[Influence of processing and sterilization on the mechanical properties of pins made from bovine cortical bone]. / Einfluss von Prozessierung und Sterilisation auf die Festigkeit von Pins aus boviner Tibiakompakta.

In a biomechanical study pins made of xenogenous cortical bone were tested in vitro. Forty pins of 3 mm diameter and 60 mm length were made of eight different cattle tibiae and allocated to five different treatment groups. Freeze-dried pins served as control group. Pins of the second group were preserved in concentrated sodium chloride solution and defatted with acetone (Tuto-plast processing). Pins of groups three to five were treated with sodium chloride and acetone and afterwards sterilized by different means (ethylene oxide, autoclavation, or gamma radiation). All pins were subjected to a three-point-bending test and a shear test. We found that bending strength and shearing strength were most increased after sodium chloride and acetone treatment, whereas after sterilization with ethylene oxide or autoclaving, the stability of the pins was similar to the control group. The stability was considerably diminished after gamma radiation. Taking into account possible toxic side effects of ethylene oxide, we conclude that Tutoplast processing followed by autoclavation presents a reliable preparation method for the clinical use of implants made of bovine cortical bone.

[Strength testing of pins made of human femur cortical bone]. / Festigkeitsuntersuchungen an Pins aus humaner Femurkortikalis.

For biomechanical evaluation of cortical bone as a potential source for internal fixation devices, pins of 2 and 3 mm in diameter were made from fresh human femora and subjected to bending loads. Some of the pins were tested without further treatment; others were defatted and dried in acetone solution. Of the acetone-treated pins, some were autoclaved either at 121 degrees C for 20 min or at 134 degrees C for 8 min. Acetone treatment of the pins caused a 5.5% increase in bending strength (p < or = 0.05) and a 6.6% increase in the elastic modulus (p < or = 0.05). The mean bending strength of the acetone-treated pins was 257 +/- 52 N/mm2 and the mean elastic modulus was 18,346 +/- 1292 N/mm2. Autoclaving of the pins at the lower temperature for a longer time led to a decrease in the bending strength of up to 16% and at the higher temperature for a shorter time to a decrease of up to 41%. To compare the strengths of the cortical and synthetic pins, 2-mm Biofix pins were also tested. The Biofix pins showed a 25% higher bending strength than the acetone-treated pins but a 12.5% lower elastic modulus. It should be noted that in animal studies the synthetic Biofix pins showed a 20% loss of strength within 2 days after implantation in situ.

Animal model of experimentally induced ectopic enchondral ossification in nude mice with xenograft of porcine epiphyseal cartilage.

In a specific animal model the induction of heterologous enchondral ossification was examined in long term follow-up. Physiologically normal and devitalized frozen porcine epiphyseal cartilage as a control group were transplanted as s.c. xenograft into athymic nude mice (nu/nu). 15 weeks after transplantation the porcine growth plate cartilage showed the development of viable cartilage tissue in the recipients, further differentiating to juvenile long bone with epiphysis, diaphysis and growth plate. Porcine growth plate cartilage increased s.c. in the recipient nude mice, showing enchondral ossification without any physiological load, and finally an unexpected development towards complete juvenile long bone.

[Clinical anatomy as an integrating element in teaching surgical subjects]. / Klinische Anatomie als integrierendes Element in der Lehre der operativen Fächer.

Different conceptions to revise the licensing regulations for physicians (Approbationsordnung für Arzte) aim to interlock preclinical and clinical subjects. Therefore a more practice-oriented anatomy has to be taught in basic and postgraduate medical education. At the Westfalian Wilhelms University of Münster we established an interdisciplinary anatomical education, executed by clinical lecturers in cooperation with the educational staff of the Department of Anatomy. The intergral element is the comprehensive constitution of clinical anatomy: clinical practitioners of different specialties together with anatomists give lessons in applied anatomy accompanying the dissection course. Clinically experienced lecturers of anatomy guide senior medical students in practical courses, refreshing their anatomical knowledge using particular prosections. These courses correlate with the topics of the distinct clinical tutorials. Conjointly clinical practitioners and anatomists plan, and perform meetings in postgraduate medical education.

