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Endometrial receptivity array (ERA)—an objective tool used in assisted reproductive technology—is used for personalized embryo transfer in in vitro fertilization. Hydrosalpinx affects implantation through various mechanisms. However, its effects on ERA are not well established. In this case report, we present the diagnosis and treatment of a 34-year-old nulligravida woman with infertility for two years, obesity, double uterus with unilateral hydrosalpinx and right kidney deficiency. Based on ERA results, endometrial microbiome metagenomic analysis (EMMA), analysis of infectious chronic endometritis (ALICE), and CD138 immunostaining, the patient was treated with hormonal replacement cycle and amoxicillin/clavulanic acid. After one week of amoxicillin/clavulanic acid administration, the vitirified-warmed 4AA blastocyst was transferred to the left uterus—which was absent of hydrosalpinx and easily accessible to transfer and pregnancy was achieved. To the best of our knowledge, this case study is the first one in which we found that there were no differences between the left and right uterus in ERA, EMMA, ALICE, and CD138 immunostainings. Hence, we suggest that hydrosalpinx does not necessarily cause endometrial changes in all cases. Further research to evaluate the effects of hydrosalpinx on implantation with ERA and EMMA/ALICE is warranted.

Objective: To determine whether endometrial thickening is an important factor for pregnancy outcomes in platelet-rich plasma (PRP) treatment for patients with thin endometrium. Methods: Data from the registry database of the Japan Gynecologic PRP Study Group from April 2019 to October 2021 were analyzed retrospectively. A total of 208 patients who underwent single blastocyst transfer (SBT) after PRP due to thin endometrium (¡8 mm) in their previous cycle were included in the study. Their pregnancy outcomes were compared with their own historical data before PRP infusion. The same patient group was then divided into 136 patients whose endometrium thickened after PRP and 72 patients whose endometrium did not, and the pregnancy outcomes of the two groups were compared. Furthermore, to eliminate embryonic confounding, 28 patients who had single euploid blastocyst transfer (SEBT) with preimplantation genetic testing for aneuploidy (PGT-A) were selected from the same patient group and divided into two groups of 22 patients whose endometrium thickened and 6 patients whose endometrium did not, and the pregnancy outcomes were compared in the same method. Results: After PRP administration, the clinical pregnancy rate, live birth rate, and miscarriage rate were all significantly improved compared with the historical controls (34.1 vs 20.0, [Formula: see text]; 22.6 vs 3.9, [Formula: see text]; 33.8 vs 73.4, [Formula: see text]). There were no statistically significant differences in the respective rates between the “thickened endometrium” group and the “unthickened endometrium” group in SBT group (36.0 vs [Formula: see text], [Formula: see text]; 25.7 vs [Formula: see text], [Formula: see text]; 28.5 vs [Formula: see text], [Formula: see text], respectively). Likewise, in the SEBT with PGT-A group, there were no statistically significant differences in results between the two groups (36.4 vs [Formula: see text], [Formula: see text]; 36.4 vs [Formula: see text], [Formula: see text]; 0 vs [Formula: see text], respectively). Conclusions: PRP administration to patients with thin endometrium improves pregnancy outcomes even when endometrial thickening is not achieved.

The actual status of fertility preservation treatments in the startup phase in Japan was investigated as a basis for discussing future directions.This study was conducted as "Research project to promote support of children and parenting 2016" which was supported by Ministry of Health in Japan with the approval of the institutional review board at St. Marianna University. Subjects of the survey were facilities registered with the Japan Society of Obstetrics and Gynecology as fertility preservation facilities, and facilities belonging to the Japan Association of Private Assisted Reproductive Technology Clinics and Laboratories. We provided questionnaires to survey both the medical care system and cases for which fertility preservation was implemented between 2006 and 2016.Responses were obtained from 68 facilities (of the 64, 59 [92.2%] responded to the questionnaire and 9 clinics cooperated). Many facilities limited the cryopreservation of oocytes and ovaries to patients 40-41 years old and the use of eggs to patients 44-45 years old. In the patient survey, 812 cases of oocyte cryopreservation and 201 cases of ovarian tissue cryopreservation were performed during study period. Breast cancer was the most indicated disease, with oocyte cryopreservation in the late 30s and ovarian tissue cryopreservation in the early 30s. Very few babies were born from fertility preservation, and no live birth cases of ovarian tissue cryopreservation were identified.Even from the early days, fertility preservation was implemented according to certain standards in Japan, but was characterized by a large variety of facilities.

