Biomedical subjects

Ulrich Fink

Publications and source records attributed to Ulrich Fink.

At least 19 recordsLinked to original sources

PubMed2007

In vitro pyrogen test--A new test method for solid medical devices.

Medical devices manufactured for implantation into humans must be free of any contamination with viable bacteria. However, remnants of dead bacteria and bacterial components alone may induce an inflammatory immune response. Pyrogen tests for such inflammatory contaminations are generally performed either by determining the content of lipopolysaccharide in rinsing solutions of batch samples by limulus amoebocyte lysate assay, by injecting the rinsing solutions into rabbits or by implanting batch samples into rabbits and measuring change of body temperature. In this study, we show that the in vitro pyrogen test (IPT), which measures the release of the inflammatory cytokine IL-1beta in fresh or cryopreserved human whole blood, can be used to assess the pyrogenic contamination of implantable medical devices. This test was used to check neurosurgical implants, namely aneurysm clips, as a proof of principle. Owing to the direct contact of the test material with the blood cells, this test does not require rinsing procedures, which have variable efficacy. The use of human blood ensures the detection of all substances that are pyrogenic for humans and reflects their relative potency. The safety of the products as delivered could be confirmed. The effects of sterilization and depyrogenization procedures on intentional pyrogenic contaminations of samples could be followed. This new application of the already internationally validated method promises to replace further rabbit pyrogen tests. It generates extremely sensitive results with an extended range of detectable pyrogenic contaminants.

Equipment and Supplies↗

PubMed2006

The thymidylate synthase tandem repeat promoter polymorphism: A predictor for tumor-related survival in neoadjuvant treated locally advanced gastric cancer.

We evaluated DNA polymorphisms in the thymidylate synthase (TS) and 5,10-methylene-tetrahydrofolate reductase (MTHFR) genes for an association with response and survival in locally advanced gastric cancer treated with 5-FU based preoperative chemotherapy (CTx). DNA of 238 patients (CTx-group: total n = 135, completely resected (R0) n = 102; without CTx: R0 n = 103) was isolated from blood or from nontumorous tissues. In the CTx-group, genotyping of the tandem repeat and the G/C polymorphism in the triple repeat in the promoter region of the TS gene and of the C677T polymorphism of the MTHFR gene was performed. None of the TS or MTHFR genotypes were associated with histopathological response and only the TS tandem repeat polymorphism was significantly related to survival (all patients n = 135, p = 0.002; R0 resected patients n = 102, p = 0.007; log-rank test). Multivariate analysis revealed ypN (p < 0.001) and the TS tandem repeat polymorphism as independent prognostic factors in the CTx-R0-group (p = 0.003). Analyzing the prognostic significance of the TS polymorphisms in the R0-group without CTx, TS genotypes were not significantly associated with survival. Comparing survival between R0 patients with and without CTx in the respective TS genotype groups of the tandem repeat polymorphism, a significant survival benefit for the patients with CTx was found for the 2rpt/2rpt (n = 49; p = 0.002) and 2rpt/3rpt genotypes (n = 99; p = 0.004), but not for the 3rpt/3rpt genotype (n = 57; p = 0.93). Patients' survival after CTx was associated with the TS tandem repeat polymorphism. CTx did not improve survival of patients with the 3rpt/3rpt genotype. Thus, a different therapy might be more appropriate for these patients.

Adult↗

PubMed2006

Hypermethylation of hMLH1, HPP1, p14(ARF), p16(INK4A) and APC in primary adenocarcinomas of the small bowel.

