Images in focus. Carcinoma with unknown primary tumor syndrome with mucosal metastasis in the duodenum mimicking angiodysplasia.
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Adenocarcinoma↗
Biomedical subjects
R Knüchel
Publications and source records attributed to R Knüchel.
The need for microdissectional tumor cell preparation during the molecular genetic analysis of prostate cancer.
For clinically localized prostate cancer, recent studies strongly indicate that the determination of p53 inactivation allows the identification of a highly aggressive subgroup of prostatic tumors associated with decreased recurrence-free and long-term survival following radical prostatectomy. However, several questions regarding the determination of p53 alterations in prostate cancer, such as the poor correlation between immunohistochemistry and molecular genetic analysis, remain to be clarified. On the DNA level, p53 gene alterations have been identified in only up to 64% of tumors exhibiting immunohistochemically detected overexpression of the p53 oncoprotein. This discrepancy can be explained either by the genetic microheterogeneity of prostate cancer or by stabilization of the wild-type protein due to posttranslational events. In the present study we tried to determine the concordance between an immunohistochemically detected p53 overexpression and the result of molecular genetic analysis. Therefore, tumor tissue obtained by microdissection from 40 prostate cancer specimens was subjected to DNA-sequence analysis. Microdissection was based either only on histopathologic criteria or on the result of the immunohistochemical staining reaction. In 8 of 14 (57%) tumors a positive immunohistochemical reaction could be confirmed by DNA sequencing, which revealed a missense point mutation at the p53 gene locus, mainly in the form of G-->A transversion in exon 5 of the p53 gene. Following the micropreparation of tumor cells exhibiting p53 oncoprotein overexpression, missense point mutation could be detected in an additional 4 cases. Following a microscopically guided tumor cell dissection according to the result of immunohistochemistry, DNA sequencing confirmed an immunohistochemically detected p53 overexpression in 86% of cases investigated. This result indicates that a microdissectional tumor cell preparation is recommended for molecular genetic analysis of histologically heterogeneous tissue specimens such as prostate cancer and should be performed according to and in addition to the result of immunohistochemistry when an immunohistochemical approach is available.
Adenocarcinoma↗
Endoscopic fluorescence detection of dysplasia in patients with Barrett's esophagus, ulcerative colitis, or adenomatous polyps after 5-aminolevulinic acid-induced protoporphyrin IX sensitization.
BACKGROUND: Surveillance of patients with Barrett's esophagus or ulcerative colitis for dysplasia is confined to biopsy specimens taken randomly during endoscopy because dysplasia remains undetectable by visual inspection. We attempted to visualize dysplastic tissue during endoscopy after sensitization with 5-aminolevulinic acid (5-ALA) leading to accumulation and formation of protoporphyrin IX and induction of characteristic red fluorescence of the latter substance using blue light illumination. METHODS: Six patients with histologically proven low- or high-grade dysplasia (Barrett's esophagus 2, ulcerative colitis 1, Billroth-II stomach 1, rectal polyps 2) were treated with oral administration of different concentrations of 5-ALA (10 to 20 mg/kg) or by local instillation of 3 gm 5-ALA in the rectum. Endoscopic fluorescence detection was performed 1 to 6 hours after sensitization using a blue light source and compared with conventional white light endoscopy. Biopsies of fluorescent and nonfluorescent areas were compared with histologic findings. RESULTS: Normal duodenal mucosa and squamous epithelium showed more intense 5-ALA-induced background red fluorescence compared with normal mucosa in the stomach or Barrett's mucosa. Histologically, dysplasia was exclusively found in areas with red fluorescence. False-positive fluorescence was associated with microscopic inflammation of the mucosa or feces in the colon. CONCLUSIONS: 5-ALA-induced protoporphyrin IX fluorescence may be useful in the detection of dysplasia in the gastrointestinal tract by enhancement of endoscopic surveillance of patients at a high risk for dysplasia.
