Günther Ruf

Long-Term Results After Intraoperative Radiation Therapy for Gastric Cancer

PURPOSE We retrospectively analyzed the impact of intraoperative radiation therapy (IORT) on long-term survival in patients with resectable gastric cancer. METHODS AND MATERIALS From 1991 to 2001, a total of 84 patients with gastric neoplasms underwent gastectomy or subtotal resection with IORT (23 Gy, 6-15 MeV; IORT-positive [IORT(+)] group). Patients with a history of additional neoadjuvant chemotherapy, histologically confirmed R1 or R2 resection, or reoperation with curative intention after local recurrence were excluded from further analysis. The remaining 61 patients were retrospectively matched with 61 patients without IORT (IORT-negative [IORT(-)] group) for Union Internationale Contre le Cancer (UICC) stage, patient age, histologic grading, extent of surgery, and level of lymph node dissection. Subgroups included postoperative UICC Stages I (n = 31), II (n = 11), III (n = 14), and IV (n = 5). RESULTS Mean follow-up was 4.8 years in the IORT(+) group and 5.0 years in the IORT(-) group. The overall 5-year patient survival rate was 58% in the IORT(+) group vs. 59% in the IORT(-) group (p = 0.99). Subgroup analysis showed no impact of IORT on 5-year patient survival for those with UICC Stages I/II (76% vs. 80%; p = 0.87) and III/IV (21% vs. 14%, IORT(+) vs. IORT(-) group; p = 0.30). Perioperative mortality rates were 4.9% and 4.9% in the IORT(+) vs. IORT(-) group. Total surgical complications were more common in the IORT(+) than IORT(-) group (44.3% vs. 19.7%; p < 0.05). The locoregional tumor recurrence rate was 9.8% in the IORT(+) group. CONCLUSIONS Use of IORT was associated with low locoregional tumor recurrence, but had no benefit on long-term survival while significantly increasing surgical morbidity in patients with curable gastric cancer.

Change of zonal bile acid processing after partial hepatectomy in the rat

The aim of this study was to analyze whether partial hepatectomy alters functional liver heterogeneity with respect to bile acid processing. One, 5 and 21 days after liver resection (approximately 80% of liver mass) in male Sprague-Dawley rats (300-400 g), isolated livers were perfused in either the antegrade or the retrograde direction, respectively, with 32 nmol cholate/min per g liver. Uptake, metabolism and biliary secretion kinetics were determined by bolus injection of 14C-cholate. Uptake and biliary recovery (within 30 min) of cholate were > 90% in all groups. One day postresection, liver mass had already doubled and it regenerated to over 80% 5 days after resection. Serum bile acid concentration increased rapidly, peaking 6 h after resection (176.7 +/- 28.5 mumol/l) (mean +/- SEM). Twenty-one days after resection it fell to control values (23.2 +/- 3.8 mumol/l). T25 (T50), the time (min) necessary to excrete 25% (50) of the bile acid load into bile, was strikingly different between periportal and pericentral cells of controls (1.8 vs 5.7 and 3.4 vs 8.1). Five days after resection this difference became smaller (1.4 vs 2.9 and 2.8 vs 5.5) due to accelerated biliary cholate secretion in pericentral cells. Pericentral cells of controls metabolized cholate more extensively to taurocholate (approximately 83%) and glycocholate (approximately 13%) than periportal cells of controls (65%, 10%), leading to a 5-fold higher proportion of unmetabolized cholate in periportal than pericentral cells (25% vs 5%). Five days after resection the percentage of taurocholate decreased significantly at the expense of an increased formation of glycocholate.(ABSTRACT TRUNCATED AT 250 WORDS)

Pattern of bile acid regurgitation and metabolism during perfusion of the bile duct obstructed rat liver

