A 27-year-old woman with multiple bilobal liver metastases of a carcinoid tumour and carcinoid syndrome was treated with the somatostatin analogue Octreotide, 450-600 micrograms daily subcutaneously. This improved previous attacks of marked epigastric pain, while endocrine activity and tumour mass remained unchanged. Shortly after treatment had begun, soft fatty stools and oxaluria were noted. After six months severe renal colics were found to be due to non-opaque caliceal calculi, and a contracted non-functioning gallbladder was discovered. The calculi consisted of oxalate. The enteric hyperoxalosis, oxaluria and urolithiasis were presumably side effects of the Octreotide treatment.

We sought to verify earlier reports of increased platelet reactivity in patients with peripheral arterial disease (PAD) during perioperative heparin administration, and to test the hypothesis of platelet hypersensitivity to heparin in these patients. Before and after incubation of platelet rich plasma with unfractionated (UH), low molecular weight heparin (LMWH), and a low molecular weight heparinoid, real-time quantitative assessment of platelet function was performed by stagnation point flow adhesio-aggregometry (SPAA) in 21 patients with PAD and 14 healthy volunteers. With SPAA the occurrence of spontaneous aggregation is pathological. In the 15 patients requiring operation, platelet function and count were measured at regular intervals. To detect heparin dependent antibodies, the heparin induced platelet activation assay (HIPA) was performed preoperatively and after 10 days of heparin therapy. Mean baseline platelet adhesion in patients was double that observed in controls (p < 0.001). Spontaneous aggregation was seen in 9 (43%) patients and no controls (p < 0.001). In controls heparinoid reduced, whereas UH and LMWH slightly increased adhesion. Spontaneous aggregation was observed once with UH. Platelets from patients showed significantly enhanced adhesiveness and aggregability (p < 0.05) with UH and LMWH when compared to controls. Effects with the heparinoid were less pronounced and non-significant. In patients requiring operation, postoperative increases in platelet function and reductions in count were significant (p < 0.001). Ten (67%) experienced a fall in platelet count of > 50%. Preoperatively the HIPA assay showed no evidence of antibodies, whereas after heparin administration antibodies were verified in 4 (32%) patients and could not be ruled out in 6 (40%). Three developed postoperative thrombosis, in one case fatal. A hypersensitive in vitro and in vivo platelet response to heparin was verified in patients with PAD and a large number developed the immunological type of heparin-associated thrombocytopenia. Our findings suggest that a thrombin antagonist which does not interact with platelets may give the best perioperative protection in these patients.

Schorr, M.; Siebeck, M.; Welcker, K.; Czwienzek, E.; Gippner-Steppert, C.; Waydhas, C.; Eibl-Eibesfeldt, B.; Waldner, H.; Jochum, M.; Redl, H. Author Information

Das von Buess et al. (1984) entwiekelte Instrumentarium zur transanal endoskopischen Mikrochirurgie (TEM) des Rektums ist ein ausgefeiltes und aufeinander abgestimmtes Werkzeug, welches in Verbindung mit der von Buess angegebenen Nahtteehnik die Resektion von Tumoren auch im mittleren und oberen Rektum ermöglicht. Diese Bereiche waren bis dahin über die peranale Methode nach Parks (1968) nicht zu erreichen und mußten über posteriore, auch transsphinktere Zugänge oder über eine anteriore Resektion behandelt werden. Buess konnte in den folgenden Jahren zeigen, daß seine Technik im Vergleich zu den therapeutischen Alternativen weniger invasiv und komplikationsärmer durchführbar ist (Buess 1989, 1991).

Retrospektiv wurden die Krankenakten von 29 Patienten untersucht, bei denen eine schwere Pankreatitis und eine Sepsis gesichert waren. In 55% der Fälle lag eine akute Pankreatitis, in 45% der akute Schub einer chronischen Pankreatitis vor. Folgende Faktoren waren signifikant mit einer höheren Letalität verbunden: 2 oder mehrere Vorerkrankungen, Vorliegen einer akuten Pankreatitis, Auftreten weiterer intraabdominaler Komplikationen wie Kolonperforation und intraabdominale Blutungen. Tendenziell mit einer höheren Letalität verbunden waren: ein Alter über 60 Jahre, eine biliäre Ätiologie, infizierte Pankreasnekrosen, eine diffuse Peritonitis.

