Biomedical subjects

R Willers

Publications and source records attributed to R Willers.

At least 55 records · Page 3Linked to original sources

PubMed1998

Use of Roche AMPLICOR Mycobacterium tuberculosis PCR in early diagnosis of tuberculous meningitis.

Several nucleic acid-based amplification tests are available for the detection of Mycobacterium tuberculosis, but few data are available on their use in the diagnosis of tuberculous meningitis (TBM). We performed a prospective study to assess the Roche AMPLICOR Mycobacterium tuberculosis PCR test (TB AMPLICOR) for use in the diagnosis of TBM and compared it with direct Ziehl-Neelsen staining of smears, radiometric culture for M. tuberculosis, and clinical and cerebrospinal fluid (CSF) findings. Eighty-three CSF specimens collected from 69 patients with suspected meningitis in South Africa were tested by TB AMPLICOR. On the basis of clinical and laboratory findings, 40 of these patients were treated for TBM and 29 patients were not treated for TBM. Ten CSF samples from 10 patients were positive by TB AMPLICOR. Seven of these 10 patients were classified as having definite TBM, 2 were classified as having probable TBM, and 1 was classified as having possible TBM. The sensitivity of TB AMPLICOR for detecting cases of definite and probable TBM in patients from whom CSF specimens had been collected less than 10 days into antituberculosis treatment was 60.0%. Specimens from all 29 patients not treated for TBM were negative by the TB AMPLICOR, giving a 100% specificity. TB AMPLICOR is therefore more sensitive than the combination of Ziehl-Neelsen staining of smears and radiometric culture for M. tuberculosis and is a rapid and highly specific diagnostic test for TBM.

Adolescent↗

PubMed1998

Expression of Bcl-X(L), an antiapoptotic member of the Bcl-2 family, in esophageal squamous cell carcinoma.

Bcl-X, a Bcl-2-related protein, is a potent antagonist of apoptosis in its long splice variant (Bcl-X(L)). The present study was performed to determine its expression in preneoplastic and neoplastic lesions of the esophagus, its correlation with other members of the Bcl-2 family, and its impact on the outcome of surgically treated esophageal cancer patients. Samples of normal esophageal squamous epithelium (n = 10), severe squamous cell dysplasias (n = 19), carcinomas in situ (n = 14), invasive squamous cell carcinomas (n = 172), and lymph node metastases (n = 21) were immunohistochemically analyzed for Bcl-X(L) expression using a polyclonal anti-Bcl-X(L) antibody. The immunostaining was evaluated according to a score system (0-12 points) based on the percentage of positive tumor cells and the relative immunostaining intensity. Cytoplasmic staining for Bcl-X(L) protein was invariably found in all cell layers of the normal esophageal squamous epithelium. In contrast, a considerable portion of preneoplastic and neoplastic lesions display a decreased Bcl-X(L) expression as compared with that in the normal esophageal epithelium. On comparison of the amount of Bcl-X(L) expression between the different types of lesions, however, no significant differences were found between severe squamous cell dysplasias (mean immunoreactive score +/- SD, 5.2 +/- 1.8), carcinomas in situ (5.2 +/- 2.2), invasive carcinomas (4.5 +/- 2.8), and lymph node metastases (4.2 +/- 2.6). In invasive carcinomas, Bcl-X(L) expression decreased continuously with decreasing tumor differentiation (P = 0.0001) and was also directly correlated with bcl-2-associated X protein expression (P = 0.0001). On the contrary, an inverse correlation was found between Bcl-X(L) expression and Bcl-2 protein expression (P = 0.0001). No correlation was found between Bcl-X(L) expression and the parameters pT category, pN category, and tumor size. In the univariate survival analysis, patients with low immunoreactive scores (< or = 4) of Bcl-X(L) expression in the tumor tissue showed lower 2-year and 5-year survival rates than patients with high immunoreactive scores (> 4; P = 0.0485). In multivariate survival analysis, however, only the parameters pN category and pT category, but not Bcl-X(L) expression, could be verified as independent prognostic factors. This tendency of decreasing levels of an antiapoptotic protein toward unfavorable outcome is supported by an increasing number of studies on the role of Bcl-2, another antiapoptotic protein, and must be interpreted against the backdrop of apoptosis as a result of the interaction of many cell death-promoting and protecting proteins.

