Long-term outcomes and quality of life after rectal carcinoma surgery.

BACKGROUND: A cohort study was undertaken to investigate the long-term oncological outcome, late adverse effects and quality of life (QOL) after treatment for rectal cancer. METHODS: This was an analysis of prospectively collected data from 268 consecutive patients with rectal carcinoma treated between 1995 and 1997 at the Department of Surgery, University Hospital Erlangen, Germany. RESULTS: Median follow-up was 8.8 years. The overall 10-year survival rate was 48.1 per cent. Of 219 patients who had a curative resection, 67 developed recurrent disease and 13 had second malignancies. Seventy patients had either a permanent stoma or a late adverse effect. Anorectal dysfunction and small bowel obstruction were significantly more common among patients who had multimodal treatment (P < 0.001 and P = 0.049 respectively). Analysis of QOL in 97 long-term survivors showed that receiving chemoradiotherapy, a permanent stoma and lower-third rectal carcinoma were associated with significantly worse outcomes on several measures. CONCLUSION: Late adverse effects and recurrences occurred in a significant number of patients during long-term follow-up. QOL varied according to tumour location and treatment type.

Long-term functional outcome after hyperthermic isolated limb perfusion (HILP).

BACKGROUND: One of the biological characteristics of melanoma is the locoregional development of metastases that are difficult to treat by conventional tumour mass reduction. Locoregionally metastasised melanoma of the limb can effectively be treated by hyperthermic isolated limb perfusion (HILP). Postoperative complication rates are acceptable. Only few studies have examined long-term complications. This is the reason why we followed up patients in respect of long-term physical and psychological complications after HILP. MATERIALS AND METHODS: 312 patients with melanoma of the limb underwent HILP in our department between 1977 and 1983. Eighty-two patients that were still alive and no older than 80 years at the time of follow-up were contacted and invited to a physical examination. On average, follow-up took place 20 years after HILP. Thirty-nine patients were willing to participate in the study. Twelve of these patients were male and 27 female. The average age was 63.1 years (range 41 to 79). The average age at the point of perfusion was 42.1 years (range 19 to 59). In 10 cases the upper extremity was involved, in 29 patients the lower extremity. Patients were questioned on impairment of daily life and their health status using a standardised questionnaire. A physical examination was performed to document the impairments quantitatively. Ranges of motion, circumference and neurological deficits of the operated limbs were compared to the healthy limbs. RESULTS: At the time of follow-up examination all patients were without recurrent disease. A definite correlation between impairment of the general health condition and the operation could only be found in one patient with persisting lymph oedema. Thirteen patients still wore elastic stockings during the day, 9 of which regularly underwent lymphatic drainage. Most of the patients (58%) saw an improvement of their condition due to the treatment. 67% of the patients reported not having any or only slight impairment of everyday life. Only a few cases had disadvantages in their social and working life due to the perfusion. The physical examination of the upper limb showed an impaired range of motion of the shoulder in all planes in 50% of the patients. Relevant decrease in range of motion in the elbow was seen in two patients. The other examination results showed no significant differences in comparison to the healthy arm. The analysis of the lower limb showed relevant clinical reduction of range of motion in all three major joints. Significant differences were also found in the circumference of the leg compared to the healthy side. SUMMARY: According to our results and results from the literature it was possible to show that hyperthermic isolated limb perfusion is associated with an elevated risk of persisting impairment of range of motion of the treated limb. The impaired function is due to a persistent swelling of the limb because of lymph oedema on the one hand and local toxicity to the ligaments of the joints on the other. Response rates and results of HILP have greatly improved in the last years due to numerous modifications so that this treatment is the method of choice in locoregionally metastasised melanoma of the limb in spite of the long-term complication rate.

Hyperthermic isolated limb perfusion (HILP) in malignant melanoma. Experience with 101 patients.

