[Intestinal transplantation in Czech Republic]. / Transplantace tenkého streva v Ceské republice.

Intestinal transplantation represents a suitable treatment for patients with intestinal failure who then develop life-threatening complications of total parenteral nutrition and for some patients with complex abdominal disorders not suitable for conventional treatment. METHODS: prior to launch of the clinical program, preparation started in 2006 initially with extensive experimentation carried out on pigs. The clinical phase involved a specialized, multidisciplinary team who examined 23 patients being considered for transplantation. Seven patients were put on a waiting list and one female, due to the improvement of her medical status, was unlisted. The first ever intestinal transplantation was done in 2014. RESULTS: three out of six transplanted patients are alive with 380 days of actual survival; median 131 days (63-763). Two patients are on a full oral diet and nutritionally independent with an excellent quality of life. One female is nutritionally independent but with the need for partial supplemental parenteral rehydration due to the stomal output. CONCLUSION: intestinal transplantation is a suitable treatment for highly selected patients with intestinal failure who meet specific listing criteria.

Muscle and fat metabolism in obesity after kidney transplantation: no effect of peritoneal dialysis or hemodialysis.

Our prospective study analyzed selected adipocytokines: adiponectin (ADPN), leptin, visfatin, and asymmetric dimethylarginine (ADMA) in the plasma of renal transplant recipients previously treated by peritoneal dialysis and hemodialysis. A total of 70 patients were on follow-up for 12 months after transplantation. Of these, 30 patients (group I) developed obesity, and 40 patients were nonobese (group II). All were receiving standard immunosuppressive therapy (cyclosporine A or tacrolimus and mycophenolate mofetil, with prednisone added in the early posttransplant period) and did not differ statistically in HLA typing, age, sex, duration of previous dialysis, history of cardiovascular disease, and rate of rejection episodes. At the end of the study period, there were significant differences between groups I and II (t test, analysis of variance) in plasma: ADPN, 22.30 ± 10.2 versus 14.3 ± 7.2 µg/mL; visfatin, 1.7 ± 0.1 versus 1.2 ± 0.1 ng/mL; ADMA, 3.60 ± 0.47 versus 2.10 ± 0.36 µmol/L; P < .01; leptin, 55.6 ± 10.2 versus 25.6 ± 8.3 ng/L; P < .01 (P < .02). In conclusion, an increase of body fat after renal transplantation was associated with an increase of ADMA and leptin, TNF-α, MCP-1, and visfatin and decrease of adiponectin. Our study documented there was now long-term beneficial metabolic effect of peritoneal dialysis in developing posttransplant obesity.

[Caecal ligation and puncture in the minipig - a model of sepsis induction]. / Cékální ligace a punkce u miniprasat - metoda studia sepse.

BACKGROUND: Sepsis belongs among the most serious conditions and animal models of sepsis are the basic tools to investigate the pathophysiological response to this condition. MATERIAL AND METHODS: A total of 16 adult minipigs with identical baseline parameters were randomized into two groups. In the sepsis group (n = 10), sepsis was induced using caecal ligation and puncture (CLP). The control group (n = 6) underwent laparotomy without CLP. Selected clinical and laboratory parameters as well as histological findings between the sepsis and control group were subsequently compared. RESULTS: All animals undergoing CLP developed diffuse peritonitis and sepsis. Compared to the control group, experimental animals showed significant increase of body temperature and heart rate (while) requiring noradrenaline to maintain their perfusion pressure. No significant differences in the monitored biochemical parameters (including C-reactive protein levels) between the two groups were found. Histological findings in organs of experimental animals were consistent with changes of organs seen in sepsis, i.e., centrilobular liver necroses, acute tubular renal necrosis, serous fibrinopurulent exudate, myocardial malacias, and pulmonary edema. CONCLUSION: Experimental caecal ligation with a predefined size of the perforation in the intestinal wall is a suitable model for assessing the pathophysiological changes occurring in the body in sepsis.

