A case of 49,XXXYY followed-up from infancy to adulthood with review of literature.

49,XXXYY is an extremely rare sex chromosomal aneuploidy (SCA), with only seven cases reported worldwide to date. Among these cases, only three have been documented into adulthood. Moreover, no cases of 49,XXXYY have been reported in Japan. This SCA has been identified in two scenarios: in vitro fertilization and abortion. Similar to 47,XXY, this aneuploidy is a type of Klinefelter syndrome. Aneuploidy of the X chromosome can lead to various progressive complications due to excess X chromosomes. Herein, we present the case of a Japanese man with 49,XXXYY. He exhibited developmental delays and external genitalia abnormalities since early infancy but was not closely monitored for these symptoms until the age of 3 years old. At that time, a chromosome test revealed his karyotype to be 49,XXXYY. Subsequent examinations were conducted due to various symptoms, including delayed motor development, intellectual disability, facial dysmorphisms, forearm deformities, hip dysplasia, cryptorchidism, micropenis, primary hypogonadism, and essential tremor. Since reaching puberty, he has undergone testosterone replacement therapy for primary hypogonadism, experiencing no complications related to androgen deficiency to date. He has maintained normal lipid and glucose metabolism, as well as bone density, for a prolonged period. There are no other reports on the long-term effects of testosterone treatment for the SCA. Appropriate testosterone replacement therapy is recommended for individuals with 49,XXXYY to prevent complications. This report will contribute to an enhanced understanding of the 49,XXXYY phenotype, aiding in the diagnosis, treatment, and genetic counseling of future cases.

Diagnostic Performance of Physician Gestalt for Bacteremia in Patients in the Process of Being Admitted With Suspected Infection.

BACKGROUND: Due to potentially fatal consequences of missed bacteremia, blood cultures are often overused. While there are several prediction models that can be used to identify patients who truly need blood cultures, physicians often rely on their gestalt. We evaluated the diagnostic performance of physician gestalt for bacteremia in comparison with 2 existing prediction models: Takeshima and Shapiro. METHODS: The study enrolled consecutive adult patients with suspected infection who were in the process of being admitted to the general medicine department at 2 hospitals between April 2017 and January 2019. Attending physicians provided gestalt regarding risk of bacteremia (0%-100%). Patients with a <10% risk estimated via each strategy (ie, physician gestalt or 2 existing models) were categorized as bacteremia excluded (ie, blood cultures were considered unnecessary). Strategies were compared in terms of safety (proportion of patients with bacteremia among those classified as bacteremia excluded) and efficiency (proportion of patients classified as bacteremia excluded among the total cohort). RESULTS: Among 2014 patients, 292 (14.5%) were diagnosed with bacteremia. The safety of physician gestalt and the Takeshima and Shapiro models was 3.7% (95% confidence interval [CI], 2.2% to 5.7%), 6.5% (95% CI, 5.0% to 7.9%), and 10.8% (95% CI, 9.4% to 12.3%), whereas the efficiency of each strategy was 22.4% (95% CI, 22.5% to 26.3%), 52.7% (95% CI, 50.5% to 54.9%), and 87.8% (95% CI, 86.3% to 89.2%), respectively. CONCLUSIONS: Physician gestalt was safer but less efficient than existing models. Clinical prediction models could help reduce the overuse of blood cultures.

Upfront rituximab therapy for thrombotic thrombocytopenic purpura in systemic lupus erythematosus: a case-based review.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of various autoantibodies and deposition of immune complexes on tissues. Acquired thrombotic thrombocytopenic purpura (TTP) is a life-threatening hematological disorder that rarely develops in SLE, mainly caused by inhibitory or clearing autoantibody against ADAMTS13. Although B cells play critical roles in the pathogenesis of two diseases, the role of B-cell depletion therapy using rituximab (RTX), a chimeric monoclonal antibody targeting CD20, in the management of TTP associated with SLE remains unclear. We present a 27-year-old woman who manifested TTP and nephritis simultaneously at diagnosis of SLE. This patient successfully responded to high-dose glucocorticoids combined with plasma exchange, and early administration of RTX-induced sustained remission of TTP without relapse over 16 months. This literature review in light of our case demonstrates relationship between early intervention with RTX and better treatment response despite the degree of ADAMTS13 activity. Moreover, we discuss the clinical features in TTP associated with SLE, risk factors for the development of TTP in SLE, and possible outcomes based on RTX dose. It is important to consider upfront RTX as a promising treatment strategy for SLE-associated secondary TTP to improve short-term response and long-term prognosis.

