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Background: This study aimed to determine the prevalence of psychiatric morbidity and distress among 189 consecutively recruited cancer patients upon admission to surgical oncology wards, and to investigate the recognition of distressed patients by medical staff. Patients and methods: Assessment consisted of a diagnostic psychiatric interview (SCID, DSM-IV), patient-reported distress using a standardised questionnaire (Hospital Anxiety and Depression Scale), and physicians’ and nurses’ estimates of patients’ distress. Twenty-eight per cent of patients were assigned a psychiatric diagnosis, with adjustment disorder predominating. Results: Surgeons accurately recognised marked distress in 77% of patients with a psychiatric disorder and nurses did so in 75%. Because of low specificity, the positive predictive value was only 39% in surgeons and 40% in nurses. However, recognition of distress translated into referral to the psychosocial liaison service for only a minor proportion of distressed patients. Conclusions: Since a remarkable proportion of distressed patients remained unrecognised by the medical staff, only systematic screening of patients upon admission allows timely support to those

Background—Reactive oxygen species contribute to tissue injury in inflammatory bowel disease (IBD). The tripeptide glutathione (GSH) is the most important intracellular antioxidant. Aims—To investigate constituent amino acid plasma levels and the GSH redox status in different compartments in IBD with emphasis on intestinal GSH synthesis in Crohn's disease. Methods—Precursor amino acid levels were analysed in plasma and intestinal mucosa. Reduced (rGSH) and oxidised glutathione (GSSG) were determined enzymatically in peripheral blood mononuclear cells (PBMC), red blood cells (RBC), muscle, and in non-inflamed and inflamed ileum mucosa. Mucosal enzyme activity of γ-glutamylcysteine synthetase (γGCS) and γ-glutamyl transferase (γGT) was analysed. Blood of healthy subjects and normal mucosa from a bowel segment resected for tumour growth were used as controls. Results—Abnormally low plasma cysteine and cystine levels were associated with inflammation in IBD (p

Six hundred sixty-six patients received 792 liver transplants between February 1, 1984 and September 30, 1991. Biliary reconstruction was by choledochocholedochostomy (CDCD) with T-tube (n = 509) or Roux-en-Y choledochojejunostomy (CDJ) (n = 283). Twenty-five patients (4%) developed biliary strictures. Anastomotic strictures were more common after CDJ (n = 10, 3.5%) than for CDCD (n = 3, 0.6%). Intrahepatic strictures developed in 12 patients. Six patients had occult hepatic artery thrombosis (HAT). The other six patients received grafts in which cold ischemia time exceeded 12 hours. Anastomotic strictures were successfully managed by percutaneous dilation (PD) in five patients (n = 10), operation in three (n = 6), with retransplantation required in two patients. Intrahepatic strictures were managed by PD in seven, retransplantation in one, and expectantly in four patients. Of 25 patients, 19 (76%) are alive with good graft function. In three of six deaths, the biliary stricture was a significant factor to the development of sepsis and allograft failure. The authors conclude that (1) anastomotic strictures are rare after LT; (2) the development of biliary strictures may signify occult HAT; (3) PD is effective for most strictures; and (4) extended cold graft ischemia (less than 12 hours) may be injurious to the biliary epithelium, resulting in intrahepatic stricture formation.

The interaction between immunocompetent cells and tumor-endothelium is essential for effective immunologic recognition. In the present study we evaluated resting and CD11b/CD18-mediated leukocyte adhesion on tumor-endothelium of experimental pancreatic carcinoma and in healthy pancreatic venules.22 male Lewis rats (120-140 g) were anesthetized. Duct-like pancreatic carcinoma (DSL6A, Am. J. Pathol. 1993; 143:292) was induced by intrapancreatic implantation of tumor fragments between inert polymethylmetacrylat plates. After 4 wks the tumor-bearing pancreas was exposed and the microcirculation studied. Parameters in tumor vessels (15-40 microns) and healthy pancreatic collecting venules (20-40 microns) included: Erythrocyte velocity, Leukocyte adhesion, Vessel diameter and wall shear rate. Measurements were obtained before and 5 min after adding f-MLP (100 mM) or PAF (50 mM), two CD11b/CD18 agonists of different potency to the immersion chamber.[table: see text]In experimental pancreatic carcinoma leukocyte adhesion of low affinity is reduced despite comparable wall shear rates. The CD11b/Cd18-mediated adhesion of high affinity, which is inducible by f-MLP and PAF in healthy pancreatic venules, is absent in tumor vessels. This may be a mechanism by which malignant tumors escape immune control.

