The PRB-dependent FOXO1/IGFBP-1 axis is essential for progestin to inhibit endometrial epithelial growth

Progestin inhibits the growth of normal and cancerous endometria via the progesterone receptor (PR), but the distinct functions and signalings of PR subtypes have not been fully understood. The aim of the present study was to dissect the key pathways of progestin to inhibit endometrial epithelial growth. Immortalized endometrial epithelial cells (EM-E6/E7/TERT) with stable PRA or PRB expression were established and used for the experiments. In vitro growth inhibition by progestin was mainly observed in EM-E6/E7/TERT cells with PRB rather than those with PRA. RT-PCR assay confirmed that FOXO1, a key gene for progestin action, was up-regulated by progestin in a PRB-dependent manner. cDNA microarray analysis identified IGFBP-1, which contains FOXO1 binding sites on its promoter, to be induced by medroxyprogesterone acetate (MPA) in EM-E6/E7/TERT cells with PRB but not with PRA. siRNA knockdown of FOXO1 disturbed the induction of IGFBP-1 by MPA, while IGFBP-1 knockdown showed no effect on MPA-induced FOXO1 expression, indicating that FOXO1 is an upstream regulator of IGFBP-1. Luciferase reporter assays showed that MPA activated the IGFBP-1 promoter, which was cancelled by FOXO1 knockdown. Chromatin immunoprecipitation assay confirmed the in vivo binding of FOXO1 to the core promoter of IGFBP-1. IGFBP-1 knockdown significantly attenuated the growth inhibitory effects of MPA. The FOXO1/IGFBP-1 axis is essential for PRB-dependent growth inhibition of endometrial epithelial cells, offering a potential therapeutic clue to enhance the progestin effect.     

Precise anatomy of the vesico-uterine ligament for radical hysterectomy

OBJECTIVES: To clarify the anatomy of the vesico-uterine ligament (VUL), we meticulously separated the VUL under magnification (x2.5) during Okabayashi's radical hysterectomy. METHODS: Fifty-nine patients (TNM nomenclature: pTIb: 39, pT2a: 5, pT2b: 7, after trans-arterial anticancer-drug infusion treatment for the cervical cancer: 8) underwent this meticulous operation. Blood loss was recorded at two separate time points: during the separation of the VUL and after removal of the uterus. RESULTS: After complete separation of the uterine artery and superficial uterine vein from the ureter, we could identify the genuine connective tissue of the anterior leaf of the VUL in which we isolate and divide a distinct bundle of blood vessels: the cervicovesical vessels that cross over the ureter from the bladder to the cervix. The remaining tissues in the anterior leaf is only avascular connective tissue. The posterior leaf of the VUL is the tissue residing under the ureter connecting the posterior wall of the bladder and the lateral cervix/upper lateral vagina. In the connective tissues, we identified the middle and inferior vesical veins connecting with the deep uterine vein. The division of these veins could separate the urinary bladder with ureters completely from the lateral cervix and upper vagina. The mean blood loss during the separation of the VUL was 20+/-10 g (N=59) and after radical hysterectomy was 189+/-91.6 g (N=59). CONCLUSION: A precise network of blood vessels in the VUL is identified. The knowledge of this anatomy is important to perform radical hysterectomy.     

Comparative results of conservative treatments for isolated anterior talofibular ligament (ATFL) injury and injury to both the ATFL and calcaneofibular ligament of the ankle as assessed by subtalar arthrography

