression analysis showed that clear cell histology (P0.05) and LN metastasis (P0. 005) are significant independent prognosticators of patient survival. Three (two with clear cell adenocarcinoma and one with mucinous adenocarcinoma) of nine patients with LN metastasis had died of the disease by the time of the present analysis. Two of the three deceased patients had recurrent tumors in distant organs (bone and brain/liver), one had pleural and peritoneal carcinomatosis, and no patients had retroperitoneal recurrence. This suggests that LN metastasis indicates that tumor cells may have already spread systemically at the time of treatment and, at the same time, retroperitoneal lymph node dissection (RPLND) may be effective in eradicating retroperitoneal metastasis in some instances of ovarian carcinoma.Clear cell histology and LN metastasis are indicators of poor prognosis for patients with tumors limited to the pelvis. Therapeutic significance of systematic RPLND for pT1M0/pT2M0 ovarian carcinomas needs to be further investigated by randomized studies.

Background. The serous adenocarcinoma (SA) and clear cell adenocarcinoma (CCA) of endometrium have been shown to be associated with high relapse rate and poor survival. It is not clear whether prognostic significance of these specific cell types of tumor is independent of retroperitoneal lymph node metastasis and other histopathologic prognostic factors in endometrial carcinoma. Methods. We examined 240 consecutive patients with clinical stage I to stage III endometrial carcinoma who were treated prospectively with radical surgery and/or platinum-based chemotherapy. Surgery included extended hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic and paraaortic lymph node dissection. Prognostic significance of various histopathologic factors was determined by Cox regression analysis. Results. SA/CCA were more frequently associated with deep myometrial invasion, high nuclear grade (G3), lymph-vascular space invasion (LVSI), and pelvic lymph node metastasis when compared to endometrioid adenocarcinoma (EMA). Of 216 clinically staged stage I or II disease, seven of 12 cases of SA/CCA had extrauterine disease. This incidence was much higher than that for EMA (46/204) (p

We report a case of mos 45, X/46, X,+mar, diagnosed prenatally by amniocentesis, whose physical examination, including external and internal organs, along with serum testosterone values were normal five years after delivery. The mosaic karyotype was seen in 146 of 240 cells examined (amniotic fluid cells, 110/65; placental chorionic villi: 5/4; cord blood, 21/81; cultured skin fibroblasts, 10/90) from 386 metaphases, and the marker chromosome appeared as a small non-fluorescent acrocentric chromosome. All autosomes appeared normal, and no normal Y chromosome could be demonstrated. Analysis of 26 Y-chromosome loci by molecular techniques such as PCR, Southern analysis using multiple Y-specific DNA probes, and Hae III restriction endonuclease assessment of male-specific repeated DNA in the heterochromatic region of the Y chromosome, and fluorescence in situ hybridization (FISH), revealed the marker was derived from a Y chromosome including p terminal to q11.23, and paracentric inversion in the remaining Y long arm. The formation of testes can be considered as existence of SRY (sex-determining region of Y) as a testis-determining factor. The present report illustrates the importance of FISH and molecular techniques as a complement to cytogenetic methods for accurate identification and characterization of chromosome rearrangements in prenatal diagnosis. Copyright © 1998 John Wiley & Sons, Ltd.

The distribution of lymph node metastasis and the clinico-pathologic risk factors for nodal involvement in ovarian carcinoma need to be clarified based on systematic lymph node dissection. We studied 115 patients with ovarian carcinoma who underwent systematic pelvic and para-aortic lymph node dissection between 1987 and 1997. The incidence and distribution of lymph node metastasis are described and the clinico-pathologic risk factors for nodal involvement are investigated. Based on the occurrence of lymph node metastasis in the early stages, the incidence of solitary node involvement and the distribution of lymph node metastasis, we conclude that the primary site of nodal involvement in ovarian carcinoma is the para-aortic node (PAN), especially PAN superior to the inferior mesenteric artery (IMA). By univariate analysis, clinical stage, histologic type (mucinous vs. others), grade, multiple peritoneal metastases, peritoneal cytology, volume of ascites and serum CA125 level were correlated with overall incidence of lymph node metastasis. By performing a multivariate analysis with the clinical stage excluded, it was revealed that grade and peritoneal cytology were independent factors for PAN metastasis (p < 0.0025 and < 0.001, respectively) and that multiple peritoneal metastases and PAN metastasis were significant predictors of pelvic node metastasis (p < 0.01 and < 0.005, respectively). In conclusion, the PANs superior and inferior to IMA should be explored in staging of ovarian carcinoma that appears to be confined to the ovaries. To determine accurately the extent of disease, both the para-aortic and pelvic areas may need to be sampled or dissected in the case of ovarian carcinoma involving the peritoneal surfaces. Int. J. Cancer (Pred. Oncol.) 79:526–530, 1998.© 1998 Wiley-Liss, Inc.

