- Email: [email protected]
UROLITHIASIS, ENDOUROLOGY AND LAPAROSCOPY
778 UROLITHIASIS, ENDOUROLOGY AND LAPAROSCOPY Adhesion Formation in Intubated Rabbits Increases With High Insufflation Pressure During Endoscopic Surgery N. YESILDAGLAR AND P. R. KONINCKX, Centre for Surgical Technologies, and Department of Gynaecology and Obstetrics, University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium Hum Reprod, 15: 687– 691, 2000 Permission to Publish Abstract Not Granted Editorial Comment: Which pneumoperitoneum pressure is the safest for performing laparoscopy? The common answer is 15 mm. Hg, however, some suggest that working at lower pressures may be beneficial, as long as the surgeon still has an adequate field of view. It is known that at 10 mm. Hg or less near normal urine output occurs, and some studies also indicate that working at lower pressure may result in less postoperative discomfort. The authors showed that at higher pressures, for example 20 versus 5 mm. Hg, or at higher flow rates, such as 10 versus 1 L. per minute, the incidence of postoperative adhesions after laparoscopy in a rabbit model was statistically significantly increased. Aside from avoiding high pressures the authors also make a case for humidifying the carbon dioxide to prevent tissue desiccation. In our experience there are only 2 times when pneumoperitoneum pressure is purposely increased above the 10 to 15 mm. range, which are at the moment of initial trocar insertion when the pressure is allowed to go to 20 to 25 mm. Hg and during venous hemorrhage when the pressure is increased to 20 mm Hg. to slow the bleeding. Ralph V. Clayman, M.D. Changes in Hemostatic Mechanisms Associated With Operative Laparoscopy J. D. BROOME, V. P. LAMARO AND T. G. VANCAILLIE, School of Obstetrics and Gynaecology, University of New South Wales and Department of Endo-Gynaecology, Royal Hospital for Women, Kensington, Australia J Am Assoc Gynecol Laparosc, 7: 149 –153, 2000 A 19-year-old woman underwent laparoscopic resection of extensive endometriosis of the cul-de-sac. At completion of surgery the abdomen was deflated for 3 minutes with the patient still in Trendelenburg position, before she was reexamined for intraoperative bleeding. The patient was taken back to surgery 7 hours postoperatively to arrest hemorrhage. Editorial Comment: The authors report a “delayed” hemorrhage after a laparoscopic procedure for endometriosis. A key observation is that the site of bleeding was likely present at the end of the procedure, “We noted a general ooze but could not identify a specific bleeding point.” When they returned to explore the patient laparoscopically 7 hours later, after evacuation of 2,500 cc of free fluid and clots, they found that the blood was coming from a median hemorrhoidal artery, which was secured with 2 endoscopic loops. The authors make several important observations: 1) at the end of a procedure pneumoperitoneum should be reduced to less than 5 mm. Hg and a careful inspection made for bleeding for at least 3 minutes, 2) the patient should be returned to a level position at final inspection, and 3) this final inspection should occur when the patient is normotensive. At this time any clots should be suctioned from the abdomen. The authors note, “Leaving clots alone in an effort to avoid ‘stirring up’ more bleeding equates to burying one’s head in the sand.” The maneuver that I trust the most for judging whether the field is dry is one I learned from Kavoussi. Once the operative site is believed to be dry, irrigate the site until there is a reasonable volume of fluid, usually 100 cc, and then look carefully at this “lake” of irrigant to see if any “red rivulets” are wending their way to the surface of the fluid, like smoke from a chimney. Any rivulet is a sign of ongoing bleeding, which should be identified and fulgurated. The final inspection of the operative site at the end of a laparoscopic procedure is an important part of the procedure, in which all concerned must be in agreement that the hemostasis is perfect. If not, you’ll be back! Ralph V. Clayman, M.D. Complications and Recommended Practices for Electrosurgery in Laparoscopy M.-P. WU, C.-S. OU, S.-L. CHEN, E. Y. T. YEN AND R. ROWBOTHAM, Gynecologic Laparoscopy Research Unit, Department of Obstetrics and Gynecology, and Departments of Pediatrics and Family Medicine, Tainan Municipal Hospital, Tainan, Taiwan, and Department of Obstetrics and Gynecology, Northwest Hospital and University of Washington, Seattle, Washington Am J Surg, 179: 67–73, 2000 BACKGROUND: Electrosurgery is one of the most commonly used energy systems in laparoscopic surgery. Two major categories of potential complications related to electrosurgery in laparoscopy are
UROLITHIASIS, ENDOUROLOGY AND LAPAROSCOPY
mechanical trauma and electrothermal injury. The latter can result from unrecognized energy transfer in the operational field or, less commonly, to unnoticed stray current outside the laparoscopic field of view. Stray current can result from insulation failure, direct coupling, or capacitive coupling. METHODS: We reviewed the literature concerning essential biophysics of electrosurgery, including electrosurgical waveform differentiation, tissue effect, and variables that determine tissue effect. The incidence of electrosurgical injuries and possible mechanisms responsible for the injuries are discussed. Different types of injuries may result in different clinical manifestations and histopathological findings. Gross and microscopic pathological check-ups of the injury sites may distinguish between different mechanisms, and thus provide further clues postoperatively. RESULTS: Several recommended practices are proposed to avoid electrosurgical injury laparoscopically. To achieve electrosurgical safety and to prevent electrosurgical injuries, the surgical team should have a good understanding of the biophysics of electrosurgery, the basis of equipment and general tissue effects, as well as the surgeon’s spatial orientation and hand-eye coordination. Some intraoperative adjuvant procedures and newly developed safety devices have become available may aid to improve electrosurgical safety. CONCLUSIONS: Knowledge of the biophysics of electrosurgery and the mechanisms of electrosurgical injury is important in recognizing potential complications of electrosurgery in laparoscopy. Procedures for prevention, intraoperative adjuvant maneuvers, early recognition of the injury with in-time salvage treatment, and alertness to postoperative warning signs can help reduce such complications. Editorial Comment: Knowledge rules! The best way to avoid the devastation of a laparoscopic electrosurgical injury is understanding how electrosurgery works and defense against any possible current related injuries. In this regard this article is an excellent introduction to understanding electrosurgery. More than 20% to 30% of general surgeons and gynecologists have had a patient experience an electrosurgical injury during a laparoscopic procedure. The mechanism of injury can be due to 4 conditions, including direct application, insulation failure, direct coupling or capacitive coupling. It is noteworthy that electrosurgical injury to bowel may not result in clinical signs for up to 10 days after the procedure. The following suggestions are helpful for avoiding these problems: 1) use the lowest wattage necessary, which is usually 30 to 35 W. for cutting and coagulation, 2) the entire activated surface of the instrument should be in your field of view whenever activating the electrosurgical generator, 3) the potential for electrosurgical injury is greater when using the coagulation compared to the cutting mode, 4) never activate the electrode in the coagulating mode unless the electrode is in direct contact with the targeted tissue, 5) never use a plastic trocar sleeve with a metal trocar, and all metal trocars are preferable but all plastic trocars are also satisfactory, 6) activate the electrosurgical probe in short bursts of less than 1 second rather than a prolonged period of time, 7) a return electrode monitoring system can protect the patient at the site of the ground pad, 8) active electrode monitoring with an Electroscope system, (Electroscope, Boulder, Colorado) inactivates the electrosurgical device if any stray current due to insulation failure or capacitive coupling is detected and 9) consider using “tissue responsive” electrosurgical machines, which deliver only the current necessary to achieve the desired cutting or coagulation effect. Ralph V. Clayman, M.D. Laparoscopic Live Donor Nephrectomy: the Recipient L. E. RATNER, R. A. MONTGOMERY, W. R. MALEY, C. COHEN, J. BURDICK, K. D. CHAVIN, D. S. KITTUR, P. COLOMBANI, A. KLEIN, E. S. KRAUS AND L. R. KAVOUSSI, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland