Katsunori Kashima

Familial risk among Japanese patients with endometriosis

Objectives: This study was designed to examine the prevalence of endometriosis among female siblings of patients with endometriosis in Japan. Methods: A total of 339 patients with endometriosis were questioned about endometriosis in their sisters. The control group consisted of 284 Japanese healthy fertile women with no history of endometriosis. Similarly, the controls were interviewed about their sisters. Results: We detected sisters with endometriosis in 8.8% of cases and 1.5% of the control population. The relative risk of endometriosis in female siblings was 5.7. However, a significant difference was not seen in age at diagnosis and clinical stage between patients with or without a family history of endometriosis. Conclusions: These data demonstrate a familial tendency for endometriosis and suggest that endometriosis has a genetic factor in the pathogenesis.

Resolution of uterine arteriovenous malformation and successful pregnancy after treatment with a gonadotropin-releasing hormone agonist.

BACKGROUND: Uterine arteriovenous malformations are a rare and potentially life-threatening condition. Medical therapy has not been popular because of the propensity for excessive bleeding in the patient. As a result, the effect of gonadotropin-releasing hormone (Gn-RH) agonists on uterine arteriovenous malformations has not been established. CASE: A 30-year-old patient presented with persistent vaginal bleeding. Based on the color Doppler ultrasound and magnetic resonance imaging findings, a uterine arteriovenous malformation was diagnosed. Because initial treatment with methylergonovine maleate was unsuccessful, the patient was treated with Gn-RH agonists. The lesion completely disappeared after 6 months of Gn-RH agonist treatment. Five months after the completion of Gn-RH agonist therapy, the patient conceived spontaneously and successfully completed a normal pregnancy. The patient has remained free from recurrence of the lesion. CONCLUSION: Gonadotropin-releasing hormone agonist therapy has the potential to be a conservative treatment modality for uterine arteriovenous malformations in hemodynamically stable patients.

Analysis of the complications after radical hysterectomy for stage IB, IIA and IIB uterine cervical cancer patients.

Aim:  This study was undertaken to assess whether radical hysterectomy and pelvic lymphadenectomy could be carried out within acceptable complications in uterine cervical cancer patients.

Screening of BRCA1 mutation using immunohistochemical staining with C-terminal and N-terminal antibodies in familial ovarian cancers

We examined the subcellular localization of BRCA1 proteins using immunohistochemical staining with C‐terminal (GLK‐2 antibody) and N‐terminal (Ab‐2 antibody) monoclonal antibodies in 44 familial ovarian cancers. Among these, 24 cases were associated with 13 independent germ‐line mutations of BRCA1, and loss of heterozygosity (LOH) at one or more BRCA1 microsatellite markers was found in all 21 informative tumors tested. With GLK‐2 antibody, cytoplasmic staining was observed in 15 of 16 tumors (93.8%) with mutation in exon 11, and BRCA1 staining was absent in 8 of 8 tumors (100%) with mutation in exons other than exon 11. When immunohistochemical staining was performed with Ab‐2 antibody, both nuclear and cytoplasmic staining were observed in 14 of 16 tumors (87.5%) with mutation in exon 11. Interestingly, nuclear staining was observed in 3 of 3 tumors (100%) with mutation downstream of exon 11, even though no staining was detected in 5 of 5 tumors (100%) with mutation upstream of exon 11. On the other hand, in familial ovarian cancers without BRCA1 mutations, nuclear staining or both nuclear and cytoplasmic staining was observed in 18 of 20 specimens (90%) and 20 of 20 specimens (100%) with GLK‐2 antibody and with Ab‐2 antibody, respectively. These results suggest that an immunohistochemical assay in combination with employing the C‐terminal and the N‐terminal antibodies appears to have potential as a reliable and useful technique for the screening of BRCA1 mutations, at least to predict the status of mutation, upstream or downstream of exon 11.

A nonsynonymous variant of IL1A is associated with endometriosis in Japanese population.

Our previous genome-wide association study has demonstrated that single-nucleotide polymorphisms (SNPs) located in intronic and downstream regions of IL1A (interleukin 1α) were associated with the risk of endometriosis. These SNPs on the genome-wide association study platform could be only surrogates for the true causal variant. Thus, we resequenced all the exons of IL1A in 377 patients with endometriosis and 457 healthy controls. We detected seven rare variants (minor allele frequency <0.01) and four common variants. All the rare variants were not associated with endometriosis. The four common variants (rs17561, rs1304037, rs2856836 and rs3783553) in IL1A were significantly associated with endometriosis (P=0.0024, 0.0024, 0.0014 and 0.0061, respectively). All the four SNPs were within a linkage disequilibrium block. Among them, only rs17561 was nonsynonymous (p.A114S), which has been reported to be associated with susceptibility to ovarian cancer. Taken together, we examined association between rs17561 and endometriosis in an independent validation data set (524 patients and 533 healthy controls) replicating significant association (P=4.0 × 10−5; odds ratio (OR), 1.91; 95% confidence interval (CI), 1.41–2.61). Meta-analysis by combining results from the two stages strengthened the evidence of association (P=2.5 × 10−7; OR, 1.90; 95% CI, 1.49–2.43). Our findings demonstrated that the nonsynonymous variant of IL1A might confer genetic susceptibility to endometriosis in Japanese population.

