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Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Surgery has been the only effective therapy. However, many patients still eventually die of disease recurrence. Chemotherapy and radiation therapy have been of limited value. Imatinib mesylate (Glivec) is an orally administered competitive inhibitor of tyrosine kinases associated with the KIT, ABL protein, licensed for the treatment of metastatic GIST since 2002 in Germany., Methods: We summarized the data of 16 patients with advanced or metastatic GIST treated with imatinib mesylate in palliative and neoadjuvant settings., Results: Overall response was 81%, with no evidence of disease (NED) in 3/16 (19%), partial response (PR) in 9/16 (56%) and stable disease (SD) in 1/16 (6%), whereas 3/16 patients (19%) suffered from progressive disease (PD). Mean follow-up was 18.6 months [range: 4-30]. Mean progression-free survival (PFS) was 17.6 months [range: 0-30], mean overall survival (OS) from initial diagnosis was 32.3 months [range: 5-122]. Most common side effects were periorbital edema and skin rash., Conclusion: Imatinib mesylate is well tolerated in a dose of up to 800 mg/day and has significant activity during long- term treatment of patients with advanced or metastatic GIST., (Copyright 2006 S. Karger AG, Basel.)

MR-guided LITT is a safe and effective treatment modality that improves survival in well-selected patients who have liver metastases. A major advantage of MR-guided LITT is that it can be easily performed under local anesthesia in an outpatient setting with a low complication rate.

Interventional therapeutic methods are presented in Carney triad, which is a syndrome defined as the simultaneous presence of gastric leiomyosarcoma, extra-adrenal paraganglioma, and pulmonary chondroma. The paragangliomas in the carotid bifurcation and the mediastinum were successfully treated via transarterial embolization with particles. Three intrapulmonary chondromas were ablated using MRI-guided laser-induced thermotherapy (LITT) after previous devascularization via transvenous pulmonary particle embolization. In summary, interventional techniques could be a therapeutic option in patients suffering from Carney triad.

To assess the benefit of routinely used three-dimensional 1H-spectroscopy of the prostate combined with magnetic resonance imaging in patients with elevated prostate-specific antigen (PSA) levels and negative or no previous prostate biopsies. Fifty-four patients were examined with our combined imaging protocol, which consisted of transversal, coronal and sagittal T2-weighted fast spin echo sequences. For spectroscopy, we used a three-dimensional chemical shift imaging spin echo (3D-CSI-SE) sequence. The study population consisted of patients with elevated PSA levels and histologically proven prostate carcinoma and patients with elevated PSA levels and negative or no previous prostate biopsies. Examination time was 31 min, a time feasible for routine use. Eighty-eight tumour voxels and 67 control voxels of 27 patients with histologically proven prostate carcinoma were analysed. Ratios of (choline + creatine)/citrate [(Cho + Crea)/Cit] below 0.6 were classified as normal and above 0.6 as pathological. Applying this classification to 20 patients with tumour-suspicious lesions of the prostate and negative or no previous prostate biopsies, we could obtain a sensitivity and specificity for tumour detection of 100% and 69%, respectively. Our combined imaging protocol is feasible for routine use and can add valuable information for the diagnostic management of patients with negative or no previous prostate biopsies.

Objective: The objective of this study was to evaluate the prognostic significance of preoperative positron emission tomography (PET) using 2-fluoro-2-deoxy-D-glucose (FDG) by calculating the mean standardized uptake values (SUV) in patients with resectable soft tissue sarcomas (STS)., Summary and Background Data: FDG-PET might be used as an adjunctive tool (in addition to biopsy and radiologic tomography) in the preoperative prognostic assessment of resectable STS., Methods: A total of 74 adult patients with STS underwent preoperative FDG-PET imaging with calculation of the SUV. Clinicopathologic data and the SUV were analyzed for an association with the clinical outcome. The first and the third quartiles of the SUV distribution function were used as cutoff values (1.59 and 3.6). Survival was estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using log-rank test and the Cox proportional hazards regression model., Results: In 55 cases, STS were completely resected (follow up 40 months): 5-year recurrence-free survival rates in patients with SUV <1.59, 1.59 to <3.6, and > or =3.6 were 66%, 24%, and 11%, respectively (P = 0.0034). SUV was a predictor for overall survival (5-year rates: 84% [SUV <1.59], 45% [SUV 1.59 to <3.6], and 38% [SUV > or =3.6]; P = 0.057) and local tumor control (5-year rates: 93% [SUV <1.59], 43% [SUV 1.59 to <3.6], and 15% [SUV > or =3.6]; P = 0.0017). By multivariate analysis, SUV was found to be predictive for recurrence-free survival. The prognostic differences with respect to the SUV were associated with tumor grade (P = 0.002)., Conclusion: The semiquantitative FDG uptake, as measured by the mean SUV on preoperative PET images in patients with resectable STS, is a useful prognostic parameter. SUV with cutoff values at the first and the third quartiles of the SUV distribution predicted overall survival, recurrence-free survival, and local tumor control. Therefore, FDG-PET can be used to improve the preoperative prognostic assessment in patients with resectable STS.