Small bowel adenocarcinoma (SB-AC) is a very rare tumor entity. Epigenetic alterations, including hypermethylation of DNA mismatch repair genes and tumor suppressor genes, seem to be important for carcinogenesis in tumors of the gastrointestinal tract, but have not yet been investigated in SB-AC. In the current study, the prevalence of hypermethylation in a panel of genes involved in gastrointestinal carcinogenesis (hMLH1, HPP1, p14(ARF), p16(INK4A), APC) was determined in a series of SB-AC. Paraffin-embedded tumor samples from 56 patients with SB-AC who underwent surgical resection between January 1985 and December 2003 were investigated for hypermethylation by means of methylation-specific real-time PCR, and compared with our findings in a previously investigated series of 50 gastric adenocarcinomas. In comparison with adenocarcinomas of the stomach, SB-AC revealed a significantly higher rate of hypermethylation of HPP1 (86% versus 54%, p = 0.0003), p16(INK4A) (32% versus 10%, p = 0.0006), and a significantly lower rate of hypermethylation of APC (48% versus 84%, p = 0.0001). Hypermethylation of hMLH1 and p14(ARF) was present in 23% and 9% of SB-AC, respectively. Locally advanced tumor categories (pT3/4) showed a higher rate of hypermethylation of HPP1 (90%) than did early tumor categories (pT1/2 categories, 40%; p = 0.0036). This was also reflected by the correlation between the HPP1 hypermethylation and high UICC stage (p = 0.02). No correlation was found between hypermethylation and other clinicopathologic parameters such as age, tumor grade and nodal status. Our findings suggest that hypermethylation of hMLH1, HPP1, p16(INK4A) and APC is frequent in primary adenocarcinomas of the small bowel. The differences in the hypermethylation spectrum of small bowel and stomach cancer indicate significant epigenetic differences between these tumors.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction.

PURPOSE: A previous study suggested that measurement of therapy-induced changes in tumor glucose metabolism by positron emission tomography (PET) with the glucose analog [18F]fluorodeoxyglucose (FDG) allows to select patients most likely to benefit from preoperative chemotherapy in adenocarcinomas of the esophagogastric junction (AEG). The aim of this study was to prospectively validate these findings by using an a priori definition of metabolic response. PATIENTS AND METHODS: Sixty-five patients with locally advanced AEGs were included. Tumor glucose utilization was quantitatively assessed by FDG-PET before chemotherapy and 14 days after initiation of therapy. Patients were classified as metabolic responders when the metabolic activity of the primary tumor had decreased by more than 35% at the time of the second PET. RESULTS: Metabolic responders showed a high histopathologic response rate (44%) with a 3-year survival rate of 70%. In contrast, prognosis was poor for metabolic nonresponders with a histopathologic response rate of 5% (P = .001) and a 3-year survival rate of 35% (P = .01). A multivariate analysis (covariates: ypT-, ypN-category, histopathologic response) demonstrated that metabolic response was the only factor predicting recurrence (P = .018) in the subgroup of completely resected (R0) patients. CONCLUSION: This study prospectively demonstrates that changes in tumor metabolic activity during chemotherapy predict response, prognosis, and recurrence. These data provide the basis for clinical trials in which preoperative treatment is changed for patients without a metabolic response early in the course of therapy. PET-guided induction therapy may even be applicable to earlier tumor stages because surgery is only minimally delayed in nonresponding patients.

Adenocarcinoma↗

PubMed2006

The clinical impact of histopathologic response assessment by residual tumor cell quantification in esophageal squamous cell carcinomas.

BACKGROUND: The objectives of this study were to investigate histomorphologic features as a response classification after neoadjuvant radiochemotherapy (RTx/CTx) and to correlate the results with clinical outcome parameters (e.g., postoperative morbidity and mortality, recurrence, and survival) in patients with locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Three hundred eleven patients with histologically proven, locally advanced, intrathoracic ESCC (clinical T3 or T4, N0-N+, M0) located at or above the level of the tracheal bifurcation underwent preoperative, combined, simultaneous RTx/CTx followed by esophagectomy. Response to RTx/CTx was classified by the quantification of residual tumor cells. A histopathologic response was defined as <10% residual tumor cells found within the specimen compared with a histopathologic nonresponse, which was characterized by >10% residual tumor cells. RESULTS: A histopathologic response was correlated significantly with complete tumor resection status (R0 resection) (P .0001), histopathologic tumor (ypT) category (P <.0001), lymph node involvement (P <.0001), lymphatic vessel invasion (P <.001), and survival (P <.0001). A multivariate Cox regression analysis revealed that histopathologic response classification according to the percentage of residual tumor cells was an independent prognostic factor (P <.0001). Nonresponders had greater postoperative pulmonary morbidity (P = .01), a greater 30-day mortality rate (P = .02), and a dismal survival rate compared to histopathologic responders (P <.0001). CONCLUSIONS: Histopathologic response evaluation based on the quantification of residual tumor cells provided meaningful information for the assessment of outcomes among patients with ESCC who have underwent neoadjuvant RTx/CTx. The current results indicated that histopathologic responders may represent a subgroup of patients who benefit from neoadjuvant therapy followed by surgery.

