Tumor type M2 pyruvate kinase expression in metastatic renal cell carcinoma.

The M2 isoenzyme of pyruvate kinase (M2-PK) is specifically expressed in tumor cells (TuM2-PK) and has been detected in the peripheral blood of patients with renal cell carcinoma (RCC). TuM2-PK is not useful as a biological marker in localized RCC. We analysed TuM2-PK in 68 patients with metastatic RCC after initial surgery and prior to or during chemoimmunotherapy of metastases. In 50 patients, the levels of TuM2-PK were measured during chemoimmunotherapy with interleukin-2, interferon-alpha2a and 5-fluorouracil for up to 8 months and were correlated to response as assessed by radiological imaging techniques. TuM2-PK was quantified with a commercially available enzyme linked immunosorbent assay kit using a cut off of 15 kU/l. In 48 of 68 patients (71%), TuM2-PK was elevated above the cut-off. TuM2-PK was significantly higher in G3 tumors than in G2 tumors. In 34 of 50 patients (68%) undergoing chemoimmunotherapy, a positive correlation between TuM2-PK values and response to treatment was observed. Based on these data, we would not recommend the routine clinical use of TuM2-PK in metastatic RCC at this point.

[Improvement of hemostasis in laparoscopic and open partial nephrectomy with gelatin thrombin matrix (FloSeal)]. / Verbesserung der Hämostase bei laparoskopischen und offenen Teilnephrektomien durch Gelatine-Thrombin-Matrix (FloSeal).

Long-term follow-up studies have demonstrated that effective local tumor control and long-term tumor-free progression rates can be achieved by nephron-sparing surgery. However, hemostasis is a major issue and the lack of effective means of hemostasis has limited a wider use of the laparoscopic approach to nephron-sparing surgery. Between January 2001 and August 2002, a total of 36 patients with renal cell carcinomas were treated by partial nephrectomies using a two-component tissue sealant (FloSeal). The median age was 55.2 years (range: 34-71 years). Follow-up time was 1-18 months (median: 5.5 months). The tumor diameter ranged from 2 to 5 cm (median: 2.9 cm). Open retroperitoneal surgery was performed in 17 cases and laparoscopic partial nephrectomy in 19 cases. The two-component tissue sealant (consisting of a gelatin matrix with granular and thrombin components) was applied after resection of the tumor and before perfusion of the kidney. The following parameters were recorded: (1) time until complete hemostasis was achieved, (2) decrease in postoperative hemoglobin level, (3) postoperative bleeding, and (4) presence or absence of a perirenal hematoma 24 h and 10 days postoperatively by ultrasound. After application of the tissue sealant for 1-2 min to the moist resection site, hemostasis was immediate in all cases. During the laparoscopic partial nephrectomies, a laparoscopic applicator was used that avoided wasting the tissue sealant within the dead space of the instrument. When reperfusion of the kidney was established, hemostasis was maintained. The decrease in postoperative hemoglobin level ranged from 0.3 to 1.2 points (median: 0.8 points). None of the patients required blood transfusions. There were no cases of postoperative bleeding. An ultrasound examination 24 h and 10 days postoperatively demonstrated the absence of a significant perirenal hematoma. The two-component tissue sealant FloSeal provided immediate and durable hemostasis in open and laparoscopic partial nephrectomies. The tissue sealant may provide a tool to expand the possibilities of laparoscopic nephron-sparing surgery.

[Laparoscopic dismembered pyeloplasty with Anderson-Hynes technique]. / Die laparoskopische Nierenbeckenplastik mit Kontinuitätstrennung nach Anderson-Hynes.