Adrenal pheochromocytoma as a rare cause of reversible left ventricular systolic dysfunction and malignant arrhythmias: a case series.

Background: Pheochromocytoma is a neuroendocrine tumour originating from the chromaffin cells of adrenal glands or sympathetic paraganglia. It produces most frequently norepinephrine, epinephrine, and dopamine. As a result of non-specific and variable clinical presentation, pheochromocytoma is difficult to diagnose. Case summary: A 37-year-old female without medical history and 57-year-old male patient with diabetes, arterial hypertension, and aortic valve replacement with a mechanical prosthesis were admitted to the hospital after successful cardiopulmonary resuscitation due to ventricular fibrillation. In both patients, coronary angiography demonstrated a normal finding, and echocardiography showed left ventricular (LV) contractile dysfunction with improvement in the subsequent examination. In the first patient, the diagnosis of stress-induced cardiomyopathy was considered as the most probable cause. She was later admitted to hospital due to acute pulmonary oedema with hypertensive crisis. Echocardiography documented reversible LV systolic dysfunction with improvement after 3 days. The course of hospitalization of the male was complicated by multi-organ dysfunction syndrome comprising renal failure, paralytic ileus, and pancreatic irritation, which normalized after 2 weeks. The diagnosis of pheochromocytoma was confirmed by laboratory tests and imaging methods. After pharmacological pre-treatment with doxazosin in both patients and bisoprolol in the female, successful adrenalectomies were performed with no relapse of tumour. Discussion: We describe an atypical clinical presentation of pheochromocytoma with initial cardiac arrest due to ventricular fibrillation and reversible LV systolic dysfunction. Our cases underline that clinical suspicion of pheochromocytoma as a potentially correctable cause should be raised in unexplained cases of severe heart failure, ventricular arrhythmias, and cardiac arrest.

[Plasma citrulline concentration--a reliable noninvasive marker of functional enterocyte mass]. / Hladina plazmatického citrulinu--spolehlivý neinvazivní ukazatel mnozství funkcních enterocytu.

Small bowel disease encompasses a broad range of pathological states starting with functional disorders through inflammatory disease to morphological injury with possible intestine loss. Some of these conditions result in major loss of function presenting as intestinal failure. The term intestinal failure refers to a condition whereby the bowel is unable fulfil its basic function in the process of digestion and absorption of nutrients. Unlike other organs, where reliable laboratory markers of injury or failure are available, no such tests are currently on hand for the bowel. Determination of the plasma citrulline level is a reliable marker for assessing the mass of functional intestinal tissue. Citrulline is an amino acid formed almost exclusively in enterocytes and not present in food proteins. The liver has only a minimal effect on citrulline production. Eighty percent of citrulline is converted in the kidney to arginine. Its impaired renal clearance results in increased citrulline levels. Clinically relevant are decreased citrulline levels as they reflect a lack of functional mass of enterocytes. The aim of the present review is to summarize current knowledge and to define the value of determining plasma citrulline levels for the diagnosis of intestinal failure and, possibly, for monitoring the bowel function.

Hybrid Repair Combined with Fresh Arterial Allograft Extra-Anatomical Reconstruction: The Treatment of Infrarenal Abdominal Aneurysm above an Aortobifemoral Bypass Complicated by an Infected Pseudoaneurysm in the Left Groin.

