Metformin therapy and risk of cancer in patients after heart transplantation.

BACKGROUND: Diabetes mellitus (DM) and malignancy are recognized among the most common complications increasing mortality in patients after heart transplantation (HTx). Clinical trials have shown a higher risk for different types of tumours in diabetic patients. This risk is potentiated by immunosuppressive therapy in transplant patients. Biguanide metformin has been shown to exhibit anti-tumour activity and we tried to find out whether this effect is valid for heart transplant patients. METHODS: We retrospectively analysed a group of 497 patients, who undergone HTx in our centre between 1998 and 2019. The primary outcome was any malignancy during the 15-year follow-up period and patient's survival. RESULTS: Out of the 497 patients enrolled in the study, 279 (56 %) had diabetes and 52 (19 %) were treated with metformin. Fifteen-year survival in treated patients without malignancy was 93 %, the remainder for the DM patients was 56 %, with survival in non-DM patients being 74 %. Untreated diabetic patients had 4.7 times higher chance of malignancy than those on metformin (p = 0.01). Fifteen-year survival in metformin treated patients was 53 %, in other DM patients 44 %, and in non-DM patients 51 %. CONCLUSION: Our study showed a significantly lower incidence of malignancies in metformin-treated patients and slightly better overall survival (Tab. 2, Fig. 3, Ref. 19) Keywords: biguanide, heart graft, malignancy, diabetes mellitus, survival.

[Liver transplant outcomes in Brno]. / Výsledky transplantací jater v Brne

The first liver transplant in the former Czechoslovakia took place in Brno on 2 February 1983; the patient concerned has lived for more than 30 years with a normally functioning liver and is one of the longest surviving patients after a liver transplant in Europe. The Cardiovascular and Transplantation Surgery Centre (CTSC) in Brno has experienced an increased development in the area of liver transplants since the mid  1990s. At present, about 30 patients a year undergo a transplantation, with 451 liver transplants in total as of 31 December 2012. The primary indication concerns liver cirrhosis of various etiologies, with an increasing number of cases of cirrhosis resulting from hepatitis C. Urgent liver transplants (for acute liver failure or primary dysfunction of first liver graft) amount to 11% of cases. There were 18 retransplants performed as of 31 December 2012, with 50% five year survival. The primary graft dysfunction was present in 7 patients (i.e. 1.5%). The 1 year survival rate of all patients after a liver transplant performed in CTSC is 92%, 5 year survival rate is 80%, and 10 year survival rate is 71%. Currently the parameters such as recipients age, donors age, and transplant waiting time has been statistically increasing; small recipients with a body weight below 70 kg especially have to wait for a significantly longer period of time (waiting median of 178 days). In CTSC Brno 14 combined simultaneous transplants (13 transplants of liver + kidney and one combined simultaneous transplants of liver + heart + kidney in 2005) have been performed as of 31 December 2012.

[Liver transplants in tumours and alcoholic cirrhoses]. / Transplantace jater u tumoru a alkoholických cirhóz.

The treatment of hepatocellular carcinoma requires a multidisciplinary approach; liver transplant is suitable only in the minority of strictly selected patients. The CSTC Brno applies the so  called Milan criteria. As of 31 December 2012 the CSTC Brno performed liver transplants in 16 patients with hepatocellular carcinoma in cirrhosis, with a five year survival rate of 40% and a 10 year survival after transplant of 20%. It is a paradox that the longest living (30 years) patient of CSTC Brno underwent the transplant for a large fibrolamellar hepatocellular carcinoma, which emphasises the prognostic significance of the tumour histology -  criterion taken into account for practical reasons only in some indication schemes. Liver transplant for cholangiocarcinoma is no longer being carried out in CSTC. Five patients underwent this operation in the past and the longest living one survived for four years after the transplant. Benign liver tumours (adenomatosis, cystadenoma, hemangioma with compression symptoms) are rather rare indications and transplant results are positive. Four patients were transplanted for liver carcinoid, with one patient experiencing recurrence. The most frequent compact indication for liver transplant in CSTC Brno concerns alcoholic cirrhosis (24%, 108 patients); the survival rate of these patients after transplant is very good (81% 5 year survival and 68% 10 year survival). Likewise, efforts are made to select patients with a low risk of alcohol abuse after the transplant, which is, however, not very successful. The recurrence of some kind of alcohol abuse occurred in 26% transplanted patients, while seven died of alcoholic cirrhosis of the graft.

[Cardiac tumor in a pregnant patient]. / Tumor srdce u gravidní pacientky.

Cardiac myxoma represents the most frequent cardiac tumor with a relatively low overall incidence. Clinical symptoms are hetereogeneous and therefore nonspecific. With regard to high success of the surgical treatment, early diagnosis is crucial. We present a case of cardiac myxoma in a pregnant woman, which was succesfully sugically removed.

[Surgical treatment of pulmonary embolism]. / Chirurgická lécba plicní embolie.

