Keita Fujikawa

SERUM C-REACTIVE PROTEIN LEVEL AND THE IMPACT OF CYTOREDUCTIVE SURGERY IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA

PURPOSEnThe prognosis of metastatic renal cell carcinoma is extremely poor. In this type of metastatic tumor cytoreductive surgery of the primary tumor is often performed to confirm the histological type or improve the response to immunotherapy with agents such as interferon or interleukin-2. However, the timing and impact of cytoreductive surgery on the success of immunotherapy require further study. We determined the type of metastatic renal cell carcinoma for which cytoreductive surgery is beneficial.nnnMATERIALS AND METHODSnWe retrospectively reviewed the records of 58 patients in whom metastatic renal cell carcinoma was diagnosed at our hospital between 1986 and 1997. Three patients were excluded from study because they were judged to be poor candidates for surgery due to poor performance status. Of the remaining 55 patients 34 consented to cytoreductive surgery of the primary tumor and 21 did not. All except 1 patient were treated with interferon therapy. We evaluated the association of pretreatment serum C-reactive protein and the effect of surgery.nnnRESULTSnWe noted no significant difference in age at diagnosis, pretreatment serum immunosuppressive acidic protein, site of metastasis or performance status in 34 patients who underwent cytoreductive surgery and 21 who did not. Of the 21 patients in whom pretreatment serum C-reactive protein was within normal limits (less than 1.0 ng./ml.) no significant difference in disease specific survival was observed in those who did and did not undergo surgery (p = 0.4133). On the other hand, of 34 patients in whom pretreatment serum C-reactive protein was elevated (1.0 ng./ml. or greater) the prognosis was significantly better in those who did versus those who did not undergo surgery (p = 0.0054). Particularly the prognosis in patients in whom postoperative nadir C-reactive protein decreased to within normal limits was markedly better than in those in whom it remained elevated (p = 0.0025).nnnCONCLUSIONSnOur study suggests that cytoreductive surgery is beneficial to patients in whom pretreatment serum C-reactive protein is elevated. Particularly, those in whom serum C-reactive protein decreases to within normal limits may expect longer survival when surgery is combined with postoperative immunotherapy. Currently to our knowledge the prognostic factor that predicts postoperative nadir C-reactive protein has not been identified, indicating that cytoreductive surgery of the primary tumor should be performed in patients with elevated pretreatment C-reactive protein and as performance status permits.

SERUM IMMUNOSUPPRESSIVE ACIDIC PROTEIN AND NATURAL KILLER CELL ACTIVITY IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA BEFORE AND AFTER NEPHRECTOMY

PURPOSEnTo our knowledge the impact of nephrectomy on stage M1 renal cell carcinoma remains to be determined. We previously reported that nephrectomy is beneficial in patients with elevated serum C-reactive protein before treatment, and those in whom nadir C-reactive protein decreases postoperatively to within the normal range may expect longer survival when surgery is combined with postoperative immunotherapy. In this study we determine the effect of nephrectomy on the immune response in patients with metastatic renal cell carcinoma.nnnMATERIALS AND METHODSnWe retrospectively reviewed the records of 40 patients with metastatic renal cell carcinoma diagnosed at our institution between 1986 and 1999. These patients underwent nephrectomy before cytokine therapy with interferon. Before and after nephrectomy we measured serum C-reactive protein, serum immunosuppressive acidic protein and peripheral blood natural killer cell activity.nnnRESULTSnIn 15 patients with pretreatment serum C-reactive protein within the normal range (less than 1 ng./ml.) there was no significant difference before and after nephrectomy in the serum immunosuppressive acidic protein level or natural killer cell activity (p = 0.4587 and 0.3892, respectively). On the other hand, in 25 patients with serum C-reactive protein elevated before treatment to 1 ng./ml. or greater serum immunosuppressive acidic protein decreased significantly and natural killer cell activity increased significantly after cytoreductive surgery (p = 0.0002 and 0.0286, respectively).nnnCONCLUSIONSnOur study implies that nephrectomy may be beneficial in patients with elevated serum C-reactive protein before treatment. Further evaluation by a prospective study is needed to make a definitive conclusion.