Apoptosis↗

PubMed1998

Expression of p21WAF1 predicts outcome of esophageal cancer patients treated by surgery alone or by combined therapy modalities.

The p21WAF1 protein is an important regulator of the cell cycle. Its expression and prognostic significance were investigated immunohistochemically in samples of normal esophageal squamous epithelium (n = 10), severe squamous cell dysplasia (n = 20), carcinoma in situ (n = 14), permanent esophageal squamous cell carcinoma cell lines (n = 3), and invasive squamous cell carcinomas treated either by potentially curative resection (n = 172) or by combined modality therapy (radiochemotherapy +/- surgery; n = 38). Whereas p21WAF1 expression in the normal epithelium was restricted to a few cells adjacent to the basal cell layer, p21WAF1 overexpression was frequently found in preneoplasias and invasive carcinomas. Expression of p21WAF1 in invasive carcinomas was not correlated with tumor differentiation, pT category, or pN category. Among carcinomas treated by potential curative resection, univariate (P = 0.0025) and multivariate (P = 0.0081) survival analysis showed significant correlation of strong p21WAF1 expression (> or =50% p21WAF1-positive tumor cells) with poor overall survival. Univariate survival analysis (P = 0.0006) revealed the same prognostic influence in the group of patients treated by combined modality therapy. We conclude that overexpression of p21WAF1 protein is a frequent event in preneoplasias and neoplasias of the esophagus. Immunohistochemical examination of p21WAF1 expression may provide important prognostic information for decision-making in the treatment of patients with esophageal cancer.

Adult↗

PubMed1998

Expression of apoptosis-regulating proteins and outcome of esophageal cancer patients treated by combined therapy modalities.

The present study retrospectively examines the correlation between the outcome of patients with locally advanced esophageal squamous cell carcinoma (LAEC) after multimodal treatment (radiochemotherapy +/- surgery) and the expression of apoptosis-regulating proteins in pretherapeutic biopsies. Thirty-eight patients with LAEC who took part in a prospective multicentric trial received radiochemotherapy, optionally followed by surgery. Pretreatment tumor biopsies were immunohistochemically investigated for expression of p53, Bcl-2, Bax (bcl-2-associated X protein), and Bcl-X(L) (bcl-2-related X protein). The overall expression of p53, Bcl-2, Bax, and Bcl-X(L) was 52.6, 57.9, 100, and 97.4% respectively. Tumors without p53 expression and tumors with weak Bcl-X(L) expression showed response to chemotherapy more frequently (55.6 and 52.6%, respectively) than tumors positive for p53 expression and tumors with strong Bcl-X(L) expression (30.0 and 31.6%, respectively); however, these differences did not attain statistical significance. No correlations were found between the expression of Bcl-2 and Bax and the response to chemotherapy. In patients treated by radiochemotherapy and surgery, p53-negative tumors showed a significantly better outcome than p53-positive tumors (mean survival, 31.1 months versus 11.3 months; P = 0.0378). Additionally, a more favorable outcome was observed in tumors positive for Bcl-2 (not significant), whereas no differences in survival were observed in relation to the expression of Bax or Bcl-X(L). No differences in survival were observed in patients treated by radiochemotherapy without subsequent resection therapy in relation to the expression of apoptosis-regulating proteins. Immunohistochemical examination of pretherapeutic tumor biopsies for expression of apoptosis-regulating proteins may help to identify patients with LAEC who may benefit from multimodal treatment and those who may not.

Adult↗

PubMed1997

Expression of Bax, a pro-apoptotic member of the Bcl-2 family, in esophageal squamous cell carcinoma.

