Retroperitoneal lymph node dissection (RPLND) and adjuvant chemotherapy are two adjuvant treatment options for patients with clinical stage I nonseminomatous germ cell tumors of the testis (NSGCT). ...Aim of this trial was to prove the advantage of one cycle of bleomycin, etoposide, and cisplatin (BEP) chemotherapy compared with RPLND in terms of recurrence.
Between 1996 and 2005, 382 patients were randomly assigned to receive either RPLND (n = 191) or one course of BEP (n = 191) after orchidectomy. The primary study end point was the rate of recurrence. The trial was powered to detect a 7% reduction (from 10% to 3%) of recurrence with chemotherapy compared with surgery.
After a median follow-up of 4.7 years, two and 15 recurrences were observed in the intention-to-treat population with chemotherapy and surgery, respectively (P = .0011). The difference in the 2-year recurrence-free survival rate between chemotherapy (99.46%; 95% CI, 96.20% to 99.92%) and surgery (91.87%; 95% CI, 86.87% to 95.02%) was 7.59% (95% CI, 3.13% to 12.05%). The hazard ratio to experience a tumor recurrence with surgery as opposed to chemotherapy was 7.937 (95% CI, 1.808 to 34.48).
To our knowledge, this is the largest randomized trial investigating adjuvant treatment strategies in clinical stage I NSGCT, which showed the superiority of one course BEP over RPLND performed according to community standards to prevent recurrence. Although not standard treatment, one course of BEP is active in an unselected group of patients with clinical stage I disease and merits further investigation.
Abstract Context The introduction of new lithotripters has increased problems associated with shock wave application. Recent studies concerning mechanisms of stone disintegration, shock wave ...focusing, coupling, and application have appeared that may address some of these problems. Objective To present a consensus with respect to the physics and techniques used by urologists, physicists, and representatives of European lithotripter companies. Evidence acquisition We reviewed recent literature (PubMed, Embase, Medline) that focused on the physics of shock waves, theories of stone disintegration, and studies on optimising shock wave application. In addition, we used relevant information from a consensus meeting of the German Society of Shock Wave Lithotripsy. Evidence synthesis Besides established mechanisms describing initial fragmentation (tear and shear forces, spallation, cavitation, quasi-static squeezing), the model of dynamic squeezing offers new insight in stone comminution. Manufacturers have modified sources to either enlarge the focal zone or offer different focal sizes. The efficacy of extracorporeal shock wave lithotripsy (ESWL) can be increased by lowering the pulse rate to 60–80 shock waves/min and by ramping the shock wave energy. With the water cushion, the quality of coupling has become a critical factor that depends on the amount, viscosity, and temperature of the gel. Fluoroscopy time can be reduced by automated localisation or the use of optical and acoustic tracking systems. There is a trend towards larger focal zones and lower shock wave pressures. Conclusions New theories for stone disintegration favour the use of shock wave sources with larger focal zones. Use of slower pulse rates, ramping strategies, and adequate coupling of the shock wave head can significantly increase the efficacy and safety of ESWL.
One cycle of adjuvant chemotherapy with bleomycin, etoposide and cisplatin (BEP) has shown superiority in recurrence-free survival over retroperitoneal lymph node dissection (RPLND) in patients with ...clinical stage (CS) I non-seminomatous germ cell tumours (NSGCTs) of the testis in the setting of a phase III trial. We report the recurrences and late toxicities of this study after 13 years of follow-up.
Questionnaires from 382 patients with CS I NSGCT treated with 1 cycle of adjuvant BEP (arm A) or RPLND + two cycles of adjuvant BEP in cases of pathological stage II disease (arm B) were evaluated regarding recurrences and late toxicity. Overall, information on recurrence status was available in 337 patients, and 170 questionnaires were evaluable for toxicity (arm A: 95; arm B: 75).
With a median follow-up of 13.8 years (0–22), 3 patients (1.6%) in arm A and 16 patients (8.4%) in arm B experienced recurrence. The 15-year PFS in arm A/B was 99% (CI 96–100%)/92% (CI 89–99%) (p = 0.0049). The 15-year OS in arm A/B was 93% (CI 87–97%)/93% (CI 86–97%) (p = 0.83). Eight patients (4.2%) in arm A and four patients (2.1%) in arm B showed metachronous secondary testicular cancer (p = 0.26). Five patients (2.6%) in arm A and four patients (2.1%) in arm B developed other malignancies. Toxicities were not significantly different apart from retrograde ejaculation, which occurred more frequently after RPLND (10% versus 24%, p = 0.01).