Background: The objective of this study was to investigate accurately the effect of the meiotic spindle imaging of human oocytes on their fertilization and embryo development by using the Piezo-ICSI. Methods: We retrospectively assessed 529 oocytes with the first polar body retrieved from 124 infertile couples (147 cycles) who attended our clinic between May 2016 and December 2018. Of these, 489 oocytes (92.4%) with visible meiotic spindle comprised the Spindle (+) group and 40 oocytes (7.6%) not observed meiotic spindle comprised the Spindle (−) group. The meiotic spindle was imaged using polarized light microscopy. The rates of fertilization, high-quality day-3 embryo, day-5 blastocyst, and high-quality day-5 blastocyst were evaluated in both groups. Results: The fertilization rates of Spindle (+) and Spindle (−) were 92.0% (450/489) and 70.0% (28/40), respectively; high-quality day-3 embryo rates were 62.9% (283/450) and 35.7% (10/28); day-5 blastocyst rates were 53.7% (205/382) and 32.1% (9/28); high-quality day-5 blastocyst rates were 29.8% (114/382) and 3.6% (1/28). Fertilization, high-quality day-3 embryo, day-5 blastocyst, and high-quality day-5 blastocyst rates were significantly higher in the Spindle (+) group than in the Spindle (−) group. Conclusion: Spindle imaging (i.e., oocytes with a visible meiotic spindle or with not observed meiotic spindle) influences the outcome of Piezo-ICSI in human oocytes, including fertilization and embryo development. To our knowledge, this study is the first to evaluate the effect of meiotic spindle imaging on fertilization or embryo development among oocytes after Piezo-ICSI. The meiotic spindle imaging could be the indicator for the quality management of medical doctors and embryologists.

PURPOSE: Male infertility is partially caused by an inappropriate lifestyle and comorbidities. In this study, we analyzed the prevalence of these factors and the effects of lifestyle modifications as part of male preconception care. METHODS: Four hundred and two male partners of couples seeking conception with abnormal parameters upon the first semen analysis were enrolled. They were advised to modify their inappropriate lifestyle as male preconception care. Afterward, their general and male reproductive health was examined. Semen quality was compared before and after the promotion. RESULTS: Smoking, chronic alcohol use, and genital heat stress were found in 22.6%, 47.0%, and 75.1% of patients, respectively. Palpable varicoceles, hypogonadism, obesity (body mass index ≧30 kg/m(2)), hypertension, zinc deficiency, hyperlipidemia, liver dysfunction, and diabetes mellitus were found in 25.9%, 17.0%, 7.0%, 14.9%, 16.2%, 37.0%, 26.9% and 3.4% of the participants, respectively; 98.8% of the patients had at least one factor. After the promotion, semen parameters and sperm DNA fragmentation were improved significantly. Improvement was found in those with palpable varicocele or hypogonadism but not in those with night work shift, abstinence (>3 days), erectile dysfunction, hypertension, obesity, zinc deficiency, or diabetes mellitus. CONCLUSIONS: Comorbidities and inappropriate lifestyle choices were common among men with infertility. The promotion of lifestyle modifications as part of male preconception care could improve semen quality without urologic intervention.

To perform complete mesocolic excision with central vessel ligation, it is important to recognize the vessel anomaly and the location of the tumor. For left-sided colon cancer, the variations in the course of the left colic artery and accessary middle colic artery must be recognized preoperatively. Here, we describe our experience with a 57-year-old man who was diagnosed with sigmoid colon cancer with complicated inter-mesenteric connections between the inferior mesenteric artery (IMA) and superior mesenteric artery (SMA), possibly due to median arcuate ligament syndrome. We performed laparoscopic sigmoidectomy with low ligation of the IMA to preserve the extremely enlarged left colic artery. The total operative time was 155 minutes, and the estimated total blood loss was 10 mL. The patient was discharged on postoperative day 9 without any postoperative complications. For patients with vascular anomalies in the left-sided mesocolon, preoperatively ruling out SMA stenosis by using angiography and 3-D CT might be important.