Samples of normal esophageal squamous epithelium (n = 10), severe squamous cell dysplasia (n = 22), carcinoma in situ (n = 15), invasive squamous cell carcinoma (n = 172), lymph-node metastasis (n = 21) and 2 permanent esophageal squamous cell carcinoma cell lines were analyzed immunohistochemically for Bax expression using a polyclonal anti-Bax antibody. Immunostaining was evaluated according to a score system (0-8 points) based on the percentage of positive tumor cells and the relative immunostaining intensity. Cytoplasmatic staining for Bax protein was found uniformly in all cell layers of the normal esophageal squamous epithelium. In contrast, a gradual loss of immunoreactivity for Bax was found in a fraction of pre-neoplastic and neoplastic lesions. Upon comparison of the amount of Bax expression between the different types of lesion, however, no significant differences were found between severe squamous cell dysplasias, carcinomas in situ, invasive carcinomas and lymph-node metastases. In both esophageal carcinoma cell lines, immunoreactivity for Bax was found and confirmed by means of Northern blot analysis. In invasive carcinomas, Bax immunoreactivity was inversely correlated with Bcl-2 expression (p = 0.0243) and decreased continuously with decreasing tumor differentiation (p = 0.0011). No correlation was found between Bax expression and the following parameters: depth of invasion, nodal status and tumor size. Bax expression had no influence on the post-operative survival of esophageal cancer patients.

Adult↗

PubMed1997

Basaloid squamous cell carcinoma of the esophagus: diagnosis and prognosis.

BACKGROUND: Basaloid squamous cell carcinoma (BSCC) is a recently recognized, poorly differentiated variant of squamous cell carcinoma (SCC), which is located predominantly in the upper aerodigestive tract. METHODS: In this study, clinical and pathologic parameters of 17 BSCCs and 133 typical SCCs of the esophagus that underwent potentially curative resection (no distant metastases, no residual tumor) were compared. In addition, light microscopic, electron microscopic, and immunohistochemical features of BSCC were investigated, to determine whether this type of carcinoma could be differentiated from other poorly differentiated carcinomas of the esophagus. RESULTS: Light microscopic study showed that BSCC was composed of relatively small tumor cells, arranged in solid lobules with abundant comedo-type necrosis. BSCC was almost invariably accompanied by areas of concomitant typical SCC, foci of squamous cell differentiation, and/or severe squamous cell dysplasia or carcinoma in situ of the adjacent mucosa. Ultrastructurally, BSCC inconsistently showed features of squamous cell differentiation. Immunohistochemically, BSCC displayed poor reactivity for antibodies against wide-range cytokeratins and cytokeratin subtypes that are typical of squamous cell epithelia (cytokeratin 13 and cytokeratin 14). Infrequently, expression of Leu7, smooth muscle actin, and S-100 protein was found. In comparison with typical SCC, the characteristic features of BSCC were older patient age, higher proliferative activity (MIB-1 labelling index), and higher apoptotic indices. No differences were found with regard to pT classification, pN classification, tumor size, blood vessel invasion, lymphatic vessel invasion, neural invasion, or patient gender. Moreover, no differences in overall survival rates were found. CONCLUSIONS: BSCC is a distinct histopathologic variant of SCC, characterized by a poor degree of differentiation and high proliferative activity. However, after potentially curative resection, the prognosis of patients with BSCC of the esophagus does not differ from that of patients with typical SCC.

Actins↗

PubMed1997

Induction of granulocyte colony-stimulating factor by acute febrile infection but not by neutropenia in HIV-seropositive individuals.

The objective of this study was to assess endogenous granulocyte colony-stimulating factor (G-CSF) serum levels in HIV-seropositive individuals with persistent neutropenia or acute febrile infection. Serum levels of G-CSF were measured by enzyme-linked immunoabsorbent assay. HIV-seropositive subjects (n = 28) with afebrile neutropenia (< 1000 neutrophils/microliter) showed low G-CSF serum levels (i.e., median was below the detection limit) not different from those of healthy volunteers (n = 66) or nonneutropenic HIV-seropositive controls (n = 75). In contrast, patients with acute myeloid leukemia and afebrile neutropenia from chemotherapy (n = 17) demonstrated markedly elevated G-CSF levels (median, 264 pg/ml; p < 0.0001). However, HIV-seropositive patients with pneumonia (n = 17) showed increases of G-CSF serum levels (median, 152 pg/ml; p < 0.0001) similar to HIV-seronegative patients (n = 17) with pneumonia (median, 123 pg/ml; p = 0.97). The results suggest that there may be a contribution of low G-CSF serum levels to persistent neutropenia in HIV-seropositive individuals. Moreover, the different G-CSF serum levels in HIV-seropositive individuals in response to neutropenia or acute febrile inflammation suggest different mechanisms for the regulation of G-CSF.