With long-term observation, one cycle of BEP remains superior to RPLND in preventing recurrence and was tolerated without any clinically relevant long-term toxicities.
•>13-year follow-up recurrences in CS I NSGCT more frequent with RPLND than after BEP x1.•No excess mortality due to secondary malignancies could be detected.•Late toxicities do not differ between 1 x BEP and RPLND.
Nerve sparing retroperitoneal lymph node dissection has been the standard diagnostic and therapeutic approach to clinical stage I nonseminoma. However, the application of prognostic risk factors and ...introduction of laparoscopy have recently called into question the clinical usefulness of nerve sparing retroperitoneal lymph node dissection. We assessed the therapeutic efficacy and associated complications of this procedure in patients with clinical stage I nonseminomatous germ cell tumor treated at 7 tertiary referral centers to evaluate its role in the modern management of low stage testis cancer.
Between January 1995 and September 2000, 239 patients with clinical stage I nonseminomatous germ cell tumor underwent nerve sparing retroperitoneal lymph node dissection in standardized fields of dissection. For retrospective analysis patient charts were reviewed. A minor complication did not prolong hospital stay and a major complication prolonged hospitalization for at least 2 days. Early complications developed within the first 30 days after retroperitoneal lymph node dissection and late complications occurred from postoperative day 31 and thereafter.
Nerve sparing retroperitoneal lymph node dissection was performed unilaterally in 209 patients (88.2%) and bilaterally in 30 (11.8%). Median operative time was 214 minutes (range 90 to 395), mean hospital stay was 8 days (range 4 to 39) and mean blood loss was less than 150 ml. A mean of 18.5 lymph nodes (range 9 to 57) were dissected with metastases detected in 67 patients (28%). An average of 2.9 lymph nodes (range 1 to 14) with a mean diameter of 2.6 cm. (range 0.3 to 6.0) showed metastasis. Disease was pathological stage I in 172 patients (71.7%), 52 (17.6%) had 3 or fewer metastatic lymph nodes, and 15 (6.3%) had 4 to 5 and 10 (4.2%) had greater than 5 positive lymph nodes. Minor complications occurred in 14.2% of the cases and major complications were observed in 5.4%. Antegrade ejaculation was preserved in 93.3% of the patients, recurrence developed in 14 (5.8%) and retroperitoneal recurrence was observed in 3 (1.2%), including 1 in field and 2 out field.
Primary diagnostic and therapeutic nerve sparing retroperitoneal lymph node dissection still has a role in the primary management of clinical stage I nonseminomatous germ cell tumor. Surgery is associated with low morbidity and patient followup is easy and cost-effective due to the concentration on extraretroperitoneal locations. Primary nerve sparing retroperitoneal lymph node dissection is curative in about 70% of clinical stage I nonseminoma cases with a maximum of 3 positive lymph nodes.
Kooperationsmodelle Köhrmann, Kai Uwe; Schneider, Andreas W
Urologe. Ausgabe A,
09/2023, Letnik:
62, Številka:
9
Journal Article
Recenzirano
Eine bedarfsgerechte Gesundheitsversorgung soll zukünftig insbesondere durch Kooperationen der Leistungserbringer sichergestellt werden. Um dies zu fördern, werden gegenwärtig die gesetzlichen ...Rahmenbedingungen abgestimmt durch Einführung der „Tagesbehandlung am Krankenhaus“, Verteilung von „Leistungsgruppen“ auf die einzelnen Kliniken und die Einführung integrierter Leitstellen und Notfallzentren. Die Leistungserbringer sollen durch finanzielle Unterstützung aber zusätzlich durch die Nutzung von Synergieeffekten sowie zur Ausbildung des Nachwuchses zur Zusammenarbeit motiviert werden. Begrenzt wird das Streben nach Zusammenarbeit durch die Pflichten bei der vertragsärztlichen Tätigkeit, Regelungen der Antikorruption und dem Interesse der Patienten nach Wahlfreiheit bis hin zu Wettbewerbs- und Kartellrecht. Die Kooperationen von Krankenhäusern mit Vertragsärzten/Praxen basieren auf den Vorgaben des Krankenhausentgeltgesetzes (Kooperation auf Honorarbasis bzw. im Angestelltenverhältnis) und des Sozialgesetzbuches (vertragsärztliche Kooperationsformen über Notfalldienst, Medizinische Versorgungszentren, vor-/nachstationäre Behandlung, ambulantes Operieren, ambulante spezialfachärztliche Versorgung, belegärztliche Kooperation und besondere Versorgungen) sowie der Niederlassung am Krankenhaus. Krankenhäuser werden aufgrund ihrer ruinösen Situation immer häufiger untereinander kooperieren in Form von strategischen Allianzen bis hin zu Fusionen. Um diese zum Erfolg zu führen, sind einige Grundsätze zu beachten. Diese Konzepte bergen Risiken und benötigen Vertrauen und ein gut austariertes Verhältnis von Kosten und Nutzen für alle Partner. Der mutige Weg von fairen Kooperationen mit dem Fokus auf hochwertige und effiziente Patientenversorgung kann die disruptive Innovation zur Bewältigung unserer Herausforderungen in der Urologie und im Gesundheitswesen allgemein darstellen.
