Differential role of CD133 and CXCR4 in renal cell carcinoma

The chemokine receptor CXCR4 and CD133, putative stem cell markers, were previously described in renal cancer (RCC). To evaluate the biological and prognostic role of CD133 and CXCR4 in RCC the expression was evaluated through qPCR and immunoblotting in human renal cancer cell lines (786-O, A498, ACHN, CAKI-1, SN12C, TK10, UO31) and patients biopsies. Renal cancer cells and surgical biopsies expressed functional CXCR4 while CD133 was not detectable. CXCR4 and CD133 expression was then evaluated in 240 renal cancer patients through immunohistochemistry. CXCR4 and CD133 were low in 19.1% and 59.6%; intermediate in 20% and 17.9%; high in 60.8% and 22.5% of the cases, respectively. CXCR4 was overexpressed in tumours (p= 0.02), while CD133 was over expressed in healthy tissues (p= 0.04). Disease free survival Kaplan Meier plots suggest that prognosis is unfavourable for patients whose primary tumours express CXCR4 (p= 0.0199) but nor CD133 (p= 0.151) neither the concomitant CXCR4-CD133 (p=0.848) high expression affected prognosis. Analysis of prognostic factors suggests that age, clinical presentation, AJCC stage and CXCR4 had a significant prognostic value at the univariate analysis. The CXCR4 predictive ability was confirmed at the multivariate analysis while no prognostic role was identified for CD133. Thus concomitant CD133 and CXCR4 evaluation is not worth in RCC patient while the CXCR4 prognostic role encourage CXCR4 antagonists as promising therapeutic option.     

Ultrasonography compared with intravenous urography in the investigation of adults with haematuria.

OBJECTIVE--To compare ultrasonography with intravenous urography in the investigation of adults with haematuria. DESIGN--Prospective study entailing the examination of all patients with both investigations concurrently. The investigations were performed independently on routine lists by different duty radiologists. Each was aware of the details of the request form but not of the findings of the other investigation. SETTING--Radiology department of a teaching hospital. PATIENTS--155 Consecutive adult patients (aged 18-93) referred from general practitioners and hospital outpatient clinics with a history of haematuria. FOLLOW UP--When results of both examinations proved normal no clinical or radiological follow up was sought. All abnormal findings of either investigation were correlated with results of subsequent imaging studies or operative findings. RESULTS--81 Patients (52%) had normal findings on urography and ultrasonography. Overall, the findings of ultrasonography concurred with those of urography in 144 cases (93%). Among the discrepant findings of the two investigations ultrasonography missed two ureteric calculi; one was in a non-dilated ureter, and in the other case ultrasonography detected the secondary ureteric dilatation. Ultrasound examination alone detected four bladder tumours not visible on urography with sizes ranging from 5 to 21 mm, representing one fifth of the 20 cystoscopically proved bladder tumours detected in the series. Ultrasonography detected all the 22 neoplastic lesions discovered in the study (20 bladder, two renal). Ultrasonography clarified the nature of renal masses evident in three urograms (simple cysts). CONCLUSIONS--Ultrasonography is a safe and accurate method of investigating the urinary tract in adults with haematuria. When combined with a single plain abdominal radiograph it proved to be superior to urography as the primary imaging study in this series. Ultrasonography should certainly be preferred to urography if cystoscopy is not planned. No urothelial tumours of the upper urinary tract were found in the series, reflecting their rarity. For those patients in whom ultrasonography and plain radiography have shown no abnormality and in whom cystoscopic appearances are normal urography would be advisable to exclude urothelial tumours of the upper urinary tract.     

