R. Schlemminger

The adaptive response of the rat small intestine after resection and segmental transplantation during the early postoperative phase

Organ harvesting from a living donor or spatial constraints in the recipients abdominal cavity are the main factors to be considered in the segmental transplantation of the small intestine. It was the aim of the following study to gain insight into the functional characteristics of different portions of the small intestine either after partial resection or syngeneic and allogeneic transplantation during the early postoperative period. Nutritional parameters (serum albumin levels, serum triglyceride levels, maltose absorption, excretion of fecal fat) and fat-stimulated neurotensin release were determined in Lewis rats that underwent small bowel resection (n=21), syngeneic (Lewis→Lewis,n=21), or allogeneic transplantation (Brown Norway→Lewis,n=24). The length of the remnant, isograft, or allograft was 27 cm (i.e. one third of the rat small intestine) and consisted of the proximal (n=7), middle (n=7), or distal (n=7) portion. Three postoperative deaths were due to ileus or pneumonia. After allotransplantation, cyclosporine (15 mg/kg BW s.c.) was administered for graft acceptance. Controls were unoperated, weight- and age-matched Lewis rats (n=7). We found that resection of two-thirds of the small intestine led to significantly lower levels of albumin and triglycerides in all the three portions investigated (P<0.01) but did not affect maltose absorption. Excretion of fecal fat was elevated after distal resection (P<0.05). When compared to resected animals, syngeneic transplantation did not affect the nutritional parameters, but caused a significantly higher hormone release (P<0.05) in all three different intestinal grafts. Allogeneic transplantion was successful when the middle or distal portion was grafted. All recipients of proximal allografts showed a severe loss of body weight and died between day 8 and 10 after transplantation. Postmortem examination revealed no signs of acute rejection. When transplantation of short intestinal segments is considered, it is of vital importance to take into account the functional differences and the influence of immunosuppressive drug therapy in the regulatory bowel function.

Gastrin-releasing peptide and cholecystokinin in the regulation of exocrine pancreatic secretion in dogs.

Exocrine pancreatic secretion in conscious dogs is significantly stimulated by the intravenous application of small doses of gastrin-releasing peptide (GRP; 30 pmol x kg-1 x h-1). There is no increase of the GRP concentrations in peripheral blood which is also the case under physiological postprandial conditions. There is also no increase in the peripheral cholecystokinin (CCK) concentrations, in contrast to previous reports. Nevertheless other CCK-related mechanisms may play an important role, since the administration of the highly specific CCK receptor antagonist MK-329 causes a marked reduction of the GRP-induced exocrine pancreatic secretion.

Fat-stimulated cholecystokinin release following transplantation of the entire small bowel or of different intestinal segments in rats

This study presents data on the fat-stimulated release of cholecystokinin (CCK) in conscious rats 11 and 84 days after one-stage transplantation of the entire small bowel, or of jejunal, jejunoileal, or ileal segments, under syngeneic and allogeneic conditions. After allotransplantation, ciclosporin (CsA) was administered for graft acceptance. The results were compared with those in unoperated controls and in animals that had undergone small-bowel resections leaving jejunal, jejunoileal, or ileal remnants. When the entire small bowel was grafted under syngeneic (92.5±8.3; 106.6±7.5) or allogeneic (110.5±5.5.; 101.2±6.9) conditions, CCK release (pg/ml per 60 min) was similar (P>0.05) to that of the controls (110.3±9.0; 94.7±6.8) at both measurement points. Recipients of jejunal or ileal segmental isografts showed a significantly elevated (P<0.05) output of CCK (jejunal graft: 176.4±18.5; 125.5±10.1—ileal graft: 55.9±9.0; 30.1±5.4) compared with corresponding small-bowel resections (jejunal remnant: 69.0±7.9; 93.5±3.9—ileal remnant: 16.7±3.7; 6.6±1.3). In contrast the difference was not significant (P>0.05) when jejunoileal segments were grafted (jejunoileal graft: 74.4±19.6; 47.0±10.4—jejunoileal remnant: 50.7±11.0; 47.0±11.9). All recipients of jejunal allografts died between day 8 and day 10 after transplantation, due to functional impairment. Two-stage segmental jejunal allotransplantation, with insertion of the graft into the continuation of the gastrointestinal tract in an accessory, non-functional position after 28 days was successful. Due to this technique, we could gather data on day 84. Recipients of jejunal (118.2±7.6), jejunoileal (87.1±19.7; 48.6±9.3), or ileal (48.1±6.7; 21.6±4.6) allografts showed no significant (P>0.05) differences in CCK output compared with isografts, either on day 11 or on day 84. Our data indicate that transplantation of the entire small bowel affects the fat-stimulated CCK release neither in the early postoperative period nor 3 months after transplantation. In contrast, transplantation of jejunal or ileal segmental isografts caused a significantly elevated output of CCK compared with corresponding resection remnants. Immunosuppression with CsA did not affect CCK release after transplantation, but led to functional impairment with fatal outcome when a short jejunal segment was grafted. This could be prevented by applying the two-stage technique.