Transplantation, 69: 2319 –2323, 2000 BACKGROUND: Laparoscopic live donor nephrectomy offers advantages to the donor in terms of decreased pain and shorter recuperation. Heretofore no detailed analysis of the recipient of laparoscopically procured kidneys has been performed. The purpose of this study was to determine whether laparoscopic donor nephrectomy had any deleterious effect on the recipient. METHODS: A retrospective review was conducted of all live donor renal transplantations performed from January 1995 through April 1998. The control group received kidneys procured via a standard flank approach (Open). Rejection was diagnosed histologically. Creatinine clearance was calculated using the Cockroft-Gault formula. RESULTS: A total of 110 patients received kidneys from laparoscopic (Lap) and 48 from open donors. One-year recipient (100% vs. 97.0%) and graft (93.5% vs. 91.1%) survival rates were similar for the Open and Lap groups, respectively. A similar incidence of vascular thrombosis (3.4% vs. 2.1%, P ⫽ NS) and ureteral complications (9.1% vs. 6.3%, P ⫽ NS) were seen in the Lap and Open groups, respectively. The incidence of acute rejection for the first month was 30.1% for the Lap group and 31.9% for the Open group (P ⫽ NS). The rate of decline of serum creatinine level in the early posttransplantation period was initially greater in the Open group, but by postoperative day 4 no significant difference existed. No difference was observed in allograft function long-term. The median length of hospital stay was 7.0 days for both groups. CONCLUSIONS: Laparoscopic live donor nephrectomy does not adversely effect recipient outcome. The previously demonstrated benefits to the donor, and the increased willingness of individuals to undergo live kidney donation, coupled with the
779
780
UROLITHIASIS, ENDOUROLOGY AND LAPAROSCOPY
acceptable outcomes experienced by recipients of laparoscopically procured kidneys justifies the continued development and adoption of this operation. Laparoscopic and Open Live Donor Nephrectomy: A Cost/Benefit Study T. BERNEY, J. MALAISE, M. MOURAD, P. MOREL AND J.-P. SQUIFFLET, Kidney and Pancreas Transplantation Unit, University of Louvain Medical School, Brussels, Belgium, and Clinic of Digestive Surgery and Visceral Transplantation, Geneva University Hospital, Geneva, Switzerland Transpl Int, 13: 35– 40, 2000 Recently, laparoscopic live-donor nephrectomy has been developed in order to increase organ donation. In this study we compare and review the records of 10 donors operated by open extraperitoneal approach and of 10 donors operated by a laparoscopic transperitoneal approach (LSC). Results show less use of postoperative parenteral narcotics in the LSC group (109 mg vs 272 mg; P ⬍0.0005) than in the extraperitoneal group. Morbidity was similar in both groups. There was no difference in postoperative stay. Allograft kidney function was similar in both groups until 6 months after donation. The use of disposable laparoscopic material bears an extra cost of 900 US$. We can thus conclude that laparoscopic live-donor nephrectomy is a safe procedure that significantly reduces postoperative pain, and is not detrimental to the allograft. The total cost of the laparoscopic procedure will be lower than that of the open approach if the length of postoperative stay is cut by 3 days. Increased Rates of Donation With Laparoscopic Donor Nephrectomy E. J. SCHWEITZER, J. WILSON, S. JACOBS, C. H. MACHAN, B. PHILOSOPHE, A. FARNEY, J. COLONNA, B. E. JARRELL AND S. T. BARTLETT, Joseph and Corrine Schwartz Division of Transplantation, Department of Surgery, Department of Urology and Red Cross Tissue Typing Laboratory, University of Maryland, Baltimore, Maryland Ann Surg, 232: 392– 400, 2000 Objective: To examine the impact of laparoscopic nephrectomy and recipient education on the proportion of kidney recipients who could identify a potential live donor, and on the live donor (LD) transplantation rate. Summary Background Data: Laparoscopic donor nephrectomy (LDN) results in less postoperative surgical pain, a shorter hospital stay, and quicker recovery than the standard open donor nephrectomy (ODN). The authors hypothesized that the availability of this less invasive surgical technique would enhance the willingness of family and friends to donate. Methods: The study population consisted of 3,298 end-stage renal disease patients referred for kidney transplant evaluation between November 1991 and February 2000, divided into three groups. The first group received no formal LD education and had only ODN available. The second group received formal education about the LD process and had only ODN available. The third group had both formal LD education and LDN available. Records were examined to determine what proportion of each group had any potential donors tissue-typed, and the rate at which they received an LD transplant. Results: Before LDN availability and formal LD education, only 35.1% of referrals found a potential donor, and only 12.2% received an LD transplant within 3 years. Institution of a formal education program increased the volunteer rate to 39.0%, and 16.5% received an LD transplant. When LDN became available, 50% of patients were able to find at least one potential donor, and within 3 years 24.7% received an LD transplant. Regression analysis indicated that availability of LDN was independently associated with a 1.9 relative risk of receiving an LD transplant. Kaplan-Meier death-censored 1- and 3-year graft survival rates for ODN transplants were 95.8% and 90.6%, versus 97.5% and 94.8% for LDN. Conclusions: The availability of LDN and an LD family education program has doubled the live donor transplantation rate, and outcomes remain excellent. Complications of Laparoscopic Live Donor Nephrectomy: The First 175 Cases D. Y. CHAN, M. D. FABRIZIO, L. E. RATNER AND L. R. KAVOUSSI, James Buchanan Brady Urological Institute and Department of Surgery, Johns Hopkins Medical Institution, Baltimore, Maryland Transplant Proc, 32: 778, 2000 Permission to Publish Abstract Not Granted Laparoscopic Live Donor Nephrectomy—is it Safe? J. R. LEVENTHAL, R. K. DEEIK, R. J. JOEHL, R. V. REGE, C. H. HERMAN, J. P. FRYER, D. KAUFMAN, M. ABECASSIS AND F. P. STUART, Department of Surgery, Northwestern University Medical School, Chicago, Illinois, and Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas Transplantation, 70: 602– 606, 2000 Background. Laparoscopic live donor nephrectomy (LDN) is a less invasive alternative to open nephrectomy (ODN) for living kidney donation. Concerns have been raised regarding the safety of LDN, the short and long term function of kidneys removed by LDN, and a potential higher incidence of urologic complications in LDN transplant recipients. Methods. Between October 1997 and May 1999, 80 LDNs were performed at our center. All patients were
UROLITHIASIS, ENDOUROLOGY AND LAPAROSCOPY
followed longitudinally with office visits and telephone interviews. These LDNs were compared with 50 ODNs performed from January 1996 to October 1997. Results. LDN procedures took significantly longer than ODN (4.6 vs. 3.1 hr). However, LDN was associated with significant reduction in i.v. narcotic use, a rapid return to diet, and shorter hospital stay. Of the 80 LDN procedures, a total of 75 (94%) were completed laparoscopically. Five patients were converted to laparotomy: three for hemorrhage and two for complex vascular anatomy. ODN conversion was associated with large donor body habitus and/or obesity. Seven LDN patients had minor complications and 4 had major complications. All major complications consisted of vascular injuries (2 lumbar vein injuries, 1 renal artery, and 1 aortic injury). All patients made complete recoveries. All LDN kidneys functioned immediately posttransplant. We have observed 100% patient and 97% 1-year actuarial graft survival in LDN transplant recipients. There have been no short- or long-term urologic complications in this series. Conclusion. With increasing experience and standardization of technique, LDN is a safe and effective procedure. Patients undergoing LDN demonstrate clinically significant, more rapid postoperative recoveries and shorter hospital stays than ODN patients. Excellent initial graft function and long-term graft survival have been observed with LDN kidneys. Urologic complications can be avoided. LDN has become the preferred surgical approach for living kidney donation at our center. Editorial Comment: These 5 articles represent a good survey of the state of the art of laparoscopic donor nephrectomy. Originally performed by Ratner, Kavoussi and colleagues at The Johns Hopkins University in 1995, this procedure has rapidly gained popularity and acceptance internationally. While the laparoscopic approach