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Biomedical subjects

Michael Schulze

Publications and source records attributed to Michael Schulze.

8 recordsLinked to original sources

Spinocerebellar ataxia type 1, 2, and 3 and restless legs syndrome: striatal dopamine D2 receptor status investigated by [11C]raclopride positron emission tomography.

In spinocerebellar ataxias (SCAs), up to 30% of patients complain of restless legs syndrome (RLS). In primary RLS, a putative role of the dopaminergic system has been postulated. To assess dopaminergic function in SCA1, 2, and 3, dopamine D(2) receptor binding potential (BP) was assessed by [(11)C]raclopride positron emission tomography in 10 SCA patients, 4 of whom suffered from RLS as demonstrated by polysomnography. BP was compared to 9 age-matched control subjects. In 2 SCA patients, striatal BP was clearly reduced (<2 SD below the mean of controls). However, there were no significant group differences between SCA and controls, largely owing to a significantly higher variance of striatal BP in SCA. BP was negatively correlated with disease duration. The fit suggests an increased BP in early stages, followed by a moderate decline in all quantified regions (caudate, dorsal putamen, ventral striatum) presumably reflecting a progressive loss of D(2) receptors. RLS in SCA was not accompanied by a significant reduction of D(2) receptor availability in the striatum. This missing correlation may point to an extrastriatal origin of RLS.

Adult↗

Targeting tomoregulin for radioimmunotherapy of prostate cancer.

Radiotherapy is an effective approach for the treatment of local prostate cancer. However, once prostate cancer metastasizes, radiotherapy cannot be used due to the distribution of multiple metastases to lymph nodes and bones. In contrast, radioimmunotherapy should still be efficacious in metastatic prostate cancer as radioisotopes are brought to tumor cells by targeting antibodies. Here we identify and validate a prostate-expressed molecule, tomoregulin, as a target for radioimmunotherapy of prostate cancer. Tomoregulin is a transmembrane protein selectively expressed in the brain, prostate, and prostate cancer, but not expressed in other normal tissues. Immunohistochemical studies of tomoregulin protein in clinical samples show its location in the luminal epithelium of normal prostate, benign prostatic hyperplasia, and prostatic intraepithelial neoplasia. More importantly, the tomoregulin protein is expressed in primary prostate tumors and in their lymph node and bone metastases. The nature of tomoregulin as a transmembrane protein and its tissue-specific expression make tomoregulin an attractive target for radioimmunotherapy, in which tomoregulin-specific antibodies will deliver a radioisotope to prostate tumor cells and metastases. Indeed, biodistribution studies using a prostate tumor xenograft model showed that the (111)In-labeled anti-tomoregulin antibody 2H8 specifically recognizes tomoregulin protein in vivo, leading to a strong tumor-specific accumulation of the antibody. In efficacy studies, a single i.p. dose of 150 microCi (163 microg) (90)Y-labeled 2H8 substantially inhibits the growth rate of established LNCaP human prostate tumor xenograft in nude mice but produces no overt toxicity despite cross-reactivity of 2H8 with mouse tomoregulin. Our data clearly validate tomoregulin as a target for radioimmunotherapy of prostate cancer.

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Laparoscopic radical prostatectomy with the Heilbronn technique: oncological results in the first 500 patients.

