Progression of Human Renal Cell Carcinoma via Inhibition of RhoA-ROCK Axis by PARG1.

Renal cell carcinoma (RCC) is the most lethal urological malignancy with high risk of recurrence; thus, new prognostic biomarkers are needed. In this study, a new RCC antigen, PTPL1 associated RhoGAP1 (PARG1), was identified by using serological identification of recombinant cDNA expression cloning with sera from RCC patients. PARG1 protein was found to be differentially expressed in RCC cells among patients. High PARG1 expression is significantly correlated with various clinicopathological factors relating to cancer cell proliferation and invasion, including G3 percentage (P = .0046), Ki-67 score (p expression is also correlated with high recurrence of N0M0 patients (P = .0084) and poor prognosis in RCC patients (P = .0345). Multivariate analysis has revealed that high PARG1 expression is an independent factor for recurrence (P = .0149) of N0M0 RCC patients. In in vitro studies, depletion of PARG1by siRNA in human RCC cell lines inhibited their proliferation through inducing G1 cell cycle arrest via upregulation of p53 and subsequent p21Cip1/Waf1, which are mediated by increased RhoA-ROCK activities. Similarly, PARG1 depletion cells inhibited invasion ability via increasing RhoA-ROCK activities in the RCC cell lines. Conversely, overexpression of PARG1 on human embryonic kidney cell line HEK293T promotes its cell proliferation and invasion. These results indicate that PARG1 plays crucial roles in progression of human RCC in increasing cell proliferation and invasion ability via inhibition of the RhoA-ROCK axis, and PARG1 is a poor prognostic marker, particularly for high recurrence of N0M0 RCC patients.

[Causes and salvage of failed urethroplasties for traumatic urethral injury].

OBJECTIVES: Salvage urethroplasty after failed repair of traumatic urethral injury is a urological challenge, and we herein describe our experience with it. METHODS: From October 2010 to January 2012, five patients underwent salvage repair of failed urethroplasties for traumatic urethral injuries: three bulbar straddle injuries and two pelvic fracture urethral injuries. One of the three failed urethroplasties for bulbar straddle injuries was a stricture excision and primary anastomosis, and its failure was due to periurethral abscess formation. Another was an augmented anastomotic urethroplasty using buccal mucosa, and its failure was due to periurethral abscess formation. The third was a tube graft urethroplasty using buccal mucosa, and its failure was due to a stricture at the anastomotic site. Two failed urethroplasties for pelvic fracture urethral injuries were perineal anastomotic repairs combined with corporal separation and inferior pubectomy, and the failures of both were due to ischemic bulbar necrosis. The urethral gap lengths estimated from urethrograms ranged from 12 to 45 mm (mean = 26 mm). RESULTS: Urethroplasties in all patients with bulbar straddle injuries were salvaged by stricture excision and primary anastomosis with corporal separation, and urethroplasties in both patients with pelvic fracture urethral injuries were salvaged by abdominal transpubic perineal urethroplasty. Although the patients who underwent transpubic urethroplasty had transient pelvic girdle pain, no severe complications were observed. All patients were for 10 to 25 months postoperatively (mean = 16 months) able to void satisfactorily without additional treatment. CONCLUSIONS: Failed urethroplasties for traumatic urethral injuries can be salvaged with a second reconstruction surgery. The procedure of choice for this salvage is anastomotic urethroplasty with techniques for tension-free anastomosis.

Increased expression of α-actinin-4 is associated with unfavorable pathological features and invasiveness of bladder cancer.

