[A Retrospective Study on the Malignancies after Renal Transplantation].

Detection of post-transplant malignant tumors and the analysis of the associated risk factors is important for monitoring the progress after renal transplantation. In this study, we retrospectively examined the medical records of 298 patients who underwent renal transplantation at two facilities in Nagasaki Prefecture (Nagasaki University Hospital and National Hospital Organization Nagasaki Medical Center). Of the 298 patients, 45 (15.1%) patients had developed malignant tumors with 50 lesions. The most common type of malignant tumor was skin cancer (eight patients; 17.8%), followed by renal cancer (six patients; 13.3%), and pancreatic cancer and colorectal cancer, (four patients; 9.0% each). Five patients (11.1%) had multiple cancers, four of whom had skin cancer. The cumulative incidence within 10 and 20 years after renal transplantation was 6.0 and 17.9%, respectively. Univariate analysis identified age at transplantation and administration of cyclosporine and rituximab as risk factors, while multivariate analysis identified age at transplantation and administration of rituximab as independent factors. The administration of rituximab was associated with the development of malignant tumors. However, further investigation is required to establish the association with post-transplant malignant neoplasms.

A case of early recurrent immunoglobulin A nephropathy and T-cell-mediated rejection in a transplant patient with Wiskott-Aldrich syndrome.

Wiskott-Aldrich syndrome (WAS) is an X-chromosome recessive immunodeficiency disease characterized by the triad of thrombocytopenia, eczema, and susceptibility to infection owing to WAS protein gene abnormalities. Kidney transplantation is rarely offered to WAS patients with end-stage renal disease because of concerns that thrombocytopenia and immune disorders may affect the clinical outcome. Here, we report the case of a 20-year-old kidney transplant patient who developed end-stage renal disease owing to immunoglobulin (Ig)A nephropathy caused by WAS. Despite recurrent IgA nephropathy and T-cell-mediated rejection 7 months after transplantation, two rounds of steroid pulse therapy attenuated his renal function and urinary abnormality. His serum creatinine level was maintained at approximately 1.5 mg/dL 1 year after transplantation. No other WAS-related complications were observed throughout the clinical course. Although WAS can cause poor prognosis in kidney transplant patients, careful follow-up may allow kidney transplantation to be performed.

Prevention of well-leg compartment syndrome following lengthy medical operations in the lithotomy position.

PURPOSE: Compartment syndrome that occurs after lengthy surgery in the lithotomy position is known as well-leg compartment syndrome. It has serious consequences for patients, including amyotrophic renal failure, limb loss, and sometimes even death. This study aimed to identify effective preventive measures against well-leg compartment syndrome using a retrospective cohort study of 1,951 patients (985 and 966 in the prevention and control groups, respectively). MATERIAL AND METHODS: The following preventive interventions were analyzed: (1) changing from the lithotomy position to the open-leg position, (2) removing lower leg pressure caused by the lithotomy position, (3) limiting leg elevation based on the height of the right atrium, (4) horizontally repositioning the operating table every 3 hours, and (5) decompressing the contact area of the lower leg in the lithotomy position during operation. RESULTS: Eight cases of well-leg compartment syndrome occurred in the control group, whereas no well-leg compartment syndrome occurred in the prevention group. CONCLUSION: These findings suggest that the five interventions assessed can prevent the development of well-leg compartment syndrome.

Comparison Between a Combined Transrectal and Transperineal Approach and a Transrectal Approach for Prostate Rebiopsy.

AIM: To evaluate whether a combination method involving the transrectal (TR) and transperineal (TP) approach can increase the cancer detection rate relative to the TR approach regarding repeat prostate biopsy. PATIENTS AND METHODS: One thousand and nineteen patients underwent initial prostate biopsies and 298 repeat prostate biopsies. All initial biopsies were conducted transrectally. Of the repeat biopsies, 179 (60.1%) were performed using the combined transrectal and transperineal (TR+TP) approach; 113 (37.9%) were carried out transrectally. All biopsies were performed under ultrasound guidance using a 16-gauge core biopsy needle; 651 were diagnosed as prostate cancer; 224 patients underwent radical prostatectomies (RPs). We evaluated the cancer detection rates between the biopsy methods in the repeat biopsy cohort and compared the clinical and pathological features of the RP specimens between the initial and repeat biopsy groups. RESULTS: A median of 12 and 20 cores were obtained in the initial and repeat biopsy patients, respectively. Cancer detection rates regarding biopsies 1, 2, 3, 4 and 5 were 49.2% (551/1,119), 34.7% (75/216), 33.3% (20/60), 26.7% (4/15) and 14.3% (1/7), respectively. There were no significant differences between the TR and the TR+TP approach (32.7% vs. 33.5%). RP specimens diagnosed using repeat biopsies showed more anterior dominant tumors relative to those diagnosed using the initial biopsies (59.5% vs. 35.9%; p<0.001). CONCLUSION: The TR+TP combination approach could not increase cancer detection rates relative to the TR approach in the repeat biopsy cohort. However, 16-gauge needle biopsy demonstrated acceptable cancer detection rates in the comparatively small number of biopsy cores.