Background Endometrial receptivity array (ERA) is used to determine the timing of embryo transfer (ET) synchronized with the window of implantation (WOI). The effectiveness and evaluation of ERAs in women with recurrent implantation failure remain controversial. We report the case of a patient with recurrent implantation failure that raises the issue of reproducibility of ERA tests. Case report A 36-year-old Japanese woman with secondary infertility who had previously given birth failed to conceive after three frozen-thawed embryo transfer (FET) cycles. An ERA test was conducted to confirm the WOI. The first ERA test was performed 125 h after progesterone exposure. The laboratory reported that the endometrium was in a non-receptive (post-receptive) phase, and recommended retesting 101 h after progesterone exposure. A simultaneous chronic endometritis (CE) test showed a score of 3. After the antibiotics administration to treat CE, the second ERA test was performed after 101 h of progesterone exposure. The laboratory reported that the endometrium had not reached the WOI and estimated the WOI to be 113 ± 3 h after progesterone exposure. The third ERA test was performed 113 h after progesterone exposure. The laboratory reported that the endometrium was in a non-receptive (pre-receptive) phase and estimated the WOI to be 137 ± 3 h after progesterone exposure. A CE test performed at the same time as the second and third ERA tests showed a score of 1 for the collected endometrium. According to the third ERA test results, the vitrified-warmed blastocyst was transferred at 137 h of progesterone exposure. Pregnancy was achieved and the patient had an uncomplicated vaginal delivery at 39 weeks. One year later, another pregnancy was achieved after FET at 137 h of progesterone exposure, and the patient delivered at 33 weeks due to an unexpected membrane rupture. Conclusion Because the results of the ERA test may vary in the presence of CE, CE should be diagnosed simultaneously with or before conducting ERA tests. If CE is diagnosed, ERA testing should be performed after treatment with antimicrobials or other drugs.

Background Jejunogastric intussusception (JGI) is a rare, but potentially fatal complication that can occur following gastric surgery, and the reported incidence of JGI is as low as 0.1%. Early diagnosis and treatment are critical for JGI to prevent major complications such as bowel necrosis and death. Although emergency surgery is the standard treatment, endoscopic reduction has also been reported to be effective in JGI patients without bowel necrosis. Several early recurrent cases treated with surgical or endoscopic reduction have been reported. We report an extremely rare case of JGI after pancreaticoduodenectomy (PD) using Child’s procedure that was successfully treated with surgical reduction and fixation. Case presentation An 81-year-old man who had undergone PD using Child’s procedure 3 years ago presented to our hospital with epigastric pain and nausea. His vital signs were stable, and abdominal examination revealed mild tenderness with a palpable mass in the mid-epigastrium. Abdominal computed tomography (CT) and gastroscopy revealed a JGI of the efferent loop, and exploratory laparotomy was immediately performed. During the operation, the efferent loop showed no adhesions and was intussuscepted through the gastrojejunostomy into the gastric lumen. An incision in the anterior wall of the stomach revealed no evidence of ischemia of the intussusceptum. The efferent loop was reduced using Hutchinson’s maneuver and fixed to the afferent loop to prevent a recurrence. The postoperative course was uneventful, and there was no sign of recurrence 12 months postoperatively. Conclusions JGI after PD is an extremely rare, but has severe complications. Surgery might be the optimal treatment for JGI in terms of preventing recurrence, even in cases without bowel necrosis.

Background The safety and feasibility of laparoscopic colectomy for T4 colorectal cancer remain controversial. We believe that setting a “Goal” that will guide the surgeons in returning from the deep layer could be the key to safe en bloc resection of neighboring organs. For descending colon cancer, the cranial-first approach makes it possible to clearly visualize the pancreas and origin of the transverse mesocolon, leading to safe splenic flexure mobilization and complete mesocolic excision, which is the strongest advantage of this approach. Case presentation A 75-year-old woman was diagnosed with T4 descending colon cancer invading the Gerota’s fascia. We performed laparoscopic left colectomy using the cranial-first approach to set a “Goal” at the inferior border of the pancreas for safe resection of the Gerota’s fascia. The total operative time was 233 min, and the estimated blood loss was 98 ml. She was discharged after surgery without postoperative complications. Pathological findings revealed the invasion into the Gerota’s fascia, and the resection margin was negative for cancer. Conclusions The cranial-first approach of laparoscopic left colectomy appears to be safe and feasible and could be a promising method for selected patients with T4 descending colon cancer invading the Gerota’s fascia.