Chronotherapy with antineoplastic drugs is a rather new strategy of reducing cytotoxic side effects. Because the circadian timing of 5-fluorouracil (5-FU) was reported to result in a higher efficacy and lower toxicity, the authors conducted a chronopharmacologic Phase I trial with 5-FU and folinic acid (FA).Eight patients with advanced colorectal cancer received 5-FU (initial dose of 500 mg/m2/day) and FA (20 mg/m2/day) as a continuous intravenous infusion over 5 consecutive days. Using a portable, ambulatory drug delivery system, 75% of the daily dose of 5-FU and FA were given from Oh00-7h00, and the remaining 25% from 7h00-24h00. Treatment courses were repeated after 28 days. Dose escalations of 250 mg/m2/day of 5-FU and 10 mg/m2/day of FA per course were performed in the absence of any toxicity greater than WHO (World Health Organization) grade 2.Dose-limiting toxicity WHO grade 3 was observed at a dose of 750 mg/m2/day of 5-FU and 30 mg/m2/day of FA in five, and 1000 mg/m2/day of 5-FU and 40 mg/m2/day of FA in two patients, respectively. One patient tolerated 1000 mg/m2/day of 5-FU and 40 mg/m2/day of FA, but the treatment was stopped before further dose escalation because of rapid disease progression. Mucositis was the dose-limiting toxicity in seven patients and diarrhea in two. Disease stabilization occurred in three patients and disease progression in five. Compared with conventional Phase I/II trials using a 5-day infusion regimen, the maximal tolerated dose of 5-FU and FA was slightly higher but significantly lower than in a chronotherapeutic trial that used a different, sinusoidal mode of drug application.Based on these results, the authors feel justified to caution that the circadian timing of 5-FU plus FA may not always allow the safe application of high dose levels. Future Phase I/II studies need to define whether specific drug delivery systems or schedules are necessary for chronotherapy with 5-FU and FA in patients with colorectal carcinoma.

PURPOSE: This study was designed to test the reproducibility of the diagnostic assessment of defecographies in patients with a suspected disorder of defecation. METHODS: To evaluate interobserver agreement, 100 defecographic series of patients with complaints suggesting a disordered defecation were evaluated independently by three observers with a standardized questionnaire. After six weeks, a random sample of 35 of 100 defecographies was evaluated a second time with clinical data provided (history, proctologic examination). To evaluate whether the position of residual volume in the rectum would affect agreement, patients with substantial retention either in the upper or lower rectum were also evaluated separately. RESULTS: Total agreement regarding rectocele and internal prolapse was 0.81 and 0.75, respectively (1.0 = complete agreement), and was significantly higher than chance agreement. Total agreement regarding residual volume in the rectum at the end of defecography and clinical relevance of findings was not different from chance agreement, providing clinical data did not significantly improve agreement. When residual volume was situated in the lower rectum, agreement regarding incompleteness of emptying and its clinical relevance was much better (0.93). CONCLUSIONS: Interobserver agreement is good regarding the deformation of the rectum during defecography but not different from chance agreement regarding the completeness of evacuation.

The records of 29 patients with severe pancreatitis and sepsis were evaluated retrospectively. In 55% an acute pancreatitis and in 45% an acute attack of chronic pancreatitis were diagnostizised. A significantly higher mortality was found: in patients with two or more chronic diseases, in case of an acute pancreatitis, in case of additional intra-abdominal complications such as perforation of the colon or intra-abdominal bleeding. Patients over 60 years did not show a significantly higher mortality rate. Furthermore biliary pancreatitis, infected pancreatic necrosis and diffuse peritonitis had no significant effect on the overall mortality rate.