The International Federation of Gynecology and Obstetrics (FIGO) adopted surgical staging criteria in 1988. Many studies have shown that histologic grade, nuclear grade, lymph-vascular space invasion and cell type are also important predictors of survival. It has not been clarified, however, how to integrate these histopathologic variables into the process of estimating individual prognosis. We performed Cox multivariate regression analysis to create models that incorporate various histopathologic factors for estimating the prognoses of patients with endometrioid adenocarcinoma of the uterine corpus. Our study was based on data from 206 patients who underwent complete surgical staging, including systematic pelvic and para-aortic lymph node dissection. Two models resulted: one included depth of myometrial invasion, para-aortic node metastasis and the number of sites involved by the tumor among the cervix, ovary and pelvic lymph nodes (which we designated as extracorporeal spread score, ECS) and the other incorporated nuclear grade and lymph-vascular space invasion as variables. These 2 models enabled the prognosis for patients with endometrioid adenocarcinoma to be stratified into several levels according to hazard ratio. Comprehensive integration of the histopathologic prognostic factors, categorized into those relating to tumor extent and those relating to tumor virulence, should facilitate the estimation of individual prognosis more accurately than FIGO staging alone.

The induction of immortalization of human fibroblasts by carcinogens is a very rare process. Hybrids between immortal cells and normal fibroblasts senesce, indicating that immortal cells must lose one or more senescence genes for immortalization. To examine the possible involvement of multiple gene alterations in extended lifespan or immortalization of normal human fibroblasts, normal human fibroblasts (WHE-7 cells) and skin fibroblasts (MDAH 087 cells) derived from a Li-Fraumeni syndrome patient with a mutated p53 allele were periodically irradiated with x rays. All six unirradiated control MDAH 087 cell cultures ceased growing by 37 population doublings (PD) and senesced. In contrast, one of six MDAH 087 cultures irradiated one to three times with x rays (2 or 4 Gy at 2 Gy/min) grew continuously for over 450 PD, indicating that the cells were immortal. All 12 WHE-7 cell cultures that were irradiated under the same conditions and all 20 uniradiated control WHE-7 cultures did not become immortal. Single-stranded DNA conformation analysis and DNA sequencing revealed that no additional mutations were induced by x-ray irradiation in exons 2–10 of the p53 gene of the immortal cells (LCS-4X2 cells) and that loss of the wild-type p53 gene was necessary but not sufficient for immortalization. Karyotypic analysis and chromosome painting analysis demonstrated that a high percentage (more than 98%) of LCS-4×2 cells had lost chromosome 6. Irradiation of WHE-7 cells nine times with x rays (2 Gy at 2 Gy/min) extended the cells' lifespans but did not immortalize them. These cells (X9 cells) exhibited a nonrandom karyotypic alteration, monosomy 6, that was confirmed by loss of heterocygosity for a polymorphic dinucleotide repeat sequence on chromosome 6. DNA analysis showed that X9 cell had no mutations in exons 2–10 of the p53 gene. DNA fingerprint analysis with a multi-locus probe detected DNA rearrangements in LCS-4×2 cells and X9 cells, indicating that both cells could have mutations at a gene or genes other than the p53 gene. The results are consistent with our previous findings that cells with a mutation in one gene involved in cellular senescence (i.e., the p53 gene in Li-Fraumeni fibroblasts) are prone to immortalization. Furthermore, we conclude that immortalization of normal human fibroblasts is a multistep process involving loss or inactivation of multiple genes, such as p53 and a gene on chromosome 6. Loss of a gene on chromosome 6 without p53 alterations extends cellular lifespan without immortalizing the cells. Mol. Carcinog. 18:7–18, 1997. © 1997 Wiley-Liss, Inc.