requires an extra 1.5 hours of operating time versus open donor nephrectomy, the donor needs half as much parenteral analgesics and leaves the hospital a day sooner. A learning curve of 30 cases has been proposed, and the majority of complications in the experience of the authors at the University of Maryland, including the need to convert, occurred during the initial 30 procedures. Although increased ureteral complications were experienced initially, the current practice of taking the ureter broadly with an EndoGIA (United States Surgical Corp., Norwalk, Connecticut) stapler appears to have greatly reduced the ureteral complication rate, which now parallels that of the open approach. The review by Chan shows an overall complication rate for laparoscopic donor nephrectomy of 14%, which compares favorably with that for open donor nephrectomy of 16%. Graft survival rates of 91% to 97% at 1 year have been achieved, which are similar to those previously reported for open donor nephrectomy. The increased equanimity to the donor in laparoscopic donor nephrectomy has possibly prompted an increase in the living donor pool as at the University of Maryland the live donor transplantation rate for local referrals has doubled. Whether this pattern is truly local or represents a national trend remains to be determined. Ralph V. Clayman, M.D. Bench to Bedside: Lessons From the Genetic Hypercalciuric Stone-Forming Rat D. A. BUSHINSKY, Nephrology Unit, University of Rochester Medical Center, Rochester, New York Am J Kidney Dis, 36: LXI–LXIV, 2000 No Abstract Editorial Comment: In this review a rat model for stone formation is described. These genetically inbred rats are hypercalciuric and form calcium hydrogen phosphate renal stones. The defect appears to be at the level of the renal tubule (decreased calcium reabsorption) and in the bone (increased sensitivity to vitamin D). It is interesting that a high oxalate diet resulted in a decrease in urinary calcium oxalate supersaturation in these genetically inbred rats. Ralph V. Clayman, M.D. Risk of Calcium Oxalate Nephrolithiasis After Calcium or Combined Calcium and Calcitriol Supplementation in Postmenopausal Women S. DOMRONGKITCHAIPORN, B. ONGPHIPHADHANAKUL, W. STITCHANTRAKUL, N. PIASEU, S. CHANSIRIKARN, G. PUAVILAI AND R. RAJATANAVIN, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Osteoporos Int, 11: 486 – 492, 2000 Although calcium supplementation can cause hypercalciuria, the risk of nephrolithiasis has been shown to decrease rather than increase among subjects who had a higher calcium intake. Hypercalciuria is also a well-established side effect of calcitriol administration. However, the risk of nephrolithiasis is not well defined. The present study was undertaken to prospectively determine the effect of calcium with or without calcitriol on physicochemical risk factors associated with calcium oxalate nephrolithiasis in Thai postmenopausal women with osteoporosis. Subjects consisted of 53 Thai women more than 10 years postmenopausal who were randomly allocated to receive 750 mg of calcium carbonate supplement alone (n ⫽ 28) or 750 mg of calcium carbonate plus 0.5 g calcitriol (n ⫽ 25) daily. Mean ⫾ SEM for age was 65.3 ⫾ 1.1 years, body weight 53.5 ⫾ 1.3 kg. Urine samples for biochemical assays were collected at baseline and 3 months after treatment. Supersaturation for
781
782
UROLITHIASIS, ENDOUROLOGY AND LAPAROSCOPY
calcium oxalate stone formation was assessed from the 24 h urine constituents by the Tiselius’s index, AP(CaOx). Three months of calcium supplement alone resulted in a modest, but not significant, increase in urinary calcium (baseline, 2.90 ⫾ 0.43 mmol/day; after treatment 3.58 ⫾ 0.54 mmol/day) with no change in urinary oxalate, citrate or magnesium. In contrast, calcium together with calcitriol caused a significant increase in urinary calcium (baseline, 2.87 ⫾ 0.41 mmol/day; after treatment, 4.08 ⫾ 0.57 mmol/day; p ⬍0.05). No significant change in other urine constituents after treatment with calcium and calcitriol was detected. Therefore, AP(CaOx) did not significantly increase either after calcium alone (baseline, 1.17 ⫾ 0.39; after treatment, 1.36 ⫾ 0.28) or after calcium plus calcitriol (baseline, 1.09 ⫾ 0.17; after treatment, 1.09 ⫾ 0.19). However, after treatments, 12 subjects (23%) – 6 receiving calcium supplement alone and 6 receiving calcium plus calcitriol supplement – had high AP(CaOx) values (greater than the upper limit of 95% CI for AP(CaOx) derived from non-stone-forming Thai women). The post-treatment/baseline ratio was 3.21 ⫾ 0.74 for urinary calcium, 1.01 ⫾ 0.19 for urinary oxalate, and 2.23 ⫾ 0.42 (median 1.15) for AP(CaOx). The post-treatment/baseline ratio of calcium, but not for urinary oxalate, had a significant correlation with the post-treatment/baseline ratio of AP(CaOx). Our findings suggest that the alteration in the risk of calcium oxalate nephrolithiasis based on urinary composition is related to the alteration in urinary calcium. The risk of calcium oxalate nephrolithiasis does not increase significantly after calcium or combined calcium and calcitriol supplement in the majority of postmenopausal women with osteoporosis. Editorial Comment: The key finding in this study is that oral calcium alone does not result in a statistically significant increase in urinary calcium in postmenopausal women but when combined with calcitriol there is a significant increase. However, neither scenario results in a significant change in the activity product for calcium oxalate, thus, the risk of urolithiasis in these women is not increased. This finding may in part be due to the decrease in oxalate levels while the patients were taking calcium or calcium plus calcitriol. In the latter group oxalate levels decreased approximately 20%. These findings are in keeping with those of Curhan et al, showing that a high calcium diet was associated with a decrease in urolithiasis.1, 2 Thus, the answer to whether increased calcium intake leads to urolithiasis in postmenopausal women appears to be no. Ralph V. Clayman, M.D. 1. Curhan, G. C., Willett, W. C., Speizer, F. E. et al: Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med, 126: 497, 1997 2. Curhan, G. C., Willett, W. C., Rimm, E. B. et al: A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N Engl J Med, 328: 833, 1993
ESWL in Hemophiliac Patients M. CZAPLICKI, T. JAKUBCZYK, J. JUDYCKI, A. BORKOWSKI, W. JAS´ KOWIAK, J. M. ZIEMSKI, R. SCHARF, A. MISIAK AND P. SZALECKI, Department of Urology, Medical University and Department of Surgery, Institute of Hematology and Transfusiology, Warsaw, Poland Eur Urol, 38: 302–305, 2000 Objective: To assess ESWL treatment of urolithiasis in patients with hemophilia, the frequency of hemorrhagic complications, and to determine the treatment outline. Patients and Methods: From 1991 to 1997, eleven patients with hemophilia were treated by ESWL for urolithiasis. Substitution of deficient coagulation factors was started on the day of treatment. Ultrasound examination was performed in all cases on the 1st day after the procedure in order to discover any potential hemorrhagic complications. Substitution withdrawal depended on the patients’ general status, lack of hematuria and the absence of signs of hemorrhage. Preliminary results were evaluated after 7–10 days on the basis of plain abdominal X-ray of the kidney, ureter and bladder and ultrasonography. Results: In total, 25 ESWL sessions were performed, 1– 6/patient. Nine patients (81.8%) discharged stones, and 2 patients are being followed up. No hemorrhagic complications were observed. Conclusions: Substitution of deficient coagulation factors makes ESWL a safe method of urinary stone management in hemophiliacs. No hemorrhagic complications were seen in our patients. Substitution withdrawal may be based on the patients’ good general status, lack of hematuria and absence of signs of hemorrhage. Editorial Comment: In this study patients with urolithiasis and hemophilia types A (factor VIII) and B (factor IX) were successfully treated with extracorporeal shock wave lithotripsy (ESWL [Dornier Medical Systems, Inc., Marietta, Georgia]) after achieving a plasma level of the deficient coagulation factor of at least 50% of normal. Infusion of the deficient factor was continued post-ESWL until any macroscopic hematuria had resolved. Postoperative ultrasound was performed in all patients to assess perirenal hemorrhage, and infusions were needed for up to 5 days after ESWL. Although 82% of patients had “stone discharge,” the authors do not state whether the patients became stone-free. An alternative to ESWL in these patients, especially in those with ureteral or renal stone burdens of 1 cm. or less, is factor replacement and ureteroscopy with the holmium laser. Ralph V. Clayman, M.D.