The role of pancreatic innervation and cholecystokinin in the intestinal phase of pancreatic polypeptide release in conscious dogs

SummaryBesides vagal cholinergic mechanisms, pancreatic polypeptide (PP) secretion is thought to be mediated by hormones. This study was performed to delineate the role of extrinsic pancreatic innervation and cholecystokinin (CCK) in amino acid- and fat-stimulated PP secretion. In ten mongrel dogs, pancreatic denervation was performed by the method of Debas et al. [3]. Total denervation of the pancreas did not alter PP response to intraduodenal application of amino acids (integrated output 24434±3260 pmol/1×120 min before vs 22797±2470 pmol/1×120 min after operation) and to intraduodenal fat solution (19595±2121 pmol/1×120 min vs 19983±2031 pmol/1×120 min). Also, no significant differences were measured in CCK release (491±71 pmol/1×120 min vs 430±57 pmol/1×120 min for amino acids, 571=63 pmol/1×120 min vs 563±89 pmol/1×120 min for fat solution). Plasma PP and CCK levels were compared by linear regression analysis. Correlations between PP and CCK were high in the intact pancreas (amino acids,r=0.92; fat,r=0.99) as well as in the denervated pancreas (r=0.93 amino acids andr=0.98 fat). These results show that extrinsic pancreatic innervation does not influence PP and CCK release after intraduodenal amino acids or fat solution and that PP secretion seems to be mediated to some extent through the release of CCK.

Stoffwechselparameter und Neurotensinfreisetzung nach Dünndarmresektion, syngener und allogener Segmenttransplantation an der Ratte