[Clinical anatomy in surgical education and graduate education]. / Klinische Anatomie in der Chirurgischen Aus- und Weiterbildung.

On the basis of the experience that knowledge of anatomy is not as sound in clinical education as it should be and with a view to the new licensing regulations for physicians, at the Westfälische Wilhelms-Universität Münster, Germany, we established an interdisciplinary anatomical education. Clinical practitioners from 14 different specialties together with anatomists give lessons in applied anatomy accompanying the dissection course, and clinical experienced anatomists guide senior medical students in parallel to the practical courses to refresh their anatomical knowledge. Conjointly clinical practitioners and anatomists initiate, organize and establish meetings in postgraduate surgical education and experimental surgery. All seminars are evaluated and have a very good compliance.

[Prognostic differences in primary malignancies of the small intestine]. / Prognoseunterschiede primärer Dünndarmmalignome.

Malignant small bowel tumours are rare, with about 320 deaths every year due to metastases. Tumours of differing histologic entitites (adenocarcinomas, leimyosarcomas, non-Hodgkin, lymphomas, carcinoids) are detected at late stages of the disease because of non-specific symptoms. Valuable diagnostic means are small bowel enema, intestinoscopy and abdominal CT/ultrasound. Five-year survival rates are poor for carcinomas (21%), for sarcomas (37%), lymphomas (44%) and best for carcinoids (100%). Surgical options are poor for carcinomas with a high number of R2 resections and bypass operations. Multivisceral surgery is beneficial for sarcomas and lymphomas, followed by local radiation therapy or chemotherapy.

SPIO-enhanced 2D-TOF MR angiography of the portal venous system: results of an intraindividual comparison.

The purpose of this study was to investigate whether MR angiography (MRA) of the portal venous system may be improved by means of superparamagnetic iron oxides (SPIOs) during accumulation phase imaging and to study the underlying contrast mechanisms. MRA of the portal venous system was performed on 48 patients before and after intravenous injection of a new SPIO (Resovist, Schering AG, Berlin, Germany). Resovist, as a predominantly liver parenchymal darkening agent on T2-weighted MR images with uptake into the reticuloendothelial cell system, was administered intravenously by bolus injection of 8 to 12 micromol Fe/kg body weight. Patients were scanned with breath-hold coronal and axial two-dimensional (2D) time of flight (TOF) MRA (TR = 31.0 msec, TE = 9.8 msec, flip angle (FA) = 50 degrees, and 6.9-second acquisition time per section) sequences. Signal intensity values of liver parenchyma, the portal venous system, and background were obtained for quantitative analysis. The clinical relevance of additional plain and contrast-enhanced MRA studies for surgical planning was assessed by independent reading of three readers. Liver signal-to-noise ratio (SNR) significantly decreased following iv injection of Resovist; however, SNR values of the portal veins or hepatic veins did not change significantly. Visibility of the portal venous system improved significantly (tertiary branches visible: pre in 15.2% versus post in 87.0% of patients). Resovist-enhanced 2D-TOF MRA may improve planning of liver resections by better demonstrating the relationship of central liver lesions and vessels on source images. The decrease in liver SNR at a constant vessel SNR after iv injection of Resovist improves MRA of the liver. SPIO-enhanced 2D-TOF MRA scans are superior to plain 2D-TOF MRA studies and may be added for the workup of preoperative patients.

Modulation of 5-fluorouracil with methotrexate and low-dose N-(phosphonacetyl)-L-aspartate (PALA) is inactive in advanced pancreatic carcinoma.

