Monocyte-derived Langerhans cells from different species-morphological and functional characterization.
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Biomedical subjects
Publications and source records attributed to F Steinbach.
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In a retrospective analysis, the DNA histograms of 65 paraffin-embedded bladder carcinomas from radical cystectomy specimens (stage pT1-pT4a, pN0, pN1, pN2) were analyzed using an automated image analysis system (Leytas 2). Automated image analysis was able to characterize invasive bladder carcinoma as being either diploid, polyploid, or aneuploid. Within the group of aneuploid tumors, the DNA content of the stem-cell line allowed further subtyping of the tumors; hypotriploid, hypertriploid, hypertetraploid, and even hyperpentaploid tumors could be distinguished. Comparing different sites of identical tumors, the DNA histogram was found to be a stable and reproducible tumor characteristic. The various tumor types differed significantly in prognosis. This technique can also be applied to smears of urine sediment or transurethrally resected tumor chips. In the case of superficial tumors, DNA cytometry defines those tumors which are potentially invasive, requiring careful follow-up and/or early aggressive treatment.
Iatrogenic ureteral lesion is a severe complication in gynecological surgery. We present a case in which the obstruction led to fornix rupture, urine extravasation and urinary ascites. The problematic diagnostic pathway is emphasized.
Our experience with urogenital fistulas are reviewed and three instances of complex ureterovesicovaginal fistulas, which can be mistaken for pure vesicovaginal fistulas because of diagnostic difficulties, are presented. If the ureterovaginal component of these fistulas is overlooked intraoperatively, urinary leakage will persist despite otherwise successful closure of the vesicovaginal component of the fistula. Because of the involvement of the terminal ureter in the fistulous system, operative therapy must combine the closure of the vesicovaginal fistula with reimplantation of the ureter into the bladder and interposition of omentum or a peritoneal patch between the bladder and vagina. Diagnosis and therapy are illustrated by patient reports and literature review.
A substantial modification of the classic technique of ureterosigmoidostomy is introduced in this article. To date, this procedure has been used in 47 patients. This article reviews the surgical technique of the antemesenterial splitting of the intestine at the recto-sigmoid junction which creates a pouch by subsequent side-to-side anastomosis.
In 133 cases of patients with renal cell carcinoma which infiltrated locally into the renal fatty tissue (stage pT3a, TNM classification of 1987), the prognostic potential of the following parameters was investigated: symptoms, patient's age at the time of operation, tumor size and localization, grade of malignancy, cell type, growth pattern, and prognostic score according to Störkel et al. [Eur Urol 1990;18(suppl 2):36]. Additionally, automated image analysis DNA cytometry was performed on 110/133 carcinomas. After an average observation period of 3.6 years (maximum 10.1 years), 59 (44.4%) of the patients died of their tumors. The cause-specific 5- and 10-year survival rates were 51.3 and 29.1%, respectively. Statistically significant differences (p < 0.05) within the individual parameters were found only for the grade of malignancy and the corresponding prognostic score. Using DNA cytometry, 13 types of renal cell carcinoma were differentiated; 90% of the tumors contained aneuploid cells. Significant differences between these relative to prognosis did not exist. In the case of locally advanced renal cell carcinoma, the DNA histogram does not seem to be superior to conventional prognostic criteria.
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Epidermal Langerhans cells (ELC) are definitively primed to differentiate into dendritic cells (DC). It is unknown at what stage of monocyte development this priming occurs. In a culture system characterized by low paracrine stimulation, i.e. Iscove's modified Dulbecco medium (IMDM) with 2% FCS, we tested the ability of peripheral blood monocytes to turn to the route of the LC-DC lineage. In this system monocytes did not develop significant yeast cell phagocytosis, although mannose receptors were available. However, they became strong stimulators of mannan specific T cell proliferation. Phenotype development was analysed by flow cytometry using the monoclonal antibodies OKT6 (CD1a), IOT2 (HLA-DR), IOM2 (CD14) and the ligand Man-BSA-FITC. CD1a was the first marker which distinguished cultured monocytes from developing macrophages, obtained by addition of 8% human serum. Like cord blood Langerhans cells (CBLC) they internalized OKT6 in deep coated pits. They maintained a phenotype of monocyte derived Langerhans cells (MoLC) during eight days of in vitro culture, expressing CD1a, mannose receptors and HLA-DR and decreasing CD14, if left in their own conditioned medium. MoLC could be converted into macrophages by addition of human serum only within the first four days in vitro. Our data suggest that monocytes acquire an LC phenotype by autocrine stimulation.
