Hypoxia-Inducible Factor-1α Expression in Kidney Transplant Biopsy Specimens After Reperfusion Is Associated With Early Recovery of Graft Function After Cadaveric Kidney Transplantation.

BACKGROUND: Ischemia/reperfusion injury during kidney transplantation (KTx) delays allograft recovery. Hypoxia-inducible factor-1α (HIF-1α) is the key regulator of the protective response to ischemia/reperfusion injury. We evaluated the impact of the HIF-1α signaling pathway on allograft recovery during cadaveric KTx. METHODS: Between 1996 and 2015, 46 patients underwent cadaveric KTx. The expression levels of HIF-1α-related proteins, including phosphoinositide 3-kinase, phosphorylated (p)-Akt, p-mammalian target of rapamycin, p-Eukaryotic translation initiation factor 4E, p-S6 ribosomal protein, and HIF-1α, were immunohistochemically evaluated and semi-quantitatively scored in graft biopsy specimens after 1 hour of revascularization. Ten kidney biopsy specimens collected during donor nephrectomy for living KTx were used as controls. Delayed graft function (DGF) was defined as the need for dialysis within 1 week of KTx. We compared the staining scores of each protein and several clinical parameters between patients with and those without DGF. RESULTS: Expression levels of all six proteins in specimens after revasculization were elevated compared with those in controls. Thirty-five patients had DGF. Expression levels of PI3K, p-AKT, p-mTOR, p-eIF4E, and HIF-1α were significantly higher in patients without DGF than in those with DGF. Univariate analysis identified expression levels of p-Akt, p-S6, and HIF-1α, in addition to donor type (heart beating/non-heart beating), cold ischemic time, and donor age as significant predictors of DGF. Of these, only expression levels of HIF-1α and donor type were independently associated with DGF in multivariate analysis. CONCLUSIONS: Up-regulation of HIF-1α in allografts after reperfusion may be a predictor of early recovery after cadaveric KTx.

A prospective randomized comparison of diagnostic efficacy between transperineal and transrectal 12-core prostate biopsy.

The aim of this study is to elucidate the diagnostic efficacy between transperineal and transrectal 12-core prostate biopsy for prostate cancer. We prospectively randomized 200 consecutive men into two groups to undergo systematic prostate biopsy. Overall positivity for cancer was similar (47% by transperineal and 53% by transrectal; P=0.480). However, in case with 'gray zone' PSA (from 4.1 to 10.0 ng/ml), significantly more cores were positive when approach was transperineal, especially among transition zone cores. Therefore, urologist preferences are sufficient for choosing an approach, except for a possible small advantage of transperineal biopsy when PSA is in gray zone.

Erectile function after brachytherapy with external beam radiation for prostate cancer.

The effect of therapeutic modalities on sexual potency is an important consideration for patients choosing a treatment for prostate cancer. We assessed erectile function after iridium-192 (1r-192) high-dose rate (HDR) brachytherapy with external beam radiation therapy (EBRT), and examined the efficacy of sildenafil after this treatment. Forty-two prostate cancer patients (T1c to T3bN0M0) were treated with 22Gy HDR brachytherapy with 36.8Gy EBRT without neoadjuvant hormone therapy. Erectile function was assessed using a 5-item version of the International Index of Erectile Function questionnaire (IIEF-5), pre, 3 and 12 months after treatment, Potency was defined as an IIEF-5 score > or = 11. Ten patients with potency before HDR brachytherapy with EBRT with or without neoadjuvant hormone therapy requested Sildenafil 3 months after treatment. The mean IIEF-5 score of all patients was 10.5 +/- 8.5, 4.5 +/- 5.3 (p < 0.001), and 3.8 +/- 4.7 (p < 0.001), pre, 3 and 12 months after treatment, respectively. Seventeen (40.4%) patients were potent before treatment. The mean IIEF-5 score of those patients was 15.8 +/- 3.2, 9.6 +/- 5.1 (p = 0.04), and 11.3 +/- 6.1 (p = 0.06), pre, 3 and 12 months after treatment, respectively. Ten of 17 (58.8%) patients maintained their potency 12 months after treatment. In 10 patients with potency before treatment who were treated with sildenafil, the mean IIEF-5 score increased from 6.2 +/- 3.5 at 3 months to 13.6 +/- 5.1 (p < 0.001) at 12 months after treatment. Eight of 10 (80%) patients treated with sildenafil had recovered 12 months after treatment. HDR brachytherapy with EBRT can be performed with favorable results for maintaining potency.

