Influence of laparoscopic surgery for endometriosis and its recurrence on perinatal outcomes.

Purpose: It is unknown whether surgery for endometriosis or recurrence of endometriosis affects obstetric outcomes. Methods: A total of 208 pregnant women with a history of endometriosis were analyzed. Patients who had endometriomas >3 cm and no history of laparoscopic surgery for endometriosis were defined as non-surgery group (n = 60), while those who had a history of surgery for endometriosis (n = 148) were defined as surgery group. We investigated the obstetric outcomes in 208 patients according to with or without postoperative recurrence of endometriosis and the time from surgery to pregnancy. Results: Among 177 cases of on-going pregnancy, in surgery group, there were lower prevalence of placenta previa compared with non-surgery group (8.5% vs. 23.4%; p = 0.020). Subgroup analysis revealed a decreased prevalence of placenta previa in postoperative non-recurrence group (6.0%: p = 0.007) compared with non-surgery (23.4%) and postoperative recurrence group (28.6%). Placenta previa was more prevalent in the patients who got pregnant more than 2 years after surgery (20.0%) than the patients who got pregnant within 2 years (2.4%: p = 0.002). Multivariate analysis revealed that the surgery was associated with a reduction in placenta previa (OR: 0.32, 95% CI [0.11-0.90]; p = 0.032). Conclusions: Pregnancy within two years after laparoscopic surgery for endometriosis may reduce placenta previa.

Chemical pleurodesis with autologous blood and freeze-dried concentrated human thrombin improved spontaneous pneumothorax and thoracic endometriosis: The first case involving a pregnant woman.

OBJECTIVE: Spontaneous pneumothorax combined with thoracic endometriosis is a rare condition during pregnancy. We present a case of chemical pleurodesis with autologous blood and freeze-dried concentrated human thrombin during pregnancy. CASE REPORT: This report presents a case of spontaneous pneumothorax combined with thoracic endometriosis that arose at 22 weeks' gestation in a 35-year-old female. The initial chest drainage was unsuccessful. At 25 weeks' gestation, video-assisted thoracoscopic surgery was performed and revealed endometriosis in the thoracic cavity. Since the leak persisted, chemical pleurodesis was performed with autologous blood and freeze-dried concentrated human thrombin at 28 weeks' gestation. The leak improved markedly and did not recur. CONCLUSION: This is the first case report about chemical pleurodesis with autologous blood and freeze-dried concentrated human thrombin during pregnancy. This procedure might contribute to the management of pneumothorax in pregnant women.

Successful Pregnancies and Deliveries in a Patient With Evolving Hypopituitarism due to Pituitary Stalk Transection Syndrome: Role of Growth Hormone Replacement.

We herein report a 31-year-old Japanese woman with evolving hypopituitarism due to pituitary stalk transection syndrome. She had a history of short stature treated with growth hormone (GH) in childhood and had hypothyroidism and primary amenorrhea at 20 years old. Levothyroxine replacement and recombinant follicle stimulating hormone-human chorionic gonadotropin (FSH-hCG) therapy for ovulation induction were started. GH replacement therapy (GHRT) was resumed when she was 26 years old. She developed mild adrenocortical insufficiency at 31 years old. She succeeded in becoming pregnant and delivered twice. GHRT was partially continued during pregnancy and stopped at the end of the second trimester without any complications.

Case of pituitary stalk transection syndrome ascertained after breech delivery.

Pituitary stalk transection syndrome (PSTS) is a rare complication that can accompany breech delivery. Early diagnosis of this syndrome is difficult, and it may cause a serious delay in the diagnosis. We present a case of PSTS ascertained after breech delivery. A 20-year-old woman presented with primary amenorrhea. The patient was born by breech delivery and had a history of treatment for pituitary dwarfism. Her laboratory findings showed pituitary hypothyroidism, and hormone replacement therapy was initiated. At 28 years old, she became pregnant and had a normal delivery at 38 weeks' gestation. One year after delivery, her thyroid hormone level changed. Laboratory test showed adrenocortical insufficiency, and magnetic resonance imaging of the pituitary gland showed transection of the pituitary stalk and development of an ectopic posterior lobe. These findings were compatible with PSTS. When a patient who has been born by breech delivery presents with symptoms of pituitary deficiency, PSTS should be considered in the differential diagnosis.