The Potential of Computed Tomography Volumetry for the Surgical Treatment in Bilateral Macronodular Adrenal Hyperplasia: A Case Report.

Although adrenal resection is a major option to control hypercortisolemia in patients with bilateral macronodular adrenal hyperplasia, a predictive method for postoperative cortisol production has not been established. A 53-year-old man with ulcerative colitis was referred to our hospital for bilateral multiple adrenal nodules and hypertension. Physical and endocrinological examination revealed inappropriate cortisol production and suppressed secretion of adrenocorticotropic hormone with no typical signs of Cushing's syndrome. Imaging analysis revealed bilateral adrenal nodular enlargement, the nodules of which had the radiological features of adrenocortical adenomas without inter-nodular heterogeneity. In addition, computed tomography volumetry demonstrated that the left adrenal gland (70 mL) accounts for three quarters of the total adrenal volume (93 mL). The patient was diagnosed as subclinical Cushing's syndrome due to bilateral macronodular adrenal hyperplasia, and subsequently underwent a left laparoscopic adrenalectomy with the estimation of 75% decrease in the cortisol level based on the adrenal volume. The surgical treatment ultimately resulted in control of the cortisol level within the normal range, which was compatible to our preoperative prediction. However, regardless of the sufficient cortisol level, ulcerative colitis was exacerbated after the surgery, which needed a systemic therapy for remission. This case indicates successful surgical control of hypercortisolemia based on computed tomography volumetry in bilateral macronodular adrenal hyperplasia, as well as the perioperative exacerbation risk for inflammatory diseases in Cushing's syndrome. We report the potential utility of computed tomography volumetry as a quantitative method with retrospective evaluation of our historical cases.

Four versus six chemotherapy cycles in endometrial carcinoma with a high risk of recurrence: a retrospective study.

OBJECTIVE: This study compared the survival outcomes and the incidence of chemotherapy-related adverse events in endometrial cancer patients who received four and six cycles of adjuvant chemotherapy to examine the optimal number of adjuvant chemotherapy cycles. METHODS: A total of 112 patients with endometrial cancer with a high risk of recurrence were retrospectively enrolled; 46 patients received four cycles and 66 received six cycles of adjuvant chemotherapy. Between-group differences of overall survival, disease-free survival, hematological and non-hematological toxicities were analyzed. Baseline patient's background differences were assessed with inverse probability of treatment weighting using propensity score. RESULTS: Overall and disease-free survivals between the two groups were not significantly different. Paclitaxel + carboplatin, every 3-4 weeks was the most frequently used chemotherapy regimen in both groups. Patients in the six-cycle chemotherapy group developed neutropenia G4 or febrile neutropenia more frequently than those in the four-cycle group; odds ratio (95% confidence interval) is 4.07 (1.51-10.96). Peripheral sensory neuropathy was the most frequently observed non-hematological toxicity; the incidence of peripheral sensory neuropathy was not significantly different between four- and six-cycle chemotherapy group, P = 0.832. The result was same in the subgroup analysis in patients who received TC regimen, P = 0.455. CONCLUSION: This study implies a possible benefit of fewer cycles of adjuvant chemotherapy in endometrial cancer patients with a high risk of recurrence because of the lower incidence of hematological toxicities without impairing survival outcomes.

Molecular analysis of virulence factors of hypermucoviscous Klebsiella pneumoniae in a diabetes patient with multifocal intramuscular and musculoskeletal abscesses.