Since the first successful pregnancies achieved by intracytoplasmic sperm injection (ICSI) were reported, ICSI has become an essential technique in assisted reproductive technology (ART). ICSI uses micropipettes with a spiking tip to penetrate the zona pellucida and membrane. Then, the cytoplasm is usually aspirated into the micropipette for membrane breakage (conventional-ICSI). The survival and fertilization rates of mouse oocytes after conventional-ICSI were as low as 16% and 8%, respectively. Kimura and Yanagimachi applied a piezo drive unit, mercury, and a micropipette with a flat tip for mouse ICSI. The membrane breakage could be performed semi-automatically by combining these types of equipment without cytoplasmic aspiration into the micropipette (piezo-ICSI). These authors reported significantly higher survival and fertilization rates (80% and 78%) compared to those of conventional-ICSI (16% and 8%). Therefore, the piezo-ICSI may be effective not only for mouse oocytes but also for human oocyte ICSI. However, only five papers are available that assessed the effectiveness of piezo-ICSI compared to conventional-ICSI for human oocytes. All of these five papers reported significantly higher fertilization rates compared to those of conventional-ICSI. The goal of the piezo-ICSI protocol described here is to improve the clinical results of ICSI compared to the conventional-ICSI.

Background Subtotal cholecystectomy is an effective surgical method to decrease the risk of complications for gallbladders that are difficult to remove. However, there is a risk for postoperative refractory bile leakage through the gallbladder stump. Here, we report a new management technique involving the use of argon plasma coagulation (APC) to stop bile leakage after a subtotal cholecystectomy. Case presentation A 74-year-old man was referred to our hospital for abdominal pain and fever. Contrast-enhanced computed tomography of the abdomen showed fluid collection, such as an abscess, surrounding the gallbladder and hepatic flexure colon. The patient was diagnosed with colonic perforative peritonitis, and he underwent emergency surgery. On laparotomy, the abscess was observed outside of the hepatic flexure colon and gallbladder necrosis was detected. The neck of the gallbladder and the area close to the hepatoduodenal ligament was severely inflamed prohibiting dissection. The hepatic flexure colon was part of the abscess wall, and resection was needed. A subtotal cholecystectomy and right hemicolectomy confirmed peritonitis caused by cholecystic perforation. The mucous membrane of the gallbladder neck that remained was necrotic or detached. Therefore, the stump of the gallbladder was closed by primary sutures without cauterization of the mucosa. On postoperative day 6, bile leakage from the gallbladder stump was revealed. Percutaneous and endoscopic retrograde cholangiography drainage were performed. However, the liquid, which seemed to be secreted from the mucosa of the remnant gallbladder, was continuously obtained. We used APC to cauterize the gallbladder mucosa through the fistula of the abdominal drainage tube. Bile leakage and mucus discharge were improved after three rounds of APC cauterization. Conclusions APC effectively treated refractory bile leakage from a gallbladder stump after subtotal cholecystectomy for severe cholecystitis.