Adenomatous Polyps↗
Predictive value of decreased p27Kip1 protein expression for the recurrence-free and long-term survival of prostate cancer patients.
The p27Kip1 gene has been identified as inductor of cell cycle arrest at the G1 checkpoint to prevent entry of somatic cells into the S phase of the cell cycle when substantial DNA damage has occurred. It has been suggested that decreased expression of the p27Kip1 protein may contribute to the development of human malignancies due to loss of critical antiproliferative mechanisms. In the present study, 95 specimens (T1-T4) from 95 randomly selected patients undergoing radical prostatectomy at the Urological Department of Hannover University (82 patients) as well as in the Josef Hospital Regensburg (13 patients) between 1981 and 1992 for whom tissue blocks for immunohistochemical investigation were available, were investigated for different biological and clinical characteristics as possible predictors for recurrence-free and long-term survival: age, depth of tumour infiltration, histological grade, lymph node status, as well as decreased expression of the p27Kip1 protein. After a median follow-up up of 56 months (24-151 months), seven of 21 (33%) patients (Group 1) with loss of p27Kip1 protein expression or a relative amount of <10% of positively stained tumour cells developed recurrent disease in contrast to 17 of 74 (23%) patients (Group 2) with retained p27Kip1 protein expression (> or =10% of positively stained tumour cells). The median recurrence-free survival was 14 months (5-40 months) for patients from Group 1 and 31 months (7-133 months) for Group 2 patients (P = 0.02). In multivariate analysis, loss of p27Kip1 protein expression was identified as the only independent prognostic parameter for recurrence-free survival. In contrast, neither the univariate nor the multivariate analysis showed a correlation between loss of p27Kip1 protein expression and the long-term survival of the patients. Prospective studies are urgently needed to confirm the independent prognostic value of decreased p27Kip1 protein expression together with overexpression of the p53 tumour suppressor protein in patients with localized prostate cancer. The availability of more refined prognostically important biological variables in addition to established prognostic factors like tumour stage or Gleason score might help decision making in patients at high risk for the development of local recurrence or systemic tumour progression.
Adenocarcinoma↗
Cytokine repertoire during maturation of monocytes to macrophages within spheroids of malignant and non-malignant urothelial cell lines.
Terminal maturation of human blood monocytes to macrophages (MAC) in vivo is believed to be important for the morphology, antigen expression and functional activity of the resulting MAC population. This process is modulated by the specific tissue micro-environment to which blood monocytes migrate upon leaving the vasculature. Tumor-associated macrophages (TAM) are a special type of MAC, and little is known about the modulating capacity of the tumor environment on monocyte-to-MAC differentiation. By co-culturing 3-dimensional multicellular spheroids (MCS) of the urothelial-bladder-carcinoma cell lines J82 and RT4 with human monocytes/MAC we generated TAM in vitro. For comparison, monocytes/MAC were co-cultured with the non-tumorigenic urothelial cell line HCV29. The effects on monocyte differentiation were analyzed, particularly with respect to cytokine release. Monocyte maturation was modulated within the tumor spheroid dependent upon the tumor cell type. Monocytes co-cultured with MCS of the poorly differentiated J82 carcinoma spontaneously produced high amounts of IL-1beta and IL-6, but only low amounts of TNF-alpha, which could be further increased by the addition of LPS. This cytokine pattern is characteristic for monocytes and remained constant for up to 8 days in J82-MCS co-cultures. However, in RT4-MCS and HCV29-MCS co-cultures, the initial cytokine pattern changed and after 8 days corresponded well to that of MAC differentiated in vitro without tumor contact. In addition to functional parameters, we analyzed the morphology of J82-MCS-TAM and found that they displayed a monocyte-like morphology. Our data indicate that (1) tumor cells can influence monocyte-to-MAC differentiation, giving rise to TAM with monocyte-specific phenotypic properties; and (2) this capacity is dependent on the type of tumor cell.