Intravital microscopy and FITC-labeled erythrocytes were used to investigate villous perfusion in the rat small intestine in a model of inflammatory bowel disease. Inflammation was induced with s.c. application of Indomethacin. It has previously been demonstrated that systemic Indomethacin leads to an increase in villous blood flow in the small intestine of the rat. In order to determine whether mast cell activation may contribute to the increase in villous perfusion, Ketotifen was used to inhibit mast cell degranulation. We found that Ketotifen significantly reduced villous perfusion in the inflamed intestine, but had no effect in the control group. We conclude that mast cell activation is one of the mechanisms leading to hyperemia in the mucosa of the small intestine in this animal model. Further studies are required to determine whether mast cell stabilizers may be beneficial in the treatment of inflammatory bowel disease in man.

In this study we investigated the effect of donor and recipient conditioning with N-acetylcysteine on the ischemia/reperfusion injury after experimental pancreas-transplantation. We performed standardized pancreaticoduodenal transplantation in male lewis rats. The pancreas was perfused with UW-solution, harvested and conserved at 4 degrees C. Cold ischemia time was 1.5 hours and 16 hours respectively. The microcirculation in the transplanted organ was quantified by means of intravital microscopy 1.5 hours after implantation and reperfusion in the recipient. After 16 hours of cold ischemia we found a significant reduction in capillary erythrocyte velocity and a significantly enhanced leucocyte/endothelium interaction. The treatment with N-acetylcysteine resulted in a significant improvement of these microcirculatory disorders after prolonged cold ischemia.

Hepatic microcirculation after warm hepatic ischemia in rats can be significantly enhanced by Antithrombin III. The number of sinusoidal stickers as a tool for characterizing the leukocyte-endothelial cell interaction was significantly reduced. The peak of serum transaminases as an indicator of hepatocellular damage was significantly decreased after the AT III application. It has to be concluded that AT III application before Pringle maneuver might significantly reduce the reperfusion damage after liver resection.

By means of thermodiffusion, monitoring of hepatic microcirculation was performed in 43 patients during the first week after liver transplantation. A significant decrease of liver perfusion was registered in 15 patients with early rejection. The disturbance of hepatic microcirculation preceded the increase of transaminases by 36 hours and the subsequent biopsy by 60 hours. Already 12 hours after the beginning of corticoid therapy liver perfusion started to recover. The quantification of hepatic microcirculation may facilitate faster diagnosis and treatment of early rejection following liver transplantation.

The prognosis of acute necrotizing pancreatitis is dependent on systemic complications. The endothelial adhesion molecule ICAM-1 mediates both leukocyte adhesion and migration. Expression of ICAM-1 was investigated at various time points in mild and severe necrotizing pancreatitis in the pancreas, lungs and intestine. A possible therapeutic effect of monoclonal antibodies against ICAM-1 was evaluated in severe necrotizing disease. The expression of ICAM-1 preceded the fulminant leukocyte Infiltration of the organs. In contrast to mild pancreatitis, ICAM-1 expression was increased at an earlier time point and systemically in severe necrotizing disease. Treatment with antibodies against ICAM-1 improved microcirculation and reduced local and systemic organ damage in severe pancreatitis.

TSH is the classic stimulator of thyroid cell function. Clinically, treatment with thyroxin to suppress TSH decreased the risk of thyroid cancer recurrence and improved patient survival. This study analyzed the effect of stably transfected human TSH receptor cDNA in an established model of metastatic follicular thyroid cancer cells (FC) compared to wild type FTC. Wild type FTC lack TSH receptors and do not depend on TSH for growth. However, they contain thyroglobulin, have intact thyroid functions and response to TSH. We tested growth, invasion, and adhesion of transfected tumor cells (FTC-TSHr) compared to parental cells. All transfected FTC-TSHr expressed TSHr mRNA. Compared to wild type cells invasion and growth of TSHr-transfected FTC were significantly inhibited (p0.001). All FTC adhered best to collagen IV and fibronectin. Compared to parental cells adhesion of unstimulated FTC-TSHr was significantly enhanced (p0.001). These in vitro data underline the important role of the human TSH receptor as the main regulator of thyroid growth and functions.

Gadolinium-DTPA enhanced dynamic MR imaging is a new method for the quantification of portal bloodflow and liver perfusion. In this study we evaluated the validity of this method comparing it with thermodiffusion and dopplerflowmetry in pigs. We found a significant correlation of tissue perfusion between dMRI and thermodiffusion and of portal bloodflow between dMRI and dopplerflowmetry. Partial occlusion of the portal vene was accurately detected by dMRI. Dynamic MRI could become a valuable diagnostic method for the quantification of liver perfusion.