Unusual community-acquired invasive Klebsiella pneumoniae infection has been reported worldwide, particularly in Asia. Recently, several virulence-associated genes of the isolates have been investigated. We report a case of multifocal intramuscular and musculoskeletal abscesses caused by K. pneumoniae in a 61-year-old male diabetes patient. A string test of the K. pneumoniae isolate, which was recovered from abscesses obtained by surgical debridement and drainage, was positive. We used whole-genome sequencing to analyze the virulence-associated gene profile of the isolate. The isolate belonged to the K2 genotype with sequence type 375. The isolate harbored rmpA and rmpA2, which induce serum resistance (hypermucoviscosity). The isolate also carried siderophores, i.e., aerobactin and salmochelin, which are associated with enhanced bacterial growth. The isolate did not harbor K1-unique virulence factors, such as colibactin, microcin, and yersiniabactin. Our K2 strain harbored a combination of virulence plasmid-associated genes-rmpA/A2 and siderophores (aerobactin and salmochelin). Hence, we advocate that essential molecular virulence factors of isolates that cannot be identified by a string test and capsular serotyping alone may exist.

High Relapse Rate in Patients with Polymyalgia Rheumatica despite the Combination of Immunosuppressants and Prednisolone: A Single Center Experience of 89 patients.

Polymyalgia rheumatica (PMR) is an inflammatory disorder in the elderly and is characterized by pain in the shoulders and lower back. Previous studies from western countries have shown that relapse is frequent; however, there are only a few reports on the relapse rate in Japan. Here we examined the relapse rate, and sought to identify factors that predict recurrence in patients with PMR. Of 110 patients who fulfilled the Bird's criteria for PMR between May 2011 and June 2019, 21 patients were excluded, and the remaining 89 patients were followed up until July 2019. Relapse was defined when clinical symptoms were exacerbated and serum C-reactive protein level increased. The relapse-free survival curves were plotted using the Kaplan-Meier method, and log-rank test was used for statistical analysis. The mean age of the 89 patients (50 males and 39 females) was 71.8 years. The mean dose of initial prednisolone (PSL) was 11.8 mg/day. The 1-, 3-, and 5-year relapse-free survival rates were 81.6%, 58.0%, and 52.3% (N = 59, 21, and 7), respectively. In patients who experienced recurrence, the 1- and 3-year second relapse-free survival rates were 58.3% and 27.3% (N = 18 and 3), respectively. Immunosuppressants, such as methotrexate and tacrolimus, were added to PSL in 19 of 30 patients who experienced relapse at the discretion of the attending physicians; however, none of the immunosuppressants worked for preventing second relapses and had steroid-sparing effects. These results indicate that effective immunosuppressants are required to suppress relapse in the treatment of PMR.

Multidisciplinary Approach to Prevent de novo Hepatitis B in Patients with Rheumatoid Arthritis.

The reactivation of hepatitis B virus (HBV) in patients with rheumatoid arthritis (RA) is currently a social problem. Our hospital has established a project team, which consisted of medical staff including doctors, nurses, pharmacists, and technicians, to prevent HBV reactivation and subsequent de novo hepatitis B in 2015. To verify the usefulness of the team, we aimed to examine the implementation rate of HBV screening tests in patients with RA in 2011, 2015, and 2018. We also examined the rate of HBV infection, as well as the rate of HBV reactivation during the course. In this study, medical records of patients who visited our hospital in 2011, 2015, and 2018 were retrospectively reviewed. HBV screening was completed when hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and hepatitis B core antibody (HBcAb) were all examined. The prevalence of patients who completed HBV screening dramatically increased from 2.4% in 2011 to 79.1% in 2015 and 86.9% in 2018. Patients who completed the screening had significantly higher rates of liver dysfunction, methotrexate use, and use of biological disease-modifying antirheumatic drugs than those who did not. Of the 767 patients who completed HBV screening in 2018, 157 patients (20.5%) had previously resolved HBV infection (HBsAg-negative but HBsAb- and/or HBcAb-positive). During a mean follow-up of 41.0 months, reactivation of HBV was observed in 10 out of the 157 patients (6.4%); however, none developed de novo hepatitis B. In conclusion, our multidisciplinary approach to prevent de novo hepatitis B is considered useful.

Molecular-targeted therapies and precision medicine for endometrial cancer.