Aged↗

PubMed2005

Combined GADD45A and thymidine phosphorylase expression levels predict response and survival of neoadjuvant-treated gastric cancer patients.

PURPOSE: We evaluated the expression of seven therapy-related genes to predict the clinical outcome of advanced gastric cancer patients treated with a neoadjuvant chemotherapeutic protocol. EXPERIMENTAL DESIGN: Pretherapeutic, formalin-fixed, and paraffin-embedded biopsies of 61 patients, who received a 5-fluorouracil (5-FU)- and cisplatin-based chemotherapy were studied. The expressions of the 5-FU-related genes TS, DPD, and TP and of the cisplatin-related genes ERCC1, ERCC4, KU80, and GADD45A were analyzed by quantitative real-time PCR. The expression levels of single genes and of various combinations were tested for an association with response and overall survival. RESULTS: High DPD levels were more frequently found in nonresponding patients and were associated with worse survival. GADD45A and TP levels showed weak associations with response, but GADD45A expression correlated with survival. There was no association with response for TS expression, but tumors with a high TS level were associated with worse survival. The combination of GADD45A and TP revealed the strongest predictive effect. High expression values of TP and/or GADD45A were exclusively found in nonresponding patients (P = 0.002) and were associated with a significantly poorer survival (P = 0.04). CONCLUSIONS: Combined gene expression levels of TP and GADD45A represent a new variable to predict the clinical outcome after neoadjuvant chemotherapy in gastric cancer. The association of DPD expression with response and survival underlines a predominant role of DPD to predict 5-FU sensitivity. The association of TS expression levels with survival but not with response suggests an importance of this gene for tumor progression.

Adult↗

PubMed2004

Clinical response to induction chemotherapy predicts local control and long-term survival in multimodal treatment of patients with locally advanced esophageal cancer.

PURPOSE: From 1991 to 1994 we performed a phase II study with intensive preoperative chemoradiation in locally advanced squamous cell carcinoma and adenocarcinoma of the esophagus. We now report on a multivariate analysis of prognostic factors based on the long-term results at a median follow-up of 6.5 years. PATIENTS AND METHODS: Eighty-eight patients were treated. Prognostic factors for overall survival and local tumor control were identified by univariate and multivariate analysis. RESULTS: Median overall survival reached 17 months, and the survival rate at 5 years was 22% (95%-confidence interval: 18-26%). Response to induction chemotherapy was the only independent factor predicting local tumor control and--beside weight loss prior to treatment--it also proved to be an independent prognostic factor for long-term survival. CONCLUSIONS: Intensive chemoradiation followed by surgery seems to be appropriate to improve long-term survival of high-risk patients with locally advanced esophageal cancer. In our trial, local tumor control and prognosis were best correlated with response to induction chemotherapy. These results may help to guide decisions regarding surgery in multimodal treatment of EC. Further efforts are needed to increase the number of treatment responders and to predict tumors not responding to chemo(radio)therapy earlier.

Adenocarcinoma↗

PubMed2004

Time course of tumor metabolic activity during chemoradiotherapy of esophageal squamous cell carcinoma and response to treatment.

