Low skeletal muscle mass index is independently associated with low bone mineral density in kidney transplant recipients: a retrospective observational cohort study.

BACKGROUND: Osteoporosis and osteopenia are more frequent in patients who have received kidney transplants than in healthy individuals. Although osteoporosis and sarcopenia are closely related, only few studies have considered them in the post-transplantation period. We aimed to investigate the relationship between lower bone mineral density and skeletal muscle in kidney transplant recipients. METHODS: We included 371 patients in the maintenance phase of kidney transplantation (> 6 months after transplantation) followed-up at our institution from January to December 2019. The primary endpoint was the association between bone mineral density and skeletal muscle mass index. As secondary endpoints, in addition to skeletal muscle mass index, we investigated other factors associated with low bone mineral density, including kidney function and 25-hydroxy vitamin D (25(OH)D) concentration. Considering the possibility that factors affecting bone mineral density differ between men and women, we explored these factors separately for both sexes. RESULTS: Of the 371 participants, 243 (65.4%) were men. The median age and time after transplantation were 52 and 14 years, respectively. Univariate analysis showed that age, female sex, time since transplantation, cystatin C-based estimated glomerular filtration rate (eGFRcysC), 25(OH)D, and skeletal muscle mass index were associated with bone mineral density. Multivariate analysis showed associations of bone mineral density with eGFRcysC, 25(OH)D, and skeletal muscle mass index. Multivariate analysis by sex showed significant associations with eGFRcysC, hemoglobin, and skeletal muscle mass index in men and with age, eGFRcysC, albumin, and skeletal muscle mass index in women. Bone mineral density was not associated with history of dialysis prior to transplantation or time since transplantation. CONCLUSIONS: In kidney transplant recipients, an independent association between lower bone mineral density and skeletal muscle mass index was observed in both sexes.

Improved detection of donor-specific HLA-class II antibody in kidney transplant recipients by modified immunocomplex capture fluorescence analysis.

Immunocomplex capture fluorescence analysis (ICFA) which basic principle is same as Luminex crossmatch (LXM), could detect donor-specific HLA antibody (DSA). The advantages of ICFA are (i) detection of DSA and (ii) no requirement of viable cells over the flow cytometry crossmatch (FCXM). However, FCXM has been widely used because of its higher sensitivity than ICFA, in particular HLA-class II antibody detection. In this study the accuracy of DSA detection against HLA-class II was investigated by modifying the original method of ICFA. Increment of the sensitivity was found when purified peripheral blood mononuclear cells (PBMCs) were used instead of whole blood. An ICFA-PBMC in addition to FCXM-T/B was conducted for 118 patients before kidney transplantation and 13 patients with de novo DSA against HLA-class II after transplantation. Significantly positive correlation was observed between the values of ICFA-PBMC and DSA mean fluorescence intensity (MFI) targeting class II (p < 0.0001). When the cutoff level of 1.4 was determined by receiver operating characteristic curve analysis, the average DSA MFI was found to be significantly higher in the ICFA-PBMC (class II) positive group comparing to that in the negative group (12,217 vs 3885, p = 0.0027). ICFA-PBMC and optimized cutoff level could provide valid information in cases of suspected DSA.

Familial Mediterranean Fever developing in a Japanese kidney transplant recipient.

Familial Mediterranean Fever (FMF) is an auto-inflammatory disease characterized by periodic febrile episodes and sterile polyserositis and is extremely rare in Asian populations. Here, we report a case of FMF in a 61-year-old Japanese man who received a kidney transplant 31 years ago but had to re-start hemodialysis. Although kidney function had been stable since his initial transplant, serum creatinine levels had been increasing over the 2 years prior to his presentation at our hospital, and a periodic fever developed at the same time. Uremic symptoms were observed, and hemodialysis was re-started, prompting the patient to choose to undergo a second kidney transplantation. We re-checked his medical history and conducted further physical examinations. Given that the patient had previously undergone an operation for olecranon bursitis in which pericardial effusion had been identified, we considered the possibility of FMF and conducted a genetic test, which identified the E202Q heterozygous mutation in the MEFV gene. The patient was therefore diagnosed with variant FMF. To our knowledge, this is the first report of a Japanese kidney transplant recipient being diagnosed as an FMF variant. We describe the relationship of FMF and kidney transplantation in terms of prognosis and important points to note for treatment.