The purpose of this study was to examine the feasibility and safety of MR-guided biopsies with a transgluteal approach in patients with uncertain or suspicious prostate lesions. Twenty-five patients with uncertain or suspicious focal prostate lesions detected by high-field MR imaging of the prostate gland using endorectal coil imaging were biopsied with a transgluteal approach in a low-field MRI system (0.2 T, Concerto, Siemens). The procedures were guided using T1-weighted FLASH sequences. The prostate gland was biopsied repeatedly with a coaxial technique through a 15-gauge pencil tip with a 16-gauge biopsy handy (median 3.8 samples per patient). Complications and biopsy findings were documented retrospectively. Using T1-weighted sequences biopsy procedures were performed successfully with MR guidance in all cases without any side effects or complications. The median intervention time was 11.3 min. Pathological findings revealed ten cases of hyperplasia or atrophy, three cases of prostatitis, ten cases of carcinoma and two cases of normal tissue. The clinical follow-up showed that in two patients prostate cancer was missed at MR-guided biopsy. Transgluteal MR-guided biopsy of the prostate gland is a safe and promising approach for histological clarification of uncertain or suspicious lesions.

Purpose: To evaluate the local tumor control rate and survival data for magnetic resonance (MR) imaging-guided laser ablation of breast cancer liver metastases by using laser-induced interstitial thermotherapy (LITT)., Materials and Methods: MR-guided LITT was performed in 232 female patients with 578 liver metastases from breast cancer. Survival rates were calculated with the Kaplan-Meier method. Indications for the procedure were defined for patients with no more than five metastases, none of which were larger than 5 cm in diameter, as follows: recurrent liver metastases after partial liver resection (8.2%), metastases in both liver lobes (45.2%), locally nonresectable tumors (19%), general contraindications for surgery (2.6%), or refusal to undergo surgical resection (25%)., Results: Local recurrence rate at 6-month follow-up after LITT was 2.3% (five of 213) for metastases up to 2 cm in diameter, 4.3% (seven of 162) for metastases 2-3 cm in diameter, 3.2% (two of 63) for metastases 3-4 cm in diameter, and 1.9% (one of 52) for metastases larger than 4 cm in diameter. No additional local tumor progression was observed beyond 6 months. The mean survival rate for all treated patients, with calculation started on the date of diagnosis of the metastases treated with LITT, was 4.9 years (95% confidence interval: 4.3, 5.4). The median survival was 4.3 years; 1-year survival, 96%; 2-year survival, 80%; 3-year survival, 63%; and 5-year survival, 41%. The mean survival after the first LITT treatment was 4.2 years (95% confidence interval: 3.6, 4.8)., Conclusion: MR-guided LITT yields high local tumor control and survival rates in patients with liver metastases from breast cancer.