ROLE OF VOLUME WEIGHTED MEAN NUCLEAR VOLUME FOR PREDICTING DISEASE OUTCOME IN PATIENTS WITH RENAL CELL CARCINOMA

PURPOSEnHistological grading of malignancy in renal cell carcinoma is based on qualitative, morphological examination and suffers from poor reproducibility. On the other hand, estimate of volume weighted mean nuclear volume, which was developed based on a stereological technique, is an easy method to perform with high reproducibility. Furthermore, it has been reported that mean nuclear volume is remarkably correlated with prognosis of bladder and prostate cancer. We compared mean nuclear volume to a histological grading method and TNM classification in determining the prognosis of renal cell carcinoma using a Cox proportional hazards model.nnnMATERIALS AND METHODSnA retrospective, prognostic study was done of 65 patients with renal cell carcinoma diagnosed by radical nephrectomy or needle punch biopsy between January 1978 and November 1995. Unbiased estimates of mean nuclear volume were compared to TNM classification and histological grading to determine prognostic value.nnnRESULTSnUnivariate analysis indicated that all TNM classifications, histological grades and estimates of mean nuclear volume were significantly correlated with prognosis of renal cell carcinoma. However, multivariate analysis revealed that estimates of mean nuclear volume and metastasis at diagnosis were the 2 most powerful independent predictors of disease specific survival.nnnCONCLUSIONSnOur results indicate that estimates of mean nuclear volume are prognostically superior to morphological grading of renal cell carcinoma. We recommend mean nuclear volume estimates as an adjunct to subjective histological grading in patients with this disease.

Low incidence of ipsilateral adrenal involvement and recurrences in patients with renal cell carcinoma undergoing radical nephrectomy: a retrospective analysis of 393 patients.

OBJECTIVESnTo evaluate, in a retrospective analysis of the outcome of 393 consecutive patients undergoing radical nephrectomy, the advantages and disadvantages of concomitant ipsilateral adrenalectomy with this operation.nnnMETHODSnThe medical records, pathologic specimens, and preoperative and postoperative computed tomography scans of 165 patients with, and 228 patients without, concomitant adrenalectomy were reviewed. The incidence of adrenal involvement in the former patients and ipsilateral adrenal recurrence in the latter patients was evaluated. The influence of adrenalectomy on the disease-specific survival was also assessed by both univariate and multivariate analyses.nnnRESULTSnOf the 165 patients, only 5 (3.0%) had adrenal involvement. All of these cases were diagnosed as cT3 or greater preoperatively, and preoperative computed tomography detected 4 of these 5 cases. Of the 228 patients without adrenalectomy, no ipsilateral adrenal recurrence was observed at a mean follow-up of 65.2 months. Ipsilateral adrenalectomy did not confer a favorable prognosis on the patients.nnnCONCLUSIONSnOur results indicate that the advantages of ipsilateral adrenalectomy in patients with normal findings on preoperative computed tomography are limited. Concomitant ipsilateral adrenalectomy is indicated in cases such as locally advanced tumors with uncertain preoperative imaging studies or those with apparent adhesion or inflammation around the adrenal gland at surgery, thus suggesting perinephric tumor involvement.

Adrenal leiomyosarcoma extending into the right atrium.

Abstract Primary soft tissue sarcoma of the adrenal gland is very rare and aggressive. In right adrenal tumors, because of direct venous drainage into inferior vena cava, the tumor may invade the vena caval wall toward the right atrium. We present a case of adrenal leiomyosarcoma extending into the right atrium.

Vardenafil 20-mg demonstrated superior efficacy to 10-mg in Japanese men with diabetes mellitus suffering from erectile dysfunction.

Aim: Vardenafil is a highly selective and potent phosphodiesterase type‐5 inhibitor for the treatment of erectile dysfunction (ED). The efficacy of vardenafil has been demonstrated in a broad range of ED populations, but has not yet been assessed in Japanese patients with diabetes mellitus (DM), although DM is frequently associated with difficult‐to‐treat ED. This is the first study to investigate whether high‐dose vardenafil (20u2003mg) can demonstrate superior efficacy to the usual dose (10u2003mg) in this subpopulation in Japan.

A CASE OF RENAL CELL CARCINOMA DURING PREGNANCY: SIMULTANEOUS CESAREAN SECTION AND RADICAL NEPHRECTOMY

A 32-year-old woman was referred to us with right flank pain and macroscopic hematuria at gestational week 22 of a second pregnancy. Abdominal Doppler ultrasonography and magnetic resonance imaging demonstrated a 14 3 15 3 16 cm. hypervascular tumor of the right kidney (fig. 1). Neither these studies nor a chest x-ray suggested involvement of other organs, including the right renal vein, liver and lungs. Blood tests revealed no abnormalities, except mild anemia. The patient and spouse wished to save the life of the fetus. After consultation with obstetricians, pediatricians and anesthesiologists, we performed right radical nephrectomy and cesarean section at gestational week 28. On March 9, 1999 a 1,065 gm. fetus was delivered transabdominally. A 1,500 gm. specimen, including the right kidney and a round, nonadherent tumor, was removed following cephalad extension of the lower abdominal midline incision for cesarean section. Pathological examination revealed chromophobe type pT2pN0M0 renal cell carcinoma (fig. 2). The patient and child were well at 9-month followup.