RENAL, URETERAL AND RETROPERITONEAL TUMORS
Long-Term Follow-up of Stone Formers Treated With a low Dose of Sodium Potassium Citrate C. JENDLE-BENGTEN AND H.-G. TISELIUS, Department of Biomedicine and Surgery, Division of Urology, Faculty of Health Sciences, University Hospital, Linko¨ ping and Department of Urology, Huddinge University Hospital, Stockholm, Sweden Scand J Urol Nephrol, 34: 36 – 41, 2000 We evaluated the clinical efficacy of long-term preventive treatment with a single evening dose of alkaline citrate. Information was collected from the files of 52 recurrent stone formers prescribed a daily intake of 3.75–5 g of sodium potassium citrate (SPC; 14 –18 mmol of citrate). The annual and cumulative rates of stone formation and the rate of recurrence were compared before and during the treatment. A comparison was also made between the patients with (Group R) and without (Group NR) recurrent stone formation during treatment in terms of urine composition and previous history of the disease. For all patients who started the treatment, the number of stones was smaller during treatment (period tT) than during a period of the same length immediately before treatment (period tB), but greater than the number formed during a corresponding period immediately after the diagnosis (period tA). Via questionnaire we found low treatment compliance, with only 62% of the patients reporting consistent taking of their medication (Group T). The patients in Group T had a smaller cumulated number of stones during period tT than that during periods tA and tB, but the Kaplan-Meier curve of the fraction of patients remaining stone-free during treatment was almost identical to that recorded in 446 recurrent stone formers without medical treatment. No significant differences were recorded in terms of relevant pretreatment urinary risk factors between Groups TR and TNR, but numerically higher values of calcium oxalate (CaOx) supersaturation and calcium/citrate quotients were observed in Group TR. When 9 patients with a daily intake of SPC and a citrate excretion below 2.5 mmol/day were compared with 16 hypocitraturic patients only given drinking advice, the cumulated percentages of patients without recurrent stone formation in the 2 groups after 3 years were 44% and 48%, respectively. Although the number of patients in this study was small, our results indicate poor long-term protection from recurrent calcium stone formation when a single evening dose of only 3.75–5 g of SPC was taken. The rate of stone formation was apparently slightly reduced, but the fraction of patients free of recurrence was no different from that in patients without medical treatment. Editorial Comment: In this study nondirected therapy with a nightly dose of sodium potassium citrate had no beneficial effects in the prevention of new stone formation. However, in the recently proposed regimen of Pak citrate is the cornerstone of nondirected therapy. Why was citrate not effective in this study? Sodium potassium citrate is different from potassium citrate and potassium magnesium citrate. The sodium load of the preparation used in this study could result in a transient increase in calcium excretion, lessening the inhibitory effect of the medication on calcium oxalate or calcium phosphate crystal formation and growth. Also, only two-thirds of patients took the medication throughout the study period. Finally, the study was not prospectively randomized or blinded. Although sodium potassium citrate appears not to be helpful, this finding should not dissuade one from following the regimen proposed by Pak, in which potassium citrate and, more recently, potassium magnesium citrate have been successfully used as nondirected therapy. Ralph V. Clayman, M.D. Endoscopic Management of Urologic Disease With the Holmium Laser F. C. DELVECCHIO AND G. M. PREMINGER, Comprehensive Kidney Stone Center, Department of Surgery, Division of Urology, Duke University Medical Center, Durham, North Carolina Curr Opin Urol, 10: 233–237, 2000 The efficiency and safety profile of the holmium laser have made this tool a versatile multipurpose instrument for use in the endoscopic treatment of a wide variety of urologic disorders. Herein are reviewed holmium laser physics and current endourologic applications, as well as the performance of new low-power holmium lasers. Editorial Comment: In this excellent article the state of the art of the holmium laser in urology is reviewed. The photothermal mechanism of stone fragmentation and the use of this laser in stone disease and tissue applications, for example treatment of upper and lower tract transitional cell cancer, prostatectomy and endoureterotomy/endopyelotomy, are reported in a lucid and detailed manner. This device is the urologist’s laser. Although the investment for a laser that will allow for transurethral prostatectomy is approximately $100,000, the same laser at lower power (20 to 35 W.) can be purchased for $60,000 to $70,000. The superiority of this laser over all other modalities for treating ureteral and renal calculi via a flexible ureteroscope and the ability to vaporize small upper tract tumors or to incise ureteral strictures make this device an important part of the armamentarium of urologists who perform rigid and, in particular, flexible ureteroscopy. Ralph V. Clayman, M.D.
783
784
RENAL, URETERAL AND RETROPERITONEAL TUMORS
Artificial Cell Biotechnology for Medical Applications T. M. S. CHANG, Artificial Cells and Organs Research Centre, Departments of Physiology, Medicine and Biomedical Engineering, Faculty of Medicine, McGill University, Montreal, Quebec, Canada Blood Purif, 18: 91–96, 2000 Artificial cells are prepared in the laboratory for medical and biotechnological applications. The earliest routine clinical use of artificial cells is in the form of coated activated charcoal for hemoperfusion. Implantation of encapsulated cells are being studied for the treatment of diabetes, liver failure and the use of encapsulated genetically engineered cells for gene therapy. We recently found that daily orally administered artificial cells containing a genetically engineered microorganism can lower the elevated urea level in uremic rats to normal levels and increase the survival of the animal. Furthermore, this can remove potassium, phosphate, uric acid and other waste metabolites from uremic plasma. Blood substitutes based on modified hemoglobin are already in phase-III clinical trials in patients with as much as 20 units infused into each patient during trauma surgery. Artificial cells containing enzymes are being developed for clinical trials in hereditary enzyme deficiency diseases and other diseases. Artificial cells are also being investigated for drug delivery and other uses in biotechnology, chemical engineering and medicine. Editorial Comment: In this relatively new area of medical technology nonimmunogenic artificial cells can be constructed to contain myriad enzymes, which can correct altered cell functions in a variety of disease states. Although artificial cells have become familiar with regard to blood substitutes, this article is intriguing because the use of artificial cells containing a nonpathogenic strain of Escherichia coli to treat uremia in a rat model is described. It is impressive that these E. coli containing cells are administered orally so that intracellular bacteria metabolize the absorbed excess uric acid, creatinine, potassium and phosphate within the artificial cell and are then excreted. In uremic rats this therapy returned plasma urea to a normal range, which was more than a 10-fold decrease in serum urea. The possibility of adapting this technology to complement or replace dialysis is fascinating and encouraging. Ralph V. Clayman, M.D.