A case of myomatous erythrocytosis syndrome associated with a large uterine leiomyoma.

Several etiologies have been proposed for erythrocytosis associated with uterine leiomyoma. We report a case of erythrocytosis associated with a large uterine leiomyoma, in which specific immunostaining for erythropoietin was positive. A 55-year-old woman, gravida 0, para 0, was referred to our hospital for treatment for a large uterine myoma and erythrocytosis. She had no vaginal bleeding after she reached menopause at 50 years old. She had severe polycythemia: hemoglobin (Hb), 19.9 g/dL; red blood cell count (RBC), 6.65 × 10(6)/mm(3); hematocrit, (Hct) 59.1%. An abdominal simple hysterectomy was performed, and a pathological examination confirmed the diagnosis of leiomyoma of the uterus. In addition, immunostaining demonstrated that the cytoplasm of the leiomyoma cells was strongly positive for erythropoietin. After the operation, the patient's hemoglobin and hematocrit levels normalized, and we diagnosed her condition as myomatous erythrocytosis syndrome.

Effects of laparoscopic radical surgery for deep endometriosis on endometriosis-related pelvic pain.

Deep endometriosis is associated with severe painful symptoms that sometimes impair the quality of life in women of reproductive age. Medical therapy does not provide for adequate pain relief, and an effective management option to reduce pelvic pain appears to be complete laparoscopic removal of as many endometriotic lesions as possible. In this study, we investigated the usefulness and risks of radical laparoscopic removal of deep endometriosis for patients diagnosed as stage III/IV endometriosis during laparoscopic surgery. Forty-seven consecutive patients undergoing conservative laparoscopic surgery alone (adhesiotomy and cystectomy of ovarian endometriosis but not removal of deep endometriotic lesion; non-DEL removal group) and 151 consecutive patients undergoing radical laparoscopic removal of deep endometriotic lesions combined with conservative surgery (DEL removal group) were compared. As a result, significant improvements in pain were obtained in both groups, however, the degree of improvement was significantly higher and the rate of recurrence was significantly lower in the DEL removal group. The addition of radical removal of deep endometriotic lesions to conservative laparoscopic surgery markedly reduces the severity of dysmenorrhea and the rate of recurrent pelvic pain. Although the surgical procedure is technically demanding, the levels of peri-operative complications and morbidity are acceptable.

Anti-N-methyl-D-aspartate receptor encephalitis associated with ovarian immature teratoma.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a treatment-responsive encephalitis associated with anti-NMDAR antibodies. Unlike classic paraneoplastic encephalitis, this disorder usually develops in young women with ovarian teratoma who typically present with marked neuropsychiatric symptoms, followed by prolonged respiratory failure, clouding of consciousness, and bizarre dyskinesia. This disorder is often treatable by resection of ovarian tumor and immunotherapy, but, delayed diagnosis results in a worse condition and sometimes fatal outcome. However, some gynecologists are not familiar with this disorder. When physicians encounter a female patient with encephalitis showing marked neuropsychiatric symptoms, search for an ovarian tumor should be promptly initiated. We present a case of anti-NMDAR encephalitis associated with ovarian immature teratoma. The symptoms were dramatically relieved by tumor resection and immunotherapy.

Ovarian squamous cell carcinoma which metastasized 8 years after cervical conization for early microinvasive cervical cancer: a case report.

Squamous cell cervical carcinoma that metastasized to the ovary is common in patients with bulky tumors or locally advanced disease; however, ovarian squamous cell carcinoma that metastasized after cervical conization surgery for early microinvasive uterine cervical carcinoma is very rare. We present a case of ovarian squamous cell carcinoma that metastasized 8 years after cervical conization surgery for early microinvasive cervical carcinoma. She had no sign of recurrence in the uterine cervix. We detected human papillomavirus type 16 DNA in both cervical tissue and ovarian tissue, suggesting that ovarian squamous cell carcinoma is derived from microinvasive cervical cancer. Although there are very few cases of early microinvasive squamous cell carcinoma that metastasized to the ovary with delayed recurrence, we should pay attention strictly not only to the cervical condition but also to the ovarian condition on regular post-operative follow-up.