PURPOSE: To evaluate the effect of biochemical modulation by PALA and methotrexate on the therapeutic activity of 5-fluorouracil (5-FU) in patients with advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: The treatment protocol consisted of phosphonacetyl-L-aspartate (PALA) 250 mg/m2 i.v. 15-minute infusion followed by methotrexate 200 mg/m2 i.v. 30-minute infusion on day 1 and 5-FU 600 mg/m2 i.v. push on day 2. Folinic acid was given at 15 mg/m2 p.o. every six hours for eight doses, starting 24 hours after methotrexate infusion. Cycles were repeated every two weeks. RESULTS: Thirty patients with advanced chemotherapynaive pancreatic cancer were included; 26 had measurable disease. Median age 56 years (27-72); median PS 1 (0-2). One PR (3.9%) was achieved; nine patients had stable disease. Median time to progression was 91 days. Median survival was 177 days and one year survival was 13.3% (4 of 30 patients). Treatment was well tolerated; diarrhea WHO grade 2 or 3 occurred in six patients; stomatitis WHO grade 2 and 3 in nine patients. CONCLUSIONS: Modulation of 5-FU by PALA and MTX given in this dose and schedule appears to be ineffective in patients with advanced pancreatic adenocarcinoma.

Effect of CYP2D1 inhibition on the behavioural effects of d-amphetamine.

In rats, amphetamine (AMP) conversion to 4-OH-AMP is metabolized by CYP2D1, the rat equivalent of the human enzyme CYP2D6. To determine the impact of impaired AMP metabolism on its behavioural effects, AMP-induced hyperactivity, AMP discrimination and AMP self-administration were examined in male Wistar rats with or without pretreatment with the CYP2D1 inhibitors quinine and budipine. In vivo, quinine (20 mg/kg) and budipine (10 mg/kg) increased the plasma area under the curve of AMP 4-fold and 3.6-fold respectively, and decreased the plasma levels of 4-OH-AMP, 3-fold and 8.6-fold, confirming that the doses used suppressed CYP2D1 activity. Both inhibitors prolonged AMP-induced hyperactivity (0.3 mg/kg) and prolonged the duration of AMP-appropriate responding for periods of up to 90 min post-AMP administration in a drug discrimination procedure. In rats given a preload dose of AMP (0.8 mg/kg) 3 h prior to the self-administration test session, CYP2D1 inhibition resulted in fewer AMP infusions being taken compared with rats receiving the AMP preload dose alone. These studies indicate that AMP is responsible for the behavioural effects seen in rats and that a rat phenocopy model of the human CYP2D6 deficiency state can be produced by CYP2D1 inhibitors.

Combined modality treatment with accelerated radiotherapy and chemotherapy in patients with locally advanced inoperable carcinoma of the pancreas: results of a feasibility study.

Between July 1990 and September 1993, 32 patients with locally advanced irresectable adenocarcinoma of the pancreas, histologically proven by laparotomy, were involved in our study. Patients were treated with hyperfractionated, accelerated radiotherapy and simultaneous application of 5-fluorouracil and folinic acid. Chemotherapy was given on days 1,2 and 3. Determination of the target volume for radiotherapy was carried out by computerized axial tomography. The total tumour dose of 44.8 Gy was applied relative to the 90% isodose in two daily fractions of 1.6 Gy, resulting in ten fractions per week. On the first three days of radiotherapy, 600 mg m-3 of 5-fluorouracil and 300 mg m-3 of folinic acid were given i.v. According to response, chemotherapy was repeated in 4-week intervals. The median survival time for all patients was 12.7 months, compared with 3-7 months after palliative surgery (historical control). The median progression-free interval was 6.6 months. Toxicity and therapy-induced morbidity were recorded according to WHO criteria. Nausea and vomiting of WHO grade I and II occurred in 72.1% and of grade III and IV in 27.9% of the patients. WHO grade I and II diarrhoea was seen in 11 patients. The overall incidence of leucopenia and thrombocytopenia was 37.4%; severe side-effects (WHO III-IV) occurred in 9.3% of all patients. One patient experienced a severe mucositis (WHO III). This combined modality treatment consisting of accelerated hyperfractionated radiotherapy and chemotherapy turned out to be feasible for patients with locally advanced, irresectable pancreatic cancer. The therapy could be applied in a short period of time, approximately half the time used in conventional therapy schemes.

Results and prognostic factors of splenectomy in idiopathic thrombocytopenic purpura.

