Microchimerism as Post-Transplant Marker of a Chronic Rejection Process.

The risk of losing a transplanted organ is high, and non-invasive markers to warn of this phenomenon are still being sought. We investigated the impact of post-transplant microchimerism on the function of the transplanted kidney. The study included 100 kidney transplant recipients, mostly women. All transplanted organs were from opposite-sex deceased donors. Microchimerism was assessed using multiplex PCR. Male DNA was detected in all urine samples from female recipients and in 13/56 blood samples from female kidney recipients. Female DNA was found in 31/44 urine samples from male recipients, but in none of the blood samples. Microchimerism in the urine of female recipients correlated positively with blood urea (Rs = 0.45; p = 5.84 × 10-4) and K+ ions (Rs = 0.29; p = 0.03), while microchimerism in the blood of female recipients also correlated positively with blood urea (Rs = 0. 28; p = 0.04), cystatin C (Rs = 0.31; p = 0.02) and the number of incompatible HLA alleles (Rs = 0.42; p = 0.01). A history of DGF was associated with higher urinary donor DNA concentrations in female recipients.: Post-transplant microchimerism may serve as a potential marker of chronic kidney rejection.

Nutritional Status, Selected Nutrients Intake, and Metabolic Disorders in Bariatric Surgery Patients.

Bariatric surgery is the most effective treatment for obesity and its complications. However, failure to adhere to dietary recommendations can result in both unsatisfactory weight loss and metabolic disorders. The aim of this study was to evaluate the effects of bariatric surgery on the anthropometric parameters and selected nutrient intake. A total of 12 months postoperatively, percent excess weight loss (%EWL) was significantly higher after laparoscopic Roux-en-Y gastric bypass (LRYGB) than laparoscopic sleeve gastrectomy (LSG) and laparoscopic adjustable gastric banding (LAGB) (93.78% vs. 56.13% and 55.65%, p < 0.001). The same was true for waist-to-hip ratio (WHR) (p = 0.017) and waist-to-height ratio (WHtR) changes (p = 0.022). There was a significant decrease in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels after RYGB. A significant decrease (p < 0.05) in daily intake was found for energy (4278.4 kcal vs. 1355.17 kcal), sucrose (122.23 g vs. 38.22 g), dietary fiber (30.90 g vs. 14.20 g), eicosapentaenoic fatty acid and docosahexaenoic acid (EPA+DHA) (142.46 mg vs. 52.90 mg) and % energy from fats (42.43% vs. 35.17%), saturated fatty acids (SAFAs) (19.96% vs. 14.11%) and alpha-linolenic fatty acid (ALA) (0.87% vs. 0.69%). Energy intake and energy % from fats positively correlated with body weight (BW), waist circumference (WC), WHR, and WHtR, and negatively with %EWL. The percentage of unsaturated fatty acids positively correlated with WC and WHR. Energy intake correlated positively with serum triglycerides (TGs) and energy % from fats and carbohydrates. Despite significant weight loss, the patient's diet deviated from recommendations and may have contributed to metabolic disorders.

Clinical Relevance of Gut Microbiota Alterations under the Influence of Selected Drugs-Updated Review.

As pharmacology and science progress, we discover new generations of medicines. This relationship is a response to the increasing demand for medicaments and is powered by progress in medicine and research about the respective entities. However, we have questions about the efficiency of pharmacotherapy in individual groups of patients. The effectiveness of therapy is controlled by many variables, such as genetic predisposition, age, sex and diet. Therefore, we must also pay attention to the microbiota, which fulfill a lot of functions in the human body. Drugs used in psychiatry, gastroenterology, diabetology and other fields of medicine have been demonstrated to possess much potential to change the composition and probably the function of the intestinal microbiota, which consequently creates long-term risks of developing chronic diseases. The article describes the amazing interactions between gut microbes and drugs currently used in healthcare.

Incidents and risk factors of biliary complications after orthotropic liver transplantation.

ABSTRACT: Biliary complications (BC) especially stenosis and strictures are the most common complications after orthotropic liver transplantation (OLT) procedure in adult recipients. The intention of this study was analyzed BC in 273 patients after OLT for the last 4 years in our department.Retrospective study of 273 patients underwent cadaveric donor liver transplantation between January 2014 and December 2017. Most of them (n = 268) have anastomosed bile duct in end to end, rest of them (n = 5) underwent hepaticojejunostomy. Statistical analysis was performed using Fischer exact test and Student t test. A P value <.05 was considered significant.BC were developed in 48/273 transplants (17.6%). The most frequent was biliary stricture (n = 42, 87.5%) followed by bile leak (n = 4, 8.3%) and choledocholitiasis (n = 2, 4.2%). Treatment was usually using endoscopic retrograde cholangiopancreatography. Recipients with hypotension during and after OLT treated by norepinephrine have a higher index of BC.Self-expanding metal stents implantation seems to be more effective than repeated balloon dilatation of anastomotic strictures with subsequent plastic biliary stent placement and associated with similar complication rate. Good fluid management against inotropic therapy may reduce risk of BC.