Operative method, course and complications were analyzed retrospectively in 140 patients who underwent a conservative operation for renal tumor between June 1969 and December 1990. In 53 patients (20 women and 33 men, mean age 61.2 years, range 38 to 77 years, with 49 renal cell carcinomas and 4 benign renal tumors) there was an imperative indication for an organ preserving operation because nephrectomy would have made dialysis obligatory. In 87 patients (29 women and 58 men, mean age 53.7 years, range 27 to 74 years, with 72 renal cell carcinomas and 15 benign renal tumors) the tumor was conservatively resected in the presence of a normal contralateral unit (elective indication) and 68 of these patients (78%) were symptom-free. In the imperative group 32 of 49 patients (65.3%) with renal cell carcinoma had no evidence of disease after a mean followup of 4.6 years. Known metastases were present in 4 of 7 patients who died of the tumors in this group. In 3 patients with an imperative indication for conservative surgery a second tumor occurred in the kidney: 2 were treated with further parenchyma sparing operations, while in 1 with poor physical condition no further measures were possible. Of 72 patients with renal cell carcinoma who underwent an elective operation 68 (94.4%) had no signs of tumor progression after a mean followup of 3.3 years. One patient died of tumor metastases, and 2 (2.7%) had tumor recurrence in the kidney requiring nephrectomy and enucleation, respectively. The 5-year cause-specific survival rates for the imperative and elective groups were 84% and 96%, respectively. Patients with a local stage T3 tumor were characterized by a significantly worse survival curve than those with a stage T1 or T2 tumor but no significant difference was noted among the various grades of differentiation.
We report on 3 patients with tumor in a horseshoe kidney, 1 of whom had bilateral tumor (renal cell cancer on the right side and urothelial cancer on the left side). Tumors that arise predominantly in the bridge of a horseshoe kidney can mimic the symptoms of an intra-abdominal disease process. Besides routine diagnostic procedures, angiography is essential to plan the surgical approach, which in principle should be organ-sparing. The literature of the embryology of the horseshoe kidney was reviewed for a relationship between the abnormal renal development and the site of tumorigenesis, and for development of a key for the wide variation of blood supply. Recently reported data suggest that the theory of a mechanical fusion is valid only for horseshoe kidneys with a fibrous isthmus but that an abnormal migration of the posterior nephrogenic area causes the majority of horseshoe kidneys in which the isthmus consists of parenchyma. Development of the isthmus through abnormal migration could predispose this location for renal cell cancer and would explain the varying forms of blood supply. Additionally, this hypothesis supports the previously raised assumption that horseshoe kidneys may be the result of teratogenic factors, which also may be responsible for the known increased incidence of related congenital anomalies and of nephroblastoma.
1. Only clear cell and chromophilic carcinomas of the kidney exhibit a considerable lymphocytic infiltration which is compatible with some immunological responsiveness. Chromophobic carcinomas and benign oncocytomas seem to be immunologically reactive. This reflects the different antigen spectrum and histogenesis of these tumors (Störkel and Jacobi, 1989). Clear cell and chromophilic carcinomas are derived from the proximal tubule and chromophobic carcinomas and oncocytomas from the collecting duct. 2. The tumor periphery seems to be the place of greatest immunological importance, as basic requirements of a sufficient lymphocyte/tumor cell interaction can only be expected there. If these data are taken into account for a therapeutical approach with biological immune modifiers the size of the tumor (tumor burden) and proliferation index must be considered too. This might be a likely explanation for the positive effect of inhaled interleukin-2 on lung metastasis in renal cell cancers. Harvesting of tumor infiltrating lymphocytes for therapeutical purposes should take these findings into account. 3. In spite of dense lymphocytic infiltration only 3% of the tumor infiltrating lymphocytes exhibit the activation marker CD 25. There seems to be a sufficient T cell locomotion in renal cell carcinomas but an insufficient T-cell activation. Whether this fact is induced by lacking cytokine stimulation of involved lymphocytes or by still unknown mediators of the tumor cells is not yet known and needs further investigation. 4. Clear cell carcinomas exhibit most adhesion molecules and the highest amount of infiltrating cytotoxic T-cells and natural killer cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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Surgery continues to be the only treatment of proven efficiency for renal cell carcinoma. Chemo- and radiotherapy must be regarded as ineffective. Antagonists of the multiple drug-resistance gene, which is responsible for the chemoresistance of renal cell carcinoma as well as immunotherapy, are new experimental approaches in the treatment of renal cell carcinoma. The broad use of ultrasonography as a screening method has led to an increase in the diagnosis of small, asymptomatic renal tumors. At present, almost 65% of the renal tumors referred for surgery at our institution are asymptomatic. We found parenchyma-sparing surgery to be adequate treatment for many of these tumors. Advanced stages of renal cell carcinoma, on the other hand, can be cured by ultra-radical surgery (e.g., tumor thrombectomy or metastasectomy) in a considerable percentage of patients, as long as diffuse distant metastases are absent. Utilization of a broad range of imaging techniques is mandatory to rule out diffuse dissemination when considering such an operation.