Measurements of chromogranin B can serve as a complement to chromogranin A

OBJECTIVE: CgA has been shown to be an excellent marker for neuroendocrine tumours. However, there are two major drawbacks with CgA measurements; elevated levels are common in patients with decreased renal function and in patients on treatment with proton pump inhibitors. These problems are not seen with CgB measurements. We have recently presented the development of 13 region-specific radioimmunoassays for measurements of CgB. A region-specific assay was identified, which measured higher concentrations of CgB than the other assays and seemed to be very useful as a marker for neuroendocrine tumours. The aim of the present study was therefore to further explore the diagnostic potential of this assay in the clinical management of patients with neuroendocrine tumours. METHODS: Measurements of CgB with two methods were compared with CgA in plasma samples from patients investigated for neuroendocrine tumours (N=86), patients with decreased renal function (N=35) and patients on treatment with proton pump inhibitors (N=29). RESULTS: The diagnostic sensitivity for the new CgB assay was almost as good as that for CgA. Furthermore, with CgB measurements we could avoid the falsely elevated levels of CgA found in patients with decreased renal function and treatment with proton pump inhibitors. CONCLUSIONS: We conclude that the new CgB assay can serve as a complement to CgA measurements as an important tumour marker for neuroendocrine tumours.     

The Natural History of Tumours of the Urinary Tract

Experimental and epidemiological evidence has implicated environmental factors in the increasing incidence of bladder cancer. Papillary tumours are less malignant than solid. Of 36 patients with papillary growths in the renal pelvis, 20 lived five years but 11 of 15 with solid tumours died within one year.Social and geographical influences have affected the incidence of adenocarcinoma of the kidney. Experimentally it has been produced by hormones, carcinogens, viruses and irradiation. Clinically the most adverse factor was histological anaplasia; renal vein invasion was three times as common in high-grade tumours. The postoperative five-year survival was 30 out of 42 patients with low-grade lesions but 12 out of 42 with high-grade lesions. In the case of low malignancy tumours without adverse factors, 25 out of 29 patients survived for five years. This unpredictable behaviour is characteristic of urinary tract tumours.     

Vascular endothelial growth factor and basic fibroblast growth factor evaluation in blood serum of patients with hormonally active and inactive adrenal gland tumours

The vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) levels of 36 patients with adrenal gland tumours were analysed. The mean age of patients was 43 years (29-67 years), and there were 25 women (69.4%) and 11 men (31.6%). In 34 patients adrenalectomy was performed and in two cases lesions were considered inoperable. In all cases VEGF and bFGF were measured preoperatively and in all operated patients the level of VEGF was measured at 1 month postoperatively. A statistically significant increase in VEGF levels before surgery in comparison with the controls was recorded in all patients with adrenal tumours. No correlation between the size of a tumour and VEGF levels was observed. The serum level of VEGF decreased in patients after surgical removal of the tumour, no matter which type of tumour, with the exception of a patient showing a recurrence of cortex cancer. A statistically significant decrease was found only in patients operated on for cortex cancers and hormonally active and inactive cortex and medulla inactive benign tumours. The postoperative recurrence of the malignant tumour may be preceded by an increase in plasma VEGF levels. Such correlations were not found with bFGF.     

Prognostic factors in renal cell carcinoma

We studied 569 cases of renal cell carcinoma in the files of the Department of Pathology of the Norwegian Radium Hospital from 1964 to 1974. A nephrectomy had been performed in all cases. Clinical information on sex, age, survival time and metastases was traced. The histological slides were examined and tumour growth pattern, cell type, cell shape, nuclear atypia, abnormal nucleoli, nuclear grade, vascular invasion and tumour demarcation were all evaluated. Besides well-known prognostic factors such as tumour stage, presence or absence of metastases and vascular invasion, nuclear grade was found to be a useful prognostic factor. Younger patients were found to do better than older, and women better than men. Smaller tumours carried a better prognosis than larger and clear cell tumours had a better prognosis than those composed of eosinophilic or basophilic cells. The presence of spindle cells was a bad prognostic omen.     