Late Recurrence of Hepatocellular Carcinoma in a Patient 10 Years after Liver Transplantation Unrelated to Transplanted Organ.

Liver transplantation (LTx) is an accepted method of hepatocellular carcinoma (HCC) treatment in cirrhotic patients; however, it has many limitations, and there is a substantial risk of recurrence. Most relapses occur within the first 2 posttransplant years. We aimed to present a late extrahepatic recurrence of HCC 10 years after LTx, and we discuss the possible risk factors and ways to improve transplantation results. A 68-year-old patient with liver cirrhosis and HCC on the background of chronic HCV and past HBV infection was transplanted urgently due to the rapid decompensation. Anti-HCV treatment before surgery was unsuccessful. Pretransplant computed tomography showed 1 focal 4.5 cm lesion consistent with HCC. Histopathology of the explanted organ showed 2 nodules outside the Milan criteria. Angioinvasion was not found. The patient achieved a sustained viral response to pegylated interferon and ribavirin 2 years post-LTx. Eight years were uneventful. CT of the abdomen performed occasionally was normal. Ten years after LTx, the patient unexpectedly presented with shortness of breath, fatigue, and weight loss. Two metastatic nodules of HCC in the lungs and pelvis were found. Although late HCC recurrence post-LTx is rare, it should be always considered, especially when risk factors such as viral infections and underestimation of tumor advancement were identified. We advocate that oncological surveillance of HCC relapse has to be continued during the whole posttransplant period. High AFP levels, the unfavorable neutrophil to lymphocyte ratio, and better estimation of primary tumor size seem to be useful in the identification of good candidates for transplantation.

Persisting bleeding from the duodenal ulcer in patients with occlusion of the celiac trunk: a case report.

INTRODUCTION: Endoscopic measures have continued to be the primary procedures in the management of ulcer bleeding. Nevertheless, in cases of failed endoscopic hemostasis and re-bleedings, endovascular techniques have gradually gained increased acceptance as an alternative to surgery, allowing to avoid surgical intervention in some cases. <br/> Case report: A case of a 42-year-old patient presenting to the authors' institution with massive bleeding from the duodenal ulcer, sprang from a pathologically enlarged gastroduodenal artery is reported. This vascular anomaly was a consequence of occlusion of the coeliac trunk (Dunbar syndrome), which was shown on an angio-CT scan. In spite of several endoscopic and endovascular measures, as well as three operations, the bleeding persistently recurred (a total of 6 episodes) and the patient eventually died. The article presents details of operative and endovascular treatments. Contemporary trends in management in cases of failed endoscopic interventions and re-bleedings form peptic ulcers are shown in the discussion.

Protein Abundance of Hepatic Drug Transporters in Patients With Different Forms of Liver Damage.

Hepatocellular transporter levels were quantified using quantitative reverse transcription polymerase chain reaction and liquid chromatography-tandem mass spectrometry methods. Liver function deterioration (Child-Pugh class C) produced significant protein abundance (mean values) increase (to healthy livers) in P-gp (to 260% (CV (coefficient of variation) 82%)) and MRP4 (CV 230%) (not detected in healthy livers), decrease in MRP2 (to 30% (CV 126%)), NTCP (to 34% (CV 112%)), OCT1 (to 35% (CV 153%)), OATP1B1 (to 46% (CV 73%)), and OATP2B1 (to 27% (CV 230%)), whereas BSEP (CV 99%), MRP3 (CV 106%), OAT2 (CV 97%), OCT3 (CV 113%), and OATP1B3 (CV 144%) remained unchanged. Alcoholic liver disease produced significant protein downregulation of MRP2 (to 30% (CV 134%)), NTCP (to 76% (CV 78%)), OAT2 (to 26% (CV 117%)), OATP1B1 (to 61% (CV 76%)), OATP1B3 (to 79% (CV 160%)), and OATP2B1 (to 73% (CV 90%)) of healthy tissue values. Hepatitis C produced BSEP (to 47% (CV 99%)) and OATP2B1 (to 74% (CV 91%)) protein reduction. Primary biliary cholangitis and primary sclerosing cholangitis demonstrated P-gp and MRP4 protein upregulation (to 350% (CV 47%) and 287% (CV 38%), respectively). Autoimmune hepatitis revealed P-gp (to 410% (CV 49%)) and MRP4 (CV 96%) increase, and MRP2 (to 18% (CV 259%)) protein decrease. Drug transporters' protein abundance depends on liver pathology type and its functional state.

Recurrence of Hepatocellular Carcinoma After Liver Transplantation: A Single-Center Experience.