Neither pre-transplant rituximab nor splenectomy affects de novo HLA antibody production after renal transplantation.

The long-term effect of rituximab and splenectomy on de novo HLA antibody production and chronic antibody-mediated rejection after renal transplantation is uncertain. In order to gain insight on this, we studied 92 ABO-incompatible and 228 ABO-identical/compatible consecutive renal transplant patients and determined their de novo HLA antibody production and graft outcome. Patients with pretransplant donor-specific antibodies had been excluded. ABO-incompatible transplants included 30 recipients treated with rituximab, 51 by splenectomy, or 11 with neither, due to low anti-A or -B antibody titer. Graft survival in ABO-identical/compatible patients (97.7% at 5 years) was significantly higher than in ABO-incompatible (87.0% at 5 years), rituximab (96.7% at 3 years), or splenectomy (85.7% at 5 years) patients. Only four patients had clinical chronic antibody-mediated rejection (two each identical/compatible and incompatible). There was no significant difference in prevalence of de novo HLA antibody, including donor-specific and nondonor-specific antibodies among ABO-identical/compatible patients (13.9%), patients receiving rituximab (14.3%) or splenectomy (13.2%), or among those receiving cyclosporine, tacrolimus, mycophenolate mofetil, mizoribine, and everolimus. Renal function remained stable in most recipients with de novo HLA antibody. Thus, neither pretransplant splenectomy nor rituximab treatment has an inhibitory effect on de novo HLA antibody production during medium-term follow-up. Further study on long-term effects is needed.

[A case of renal salt wasting syndrome progressing to severe hyponatremia after gemcitabine-cisplatin chemotherapy].

Renal impairment with a decreased glomerular filtration rate is a classical nephrotoxicity associated with cisplatin (CDDP). Renal salt wasting syndrome (RSWS), which is characterized by water and salt wasting, is a rare nephrotoxicity associated with CDDP. This syndrome shares many similarities with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Thus, it is important to differentiate between RSWS and SIADH because the treatment of one affects the pathogenesis of the other. Here, we report a case of RSWS after chemotherapy with CDDP. A 72-year-old man with bladder urothelial carcinoma (cT2N0M0) was admitted to our hospital for the first cycle of neoadjuvant chemotherapy with CDDP and gemcitabine. He was administered intravenous fluids on day 2 before chemotherapy. Five days later, he developed nausea, dysorexia, delirium, hyponatremia (serum sodium level 115 mEq/l), and renal dysfunction. Thus, we administered a normal saline infusion. Over the next 6 days, his serum sodium level increased to 137 mEq/l, and we stopped normal saline infusion. Three days after discontinuation of saline infusion, his serum sodium level again decreased to 128 mEq/l, and the next day, his systolic blood pressure dropped gradually between 70 and 80 mmHg. Therefore, we resumed the normal saline infusion, and after 3 days, his serum sodium level increased to 135 mEq/l and systolic blood pressure ranged between 110 and 130 mmHg. On the basis of dehydration and high urinary sodium excretion at the onset of chemotherapy, we diagnosed this clinical condition as RSWS. We abandoned neo-adjuvant chemotherapy, and performed total cystectomy and ileal conduit. Since 4 months after surgery, he has been free from recurrence and metastasis.

[A case of micropapillary bladder carcinoma].

A case of urothelial carcinoma containing micropapillary variant in the urinary bladder is reported. The micropapillary bladder carcinoma isa rare variant of urothelial carcinoma and has an aggressive clinical course. A 45-year-old man complained of hematuria in October, 2009. He visited a hospital and was diagnosed with a bladder tumor. Transurethral resection of the bladder tumor was performed at the hospital. The transurethral resection demonstrated poorly differentiated adenocarcinoma invading the bladder muscle layer. Then he consulted our hospital. Our pathologist diagnosed the case as micropapillary variant of urothelial carcinoma in the urinary bladder. Accordingly, radical cystectomy and pelvic lymph nodes dissection were performed. After the operation, he received three courses of gemcitabine and cisplatin as adjuvant chemotherapy. The patient remains free of tumor recurrence and metastasis for 28 months after the cystectomy.

