Hereditary melanoblastoma in miniature pigs and its successful therapy by devitalization technique.

Applying selective breeding for 10 years we established the MeLiM (Melanoblastoma-bearing Libechov Minipigs) strain. Melanoblastoma (MB) in this strain shows a hereditary occurrence. Cutaneous tumours are usually nodular, multiple and distributed on various parts of body. They appear in darkly pigmented animals already at the birth or during two months thereafter (57% of all animals). Numerous organ metastases mainly into the spleen, lymph nodes and lungs are regularly ascertained in animals with cutaneous MB. Tumour cells were surprisingly found also in the inner organs of phenotypically healthy minipigs in which no cutaneous MBs were observed visually (27% of all animals). About 34% of all affected piglets die during the first 2 months of age. These features document a malignancy of this tumour in the MeLiM strain. Original surgical technique was applied in more than 40 affected minipigs at 1-2 months of age. It consists in a devitalization (ischemization) of one of cutaneous tumours by the mattress sutures conducted around the tumour base without any excision of tumour tissue. This simple procedure causes a total destruction of MB cells in all cutaneous tumours as well as in all organ metastases during 4-6 months. Animals treated by this technique were fully healed of tumour cells and no relapses were observed. This technique could bring similar positive results also in therapy of human MB.

[Melanoblastoma in laboratory minipigs: a model for studying human malignant melanoma]. / Melanoblastomová nemoc u laboratorních miniprasat: model pro studium lidských maligních melanomu.

Human malignant melanoma is a progressively growing tumour mostly with a fatal prognosis during short time. Its frequency has doubled in some states of the USA during the last few years. Surgical treatment, which is still generally used, has very low efficiency due to the numerous metastases in different organs. An animal model is a necessary prerequisite to develop a new therapy methods. We have recorded primary cutaneous malignant melanomas as well as extensive metastases in the visceral organs in darkly pigmented laboratory minipigs. The primary skin tumours were mostly multiple and they showed a tuberous nodular form. The regular occurrence of tumours in a progeny of three specific mating types suggests the existence of genetic predisposition to malignant transformation. We discuss the use of this animal model for further studies and treatment of human malignant melanoma by our ischemization technique developed previously.

[Use of the tourniquet in gastrointestinal surgery]. / Pouzití turniketu v gastrointestinální chirurgii.

Experimentally induced total or partial intestinal obstructions (ileus) in pigs were surgically treated by means of a tourniquet technique. A lace used in obstetrics for ligation of umbilicus served as the tourniquet. The lace was protracted around an intestine, both ends were threaded through 7-10 cm long rubber tube and fixed by Pean's forceps. During application of the tourniquet we performed suction of the ileus content, devitalization or resection of the affected intestinal segments and intestinal anastomoses. Since the tourniquet provides a flexible compression of intestine with minimum mechanical damage, manipulation without danger of instrument release, and it has negligible cost, this tool gives supposition for the possible use in human surgical praxis.

Experimental devascularization (devitalization) of the rectum and sigmoideum.

In 6 laboratory pigs, devascularization (devitalization) of the rectum and the adjacent part of the sigmoideum was carried out by the vasa rectalia cranialia et media ligatures with simultaneous aboral closure of the rectum at the base of the lesser pelvis and oral closure at the borderline between the rectum and the sigmoideum. The devascularized rectum was not removed but left in situ. Terminal colostomy was established. Laparotomic revision was carried out after 12 weeks, colostomy was removed and continuity of the intestine was reestablished by insertion anastomosis, by suture of the end of the colon to the anal mucosa and skin. In further two pigs, devascularization of the rectosigmoideum was carried out with colostomy and reconstruction was carried out after 12 weeks by procto-sigmoideo-anastomosis. In another 2 animals, devascularization was carried out on the lower part of the sigmoideum and continuity was immediately renewed by end-to-side sigmoideo-sigmo-ideoanastomosis. All revisions indicated that the devascularized necrotic segment shrank to form a minute fibrous tissue residue, anastomosis was patent and continence was retained for colo-proctoanastomosis. The described techniques are technically simple and could be employed as palliative surgical methods for inoperable tumours in the region of the rectum and lower part of the sigmoideum.

Changes of clinical biochemical values after bilateral nephrectomy and allotransplantation of the kidney in pigs.