PURPOSE: Laparoscopic radical prostatectomy has become an accepted alternative to open surgery. However, there is still a lack of data concerning the oncological outcome. MATERIALS AND METHODS: From March 1999 to July 2004, 1,078 patients underwent laparoscopic radical prostatectomy at our institution. Oncological results in the first 500 patients with a minimal followup of 23 months were analyzed, focusing on positive margins, prostate specific antigen (PSA) failure, clinical progression and survival. RESULTS: Median followup was 40 months (range 23 to 65). Of the patients 417 underwent pelvic lymph node dissection, which revealed positive nodes in 6 (1.2%). Positive margins were documented in 22 of 296 pT2 tumors (7.4%), 27 of 107 pT3a tumors (25.2%) and 29 of 69 pT3b tumors (42.0%). PSA recurrence was diagnosed in 55 patients (11.0%) at a mean of 20.8 months (range 6 to 36) that is stages pT2a, pT2b, pT3a and pT3b/4 in 3.2%, 6.5%, 15.9% and 23.9%, respectively. PSA progression-free rates were 83.0% at 3 years and 73.1% at 5 years. Two patients died of disease and 6 died of other causes (99.2% overall survival). The clinical progression rate was to 4.1% at 3 years and 9.8% at 5 years. No port site metastasis was observed. CONCLUSIONS: At centers of expertise laparoscopic radical prostatectomy may provide an oncological outcome similar to that of the open procedure. However, it offers the advantages of minimally invasive surgery.

Adult↗

Laparoscopic nephroureterectomy for upper urinary tract transitional cell carcinoma: is it better than open surgery?

OBJECTIVE: In 1991, laparoscopic nephroureterectomy has been introduced as a treatment option for upper tract transitional cell carcinoma. Based on the review of the current literature and personal experience we want to analyze the actual results of this technique in comparison to open surgery. MATERIALS AND METHODS: We performed a MEDLINE/PubMed search and reviewed the literature on laparoscopic and open nephroureterectomy between 1991 and 2004 (n = 1365 patients) including the results of 45 patients who underwent either laparoscopic (n = 23) or open nephroureterectomy (n = 21) during the same period of time at the Klinikum Heilbronn. Demographic, perioperative and follow-up data were compared. RESULTS: The analysis revealed a slightly longer OR-time (276.6 vs. 220.1 min), and significantly lower blood loss (240.9 vs. 462.9 ml) in the laparoscopic series. No differences of minor (12.9 vs. 14.1%) or major complication rate (5.6 vs. 8.3%) were observed. All nine comparative studies revealed a significant dose reduction of the morphine-equivalents after laparoscopy. In all ten comparative series the hospital stay was shorter after laparoscopy, but only in 6 series the difference was statistically significant. The frequency of bladder recurrence (24.0 vs. 24.7%), local recurrence (4.4 vs. 6.3%), and distant metastases (15.5% vs. 15.2) did not differ significantly in both groups. The actual disease-free two-year survival rates (75.2 vs. 76.2%) were similar. The five-year survival rates averaged 81.2% in the three laparoscopic (n = 113 pat.) and 61% in the ten open series (n = 681 pat.) Six port site metastases were reported in 377 (1.6%) analyzed patients occurring 3 to 12 months following laparoscopy. CONCLUSION: Open radical nephroureterectomy still represents the golden standard for the management of upper tract transitional cell carcinoma, however, laparoscopic radical nephroureterectomy offers the advantages of minimally invasive surgery without deteriorating the oncological outcome. In case of advanced tumors (pT3,N+) open surgery is still recommended.

Adult↗

Laparoscopic radical prostatectomy: functional and oncological outcomes.

PURPOSE OF REVIEW: Laparoscopic radical prostatectomy has become an accepted alternative to open surgery, however data on the functional and oncological outcome are still lacking. In this study we present an analysis based on a survey of the current literature and the first 500 patients treated with the Heilbronn technique. Additionally, we compare the results of laparoscopy with those of open radical prostatectomy. RECENT FINDINGS: We conducted an extensive MEDLINE search of laparoscopic and open radical prostatectomy from 1999 through 2003, focusing on the last 3 years. The articles as well as our own results were analyzed with respect to continence, potency, positive margins, prostatic specific antigen failure, and clinical progression. No significant differences were found between the laparoscopic and open approach with respect to overall continence at 12 months (60-94% versus 61-98%) or at 3 months (51-63% versus 62-69%), varying from 4.1% at pT2, 12% at pT3 to 19% at pT4 stages. We found no significant differences between the two techniques in the recovery of potency (34-67% versus 31-79%), if one excludes the selected series of Walsh with a mean age of 57 years. Furthermore, we did not detect any significant differences in positive margins and short-term prostatic specific antigen recurrence (3 years). SUMMARY: At centers of expertise, laparoscopic radical prostatectomy is able to provide similar functional and oncological results as its open counterpart, however with the advantages of minimally invasive surgery.

