Conjugated Bile Acids Accelerate Progression of Pancreatic Cancer Metastasis via S1PR2 Signaling in Cholestasis.

BACKGROUND: Pancreatic cancer (PC) has an extremely high mortality rate, where obstructive jaundice due to cholestasis is a classic symptom. Conjugated bile acids (CBAs) such as taurocholic acid (TCA) have been reported to activate both the ERK1/2 and AKT signaling pathways via S1P receptor 2 (S1PR2) and promote growth of cholangiocarcinoma. Thus, we hypothesize that CBAs, which accumulate in cholestasis, accelerate PC progression via S1PR2. METHODS: Murine Panc02-luc and human AsPC-1, MIA PaCa2, and BxPC-3 cells were treated with TCA, S1PR2 agonist CYM5520, S1PR2 antagonist JTE-013, sphingosine-1-phosphate (S1P), and functional S1P receptor antagonist (except S1PR2) FTY720. Bile duct ligation (BDL) was performed on liver implantation or intraperitoneal injection of Panc02-luc cells. RESULTS: Panc02-luc and AsPC-1 cells predominantly expressed S1PR2, and their growth and migration were stimulated by TCA or CYM5520 in dose-dependent manner, which was blocked by JTE-013. This finding was not seen in PC cell lines expressing other S1P receptors than S1PR2. Panc02-luc growth stimulation by S1P was not blocked by FTY720. BDL significantly increased PC liver metastasis compared with sham. PC peritoneal carcinomatosis was significantly worsened by BDL, confirmed by number of nodules, tumor weight, bioluminescence, Ki-67 stain, ascites, and worse survival compared with sham. CYM5520 significantly worsened PC carcinomatosis, whereas treatment with anti-S1P antibody or FTY720 also worsened progression. CONCLUSIONS: CBAs accelerated growth of S1PR2 predominant PC both in vitro and in vivo. This finding implicates S1PR2 as a potential therapeutic target in metastatic S1PR2 predominant pancreatic cancer.

[A case of primary mesenteric schwannoma with secondary ossification].

Schwannoma is a tumor that usually originates soft tissue peripheral nerves. Primary mesenteric schwannomas are rare, and furthermore, there are few reports of this with secondary ossification, which is extremely rare. Herein we report a case of primary mesenteric schwannoma with secondary ossification in a 46-year-old Japanese woman with recurrent postprandial abdominal pain and weight loss. Her vital signs were stable, and her blood test was almost normal except for a slight elevation of CA125. Computed tomography revealed a whirl sign indicative of superior mesenteric torsion. In contiguity with a constricted portion of the intestine, an approximately 70-mm, well-circumscribed tumor with calcifications, which was fed by the superior mesenteric artery was visible. On magnetic resonance imaging, the tumor appeared hypointense on T1-weighted images and inhomogeneous hyperintense on T2-weighted images. As a gastrointestinal mesenchymal tumor was suspected, we performed partial small intestinal resection including the tumor. Intraoperatively, the tumor was found to be incarcerated into a hernial orifice created by the adhesion of the sigmoid colon with the abdominal wall and uterus. Pathologically, the tumor had no continuity with the intestinal wall. It mainly consisted of hypocellular mucous, and spindle-shaped cells were sparsely distributed. Some areas were hypercellular with palisading arrangement cells. This was suggestive of an Antoni B>Antoni A type schwannoma. It also included secondary ossification and blood vessel assembly. The patient has had an uneventful postoperative course without recurrence for about 17 months. Primary mesenteric schwannoma is rare, and to our knowledge, only 20 cases including this case have been reported. Moreover, there has only been one report of primary mesenteric ossified schwannoma in 2018, and there has been no report in Japan so far. We report our experience with the successful treatment of primary mesenteric ossified schwannoma and review the literature.

Short- and long-term outcomes of laparoscopic versus open gastrectomy for locally advanced gastric cancer following neoadjuvant chemotherapy.