UROLOGICAL ONCOLOGY: RENAL, URETERAL AND RETROPERITONEAL TUMORS Phase I Trial of Twice-Weekly Intravenous Interleukin 12 in Patients With Metastatic Renal Cell Cancer or Malignant Melanoma: Ability to Maintain IFN-␥ Induction is Associated With Clinical Response J. A. GOLLOB, J. W. MIER, K. VEENSTRA, D. F. MCDERMOTT, D. CLANCY, M. CLANCY AND M. B. ATKINS, Beth Israel Deaconess Medical Center, Division of Hematology/Oncology, Boston, Massachusetts Clin Cancer Res, 6: 1678 –1692, 2000 The aim of this study was to examine the tolerability, antitumor activity, and biological effects of a new schedule of i.v. recombinant human interleukin 12 (rhIL-12). Twenty-eight patients were enrolled in a Phase I trial in which rhIL-12 was administered twice weekly as an i.v. bolus for 6 weeks. Stable or responding patients were eligible to receive additional 6-week cycles until there was no evidence of disease or until tumor progression. Patient cohorts were treated with escalating doses of rhIL-12 (30 –700 ng/kg). The maximum tolerated dose (MTD) was 500 ng/kg, with dose-limiting toxicities consisting of elevated hepatic transaminases and cytopenias. At the MTD (n ⫽ 14), there was one partial response occurring after 6 cycles of rhIL-12 in a patient with renal cell cancer. Two additional renal cell cancer patients treated at the MTD had prolonged disease stabilization, with one of these exhibiting tumor regression after 8 cycles of rhIL-12. IFN-␥, IL-15, and IL-18 were induced in patients treated with rhIL-12. Whereas IFN-␥ and IL-15 induction were attenuated midway through the first cycle in patients with disease progression, those patients with tumor regression or prolonged disease stabilization were able to maintain IFN-␥, IL-15, and IL-18 induction. The down-modulation of IFN-␥ induction during rhIL-12 treatment did not relate to IL-10 production or alterations in rhIL-12 bioavailability but was associated with an acquired defect in lymphocyte IFN-␥ production in response to IL-12, IL-2, or IL-15. This defect could be partially overcome in vitro through combined stimulation with IL-12 plus IL-2. These findings show that the chronic administration of twice-weekly i.v. rhIL-12 is well-tolerated, stimulates the production of IL-12 costimulatory cytokines
UROLITHIASIS, ENDOUROLOGY AND LAPAROSCOPY
mechanical trauma and electrothermal injury. The latter can result from unrecognized energy transfer in the operational field or, less commonly, to unnoticed stray current outside the laparoscopic field of view. Stray current can result from insulation failure, direct coupling, or capacitive coupling. METHODS: We reviewed the literature concerning essential biophysics of electrosurgery, including electrosurgical waveform differentiation, tissue effect, and variables that determine tissue effect. The incidence of electrosurgical injuries and possible mechanisms responsible for the injuries are discussed. Different types of injuries may result in different clinical manifestations and histopathological findings. Gross and microscopic pathological check-ups of the injury sites may distinguish between different mechanisms, and thus provide further clues postoperatively. RESULTS: Several recommended practices are proposed to avoid electrosurgical injury laparoscopically. To achieve electrosurgical safety and to prevent electrosurgical injuries, the surgical team should have a good understanding of the biophysics of electrosurgery, the basis of equipment and general tissue effects, as well as the surgeon’s spatial orientation and hand-eye coordination. Some intraoperative adjuvant procedures and newly developed safety devices have become available may aid to improve electrosurgical safety. CONCLUSIONS: Knowledge of the biophysics of electrosurgery and the mechanisms of electrosurgical injury is important in recognizing potential complications of electrosurgery in laparoscopy. Procedures for prevention, intraoperative adjuvant maneuvers, early recognition of the injury with in-time salvage treatment, and alertness to postoperative warning signs can help reduce such complications. Editorial Comment: Knowledge rules! The best way to avoid the devastation of a laparoscopic electrosurgical injury is understanding how electrosurgery works and defense against any possible current related injuries. In this regard this article is an excellent introduction to understanding electrosurgery. More than 20% to 30% of general surgeons and gynecologists have had a patient experience an electrosurgical injury during a laparoscopic procedure. The mechanism of injury can be due to 4 conditions, including direct application, insulation failure, direct coupling or capacitive coupling. It is noteworthy that electrosurgical injury to bowel may not result in clinical signs for up to 10 days after the procedure. The following suggestions are helpful for avoiding these problems: 1) use the lowest wattage necessary, which is usually 30 to 35 W. for cutting and coagulation, 2) the entire activated surface of the instrument should be in your field of view whenever activating the electrosurgical generator, 3) the potential for electrosurgical injury is greater when using the coagulation compared to the cutting mode, 4) never activate the electrode in the coagulating mode unless the electrode is in direct contact with the targeted tissue, 5) never use a plastic trocar sleeve with a metal trocar, and all metal trocars are preferable but all plastic trocars are also satisfactory, 6) activate the electrosurgical probe in short bursts of less than 1 second rather than a prolonged period of time, 7) a return electrode monitoring system can protect the patient at the site of the ground pad, 8) active electrode monitoring with an Electroscope system, (Electroscope, Boulder, Colorado) inactivates the electrosurgical device if any stray current due to insulation failure or capacitive coupling is detected and 9) consider using “tissue responsive” electrosurgical machines, which deliver only the current necessary to achieve the desired cutting or coagulation effect. Ralph V. Clayman, M.D. Laparoscopic Live Donor Nephrectomy: the Recipient L. E. RATNER, R. A. MONTGOMERY, W. R. MALEY, C. COHEN, J. BURDICK, K. D. CHAVIN, D. S. KITTUR, P. COLOMBANI, A. KLEIN, E. S. KRAUS AND L. R. KAVOUSSI, Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland Transplantation, 69: 2319 –2323, 2000 BACKGROUND: Laparoscopic live donor nephrectomy offers advantages to the donor in terms of decreased pain and shorter recuperation. Heretofore no detailed analysis of the recipient of laparoscopically procured kidneys has been performed. The purpose of this study was to determine whether laparoscopic donor nephrectomy had any deleterious effect on the recipient. METHODS: A retrospective review was conducted of all live donor renal transplantations performed from January 1995 through April 1998. The control group received kidneys procured via a standard flank approach (Open). Rejection was diagnosed histologically. Creatinine clearance was calculated using the Cockroft-Gault formula. RESULTS: A total of 110 patients received kidneys from laparoscopic (Lap) and 48 from open donors. One-year recipient (100% vs. 97.0%) and graft (93.5% vs. 91.1%) survival rates were similar for the Open and Lap groups, respectively. A similar incidence of vascular thrombosis (3.4% vs. 2.1%, P ⫽ NS) and ureteral complications (9.1% vs. 6.3%, P ⫽ NS) were seen in the Lap and Open groups, respectively. The incidence of acute rejection for the first month was 30.1% for the Lap group and 31.9% for the Open group (P ⫽ NS). The rate of decline of serum creatinine level in the early posttransplantation period was initially greater in the Open group, but by postoperative day 4 no significant difference existed. No difference was observed in allograft function long-term. The median length of hospital stay was 7.0 days for both groups. CONCLUSIONS: Laparoscopic live donor nephrectomy does not adversely effect recipient outcome. The previously demonstrated benefits to the donor, and the increased willingness of individuals to undergo live kidney donation, coupled with the