Apoptosis plays a crucial role in the regulation of spermatogenesis in male germ cells and is, at least in part, modulated by Bcl‐2, Bax, and the Fas pathway. Seminomas have a favourable outcome and ...respond to radio‐/chemotherapy with an increased rate of apoptosis. The expression of Bax, Bcl‐2, Fas and Fas‐ligand (Fas‐L) in human seminoma was evaluated and correlated with the apoptotic index.
Twenty‐nine classical seminomas were examined by immunohistochemistry and Western blotting using antibodies against Bax, Bcl‐2, Fas and Fas‐L. Apoptosis was detected by in‐situ end‐labeling of fragmented DNA and the apoptotic index (AI) was determined.
Expression of Fas was found in 26 (89.7%) of Fas‐L in 24 seminomas (82.2%); none of the tumours expressed Bcl‐2. No correlation between the AI and Fas, Fas‐L or Bcl‐2 expression was found. Bax was demonstrated in 20/29 tumours (69%). Bax‐positive tumours showed an increased AI of 4.75±2.38% in contrast to 2.60±1.23% of the Bax‐negative tumours (P=0.002). The number of Bax‐positive tumour cells and apoptotic cells revealed a significant correlation using χ2‐test (P=0.04) and linear regression (r=0.54, P=0.001).
Therefore, Bax seems to play a determinant role in the modulation of apoptosis in human seminoma that may be linked to a favourable outcome.
Urinary diversion with percutaneous nephrostomy or ureteral stent is indicated by symptoms, such as persistent colic, high temperature and uremia, of hydronephrosis caused by stones. We evaluate ...which of these 2 methods is superior concerning the course of procedure, relief of accompanying symptoms and quality of life in regard to patient age and sex.
A total of 40 patients with stone induced hydronephrosis were randomized into either percutaneous nephrostomy or stent insertion groups. These patients were then evaluated by procedure (use of analgesics, x-ray exposure, success of insertion), relief of accompanying symptoms (duration of diversion, intravenous administration of antibiotics for high temperature) and quality of life (questionnaire immediately and 2 to 4 weeks postoperatively).
Two comparable groups of patients were formed, with an average age of 55 versus 49 years and a male-to-female ratio of 12:8 versus 9:11 for those who underwent percutaneous nephrostomy versus those who received a stent, respectively. Percutaneous nephrostomy was successfully completed in 100% of patients and stents were successful in 80%, with a 20% conversion to percutaneous nephrostomy. The x-ray exposure was shorter in the percutaneous nephrostomy group (p = 0.052). Administration of analgesics was more frequent in the stent group (p = 0.061). Percutaneous nephrostomy indwelling time was shorter (50% less than 2 weeks) than that of stents (25% less than 2 weeks, p = 0.043). Antibiotics were administered for greater than 5 days in 0% of patients who underwent percutaneous nephrostomy versus 64% in those with stents (p = 0.174). Reduction in quality of life was moderate but more pronounced in patients with stents compared to those who underwent percutaneous nephrostomy, and was more distinct in males and younger patients. The quality of life progressively improved in the course of diversion with percutaneous nephrostomy but deteriorated with stents.
Our results demonstrated that percutaneous nephrostomy is superior to ureteral stents for diversion of hydronephrosis caused by stones, especially in patients with a high temperature, as well as in males and juveniles.
