生水 真紀夫

BACKGROUND: Ovarian carcinomas sometimes grow in the pelvic cavity, adhering firmly to the pelvic sidewall. These cases are often considered as inoperable or result in the incomplete resection because the tumors are not mobile. We performed en bloc resection of the tumors along with the entire internal iliac vessel system to achieve complete resection. METHODS: Twenty of 237 consecutive patients with FIGO stage II-IV ovarian, fallopian tubal, or primary peritoneal carcinoma who underwent cytoreductive surgery at Chiba University Hospital between January 2008 and December 2016 had locally advanced tumors adhered firmly to the pelvic sidewall. We performed isolation of the tumors from the pelvic sidewall using the following procedure: the trunk of internal iliac vessels, the obturator vessels, the inferior gluteal and internal pudendal vessels were isolated and divided. The tumor together with the entire internal iliac vessel system was isolated from the sacral nerve plexus and piriform muscle. We examined the surgical outcomes, perioperative complications, and prognosis for the patients who underwent this procedure. RESULTS: All patients successfully underwent complete resection, resulting in no gross residual disease in the pelvic cavity. There was no mortality within 90 days postoperatively. Two patients had Grade IIIb complications, comprising wound dehiscence and vesicovaginal fistula. Recurrence occurred in nine of the patients. However, no recurrence was observed in the pelvic sidewall. The median progression-free survival was 43 months. CONCLUSIONS: Removal of the entire internal iliac vessel system is feasible for the complete resection of locally advanced ovarian carcinomas adhered firmly to the pelvic sidewall.

PURPOSE: This study evaluated the safety and efficacy of carbon-ion radiation therapy (C-ion RT) with concurrent chemotherapy for locally advanced uterine cervical squamous cell carcinoma in a phase 1/2 clinical trial. METHODS AND MATERIALS: Twenty-two patients were treated with C-ion RT with concurrent weekly cisplatin at a dose of 40 mg/m2. The phase 1 component evaluated the safety of 72.0 Gy (relative biological effectiveness) of C-ion RT with concurrent chemotherapy. In the phase 2 component, the safety and efficacy of C-ion RT with concurrent chemotherapy were assessed using the dose determined in phase 1. RESULTS: The median follow-up period was 32 months, and the median tumor size was 71 mm (range, 51-150 mm). No patient had dose-limiting toxicities in the phase 1 component; the recommended dose was determined to be 72.0 Gy (relative biological effectiveness) with 40 mg/m2 of cisplatin. In the phase 2 component, 2 patients developed grade 3 gastrointestinal tract toxicities. In patients treated with the recommended dose, the 2-year local control (LC), LC including salvage therapy, and overall survival rates were 67%, 81%, and 82%, respectively. The 2-year LC and overall survival rates for patients with tumor sizes ≤7.1 cm were 92% and 100%, respectively; for those with tumor sizes >7.1 cm they were 33% and 60%, respectively. CONCLUSIONS: C-ion RT with concurrent weekly cisplatin was tolerated by patients with locally advanced uterine cervical squamous cell carcinoma. Outcomes were good in patients with tumor sizes ≤7.1 cm but not in those with larger tumors. The results of the present study should be validated with larger multi-institutional prospective studies. Further study is needed, and perhaps incorporating carbon ion external beam radiation with brachytherapy will further reduce the risk of central recurrence.

Surgical resection is considered a standard therapy for malignant melanoma (MM). However, it has not yet been established as an optimal treatment strategy for gynecological MMs, particularly owing to their very low incidence rates. We retrospectively analyzed clinical outcomes of carbon-ion radiotherapy (C-ion RT) for gynecological MMs. The eligibility criterion was the presence of histologically confirmed gynecological MM. Patients with pelvic or inguinal lymph node metastases were included, while those with distant metastases were excluded. The pelvic and inguinal lymph node regions were irradiated with up to 36 gray relative biological effectiveness (Gy (RBE)) followed by a gross tumor volume boost of up to 57.6 Gy (RBE) or 64 Gy (RBE) in 16 fractions over 4 weeks. Thirty-seven patients (median age: 71 years) were examined. In total, 22 patients had vaginal tumors, 12 had vulval tumors, and 3 had cervical uterine tumors. The median follow-up periods were 23 months (range: 5-103 months) for all patients and 53 months (range: 16-103 months) for survivors. Thirty of 37 patients (81%) achieved complete tumor disappearance. The 2-year local control, overall survival, and progression-free survival rates were 71%, 53%, and 29%, respectively. C-ion RT may be a definitive treatment option for patients with gynecological MM.