Despite R0-resection up to 30% of patients with colorectal cancer stage UICC I and II die of recurrent disease. This tumor progression could be caused by isolated disseminated tumor cells in lymph nodes which are not detected by current staging methods. The purpose of this study was to develop a system for detecting lymphogenic tumor cell dissemination in colorectal cancer. With the established CK 20-RT-PCR we detected tumor cells in 32 of 107 histopathologically negative lymph nodes from patients with colorectal cancer. We conclude that the CK 20-RT-PCR is more sensitive than immunohistochemical methods in detecting isolated disseminated tumor cells of colorectal cancer in lymph nodes. To evaluate the prognostic significance of lymphogenic disseminated tumor cells the examination and follow-up of more patients is necessary.

The Ileo-Pouch-Anal-Anastomosis (IPAA) is the standard restorative procedure for Ulcerative Colitis and Familial Adenomatous Polyposis (FAP). IPAA may lead to considerable losses of fluids, especially in association with a protective loop ileostomy.The aim of this study was to investigate adrenal mechanisms in the regulation of volume homeostasis immediately after IPAA and protective ileostomy.For that purpose, 20 patients out of our patient population with elective IPAA with ileostomy participated in this study between 1993 and 1997. In all patients, routine laboratory tests and gluco- and minealocorticoid hormone measurements were performed preoperatively and 10 days after operation.These blood analyses indicated functional hyperaldosteronism immediately after IPAA. Significantly elevated levels of Aldosterone (36.4 +/- 25.1 ng/dl) and 18-OH-Corticosterone ( 173 +/- 11.3 ng/dl) were found. Among hormones with glucocorticoid effects, blood levels of Cortisol (10.4 +/- 4.8 microg/dl) were significantly elevated, while 11-Desoxycortiosterone (13.9 +/- 8.4 ng/dl) and Corticosterone (0.8 +/- 0.6 microg/dl) were not significantly elevated. Serum electrolytes remained unchanged.Our results indicate that hormones with mineralocorticoid effects play a predominant role in the compensation of ileostomy losses after IPAA.

A common pathway in the pathogenesis of acute pancreatitis is the generation of free oxygen radicals. The most important defense mechanisms are free radical scavengers, especially glutathione. This study evaluates the influence of the inhibition of glutathione synthesis with L-buthionine-(S,R)-sulfoximine (BSO) on the course of experimentally induced acute pancreatitis in rats and the effects on isolated pancreatic acini and their secretion pattern. Thus acute necrotizing pancreatitis was induced with intraductal infusion of low-dose glycodeoxycholic acid and subsequent hyperstimulation with cerulein with and without pretreatment with BSO. In vitro pancreatic acini were isolated and stimulated with different concentrations of cerulein with and without BSO. The BSO-treated group showed a significantly reduced survival, more necrosis, and a decreased secretion of amylase in vivo. No effect on secretion pattern in either groups was seen in vitro and BSO did not exert toxic effects. Based on the data presented, this study demonstrates deleterious effects of scavenger depletion on the course of experimental pancreatitis. This is due to the systemic effects of free oxygen radicals rather than to local effects.

The course of pancreatitis is paralleled by a drastic reduction in organ perfusion and increased ICAM-1-mediated leukocyte-endothelial interaction. We aimed to evaluate the effect of oxygen radicals on ICAM-1 expression and the microcirculation in severe acute pancreatitis using the oxygen radical scavenger dimethylsulfoxide (DMSO).Severe pancreatitis was induced in rats (n = 32) who were randomly assigned to one of two groups: either 4 ml/kg 50% DMSO/saline (v/v) started 3 h after induction of pancreatitis or 4 ml/kg saline (control). Microcirculation was evaluated by intermittent intravital microscopy. Serum amylase and lipase, histomorphometric changes, immunohistochemistry for ICAM-1 expression and 24-hour survival were investigated.Leukocyte adherence was significantly reduced (4.4 +/- 0.47 vs. 5.58 +/- 0.69 sticker/100 micro m, p0.05), and mean capillary (0.96 +/- 0.06 vs. 0.45 +/- 0.13 mm/s; p0.01) and venous erythrocyte velocity (1.16 +/- 0.12 vs. 0.58 +/- 0.16 mm/s, p0.01) were significantly increased by DMSO treatment. Microcirculatory disturbances were paralleled by an increase in endothelial ICAM-1 expression, whereas DMSO reduced ICAM-1 expression.DMSO improves pancreatic microcirculation and reduces ICAM-1 expression and subsequent leukocyte adhesion, suggesting an important role of oxygen free radicals in the pathway of endothelial ICAM-1 expression and microcirculatory disturbances in acute pancreatitis.

