Daniel Mettler

A novel colon pouch and its comparison with a straight coloanal and colon J-pouch–anal anastomosis: Preliminary results in pigs

BACKGROUND Early functional results after complete rectal resection and straight coloanal anastomosis are often characterized by frequent bowel movements, urgency, and varying degrees of stool incontinence. The formation of a colon reservoir improves early and long-term function. We evaluated the feasibility of a novel, modified design of a colon pouch--anal anastomosis in pigs and compared the results with those of pigs with straight coloanal anastomosis and colon J-pouch. METHODS Complete rectal resection followed by either a straight coloanal anastomosis, a colon J-pouch, or a novel design of a colon pouch was performed in equal numbers in 15 pigs. By transversely closing a longitudinal colotomy, the new, technically simpler pouch is formed. Functional results were assessed during a period of 6 weeks. RESULTS All 15 procedures were successful. The novel colon pouch required less surgical time than the colon J-pouch, and the formation of the pouches did not reduce tissue perfusion as assessed by laser Doppler flowmetry. The mean volume of the novel colon pouch was significantly smaller than the volume of the colon J-pouch. All the pigs with the novel colon pouch had normal stool frequency and consistency during a period of 6 weeks. In the group with straight coloanal anastomosis, two pigs had increased frequency of defecation, one pig showed signs of urgency and perianal dermatitis, and three had substantially reduced stool consistency. Of the four pigs with colon J-pouch, three had signs of impaired pouch evacuation and two had reduced stool frequency. CONCLUSIONS The novel colon pouch is feasible in pigs and technically simpler than the colon J-pouch. These preliminary results indicate that the smaller capacity of this pouch seems sufficient for normal defecation. Its short-term functional results were better than those after reconstruction with a colon J-pouch or a straight coloanal anastomosis.

SYSTEMIC AND TOPICAL DRUG ADMINISTRATION IN THE PIG URETER: EFFECT OF PHOSPHODIESTERASE INHIBITORS α1, β AND β2-ADRENERGIC RECEPTOR AGONISTS AND ANTAGONISTS ON THE FREQUENCY AND AMPLITUDE OF URETERAL CONTRACTIONS

Purpose: We searched for compounds that are pharmacologically active on ureteral motility for treating ureteral colic to ease retrograde access into the ureter and improve the clearance of stones or stone particles from the ureter. The effects of the α1-adrenergic receptor agonist phenylephrine, the nonselective β and β2-adrenergic receptor agonists isoproterenol and fenoterol, and the phosphodiesterase inhibitors papaverine (nonspecific) and rolipram (type IV) on the frequency and amplitude of ureteral contractions when administered intravenously or topically were investigated in pigs.Materials and Methods: A total of 52 pigs were anesthetized. A double lumen 6Fr catheter was inserted through each renal pelvis and into the ureter, allowing perfusion of saline or drug solution into the renal pelvis and the recording of contractions from the mid portion of the ureter.Results: The α1 and β-adrenergic receptors of the ureter are not tonically activated by endogenous epinephrine or norepinephrine. Phenylephri...

Circulatory and Anatomic Differences among Experimental Gastric Tubes as Esophageal Replacement

Abstract. In this experimental study we measured microcirculatory and anatomic differences among a newly developed technique of gastroplasty—fundus rotation gastroplasty (FRG)—and conventional (CG) and reversed (RG) gastric tubes as substitutes for the thoracic and cervical esophagus. After transhiatal esophageal resection, 36 large white pigs were randomly assigned to have an FRG, CG, or RG. Tube length, gastric volume, and compliance as well as blood flow in the tube and the remaining gastric reservoir (by laser Doppler flowmetry) were measured. The FRG tubes were 35.9 ± 3.1 cm long, RG 38.7 ± 3.3 cm, and CG 27.3 ± 2.1 cm (p< 0.05). Gastric compliance was 20.8 ml in the FRG and 3.2 ml and 2.9 ml in the CG and RG, respectively (p < 0.001). Blood flow was significantly higher in FRG tubes than in RG tubes or CG tubes, resulting in a lower anastomotic failure rate (2/12 FRG, 6/12 CG, 7/12 RG). Hence a rotation flap of the gastric fundus (FRG) yields a long, well perfused tube by maintaining the blood supply of the gastric lesser curvature. FRG appears to be a good alternative to CG or RG as a substitute for the thoracic and cervical esophagus.