Significance of cancer detection in the anterior lateral horn on systematic prostate biopsy: the effect on pathological findings of radical prostatectomy specimens.

OBJECTIVE: To clarify the significance of cancer detection in the anterior lateral horn (ALH) on systematic prostate biopsy in relation to its effect on the pathological findings from retropubic radical prostatectomy (RRP) specimens. PATIENTS AND METHODS: The study included 84 consecutive patients who underwent RRP at our institution between January 1999 and December 2002, after being diagnosed as having prostate cancer, based on systematic prostate biopsies that included the areas taken by standard sextant biopsies and the bilateral ALHs. Several clinicopathological factors of these patients were analysed in relation to the presence or absence of cancer in the ALH on systematic biopsy. RESULTS: Of the 84 patients, cancer was detected in the ALH in 44 (group A), but not in the remaining 40 (group B). There were no significant differences in age, preoperative serum prostate-specific antigen level, or prostate volume between the groups. However, the incidence of bilateral positive cores and the percentage of positive biopsy cores in group A were significantly higher than those in group B. Pathological examinations of RRP specimens showed no significant differences in the incidence of lymphatic invasion, vascular invasion and perineural invasion, or Gleason score between the groups, but group A had a significantly larger tumour volume and higher incidence of extraprostatic disease than group B. CONCLUSIONS: Despite similar biological tumour characteristics and irrespective of the cancer location in the ALH, advanced and extensive disease frequently involves the ALH. Therefore, more aggressive treatment should be considered if cancer is detected in the ALH by systematic prostate biopsy.

Significance of early biopsy in pediatric kidney transplantation.

Long-term renal allograft survival is limited mainly by the progressive process termed chronic allograft nephropathy (CAN) or chronic rejection. A pathological feature of CAN is characterized by progressive interstitial fibrosis. Transforming growth factor (TGF)-beta(1) plays an important role in fibrogenesis. We investigated whether the degree of TGF-beta(1) expression in early biopsy specimens routinely obtained from stable allografts at 100 days could predict fibrosis and graft dysfunction in the late phase by immunohistochemistry. Patients were children with a graft from related donors. We immunohistochemically determined intracellular and extracellular expression of TGF-beta(1) in the graft at 100 days using LC antibody (LC) for intracellular TGF-beta(1) and CC antibody (CC) for extracellular TGF-beta(1). We used the change in creatinine clearance between 100 days and 3 years after transplantation (Delta Ccr) as an index of long-term graft function. Image analysis was used to calculate the relative area involved by interstitial fibrosis in trichrome-stained sections of graft biopsy specimens at 100 days and 3 years, designating the change as Delta FI. Delta Ccr was - 4.2 +/- 9.4 mL/min in subjects with minimal early immunoreactivity for CC and - 20.5 +/- 5.9 mL/min in subjects with strong reactivity (p < 0.05). Delta Ccr was - 14.5 +/- 18.6 mL/min in subjects with minimal early immunoreactivity for LC and - 11.7 +/- 12.8 mL/min in those with strong reactivity. Delta FI in subjects with minimal CC reactivity (1.28 +/- 4.11 %) tended to be lower than in subjects with strong reactivity (8.45 +/- 15.47 %). Neither fibrosis at 100 days nor Delta FI differed between subjects with minimal and strong LC reactivity. Thus, extracellular TGF-beta(1) expression in grafts at 100 days after transplantation has an influence on long-term graft function and tends to be associated with increased graft fibrosis at 3 years.