Noninvasive tumor ablation can be achieved by extracorporeally induced high intensity focused ultrasound. Clinical high intensity focused ultrasound performed to date for renal tumors have only been ...experimental in nature. We present specific details on a patient with renal cell carcinoma who underwent high intensity focused ultrasound with curative intent and long-term followup examinations.
Ultrasound waves were generated by a cylindrical piezoelectric element focused by a paraboloid reflector. High intensity focused ultrasound was applied to 3 tumors in 3 sessions with the patient under general anesthesia or sedation analgesia, followed by magnetic resonance imaging for 6 months.
After treatment magnetic resonance imaging showed necrosis in the 2 tumors in the lower kidney pole within 17 and 48 days, respectively. The necrotic tumor area shrank thereafter within 6 months. The tumor in the upper pole was not affected by treatment due to absorption of the ultrasound energy by the interposed ribs. General anesthesia was required to apply high energy levels of focused ultrasound. Absorption of high intensity focused ultrasound in the tissue induced sharply demarcated thermonecrosis. For 50 years patients have been treated with high intensity focused ultrasound for different indications, focusing on the brain, eyes, prostate, liver and bladder. For the kidney experimental but only few clinical studies indicate sufficient tissue ablation.
In our case contactless noninvasive application of high intensity focused ultrasound to 2 renal carcinomas achieved thermal ablation. When high intensity focused ultrasound energy was coupled correctly, no lesions occurred outside of the target area. Successful high intensity focused ultrasound application depended on optimum energy coupling, a sufficiently high ultrasound energy level and general anesthesia.
Endoscopic examinations of stone-forming kidneys show a coincidence of plaques and microliths on the surface of and within papillary epithelial tissue. These calcifications are thought to be ...precursors of calcium oxalate urolithiasis. We hypothesized that minimally invasive endoscopic laser ablation of microliths and necrotic cell layers enables epithelial regeneration and prevents recurrent urolithiasis. The aim of this study was to determine the most suitable laser type and dose intensity for selective superficial cell ablation.
Conventional Nd:YAG (1-40 W) or Ho:YAG (0.5-3 J/single impulse) lasers were used endoscopically on an ex vivo blood-perfused porcine kidney model. Defined doses were applied to the papillary surface in the contact and noncontact modes for 10 to 30 seconds. Papillae were excised after treatment and histopathologically analyzed in continuous sections. Lesions were microscopically assessed with the aid of a Leica Quantimed computer program.
Depending on the time and dose, vaporization by the Nd:YAG laser caused large tissue defects and coagulation necrosis at energy levels over 5 W (contact and noncontact mode). Lower energy levels with tissue contact produced only superficial cell defects (<20 cell layers) but more extensive coagulation necrosis, whereas no histologic effects were observed at the same energy level without contact. In contrast, independent of delivered energy but dependent on time, Ho:YAG laser application caused pure tissue loss without relevant coagulation necrosis. The generation of small lesions (6-10 cell layers) without tissue contact was possible at energy levels under 2 J.
Selective superficial papillary cell ablation is possible. Low-energy Nd:YAG treatment in the contact mode and Ho:YAG treatment in the noncontact mode led to superficial vaporization with no (Ho:YAG) or minimum (Nd:YAG) coagulation defects.
Cisplatin is one of the most potent cytotoxic drugs and in chemotherapy has ameliorated numerous tumors. Nevertheless, resistance to cisplatin is a problem that is encountered in the chemotherapy of ...urologic tumors, especially transitional cell carcinomas. In order to improve definition of the mechanisms of cisplatin-resistance we established a series of cisplatin-resistant sublines from the cell line RT 112 in increasing concentrations of cisplatin. The most resistant subline CP3 is approximately 10 times more resistant than the parental line and shows a 10-fold cross-resistance against methotrexate, whereas vinblastine and doxorubicin are equally effective in the parental and sublines. Combined treatment of CP3 cells with cisplatin and buthionine sulfoximine (BSO) does not result in enhanced cell kill, thereby ruling out glutathione as a resistance mechanism. However, in comparison with parental cells, CP3 cells are about 1.5 times more resistant against cadmium. On the protein level, the cisplatin-resistant cells reveal an enhanced expression of metallothionein II (MTII), but not MTI, suggesting that the cisplatin resistance we observed in these sublines is at least partly mediated by MTII. These sublines will in the future serve as valuable tools for the analysis of cisplatin resistance, especially in view of metallothionein-mediated resistance mechanisms.
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