Over the past decade various clinical trials have used monoclonal antibodies as therapeutic agents against solid tumours. No consistent pattern of response or improved survival has yet emerged although antigenic heterogeneity and insufficient accessibility of cells in advanced tumours have been offered as explanations for these failures. We designed a study in which a monoclonal antibody was used to target minimal residual disease in an early stage of tumour cell dissemination in patients with colorectal cancer. Only patients in Dukes' stage C who had undergone curative surgery and were free of manifest residual tumour were admitted.189 patients with colorectal cancer of stage Dukes' C were randomly assigned to an observation regimen or to postoperative treatment with 500 mg of 17-1A antibody, followed by four 100 mg infusions each month. A balance of risk factors in the two groups was achieved by dynamic randomisation procedure. After a median follow-up of 5 years, antibody treatment reduced the overall death rate by 30% (Cox's proportional hazard, p = 0.04, log-rank p = 0.05) and decreased the recurrence rate by 27% (p = 0.03, p = 0.05). The effect of antibody was most pronounced in patients who had distant metastasis as first sign of a relapse (p = 0.0014, p = 0.002), an effect that was not seen for local relapses (p = 0.74, p = 0.67). Toxic effects of 17-1A antibody were infrequent, consisting mainly of mild constitutional and gastrointestinal symptoms. During 371 infusions four anaphylactic reactions were seen, all controllable by intravenous steroids and none necessitated admission to hospital.Adjuvant therapy with 17-1A antibody extends life and prolongs remission in patients with colorectal cancer of Dukes' stage C.

Background. Chronotherapy with antineoplastic drugs is a rather new strategy of reducing cytotoxic side effects. Because the circadian timing of 5-fluorouracil (5-FU) was reported to result in a higher efficacy and lower toxicity, the authors conducted a chronopharmacologic Phase I trial with 5-FU and folinic acid (FA).Methods. Eight patients with advanced colorectal cancer received 5-FU (initial dose of 500 mg/m(2)/day) and FA (20 mg/m(2)/day) as a continuous intravenous infusion over 5 consecutive days. Using a portable, ambulatory drug delivery system, 75% of the daily dose of 5-FU and FA were given from 0h00-7h00, and the remaining 25% from 7h00-24h00. Treatment courses were repeated after 28 days. Dose escalations of 250 mg/m(2)/day of 5-FU and 10 mg/m(2)/day of FA per course were performed in the absence of any toxicity greater than WHO (World Health Organization) grade 2.Results. Dose-limiting toxicity WHO grade 3 was observed at a dose of 750 mg/m(2)/day of 5-FU and 30 mg/m(2)/day of FA in five, and 1000 mg/m(2)/day of 5-FU and 40 mg/m(2)/day of FA in two patients, respectively. One patient tolerated 1000 mg/m(2)/day of 5-FU and 40 mg/m(2)/day of FA, but the treatment was stopped before further dose escalation because of rapid disease progression. Mucositis was the dose-limiting toxicity in seven patients and diarrhea in two. Disease stabilization occurred in three patients and disease progression in five. Compared with conventional Phase I/II trials using a 5-day infusion regimen, the maximal tolerated dose of 5-FU and FA was slightly higher but significantly lower than in a chronotherapeutic trial that used a different, sinusoidal mode of drug application.Conclusion. Based on these results, the authors feel justified to caution that the circadian timing of 5-FU plus FA may not always allow the safe application of high dose levels. Future Phase I/II studies need to define whether specific drug delivery systems or schedules are necessary for chronotherapy with 5-FU and FA in patients with colorectal carcinoma.