BACKGROUND: This study aimed to investigate the short- and long-term outcomes of laparoscopic gastrectomy (LG) in patients with advanced gastric cancer following neoadjuvant chemotherapy (NAC) to determine its safety and feasibility. METHODS: We retrospectively investigated 51 patients who underwent gastrectomy for locally advanced gastric cancer [cT3-4/N1-3 or macroscopic type 3 (> 80 mm) or type 4] following NAC between November 2009 and January 2018. After excluding two patients who underwent palliative surgery due to peritoneal dissemination, 49 patients were ultimately selected for this cohort study. The patients were then divided into the LG group and open gastrectomy (OG) group, after which the clinicopathological characteristics as well as short- and long-term outcomes were examined. RESULTS: Compared with the OG group, the LG group demonstrated a significantly lower amount of intraoperative blood loss and a shorter hospital stay. The overall complication rates were 10% (2 of 20 patients) and 24% (7 of 29 patients) in the LG and OG groups (P = 0.277), respectively. No significant differences in 5-year disease-free (LG 44.4% vs. OG 53.3%; P = 0.382) or overall survival rates (LG 46.9% vs. OG 54.0%; P = 0.422) were observed between the groups. Multivariate analysis revealed that the surgical procedure (LG vs. OG) was not an independent risk factor for disease-free (P = 0.645) or overall survival (P = 0.489). CONCLUSIONS: LG may be a potential therapeutic option for patients with gastric cancer following NAC considering its high success rates and acceptable short- and long-term outcomes.

Safety assessment of the prophylactic use of silicone gel sheets (Lady Care®) for the prevention of hypertrophic scars following caesarean section.

This study aimed to investigate the side effects of silicone gel sheet (Lady Care®) and evaluate its prophylactic efficacy in preventing abnormal scarring. Sixty women who underwent caesarean section were recruited from September 2016 to September 2017 in this prospective study. Lady Care® was applied from the 2nd to the 6th postoperative months. Side effects of Lady Care® were evaluated through medical examinations and questionnaires. A plastic surgeon diagnosed abnormal scarring. Pruritus was diagnosed in 25 (47.2%) patients; folliculitis, four (7.5%); dry skin, four (7.5%); contact dermatitis, three (5.7%); wound infection, two (3.8%); and epidermolysis, one (1.9%), albeit with mild severity. Following Lady Care® application, no abnormal scarring and mild hypertrophic scarring was observed in 32 (64.0%) and 18 (36.0%) patients respectively. Of seven patients with pre-existing hypertrophic scars, only two showed hypertrophic scarring after Lady Care® application. Our findings support the safety and prophylactic efficacy of Lady Care®.Impact StatementWhat is already known on this subject? The incidence of abnormal scarring, i.e. keloid or hypertrophic scar formation after caesarean section (CS) is reported to be ∼41%. Abnormal or excessive scar formation can lead to functional limitations, pruritus, pain and cosmetic issues. Studies have also shown a prophylactic effect of the application of silicone materials against the development of hypertrophic and keloid scars, though prohibitive cost and lack of adhesiveness of such gel sheets are known factors limiting their usage.What the results of this study add? The new silicone gel sheet 'Lady Care®' has strong adhesive properties and is consequently not easily peeled off. Furthermore, it is easy to use and economically efficient.What the implications are of these findings for clinical practice and/or further research? This is the first clinical trial on the application of Lady Care® silicone gel sheet for the prevention of CS scarring. Our findings support the safety and prophylactic efficacy of Lady Care®.

Isolation and characterization of fetal nucleated red blood cells from maternal blood as a target for single cell sequencing-based non-invasive genetic testing.

PURPOSE: Although non-invasive prenatal testing (NIPT) based on cell-free DNA (cfDNA) in maternal plasma has been prevailing worldwide, low levels of fetal DNA fraction may lead to false-negative results. Since fetal cells in maternal blood provide a pure source of fetal genomic DNA, we aimed to establish a workflow to isolate and sequence fetal nucleated red blood cells (fNRBCs) individually as a target for NIPT. METHODS: Using male-bearing pregnancy cases, we isolated fNRBCs individually from maternal blood by FACS, and obtained their genomic sequence data through PCR screening with a Y-chromosome marker and whole-genome amplification (WGA)-based whole-genome sequencing. RESULTS: The PCR and WGA efficiencies of fNRBC candidates were consistently lower than those of control cells. Sequencing data analyses revealed that although the majority of the fNRBC candidates were confirmed to be of fetal origin, many of the WGA-based genomic libraries from fNRBCs were considered to have been amplified from a portion of genomic DNA. CONCLUSIONS: We established a workflow to isolate and sequence fNRBCs individually. However, our results demonstrated that, to make cell-based NIPT targeting fNRBCs feasible, cell isolation procedures need to be further refined such that the nuclei of fNRBCs are kept intact.

Sphingosine-1-Phosphate Facilitates Skin Wound Healing by Increasing Angiogenesis and Inflammatory Cell Recruitment with Less Scar Formation.