Acute Disease↗

PubMed1997

Cytokine removal and cardiovascular hemodynamics in septic patients with continuous venovenous hemofiltration.

OBJECTIVES: To determine whether continuous venovenous hemofiltration leads to extraction of tumor necrosis factor alpha (TNF alpha) and cytokines from the circulation of critically ill patients with sepsis and acute renal failure and to quantitate the clearance and the removal rate of these cytokines and their effect on serum cytokine concentrations. DESIGN: Prospective, controlled study in patients with continuous venovenous hemofiltration (24 1/24 h) using a polysulphone membrane in patients with acute renal failure. PATIENTS: 33 ventilated patients with acute renal failure of septic (n = 18) and cardiovascular origin (n = 15) were studied. INTERVENTIONS: Hemodynamic monitoring and collection of blood and ultrafiltrate samples before and during the first 72 h of continuous hemofiltration. MEASUREMENTS AND MAIN RESULTS: Cardiovascular hemodynamics (Swan-Ganz catheter), Acute Physiology and Chronic Health Evaluation II score, creatinine, electrolytes, and blood urea nitrogen were recorded daily. Cytokines (TNF alpha, TNF alpha-RII, interleukin (IL) 1beta, IL1RA, IL2, IL2R, IL6, IL6R, IL8, IL10) were measured in prefilter blood and in ultrafiltrate immediately preceding and 12, 24, 48, and 72 h after initiating continuous venovenous hemofiltration (CVVH). Septic patients showed elevated cardiovascular values for cardiac output (7.2 +/- 2.1 l/min), cardiac index (4.2 +/- 1.3 l/min per m2), and stroke volume (67 +/- 23 ml) and reduced values for systemic vascular resistance (540 +/- 299 dyn x s x cm(-5)). All hemodynamic values normalized within the first 24 h after initiating CVVH treatment. TNF alpha was 1833 +/- 1217 pg/ml in septic patients and 42.9 +/- 6.3 pg/ml in nonseptic patients (p < 0.05) prior to CVVH. TNF alpha was detected in ultrafiltrate but did not decrease in blood during treatment with CVVH. There was no difference in IL 1beta between septic (3.8 +/- 1.9 pg/ml) and nonseptic patients (1.7 +/- 0.5 pg/ml). No significant elimination of cytokines was achieved in the present study by CVVH treatment. CONCLUSIONS: These findings demonstrate that CVVH can remove TNF alpha and special cytokines from the circulation of critically ill patients. Cardiovascular hemodynamics seemed to improve in septic patients after induction of hemofiltration treatment, although there was no evidence that extracorporeal removal of cytokines achieved a reduction in blood levels. The study indicates that low volume continuous hemofiltration with polysulphone membranes in patients with acute renal failure is not able to induce significant removal of cytokines.

APACHE↗

PubMed1997

Risk factors for capillary leakage syndrome after bone marrow transplantation.

Age, hematopoietic growth factors, cyclosporin A, mode of bone marrow transplantation (BMT) (autologous, allogeneic-related, unrelated), and underlying disease were assessed as potential risk factors for capillary leakage syndrome (CLS) in 96 patients after BMT. CLS was defined as unexplained weight gain of > 3% within 24 h and nonresponsiveness to furosemide. CLS occurred in 9/21 patients after unrelated compared with 2/33 after allogeneic-related BMT (p = 0.0017) for hematopoietic disorders (n = 54) and in 6/7 patients after allogeneic-related compared with 3/35 after autologous BMT (p = 0.001) for solid tumors (n = 42). Hematopoietic growth factors and cyclosporin A were no significant risk factors on their own. We conclude that unrelated BMTs or high-intensity conditioning regimens used in combination with allogeneic-related BMT are the main risk factors for CLS.

Bone Marrow Transplantation↗

PubMed1997

[Acute coronary vessel occlusion after PTCA--possibility of risk stratification using quantitative coronary angiography, clinical determinants and laboratory chemistry parameters].

