Perioperative Serum Creatinine Change and Delayed Urologic Complications Following Total Laparoscopic Hysterectomy for Benign Indications.

Objectives: The objective of the study was to investigate the association between perioperative serum creatinine change and delayed urologic complications following total laparoscopic hysterectomy (TLH) for benign indications. Materials and Methods: A total of 510 cases (503 cases without delayed urologic injuries and 7 cases with delayed urologic injuries) in which TLH was performed for benign indications were retrospectively reviewed. The patient characteristics and surgical outcomes were compared between patients with and without delayed urologic injuries. Laboratory markers (serum creatinine level at the preoperative and postoperative periods, white blood cell [WBC] ratio, and C-reactive protein [CRP] ratio) were analyzed to evaluate the diagnostic value of these laboratory markers. Results: There were no statistically significant differences in age, parity, body mass index, the presence of diabetes mellitus, preoperative GnRH agonist use, previous history of abdominal surgery or the performance of adnexal surgery, ASRM score, the presence of cul-de-sac obliteration, operative time, blood loss or weight of the resected specimens between the two groups. The proportions of patients who showed an elevated creatinine level on postoperative day 1 was significantly higher in the delayed urologic injury group (9.9% vs. 57%, P < 0.001). The combination of the three laboratory markers yielded an area under the ROC curve value of 0.75 (95% confidence interval, 0.491-1) in the detection of delayed urologic injuries. Conclusion: A change in the serum creatine level over baseline after surgery may indicate the possibility of urologic injuries. The combination of creatinine change and other factors, such as WBC or CRP would be helpful for detecting urologic complications after TLH.

Oncologic outcomes in elderly patients who underwent hysterectomy for endometrial cancer: a multi-institutional survey in Kinki District, Japan.

BACKGROUND: The goal of this study is to assess the oncologic outcomes of elderly patients who underwent hysterectomy for endometrial cancer across three variables: hysterectomy approach, lymph node resection, and adjuvant therapy. METHODS: Hospital records of patients aged ≥ 70 years who underwent hysterectomy for endometrial cancer were obtained from 19 institutions. Patients were categorized into three risk groups: low, intermediate, and high. In each group, disease-free survival and overall survival were compared according to hysterectomy approach, lymph node resection, and adjuvant therapy using Kaplan-Meier method. Cox regression analysis with a 95% confidence interval was performed to estimate relative risk (RR) of death. RESULTS: A total of 1246 patients were included. In the low-risk group, the adjusted RR for death for minimally invasive surgery (MIS) versus laparotomy and lymph node resection versus no lymph node resection were 0.64 (0.24-1.72) and 0.52 (0.24-1.12), respectively. In the intermediate-risk group, the adjusted RR for death for MIS versus laparotomy, lymph node resection versus no lymph node resection, and adjuvant therapy versus no adjuvant therapy were 0.80 (0.36-1.77), 0.60 (0.37-0.98), and 0.89 (0.55-1.46), respectively. In the high-risk group, the adjusted RRs for death for lymph node resection versus no lymph node resection and adjuvant therapy versus no adjuvant therapy were 0.56 (0.37-0.86) and 0.60 (0.38-0.96), respectively. CONCLUSIONS: MIS is not inferior to laparotomy in uterine-confined diseases. Lymph node resection improved the outcome for all disease stages and histological types. In contrast, adjuvant therapy improved the outcomes only in high-risk patients.

Remote reprogramming of hepatic circadian transcriptome by breast cancer.

Cancers adversely affect organismal physiology. To date, the genes within a patient responsible for systemically spreading cancer-induced physiological disruption remain elusive. To identify host genes responsible for transmitting disruptive, cancer-driven signals, we thoroughly analyzed the transcriptome of a suite of host organs from mice bearing 4T1 breast cancer, and discovered complexly rewired patterns of circadian gene expression in the liver. Our data revealed that 7 core clock transcription factors, represented by Rev-erba and Rorg, exhibited abnormal daily expression rhythm in the liver of 4T1-bearing mice. Accordingly, expression patterns of specific set of downstream circadian genes were compromised. Osgin1, a marker for oxidative stress, was an example. Specific downstream genes, including E2f8, a transcriptional repressor that controls cellular polyploidy, displayed a striking pattern of disruption, "day-night reversal." Meanwhile, we found that the liver of 4T1-bearing mice suffered from increased oxidative stress. The tetraploid hepatocytes population was concomitantly increased in 4T1-bearing mice, which has not been previously appreciated as a cancer-induced phenotype. In summary, the current study provides a comprehensive characterization of the 4T1-affected hepatic circadian transcriptome that possibly underlies cancer-induced physiological alteration in the liver.

