Novel Genetic Variants in Carboxylesterase 1 Predict Severe Early-Onset Capecitabine-Related Toxicity.

An important concern with the anticancer drug capecitabine (Cp), an oral prodrug of 5-fluorouracil, are dose-limiting adverse effects, in particular hand-foot syndrome (HFS) and diarrhea. Here we evaluated the association of genetic variability in all enzymes of the Cp-activation pathway to 5-fluorouracil with Cp-related early-onset toxicity in 144 patients receiving Cp. We identified a haplotype encompassing five variants in the carboxylesterase 1 (CES1) gene region including an expression quantitative trait locus associated with early-onset Cp-toxicity (Haplotype A3: ORadditive = 2.2, 95% CI 1.2-4.0, Padjusted = 0.012; ORrecessive = 10.3, 95% CI 2.1-49.4, Padjusted = 0.0038). Furthermore, the association of two linked cytidine deaminase (CDA) promoter variants (c.1-451C>T: ORdominant = 4.3, 95% CI 1.3-14.2, Padjusted = 0.017; and c.1-92A>G: ORdominant = 4.4, 95% CI 1.3-14.5, Padjusted = 0.015) with Cp-related diarrhea was replicated. This first study identifying an association of genetic variation in CES1 with Cp-related toxicity provides further evidence for the existence of a functional noncoding CES1-variant with a possible regulatory impact.

Initial clinical experience with a new pulsed dye laser device in angioplasty of limb ischemia and shunt fistula obstructions.

Selective plaque ablation with laser radiation at 405-530 nm in vitro has been reported. We investigated the possibilities of a new pulsed dye laser device for in vivo recanalization of arteries in ischemic lower limbs and stenoses/occlusions of arterio-venous hemodialysis shunt fistulae. A specially designed 9F or 7F multifiber catheter was used for treatment of 10 patients with lower limb artery obliterations and 11 patients with malfunctioning hemodialysis access fistulae (HAF). The recanalization technical success was 5/5 in the iliac arteries (IA), 4/5 in the superficial femoral arteries (SFA), and 11/11 in the HAF. Early re-occlusions occurred in one SFA and one IA, respectively, caused by very bad run-off. There was one clinically insignificant SFA perforation. Additional balloon angioplasty was considered necessary in 10/16 lesions. Mean ankle-arm index increased from 0.68 to 0.97. With two exceptions all HAF patients were re-integrated in the dialysis program. Pulsed dye laser angioplasty promises to be an effective and fast method for plaque ablation/debulking. The first clinical experience confirms previous in vitro results. In particular laser recanalization may become the method of choice for treatment of rigid HAF obstructions and it seems to be superior to vascular surgery or balloon angioplasty alone.

[Acute arterial thrombosis: diagnosis and surgical therapy]. / Akute arterielle Thrombose: Diagnostik und operative Therapie.

There is an increasing frequency of acute ischemic occlusion due to arterial thrombosis; the incidence has a range from 17% to 60%. In contrast to embolism we can observe a prolonged therapy less interval due to a lesser dramatic clinical course; in thrombotic occlusion only 10% can be treated within 6 h after onset of symptoms. In 11 to 93% of all cases extensive and comprehensive surgical techniques have to be performed for limb salvage. Nevertheless this aim only can be achieved in 60-84%.

[Surgical treatment of asymptomatic carotid stenosis]. / Die operative Behandlung der asymptomatischen Carotisstenose.

A total of 274 patients (mean age 67.1 +/- 8.2 years) with asymptomatic stenosis of the internal carotid artery greater than 70% was treated by desobliteration and patchplasty; 332 reconstructions were performed either uni- or bilaterally. In this group only 29% revealed a one vessel disease. Lethality within 30 days was 1.5%; the incidence of complete stroke amounted to 0.9%. In a mean follow up period of 30.8 +/- 20.2 month to lethality rate was 4.4%; 7.8% developed a completed stroke and only 3.8% were related to the operated site. The 5-year-survivalrate was 88.9% and 93.2% of this cohort was neurological free of symptoms.

[Operative treatment of asymptomatic carotid stenosis]. / Operative Behandlung asymptomatischer Carotisstenosen.

Over a period of five-and-a-half years 183 patients with high-grade asymptomatic carotid stenoses in stage I were operated upon. Postoperative mortality was 0.5%; there was no permanent morbidity. Cumulative survival rate after four years was 68%. The proportion of patients without neurological disorders after five years was nearly 100%. Asymptomatic re-stenoses were found in 6% of patients. Principal cause of death during the follow-up period was of cardiac origin (9 of 17).

[Comparison of Doppler ultrasound, intravenous DSA and conventional film angiography in diagnosing stenosing changes in the area of the carotid bifurcation]. / Vergleich von Doppler-Ultraschall, intravenöser DSA und konventioneller Filmangiographie bei der Diagnostik stenosierender Veränderungen im Bereich der Karotisgabel.

The findings on Doppler ultrasound, intravenous DSA and conventional film angiography were compared in 66 examinations of the carotids with regard to their specificity, sensitivity and accuracy. Comparisons with the literature show that intravenous DSA equals Doppler ultrasound only if good or excellent results of the latter are considered. If poorer DSA results are included, diagnostic precision of this method is 5 to 10% less than that of Doppler ultrasound. Mural ulceration can be diagnosed by means of intravenous DSA in only about 50% of cases, whereas Doppler ultrasound is unable to diagnose this. Improved image quality of intravenous DSA, with better diagnostic precision, could be achieved by using ECG gating.

[Noninvasive diagnosis of cerebral circulatory disorders]. / Nichtinvasive Diagnostik der zerebralen Durchblutungsstörungen.

Percutaneous measurements by Doppler sonography over the carotid and vertebral arteries of the neck may detect the presence of stenosis in arteries with a high precisions especially for the carotid arteries. This paper shall give a survey of the methods of directional Dopplersonography, its principle and techniques.

[Stomach replacement by iso-anisoperistaltic jejunum interposition (Tübinger replacement stomach)]. / Magenersatz durch iso-anisopeistaltische jejunuminterposition (Tübinger Ersatzmagen).

Since 1972 we have been using a new method of gastric replacement which was developed at our hospital. The reconstruction of passage is achieved by iso-anisoperistaltic interposition of two jejunal segments (30:10 cm). The reversed segment causes delayed and intermittent emptying of the above located isoperistaltic segment. Until now this type of gastric replacement has been performed in 62 patients. Postoperative mortality was 11.3%; so far the longest survival time is nearly 8 years. By the reservoir function of the jejunal interposition digestion and absorption are essentially improved, resulting in a better quality of life for the patient. This type of gastric replacement is now used as a routine in all curative gastrectomies, provided there are no contraindications on account of the patient's age or general condition.

[Choice of operative technic in the treatment of liver diseases]. / Operative Verfahrenswahl in der Therapie von Lebererkrankungen. Ein Erfahrungsbericht.

Between 1974 and 1979 resection of the liver was carried out for malign or benign tumors in 42 patients. Lobectomy was performed in 17 and hemihepatectomy in 25 cases (11 times right-sided, 14 times left-sided). Hemihepatectomy with preliminary ligation of the vessels showed a lower rate of complication than the time-saving lobectomy. Mortality rate was 0% in left-sided hepatectomy, 12% in lobectomy, and 27% in right-sided hepatectomy. The cause of death was liver failure in three cases of hepatectomy because of preexisting damage of the remaining lobe showing no compensatory hypertrophy. In accordance with the literature, we conclude that right-sided hepatectomy can be performed only if hypertrophy of the left lobe is present.