Wound healing starts with the recruitment of inflammatory cells that secrete wound-related factors. This step is followed by fibroblast activation and tissue construction. Sphingosine-1-phosphate (S1P) is a lipid mediator that promotes angiogenesis, cell proliferation, and attracts immune cells. We investigated the roles of S1P in skin wound healing by altering the expression of its biogenic enzyme, sphingosine kinase-1 (SphK1). The murine excisional wound splinting model was used. Sphingosine kinase-1 (SphK1) was highly expressed in murine wounds and that SphK1-/- mice exhibit delayed wound closure along with less angiogenesis and inflammatory cell recruitment. Nanoparticle-mediated topical SphK1 overexpression accelerated wound closure, which associated with increased angiogenesis, inflammatory cell recruitment, and various wound-related factors. The SphK1 overexpression also led to less scarring, and the interaction between transforming growth factor (TGF)-ß1 and S1P receptor-2 (S1PR2) signaling is likely to play a key role. In summary, SphK1 play important roles to strengthen immunity, and contributes early wound healing with suppressed scarring. S1P can be a novel therapeutic molecule with anti-scarring effect in surgical, trauma, and chronic wound management.

The role of sphingosine 1-phosphate receptor 2 in bile-acid-induced cholangiocyte proliferation and cholestasis-induced liver injury in mice.

Bile duct obstruction is a potent stimulus for cholangiocyte proliferation, especially for large cholangiocytes. Our previous studies reported that conjugated bile acids (CBAs) activate the protein kinase B (AKT) and extracellular signal-regulated kinase 1 and 2 (ERK1/2) signaling pathways through sphingosine 1-phosphate receptor (S1PR) 2 in hepatocytes and cholangiocarcinoma cells. It also has been reported that taurocholate (TCA) promotes large cholangiocyte proliferation and protects cholangiocytes from bile duct ligation (BDL)-induced apoptosis. However, the role of S1PR2 in bile-acid-mediated cholangiocyte proliferation and cholestatic liver injury has not been elucidated. Here, we report that S1PR2 is the predominant S1PR expressed in cholangiocytes. Both TCA- and sphingosine-1-phosphate (S1P)-induced activation of ERK1/2 and AKT were inhibited by JTE-013, a specific antagonist of S1PR2, in cholangiocytes. In addition, TCA- and S1P-induced cell proliferation and migration were inhibited by JTE-013 and a specific short hairpin RNA of S1PR2, as well as chemical inhibitors of ERK1/2 and AKT in mouse cholangiocytes. In BDL mice, expression of S1PR2 was up-regulated in whole liver and cholangiocytes. S1PR2 deficiency significantly reduced BDL-induced cholangiocyte proliferation and cholestatic injury, as indicated by significant reductions in inflammation and liver fibrosis in S1PR2 knockout mice. Treatment of BDL mice with JTE-013 significantly reduced total bile acid levels in serum and cholestatic liver injury. CONCLUSION: This study suggests that CBA-induced activation of S1PR2-mediated signaling pathways plays a critical role in obstructive cholestasis and may represent a novel therapeutic target for cholestatic liver diseases. (Hepatology 2017;65:2005-2018).

Improving the Accuracy of Diagnosing Placenta Previa on Transvaginal Ultrasound by Distinguishing between the Uterine Isthmus and Cervix: A Prospective Multicenter Observational Study.

OBJECTIVE: To clarify whether distinguishing between the uterine isthmus and cervix can improve the accuracy of diagnosing placenta previa at term. METHODS: A multicenter prospective observational study was conducted among pregnant women with suspected placenta previa at 20-24 weeks' gestation. Subjects were divided into the open isthmus group and closed isthmus group. The accuracy of diagnosing placenta previa at term was compared between the 2 groups. RESULTS: We screened 9,341 patients, and 53 (0.6%) met the inclusion criteria. Nineteen cases with an open isthmus and 34 with a closed isthmus were followed. The accuracy for diagnosing placenta previa or a low-lying placenta at term was 94.7% in the open isthmus group and 26.5% in the closed isthmus group (p < 0.001). Elective or emergency Cesarean section was required in 100% of cases in the open isthmus group and 20.6% in the closed isthmus group (p < 0.001). CONCLUSION: A high prediction rate of placenta previa was obtained by using transvaginal ultrasound at 20-24 weeks' gestation after the isthmus opened by carefully distinguishing between the cervix and isthmus.