779
780
UROLITHIASIS, ENDOUROLOGY AND LAPAROSCOPY
acceptable outcomes experienced by recipients of laparoscopically procured kidneys justifies the continued development and adoption of this operation. Laparoscopic and Open Live Donor Nephrectomy: A Cost/Benefit Study T. BERNEY, J. MALAISE, M. MOURAD, P. MOREL AND J.-P. SQUIFFLET, Kidney and Pancreas Transplantation Unit, University of Louvain Medical School, Brussels, Belgium, and Clinic of Digestive Surgery and Visceral Transplantation, Geneva University Hospital, Geneva, Switzerland Transpl Int, 13: 35– 40, 2000 Recently, laparoscopic live-donor nephrectomy has been developed in order to increase organ donation. In this study we compare and review the records of 10 donors operated by open extraperitoneal approach and of 10 donors operated by a laparoscopic transperitoneal approach (LSC). Results show less use of postoperative parenteral narcotics in the LSC group (109 mg vs 272 mg; P ⬍0.0005) than in the extraperitoneal group. Morbidity was similar in both groups. There was no difference in postoperative stay. Allograft kidney function was similar in both groups until 6 months after donation. The use of disposable laparoscopic material bears an extra cost of 900 US$. We can thus conclude that laparoscopic live-donor nephrectomy is a safe procedure that significantly reduces postoperative pain, and is not detrimental to the allograft. The total cost of the laparoscopic procedure will be lower than that of the open approach if the length of postoperative stay is cut by 3 days. Increased Rates of Donation With Laparoscopic Donor Nephrectomy E. J. SCHWEITZER, J. WILSON, S. JACOBS, C. H. MACHAN, B. PHILOSOPHE, A. FARNEY, J. COLONNA, B. E. JARRELL AND S. T. BARTLETT, Joseph and Corrine Schwartz Division of Transplantation, Department of Surgery, Department of Urology and Red Cross Tissue Typing Laboratory, University of Maryland, Baltimore, Maryland Ann Surg, 232: 392– 400, 2000 Objective: To examine the impact of laparoscopic nephrectomy and recipient education on the proportion of kidney recipients who could identify a potential live donor, and on the live donor (LD) transplantation rate. Summary Background Data: Laparoscopic donor nephrectomy (LDN) results in less postoperative surgical pain, a shorter hospital stay, and quicker recovery than the standard open donor nephrectomy (ODN). The authors hypothesized that the availability of this less invasive surgical technique would enhance the willingness of family and friends to donate. Methods: The study population consisted of 3,298 end-stage renal disease patients referred for kidney transplant evaluation between November 1991 and February 2000, divided into three groups. The first group received no formal LD education and had only ODN available. The second group received formal education about the LD process and had only ODN available. The third group had both formal LD education and LDN available. Records were examined to determine what proportion of each group had any potential donors tissue-typed, and the rate at which they received an LD transplant. Results: Before LDN availability and formal LD education, only 35.1% of referrals found a potential donor, and only 12.2% received an LD transplant within 3 years. Institution of a formal education program increased the volunteer rate to 39.0%, and 16.5% received an LD transplant. When LDN became available, 50% of patients were able to find at least one potential donor, and within 3 years 24.7% received an LD transplant. Regression analysis indicated that availability of LDN was independently associated with a 1.9 relative risk of receiving an LD transplant. Kaplan-Meier death-censored 1- and 3-year graft survival rates for ODN transplants were 95.8% and 90.6%, versus 97.5% and 94.8% for LDN. Conclusions: The availability of LDN and an LD family education program has doubled the live donor transplantation rate, and outcomes remain excellent. Complications of Laparoscopic Live Donor Nephrectomy: The First 175 Cases D. Y. CHAN, M. D. FABRIZIO, L. E. RATNER AND L. R. KAVOUSSI, James Buchanan Brady Urological Institute and Department of Surgery, Johns Hopkins Medical Institution, Baltimore, Maryland Transplant Proc, 32: 778, 2000 Permission to Publish Abstract Not Granted Laparoscopic Live Donor Nephrectomy—is it Safe? J. R. LEVENTHAL, R. K. DEEIK, R. J. JOEHL, R. V. REGE, C. H. HERMAN, J. P. FRYER, D. KAUFMAN, M. ABECASSIS AND F. P. STUART, Department of Surgery, Northwestern University Medical School, Chicago, Illinois, and Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas Transplantation, 70: 602– 606, 2000 Background. Laparoscopic live donor nephrectomy (LDN) is a less invasive alternative to open nephrectomy (ODN) for living kidney donation. Concerns have been raised regarding the safety of LDN, the short and long term function of kidneys removed by LDN, and a potential higher incidence of urologic complications in LDN transplant recipients. Methods. Between October 1997 and May 1999, 80 LDNs were performed at our center. All patients were
UROLITHIASIS, ENDOUROLOGY AND LAPAROSCOPY
followed longitudinally with office visits and telephone interviews. These LDNs were compared with 50 ODNs performed from January 1996 to October 1997. Results. LDN procedures took significantly longer than ODN (4.6 vs. 3.1 hr). However, LDN was associated with significant reduction in i.v. narcotic use, a rapid return to diet, and shorter hospital stay. Of the 80 LDN procedures, a total of 75 (94%) were completed laparoscopically. Five patients were converted to laparotomy: three for hemorrhage and two for complex vascular anatomy. ODN conversion was associated with large donor body habitus and/or obesity. Seven LDN patients had minor complications and 4 had major complications. All major complications consisted of vascular injuries (2 lumbar vein injuries, 1 renal artery, and 1 aortic injury). All patients made complete recoveries. All LDN kidneys functioned immediately posttransplant. We have observed 100% patient and 97% 1-year actuarial graft survival in LDN transplant recipients. There have been no short- or long-term urologic complications in this series. Conclusion. With increasing experience and standardization of technique, LDN is a safe and effective procedure. Patients undergoing LDN demonstrate clinically significant, more rapid postoperative recoveries and shorter hospital stays than ODN patients. Excellent initial graft function and long-term graft survival have been observed with LDN kidneys. Urologic complications can be avoided. LDN has become the preferred surgical approach for living kidney donation at our center. Editorial Comment: These 5 articles represent a good survey of the state of the art of laparoscopic donor nephrectomy. Originally performed by Ratner, Kavoussi and colleagues at The Johns Hopkins University in 1995, this procedure has rapidly gained popularity and acceptance internationally. While the laparoscopic approach requires an extra 1.5 hours of operating time versus open donor nephrectomy, the donor needs half as much parenteral analgesics and leaves the hospital a day sooner. A learning curve of 30 cases has been proposed, and the majority of complications in the experience of the authors at the University of Maryland, including the need to convert, occurred during the initial 30 procedures. Although increased ureteral complications were experienced initially, the current practice of taking the ureter broadly with an EndoGIA (United States Surgical Corp., Norwalk, Connecticut) stapler appears to have greatly reduced the ureteral complication rate, which now parallels that of the open approach. The review by Chan shows an overall complication rate for laparoscopic donor nephrectomy of 14%, which compares favorably with that