Regional immunotherapy of metastatic renal cell carcinoma

We summarized the current literature concerning regional immunotherapy of pulmonary metastases in metastatic renal cell carcinoma and other malignancies using inhaled interleukin-2 (IL-2). Inhaled IL-2 therapy is associated with minimal toxicity and is effective in preventing progression in metastatic renal cell carcinoma, melanoma, and possibly other diseases such as breast cancer. Local (physiologic) use and systemic (pharmacologic) use of IL-2 are not mutually exclusive; a combination may be very appropriate in metastatic cancer. Local physiologic therapy intensifies treatment without intensifying toxicity.     

Systemic immunotherapy of metastatic renal cell carcinoma and long-term outcome

Within the last 10 years, immunotherapy has progressively become an established treatment for patients with metastatic renal cell carcinoma. The cytokines interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) are the substances that have shown the greatest effects. Both have been approved for the treatment of patients with metastatic renal cell carcinoma in Germany. Subcutaneous application of these frequently combined cytokines is the schedule of immunotherapy used most often in Germany. Combined cytokine therapy (IL-2 and IFN-alpha) achieves response rates comparable to more aggressive immunotherapies. The retrospective analysis of treatment results from 66 patients with a follow-up of at least 5 years after the start of combined s.c. IL-2 and s.c. IFN-alpha +/- 5-fluorouracil (response classification: CR: 7, PR: 11, SD: 20, PD: 28) shows that the classification of the treatment results according to WHO criteria is the strongest predictor for survival compared with basic factors such as TNM status, grading, or number of metastatic sites. The combination of cytokine treatment with other treatment modalities (for example, surgical intervention) leads to a differentiated treatment according to the tumor status of the patient with metastatic renal cell carcinoma. Specific immunotherapies are still experimental. No approval has been granted for any of these treatments. Only standardization of these protocols can lead to a supplemental form of immunotherapy. Although several aspects of cytokine-based immunotherapy need further scientific evaluation, it is the treatment of choice for patients with metastatic renal cell carcinoma. However, for further progress in this field, prospective evaluation of immunotherapy for metastatic renal cell carcinoma is still needed. The German society for immunotherapy serves as a platform for this research.     

Ambulatory radiosurgery in cerebral metastatic renal cell carcinoma. 5-year outcome in 58 patients

Brain metastases (BM) indicate an advanced stage of renal cell cancer (RCC). They pose an increasing challenge to urologists as a result of improved survival due to modern therapy. Median survival of untreated patients with BM who often suffer from neurological deficits is 3 months. Radiosurgery with the Gamma Knife (GK) has increased in use as an alternative to whole brain radiation therapy (WBRT) and/or surgery. This study reports the results of a consecutive series of RCC patients treated for BM by GK radiosurgery during a 5-year period. Between 1994 and 1999, 58 patients with a total of 277 BM and 3.0 (1-19) BM/patient were treated. Because of recurrent BM, 23 (40%) patients received repeated (multiple) GK sessions. The median tumor volume was 3.4 cm3 (0.1-19.1). The median interval between diagnosis of RCC and GK treatment was 2.2 years (0.1-17.2). Symptomatic side effects were detected in 9 (16%) of 58 patients. The median actuarial survival time was 9.9 months. Local tumor control could be achieved in 95% of patients. The GK therapy induced a significant tumor remission accompanied by rapid neurological improvement in 70% of patients. Compared to standard radiotherapy, GK radiosurgery is more effective, less time consuming, and can be repeated. Compared to surgery, radiosurgery is less invasive and better suited to treat multiple metastases in one single session. Surgery and radiosurgery, however, are supplementary methods that are highly effective to control intracerebral metastasizing RCC.     

Leiomyoma of the kidney. Differential diagnostic aspects of renal cell carcinoma with increasing clinical relevance

Renal leiomyoma is a rare benign tumor which has its origin in smooth muscle cells of different structures of the kidney. The clinical incidence of renal leiomyoma is much lower than the frequency described in large autopsy studies. Renal leiomyomas are mainly located in the renal capsula and pelvis or next to those structures. Clinical symptoms are nonspecific (e.g., flank pain or flank tumor) or completely absent, making most of the leiomyomas an incidental finding during routine diagnostics. A differential diagnosis between renal leiomyoma and renal cell carcinoma on the basis of medical imaging is extremely difficult. Therefore, laparotomy and nephrectomy are performed in most cases of suspected renal cell carcinoma. The definitive diagnosis of a leiomyoma is only possible after histological examination of the tumor. Due to the rising number of diagnoses resulting from improved medical imaging, renal leiomyomas are gaining more importance in the differential diagnosis of renal cell carcinoma, especially with respect to kidney-sparing surgery.     