In the present study, the association between clinicopathological parameters and α-actinin-4 (ACTN4) expression in bladder cancer specimens was evaluated, and the functional role of ACTN4 in bladder cancer cells was investigated. Immunohistochemistry using anti-ACTN4 antibody was performed in bladder cancer specimens (53 superficial and 42 muscle-invasive cases) from 95 patients who underwent radical cystectomy (n=46) or transurethral resection (TUR) only (n=49). We divided the levels of ACTN4 expression into 2 groups (low or high) by comparing the staining intensity in each specimen with that of the vascular endothelial cells in the same specimen, and we evaluated the correlations between these levels and pathological parameters, recurrence and prognosis. We also investigated the effects of ACTN4 suppression by siRNA on the invasive ability and proliferation of T24 and KU19-19 cells. High ACTN4 expression was significantly associated with higher tumor grade and higher pT stage. In patients with superficial bladder cancer treated only by TUR, the rate of intravesical recurrence did not differ significantly between patients with high ACTN4 expression and patients with low ACTN4 expression. In patients who had muscle­invasive tumors and underwent radical cystectomy, high ACTN4 expression was associated with neither recurrence nor poor prognosis. Nonetheless, high ACTN4 expression was shown by a large percentage (81%) of patients with muscle-invasive bladder cancer and by a small percentage (17%) of patients with superficial bladder cancer. Furthermore, the leading edges of the invasive bladder cancer showed increased ACTN4 expression. ACTN4 suppression significantly reduced the number of invading bladder cancer cells but unexpectedly increased the proliferation of bladder cancer cells. ACTN4 suppression increased the phosphorylation of ERKs but not AKT or STAT3, suggesting that the increased proliferation due to ACTN4 suppression was mediated in part by the ERK pathway. ACTN4 expression may suppress the proliferation of bladder cancer cells and may produce conditions which facilitate cancer cell invasion.

[The diagnostic value of pre-biopsy magnetic resonance imaging for precise detection of clinically localized prostate cancer compared to post-biopsy setting].

A total of 136 patients who underwent radical prostatectomy following histological diagnosis of prostate cancer by transrectal biopsy and 3-Tesla magnetic resonance imaging (MRI) were evaluated. MRI was performed on 26 patients before prostate biopsy (pre-biopsy group) and on 110 patients after prostate biopsy (post-biopsy group). We defined the largest tumor focus in a radical prostatectomy specimen as the index cancer. We compared the accuracy of MRI in detecting and localizing the index cancer in the groups. The sensitivity of detecting the index cancer by MRI was significantly (p = 0.012) higher in the pre-biopsy group (96.2%) than in the post-biopsy group (77. 3%). The negative predictive value of extracapsular invasion was 84.6% in the pre-biopsy group and 80.7% in the post-biopsy group. The average interval between biopsy and MRI was 42.8 days. Artifacts due to post-biopsy hemorrhage were observed in 32 (29.1%) of the patients in the post-biopsy group. The sensitivity of detecting the index cancer by MRI was significantly (p = 0.022) higher in 78 patients without artifacts due to hemorrhage (83.3%) than in the 32 patients with artifacts due to hemorrhage (62.5%). Even if MRI is delayed until after prostate biopsy,the artifact due to hemorrhage markedly interferes with the accuracy of MRI. Although pre-biopsy MRI is more accurate than post-biopsy MRI,there are some problems to be solved,such as cost effectiveness and the detectability of low-malignant and small cancers.

Impact of increased erythropoietin receptor expression and elevated serum erythropoietin levels on clinicopathological features and prognosis in renal cell carcinoma.

Erythropoietin (EPO) expression and EPO receptor (EpoR) expression have been demonstrated in various malignant tumors. EPO-EpoR signaling can activate several downstream signal transduction pathways that enhance tumor aggressiveness. The present study was undertaken to evaluate the impact of overexpression of EpoR and elevated serum EPO (sEPO) levels on the clinicopathological features and prognosis of patients with renal cell carcinoma (RCC). EpoR expression was evaluated immunohistochemically in 56 patients. Tumors with a staining intensity greater than that of surrounding proximal tubules were defined as tumors with high EpoR expression. The association between EpoR expression levels and various clinicopathological factors was analyzed. sEPO levels were determined in 138 patients and its correlation to clinicopathological factors was also analyzed, and EpoR expression was determined in surgical specimens removed from 47 of those 138 patients. Patients with high EpoR expression and patients with sEPO elevation had clinicopathological features less favorable than those of other patients. Tumors demonstrating high EpoR expression had a significantly higher number of Ki-67-positive cells compared to those with low EpoR expression. Tumor assemblies in microvessels demonstrated high EpoR expression. Patients whose tumors demonstrated high EpoR expression and those with sEPO elevation had a significantly lower survival rate compared to other patients, and patients with both high EpoR expression and sEPO elevation had an extremely poor prognosis. Microvascular invasion was an independent factor associated with sEPO elevation, suggesting that EPO-EpoR signaling might be important in RCC metastasis. EPO-EpoR signaling may be involved in tumor growth and progression in RCC and the combination of EpoR expression and sEPO levels may effectively predict clinical outcome.