Host sphingosine kinase 1 worsens pancreatic cancer peritoneal carcinomatosis.

BACKGROUND: There are no effective treatments for pancreatic cancer peritoneal carcinomatosis (PC) or cancer dissemination in abdominal cavity. Sphingosine-1-phosphate (S1P), a bioactive lipid mediator produced by sphingosine kinases (SphK1 and SphK2), plays critical roles in cancer progression. We reported that SphK1, but not SphK2, is responsible for S1P export from breast cancer cells and recently discovered that S1P is linked to inflammation and cancer in colitis-associated cancer progression. Given the fact that inflammation is known to be essential for the establishment and progression of PC, we hypothesized that SphK1 in the host animals is involved in progression of pancreatic cancer PC. METHODS: Murine pancreatic adenocarcinoma panc02-luc cells were intraperitoneally injected into wildtype or SphK1 knockout (KO) mice to generate a syngeneic PC model. Cell proliferation and apoptosis were determined by Ki67 and TUNEL staining, respectively. RESULTS: All the animals developed panc02-luc PC. SphK1 KO mice developed significantly less tumor burden, less total tumor weight, and fewer number of PC nodules at 14 d after implantation. Histologically, less inflammatory cell infiltration and less cancer cell proliferation were observed in the tumors. There was no difference in apoptosis. CONCLUSIONS: Our results raise an intriguing possibility that S1P generated by SphK1 in the host promotes pancreatic cancer PC progression by stimulation of proliferation of cancer cells.

Murine model of long-term obstructive jaundice.

BACKGROUND: With the recent emergence of conjugated bile acids as signaling molecules in cancer, a murine model of obstructive jaundice by cholestasis with long-term survival is in need. Here, we investigated the characteristics of three murine models of obstructive jaundice. METHODS: C57BL/6J mice were used for total ligation of the common bile duct (tCL), partial common bile duct ligation (pCL), and ligation of left and median hepatic bile duct with gallbladder removal (LMHL) models. Survival was assessed by Kaplan-Meier method. Fibrotic change was determined by Masson-Trichrome staining and Collagen expression. RESULTS: Overall, 70% (7 of 10) of tCL mice died by day 7, whereas majority 67% (10 of 15) of pCL mice survived with loss of jaundice. A total of 19% (3 of 16) of LMHL mice died; however, jaundice continued beyond day 14, with survival of more than a month. Compensatory enlargement of the right lobe was observed in both pCL and LMHL models. The pCL model demonstrated acute inflammation due to obstructive jaundice 3 d after ligation but jaundice rapidly decreased by day 7. The LHML group developed portal hypertension and severe fibrosis by day 14 in addition to prolonged jaundice. CONCLUSIONS: The standard tCL model is too unstable with high mortality for long-term studies. pCL may be an appropriate model for acute inflammation with obstructive jaundice, but long-term survivors are no longer jaundiced. The LHML model was identified to be the most feasible model to study the effect of long-term obstructive jaundice.

Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential.

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite involved in many critical cell processes. It is produced by the phosphorylation of sphingosine by sphingosine kinases (SphKs) and exported out of cells via transporters such as spinster homolog 2 (Spns2). S1P regulates diverse physiological processes by binding to specific G protein-binding receptors, S1P receptors (S1PRs) 1-5, through a process coined as "inside-out signaling." The S1P concentration gradient between various tissues promotes S1PR1-dependent migration of T cells from secondary lymphoid organs into the lymphatic and blood circulation. S1P suppresses T cell egress from and promotes retention in inflamed peripheral tissues. S1PR1 in T and B cells as well as Spns2 in endothelial cells contributes to lymphocyte trafficking. FTY720 (Fingolimod) is a functional antagonist of S1PRs that induces systemic lymphopenia by suppression of lymphocyte egress from lymphoid organs. In this review, we summarize previous findings and new discoveries about the importance of S1P and S1PR signaling in the recruitment of immune cells and lymphocyte retention in inflamed tissues. We also discuss the role of S1P-S1PR1 axis in inflammatory diseases and wound healing.

Corrigendum to "Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential".

[This corrects the article DOI: 10.1155/2016/8606878.].

Successful use of single-port laparoscopic surgery for ovarian cyst removal during pregnancy: a case series of three cases.

