Diagnostik und individualisierte Therapie des lokoregionären Prostatakarzinoms

Durch die Früherkerkennung mit nachfolgender kurativer Therapie konnte – wie mehrere Studien zeigten – die Mortalit?t des Prostatakarzinoms gesenkt werden. Dabei ist das operative Standardverfahren des klinisch lokal begrenzten Prostatakarzinoms bei Patienten mit einer Lebenserwartung von mindestens 10 Jahren nach wie vor die radikale Prostatektomie. Durch sie werden tumorspezifische 10-Jahres-überlebensraten von über 90% erreicht. Durch die zunehmende operative Erfahrung mit diesem Eingriff (v. a. an gro?en Zentren) sind perioperative Morbidit?t und Mortalit?t auch bei betagten Patienten gering. In erfahrenen H?nden bleibt die Harnkontinenz in über 90% der F?lle erhalten. Abh?ngig vom Alter und der Form des Nervenerhalts (ein- oder beidseitig) ist unter Verwendung von Sildenafil der Erhalt der sexuellen Potenz bei 50–100% der Patienten m?glich. Bisher konnte in keiner Studie – beim Fehlen prospektiv randomisierter Vergleiche – eine bessere Tumorkontrolle durch alternative Therapien erreicht werden. Dagegen gibt es deutliche Hinweise, dass die radikale Prostatektomie v. a. bei aggressiveren Tumoren das sicherere Verfahren ist. Als weitere Therapieoptionen mit kurativem Ziel stehen die externe und die interstitielle Strahlentherapie zur Verfügung. Hochbetagte, multimorbide Patienten und solche mit fortgeschrittenem Karzinom sind wegen des eher langsamen Krankheitsverlaufs Kandidaten für eine konservative Behandlung. In den USA ist das Prostatakarzinom gegenw?rtig der am h?ufigsten und in Deutschland der am zweith?ufigsten diagnostizierte b?sartige Tumor des Mannes. Für das Jahr 2000 wird in den USA mit 180.400 Neuerkrankungen gerechnet [1]. Mit (im Jahr 2000) gesch?tzten 31.900 Verstorbenen liegt dieser Tumor in den USA an zweiter Stelle der Statistik tumorbedingter Todesf?lle [21]. In Deutschland lag die Inzidenz im Zeitraum von 1994–1997 bei sch?tzungsweise 16,6 j?hrlichen Neuerkrankungen pro 100.000 Einwohnern [21]. Das Screening mit Hilfe des prostataspezifischen Antigens (PSA) führte in den vergangenen 1 1/2 Jahrzehnten zu einem dramatischen Anstieg diagnostizierter lokal begrenzter Prostatakarzinome bei einer gleichzeitigen Abnahme der Zahl neuentdeckter metastasierter Tumoren [43].     

Epidermal growth factor receptors and prognosis in primary breast cancer

A retrospective study was performed on 109 human breast tumors stored in liquid nitrogen in order to assess the prognostic value of epidermal growth factor receptor (EGF-R) (median patient follow-up 5 years). A significant inverse relationship was observed between EGF-R and both estrogen (ER) and progesterone receptors (PR). Univariate analysis showed a trend towards a shorter metastasis-free survival both in the overall population and in node-negative patients with EGF-R positive tumors. Multivariate analysis of the overall population showed that lymph-node involvement and PR status were the only significant variables in predicting metastasis-free survival. However, in patients receiving no adjuvant treatment (hormone therapy or chemotherapy), EGF was the only significant variable in the multivariate Cox analysis. No c-erbB-1 amplification was detected in these tumors.     

Cardiac and microcirculatory effects of different doses of prostaglandin E1 in man

Summary A cumulative dose response to intravenous PGE₁ was established in 12 healthy volunteers. Systolic time intervals, including pre-ejection period (PEP), the ventricular ejection time (VET) and the RR-interval, were continuously determined, and transcutaneous oxygen pressure (tcpO₂) was recorded.RR-intervals fell in a dose dependent manner, reaching a significantly lower level at 128 ng·kg^–1·min^–1 of PGE₁ (basal value 842 ms falling to 756 ms). PEP decreased from 89 ms to 74 ms and the ratio PEP/VET decreased from 35% to 30%, indicating increased myocardial contractility. The maximal increase in tcpO₂ was 125% on the calf and 60% on the foot. The peak tcpO₂ was observed at an infusion rate of 16 ng·kg^–1·min^–1 PGE₁. A decline in tcpO₂ was seen at infusion rates >64 ng·kg^–1·min^–1 PGE₁, indicating a decrease in skin perfusion.The results indicate that the effects of intravenous PGE₁ on skin perfusion occur at a lower threshold than the increase in myocardial contractility. A maximal increase in skin perfusion can be achieved with doses of PGE₁ devoid of systemic haemodynamic effects.     