[The efficacy of direct vision internal urethrotomy for male urethral stricture].

OBJECTIVE: Direct vision internal urethrotomy (DVIU) has been considered to be a low invasive and widely used therapeutic modality for male urethral stricture. However, its efficacy is still controversial. We herein evaluated the efficacy of DVIU for male urethral stricture. PATIENTS AND METHODS: Nineteen patients 27 to 78 years old (median age = 59) underwent DVIU for urethral strictures at our hospital were included in this study. Strictures were at bulbar urethra in 17 patients, membranous urethra in 1 patient, and pendulous urethra in 1 patient. The stricture lengths estimated on retrograde urethrography were less than 1 cm in 13 patients, 1-2 cm in 2 patients, and more than 2 cm in 4 patients. The etiology of stricture was straddle injury in 7 patients, post transurethral surgery in 7 patients, pelvic fracture in 1 patient, and unknown in 4 patients. The operation was done by cold knife incision using guidewire. The duration of postoperative urethral catheterization was 5 to 35 days (mean 12.8 days). Follow up duration ranged from 1 month to 139 months (mean 48.2 months). The definition of postoperative re-stricture was the confirmation of re-stricture on retrograde urethrography or deterioration of symptom. RESULTS: While no severe complication was observed, postoperative re-stricture was seen in 13 patients. Stricture-free rates at 3 months, 6 months, and 5 years after the first DVIU were 44.4%, 38.1%, 20.3% respectively. Although second DVIU was done for 7 patients with re-stricture, six patients resulted in failure. Stricture-free rates at 3 months, 6 months, and 5 years after the second DVIU were 42.2%, 28.6%, 14.3% respectively. Though the third DVIU was done for two of them, they were unable to void just immediately after the removal of urethral catheters. Stricture-free rate in stricture less than 1 cm was higher than that in 1 cm or longer, though it did not reach significant difference (p = 0.1813). CONCLUSION: The efficacy of DVIU is lesser than we expected. DVIU seems to be excessively applied to male urethral strictures and should not be performed for long and recurrent urethral stricture.

Glucose-regulated protein 78 positivity as a predictor of poor survival in patients with renal cell carcinoma.

INTRODUCTION: Glucose-regulated protein 78 (GRP78), a chaperone for newly formed proteins during folding and glycosylation, is associated with resistance to apoptosis in some forms of cancer. We assessed GRP78 expression and its correlation with clinicopathological parameters and survival. PATIENTS AND METHODS: Immunohistochemistry was performed using formalin-fixed, paraffin-embedded specimens: 128 primary renal cell carcinoma (RCC) specimens (120 conventional and 8 other cell types) and 9 metastatic specimens. GRP78 positivity was determined based on intensity of staining and percentage of cells stained. Correlation of GRP78 positivity with clinicopathological parameters including patients' survival was evaluated. RESULTS: A statistically significant association was found between GRP78 positivity and higher tumor grade (G3; p <0.0001), advanced T stage (≥pT3; p = 0.0002), lymphovascular invasion (positive; p <0.0001), regional nodal involvement (≥N1; p = 0.0086), and distant metastases at presentation (M1; p = 0.001). Positivity of GRP78 expression was significantly associated with shorter disease-specific survival and shorter progression-free survival. Cox proportional hazard model showed that strong GRP78 positivity was an independent predictor of shortened progression-free survival in N0M0 RCC patients. CONCLUSIONS: There was a significant relationship between GRP78 expression levels and aggressiveness of RCC. Increased expression of GRP78 might be a useful parameter to predict shortened survival in patients with RCC.

