Results of isolated limb perfusion for metastasized malignant melanoma.

BACKGROUND AND OBJECTIVES: Locoregional metastases are typical biological manifestations of advanced malignant melanomas. Treatment with hyperthermic isolated limb perfusion (HILP) should be considered in affected patients. In the present study, we have analyzed the results of HILPs performed in our department. PATIENTS AND METHODS: Eighty patients with locoregional metastases of the extremities received HILP at the Department of Surgery between January 2007 and December 2016. The mean follow-up was 38 months. RESULTS: The study included 50 men and 30 women (mean age: 63 years). The median time between melanoma diagnosis and HILP was 25 months (range: 1-219 months). HILP was performed in curative (n = 45) and palliative (n = 35) intention. Seventy-five patients received a drug combination of melphalan/dactinomycin and five patients received a drug combination of melphalan/tumor necrosis factor-alpha. Remission rates were determined in 72 of 80 patients (90%) as follows: partial response n = 28, complete response n = 25, no response n = 19. Of the 25 patients with complete response, 13 patients developed a new tumor manifestation during follow-up (locoregional recurrences n = 4; distant metastases n = 3; both n = 6). The median overall survival rate was 33 months. Tumor stage influenced the survival rate significantly (p = 0.001). Patients with complete response showed a significantly better overall survival than patients with partial or no response (p = 0.016). CONCLUSION: HILP is an effective therapeutic option in patients with locoregional metastases. This procedure carries a certain risk of side effects and adverse events but overall results in good response rates. Therefore, HILP should be offered to selected patients based on an individual discussion, considering their health status and oncological prognosis.

Long-term outcome of hyperthermic isolated limb perfusion (HILP) in the treatment of locoregionally metastasised malignant melanoma of the extremities.

OBJECTIVE: The aim is to analyse a modified standardised HILP procedure regarding the response rates, local recurrences and complication rates. PATIENTS AND METHODS: 152 patients (101 females, 51 males) with an average age of 62 years and locoregionally metastasised malignant melanoma underwent HILP using melphalan and dactinomycin between 1992 and 2007. Using M.D. Anderson's classification at the time of the perfusion 51 patients presented in stage IIIA, 43 patients in stage IIIAB and 58 patients in stage IV. If indicated, lymph node dissection was performed simultaneously just before perfusion of the extremity. RESULTS: Complete remission was observed in 91 (62.7%) of 145 patients, partial remission in 26 (17.9%) patients. 28 (19.3%) patients showed no response. The overall response rate was 80.7% (117 of 145 patients). Severe complications (Wieberdink IV/V) were seen in eight cases. The average recurrence-free survival was 17 months. The median survival was 39 months; the five-year overall survival rate was 38%. The overall survival rate was significantly influenced by the stage of the disease. CONCLUSION: HILP is an efficient therapy for multiple or recurrent in-transit metastases of malignant melanoma of the lower extremities. The efficiency increased by improving the technique of the perfusion. Long-term survival can be observed in patients without regional lymph node metastases or distant metastases.

Multivisceral resection for colon carcinoma.

PURPOSE: The aim of curative surgery for colon carcinoma is the complete resection of the neoplasm. In locally advanced colon carcinomas with adhesion to neighboring organs, standard surgical procedures often turn into multivisceral resections. The purpose of this study was to investigate the value of multivisceral resection in primary colon carcinomas and factors influencing its success. METHODS: Prospectively collected data for 174 patients from the Erlangen Registry for Colorectal Carcinomas who underwent multivisceral resection for colon carcinoma from 1978 through 2002 were analyzed. Multivisceral resection was defined as the excision or resection of at least one further organ in addition to the carcinoma-affected colon. Postoperative complications, locoregional tumor recurrence, distant metastases, and cancer-related survival were evaluated after a five-year follow-up. RESULTS: Multivisceral resection most commonly involved parts of the small intestine (31.6%), urinary bladder (27.0%), and the abdominal wall (15.5%). R0 resection (no residual tumor) was achieved in 93.1%. Overall, postoperative complications occurred in 25.8%, and the postoperative mortality rate was 6.9%. For patients with R0 resection, the Kaplan-Meier estimate of five-year cancer-related survival was 80.7%; no patient with R1 or R2 resection survived for 5 years. The five-year rate of locoregional tumor recurrence was 6.5%, and the five-year rate of distant metastases was 24.2%. The presence of lymphatic metastases was a significant prognostic factor for locoregional tumor recurrence, distant metastases, and cancer-related survival. CONCLUSION: The high percentage of R0 resections achieved through multivisceral resection justifies this procedure for locally advanced colon carcinomas and highlights the importance of experienced, well-trained surgeons to decrease the incidence of locoregional recurrence.

The impact of surgery and mild hyperthermia on tumor response and angioneogenesis of malignant melanoma in a rat perfusion model.

BACKGROUND: The aim of this experimental study was to determine the effect of mild hyperthermia on tumor response and angioneogenesis in an isolated limb perfusion model with a human melanoma xenograft. METHODS: A human melanoma xenograft was implanted into the hindlimbs of 30 athymic nude rats. The animals were randomized into five groups: group I: control, group II: sham group, group III: external hyperthermia with a tissue temperature of 41.5 degrees C for 30 minutes without ILP, group IV: normothermic ILP (tissue temperature 37 degrees C for 30 minutes, group V: hyperthermic ILP (tissue temperature 41.5 degrees C for 30 minutes). Tumor response was evaluated by tumor size determination and immunohistochemical analysis 6 weeks postoperatively. Tissue sections were investigated for expression of CD34 and basic fibroblast growth factor (bFGF). RESULTS: Average tumor volumes of the controls (I) increased from 105 mm3 to 1388 mm3. In the sham operated group (II) tumor volumes were significantly larger than in group I. Tumor volumes in group IV were significantly smaller than in group I and lowest in group V. There were no significant differences in size between group I and group III after six weeks. In group III and IV each, 5 animals showed tumor progression and one had a partial tumor response. In group V only 2 animals showed tumor progression. Immunhistochemical analysis of the tissue sections demonstrated that angioneogenesis was more pronounced in group II than in group I and less pronounced in group IV and V compared with group I. CONCLUSIONS: Our results suggest that even a surgical manipulation such as a skin incision promotes tumor growth, probably by induction of growth factors like bFGF. External hyperthermia of 41.5 degrees C tissue temperature for 30 minutes only has no impact on tumor growth and angioneogenesis in vivo.