Cross-reactivity of lung cancer patients' leucocytes in the leucocyte migration inhibition test

Summary Panels of 3 M KCl extracts of squamous-cell carcinomas, adenocarcinomas and oat-cell carcinomas of the lung were used for a comprehensive analysis of cross-reactivity in the leucocyte migration test. Lung cancer patients' leucocytes showed positive reactivity in 69%–100% of cases (n=353). No significant differences were observed when data were grouped with respect to the histological type of the tumours used for extraction or of the tumours of the leukocyte donors. Leukocytes of patients bearing tumours of nonpulmonary origin exposed to lung cancer extract panels and leukocytes of lung cancer patients exposed to gastrointestinal cancer extract panels were definitely less reactive (35%–47% and 6%–38%, respectively). However, a high reaction frequency was found in patients with lung metastases from different nonpulmonary tumours. This group of patients also frequently showed reactivity (52%) with normal lung tissue extracts. Patients with benign lung diseases reacted positively with lung tumour extracts in 25%–39% of cases, but donors with other benign disease and healthy controls were virtually nonreactive (0–14%).Hence, a high degree of cross-reactivity occurs in the lung cancer system and restricted cross-reactivity occurs with tumours of other organs. Possible explanations for the lung-oriented reactivity of patients with lung metastases are discussed.Abbreviations LMI leucocyte migration inhibition - MI migration index - LMT leucocyte migration test - SCC squamous-cell carcinoma - OCC oat-cell carcinoma - AC adenocarcinoma     

Complications of ileal conduit diversion in adults with cancer followed up for at least five years.

A total of 111 adults with malignant disease of the bladder were studied to determine the long term complications of ileal conduit diversion. Each patient had survived at least five years (mean 10 years) after cystectomy. At final follow up the radiological appearance of one or both kidneys had deteriorated in 50 (47%) of 107 patients: deterioration worsened significantly (p less than 0.01) with increasing duration of follow up. Eighteen patients (16%) developed biochemical evidence of impaired renal function, of whom four died of complications of renal failure. Bilateral upper tract dilatation was noted in 30 patients (28%), and in 21 its cause was obscure. Ten patients formed renal stones, and an additional 12 required further operations on the conduit or stoma. Despite the age of patients with bladder cancer and the poor prognosis of those with invasive tumours clinically important side effects were observed in a significant proportion of the long term survivors. Further efforts to determine the aetiology of upper tract dilatation in patients with an ileal conduit diversion are justified.     

Intratumoural heterogeneity of nuclear DNA-content and proliferation in clear cell type carcinomas of the kidney.

Clear celled renal carcinomas (n = 37) were investigated by flow cytometry for intratumoural heterogeneity in DNA-ploidy and proliferation (S-phase rate). Using gross sections of the tumours, 178 regions of interest were selected and excised from the paraffin blocks. Of the tumours examined 30% (n = 11) were DNA-diploid and 70% (n = 26) were DNA-aneuploid. In six tumours (16%) homogenous DNA-aneuploidy was detected, and in 20 others (54%) there was intratumoural heterogeneity of DNA-content with a blend of either DNA-diploid and DNA-aneuploid regions (n = 16; 43%) or different aneuploid stemlines (n = 4; 11%). DNA-aneuploidy was present both in areas of the tumours composed of clear cells and in regions containing cells with cytoplasmatic eosinophilia. However, DNA-aneuploidy was correlated in a statistically highly significant manner with the degree of cytoplasmatic eosinophilia and the nuclear grading of tumour cells. The results were confirmed by comparative analysis of fresh-frozen and paraffin-embedded material. The DNA-aneuploid portions of the tumours, and the regions with increased cytoplasmatic eosinophilia, proved to have significantly higher S-phase rates than DNA-diploid and clear tumour cells. These results agreed well with the immunohistochemically determined percentage of Ki-67 (proliferation associated)-antigen positive cells. Our findings indicate that tumour cells with increased eosinophilia in renal cell carcinomas are distinct from real clear cells by virtue of their higher rates of aneuploidy and proliferative activity. These cells might therefore be regarded as a subclass with a more aggressive biological behaviour.     