Endorectale Ultraschalluntersuchungen wurden zur Erfassung und zur Beurteilung der Ausdehnung anorectaler und pelviner Enzündungen von 3/88 bis 10/92 78 mal bei 63 Pat. durchgeführt. Diagnosen: Douglas-Abszeß [11], perianaler Abszeß oder Fistel [24], Abszeß oder Fistel bei Crohn oder Colitis ulcerosa [10] pararectale Abszesse [5], Anastomoseninsuffizienz [3], verschiedene [15]. Die Aussagekraft bezüglich der Entdeckung zuvor unbekannter Enzündungsherde wurde mit dem klinischen Verlauf und operativen Befunden verglichen. Es ergibt sich: Sensitivität 100%, Spezifität 94%, pos. präd. Wert 83% und neg. präd. Wert 100%. Bei bekannten anorectalen Infekten wurde die Aussagekraft bezüglich chirurgisch relevanter klinisch schwer erfassbarer Abszeßausbreitungen nach hoch intersphinctär, pararectal oder transsphinetär erfaßt und mit dem operativen Befund verglichen. Sensitivität 93%, Spezifität 80%, pos. präd. Wert 87%, neg. präd. Wert 89%. Durch Endosonographie sind anorectale und pelvine Entzündungen sicher zu entdecken und hinsichtlich ihrer Ausdehnung zu erfassen.

The intention of this study was to correlate the retained volume at the end of defecography to certain defecographic findings and to the sense of incomplete emptying. In 170 defecographic series, the retained barium was estimated planimetrically. No particular defecographic finding determined a higher or lower amount of remaining volume, and the sense of incomplete evacuation did not depend on the amount of retained volume. Thresholds of urge and perception on anorectal manometry did not differ between patients with and without the feeling of incomplete evacuation. A rectocele, isolated or combined with an internal prolapse, caused the retained volume to be in the lowermost part of the rectum, whereas, in the case of an isolated intussusception, the remaining volume was located in the middle or higher part of the rectum. It is concluded that defecographic findings do not in general explain incomplete emptying or the sense of incomplete emptying, but they may determine the localization of the retained volume.

In a prospective study we examined the diagnostic value of MRI and MR cholangiography (MRC) in patients suffering from hepatobiliary disease. By using hepatobiliary contrast media (Mn-DPDP, Gd-BOPTA), sensitivity and specificity of MRI were significantly increased. In 65 patients we comparatively analyzed the diagnostic results of MRI and MRC versus ultrasound, CT and invasive techniques such as ERCP. We conclude that the use of MRI and MRC improves the diagnostic evaluation of patients with hepatobiliary disease.

Der Wert der endorektalen Ultraschallunterschung bei pelvinen und perirektalen Infektionen wurde untersucht.Seit 1988 wurden 56 Untersuchungen durchgeführt. Dargestellt wurden Douglas-Abzesse, Anastomoseninsuffizienzen, komplizierte Abszesse wie hohe Rektumwandabszesse, hohe pararektale Ausdehnung bei Intersphinkterabszessen, Ischiorektalabszesse und chronische Fistelungen bei M.Crohn mit teils ausgedehnten perirektalen Flüssigkeitsansammlungen. Es ergab sich für die ersten 29 Untersuchungen eine Sensitivität von 100%, eine Spezifität von 87%, ein positiver Vorhersagewert von 88% und ein negativer Vorhersagewert von 100%.Die Untersuchungemethode kann zur Routinediagnostik empfohlen werden.

In an open prospective study the tolerance and diagnostic value of the new hepatobiliary contrast agent Mn-DPDP in MR imaging was evaluated in 20 patients suspected of having focal liver lesions. T1- and T2-weighted spin-echo sequences and T1-weighted gradient-echo sequences were obtained before and after intravenous application of Mn-DPDP. In all patients the signal to noise (S/N) values of normal liver tissue increased significantly after application of Mn-DPDP. All focal lesions could be better localized and differentiated due to increased contrast to noise ratios of lesion to liver. Pathological examination revealed in 14 patients malignant and in 5 patients benign liver lesions; one patient had no pathological findings. In metastatic disease of the liver 25-120% more lesions could be detected in MRI after Mn-DPDP-application, compared with the unenhanced images. In 5 patients the lesions showed significant enhancement of Mn-DPDP (2 cirrhotic nodules, 2 hepatocellular carcinomas, 1 focal nodular hyperplasia). Our preliminary results indicate that Mn-DPDP is a well-tolerated contrast agent useful for the detection and differentiation of liver lesions in MR imaging.