Folinic acid modulation of fluorouracil: tissue kinetics of bolus administration

Summary Thymidylate synthase (TS) is the enzyme target of 5-fluorouracil (FUra) that recent laboratory and clinical studies with folinic acid (calcium leucovorin) suggest may mediate important antitumor cytotoxicity. Measurement in carcinoma tissue of parameters related to TS inhibition by 5-fluorodeoxyuridylate (FdUMP), by analogy to hormone receptor analysis, should be useful to determine which patients should receive fluoropyrimidine drug therapy and to evaluate folinic acid requirements. Folinic acid is metabolized to 5,10-methylenetetrahydropteroylglutamine (CH₂FH₄), which must be present in large excess to effect desired levels of maximal inhibition of TS, by promoting formation and stabilization of TS-FdUMP-CH₂FH₄ ternary complexes. In patients with metastatic disease, serial biopsies of tumor and normal tissues for studies of pharmacodynamic responses to test-dose FUra or folinic acid are shown to be easily added to routine intraoperative management. A suitable methodologic approach is described and examples given of assays of free TS, FdUMP, dUMP, and CH₂FH₄ levels after FUra or folinic acid, that may be useful in future studies aimed at improving the cost-effectiveness of FUra-folinic acid combinations.Abbreviations TS Thymidylate Synthase (EC 2.1.1.45) - FUra 5-fluorouracil - FdUMP 5-fluorodeoxyuridylate - dUMP deoxyuridylate - CH₂FH₄ 5,10-methylenetetrahydropteroylglutamate - 5-CH₃FH₄ 5-methyltetrahydropteroylglutamate     

Beclomethasone dipropionate versus flunisolide as topical steroid treatment in patients with perennial rhinitis

After a 2-week run-in period 23 atopics and non-atopics with perennial rhinitis were treated with intranasally nebulized aqueous flunisolide or aqueous beclomethasone dipropionate in a randomized, double-blind cross-over study, each treatment period being 4 weeks. Before and after each treatment period daily rhinitis symptoms were recorded, and additional determination of nasal airway resistance was performed by posterior rhinomanometry. No statistically significant difference between drugs was observed for any effect parameter recorded, and furthermore no difference in patient preference for either drug was found. It is concluded that both steroids are effective for the improvement of nasal airway in patients with perennial, atopic and non-atopic rhinitis.     

Clinical staging of malignant tumors by the TNM system. Contribution of modern imaging procedures in patients with testicular tumors

For classification of testicular tumors in the TNM-System several modern imaging methods are available: sonography, conventional radiography, lymphography, computer-tomography, nuclear magnetic resonance and scintigraphy. Sonography--usually the first method to be used for reasonable classification--is significantly inferior to lymphography and CT for N and M staging. It remains to be seen if the NMR-methods will reach the good informative standard of CT. Only in the case of extensive lymphatic metastasis (bulky disease) are i.v. pyelogram and cavography still used to verify displacement of the ureter or infiltration of the tumor into the cava. In the nuclear medical field bone scintigraphy plays the main role for testicular tumor metastases.     