BACKGROUND: Splenectomy is the therapy of choice after relapse following different immunosuppressive treatments for idiopathic thrombocytopenic purpura, which is still the most frequent cause of thrombocytopenia. STUDY DESIGN: A prospective clinical study was undertaken to evaluate the rate of complete remission in idiopathic thrombocytopenic purpura after splenectomy, to reveal the influence of preoperative immunosuppression on the postoperative course in groups of patients with different responses to treatment, and to describe possible prognostic factors predicting the postoperative course of idiopathic thrombocytopenic purpura. Difino's classification of remission was used. After fulfilling criteria for admission into the study, 72 patients who had undergone splenectomy (male to female ratio, 1:1.4) were examined. RESULTS: Early postoperative mortality and morbidity rates were 3 percent each. The following degrees of remission were achieved: complete remission, 72 percent; partial remission, 15 percent; partial remission affording further medical support, 6 percent; and no remission, 4 percent. Platelet counts differed significantly between complete and partial remission, but not between patients who did or did not experience a response to different preoperative medical strategies (Tukey-Kramer test, p < .05; t test, not significant). The correlation of megakaryocytopoiesis and the site of thrombocytolysis to the stages of remission was significant (Fisher's exact test). Patients with hyperplasia of splenic follicles had significantly higher platelet counts 2 years after operation than did those without hyperplastic splenic follicles (Student-Newman-Keuls test). CONCLUSIONS: Splenectomy is a low morbidity and low mortality procedure. It is, therefore, a treatment of choice after relapse following immunosuppressive courses. Isolated splenic thrombocytolysis and hyperplasia of megakaryocytopoiesis and of splenic follicles correlated with better postoperative outcome (ie, stable remission and platelet counts) and could serve as possible prognostic factors for the postoperative course in idiopathic thrombocytopenic purpura.

[The value of 3-phase spiral CT and magnetic resonance tomography in preoperative diagnosis of pancreatic carcinoma]. / Die Wertigkeit der 3-Phasen-Spiral-CT und der Magnetresonanztomographie in der präoperativen Diagnostik des Pankreaskarzinoms.

UNLABELLED: The purpose of this study was to assess the role of spiral computed tomography (SCT) and magnetic resonance imaging (MRI) in the preoperative work-up of patients with pancreatic carcinoma, regarding local resectability and vascular involvement. METHODS AND MATERIALS: A total of 28 patients (19 men and 9 women; mean age 58 years) with known or highly suspected carcinoma of the pancreas were included in this study. All patients prospectively underwent MRI ( +/- gadolinium-DTPA ) and SCT (3-phase examination) as preoperative diagnostic imaging studies, and laparotomy was carried out within 7 days, irrespective of the MRI or SCT findings. SCT and MR studies were reviewed independently by two radiologists, without knowing the results of the surgical exploration. Standardized image analysis was correlated with findings at laparatomy. RESULTS: Laparotomy identified 10 patients to be suitable for surgical resection and 18 pancreatic carcinomas to be unresectable. In 17 of 18 non-resectable carcinomas MRI and SCT were able to obtain correct information about unresectability (sensitivity 94%), in 7 (MRI), resp. 8 (SCT) carcinomas were correctly considered to be resectable (sensitivity 70% of MRI and 80% for SCT). The presence of vascular involvement was depicted by SCT with a sensitivity of 82-100% and 62-100% by MRI. The specificity varied between 85-100% for SCT and 77-100% for MRI. CONCLUSION: Both MRI and SCT are good techniques for the preoperative work-up of pancreatic carcinomas in order to obtain a correct assessment of local resectability.

Phase II clinical evaluation of Gd-EOB-DTPA: dose, safety aspects, and pulse sequence.

PURPOSE: To investigate the efficacy of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) in the detection of focal liver lesions with respect to dose, side effects, and pulse sequence. MATERIALS AND METHODS: A randomized double-blinded trial was performed in 33 patients with focal solid liver lesions. A bolus of Gd-EOB-DTPA, a liver-specific contrast agent, was intravenously administered at three different doses (12.5, 25, and 50 mumol per kilogram of body weight). Magnetic resonance imaging with different T1-weighted techniques was performed 20 and 45 minutes after administration of Gd-EOB-DTPA. Changes in liver signal intensity, lesion-liver contrast-to-noise ration (C/N), detectable liver lesions, side effects, and adverse events were evaluated. RESULTS: Gd-EOB-DTPA significantly (P < .05) increased liver signal intensity and lesion-liver C/N within the dose range tested. Lesion detection was improved 20 and 45 minutes after administration of Gd-EOB-DTPA. A dose of 12.5 mumol was sufficient for the detection of focal liver lesions, and the breath-hold, T1-weighted, fast low-angle shot pulse sequence was the most useful. No significant changes in vital signs, clinical laboratory test results, and urinalysis were observed. CONCLUSION: Gd-EOB-DTPA is an efficient, diagnostically useful, and safe contrast agent.