Abrupt vessel closure of the dilated vessel continues to represent a significant limitation of coronary angioplasty. Despite increasing operator experience and improved technology, abrupt vessel closure continues to represent the most important complication of balloon angioplasty. Intracoronary stent implantation and pharmaceutical blockade of the GPIIb/IIIa receptor serve as effective tools in the prevention of abrupt vessel closure without completely resolving this problem. About 50% of patients presenting with abrupt vessel closure exhibit additional complications including myocardial infarction, necessity of CABG or death occurring in up to 10% of acute occlusions. The purpose of this study is to evaluate if quantitative coronary angiography and assessment of clinical and laboratory data allows risk stratification concerning the probability of abrupt vessel closure. PTCA in the setting of acute coronary syndrome is associated with a markedly increased risk of abrupt vessel closure, indicating that different risk factors may contribute to the development of abrupt vessel closure in patients presenting with stable angina or acute coronary insufficiency syndromes. 798 uncomplicated PTCA procedures for stable angina pectoris were compared with 68 interventions that were complicated by abrupt vessel closure. Furthermore, 133 successful angioplasty procedures for acute coronary syndromes defined as acute myocardial infarction or unstable angina pectoris were matched with 31 procedures for acute coronary syndromes with consecutive abrupt vessel closure. In patients presenting with stable angina pectoris stenosis length, stenosis eccentricity, minimal lumen diameter, degree of the stenosis after angioplasty, female gender, and fibrinogen could be defined as independent predictors of abrupt vessel closure. In acute coronary syndromes, only minimal lumen diameter, recanalization of completely occluded coronary arteries and fibrinogen were associated with an increased risk of abrupt vessel closure.

Aged↗

PubMed1997

The prognostic value of salpingoscopy.

Salpingoscopy enables the visual inspection of the ampullary mucosa during either laparotomy or laparoscopy. This prospective study correlates the salpingoscopic results with the postoperative pregnancy rates and evaluates the value of salpingoscopy against already existing classification systems. A total of 226 women diagnosed as having pelvic inflammatory disease were treated by microsurgery. There were no other causes of infertility in these patients. The collective was divided into patients with pure adhesive disease and those with supplementary distal tubal occlusion. Salpingoscopy was performed at the end of a microsurgical laparotomy. All laparotomies were performed between 1989 and 1992. The occurrence of pregnancy was checked after 42 months follow-up. A correlation between salpingoscopy and the American Fertility Society classification for each tube is discussed. The crude and cumulative intrauterine pregnancy rates are reported for the two patient groups.

Female↗

PubMed1997

Comparison of a lactate-versus acetate-based hemofiltration replacement fluid in patients with acute renal failure.

The objective of the study was to determine the impact of a lactate- and an acetate-based hemofiltration replacement fluid (HF) on the acid-base status in patients with acute renal failure (ARF) and continuous venovenous hemofiltration (CVVH). The prospective, cohort study was carried out in the intensive care unit of the Heinrich-Heine University Hospital, Düsseldorf, FRG. Subjects were 84 critically ill patients with ARF and CVVH. Fifty-two patients were subjected to lactate-based (group 1) and 32 to acetate-based hemofiltration (group 2). Thirty-eight patients had a septic, 46 a cardiovascular origin of the ARF. Creatinine, BUN, serum bicarbonate, arterial pH, lactate and APACHE II score were noted daily. Mean CVVH duration was 9.8 +/- 8.1 days; mortality was 65%. The groups did not differ with regard to the main clinical parameters. Lacate-based hemofiltration led to significantly higher serum bicarbonate and arterial pH values as compared to the acetate-based hemofiltration. Baseline serum bicarbonate values were 23.3 +/- 8.3 mmol/L in group 1 and 21.6 +/- 4.3 mmol/L in group 2 (NS); values at 48 h after initiating CVVH treatment were 25.7 +/- 3.8 mmol/L and 20.6 +/- 3.1 mmol/L, respectively (p < 0.001). Arterial pH prior to CVVH treatment was 7.36 +/- 0.1 in group 1 and 7.34 +/- 0.1 in group 2 (NS), and 7.43 +/- 0.07 versus 7.37 +/- 0.06 (p < 0.001) on day 2. These findings were maintained throughout therapy. While a lack of increase in serum bicarbonate and arterial pH was correlated to a poor prognosis in lactate-based hemofiltration, no such observation could be made in acetate-based hemofiltration. Septic patients did not differ in their acid-base status from nonseptic patients. Lactic acidosis occurred in 8 septic patients irrespective of the substitution fluid. All 8 patients died. There was a significant increase in HCO3 and arterial pH values in lactate-based as compared to acetate-based HF.