Stage I ovarian cancer cases during early, mid and late pregnancy periods: three case reports and review of the literature.

Since ovarian cancer during pregnancy is rare, the decisions regarding pregnancy discontinuation or fertility preservation are often difficult. We report three ovarian cancer cases detected at early, mid and late pregnancy periods in which both babies and mothers were saved. In particular, case 2 is the first reported instance of a sertoliform endometrioid carcinoma of the ovary during pregnancy. In addition, we review the clinical characteristics of previously reported patients with stage I ovarian cancer diagnosed during pregnancy. Even with stage Ia ovarian cancer, restaging laparotomy at cesarean section or post-delivery may be important to determine the treatment plan because staging during pregnancy is rarely complete.

Endometrioid adenocarcinoma of the vagina with a microglandular pattern arising from endometriosis after hysterectomy.

Primary endometrioid adenocarcinoma rarely occurs in the vagina. Occasionally, endometrioid adenocarcinoma has a microglandular pattern. Herein, a case of primary endometrioid adenocarcinoma of the vagina with a microglandular pattern arising from pre-existing endometriosis long after a hysterectomy, is described. A 57-year-old postmenopausal woman developed a vaginal discharge over one decade after undergoing a hysterectomy. Microscopic examination of the vaginal smear and a biopsy specimen demonstrated an atypical glandular proliferation composed of columnar cells with occasional intracytoplasmic mucin and bland nuclear morphology, showing microcysts and numerous neutrophils within and around cysts. Immunohistochemically, the neoplastic cells were diffusely positive for CK7, MUC1, ER, and PR, and focally positive for vimentin, CEA, CK5/6, p63, p16(INK4a), and p53. A portion of residual endometrioid adenocarcinoma was identified adjacent to foci of endometriosis in the vaginectomy specimen. The patient has done well without evidence of recurrent disease for 1 year after surgery. Pathologists are encouraged to be aware of the occurrence of endometrioid adenocarcinoma associated with endometriosis in the vaginal stump after hysterectomy, and microglandular morphology which might be a source of misinterpretation.

Carcinomatous meningitis associated with ovarian cancer complicated by SIADH.

We experienced a case of carcinomatous meningitis originating from stage IIIc ovarian cancer complicated by syndrome of inappropriate antidiuretic hormone secretion (SIADH). A 51-year-old woman had been treated with multiple chemotherapy regimens after an initial operation for ovarian cancer. During the last chemotherapy regimen, she suffered headache, mood changes and ataxia. After one week, she had a convulsive seizure and lost consciousness. Laboratory studies showed hyponatremia, low serum osmolality, elevated urinary sodium level and urine osmolality. Cranial-enhanced magnetic resonance imaging (MRI) revealed abnormal meningeal enhancement. A lumbar puncture examination revealed that numerous atypical cells were present. Carcinomatous meningitis complicated by SIADH was diagnosed and treatment for hyponatremia and whole brain radiotherapy were performed; however, she died two weeks after the radiation therapy. Clinicians should consider carcinomatous meningitis when there are findings of SIADH.

Systemic lymphadenectomy cannot be recommended for low-risk corpus cancer.

Objective. The objective of this study is to ascertain whether omission of lymphadenectomy could be possible when uterine corpus cancer is considered low-risk based on intraoperative pathologic indicators. Patient and Methods. Between 1998 and 2007, a total of 83 patients with low risk corpus cancer (endometrioid type, grade 1 or 2, myometrial invasion <==50%, and no intraoperative evidence of macroscopic extrauterine spread, including pelvic and paraaortic lymph node swelling and adnexal metastasis) underwent the total abdominal hysterectomy and bilateral salpingo-oophorectomy without lymphadenectomy. A retrospective review of the medical records was performed, and the disease-free survival (DFS), overall survival (OS), peri- and postoperative morbidities and complications were evaluated. Results. The 5-year DFS rates and the 5-year OS rates were 97.6% and 98.8%, respectively. No patient presented postoperative leg lymphedema and deep venous thrombosis. Conclusion. Omission of lymphadenectomy did not worsen the DFS or OS. The present findings suggest that systemic lymphadenectomy could be omitted in low-risk endometrial carcinoma.

A role for IL-17 in induction of an inflammation at the fetomaternal interface in preterm labour.