Objective: The objective of this study was to assess the intracochlear position and the extent of trauma to cochlear structures using a new prototype electrode carrier (Flex EAS). Special emphasis was placed on the practicality for combined electric and acoustic stimulation of the auditory system., Study Design: Human temporal bones were evaluated histologically after insertion of the electrodes, and insertion forces were measured in an acrylic model of the scala tympani., Methods: 1) Insertion forces with the regular C40+ array and the new electrode prototype were measured in an acrylic model of the scala tympani. 2) Ten human temporal bones were implanted using the same surgical procedure as in vivo. All bones underwent fixation methylmethacrylate embedding to allow cutting of the undecalcified bone with the electrode in situ. In addition, radiography of the implanted devices was performed and correlated to histologic results. Electrode positions and trauma to cochlear structures were then evaluated histologically., Results: All insertions of the new electrode array were performed in the scala tympani of the cochlea. All insertions were atraumatic and covered one cochlear turn. The only effect on cochlear structures that could be observed was a slight lifting of the basilar membrane in the middle turn limited to the tip of the electrode. In three bones, basal trauma, which resulted from the cochleostomy itself, could be observed as well. All neural structures remained intact., Conclusions: The new electrode prototype provides very good mechanical properties for safe and atraumatic implantation. All criteria for the use in hearing-preservation cochlear implantation for electric and acoustic stimulation were fulfilled. Surgical measures to prevent basal trauma appear to be very important.

Background & Aims: The biliary epithelium of bile ducts and gallbladder modifies the composition of primary hepatic bile by absorption and secretion of an electrolyte-rich fluid. The underlying transport mechanisms, however, are still incompletely understood. We investigated the expression, the cellular localization, and the functional role of guanylin, a bioactive intestinal peptide involved in the cystic fibrosis transmembrane conductance regulator (CFTR)-regulated electrolyte/water secretion, in the human gallbladder., Methods: Peptide-specific antibodies were raised to localize guanylin and its affiliated signaling proteins, i.e., the guanylin receptor, guanylate cyclase C (GC-C), cGMP-dependent protein kinase type II (cGKII), and CFTR in the human gallbladder and cholangiocarcinoma cells (Mz-Cha-1) by RT-PCR, Western blot, and immunocytochemistry. A sensitive ELISA was used to assess the range of guanylin concentration in human bile fluid. The functional role of guanylin was investigated in subconfluent Mz-Cha-1 cell monolayers by isotope efflux experiments., Results: Guanylin and its affiliated signaling proteins are highly expressed in the human gallbladder. Guanylin is localized to secretory epithelial cells of the gallbladder and is present in the bile, whereas GC-C, cGKII, and CFTR are confined exclusively to the apical membrane of the same epithelial cells. Functional studies in Mz-Cha-1 cells identify guanylin as a specific regulator of biliary Cl(-) secretion that very likely is mediated by an intracellular increase of cGMP-concentration., Conclusions: Based on the present findings and on the functional role of guanylin in other epithelia, it is likely that gallbladder epithelial cells synthesize and release guanylin into the bile to regulate electrolyte secretion by a paracrine/luminocrine signaling pathway.

Gastrointestinal stromal tumours (GISTs), the most common mesenchymal tumours of the digestive tract, are largely resistant to chemo- and radiotherapy. They are currently defined by their overexpression of the KIT receptor tyrosine kinase (CD117), a member of the family of receptor tyrosine kinases (RTKs), and exhibit KIT mutations in more than 85% of cases. Additionally, in more than one-third of KIT wild-type GISTs, mutations of platelet-derived growth factor receptor alpha (PDGF-R alpha), which also belongs to the family of RTKs, were recently found. Since these data indicate that uncontrolled RTK signalling may be implicated in the pathogenesis of GISTs, RTKs and the activated downstream signalling cascades are attractive targets in the therapy of these tumours. Imatinib is a small-molecule inhibitor that selectively blocks the activity of the PDGF-R, ABL and KIT receptor tyrosine kinases by competitive binding to the adenosine triphosphate binding site of their catalytic domains. We herein review the molecular pathological, preclinical and clinical data that identify imatinib as a valuable new agent in the treatment of GISTs.

Background/aims: Apoptosis is a key event in the pathophysiology of many liver diseases. Primary human hepatocytes (PHH) provide a useful model to study physiological and pathophysiological processes in the liver. Our aim was to optimize PHH cultures to allow studies on induction of apoptosis and of hepatitis B virus (HBV) infection., Methods: PHH were isolated from human liver tissue by two-step collagenase perfusion. PHH and hepatoma cells were treated with different apoptosis-inducing agents in parallel. PHH cultures were infected with wild type HBV and transduced with HBV genomes using adenoviral vectors., Results: PHH were successfully isolated from 40 different tissue samples with high viability and purity. Perfusion time and seeding density turned out to be critical parameters for optimal cell yield and culture conditions, respectively. Serum addition to the medium reduced viability of PHH. PHH allowed reproducible studies of CD95-dependent and -independent apoptosis. Sensitivity towards CD95-mediated apoptosis was markedly higher than in hepatoma cells. PHH could efficiently be infected with HBV, but infection did neither induce apoptosis nor prevent CD95-induced cell death., Conclusions: Our data show that PHH provide an excellent tool for the investigation of apoptosis induced by agents like death receptor-ligands and hepatotropic viruses.