A husband and his wife, both 34 years old, consulted our clinic because of primary infertility. Sperm analysis revealed that the sperm concentration, motility, and progressive motility were (42.8±22.8)×10(6)/mL, 23.3%±12.2%, and 12.9%±6.1%, respectively. Based on Krugar strict morphology criteria, 100% of the sperm were teratozoospermic, with 7.9% DNA fragmentation index. Observation of the sperm under a transmission electron microscope revealed that most parts of the fibrous sheath (FS) surrounding the tails of the sperm were missing from midway through the principal piece to the end piece, although the sperm’s heads, necks and midpieces were morphologically normal. To collect oocytes, the gonadotropin-releasing hormone antagonist protocol was carried out, and 7 oocytes were retrieved. Intracytoplasmic sperm injection (ICSI) was performed for all the teratozoospermic sperm. Of the 7 oocytes, 3 were fertilized, and one 8-cell embryo and 2 expanded blastocysts were vitrified. Although repeated transfers of expanded blastocysts resulted in no implantation, one 8-cell embryo transfer in a hormone replacement therapy cycle led to pregnancy. The pregnancy using an 8-cell vitrified embryo resulted in the delivery of a healthy female baby at 38 weeks of gestation. No congenital malformations were found until 28 days after birth. Our results demonstrated that healthy birth could be achieved following the transfer of an embryo derived from ICSI using teratozoospermic sperm exhibiting the dysplasia of the fibrous sheath (DFS). Furthermore, while the previous reports on DFS have not investigated male infertility, we evaluated sperms from various aspects such as Kruger sperm function test, chromatin dispersion test, electron microscopy findings, time-lapse images of the obtained embryos, and concluded that ICSI could be desirable as a treatment policy for DFS.

The feasibility and safety of laparoscopic surgery for locally advanced colorectal cancer remain controversial due to the high rate of incomplete resection and conversion to open surgery. Especially for T4 colorectal cancer, laparoscopic techniques are still demanding mainly because of the difficulty in distinguishing between inflammation and tumor involvement, which often lead surgeons to do overtreatment in surgery. We believe laparoscopic magnified and multidirectional approach might be useful for pathologically complete resection and minimizing an unnecessary extended surgery for these cases. A 49-year-old man was diagnosed with locally advanced T4 sigmoid colon cancer invading the urinary bladder and ureter. We performed laparoscopic anterior resection with en bloc resection of the urinary bladder and the left ureter. Total operative time was 462 min, and the estimated blood loss was 50 ml. This patient was discharged on the 28th day after surgery without any ostomies and urinary functional disorders. The magnified view by laparoscopic techniques from multiple directions would enable surgeons to set surgical landmarks for another approach, which is the key for safe and feasible laparoscopic surgery in patients with locally advanced T4 colorectal cancer.

Case 1 involved a 54-year-old woman with a complaint of a lump in the left breast since October. A diagnosis of invasive micropapillary carcinoma(IMPC)was made by core needle biopsy. The profile of the carcinoma was as follows: ER(Allred 8=5+3), PgR(Allred 8=5+3), HER2(1+), Ki-67 index 30%. The patient underwent 4 courses of EC(epirubicin 90mg/ m2, cyclophosphamide 600 mg/m2), followed by 4 courses of triweekly docetaxel and nab-paclitaxel chemotherapy. Bp+Ax was underwent in May 2013. Pathologically, no residual tumor was observed. Case 2 involved a 61-year-old woman with the chief complaint of a lump in the right breast, diagnosed as IMPC by core needle biopsy. The profile of the carcinoma was as follows: ER(Allred 8=5+3), PgR(Allred 0=0+0), HER2(1+), Ki-67 index 30%. Pre-operative treatment consisted of letrozole(2.5mg/day)from May 2013 and hormone therapy for 6 months. Bp+SNB was performed in November 2013. Histopathologically, no remnant of IMPC component was observed apart from an 11mm papillo-tubular carcinoma. In spite of the fact that IMPC is considered highly malignant, pre-operative chemotherapy and hormonal therapy may be effective.