One‐step radiosynthesis of [18F]LBT‐999: a selective radioligand for the visualization of the dopamine transporter with PET

LBT‐999 (8‐((E)‐4‐fluoro‐but‐2‐enyl)‐3‐beta‐p‐tolyl‐8‐aza‐bicyclo[3.2.1]octane‐2‐beta‐carboxylicacid methyl ester) is a recently developed cocaine derivative belonging to a new generation of highly selective dopamine transporter (DAT) ligands (K_D : 9 nM for the DAT and IC₅₀ > 1000 nM for the serotonin and norepinephrine transporter). Initial fluorine‐18‐labelling of LBT‐999 was based on the robust and reliable two‐step radiochemical pathway often reported for such tropane derivatives, involving first the preparation of (E)‐1‐[¹⁸F]fluoro‐4‐tosyloxybut‐2‐ene followed by a N‐alkylation reaction with the appropriate nor‐tropane moiety. In the present work, a simple one‐step fluorine‐18‐labelling of LBT‐999 is reported, based on a chlorine‐for‐fluorine nucleophilic aliphatic substitution, facilitating as expected both automation and final high‐performance liquid chromatography (HPLC) purification. The process involves: (A) reaction of K[¹⁸F]F–Kryptofix^®222 with the chlorinated precursor (3.5–4.5 mg) at 165°C for 10 min in DMSO (0.6 mL) followed by (B) C‐18 PrepSep cartridge pre‐purification and finally (C) semi‐preparative HPLC purification on a Waters Symmetry^® C‐18. Typically, 3.70–5.92 GBq of [¹⁸F]LBT‐999 (> 95% chemically and radiochemically pure) could be obtained with specific radioactivities ranging from 37 to 111 GBq/µmol within 85–90 min (HPLC purification and Sep‐Pak‐based formulation included), starting from a 37.0 GBq [¹⁸F]fluoride batch (overall radiochemical yields: 10–16%, non‐decay‐corrected). Copyright © 2007 John Wiley & Sons, Ltd.     

Fluorine‐18 labelling of small interfering RNAs (siRNAs) for PET imaging

Small interfering RNAs (siRNAs), a class of macromolecules constituted by the association of two single‐stranded ribonucleic acids of short sequences, have been labelled with the positron‐emitter fluorine‐18 (T_1/2: 109.8 min). The strategy involves (1) prosthetic conjugation of a single‐stranded oligonucleotide with [¹⁸F]FPyBrA (N‐[3‐(2‐[¹⁸F]fluoropyridin‐3‐yloxy)‐propyl]‐2‐bromoacetamide) followed by (2) formation of the target duplex by annealing with the complementary sequence, therefore, permitting parallel and combinatorial preparation of [¹⁸F]siRNAs. Pure fluorine‐18‐labelled siRNAs (0.55–1.11 GBq, specific activity: 74–148 GBq/µmol at EOB) could be obtained within 165 min starting from 37.0 GBq of starting [¹⁸F]fluoride (1.5–3.0%, non‐decay‐corrected isolated yields). Copyright © 2007 John Wiley & Sons, Ltd.     

Massive hemoptysis: what place for medical and surgical treatment.

OBJECTIVE: The objective of the study was to define timing of surgical treatment in management of massive hemoptysis. METHODS: We performed a retrospective review of all patients admitted for massive hemoptysis in the intensive care unit of our thoracic surgery department. Treatment was managed according to the patient's status, the etiology of bleeding, the findings of bronchoscopy and computed tomographic scan. Therapeutic measures available were medical treatment, tracheal intubation (single or double lumen tube), interventional endoscopy, arterial embolisation and surgical treatment. RESULTS: Between September 1996 and December 2001, 43 patients were treated (nine females and 34 males with mean age of 54 years, range from 32 to 79). The mean red cell blood transfusion per patient was 1.57 Units. The patients were classified into three groups: Group 1, 11 patients were operated on immediately close to the bleeding crise (five pneumonectomy and six lobectomy); Group 2, five patients for whom operation was delayed from the 7th to the 22nd day after cessation of bleeding (five lobectomy); Group 3, 27 patients were treated by non-surgical methods (medical treatment, endobronchial treatment, percutaneous embolisation). Fifteen patients underwent an arterial embolization, which was complete in 13 cases. Among the five patients of group 2, cessation of bleeding was obtained by bronchial embolisation in four cases. Considering the whole series, 10 (23%) patients died: three (19%) patients in group 1, zero in group 2, seven (26%) in group 3. In two patients who were suffering from tumor necrosis, hemoptysis relapsed leading to death. CONCLUSION: Emergency thoracotomy for massive hemoptysis is at high risk. In case of bleeding from the arterial bronchial vessels, embolization may enable to postpone surgery and operate secondarily. In case of bleeding from the pulmonary vessels (tumor necrosis), surgical treatment must be immediate. An algorithm for management is proposed.