Yoshinari Ono

LONG-TERM FOLLOWUP AFTER LAPAROSCOPIC RADICAL NEPHRECTOMY

PURPOSE Laparoscopic radical nephrectomy has been shown to be less morbid than traditional open radical nephrectomy. The long-term oncological effectiveness of laparoscopic radical nephrectomy remains to be established. MATERIALS AND METHODS At 3 centers patients undergoing laparoscopic radical nephrectomy before November 1, 1996 with pathologically confirmed renal cell carcinoma were identified. A representative group of patients undergoing open radical nephrectomy for clinical T1, T2 lesions was also identified. Staging, operative details and postoperative course were reviewed. Followup consisted of review of clinical, laboratory and radiological records. Kaplan-Meier analysis was performed. RESULTS The study included 64 patients treated with laparoscopic and 69 treated with open radical nephrectomy with respective average ages of 60.6 and 61.3 years at surgery. On preoperative imaging open lesions were larger (6.2 cm., range 2.5 to 15) than laparoscopic radical nephrectomy lesions (4.3 cm., range 2 to 10, p <0.001). Pathology reports revealed no difference in specimen weight (425 and 495 gm., p = 0.146) or average Fuhrman grade (1.88 and 1.78, p = 0.476) between laparoscopic and open radical nephrectomy, respectively. Median followup was 54 months (range 0 to 94) for laparoscopic and 69 months (range 8 to 114) for open radical nephrectomy. Kaplan-Meier analysis with log rank comparison revealed 5-year recurrence-free survival of 92% and 91% for laparoscopic and open radical nephrectomy, respectively (p = 0.583). At 5 years cancer specific survival was 98% and 92% (p = 0.124), and nonspecific survival was 81% and 89% (p = 0.260) for laparoscopic and open radical nephrectomy, respectively. CONCLUSIONS Laparoscopic radical nephrectomy confers long-term oncological effectiveness equivalent to traditional open radical nephrectomy.

Laparoscopic nephrectomy for renal cell cancer: evaluation of efficacy and safety: a multicenter experience

OBJECTIVES Although laparoscopic radical nephrectomy is a safe and minimally invasive alternative to open surgery, the long-term disease-free outcome of this procedure has not been reported. We evaluated our experience with the laparoscopic management of renal cell carcinoma to assess the clinical efficacy of this surgical modality. METHODS Between February 1991 and June 1997, 157 patients at five institutions were retrospectively identified who had clinically localized, pathologically confirmed, renal cell carcinoma and had undergone laparoscopic radical nephrectomy. Operative and clinical records were reviewed to determine morbidity, disease-free status, and cancer-specific survival. Of the patients followed up for at least 12 months (n = 101), 75% had an abdominal computed tomography scan at their last visit. RESULTS The mean age at surgery was 61 years (range 27 to 92) and all patients were clinical Stage T1-2,NO,MO. Fifteen patients (9.6%) had perioperative complications. During a mean follow-up of 19.2 months (range 1 to 72; 51 patients with 2 years or more of follow-up), no patient developed a laparoscopic port site or renal fossa tumor recurrence. Four patients developed metastatic disease, and 1 patient developed a local recurrence. The 5-year actuarial disease-free rate was 91%+/-4.8 (SE). At last follow-up, there were no cancer-specific mortalities. CONCLUSIONS The laparoscopic surgical management of localized renal cell carcinoma is feasible. Short-term results indicate that laparoscopic radical nephrectomy is not associated with an increased risk of port site or retroperitoneal recurrence. Longer follow-up is necessary to compare long-term survival and disease-free rates with those of open surgery.

Renal L-Type Fatty Acid–Binding Protein in Acute Ischemic Injury

Fatty acid-binding proteins (FABPs) bind unsaturated fatty acids and lipid peroxidation products during tissue injury from hypoxia. We evaluated the potential role of L-type FABP (L-FABP) as a biomarker of renal ischemia in both human kidney transplant patients and animal models. Urinary L-FABP levels were measured in the first urine produced from 12 living-related kidney transplant patients immediately after reperfusion of their transplanted organs, and intravital video analysis of peritubular capillary blood flow was performed simultaneously. A significant direct correlation was found between urinary L-FABP level and both peritubular capillary blood flow and the ischemic time of the transplanted kidney (both P < 0.0001), as well as hospital stay (P < 0.05). In human-L-FABP transgenic mice subjected to ischemia-reperfusion injury, immunohistological analyses demonstrated the transition of L-FABP from the cytoplasm of proximal tubular cells to the tubular lumen. In addition, after injury, these transgenic mice demonstrated lower blood urea nitrogen levels and less histological injury than injured wild-type mice, likely due to a reduction of tissue hypoxia. In vitro experiments using a stable cell line of mouse proximal tubule cells transfected with h-L-FABP cDNA showed reduction of oxidative stress during hypoxia compared to untransfected cells. Taken together, these data show that increased urinary L-FABP after ischemic-reperfusion injury may find future use as a biomarker of acute ischemic injury.