12119 Background: Although ASCO revised Guidelines (2013) recommends referring to psychological professionals if cancer patients show concerns or anxiety about fertility, there is no evidence regarding the efficacy of psychotherapy. The aim of this study is to examine whether the Psycho-Education And Couple Enrichment (O!PEACE) therapy can reduce psychiatric symptoms and improve stress coping and marital relationship in breast cancer patients. Methods: Trial design: multicenter randomized controlled trial, pre-post design. Subjects were women aged 20–39 years with breast cancer before cancer treatment and their husbands. Couples were randomly assigned to receive O!PEACE therapy (n = 37) or not (usual care: n = 37). Assessments of PTSD symptoms, depression and anxiety were made as the primary end points at baseline and at the end of therapy before cancer treatment. Stress coping strategies, resilience, marital relationships, and marital communication were examined as secondary end points. Results: Four participants in O!PEACE therapy and one participant in the usual care withdrew from the trial. Intention-to-treat analyses were conducted using analysis of covariance after multiple imputation by R and SPSS. Series of ANCOVAs were integrated according to Rubin’s rule. A significant decrease was observed in the primary outcome of PTSD symptoms, from baseline to post-intervention, in women who participated in O!PEACE therapy (p = .011, ηp2 = .089). According to post-hoc analyses, for patients with a higher baseline IES-R-J score, O!PEACE therapy resulted in a significantly higher reduction in follow-up assessment IES-R-J score when compared with usual care (U = 172.80, p = .027, r = .258): 59.3% of the women in O!PEACE therapy showed a 5-point or greater reduction, whereas in usual care, 30.0% showed a 5-point or greater reduction. For husbands, the O!PEACE therapy also showed a significant improvement of giving up and blaming others as the stress coping strategy and escape-avoidance coping strategy in their marital communication. For breast cancer patients, the O!PEACE therapy significantly improved support from husbands and the patients’ knowledge level of oncofertility compared with those receiving usual care. Conclusions: Only two counseling sessions of O!PEACE therapy can reduce patients’ distress, improve their husbands’ coping style, and may build a better cooperative relationship for couples in terms of fertility preservation and cancer treatment. Clinical trial information: UMIN000017754 .

Purpose Fertility preservation is an important issue for young cancer patients. Random‐start controlled ovarian stimulation and double ovarian stimulation have been proposed for efficient oocyte retrieval within the limited time before cancer therapy. We aimed to clarify the efficacy of these new protocols within the Japanese population. Methods We performed a retrospective observational study at a multicenter from February 2012 to August 2017. The study entailed 50 cycles with 34 patients who underwent fertility preservation due to breast cancer. Follicular phase or luteal phase ovarian stimulation with aromatase inhibitor was performed. A second ovarian stimulation was started with or without waiting until the next menstruation. We measured the number of retrieved oocytes and cryopreserved oocytes/embryos, the ratio of mature oocytes, and the fertilization rate. Results The numbers of retrieved oocytes and frozen oocytes/embryos were not significantly different between follicular phase and luteal phase ovarian stimulation. The number of retrieved oocytes was not reduced at the second ovum pick up compared to the first ovum pick up in the double ovarian stimulation. Conclusions Random‐start controlled ovarian stimulation and double ovarian stimulation with aromatase inhibitor for breast cancer patients were effective protocols for retrieving a greater number of oocytes within the limited time.

Aims The objective of this study was to investigate the effect of the head-first or tail-first injection of sperm into the cytoplasm by Piezo-ICSI (PICSI) on oocyte survival, fertilization, embryo development and implantation ability in humans. Methods We retrospectively investigated 632 mature oocytes retrieved from 152 infertile patients who attended our PICSI-ET program at the Niji Clinic between October 2010 and January 2014. Of these, 342 mature oocytes retrieved from 75 patients were injected with sperm head first, and 290 mature oocytes retrieved from 77 patients were injected with sperm tail first into the cytoplasm. The rates of oocyte survival, fertilization, good-quality day-3 embryos, pregnancy, implantation and live birth were evaluated in both groups. Results There were no differences among the two groups with respect to survival, fertilization, good-quality day-3 embryos, pregnancy, implantation and live birth rates. Conclusion Sperm direction (i.e., head first or tail first) does not influence the outcome of PICSI in human oocytes, including oocyte survival, fertilization, embryo development and implantation ability. These findings contribute to an understanding of factors that influence the success of human intracytoplasmic sperm injection (ICSI) techniques.

The objective of this study was to investigate the effect of the head-first or tail-first injection of sperm into the cytoplasm by Piezo-ICSI (PICSI) on oocyte survival, fertilization, embryo development and implantation ability in humans.We retrospectively investigated 632 mature oocytes retrieved from 152 infertile patients who attended our PICSI-ET program at the Niji Clinic between October 2010 and January 2014. Of these, 342 mature oocytes retrieved from 75 patients were injected with sperm head first, and 290 mature oocytes retrieved from 77 patients were injected with sperm tail first into the cytoplasm. The rates of oocyte survival, fertilization, good-quality day-3 embryos, pregnancy, implantation and live birth were evaluated in both groups.There were no differences among the two groups with respect to survival, fertilization, good-quality day-3 embryos, pregnancy, implantation and live birth rates.Sperm direction (i.e., head first or tail first) does not influence the outcome of PICSI in human oocytes, including oocyte survival, fertilization, embryo development and implantation ability. These findings contribute to an understanding of factors that influence the success of human intracytoplasmic sperm injection (ICSI) techniques.