[Clinical experience of 52 patients undergoing laparoscopic radical prostatectomy].

Perioperative results and oncological and functional results were evaluated for 52 patients who underwent laparoscopic radical prostatectomy (LRP). Median operative time was 341 minutes and median blood loss was 828 ml. The intraoperative complications were hemorrhage exceeding 3,000 ml (five cases), ureteral injury (two cases), and rectal injury (one case). The median day of catheter removal was postoperative day 7. Postoperative complications were temporal arrhythmia, mild hydronephrosis, port site hernia, urethral stricture, and a giant lymphocele. When surgical results were compared between the firsthalf cases and second-half cases who were operated on by a single surgeon, median operative time and intraoperative hemorrhage did not differ significantly between the two halves but the day of catheter removal after LRP was significantly earlier for the second-half group. The pathological stage was pT3 in 41.2% of the patients and the negative surgical margin rate was 62.7%. The 3-year PSA-failure-free survival rate was 64. 1%. Pad-free status (0-1 pad/day) was achieved in 84.4% of the patients. Erectile function was preserved in 58.3% of patients undergoing nerve-sparing LRP. Although the complication rate and the quality of operative procedures gradually improved, efforts to improve the oncological and functional outcomes of LRP must continue.

A case report of retroaortic left renal vein with tumor thrombus of renal cell carcinoma.

A 75-year-old woman was referred to our department for evaluation of a left renal tumor. Computed tomography and other imaging studies demonstrated a left renal mass and tumor extension into the left renal vein passing caudally behind the aorta. We clinically diagnosed the tumor as renal cell carcinoma (RCC) associated with a retroaortic left renal vein thrombus, and performed a radical nephrectomy. Pathological examination of the surgical specimen showed a grade 2, clear cell carcinoma with a renal vein thrombus and negative surgical margin. Retroaortic left renal vein is a rare anomaly with a prevalence of 1.8-2.4%. RCC associated with a retroaortic left renal vein thrombus is rarer still. To our knowledge, this is only the third case report to describe an RCC associated with a tumor thrombus in the retroaortic left renal vein.

[Spontaneous rupture of the ureter as the primary symptom of malignant lymphoma].

We report a rare case in which upper ureteral rupture was the primary symptom of malignant lymphoma. A 74-year-old female visited our hospital with left flank pain. Computed tomography showed urinoma around the left kidney and retrograde pyelography showed a diffuse filling defect in the left ureter and a rupture of the upper portion of that ureter. A urine cytology specimen from the left ureter was class V, suggesting undifferentiated carcinoma or malignant lymphoma. An open laparotomy revealed a nodule on the omentum and diffuse fibrosis around both ureters, and the histopathological diagnosis was diffuse large B-cell lymphoma. The patient' s ureteral stenosis disappeared after she received six cycles of R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone and rituximab) chemotherapy. We should be aware that malignant lymphoma can be the cause of a spontaneous ureteral rupture.

[Clinical experience of treatment of liver metastasis of renal cell carcinoma treated with SMANCS/Lipiodol therapy].