[A case of interstitial pneumonia during gemcitabine and cisplatin chemotherapy for locally advanced bladder cancer].

A 76-year-old woman received chemotherapy with gemcitabine and cisplatin (GC therapy) for local advanced bladder cancer. She suffered from dyspnea on day 19 during the first course of GC therapy. Both chest X-ray and computed tomography (CT) images revealed diffuse bilateral interstitial infiltrates. She was diagnosed as having drug-induced interstitial pneumonia. We identified gemcitabine as the causative agent based on the results of examinations (CT, X-ray, KL-6 level, drug lymphocyte stimulation test (DLST)). After three months of steroid therapy, her interstitial pneumonia was completely resolved on CT scans. Although gemcitabine-induced interstitial pneumonia is a rare adverse event, it should be considered a severe complication because delayed diagnosis and treatment can lead to a fatal outcome. Thus, early detection of drug-induced interstitial pneumonia is extremely important during GC therapy.

[A case report of transurethral resection of eroding urethral mesh after a tension-free vaginal tape procedure].

A 72-year-old woman presented with lower urinary tract symptoms (incomplete voiding, voiding pain, and gross hematuria) 2 years after a tension-free vaginal tape (TVT) procedure for stress urinary incontinence. Cystoscopy revealed erosion of the urethra associated with a urethral stone attached to a polypropylene mesh. We performed transurethral resection of the polypropylene mesh and transurethral lithotripsy. After removal of the mesh, she had stress urinary incontinence but her symptoms resolved. Urethral erosion is a rare complication of TVT, and the method of handling the intrusive mesh has not been standardized. Transurethral endoscopic resection of the eroding mesh is a minimally invasive and successful procedure that should be considered for the treatment of this complication resulting from TVT.

Stromal macrophage expressing CD204 is associated with tumor aggressiveness in lung adenocarcinoma.

BACKGROUND: Tumor tissue is composed of variable numbers of cancer cells and stromal cells, and tumor-associated macrophages are recruited into cancer-induced stroma and produce a specific microenvironment. Alternatively, activated macrophages (M2 phenotype) are known to be related to tumor progression and outcome, and CD204 has been reported to be expressed in M2 macrophages in some tumors. METHODS: To investigate whether CD204-positive macrophages reflect tumor aggressiveness in adenocarcinoma of the lung, we investigated the relationships between the numbers of CD204-positive stromal macrophages and both clinicopathological features and outcome in 170 consecutive resected cases. We also examined the relationships between the numbers of CD204-positive macrophages and the expression levels of cytokines involved in the migration and differentiation of M2 macrophages. RESULTS: The numbers of CD204-positive macrophages were significantly correlated with several prognostic factors. The log-rank test showed a significant association between the numbers of CD204-positive macrophages and a poor outcome (p = 0.0073), whereas the numbers of macrophages expressing CD68, a pan-macrophage/monocyte marker, were of marginal prognostic significance (p = 0.0789). We evaluated associations between the levels of expression of the cytokines IL-6, IL-10, IL-12a, IL-12b, M-colony-stimulating factor, IFN-gamma-., and monocyte chemoattractant protein-1 in cancer tissue and the numbers of CD204-positive macrophages. The expression levels of IL-10 and monocyte chemoattractant protein-1, which are involved in differentiation, accumulation, and migration of M2 macrophages, were significantly correlated with the numbers of CD204-positive macrophages (p = 0.031 and p = 0.031, respectively). CONCLUSION: These findings demonstrated that CD204-positive macrophages clearly reflect the tumor-promoting phenotype of tumor-associated macrophages in lung adenocarcinoma.

[A case of complicated perioperative management of radical nephrectomy in a patient with a drug-eluting stent].