The main progress in surgical oncology regarding colonic cancer has been made by standardizing the mode of resection: En block resection of the tumor-bearing colon segment together with the draining lymph nodes, including the lymph nodes at the origin of the respective main vessel, is mandatory. Minimal invasive surgery is an option for resection, however, results of ongoing multicenter trials have to clarify the situation. Adjuvant therapy is used for patients in stage III, who are not included in studies. Since quality of surgery has a major influence on prognosis, this factor also needs to be taken into account when judging the impact of adjuvant therapy. New chemotherapeutic agents have been proven to be valid for palliative and probably also for adjuvant treatment. Prophylactic surgery is routine for patients with ulcerative colitis and FAP, the benefit for patients with HNPCC has to be further evaluated. New knowledge on the individual prognosis might optimize treatment; most probably this will be accomplished by detection of minimal residual disease. The impact of the sentinel node concept in colon cancer is unclear. New progress will be possible by an approach adapted to the individual problem together with accumulating and linking experience and knowledge.

Surgery has the optimal possibility for theoretical-clinical transfer of molecular biological knowledge. On the basis of the existing research emphasis on clinical molecular biology at the Department of Surgery, University of Heidelberg, this is shown by the example of colorectal cancer: Establishment of a large clinical register for hereditary colorect cancer, use of molecular biological methods to improve phenotype/genotype correlations, definition of risk groups, decision on surgical therapeutical concepts for hereditary cancers and considerations on the creation of problem-orientated centers for hereditary cancer. A further example for the application of molecular methods is the detection of minimal residual disease or tumor cells in the different compartments (blood, lymph nodes, bone marrow and peritoneum) in order to achieve a better risk evaluation exceeding the standard pathohistological stage definition. The goal is an individualized or more focused therapy for each patient. Transfer of research from the basic sciences into the clinical setting, integrated into the daily clinical work, is possible in a so-called tandem model.

The two-phase restorative proctocolectomy is the treatment of choice for surgical therapy of the familial adenomatous polyposis (FAP) and also for the ulcerative colitis (UC). Besides the well-known complications the entire removal of the colorectum leads to an impairment of fluid and electrolyte resorption.Over a time period of two years we observed 320 proctocolectomized patients with ileal pouch-anal anastomosis (IPAA). All patients with high pouch output but without organic malfunction were identified. The organic reasons were excluded with the help of pouchoscopy, radiography or MR imaging. We evaluated routine parameters, the kidney function, the electrolyte changes, the acid-base balance and the urine pH, as well as the hormonal changes of the suprarenal glands. We identified seven patients with 'high pouch output' out of 320 patients observed. The control group consisted of 14 proctocolectomized patients without hints of complications in the endoscopic, radiographic and routine laboratory diagnostics.Neither group showed any significant differences in the analysis of the routine parameters. A significant drop of the urine sodium concentration of 40.5 +/- 18.7 mmol/l (control group 98 +/- 43.4 mmol/l) was observed in the group with 'high pouch output'. In this group the plasma aldosterone values were strongly increased with an average of 42.6 +/- 28.9 ng/dl (control group 13.2 +/- 6.8 ng/dl) as well as the plasma 18-hydroxycorticosterone with an average of 153.7 +/- 121.1 ng/dl (control group 153.7 +/- 121.1 ng/dl). Neither group of patients showed increased activity of free corticosterone and free cortisol. Only free 11-desoxycorticosterone was elevated in the group with 'high pouch output'.Our results prove that the mineralocorticoid adrenal activity plays a central role in order to preserve the volume and electrolyte homeostasis. The low frequency of 'high-pouch-output'-complications in realms of the restorative proctocolectomy proves the excellent compensation of the removal of the colon mucosa. Plasma aldosterone seems to be a diagnostic marker encapsulating the reabsorption problems of intestinal salt and volume losses after proctocolectomy.