The treatment for metastatic renal cell carcinoma (RCC) has changed dramatically after the beginning of molecular-targeted therapies. However,the treatment for liver metastasis is still difficult in patients with metastatic RCC. We treated liver metastases (8 target lesions) of RCC with stylene-maleic acid neocarzinostatin (SMANCS)/Lipiodol therapy. At the treatment procedure,a catheter was inserted at the femoral artery (Seldinger's method),a microcatheter was selectively inserted into the branch of hepatic artery which fed the liver metastasis,and then SMANCS/Lipodol was infused. We treated 1,2 and 1 patient 4,2, and 1 time,respectively. One lesion treated with SMANCS/Lipodol was further treated by radiofrequency ablation 13 days later. Of 6 metastatic lesions which could be followed up for more than 6 months after the treatment,one had partial response for 4 months and 4 had stable disease for more than 6 months. Four of the 6 lesions shrunk after SMANCS/Lipiodol treatment. Two of 4 patients survived more than 18 months after the first SMANCS/Lipiodol therapy. In all 9 SMANCS/Lipiodol treatments,grade 1 liver dysfunction (44.4%),ascites (11.1%) and fatigue (11.1%) occurred after the treatments. These adverse events were all improved by conservative treatments. SMANCS/Lipiodol therapy can be a treatment option as local treatment for liver metastasis of RCC.

[Case of primary amelanotic malignant melanoma of the female urethra].

We report a rare case of primary amelanotic malignant melanoma of the female urethra. A 58-year-old female with complaint of nodule on the external urethral meatus was referred to our hospital. Pathological diagnosis of the biopsy specimen from the nodule was malignant melanoma. Computed tomography of the chest and abdomen as well as bone scan showed no evidence of metastasis. Sentinel biopsy from the inguinal lymph nodes revealed no metastasis. Thereafter, the patient underwent radical urethrectomy, whose limits of resection were the bulbocavernosal muscles bilaterally, the arch of the pubic symphysis anteriorly, the anterior vaginal wall posteriorly, and the urethra up to the level of the bladder neck superiorly. The histopathological diagnosis was amelanotic malignant melanoma of the urethra. The patient had received six cycles of DAV-Feron (dacarbazine, nimustine, vincristine, and interferon-beta) in an adjuvant setting, and there is no sign of recurrence 25 months after operation.

Severe polyuria after the resection of adrenal pheochromocytoma.

A 73-year-old male patient with hypertension and hyperglycemia was referred to our hospital because of a diagnosis regarding his left adrenal tumor. Because the levels of urinary metanephrine and normetanephrine were elevated, and (131) I-MIBG scintigraphy showed intense uptake in the adrenal tumor, the tumor was diagnosed as a pheochromocytoma. An adrenalectomy was carried out. Severe polyuria, which was accompanied by a rapid decrease in central venous pressure, started 1 hour after the operation. Urine output of more than 8000 mL/day continued until the 16th postoperative day. Plasma antidiuretic hormone (ADH) levels were within the normal range. Plasma human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were elevated postoperatively, and the elevation of these peptides was one possible cause for the severe polyuria. Because ADH levels in the tumor fluid were not elevated, the tumor was not an ADH-secreting tumor. Urinary ß2-microglobulin was significantly elevated after the operation, thus suggesting that renal tubule dysfunction might also have been involved in the polyuria. However, the mechanism of polyuria after the resection of adrenal pheochromocytoma is not fully understood. Polyuria after the resection of adrenal pheochromocytoma is extremely rare, and the present subject is the second case to date.

[Oral mucosa graft urethroplasty for complicated urethral strictures].

OBJECTIVE: We evaluated the efficacy and outcome of one-stage oral mucosa graft urethroplasty, which is currently the procedure of choice for treating lengthy and complicated urethral strictures not amenable to excision and primary end-to-end anastomosis. PATIENTS AND METHODS: Seven patients 33 to 74 years old (mean age = 53.7) underwent one-stage oral mucosa graft urethroplasty for a stricture in either the bulbar urethra (four patients), penile urethra (two patients), or pan-anterior urethra (one patient). Three of the strictures were due to trauma, one was due to inflammation, and one was due to a failed hypospadia repair. The other two were iatrogenic. All patients had previously undergone either internal urethrotomy or repeated urethral dilation. Three patients received a tube graft, three received a ventral onlay, and one received a dorsal onlay. A free graft of oral mucosa was harvested from the inside of each patient's left cheek, and if necessary to obtain a sufficient length, the harvest was extended to include mucosa from the lower lip and the right cheek. The graft lengths ranged from 2.5 to 12 cm (mean = 4.6 cm). A urethral catheter was left in place for 3 weeks postoperatively. RESULTS: While no severe complications at the donor site were observed during follow-up periods ranging from 3 to 55 months (mean = 14 months), two patients who had received a tube graft developed distal anastomotic ring strictures that were managed by internal urethrotomy. The other five required no postoperative urological procedure even though one who had received a ventral onlay developed a penoscrotal fistula. CONCLUSION: Oral mucosa is an ideal urethral graft, and oral mucosa graft urethroplasty is an effective procedure for repairing complicated urethral strictures involving long portions of the urethra.