APACHE↗

PubMed1997

Prognostic significance of urokinase-type plasminogen activator expression in squamous cell carcinomas of the esophagus.

In the present study, urokinase-type plasminogen activator (uPA) expression in 150 potentially curatively resected SCCs of the esophagus was analyzed immunohistochemically by means of a murine monoclonal antibody (American Diagnostica, Greenwich, CT) and correlated with survival. Altogether, 122 of the 150 tumors (81.3%) expressed different levels of uPA. Among the 122 uPA-positive tumors, 104 (85.2%) showed a weak staining intensity, and 18 (14.8%) showed a strong staining intensity. Among the uPA-positive tumors, 29 (23. 8%) tumors showed a uPA immunoreactivity in 6-25% of all tumor cells, 30 (24.6%) showed a uPA immunoreactivity in 26-50% of all tumor cells, 41 (33.6%) showed a uPA immunoreactivity in 51-75% of all tumor cells, and 22 (18.0%) showed a uPA immunoreactivity in 76-100% of all tumor cells. No significant correlation could be shown between the different patterns of uPA expression and various clinicopathological parameters, such as pT category, pN category, tumor size, histological grade, blood vessel invasion, lymphatic vessel invasion, and inflammatory response. Concerning the overall postoperative survival, no significant differences between uPA-positive and uPA-negative tumors could be verified. This also held true when different cut points in the percentage of uPA-positive tumor cells were used. In contrast, the intensity of uPA staining provided significant prognostic information in that patients with strongly uPA-positive tumors had a poorer outcome than patients with weakly uPA-positive or uPA-negative tumors. Moreover, as shown by stepwise multivariate Cox regression analysis, the intensity of uPA expression was an independent prognostic factor.

Adult↗

PubMed1996

bcl-2 expression and prognosis in squamous-cell carcinomas of the esophagus.

The bcl-2 proto-oncogene is a known inhibitor of apoptosis and may be an important regulator of tumor growth. In the present study, bcl-2-protein expression was investigated by immunohistochemistry and correlated with prognosis in a series of 150 potentially curatively resected squamous-cell carcinomas of the esophagus. For comparison, bcl-2-protein expression was analyzed in normal esophageal mucosa, severe squamous dysplasias and carcinomas in situ. bcl-2 immunoreactivity was found in 40 out of 150 invasive squamous-cell carcinomas; the remaining carcinomas were completely negative. bcl-2-protein expression was found more frequently among poorly differentiated than among well-differentiated tumors (p < 0.0001). No correlation was found between bcl-2-protein expression and the parameters tumor size, depth of invasion and nodal status. Moreover, bcl-2-protein expression had no significant influence on overall survival. Whereas in normal mucosa bcl-2 immunoreactivity was restricted to the basal-cell layer, in 9 out of 15 severe squamous dysplasias and in 7 out of 14 carcinomas in situ bcl-2 staining was detected in all epithelial layers. Thus, bcl-2-protein is frequently expressed in invasive squamous-cell carcinomas of the esophagus and in precursor lesions of esophageal cancer, but has no significant impact on the outcome of esophageal cancer.

Adult↗

PubMed1996

Combination therapy with ZDV + DDI versus ZDV + DDC in patients with progression of HIV-infection under treatment with ZDV.

HIV-seropositive patients (n = 67) who had tolerated zidovudine for at least 24 weeks and deteriorated clinically or immunologically within 12 weeks prior to study entry were allocated in an alternating manner to didanosine chewable tablets (400 mg/day) plus zidovudine (500 mg/day) or dideoxicytidine capsules (2.25 mg/day) plus zidovudine (500 mg/day). The combination of didanosine and zidovudine resulted in a more pronounced increase of CD4 cells over time compared to the combination of dideoxicytidine with zidovudine (p < 0.002). The increase of CD4 cells was almost exclusively due to patients with more than 100 CD4 cells/microliters. Clinical end points (death, AIDS-defining disease, CDC IV event) were less frequent under didanosine plus zidovudine but failed to reach statistical significance (p = 0.07). For didanosine plus zidovudine the median time on medication during study was shorter (63% vs. 100%, p < 0.05) and the number of patients discontinuing medication prematurely due to side effects was higher (59% vs. 30%, p < 0.02). The present study favors the combination of didanosine and zidovudine in patients deteriorating while receiving zidovudine for > 24 weeks in respect to the time course of the CD4 cells. In this small sized study, there seemed to be fewer clinical events in patients on the didanosine combination compared to the combination with dideoxicytidine; however, this trend failed to reach statistical significance and needs therefore to be substantiated by larger studies. However, the lower compliance of the patients may hamper the efficacy of didanosine.