Einleitung: Eine Laparotomie ist bei Patienten mit Magenkarzinom, wenn eine Peritonealkarzinose oder diffuse Lebermetastasierung vorliegt, nicht indiziert. Diese Befunde entgehen jedoch oft der praoperativen bildgebenden Diagnostik. Verbesserung der praoperativen Diagnostik durch den Einsatz der Laparoskopie konnte die explorative Laparotomie vermeiden. Die routinemasige Anwendung der Laparoskopie bei allen Patienten mit Magenkarzinom konnte zur unnotigen Erweiterung der invasiven Diagnostik und zum Anstieg der damit verbundenen Komplikationen fuhren. Patienten und Methode: Alle Patienten, die im Zeitraum von 6/99 bis 8/01 in der Chirurgischen Universitatsklinik Heidelberg mit einem primaren Magenkarzinom behandelt wurden, wurden prospektiv erfasst. Bei allen Patienten wurde praoperativ eine Gastroskopie, EUS, Sonographie des Abdomens und Rontgen-Thorax durchgefuhrt und ggf. durch CT und MRT erganzt. Die Indikation zur Laparoskopie wurde gestellt, wenn die bildgebenden Verfahren (EUS, CT, MRT) bei asymptomatischen Patienten eine lokale Infiltration, Peritonealkarzinose oder diffuser Lebermetastasierung nicht sicher ausschliesen konnten. Bei symptomatischen Patienten (Stenose, Perforation, Blutung) mit Indikation zu palliativen Masnahmen, wurde auf die diagnostische Laparoskopie verzichtet. Ergebnisse: Seit Juni 1999 bis September 2001 wurden in unserer Klinik 130 Patienten wg. eines primaren Magenkarzinoms behandelt. 105 Patienten (81%) wurden nach o.g. Kriterien primar laparotomiert: 77 mal mit kurativer Zielsetzung, 28 mal mit palliativer Zielsetzung. Bei 2 Patienten (1,5%), die mit kurativer Zielsetzung laparotomiert wurden, zeigte sich intraoperativ eine Peritonealkarzinose. Zehn weitere Patienten mit weit fortgeschrittenem, nicht resektablem Tumorleiden wurden direkt einer palliativen Chemotherapie zugefuhrt. 15 mal stellten wir die Indikation zur diagnostischen Laparoskopie. In 6 Fallen wurde nach der diagnostischen Laparoskopie die Operabilitat als gegeben angesehen und es konnte eine potentiell kurative Operation durchgefuhrt werden. Bei 6 Patienten (5%) haben wir bei der diagnostischen Laparoskopie eine Peritonealkarzinose bzw. Lebermetastasen nachweisen konnen, so dass auf eine Laparotomie verzichtet werden konnte. Bei 3 weiteren Fallen wurde laparoskopisch eine Peritonealkarzinose nicht erkannt, die erst bei der nachfolgenden explorativen Laparotomie gesichert werden konnte. Schlussfolgerung: Bei sorgfaltiger klinischer und bildgebender Diagnostik hat sich die selektive Indikationsstellung zur diagnostischen Laparoskopie bewahrt.

Rektumkarzinomrezidive werden bei 3 - 50% der Patienten nach Primaroperation beschrieben. Wir untersuchten den Einflus des operativen Vorgehens und des Einsatzes multimodaler Therapieverfahren intervallbezogen (82 - 89 und 90 - 97) im Hinblick auf das rezidivfreie und Gesamtuberleben. Patienten und Methodik:In die retrospektive Auswertung der prospektiv dokumentierten Patientendatei (82 - 97) wurden insgesamt 247 Patienten mit einem Rektumkarzinomrezidiv (Primar-OP: 121 [49%] in HD, 126 [51%] auswarts) eingeschlossen. Daruberhinaus erfolgte eine Einteilung in konservativ (n = 96) und operativ (n = 151) behandelte Patienten sowie in 2 gleichgrose Zeitintervalle (Int. I: 82 - 89, n = 119; Int. II: 90-97, n = 128). Die Daten wurden auf einem eigens konzipierten Erhebungsbogen erfasst und computergestutzt ausgewertet. Die Berechung der uLR erfolgte nach dem Verfahren von Kaplan-Meier. Ergebnisse:Fur alle Patienten betrug das mittlere rezidivfreie uberleben nach Primaroperation 22,8 Monate (I: 19,1 ± 17,3 vs II: 23,9 ± 19,8). Knapp 70% der Rezidive traten innerhalb der ersten 2 Jahre (34,5% asymptomatisch) auf. Sie waren in 34% auf die Anastomose beschrankt, bei 66% lag ein extraluminales Rezidiv vor. Insgesamt wurden 151 Patienten (61%) mit einem Rezidiv operiert. R-Status: RO: n = 44 (33%), Rl:n = 9, R2: n = 79 (60%), keine Resektion: n= 19 (13%). Fur die mit Rezidiv RO-resezierten Patienten lag das mittl. rezidivfreie uberleben bei 20,7 ± 18,1 (Int. I) vs 24,3 ± 13,3 (Int. II) und mit einer 18% 5J.-uLR signifikant Uber den inoperablen/R1/R2- Patienten (5J.-ULR: 0 -7%) (p < 0,001). Die Zahl der RO- resezierten Patienten stieg von 12/60 (Int.I: 20%) auf 32/91 (Int.II: 35%) verbunden mit einer Verbesserung der 5 J. ULR von 8 auf 23% (p < 0,05).Bei kurativem Ansatz wurde nahezu durchwegs eine abdomino-perineale Exstirpation (insgesamt bei 40%) durchgefuhrt. Dabei stieg die Anzahl der erweiterten Eingriffe von 25% (Int.I) auf uber 80% (Int.II). Wenngleich bereits knapp 47% zum Zeitpunkt der Diagnose Fernmetastasen aufwiesen wurde als Hauptursache fur die nicht kurative Einschatzung zu 75% das regionale Tumorwachstums genannt. Der intra-und postoperative Blutverlust lag im Mittel bei 1530 ml, die postoperative Komplikationsrate bei 34%. Die 30 Tage Letalitat war rucklaufig (Int.I: 6%, Int.II: 3,9%, R0-resezierte Patienten: 0%). Zusammenfassungg:Die Prognose RO-resezierter Patienten ist mit den Ergebnissen nach primar OP vergleichbar. Die Radikalitat (RO-Resektionen) nahm im Intervall zwischen 1990 - 97 am ehesten auch infolge der neoadjuvanten Radiochemotherapie (+ IORT) zu. Gleichzeit kam es zu einem Abfall der Mortalitat bei signifikantem Anstieg der 5 J. ULR.

