Immune inhibitory effects of renal cell carcinoma extract on lectin and alloantigen-induced peripheral blood and tumor infiltrating lymphocyte blastogenesis.

The presence of tumor infiltrating lymphocytes (TIL) has been attributed to the host cell mediated immune response against the evolving malignancy. However, due to specific evasive and escape mechanisms, the immune competent cells are rendered ineffective. One such mechanism may be the production of immune suppressor substance(s), inhibiting lymphocyte proliferation, and subsequently, their transformation into effector cells. To evaluate a possible impact of RCC extract on lectin and alloantigen-induced proliferation of TIL and peripheral blood lymphocytes (PBL) from renal cell carcinoma (RCC) patients and from healthy control human subjects. Tumor extract and TIL were derived from 13 patients with RCC undergoing radical nephrectomy. Tumor infiltrating lymphocytes and PBL from these patients were activated with Concanavalin A (Con-A), Phytohemoglutinine (PHA) or Pokeweed (PW) and the rate of blastogenesis was measured by (3)H Thymidine incorporation. The same procedure was used in assay with PBL from control healthy blood donors. There was a significant reduction (88.6%) in the proliferative response to ConA of TIL compared to PBL from the same patients (P = 0.007). A similar decrease was seen following stimulation by PHA (85.8%, P = 0.01) and PW mitogen (78.5%, P = 0.001). A 79.5% decrease in response level of TIL to alloantigens compared to PBL from RCC patients (P = 0.021), was observed. Lectin induced proliferative response of RCC patients was significantly lower in the presence of RCC extract (82.9%) compared to normal kidney extract (P = 0.008). Alloantigenic stimulation of healthy individual PBL was also decreased significantly in the presence of RCC extract (92.9%, P = 0.0001) compared to normal kidney extract. Similarly, lectin induced stimulation of healthy control PBL in the presence of RCC extract was significantly lower (83.2%, P = 0.003). Our data suggest that RCC extract contains an immune suppressive substance(s), capable of inhibiting lymphocyte proliferative response of tumor infiltrating lymphocytes as well as of PBL from patients and healthy individuals alike. This may be one of the mechanisms by which the tumor evades the transformation of lymphocytes into effector killer cells, and thus affects the biological inter-relationship between tumor and host. Identification of this substance and its gene may provide an effective anti-tumoral treatment modality.

Increased expression of activation markers in renal cell carcinoma infiltrating lymphocytes.

PURPOSE: As manifested by the presence of immune competent cells, failure to control the progression of renal cell carcinoma by a local immune response attests to impaired local cell mediated immunity. To test this hypothesis we compared the expression of T-cell activation markers in renal cell carcinoma infiltrating lymphocytes with the expression of activation markers of peripheral blood lymphocytes in the same patients. MATERIALS AND METHODS: Tumor infiltrating lymphocytes were harvested from a patient with renal cell carcinoma undergoing radical nephrectomy. Peripheral blood was obtained before surgery. Tumor infiltrating and peripheral blood lymphocytes were incubated with monoclonal antibodies defining specific differentiation and activation markers on the cell surface, and analyzed by flow cytometry. Cell subsets are expressed as a fraction of the total number of mononuclear cells. RESULTS: The T-cell subset level was significantly higher in peripheral blood than in renal cell carcinoma tissue of the same patient. However, the level of activated T-cell subset expressing HLA-DR was significantly higher in renal cell carcinoma tissue than in peripheral blood. The levels of interleukin-2 receptor and transferrin receptors expressing T-cell subsets were also significantly higher in carcinoma tissue than in peripheral blood. Natural killer cells were found in significantly higher proportions in renal cell carcinoma than in peripheral blood. CONCLUSIONS: These results point to significant activation of T, B and natural killer tumor infiltrating lymphocytes. The inability of tumor infiltrating lymphocytes to mount an effective immune response to renal cell carcinoma may be secondary to the presence of suppressive factors in the tumor that prevent tumor infiltrating lymphocytes from transforming into effector cells. These factors may be particularly valuable for the further study of renal cell carcinoma-host interactivity.

Surgically correcting a vesicouterine fistula with a myouterine flap. A case report.

BACKGROUND: The incidence of vesicouterine fistula has been increasing, most probably secondary to a corresponding increase in the use of low segment cesarean section. CASE: A 37-year-old woman with a history of two cesarean sections, 14 years and 5 months earlier, presented with urge incontinence, cyclic hematuria and amenorrhea. Hysterosalpingography demonstrated contrast with the bladder and suggested a vesicouterine fistula. Following exploratory laparotomy and dissection of the bladder from the uterus, a fistula was seen connecting the anterior surface of the uterus and the posterosuperior aspect of the bladder. The fistula, with a cuff of uterus and bladder, was excised and the remaining defects repaired. In addition, a myouterine flap was raised to reinforce the repair. Upon follow-up the patient reported no difficulty in urination, complete urinary continence, normal menses and no hematuria. CONCLUSION: This is the first case of vesicouterine fistula repaired with a myouterine flap. This technique strengthens the repair and is especially convenient due to its easy accessibility. A myouterine flap can be utilized if the omentum is of insufficient length or absent. The risk of postoperative bowel obstruction may be decreased as compared to omental interposition.

Paradoxical effects of cyclosporine on concanavalin A-induced blastogenesis.