The aim of the following study was to gain some insight into the functional characteristics of different portions of the small intestine after either partial resection or syngeneic and allogeneic transplantation 3 months postoperatively. Nutritional parameters (serum albumin levels, serum triglyceride levels, maltose absorption, excretion of fecal fat) and fat-stimulated neurotensin release were determined in Lewis rats that underwent small-bowel resection (n = 21), syngeneic (Lewis→Lewis, n = 21), or allogeneic transplantation (Brown Norway→Lewis, n = 24). The length of the remnant, isograft, or allograft was 27 cm (i.e., one-third of the rat small intestine) and consisted of the proximal (n = 7), middle (n = 7), or distal (n = 7) portion. Three postoperative deaths were due to ileus or pneumonia. After allotransplantation cyclosporine (15 mg/kg body wt. s.c.) was administered for graft acceptance. The control group was not operated upon, but was composed of weight- and age-matched Lewis rats (n = 7). We found that resection of two-thirds of the small intestine led to significantly lower levels of albumin and triglycerides in all three portions investigated (P < 0.01), but did not affect maltose absorption. Excretion of fecal fat was elevated significantly only after distal resection (P < 0.05). When compared to resected animals, syngeneic transplantation did not affect the nutritional parameters, but caused a significantly higher hormone release (P < 0.05) in all three different intestinal grafts. Allogeneic transplantation was successful when the middle or distal portion was grafted. All recipients of proximal allografts showed a severe loss of body weight and died between day 8 and 10 after transplantation. Postmortem examination revealed no signs of acute rejection. We conclude that when transplantation of short intestinal segments is considered, it is of vital importance to take into account the functional differences and the influence of immunosuppressive drug therapy in the regulation of bowel function.ZusammenfassungDie vorliegende Studie hatte zum Ziel, die Adaptation verschiedener Dünndarmabschnitte nach Resektion und Transplantation an der Ratte zu untersuchen. Stoffwechselparameter (Serumalbumin, Serumtriglyceride, Maltoseabsorption, Stuhlfettausscheidung) und Fett-stimulierte Neurotensinfreisetzung wurden 3 Monate postoperativ in Lewis-Ratten bestimmt, bei denen eine 2/3-Resektion (n = 21), eine syngene (Lewis→Lewis, n = 21) oder eine allogene (Brown Norway→ Lewis, n = 24) Segmenttransplantation durchgeführt worden war. Letale postoperative Komplikationen traten bei 3 Tieren nach allogener Transplantation auf (Ileus in 2 Fdllen, Pneumonie in einem Fall). Betrachtet wurde jeweils der proximale, mittlere oder distale Abschnitt (27 cm, etwa ein Drittel des Rattendünndarms) und zu nicht operierten Tieren (Kontrollen, n = 7), sowie zu Isotransplantaten (n = 7) und zu Allotransplantaten (n = 7) des gesamten Dünndarms in Beziehung gesetzt. Nach Allotransplantation wurde Cyclosporin (15 mg/kg KG i.m. Tag 0–2, 15 mg/kg KG s.c. Tag 3–14, 10 mg/kg KG s.c. Tag 15–28) verabreicht. Die Dünndarmresek-tion führte unabhdngig vom verbliebenen Anteil zu einer signifikanten Verringerung der Alnumin- und Triglyzeridwerte (p < 0,01) im Vergleich zum nicht operierten Tier, während die Maltoseabsorption unbeeinflulßt blieb. Die Stuhlfettausscheidung war lediglich nach distaler 2/3-Resektion signifikant erhöht (p < 0,05). Verglichen mit der Resektion ergab die syngene Transplantation keine Veränderung im Hinblick auf die Stoffwechselparameter, führte jedoch zu einer signifikanten Erhöhung der Hormonausschüttung (p < 0,05). Nach Allotransplantation verstarben alle Empfänger proximaler Dünndarm anteile zwischen Tag 8 und 10 nach Transplantation, ohne daß sich Hinweise auf eine akute Abstoßung oder chirurgische Komplikationen ergaben. Allotransplantationen mittlerer oder distaler Dünndarmanteile verliefen erfolgreich und zeigten keinerlei Nachteile im Vergleich zu Allotransplantaten des gesamten Dünndarms Bowie zu Isotransplantaten. Unsere Ergebnisse deuten darauf hin, daß im Fall einer Segmenttransplantation die unterschiedliche Adaptation verschiedener Dünndarmab-schnitte unter dem Einfluß einer immunsuppressiven Therapie beachtet werden sollte.

Die Bedeutung der Peritonitis und Sepsis als determinierende Faktoren bei der Behandlung der perforierten Sigmadivertikulitis

Die Perforation stellt die haufigste und gefahrlichste Komplikation der Sigmadivertikulitis dar. Der weitere Verlauf wird entscheidend durch das gewahlte Therapiekonzept beeinfluβt. Dabei steht neben der chirurgischen Therapie die intensivmedizinische Behandlung im Vordergrund. Als determinierende Faktoren kommen der Sepsis und der Peritonitis eine besondere Bedeutung zu. Die fruhzeitige operative Intervention, die intensivmedizinische Behandlung und die spezifische Therapie der Peritonitis und der septischen Komplikationen dieses gravierenden Krankheitsbildes sind von groβter Bedeutung in der Behandlung der schwerkranken Patienten. Dennoch geht diese Erkrankung auch unter dem Einsatz aller Mittel noch mit einer hohen Letalitat einher

