[Hemodialysis Increases the Incidence of Post-Traumatic Seizure in Hemodialysis Patients with Traumatic Intracranial Hemorrhage].

BACKGROUND: In Japan, the number of hemodialysis patients increases every year, along with the average age of this patient population. Further, certain complications of hemodialysis make the care of traumatic head injury(THI)patients particularly difficult. OBJECTIVE: This study was aimed at investigating the occurrence of and risk factors for post-traumatic seizures in hemodialysis patients with a history of THI, and determining patient outcomes. METHODS: Subjects were selected from patients who were admitted to Yaizu Municipal Hospital in Shizuoka, Japan for traumatic intracranial hemorrhage(TICH). Retrospective medical histories of TICH patients who were and were not receiving hemodialysis were reviewed to investigate the risk factors for seizures and to determine patient outcomes. RESULTS: We identified 18 THI patients on hemodialysis and 86 THI patients not on hemodialysis treatment. We determined that predictive factors of post-traumatic seizure include:current hemodialysis treatment, enlargement of an existing hematoma, and an acute subdural hematoma. Moreover, 66.7% of seizures in our dialysis patients occurred during hemodialysis. Our data also suggest that Glasgow Coma Scale(GCS)scores on admission are a predictive factor for patient outcomes following discharge. CONCLUSION: Current hemodialysis treatment, enlargement of an existing hematoma, and an acute subdural hematoma are predictive factors of seizure occurrence in THI patients. As post-traumatic seizures triggered unfavorable outcomes in some dialysis patients, it is important to create appropriate plans for preventing dialysis disequilibrium syndrome that may lead to seizures in TICH/TIH patients on hemodialysis. We also determined that a low GCS score upon admission is a significant predictor of unfavorable outcomes.

How Should Disaster Base Hospitals Prepare for Dialysis Therapy after Earthquakes? Introduction of Double Water Piping Circuits Provided by Well Water System.

After earthquakes, continuing dialysis for patients with ESRD and patients suffering from crush syndrome is the serious problem. In this paper, we analyzed the failure of the provision of dialysis services observed in recent disasters and discussed how to prepare for disasters to continue dialysis therapy. Japan has frequently experienced devastating earthquakes. A lot of dialysis centers could not continue dialysis treatment owing to damage caused by these earthquakes. The survey by Japanese Society for Dialysis Treatment (JSDT) after the Great East Japan Earthquake in 2011 showed that failure of lifelines such as electric power and water supply was the leading cause of the malfunction of dialysis treatment. Our hospital is located in Shizuoka Prefecture, where one of the biggest earthquakes is predicted to occur in the near future. In addition to reconstructing earthquake-resistant buildings and facilities, we therefore have adopted double electric and water lifelines by introducing emergency generators and well water supply systems. It is very important to inform politicians, bureaucrats, and local water departments that dialysis treatment, a life sustaining therapy for patients with end stage renal diseases, requires a large amount of water. We cannot prevent an earthquake but can curb the extent of a disaster by preparing for earthquakes.

A case of primary adrenal diffuse large B cell lymphoma presenting with severe hyponatremia.

We herein report a case of primary adrenal lymphoma with severe hyponatremia. The patient was admitted for an evaluation of severe hyponatremia and an enlarged bilateral adrenal mass, which were found in a previous examination for causes of general fatigue and anorexia. Laboratory data, including the serum levels of sodium (115 mEq/L), osmolality (239 mOsm/kgH2O), ADH (5.8 pg/mL), cortisol (11.6 µg/dL), free T3 (2.42 pg/mL), urinary Na (117 mEq/L) and urine osmolality (490 mOsm/kgH2O), fulfilled the diagnostic criteria for the syndrome of inappropriate secretion of ADH (SIADH). An abdominal computed tomography scan revealed a large bilateral adrenal mass. A biopsy of the enlarged left adrenal mass revealed diffuse large B cell lymphoma, which was negative for ADH protein. Hydrocortisone treatment normalized the patient's body temperature and serum sodium concentration. In this case, hyponatremia developed when both adrenal glands were involved and was normalized with hydrocortisone. These findings suggest that adrenal insufficiency was the cause of hyponatremia, although the basal serum cortisol was normal. The current case suggests that the administration of hydrocortisone is recommended if suspicious clinical signs or symptoms are found in severe hyponatremia, even if hyponatremia is associated with a normal serum cortisol level and fulfills the diagnostic criteria for SIADH.