The effects of increasing in vitro cyclosporine concentrations (0, 50 100 or 200 ng./ml.) on lymphocyte blastogenesis, measured by incorporation of tritiated thymidine and induced by varying levels of concanavalin A (0, 0.25, 1.0 or 5.0 ng./ml.), were studied in regard to mean serum level of cyclosporine in 26 renal allograft recipients. Results were compared to similar data obtained in healthy controls. Patients were divided into group 1 (13 patients, mean serum cyclosporine trough level less than 150 ng./ml.) and group 2 (13 patients, cyclosporine level greater than 150 ng./ml.). With no cyclosporine added to the assay proliferation of lymphocytes obtained from all patients inversely correlated to the mean serum trough cyclosporine level at all stimulatory levels of concanavalin A (0.25 ng./ml., p less than 0.01; 1.0 ng./ml., p less than 0.001 and 5.0 ng./ml., p less than 0.001) and was significantly lower than in controls (p less than 0.0002). Whereas increasing in vitro cyclosporine concentrations has produced the expected increase in suppression of blastogenesis in controls and group 1, a paradoxical effect became evident in group 2. Under stronger stimulatory conditions (concanavalin A 1.0 or 5.0 ng./ml.) increasing in vitro cyclosporine concentrations were associated with significantly decreased suppression of blastogenesis (p less than 0.01) compared to group 1. These results confirm previous reports and suggest that the duality of effect of cyclosporine in this in vitro model may be related to its functional relationship to the calcium ion (Ca++)/calmodulin complex and to its cellular concentration/solubility curve. These considerations may be of importance in adjusting cyclosporine dosage based on serum trough levels of cyclosporine.

Rectus muscle flap for repair of refractory bladder fistula following renal transplantation: a case report.

We report a case of refractory bladder fistula in a diabetic renal allograft recipient that recurred shortly after conventional operative repair without any detectable external cause. After reoperation and use of a vascularized rectus muscle flap the fistula closed and the patient has retained excellent graft function. It is suggested that this technique should be considered as the primary repair modality for bladder fistulas in diabetic recipients, when wound healing is impaired seriously as a consequence of the combined effects of diabetic microangiopathy and steroid therapy.

Multivariate and Boolean factor analysis of immune complex/complement deposits and their effects on renal blood flow during allograft rejection.

The role of humoral immune factors in graft destruction is not fully understood. With immunofluorescence techniques the possibility of a specific pattern and/or clustering of immune complex or complement deposits was analyzed in 140 percutaneous kidney needle biopsies performed in 73 patients with renal allograft dysfunction. The results were correlated with concomitant alterations in renal blood flow as measured by cortical and global perfusion indexes and graft survival. The deposition of IgG, IgM, C3 and C4 correlated significantly with acute rejection confirmed by biopsy (p less than 0.05, less than 0.001, less than 0.02 and less than 0.001, respectively). Subsequent graft survival was compromised when IgA, IgG, IgM, C3, C4 and properdin were present together in biopsy specimens (p less than 0.05). There was a significant clustering of IgA with C3, of IgG with C3 and C4, and of IgM with C1, C3 and C4 (p less than 0.001). There also was a significant association among alterations in renal blood flow, deposition of IgA (p less than 0.05) and C4 (p less than 0.02), and graft outcome. Higher perfusion indexes, indicative of decreased blood flow, showed significant associations (p less than 0.007 and less than 0.04 for the cortical and global perfusion indexes, respectively) with a greater risk of graft loss. Although it primarily is a cellular event, the data suggest that acute rejection is associated with a deposition of various humoral factors that may mediate alterations in renal blood flow. The latter may affect graft function and structural integrity, and, thus, may show a direct correlation with the outcome of a graft.

Malakoplakia in renal transplantation: an expression of altered tissue reactivity under immunosuppression.

This report describes the successful treatment in a transplant recipient of a case of MK originating from the native urinary tract. As demonstrated, MK may pursue unexpected patterns to which conventional therapeutic guidelines may not be applicable. The type of surgical intervention used must be dictated by the extent and location of the disease and its complications. Withdrawal of immunosuppressive medication was useful in improving the patient's prognosis.

Bilateral transitional cell carcinoma of the renal pelvis in the cancer family syndrome.

The cancer family syndrome is an unusual hereditary disease rarely associated with transitional cell carcinoma of the urinary tract. We describe the occurrence of this syndrome in a patient with bilateral transitional cell malignancies.

Renal bleeding: scintigraphic detection in a canine model.

The authors evaluated a method of detecting urinary tract bleeding using Tc-99m sulfur colloid in a canine model.

Retroperitoneal haemorrhage with abscess formation complicating Waldenström's macroglobulinaemia.

The complications of bleeding in patients with Waldenström's macroglobulinaemia (WM) are relatively well described. The pathophysiology of such a haemorrhagic diathesis is complex and involves the inhibition and depression of coagulation factors as well as qualitative and quantitative platelet abnormalities. Treatment of WM must be targeted at the underlying lymphocellular malignancy, but amelioration of the hyperviscous state and component transfusion(s) to correct abnormal coagulation parameters will decrease the incidence of bleeding. A case of WM with E. coli urinary tract infection and subsequent retroperitoneal haemorrhage with abscess formation and sepsis is presented. The pathophysiology and management of such patients is described.

Ureteral replacement with ileum in transverse colon conduit.

A case of replacement of a damaged ureter with ileum, in a previously constructed transverse colon conduits, is reported. This is an attractive surgical alternative that deserves a place as a reconstructive procedure in the management of ureteral complications following urinary diversion.