Laparoscopic radical nephrectomy for renal cell carcinoma: a five-year experience

OBJECTIVES To evaluate the efficacy of laparoscopic radical nephrectomy for patients with small renal cell carcinoma by comparing the clinical results of patients treated laparoscopically with those of patients treated with traditional open radical nephrectomy. METHODS Of 100 patients with localized, small (less than 5 cm in diameter) renal cell carcinoma treated by the same surgical team between 1992 and 1998, 60 patients underwent laparoscopic radical nephrectomy and 40 underwent open radical nephrectomy. Of the 60 laparoscopically treated patients, the first 11 and the most recent 34 patients were operated on transperitoneally and the other 15 retroperitoneally. RESULTS The mean operative time of the laparoscopically treated patients was longer than that of the open nephrectomy patients (5.2 versus 3.3 hours, P<0.001). The mean blood loss of the laparoscopically treated patients was less than that of the open nephrectomy patients (255 versus 512 mL, P<0.001). One laparoscopically treated patient needed conversion to open surgery. The time to full convalescence of the laparoscopically treated patients was shorter than that of the open nephrectomy patients (23 versus 57 days, P<0.001). Two of the 59 laparoscopically treated patients and 1 of the 40 open nephrectomy patients had metastatic disease. The former 2 are alive with stable disease and the latter died of progressive disease 11 months after surgery. The 5-year disease-free rate was 95.5% in laparoscopy patients and 97.5% in open nephrectomy patients (P = NS). CONCLUSIONS Laparoscopic radical nephrectomy is a less invasive alternative to open surgery for patients with localized small renal cell carcinoma.

THE LONG-TERM OUTCOME OF LAPAROSCOPIC RADICAL NEPHRECTOMY FOR SMALL RENAL CELL CARCINOMA

PURPOSE To evaluate the efficacy of laparoscopic radical nephrectomy in patients with small renal cell carcinoma, we analyzed the long-term results in those treated with laparoscopy and those undergoing open surgery. MATERIALS AND METHODS A total of 149 patients with tumors less than 5 cm. in diameter enrolled in a radical nephrectomy program between January 1992 and March 2000. Of these patients 103 were treated laparoscopically and the remaining 46 underwent open surgery. Patient followup was until June 30, 2000. RESULTS Laparoscopy followup was from 3 to 95 months (median 29). A total of 100 patients survived, 2 died without any recurrent disease in months 34 and 45, respectively, and 1 dropped out in postoperative month 3. Seeding of the port sites did not develop in any of the patients. There were 3 patients who had metastatic disease in months 3, 19 and 61, respectively, and 1 had local recurrence in postoperative month 43. The 5-year disease-free and patient survival rates were 95.1%, and 95.0%, respectively. Except for 2 patients who dropped out in months 10 and 16, respectively, 44 who underwent open surgery were followed from 11 to 101 months (median). Of the 44 patients 41 survived without any recurrent disease, 1 also survived with metastasis and 2 died of metastatic disease in months 7 and 11, respectively. The 5-year disease-free and patient survival rates were 89.7% and 95.6%, respectively. CONCLUSIONS Laparoscopic radical nephrectomy can be an alternative to open nephrectomy in patients with localized small renal cell carcinoma.

A prospective study of human herpesvirus-6 infection in renal transplantation

Sixty-five kidney transplant recipients and their (22 living related and 43 cadaveric) donors were studied prospectively to determine the relationship between kidney transplantation and human herpesvirus-6 (HHV-6) infection. The virus isolation from peripheral blood and other tissues and sequential determination of neutralizing antibodies to HHV-6 were performed during 3 months following the transplantation. All of the donors and their recipients examined had neutralizing antibodies to HHV-6 at the time of renal transplantation and the virus was not isolated from them. HHV-6 was isolated from 3 renal tissues (2 living related and 1 cadaveric) obtained during transplant surgery, but not from their blood at that time. HHV-6 viremia occurred in 9 (14%) of the 65 recipients around 2 to 4 weeks after the transplantation. An additional 27 recipients showed a significant rise in the antibody titer. Thus, the infection with HHV-6 was confirmed in 36 (55%) of the 65. These results indicate that the virus is activated in many cases in the early posttransplant period and that HHV-6 establishes in vivo latency in the kidney tissue. There was no correlation between HHV-6 infection and acute rejection or the antirejection prophylaxis.