The epigenetic status of the genome changes dynamically from fertilization to implantation. In addition, the physiological environment during the process of gametogenesis, including parental age, may affect the epigenome of the embryo after fertilization. It is important to clarify the influence of parental age on gene expression in the embryo in terms of transgenerational epigenetics to improve the techniques currently used in assisted reproductive medicine. Here, we performed single-embryo RNA-seq analysis on human blastocysts fertilized by intracytoplasmic sperm injection, including from relatively elderly mothers, to elucidate the effects of parental age on the embryonic gene expression profile. We identified a number of genes in which the expression levels were decreased with increasing maternal age. Among these genes, several are considered to be important for meiotic chromosomal segregation, such as PTTG1, AURKC, SMC1B and MEIKIN. Furthermore, the expression levels of certain genes critical for autophagy and embryonic growth, specifically GABARAPL1 and GABARAPL3, were negatively correlated with advanced paternal age. In addition, levels of transcripts derived from major satellite repeats also decreased as the maternal age increased. These results suggest that epigenetic modifications of the oocyte genome may change with parental age and be transmitted to the next generation.

A 69-year-old woman underwent total gastrectomy for advanced gastric cancer with pyloric stenosis. She had a good postoperative course and was discharged 2 weeks after surgery. She received adjuvant chemotherapy with S-1 after discharge. One month after the initiation of the adjuvant chemotherapy, she complained of wobbling and weakness of her limbs. She stopped intake of S-1, but the symptoms did not improve. She was admitted to the hospital, but she became unconscious and had headache and blurred vision. We conducted a cerebrospinal fluid examination and made a diagnosis of meningeal carcinomatosis. After we started intrathecal infusion of methotrexate and Ara-C, referring to case reports clinical symptoms, including unconsciousness, headache, and left upper limb paralysis, improved and the CEA level in cerebrospinal fluid decreased.

The first patient was a 62-year-old woman who was referred to our hospital with the complaint of a left breast tumor. She was diagnosed with invasive ductal carcinoma(T1N0M0, stage I). The tumor was ER-positive, PgR-negative, and HER2- negative. She was treated with toremifene, letrozole, and anastrozole as neoadjuvant hormone therapy for 4 months, but the tumor increased in size. The clinical response was judged as progressive disease, and a left partial mastectomy and axillary lymph node dissection were performed. Chemotherapy and radiotherapy were performed after surgery. The second patient was a 68-year-old woman who was referred to our hospital with the complaint of a right breast tumor. She was diagnosed as invasive ductal carcinoma(T1N0M0, stage I). The tumor was ER-positive, PgR-negative, and HER2-negative. She was treated with letrozole as neoadjuvant hormone therapy for 4 months, but the tumor increased in size. The clinical response was judged as progressive disease, and a right partial mastectomy and axillary lymph node dissection were performed. Chemotherapy and radiotherapy were performed after surgery. Although the evidence is still insufficient, with neoadjuvant hormone therapy for hormone-sensitive breast cancer, improved tumor shrinkage and breast conservation have been reported. We experienced two cases in which the tumor increased in size during neoadjuvant hormone therapy; however, even though these cases showed no apparent effect, chemotherapy may be effective in future cases.