Role of fine needle aspiration cytology in the diagnosis of soft tissue tumours and tumour-like lesions

In this study, we evaluated the usefulness of fine needle aspiration cytology (FNAC) in the diagnosis of soft tissue tumours. We have also assessed the various pitfalls of FNAC of soft tissue tumours. This was a retrospective study and here we analysed only 82 histopathology proven cases of FNAC of soft tissue tumours diagnosed in a five and half year period. On histopathological examination, 55 of these cases were malignant and 27 were benign. There was a total of 15 recurrences and histopathology was available prior to FNAC in only eight of these cases. Therefore, excluding these eight cases, malignant tumours were primarily diagnosed by FNAC in 47 cases. The sensitivity, specificity and positive predictive value of FNAC in diagnosis of soft tissue tumours were 91.5%, 92.5% and 95.5%, respectively. Only 22 of 47 cases (46.8%) were correctly categorized. There were two false-positive and four false-negative cases. One case each of fibromatosis and schwannoma were reported as sarcoma. False-negative cases were fibrosarcoma (1), malignant nerve sheath tumour (2) and haemangiopericytoma (1). FNAC was very useful in distinguishing benign from malignant soft tissue tumours. However, it was not so effective in exact categorization of tumours.     

Flow-cytometric analysis of the DNA-content in paraffin-embedded tissue from colorectal carcinomas and its prognostic significance.

The nuclear DNA content of 163 colorectal carcinomas was determined by flow-cytometry (FCM) on formalin-fixed, paraffin-embedded tissue. DNA-aneuploidy was found in 97 cases (59.5%), in which no statistically significant correlations with sex, mean age, tumour stage (Dukes and pTNM) and tumour grade were noted. The frequency of aneuploidy was significantly higher in patients less than 70 years of age (p less than 0.01) and in tumours localized in the left colon and rectum (p less than 0.002), irrespective of their stage. The tumours in which different areas could be analysed (n = 80) showed a heterogeneous DNA-ploidy pattern in 18%. Comparison of the DNA content in primary tumours and in lymph node metastases (n = 49) showed a difference in DNA-ploidy in 38% of the DNA-aneuploid tumours, but in only 6% of the DNA-diploid carcinomas (p less than 0.02). DNA-aneuploid carcinomas tended to show a higher rate of local recurrence and were associated with an unfavourable prognosis (p = 0.04) in those patients in which complete resection of their tumours was possible (n = 72). The significantly higher mortality of patients with DNA-aneuploid carcinomas of stage pT3, as well as those with Dukes stage A and B tumours indicates that DNA-aneuploidy may be a stage-independent additional risk factor in colorectal cancer.     

A morphometric analysis of individual cell death in bronchial carcinoids

Abstract. The incidence and morphometric characteristics of individual dead cells have been measured in 51 cases of broncho-pulmonary carcinoid tumours. In both typical and atypical carcinoids, these dead cells were distinguished by nuclei that were significantly smaller and less regular than those of 'intact' tumour parenchymal cells. The proportion of dead to all tumour cells was not significantly different for typical and atypical carcinoids (17 and 13%, respectively). For 33 of these tumours, their ploidy status had also been established. In diploid tumours, the proportion of dead cells was 18% and in aneuploid tumours 12%. The prognosis of patients with atypical carcinoids was significantly worse and such tumours were more commonly aneuploid. Thus the incidence of individual cell death does not appear to be positively associated with poor prognosis in this series. The association between 'necrosis' and poor prognosis commented on in the literature may relate more to a different form of cell death, expressed histopathologically as gross coagulative necrosis, the incidence of which is significantly higher among the atypical, aneuploid tumours.     

A morphometric analysis of individual cell death in bronchial carcinoids

The incidence and morphometric characteristics of individual dead cells have been measured in 51 cases of broncho-pulmonary carcinoid tumours. In both typical and atypical carcinoids, these dead cells were distinguished by nuclei that were significantly smaller and less regular than those of 'intact' tumour parenchymal cells. The proportion of dead to all tumour cells was not significantly different for typical and atypical carcinoids (17 and 13%, respectively). For 33 of these tumours, their ploidy status had also been established. In diploid tumours, the proportion of dead cells was 18% and in aneuploid tumours 12%. The prognosis of patients with atypical carcinoids was significantly worse and such tumours were more commonly aneuploid. Thus the incidence of individual cell death does not appear to be positively associated with poor prognosis in this series. The association between 'necrosis' and poor prognosis commented on in the literature may relate more to a different form of cell death, expressed histopathologically as gross coagulative necrosis, the incidence of which is significantly higher among the atypical, aneuploid tumours.     