Composite pheochromocytoma of the adrenal gland: a case series.

BACKGROUND: Composite pheochromocytoma is a rare pathological condition characterized by elements of both pheochromocytoma and neurogenic tumors. However, detailed clinical outcomes of this tumor have not been fully shown. From 2007 to 2013, we experienced three cases of adrenal composite pheochromocytoma. In this report, we investigate the clinicopathological features of these three cases of composite pheochromocytoma and compare them with previously reported cases. CASE PRESENTATIONS: Cases 1 and 2 were a 29-year-old Japanese woman and a 59-year-old Japanese man, respectively. They underwent laparoscopic left adrenalectomy, and pathological examination revealed composite pheochromocytoma-ganglioneuroma. Case 3 was a 53-year-old Japanese man who had been receiving hemodialysis for 17 years. He underwent laparoscopic right adrenalectomy, and pathological examination revealed composite pheochromocytoma-ganglioneuroblastoma. Although the Ki67-positive rates varied from 1.0 to 6.2% among the three cases, no clinical recurrences occurred. Despite the relatively high rate of Ki67 positivity, complete tumor resection resulted in favorable clinical outcomes. CONCLUSION: We experienced three cases of adrenal composite pheochromocytoma. Although the clinical findings and treatment outcomes of composite pheochromocytoma were similar to those of ordinary pheochromocytoma, further studies of the biological behavior and genetic profiles of composite pheochromocytoma are necessary to achieve a better understanding of this tumor.

[Clinical evaluation of ureteral stenting for managing extrinsic ureteral obstruction due to gynecological and gastrointestinal cancer].

We retrospectively reviewed patients who were treated with an indwelling ureteral stent to manage extrinsic ureteral obstruction due to advanced gynecological and gastrointestinal cancers. A total of 34 patients, including 17 with gynecological cancer and 17 with gastrointestinal cancer, underwent a successful initial ureteral stent placement from January 2007 to December 2011. Functional ureteral stent failures, which required percutaneous nephrostomy within 3 months after initial ureteral stenting, occurred in 14 of the 34 patients (41%) during follow-up. The risk factors of functional ureteral stent failure were bilateral ureteral obstruction, elevated serum creatinine level, poor performance status, subsequent therapy for primary cancer after ureteral stent placement, presence of peritonitis carcinomatosa, and gastrointestinal cancer. Patients with gastrointestinal cancer had a higher rate of stent failure than did those with gynecological cancer (p = 0.01). Median survival from the diagnosis of hydronephrosis for patients with gastrointestinal and gynecological cancers was 9 and 23 months, respectively (p = 0. 02). Retrograde ureteral stenting is a useful treatment for malignant ureteral obstruction. However, patients with gastrointestinal cancer had a high stent failure rate and a short survival time from the diagnosis of hydronephrosis. Indications for retrograde ureteral stenting for malignant ureteral obstruction should be carefully considered while taking into account stent failure risk, patient prognosis and quality of life.

Stability of [-2]Pro-PSA in whole blood and serum: analysis for optimal measurement conditions.

BACKGROUND: The clinical usefulness of [-2]pro-PSA (where PSA is prostate-specific antigen) in prostate cancer diagnosis has been emphasized in recent studies. To determine proper blood sample handling conditions for [-2]pro-PSA evaluation, we analyzed the preanalytical stability of [-2]pro-PSA. METHODS: Blood samples from 22 Japanese males were stored under various conditions before total PSA (tPSA), free PSA, and [-2]pro-PSA concentrations were measured, and the preanalytical stability of [-2]pro-PSA and the changes in the Prostate Health Index (phi) were assessed. RESULTS: [-2]Pro-PSA was stable in serum for at least 24 hr at both room temperature (RT) and at 4°C. However, [-2]pro-PSA levels in whole blood increased rapidly over time, particularly at RT. Mean recovery (%) of [-2]pro-PSA in whole blood at RT was >110% at 1 hr after drawing of blood. The phi tended to increase over time in a pattern similar to the change in[-2]pro-PSA. CONCLUSIONS: Preanalytical stability was lower for [-2]pro-PSA than for free PSA or tPSA. Whole-blood [-2]pro-PSA increased in a time-dependent manner, particularly at RT. Thus, whole blood samples collected at RT should be centrifuged within 1 hr after drawing. The [-2]pro-PSA in serum is stable for at least 24 hr at both RT and at 4°C.