Rationelle Diagnostik und operative Therapie des Nierenzellkarzinoms mit Tumorthrombus in der V. cava

Zusammenfassung Ein Tumorthrombus in der V. cava beim Nierenzellkarzinom als Ausdruck einer fortgeschrittenen Tumorerkrankung ist nicht mit einer schlechten Prognose gleichbedeutend. Fortschritte auf dem Gebiet der operativen Medizin erm?glichen es heute, entsprechende Tumorstadien kurativ operieren zu k?nnen, sofern keine Metastasen nachgewiesen sind. Das operative Vorgehen wird durch die kraniale Ausdehnung des Tumorthrombus determiniert. Eine rationelle, an den therapeutischen M?glichkeiten und der Prognose orientierte Diagnostik sollte vorrangig dem Metastasenausschlu? sowie der Evaluation der Ausdehnung des Tumorthrombus dienen. Bildgebende Untersuchungen müssen nicht nur eine Selektion derjenigen Patienten erm?glichen, die von einer Operation profitieren k?nnen, sondern auch die für die Operationsplanung relevanten Informationen liefern. Moderne sonographische und CT-Untersuchungsverfahren oder die MRT erlauben sowohl eine zuverl?ssige Beurteilung des Lokalbefunds, der region?ren Lymphknoten und Pr?dilektionsstellen einer m?glichen Fernmetastasierung als auch die exakte Bestimmung der Ausdehnung des Tumorthrombus. Beim Nierenzellkarzinom mit Beteiligung der V. cava kann daher heute auf invasive angiographische Untersuchungen weitestgehend verzichtet werden.      

Ösophagusperforation Entstehung,Diagnostik, Therapie

Method. Between 10/1997 and 2/2000 we treated eight patients (～66,5 y, 31–92 y, 5 male, 3 female). These cases were analyzed retrospectively. Results. In one case the the perforation was located in the cervical part, in three cases in the intermediate part, and in four cases in the distal part ofesophagus. In seven cases the perforation was caused by endoscopic and one acid burn in suicidal intention. Surgical treatment was performed in seven cases (87,5%), five of them with primary suture, two with primary esophageal resection. The mortality rate was 50%. There was no insufficieny of the suture, but two patients died because of pulmonal complications, one patient with known hepatic cirrhosis (Child C) because of an uncontrollable bleeding of his fundus and esophageal complications 5 days after successful surgical treatment, and one patient because of fulminant sepsis after dislocation of an enteral catheter. Three of the patients were operated within 12 hours after perforation, seven of them were operated within less than 24 hours. Conclusions. Surgical treatment of esophageal perforation within 24 hours after perforation shows good results. The outcome of the treatment depends on whether there are postoperativ pulmonal complications and concomitant diseases. Enteral nutrition should be avoided in cases of primary esophageal resection to facilitate the surgical reconstruction at the second operation.     

Thymoma with primary osseous and pulmonary metastases. Case report and review of the literature

Bone metastases can be the first symptom of a tumor. The case of a 65-year-old patient with a thymoma exhibiting primary metastases in the lung and bone is presented. Initially, a tumor was suspected because of an osteolytic destruction of the right proximal femur posing a high risk of fracture. Further diagnostic procedures detected a partially sclerosing mediastinal bulk and bilateral lung metastases. The histological investigation of the resected proximal femur and needle biopsy of the mediastinal bulk showed an extrathoracically metastasized polygonal cell thymoma. This metastasizing pattern is common in thymic carcinoma but very rare in thymoma. In addition to the case presentation, a review of the current literature on histological classification, therapy, and prognosis is given.     