PURPOSE: To evaluate the time course of therapy-induced changes in tumor glucose use during chemoradiotherapy of esophageal squamous cell carcinoma (ESCC) and to correlate the reduction of metabolic activity with histopathologic tumor response and patient survival. PATIENTS AND METHODS: Thirty-eight patients with histologically proven intrathoracic ESCC (cT3, cN0/+, cM0) scheduled to undergo a 4-week course of preoperative simultaneous chemoradiotherapy followed by esophagectomy were included. Patients underwent positron emission tomography with the glucose analog fluorodeoxyglucose (FDG-PET) before therapy (n = 38), after 2 weeks of initiation of therapy (n = 27), and preoperatively (3 to 4 weeks after chemoradiotherapy; n = 38). Tumor metabolic activity was quantitatively assessed by standardized uptake values (SUVs). Results Mean tumor FDG uptake before therapy was 9.3 +/- 2.8 SUV and decreased to 5.7 +/- 1.9 SUV 14 days after initiation of chemoradiotherapy (-38% +/- 18%; P <.0001). The preoperative scan showed an additional decrease of metabolic activity to 3.3 +/- 1.1 SUV (P <.0001). In histopathologic responders (< 10% viable cells in the resected specimen), the decrease in SUV from baseline to day 14 was 44% +/- 15%, whereas it was only 21% +/- 14% in nonresponders (P =.0055). Metabolic changes at this time point were also correlated with patient survival (P =.011). In the preoperative scan, tumor metabolic activity had decreased by 70% +/- 11% in histopathologic responders and 51% +/- 21% in histopathologic nonresponders. CONCLUSION: Changes in tumor metabolic activity after 14 days of preoperative chemoradiotherapy are significantly correlated with tumor response and patient survival. This suggests that FDG-PET might be used to identify nonresponders early during neoadjuvant chemoradiotherapy, allowing for early modifications of the treatment protocol.

Aged↗

PubMed2003

Prediction of response to preoperative chemotherapy in gastric carcinoma by metabolic imaging: results of a prospective trial.

PURPOSE: We prospectively evaluated the predictive value of therapy-induced reduction of tumor glucose use for subsequent response and patient survival in patients with gastric cancer treated by preoperative chemotherapy. PATIENTS AND METHODS: Forty-four consecutive patients with locally advanced gastric carcinomas were studied by positron emission tomography with the glucose analog fluorine-18 fluorodeoxyglucose (FDG-PET) at baseline and 14 days after initiation of cisplatin-based polychemotherapy. On the basis of a previous study, a reduction of tumor FDG uptake by more than 35% was used as a criterion for a metabolic response. The metabolic response in FDG-PET was correlated with histopathologic response after completion of therapy (< 10% viable tumor cells in the resected specimen) and patient survival. RESULTS: Thirty-five (80%) of the 44 tumors were visualized with sufficient contrast for quantitative analysis (two of 19 intestinal and seven of 25 nonintestinal tumors showed only low FDG uptake). In the 35 assessable patients, PET imaging after 14 days of therapy correctly predicted histopathologic response after 3 months of therapy in 10 (77%) of 13 responders and 19 (86%) of 22 nonresponders. Median overall survival for patients with a metabolic response has not been reached (2-year survival rate, 90%); for patients without a metabolic response, median survival was only 18.9 months (2-year survival rate, 25%; P =.002) CONCLUSION: This study prospectively demonstrates that in patients with gastric cancer, response to preoperative chemotherapy can be predicted by FDG-PET early during the course of therapy. By avoiding the morbidity and costs of ineffective therapy, FDG-PET imaging may markedly facilitate the use of preoperative chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Histomorphology and grading of regression in gastric carcinoma treated with neoadjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy has shown some success in the treatment of gastric carcinoma, but objective parameters for measuring its effects are lacking. The authors performed the current study to determine which histomorphologic features are correlated with patient prognosis after chemotherapy. METHODS: Thirty-six patients with gastric carcinoma were treated with a combination of etoposide, doxorubicin, and cisplatin. The entire tumor beds of the specimens were evaluated histologically and compared with specimens treated with surgery alone. Thirty-four patients were available for survival analysis (follow-up period, 60-130 months). RESULTS: None of the 36 patients had complete tumor regression, 4 patients had marked regression (less than 10% viable tumor), 9 patients had regression to 10-50% remaining viable tumor, and 23 patients had more than 50% viable tumor remaining. Currently, 9 patients are still alive (5-year survival rate, 27%). Tumor regression was found to be correlated significantly with survival (P = 0.01), but tumor size (P = 0.002) and lymphatic vessel invasion (P = 0.003) were better predictors of prognosis. CONCLUSIONS: Histologic tumor regression grade is an objective measure of the effects of neoadjuvant chemotherapy in patients with gastric carcinoma, but its accuracy may be improved by adding additional staging variables such as tumor size and lymphatic vessel involvement. Cancer 2003;98:1521-30.