Follow-Up Studies↗

Technical evolution of laparoscopic radical prostatectomy after 450 cases.

BACKGROUND AND PURPOSE: In 1998, laparoscopic radical prostatectomy with primary access to the seminal vesicles was introduced. In 1999, we developed a laparoscopic technique similar to the classic retropubic radical prostatectomy. We focus here on the continuous technical evolution of our technique. PATIENTS AND METHODS: From March 1999 to May 2002, we performed 450 laparoscopic radical prostatectomies. All important data of the patients; data concerning the performance of the procedure, including technical modifications, conversion, reintervention, and complication rate; as well as follow-up information were documented contemporaneously. The patients were divided into three groups of 150 individuals each in order to analyze the influence of the technical evolution of the procedure. Additionally, we studied the transferability of our technique, comparing the learning curves of the three surgeons involved in the program. RESULTS: The technical modifications included the routine use of a voice-controlled robot (AESOP) for the camera, exposure of the apex with 120 degrees retracting forceps, a free-hand suturing technique instead of the Endostitch device for the dorsal vein complex, 5-mm clipping instead of bipolar coagulation for the nerve-sparing technique, initial 6 o'clock suturing of the urethra before complete division, control of the prostatic pedicles by use of 12-mm Hemo-lok clips instead of the Ultracision or Endo-GIA, the bladder neck-sparing technique in cases of T(1c) and T(2a) tumors, and interrupted instead of continuous sutures for the vesicourethral anastomosis. All these modifications resulted in a significant decrease in operating time and the rates of transfusion, open conversion, and reintervention. The introduction of the nerve-sparing technique increased the number of tumor-positive margins. The mean operating time of the third surgeon was significantly less than that of the first surgeon, but the transfusion, conversion, and reintervention rates did not differ significantly among the surgeons. CONCLUSIONS: Laparoscopic radical prostatectomy has undergone continuous technical evolution resulting in a significant improvement of the operative results. Although we were able to demonstrate the transferability of this difficult procedure, we feel that it should be performed only at centers of expertise.

Adult↗

Laparoscopic versus open radical prostatectomy: a comparative study at a single institution.