OBJECTIVE: To compare the efficacy and safety of blastocyst transfer derived from small follicles (SF; ≤10 mm) and large follicles (LF; ≥11 mm). DESIGN: Retrospective cohort study. SETTING: Private clinic. PATIENT(S): Patients (n = 1,072) 30-40 years old who underwent blastocyst transfer (BT; n = 1,247) between January 2012 and December 2014. INTERVENTION(S): Oocytes retrieved during a modified natural cycle from both LF and SF were fertilized by a conventional method or intracytoplasmic sperm injection. The blastocysts were frozen, thawed, and transferred one by one in the following spontaneous ovulatory cycles or hormone replacement cycles. MAIN OUTCOME MEASURE(S): BT resulted in live births and major congenital anomalies. RESULT(S): SF-derived BTs (n = 597) yielded 55 chemical abortions (9.2%), 73 clinical abortions (12.2%), and 261 live births (43.8%), whereas LF-derived BTs (n = 650) yielded 71 chemical abortions (10.9%), 73 clinical abortions (11.2%), and 311 live births (47.9%). These incidences were not statistically different between SF- and LF-derived BTs. The incidence of abnormal karyotypes was also not statistically different between SF- and LF-derived spontaneous abortions (71% [39/55] vs. 72% [40/55], respectively). The incidence of major congenital anomalies in neonates did not differ between SF- and LF-derived pregnancies (1.5% and 1.3%, respectively; relative risk = 1.10, 95% confidence interval [0.55-3.21]). CONCLUSION(S): SF-derived BT is as efficacious and safe as LF-derived BT.

Uterine leiomyoma is characterized by abundant extracellular matrix and broad avascular areas, both constantly resulting in hypoxia, suggesting some hypoxia-induced response function. Here, we examined whether hypoxia-inducible factor 1α (HIF-1α)- mediated hypoxic response function in uterine leiomyoma. Immunoblotting detected higher basal HIF-1α protein expression in nuclear extracts from uterine leiomyoma tissues than in those from the adjacent myometrium ( P = .0011). Immunohistochemical analysis revealed the presence of HIF-1α-positive cellular components in both leiomyoma and surrounding myometrial tissues. Hypoxia decreased HIF-1α messenger RNA (mRNA), but increased HIF-1α protein in primary culture leiomyoma smooth muscle cells, and caused translocation of HIF-1α from the cytoplasm to the nucleus. Hypoxia upregulated mRNAs of 6 potential HIF-responsive genes ( ALDOA, ENO1, LDHA, VEGFA, PFKFB3, and SLC2A1). Chromatin immunoprecipitation quantitative polymerase chain reaction revealed that hypoxia significantly increased recruitment of HIF-1α binding to putative HIF-responsive elements in the HIF-responsive genes, suggesting that the HIF transcriptional complex initiates hypoxia-induced transcription of HIF-responsive genes. These results demonstrated a HIF-1α-mediated hypoxic response in uterine leiomyoma.

Aim To provide information including the trend of gynecological malignancies in Japan, we hereby present the Annual Patient Report for 2015 and the Annual Treatment Report for 2010 on the outcomes of patients who started treatment in 2010. Methods The Japan Society of Obstetrics and Gynecology maintains an annual tumor registry where information on gynecological malignancies from various participating institutions is gathered. The data of patients whose treatment was initiated in 2015 were analyzed retrospectively. Survival of the patients who started treatment in 2010 was analyzed by using the Kaplan-Meier, log-rank and Wilcoxson tests. Results Treatment was initiated in 2015 for 7527 patients with cervical cancer, 10 119 with endometrial cancer, 6424 with ovarian cancer and 2181 with ovarian borderline tumors. This clinicopathological information was summarized as the Patient Annual Report. Prognoses were analyzed across 4309 patients with cervical cancer, 5054 with endometrial cancer and 3423 with ovarian cancer, whose treatment was initiated in 2010. The 5-year survival rates of the patients with cervical cancer were 92.1%, 74.2%, 52.0%, and 29.8% for stages I, II, III, and IV, respectively. The 5-year survival rates for the patients with endometrial cancer were 94.3%, 88.8%, 74.0% and 26.6% for stages I, II, III and IV, respectively. The 5-year survival rates for the patients with ovarian cancer (surface epithelial-stromal tumors) were 88.5%, 80.1%, 46.3% and 36.2% for stages I, II, III and IV, respectively. Conclusion The annual tumor report is an important survey that provides knowledge on gynecological malignancy trends in Japan.