Outcomes of fertility‐sparing surgery for women of reproductive age with FIGO stage IC epithelial ovarian cancer

To report the clinical outcomes of patients with FIGO stage IC epithelial ovarian cancer (EOC) treated by fertility‐sparing surgery (FSS).

Primary retroperitoneal mucinous cystadenocarcinoma associated with pregnancy

Primary retroperitoneal mucinous cystadenocarcinoma (PRMC) is an extremely rare tumor. Only 30 cases have been reported previously in the English literature, and little information is available concerning its treatment and prognosis. The patient was a 28-year-old woman, presenting with a right mid-abdominal tumor at 26 weeks of gestation. At 31 weeks of gestation, she underwent an exploratory laparotomy and was diagnosed with a PRMC. No disseminated tumor was observed, and an excision of only the tumor was performed. She had an uneventful vaginal delivery at 38 weeks of gestation and remains free of disease at 13 months after the operation. This report describes a case of PRMC associated with pregnancy. The optimal management of these retroperitoneal masses during pregnancy is discussed. Based on limited experience and the current literature, a PRMC with an intact capsule and no dissemination appears to have a good prognosis and can be treated by tumor excision alone in patients who wish to preserve fertility

Possible involvement of the E-cadherin gene in genetic susceptibility to endometriosis

BACKGROUND Endometriotic cells display invasive characteristics, despite their benign histological appearance. Recently, the epithelial-mesenchymal transition, in which epithelial cells acquire mesenchymal and migratory properties, has attracted attention as a mechanism of tumor invasion. We aimed to investigate the association between endometriosis and polymorphisms of the E-cadherin gene, a central player in the epithelial-mesenchymal transition, in Japanese women. METHODS Twelve single-nucleotide polymorphisms (SNPs) in the E-cadherin gene were identified by real-time polymerase chain reaction using a TaqMan assay in 511 women with endometriosis (the majority in Stages III and IV) and 498 healthy controls. RESULTS Allele frequency analysis indicated that there was a marginally higher frequency of the rs4783689 C allele in women with endometriosis compared with controls (corrected P = 0.007; odds ratio = 1.37; 95% confidence interval, 1.14-1.64). No significant associations with endometriosis were found for the other 11 SNPs. CONCLUSIONS Although this study was limited by sample size, the E-cadherin gene polymorphism rs4783689 was marginally associated with endometriosis in the Japanese population, suggesting that E-cadherin might be involved in genetic susceptibility to endometriosis.

Preoperative ultrasound-guided needle biopsy of 63 uterine tumors having high signal intensity upon T2-weighted magnetic resonance imaging.

Objective The differential diagnosis between uterine sarcoma and benign leiomyoma is difficult when made only by magnetic resonance imaging (MRI); it usually requires an additional preoperative diagnostic procedure. We report our results using ultrasound-guided needle biopsy for these types of uterine tumors. Methods Ultrasound-guided needle biopsy was performed on 63 patients with uterine smooth muscle tumors suspected of malignancy by MRI. We compared the results of presurgical biopsy against the postsurgical pathology of the tumor. Results Among 63 patients with a high signal intensity of the uterine tumor on T2-weighted MRI (1 case was undetermined), 12 cases (19.3%) were diagnosed by the needle biopsy as malignant, and 51 cases (80.6%) were benign. Among the 12 diagnosed as malignant tumors, 11 had surgery performed, and one was treated with chemotherapy. Among the 51 patients diagnosed with a benign tumor, 27 had surgery performed, and 24 were put on a wait-and-see clinical follow-up schedule. One of the 27 surgical patients with a benign tumor had a postsurgical diagnosis of a low-grade endometrial stromal sarcoma. In the 38 cases where surgery was performed, we found the sensitivity, specificity, and the positive and negative predictive values of the needle biopsy were 91.7%, 100%, 100%, and 96.2%, respectively. Conclusions Ultrasound-guided needle biopsy may be a reliable preoperative diagnostic procedure for uterine tumors with suspected malignancy.

Increased apoptosis of germ cells in patients with AZFc deletions

PurposeAZFc deletions are associated with variable testicular histology ranging from the Sertoli cell only to spermatogenic arrest and hypospermatogenesis. Such variable phenotypes may be explained by progressive germ cell regression over time. Increased apoptosis is likely responsible for progressive regression of spermatogenic potential. This study evaluated germ cell apoptosis as a cause of the progressive decrease in the number of germ cells in patients with AZFc deletions.MethodsThis study evaluated germ cell apoptosis in patients with AZFc deletions. A total of 151 patients who were diagnosed with either severe oligozoospermia or non-obstructive azoospermia were screened for Y chromosome microdeletions. Germ cell apoptosis was examined using terminal deoxy-nucleotidyl transferase-mediated digoxigenin-dUTP nick-end labeling (TUNEL) on formalin-fixed 5-µm sections of testicular specimens.ResultsSeven out of 117 (6.0%) patients with azoospermia and 4 of 34 (11.8%) patients with severe oligozoospermia had Y chromosome microdeletions. The percentage of apoptotic germ cells in the testes of patients with AZFc deletions were significantly increased compared to those of patients without AZFc deletions.ConclusionsThese results suggest that increased apoptosis of germ cells is responsible for the progressive decline of spermatogenic potential in patients with AZFc deletions.