Cell Differentiation↗
[Photodynamic diagnosis of gastrointestinal precancerous lesions after sensitization with 5-aminolevulinic acid. A pilot study].
BASIC PROBLEM AND OBJECTIVE: Endoscopic diagnosis of gastrointestinal precancerous and cancerous lesions is difficult, often even impossible. This study was undertaken to find out whether premalignant or suspected malignant tumors can be diagnosed by preceding sensitization with 5-aminolaevulinic acid (ALA), which in tumors is transformed in increased amounts into photosensitizing protoporphyrin IX, the latter being recognized by its characteristic red fluorescence on exposure to blue light. PATIENTS AND METHODS: 20 patients with known mild or moderately severe dysplasias (Barrett's esophagus, n = 8; colorectal adenoma, n = 3; ulcerative colitis n = 2, and gastric polyps or mucosal changes suspicious of malignancy, n = 5. Two patients with squamous-cell carcinoma, who after radio- and chemotherapy were endoscopically free of tumor, were sensitized with different concentrations of ALA (orally: 5-30 mg/kg; or locally: 3 g in 100 ml 0.9% NaCl). Photodynamic diagnosis (PDD) took place 4-8 h after oral and ca. 1-2 h after local sensitization with blue light (D-light, Storz, Tuttlingen, Germany). RESULTS: Definite red fluorescence with demonstration of dysplasia was found in three of four patients with Barrett's esophagus. Biopies from nonfluorescent areas were free of dysplasia. Two gastric adenomas (10 mg/kg ALA with high-grade dysplasia were definitively endoscopically by their red fluorescence. In one patient mild dysplasia was found in a non-fluorescent area after radio- and chemotherapy of an esophageal carcinoma. Dysplasias were also seen in the rectal biopsy after local applications. CONCLUSIONS: PDD makes it possible for the first time to visualize precancerous lesions of the gastrointestinal tract after preceding ALA sensitization. PDD is a highly promising method for monitoring patients with gastrointestinal disease and an increased risk of cancer, and for clarifying the diagnosis of mucosal changes suspicious of malignancy.
Adenoma↗
Plasmid maintenance assay based on green fluorescent protein and FACS of mammalian cells.
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DNA Replication↗
The immunohistochemical marker Ki-S2: cell cycle kinetics and tissue distribution of a novel proliferation-specific antigen.
The monoclonal antibody Ki-S2 binds to a recently characterized proliferation-specific protein, p100. To assess its distribution pattern under physiologic and pathologic conditions, we performed immunohistochemical analyses on an exhaustive spectrum of normal tissues, 624 miscellaneous solid cancers, and 95 hematologic malignancies, and compared the results with Ki-67 immunostaining on consecutive sections. In addition, Ki-S2 expression was related to the DNA content by dual parameter flow cytometric analysis in parallel with Ki-67 labeling using a human cancer cell line. Immunoreactivity was enhanced at the G1/S transition and persisted through G2 and M phase. After adequate antigen retrieval, the antibody was found to yield identical results on fresh and formalin-fixed, paraffin-embedded material. The antibody specifically labeled actively proliferating cells, which constitute a subset of the population recognized by Ki-67. In normal human tissues, Ki-S2 immunolabeling hardly ever exceeded 40% of the Ki-67+ cell fraction. Immunoreactive scores of the two antibodies exhibited a linear correlation, but statistically significant differences in the ratio of Ki-S2-positive to Ki-67-positive cells were nevertheless observed between different tissue types. In contrast, the ratio of Ki-S2 and Ki-67 immunoreactive scores varied widely in neoplastic cells and tissues, occasionally attaining a ratio of almost 1:1. This suggests that loss of growth regulatory mechanisms in malignant cells might result in an extreme reduction of the G1 phase fraction and thus in a significantly shorter doubling time. Therefore, antibody Ki-S2 is likely to allow a more precise evaluation of the cell fraction that will complete a division cycle and a more confident appraisal of the malignancy potential of a neoplastic process.