INTRODUCTION: A 72-year-old male patient was admitted into our centre with large infected pseudoaneurysm (PSA) in the left groin. The patient underwent a CT angiography (CTA) that confirmed a large partly thrombosed 6.5 × 5.5 cm PSA in the left groin arising from the distal anastomosis of the aortobifemoral bypass (ABF). Furthermore, the CTA revealed 11 cm juxtarenal abdominal aortic aneurysm (JAAA) from which the proximal anastomosis of the ABF was arising. METHOD: Aorto-uni-iliac stent graft Cook was placed from the right groin trough native severely stenotic right iliac arteries with proximal landing zone below the renal arteries, excluding the JAAA and the ABF. The distal landing zone was in the common iliac artery maintaining patent right internal iliac artery. Afterwards, a femoro-femoral crossover bypass from right to left was performed using a fresh arterial allograft. Postprocedurally, the hospital stay was uneventful. The left groin PSA cultures came positive for Staphylococcus epidermidis and Corynebacterium tuberculostearicum, both sensitive to vancomycin and rifampicin. RESULT: The patient underwent intravenous ATB treatment with vancomycin for two weeks, followed by four weeks of oral rifampicin. The patient was discharged on the 20th postoperative days. CONCLUSION: Hybrid repair combining aortic stent graft and extra-anatomical bypass in the treatment of infected distal parts of an aortofemoral bypass is an acceptable treatment modality.

Acute appendicitis in a patient after a uterus transplant: A case report.

BACKGROUND: Acute appendicitis in a solid organ transplant recipient is a rare occurrence, and experience remains limited. Appendicitis in uterine transplant recipients has never been reported. Immunocompromised patients with acute abdomen often present late and with attenuated symptoms. The differential diagnosis in a transplanted patient is broad and challenging due to possible existing complications associated with the graft, effects of immunosuppression, and altered anatomical relations. CASE SUMMARY: A 26-year-old woman suffering from absolute uterine factor infertility received a uterus transplant. In the post-transplant period, she suffered from leukopenia and recurrent acute cellular rejection. Her compliance was suboptimal. She travelled to an exotic destination despite the physician's recommendation not to do so. Following her vacation, she presented with abdominal discomfort, nausea and diarrhoea. There was no sign of acute abdomen; the abdominal ultrasound was negative on day 0. Clostridium difficile colitis was verified and treated with perorally administered vancomycin. On day 4, the discomfort changed to pain; the ultrasound scan revealed a finding suggestive of appendicitis. Surgical exploration revealed perforated appendicitis, and appendectomy was performed. From a surgical point of view, the patient's follow-up was uneventful. The patient underwent a successful embryo transfer 6 months after the appendectomy. The patient gave birth to a healthy boy at the 35th week of gestation. CONCLUSION: A high index of suspicion of an atypical course and symptomatology of acute abdomen should be maintained in immunosuppressed patients.

Familial Adenomatous Polyposis and Desmoid Tumor Treated with Multivisceral Transplantation and Kidney Autotransplantation: Case Report and Literature Review.

INTRODUCTION: Desmoid tumours (DT) are commonly associated with Gardener's syndrome. Their surgical resection may be complicated by their close proximity to major vessels, multiple organ involvement, and frequent local recurrence. Multivisceral transplantation (MVTx) is an alternative treatment for patients with intestinal and liver failure. In patients with DT closely associated with renal structures but without end-stage kidney disease, concomitant excision of the patient's own kidney, ex vivo tumour resection with nephron-sparing surgery, or autotransplantation has been proposed. CASE PRESENTATION: A 36-year-old Caucasian female weighing 60 kg with Gardener's syndrome with a history of abdominal surgery was presented to our department with progressive abdominal distention associated with paroxysmal pain. With the use of CT, the patient was diagnosed with a mass arising from the mesenterial region. The patient had normal kidney function and nonalcoholic steatohepatitis. The patient was indicated for MVTx. MANAGEMENT AND OUTCOME: After 16 months on the waiting list, the patient received a multivisceral graft from a deceased donor. Following the restoration of graft vascular flow, the patient's right kidney was removed and the DT dissected ex vivo before autotransplantation into the right pelvic fossa. The patient received immunosuppressive, antithrombotic, and antibiotic treatment. There was no acute rejection, though the patient experienced pulmonary infection, dysphagia, and oesophageal reflux with fungal infection. The patient had required temporary dialysis for acute renal failure for 75 days. One year after the surgery, nausea and violent vomiting caused delayed gastric emptying caused by spastic pylorus. Clinical improvement was achieved using gastric peroral endoscopic myotomy (G-POEM). CONCLUSION: MVTx with kidney autotransplantation is a feasible treatment option in patients with familiar adenomatous polyposis complicated by an abdominal DT. Precise tumour dissection with nephron-sparing surgery was carried ex vivo. G-POEM was used to relieve MVTx-related gastroparesis. The patient had no disease reoccurrence after one-year follow-up.