Die Therapie des Harnleitertumors

Nephroureterectomy is the standard treatment of tumors in the upper and middle third of the ureter. Whereas, resection of the distal ureter and uretercystoneostomy is the treatment of choice of tumors in the lower third, as long as there is enough renal function which is worthwhile to be preserved. Lymphadenectomy should be performed in all patients suspicious for invasion of the ureteral wall since already 10% of patients with pT1 and pT2 tumors will present with metastases to the lymphnodes. In case of functional or anatomic single kidney therapy has to be adapted to the patient and tumor appropriately. Endoscopic resection, partial or complete resection of the ureter with substitution by ileum or autotransplantation with pyelovesicostomy are the operative options. Elective endoscopic treatment of ureteral tumors should be done in patients with G1 tumors only. However, the recurrence rate is as high as 30 to 60% and the mean interval to recurrence is about 9 months. Regular followup by means of cytology and endoscopy is mandatory. Laparoscopic nephroureterectomy is still a experimental treatment at present time and should be not considered in the treatment of ureteral tumors because of the complexity of the procedure and the risk of tumor spillage.     

Stellenwert der Metastasenchirurgie beim metastasierten Nierenzellkarzinom

Metastasectomy in patients with renal cell carcinoma has to be considered as a palliative approach for symptomatic metastases (e.g., pathologic fracture) or as a curative approach in patients with the option for radical resection of all metastases. By modern perioperative management, even extended resections can be performed with limited morbidity and mortality. The survival rate is significantly higher after resection of pulmonary metastases than after resection of extrapulmonary metastases. Solitary metastases show a better prognosis than multiple metastases. Metachronous metastases that develop after a tumor-free interval of at least 12 months after tumor nephrectomy have a better prognosis than earlier metastases. For metastases that are resected with a curative intent, the best long-term results can be achieved after complete or radical resection.     

Immunchemotherapie des metastasierten Nierenzell- karzinoms mit Interleukin-2, Interferon-α und 5-Fluorouracil

Zusammenfassung Ziel dieser Untersuchung war es, die Effektivit?t und Toxizit?t einer Immunchemotherapie beim metastasierten Nierenzellkarzinom zu überprüfen. Die Zytokine Interleukin-2 (IL-2) und Interferon-α (IFN-α) – jeweils subkutan (sc) injiziert – wurden mit i. v.-appliziertem 5-Fluorouracil (5-FU) kombiniert. Das Therapieschema bestand aus einem 8 w?chigen Behandlungszyklus. Dabei wurde IFN-α in jeder dieser 8 Wochen mit unterschiedlicher Dosierung (6-9 Mio. U/m² K?rperoberfl?che (KO) 1- bis 3 mal pro Woche) appliziert. Zus?tzlich erfolgte nacheinander jeweils für 4 Wochen die Gabe von IL-2 (5–20 Mio. IU/m² KO 3 mal pro Woche) bzw. 5-FU (750 mg/m² KO einmal w?chentlich). Bei Ansprechen der Therapie wurde dieser Zyklus ggf. 1- bis 2 mal wiederholt. 30 Patienten wurden nach diesem Schema behandelt. Die Nachbeobachtungszeit betrug durchschnittlich 11 (3–18) Monate. In 2 F?llen war eine komplette (CR: Dauer 3 und 9 Monate) und in 9 F?llen eine partielle Remission (PR: 3–14 Monate) überwiegend bei Lungen- und Skelettmetastasen nachzuweisen. Dies entspricht einer objektiven Ansprechrate (CR + PR) von 37 %. Bei 10 Patienten war für die Dauer von 3–18 Monaten ein stabiler Krankheitszustand zu beobachten. Die Nebenwirkungen waren gering und entsprachen einer Toxizit?t Grad I (n = 2), Grad II (n = 22) und Grad III (n = 6) nach der WHO-Klassifikation; 7 Patienten sind zwischenzeitlich an einer Progredienz der Erkrankung nach durchschnittlich 12 (4–18) Monaten verstorben. Zusammenfassend ist festzustellen, da? diese Immunchemotherapie eine ebenso hohe klinische Effektivit?t aufweist wie wesentlich aggressivere Therapieschemata mit i. v.-appliziertem IL-2, jedoch ohne deren ausgepr?gte Toxizit?t.      