Antibodies, Monoclonal↗
Analysis of cell cycle-related Ki-67 and p120 expression by flow cytometric BrdUrd-Hoechst/7AAD and immunolabeling technique.
Flow cytometric multiparameter analysis of two proliferation associated antigens, Ki-67 and p120, was combined with cell cycle kinetic analysis, achieved by continuous labeling with 5-Bromodeoxyuridine (BrdUrd), followed by staining with Hoechst 33258 and 7-Aminoactinomycin D (7AAD). Exponential and plateau phase monolayer cultures of the human bladder carcinoma cell line J82 were examined. Resting cells, characterized by their absent BrdUrd incorporation, showed no reactivity with the MIB1 antibody, which was used for the detection of the Ki-67 antigen. Proliferating cells revealed a cell cycle phase dependent Ki-67 staining intensity, which was partially related to the time period spent in G1 after mitosis. In contrast to the Ki-67 antigen expression, no decrease in p120 immunofluorescence staining intensity of non-cycling cells could be observed. We could demonstrate that a dissection of the history of cell replication, obtained by the BrdUrd/Hoechst technique combined with a simultaneous immunofluorescence staining reveals detailed information, on a single cell level, about time dependent expression of proliferation associated antigens in all cell cycle compartments.
Antigens, Neoplasm↗
Increased incorporation of chimeric human immunodeficiency virus type 1 gp120 proteins into Pr55gag virus-like particles by an Epstein-Barr virus gp220/350-derived transmembrane domain.
Noninfectious Pr55gag virus-like particles containing high quantities of oligomeric human immunodeficiency virus type 1 (HIV-1) envelope (Env) proteins represent potential candidate immunogens for a vaccine against HIV-1 infection. Thus, chimeric env genes were constructed encoding the HIV-1 exterior glycoprotein gp120 which was covalently linked at different C-terminal positions to a transmembrane domain (TM) from the Epstein-Barr virus (EBV) major Env glycoprotein gp220/ 350. All chimeric Env-TM polypeptides as well as the wild-type HIV Env proteins were equally produced and incorporated at the outer surface of insect cells using the baculovirus expression system. In the presence of coexpressed HIV Pr55gag polyproteins significantly decreased amounts of wild-type Env proteins were presented at the cell surface, whereas the membrane incorporation of the Env-TM chimeras was not affected. Biochemical and immunoelectron microscopical analysis of particles that were efficiently released from these cells displayed the incorporation of both wild-type Env and chimeric Env-TM proteins on the surface of VLPs. However, the quantities of particle-associated chimeric Env-TM proteins exceeded those of incorporated wild-type Env proteins by a factor of 5-10. Chemical cross-linking and subsequent polyacrylamide gel electrophoresis of VLP-entrapped Env proteins revealed that the chimeric Env-TM proteins form homodimers and a higher-order oligomer, similar to that observed for wild-type Env proteins. Thus, the results of this study clearly demonstrate that the replacement of the gp41 transmembrane protein of gp160 by a heterologous, EBV gp220/350-derived membrane anchor provides an effective strategy to incorporate high quantities of oligomeric HIV gp120 proteins on the surface of Pr55gag virus-like particles.
Amino Acid Sequence↗
[Immunocytochemical venous blood studies in patients with manifest oral cavity carcinomas, oral precancerous conditions, benign tumors and in chronic alcoholic patients].