Cytostatic Lung Perfusion by Use of an Endovascular Blood Flow Occlusion Technique

BACKGROUND Different modalities of cytostatic lung perfusion were compared regarding plasma and tissue drug concentrations to assess the efficacy of an endovascular blood flow occlusion technique. METHODS A cytostatic lung perfusion study with doxorubicin hydrochloride was performed on large white pigs (n = 12). Plasma and tissue concentrations of doxorubicin were compared for isolated lung perfusion with open cannulation (ILP), blood flow occlusion perfusion with open cannulation of the pulmonary artery alone (BFO), and intravenous drug administration (i.v.). In a fourth group, thoracotomy-free BFO perfusion was performed by endovascular balloon catheterization of the pulmonary artery (endovascular BFO). The 3 animals in this group were used to compare the doxorubicin-perfused pulmonary tissue with the contralateral nonperfused lobes after 1 month. RESULTS The mean lung tissue doxorubicin concentration at the end of perfusion was 19.8 +/- 1.6 microg/g after ILP, 27.6 +/- 2.2 microg/g after BFO (p = not significant), and 3.0 +/- 0.8 microg/g after i.v. perfusion (p < 0.01). Whereas doxorubicin was not detectable in the plasma in the ILP group, concentrations ranged from not detectable to 0.44 microg/mL in the BFO group and from 0.31 to 0.84 microg/mL in the i.v. group (p < 0.05). Mean myocardial tissue concentration was not significantly different after BFO than i.v. perfusion (1.1 +/- 0.5 microg/g and 1.8 +/- 0.1 microg/g, respectively). In the endovascular BFO group, balloon-blocked pulmonary artery perfusion was successfully performed in all animals, and after 1 month, lung tissue showed no cytostatic-induced histologic changes. CONCLUSIONS Compared with ILP, BFO cytostatic lung perfusion produced an insignificantly higher lung-tissue concentration, corresponding to a sixfold to ninefold higher level than after i.v. perfusion. Plasma drug levels during BFO perfusion were lower than during i.v. perfusion. Endovascular BFO may be a promising technique for repeated cytostatic lung perfusion.

Hepatic artery embolisation with a novel radiopaque polymer causes extended liver necrosis in pigs due to occlusion of the concomitant portal vein.

BACKGROUND/AIM In an attempt to overcome some of the problems encountered with the materials available for liver embolisation, we investigated a novel radiopaque polymer of the polyurethane family (Degra-Bloc). METHODS Hepatic artery embolisation of one liver lobe using polyurethane was performed in 19 healthy pigs. Microcirculatory changes were assessed by laser Doppler flowmetry. Radiological and pathological examinations of the livers, hearts and lungs removed provided information about the extent and effect of the embolisation. RESULTS None of the pigs died due to hepatic failure or toxicity of polyurethane. Microcirculation of embolised liver lobes significantly decreased from 106 (+/-15) perfusion units (PU) to 45 (+/-6) PU immediately after embolisation and further to 28 (+/-7) PU before euthanasia. At this time conventional and angiographic X-ray controls demonstrated the radiopaque casts extending up to the peripheral arteries with signs of degradation over time but without formation of collateral vessels. The main pathological findings consisted of destruction of the portal tract structures and also of large areas of liver necrosis. Polyurethane was encountered in arterioles as small as 10-20 microm, but not in liver sinusoids, hearts or lungs. CONCLUSIONS The novel polymer called DegraBloc is a biocompatible, slowly degradable, radiopaque embolic agent. The occlusion of the arterial tree up to the smallest arteriolar diameter combined with concomitant portal vein occlusion leads to sharp segmental necrosis in pig livers without formation of significant collaterals and without systemic embolism. In the treatment of liver tumours polyurethane might provide a promising alternative to conventional embolic materials, provided that it is used with care in patients with advanced liver cirrhosis.