The overall survival rate of patients with early-stage endometrial cancer is relatively high; however, there are few treatment options for patients with advanced or recurrent endometrial cancer, and the prognosis of such patients remains poor. Recent progress in molecular-targeted therapies demonstrated that they have the potential to improve the long-term survival of cancer patients with appropriate biomarkers. However, the median progression-free survival of patients who received single-agent molecular-targeted therapy was <5 months, and the development of molecular-targeted therapies for endometrial cancer patients is urgently needed. This review highlights the previous efforts, including antiangiogenesis therapy, PI3K/AKT/mTOR pathway inhibitor treatment and epidermal growth factor receptor inhibitor treatment and reports on ongoing phase 2 clinical trials, including immune checkpoint inhibitor and PARP inhibitor. We also summarized the genetic background of endometrial cancer according to The Cancer Genome Atlas data and considered the theoretical background for future efforts to prolong the survival of patients with refractory endometrial cancer and for other interesting challenges.

Laparoscopic Sleeve Gastrectomy on Severe Obesity after Intracranial Germinoma Treatment: A Case Report.

Hypothalamic obesity is a clinical syndrome characterized by severe and refractory obesity that is caused by hypothalamic function impairment. Recently, bariatric surgery has been attempted for patients with hypothalamic obesity after craniopharyngioma, but experiences have not yet been accumulated in other hypothalamic disorders. Here, we report the case of a 39-year-old male patient with panhypopituitarism who received laparoscopic sleeve gastrectomy (LSG) after intracranial germinoma treatment. The patient was diagnosed with intracranial germinoma at age 15 and achieved complete remission after radiotherapy (total 50 Gy). He was obese during diagnosis [body mass index (BMI), 29.2 kg/m2], and his obesity gradually worsened after the intracranial germinoma treatment, and LSG was considered when his BMI was 48.6 kg/m2. After 1 month of hospitalized diet-exercise program, LSG was performed. After LSG, his BMI gradually decreased and reached 38.8 kg/m2 on the day of discharge (6 weeks after the surgery). Five months after LSG, his insulin resistance improved, but insulin hypersecretion remained. Fifteen months after the surgery, his BMI was 31.2 kg/m2, with marked decrease in visceral and subcutaneous fat areas (from 393.8 cm2 and 168.2 cm2 before the surgery to 111.5 cm2 and 56.3 cm2, respectively.). To our knowledge, this is the first case of LSG for hypothalamic obesity after intracranial germinoma treatment. Although the pathophysiology of hypothalamic obesity is different from that of primary obesity, LSG could be a successful therapeutic choice for patients with hypothalamic obesity after the intracranial germinoma treatment.

Effects of surgical treatment for acromegaly on knee MRI structural features.

Acromegalic arthropathy is a common complication of acromegaly and harms the quality of life of the patients even after acromegaly is in long-term remission. A recent study demonstrated by knee MRI the characteristic structural features of acromegalic arthropathy. However, the effects of treatment for acromegaly on such structural features are almost unknown. This study was undertaken to analyze the effects of transsphenoidal surgery (TSS) on acromegalic arthropathy and elucidate whether knee MRI findings are reversible or irreversible. We analyzed 22 patients with acromegaly (63.7% females, median age 58 years) by knee MRI at diagnosis. Out of these 22 patients, 16 who underwent TSS (68.9% female, median age 58 years) were also subjected to knee MRI 2 months after TSS. As for X-ray undetectable findings, MRI detected synovial thickening, bone marrow lesion, ligament injury and meniscus injury in 22.7%, 22.7%, 4.7% and 59.1% of the patients, respectively. With respect to the 16 patients who underwent TSS, clinical and structural improvements were observed respectively in 100%, 66.7% and 66.7% of the patients who showed knee joint pain, synovial thickening and bone marrow lesion before TSS. However, no patient showed structural improvement of meniscus injury after TSS. In acromegalic arthropathy, synovial thickening and bone marrow lesions are reversible while meniscus injury is irreversible. Because all those findings are associated with the exacerbation of arthropathy, they may be therapeutic targets for preventing the progression of arthropathy by endocrinological and orthopedic intervention.