In a prospective pilot study we investigated the percentage of immunocompetent cells in the peripheral blood in 146 patients (lymphocytes, leucocytes, monocytes, T cells, B cells, NK cells, T-helper cells, T-suppressor cells, ratio T-helper/T-suppressor cells, activated T cells HLA-DR) by flow cytometry. The immunologic parameters were derived from patients with oral and oropharyngeal squamous cell carcinomas, precancerous lesions and benign tumours and from a group of heavy smokers and alcoholics. Carcinoma patients (n = 46) were compared with risk groups and a reference group consisting of patients with inflammatory disease. Within the collective of carcinoma patients we measured the immune status before and after chemo-, radio- and operative therapy. We also analysed the immune parameters in relation to clinical and histomorphological parameters (TNM status, grading). The univariate analysis of monocytes showed significant relationships between on the one hand carcinoma patients and on the other alcoholics and those with benign tumours and precancerous lesions. In precancerous lesions NK cells were significantly increased compared with alcoholics and the reference group. A significant decrease in B cells in carcinoma patients may show incipient insufficiency of the humoral immunity. The immune parameters showed a different reaction depending on therapy. After irradiation we found a significant increase of T-suppressor cytotoxic cells and decreases in B and T-helper cells. Chemotherapy showed an increase in T and T-helper cells and a decrease in B cells. Surgical therapy alone yielded an increase in B cells. The comparison of all pre- and posttherapeutic parameters showed significant changes only in activated T cells HLA-DR. We found no correlation between prognostic clinico-pathological factors and immune parameters. No changes were found in a multivariate analysis.
Alcoholism↗
[Recurrent angina pectoris in stress caused by hemangioma of the heart].
We present the case of a 73-year-old man with a 3-week history of recurrent exertional angina confirmed by exercise stress testing. The symptoms were caused by hemangioma situated between the pulmonary artery and the left auricle. The diagnosis was confirmed by ventriculography, coronary angiography, and CT-scanning. The tumor was completely removed through a midline sternotomy without extracorporeal circulation. Histology revealed the diagnosis of a cavernous hemangioma with endothelial lined vascular channels of varying size. The patient made an uneventful recovery and remained asymptomatic during follow up. Cardiac hemangioma are rare tumors of the heart that may cause angina by interfering with the coronary blood flow. Surgery is curative for most patients.
Aged↗
Influence of a haematoporphyrin derivative on the protoporphyrin IX synthesis and photodynamic effect after 5-aminolaevulinic acid sensitization in human colon carcinoma cells.
Haematoporphyrin derivatives (HPDs) are potent sensitizers in photodynamic therapy (PDT), associated with prolonged skin photosensitivity. 5-Aminolaevulinic acid (5-ALA), a natural precusor of haem, is converted intracellularly into the photosensitive agent protoporphyrin IX (PPIX), causing direct cytotoxicity after laser light irradiation but limited skin photosensitivity over 1-2 days and higher tumour selectivity. Unfortunately, the use of 5-ALA in PDT has been shown to cause only superficial tissue necrosis. Therefore, a combination of HPD and 5-ALA could be of great clinical value in the treatment of tumours if a synergistic effect of both sensitizers on tumour cell necrosis with less skin photosensitivity could be demonstrated. Human colon adenocarcinoma cells (HT-29) were cultured with either HPD or 5-ALA alone, simultaneously for 24 h with 5-ALA and HPD or in succession with 5-ALA (18 h) followed by HPD (6 h at different concentrations. Intracellular PPIX concentrations were determined by high-performance thin-layer chromatography. Furthermore, PDT was performed with an incoherent light source (lambda = 580-740 nm) using a light dose of 30 J cm(-2) and an output power of 40 mW cm(-2). The intracellular PPIX concentration correlated well with 5-ALA drug dose and incubation time and was highest after single 5-ALA sensitization. In the presence of HPD, either simultaneously or sequentially, PPIX decreased significantly. The PDT effect after simultaneous incubation with both sensitizers for 24 h was not superior to incubation with HPD alone. If 5-ALA incubation (18 h) was followed by HPD (6 h) cytotoxicity after PDT was higher than with either single drug. 5-ALA (80 microg ml(-1)) led to a decrease in tumour cell viability by 40%. A similar effect could be observed when 5-ALA and HPD were sequentially combined allowing for a reduction of the 5-ALA dose from 80 microg ml(-1) in the absence of HPD to 60 microg ml(-1) and 5 microg ml(-1) together with 0.5 microg ml(-1) and 2 microg ml(-1) HPD respectively. We speculate that the enhanced PDT effect after the combined administration of 5-ALA and HPD to cultures of colon carcinoma cells should be even more impressive in the tumour in vivo, since HPD primarily targets the tumour microvasculature and secondarily tumour cells.