for open donor nephrectomy of 16%. Graft survival rates of 91% to 97% at 1 year have been achieved, which are similar to those previously reported for open donor nephrectomy. The increased equanimity to the donor in laparoscopic donor nephrectomy has possibly prompted an increase in the living donor pool as at the University of Maryland the live donor transplantation rate for local referrals has doubled. Whether this pattern is truly local or represents a national trend remains to be determined. Ralph V. Clayman, M.D. Bench to Bedside: Lessons From the Genetic Hypercalciuric Stone-Forming Rat D. A. BUSHINSKY, Nephrology Unit, University of Rochester Medical Center, Rochester, New York Am J Kidney Dis, 36: LXI–LXIV, 2000 No Abstract Editorial Comment: In this review a rat model for stone formation is described. These genetically inbred rats are hypercalciuric and form calcium hydrogen phosphate renal stones. The defect appears to be at the level of the renal tubule (decreased calcium reabsorption) and in the bone (increased sensitivity to vitamin D). It is interesting that a high oxalate diet resulted in a decrease in urinary calcium oxalate supersaturation in these genetically inbred rats. Ralph V. Clayman, M.D. Risk of Calcium Oxalate Nephrolithiasis After Calcium or Combined Calcium and Calcitriol Supplementation in Postmenopausal Women S. DOMRONGKITCHAIPORN, B. ONGPHIPHADHANAKUL, W. STITCHANTRAKUL, N. PIASEU, S. CHANSIRIKARN, G. PUAVILAI AND R. RAJATANAVIN, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Osteoporos Int, 11: 486 – 492, 2000 Although calcium supplementation can cause hypercalciuria, the risk of nephrolithiasis has been shown to decrease rather than increase among subjects who had a higher calcium intake. Hypercalciuria is also a well-established side effect of calcitriol administration. However, the risk of nephrolithiasis is not well defined. The present study was undertaken to prospectively determine the effect of calcium with or without calcitriol on physicochemical risk factors associated with calcium oxalate nephrolithiasis in Thai postmenopausal women with osteoporosis. Subjects consisted of 53 Thai women more than 10 years postmenopausal who were randomly allocated to receive 750 mg of calcium carbonate supplement alone (n ⫽ 28) or 750 mg of calcium carbonate plus 0.5 g calcitriol (n ⫽ 25) daily. Mean ⫾ SEM for age was 65.3 ⫾ 1.1 years, body weight 53.5 ⫾ 1.3 kg. Urine samples for biochemical assays were collected at baseline and 3 months after treatment. Supersaturation for
781
782
UROLITHIASIS, ENDOUROLOGY AND LAPAROSCOPY
calcium oxalate stone formation was assessed from the 24 h urine constituents by the Tiselius’s index, AP(CaOx). Three months of calcium supplement alone resulted in a modest, but not significant, increase in urinary calcium (baseline, 2.90 ⫾ 0.43 mmol/day; after treatment 3.58 ⫾ 0.54 mmol/day) with no change in urinary oxalate, citrate or magnesium. In contrast, calcium together with calcitriol caused a significant increase in urinary calcium (baseline, 2.87 ⫾ 0.41 mmol/day; after treatment, 4.08 ⫾ 0.57 mmol/day; p ⬍0.05). No significant change in other urine constituents after treatment with calcium and calcitriol was detected. Therefore, AP(CaOx) did not significantly increase either after calcium alone (baseline, 1.17 ⫾ 0.39; after treatment, 1.36 ⫾ 0.28) or after calcium plus calcitriol (baseline, 1.09 ⫾ 0.17; after treatment, 1.09 ⫾ 0.19). However, after treatments, 12 subjects (23%) – 6 receiving calcium supplement alone and 6 receiving calcium plus calcitriol supplement – had high AP(CaOx) values (greater than the upper limit of 95% CI for AP(CaOx) derived from non-stone-forming Thai women). The post-treatment/baseline ratio was 3.21 ⫾ 0.74 for urinary calcium, 1.01 ⫾ 0.19 for urinary oxalate, and 2.23 ⫾ 0.42 (median 1.15) for AP(CaOx). The post-treatment/baseline ratio of calcium, but not for urinary oxalate, had a significant correlation with the post-treatment/baseline ratio of AP(CaOx). Our findings suggest that the alteration in the risk of calcium oxalate nephrolithiasis based on urinary composition is related to the alteration in urinary calcium. The risk of calcium oxalate nephrolithiasis does not increase significantly after calcium or combined calcium and calcitriol supplement in the majority of postmenopausal women with osteoporosis. Editorial Comment: The key finding in this study is that oral calcium alone does not result in a statistically significant increase in urinary calcium in postmenopausal women but when combined with calcitriol there is a significant increase. However, neither scenario results in a significant change in the activity product for calcium oxalate, thus, the risk of urolithiasis in these women is not increased. This finding may in part be due to the decrease in oxalate levels while the patients were taking calcium or calcium plus calcitriol. In the latter group oxalate levels decreased approximately 20%. These findings are in keeping with those of Curhan et al, showing that a high calcium diet was associated with a decrease in urolithiasis.1, 2 Thus, the answer to whether increased calcium intake leads to urolithiasis in postmenopausal women appears to be no. Ralph V. Clayman, M.D. 1. Curhan, G. C., Willett, W. C., Speizer, F. E. et al: Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med, 126: 497, 1997 2. Curhan, G. C., Willett, W. C., Rimm, E. B. et al: A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N Engl J Med, 328: 833, 1993
ESWL in Hemophiliac Patients M. CZAPLICKI, T. JAKUBCZYK, J. JUDYCKI, A. BORKOWSKI, W. JAS´ KOWIAK, J. M. ZIEMSKI, R. SCHARF, A. MISIAK AND P. SZALECKI, Department of Urology, Medical University and Department of Surgery, Institute of Hematology and Transfusiology, Warsaw, Poland Eur Urol, 38: 302–305, 2000 Objective: To assess ESWL treatment of urolithiasis in patients with hemophilia, the frequency of hemorrhagic complications, and to determine the treatment outline. Patients and Methods: From 1991 to 1997, eleven patients with hemophilia were treated by ESWL for urolithiasis. Substitution of deficient coagulation factors was started on the day of treatment. Ultrasound examination was performed in all cases on the 1st day after the procedure in order to discover any potential hemorrhagic complications. Substitution withdrawal depended on the patients’ general status, lack of hematuria and the absence of signs of hemorrhage. Preliminary results were evaluated after 7–10 days on the basis of plain abdominal X-ray of the kidney, ureter and bladder and ultrasonography. Results: In total, 25 ESWL sessions were performed, 1– 6/patient. Nine patients (81.8%) discharged stones, and 2 patients are being followed up. No hemorrhagic complications were observed. Conclusions: Substitution of deficient coagulation factors makes ESWL a safe method of urinary stone management in hemophiliacs. No hemorrhagic complications were seen in our patients. Substitution withdrawal may be based on the patients’ good general status, lack of hematuria and absence of signs of hemorrhage. Editorial Comment: In this study patients with urolithiasis and hemophilia types A (factor VIII) and B (factor IX) were successfully treated with extracorporeal shock wave lithotripsy (ESWL [Dornier Medical Systems, Inc., Marietta, Georgia]) after achieving a plasma level of the deficient coagulation factor of at least 50% of normal. Infusion of the deficient factor was continued post-ESWL until any macroscopic hematuria had resolved. Postoperative ultrasound was performed in all patients to assess perirenal hemorrhage, and infusions were needed for up to 5 days after ESWL. Although 82% of patients had “stone discharge,” the authors do not state whether the patients became stone-free. An alternative to ESWL in these patients, especially in those with ureteral or renal stone burdens of 1 cm. or less, is factor replacement and ureteroscopy with the holmium laser. Ralph V. Clayman, M.D.