Loss of luteotropic prostaglandin E plays an important role in the regulation of luteolysis in women.

STUDY QUESTION: Do intraluteal prostaglandins (PG) contribute to luteal regulation in women? SUMMARY ANSWER: Prostaglandin E (PGE), which is produced in human granulosa-lutein cells stimulated with luteotropic hCG, exerts similar luteotropic effects to hCG, and the expression of PG synthetic and metabolic enzymes in the human CL is driven toward less PGE but more prostaglandin F (PGF) during luteolysis. WHAT IS KNOWN ALREADY: Uterine PGF is a major luteolysin in many non-primate species but not in women. Increases in the PGF synthase, aldo-ketoreductase family one member C3 (AKR1C3), have been observed in the CL of marmoset monkeys during luteolysis. PGE prevents spontaneous or induced luteolysis in domestic animals. STUDY DESIGN, SIZE, DURATION: Human CL tissues staged as the early-luteal (n = 6), mid-luteal (n = 6), late-luteal (n = 5) and menstrual (n = 3) phases were obtained at the time of hysterectomy for benign gynecological conditions. Luteinized granulosa cells (LGCs) were purified from follicular fluids obtained from patients undergoing assisted conception. PARTICIPANTS/MATERIALS, SETTING, METHODS: Upon collection, one half of the CL was snap-frozen and the other was fixed with formalin and processed for immunohistochemical analysis of a PGE synthase (PTGES). Quantitative RT-PCR was employed to examine changes in the mRNA abundance of PG synthetic and metabolic enzymes, steroidogenic enzymes, and luteolytic molecules in the staged human CL and in human LGCs in vitro treated with hCG, PGE and PGF. A PGE withdrawal experiment was also conducted in order to reveal the effects of the loss of PGE in LGCs. Progesterone concentrations in the culture medium were measured. MAIN RESULTS AND THE ROLE OF CHANCE: The key enzyme for PGE synthesis, PTGES mRNA was abundant in the functional CL during the mid-luteal phase (P < 0.01), while mRNA abundance for genes involved in PGF synthesis (AKR1B1 and AKR1C1-3) increased in the CL during the late-luteal phase and menstruation (P < 0.05-0.001). PTGES mRNA expression positively correlated with that of 3ß-hydroxysteroid dehydrogenase (HSD3B1; r = 0.7836, P < 0.001), while AKR1C3 expression inversely correlated with that of HSD3B1 (r = -0.7514, P = 0.0012) and PTGES (r = -0.6923, P = 0.0042). PGE exerted similar effects to hCG-promoting genes, such as steroidogenic acute regulatory protein (STAR) and HSD3B1, to produce progesterone and luteotropic PGE, suppress PGF synthetic enzymes and down-regulate luteolytic molecules such as ßA- and ßB-inhibin subunits (INHBA and INHBB) and bone morphogenetic proteins (BMP2, BMP4 and BMP6). PGE withdrawal resulted in reductions in the enzymes that produce progesterone (STAR; P < 0.001) and PGE (PTGES; P < 0.001), and the capacity to produce PGE decreased, while the capacity to produce PGF increased during the culture. The addition of PGF did not recapitulate the luteolytic effects of PGE withdrawal. LARGE SCALE DATA: None. LIMITATIONS, REASONS FOR CAUTION: Changes in mRNA expression of PG synthetic and metabolic enzymes may not represent actual increases in PGF during luteolysis in the CL. The effects of PGF on luteal cells currently remain unclear and the mechanisms responsible for decreases in the synthesis of PGE in vitro and at luteolysis have not been elucidated in detail. WIDER IMPLICATIONS OF THE FINDINGS: The results obtained strongly support a luteotropic function of PGE in regulation of the human CL. They suggest that the main PG produced in human luteal tissue changes from PGE to PGF during the maturation and regression of the CL, and the loss of PGE is more important than the effects of PGF during luteolysis in women. This may be accompanied by reduced effects of LH/hCG in luteal cells, particularly decreased activation of cAMP/protein kinase A; however, the underlying mechanisms remain unknown. STUDY FUNDING AND COMPETING INTEREST(S): This study was supported by the Cunningham Trust to WCD, a Postdoctoral Fellowship for Research Abroad from the Japan Society for the Promotion of Science and the Suntory Foundation for Life Sciences to J.N.-K.; W.C.D. is supported by an MRC Centre Grant G1002033 and a Scottish Senior Clinical Fellowship. The authors have nothing to disclose.