Pregnant patients have an increased risk of torsion compared to that seen in nonpregnant patients, and those with larger cysts undergo torsion more frequently, which can cause obstructions during labor. The risks associated with emergent surgery are higher than those with elective surgery. Laparoscopic surgery can be safely performed during pregnancy. Single-port laparoscopic surgery is reported to be a minimally invasive laparoscopic technique. We report three cases of ovarian dermoid cysts, which were successfully removed during pregnancy through elective single-port laparoscopic surgery. In all cases, imaging showed a dermoid cyst and the cyst size was greater than 6 cm. All patients requested the surgery. The ovarian cysts were successfully removed by single-port laparoscopy without additional ports and without intra- or postoperative complications. All pregnancies progressed well and delivered vaginally at full term. The single-port laparoscopic approach is useful for removing ovarian cysts during pregnancy.

A rare case of colorectal metastasis found 8 years and 10 months after gastrectomy for advanced gastric cancer: A case report and literature review.

Colorectal metastasis from gastric cancer is rare and may develop several years after gastric cancer surgery. Therefore, colonoscopic findings provide useful diagnostic information. The present report describes a case of gastric cancer colon metastasis diagnosed 8 years and 10 months after gastrectomy for advanced gastric cancer. A 64-year-old male patient underwent gastrectomy in December 2010 and received chemotherapy for 4 years and 10 months after the surgery. Subsequently, the patient was diagnosed as having colorectal cancer by computed tomography in February 2019. Colonoscopy revealed linitis plastica-like colon stenosis; however, biopsy pathology did not reveal any findings indicating malignancy. Right hemicolectomy was performed, and pathological examination revealed colon metastasis from gastric cancer. The patient received chemotherapy but died of peritoneal carcinomatosis 1 year and 8 months after the colectomy. According to literature, colorectal metastasis from gastric cancer is often attributed to hematogenous metastasis and often exhibits characteristic macroscopic features. Treatments, such as chemotherapy for gastric cancer and/or colorectal resection, are considered effective for gastric cancer colorectal metastasis.

Uterine contraction may not be an independent risk factor for spontaneous preterm birth before 35 weeks in women with cervical shortening.

OBJECTIVE: To compare the risk of spontaneous preterm birth (SPTB) before 35 weeks in symptomatic and asymptomatic women with cervical shortening at 16-34 weeks under mid-trimester universal screening of cervical length (CL). METHOD: Multicenter retrospective cohort study involving six secondary/tertiary perinatal centers was planned in 2016. Primary outcomes were SPTB before 35 weeks. In all, 407 women were analyzed using multivariable logistic regression analysis for predicting SPTB before 35 weeks while adjusting for presence/absence of uterine contraction, gestational weeks, vaginal bleeding, and CL classification (1-9, 10-14, 15-19, and 20-24 mm) at admission, the execution of cervical cerclage, and the presence/absence of past history of preterm delivery. RESULTS: SPTB before 35 weeks of pregnancy occurred in 14.5%. Presence of uterine contraction was not an independent risk factor for SPTB before 35 weeks (adjusted odds ratio [aOR] 1.22, 95% confidence interval [CI] 0.67-2.20). CL of 1-9 mm, CL of 10-14 mm, and vaginal bleeding at admission were independent risk factors for SPTB before 35 weeks (aOR 5.35, 95% CI 2.11-13.6; aOR 2.79, 95% CI 1.12-6.98; and aOR 2.37, 95% CI 1.12-5.10, respectively). CONCLUSION: In women with a cervical shortening at 16-34 weeks, presence of uterine contractions at admission may not be an independent risk factor for the occurrence of SPTB before 35 weeks.

Preoperative determination of appropriate cutting line for proximal gastrectomy to avoid postoperative jejunal ulcer.

BACKGROUND/AIMS: Although proximal gastrectomy has become a procedure of choice for patients' early cancer in the upper third of stomach, no clinical guide for optimal gastric resection in order to avoid postoperative jejunal ulcer is available. The aim of this study was to investigate whether determining the distribution of parietal and chief cells of the stomach using Congo red test is clinically relevant. METHODOLOGY: The F-line was defined as a boundary line between fundic and intermediate area of the stomach according to the pathological findings in 29 patients who underwent total gastrectomy for early gastric cancer, whereas the f-line was regarded as a boundary line between intermediate and pyloric area. In the additional 6 patients undergoing vagus-preserving proximal gastrectomy with jejunal pouch interposition, endoscopic Congo red test was preoperatively performed to determine the F-f-line. RESULTS: The distances from the pyloric ring to f-line on the lesser and greater curvatures were variable. Long-term outcomes of proximal gastrectomy guided by preoperative endoscopic Congo red test were favorable. CONCLUSIONS: It is suggested that preoperative endoscopic Congo red test is useful to determine the appropriate cutting line in order to avoid postoperative jejunal ulcer after proximal gastrectomy.