Rabies virus-mediated oligodendrocyte labeling reveals a single oligodendrocyte myelinates axons from distinct brain regions.

Oligodendrocytes myelinate neuronal axons during development and increase conduction velocity of neuronal impulses in the central nervous system. Neuronal axons extend from multiple brain regions and pass through the white matter; however, whether oligodendrocytes ensheath a particular set of axons or do so randomly within the mammalian brain remains unclear. We developed a novel method to visualize individual oligodendrocytes and axon derived from a particular brain region in mouse white matter using a combinational injection of attenuated rabies virus and adeno-associated virus. Using this method, we found that some populations of oligodendrocytes in the corpus callosum predominantly ensheathed axons derived from motor cortex or sensory cortex, while others ensheathed axons from both brain regions, suggesting heterogeneity in preference of myelination toward a particular subtype of neurons. Moreover, our newly established method is a versatile tool for analyzing precise morphology of each oligodendrocyte in animal models for demyelinating disorders and addressing the role of oligodendrocyte in higher brain functions. GLIA 2016. GLIA 2017;65:93-105.

Post-partum hypoglycemia and hypothermia as first manifestations of lymphocytic adenohypophysitis: A case report.

Lymphocytic adenohypophysitis is a very rare autoimmune disease characterized by an anterior pituitary infiltration of lymphocytes that cause various symptoms, such as headache, visual disturbance, and hypopituitarism. Lymphocytic adenohypophysitis is more common in women and has a remarkable association with the perinatal period. Recently, we experienced a case of lymphocytic adenohypophysitis shortly after delivery. A 37-year-old primiparous woman delivered her baby at 38 weeks' gestation. The next morning, she presented symptoms of hypoglycemia and hypothermia. Blood testing revealed hypoadrenalism and hypothyroidism. Pituitary magnetic resonance imaging showed characteristic findings consistent with lymphocytic adenohypophysitis. We immediately initiated medication with steroids and levothyroxine. Currently, her pituitary size has normalized and its function has fully recovered. Physical stress resulting from labor and delivery may unmask subclinical lymphocytic adenohypophysitis. Practitioners should keep in mind the possibility of lymphocytic adenohypophysitis in any pregnant women with symptoms of hypoglycemia and hypothermia after delivery.

Abnormal pressure-wave reflection in pregnant women with chronic hypertension: association with maternal and fetal outcomes.

The current study tested the hypothesis that abnormal pressure-wave reflection may have an important role in identifying pregnant women with chronic hypertension who might develop pre-eclampsia (PE) and/or fetal growth restriction. Pulse-wave analyses were performed to assess maternal arterial stiffness during 26-32 weeks of gestation in 41 women with chronic hypertension. We measured the central systolic pressure (CSP) and augmentation index (AIx) noninvasively using pulse waveforms of the radial artery with an automated applanation tonometric system. In a multiple regression analysis that included AIx-75 (AIx at a heart rate of 75 beats per minute), brachial systolic pressure, maternal height, smoking status, gestational age at testing and the presence of antihypertensive treatment at testing as independent determinants, AIx-75 was the only significant determinant of birth weight, whereas the brachial systolic pressure was not. In pregnant women with chronic hypertension who subsequently developed both superimposed PE and fetal growth restriction, CSP, AIx, AIx-75, and the brachial systolic and pulse pressures were all significantly higher than those who did not develop superimposed PE nor small for gestational age. In contrast, AIx-75 was the only significantly elevated hemodynamic parameter in patients who developed fetal growth restriction but not superimposed PE. In addition, CSP was the only significantly elevated hemodynamic parameter in patients who developed superimposed PE but not fetal growth restriction. Abnormal pressure-wave reflection during 26-32 weeks of gestation showed a stronger correlation with birth weight than conventional brachial blood pressure. Our findings might provide new insight into the pathophysiology of fetal growth restriction as well as superimposed PE in pregnancies complicated with chronic hypertension.

Hand-assisted laparoscopic surgery for a mesenteric teratoma.