BACKGROUND: Surgical embolectomy is established method of treatment of pulmonary embolism. The aim of the study is to evaluate the experience with this procedure. PATIENTS AND METHODS: Twenty two patients, aged 22-77 years, were operated on in Centre of cardiovascular surgery and transplantation in Brno from 1999 to 2009. Nine patients suffered from massive pulmonary embolism with hemodynamic instability, 13 were stable. All the operations were performed in cardiopulmonary bypass with cross clampimg time 50.4 minutes on average. In six patients the retrograde perfusion via pulmonary veins were used. Emboli in the main trunk and/or in both pulmonary branches were found in 16 patients (72.7%). No macroscopic emboli were found in three patients, but they were flushed from the pulmonary vessels during the retrograde perfusion in two of them. Emboli or thrombi in cardiac atria or ventricles were detected in 8 patients simultaneously. RESULTS: Five patients died early after operation (mortality 22.7%). The mortality was different in the group of patients with massive pulmonary embolism and cardiogenic shock (44.4%) and with submassive embolism and hemodynamic stability (7.7%). CONCLUSION: Developments in surgical technique with retrograde perfusion offer removing of emboli not only from the pulmonary trunk and main branches, but also from the peripheral branches. It improves results and facilitates extension of indications for surgical treatment.

Blood phagocyte activation during open heart surgery with cardiopulmonary bypass.

Open heart surgery with a cardiopulmonary bypass (CPB) is associated with a systemic inflammatory response which significantly contributes to adverse postoperative complications. The purpose of this study was to characterize the activation of blood phagocytes during open heart surgery with CPB. Blood samples were collected during and up to 24 h after surgery. The production of reactive oxygen species (ROS) in whole blood, the expression of surface molecules by blood phagocytes and complement activity in the plasma were determined. A cDNA microarray analysis of leukocyte RNA profile of genes was performed related to the inflammatory response. Activation of the complement was already observed at the beginning of CPB. This was followed by an increase in the neutrophil number and in both spontaneous and opsonized zymosan-activated ROS production after the onset of reperfusion. The activation of blood phagocytes was affirmed by changes in surface receptors involved in the adhesion and migration of leukocytes (CD11b, CD62L and CD31). Gene arrays also confirmed the activation of leukocytes 4 h after reperfusion. In conclusion, open heart surgery with a cardiopulmonary bypass was found to be associated with a rapid and pronounced activation of blood phagocytes and complement activation which was partly independent at the onset of CPB.

[Liver transplantation for hepatitis B]. / Transplantace jater pro hepatitidu B.

Up to now the outcomes of liver transplantation in patients with chronic viral hepatitis B have not been very good because the recurrence of viral hepatitis in the graft has been high and resulted in a high early graft failure of liver transplant recipients. However, the administration of a combined therapy with lamivudine and hyperimmune anti-HBs globulin has led to a marked improvement in transplantation results and an increase in the number of liver transplantations for this indication. Four men (aged 47 to 55 years) underwent liver transplantation for cirrhosis, caused by chronic viral hepatitis B, at our centre. All were HBsAg carriers. They were our first patients who received therapy with the combined immunoprophylactic regimen of lamivudine and hyperimmune anti-HBs globulin. HBV DNA negativity was achieved in all patients prior to transplantation; three of them were pretreated with lamivudine. At 4 to 17 months of follow-up, sustained suppression of HBV replication (HBV DNA negativity) was maintained in all four patients. No complications associated with this treatment were observed and no emergence of resistant mutants was detected. The combined therapy for chronic viral hepatitis B administered to liver transplant recipients at our centre showed very good outcomes. However, the development of resistant mutants during this therapy poses a problem, which may hopefully be overcome with the use of new antivirotics, such as adefovir or tenofovir.

[The piggyback technique in venous outflow tract reconstruction in liver transplantation]. / Význam piggyback techniky pri rekonstrukci venózního odtoku pri transplantaci jater.

Nowadays, the piggyback technique of venous outflow tract reconstruction has been adopted by an increasing number of transplant teams. From January 1996 to August 2000, we used it in 73 of 84 liver transplantations (86.9%) in our institution. We observed one postoperative complication (1.4%) in direct relation to this technique. The main advantages of the piggyback are 1. maintaining of the haemodynamic stability during the anhepatic phase, 2. avoiding of the veno-venous bypass, 3. diminution of blood loss, 4. easier solution of the graft size mismatch problem, 5. shorter manipulation time and 6. easier retransplantation. Disadvantages of the piggyback technique include 1. more technically demanding recipient's hepatectomy, 2. the potential for venous outflow tract obstruction and 3. possible thrombosis in a blind caval pouch. According to our results and experience in the literature, we consider the piggyback technique as a method of choice for venous outflow tract reconstruction in liver transplantation. It can be used in the majority of patients after gaining some experience.

Biliary complications in liver transplantation.