Differences in antitumor effects of various statins on human pancreatic cancer.

Statins are widely used for the treatment of hypercholesterolemia. However, their inhibitory action on HMG-CoA reductase also results in the depletion of intermediate biosynthetic products, which importantly contribute to cell proliferation. The aim of the present study was to compare the effects of the individual commercially available statins on experimental pancreatic cancer. The in vitro effects of individual statins (pravastatin, atorvastatin, simvastatin, lovastatin, cerivastatin, rosuvastatin and fluvastatin) on the viability of human pancreatic cancer were evaluated in CAPAN-2, BxPc-3 and MiaPaCa-2 cell lines. The in vivo experiments were performed on nude mice xenotransplanted with CAPAN-2 cells. The mice received oral treatments either with a placebo, or with the statins mentioned earlier in a daily dose corresponding to a hypocholesterolemic dose in humans. The effect of these statins on the intracellular Ras protein, trafficking in MiaPaCa-2 transfected cells, was also investigated. Substantial differences in the tumor-suppressive effects of all statins were detected in both in vitro and in vivo experiments. While simvastatin exerted the highest tumor-suppressive effects in vitro, rosuvastatin (p = 0.002), cerivastatin (p = 0.002) and fluvastatin (p = 0.009) were the most potent compounds in an animal model. All statins (except pravastatin) inhibited intracellular Ras protein translocation. In summary, substantial tumor-suppressive effects of various statins on the progression of experimental pancreatic adenocarcinoma were demonstrated, with marked differences among individual statins. These results support greatly the potential of statins for the chemoadjuvant treatment of pancreatic cancer.

Highly sensitive method for quantitative determination of bilirubin in biological fluids and tissues.

Unconjugated bilirubin (UCB) exhibits potent antioxidant and cytoprotective properties, but causes apoptosis and cytotoxicity at pathologically elevated concentrations. Accurate measurement of UCB concentrations in cells, fluids and tissues is needed to evaluate its role in redox regulation, prevention of atherosclerotic and malignant diseases, and bilirubin encephalopathy. In the present study, we developed and validated a highly sensitive method for tissue UCB determinations. UCB was extracted from rat organs with chloroform/methanol/hexane at pH 6.2 and then partitioned into a minute volume of alkaline buffer that was subjected to HPLC using an octyl reverse phase (RP) column. Addition of mesobilirubin as an internal standard corrected for losses of UCB during extraction. Recoveries averaged 75+/-5%. The detection limit was 10pmol UCB/g wet tissue. Variance was +/-2.5%. When used to measure UCB concentrations in tissues of jaundiced Gunn rats, this procedure yielded UCB levels directly comparable to published methods, and accurately determined very low tissue bilirubin concentrations (

Asymmetric dimethylarginine in obesity after renal transplantation.