Isolated Lung Perfusion: Single-Pass System Versus Recirculating Blood Perfusion in Pigs

BACKGROUND Cytostatic isolated lung perfusion has been advocated for treating pulmonary metastasis of soft tissue sarcoma. Different techniques of isolated lung perfusion have been developed. METHODS Isolated lung perfusion with and without doxorubicin was performed on white pigs during 15 minutes either by a single-pass system (n = 7) or by a recirculating-blood perfusion system (n = 7). Three animals with endovenous drug application served as controls. Leakage was assessed using isotopic tracers. Perfusion-induced lung tissue injury was determined by postperfusion chest radiographs, by angiotensin-converting enzyme-to-protein ratio in the plasma and in the bronchioalveolar lavage fluid, and by wet-to-dry weight ratio and histologic examination of lung biopsy specimens at 20 and 50 minutes. Doxorubicin concentration in lung tissue and plasma was compared between the three study groups. RESULTS All isolated lung perfusion studies were successfully performed without significant systemic leakage (< 0.6%). Wet-to-dry weight ratio was significantly lower after single-pass as compared with recirculating-blood perfusion and endovenous drug application at both time points (5.0 +/- 1.1 and 5.3 +/- 0.8 for single-pass versus 6.6 +/- 1.1 and 6.9 +/- 0.5 for recirculating-blood versus 6.6 +/- 0.2 and 5.9 +/- 0.7 for the control group, respectively; p < 0.05). Angiotensin-converting enzyme-to-protein plasma ratio in the single-pass group was significantly lower only at 20 minutes (6.3 +/- 2.4 versus 9.3 +/- 1.0 versus 9.7 +/- 1.9, respectively; p < 0.05) but not at 50 minutes. Angiotensin-converting enzyme-to-protein ratio in bronchoalveolar lavage fluid, histology of lung biopsy specimens, and chest radiographs did not differ significantly between the three groups. Doxorubicin lung tissue concentration was not significantly different after single-pass (17.5 micrograms/g) and recirculating-blood perfusion (21.9 micrograms/g), but was significantly higher than after endovenous drug application (3.0 micrograms/g; p < 0.01). CONCLUSIONS Both isolated lung perfusion techniques resulted in a sixfold to sevenfold higher doxorubicin lung tissue concentration than after endovenous application. Isolated lung perfusion-induced lung injury was similar for both techniques, but recirculating-blood perfusion appeared to result in more acute lung injury and was technically more demanding than single-pass perfusion.

Experimental assessment of photodynamic therapy with chlorins for malignant mesothelioma

OBJECTIVE Photodynamic therapy (PDT) with two chlorin sensitisers was assessed on nude mice bearing human mesothelioma xenografts, and on intrathoracic tissues of minipigs with the same drug-light conditions to optimise the antitumour activity of PDT while preventing photosensitising injury to normal tissues. METHODS Laser light (20 J/cm2) at 652 nm was delivered to the xenografts 1-4 days after i.p. administration of 0.1 mg/kg m-tetrahydroxyphenyl-chlorin (mTHPC) or an equimolar dose of polyethylene glycol-derived mTHPC (pegylated mTHPC), respectively. The extent of tumour necrosis was assessed by histomorphometry. Intraoperative PDT was then performed to the thoracic cavity of minipigs through a sternotomy with the same drug-light conditions at drug-light intervals ranging from 12 h to 6 days after i.v. administration of mTHPC and pegylated mTHPC, respectively. RESULTS Both, mTHPC and pegylated mTHPC, resulted in photosensitised necrosis of mesothelioma xenografts at drug-light intervals from 1 to 4 days but the extent of necrosis was significantly larger by use of pegylated mTHPC instead of mTHPC at a drug-light interval of 3 and 4 days. The optimal tumourcidal effect was achieved with pegylated mTHPC at a drug-light interval of 4 days. The photosensitising effect of mTHPC on intrathoracic tissues of minipigs revealed severe damage of virtually all tissues except nerves at short drug-light intervals. Tissue damage gradually became less at longer drug-light intervals and was absent at intervals of 3 days and longer. In contrast, pegylated mTHPC resulted in no obvious change to any structure at any drug-light interval assessed. CONCLUSIONS PDT with pegylated mTHPC reveals the potential of selective tumour destruction in this experimental setting and deserves further evaluation for intraoperative application in patients with malignant mesothelioma.