Mature cystic teratomas are benign neoplasms of germ cell tumors that occur most frequently in gonadal sites. The tumors usually contain 2 or 3 well-differentiated elements of endodermal, ectodermal, and mesodermal origin. Although relatively uncommon, teratomas can be composed of mature tissue originating from only 1 germ cell layer. This is known as a monodermal teratoma. Extragonadal teratomas, especially mesenteric teratomas, are extremely rare. Currently, only 21 cases of mesenteric teratoma have been described in the English literature. Mesenteric teratomas are rarely diagnosed preoperatively because pathological examination is necessary to make a definitive diagnosis. We herein report a rare case of mesenteric monodermal teratoma and review the literature. To the best of our knowledge, this is the first case of mesenteric teratoma treated with hand-assisted laparoscopic surgery.

Laparoscopic repair of a post-myomectomy spontaneous uterine perforation accompanied by a bizarre tumor resembling polypoid endometriosis.

Among various long-term complications after previous myomectomy, increasing risk of uterine rupture or dehiscence during pregnancy, and in particular during labor, has been widely recognized. In contrast, the world literature includes no case report of spontaneous uterine perforation or rupture after myomectomy in a nonpregnant woman, and only 1 case of iatrogenic uterine perforation after uterine artery embolization has been reported. Recently, we encountered an extremely rare case of spontaneous uterine perforation after previous myomectomy accompanied by a bizarre tumor resembling polypoid endometriosis, which was successfully treated via laparoscopic surgery. The patient reported genital bleeding and lower abdominal pain. Preoperative magnetic resonance imaging and intraoperative findings clearly demonstrated the presence of a uterine wall defect and a multicystic tumor that had developed from the perforated portion of the uterus. The patient underwent successful laparoscopic surgery for repair of the perforated uterus and resection of the tumor. The clinicopathologic diagnosis of the tumor was tentatively confirmed as an endometriosis-like lesion resembling polypoid endometriosis. We speculate that the cause of the tumor was retrograde menstruation, as in the pathogenesis of endometriosis.

Complex Müllerian malformation without any present classification: unilateral ovarian and tubal absence with an arcuate uterus.

Müllerian duct anomalies are known to cause infertility and reproductive problems. The true incidence of such abnormalities is not well defined. The most widely accepted method of classification for a Müllerian duct anomaly is the American Society of Reproductive Medicine classification (1988). However, there are some rare anomalies inconsistent with the current classification. Herein, we report a rare case of Müllerian duct anomaly, unilateral ovarian and tubal absence with an arcuate uterus. The failure of the Müllerian ducts to canalize can also lead to the development of a unicornuate uterus and adnexal agenesis. An arcuate uterus indicates incomplete septal absorption after normal fusion of the Müllerian ducts. Therefore, its coexistence with adnexal absence and an arcuate uterus is considered to be extremely unlikely.

Ovarian vein thrombosis following total laparoscopic hysterectomy.

Ovarian vein thrombosis usually occurs in pregnant patients, especially during the postpartum period. However, it is a rare complication following laparoscopic surgery in gynecology. The risk of a thromboembolic event is not well defined, and evidence-based guidelines regarding deep vein thrombosis prophylaxis in gynecological laparoscopic surgery are still lacking. Herein we report a rare case of ovarian vein thrombosis following total laparoscopic hysterectomy in a 35-year-old woman who developed a fever of unknown origin on postoperative day 3. A complete fever work-up was done. Her urine, vaginal stump and blood culture were all negative, and her white blood cell count was normal. CT revealed left ovarian vein thrombosis. The patient responded well to anticoagulation in conjunction with antibiotic therapy.

Pseudomyxoma peritonei originating from colorectal cancer during pregnancy.

Pseudomyxoma peritonei is an extremely rare condition characterized by the presence of gelatinous ascites and disseminated intra-peritoneal mucinous tumors. To our knowledge, there have been only two case reports of pseudomyxoma peritonei during pregnancy in 2009, both of which originated from the appendix. We present the first case of pseudomyxoma peritonei originating from colorectal cancer during pregnancy. Prenatal ultrasound examination of a 34-year-old, asymptomatic woman revealed characteristic features of pseudomyxoma peritonei at 24 weeks gestation. At laparotomy, both ovaries were involved with copious amounts of mucinous tumors and fluid, an advanced colorectal cancer had invaded the peritoneal cavity and multiple disseminated tumors were noted around the intraperitoneal cavity. All clinicians practicing obstetrics and gynecology must consider the possibility of a malignant neoplasm presenting in a pregnant woman and should recognize the highly characteristic features of pseudomyxoma peritonei to enable detection of this rare condition incidentally during routine screening ultrasound examinations.

A case of complete hydatidiform mole with coexistent fetus: conclusive diagnosis of androgenesis of the molar placenta by variation of paternal acrocentric short arms.