Cloud cavitation control for lithotripsy using high intensity focused ultrasound.

Cloud cavitation is potentially the most destructive form of cavitation. When the cloud cavitation is acoustically forced into a collapse, it has the potential to concentrate a very high pressure, more than 100 times the acoustic pressure, at its center. We experimentally investigate a method to control the collapse of high intensity focused ultrasound (HIFU)-induced cloud cavitation to fragment kidney stones. Our study examines a novel two-frequency wave designed to control the cloud cavitation (cavitation control [C-C] waveform); a high-frequency ultrasound pulse (1 to 4 MHz) to create the cloud cavitation and a low-frequency trailing pulse (545 kHz) following the high-frequency pulse to force the cloud into collapse. High-speed photography has revealed that a localized distribution of the cloud cavitation can be produced within 1 mm on the solid surface by the high-frequency pulse. The low-frequency ultrasound was irradiated to the high-frequency-induced cloud cavitation. A subsequent shock wave emitted from the cloud cavitation was observed both in the shadowgraph photography and the remote hydrophone measurement. Furthermore, in vitro erosion tests of model and natural stones were conducted. In the case of model stones, the erosion rate of the C-C waveform showed a distinct advantage with the combined high- and low-frequency waves over either wave alone. Natural stones were eroded and most of the resulting fragments were less than 1 mm in diameter. The results show that the control of the cloud cavitation has untapped potential for the lithotripsy applications upon further optimization of the ultrasound parameters and complementary in vivo studies.

Interferon-related mental deterioration after craniotomy for removal of metastatic renal cancer.

Interferon-related severe adverse events on the central nervous system are relatively rare, because interferon-alpha (INF-alpha) can not cross an intact blood-brain barrier. We experienced remarkable mental deterioration caused by INF-alpha administration in a 43-year-old man with renal cell carcinoma after surgical removal of a metastatic brain tumor. We detected a high concentration of INF-alpha in a cerebrospinal fluid sample, which was comparable to that in the serum at 24 h after the administration of INF-alpha; 5x10(6) IU i.m., suggesting that the blood-brain barrier was damaged somehow by the craniotomy. The mental deterioration improved shortly after discontinuation of the INF-alpha administration.

Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study.

We report a multicenter trial with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate 500TM HIFU device (Focus Surgery, Indianapolis, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and prostate specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The median follow-up period for all patients was 14.0 months. Biochemical disease-free survival rates in all patients at 1 and 2 years were 78% and 76%, respectively. Biochemical disease-free survival rates in patients with stage T1c, T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10 at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75% and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant differences were noted in International Prostate Symptom Score, maximum urinary flow rate and quality of life analysis with Functional Assessment of Cancer Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer with pretreatment PSA levels less than 20 ng/ml.

The Val158Met polymorphism of the catechol-O-methyltransferase gene is associated with the PSA-progression-free survival in prostate cancer patients treated with estramustine phosphate.

OBJECTIVE: The aim of our study is to find out the good responders for estramustine phosphate (EMP) therapy in patients with prostate cancer. We have focused on the metabolism of EMP and studied the association between a functional single-nucleotide polymorphism in the catechol-O-methyltransferase gene (Val158Met of COMT) and PSA-progression-free survival in Japanese patients with prostate cancer treated by EMP. METHODS: Seventy-two Japanese patients with previously untreated prostate cancer who were found to be eligible for low-dose EMP therapy were enrolled in the study. Genotyping of the Val158Met polymorphism of COMT was conducted by both the polymerase chain reaction-based restriction fragment length polymorphism method and TaqMan assay. RESULTS: Patients with the Val/Val genotype of COMT had a significantly higher PSA-progression-free rate as compared to those with the Val/Met or Met/Met genotype (p=0.027). The adjusted hazard ratio of biochemical PSA failure for the Val158Met genotype of COMT was 2.164 (95% CI, 1.111 to 5.525). CONCLUSIONS: The Val158Met polymorphism of COMT is associated with the PSA-progression-free rate of EMP-treated patients in prostate cancer.