Surgical repair of the kidney after blunt lesions of intermediate degree using a Vicryl mesh: an experimental study.

Twelve experimentally induced blunt renal lesions in pigs were treated either with an alloplastic renal capsule made of semi-elastic Vicryl mesh or with homologous pig fibrin adhesive or with through-and-through chromic catgut sutures as controls. The Vicryl mesh capsule was made by the Ethnor Company (Paris, France) to our specifications. The postoperative isotope nephrograms, which were repeated until the Vicryl had been fully resorbed, showed good renal function in every case. However, when compared to the controls, the kidneys which had been repaired with Vicryl mesh contained considerably less scar tissue at the site of parenchymal rupture and showed neither perirenal fibrosis nor atrophy of the parenchyma in the vicinity of the capsule. Our preliminary results seem to confirm that simple and rapid surgical treatment of moderately severe blunt renal lesions is possible using the alloplastic Vicryl mesh capsule. The method may also be suitable for reconstruction of the parenchyma following multiple nephrotomies, such as for removal of staghorn calculus, and experimental investigations are under way to clarify this point.

Endobronchial photodynamic therapy: Comparison of mTHPC and polyethylene glycol-derived mTHPC on human tumor xenografts and tumor-free bronchi of minipigs

Photodynamic therapy (PDT) with mTHPC and polyethylene glycol‐derived mTHPC (pegylated mTHPC) was compared on nude mice bearing human squamous cell carcinoma and adenocarcinoma xenografts. The same treatment regimens were applied to the bronchi of tumor‐free minipigs to assess injury to normal tissue.

VATS-guided epicardial pacemaker implantation : Hand-sutured fixation of atrioventricular leads in an experimental setting

AbstractBackground: In neonates and infants epicardial stimulation may be preferred to endocardial stimulation because of growth-associated lead problems and the risk of vascular complications associated with transvenous electrodes. This study analyzes the feasibility of atrioventricular implantation of a new epicardial lead using the video-assisted thoracic surgical (VATS) technique in an animal model. Methods: Bipolar steroid-eluting epicardial leads were implanted in seven young white pigs. In five animals bipolar atrial and ventricular pacing leads (n= 10) were inserted and fixed by the VATS technique, while two animals served as controls and underwent implantation through anterolateral thoracotomy. Surgical feasibility, pacing, and sensing thresholds of the leads as well as hemodynamic parameters during pacing were studied. Histological changes beneath the electrodes were evaluated 1 week after the implantation. Results: All animals survived the pacemaker lead implantation. One animal which underwent thoracotomy died because of irreversible ventricular fibrillation induced by rapid ventricular pacing. One animal in the VATS group exhibited intraoperative herniation of the heart through the pericardial window. All animals with left-sided VATS implantations demonstrated good individual pacing and sensing threshold values. The mean cardiac output was 1.6 times higher during AAI-mode pacing as compared to VVI-mode pacing at a heart rate of 140/min. One animal died postoperatively due to respiratory failure. No displacements of the pacemaker leads were observed in the survivors. Conclusion: While VATS-guided implantation of epicardial, atrial, and ventricular leads is feasible, technical improvements of the system are mandatory for safe clinical application.