In healthy humans, parathyroid hormone (PTH) is secreted via basal mode with superimposed oscillatory bursts every 8 to 12 min. Amplitude and frequency changes mediate the instantaneous response of the parathyroids to changes in ambient Ca(2+) concentrations. The parathyroid gland tetrad may be synchronized by autonomic innervation. This study investigated the effect of total parathyroidectomy and heterotopic autotransplantation of parathyroid tissue (PTX) on PTH secretion patterns in nine patients with end-stage renal disease. Intact-PTH versus time concentration profiles were obtained early (1 to 8 wk, n = 4) or late (15 to 33 mo, n = 5) after PTX. In four patients late after PTX, Ca(2+) responsiveness of PTH secretion was additionally investigated by citrate and calcium clamp studies. The nonrandomness of plasma PTH fluctuations was assessed by the approximate entropy (ApEn) statistic, and secretion characteristics by multiparametric deconvolution analysis. Results were compared with those of matched normal subjects and chronic renal failure (CRF) patients without PTX. PTH burst frequency was 2.9 +/- 0.1 h(-1) early and 7 +/- 0.4 h(-1) late after PTX as compared with 8.1 +/- 0.4 h(-1) in CRF and 7 +/- 0.3 h(-1) in healthy controls. Fractional pulsatile PTH secretion was diminished after PTX (18 +/- 2%) compared with healthy controls (32 +/- 5%, P < 0.05) and CRF patients (25 +/- 4%, P = 0.05). The orderliness of PTH release was significantly reduced after PTX (ApEn: 1.59 +/- 0.03 versus 1.41 +/- 0.09 in healthy and 1.46 +/- 0.03 in CRF controls, P < 0.01). Acute hypocalcemia elicited a lesser increase in pulsatile PTH secretion in PTX patients (147 +/- 134%) than in the CRF (500 +/- 92%, P = 0.05) and healthy controls (1410 +/- 290%, P < 0.05), mainly due to a diminished mass of PTH secreted per burst. Pulsatile PTH secretion was also resistant to hypercalcemia, wherein the suppression of burst mass was significantly reduced compared with that in healthy controls. In conclusion, pulsatile PTH secretion is partially restored within 2 yr of PTX. However, the capacity of the autotransplanted tissue to adapt to changes in ionized calcium remains profoundly disturbed.

Purpose: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells and may be involved in protection from metastases. TRAIL receptor (TRAIL-R) 1 and TRAIL-R2, but not TRAIL-R3 and TRAIL-R4, mediate apoptosis. We examined the expression of TRAIL and its receptors in normal and neoplastic colon epithelium, and studied its correlation with prognosis in colon cancer., Experimental Design: Immunohistochemistry was performed on normal colon mucosa (n = 10), colon adenomas (n = 20), and R0-resected Unio Internationale Contra Cancrum stage II/III colon carcinomas (n = 129). Disease-free survival was examined by Kaplan-Meier estimates and the log-rank test. Prognostic factors were determined by multivariate Cox-analysis., Results: In normal colon mucosa, TRAIL and TRAIL-R2 were expressed mostly in the surface epithelium, whereas TRAIL-R1 and TRAIL-R4 were detected all along the crypt axis. In adenomas, this expression pattern was mostly retained, although some adenomas also neoexpressed TRAIL-R3. In carcinomas, the expression of TRAIL and TRAIL receptors was much more variable. TRAIL, TRAIL-R2, TRAIL-R3, and TRAIL-R4 expression did not correlate statistically with disease-free survival (multivariate analysis: P = 0.54, P = 0.67, P = 0.45, and P = 0.69, respectively), but TRAIL-R1 expression was significantly associated with disease-free survival in colon cancer (multivariate analysis: P = 0.003)., Conclusions: TRAIL-R1 is an independent prognostic factor in R0-resected Unio Internationale Contra Cancrum stage II/III colon cancer.