Drug-eluting stents (DES) are commonly used for coronary artery disease and patients with DES require antiplatelet therapy because of the risk of late stent thrombosis. Accordingly problems can occur in the perioperative period due to late thrombosis of a stent after discontinuation of antiplatelet therapy before surgery. A 64-year-old man was diagnosed as having a right renal tumor (T1aN0M0) and his performance status was 4. Three years earlier, a DES had been placed in a coronary artery and he was taking aspirin plus ticlopidine. These drugs were stopped at 7 days before surgery and we started heparin (15,000 U/day). Heparin was continued during and after radical nephrectomy. Although operative blood loss was only 178 ml, the amount of bleeding within 5 hours after surgery was 1,620 ml. The wound was re-opened, but there was no obvious bleeding source, so oozing from the muscle was controlled. His blood pressure dropped and cardiac arrest occurred at 22 hours after re-operation, but he was resuscitated with blood transfusion and the bleeding stopped after the dose of heparin was reduced. Three days after the operation, antiplatelet therapy was re-started and heparin was ceased at 10 days after surgery. The blood clot in the right retroperitoneal space formed an abscess at 28 days after radical nephrectomy. After drainage, the retroperitoneal space was washed twice a day for about 40 days. The wound healed, and he currently has no evidence of recurrence or metastasis and has no cardiac sequelae.

Targeting of bone-derived insulin-like growth factor-II by a human neutralizing antibody suppresses the growth of prostate cancer cells in a human bone environment.

PURPOSE: Advanced prostate cancer frequently involves the bone, where the insulin-like growth factor (IGF)-II is abundant. However, the importance of IGF-II in bone metastasis from prostate cancer is uncertain. The present study was aimed at examining the therapeutic importance of targeting IGF-II in bone metastases from prostate cancer. EXPERIMENTAL DESIGN: We investigated whether inhibiting IGF-II using a human neutralizing antibody (m610) suppresses the growth of prostate cancer cells in a human bone environment. Human MDA PCa 2b prostate cancer cells were inoculated into human adult bone implanted into mammary fat pad of nonobese diabetic/severe combined immunodeficient mice or inoculated into mammary fat pad of the mice without human bone implantation. The mice were treated with m610 or a control antibody (m102.4) once weekly for 4 weeks immediately after inoculation with MDA PCa 2b cells. RESULTS: Histomorphologic examination indicated that m610 treatment significantly decreased the MDA PCa 2b tumor area in the human bone compared with the control. Ki-67 immunostaining revealed that the percentage of proliferating cancer cells in the m610-treated bone tumor sections was significantly lower than that in the control. m610 had no effect on MDA PCa 2b tumor growth in the absence of implanted human bone. m610 prevented the in vitro IGF-II-induced proliferation of MDA PCa 2b cells. CONCLUSIONS: Our results indicate that IGF-II plays an important role in the prostate cancer cell growth in human bone, suggesting that targeting it by neutralizing antibodies offers a new therapeutic strategy for bone metastasis from prostate cancer.

[Clinical importance of guideline for decontamination of endoscopes in urological field: verification of 3 processes].

UNLABELLED: Clinical guideline for decontamination of endoscopes in urological field has not been provided, although endoscopic examination should be done in aseptic circumstance. MATERIAL AND METHOD: From decontamination processes, following 3 points were selected for verification: 1) Volume of residual water in flexible scope after rinsing, estimated by weight change. 2) Concentration of eluted disinfectant from flexible scope after standard rinsing procedure for gastrointestinal endoscope. 3) Observation of possible damage of telescope, caused by repeat autoclaving. RESULTS: Wet condition of flexible scope could be suspected in 60 hours in room temperature. Eluted disinfectants were detected, but in harmless level. Repeated autoclaving merely caused minor damage, which does not interfere clinical use. CONCLUSION: We obtained a couple of evidences with cautions in decontamination processes for endoscopes. Urgent requirement of standardization in this field should be discussed widely.

The bisphosphonate YM529 inhibits osteoblastic bone tumor proliferation of prostate cancer.