Because of the minimal invasiveness of the laparoscopic approach, we introduced the laparoscopic dismembered pyeloplasty in our treatment modalities for patients with primary UPJ obstruction. We report on our technique and the results after a median follow-up of more than 2 years. Between August 1997 and September 2002, 52 patients underwent a laparoscopic dismembered pyeloplasty at our institution. All patients had a symptomatic primary PJ obstruction. We prefer the transperitoneal route with laterocolic exposure of the kidney. After preparation and exposure of the ureter and the renal pelvis, we performed in each case the dismembered Anderson-Hynes pyeloplasty with resection of the pelvis and reanastomosis between the ureter and renal pelvis. Intracorporeal suturing and knotting techniques were used exclusively. All procedures could be performed successfully. In no case was conversion to open surgery necessary. The mean operative time was 180 min. Crossing vessels were present in 57% of patients. The mean postoperative hospital stay was 4 days. The first patient had an anastomosis insufficiency, which required laparoscopic repair. The same patient failed in the follow-up. He developed a late recurrence of the stenosis and needed an open repair. In all other patients the obstruction was resolved or significantly improved. The long-term success rate is 98% with a follow-up of 25 months. Our results with laparoscopic dismembered pyeloplasties compare favorably with those achieved by open pyeloplasties with less perioperative morbidity and discomfort. We do believe that laparoscopic dismembered pyeloplasty will be the method of choice in the treatment of UPJ obstruction.

[Laparoscopic radical nephrectomy: indications, techniques, and oncological outcome]. / Die laparoskopische transperitoneale Tumornephrektomie. Indikation, Technik und onkologisches Outcome.

Renal cell carcinoma is likely to become one of the most important indications for laparoscopic surgery worldwide. The laparoscopic technique combines the benefits of the minimally invasive approach with established surgical principles. In our institution the laparoscopic transperitoneal approach with intact specimen extraction has become the standard technique for radical nephrectomies. We report the indications, techniques, and oncological outcome in a single center experience in 100 cases. The mean tumor size was 5.9 cm (range: 2-11 cm), the blood loss was 220 ml, and the mean surgical time was 211 min, including the learning curves of five surgeons. Histological findings were pT1 in 66 (66%), pT2 in 11 (11%), and pT3 in 19 (19%) patients with an increasing tumor size according to the experience of the surgeons. In four cases (4%) histology did not prove malignant disease. Positive lymph nodes were detected in three cases (3%) and surgical margins were negative for tumor in all patients. To date 61 patients were available for follow-up; patients with primary metastatic disease were excluded from this analysis. Follow-up was between 1 and 30 months with an average of 12.9 months. Progressive disease occurred in two cases in patients with pT3G3 tumors. No cases of local recurrence or port metastasis occurred during observation. Laparoscopic radical nephrectomy is a routine, effective treatment for patients with renal cell carcinoma. Our follow-up data up to 30 months confirm the effectiveness of laparoscopic radical nephrectomy in terms of surgical principles and oncological outcome.

[Renal carcinoma with invasion of the suprahepatic vena cava (Staehler stage III and IV): surgical treatment and results]. / Nierenzellkarzinom mit suprahepatischem V.-cava-Befall (Stadium III und IV nach Staehler). Operative Therapie und Ergebnisse.

The operative treatment of patients with renal cell carcinoma (RCC) and suprahepatic infradiaphragmatic or supradiaphragmatic vena cava invasion (Staehler stage III and IV) is still an interdisciplinary challenge. The potential high complication rate and the enormous operative-technical efforts have to be brought into line with the individual benefit for the patient. In this study, we have retrospectively analyzed the operative results of 24 patients. We have further compared the patients during follow-up and immunotherapy due to metastasis with a control group of 75 patients without vena cava invasion. Perioperative mortality in the 24 patients was 4%. Four patients had metastasis at presentation and 14 further patients developed metastatic disease during median follow-up of 23.5 months. Median survival was 45 months with a 1-, 3-, and 5-year survival rate of 92, 57, and 33%, respectively. In a multivariate analysis, only the presence of metastasis (p=0.002) and marginal immunotherapy (p=0.1), but not vena cava invasion (p=0.259) or a positive lymph node status (p=0.624) were significant predictors of a poor survival. For patients with RCC and suprahepatic infradiaphragmatic or supradiaphragmatic vena cava invasion (Staehler stage III and IV), the combination of an aggressive surgical treatment combined with subsequent immunotherapy in the presence of metastatic disease offers a realistic therapeutic option with reasonable survival rates.

[Laparoscopic transperitoneal donor nephrectomy. Technique and results]. / Die laparoskopische transperitoneale Donornephrektomie. Technik und Ergebnisse.