Adult↗

PubMed1996

The prognostic significance of DNA ploidy in adenocarcinomas of the esophagogastric junction.

DNA aneuploidy, as determined by flow cytometry, was detected in 36 out of 59 adenocarcinomas of the esophagogastric junction (61.0%). DNA aneuploidy was more frequent in tumors with infiltrative growth pattern and in high pT categories. No correlation was found with pN category, grading and Laurén's classification. In contrast to clinicopathological parameters, DNA ploidy has no impact on patients survival in univariate survival analysis.

Adenocarcinoma↗

PubMed1996

The prognostic significance of tumour cell proliferation in squamous cell carcinomas of the oesophagus.

Tumour samples from 150 patients with squamous cell carcinoma of the oesophagus were investigated immunohistochemically with the monoclonal antibody MIB-1, which recognises proliferating cells. Using light microscopy, the number of MIB-1-positive tumour cells was counted in the areas with the highest proliferative activity. The MIB-1 index was determined as the proportion of MIB-1-positive and MIB-1-negative tumour cells. A considerable variation of the MIB-1 indices was found between the different tumours with a minimum of 6% and a maximum of 95% (median, 33%). The MIB-1 index correlated significantly with the mitotic activity in the tumour tissue (r = 0.33; P = 0.0001) and with the proportion of apoptotic tumour cells (r = 0.25; P = 0.0017). No significant correlation was found between the MIB-1 index and various other prognostic parameters including pT classification, pN classification, tumour grade, blood vessel invasion and lymphatic vessel invasion. In the univariate survival analysis no significant difference was found between tumours with low (< or = 33%) and high MIB-1 index (> 33%) 5-year survival rate: low MIB-1 index, 19.2%; high MIB-1 index, 22.2%). In a Cox proportional hazard regression analysis only the parameters lymphatic vessel invasion (P = 0.0001), pT classification (P = 0.0034) and pN classification (P = 0.0256), but not the MIB-1 index, could be verified as independent prognostic variables. In conclusion, evaluation of the MIB-1 index does not provide prognostic information for oesophageal cancer patients.

Adult↗

PubMed1995

Prognostic value of histopathologic parameters of esophageal squamous cell carcinoma.

BACKGROUND: The grading of squamous cell carcinoma (SCC) of the esophagus as proposed by the World Health Organization (WHO) has not yet proved to be prognostically significant. Therefore, the prognostic impact of various histologic parameters was investigated and compared with that of the WHO grading. METHODS: Hematoxylin and eosin-stained tumor samples from 138 patients with SCC of the esophagus who underwent potentially curative resection (no residual tumor or distant metastases) were evaluated for the following histologic parameters: degree of keratinization, nuclear polymorphism, pattern of invasion, mitotic activity, and inflammatory response. The prognostic impact of these parameters was analyzed by univariate and multivariate survival analyses. RESULTS: In the univariate analysis, the inflammatory response (P = 0.0006), pattern of invasion (P = 0.0011), and nuclear polymorphism (P = 0.0161) were the only parameters that correlated with survival. However, in a multivariate survival analysis including these parameters, only pattern of invasion (P = 0.0010) and inflammatory response (P = 0.0076) were prognostically significant. Based on these results, a new prognostic score system was defined that correlated significantly with survival in the univariate survival analysis (P = 0.0002). In contrast, the WHO histologic grade was not prognostically significant. In the multivariate Cox regression analysis, the new prognostic score system proved to be an independent prognostic parameter (P = 0.0062), ranking next to pT classification (P = 0.0001) and pN classification (P = 0.0014). CONCLUSIONS: For SCC of the esophagus, histologic grading based on pattern of invasion and inflammatory response had an independent prognostic impact, whereas the grading system proposed by the WHO had no significant prognostic value.

Adult↗