Relative contribution of humoral and metastatic factors to the pathogenesis of hypercalcaemia in malignancy.

Some relations between metastatic bone disease and calcium homoeostasis were determined in a consecutive series of 81 patients with solid malignant tumours attending for radionuclide bone scans. Biochemical evaluation showed that bone resorption from metastatic disease was generally not enough to account for hypercalcaemia. While skeletal metastases were present in about half of the patients who developed hypercalcaemia, biochemical indices of bone resorption in these subjects were greatly increased and disproportionate to the extent of metastatic disease detected by the bone scans. Furthermore, a reduced renal phosphate threshold and increased tubular calcium reabsorption were generally observed in hypercalcaemic patients when compared with their normocalcaemic counterparts. These findings suggest that in most cases malignancy associated hypercalcaemia may be caused by the release of a humoral factor by tumour tissue which exhibits "parathyroid-hormone-like" activity with regard to bone resorption, renal phosphate threshold, and renal calcium handling. It may be postulated that this putative humoral mediator predisposes to hypercalcaemia both by stimulating generalised osteolysis and in most cases also by impairing the renal excretion of the resultant increase in filtered calcium load. While hypercalcaemia may arise as a result of metastatic bone disease alone, these data indicate that this may be the exception rather than the rule. Hence the term "metastatic hypercalcaemia" should probably be reserved for patients with extensive skeletal tumour disease in whom biochemical evaluation fails to yield evidence of an underlying humorally mediated cause.     

Neurotoxic effects during vidarabine therapy for herpes zoster.

Two cases of neurotoxic effects resulting from therapy with vidarabine are described. Both patients were undergoing treatment for cutaneously disseminated herpes zoster complicating therapy for solid malignant tumours. Both had normal renal function. The serum levels of hepatic enzymes were normal in one patient and slightly elevated in the other. Neurotoxicity was first manifested in both patients by the development of intention tremors that progressed to gross tremors. Obtundation, coma and death ensued in one patient and pain syndromes in the other. Vidarabine-induced neurotoxic effects, which may occur in the absence of hepatic or renal dysfunction or treatment with another drug, may be mild initially but may progress rapidly to more serious, even life-threatening, conditions. Presentation of neurotoxic effects should be considered an indication for withdrawal of vidarabine.     

An update on the current epidemiological status of metastatic neoplasms to the thyroid

Secondary tumours to the thyroid gland are uncommon with an overall prevalence of 5.9% in autopsy studies. In recent clinical series, secondary thyroid cancer is seen in only 1.9% of malignant thyroids. There is no gender predominance both overall (female to male 1.07:1) and when stratified by common histological subtypes (renal cell carcinoma, lung adenocarcinoma and colorectal adenocarcinoma). The median age of patients diagnosed with metastatic thyroid tumours in major studies ranges from 54 to 68 years. Metastases are more frequent in patients with pre-existing or concurrent thyroid pathology. In autopsy studies, the most common primary sites are breast carcinoma and lung carcinoma. Renal cell carcinoma, lung carcinoma and breast carcinoma predominate in clinical series. Upper aerodigestive tract primaries often directly infiltrate the thyroid gland. The underlying frequency of a histological subtype, geographic prevalence and aggressiveness of primary cancer likely contributes to the incidence of metastasis in the thyroid gland. This is seen in case series from Asia where gastric and oesophageal primary cancers predominate. Secondary thyroid cancer can present metachronously (60%), synchronously (34%), or as the first presentation of the underlying cancer (6%). Late metastases and first clinical presentations of disease often originate from renal cell carcinomas while synchronous cases tend to originate from the lungs. Other common primary sites for first presentation of secondary thyroid cancer include the lung and oesophagus. Although rare, secondary thyroid cancer should be considered as a differential particularly in patients with previous malignancy, such as from the kidney, lung, or breast.     