BACKGROUND Prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) is associated with the subsequent development of clear cell adenocarcinoma of the lower reproductive tract in young women, and data concerning the molecular genetic alterations involved in the etiology of this tumor type have not previously been reported. Such knowledge would be of potential value by providing insight into the molecular mechanisms of hormonal carcinogenesis in general, as well as by suggesting molecular markers for risk assessment in the estrogen-exposed population. METHODS A total of 24 samples of clear cell adenocarcinoma of the vagina or cervix, 16 associated with exposure in utero to DES and 8 with no history of DES exposure, were obtained as archival fixed and embedded tissue specimens. DNA was purified from these tissues and used to examine a number of biologically plausible molecular genetic endpoints for tumor specific alterations. RESULTS No evidence was found for mutations in the K-ras or H-ras protooncogenes, the Wilms' tumor (WT1) tumor suppressor gene, or the estrogen receptor gene. Sporadic overexpression of the p53 tumor suppressor gene was detected in some tumor cell nuclei by immunohistochemistry, but in the absence of detectable p53 gene mutation. Genetic instability as manifested by somatic mutation of microsatellite repeats was widespread in these tumors, with evidence of microsatellite instability in all DES-associated tumors examined, and in 50% of those tumors not associated with DES exposure. CONCLUSIONS These data are consistent with the hypothesis that the induction of genomic instability may be an important mechanism of DES-induced carcinogenesis. Cancer 1996;77:507-14.

Laparoscopic resection of deep infiltrating endometriosis (DIE) has been reported to be an effective method for reduction of endometriosis-associated pain. As its complications, bowel perforation, urinary tract injury and neurogenic bladder are well known; however, uterine vein rupture during pregnancy has not been reported previously. We encountered a case of hemoperitoneum resulting from uterine vein rupture at a delivery as a delayed consequence of laparoscopic resection of DIE. A 31-year-old, para 2 woman underwent laparoscopic resection of lateral pelvic peritoneum, uterosacral ligaments, and bilateral endometriomas, exposing uterine vessels, which we covered with fibrin glue. Endometriosis-associated pain disappeared, and then the patient conceived 4 months later. The course of pregnancy and induction of labor with controlled oxytocin infusion was uneventful, and the patient delivered a female baby without asphyxia. Immediately after delivery, low abdominal pain with hypotension occurred despite absence of abnormal vaginal bleeding. Ultrasonography and the blood hemoglobin value suggested hemorrhagic shock owing to hemoperitoneum; therefore emergency exploratory laparotomy was performed. Active bleeding was found at the right uterine vein, which was then sutured for hemostasis. The patient received a blood transfusion and recovered without any problems. The bleeding lesion was located at the vein on which the peritoneum had been removed at the first laparoscopy, which suggested that the operation for DIE included a risk of uterine vessel rupture during pregnancy.

The adolescent is an important period in which the peak bone mass is acquired. A sufficient attainment of peak bone mass is important as well as a prevention of bone loss in postmenopausal period in order to prevent osteoporosis in future. It is well known that the estrogen deficiency is at risk of developing osteopenia. Anorexia nervosa, excessive exercises, Turner's syndrome and premature ovarian failure are leading causes of prolonged amenorrhea in young women. However, estrogen deficiency is not the only cause of low bone mass in these women. Although hormone replacement therapy is effective to increase bone mineral density in these women, management of amenorrhea should be individualized according to the status of bone metabolism.

We report the first case of an intrauterine treatment for cystic hygroma. Guided by ultrasonography, we first removed intracystic fluid from two cysts and then injected OK-432 into each fetal cyst at 21 and 28 weeks of gestation. No re-enlargement of the cysts was subsequently observed. At 38 weeks of gestation, a male infant was delivered transvaginally. Only a slight skin fold was observed in the nuchal area of the neonate, indicating the effectiveness of OK-432 for the intrauterine treatment of cystic hygroma.