Adrenomedullin increases renal nitric oxide production and ameliorates renal injury in mice with unilateral ureteral obstruction.

PURPOSE: We evaluated the effects of adrenomedullin (Peptide Institute, Minoh-shi, Osaka, Japan) on mediators, including nitric oxide and transforming growth factor-beta, and parameters of renal injury in a murine unilateral ureteral obstruction model. MATERIALS AND METHODS: Three study groups of control, adrenomedullin treated and adrenomedullin plus L-NAME treated BALB/C mice, respectively, underwent left unilateral ureteral obstruction. A 24-hour urine sample was collected to measure urinary NO(2)/NO(3) 1 day before unilateral ureteral obstruction and kidneys were harvested on postoperative day 14. Tubulointerstitial damage markers were evaluated by immunohistochemistry. Tissue transforming growth factor-beta was determined by enzyme-linked immunosorbent assay. Endothelial and inducible nitric oxide synthase immunolocalization was also determined. RESULTS: Urinary NO(2)/NO(3) was significantly higher in the adrenomedullin group than in controls, confirming increased renal nitric oxide production. Immunohistochemistry showed increased endothelial nitric oxide synthase in vascular endothelial cells in the adrenomedullin group but tissue transforming growth factor-beta did not significantly differ in controls vs the adrenomedullin group. Interstitial collagen deposition and fibroblasts in the obstructed kidney were significantly decreased in the adrenomedullin group. The number of leukocytes and apoptotic cells in the obstructed kidney were significantly decreased by adrenomedullin. Renal injury amelioration resulting from adrenomedullin was blunted by the nitric oxide synthase inhibitor L-NAME. CONCLUSIONS: Adrenomedullin increased renal nitric oxide, and suppressed tubular apoptosis, interstitial fibrosis and inflammatory cell infiltration in mice with unilateral ureteral obstruction. The renoprotective peptide adrenomedullin may be useful for that condition.

Bilateral adrenal leiomyosarcoma treated with multiple local therapies.

A 62-year-old woman presented with right flank pain, and computed tomography (CT) showed bilateral adrenal tumors (right, 8 cm; left, 4 cm). There were no abnormal findings on physical examination, and adrenal hormone levels in serum and urine were within normal limits. Radiological studies showed a right adrenal tumor with intratumoral hemorrhage, a cystic tumor in the left adrenal gland, and no sign of distant metastasis. Because laboratory tests showed normal levels of adrenal hormones, we considered the tumors to be nonfunctioning adrenal tumors. The right adrenal tumor was surgically removed because it was thought to be malignant, and histological examination revealed that it was a leiomyosarcoma. Postoperative CT showed a pleural metastasis in the right chest wall. The patient received combination chemotherapy with cyclophosphamide, vincristine, adriamycin, and dacarbazine. The metastasis was also treated with radiofrequency ablation (RFA). Because the left adrenal tumor grew rapidly despite two courses of the chemotherapy, it too was surgically removed. After the operation, metastasis in the right iliac bone was treated with RFA and radiotherapy. Positron emission tomography detected bilateral femoral metastases, and these were treated with radiotherapy in combination with a low dose of cisplatin. A liver metastasis and a small metastasis in the left kidney were treated with RFA and a metastasis in the pancreatic tail was removed surgically. Sixteen months after the right adrenalectomy, the patient died due to systemic spread of the disease. Multiple local treatments including RFA, radiotherapy, and resection were effective for the local control of metastatic lesions of adrenal leiomyosarcoma.