Adult↗

PubMed2003

Current status of neoadjuvant therapy for adenocarcinoma of the distal esophagus.

Prospective studies dealing with preoperative therapy in adenocarcinoma of the esophagus alone are rare. The interpretation of the preferential phase II trials and a few phase III trials is complicated, as most studies include adenocarcinoma of the esophagus (i.e., Barrett's carcinoma), adenocarcinoma of the esophagogastric junction (including cardia carcinoma and subcardia carcinoma), or squamous cell carcinoma. Preoperative chemotherapy, generally well tolerated, cannot decrease the incidence of local failure beyond the level achieved with surgery alone, but it might delay systemic relapse. Preoperative radiotherapy can enhance local control, but it fails to improve overall survival. Neoadjuvant chemoradiation was demonstrated in only one randomized trail to have a survival benefit, but survival in the surgery-alone group was unusually low. Generally, survival was ameliorated in patients responding to neoadjuvant treatment. However, preoperative chemoradiation was often accompanied by a remarkable increase in postoperative morbidity and mortality. Nonresponding patients have, in this respect, a worse prognosis than responders after resection. The prediction of responding patients to neoadjuvant therapy as well as the early identification of patients who will not respond is of utmost clinical importance. Today, there is no absolute evidence that neoadjuvant treatment for patients with potentially resectable Barrett's cancer prolongs survival. In patients with locally advanced, presumably not completely resectable adenocarcinoma of the esophagus, preoperative treatment appears to increase the chance for a curative resection and enhance survival in responding patients. Neoadjuvant treatment of adenocarcinoma of the esophagus, as a consequence, is currently not the standard treatment and should be performed only within controlled clinical trials.

Adenocarcinoma↗

PubMed2003

Fluorodeoxyglucose-positron emission tomography in adenocarcinomas of the distal esophagus and cardia.

Adenocarcinomas of the esophagogastric junction (AEG) are now recognized as a separate tumor entity with increasing incidence. The aim of the present study was to evaluate whether positron emission tomography (PET) using the glucose analog F-18-fluorodeoxyglucose (FDG) can be used for metabolic characterization of this tumor type. Fifty-two patients with histologically proven, locally advanced AEG (distal esophagus, type I: n = 31; cardia, type II: n = 21) were studied by FDG-PET. None of the tumors had been previously treated. Findings of endoscopy (growth type), endoluminal ultrasound (uT, uN), computed tomography (cN, cranio-caudal extent, tumor thickness), histological evaluation (Lauren classification, tumor grade), anatomical classification, and survival were correlated with the results of FDG-PET. There was no correlation between FDG uptake and clinical stage, grade, Lauren classification, or survival. All AEG I tumors were visualized by FDG-PET with high contrast, whereas FDG uptake by five AEG II tumors (24%) did not differ from background activity. In a quantitative analysis, mean FDG uptake of AEG I tumors was 1.6 times higher than that of AEG II tumors ( p = 0.0005). PET can be used to visualize type I adenocarcinomas of the esophagogastric junction (AEG I). In AEG II tumors, however, the use of FDG-PET appears to be limited. The significantly higher FDG uptake of AEG I tumors compared to AEG II tumors suggests that these two tumor types differ in glucose utilization. This finding strengthens the hypothesis that AEG I and AEG II are two different tumor entities.