Intra-adrenal Aldosterone Secretion: Segmental Adrenal Venous Sampling for Localization.

PURPOSE: To use segmental adrenal venous sampling (AVS) (S-AVS) of effluent tributaries (a version of AVS that, in addition to helping identify aldosterone hypersecretion, also enables the evaluation of intra-adrenal hormone distribution) to detect and localize intra-adrenal aldosterone secretion. MATERIALS AND METHODS: The institutional review board approved this study, and all patients provided informed consent. S-AVS was performed in 65 patients with primary aldosteronism (34 men; mean age, 50.9 years ± 11 [standard deviation]). A microcatheter was inserted in first-degree tributary veins. Unilateral aldosterone hypersecretion at the adrenal central vein was determined according to the lateralization index after cosyntropin stimulation. Excess aldosterone secretion at the adrenal tributary vein was considered to be present when the aldosterone/cortisol ratio from this vein exceeded that from the external iliac vein; suppressed secretion was indicated by the opposite pattern. Categoric variables were expressed as numbers and percentages; continuous variables were expressed as means ± standard errors of the mean. RESULTS: The AVS success rate, indicated by a selectivity index of 5 or greater, was 98% (64 of 65). The mean numbers of sampled tributaries on the left and right sides were 2.11 and 1.02, respectively. The following diagnoses were made on the basis of S-AVS results: unilateral aldosterone hypersecretion in 30 patients, bilateral hypersecretion without suppressed segments in 22 patients, and bilateral hypersecretion with at least one suppressed segment in 12 patients. None of the patients experienced severe complications. CONCLUSION: S-AVS could be used to identify heterogeneous intra-adrenal aldosterone secretion. Patients who have bilateral aldosterone-producing adenomas can be treated with adrenal-sparing surgery or other minimally invasive local therapies if any suppressed segment is identified at S-AVS.

Dynamic multidetector CT and non-contrast-enhanced MR for right adrenal vein imaging: comparison with catheter venography in adrenal venous sampling.

OBJECTIVES: To evaluate visualization of the right adrenal vein (RAV) with multidetector CT and non-contrast-enhanced MR imaging in patients with primary aldosteronism. METHODS: A total of 125 patients (67 men) scheduled for adrenal venous sampling (AVS) were included. Dynamic 64-detector-row CT and balanced steady-state free precession-based non-contrast-enhanced 3-T MR imaging were performed. RAV visualization based on a four-point score was documented. Both anatomical location and variation on cross-sectional imaging were evaluated, and the findings were compared with catheter venography as the gold standard. RESULTS: The RAV was visualized in 93.2% by CT and 84.8% by MR imaging (p = 0.02). Positive predictive values of RAV visualization were 100% for CT and 95.2% for MR imaging. Imaging score was significantly higher in CT than MR imaging (p < 0.01). The RAV formed a common trunk with an accessory hepatic vein in 16% of patients. The RAV orifice level on cross-sectional imaging was concordant with catheter venography within the range of 1/3 vertebral height in >70% of subjects. Success rate of AVS was 99.2%. CONCLUSIONS: Dynamic CT is a reliable way to map the RAV prior to AVS. Non-contrast-enhanced MR imaging is an alternative when there is a risk of complication from contrast media or radiation exposure. KEY POINTS: Dynamic CT and non-contrast-enhanced MR imaging detect the right adrenal vein (RAV). Dynamic CT can visualize the RAV more than non-contrast-enhanced MR imaging. Mapping the RAV helps to achieve successful adrenal venous sampling. Sixteen per cent of RAVs share the common trunk with accessory hepatic veins.

Regulated C-C motif ligand 2 (CCL2) in luteal cells contributes to macrophage infiltration into the human corpus luteum during luteolysis.