Background There have been no reports describing the results of conservative treatment of acute lateral ligament injury of the ankle in detail in terms of the severity of the injury, and the results of conservative treatment for injury with severe instability are still controversial. The purpose of this study was to assess the results of nonoperative treatment of acute lateral ligament injury according to its severity. Methods Fifty-five consecutive acute lateral ankle ligament injuries in 54 patients who were treated nonoperatively were followed up as a prospective study. Twenty-seven were male patients and 27 were female patients; the average age was 23.9 years (12–55 years). The patients were divided into two groups according to the extent of the ligament injury: patients with an isolated injury of the anterior talofibular ligament and those with combined injuries of the anterior talofibular ligament and the calcaneofibular ligament. In addition to the routine examinations for inversion ankle sprain, subtalar arthrography was mainly used to assess the condition of the calcaneofibular ligament. The arthrography was performed an average of 3.5 days after the injury (0–5 days). Results Fifty-five ankles of patients who were treated nonoperatively according to the same protocol were included in this study, and were followed up for an average of 5.0 years (37–86 months). At the time of the final follow-up, 22 of 25 (88%) ankles with an isolated injury to the anterior talofibular ligament were asymptomatic; in contrast, only 9 of 30 (30%) ankles with combined injuries of the anterior talofibular and calcaneofibular ligament were asymptomatic. The average American Orthopaedic Foot and Ankle Society score of the isolated injuries was 97.8 points, in contrast to 92.4 points for the combined injuries. Conclusions The results of nonoperative treatment with 1 week immobilization followed by a functional brace were excellent in patients with an isolated injury of the anterior talofibular ligament, but were unsatisfactory in those with combined injuries of the anterior talofibular and calcaneofibular ligaments.     

Statistical analysis of fatal bleeding pelvic fracture patients with severe associated injuries

Background Bleeding pelvic fracture patients with severe associated injuries have a high mortality rate that is exacerbated by several factors. To gain deeper etiological insights into this injury, we investigated the specific risk factors associated with the high mortality rate. Methods A total of 102 bleeding pelvic fracture patients with severe associated injuries (abbreviated injury score ≥3) were treated at our level I trauma center between January 1994 and December 2004. Predictors of death within 24 h of arrival were determined by univariate and multivariate analyses using anatomic and physiologic parameters, including injured body part, shock symptoms, age, sex, injury severity score (ISS), and fracture type. Results Overall, 47 of the 102 patients died within 24 h of arrival. Hemorrhage shock was responsible for the majority of deaths (47%). Other causes included central nervous system injury (21%), multiple injuries (central nervous system injury plus shock, 18%) and multiple organ failures (7%). Univariate analyses revealed that patients presenting with head and neck injuries and shock symptoms on arrival were associated with an increased risk of death (P < 0.01 for both variables). Multivariate analyses revealed that these injuries and shock symptoms were independently associated with a higher risk of death (odds ratios of 2.704 and 4.632, respectively). The mechanism of injury, fracture type, age, sex, and ISS were not associated with an increased risk of death. Conclusions Statistically significant risk factors were brain injuries and shock symptoms on arrival. Brain injuries should be heavily weighted when evaluating the prognosis of bleeding pelvic fracture patients.     

Risk factors for invasive aspergillosis in living donor liver transplant recipients.

Invasive aspergillosis (IA) is a severe complication of liver transplantation. Risk factors for IA after deceased donor liver transplantation (DDLT) have been presented in several reports, but are not well established for living donor liver transplant recipients. Here, a retrospective case-control study was performed. Five cases with IA were investigated after living donor liver transplantation (LDLT) between January 1999 and December 2002 at Kyoto University Hospital. For comparison, living donor liver transplant recipients without IA were taken as controls. These patients had undergone LDLT 1 month before or after each IA case and had the same survival times as the latter. We evaluated the clinical and laboratory findings for both groups up until their demise. Patients with IA after LDLT had a very poor prognosis. By univariate analysis, risk factors for IA were preoperative intensive care unit stay (P = 0.02) and preoperative steroid administration (P = 0.02). Preoperative steroid administration for fulminant hepatitis possibly predisposed to the development of IA after LDLT.     

Redo living‐donor lobar lung transplantation for bronchiolitis obliterans associated with antibody‐mediated rejection

Living‐donor lobar lung transplantation (LDLLT) is an established therapy for patients with end‐stage lung disease, but living‐donor lobar lung retransplantation (re‐LDLLT) is rarely reported. We previously reported a case of unilateral antibody‐mediated rejection after LDLLT in the presence of newly formed donor‐specific antibodies against a right‐lobe donor. The same patient developed contralateral bronchiolitis obliterans, resulting in bilateral bronchiolitis obliterans, but re‐LDLLT was successful. Pathological findings of the explanted lungs were consistent with the clinical course of the patient. One year after re‐LDLLT, the patient is doing well without any anti‐human leukocyte antigen antibodies. Four lobes from four different donors were transplanted in this patient. The first two lobes were rejected eventually, but the two lobes implanted later presented no signs of rejection at least for 1 year after the transplant. Herein, we report this rare case and compare the clinical course and pathological findings.     