Transforming growth factor-beta1 expression in early biopsy specimen predicts long-term graft function following pediatric renal transplantation.

The main cause of late graft loss or declining long-term graft function is chronic allograft nephropathy (CAN), characterized by progressive interstitial fibrosis. Transforming growth factor (TGF)-beta1 plays a key role in fibrogenesis. We immunohistochemically investigated whether the degree of TGF-beta1 expression in early biopsy specimens routinely obtained from stable allografts at 100 d could predict fibrosis and graft dysfunction in the late phase. Patients were children with grafts from related donors. We immunohistochemically determined intracellular and extracellular expression of TGF-beta1 in the graft using LC antibody (LC) for intracellular TGF-beta1 and CC antibody (CC) for extracellular TGF-beta1. The change in creatinine clearance between 100 d and 3 yr after transplantation (DeltaCcr) was used as an index of long-term graft function. We also used image analysis to calculate the relative area involved by interstitial fibrosis in the trichrome-stained section of graft biopsy specimens at 100 d and 3 yr, designating the change as DeltaFI. DeltaCcr was -4.2+/-9.4 mL/min in subjects with minimal early immunoreactivity for CC and -20.5+/-15.9 mL/min in subjects with strong reactivity (p<0.05). DeltaCcr was -14.5+/-18.6 mL/min in subjects with minimal early immunoreactivity for LC and -11.7+/-12.8 mL/min in those with strong reactivity. DeltaFI in subjects with minimal CC reactivity (1.28+/-4.11%) tended to be lower than that in subjects with strong reactivity (8.45+/-15.47%). Neither fibrosis at 100 d nor DeltaFI differed between subjects with minimal and strong LC reactivity. Thus, strong extracellular TGF-beta1 expression in grafts at 100 d after transplantation is associated with a long-term decline in graft function and tends to be associated with increased graft fibrosis at 3 yr.

A novel antireflux uretero-ileal anastomosis for urinary diversion: an experimental study.

OBJECTIVES: To assess a new antireflux valve technique in a dog model of urinary diversion, and thus provide a reliable and easily constructed antireflux system for an ileal reservoir. MATERIALS AND METHODS: In five female beagle dogs, 3 cm of ileum were intussuscepted into the reservoir formed using the adjacent 10 cm of ileum. The intussuscepted ileum was sutured to the reservoir wall after stripping the mucosa of the reservoir in a trapezoidal zone opposite the similarly stripped mucosa of the intussuscepted ileum, to avoid dessusception. After the distal 4 cm of the ureters was united and pulled through the intussuscepted segment of ileum, the combined distal ureter was sutured to the labial edge of the intussuscepted segment. Finally, the reservoir was anastomosed to the bladder as an enterocystoplasty. Dogs were evaluated by ascending cystography and intravenous pyelography at 1 and 6 months. The valve and upper urinary tract were evaluated histopathologically at 6 months. RESULTS: In all dogs the antireflux system remained intact and prevented reflux. The intussuscepted ileum was firmly attached to the reservoir wall and the submucosa of each segment was united. The upper urinary tract was normal with no ureteric stenosis. Histopathologically, the ureter was surrounded by intact ileal serosa and showed no inflammation or scarring. CONCLUSIONS: The very short ileal segment required and the firm attachment of the constructed valve to the reservoir were the advantages of this practical and reliable new antireflux system.

Efficacy of prophylactic aerosol amphotericin B lipid complex in a rat model of pulmonary aspergillosis.