[New MR contrast media in liver diagnosis. Initial clinical results with hepatobiliary Eovist (gadolinium-EOB-DTPA) and RES-specific Resovist (SH U 555 A)]. / Neue MR-Kontrastmittel in der Leberdiagnostik. Erste klinische Ergebnisse mit hepatobilliärem Eovist (Gadolinium-EOB-DTPA) und RES-spezifischem Resovist (SH U 555 A).

The purpose of this work is to describe our initial clinical experience (in 66 patients) with Resovist and Eovist, two new liver-specific MR contrast agents. We focus our report on safety aspects, dose finding, and optimization and technical parameters. Both contrast agents were well tolerated and improved the detectability of focal liver lesions. With Resovist, postcontrast MRI may be started as early as 10 min following injection. The dose of 8 mumol Fe/kg bodyweight was sufficient to achieve diagnostic tumor-liver contrast levels. Since Eovist can also be administered as a bolus, dynamic enhancement patterns may be studied for tumor characterization as well. Breath-hold T1-weighted FLASH images were superior to other T1-weighted techniques with and without fat saturation.

[New super-paramagnetic iron particles for MRI. Phase II study of malignant liver tumors]. / Neue superparamagnetische Eisenpartikel für die MRT. Phase-II-Studie bei malignen Lebertumoren.

The clinical tolerability and diagnostic value of Resovist as a new superparamagnetic iron oxide contrast medium was studied in 30 patients with malignant focal liver lesions (28 metastases, 2 HCC) within a phase II multicenter study. Magnetic resonance imaging (MRI) was performed at 1.0 Tesla with T1-weighted FLASH- and T2-weighted spin echo sequences before and following intravenous injection of Resovist at three different dose groups (4, 8 and 16 mumol Fe/kg). Liver signal intensity was significantly reduced on post-contrast images, while malignant focal liver lesions showed no signal changes. Resovist improved tumor liver contrast and lesion-conspicuity, especially for lesions smaller than 1 cm. The dose of 8 mumol Fe/kg was sufficient to achieve diagnostic tumor-liver contrast. Compared to images directly after injection, the number of detected lesions did not improve until 70 min later. There were no significant changes in vital signs (heart rate, blood pressure) or laboratory values until 72 h post-injection.

Clinical results with Resovist: a phase 2 clinical trial.

PURPOSE: To investigate the superparamagnetic iron oxide (Resovist) designed for contrast material-enhanced magnetic resonance imaging of the liver. MATERIALS AND METHODS: A phase 2 trial was performed in 33 patients with no more than five known focal solid liver lesions. Resovist was administered intravenously at doses of 4, 8, and 16 mumol of iron per kilogram of body weight. Postcontrast 1.0-T imaging was started 30 minutes after injection. RESULTS: Resovist significantly (P < or = .05) decreased liver signal intensity and increased lesion-to-liver contrast-to-noise ratio (C/N) and the number of detectable liver lesions: fast spin-echo (SE) (echo time, 90 msec) precontrast C/N, 11.7 +/- 7.9 [standard deviation]; postcontrast [8-mumol Fe/Kg] C/N, 29.2 +/- 14.2). The dose of 8 mumol Fe/kg was sufficient for the detection of focal liver lesions, and T2-weighted fast SE with an echo time of 90 msec was the overall best pulse sequence. CONCLUSION: Resovist is a safe contrast agent, and a dose of 8 mumol Fe/kg is sufficient to enhance detection of focal liver lesions at T2-weighted fast SE MR imaging.