OBJECTIVES: Biliary complications (BC) continue to be a major cause of morbidity among liver transplant recipients. The aim of this study was to analyse the incidence, risk factors and management of biliary tract complications at the Centre for Cardiovascular Surgery and Transplantations in Brno. METHODS: Between January 1992 and December 2000, 118 orthotopic LT were performed in 113 patients. Reconstructions of biliary tract included four methods: end-to-end choledochocholedochostomy with a drain in the retained gallbladder in 15 cases, end-to-end or side-to-side choledochocholedochostomy with a T tube in 29 cases, end-to-end choledochocholedochostomy without a T tube in 67 cases and choledochojejunostomy over the drain in 7 cases. Biliary complications were divided into three groups: stenosis, leaks and cholangitis. RESULTS: Biliary complications occurred after 33 LT (27.9%), affecting 28.3% of the recipients. They occurred most frequently when CCwT or CJ types of reconstruction were used (44.8% and 57.1%, respectively) and least frequently in the CCw/oT group of patients (16.4%). The most common type of biliary complication was stenosis which occurred in 20 patients (in 12 at the anastomotic site, in 5 it was caused by external compression and 3 had nonanastomotic strictures); biliary leaks were in 13 patients and cholangitis in 10 patients. Twenty three biliary complications occurred in the early postoperative period and 12 during the follow-up. Endoscopic treatment was used as primary therapy in 17 patients, primary surgical intervention was used in 12 patients and five patients were treated conservatively. Five patients died due to biliary complications (mortality, 15.1%). CONCLUSIONS: It can be concluded that BC is a common cause of morbidity after LT. In the last few years, its frequency has remained constant. Technical failure or local ischemia are major causes. Biliary leaks predominate in the early posttransplant period. Since end-to-end choledochocholedochostomy without a T tube is associated with the lowest incidence of BC, it is considered to be the method of choice. BC can usually be managed endoscopically, although early leaks frequently require reoperation. Aggressive and early management of BC can reduce mortality in patients after LT.

Hemodynamic measurement in liver transplantation. Piggyback versus conventional techniques.

The piggyback technique in venous outflow tract reconstruction has been proposed as an alternative to the conventional technique in liver transplantation. Maintaining caval flow during the anhepatic phase with hemodynamic stability is regarded as one of the main advantages of this method. Between November 1994 and November 1998, the piggyback technique was used in 47 patients in our Center. Hemodynamic measurements during the operation showed hyperdynamic circulation with an increase in cardiac output (9.3+/-3.5 L/min) and the calculated cardiac index (5.0+/-1.9 L/min/m2). There was a statistically significant increase in heart rate and a decrease in systolic arterial pressure, cardiac output (CO) and cardiac index (CI) during inferior vena cava clamping ( simulated conventional technique). Only a non-significant decrease in CO and CI was observed during the partial clamp on the inferior vena cava (piggyback technique). Out of those two techniques, piggyback proved to be a safer approach to venous outflow tract reconstruction from the hemodynamic point of view.

[Use of drains in the biliary tract in liver transplantation]. / Pouzití drénu do zlucových cest pri transplantaci jater.

Between January 1995 and December 1997 42 liver transplantations were performed in Centre for cardiovascular surgery and transplantation's in Brno. The patients were divided into two groups. The first group consist of 27 transplantations, where the biliary reconstruction was performed by means of choledochocholedochostomy or choledochojejunostomy over a drain. The drain was used on the first 20 patients for initial irrigation and for the decompression of the biliary tree later on. It was used only for the decompression in the last 7 patients of this group. The second group consist of 14 patients, where the choledochocholedochostomy was performed without any drain. The rate of the biliary complications was significantly higher in the first group. Nine biliary obstructions, 6 leaks a and 6 cholangitis occurred. Four patients died in consequence of the biliary complications. There was no biliary complication in the second group. Choledochocholedochostomy without a drain is considered as a method of choice for biliary tract reconstruction in liver transplantation.

[Subcutaneous chamber systems (ports) for long-term care in cancer patients]. / Podkozní aplikacní komurkový systém ("port") pri dlouhodobé lécbe onkologicky nemocných.

Maintenance of satisfactory and safe venous access in cancer patients is part of a comprehensive care of cancer patients. As the Hickman/Broviac catheter is today used an implantable port. This port is placed in a subcutaneous pocket. The catheter connected to the port leads into the central vein, usually through the subclavian vein. An application of drugs in the port is done trough the skin. In this time could be used different types of ports, one or two chambers port, low profil port, peripheral port and others. In this paper we reported our two-years experience with 33 totally implantable access systems, which has been implanted in patients with cancer in Masaryk University Hospital Brno Bohunice. In our department was most frequently used port the nonmetallic port IMPLANTOFIX (BRAUN MELSUNGEN). All ports were in place for a total of 5,582 days, in average of 169 days. A frequency of complications were 2.15 on 1,000 days. Four ports were in place for longer than 1 year. A comparison of the incidence of complications in the present study with an analysis of 23 studies reported in literature was satisfactory. Minimal maintenance care, no restriction of life activity, improving quality of life and probably less frequency of infection complications, identify it as a significant advantage for the satisfactory maintenance of venous access of oncology patients in comparison with Hickman/Broviac catheter. Both the patients and the nursing staff showed a very high degree of satisfaction with this system. In cancer patients, especially with poor venous access, and prognosis longer than 6 months can be indicated this system with the advantage for patients.