Erste Ergebnisse der neoadjuvanten simultanen Radiochemotherapie bei fortgeschrittenen Rektumkarzinomen

Hintergrund: Bei lokal weit fortgeschrittenen Rektumkarzinomen ist das Erreichen eine R0-Resektion schwierig. Muss jedoch makroskopisch oder mikroskopisch Tumorrest zurückgelassen werden, ist die Prognose der Patienten schlecht. In den Leitlinien empfiehlt die Deutsche Krebsgesellschaft deshalb bei Patienten mit T4-Tumoren eine präoperative simultane Radiochemotherapie. Patienten und Methodik: Vom 1.5.1997 bis 30.11.1999 wurde bei 22 Patienten eine neoadjuvante Radiochemotherapie durchgeführt. Appliziert wurde eine Dosis von 45 Gy zuzüglich eines Boostes von 5,4 Gy. In der ersten und fünften Bestrahlungswoche erhielten die Patienten an fünf aufeinander folgenden Tagen eine Dosis von täglich 1000 mg/m² 5-FU als intravenöse Dauerinfusion über 24 Stunden. Bei auftretender Kardiotoxizität wurde die Chemotherapie auf 5-FU-Bolusinfusion oder Ralitrexed umgestellt. Ergebnisse: 19/22 Patienten konnten einer Operation zugeführt werden. Bei 16/19 (84%) der operierten Patienten konnte eine R0-Resektion erreicht werden. Eine funktionserhaltende Behandlung war bei 9/19 (47%) Patienten möglich. Ein Downstaging um mindestens eine T-Kategorie wurde bei 12/19 (63%) Patienten erzielt. Bei einer medianen Nachbeobachtungszeit von 16 Monaten ist bisher kein lokales Rezidiv bei den operierten Patienten aufgetreten. Das progressionsfreie Überleben der operierten Patienten (R0/R1) beträgt nach zwei Jahren 62%, die Überlebensrate 89%, bezogen auf alle Patienten 76%. Schlussfolgerung: Die präoperative simultane Radiochemotherapie kann zu einer verbesserten Rate an R0-Resektionen und sphinktererhaltenden Eingriffen betragen. Purpose: In locally advanced rectal cancer tumor-negative margins often cannot be obtained by surgery alone. Nevertheless only patients with complete tumor resection can be cured. Due to the poor prognosis of patients with R1/R2 resection the "Deutsche Krebsgesellschaft" recommends concurrent preoperative radiochemotherapy for patients with locally advanced rectal cancer. Patients and Methods: Between May 1997 and November 1999 22 patients were treated with preoperative radiochemotherapy. A total dose of 45 Gy with a small-volume boost of 5.4 Gy was delivered in conventional fractionation (single dose 1,8 Gy). On days 1 to 5 and 29 to 33 patients received concurrently 5-fluorouracil (5-FU) as continuous infusion of 1,000 mg/m². If there was any sign of cardiac toxicity chemotherapy was changed to 5-FU/folinic acid or ralitrexed. Results: Surgery following radiochemotherapy was performed in 19/22 patients. Resections with negative margins were achieved in 16/19 (84%) patients. Sphincter-conserving surgery was possible in 9/19 (47%) patients. A downstaging of at least 1 T category was found in 12/19 (63%) patients. With a median follow-up of 16 months no locoregional recurrences occurred in patients who underwent surgery. Two-year disease-free survival of resected patients is 62%, 2-year overall survival is 89%, of the whole population 76%. Conclusion: Preoperative radiochemotherapy followed by surgery is able to achieve clear resection margins in more than 70% of patients with locally advanced rectal cancer and may improve the rate of sphincter-conserving surgery.     

Long-term survival of glioblastoma multiforme: importance of histopathological reevaluation

The overall prognosis for patients with glioblastoma multiforme is extremely poor. However, a small proportion of patients enjoy prolonged survival. This study investigated retrospectively the extent to which erroneous histopathological classification may contribute to long-term survival of patients initially diagnosed with “glioblastoma multiforme”. We compared two age- and gender-matched patient groups with different postoperative time to tumor progression (TTP), defined as “short-term” for TTP of less than 6 months (n=54) and “long-term” for TTP of more than 12 months (n=52). Histological specimens of the corresponding tumors, all primarily diagnosed as glioblastome multiforme, were reevaluated according to the current World Health Organization (WHO) classification of central nervous system tumors, with the investigators being blinded to clinical outcome. Among the tumors from short-term TTP patients, one tumor (2%) was reclassified as anaplastic oligoastrocytoma (WHO grade III) while the remaining 53 were confirmed as glioblastoma multiforme. In contrast, 13 tumors (25%) from the long-term TTP patients were reclassified, mostly as anaplastic oligodendroglioma (WHO grade III; n=7) or anaplastic oligoastrocytoma (WHO grade III, n=2), respectively. In addition, three were reclassified as anaplastic astrocytoma (WHO grade III), and one was identified as anaplastic pilocytic astrocytoma (WHO grade III). Our data indicate that a sizable proportion of glioblastoma patients with long-term survival actually carry malignant gliomas with oligodendroglial features. The correct histopathological recognition of these tumors has not only progrostic but also therapeutic implications, since oligodendroglial tumors are more likely to respond favorably to chemotherapy. Received: 9 November 1999, Received in revised form: 13 January 2000, Accepted: 3 February 2000     