Living donor kidney transplantation is one possibility to meet the growing demand for organs in patients with chronic renal failure. In 1995 the first laparoscopic living donor nephrectomy (LDN) was performed in the United States. More than 100 transplant centers worldwide perform LDN. The expectations of a larger number of willing organ donors were fulfilled due to the less traumatic operation. Meanwhile, several techniques exist to retrieve a kidney laparoscopically, including the trans- or retroperitoneal, strictly laparoscopic, or hand-assisted approach. From February 1999 to September 2002, 63 strictly laparoscopic, transperitoneal LDNs were performed at the Department of Urology of the Charité University Hospital, Berlin. Warm ischemic time was 148 s (105-360) and operating time was 203 min (110-305). Intraoperative complications were due to insufficient closure of the vessels in four patients. Mean postoperative hospital stay was 5.7 days (3-9). One year after LDN, renal function as well as creatinine levels of the recipient showed no difference compared to the organs harvested via the approach at our department prior to implementation of LDN. Strictly laparoscopic transperitoneal donor nephrectomy is a safe method for kidney retrieval and ensures excellent graft function.

[Laparoscopic living donor nephrectomy of kidneys with multiple renal vessels]. / Multiple Nierengefässe bei der laparoskopischen Lebendnierenspende.

Due to the increasing waiting time for transplantation of a cadaveric kidney, living donor kidney transplantation is an increasingly oncoming issue. Laparoscopic donor nephrectomies (LDN) have been performed since 1995 and presently more than 100 transplant centers offer this minimally invasive surgical approach. The advantages for the donor of less pain, shorter hospital stay, earlier return to work, better cosmetic results in combination with an organ function equal to open donor nephrectomy are the reasons for an enormous increase in LDN. Since up to 30% of the donor kidneys have multiple vessels for blood supply, an increase of these organs for LDN can be expected. We performed a retrospective study of LDN at our center and compared donors with multiple vs single vessel supply. From February 1999 to September 2002, 63 LDN were performed at the department of Urology, Charité University Hospital, Berlin. A comparison between 18 donor kidneys with multiple vessel supply and 45 donor organs with single vessels showed no difference for the time of laparoscopic explantation (207 vs 201 min, p=0.4) or the warm (166 vs 148 s, p=0.2) and cold ischemic times (117 vs 103 min, p=0.66). As could be expected, the mixed ischemic time, i.e., the time for anastomosis of the kidney with the recipient's vessels, showed a significant difference (53 vs 46 min, p=0.02). Intra- and postoperative complication rates for donors and recipients were not different in both groups. Laparoscopic donor nephrectomy for kidneys with multiple vessels is feasible and safe for donor and recipient.

[Laparoscopic radical cystectomy with intracorporeal creation of a continent urinary diversion. Future or present?]. / Laparoskopische radikale Zystektomie mit intrakorporaler Anlage einer kontinenten Harnableitung. Zukunft oder Gegenwart?

Once laparoscopic radical prostatectomy has been mastered, the step to performing a radical cystectomy is not that far. The challenge is to create the urinary diversion by laparoscopy. In this report we describe our experience with 11 laparoscopic radical cystectomies and intracorporeal construction of a continent urinary diversion (Mainz pouch II) as a treatment option in patients with muscle-invading bladder cancer. All 11 procedures could be performed successfully. A conversion to open surgery was not required in any case. The mean surgery time was 6.7 h. Except for two pouch fistulas we did not observe any intra- or postoperative complications. The functional as well as the oncological results are convincing. Less morbidity and faster recovery are the main advantages of this minimally invasive procedure. In addition, the low levels of blood loss, fluid shifts, and electrolyte loss considerably reduce cardiovascular stress. Radical cystectomy and construction of a continent urinary diversion represent the limit of technically feasible laparoscopy and should be done exclusively in specialized centers.

[Radical prostatectomy in clinically localized prostate carcinoma. Pro laparoscopic approach]. / Die radikale Prostatektomie beim klinisch lokalisierten Prostatakarzinom. Pro laparoskopischer Zugangsweg.