A twin pregnancy consisting of complete hydatidiform mole with coexisting fetus is an extremely rare condition. Recent advances in obstetric ultrasonography and cytogenetic analysis have made the prenatal diagnosis of this rare pregnancy possible. Recent literature advocating DNA polymorphism analysis being required for the accurate diagnosis of complete hydatidiform mole with coexisting fetus is discussed. We present a case of complete hydatidiform mole with coexisting fetus terminated at 16 weeks' gestation. After successful termination of the pregnancy with intravaginal gemeprost, androgenesis of the molar placenta was proven by karyotyping analysis only, without DNA polymorphism analysis, because the short arm of chromosome 21 of the paternal allele had the normal variant satellite. To our knowledge, this is the first case report of complete hydatidiform mole with coexisting fetus diagnosed by variation of the acrocentric short arms, followed by termination with intravaginal gemeprost. We describe the clinical course of our case and review some literature concerning complete hydatidiform mole with coexisting fetus.

Immunisation of male mice with a plasmid DNA vaccine encoding gonadotrophin releasing hormone (GnRH-I) and T-helper epitopes suppresses fertility in vivo.

Immunisation against mammalian gonadotrophin releasing hormone (GnRH-I) linked to large carrier proteins has been shown to disrupt fertility. However, various studies have shown that the carrier protein causes epitope suppression of the hapten response, resulting in short-lived immunoneutralisation, followed by a return of fertility. A range of strategies has been used to resolve this, with limited success. The aim of this study was to construct a plasmid DNA vaccine encoding GnRH-I and T-helper epitopes. A 498 bp long vaccine construct in pcDNA3.1+ was administered to male mice in conjunction with a Hemagglutinating Virus of Japanese Envelop (HVJ-E) vector or in saline solution. The vaccine efficacy was evaluated in terms of GnRH-I specific IgG antibody response, serum testosterone levels, testicular spermatogenesis and the ability to produce offspring. The vaccine appeared to induce higher anti-GnRH-I IgG antibody response and insult the fertility axis, which was characterised by a drop of epididymal sperm counts, reduction of serum testosterone levels, suppressed testicular spermatogenesis and a significant decrease in litter numbers compared to control animals. The end-point vaccine efficacy was much higher in the HVJ-E vector mediated immunisation, than in saline alone.

Mouse model of human infertility: transient and local inhibition of endometrial STAT-3 activation results in implantation failure.

Embryo implantation involves a series of biochemical reactions and its failure is an important therapeutic target of infertility treatment. We established an infertile mouse model using transient and local suppression of signal transducer and activator of transcription-3 (STAT-3) activity by STAT-3 decoy transfer into the uterine cavity during implantation, resulting in <30% implantation. This infertility is caused by suppression of decidualization, which is indispensable for implantation, and independent of progesterone. These conditions may mimic clinically unexplained infertility. Our results suggest that STAT-3 could be a useful target for diagnosis and therapy of human implantation failure.

Occurrence of fetal choroid plexus cysts in siblings: concerns regarding recurrence and chromosomal abnormality.

Choroid plexus cysts (CPC) are a well-known ultrasound aneuploidy marker easily detectable at second-trimester ultrasound examination. However, their genetic etiology is totally unknown. We report two cases of Japanese mothers who carried two and three siblings respectively; all the fetuses that had CPC were noticed at second trimester. Genetic amniocentesis revealed that each fetus had different karyotypes, that is, trisomy 18 and 46,XX in the case of one mother, and trisomy 18, 46,XY and trisomy 21 in the case of the other. These observations indicate that the genetic basis of the cysts is not linked to abnormal chromosomes. We propose that careful ultrasound observation and genetic counseling of the siblings should be offered to patients who have previously had a baby with CPC, despite that baby having a normal karyotype.

Tension-free vaginal tape procedure with manual-tapping method: a potentially useful technique.