Function of the lower urinary tract in mice lacking alpha1d-adrenoceptor.

PURPOSE: alpha1-Adrenoceptor (AR) blockers are known to relieve not only voiding symptoms, but also storage symptoms in elderly men. We investigated lower urinary tract function in mice lacking alpha1d-AR using frequency/volume analysis and filling cystometry. MATERIALS AND METHODS: A total of 10, 12-week-old female alpha1d-knockout (KO) mice and 10 age matched female wild-type (WT) mice were studied. Each mouse was placed in a metabolic cage connected to a digital scale and personal computer. Under a 12/12-hour dark/light photocycle voiding frequency and volume were recorded for 48 hours. After frequency/volume analysis filling cystometry was performed with the mice awake and without restraint. The expression of alpha1-AR subtype mRNA in the bladder of mice in each group was quantified using real-time polymerase chain reaction. RESULTS: Mean daily voiding frequency +/- SD in alpha1d-KO mice was 9.0 +/- 2.1, significantly lower than 15.9 +/- 5.2 in WT mice (p = 0.0048). Mean volume per void in alpha1d-KO mice was significantly larger than in WT mice (0.24 +/- 0.02 vs 0.16 +/- 0.03 ml, p = 0.0096). Similarly cystometric analysis demonstrated larger bladder capacity (140%, p = 0.0008) and voided volume (146%, p = 0.0048) in alpha1d-KO mice compared with those in WT mice. No significant difference in maximum pressure at void was observed between the 2 groups. In WT mice the amount of alpha1a, alpha1b and alpha1d-AR subtype mRNA in the bladder was 5.2 +/- 0.7, 1.0 +/- 0.1 and 6.3 +/- 0.7 gene copies per ng total RNA, respectively. In contrast, alpha1d-AR transcript was not detectable in alpha1d-KO mice but alpha1a and alpha1b-AR expression was similar to that in WT mice. CONCLUSIONS: The results demonstrate that the alpha1d-AR subtype has an important role in regulating bladder function. They theoretically support a clinical finding that alpha1-blockers with significant affinity for alpha1d-AR are effective for treating storage symptoms associated with benign prostatic obstruction.

Subtypes of BK virus prevalent in Japan and variation in their transcriptional control region.

BK polyomavirus (BKV) is ubiquitous in the human population, infecting children without obvious symptoms, and persisting in the kidney in a latent state. In immunosuppressed patients, BKV is reactivated and excreted in urine. BKV isolates have been classified into four subtypes (I-IV) using either serological or genotyping methods. To elucidate the subtypes of BKV prevalent in Japan, the 287 bp typing region in the viral genome was PCR-amplified from urine samples of 45 renal transplant (RT) and 31 bone-marrow transplant (BMT) recipients. The amplified fragments were subjected to a phylogenetic or RFLP analysis to determine the subtypes of BKV isolates in urine samples. Subtypes I, II, III and IV were detected, respectively, in 70-80, 0, 2-3 and 10-20 % of the BKV-positive patients in both patient groups. This pattern of distribution was virtually identical to patterns previously demonstrated in England, Tanzania and the United States, suggesting that BKV subtypes are distributed similarly in various human populations. Furthermore, transcriptional control regions (TCRs) were PCR-amplified from the urine samples of 25 RT and 20 BMT recipients, and their nucleotide sequences were determined. The basic TCR structure (the so-called archetype configuration) was observed in most isolates belonging to subtypes I, III and IV (subtype II isolates were not available), albeit with several nucleotide substitutions and a few single-nucleotide deletions (or insertions). Only three TCRs carried extensive sequence rearrangements. Thus, it was concluded that the archetypal configuration of the BKV TCR has been conserved during the evolution of BKV.