[Two cases of unilateral adrenalectomy for bilateral adrenal Cushing syndrome].

For treatment of bilateral adrenal Cushing syndrome (CS) unilateral adrenalectomy (UAdx) is less invasive than bilateral adrenalectomy and lifetime replacement of glucocorticoids can be avoided. Laparoscopic UAdxs was performed on 2 patients with bilateral adrenal CS. In both cases, symptoms associated with CS were improved after UAdx. Although serum adrenocorticotropic hormone levels remained lower than normal after UAdxs, cortisol levels in both serum and urine have been maintained within normal ranges for more than 1 year in both cases.

[Case of pelvic retroperitoneal fibrosis].

A 66-year-old man visited his nearby clinic with a complaint of left lower abdominal pain. Abdominal CT scan showed left hydronephrosis due to lower ureteral involvement by infiltrative retroperitoneal mass located outside of the left posterior wall of the bladder and left seminal vesicle. He was referred to our hospital for further examination. Pathological diagnosis of the percutaneous CT-guided biopsy of retroperitoneal mass was fibrosis without any malignant tumor. Because we could not rule out the possibility of the secondary fibrosis accompanied by malignant tumor, we performed surgical resection of the retroperitoneal mass involving left ureter and confirmed that the mass contains no malignant tumor by frozen section analysis. We augmented the defected ureter by Boari flap method. We should be noticed that retroperitoneal fibrosis could be a differential diagnosis of retroperitoneal pelvic mass.

Clinical impact of the presence of the worst nucleolar grade in renal cell carcinoma specimens.

OBJECTIVE: Renal cell carcinoma (RCC) with a high-nucleolar-grade component is considered to be an aggressive type of tumor. In the present study, we evaluated the impact of the presence of the worst-nucleolar-grade component and also tried to determine predictors for recurrence and prognosis in patients with the worst grade component. METHODS: We evaluated 314 patients with RCC. A three-graded system was used for nucleolar grading, the patients were classified into four groups according to the presence of the worst nucleolar grade (Grade 3) and the occupancy of each grade, and clinicopathological factors and clinical outcomes were compared. In patients of Grade 3 components (Groups 1 and 2), factors influencing on prognosis and recurrence were evaluated by multivariate analysis. RESULTS: There was no significant difference in clinicopathological factors between Group 1 (with Grade 3-dominant tumors) and Group 2 (with tumors in which Grade 1 or 2 was dominant and there were Grade 3 components). Neither did cause-specific survival or recurrence-free survival differ significantly between those two groups. In multivariate analysis, only distant metastasis was an independent predictor for prognosis in all patients with Grade 3 components. Moreover, an elevated C-reactive protein (CRP) level (>or=1 mg/dl) was the only independent predictor of recurrence in N0M0 patients. CONCLUSIONS: Regardless of dominancy, the presence of the worst grade component has a significant clinical impact in RCC patients. N0M0 patients whose RCC has worst-grade components but whose CRP levels are <1 are expected to have longer recurrence-free intervals and to survive longer than those whose CRP levels are higher.

[Severe hypoglycemia after resection of adrenal pheochromocytoma: a case report].

A 55-year-old female presented with subarachnoid hemorrhage and was admitted to the department of neurosurgery. Because she had severe hypertension, systemic evaluation was performed. Computed tomography showed a right adrenal tumor which was suspected to be a pheochromocytoma because catecholamine levels were very high in both serum and 24-hour urine. She did not awaken from anesthesia after laparoscopic adrenalectomy and laboratory tests showed that her blood sugar concentration was 33 mg/dl. This hypoglycemia was controlled by continuous infusion of a 50% glucose solution at 40 ml/h and she became conscious the next morning. We gradually decreased the amount of glucose infused and stopped the infusion on postoperative day 4. The tumor was pathologically diagnosed as a pheochromocytoma.