In a series of 10 healthy pigs, the normal ranges of the following biochemical parameters in blood serum were assessed: creatinine, urea, mineralogram (Na, K, Cl), uric acid, bilirubin, total protein, cholesterol, blood lipid level, thymol turbidity reaction and activities of alkaline phosphatase, alpha-amylase and transaminases. The changes of these values were followed up in two pigs after bilateral nephrectomy and in 18 pigs subjected to orthotopic allotransplantation of the kidneys. The examination confirmed that creatinine and urea are the most important values with a prognostic impact. However, other biochemical values signalize also renal dysfunction. In the mineralogram, values of Na and K ions are important indicators. Deterioration of renal functions was associated as a rule with a decline of alpha-amylase and alkaline phosphatase. The other examinations did not display any marked changes during renal damage.

The devitalization of the stomach by a devascularization technique.

Different parts of the stomach in healthy animals (pigs) were devitalized (devascularized) by eliminating the blood supply and left in situ. In model experiments, parts of the stomach were chosen for the devitalization with respect to most frequent location of carcinomas. The operation technique consisted of a complete ligature of perigastric vessels, bling enclosure of the cranial part of the duodenum with two ligatures with a possible application of a seromuscular suture and transverse cutting of the oral part of the stomach and its enclosing by a suture with a partial invagination of the wall. The passage was renewed by a gastroenteroanastomosis, some of the used modifications of the operation technique according to Billroth II (Schlater-Pólya). A method was mostly proposed with an interposition of the jejunal loop, which bridged the site of the devitalized part of the stomach. In 10 to 20 weeks the stomach tissue was stepwise degraded and it was replaced by fibrous tissue. The operation technique is simple; it could be applicable as a palliative or possibly therapeutic intervention in the case of inoperable tumours in human practice.

A technique of the segmental devitalization of kidneys in experiment.

With the help of partially overlapping parenchymatous sutures, different renal segments were devitalized. After 8 weeks, a fibrous conversion occurred in devitalized part of the kidney. For the orientation during establishing the sutures, a topographic schematic diagram was used, which is simple and quite satisfactory for the use in practice. The study was performed on minipigs (21 x unilaterally, 3 x bilaterally) without any exitus of the experimental animals. A long series of experiments was performed in 37 rats on one kidney and in 40 rats bilaterally. Only in 3 rats the cause of the exitus was obviously in a connection with eliminating more than 70 to 75% of the renal parenchyma from the function. The devitalization technique presents good results in both series of the experiments. Possibilities of its use in the clinical practice in cases, where the resection therapy is being used currently, are discussed.

Morphology of regressive changes in the kidney following experimental ischaemia.

Total or partial renal ischaemia was studied in rats and pigs in a series of experiments, after total devascularization (ligature of renal vessels and ureter); ligature of isolated renal artery; experimental embolization of renal artery by non-resorbable material; devascularization of a specific renal segment by deep, strangulating sutures. Morphological studies showed that the resulting necrotization is represented most frequently by coagulation necrosis, less frequently by colliquating necrosis. Occlusion of the renal artery by embolization or ligature leads only to partial necrotization or atrophy. Total devascularization of the renal hilus or total devascularization of a specific renal segment by strangulating sutures leads to total destruction of the devascularized (devitalized) tissues. Within 8-12 weeks, the whole organ changes into a small residue of connective tissue. The possibility of the use of the devascularization technique in the treatment of tumours is discussed.

[Intestinal invagination in pigs]. / Strevní invaginace u prasete.

The invaginations of small intestine are being described which represent one of possible causes of intestinal ileus. In connection with multiple invaginations, a case of two intussusceptions is being mentioned, in which the peaks of invaginates are directed towards each other. At the same time four theoretically possible double invaginations are presented as well as a proposal for their distinction and indication.

[Small and large intestine devascularization (devitalization) and potentials in the therapeutic use of this operative method]. / Die Dünn- und Dickdarmdevaskularisation (Devitalisation) und einige Möglichkeiten der therapeutischen Ausnutzung dieser Operationsmethode.

The experimental findings with devitalization of various intestinal segments by means of devascularization showed that the isolated segments left in peritoneal cavity (together with their contents) were gradually destroyed and changed into a slight fibrous residue. The retaining of the up to 180 cm long segment did not endanger the life of experimental animals. This experience was used in the surgical treatment of inoperable tumours in left half of large intestine and in rectosigmoideum. The case report of four successful operations is given together with two cases of invagination of the devitalized part into intestinal lumen.

Subcutaneous transposition of a kidney (an experimental study in the rat).

To make the kidney better available for requirements of experimental practice, the authors evolved a technique for subcutaneous transposition of a kidney in the rat. If saline with antibiotics (PEN, STM) is infused intraperitoneally during the operation, the technique gives very good results.