STUDY OBJECTIVE: To evaluate the efficacy of a nonsurgical treatment for cervical pregnancy (CP) and cesarean section scar pregnancy (CSP). DESIGN: Retrospective clinical study (Canadian Task Force classification III). SETTING: Private assisted reproductive technology practice. PATIENTS: Nineteen women with CP (n = 16) or CSP (n = 3), including 6 patients with positive fetal heartbeat. INTERVENTION: Transvaginal local injection of absolute ethanol (AE) into the hyperechoic ring (lacunar space) around the gestational sac under ultrasound guidance. MEASUREMENTS AND MAIN RESULTS: Serum beta-human chorionic gonadotropin (β-hCG) was measured at frequent intervals, and ultrasound and/or magnetic resonance imaging was used to observe the gestational sac. In 9 patients, the serum β-hCG level was effectively reduced with a single AE injection at 2 hours. In the remaining 10 patients, the level decreased but then increased in 4 and slowly decreased in the other 6; all of these 10 patients required 2 to 5 repeat AE injections. In all patients, serum β-hCG level was reduced by 50% within 3 days and decreased to <10% of the initial level within 14 days. In 18 patients (95%), the level was decreased to 1.0 mIU/mL within 40 days. Seven patients were treated on an outpatient basis. Twelve patients received no anesthesia. Five patients subsequently became pregnant, and each had a live birth. There was no recurrent CP or CSP. The procedure was successful in all 19 patients. CONCLUSION: This procedure is an effective treatment for CP or CSP that could be used in place of conventional surgical interventions and medical treatment using MTX.

Uterine torsion of a nongravid uterus is rare, and proper diagnosis is challenging. Herein, we report a case of torsion of a large myomatous uterus in an 86-year-old woman who was presented with progressive renal failure and paralytic ileus. She was presented with abdominal discomfort, loss of appetite, and oliguria. A large myomatous uterus with broad calcification was identified when she underwent surgery to repair an umbilical hernia one year before the symptoms developed. Computed tomography revealed that one year later, the myomatous uterus significantly increased in size and the calcified lesion of the fibroid was largely displaced. She was also presented with paralytic ileus, and her general condition progressively worsened. Her serum creatinine levels were increased (3.5 mg/dL) and hemoglobin levels were low (8.5 g/dL). Emergency laparotomy revealed that the uterus was rotated 360 degrees clockwise at the level of the isthmus. The uterus was discolored, appearing dark red, and accompanied by broad congestion, and the cervix was elongated. The patient's renal function and ileus recovered after a hysterectomy. In conclusion, torsion of a large myomatous uterus could become life-threatening in an oldest-old woman, and early release of the torsion is necessary to avoid serious complications.