Invasive pulmonary aspergillosis remains an important cause of morbidity and mortality among transplant recipients and patients receiving cancer chemotherapy. The lipid-associated formulation of amphotericin B (AmB), AmB lipid complex (ABLC), was evaluated for its prophylactic efficacy when it was administered as an aerosol in a rat model of pulmonary aspergillosis. Aerosol ABLC (aero-ABLC), in doses from 0.4 to 1.6 mg/kg of body weight given 2 days before infection, significantly delayed mortality compared to the mortality of rats given placebo (P < 0.001). At day 10 postinfection, 50% of rats in the 0.4-mg/kg group and 75% of rats in the 1.6-mg/kg group were alive, while all control animals had died. In a second trial aero-ABLC was more effective than an equivalent dose of aerosol AmB (aero-AmB) in prolonging survival, with 100% survival at day 14 postinfection in the ABLC group, compared to 62.5% survival in the AmB group. Mean concentrations of AmB in lungs were 3.7 times higher at day 1 (P < 0.002) and almost six times higher at day 7 (P < 0.001) after treatment with aero-ABLC than after treatment with a similar dose of aero-AmB. We conclude that aero-ABLC provided higher and more prolonged levels of the parent compound in the lungs than aero-AmB and was more effective in delaying mortality from aspergillosis in this model.

Peritoneal endometriosis: endometrial tissue implantation as its primary etiologic mechanism.

The mechanisms involved in primary implantation of pelvic endometriosis were investigated in women undergoing laparoscopy as part of an infertility evaluation. Among the women with a diagnosis of endometriosis, those with no observed lesions in the ovaries and no adhesions in the pelvic cavity were classified as being in stage I. These women were further subdivided into two groups: the stage Ia group in which implants were found in one area (25 women) and the stage Ib group in which implants were found in two or more areas (29 women). In both groups the most frequent site was the uterosacral ligaments followed by the posterior uterine serosa, the posterior cul-de-sac, and the posterior broad ligaments in that order. Regardless of the position of the uterus, endometriosis was found significantly more frequently in the posterior compartment. The finding that the most frequent implants on the uterosacral ligaments were near the tubal ostium and, in the stage Ia group, the absence of implants on the anterior uterine serosa but a 33% frequency on the posterior uterine serosa, which is more frequently exposed to menstrual blood, suggest that implantation of endometriosis is the result of retrograde menstruation. However, the possibility that metaplasia of the serosal epithelium is stimulated by menstrual blood cannot be ruled out, inasmuch as the process of implantation in the peritoneum has not yet been proved.

Angiographic comparison of the internal mammary artery graft and the saphenous vein graft within 2 months and 6 to 12 months after coronary artery bypass surgery.

Angiographic status of the saphenous vein graft (SVG) and the internal mammary artery graft (IMAG) anastomosed to the left anterior descending artery were compared at two different postoperative periods; - within 2 months and at 6 to 12 months after the operation. In 50 SVGs and 35 IMAGs which were studied at the early postoperative period, the rate of intact, stenosed and occluded grafts were almost the same in these two kinds of grafts. However, in 35 SVGs and 25 IMAGs which were studied at the later period, the stenosis of SVG increased significantly while IMAG remained intact. The rate of intact, stenosed and occluded grafts at postoperative 6 to 12 months were 71%, 23% and 6% in SVG, and 88%, 8% and 4% in IMAG, respectively. Considering the better angiographic quality of IMAG, use of IMAG to bypass the most important coronary artery should be considered especially when the patients are younger.

A 31-year-old woman with homozygous familial hypercholesterolemia without significant lesions in the coronary arteries.

Cardiovascular complications were examined in a 31-year-old woman with homozygous familial hypercholesterolemia (FH) (LDL receptor defective type), who had had no clinical symptoms of coronary artery disease. She had delivered 2 children without any cardiac complications, and her exercise electrocardiogram showed no positive findings for ischemic heart disease. Coronary angiography showed no significant arterial lesions, and left ventriculography revealed good contraction of the left ventricle (ejection fraction: 67%). This is considered to be a very rare case of homozygous FH without significant lesions in the coronary arteries. This might be attributed at least in part to her dietary regimen consisting of a very low fat and low calorie diet, to the residual LDL receptor activity or to the low value of prothrombin time.