Aminolevulinic Acid↗
Enhanced effectiveness of photodynamic therapy with laser light fractionation in patients with esophageal cancer.
BACKGROUND AND STUDY AIMS: The fractionated application of laser light has been shown to enhance the effect of photodynamic therapy (PDT) on normal rat colon after photosensitization with 5-aminolevulinic acid. In a pilot study, we examined whether this modified laser treatment can also enhance the effect of PDT in patients with esophageal cancer after sensitization with hematoporphyrins. PATIENTS AND METHODS: Six patients (four cases of early esophageal carcinoma and two cases of advanced esophageal carcinoma, one of the latter patients having tumor overgrowth on a metal stent) were treated in nine sessions. In four sessions, laser energy was fractionated to enhance the PDT effect using a hematoporphyrin polyester. Irradiation was carried out 48 hours after sensitization. The total laser energy of 150 J/cm2 was applied either continuously or in fractions, with a single break of five minutes after 75 J/cm2. RESULTS: Among the three patients who underwent continuous laser light irradiation, one patient experienced a complete remission of two of three superficial esophageal cancers. The patient with tumor overgrowth on an implanted metal stent showed a partial response, with improvement of dysphagia without destruction of the stent, while in another patient with advanced esophageal cancer, the dysphagia did not improve after continuous laser treatment. Fractionated laser therapy led to complete remission in all three patients with early cancers, one of whom had failed to respond to previous treatment with continuous PDT. A partial remission was obtained in a fourth patient with a uT2 cancer who had also shown no remission after continuous PDT treatment. However, after fractionated laser therapy, three mild esophageal stenoses occurred, in comparison with none after continuous PDT. CONCLUSIONS: Light fractionation during PDT improved the effectiveness of the treatment in a small number of patients, and increased side effects such as the occurrence of mild esophageal stenosis. This modified treatment can be a promising approach in the effort to reduce the dose of hematoporphyrins or other sensitizers required, and to avoid prolonged skin sensitization or local stenosis.
Aged↗
Wavelength dependent photodynamic effects on chemically induced rat bladder tumors following intravesical instillation of 5-aminolevulinic acid.
PURPOSE: The aim of the study was to determine photodynamic effects in chemically induced rat bladder tumors after intravesical instillations of 5-aminolevulinic acid (5-ALA) and PDT-dependence on laser wavelength and light dose. MATERIAL AND METHODS: Following intravesical instillation of a 5-ALA solution (40 mg 5-ALA in isotonic saline and sodium-bicarbonate) rat bladder tumors have been treated with integral irradiation using laser light at wavelengths of lambda = 630 nm and lambda = 635 nm in a light dose range of 15 to 100 J/cm2. RESULTS: A significantly higher amount of necrosis including damage of normal urothelium was obtained in rat bladder tumors using laser light at lambda = 635 nm. CONCLUSIONS: For 5-ALA assisted photodynamic treatment of superficial bladder cancer in patients the irradiation wavelength of lambda = 635 nm is recommended.
Aminolevulinic Acid↗
Three-dimensional co-culture of human monocytes and macrophages with tumor cells: analysis of macrophage differentiation and activation.