Successful treatment for retroperitoneal cavernous hemangioma adjacent to the renal hilum via the laparoscopic approach: a case report.

INTRODUCTION: Cavernous hemangiomas are common benign tumors of the skin or liver but can also rarely originate from the retroperitoneal space, especially adjacent to the renal hilum. Qualitative characterization of these retroperitoneal tumors using available imaging modalities is relatively difficult. CASE PRESENTATION: A 40-year-old Japanese woman was incidentally noted to have a round homogenous tumor adjacent to the left renal hilum on computed tomography. The preoperative diagnosis was paraganglioma according to hormonal and clinical findings. The tumor was successfully resected via a laparoscopic approach, and histopathological examination of the tumor revealed cavernous hemangioma. CONCLUSIONS: Cavernous hemangioma is a rare but relatively benign disease when considering the different types of retroperitoneal tumors. We were able to effectively treat the retroperitoneal cavernous hemangioma via laparoscopy.

[A case report of bilateral spermatocytic seminoma].

Spermatocytic seminoma is a rare germ cell tumor which was first described by Masson in 1946. We experienced a case of bilateral spermatocytic seminoma. A 56-year-old man presented with painless swelling of left scrotal contents. This patient was diagnosed with bilateral testicular tumor after various image examinations (ultrasonography/computerized tomography/magnetic resonance imaging) and bilateral high orchidectomy was performed. Histological diagnosis was bilateral spermatocytic seminoma, pT1. After the operation, this patient was followed closely without adjuvant therapy. There has been no sign of recurrence at five months after the operation.

[Efficacy of naftopidil in patients with overactive bladder associated with benign prostatic hyperplasia: prospective randomized controlled study to compare differences in efficacy between morning and evening medication].

A total of 100 patients with benign prostatic hyperplasia (BPH) and overactive bladder (OAB) symptoms (BPH/OAB), enrolled between June 2006 to March 2008, were randomly divided into 2 groups of morning medication (M) and evening medication (E) groups, then 50 mg of naftopidil was given once a day after breakfast or supper for 8 weeks. Data were available for efficacy analysis on 80 patients (M group ; 43, E group ; 37). Naftopidil significantly improved the overall international prostatic symptom score ; from 19.2±7.9 to 11.7±5.8 in the M group and from 19.4±6.4 to 12.3±6.8 in the E group (p<0.0001), QOL score from 4.9±0.8 to 3.2±1.4 in the M group and from 5.0±0.8 to 3.6±1.3 in the E group (p<0.0001), and OAB symptom score from 7.8±2.6 to 5.0±2.5 in the M group (p<0.0001) and from 8.6±2.9 to 5.8± 3.3 in the E group (p<0.0001). There was no significant difference in the incidence of adverse effects between the M group (6.1%) and E group (2.2%). These results suggest that naftopidil improves storage symptoms as well as voiding symptoms regardless of timing of administration.

[Secondary endocrine therapy with oral estrogen for relapsed prostate cancer].

We report clinical outcomes of secondary endocrine therapy with oral estrogen for relapsed prostate cancer. A total of 18 patients were treated with oral estrogen as a secondary endocrine therapy for relapsed prostate cancer between February 2002 and December 2007. One mg/day of ethinylestradiol was administered orally and the dose was increased to 3 mg/day if necessary. A decrease of serum prostate specific antigen (PSA) level was seen in all of the 15 patients who were able to take ethinylestradiol without severe side effects. The PSA level was decreased more than 50% in 11 out of 15 (73.3%) patients. Median re-relapse-free survival was 15 (3-32) months. This effectiveness was as good as intravenous high-dose diethylstilbestrol diphosphate (DES-DP) treatment which was used as a secondary endocrine therapy for relapsed prostate cancer at our institute previously. Oral administration of ethinylestradiol is effective and outpatients can be treated at a low cost, so it should be considered as one of the treatment options for relapsed prostate cancer after initial endocrine therapy.

[A case of retroperitoneal schwannoma extracted by a nerve sparing procedure under microscopic surgery].

We report a case in which we extracted retroperitoneal schwannoma by a nerve sparing procedure under microscopic surgery. A 63-year-old male was diagnosed with left ureter stone and left hydronephrosis. A left retroperitoneal tumor was found by the abdominal ultrasound sonography. Abdominal computed tomography and magnetic resonance imaging revealed the mass 20 mm in diameter in the retroperitoneal cavity. We considered that the tumor arose from the left femoral nerve, and removed it under microscopic surgery. There was no malignancy. There was neither recurrence nor neuropathy after operation. Since it is rare to find the origin nerve of schwannoma before operation, we report our experience.

Correlation study showing no concordance between EPAS-1/HIF-2alpha mRNA and protein expression in transitional cellcancer of the bladder.