5-Fluorouracil, folinic acid, etoposide and cisplatin chemotherapy for locally advanced or metastatic carcinoma of the oesophagus.

38 patients with advanced oesophageal carcinoma were treated with intravenous (i.v.) folinic acid (300 mg/m2), 5-fluorouracil (500 mg/m2), etoposide (100 mg/m2), and cisplatin (30 mg/m2) (FLEP), on days 1, 2 and 3, every 22-28 days. 26 patients had locally advanced disease (LAD) and 12 had metastatic disease (M1). Oesophagectomy was planned for patients with LAD in case of tumour regression after chemotherapy, while patients with M1 disease received chemotherapy only. The overall remission rate was 45% (17/38) including four clinical and two pathologically confirmed complete remissions. 16 patients underwent oesophagectomy, 12 after response to FLEP, and 4 after FLEP and subsequent irradiation +/- 5-fluorouracil/mitomycin. Toxicity was mainly haematological, with WHO grade 3 and 4 leukocytopenia in 50% and thrombocytopenia in 31% of the patients. Two treatment-related deaths were observed; one due to chemotherapy and one postoperatively. Median survival time of LAD patients was 13 months, and actuarial 2-year survival was 31%. Patients with complete tumour resection after FLEP had a median survival time of 18 months and a 2-year survival rate of 42%. Median survival of M1 patients was 6 months. FLEP is an active combination for oesophageal cancer, especially when used preoperatively in LAD.

Clinical and functional results of abdominal rectopexy with absorbable mesh-graft for treatment of complete rectal prolapse.

OBJECTIVE: To report the long term results of abdominal rectopexy in patients with complete rectal prolapse. DESIGN: Ongoing prospective randomised study. SETTING: Department of Surgery, Westfälische Wilhelms-University, Münster. SUBJECTS: 47 patients with complete rectal prolapse operated on between 1982 and 1989. INTERVENTIONS: Abdominal rectopexy with absorbable mesh made of either polyglycolic acid (n = 17) or polyglactine 910 (n = 30). MAIN OUTCOME MEASURES: Postoperative complications and late results at a mean of 50.5 (range 2-102) months after operation. RESULTS: Thirteen patients (28%) developed postoperative complications, most of them minor; there was one enterocutaneous fistula. Thirty five patients (74%) were available for late follow up. There were no case of recurrent prolapse and 5 (14%) had developed mucosal prolapse. Of the 22 patients who had been incontinent before operation, 8 had become totally continent and 6 partially continent Overall continence improved in 18 (51%) of the 35 patients. Three patients who were continent before operation had become incontinent. CONCLUSION: Absorbable mesh is a suitable material for abdominal rectopexy.

[Therapeutic problems of cancers of the gallbladder]. / Problèmes thérapeutiques posés par les cancers de la vésicule biliaire.

Data of 32 patients who were operated for gallbladder carcinoma were evaluated in a retrospective meta-analysis. Results were compared with endoscopic retrograde cholangio-drainage (ERCP) using large size 12/14-French gauge endo-prostheses with side flaps to prevent migration. According to the TNM classification 84% of patients were classified as stage IV, 12.5% were in a stage III and 3% were in a stage II. Only 22% of cases were operated for cure (cholecystectomies, lymphadenectomy, wedge resection of the liver). All patients died in between one year on cancer, average survival was 158 days in TNM stage II, 183 days in stage III and 75 days in stage IV. Early complication rate was in stage III and 75 days in stage IV. Early complication rate was at 28% due to cardiac and pulmonary complications. No one died as a result of the operation. Endoscopic bile duct drainage (ERCP) for gallbladder carcinoma (n = 21) was shown to be superior to surgical results with an average survival of 160 days. Early complication rate (30 day interval) was at 5.6% (n = 1014), mostly due to tube occlusion with cholangitis; clinical mortality was 2.6% only (n = 393). Occlusion of the endoscopic 12/14-French gauge tube was seen after 213 days in average. Endoscopic therapy was shown to represent an independent way in gallbladder cancer treatment not only for patients defined as not suitable for operation. All own results were compared to the literature, therapeutic regimen in gallbladder carcinoma is summarized as an organigramm.