Detection of nucleotide variability in rpoB in both rifampin-sensitive and rifampin-resistant strains of Chlamydia trachomatis

A 656-bp PCR fragment from rpoB was sequenced from five rifampin-resistant Chlamydia trachomatis variants selected in vitro from a wild-type parent with a surprising level of genetic variability in this region. Three variants (MIC, 4 microg/ml) showed Ala522-->Val in cluster I (codons 507 to 533), which harbors mutations in most rifampin-resistant bacteria. Two high-level resistance variants (MICs, 64 and 256 microg/ml) showed His526-->Tyr in cluster I with additional genetic variation, some of which resulted in amino acid substitutions. None of the latter was situated in clusters related to rifampin resistance in other bacteria.     

Mere surgery will not cure cluster headache--implications for neurostimulation

This case study concerns a patient with primary chronic cluster headache, who was unresponsive to all treatments and consecutively underwent hypothalamic deep brain stimulation (DBS). DBS had no effect on the cluster attacks, but cured an existing polydipsia as well as restlessness. However, hypothalamic DBS produced a constant, dull headache without concomitant symptoms and a high-frequent tremor. All of these effects were repeated when the stimulation was stopped and than started again. DBS had no effect on a pathological weight gain from 70?kg to 150?kg due to bulimia at night, usually during headache attacks. This case illustrates that cluster headache is, in some patients, only one symptom of a complex hypothalamic syndrome. This case also underlines that the stimulation parameters and anatomical target area for hypothalamic DBS may be too unspecific to do justice to the clinical variety of patients and concomitant symptoms. Hypothalamic DBS is an exquisite and potentially life-saving treatment method in otherwise intractable patients, but needs to be better characterised and should only be considered when other stimulation methods, such as stimulation of the greater occipital nerve, are unsuccessful.     

A hybrid approach for quantification of aortic valve stenosis using cardiac magnetic resonance imaging and echocardiography.

BACKGROUND: Doppler-derived calculation of aortic valve area (AVA) using the continuity equation can be difficult at times, e.g. due to poor acoustic windows, heavy calcification of the aortic valve, or significant flow acceleration in the left ventricular outflow tract. The aim of this study was to compare AVA as assessed by means of transthoracic echocardiography (TTE) with a hybrid approach, where the Doppler-derived numerator in the continuity equation was replaced by cardiovascular magnetic resonance (CMR) determination of stroke volume. METHODS: Twenty consecutive patients admitted for evaluation of aortic stenosis underwent transthoracic echocardiography and CMR determination of stroke volume within a time period of 3 weeks. Additionally, continuous-wave Doppler spectra of the aortic valve were acquired immediately after the CMR examination. RESULTS: There was no statistically significant difference for mean AVA between the two methods (0.88 +/- 0.23 cm2 by the standard continuity equation versus 0.86 +/- 0.23 cm2 by the hybrid approach, p = 0.55; r = 0.73, p < 0.01). The mean difference was 0.02 cm2 and the limits of agreement were -0.32 to 0.36. Only 2 patients were classified differently by the two methods. Intraobserver and interobserver variability and reproducibility were superior for the hybrid approach. CONCLUSION: The hybrid method for determination of AVA is an excellent alternative to the standard approach by TTE.     

Importance of murine study design for testing toxicity of retroviral vectors in support of phase I trials.

Although retroviral vectors are one of the most widely used vehicles for gene transfer, there is no uniformly accepted pre-clinical model defined to assess their safety, in particular their risk related to insertional mutagenesis. In the murine pre-clinical study presented here, 40 test and 10 control mice were transplanted with ex vivo manipulated bone marrow cells to assess the long-term effects of the transduction of hematopoietic cells with the retroviral vector MSCV-MGMT(P140K)wc. Test mice had significant gene marking 8-12 months post-transplantation with an average of 0.93 vector copies per cell and 41.5% of peripheral blood cells expressing the transgene MGMT(P140K), thus confirming persistent vector expression. Unexpectedly, six test mice developed malignant lymphoma. No vector was detected in the tumor cells of five animals with malignancies, indicating that the malignancies were not caused by insertional mutagenesis or MGMT(P140K) expression. Mice from a concurrent study with a different transgene also revealed additional cases of vector-negative lymphomas of host origin. We conclude that the background tumor formation in this mouse model complicates safety determination of retroviral vectors and propose an improved study design that we predict will increase the relevance and accuracy of interpretation of pre-clinical mouse studies.