Purpose: Traditionally, liver surgery relies on Couinaud's liver segment classification. As the position and shape of these segments are variable and their borders are hidden within the homogeneous liver mass, the accuracy of segment identification methods needs computer-aided reevaluation., Method: The segmental liver anatomy of 23 patients receiving diagnostic helical CT scans because of suspected intrahepatic lesion was analyzed with the aid of a computer-based operation-planning system. We compared the standard Couinaud classification, which depends particularly on the main stems of portal and hepatic veins, with a method that calculates the segment borders by analyzing the complete portal venous tree. Volume, shape, and position of the liver segments found by each method were compared., Results: With reference to the portal vein-based method, segmental volumes were overestimated by the classic Couinaud method by up to 24% and underestimated to 13%. Volumes of Couinaud segments 4a, 7, and 8 were generally larger compared with those obtained by the portal vein-based method, whereas segments 3 and 6 were smaller. Gross variations were found in segments 5, 7, and 8. When shape and position were considered, poor correlation was found for five segments (median kappa = 0.35-0.45). Only segments 2, 7, and 8 had kappa values clearly above 0.45 in the majority of cases. The plane that divides the two hemilivers along the middle hepatic vein and the border between the left sector (segments 2 and 3) and the medial sector (4a and 4b) were found in both methods with very good conformity (kappa > 0.75)., Conclusion: Couinaud's method of dividing the liver into eight autonomous liver segments has to be accepted as a good approximation. Nevertheless, the volume, position, and shape of these segments and their segmental borders show significant variability.

Using comparative genomic hybridization, DNA copy number changes were studied in 14 pleomorphic liposarcomas and compared to those detected in high-grade areas of 9 dedifferentiated liposarcomas. A total of 251 gains and 84 losses were detected. The most frequent gains involved subregions of chromosomal arms 12q and 20q (70% each), 5p (57%), 6q and 9q (52% each), 1q, 7p and 17p (48% each), 1p (43%), 6p and 17q (39% each), 20p and 22q (35% each) as well as 7q and 12p (30% each). The same subregions were also affected by 30 high level amplifications. The most frequent losses were found in subregions of chromosomal arms 13q (35%) as well as 11q and 12p (30% each). Overall, gains of chromosomal material were more frequent than losses (p < 0.001). There were significant differences in the frequency and distribution of recurrent chromosomal imbalances between pleomorphic liposarcomas and the dedifferentiated areas of dedifferentiated liposarcomas. Gains of chromosomal material detected predominantly in pleomorphic liposarcomas involved subbands 5p13-p15 (p < 0.010), 1p21 (p < 0.019), 1q21-q22 (p < 0.040) and 7q22 (p < 0.049). Conversely, high level amplifications within chromosomal subregion 12q13-q21 were only found in the dedifferentiated components of dedifferentiated liposarcomas (p < 0.001). Overall, both gains and the less pronounced losses of chromosomal material were more frequent in pleomorphic than in dedifferentiated liposarcomas (p < 0.001 and p < 0.025, respectively). These results show that pleomorphic liposarcomas display a considerable number of recurrent chromosomal imbalances that are essentially different from those present in high-grade areas of dedifferentiated liposarcomas. Therefore, genetic data are considered as a helpful diagnostic adjunct for the discrimination between these 2 types of liposarcoma. The overall higher frequency of chromosomal imbalances in pleomorphic as compared to dedifferentiated liposarcomas could account for the more aggressive biological behavior of pleomorphic relative to dedifferentiated liposarcoma types., (Copyright 2002 Wiley-Liss, Inc.)