OBJECTIVE: We have assessed in obese renal transplant recipients a course of selected proinflammatory factors liable to influence the long-term outcome of transplant patients and kidney grafts. DESIGN AND PATIENTS: In a prospective cohort study, we examined a total of 68 obese renal transplant recipients (body mass index [BMI] >or= 30 kg/m(2)) for a period of 12 months (Group I). A control group consisted of 72 comparable non-obese renal transplant recipients (Group II). RESULTS: Significant differences were found in plasma 12 months after renal transplantation (Group I versus Group II) in asymmetric dimethylarginine (ADMA; 3.68 micromol/L +/- 0.42 micromol/L vs 2.10 micromol/L +/- 0.34 micromol/L; P < .01), adiponectin (ADPN; 15.1 microg/mL +/- 6.0 microg/mL vs 22.80 microg/mL +/- 7.2 microg/mL; P < .01), leptin (50.4 ng/L +/- 10.2 ng/L vs 22.0 ng/L +/- 8.4 ng/L; P < .01), solubile leptin receptor (ObRe; 23.6 U/mL +/- 7.4 U/mL vs 47.2 U/mL +/- 10.7 U/mL; P < .01), resistin (21.2 microg/mL +/- 10.2 microg/mL vs 15.0 microg/mL +/- 6.2 microg/mL; P < .025) and triglycerides (3.9 mmol/L +/- 1.6 mmol/L vs 2.8 mmol/L +/- 1.6 mmol/L; P < .01). There were significant correlations between ADMA and BMI (r = 0.525, P < .001), ADPN and BMI (r = -0.574, P < .001), and ADMA and ADPN in visceral fat (r = -0.510, P < .001). Correlation between ADMA and Cin was weak, but significant (r = -0.190, P < .05). CONCLUSION: The results indicate that obesity after renal transplantation was associated with increased plasma ADMA and decreased ADPN in plasma and in fat tissue and may represent a risk factor for renal transplant recipients.

Asymmetric dimethylarginine and adiponectin after renal transplantation: role of obesity.

BACKGROUND: In obese renal transplant recipients, we assessed the course of selected proinflammatory factors liable to influence long-term outcomes of transplant patients and kidney grafts. METHODS: In a prospective cohort study, we examined a total of 140 renal transplant recipients for a period of 12 months. Based on body mass index (BMI), patients were divided into Group I (BMI > or = 30 kg/m2, 68 patients) and Group II (BMI < or = 30 kg/m2, 72 patients). RESULTS: Twelve months after renal transplantation, significant differences were found between Group I versus Group II in plasma levels of asymmetric dimethylarginine (ADMA) (3.65 [SD +/- 0.47 micromol/L] versus 2.01 [SD +/- 0.36 micromol/L], P < .01), adiponectin (ADPN) (15.4 [SD +/- 6.6 microg/mL] versus 22.3 [SD +/- 8.2 microg/mL], P < .01), leptin (51.3 [SD +/- 11.2 ng/L] versus 21.3 [SD +/- 9.2 ng/L], P < .01), soluble leptin receptor (24.6 [SD +/- 8.4 U/mL] versus 46.1 [SD +/- 11.4 U/mL], P < .01), resistin (20.8 [SD +/- 10.1 microg/mL] versus 14.6 [SD +/- 6.4 microg/mL], P < .025), and triglycerides (3.9 [SD +/- 1.6] versus mmol/L 2.8 [SD +/- 1.6 mmol/L], P < .01). There were significant correlations between ADMA and BMI (r = 0.520; P < .001), and ADPN and BMI (r = -0.570, P < .001). The correlation between ADMA and inulin clearance (Cin) was weak (r = -0.185, P < .05). CONCLUSIONS: Obesity after renal transplantation is associated with increased ADMA and decreased ADPN in plasma, and this may represent a risk factor for renal transplant recipients.

Preservation injury to the human small bowel graft: jejunum vs. ileum.

BACKGROUND: Early postoperative complications after small bowel transplantation (SBT) including endotoxemia, bacterial translocations, and stimulation of the recipient's immune response have been attributed to preservation injury. Small intestine is notoriously sensitive to ischemia and there is still no general agreement as to which segment of the small bowel is preferred (jejunum or ileum) for clinical use. AIM OF STUDY: In our study, using light microscopy and concentrations of tissue serotonin-positive cells we sought to identify the part of the human intestine, which is more resistant to preservation injury sustained by HTK preservation solution with 1-24 hr cold ischemia time. RESULTS: Statistical analysis of both parameters did not reveal any significant differences between the jejunum and ileum. CONCLUSIONS: Judging by our data, there is no difference between jejunal and ileal grafts in susceptibility to ischemic injury due to cold ischemia within 24 hours when using HTK preservation solution. Significant difference was observed in histological pictures only after 12-hour of cold ischemia time in both experimental groups (jejunum and ileum).