RENAL, URETERAL AND RETROPERITONEAL TUMORS
Long-Term Follow-up of Stone Formers Treated With a low Dose of Sodium Potassium Citrate C. JENDLE-BENGTEN AND H.-G. TISELIUS, Department of Biomedicine and Surgery, Division of Urology, Faculty of Health Sciences, University Hospital, Linko¨ ping and Department of Urology, Huddinge University Hospital, Stockholm, Sweden Scand J Urol Nephrol, 34: 36 – 41, 2000 We evaluated the clinical efficacy of long-term preventive treatment with a single evening dose of alkaline citrate. Information was collected from the files of 52 recurrent stone formers prescribed a daily intake of 3.75–5 g of sodium potassium citrate (SPC; 14 –18 mmol of citrate). The annual and cumulative rates of stone formation and the rate of recurrence were compared before and during the treatment. A comparison was also made between the patients with (Group R) and without (Group NR) recurrent stone formation during treatment in terms of urine composition and previous history of the disease. For all patients who started the treatment, the number of stones was smaller during treatment (period tT) than during a period of the same length immediately before treatment (period tB), but greater than the number formed during a corresponding period immediately after the diagnosis (period tA). Via questionnaire we found low treatment compliance, with only 62% of the patients reporting consistent taking of their medication (Group T). The patients in Group T had a smaller cumulated number of stones during period tT than that during periods tA and tB, but the Kaplan-Meier curve of the fraction of patients remaining stone-free during treatment was almost identical to that recorded in 446 recurrent stone formers without medical treatment. No significant differences were recorded in terms of relevant pretreatment urinary risk factors between Groups TR and TNR, but numerically higher values of calcium oxalate (CaOx) supersaturation and calcium/citrate quotients were observed in Group TR. When 9 patients with a daily intake of SPC and a citrate excretion below 2.5 mmol/day were compared with 16 hypocitraturic patients only given drinking advice, the cumulated percentages of patients without recurrent stone formation in the 2 groups after 3 years were 44% and 48%, respectively. Although the number of patients in this study was small, our results indicate poor long-term protection from recurrent calcium stone formation when a single evening dose of only 3.75–5 g of SPC was taken. The rate of stone formation was apparently slightly reduced, but the fraction of patients free of recurrence was no different from that in patients without medical treatment. Editorial Comment: In this study nondirected therapy with a nightly dose of sodium potassium citrate had no beneficial effects in the prevention of new stone formation. However, in the recently proposed regimen of Pak citrate is the cornerstone of nondirected therapy. Why was citrate not effective in this study? Sodium potassium citrate is different from potassium citrate and potassium magnesium citrate. The sodium load of the preparation used in this study could result in a transient increase in calcium excretion, lessening the inhibitory effect of the medication on calcium oxalate or calcium phosphate crystal formation and growth. Also, only two-thirds of patients took the medication throughout the study period. Finally, the study was not prospectively randomized or blinded. Although sodium potassium citrate appears not to be helpful, this finding should not dissuade one from following the regimen proposed by Pak, in which potassium citrate and, more recently, potassium magnesium citrate have been successfully used as nondirected therapy. Ralph V. Clayman, M.D. Endoscopic Management of Urologic Disease With the Holmium Laser F. C. DELVECCHIO AND G. M. PREMINGER, Comprehensive Kidney Stone Center, Department of Surgery, Division of Urology, Duke University Medical Center, Durham, North Carolina Curr Opin Urol, 10: 233–237, 2000 The efficiency and safety profile of the holmium laser have made this tool a versatile multipurpose instrument for use in the endoscopic treatment of a wide variety of urologic disorders. Herein are reviewed holmium laser physics and current endourologic applications, as well as the performance of new low-power holmium lasers. Editorial Comment: In this excellent article the state of the art of the holmium laser in urology is reviewed. The photothermal mechanism of stone fragmentation and the use of this laser in stone disease and tissue applications, for example treatment of upper and lower tract transitional cell cancer, prostatectomy and endoureterotomy/endopyelotomy, are reported in a lucid and detailed manner. This device is the urologist’s laser. Although the investment for a laser that will allow for transurethral prostatectomy is approximately $100,000, the same laser at lower power (20 to 35 W.) can be purchased for $60,000 to $70,000. The superiority of this laser over all other modalities for treating ureteral and renal calculi via a flexible ureteroscope and the ability to vaporize small upper tract tumors or to incise ureteral strictures make this device an important part of the armamentarium of urologists who perform rigid and, in particular, flexible ureteroscopy. Ralph V. Clayman, M.D.
783
784
RENAL, URETERAL AND RETROPERITONEAL TUMORS
Artificial Cell Biotechnology for Medical Applications T. M. S. CHANG, Artificial Cells and Organs Research Centre, Departments of Physiology, Medicine and Biomedical Engineering, Faculty of Medicine, McGill University, Montreal, Quebec, Canada Blood Purif, 18: 91–96, 2000 Artificial cells are prepared in the laboratory for medical and biotechnological applications. The earliest routine clinical use of artificial cells is in the form of coated activated charcoal for hemoperfusion. Implantation of encapsulated cells are being studied for the treatment of diabetes, liver failure and the use of encapsulated genetically engineered cells for gene therapy. We recently found that daily orally administered artificial cells containing a genetically engineered microorganism can lower the elevated urea level in uremic rats to normal levels and increase the survival of the animal. Furthermore, this can remove potassium, phosphate, uric acid and other waste metabolites from uremic plasma. Blood substitutes based on modified hemoglobin are already in phase-III clinical trials in patients with as much as 20 units infused into each patient during trauma surgery. Artificial cells containing enzymes are being developed for clinical trials in hereditary enzyme deficiency diseases and other diseases. Artificial cells are also being investigated for drug delivery and other uses in biotechnology, chemical engineering and medicine. Editorial Comment: In this relatively new area of medical technology nonimmunogenic artificial cells can be constructed to contain myriad enzymes, which can correct altered cell functions in a variety of disease states. Although artificial cells have become familiar with regard to blood substitutes, this article is intriguing because the use of artificial cells containing a nonpathogenic strain of Escherichia coli to treat uremia in a rat model is described. It is impressive that these E. coli containing cells are administered orally so that intracellular bacteria metabolize the absorbed excess uric acid, creatinine, potassium and phosphate within the artificial cell and are then excreted. In uremic rats this therapy returned plasma urea to a normal range, which was more than a 10-fold decrease in serum urea. The possibility of adapting this technology to complement or replace dialysis is fascinating and encouraging. Ralph V. Clayman, M.D.
UROLOGICAL ONCOLOGY: RENAL, URETERAL AND RETROPERITONEAL TUMORS Phase I Trial of Twice-Weekly Intravenous Interleukin 12 in Patients With Metastatic Renal Cell Cancer or Malignant Melanoma: Ability to Maintain IFN-␥ Induction is Associated With Clinical Response J. A. GOLLOB, J. W. MIER, K. VEENSTRA, D. F. MCDERMOTT, D. CLANCY, M. CLANCY AND M. B. ATKINS, Beth Israel Deaconess Medical Center, Division of Hematology/Oncology, Boston, Massachusetts Clin Cancer Res, 6: 1678 –1692, 2000 The aim of this study was to examine the tolerability, antitumor activity, and biological effects of a new schedule of i.v. recombinant human interleukin 12 (rhIL-12). Twenty-eight patients were enrolled in a Phase I trial in which rhIL-12 was administered twice weekly as an i.v. bolus for 6 weeks. Stable or responding patients were eligible to receive additional 6-week cycles until there was no evidence of disease or until tumor progression. Patient cohorts were treated with escalating doses of rhIL-12 (30 –700 ng/kg). The maximum tolerated dose (MTD) was 500 ng/kg, with dose-limiting toxicities consisting of elevated hepatic transaminases and cytopenias. At the MTD (n ⫽ 14), there was one partial response occurring after 6 cycles of rhIL-12 in a patient with renal cell cancer. Two additional renal cell cancer patients treated at the MTD had prolonged disease stabilization, with one of these exhibiting tumor regression after 8 cycles of rhIL-12. IFN-␥, IL-15, and IL-18 were induced in patients treated with rhIL-12. Whereas IFN-␥ and IL-15 induction were attenuated midway through the first cycle in patients with disease progression, those patients with tumor regression or prolonged disease stabilization were able to maintain IFN-␥, IL-15, and IL-18 induction. The down-modulation of IFN-␥ induction during rhIL-12 treatment did not relate to IL-10 production or alterations in rhIL-12 bioavailability but was associated with an acquired defect in lymphocyte IFN-␥ production in response to IL-12, IL-2, or IL-15. This defect could be partially overcome in vitro through combined stimulation with IL-12 plus IL-2. These findings show that the chronic administration of twice-weekly i.v. rhIL-12 is well-tolerated, stimulates the production of IL-12 costimulatory cytokines