Adenocarcinoma↗

PubMed2003

Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study.

BACKGROUND: Patients with locally advanced gastric cancer (cT3, cT4, N+, M0) have a dismal prognosis, despite complete resection. The objective of this study was to evaluate the toxicity and efficacy of neoadjuvant chemotherapy using the PLF (cisplatin/leucovorin [folinic acid]/5-fluorouracil [FU]) regimen in these patients. Primary endpoints of the study were the toxicity and the response to chemotherapy. Secondary endpoints were the rate of complete resection, survival, and first site of failure. METHODS: Forty-nine patients with adenocarcinoma of the stomach were enrolled. Staging was based on abdominal computed tomography (CT) scans, endosonography, and laparoscopy. The intention was to administer two cycles (each containing six courses) of preoperative chemotherapy, consisting of cisplatin 50 mg/m(2), high-dose folinic acid (HD-FA) 500 mg/m(2), and HD 5-FU (HD-5-FU) 2000 mg/m(2) (PLF). Following chemotherapy all patients were referred to surgery. To be evaluable for response, survival, and first site of failure, the patient had to receive at least one cycle of chemotherapy. RESULTS: Toxicity observed was low, with grade 3 toxicity in fewer than 5% of the patients and two events of grade 4 toxicity (diarrhea and pulmonary embolism). Forty-two of the patients (86%) received at least one cycle of chemotherapy. The clinical response rate in these patients was 26% (11/42 patients). In 76% of the patients (32/42), a complete resection was possible. The median duration of follow-up for the surviving patients was 58 months (range, 38 to 80+ months). The median survival time for the 42 patients assessable for response was 25.4 months (range, 6 to 80+ months). After complete resection, median survival time was 32 months (range, 7.6 to 80+ months). The median survival time for clinically responding patients has not yet been determined, but 5-year survival is 90%. Twenty of the 32 completely resected patients (62.5%) had recurrences. First site of failure was peritoneal dissemination in 10 patients; locoregional and distant recurrences were rare. CONCLUSION: Neoadjuvant chemotherapy with PLF in patients with locally advanced gastric cancer has low toxicity and reasonable efficacy, allowing administration on an outpatient basis. Clinically responding patients have an excellent outcome after complete resection. The development of peritoneal dissemination even after neoadjuvant chemotherapy and complete resection remains an unsolved problem in patients with nonintestinal type tumors.

Adenocarcinoma↗

PubMed2003

Chromosomal instability rather than p53 mutation is associated with response to neoadjuvant cisplatin-based chemotherapy in gastric carcinoma.

PURPOSE: The objective of the study was to evaluate microsatellite alterations [microsatellite instability (MSI) and loss of heterozygosity (LOH)] and mutation in the p53 gene in relation to response and patient survival to a cisplatin-based neoadjuvant chemotherapy in gastric cancer. EXPERIMENTAL DESIGN: Fifty-three pretherapeutic gastric carcinoma biopsies were analyzed with 11 microsatellite markers. The entire coding region of the p53 gene (exons 2-11) was analyzed for mutations by denaturing high-pressure liquid chromatography and sequencing. p53 protein expression was evaluated by immunohistochemistry. Patients were treated with a cisplatin-based, neoadjuvant chemotherapy regimen. Therapy response was evaluated by computed tomography scan, endoscopy, and endoluminal ultrasound. The median follow-up of the patients was 45.6 months. RESULTS: p53 mutations were identified in 19 of the 53 (36%) analyzed tumors. No significant association with response or survival was found for p53 mutation or for p53 protein expression. MSI (either high-grade MSI or low-grade MSI) did not show a correlation with response. With respect to LOH, LOH at chromosome 17p13 showed a significant association with therapy response (P = 0.022) but did not reach statistical significance in terms of patient survival. The global LOH rate, expressed as fractional allelic loss (FAL), was assessed, and tumors were classified into tumors with a high (>0.5), medium (>0.25-0.5), and low (0-0.25) FAL value. A statistically significant association of FAL with therapy response was found (P = 0.003), with a high FAL being related to therapy response. The sensitivity, specificity, positive predictive value, and negative predictive value for FAL > 0.5 were 45%, 93%, 82%, and 72%, respectively. CONCLUSIONS: A high level of chromosomal instability (high FAL value) defines a subset of patients who are more likely to benefit from cisplatin-based neoadjuvant chemotherapy. p53 mutation status is not significantly associated with therapy response and is not a useful marker for response prediction.

