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.

Quadruple coronary artery bypass grafting.

In our last 150 consecutive revascularization operations, 30 patients (20%) have had 4 or more bypass grafts. One patient died after quadruple grafting (mortality, 3%). Twenty-two (75%) of the survivors have been rehabilitated to active work status and 25 (86%) were considered by their cardiologists to have improved function postoperatively by New York Heart Association criteria. Preoperatively 15 patients (50% of the group) had either a markedly diminished ejection fraction (EF) or extreme elevation in left ventricular end-diastolic pressure (LVEDP) or both. Complete revascularization, with resection of ventricular aneurysms when present, can be carried out successfully in a high-risk group of patients. Elevated LVEDP or diminished EF per se is not a valid contraindication to myocardial revascularization.

Platelet dysfunction associated with cardiopulmonary bypass.

The clinical significance and pathogenesis of the platelet dysfunction following cardiopulmonary bypass were studied in conjunction with the degree of functional impairment associated with the use of membrane and bubble oxygenators. Forty consecutive patients had the following tests preoperatively and postoperatively: complete blood count (CBC), platelet count, prothrombin consumption time, bleeding time, prothrombin time, partial thromboplastin time, fibrinogen, euglobulin clot lysis, fibrin degradation products, and platelet aggregation tests. Six patients were given 14C-serotonin tests before and after operation, and preoperative and postoperative electron micrographs were made of the platelets of 3 patients. The amount of blood lost, the blood transfused, and plasma hemoglobin levels were also measured. Abnormal aggregation of platelets was found, with no difference between the membrane and bubble oxygenators. In vitro aggregation tests with protamine sulfate and hemoglobin solutions, as well as the 14C-serotonin studies and electron micrographs, suggest that platelets acquire storage pool deficiency and an abnormal membrane during cardiopulmonary bypass.

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.

[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.

[Wound-healing disorders and mortality in one- and multi-stage sigma and rectum resections]. / Wundheilungsstörungen und Letalität bei ein- und mehrzeitiger Sigma- und Rectumresektion.

From 1958 to 1978, the Surgical Clinic of the Tübingen University carried out 427 sigmoidal and rectal resections with a one-, two-, or three-stage proceeding. The comparison proves that, as was to be expected, the one-stage resection more often shows an anastomotic insufficiency. On the other hand, there occur less infections of the abdominal wall because of the absence of a smear-infection deriving from the temporary intestinal fistula. The primary lethality through anastomotical complications does not differ in the one-, two-, or three-stage proceeding if in the latter you effect an only mechanical cleaning of the inactive colon leg. The irrigation of the inactivated colon with an antibiotic solution before the tumor resection leads, compared to the cleaning with saline solution, to much less infections of the abdominal wall, less anastomotic insufficiencies and to the reduction of the primary lethality. This three-stage proceeding is, with a lethality of 1,5%, still the most secure action for the patient.

[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.

[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.

[Combined use of iso and aniso-peristaltic jejunal loops to reestablish continuity after total gastrectomy (author's transl)]. / Rétablissement de la continuité après gastrectomie totale par double interposition d'une anse jéjunale iso et anisopéristaltique (néogastre type Tübingen).

Following experiments in animals, a new procedure for gastric replacement after total gastrectomy has been employed since 1972. Digestive tract continuity is reestablished by interposing two jejunal segments, on iso- and the other aniso-peristaltic, between the esophagus and the duodenum. The proximal isoperistaltic segment should be between 30 and 40 cm in length, while the distal anisoperistaltic segment should measure 10 cm. The latter segment replaces the pylorus and produces delayed intermittent emptying of the proximal iso-peristaltic segment. Their progressive dilatation results in the development of a new reservoir which reaches its maximum volume after 6 to 12 months. Radiological, cinematographic, and endoscopic examination in 58 patients in whom this reconstruction had been performed demonstrated that function was excellent. Results of metabolic studies and tests for clinical function confirmed the value of the method, which has definite advantages over previous techniques employed to reestablish continuity. For this reason, the method has become a routine procedure in patients requiring extensive total gastrectomies.

[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.