Surgical site infection in living-donor liver transplant recipients: a prospective study

BACKGROUND: Infection is a constant threat for the living-donor liver transplantation (LDLT) recipients, although little information is available on the occurrence of infection in such patients. METHODS: One hundred and thirteen consecutive LDLT recipients were prospectively followed for the presence of surgical site infections (SSIs) defined by CDC from April 2001 to March 2002. Risk factors for SSIs were evaluated by univariate and multivariate analysis. RESULTS: Of the 113 LDLT recipients, 42 (37%) developed 57 episodes of SSIs (21 intraabdominal abscess, 20 peritonitis, 8 cholangitis, and 9 wound). Of the 57 episodes, 29 (51%) had secondary bacteremia in 19 patients. Causative pathogens, including 17 episodes of polymicrobial infections, were 37 gram-positive cocci (17 Staphylococcus aureus, 16 Enterococcus spp., and 4 others), 40 gram-negative rods (25 Enterobacteriaceae, 13 Pseudomonas aeruginosa, and 4 others), and 2 Candida albicans. Univariate analysis revealed that ABO incompatibility and repeat surgery were associated with the development of SSIs. Also, univariate analysis revealed that adult recipients, ABO incompatibility, total operation duration, repeat surgery, and NNIS risk index were associated with secondary bacteremia. Multivariate analysis revealed that ABO incompatibility (OR: 14.0; 95% CI, 2.52-77.2) and repeat surgery (OR: 9.29; 95% CI, 2.00-43.1) were independently associated with secondary bacteremia. Eleven of the 42 cases (26%) who developed SSIs died. Of these 11 cases, 5 (45%) developed secondary bacteremia within 30 days before death. CONCLUSION: SSIs occurred in 37% of LDLT recipients. ABO incompatibility and repeat surgery increased the risk of developing SSIs with secondary bacteremia, which correlated with poor prognosis.     

Severe outflow block syndrome caused by compression by the swollen caudate lobe after living donor liver transplantation: report of a case

A 50-year-old man with primary biliary cirrhosis underwent living-donor liver transplantation (LDLT) using a graft of a left hemiliver with a left caudate lobe and duct-to-duct hepaticocholedochostomy. Postoperative bile leakage necessitated percutaneous drainage 22 days after LDLT. The patient presented to our hospital 205 days after the LDLT with abdominal distension and fever. Computed tomography showed ascites and a diffusely mottled pattern in the graft. The caudate lobe was swollen, and its bile ducts were dilated. The inferior vena cava was forced to the right by the swollen caudate lobe, and the root of the hepatic vein was stretched. The hepatic vein was not contrasted. Endoscopic retrograde cholangiography showed a biliary anastomotic stricture. Based on these findings, we diagnosed a severe outflow block of the hepatic vein and biliary anastomotic stricture. We performed balloon dilation of the biliary anastomosis and implanted a metallic stent in the hepatic vein. Thereafter, his clinical symptoms improved dramatically.     

Extensor pollicis longus tendon rupture as a result of scapholunate dissociation: a case report.

A 39-year-old patient was presented with, to our knowledge, the first ever diagnosed case of extensor pollicis longus (EPL) tendon rupture as a result of scapholunate (S-L) dissociation. Arthroscopic findings showed that the dorsal aspect of the S-L ligament was ruptured and severe synovitis was revealed around the S-L joint. Direct observation revealed synovium at the rupture site of the EPL tendon. After careful resection of this synovium, an aperture in the S-L joint was observed. Thus, it was considered that the synovium in the S-L joint was connected to the rupture site of the EPL tendon, passing through the dorsal capsule of the S-L joint. The ruptured EPL tendon was reconstructed with extensor indicis proprius tendon transfer, and S-L dissociation was treated with a bone-retinaculum-bone autograft taken from the third dorsal compartment region.