Background: Pregnant and postpartum women with psychosocial problems are prone to face limited or absent perinatal functional support from biological grandmothers due to familial dysfunction. The study aimed to investigate whether the involvement and presence of biological maternal grandmothers providing practical support for their pre/postnatal daughters (ie, pregnant women) during the perinatal period may influence the number of support services provided by multidisciplinary agencies, including child consultation centers and municipal offices. Participants and methods: This is a retrospective cohort study based on the medical records of all pregnant women with psychosocial problems that visited, gave birth, and received intervention from the hospital-based child protection unit at the Chiba University Hospital between February 2018 to March 2019. The primary outcome was to identify whether there was a difference in the number of multidisciplinary agencies providing perinatal support between pregnant women with and without the presence of functional support from biological maternal grandmothers during the perinatal period. Results: We identified 114 pregnant and postpartum women with psychosocial problems. Seventy-six of these participants (66.7%) had functional support from their biological maternal grandmothers during the perinatal period, and 38 participants (33.3%) did not. The number of agencies involved with participants who lacked functional support was significantly higher than participants with functional support (t(55.14) = 2.98, p < 0.01). This finding was consistent among pregnant and postpartum primipara participants (n = 70) (t(68) = 3.87, p < 0.001), but not multipara (n = 44). Conclusion: The findings indicate that the presence and functional support of biological maternal grandmothers influence the support that is needed from multidisciplinary perinatal support systems by pregnant and postpartum women with psychosocial problems. Primipara mothers without support from their own mothers may need greater multidisciplinary support.

A loss-of-function variant in the gene encoding the prolactin receptor ( PRLR) was reported previously in a woman with persistent postpartum galactorrhea; however, this paradoxical phenotype is not completely understood. Here we describe a 35-year-old woman who presented with idiopathic hyperprolactinemia that was associated with a complete lack of lactation after each of her two deliveries. She is a compound heterozygote for loss-of-function variants of PRLR. Her unaffected parents are heterozygotes. These findings are consistent with previous work showing that mice deficient in functional Prlr do not lactate.

OBJECTIVE: Advanced ovarian cancer commonly disseminates to the diaphragm. A complete removal of a bulky diaphragmatic disease is sometimes difficult. We present the surgical technique that we used for resecting a large nodular and disseminated subphrenic tumor that occupied the subphrenic space using liver mobilization and the Pringle maneuver. METHODS: The patient was a 78-year-old woman with FIGO IIIC left ovarian carcinosarcoma. She had a metastatic subphrenic tumor measuring 12 cm in diameter. The subphrenic tumor resection was performed as a part of cytoreductive surgery. Owing to the adherence between the right diaphragm and the liver, the diaphragm was resected in full thickness. The liver was mobilized by keeping the resected part of the diaphragm attached to the liver. The subphrenic tumor and the attached diaphragm were resected en bloc by excising the liver which was adjacent to the tumor. During the resection, the hepatoduodenal ligament was clamped with a Satinsky clamp (Pringle maneuver) to reduce blood loss from the liver. The diaphragmatic defect was closed with permanent mesh. RESULTS: We achieved complete cytoreduction with no residual tumor without ICU admission. No severe intraoperative or postoperative complications were observed. The patient was discharged on postoperative day 22 and started adjuvant chemotherapy on postoperative day 27. The histological examination revealed the carcinosarcoma in the diaphragmatic peritoneum, although the carcinosarcoma did not infiltrate the adjacent liver. CONCLUSION: Resection of a metastatic bulky subphrenic tumor using liver mobilization and the Pringle maneuver is a feasible technique for the treatment of advanced ovarian cancer.

OBJECTIVE: Ovarian carcinomas sometimes metastasize to the cardiophrenic lymph node. We present a surgical technique for metastatic cardiophrenic lymph node resection following full-thickness resection of the right diaphragm. METHODS: A 51-year-old woman presented with ovarian carcinoma and cardiophrenic lymph node metastasis with peritoneal dissemination. The surgical procedure for metastatic cardiophrenic lymph node resection following full-thickness resection of the right diaphragm was as follows. (1) Stripping of the right diaphragm peritoneum was started from the ventral side toward the dorsal side. At the area where stripping was ceased due to tendon or muscle invasion, the thoracic cavity was opened. Full-thickness resection of the diaphragm was proceeded in the left-right direction. (2) The bare area was exposed. Full-thickness resection of the diaphragm was continued along the bare area. (3) After the right diaphragm resection was completed, the remaining right diaphragm was cut toward the cranial side. The metastatic cardiophrenic lymph node was grasped and pulled by forceps, and subsequently resected using a vessel-sealing device. (4) After thoracic chest tube placement, the diaphragmatic defect was closed by continuous non-absorbable sutures. RESULTS: We successfully achieved metastatic cardiophrenic lymph node resection following full-thickness resection of the right diaphragm without intra- or postoperative complications. CONCLUSION: Metastatic cardiophrenic lymph node resection is a simple procedure for gynecologic surgeons who are able to perform full-thickness resection of the diaphragm.

