Shigeki Fukuzawa

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

PURPOSE The 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. MATERIALS AND METHODS We 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. RESULTS We 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). CONCLUSIONS Our 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

PURPOSE To 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. MATERIALS AND METHODS We 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. RESULTS In 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). CONCLUSIONS Our 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.

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

OBJECTIVES To 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. METHODS The 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. RESULTS Of 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. CONCLUSIONS Our 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.

Transurethral microwave thermotherapy for benign prostatic hyperplasia: Relation between clinical response and prostate histology

The effectiveness of transurethral microwave thermotherapy (TUMT) for BPH has been confirmed. To identify the characteristics of the ideal candidate, retrospective analysis and morphometric study of prostatic tissue were performed. Forty‐two patients with symptomatic BPH were included in the study; these comprised 10 patients treated for more than 3 months with anti‐androgen pre‐TUMT (group A) and 32 fresh cases (group B). Subjective and objective responses were evaluated at 2 months post TUMT. In 12 fresh cases who underwent pre‐TUMT biopsy of the prostate, the stromal‐to‐epithelial ratio was determined via quantitative image analysis on a computer‐assisted morphometry system. No significant differences in baseline patient characteristics were found between the two groups: age, prostate volume, peak flow rate (PFR), or International Prostate Symptom Score (I‐PSS). However, significant differences in treatment outcome were found between the two groups (group A vs. group B, respectively): total energy delivered to the prostate: 96 kJ vs. 125 kJ; I‐PSS decrease from baseline: 5.9 vs. 11.6; PFR increase from baseline: 1.1 vs. 4.7 ml/sec. There was a positive correlation between the I‐PSS change from baseline and the stromal‐to‐epithelial ratio of the prostatic tissue (r = 0.4857). The results suggest that microwave interacts poorly with the prostate due to the artificially created “lack” of glandular tissue. The morphometric study also supports the contention that the histological composition of the prostatic tissue plays an important role in terms of microwave thermal interactions and treatment outcome.

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.

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.

Anti-promoting effect of nordihydroguaiaretic acid on N-butyl-N-(4-hydroxybutyl)nitrosamine and sodium saccharin-induced rat urinary bladder carcinogenesis.

The effects of oral administration of nordihydroguaiaretic acid (NDGA), an antioxidant and inhibitor of arachidonic acid metabolism, on rat bladder carcinogenesis were examined. Six‐week‐old male Fischer 344 rats were given drinking watar containing 0.05% N‐butyl‐N‐(4‐hydroxybutyl)nitrosamine for 4 weeks. Following this 4‐week period, diet containing 5% sodium saccharin (SS) with or without 0.1% NDGA supplement was given to the rats for 36 weeks. The incidences of papillary or nodular (PN) hyperplasia and of papilloma in the group treated with SS plus NDGA were significantly lower than those in the group treated with SS alone. The number of PN hyperplasic foci per 10 cm of basement membrane in rats treated with SS plus NDGA was also lower than that in the group treated with SS alone. These results suggest that NDGA has an anti‐tumor‐promoting effect on rat bladder carcinogenesis.

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.

Prostate–Specific Antigen Levels and Clinical Response to Flutamide as the Second Hormone Therapy for Hormone–Refractory Prostate Carcinoma

Background: Some authors have recently reported that maximum androgen block (MAB), in which the nonsteroidal anti–androgen, flutamide, is used together with conventional hormone therapy such as castration or luteinizing hormone–releasing hormone analogue, is more effective for prostate cancer than conventional methods. However, others have reported that the effect of MAB on survival is minimal, and definite conclusions concerning MAB remain unclear. Conversely, using flutamide as a second–line hormone therapy after recurrence is also considered, but few authors have reported whether this therapeutic option is effective or for which patients it is effective.Materials and Methods: 124 patients with prostate cancer were diagnosed and followed at Kobe City General Hospital between 1995 and 1997. Twenty–two of these cases developed recurrence during first–line hormone therapy, and flutamide was prescribed in these cases. The prognostic value and effectiveness of flutamide were evaluated by measurement of serum prostate–specific antigen (PSA) at diagnosis, posttreatment nadir PSA level, PSA at the time of flutamide use, histological grade, recurrence–free time after firstline hormone therapy and age at the time of diagnosis.Results: Six of 9 cases whose post–treatment nadir PSA levels after initial hormone therapy were within the normal limit (<4 ng/ml) achieved complete remission (CR) with flutamide use, but no patient whose post–treatment nadir PSA level remained elevated achieved CR. PSA at diagnosis and PSA at the start of flutamide use were significantly lower for patients with CR. However, the results of multivariate logistic regression analysis demonstrated that only the post–treatment nadir PSA level was significantly correlated with prognosis of flutamide use.Conclusions: Flutamide use as second–line hormone therapy should be limited to cases in which first–line hormone therapy has been highly effective and for whom the post–treatment nadir PSA level was within normal limits, and other patients should undergo other therapies. By limiting flutamide use to patients in whom the effect of flutamide is considered to be maximal, the incidence of complications and medication costs can be decreased.