Objective: To review a single-center experience with 201 multivisceral resections for primary colorectal cancer to determine the accuracy of intraoperative prediction of potential curability, to identify prognostic factors, and to examine the effect of surgical experience on immediate outcome and long-term results., Summary Background Data: Locally advanced colorectal cancer may require an intraoperative decision for en bloc resection of surrounding organs or structures to achieve complete tumor removal. This decision must weigh the risk of complications and death of multivisceral resection against a potential survival benefit. Little is known about prognostic factors and the influence of surgical experience on the outcome of multivisceral resection for colorectal cancer., Methods: Patients undergoing multivisceral resection for primary colon or rectal cancer between 1982 and 1998 were identified from a prospective database. Patients were followed up according to a standard protocol., Results: Multivisceral resection was performed in 201 of 2,712 patients with a median age of 64 years. Postoperative rates of complications and death in 201 patients were 33% and 7.5%, respectively. A potentially curative resection was possible in 130 of 201 patients (65%) and histologic tumor infiltration was shown in 44% of patients with curative resection. Intraoperative assessment of curability was unreliable. After curative resection, the local recurrence rate was 11% and the overall 5-year survival rate was 51%. Multivariate analysis identified intraoperative blood loss (relative risk 1.7-6.4, P <.001), age 64 years or older (RR 3.7; P <.001), and UICC stage as independent prognostic factors (RR 2.0; P =.009). No prognostic significance was found for histologic tumor infiltration, the number of resected organs, or surgical experience., Conclusions: Multivisceral resection is safe, and long-term survival after curative resection is similar to that after standard resection. Because palliative resections cannot be predicted accurately at the time of surgery, every effort should be made to achieve complete tumor resection. Major blood loss but not surgical experience per se is an independent prognostic factor.

Malignancy following renal transplantation is an important medical problem during the long-term follow-up. The overall incidence of malignancy at this time is 3 to 5 times higher than in the general population. The most common malignancies are lymphoproliferative disorders (early after transplantation) and skin carcinomas (late after transplantation). The type of malignancy is different in various countries and dependent on genetic and environmental factors. Another important confounder for risk of malignancy after renal transplantation is the type of immunosuppression. Previous use of cytotoxic drugs (eg, cyclophosphamide) or a history of analgesic abuse are additional risk factors. Malignancy may even be transplanted by the graft. Previous cancer treatment in a uremic patient on the transplant waiting list is of great importance in relation to waiting time and postmalignancy screening. Finally, every dialysis patient on the waiting list should undergo a regular screening program before and after renal transplantation to detect a potentially malignant tumor in an early stage. In addition to specific oncological treatment, managing a malignancy after renal transplantation should include modification of immunosuppression., (Copyright 2002 by the National Kidney Foundation, Inc.)

Background: Local and multimodal therapeutic strategies for tumours of the oesophagus and gastric cardia, require precise preoperative staging. Endosonography is considered the most accurate staging method, while computed tomography (CT) has limitations especially in the evaluation of local infiltration. Macroscopic endoscopic evaluation was reported to be accurate in selected series, but no study has yet compared all three staging modalities., Methods: One hundred and seventeen unselected patients with tumours of the oesophagus and gastric cardia were prospectively staged first by the endoscopic macroscopic appearance and then by endosonography. All patients had preoperative CT scans, however, only the 36 patients receiving the scans at our institution were included in the study. The preoperative staging results were then compared to postoperative histology which was available as the gold standard in all included patients. Kappa statistics were used to exclude chance agreement of the clinical staging results with the pathohistological findings. Differences between the resulting kappa values for the different staging modalities were analysed with a jack-knife test., Results: Endoscopic macroscopic staging and endosonography (accuracy 67 and 69%, weighted kappa 0.78 and 0.84) were significantly more accurate than CT (accuracy 33%, weighted kappa 0.44) for determination of the T category (p = 0.006 and p = 0.001). After exclusion of tumours of the cardia (n = 33), the accuracy of macroscopic and endosonographic staging (accuracy 72 and 75%, weighted kappa 0.86 and 0.88) increased and remained more accurate than CT (accuracy 50%, weighted kappa 0.62). The main pitfall in our series in staging the T category was the overestimation of T2 tumours in the cardia as T3 or even as T4 tumours due to the inability to visualise the serosa. The accuracy of predicting lymph node metastasis was 68% for macroscopic endoscopic, 79% for endosonographic, and 67% for CT staging. Only endosonographic staging was significantly different from chance agreement with histology (weighted kappa = 0.56). Endosonographic staging was significantly more accurate than endoscopic macroscopic and CT staging (p = 0.03)., Conclusions: Endosonography is the most accurate staging modality for overall preoperative staging of oesophageal and cardial tumours. Endoscopic macroscopic staging allows a reasonably accurate assessment of the T category., (Copyright 2002 S. Karger AG, Basel)