In the setting of isolated limb perfusion, TNF is an active anticancer drug in patients. The ILP with TNF + melphalan can be performed safely in many centers and is an effective induction treatment with a high response rate that can achieve limb salvage in patients with locally advanced extremity soft tissue sarcoma.
Lymphatic mapping with selective lymphadenectomy is an attractive approach in breast-cancer patients. It uses existing technology to exploit logical anatomic and physiological principles to identify occult regional lymph-node metastases. The lymphatic flow is visualized and the first (sentinel) lymph node on a direct drainage pathway from the primary tumour is identified. This is the node at greatest risk of harbouring metastatic deposits. Retrieving this node requires a concerted effort from the nuclear medicine physician, surgeon and pathologist. Lymphoscintigraphy can indicate the number of sentinel nodes and their location. The surgeon can use two techniques to find the node. A vital dye injected at the tumour site will stain the lymphatic duct as well as the sentinel node and allow their visual identification. Alternatively, a lymph-node-seeking radiopharmaceutical will also migrate from the tumour site to the sentinel node and will enable its retrieval with the use of a gamma detection probe. The pathologist has a number of techniques to identify tumour deposits in the lymph node. A review of the literature shows that the sentinel node can be found in more than 90% of the patients. With experience, the false-negative rate can be kept down to about 5%. This novel approach of lymphatic mapping with selective lymphadenectomy may lead to a substantial reduction in the need for axillary node dissection in patients with breast cancer without compromising survival and regional control, and without loss of prognostic and staging information. This development will translate into a great reduction in patient morbidity and medical expenses.
Melanoma frequently disseminates to the gastrointestinal tract, being found post-mortem in 60 per cent of patients with disseminated disease, while during life it is diagnosed in only 4 per cent. During the period 1981-87, 835 melanoma patients were referred and 30 developed complaints caused by gastrointestinal metastatic melanoma. Twenty-three patients were treated surgically. The interval between treatment of the primary melanoma and detection of intestinal involvement was a median of 34 months (range 2-87 months). In four patients recurrence in the gut was the first evidence of dissemination. Major complaints were nausea and vomiting, abdominal pain, signs of anaemia, and blood in the stools. Complications were bleeding (ten cases), ileus due to intussusception (five cases), bowel perforation (four cases) and cholecystitis (one case). The metastases, mainly localized in the small bowel, were removed by relatively simple procedures. Symptoms were reduced in 19 patients. Two patients died after operation: one from sepsis due to suture leakage, the other from pneumonia and a cerebrovascular accident. Of the remaining patients, 16 survived a median of 7.5 (range 0.7-32.0) months. Five patients are still alive 72, 72, 70, 7 and 2 months after the metastasectomy, three of whom are tumour-free. The actuarial 5-year survival of all patients is 19 per cent. These results support surgical intervention for patients with complaints and/or complications attributable to gastrointestinal metastatic melanoma.
Faint lymph uptake may hamper sentinel node (SN) identification by scintigraphy and subsequent gamma probe localization. The aim of the present study was to evaluate an adjustment in the colloid particle concentration and tracer dosage to optimize mammary lymphoscintigraphy. Scintigraphy was performed in 151 patients with a palpable breast carcinoma and clinically negative axilla: for the first 75 patients (group A) a standard labelling of 0.5 mg nanocolloid with 99Tcm was performed, for the subsequent 76 patients (group B) the labelling dilution volume was reduced from 4 to 2 ml. For both groups the volume of injection was 0.2 ml. Lymph node uptake was evaluated by a 4-step visual score (from 0 = absent to 3+ = very intense), and by count quantification of at 4 h in the first draining SN. The SN visualization rate increased from 93% (70/75) in group A (mean dosage 93.4 MBq, range 57-130 MBq) to 99% (75/76) in group B (mean dosage 106.5 MBq, range 74-139 MBq). The percentage of patients with uptake 3+ was significantly higher (P = 0.001) in group B (51% vs 35% in group A). SN counts were significantly higher for group B (P<0.001). The percentage of patients with less than 2000 counts/node diminished from 45% in group A to 9% in group B (P = 0.001). In group B (P = 0.033) more lymph channels (53% vs 35% in group A) were visualized and for a longer time (26% vs 4% at 4 h). Axillary drainage was seen in 96% in group A and 98% in group B whereas non-axillary drainage was observed in 19% and 25%, respectively. Intraoperative SN identification rate was 97% in group A and 100% in group B. SN metastases were found in 41% of group A and 47% of group B. It is concluded that enhancement of colloid particle concentration and adjustment of tracer dosage led to improved SN identification by substantial increase in lymph node uptake and lymph vessel depiction. A significant reduction of cases with faint SN uptake enables better surgical efficacy.
Twenty-nine stage IIIA/B melanoma patients treated by isolated limb perfusion (ILP) with a high dose of recombinant human tumour necrosis factor alpha (rHuTNF alpha), interferon gamma (IFN gamma), and melphalan were histologically documented with emphasis on therapy-induced changes of the tumour vasculature. Sequential biopsies were taken at various intervals before and after the treatment to compare the morphological change. In order to visualize microvascular changes, immunostaining was performed for von Willebrand factor (VWF), type IV collagen, alpha-smooth muscle actin, endothelial antigen PAL-E, tissue factor, CD41 (thrombocyte marker), and fibrin. In biopsies prior to perfusion, necrosis, haemorrhage, and fibrin thrombi were not found. Within 3 h following triple combination therapy, a change in the distribution of VWF staining occurred, from a discrete endothelial pattern in the untreated lesions to a fuzzy perivascular and subepidermal pattern in the treated lesions. Within 24 h, this was accompanied by intravascular thrombocyte aggregation and erythrostasis, in the absence of tissue factor and fibrin deposits. These findings indicate that the thrombocyte aggregation observed is not caused by local procoagulant activity, but is rather the result of the therapy-associated vascular damage or haemostasis. Although it is difficult to derive the dynamics of this process from static images, we assume that TNF alpha induced endothelial cell damage, leading to VWF release. Release VWF may play a role in the adhesion between thrombocytes and the damaged endothelium or the denuded subendothelium. As a consequence, the blood flow is impaired, leading to congestion and oedema, compatible with an early stage of haemorrhagic infarction.
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