To investigate the beneficial effects of inchinkoto (ICKT) in the liver after 70% hepatectomy following ischemia reperfusion.Wistar rats were divided into 3 groups: simple laparotomy and 70% hepatectomy (Hx), 70% hepatectomy following ischemia reperfusion (IR) with vehicle (IRHxV), 70% hepatectomy following IR with ICKT (1 or 2 g/kg of body weight; IRHxK). Vehicle or ICKT was administered for 3 days preoperatively. The hepatoduodenal ligament was clamped for 15 minutes before hepatectomy in the IRHx groups. Rats were killed 1 hours after hepatectomy. In other experiments, the hepatoduodenal ligament was clamped for 30 minutes, with or without ICKT treatment, to evaluate the effect of ICKT on IR injury-induced mortality. Serum transaminase levels and the gene expression of inflammatory cytokines and inducible nitric oxide synthase in the remnant liver were determined. Furthermore, the expression of antioxidant genes was evaluated by PCR array.The elevation of serum transaminase levels, the upregulation of genes for inflammatory cytokines and inducible nitric oxide synthase, and the increased formation of nitrotyrosine observed in the remnant livers of the IRHxV group were all significantly attenuated by preoperative administration of ICKT in the IRHxK group. The expression of antioxidant genes was also higher in the IRHxK group compared with that of the IRHxV group. Moreover, administration of ICKT significantly reduced the mortality induced by IRHx after 30-minute ischemia.Preoperative administration of ICKT provides beneficial effects through attenuating inflammatory responses and oxidative stress in the liver following IR and subsequent hepatectomy.

Acute obstructive cholangitis is a common disease with a high mortality rate. Ligands for peroxisome proliferator-activated receptor-γ (PPARγ), such as 15-deoxy-Δ12,14-prostaglandin J2 (15D-PGJ2), have been proposed as a new class of anti-inflammatory compounds. This study investigated the effect of 15D-PGJ2 treatment on lipopolysaccharide (LPS)-induced acute obstructive cholangitis. The rats were randomly assigned to five groups: sham operation (Sham; simple laparotomy), sham operation with intraperitoneal saline infusion (Sham+Saline), sham operation with intraperitoneal LPS infusion (Sham+LPS), bile duct ligation (BDL) with saline infusion into the bile duct (BDL+Saline), and BDL with LPS infusion into the bile duct (BDL+LPS). Biochemical assays of blood samples, histology of the liver, portal venous pressure, hyaluronic acid clearance, and expression of inflammation-associated genes in the liver were evaluated. Furthermore, the Sham+LPS and the BDL+LPS group were divided into two groups (with and without 15D-PGJ2 treatment), and their survival rates were compared. Biochemical assays of blood samples, portal venous pressure, hyaluronic acid clearance, and expression of inflammation-associated genes in the liver were all significantly higher in the BDL+LPS group compared with those in the BDL+Saline group, indicating the presence of increased liver damage in the first group. However, preoperative administration of 15D-PGJ2 significantly improved these outcomes. Furthermore, the survival rate after establishment of cholangitis was significantly improved by the administration of 15D-PGJ2 in the BDL+LPS group. These results clearly demonstrate that 15D-PGJ2 inhibits the inflammatory response and endothelial cell damage seen in acute obstructive cholangitis and could contribute to improve the outcome of this pathology.

The aim of this study was to determine if estrogen plays any role in the process of hepatic regeneration of nonligated lobe after portal vein branch ligation (PBL). We also investigated whether estrogen has any association with serotonin action during liver regeneration. Ovariectomized female rats with (E group) or without (non-E group) estrogen pellet were subjected to PBL on the left and middle lobes. Thereafter, the rats were killed, and blood, liver, and small intestine were sampled and analyzed. Sham animals underwent only ovariectomy and laparotomy. The E group showed a significantly greater regeneration rate than the non-E group at days 1, 2, and 7 after PBL. The activation of hepatic regeneration-related genes (such as IL-6, TNF-alpha, hepatic growth factor, c-fos, and c-myc) was also significantly higher in the E group as compared with the non-E group. Gene expression of serotonin receptor (5-HT2A) in the liver and tryptophan hydroxylase 1 in the small intestine were also up-regulated in the E group, indicating an activation of serotonin system in the E group. Additionally, total intestinal flow, portal venous flow, and hepatic arterial flow determined by fluorescent microsphere were significantly higher in the E group compared with the non-E group. Moreover, serotonin receptor antagonist (ketanserin) significantly attenuated liver regeneration rate in the E group. These results indicated that estrogen plays an important role in the process of liver regeneration after PBL. Our results also indicated that estrogen is at least partly related to the activation of serotonin system, which is also important in the process of liver regeneration.