Laparoscopic Radical Nephrectomy: The Nagoya Experience

PURPOSE We evaluated the efficacy of laparoscopic radical nephrectomy for removing kidneys with small volume renal cell carcinoma. MATERIALS AND METHODS 25 patients (19 men and 6 women, mean age 59) who had a kidney with small volume renal cell carcinoma (diameter less than 5 cm.), underwent laparoscopic radical nephrectomy. The kidney was dissected laparoscopically together with the adrenal gland, perirenal fatty tissue and Gerotas fascia. In 11 patients, we used the transperitoneal approach and in the remaining 14 we used the retroperitoneal approach, in which a working space is created by finger and balloon dissection. We maneuvered the kidney into the laparoscopy sack, which was then removed through an additional 5 to 6 cm. incision. RESULTS All 25 kidneys were removed successfully. Mean operation time was 5.3 hours and mean estimated blood loss was 335 ml. There were 5 complications, including a patient who suffered an injury to the duodenum, which was treated by open duodenojejunostomy. Full convalescence occurred at an average 23 days. No metastatic disease, no local recurrence and no seeding at the port sites occurred during the followup of 7 to 49 months (mean, 22 months). CONCLUSIONS Laparoscopic radical nephrectomy is recommended as a minimally invasive procedure for removing kidneys with small volume renal cell carcinoma.

Immunopharmacological monitoring of cyclosporin A-treated recipients of cadaveric kidney allografts

Twelve cadaveric kidney allograft recipients, who were established preoperatively to be strong responders, were treated with cyclosporin A (Cy A) and subjected to postoperative monitoring of drug levels and immune performances. The Cy A-treated recipients were compared with 72 historical (36 strong and 36 weak immune responders) and 18 current, strong responder, azathioprine-treated control patients. Estimation of Cy A levels in plasma and whole blood revealed that 75% of the drug at trough and 44% at peak was cell bound. Concomitant radioimmunoassay (RIA) and high performance liquid chromatography (HPLC) determinations on whole blood yielded concordant values. Trough levels above 200 ng/ ml in plasma and 600 ng/ml in whole blood were associated with toxic manifestations. Although absolute peak levels were not helpful, calculation of peak to trough ratios yielded values which when less than 3.0 predicted toxicity. Post-transplant immune monitoring showed administration of Cy A to be associated with fewer (1) rejection episodes; (2) nonspecific immune events; and (3) donor-specific in vitro reactions than were observed after treatment with azathioprine. Although the activity of peripheral blood mononuclear cells as natural killers of K562 target cells was not affected by Cy A treatment, their capacity to suppress the generation of a third-party mixed lymphocyte culture was enhanced to the same degree as cells from azathioprine-treated patients. Enumeration of peripheral blood lymphocyte T cell subpopulations using monoclonal xeonoantisera revealed (1) the total number of T cells to be unaffected by administration of either Cy A or azathioprine and (2) a reduction in the ratio of helper-inducer to suppressor-cytotoxic cells specificially in Cy A-treated recipients compared with normal individuals, hemodialysis patients, or azathioprine-treated recipients. Although pharmacological monitoring of blood levels may be useful to discern patients at high risk for toxic complications, the achievement of maximal therapeutic efficacy may depend upon identifying and quantitating the cellular target responsible for the disruption of immune homeostasis observed during Cy A administration.

Laparoscopic Nephrectomy, Radical Nephrectomy and Adrenalectomy: Nagoya Experience

A total of 37 patients with various renal and adrenal diseases underwent laparoscopic nephrectomy, radical nephrectomy and adrenalectomy since July 1991. The underlying diseases included renal calculi, vesicoureteral reflux, ureteropelvic junction obstruction, ureteral stenosis, ectopic ureter, vascular disease, renal cell carcinoma and adrenal tumors. Twenty-nine kidneys (including 5 with renal cell carcinoma) and 5 adrenal glands were removed successfully. Three cases failed because of dense adhesion to the surrounding structures, hemorrhage from the renal vein and hemorrhage from the vena cava, respectively. Of the remaining 34 patients 3 required additional open laparotomy to control bleeding or remove lost calculi. Mean operating time was 265 minutes for nephrectomy, 383 minutes for radical nephrectomy and 199 minutes for adrenalectomy, and mean estimated blood loss was 455 ml., 430 ml. and 80 ml., respectively. Average hospital stay was 10 days for the 31 patients without open laparotomy and convalescence was completed by postoperative day 21. These results indicate that laparoscopic surgery for renal and adrenal disease is a feasible, minimally invasive procedure. In the case of laparoscopic radical nephrectomy, however, longterm followup is necessary to confirm the efficacy.

Randomized study of single early instillation of (2″R)-4′-O-tetrahydropyranyl-doxorubicin for a single superficial bladder carcinoma

Although transurethral resection of a bladder tumor (TUR‐Bt) alone has been standard treatment for single superficial bladder carcinoma, some authors reported a certain prophylactic effect of a single immediate intravesical instillation of chemotherapeutic agent after TUR‐Bt. A prospective randomized study was conducted to determine whether a single (2″R)‐4′‐O‐tetrahydropyranyl‐doxorubicin (THP) instillation immediately after TUR‐Bt is beneficial to patients with a single superficial bladder carcinoma.