Prolonged renal parenchymal retention of 99mTc mercaptoacetyltriglycine after nephron-sparing surgery.

OBJECTIVE: Nephron-sparing surgery is a treatment in which a part of a diseased kidney is resected and some parenchyma of the kidney is spared. Impairment of spared renal parenchyma after the surgery may cause prolonged prarenchymal retention in renal scintigraphy with Tc mercaptoacetyltriglycine (Tc-MAG3). The aim of this study was to determine whether or not parenchymal retention of Tc-MAG3 is prolonged after nephron-sparing surgery. METHODS: Twenty-two patients underwent a total of 29 Tc-MAG3 studies within 1 year after nephron-sparing surgery. In 17 patients (23 examinations) who had bilateral kidneys, the presence of diffuse prolongation of parenchymal retention was determined for the operated kidney. In all patients, the presence of regional prolongation around the surgical margin was assessed. RESULTS: Diffuse prolongation was observed in four of 10 examinations performed within 1 month after surgery and in none of 13 examinations performed later than 1 month after surgery. Regional prolongation was shown in 10 of 14 examinations performed within 1 month after surgery and in three of 15 examinations performed later than 1 month after surgery. In five patients who were studied both prior to and later than 1 month after surgery, regional prolongation was noted on the first study. On the second study, regional prolongation was improved and initial renal uptake around the surgical margin was intensified. CONCLUSIONS: Renal parenchymal retention of Tc-MAG3 is frequently prolonged in the early period after nephron-sparing surgery. Renal scintigraphy with Tc-MAG3 may aid in characterizing acute renal damage after nephron-sparing surgery.

Tiny nodule in the testicle: case report of a sertoli cell tumor.

Sex cord-stromal tumors of the testis are rare. We report on a small Sertoli cell tumor in the testicle. According to published reports, a nodular lesion on the testicle has a variety of differential diagnoses. Preoperatively, it is very difficult to differentiate between a tumorous lesion and an inflammatory change. When a tiny nodule in the testicle is encountered, we propose limited, testicular-sparing surgery according to the frozen section diagnosis.

EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer.

Many chemotherapeutic regimens combined with estramustine phosphate (EMP) have been elaborated for the treatment of hormone-refractory prostate cancer over 30 years. However, older EMP-based combination chemotherapies with vinblastine, vinorelbine, doxorubicin or cyclophosphamide showed relatively low PSA response rate (25-58%) accompanied with high toxicities. On the other hand, newly developed EMP-based combination regimens with etoposide, pacitaxel, carboplatin or docetaxel demonstrated promising PSA response rate (43-77%) with moderate to severe toxicity in the rate of thromboembolic event (5-18%) and of neutropenia (9-41%). Treatment-related death was less in the latter combination group (5/615, 0.8%) than that in the former group (3/234, 1.3%). Of note, in the docetaxel combination with EMP, PSA response rate is as high as 77% with high rate (41%) of neutropenia but no treatment-related death was observed. Docetaxel combination with EMP seems to be the best regimen, though not completely justified by randomized trials, to be selected in the modern era, which will be followed by paclitaxel, carboplatin and EMP combination with PSA response rate of 71%. In addition, an interim report in 83 patients was presented. They were not consecutively enrolled but were treated on low-dose EMP monotherapy for previously untreated advanced prostate cancer in Department of Urology of Tokyo University and our 21 affiliated hospitals. Overall PSA response rate was as high as 93.4% out of 76 assessable patients. However, overall toxicity rate was abnormally high (39.5%) with drug discontinuation rate of 32.1%. The reason of low drug compliance may be attributed to gastrointestinal symptoms. To overcome the low drug compliance, appropriate patients for EMP administration should be selected by using gene analysis on the basis of sophisticated tailor-made medicine.