The purpose of the present study was to investigate the possible roles of PvuII and XbaI polymorphisms of the estrogen receptor alpha (ER(alpha)) in bone mineral density (BMD), vertebral fracture, bone loss rate after menopause and response to hormone replacement therapy (HRT).All 286 women were grouped according to the genotypes of PvuII or XbaI polymorphisms of the ER(alpha) gene. We compared the BMD Z-score, incidence of vertebral fracture, changes in Z-score after menopause and response of BMD to HRT among the genotypes.Subjects with the PPxx genotype had significantly (P0.05) lower Z-scores than did subjects with the other genotypes. A negative correlation was observed between the length of time after menopause and the decrease of the Z-score only in women with the pp genotype, suggesting faster bone loss in this group. In the analysis of the ER(alpha) polymorphism with regard to the effect of HRT on BMD, there appears to be a significantly greater increase of BMD (P0.01 and 0.05) in women with the pp genotype than in those with the Pp or PP genotype.PvuII and XbaI polymorphisms of the ER(alpha) gene were associated with BMD in postmenopausal Japanese women. Also, the polymorphisms may be useful genetic markers for predicting vertebral fracture in relatively young postmenopausal women. The PvuII polymorphism may be associated with susceptibility to changes in estrogen level.

Cefpirome sulphate is a fourth-generation cephem antibiotic, which has a broad spectrum of antibacterial activity against Gram-positive and -negative bacteria, and is highly stable to β-lactamase. Cefpirome sulphate was administered to 166 patients with obstetric or gynaecological infections, and its clinical and antibacterial effect was evaluable in 139. Excluding seven patients who violated the study protocol by receiving concomitant drugs, the safety of cefpirome sulphate was assessed in 159 patients. In the 139 patients in whom efficacy was evaluated, the improvement rate was 80.6% (112/139) and the eradication rate 72.6% (45/62). The eradication rate for bacteria isolated from the patients at the start of the study was 84.7% (111/131). No resistance to cefpirome sulphate was observed in Enterococcus faecalis or Bacteroides species. Systemic erythema and nausea each occurred in one patient, and nine patients showed abnormal hepatic function test results. These results suggest that cefpirome sulphate is effective in the treatment of obstetric and gynaecological infections and has a good side-effect profile.

Telomerase activity has been implicated in the progression of various human tumors. Our aim was to evaluate telomerase activity and to compare it with histo-pathological factors in uterine endometrial carcinoma, to look for possible correlations. Telomerase activity was measured by dilution analysis using a PCR-based telomeric repeat amplification method and detected in 31 of 35 primary endometrial carcinoma tumor specimens. High telomerase activity, detected after 100-fold dilution of extracts, was identified in 15 specimens. There was no significant correlation between the positive telomerase activity and tumor surgical stage or histo-pathological factors. However, high telomerase activity was significantly correlated with advanced surgical stage and with pelvic lymph node metastasis. Our findings suggest that an increase in telomerase activity may be associated with tumor progression and that its level may have a prognostic value in endometrial carcinoma.

BACKGROUND The incidence and distribution pattern of retroperitoneal lymph node metastasis in patients with cervical carcinoma should be investigated based on data from systematic pelvic lymph node (PLN) and paraaortic lymph node (PAN) dissection, so that a basis can be established for determining the site of selective lymph node dissection or sampling. METHODS A total of 208 patients with Stages IB, IIA, and IIB cervical carcinoma who underwent radical hysterectomy and systematic pelvic and PAN dissection were investigated for lymph node metastasis and histopathologic risk factors for lymph node metastasis. RESULTS Fifty-three patients (25.5%) had lymph node metastasis. The obturator lymph nodes were most frequently involved, with a rate of 18.8% (39/208). Forty-nine of 53 node-positive patients had lymph node metastasis in the obturator, internal iliac, or common iliac lymph nodes. Of 26 solitary lymph node metastases confined to one node group, 18 were in the obturator, 3 in the internal iliac, 3 in the parametrial, and 2 in the common iliac lymph nodes. A multiple logistic regression analysis revealed that deep cervical stromal invasion and lymph-vascular space invasion were related to PLN metastasis. It was also shown that metastasis to bilateral PLNs (excluding the common iliac lymph nodes) as well as metastasis to the common iliac lymph nodes were significantly related to PAN metastasis. CONCLUSIONS The results of this study suggest that the obturator lymph nodes can be sentinel lymph nodes of cervical carcinoma. PAN metastasis appears to occur secondarily to wide-spread PLN metastasis. These results provide a basis for determining the site of selective lymph node dissection and for estimating the existence of PAN metastasis from the pattern of metastasis in PLN in patients with cervical carcinoma. Cancer 1999;85:1547–54. © 1999 American Cancer Society.