Bile acid processing in the long-term, bile duct obstructed rat liver was studied ex vivo. Twenty four and 72 h, respectively, after bile duct obstruction the isolated liver was perfused with taurodeoxycholate (16 nmol/min per g liver) the bile duct still being closed. Uptake, metabolism and regurgitation profile were traced by bolus injection of tritium-labeled bile acid; in addition, concurrent histological changes were examined by light- and electron microscopy. Ligation caused dilatation of the intrahepatic ductular branches and increased the serum bile acid concentration to 740 +/- 75 microM (controls: 16 +/- 2.12), reaching its maximum within 24 h. At 16 nmol/min per g liver uptake rate was > 96% in controls and in bile duct obstructed rats. Maximal uptake rates (assessed separately) differed between controls and bile duct obstructed rats (700 nmol/min per g liver vs. 460). Controls excreted more than 80% of labeled bile acid in bile within 10 min after bolus injection. Biliary recovery of label was virtually completed after 30 min. In bile duct obstructed rats excretion of label back to the perfusate effluent (regurgitation) started quantitatively 5 min after bolus application and peaked between 10 and 40 min; after 80 min, effluent recovery was incomplete (about 60% of bolus injected). Biliary bile acids of controls consisted of about 20% taurodeoxycholate-metabolites; bile acids in the perfusate effluent of bile duct obstructed rats of about 55%. The major metabolite in all animal groups was taurocholate; minor metabolites were tauroursocholate, tauro-3 alpha,7 = 0,12 alpha-cholanoic acid and 3-sulfo-taurodeoxycholate. Histologically, inflammation and periportal edema were present after 1 day of bile duct obstruction. After 3 days, marked proliferation of bile ductules was the dominant histological feature. It is concluded that during initial bile duct obstruction, bile acid processing is not altered, although ultrastructural alterations occur early.

Monitoring of the inflammatory response in early peritonitis

The inflammatory response which is similar in all forms of peritonitis was recorded by determining the levels of parameters shown to represent the activation state of plasmatic and cellular systems as well as the inhibitory capacity of the plasma. In a selected series of patients with different underlying diseases, blood sampling was started at the time of admission when the clinical finding of an acute abdomen led to emergency laparotomy. Depending upon the duration of the illness and the severity of the peritonitis, a significant increase in fibrinopeptide A and of C3a could be detected within a few hours, which was followed by an increase in the elastase alpha-1-proteinase inhibitor complex. Differences due to variable cause could not be found. There was a striking correlation between the preoperative values of these three parameters and the postoperative course of the patients. Additionally, there was a significant enhancement of an endothelial proliferation-inhibiting capacity in the serums of the lethal group, whereas endotoxin could only be detected in trace amounts in four patients with intraabdominal infection in the preoperative period.

Chirurgische Strategie und Prognosefaktoren bei gastrointestinalen Stromatumoren

Klinisches Merkmal gastrointestinaler Stromatumoren (GIST) ist das variable biologische Verhalten, welches von benignen Zufallsbefunden bis zu metastasierenden Tumoren reicht. In dieser Arbeit wurden klinischer Verlauf und pathohistologische Parameter von 26 Patienten retrospektiv untersucht mit dem Ziel, Prognosefaktoren zu definieren. Das Risiko eines Tumorrezidives war bei Tumoren > 4 cm signifikant (p = 0,024) erhoht. Ein erhohter Proliferationsindex gemessen mit dem Anti-Ki-67-Antikorper MIB-1 war bei MIB-1 > 3 auch mit einer signifikant (p = 0,0031) gesteigerten Rezidivrate assoziiert. Der MIB-1 Index erscheint daher zur Abschatzung der Prognose geeignet.

Strategie und Ergebnisse der chirurgischen Therapie bei zystischer Echinokokkose

In einer retrospektiven Studie wurden 36 Patienten mit zystischer Echinokokkose hinsichtlich Einzugsgebiet, Risikofaktor und chirurgischer Morbiditat und Letalitat analysiert.70% kamen aus Mittelmeerlandern,30% aus Deutschland. Hundehaltung oder Wildtierexposition waren unabhangige Risikofaktoren. 97% der Patienten zeigten einen Leberbefall, ein Patient einen Milzbefall. Bei 77,8% war eine einfache Perizystektomie moglich. Eine Hemihepatektomie rechts war bei 8,3% erforderlich, links bei 5,6%. Lebersegmentresektionen wurden bei 5,6% durchgefuhrt. Die Lokalrezidivrate lag bei 0%. Die haufigsten Komplikationen waren Abszess (8,3%), Wundinfekt (8,3%), und Biliom (5,5%).Die Mortalitat lag bei 2,7% (Sepsis). Schlusfolgernd last sich feststellen, das Morbiditat und Letalitat die chirurgische Therapie rechtfertigen.