群体反应性抗体对再次肾移植患者的影响研究

目的:研究群体反应性抗体(PRA)对再次肾移植患者移植肾长期存活和肾功能的影响。方法:采用美国GTI公司提供的ELISA筛选HLA-I类、Ⅱ类混合抗原板,对59例再次肾移植患者进行PRA检测。鉴定抗体类型采用美国One lanmbda公司鉴定抗原板(LAT.1240)。同时检测移植肾功能。结果:59例再次肾移植患者中,抗体阳性患者16例,占27.12%(16/59),其中抗HLA-I类抗体3例,占5.08%(3/59),抗HLA-II类抗体9例,占15.25%(9/59),抗HLA-I+II类抗体4例,占6.78%(4/59)。抗体阳性与抗体阴性患者比较,肾功能下降或丧失具有显著性差异(x2=33.634,P0.001)。结论:抗HLA抗体阳性是影响再次肾移植患者移植肾长期存活的重要因素。     

A morphometric filter improves the diagnostic value of morphometric analyses of frozen histopathological sections from mammary tumours.

Frozen sections of 202 consecutive breast tumour cases were analyzed by morphometric quantitation of nuclear features. Nuclei were selected at random. Conventional light microscope examination of the paraffin-embedded specimens revealed 144 cases of cancer and 56 benign tumours. Using multivariate discriminant analysis of morphometric features, all but two of the benign cases and 79% of the malignant tumours were correctly classified. When a morphometrically based dynamic filter set to exclude 'non-diagnostic' nuclei was used, the correctly classified malignant cases rose to 86% Morphometry is a fast, reproducible and efficient method that can be used in conjunction with the histomorphological diagnosis of mammary frozen sections. The combination of systematic sampling and an objective dynamic filter may be a powerful approach to quantitative analyses of tumours from other sites. However, it is also likely that efficiency can be improved by combining nuclear morphometric features with structural, histochemical and molecular biological data. The combination of traditional histomorphological examination with quantitative information may well increase the diagnostic accuracy in individual patients.     

Morphometry of bladder carcinoma: morphometry and grading complement each other

Subjective grading of bladder carcinoma is a good predictor of the clinical outcome in those patients whose tumours are grade 1 or grade 3. However, in grade 2 tumours, which account for 45% of cases, grading has little predictive value in an individual patient. We have complemented the use of subjective grading with measurement of nuclear area and used a calculation of the distribution of nuclear sizes as a predictor of the clinical course. When subjective grading was complemented by morphometry the outcome was correctly predicted in 55 of 58 cases and all cases with poor clinical outcome were identified.     

Flow-cytometric analysis of the DNA-content in paraffin-embedded tissue from colorectal carcinomas and its prognostic significance

The nuclear DNA content of 163 colorectal carcinomas was determined by flow-cytometry (FCM) on formalin-fixed, paraffin-embedded tissue. DNA-aneuploidy was found in 97 cases (59.5%), in which no statistically significant correlations with sex, mean age, tumour stage (Dukes and pTNM) and tumour grade were noted. The frequency of aneuploidy was significantly higher in patients less than 70 years of age (p < 0.01) and in tumours localized in the left colon and rectum (p< 0.002), irrespective of their stage. The tumours in which different areas could be analysed (n = 80) showed a heterogeneous DNA-ploidy pattern in 18%. Comparison of the DNA content in primary tumours and in lymph node metastases (n = 49) showed a difference in DNA-ploidy in 38% of the DNA-aneuploid tumours, but in only 6% of the DNA-diploid carcinomas (p<0.02). DNA-aneuploid carcinomas tended to show a higher rate of local recurrence and were associated with an unfavourable prognosis (p = 0.04) in those patients in which complete resection of their tumours was possible (n = 72). The significantly higher mortality of patients with DNA-aneuploid carcinomas of stage pT3, as well as those with Dukes stage A and B tumours indicates that DNA-aneuploidy may be a stage-independent additional risk factor in colorectal cancer.