Here we report on an experimental system for generating TAM in vitro by culturing human MO and MO-derived macrophages (MAC) within 3-dimensional multicellular tumor spheroids (MCS). MO as well as MO-derived MAC migrate into tumor spheroids and spread throughout the entire spheroid within 16 hr. In contrast, fibroblast-spheroids were not infiltrated. The regular expression of MAC maturation-associated antigens on infiltrating MO was suppressed within MCS of the undifferentiated bladder carcinoma line J82 with regard to carboxypeptidase M (CPM), MAX.3 antigen and CD105. However, MAC within spheroids of highly differentiated papillary RT4 cells failed only the single antigen CD51, whereas MAC expressed the complete maturation-associated phenotype within non-tumorigenic HCV29 spheroids. Interestingly, the suppressive effect of J82 carcinoma cells could only be observed in 3-dimensional but not in monolayer cultures. The J82-MCS induced suppression of CPM and MAX.3 expression was only seen to be operative on infiltrating blood MO: MO first differentiated for 2 days and subsequently co-cultured with J82-MCS showed normal expression of MAX.3 and CPM within the spheroid. Besides the modulation of MAC phenotype, the cytokine response of intraspheroidal MAC was analyzed: upon co-culture MO secreted high IL-1beta and IL-6 but low amounts of TNF-alpha as compared to MAC. This MO typical cytokine pattern remained constant for up to 8 days in culture, again indicating a disturbed MO to MAC maturation within tumor spheroids. In conclusion, a 3-dimensional interaction with tumor cells in vitro results in significant changes in the phenotype and function of the spheroid-associated MO and MAC.
Antigens, Neoplasm↗
Expression of proliferating cell nuclear antigen (PCNA) and Ki-67 in dysplasia in inflammatory bowel disease.
OBJECTIVE: Previous studies have revealed large variations in the interobserver agreement of dysplasia grading in inflammatory bowel disease. Therefore, we investigated the diagnostic value of two novel monoclonal antibodies (MIB 1 against Ki-67 and PC 10 against PCNA) in the detection of dysplasia. METHODS: A total of 62 biopsies were investigated and histologically classified as follows: 13 probably positive for dysplasia; 15 low-grade dysplasia; five high-grade dysplasia; and 15 inflammation without dysplasia and 14 normal controls. The percentage of positive Ki-67- or PCNA-stained nuclei (= labelling index) was determined in relation to the distribution throughout the mucosa. RESULTS: In all biopsies PCNA-labelling index exceeded that of Ki-67-labelling index. In the superficial half of the crypt PCNA- and Ki-67-labelling indices in the biopsies with 'indefinite for dysplasia, probably positive' or low-grade dysplasia exceeded that of normal tissue (P < 0.001). However, an unequivocal discrimination between biopsies with 'indefinite for dysplasia, probably positive' or low-grade dysplasia and inflammation was not possible. PCNA- and Ki-67-labelling indices were significantly higher in high-grade than in low-grade dysplasia (PCNA 81.4% vs. 44.3%, Ki-67 54.8% vs 30.9%, P < 0.001). Most interestingly, labelling indices of both markers were significantly (P < 0.0001) higher in biopsies with high-grade dysplasia than with active inflammation in the superficial half of the crypt. CONCLUSION: PCNA and Ki-67 are useful adjuncts in the diagnosis of high-grade dysplasia, because high-grade dysplasia can easily be distinguished from low-grade dysplasia or active inflammation if the distribution of the positive-stained cells within the mucosa is taken into account. Lower unspecific binding and lower influence on proliferation activity by inflammation prompts us to prefer Ki-67 (MIB 1).
Biopsy↗
Detection of early bladder cancer by 5-aminolevulinic acid induced porphyrin fluorescence.
PURPOSE: We determined whether the sensitivity of detecting dysplasia or early bladder cancer can be improved by 5-aminolevulinic acid induced porphyrin fluorescence. MATERIALS AND METHODS: A 3% 5-aminolevulinic acid solution was instilled intravesically before cystoscopy in 104 patients. The 5-aminolevulinic acid induced porphyrin fluorescence was excited by violet light from a krypton ion laser (wavelength 406.7 nm.). RESULTS: The sensitivity of the fluorescence cystoscopy (96.9%) was significantly (p < 0.0001) greater than that of white light cystoscopy (72.7%). There was no impact on specificity. CONCLUSIONS: Due to the high sensitivity of the procedure fluorescence guided biopsies are recommended instead of random biopsies.
Administration, Intravesical↗