Cost-Effectiveness Analysis of Hypertension Treatment: Controlled Release Nifedipine and Candesartan Low-Dose Combination Therapy in Patients with Essential Hypertension —The Nifedipine and Candesartan Combination (NICE-Combi) Study—

Societal interest in pharmaco-economic analysis is increasing in Japan. In this study, the cost-effectiveness of low-dose combination therapy with controlled release nifedipine plus candesartan and up-titrated monotherapy with candesartan was estimated, based on the results of the NICE-Combi study. The NICE-Combi study was a double-blind, parallel arm, randomized clinical trial to compare the efficacy of low-dose combination therapy of controlled release nifedipine (20 mg/day) plus candesartan (8 mg/day) vs. up-titrated monotherapy of candesartan (12 mg/day) on blood pressure control in Japanese patients with mild to severe essential hypertension who were not sufficiently controlled by the conventional dose of candesartan (8 mg/day). The incremental cost effectiveness of each cohort during the 8-week randomization period was compared, from the perspective of a third-party payer (i.e., insurers). The average total cost per patient was 29,943 Japanese yen for the combination therapy group and 33,182 Japanese yen for the candesartan monotherapy group, while the rate of achievement of the target blood pressure was significantly higher in the combination therapy group than in the up-titrated monotherapy group. In the combination therapy group, higher efficacy and lower incremental treatment cost (“Dominance”) were observed when compared to the monotherapy group. The sensitivity analyses also supported the results. In conclusion, these results suggest that combination therapy with controlled release nifedipine and low-dose candesartan (8 mg) is “dominant” to up-titrated candesartan monotherapy for the management of essential hypertension. This conclusion was robust to sensitivity analysis.

Predicting disease outcome of non-invasive transitional cell carcinoma of the urinary bladder using an artificial neural network model: results of patient follow-up for 15 years or longer.

Background: Patients with non‐invasive (Ta/T1) transitional cell carcinoma (TCC) of the urinary bladder are often observed without progression in the long‐term follow‐up period, although many of them experience recurrence of disease. It is difficult to accurately predict the disease outcome of each patient with Ta/T1 TCC using conventional prognostic criteria. In this study, we examined the usefulness of artificial neural networks (ANNs) to predict the long‐term disease outcome of patients with TCC of the urinary bladder.

Application of the Microwave Tissue Coagulator: Is It Beneficial to Partial Nephrectomy?

Background/Aim: The indications of partial nephrectomy have expanded after the introduction of new techniques for preventing excessive blood loss and avoiding deterioration of the renal function after clamping the renal pedicle. We present our clinical experience of partial nephrectomy for renal tumors using a microwave tissue coagulator. Patients and Methods: Between April 1996 and January 2000, 34 patients underwent open partial nephrectomies in the Kobe City General Hospital. The microwave tissue coagulator was used for resection of the renal parenchyma, but in deeper lesions a sharp dissection was performed. Twenty-two patients (groups 1 and 2) underwent partial nephrectomy without vascular control (14 renal pedicles were not disturbed in group 1 patients, and 8 renal pedicles were dissected but not clamped in group 2 patients). Another 12 patients (group 3) underwent vascular control with ligation of the tumor-feeding segmental arteries before parenchymal resection. The patients of group 1 underwent wedge resections, while those of groups 2 and 3 underwent segmental or transverse partial nephrectomies. Results: Complete tumor resection was done in all 34 patients. In group 1, the microwave tissue coagulator was very effective to control the blood loss (mean 330 ml). In larger resections, this method only was inadequate to control the blood loss (mean 489 ml in group 2), so that we needed vascular control. However, despite vascular control, mean blood losses of about 943 ml because of deeper venous bleeding occurred in group 3, and, moreover, postoperative renal infarctions occurred in 2 patients. Other complications were urinary fistula formation in 16 patients (47%) and renal pelvic stenoses in 2 patients (5.8%). All of the urinary fistulas were easily repaired by simple suturing intraoperatively. Conclusions: Especially in wedge resection, the microwave tissue coagulator achieved safe resection without vascular control which differs from other new techniques. However, in larger resections, a combination with other techniques may be necessary to decrease blood loss and the rate of complications.