BACKGROUND: In men, prostate cancer frequently metastasizes to the bones, where it forms osteoblastic lesions with an osteolytic element that cause pain. However, the role of osteoclastogenesis in bone metastasis of human prostate cancer is unknown. Bisphosphonates are already known to be beneficical for treating osteolytic bone metastases, so we employed a model of osteoblastic bone tumor of human prostate cancer to investigate whether a new bisphosphonate (YM529: minodronate) could inhibit both the formation of bone tumors and the progression of established osteoblastic tumors. METHODS: Human prostate cancer cells (LNCaP) were injected into adult human bone implants in nonobese diabetic/severe combined immunodeficient mice, after which osteoblastic bone tumors developed. YM529 (1 microg/day) was administered subcutaneously every day for 2 weeks, starting either immediately or 2 weeks after implantation of the tumor cells, and the mice were sacrificed at 4 weeks after implantation. The bone tumors were examined histologically and the number of tartrate-resistant acid phosphatase-stained osteoclasts in each tumor focus was counted. RESULTS: Histomorphometric analysis revealed that YM529 markedly inhibited both the formation of bone tumors and the progression of established tumors, as well as markedly reducing the number of osteoclasts. CONCLUSIONS: YM529 reduced the tumor burden in bone by inhibiting both the formation of new lesions and the progression of existing tumors, suggesting that osteoclasts are involved in the formation of bone tumors by prostate cancer. Treatment with this bisphosphonate may potentially be beneficial for patients with bone metastases of prostate cancer.

Serum amino acids as indicators of cerebrospinal neuronal activity in patients with micturition disorders.

OBJECTIVE: Our previous study showed that the spinal glycine level in rats was changed by spinal injury or bladder outlet obstruction, and this change was reflected by serum glycine levels. Therefore, we measured the serum glutamate and glycine levels in healthy volunteers and patients with cerebrospinal damage or benign prostatic hyperplasia (BPH) to confirm whether the change of serum amino acid levels was obtained from these patients as well as the animal experiment. METHODS: We measured the serum glutamate and glycine levels in 170 healthy controls, 57 patients with cerebrovascular disease (CVD), 68 patients with spinal cord injury (SCI), and 70 patients with BPH. Amino acid levels were compared between the controls and patients, according to gender, level of spinal injury and the type of bladder activity. RESULTS: In the healthy controls, glutamate levels were higher and glycine levels were lower in men than in women. On group comparison of each gender, there were no differences of glutamate levels. However, glycine levels were lower in male and female SCI patients and BPH patients than in controls. According to the level of spinal injury or the pattern of bladder activity and amino acid levels, there were no relationships among them. CONCLUSIONS: Serum glutamate and glycine levels were not related to the spinal injury level or bladder activity. However, serum glycine levels changed in patients with SCI or BPH patients, so it may be possible to use it as an indicator of spinal glycinergic neuronal activity.

Langerhans cell histiocytosis on the penis: a case report.

BACKGROUND: Langerhans cell histiocytosis affects mainly young children and features an accumulation of CD1a+ dendritic Langerhans cells in the bone, skin, and other organs. A few cases of Langerhans cell histiocytosis on the penis have been reported in the literature. We present a case of Langerhans cell histiocytosis on the penis and review the similar cases in the literature. CASE PRESENTATION: The patient was a 13-year-old boy who had a history of lymph node, femur bone, and pituitary-thalmic axis lesions from Langerhans cell histiocytosis who noticed a painful nodule on the prepuce of his penis. The histological and immunohistochemical examination fulfilled the criteria of Langerhans cell histiocytosis. CONCLUSION: We herein describe the case reported of Langerhans cell histiocytosis on the penis.

Intrathecal or dietary glycine inhibits bladder and urethral activity in rats with spinal cord injury.