Adult↗

PubMed2002

FDG PET imaging of locally advanced gastric carcinomas: correlation with endoscopic and histopathological findings.

Gastric cancer carries a poor prognosis and is the second most frequent cause of cancer-related death worldwide. In spite of the clinical importance of this tumour entity, only a few fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) studies have been published on gastric carcinomas. The aim of this study was to characterise the FDG uptake of gastric carcinomas by relating it to the histopathological properties of the tumours. Within this context, we focussed particularly on the microscopic growth type according to Lauren since our preliminary observations indicated low FDG accumulation in the non-intestinal growth type compared with the intestinal type. Forty patients with locally advanced gastric carcinomas and ten control subjects were studied by FDG PET (300 MBq i.v., emission scan: 40 min p.i., one bed position, measured transmission, filtered back-projection). Detectability of the tumours was qualitatively assessed by two independent observers. For quantitative analysis the regional tumour uptake was measured by standardised uptake values (SUV normalised to the body surface area) using a region of interest technique. Qualitative and quantitative analyses were performed with respect to the microscopic growth type according to Lauren (intestinal type vs non-intestinal type). Other histopathological characteristics were also assessed: mucus content, grading, tumour extension and tumour location. In 36 patients the survival rates were compared for detectable vs non-detectable tumours and for tumour FDG uptake above and below the median. Only 24 of the 40 locally advanced gastric carcinomas (60%) were detected by FDG PET. The detection rate for tumours of the intestinal type was significantly higher than that for tumours of the non-intestinal type (83% vs 41%, P=0.01). Only 2/18 intestinal type tumours contained extracellular or intracellular mucus whereas 17/22 non-intestinal tumours did so (P<0.01). The mean SUV was significantly different between the intestinal type and the non-intestinal type (6.7+/-3.4 vs 4.8+/-2.8, P=0.03), between non-mucus-containing tumours and mucus-containing tumours (7.2+/-3.2 vs 3.9+/-2.1, P<0.01) and between grade 2 tumours and grade 3 tumours (7.4+/-2.3 vs 5.2+/-3.3, P=0.02). The survival rate was not significantly different in patients with detectable tumours on FDG PET and patients with non-detectable tumours (P=0.85). It is concluded that advanced malignant tumours with a poor prognosis may show low FDG uptake due to special histopathological characteristics. The overall low detection rate of gastric carcinomas is attributable to the frequent occurrence of diffusely growing and mucus-containing tumour types. This may limit the value of FDG PET for diagnosis and therapy monitoring in patients with gastric carcinomas. Furthermore, the intensity of tumour FDG uptake is not predictive of survival in gastric carcinomas.

Fluorodeoxyglucose F18↗

PubMed2002

PET imaging with [11C]methyl- L-methionine for therapy monitoring in patients with rectal cancer.

In this study we evaluated whether positron emission tomography (PET) using the amino acid [11C]methyl- L-methionine (MET) may be used for therapy monitoring in patients with rectal cancer who are undergoing preoperative chemoradiotherapy. A total of 41 MET-PET scans were performed in 26 patients with locally advanced rectal cancers. All patients were examined prior to chemoradiotherapy. In 15 patients, MET-PET was repeated after preoperative chemoradiotherapy (45 Gy radiation dose, 250 mg 5-fluorouracil as continuous infusion). MET uptake prior to and after the completion of chemoradiotherapy was correlated with changes in T stage and histopathological regression. All tumours were visualised with high contrast and had a significantly higher SUV (5.7+/-2.2) than normal rectum (2.7+/-0.9) and all other organs in the field of view except the small intestine (3.9+/-1.7). In all tumours studied prior to and after chemoradiotherapy, MET uptake decreased during therapy (SUV before therapy, 6.2+/-2.3; SUV after therapy, 2.6+/-1.2; P=0.0007). However, the degree of change in MET uptake was not correlated with histopathological tumour response. In conclusion, primary rectal cancer can be imaged with MET-PET. However, for the studied chemoradiotherapy regimen, MET-PET did not allow an assessment of the response to therapy.