Die Umwandlung eines ileozökalen (von Flüe) in einen koloanalen Pouch

In order to reduce the high frequency of bowel movement after resection of the rectum in cases of rectal cancer, the creation of a colonic J-pouch was developed. Meanwhile this operation is well established. As a variation to the standard technique, von Flüe introduced in 1994 the interposition of an ileocecal segment, intended to improve the reservoir function via its own distensibility. Despite the conserved neural and vascular integrity of the ileocecal segment, major complications arise such as pouchitis with necrosis. In these cases, resection of the pouch and permanent discontinuity of stool passage is routine therapy. Patients with permanent stoma face many difficulties both physical and psychological, and often the quality of life diminishes. In the literature there is no detailed case of colonic J-pouch reconstruction following resection of an insufficient ileocecal pouch. This operation is technically highly demanding but feasible.     

Adenome der Ampulla Vateri und des Duodenums Darstellung von Diagnostik und Therapie durch endoskopisch interventionelle und chirurgische Methoden

Background. Adenoma of the ampulla of Vater and the duodenum are rare tumors. The leading symptoms are unspecific; sometimes they are due to the disturbances of the passage or erosion of the tumor. Early and correct diagnosis and the appropriate therapy are of decisive importance because these tumors are precancerous. Patients and methods. We report the cases of seven patients with periampullary adenoma of the duodenum, in one case with incorporation of the the distal bile duct. The diagnostic steps and the surgical treatment are reported and discussed. In achieving a definitive diagnosis, endoscopic retrograde cholangiopancreatography is of paramount importance. Three patients subsequently underwent partial pancreatoduodenectomy (Whipple's procedure); in three patients transduodenal local tumor excision was performed. Postoperative course was without complications in each case and no operative mortality occurred. One patient was treated by argon-coagulation. Results. The histopathological examination showed a tubular villous adenoma in six cases and in one case a villous adenoma (ranging from low to high grade dysplasia). Because there is evidence of an adenoma-carcinoma-sequence, radical surgical treatment is recommended, even in adenoma with low grade dysplasia, in spite of the absence of malignancy.     

Stand der Therapie der Schultereckgelenkverletzung Ergebnisse einer Umfrage an Unfallchirurgischen Kliniken in Deutschland

The therapy of acromioclavicular dislocations remains controversial. In particular, for injuries classified as Rockwood/Tossy Type III good results have been reported with different operative techniques as well as with conservative treatment. The objective of this study was to obtain data about the current treatment for Rockwood/Tossy III injuries in German trauma departments. In a countrywide anonymous survey 210 German trauma departments were asked about their diagnostic procedures and their treatment strategies for acromioclavicular injuries. 104 questionaires (49%) were returned and evaluated. In Rockwood/Tossy I/II injuries most clinics recommend conservative treatment (Rockwood/Tossy I/II: 99% / 87%). On the other hand, 84% of the clinics would operate on Type III acromioclavicular injuries – especially in athletes or overhead workers. Although 38 percent of the clinics believe that conservative treatment is equal or better than operative treatment, only 13 percent manage Type III injuries conservatively. For more severe acromioclavicular injuries (Rockwood IV to VI) all clinics recommend an operative treatment. The operative techniques of choice for acromioclavicular injuries are K-wire fixation (37%) or a coraco-clavicular cerclage (32%). Of the latter, 73% use a resorbable material, while the remainder use wires.     

Spezifische zelluläre Immuntherapie des Nierenzellkarzinoms Stand und Perspektiven

Renal cell carcinoma (RCC) is susceptible to immunomodulating therapies. This is proven by clinical responses to unspecific immunotherapy with cytokines. Understanding the mechanisms of antigen presentation and recognition by T cells enables us to expand T-cell clones which are capable of recognizing specific tumor-associated antigens (TAA). The use of dendritic cells (DC) in specific cellular immunotherapy could be beneficial because of their outstanding properties in antigen presentation and T-cell costimulation. In order to circumvent the escape of some tumor cells under T-cell pressure, polyvalent vaccination strategies should be developed. This goal can be achieved by either pulsing respective transfecting DC with tumor cell lysates, RNA or DNA libraries, or a pool of peptide antigens. Careful monitoring of the elicited T-cell response and quality assurance (GMP and GCP) are mandatory to establish a rationale for specific immunotherapy against RCC and to bring it from the bench to the bedside.     