FACS-Analyse immunozytärer Membranantigene in mesenterialen Lymphknoten langzeitüberlebender Ratten nach allogener Dünndarmtransplantation

Nur das grundlegende Verstandnis der Langzeitakzeptanz allogener Transplantate — und die dafur erforderlichen immunologischen Untersuchungen — kann als Basis fur eine gezieltere und effektivere Therapie der Abstosung fremder Gewebe und Organe dienen. Fur die vorliegende Studie wurde daher der langfristige Einflus einer Immunsuppression mit Cyclosporin A (CsA) auf die Immunzellen transplantatdrainierender Lymphknoten untersucht. In unserem Fall lag die besondere Situation der Ubertragung des gesamten Dunndarms (DD) bzw. des distalen Dunndarmdrittels und des mit diesem Organ assozuerten immunkompetenten Gewebes vor. Wir verglichen die Expression ausgewahlter Leukozyten-Antigene [1] aus mesenterialen Lymphknoten (mLK) allotransplantierter Ratten und Kontroll-Lymphknoten. Diese Antigene erlauben die Identifikation definierter Immunzelltypen und die Analyse der Membranexpression von Adhasionsmolekulen, die fur eine effektive Immunantwort [1] und das Horning wandernder Immunzellen [2] essentiell sind.

New Aspects of Large-Bowel Surgery

Die Anwendung biofragmentabler Anastomosentechniken hat im Vergleich zu herkommhchen Methoden keinerlei Nachteile erbracht. Die perioperative Bluttransfusion bei colorectalen Carcinomen beeinflust die Prognose und die Wirksamkeit der perioperativen portalen Chemotherapie negativ. Unter Berucksichtigung erwiesener Risikofaktoren fur die Tumorrezidiventstehung zeigt sich prognostisch kein Unterschied nach kurativer anteriorer Resektion oder abdomino-perinealer Rektumamputation. Fur eine onkologisch adaquate Primartumorchirurgie kommt der Lymphknotendissektion erhebhche Bedeutung zu.

150. Ergebnisse nach transthorakaler trunculärer Vagotomie beim Ulcus pepticum jejuni

SummaryAt the Department of Surgery of the University of Göttingen, 40 patients were diagnosed from 1976–1983 as having a jejunal peptic ulcer. In 12 patients transthoracic vagotomy was performed, depending on the size of the remaining stomach, undisturbed passage, anamnesis, and exclusion of endocrine disorders. Postoperative complications were seen in 4 patients (pleural exudate, dystelectasis), and 1 patient died of gastrointestinal bleeding (liver cirrhosis). Marginal ulcers were seen in 3 patients; two re-resections were necessary. Transthoracic vagotomy showed a smaller rate of complications in comparison with re-resection. Marginal ulcers amounted to up to 10%. Preoperative exclusion of endocrine disorders in necessary.ZusammenfassungIn der Chirurgischen Uni-Klinik Göttingen wurden von 1976–1983 40 Patienten mit einem Ulcus pepticum jejuni diagnostiziert. Eine transthorakale Vagotomie wurde 12mal durchgeführt. Die Indikationsstellung richtete sich nach der Größe des Restmagens, der Magenentleerung, der Anamnese und dem Ausschluß endokriner Ursachen. Postoperative Komplikationen traten in 4 Fällen auf (Pleuraerguß, Dystelektase). 1 Patient verstarb an einer Oesophagusvaricenblutung. 3 Patienten wiesen Rezidive auf, 2 Nachresektionen waren erforderlich. Die transthorakale Vagotomie ist im Vergleich zur Nachresektion risikoärmer. Die Rezidivrate beträgt etwa 10%. Präoperative Diagnostik zum Ausschluß endokriner Störungen ist erforderlich.