The prognostic assessment of cancer patients is of special importance clinically and scientifically. Prognostic factors are divided into three groups: patient-, treatment- and tumor-related factors. Only a minority of those factors, for example the UICC TNM classification, have been proven by multivariate studies to be of prognostic significance and have an impact on patient management, even then only as prognostic groups. The individual prognosis of a specific patient, which would allow an individualized therapy, cannot yet be adequately assessed. New prognostic factors may result in improved prognostic predictions; currently it is unclear whether this will be accomplished by molecular prognostic parameters assessed on the basis of the primary tumor or rather by the detection of disseminated cancer cells. Of major importance are well-designed clinical studies, in order to prove the clinical benefit of an individualized patient management.

Endothelin (ET) and its precursor big-ET were synchronously analyzed by RIA in liver biopsies and systemic plasma during porcine orthotopic liver transplantation (OLT) before graft harvesting (phase A), after cold storage (phase B), and early (phase C) and late reperfusion (phase D). Tissue and plasma concentrations were correlated with length of survival and reperfusion. Increased tissue ET/big-ET levels were already detected during phase B (ET: 46 ± 20; big-ET: 245 ± 119 pg/mg cytosolic protein) and remained elevated in phase C (ET: 49 ± 16; big-ET: 306 ± 144 pg/mg) compared to baseline (ET: 32 ± 13; big-ET: 185 ± 164 pg/mg; p < 0.05). In phase D, a rapid concentration decline was detected (ET: 36 ± 26; big-ET: 163 ± 138 pg/mg). Systemic ET levels were elevated in phase B (3.4 ± 3.0 pg/ml), C, (2.8 ± 1.2 pg/ml) and D (2.6 ± 2.0 pg/ml), compared to baseline (1.7 ± 1.1 pg/ml; p < 0.05). ET/big-ET kinetics in liver tissue and systemic plasma showed analogous characteristics. Intrahepatic ET accumulation during storage and early reperfusion could be of relevance for harvest-related disturbances of hepatic microcirculation.

Optimized surgical management is the most important factor influencing prognosis of patients suffering for rectal carcinoma. Oncologically radical surgical procedures with the intent of histologically complete resection should be performed, including excision of the tumour in total with sufficient margins in the oral and aboral directions. Total excision of the mesorectal tissue, at least in low-lying rectal tumours, is strongly recommended. Several retro- and prospective studies show that the surgeon him- or herself, using these adequate techniques, is the most important, statistically significant independent prognostic factor in patients with rectal carcinoma. In addition, adjuvant radiochemotherapy, given before or after surgery, decreases the local failure rates of high-risk patients (UICC stages II and III). Such radiochemotherapy is, to the great variety of different local failure rates in different surgical departments mandatory as recommended by the consensus conference of the German Cancer Society in July 1999. New and improved radiation techniques (conformal radiotherapy, intraoperative radiotherapy) could significantly decrease therapy-related toxicity, and innovative schedules (continuous low-dose 5-FU) may show increased therapeutic benefit of adjuvant treatment. Combined radiochemotherapy prior to surgery seems to increase the rate of sphincter-preserving procedures in low-lying rectal cancer. Definitive results and a clear advantage of pre- over postoperative radiochemotherapy (currently being tested in a German multicenter study) are still pending.