Chorioamnionitis (CAM) is a major cause of preterm delivery. Inflammatory cytokines and chemokines play important roles in the pathogenesis of preterm delivery. Interleukin (IL)-17 is a key cytokine which induces inflammation and is critical to host defense. In this study, we examined the role of IL-17 in the pathogenesis of preterm delivery. The levels of cytokines including IL-17, IL-8 and tumor necrosis factor (TNF) alpha were measured by ELISA in amniotic fluid from 154 cases of preterm labor. Flow cytometry and immunohistochemical staining were performed to determine the distribution of IL-17-producing cells. IL-8 secretion was evaluated in primary cultured human amniotic mesenchymal (HAM) cells and human amniotic epithelial (HAE) cells stimulated with IL-17, TNFalpha or IL-1beta. We also studied the signaling pathway of IL-17 and TNFalpha in HAM cells. Levels of inflammatory cytokines in amniotic fluid were higher in preterm delivery cases than in term delivery cases. Furthermore, IL-8, IL-17 and TNFalpha levels were significantly higher in the preterm cases with CAM stage II or III than those without CAM. Flow cytometry and immunohistochemical staining revealed that CD3(+)CD4(+) T cells were the main source of IL-17 in the chorioamniotic membrane. Interestingly, TNFalpha-induced IL-8 secretion was enhanced by IL-17 in a dose-dependent manner in HAM cells. The IKK inhibitor BMS-345541 and mitogen-activated protein kinase (MAPK) inhibitors p38, JNK and p42/44 (ERK1/2 pathway) reduced IL-8 secretion by IL-17-stimulated and TNFalpha-stimulated HAM cells. These results indicate that IL-17, produced by T cells, promotes inflammation at the fetomaternal interface in preterm delivery.

Herbal medicine Shakuyaku-kanzo-to reduces paclitaxel-induced painful peripheral neuropathy in mice.

OBJECTIVES: Paclitaxel is widely used in cancer chemotherapy for the treatment of solid tumors such as breast, ovarian and lung cancer. However, it sometimes induces moderate to severe muscle pain, and impairs the patients' quality of life. An appropriate method for relieving this pain is not well established. Shakuyaku-kanzo-to, a herbal medicine, is known to relieve menstrual pain, muscle spasm, and muscle pain, and its effectiveness is expected. To ascertain the effectiveness of Shakuyaku-kanzo-to on paclitaxel-induced pain, we investigated the effects of Shakuyaku-kanzo-to and its constituent herbal medicines in a mouse model. METHODS: Seven-week-old male ddY mice were used. To make a mouse model of paclitaxel-induced pain, different single, intraperitoneally injected doses of this drug were tested in various groups of mice, and the optimal dose was determined. To estimate the effects of Shakuyaku-kanzo-to, the constituent herbal medicines Shakuyaku and Kanzo, and loxoprofen sodium as a non-steroidal anti-inflammatory drug on paclitaxel-induced pain, mechanical allodynia and hyperalgesia of the hind paw were assessed. RESULTS: Paclitaxel administered at a dose of 10mg/kg or more produced allodynia and hyperalgesia; the time courses were similar to those of pain after paclitaxel administration in cancer patients. Shakuyaku-kanzo-to significantly relieved the allodynia and hyperalgesia induced by paclitaxel (10mg/kg). Shakuyaku and Kanzo inhibited the allodynia and hyperalgesia to some extent, but not significantly, while loxoprofen sodium was without effects. CONCLUSIONS: A single administration of paclitaxel (10mg/kg) produced allodynia and hyperalgesia in mice, suggesting that it could be used as an animal model resembling the painful conditions observed in humans medicated with this drug. Using this model, Shakuyaku-kanzo-to was shown to relieve paclitaxel-induced painful peripheral neuropathy.

Expression of indoleamine 2, 3-dioxygenase and the recruitment of Foxp3-expressing regulatory T cells in the development and progression of uterine cervical cancer.