Intense macrophage infiltration is observed during luteolysis in various animals including women; however, we still do not know how macrophage infiltration into the human corpus luteum (CL) during luteolysis is regulated. In this study, we examined the expression, localization and regulation of an important chemokine for the recruitment of monocyte/macrophage lineages, C-C motif ligand 2 (CCL2), in the human CL across the luteal phase and in cultured human luteinized granulosa cells (LGCs), with special reference to the number of infiltrating macrophages and luteal cell function. CCL2 mRNA increased in the non-functional regressing CL during menstruation (P < 0.01), corresponding to an elevated mRNA expression of a macrophage-derived cytokine, tumor necrosis factor (TNF), and an increased number of infiltrating macrophages positively stained with a macrophage marker, CD68. CCL2 protein was immunohistochemically localized to the cytoplasm of granulosa-lutein and theca-lutein cells, and CCL2 mRNA was significantly reduced by hCG both in vivo (P < 0.05) and in vitro (P < 0.01). CCL2 was also down-regulated by luteotrophic prostaglandin (PG) E (P < 0.0001), but up-regulated by luteolytic PGF (P < 0.05) in vitro. Administration of TNF significantly enhanced the CCL2 mRNA expression in cultured LGCs (P < 0.01). A greater abundance of infiltrating macrophages were found around granulosa-lutein cells lacking 3ß-HSD or PGE synthase (PGES) immunostaining. CCL2 mRNA expression was negatively correlated with both HSD3B1 and PGES, suggesting that locally produced progesterone and PGE suppress macrophage infiltration into the CL. Taken together, the infiltration of macrophages in the human CL is regulated by endocrine and paracrine molecules via regulation of the CCL2 expression in luteal cells.

Management of secondary infertility following cesarean section: Report from the Subcommittee of the Reproductive Endocrinology Committee of the Japan Society of Obstetrics and Gynecology.

AIM: The aim of this study was to examine the current status and management of secondary infertility following cesarean section in Japan. MATERIAL AND METHODS: A two-step questionnaire survey was performed in 1092 facilities, including teaching hospitals and artificial reproductive technology clinics, registered with the Japan Society of Obstetrics and Gynecology. In our questionnaires, we obtained data about symptoms, clinical findings, diagnostic methods, and pregnancy outcomes. Treatments were sorted into three groups, namely typical infertility treatment (group A), conservative treatment (group B), and operative treatment (group C). RESULTS: Of the 1092 facilities, 616 (56%) sent back reply forms to the first questionnaire; 56 (32%) of 176 facilities answered the second questionnaire, and 189 cases were able to be analyzed after completion of the two questionnaires. The commonest symptom was abnormal uterine bleeding during the follicular phase (91 cases; 48% of the 189 eligible cases), and the commonest clinical finding was fluid pooling in the area of cesarean scar dehiscence during the ovulatory phase (142 cases; 75%). The most commonly used diagnostic method was transvaginal ultrasound (153 cases, 81%). The pregnancy rate was 33% in group A, 50% in group B, and 60% in group C. In patients with abnormal uterine bleeding, painful symptoms and fluid pooling at the cesarean scar dehiscence, the pregnancy rate was significantly higher in group C (64%) than in group A (16%; P = 0.0063). CONCLUSIONS: We recommend operative treatment for secondary infertility following cesarean section with painful symptoms and fluid pooling at the site of cesarean scar dehiscence.

[Present condition and new vista of the future in robotic-assisted laparoscopic surgeries].

The introduction of robotic surgical system is one of the most exciting topic in the field of the surgery. In this symposium, we presented and explained the present condition of robotic-assisted laparoscopic surgeries performed in the department of Urology, Gastroenterology and Gynecology of the Hokkaido University Hospital. By using this surgical system, laparoscopic surgery, which is generally considered to be difficult, can be safely performed by surgeons. Especially in radical prostatectomy against localized prostate cancer, this surgical approach brought the decrease in peri- and postoperative problems including blood loss and postoperative urinary incontinence in comparison with open or laparoscopic radical prostatectomy. We wish that this symposium would help the audience to understand the present condition and new vista of the future in robotic-assisted laparoscopic surgeries.