Soft tissue sarcomas (STS) are frequently resected incompletely or without an adequate margin. In such clinical situations an oncological re-resection (wide or compartmental resection or amputation) is recommended. Here, we evaluate the results of oncological re-resection for STS.Prospectively gathered data on 67 patients who underwent oncological re-resection after inadequate (intracapsular or marginal) surgery for primary soft tissue sarcomas were analyzed.STS were located in the extremities (85%) and trunk (15%). Advanced UICC stages (1992, 4th edn., 2nd Rev.), IIB-IIIB predominated (66%). Twenty-five patients received intraoperative radiotherapy. Morbidity of re-resection was 28.4%. Residual tumor was detected in 64% of the specimens and clear margins were obtained in 60 patients (90%). With a median follow-up of 57 months the overall local control in patients with tumor-free resection margins was 88% (UICC IA-IIA 100%, IIB-IIIB 82%). Patients treated by adjuvant intraoperative radiotherapy for UICC stages IIB-IIIB with clear margins achieved 90% local control. The 5-year overall survival rate was 87% in patients with tumor-free resection margins.These findings support the strategy of oncological re-resection after previously non-oncological surgery of STS and imply that re-resection is the prerequisite for any effective adjuvant therapy modality.

To determine the effect of phosphodiesterase inhibitors, milrinone and zaprinast on a hepatic warm ischemia-reperfusion injury, changes in hepatic microcirculation and liver injury were examined in a partial hepatic warm ischemia-reperfusion model in rats. In milrinone- and zaprinast-pretreated rats, leukocyte-endothelial interaction was suppressed and hepatic microcirculation was ameliorated after reperfusion. ALT blood level was significantly suppressed by these treatments. Milrinone augmented cAMP and zaprinast elevated cAMP and cGMP concentrations in the liver tissue. These data suggested that cyclic nucleotides may have some important function in this tolerance induction mechanism against ischemia-reperfusion injury.

Background: Lipopolysaccharides reaching the liver over the portal vein during intraabdominal sepsis activate Kupffer and endothelial cells, leading to hepatic microcirculatory disturbances and reduced hepatic microperfusion. The resulting hepatocellular dysfunction aggravates the MODS during the course of sepsis. Our investigation was designed to study the influence of heparin on hepatic microperfusion, leukocyte-endothelial interaction and hepatocellular damage during experimental intraabdominal sepsis. Methods: A total of 18 male Wistar rats (245 ± 26 g) underwent laparotomy. The abdomen of the control group (LAP) was closed without manipulation. Cecal ligation and puncture (CLP) was performed on 12 animals. At 2 h after CLP one group received 50 I.E./kg/BW heparin i.v., followed by an infusion of 80 I.E./kg/BW/h for 18 h (CLP+Hep; n=6). The other CLP group (CLP+NaCl; n=6) and the LAP group (LAP+NaCl; n=6) were treated with sodium cloride 0.9%. Results: At 18 h after heparin application the PTT was significantly elevated in the CLP + Hep vs. the LAP group (19.2±4.3 s vs. 6.6±1.1 s , p< 0.001). The mean erythrocyte velocity in liver sinusoids and postsinusoidal venules measured by intravital microscopy was significantly higher in the CLP + Hep vs. the CLP+NaCl-group (p

Die Entwicklung der hepatobiliaren Chirurgie als eigenes Spezialgebiet reflektiert die zunehmende Weiterentwicklung in der operativen Therapie der Lebermalignome. Die Zunahme der Chirurgie der Lebertumoren beruht zum einen auf einem Anstieg der Inzidenz sowie einer verbesserten Diagnostik, zum anderen auf anhaltendem Enthusiasmus uber den Erfolg chirurgischen Vorgehens als Teil multimodaler Therapie, um auch in scheinbar inkurablen Situationen eine Tumorreduktion zu erreichen. Des weiteren sind in den letzten 30 Jahren einige neue Tumorkategorien erkannt und neue atiologische Faktoren fur die Malignomentstehung identifiziert worden.