Adult↗

PubMed2002

Emergency diagnosis with spiral CT angiography in case of suspected ventral perforation following lumbar disc surgery.

BACKGROUND: Ventral perforation and vascular lesions are rare but life-threatening complications in lumbar disc surgery. In some cases, however, it remains unclear from the clinical situation whether a laparotomy is necessary to save the patient. The goal of this study is to demonstrate the value of spiral CT (computed tomography) angiography for emergency vascular diagnosis in two cases. METHODS: Spiral CT angiography with an intravenous bolus contrast medium injection and reconstruction with images in sagittal, coronal, and oblique planes was performed. RESULTS: Spiral CT angiography confirms or excludes a vascular lesion, as demonstrated in two case reports. CONCLUSION: In unclear cases when ventral perforation in lumbar disc surgery is suspected, the need for emergency laparotomy can be confirmed quickly by noninvasive spiral CT angiography.

Adult↗

PubMed2002

Ceramic and PMMA particles differentially affect osteoblast phenotype.

There is increasing evidence that wear debris particles present in periprosthetic tissues have direct effects on osteoblasts. The nature of the cell response varies with the chemistry of the particle and the number of particles. Most studies have used Ti, Ti-6Al-4V, and ultrahigh molecular weight polyethylene (UHMWPE) particles since these materials are most frequently used in implants and as a result, these particles predominate in peri-prosthetic tissues. Ceramics have also been used successfully as load-bearing surfaces in implants for years, although it is unknown how wear debris from these surfaces may contribute to aseptic bone loss. Further, particles resulting from polymethylmethacrylate (PMMA) cements used for fixation may also be involved in aseptic loosening of implants, but how these particles may affect bone formation is unknown. In the present study, we examined whether aluminum oxide (Al2O3), zirconium oxide (ZrO2), and PMMA particles exert effects on osteoblast proliferation, phenotypic expression, and local factor production, and if so, whether the effects were specific to the particle type. ZrO2 particles were produced in a custom-made axial mixer in which ZrO2 containers were filled with ZrO2 bars and 95% ethanol and then rotated continuously at room temperature. PMMA particles were prepared in a ZrO2 roller mill. Al2O3 was produced and provided by Aesculap AG. Particles were endotoxin-free with equivalent circle diameters <3 microm; Al2O3 particles were significantly smaller than ZrO2 or PMMA particles. Particle suspensions were added to confluent cultures of MG63 osteoblast-like cells after diluting them 1:100, 1:10, and 1:1 with culture medium. Cells were incubated with the particles for 24 h. Transmission electron microscopy showed that MG63 cells phagocytosed Al2O3 particles and exhibited ultrastructural changes consistent with cytotoxicity. This was supported by biochemical changes as well. Proliferation, alkaline phosphatase activity, and TGF-beta1 levels were decreased. ZrO2 and PMMA particles increased proliferation and alkaline phosphatase specific activity. The effect of ZrO2 on alkaline phosphatase was targeted to matrix vesicles, the effect of PMMA was greater on the cells. All particles increased prostaglandin E2 production. These results show that Al2O3, ZrO2, and PMMA particles elicit direct effects on osteoblasts and that cell response depends on the particle type. None of the particles tested had the same effect as noted previously for UHMWPE: increased proliferation and decreased alkaline phosphatase. These results may indicate that the response of peri-prosthetic tissues to wear particles may be modulated by the relative contributions of the various particle types present.

Alkaline Phosphatase↗