OBJECTIVES: Endothelial Per-ARNT-Sim (PAS) domain protein-1 (EPAS-1)/hypoxia-inducible factor (HIF)-2alpha is a recently identified, endothelial-specific, hypoxia-induced transcription factor and is reputed to have an important role in tumor angiogenesis and tumor progression. Only a few studies have reported on the clinical correlation with grade, stage, necrosis, and microvessel density in transitional cell carcinoma of the bladder. In vitro studies have reported no concordance of EPAS-1/HIF-2alpha mRNA and protein expression. We sought to elucidate these two issues. METHODS: Surgical specimens from 110 patients with transitional cell carcinoma comprised the study, including 51 from radical cystectomy and 59 from transurethral resection of bladder tumor. Immunohistochemistry and in situ hybridization were performed with antibodies against EPAS-1/HIF-2alpha, CD31, and a human EPAS-1/HIF-2alpha cDNA subclone probe. RESULTS: EPAS-1/HIF-2alpha protein expression was found almost exclusively in high-grade and high-stage tumors (P <0.0001). EPAS-1/HIF-2alpha mRNA expression was detectable only in high-grade (grade 3) and high-stage (pT3a or greater) cases with positive EPAS-1/HIF-2alpha protein expression (P = 0.0017). The presence of necrosis correlated with EPAS-1/HIF-2alpha expression, tumor grade, and tumor stage (P <0.0001). Microvessel density was much lower in invasive, larger tumor nodules in EPAS-1/HIF-2alpha-positive cases than in the negative cases (P <0.0001). CONCLUSIONS: EPAS-1/HIF-2alpha protein and mRNA levels correlate with higher grade and advanced bladder transitional cell carcinoma. In lower stage cases, no concordance was found between transcription and translation of EPAS-1/HIF-2alpha gene expression. Because EPAS-1/HIF-2alpha mRNA is only detectable in highly invasive cancer cases, it may serve as a therapeutic target (eg, by an antisense mRNA approach) for bladder cancer.

Hypoxia-induced, perinecrotic expression of endothelial Per-ARNT-Sim domain protein-1/hypoxia-inducible factor-2alpha correlates with tumor progression, vascularization, and focal macrophage infiltration in bladder cancer.

Endothelial Per-ARNT-Sim (PAS) domain protein-1 (EPAS-1)/hypoxia-inducible factor-2alpha (HIF-2alpha) is a member of the basic helix-loop-helix/PAS domain protein family and is considered to be an endothelial-specific, hypoxia-inducible transcription factor. Because hypoxia is a fundamental element of tumor biology determining clinical outcome, we performed an immunohistochemical study of EPAS-1 expression in a cohort of bladder cancer cases and assessed the possible correlation of EPAS-1 expression with tumor hypoxia and growth. In the 67 cases (37 radical cystectomy and 30 transurethral resection) studied, overexpression of EPAS-1/HIF-2alpha protein was not found in cancer cells or in normal tissues but was mostly found in stroma around cancer cells, and strong positive staining was noted in perinecrotic regions. The perinecrotic/tumorous expression of EPAS-1/HIF-2alpha was correlated statistically with higher histological grade (P < 0.001), advanced pathological T stage (P < 0.001), and presence of necrosis (P < 0.001). A parallel immunohistochemical analysis of a marker gene of vascular endothelial growth factor demonstrated its positive correlation with tumor grade, stage, and EPAS-1/HIF-2alpha overexpression, supporting the correlation of EPAS-1/HIF-2alpha up-regulation with tumor angiogenesis. To further clarify the relationship between hypoxia and vascularity in the perinecrotic/tumorous area with EPAS-1/HIF-2alpha expression, tissue microvessel density (MVD) was assessed. No significant correlation (P = 0.442) was found between EPAS-1/HIF-2alpha expression and MVD if the 67 tumors of different stages were all included. However, EPAS-1/HIF-2alpha-positive cases had lower MVD than EPAS-1/HIF-2alpha-negative cases (P = 0.001) if only invasive cancer cases were analyzed. In addition, in all EPAS-1/HIF-2alpha-positive staining cases, EPAS-1/HIF-2alpha-positive foci had lower MVD than EPAS-1/HIF-2alpha-negative foci (P < 0.001). Finally, using serial sections, the location of EPAS-1/HIF 2alpha expression was identified mainly in tumor-associated macrophage (TAM) as well as in some fibroblast cells. Focal TAM infiltration was identified at a higher level in EPAS-1-positive cases than EPAS-1-negative cases (P < 0.001). This is the first clinical report suggesting that hypoxia-induced, perinecrotic EPAS-1/HIF-2alpha expression is correlated with tumor progression and angiogenesis at higher grade and stage through focal TAM infiltration in invasive bladder cancer.