PURPOSE: There is an ongoing debate about the benefits of laparoscopic radical prostatectomy compared to the open retropubic approach. We compared the last 219 patients treated with open retropubic prostatectomy with 438 patients treated with laparoscopic radical prostatectomy at our institution, focusing on operative data, complications and mid-term outcome. MATERIALS AND METHODS: From December 1994 to November 1999 a total of 219 patients were treated with open prostatectomy and pelvic lymph node dissection (group 1). From March 1999 to September 2002, 219 patients underwent early (group 2) and 219 underwent late (group 3) laparoscopic radical prostatectomy and pelvic lymph node dissection. The same surgeons performed both operations. All 3 groups were similar with respect to mean patient age, mean prostate specific antigen value, median Gleason score, previous transurethral resection of the prostate and neoadjuvant treatment, although there was a slight stage shift in favor of the 2 laparoscopic groups. RESULTS: Mean operating time was significantly shorter after open surgery (196 minutes) compared to the early laparoscopic group (288) but it did not differ significantly from the late laparoscopic group (218). Mean blood loss (1,550 versus 1,100 versus 800 cc) and transfusion rates (55.7% versus 30.1% versus 9.6%) in groups 1 to 3 favored the laparoscopic groups. The complication rate in groups 1 to 3 was lower for laparoscopy (19.2% versus 13.7% versus 6.4%), but the spectrum differed. The early laparoscopic group had a higher incidence of rectal injuries (1.8% versus 3.2% versus 1.4% in groups 1 to 3, respectively) and urinary leakage (0.5% versus 2.3% versus 0.9%), whereas more lymphoceles (6.9% versus 0% versus 0%), wound infection (2.3% versus 0.5% versus 0%), embolism/pneumonia (2.3% versus 0.5% versus 0.5%) and anastomotic strictures (15.9% versus 6.4% versus 4.1%) occurred after open surgery. The amount of postoperative analgesia was significantly greater after open surgery (50.8 versus 33.8 versus 30.1 mg. in groups 1 to 3, respectively). Median catheter time was longer after open retropubic prostatectomy (12 versus 7 versus 7 days in groups 1 to 3, respectively) but the continence rates were similar in all 3 groups at 12 months (89.9% versus 90.3% versus 91.7%). The rate of positive margins did not differ significantly in groups 1 to 3 (28.2% versus 21.0% versus 23.2%), prostate specific antigen recurrence was equivalent related to the different observation periods. CONCLUSIONS: Laparoscopic radical prostatectomy is technically demanding, with an initially longer operative time, higher incidence of rectal injuries and urinary leakage. The overall outcome after 219 cases favors the laparoscopic approach. Consequently, at our institution laparoscopic radical prostatectomy has become the method of choice.

Adult↗

Laparoscopic radical nephroureterectomy: results of an international multicenter study.

OBJECTIVE: To report a multicenter analysis after laparoscopic radical nephroureterectomy for pathologically confirmed upper tract transitional cell carcinoma. MATERIALS AND METHODS: A total of 116 patients (72 males; mean age 68 years) underwent laparoscopic radical nephroureterectomy at five international institutions: 51 transperitoneally, 65 retroperitoneally. Location of the primary tumor was pelvicalyceal in 70 patients (60%), ureteral in 27 (23%), and multifocal in 19 (17%). In 18 patients (15%), transurethral resection was performed for concomitant bladder tumor. The median follow-up time was 25 months (range 3-93). A minimum follow-up of 1 and 2 years was available in 77 and 41 patients, respectively. RESULTS: Five patients (4%) were converted to open surgery. The specimen was extracted intact in all 116 patients: using an Endocatch bag in 78 patients, a Lapsac in 5, and manually in 33. Pathologic staging was pTis in 5 (4%), pTa in 41 patients (35%), pT1 in 31 (26%), pT2 in 18 (15%), pT3 in 16 (13%), and pT4 in 5 (4%). Pathological grade was grade I in 26 patients (23%), grade II in 41 (35%), grade III in 34 (29%) and grade IV in 15 (12%). Histopathology revealed a positive surgical margin in five patients (4.5%): renal hilum (one), periureteral soft tissue (two), distal edge of the ureter/ bladder cuff (two). Local recurrence was noted in two patients (1.7%). Bladder recurrence was noted in 28 patients (24%) with a mean time to recurrence of 13.9+/-11.5 months. Distant metastases occurred in 11 patients (9%): lung (5), liver (3), bones (2), adrenal (1); mean time to metastasis was 13 months. Overall, 23 patients (20%) died. One-year and 2-year cancer-specific survival was 92% and 87%, respectively. Two-year cancer-specific survival according to pathologic stage was 89% for patients with pT1 disease, 86% for pT2, 77% for pT3, and 0% for pT4 (p=0.0001). Two-year survival according to pathologic grade was 88% for grade I, 90% for grade II, 80% for grade III, and 90% for grade IV (p>0.05). CONCLUSION: Laparoscopic radical nephroureterectomy appears to be an effective minimally invasive treatment for select patients with upper tract transitional cell carcinoma. Although the 2-year survival data reported herein are encouraging, longer follow-up is needed before laparoscopy can be considered as a standard treatment.

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