Die Behandlung von Malignomen der Gallenblase und der extrahepatischen Gallenwege stellt eine besondere Herausforderung dar. Bis heute ist wegen der bei diesen Tumoren nur selten realisierten Fruhdiagnose und ihrer engen anatomischen Lagebeziehung zu komplexen Nachbarstrukturen bzw. anderen Organen allenfalls eine Minderheit der betroffenen Patienten chirurgisch kurativ resezierbar. Endoskopische und/oder radiologisch-interventionelle Verfahren haben eine zunehmende Bedeutung innerhalb interdisziplinarer Palliationskonzepte. Primar palliativ orientierte chirurgische Operationsverfahren verlieren komplementar an Stellenwert. Ausgewahlten Patienten kann jedoch durch eine adaquate chirurgische Therapie eine ernstzunehmende Heilungschance bei akzeptabler perioperativer Morbiditat eroffnet werden. Hierzu adjuvante chemo- wie auch strahlentherapeutische Verfahren befinden sich meist noch in Entwicklungs- bzw. Erprobungsstadien. In den folgenden Abschnitten werden die Grundsatze heute etablierter chirurgischer Behandlungsstrategien aufgezeigt.

Die meisten Erfahrungen mit der chirurgischen Therapie von Lebermetastasen existieren weltweit mit Metastasen kolorektaler Karzinome. Trotz fehlender randomisierter Studien muss den Resektionsverfahren eine Prognoseverbesserung zugebilligt werden. Das Funfjahresuberleben kurativ operierter Patienten mit Lebermetastasen betragt zwischen 24 und 40%. Spontanverlaufe ohne Operation uberleben fast nie die 5 Jahre nach Diagnosestellung. Einschrankungen in der chirurgischen Therapie dieser Absiedlungen werden zunehmend liberaler gehandhabt. Jede Lebermetastase, die sich technisch und funktionell entfernen lasst, kann einer Leberresektion zugefuhrt werden, vorausgesetzt jeglicher extrahepatischer Tumor ist beherrscht. Diese weitreichende Indikationsstellung wird zunehmend auf andere Tumorentitaten ubertragen. Hier fehlen jedoch noch verlassliche Zahlen. Je aggressiver die Indikationsstellung erfolgt, desto exakter muss die Planung der Resektion sein, um ein grostmogliches Restlebervolumen mit maximaler Funktion zu erhalten. Dies wird bereits an einzelnen Zentren mit Hilfe virtueller OP-Planung am Computer durchgefuhrt.

Soft tissue sarcoma has a high risk of local recurrence. Therefore, extensive surgical resection has been combined with radiotherapy to improve long-term results. Because external beam radiation doses may be limited by adjacent radiosensitive tissue, intraoperative boost radiation has been devised to achieve a higher total radiation dose in combination with external beam radiotherapy. We report our experience with this multimodal approach for primary and recurrent soft tissue sarcoma.Clinical and pathological data were extracted from a prospective data base including all patients with a diagnosis of soft tissue sarcoma treated at the Department of Surgery, University of Heidelberg between 1988 and 1999. Intraoperative radiotherapy dosages were 12-15 Gy for the extremities and 15-18 Gy for the trunk and the retroperitoneum. Additional external beam radiotherapy was given at 40 Gy, whenever possible.Between 1988 and 1999, a total of 251 patients with primary or recurrent soft tissue sarcoma of the extremities, the trunk or the retroperitoneum were treated. The mean (+/- SD) age of 136 men and 115 women was 53+/-16 years. Five of 251 patients died post-operatively, giving a mortality rate of 2.0%. Intraoperative radiotherapy (IORT) was used in 92 patients (37%). Surgical complications were more frequent in IORT patients (30 of 92; 33%) compared to non-IORT patients (36 of 159; 23% P=0.1). Infectious complications were significantly more frequent in patients receiving IORT (P=0.03). Two hundred and four patients were macroscopically tumour-free (R0, R1 resection). For these patients multivariate analysis identified grading (relative risk (RR) 3.1-6.6; P0.001), age (over 55 years; (RR) 1.8: P0.008) and tumour location in the retroperitoneum (RR 2.2; P0.004) as independently associated with recurrence-free survival. The use of IORT (P0.02) reduced the relative risk of death or recurrence by 40% (RR 0.6; P0.02). Sex, primary vs. recurrent tumour, T classification and R-status (R0 vs. R1) were not significantly related to recurrence-free survival.In this prospective, non-randomized study of soft tissue sarcoma IORT was associated with a higher rate of infectious complications, but the the risk of death or recurrence was reduced by 40%.