＜文献概要＞胞状奇胎患者の多くは挙児希望を持つ。2010〜2016年に当院で管理した胞状奇胎自然寛解例309例を対象に後方視的調査を行い,胞状奇胎自然寛解後の妊娠予後を検討した。結果は,181例(58.6%)で延べ233妊娠が確認され,生産率,早産率,流産率は一般集団と同等であった。胞状奇胎反復率は2.1%(5/233)であった。自然寛解後に続発症を発症した症例はなかった。また,当院の2000〜2009年のデータと比較したところ,患者平均年齢の有意な上昇(32.9歳 vs 31.0歳)を認めたが,胞状奇胎後妊娠率(58.6% vs 52.0%),生児獲得率(45.6% vs 44.9%)は変化がなかった。

We herein reported a rare case of an occult fallopian tube carcinoma first detected from the diaphragm metastasis. An 83-year-old woman who had a 30-mm tumor on the right diaphragm underwent radical resection. Pathologically, the tumor was diagnosed as a high-grade serous adenocarcinoma, suggesting metastasis from the pelvic visceral carcinoma. Although the primary site could not be detected by imaging examinations, laparoscopy revealed multiple peritoneal disseminations; therefore, total hysterectomy was performed. Finally, microscopic tumor invasion into the right fimbriae of the fallopian tube was found. A precise and detailed pathological and immunohistochemical examinations of the resected metastatic diaphragm tumor helped us obtain a proper diagnosis of the primary lesion and treat the patient appropriately. Since it is difficult to diagnose diaphragm tumors before surgery based on the anatomy, surgical options have played an important role in their treatment and diagnosis clinically.

＜文献概要＞胞状奇胎患者の多くは挙児希望を持つ。2010〜2016年に当院で管理した胞状奇胎自然寛解例309例を対象に後方視的調査を行い,胞状奇胎自然寛解後の妊娠予後を検討した。結果は,181例(58.6%)で延べ233妊娠が確認され,生産率,早産率,流産率は一般集団と同等であった。胞状奇胎反復率は2.1%(5/233)であった。自然寛解後に続発症を発症した症例はなかった。また,当院の2000〜2009年のデータと比較したところ,患者平均年齢の有意な上昇(32.9歳 vs 31.0歳)を認めたが,胞状奇胎後妊娠率(58.6% vs 52.0%),生児獲得率(45.6% vs 44.9%)は変化がなかった。

Brain damage caused by hypoxic ischemic insult during the perinatal period causes hypoxic ischemic encephalopathies (HIEs). Therapeutic hypothermia is indicated for HIE, but because the therapeutic burden is large for its limited therapeutic effectiveness, another strategy is needed. Progesterone (P4) plays a neuroprotective role through the actions of its metabolite, allopregnanolone (Allo), on P4 receptor, g-aminobutyric acid type A receptors or both. We examined the therapeutic potential of P4 using a newborn ratmodel ofHIE. Fetal rats were exposed to transient ischemic hypoxia by 30-minute bilateral uterine artery clamping on gestational day 18. After spontaneous birth, newborn pups were subcutaneously injected with P4 (0.10 or 0.01 mg), medroxyprogesterone acetate (MPA; 0.12 mg), or Allo (0.10 mg) through postnatal days (PDs) 1 to 9. Brain damage in the rats was assessed using the rotarod test at PD50. The HIE insult reduced the rats-ability in the rotarod task, whichwas completely reversed by P4 and Allo, but not by MPA. Histological examination revealed that the HIE insult decreased neuronal (the cortex and the hippocampal CA1 region) and oligodendroglial cell density (the corpus callosum) through PD0 to PD50. The axon fiber density and myelin sheath thickness in the corpus callosum were also reduced at PD50. The time-course study revealed that P4 restored oligodendroglial cells by PD5, which was followed by neuroprotective action of P4 that lasted long over the injection period. These results suggest that P4 protects the neonatal brain from HIE insult via restoration of oligodendroglial cells.