Systematic development of laparoscopy during the last decade has led to establishing laparoscopic radical prostatectomy (LRP) as a surgical procedure. On the basis of extensive experience at our center, the advantages of the minimally invasive method are described as well as the problems still in existence. Reduced trauma caused by laparoscopic access in combination with clearly reduced blood loss has resulted in less morbidity after laparoscopic procedures. This is reflected in a shorter postoperative stay in hospital and faster convalescence. LRP as an ambitious and complex procedure has an average complication rate of 12%, which shows that the method has surpassed the stage of experimental surgery. By direct comparison, the costs of LRP are higher than for the open surgical procedure, but on the whole this is economically balanced by the lower morbidity, shorter hospital stay, and faster convalescence. The progress in technology to be expected in the field of laparoscopy will further increase quality, precision, and safety of LRP and thus contribute to the establishment of laparoscopic radical prostatectomy as a surgical method of choice.

Laparoscopic radical prostatectomy. Technical aspects and experience with 125 cases.

PURPOSE: The laparoscopic access for radical prostatectomy offers an alternative to the open surgical procedure with less morbidity. We report on our experience with 125 laparoscopic prostatectomies, especially with respect to making the laparoscopic approach a routine procedure and with a view to the oncological and functional results. MATERIAL AND METHODS: From June 1999 to September 2000, we performed 125 laparoscopic prostatectomies. These included only patients with cancer stages T1 or T2. The mean PSA concentration was 10.5 ng/ml. Forty-four percent of the patients had undergone previous abdominal and 19% previous transurethral surgery. For our laparoscopic prostatectomies we used the descending technique. Free-hand laparoscopic suturing and in situ knot-tying technique were used for the urethrovesical anastomosis. The mobilized specimens were removed in an endobag via a muscle splitting incision. RESULTS: All 125 procedures could be completed successfully. No case required conversion to open surgery. The average operating time was 255 min, the last 40 procedures taking 200 min only. Mean blood loss was 185 ml. Two patients (2%) required postoperative blood transfusion. After an initial learning curve, catheter remained in place for an average of 5.5 days, and the average postoperative stay in hospital was 8 days. Intraoperative complications were seen in 5 patients (4%). In 13 patients (10.4%) postoperative complications were observed. 86% of the patients are continent 6 months postoperatively. Preservation of the neurovascular bundle and sexual potency is possible. CONCLUSION: Laparoscopic radical prostatectomy is an ambitious procedure with a steep learning curve, especially for the laparoscopic dissecting and suturing technique. The excellent sight for dissection results in a reduced blood loss and faster convalescence with an overall lower morbidity. Also with regard to oncological and functional (continence) results the minimally invasive access is at least equivalent to the open procedure. In our opinion, laparoscopic prostatectomy will be the future method of choice for radical prostatectomy.

[Brachytherapy of local prostatic carcinoma]. / Brachytherapie des lokalen Prostatakarzinoms.

Brachytherapy of prostate cancer has become attractive in recent years in Germany. There are several radioactive sources available, which are physically different. Some of them are used as permanent or temporary implants. The permanent sources most frequently used are iodine 125, palladium 103, and gold 198. Iridium is a temporary implant. The techniques used in Germany are low-dose rate (LDR) and high-dose rate brachytherapy, which differ in dose distribution and patient population. The success of prostate cancer brachytherapy depends on patient selection and choosing the right source for the technique used. Best suited for LDR monotherapy is the low-risk patient with a prostate-specific antigen (PSA) level below 10 ng/ml, maximal tumor stage T2b, and a Gleason score of less than 7.

[Thermoradiotherapy with interstitial thermoseeds in treatment of local prostatic carcinoma. Initial results of a phase II study]. / Thermoradiotherapie mit interstitiellen Thermoseeds bei der Behandlung des lokalen Prostatakarzinoms. Erste Ergebnisse einer Phase-II-Studie.