Foxp3(+) CD4(+)CD25(+) regulatory T (Treg) cells and immunoregulatory enzyme indoleamine 2,3-dioxygenase (IDO) play an important role in immunoregulation. Accumulating evidence shows that IDO and Treg cells have potent regulatory properties for immune escape in cancer. To evaluate the expression of IDO and the localization of Foxp3(+) Treg cells in the development and progression of uterine cervical cancer, IDO expression and Foxp3(+) Treg cells in the primary and metastatic lesions were studied using immunohistochemistry. IDO expression in tumor cells appeared in cervical intraepithelial neoplasia (CIN)-3 of the uterine cervix and marked expression in microinvasive cancer cells was observed. Interestingly, IDO expression in invasive cancer was confined to the cancer cells at the invasive front. Moreover, antigen-presenting cells (APC) at the invasive front in primary and metastatic lesions were also expressing IDO. Stromal Foxp3(+) Treg cells appeared in CIN-3 and increased in microinvasive and invasive cancer. Intraepithelial Foxp3(+) Treg cells were restricted within microinvasive and invasive cancer. No significant differences in the proportion of Foxp3(+)/CD4(+) in the stroma or epithelium, or between non-metastatic and metastatic invasive cancers, were observed in primary lesions of cervical cancer, while there was a significant increase (P < 0.005) in the proportion of Foxp3(+)/CD4(+) in metastatic lymph nodes compared with non-metastatic lymph nodes. Some of the Foxp3(+) Treg cells in metastatic lymph nodes contacted the IDO(+) APC. IDO expression at the invasive front of cancer cells and APC, and the localization of Foxp3(+) Treg cells in front of cancer tissues, may create a network between IDO and Treg for the induction of immune escape.

Paclitaxel/carboplatin versus cyclophosphamide/adriamycin/cisplatin as postoperative adjuvant chemotherapy for advanced endometrial adenocarcinoma.

AIM: There is no standard chemotherapy regimen for patients with advanced endometrial adenocarcinoma. In our hospital, a cyclophosphamide/adriamycin/cisplatin (CAP) regimen was commonly used as adjuvant chemotherapy. However, since October 1999 a paclitaxel/carboplatin regimen has been substituted for CAP. To evaluate the antitumor activity and toxic effects of those regimens, we retrospectively reviewed cases that were treated in our hospital. METHODS: Twenty-eight patients who underwent surgery and had histologically confirmed advanced endometrial adenocarcinoma, International Federation of Gynecology and Obstetrics stage III/IV, received combination chemotherapy. Treatment consisted of cisplatin, adriamycin and cyclophosphamide (CAP group, n = 16), or paclitaxel and carboplatin (paclitaxel/carboplatin group, n = 12). The response rate (RR), progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. RESULTS: In the CAP group, complete response (CR) was observed in six patients and partial response (PR) in three, for an RR of 64.3%. In the paclitaxel/carboplatin group, CR was observed in five and PR in two, for an RR of 77.8%. The 3-year PFS and OS rates were 50.0% and 75.0% in the paclitaxel/carboplatin group, and 37.5% and 50.0% in the CAP group, respectively, and there was no significant difference between the two groups. National Cancer Institute Common Toxicity Criteria grade 3-4 thrombocytopenia and gastrointestinal toxicities occurred significantly less frequently in the paclitaxel/carboplatin group (0% and 16.7%) than in the CAP group (31.3% and 68.8%) (P = 0.0389 and P = 0.0062). CONCLUSIONS: We conclude that paclitaxel/carboplatin is a promising regimen which could be substituted for CAP, with major activity and a highly acceptable toxicity profile for the treatment of advanced endometrial adenocarcinomas.

Cerebral metastasis from a primary adenocarcinoma of the fallopian tube.

BACKGROUND: Primary adenocarcinoma of the fallopian tube is a rare disease, and cerebral metastasis from this tumor is an extremely rare event. CASE: A 61-year-old female, who had been thought to be in a disease-free state after the initial treatment for stage IIIc fallopian tube adenocarcinoma, presented with severe headache, dizziness, nausea, and vomiting. Brain CT and MRI revealed solitary metastatic lesion in the cerebrum, which was the only site of recurrence. It was removed surgically, followed by platinum-based combination chemotherapy, and a clinical remission was achieved for 36 months. CONCLUSION: Attention should be paid to the possibility of cerebral metastasis in patients who develop neurogenic signs and symptoms. Prolonged survival could be achieved with aggressive treatment containing surgical debulking and adjuvant chemotherapy for solitary cerebral metastasis.