We report an unusual case of a 55 year old Japanese woman with a seminoma but relatively normal menses. The patient was a phenotypic female with late onset menarche (18 years of age), who was amenorrhoeic for the first year, followed by menses of one to three days' slight flow with dysmenorrhoea, but an otherwise normal menstrual history. A typical seminoma was removed from the left adnexal region and an immature testis was identified separately as an associated right adnexal mass. Repeated karyotypic studies on peripheral blood lymphocyte cultures showed only 46,X,-Y,t(Y;15)(q12;p13). Cytogenetic examination of the patient's younger brother, who had fathered three healthy children, showed an identical karyotype. Mosaicism of 46,X,-Y,t(Y;15)(q12;p13)/45,X cell lines was found in skin samples from the patient's elbow and genital regions, although there were no clinical stigmata of Turner syndrome. An androgen receptor binding assay of cultured genital skin fibroblasts was negative. Molecular analysis using Southern blot hybridisation, PCR, and direct DNA sequencing showed that neither the patient nor her brother had a detectable deletion or other abnormalities of Y chromosome sequences, including the SRY (sex determining region of the Y chromosome) gene sequence. These findings suggest that Turner mosaicism of the 45,X cell line may have contributed to this atypical presentation in an XY female, although we cannot exclude abnormalities of other genes related to sex differentiation.

A genomic HLA-G clone named 7.0E was isolated from a Japanese placenta. The deduced amino acid sequence of the 7.0E was identical to two HLA-G genomic clones and two cDNA clones previously described. The DNA sequences of alpha 1 and alpha 2 domains of the HLA-G gene from 5 cell lines also encoded the same amino acids. However, a 14 bp insertion, ATTTGTTCATGCCT, was present in the 3' untranslated region of 7.0E compared with the originally described HLA-G clone (HLA 6.0). Polymerase chain reaction (PCR)/single strand conformational polymorphism (SSCP) analysis of exon 8 allowed the HLA-G gene to be classified into two alternative types, G6.0 and 7.0 E, those correlated to the absence or the presence of the 14 bp stretch. Each group had minor sequence variant(s), and the alleles of the 7.0E-type were more heterogeneous than those of the G6.0-type. The 14 bp deletion is present only in the G6.0-type of HLA-G alleles among HLA class I genes. Thus it was suggested that G6.0 alleles were generated after diversification of the HLA-G.

Complete hydatidiform moles may originate from either the fertilization of an empty egg by a haploid sperm followed by duplication (producing a monospermic, homozygous mole) or the fertilization of such an egg by two haploid sperms (producing a dispermic, heterozygous mole). This difference in the mechanism leading to the formation of complete moles raises the question of whether the risk of subsequent malignancy is influenced by the zygosity of the mole. We have compared the incidence of postmolar sequelae in patients with homozygous and heterozygous moles. Using chromosomal heteromorphisms, human lymphocyte antigen (HLA) and phosphoglucuromutase i (PGM1) polymorphisms, we established the androgenetic origin of complete mole in 84 of 91 cases. Homozygosity was confirmed in 51 moles, and we found ten heterozygous moles. Five of ten patients with heterozygous moles developed postmolar trophoblastic disease, whereas only two of the 51 patients with homozygous moles had postmolar trophoblastic disease (an additional five patients showed signs of degenerating residual trophoblasts). The XY sex chromosome constitution of the two in vitro choriocarcinoma cell lines examined here provides further evidence of the propensity to malignancy of heterozygous moles.