Model of small bowel transplantation with systemic venous drainage in rats.

Authors in details describe microsurgical technique of heterotopic small bowel transplantation (SBT) with systemic venous drainage in rats. Surgical technique was practiced on laboratory Wistar rat (n = 40), male with weight 240-300 g. This paper in details analyzes the surgical procedure and includes methods of anesthesia, organ harvest, methods of conservation, transplantation and their complications. The aim of authors is to describe a reproducible model of small bowel transplantation in rat and to get a basis for next experimental studies, which will investigate others aspects of SBT like preservation-reperfusion injury and immunological aspect as rejection. Five days of surviving of rats was accepted as successful.

Increased production of proinflammatory cytokines in adipose tissue of patients with end-stage renal disease.

OBJECTIVE: The number of patients with end-stage renal disease (ESRD) is rising and these patients are at higher risk of cardiovascular disease. We studied the role of hormonal production of adipose tissue in the development of chronic inflammation in patients with ESRD before kidney transplantation. METHODS: Fifteen women with ESRD and 17 healthy women (control) underwent single blood drawing and visceral and subcutaneous adipose tissue sampling during surgery (kidney transplantation in the ESRD group or cholecystectomy in the control group). Serum concentrations of C-reactive protein, interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, resistin, monocyte chemoattractant protein-1 were measured. Messenger RNA expression of the same hormones, adiponectin receptors 1 and 2 and immunocompetent cell marker CD68 in subcutaneous and visceral samples were measured using real-time polymerase chain reaction. Adipose tissue was examined immunohistochemically for CD68-positive cells. RESULTS: Serum concentrations of C-reactive protein, adiponectin, resistin, interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 were significantly higher in the ESRD versus control group. Subcutaneous and visceral mRNA expressions of tumor necrosis factor-alpha and CD68 were significantly increased in the ESRD versus control group. Adiponectin receptor-1 and monocyte chemoattractant protein-1 mRNA expressions were significantly higher in visceral but not in subcutaneous adipose tissue of the ESRD group. Messenger RNA expressions of resistin, leptin, adiponectin, interleukin-6, and adiponectin receptor-2 in both fat depots did not significantly differ between groups. Increased infiltration of subcutaneous and visceral adipose tissue with CD68-positive immunocompetent cells was found in the ESRD group by histologic examination. CONCLUSION: Subcutaneous and visceral adipose tissues in ESRD express higher amounts of proinflammatory cytokines and may play a role in the development of systemic inflammation.

Gemcitabine does not prevent acute rejection of the transplanted liver in rats.

Our study was designed to determine effect of gemcitabine on acute rejection of liver in rats. Liver transplantation was performed in rats of the Dark Agouti (DA) and Lewis (LEW) strains. Recipients were divided into three groups: A, DA-to-LEW without immunosuppression; B, DA-to-LEW, treated with cyclosporine A; C, DA-to-LEW, treated with gemcitabine. Immunosuppressants were subcutaneously injected for seven consecutive days after transplantation. On day 7, blood samples and liver graft tissue specimens were harvested. Group A showed severe rejection changes (RAI 8/9); in group B no rejection changes were present (RAI 0/9), and in group C moderate rejection changes were observed (RAI 6/9). Differences were significant between B vs C and A vs C groups; P<0.05. Serum creatinine and urea levels in the gemcitabine group were significantly lower than those in the cyclosporine A group. We did not confirm gemcitabine ability to prevent liver allograft rejection.