Increased rate of cesarean section in primiparous women aged 40 years or more: a single-center study in Japan.

PURPOSE: To investigate perinatal outcomes in late primiparous women aged 35-39 and ≥40 years. Our main research question: "Was the rate of cesarean section similar between these 2 groups of advanced maternal age?" METHODS: Primiparous women aged ≥35 years, who delivered in our center between April 2004 and March 2007, were enrolled in this study. They were divided into two groups: women aged 35-39 years and those aged ≥40 years. Antenatal complications, deliveries, and neonatal outcomes were analyzed. Fetal abnormalities, abortions, and multiple gestations were excluded. RESULTS: We assessed 752 cases (35-39 years, 610 cases; ≥40 years, 142 cases). Incidence of cesarean section (CS) was significantly higher in pregnant women aged ≥40 years (P < 0.01). The CS rate amounted to 50.0% of all deliveries in this age group. Among patients with labor deliveries, the CS rate was also significantly higher in the older age group (P < 0.05). With regard to indication for CS with labor deliveries, the rate of non-progressive labor/dystocia was 19.4% in primiparous women aged ≥40 years and 11.0% in those aged 35-39 years, respectively (P < 0.05). In contrast, the rates of antenatal complications were not different between the two groups, except for gestational diabetes or leiomyoma. No significant differences between the two groups could be found for neonatal outcomes such as birth weight, Apgar score, and admission to neonatal intensive care unit. CONCLUSIONS: CS rate was 50.0% in primiparous women aged ≥40 years. In addition, CS caused by dystocia was almost twice as frequent in primiparous women aged ≥40 years as in women aged 35-39 years. Among late pregnancies, primiparous women aged 40 years and older had higher risk of CS.

Disinfective process of strongly acidic electrolyzed product of sodium chloride solution against Mycobacteria.

Electrolyzed acid water (EAW) has been studied for its disinfective potential against pathogenic microbes; however, the bactericidal process against Mycobacteria has not been clearly presented. In this study, to clarify the disinfective process against Mycobacteria, EAW-treated bacteria were examined against laboratory strains of Mycobacterium bovis (M. bovis), Mycobacterium smegmatis (M. smegmatis), and Mycobacterium terrae (M. terrae) by recovery culture and observation of morphology, enzymatic assay, and the detection of DNA. All experiments were performed with the use of EAW containing 30 ppm free chlorine that kills Mycobacteria, including three pathogenic clinical isolates of Mycobacterium tuberculosis (M. tuberculosis) and six isolates of other Mycobacteria, within 5 min. In morphology, the bacterial surface became rough, and a longitudinal concavity-like structure appeared. The intrabacterial enzyme of EAW-contacted bacteria was inactivated, but chromosomal DNA was not totally denatured. These results suggest that the bactericidal effect of EAW against Mycobacteria occurs by degradation of the cell wall, followed by denaturation of cytoplasmic proteins, but degeneration of the nucleic acid is not always necessary.

[Rehabilitation for intravaginal ejaculatory dysfunction with using a masturbation aid].

OBJECTIVES: Recently the incidence of intravaginal ejaculatory dysfunction is increasing among infertile couples in Japan. Some unusual ways of masturbation and psychogenic issues were reported to cause this disorder. Patients, who had done masturbation in an unusual way for long time since their adolescence, were difficult to gain normal intravaginal ejaculation by the behavior therapy which was used for erectile dysfunction. We, therefore, used a masturbation aid (TENGA) for rehabilitation of ejaculation to overcome this condition. PATIENTS AND METHODS: From January, 2010 through March, 2011, a total of 16 patients with intravaginal ejaculatory dysfunction underwent rehabilitation of ejaculation using TENGA. Patients' satisfaction and achievement of intravaginal ejaculation were evaluated by the questionnaire. RESULTS: Twelve patients (75%) could ejaculate in the masturbation aid (TENGA). Five patients (31%) succeeded to ejaculate in the partner's vagina after rehabilitation. CONCLUSIONS: A masturbation aid (TENGA) was a useful tool to correct the way of masturbation and achieve normal intravaginal ejaculation. This masturbation aid can be one of the effective options for the treatment of intravaginal ejaculatory dysfunction.