Several experimental data are available regarding the efficacy of the combination of interstitial hyperthermia and conformal radiation therapy. We planned a phase II trial as a member of the special hyperthermia research group of the Deutsche Forschungsgemeinschaft (German Research Society) to determine the efficacy of thermoradiotherapy using interstitial cobalt-palladium thermoseeds in the treatment of patients with localized prostate cancer. Forty-one patients with localized prostate cancer were enrolled in the study between July 1997 and April 2000. The interstitial hyperthermia induced in a magnetic field was applied in six sessions once a week. Conformal three-dimensional radiation therapy was given simultaneously in daily fractions of 1.8 Gy with a total dose of 68.4 Gy. We measured intraprostatic temperatures between 42 degrees and 46 degrees C. No major side effects were observed during the hyperthermia session. The median level of prostate-specific antigen (PSA) decreased from 11.25 ng/ml to 0.88 ng/ml 3 months after treatment and to 0.38 ng/ml 12 months after treatment with a median follow-up of 10 months. The mean prostate volume decreased from 32.6 ml to 26 ml after 3 months of treatment and to 18.5 ml after 12 months. Interstitial hyperthermia is a feasible, well-tolerated procedure in prostate cancer therapy. A significant PSA decrease was observed. Longer follow-up is necessary to determine the efficacy.

[Laparoscopic radical prostatectomy. Experiences with 145 interventions]. / Die laparoskopische radikale Prostatektomie. Erfahrungen mit 145 Eingriffen.

Encouraged by the groups in Paris, we performed 145 laparoscopic radical prostatectomies between June 1999 and the end of November 2000. The indication for laparoscopic prostatectomy is the same as for open surgery: an organ-confined cancer. Previous abdominal surgery, transurethral resection, and/or relative adiposity are not considered to be contraindications for this laparoscopic procedure. The mean operating time was 255 min; the last 60 procedures took an average of 200 min. In no case was it necessary to convert to open surgery. Worthy of note was the low blood loss of 185 ml on average so that in 98% of the patients no blood transfusion was required. After completing the learning curve, the average indwelling catheter time was only 5.5 days. The postoperative complication rate was 11.7%, consisting mainly of minor complications. Also with regard to continence and potency, the results were representative. Postoperatively, 75%, 86%, 92%, and 93% of the patients were continent after 3, 6, 9, and 12 months, respectively. In our opinion, laparoscopic radical prostatectomy is an alternative to open prostatectomy, offering a number of advantages for the patient and surgeon as well.

Laparoscopic radical cystectomy with continent urinary diversion (rectal sigmoid pouch) performed completely intracorporeally: the initial 5 cases.

PURPOSE: We present our experience with the first 5 patients who underwent radical cystectomy with bilateral pelvic lymphadenectomy and continent urinary diversion (rectal sigmoid pouch) performed with an intracorporeal laparoscopic technique at our center. MATERIALS AND METHODS: There were 3 males and 2 females 59 to 65 years old with organ confined, muscle invasive transitional cell carcinoma of the bladder who underwent surgery. The procedure included pelvic lymph node dissection, radical cystectomy with prostate or uterus and tubal structures, creation of the rectal sigmoid pouch and bilateral stented antireflux implantation of the ureters into the pouch. Freehand laparoscopic suturing and in situ knot tying techniques were used exclusively. The mobilized specimens were removed in an endoscopy bag via the rectum or vagina. Laparotomy was not required. RESULTS: Operating time was 6.9 to 7.9 hours (median 7.4) and blood loss was 190 to 300 ml. (median 245). None of the 5 patients none needed blood transfusion. Oral intake was started on hospital day 3, ureteral stents were removed on day 8 and the pouch catheter was removed on day 9. The hospital stay was 10 days for all cases. Histopathological examination of the specimens revealed stage pT1 G3 urothelial carcinoma in case 1, pT2b G2 in cases 2 and 3, pT3a G2 in case 4 and pT3aG3 in case 5. The lymph nodes and resection margins were tumor-free. No intraoperative or postoperative complications were observed. CONCLUSIONS: To our knowledge, this is the first series of laparoscopic radical cystectomy with intracorporeal continent urinary diversion (rectal sigmoid pouch), and our results are promising. With more experience and improvement of the surgical technique, laparoscopic radical cystectomy with continent urinary diversion may become an alternative surgical method for treating select patients with localized muscle invasive bladder cancer.