Cisplatin enhances the p53-independent apoptosis induced by a topoisomerase I inhibitor (CPT-11) in the lens epithelial tumors in transgenic mice.

We reported that CPT-11 could induce apoptosis in mouse lens epithelial tumors when it was administered to pregnant alphaT3 mice which developed epithelial cell carcinoma in situ in the lens in the perinatal period. p53-deficient alphaT3 mice were generated to analyze the influence of p53 status on tumor cells under combined chemotherapy. On the 16-18th gestational day, alphaT3 received a single i.p. administration of both CPT-11 and Cisplatin, and fetal lens epithelial tumors were examined two days later. Apoptosis in the p53-wild-type alphaT3 tumors was observed in a Cisplatin dose-dependent manner. In addition, it was found that Cisplatin augmented CPT-11-induced p53-independent apoptosis in p53-deficient alphaT3 mice.

Mirimostim (macrophage colony-stimulating factor; M-CSF) improves chemotherapy-induced impaired natural killer cell activity, Th1/Th2 balance, and granulocyte function.

The purpose of this study was to clarify the effects of mirimostim (macrophage colony-stimulating factor; M-CSF) on immunological functions after chemotherapy. The percentage of natural killer (NK) cells in peripheral blood mononuclear cells (PBMCs), NK cell activity, T-helper cell 1/T-helper cell 2 (Th1/Th2) ratio, and superoxide anion production by granulocytes (granulocyte function) were measured as immunological parameters before and after chemotherapy in 44 patients with primary ovarian cancer who received at least three consecutive courses of postoperative chemotherapy. Patients were observed during the first course of chemotherapy, and 39 patients who presented grade III or IV neutropenia were entered into this study and randomly allocated to an M-CSF-administered group (group 1; 19 patients) and a non-M-CSF-administered group (group 2; 20 patients) for the second course. For the third course, a crossover trial was conducted. In the observation period, chemotherapy significantly impaired the immunological parameters. In particular, those parameters were significantly decreased at day 14 compared to the level before chemotherapy. The values of the parameters of group 1 were significantly higher than those of group 2. In the course of chemotherapy during which M-CSF was administered, 19 of the 39 patients presented grade IV neutropenia, and received granulocyte colony-stimulating factor (G-CSF) between days 7 and 14. We compared the changes of those immunological parameters in the M-CSF alone group and the M-CSF + G-CSF group, and found that the concomitant use of G-CSF did not further improve the parameters. These results indicate that chemotherapy markedly impaired the immunological functions, and that the administration of M-CSF significantly improved the impaired immunological functions.

HER2 is frequently over-expressed in ovarian clear cell adenocarcinoma: possible novel treatment modality using recombinant monoclonal antibody against HER2, trastuzumab.

Ovarian clear cell adenocarcinoma (CCA) is generally chemo-resistant. Recently the poor prognosis and resistance to chemotherapeutic agents of HER2/neu over-expressing tumors have become clear. Thus, we investigated the expression level of HER2 in surgically resected CCA and ovarian serous adenocarcinoma, endometrioid adenocarcinoma, and mucinous adenocarcinoma specimens, as well as CCA cell lines, by an immunohistochemical method. HER2 was over-expressed in 42.9% of CCA (P=0.026, vs. ovarian serous adenocarcinoma), 20.8% of ovarian serous adenocarcinoma, 23.1% of ovarian endometrioid adenocarcinoma, and 30.0% of mucinous adenocarcinoma specimens. Three CCA cell lines, RMG-1, HAC-II and KK were also positively stained for HER2. A flow-cytometric study of HER2 revealed 7.2-, 6.4- and 4.5-fold greater expression of HER2 than that of normal mammary gland, respectively. Trastuzumab, a humanized recombinant monoclonal antibody against HER2 significantly and dose-dependently reduced the growth of CCA cell lines in vitro. The extent of the inhibitory effect of trastuzumab was dependent on the expression level of HER2. Trastuzumab also dose-dependently inhibited the growth of xenografted RMG-1 tumor. The survival period of trastuzumab-treated mice was longer than that of the control group. From these findings, trastuzumab appears to be a candidate as a treatment modality for HER2 over-expressing ovarian CCA.