PURPOSE: We examined the influence of intrathecal or dietary glycine on bladder and urethral activity in rats with spinal cord injury. MATERIALS AND METHODS: A total of 20 female Sprague-Dawley rats were used 4 weeks after lower thoracic spinal cord injury. The rats were divided into standard and 1% glycine diet groups. In the standard diet group isovolumetric cystometry and urethral pressure measurement were performed before and after intrathecal injection of glycine. In the 1% glycine diet group bladder and urethral activity were compared with control recordings in the standard diet group. RESULTS: In the standard diet group intrathecal injection of glycine prolonged the interval and decreased the amplitude of bladder contractions, decreased baseline urethral pressure and altered urethral activity during bladder contraction from a pattern of detrusor-sphincter dyssynergia to detrusor-sphincter synergy at 100 mug glycine. In the 1% glycine diet group the interval and amplitude of bladder contractions were prolonged and decreased, respectively, compared with those in the standard diet group. Baseline urethral pressure was lower than in the standard diet group even after intrathecal injection of 100 mug glycine. Urethral pressure did not change during bladder contraction and it was the same as baseline pressure. Residual urine volume was lower than in the standard diet group. CONCLUSIONS: Intrathecal or dietary glycine inhibits bladder and urethral activity, and improves detrusor hyperreflexia and detrusor-sphincter dyssynergia.

Distal ureteral atresia: recovery of renal function after relief of obstruction at ten months old.

A large cystic mass that occupied more than half of the abdomen was identified by ultrasound in a 10-month-old boy. Intravenous pyelography failed to visualize the right kidney, so we created a loop ureterocutaneostomy followed by temporary nephrostomy to improve renal function. Exploratory surgery revealed complete atresia of the distal right ureter. A ureteral stricture developed after ureteroneocystostomy and undiversion of the loop, so a second reconstruction procedure was required (pelvi-ureteroplasty and reimplantation of the right ureter with a psoas hitch) to free the patient from dependence on catheters. Despite the occurrence of giant hydronephrosis secondary to complete ureteral obstruction at the age of 10 months, the function of the right kidney could be preserved. Accordingly, aggressive attempts to promote functional recovery may be justified even when patients have advanced hydronephrosis.

[Risk factors for duration of urinary incontinence after radical prostatectomy].

PURPOSE: In this study, we examined risk factors for duration of incontinence after radical prostatectomy at our hospital. MATERIALS AND METHODS: From April 1988 to March 2000, 45 patients with prostate cancer underwent retropubic radical prostatectomy at our hospital. Thirty-eight of 45 patients could be followed up. The patients' age, height, weight, body mass index (BMI), preoperative prostatic specific antigen level, clinical stage, nerve-sparing surgery or none, operation time, bleeding volume, resected prostate weight, cancer positive or negative at surgical margins, postoperative stage, radiation therapy or none, anti-androgen therapy or none, duration of postoperative incontinence, and follow-up period were examined. RESULTS: All patients had postoperative stress incontinence, and no one had urge incontinence. Medians of duration of postoperative incontinence and follow-up period were 5.5 and 12 months, respectively. When the patients were divided into 2 groups by the value of each parameter, postoperative anti-androgen therapy (chi 2 test, p = 0.0429) and high BMI (> or = 25.0 kg/m2, p = 0.0206) were related to the long duration (> or = 5.5 months) of postoperative incontinence. CONCLUSION: These results suggest that common factors are involved in the etiology of prolonged incontinence after radical prostatectomy and genuine stress incontinence in women. Therefore, both body weight control and pelvic floor muscle exercise might be also important for the treatment of incontinence after radical prostatectomy.

Kidney autotransplantation in a patient with renal pelvic and bladder carcinomas.

A 66-year-old Japanese woman, whose left kidney was non-functioning, was referred to us with a diagnosis of invasive bladder carcinoma and right renal pelvic carcinoma. The latter tumor was clearly packed in the renal calyx and was considered to be of low-grade malignancy. Nephron preserving surgery of the right kidney was performed, followed by radical cystectomy and construction of an ileal conduit. The postoperative course was good, without significant complications. Renal function was restored and a postoperative imaging study showed a well-functioning transplanted kidney. At present (20 months after surgery), the patient is doing well and has presented no signs of recurrence of the disease.