AIMS: To analyse results with a standardized HILP procedure in terms of response rate, recurrence pattern and complication rate. PATIENTS AND METHODS: From 1992 to 2003 HILP with melphalan and dactinomycin was performed in 101 patients with loco-regional metastases of malignant melanoma of the limbs. Among these were 66 women and 35 men with a median age of 62 years. Forty patients were in M. D. Anderson stage IIIA, 51 patients in stage IIIAB and 9 had stage IV disease at the time of perfusion. If not been done before, regional lymph node dissection preceded limb perfusion in the same setting. RESULTS: A complete response (CR) was observed in 58 out of 87 evaluable patients. Twenty-one patients achieved a partial response (PR) and eight patients were non-responders. The overall response rate was 90.8%. The median recurrence-free interval after CR was 21 months. Severe toxicity (Wieberdink IV/V) was observed in five patients necessitating fasciotomy in four of them and above knee amputation in one patient. All further cases presented with grade II-III toxicity. The overall survival was 42 months, with a 5-year survival rate of 38%. Survival significantly differed according to stage of disease. CONCLUSION: HILP is an effective treatment for loco-regional tumour relapse of malignant melanoma of the extremities and has improved by modification of technique. In the absence of regional lymph node and distant metastases long-term survival can be achieved in responders.

Pharmacokinetics of melphalan in isolated limb perfusion.

The pharmacokinetics of melphalan was studied by sampling of tissue and plasma in 72 rats that underwent isolated hyperthermic limb perfusion under different conditions. A miniaturized extracorporeal circulation system for small animals was used for perfusion of the rat hindlimb. Melphalan levels (L-phenylalanine mustard, L-PAM) were determined by high-performance liquid chromatography (HPLC). The temperature of the perfusate plasma and tissue, pH, administration method, and flow rate were modified and compared with regard to their influence on pharmacokinetic parameters. The highest tissue penetration of melphalan was observed under the following conditions: (a) pH range of the perfusate plasma between 7.3 and 7.7 (physiological environment), (b) temperature range of the perfusate from 40 degrees to 41.5 degrees C (destruction of cellular carrier systems at higher temperatures and increased inactivation by hydrolysis of melphalan above 41.5 degrees C), (c) application of melphalan as a single dose into the reservoir of the extracorporeal circuit (optimal tissue penetration), and (d) reduced perfusate flow (prolonged contact time between perfusate and tissue).

Long-term survival after extended surgical resection of melanoma metastasis and immunotherapy.

A patient with a huge melanoma metastasis to the left adrenal gland was treated by multivisceral surgical resection. Progression of disease could be controlled by systemic immunotherapy resulting in long-term survival. In selected cases, above all with late manifestation of distant melanoma metastases, even major surgical resection of such lesions can be worthwhile.

Surgical therapy for distant metastases of malignant melanoma.

BACKGROUND: Manifestation of distant metastases in melanoma patients commonly indicates a poor prognosis. The aim of the current study was to examine the role of surgical treatment in these patients. METHODS: Data from 444 patients with distant melanoma metastases were gathered prospectively from January 1978 through December 1997. Characteristics of the primary tumor, time until the first occurrence of distant metastases, frequency and site of distant metastases, surgical therapy, and survival were evaluated by univariate and multivariate analyses. RESULTS: Histology, Breslow thickness, Clark level, and pT and pN categories (UICC 1997) significantly influenced the median interval from initial diagnosis to manifestation of distant metastases. The most common single localization was the lung (n = 83), followed by distant lymph node (n = 79), and skin metastases (n = 51). One hundred seventy-four patients received surgical treatment (39%) and 111 (25%) patients received surgical treatment with curative resection (R0, UICC 1997), most frequently in distant lymph node or skin metastases (57% and 59%, respectively). Median survival time and 2-year survival rate for all patients were 7 months and 15.8%, respectively, 17 months and 36.1% following curative resection, 6 months and 12.7% after incomplete resection (n = 63) (P < 0.0001). Conservatively treated patients survived for a median of only 4 months with a 2-year survival of 8.1%. Multivariate survival analysis showed localization of the primary tumor (head/neck/trunk vs. extremities), the number of involved sites, and surgical therapy to be independent prognostic factors. CONCLUSIONS: Surgical therapy of distant metastases was most beneficial when complete removal of metastatic tissue was achieved. Selection of patients for surgical excision should be determined by individual patient indications.