Ex vivo activated memory T-lymphocytes as adoptive cellular therapy of human renal cell tumour targets with potentiation by cis-diamminedichloroplatinum(II).

OBJECTIVE: To determine if cis-diamminedichloroplatinum(II) (CDDP) enhances, by immunomodulation, ex vivo anti-tumour cytotoxicity of autolymphocyte therapy (ALT) against a chemotherapy-resistant tumour, and if lysis is mediated through T-cells, NK-cells, or both. MATERIALS AND METHODS: Human renal cell carcinoma (RCC) target cells were derived from surgical specimens and incubated in complete medium (CM) with CDDP, or in CM alone (control group). ALT-cells were prepared from autologous whole peripheral blood mononuclear cells (PBMC) or NK-cell (CD56)-depleted PBMC obtained before surgery. Tumour cells from each group were labelled with chromium-51(51Cr) and used as targets for ALT-cells and PBMC in a standard (4 h) and delayed (18 h) 51Cr-release assay at varying effector/target ratios (E:T). RESULTS: Tumour cells incubated in CDDP showed enhanced lysis, as measured by the 51Cr-release assay, at all E:T tested. This lysis was significantly greater during the 18 h assay and when ALT-cells were used as the effector cells rather than PBMC. Depletion of CD45RO+ (memory) T-cells from the ALT cell population precluded both the 4 and 18 h tumour cell lysis. Depletion of NK-cells (CD56+) diminished the ex vivo lysis of autologous targets during the 4 but not the 18 h assay. ALT-cells derived from two patients demonstrated ex vivo tumour-specificity against autologous and allogeneic RCC. CONCLUSIONS: These data suggest that: (i) ex vivo activated memory T-cells are the principal component demonstrating significant tumour-specific cytotoxicity of ALT-cells against RCC tumour targets; (ii) CDDP may alter the physical properties of tumour cells rendering them susceptible to immune-mediated attack; (iii) the combination of ALT and CDDP may lead to increased therapeutic efficacy in patients with metastatic RCC.

Post-lymphangiography fine needle aspiration lymph node biopsy in staging carcinoma of the prostate: preliminary report.

Five cases of clinical stage B carcinoma of the prostate are reported. Bipedal lymphangiography showed unequivocal involvement of the pelvic nodes in 3 patients and was equivocal in the other 2. Percutaneous transabdominal fine needle aspiration biopsy of abnormal or suspicious iliac nodes was performed and a positive cytolocal diagnosis of metastasis was obtained in all 5 patients. Therefore, staging lymphadenectomy and an extensive radical operation were avoided. Percutaneous fine needle biopsy is a reliable, easy and safe technique that should be used in staging prostatic carcinoma whenever there is evidence of metastatic nodal involvement by lymphangiography.

The gastric bladder: a continent reservoir for urinary diversion.

A continent reservoir ("gastric bladder") has been developed as an alternative to ileal conduits after urinary diversion procedures. The reservoir is fashioned from vagally denervated gastric fundus and has antireflux ureterogastric anastomoses and a continent "neourethra," the latter which is easily catheterized to empty the contents; the main stomach retains vagal innervation. Continent reservoirs were prepared in six dogs, and Heidenhain pouches (without urinary diversion) were prepared in six control dogs. Effects of short-term and long-term exposure of gastric mucosa to urine and 1M, 2M and 4M urea solutions were studied. Basal and food-stimulated acid outputs were unaffected by prolonged exposure. Mucosal permeability to H+, Na+, K+ and Cl- after exposure to urine remained unaltered, but 4M urea solutions produced a temporary increase in permeability. Mucosal blood flow was unchanged. Reservoir capacity rapidly increased up to 2,000 ml without any change in serum electrolytes. No precipitation of uric acid occurred. No histologic differences were noted between the main stomach and the reservoir. Because gastric mucosa (especially when acidified) is relatively impermeable to ions, secretes rather than absorbs Cl-, and is unaffected by prolonged exposure to urine, a gastric pouch may be useful as a continent urinary reservoir while allowing the maintenance of normal serum electrolytes.