The DNA histograms of 57 conservatively resected renal tumors were studied using automated image analysis DNA cytometry (Leytas II). Forty-nine of the analyzed tumors were renal cell carcinomas, six were oncocytomas, one was an angiomyolipoma, and one was a renal cell adenoma. On the basis of their DNA histograms, diploid, tetraploid, and aneuploid tumors could be distinguished. Aneuploid tumors could be subtyped further according to the DNA content of the stem cell line as hyperdiploid, hypertriploid, or hypertetraploid. Eight of the tumors were characterized by a combination of diploid and hypertriploid stem cell lines. During a mean follow-up of 5 years, only the two patients with a pure hypertriploid tumor died of distant metastases. These results indicate that automated DNA image analysis cytometry is able to differentiate among several types of renal tumors with obviously different prognoses.
Operative method, course and complications were analysed retrospectively in 120 patients in whom a kidney tumour had been resected without nephrectomy. In 49 patients (18 women and 31 men, mean age 59 [38-77] years; 45 renal-cell carcinomas, 4 benign renal tumours) there was an "imperative indication" for an organ-preserving operation, because nephrectomy would have made dialysis obligatory. In 74 patients with a healthy contralateral kidney (25 women, 49 men, mean age 55 [31-74] years; 61 renal-cell carcinomas, 13 benign tumours) the tumour was enucleated by choice; 55 of these patients were symptom-free. 36 of 49 patients with an imperative indication are without sign of tumour progression after a mean follow-up period of 4.5 years. In two there was a recurrence after 4 and 5 years, respectively, requiring a second organ-preserving operation. Known metastases were present in 3 of 6 patients who died of their tumours. 68 of 74 patients operated on electively are without signs of tumour progression after a mean follow-up period of 3.3 years. One patient died from tumour metastases. Two patients had tumour recurrence, requiring nephrectomy and enucleation, respectively.
Magnetic resonance imaging (MRI) was used to study vascular anatomy in 3 patients with the nutcracker syndrome and in 10 healthy volunteers. From these studies an abnormal branching of the superior mesenteric artery from the aorta was identified as being the cause of the nutcracker syndrome. Consequently, surgical transposition of the left renal vein to achieve an unobstructed renal venous backflow was performed successfully in 2 patients, while 1 underwent nephrectomy. In 1 patient adjuvant ureteral instrumentation became necessary to aid occlusion of persisting shunts between peripelvic venous varicosities and the urinary tract. Awareness of the pathophysiology of the nutcracker syndrome ensures an early diagnosis, which should be confirmed by a combination of diagnostic procedures, including MRI.
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The surgical technique, course and complications were analysed in 123 patients in whom a kidney tumor had been enucleated. Fifty-seven enucleated tumors were available for image analysis DNA-cytometry. In 49 patients there was an imperative indication for an organ-preserving operation, because nephrectomy would have made dialysis obligatory. In 74 patients with a healthy contralateral kidney the tumor was enucleated by choice. Thirty-five of 49 patients with an imperative indication are without sign of tumor progression after a mean follow-up of 4.5 years. In two patients there was a recurrence after 4 and 5 years, respectively, requiring a second organ-preserving operation. In one further patient there is a suspicion of multiple small tumor lesions 2 years after the first operation. Known metastases were present in 3 of 6 patients who died of their tumors. Sixty-eight of 74 patients operated on electively are without signs of tumor progression after a mean follow-up period of 3.3 years. One patient died from tumor metastases. Two patients had tumor recurrence, requiring nephrectomy and enucleation, respectively.