Laparoskopische Tumornephrektomie

Initially, laparoscopic surgery in urology was restricted to the treatment of benign diseases, whereas its role in the management of malignant disease was restricted to purely diagnostic procedures. Only recently has laparoscopy been introduced for the treatment of low stage renal cell carcinoma (RCC), and the data on both surgical efficiency and oncologic efficacy are very promising. Therefore, we present our experience with laparoscopic radical nephrectomy and data from literature. The technique of the transperitoneal approach is described in detail. Retroperitoneoscopy is a good alternative, however. Intact removal of the specimen within an organ bag to avoid tumor spillage is an important detail of our technique. Our experience amounts to radical nephrectomy in 121 patients. The indication was clinical stage T1-T2. Mean operative time and blood loss was 2.4 h and 154 ml, respectively. The rate of minor or major complications was 5% and 4%, respectively. There was no conversion to open surgery in any patient. Mean postoperative hospital stay was 6.1 days. Data on tumor control are available for 73 patients with a mean follow-up of 13.3 months. There was no recurrence within this period. Radical nephrectomy for low-stage RCC is associated with low morbidity and great surgical efficiency. The rates for local recurrences and metastases are low, tumor-specific survival is high. However, there is still a lack of long-term data on large series of patients. Despite this fact, laparoscopy is already widely accepted for this indication, and it is quite likely that it will become the standard treatment.     

Adrenalektomie im Rahmen der Tumornephrektomie – ein Overtreatment?

Metastatic spread to the ipsilateral adrenal gland occurs in 1.2-10% of patients with renal cell carcinoma (RCC). In the majority of these cases, the primary tumor is locally advanced with poor differentiation, venous invasion, and involvement of the regional lymph nodes. Adrenal metastases are usually detected preoperatively by CT scan or MRI. Adrenal metastases are indicators of systemic disease with poor prognosis quo ad vitam. Only 0.5-2.3% of patients with RCC and adrenal metastases are free of venous invasion or lymphatic disease. In this small subset of patients, cure is possible by surgical removal of the adrenal gland. In 97.7-99.5% of patients with RCC, ipsilateral adrenalectomy has no impact on their prognosis. We therefore conclude that this procedure should be performed only if there is radiological suspicion of an adrenal mass.     

Therapie des Nierenbeckenkarzinoms

Transitional cell carcinoma of the renal pelvis is relatively uncommon, and only 5% of all urothelial carcinomas occur in the renal collecting system. Invasive tumors are often aggressive in their biological behavior and show a high tendency for systemic progression. Conservative therapy should only be considered an option in patients with imperative indications (solitary functioning kidney, bilateral tumor, renal insufficiency). In some cases, organ-sparing techniques such as open resection or endourological treatment (percutaneous or by ureteroscopy) can be performed. However, nephroureterectomy with excision of a bladder cuff is considered to be the standard treatment and should be performed whenever possible.     

MRSA als Herausforderungan die klinische Organisation

Epidemics, caused by methicillin-resistant Staphylococcus aureus (MRSA) are an increasing problem in surgical hospitals. About 10 years ago, Germany only had sporadic cases with MRSA; currently, about 15% of all Staphylococcus aureus in Germany are methicillin-resistant. The most important measures in management and therapeutic strategies regarding MRSA are presented.     

Simulation von Operationstechniken in der Weiterbildung zum Chirurgen Eine Analyse über Nutzen und Effekt

The course in Gastrointestinal Surgery (GISC) aims at teaching and training resection, reconstruction and suture techniques of the upper gastrointestinal tract. Prior to, after and 5 years following the first course, participants were asked to answer a questionnaire requesting information regarding the adequacy of surgical training in their residency program and how much they had benefited from the GISC. While 1/3 of the participants described the surgical training during their residency as inadequate, more than 90% benefited from the GISC. Although the single-layer-continuous suture technique was implemented by only 8% of the participating surgeons, other techniques such as cross-section gastroenterostomy were accepted by 38%. Only 7% of the participants rejected these new techniques, while 41% of the senior surgeons at home could not be convinced. Besides the teaching of new techniques, participants benefited above all from the repetitive training in surgical procedures.