AIM: Stress urinary incontinence (SUI) is accompanied by pelvic organ prolapse (POP) in many cases. We investigate a procedure to adjust the level of suspension of the mid-urethra using tension-free vaginal tape (TVT) under general anesthesia at the time of POP repair surgery. METHODS: Preliminary examination carried out prior to this study showed that the pressure stress applied by a surgeon is less than half of that induced using the cough-stress method: the manual-tapping method (MTM) showed an average intravesical urinary leak point pressure (IULPP) of 21.4 mmHg (range 19-23 mmHg), when the cough-stress method demonstrated an average IULPP >52.4 mmHg (range 45-58 mmHg; n = 3). An attempt was made to predict postoperative SUI by packing sponge gauze into the manually replaced vagina preoperatively. If SUI appeared, TVT was added to the repair operation for POP in those patients (n = 11). Lastly, the MTM was used to decide the level of urethral suspension during the TVT procedure following POP repair surgery under general anesthesia (n = 11). RESULTS: Eleven patients underwent the TVT procedure combined with POP repair surgery. The mean postoperative follow-up period was 23.8 months (range 9-40 months). There was no case of post-surgical ischuria. One patient showed a cystocele during the postoperative course. However, all other patients were relieved from the symptoms of POP, and none complained of SUI following the procedure. CONCLUSION: The MTM seems to be a more appropriate indicator by which to adjust the level of urethral suspension during the TVT procedure than the conventional method, particularly under general anesthesia. To prevent and cure perioperative SUI, the MTM as a TVT procedure combined with POP repair surgery under general anesthesia is a useful procedure.

Effect of proteasome pathway on initiation of mouse labor induced by antiprogesterone.

PROBLEM: Various kinds of contraction-associated molecules are up-regulated at the initiation of labor. However, expression profiling has revealed that many molecules are also down-regulated. The effect of down-regulation of molecules by protein degradation on parturition is not known. METHODS OF STUDY: We administered lactacystin, a specific proteasome inhibitor, to mouse preterm birth model induced by antiprogesterone RU486 on day 16.0 post-coitus. NF-kappaB activity, and the levels of transcripts for oxytocin receptor, prostaglandin F(2alpha) receptor (FP), cyclooxygenase-1, -2, and interleukin-1beta in the uterus were examined by electrophoretic mobility shift assay and semi-quantitative reverse transcriptase-polymerase chain reaction, respectively. RESULTS: Administration of lactacystin significantly prolonged the time until the delivery of the first pup. FP mRNA level was solely elevated by RU486 treatment, and lactacystin significantly suppressed this up-regulation. CONCLUSIONS: Proteolysis by proteasomes in the uterus regulates the initiation of labor, at least in part, via control of contraction-associated molecules such as FP.

Alteration of the timing of implantation by in vivo gene transfer: delay of implantation by suppression of nuclear factor kappaB activity and partial rescue by leukemia inhibitory factor.

Nuclear factor kappaB (NF-kappaB) is activated in the murine endometrium during implantation period [Am. J. Reprod. Immunol. 51 (2004) 16]. Transient transfection of IkappaBalpha mutant (IkappaBalphaM) cDNA into the mouse uterine cavity using hemagglutinating virus of Japan envelope vector suppressed uterine NF-kappaB activity less than half of that observed in control on days 3.5 and 4.5 p.c. IkappaBalphaM cDNA transfection led to significant delay of implantation. After IkappaBalphaM cDNA transfection, LIF mRNA expression in the uterus was significantly suppressed on days 3.5 and 4.5 p.c. Co-transfection of LIF cDNA with IkappaBalphaM cDNA in the uterus partially rescued the delay of implantation induced by suppression of NF-kappaB activity. Taken together, these findings indicate that NF-kappaB activation determines the timing of the implantation, at least in part, via control of LIF expression.

Highly efficient and minimally invasive in-vivo gene transfer to the mouse uterus using haemagglutinating virus of Japan (HVJ) envelope vector.

The uterus is obviously critical in implantation, development of the fetus and parturition. Endometrial cancer derived from endometrial epithelium is one of the common malignancies in the female reproductive tract. In order to clarify the local mechanisms of reproductive physiology and establish a non-systemic therapeutic strategy for reproductive failure as well as for endometrial cancer, we applied haemagglutinating virus of Japan envelope (HVJ-E) vector to in-vivo gene transfer into the uterine cavity of IVCS mice. Injection of HVJ-E vector into mouse uterine cavity on day 1.5 post coitum (p.c.) introduced a reporter gene approximately 120-fold more efficiently than introduction using the cationic liposome method. The expression of the introduced gene continued for at least 3 days. The plasmid vector was localized in the endometrial epithelium, whereas oligo deoxynucleotides were distributed throughout the epithelium, stromal cells and myometrium. HVJ-E vector did not affect the pregnancy rate, course of pregnancy, litter size, fetal growth in utero or parturition, and did not transfect the exogenous gene to the fetus. These results indicate that gene transfer into the uterus using HVJ-E vector is highly efficient and safe during pregnancy, and results in a well controlled distribution of the exogenous DNA. We believe that this procedure should be widely applicable for investigations of reproductive physiology as well as for methods of local gene therapy in the uterus.