Dendritic cell immunotherapy for patients with metastatic renal cell carcinoma: University of Tokyo experience.

BACKGROUND: Dendritic cells (DC) are the most potent antigen-presenting cells and induce host antitumor immunity through the T-cell response. A clinical study of immunotherapy using cultured DC loaded with tumor antigen, for patients with metastatic renal cell carcinoma (RCC) was performed. METHODS: Dendritic cells were generated by culturing monocytes from peripheral blood for 7 days in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. On day 6 the DC were pulsed with lysate from autologous tumor as the antigen and with keyhole limpet hemocyanin (KLH) as immunomodulator. The patients were given four doses of lysate-pulsed DC by intradermal injection with a 2-week interval between doses. Clinical effect and immune response were, respectively, evaluated by radiological examination and delayed-type hypersensitivity (DTH) test. RESULTS: Three patients were enrolled and the immunotherapy was well tolerated without significant toxicity. The vaccination induced a positive DTH reaction to tumor lysate in two patients and to KLH in all patients. Clinical responses consisted of one case of no change and two cases of progression of disease. However, we did not see a significant reduction of tumor volume in any case. CONCLUSION: Dendritic cell vaccination can safely induce an immunological response against RCC. Further trials are needed to fully evaluate its efficacy.

[Surgical outcomes of nephron-sparing surgery for renal tumors].

PURPOSE: We retrospectively assessed the surgical outcomes of nephron-sparing surgery (NSS) for patients with renal tumors. PATIENTS AND METHODS: From 1985 to March 2001, a total of 99 NSSs were performed on 94 patients with renal tumors. The patients were divided into three groups. Group I comprised of 22 patients who underwent imperative surgeries for renal cell carcinoma (RCC). The tumors were found in 18 patients bilaterally (including 8 patients with von Hippel-Lindau disease), in 3 with solitary kidney, and in 1 with chronic renal failure. The mean +/- standard deviation of patient age and tumor diameter was 46 +/- 23 years and 36 +/- 23 mm, respectively. Twenty-three in situ NSSs were performed on 18 patients in Group I, and the remaining 4 patients were treated with 3 simultaneous operations for bilateral renal tumors with or without 2 ex vivo surgeries. Group II consisted of 49 patients who had small RCCs with the normal contralateral kidney and underwent NSSs (elective indication). The mean age and tumor diameter was 54 +/- 10 years and 28 +/- 11 mm, respectively. Group III consisted of 23 patients with non-RCC tumor (10 angiomyolipomas, 8 cystic tumors, 2 adenomas, 2 metastatic tumors, and 1 degenerative lesion), all of whom were treated with NSS. The mean age and tumor diameter was 47 +/- 14 years and 41 +/- 29 mm, respectively. RESULTS: In Group I, 3 patients died of cancer including 2 patients who had had multiple lung metastases preoperatively. The five-year tumor specific survival rate was 87.3% with a postoperative follow-up of 49 +/- 36 months. In Group II, there were few peri-operative complications or no local recurrence at follow-up of 52 +/- 38 months. A patient developed lung metastasis, which was removed surgically with no evidence of recurrence at 159 months after NSS. Postoperative renal scintigraphy on 35 patients showed well-preserved renal function of the operated kidney. Improvement in surgical techniques resulted in less-invasive surgery in 22 operations during the last 4 years. The patients of Group III were also operated uneventfully, although 1 experienced postoperative bleeding. In 12 patients with solitary kidney (11 in Group I and 1 in Group III) serum creatinine level increased transiently, decreased to 1.3 times of preoperative values within 3 months, and almost recovered at 1-year follow-up. CONCLUSION: Excellent outcomes in cancer control and preservation of renal function support the validity of nephron-sparing surgery to treat renal tumors. The candidate patients may include those with bilateral kidney tumors, tumor occuring in the solitary kidney or small renal cell carcinomas with the normal contralateral kidney. Earlier detection of small lesions and less invasive surgical techniques will facilitate a wider indication of NSS.