BACKGROUND There is a worldwide increase in use of liver transplantation (LT) for treatment of hepatocellular carcinoma (HCC). We analyzed our experience with LT for HCC to determine long-term and recurrence-free survival, accuracy of imaging diagnosis of HCC compared to the explant pathology, recurrence rate of HCC, and predictors of recurrence. MATERIAL AND METHODS The whole explant was examined by the same pathologist and compared with the baseline diagnosis established according to clinical, laboratory, and radiological data. A group of patients with pathologically confirmed HCC was characterized, with special attention to etiology, survival, recurrence, and diagnostic accuracy of imaging techniques. RESULTS Among 718 patients transplanted from 2000 to 2018 in our center, HCC was found in 166 explanted livers. In 42 cases the clinical diagnosis of HCC was not accurate, being either false positive or negative; however, the specificity and sensitivity of CT/MRI in HCC recognition was 97.87% and 88.24%, respectively. Five- and 10-year survival was 81.27% and 66.57%, respectively, and it was inferior to the overall survival. The recurrence rate was 9.6% with a median time to recurrence of 14 months and a median survival time of 9 months. Poor differentiation of HCC and HCV etiology of the baseline disease, but not previous DAA treatment, were the risk factors of HCC recurrence. CONCLUSIONS Adherence to strictly defined selection criteria for LT in HCC patients guarantees the success of LT in HCC treatment.

Biocompatibility of synthetic ultraviolet radiation cross-linked polymers - Subcutaneous implantation study.

Photo-cross-linked polymers have attracted a lot of attention in the biomedical field. The main benefits of these materials are related to the fact that they are most of the time viscous liquids or pastes that adapt a custom and fixed shape on demand of the user. Present study deals specifically with the biological response upon subcutaneous implantation of four different materials in rabbits. In the study 20 rabbits were divided into four groups (each five rabbits): Groups 1-3 were implanted with tested new obtained by us macromonomers (P1838-DMA; P1838-UR; PDEGA-UR - respectively), while group 4 (control) was implanted with the mesh (PLA) routinely used for surgical treatment of a hernia. The new compounds were polarized earlier using ultraviolet radiation to obtain cross-linked networks. The polymers in the form of discs were then implanted subcutaneously in dorsal region of rabbits. After 28 days polymers were explanted and examined. Microscopic observation evaluated: thickness of the connective tissue capsule around the discs, cells of inflammatory response, disc surface erosion, spectroscopic analysis. The examined materials cause no chronic inflammation, abscesses or tissue necrosis, and the biological response is similar to observed in control group. Therefore, new synthetic materials could be considered as biocompatible and safe. Materials undergo slow degradation of ester bonds and surface erosion and degradation products could be eliminated probably by phagocytosis. On the basis on the afore mentioned knowledge, we formulated hypothesis, that the new polymers are well tolerated by the adjacent tissues. The aim of the following study was to examine reaction of the tissue on new types of prepolymerized material implanted subcutaneously. The obtained results suggest, that the new UV cross-linked polymers do not affect negatively on the connective tissue that is in the contact with the implants. Furthermore, the used materials are in the liquid form, thus they could be easily performed in in minimally invasive laparoscopic treatment of abdominal hernias. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1889-1897, 2019.

Application of Fully Covered Self-Expandable Metallic Stents with and without Antimigration Waist Versus Repeated Plastic Biliary Stent Placement in Management of Anastomotic Biliary Strictures After Orthotopic Liver Transplantation.

BACKGROUND Standard methods for endoscopic retrograde cholangiopancreatography (ERCP) management of anastomotic strictures (AS) after OLT includes repeated balloon dilation of the stricture with subsequent insertion of a plastic biliary stent (PBS). In post-OLT patients not responding to standard endoscopic treatment, the placement of fully covered self-expanding metal stents (FCSEMS) is a valid alternative to surgical treatment. The aim of this study was to compare the results of new FCSEMS implantation with the standard ERCP stricture management protocol and with conventional FCSEMS insertion. MATERIAL AND METHODS This retrospective study involved 39 post-OLT patients with confirmed diagnosis of biliary AS. Enrolled subjects were divided into 2 groups: the FCSEMS group (study group) and the PBS group (control group). The study group was divided into 2 subgroups: the conventional FCSEMS group and the new-type FCSEMS group. RESULTS Stricture recurrence after PBS placement was observed in 36.36% of controls and in only 9.52% of study group members (P=0.170). Recurrence rates in patients after conventional FCSEMS and new type FCSEMS implantation was similar (10% vs. 9.09%; P=0.501). The applied treatment was successful in 82.61% of study group members and only 43.75% of controls (P=0.029). Success rates of conventional FCSEMS and new-type SEMS insertion did not differ significantly (81.82% vs. 83.33%, P=0.649). There was no statistically significant difference in complication rates between groups (P=0.879). CONCLUSIONS Implantation of FCSEMS is more effective than repeated balloon dilatation of AS with subsequent PBS placement and is they have similar complication rates. Application of new-type FCSEMS gives results comparable to conventional FCSEMS.

Impact of antiviral treatment on survival in HCV-positive liver recipients.

BACKGROUND: Sequels of chronic HCV infection are currently one of the most common indications for liver transplantation (LTx). Because HCV reinfection and allograft injury are inevitable, it may influence survival. Earlier studies have not reported higher mortality among HCV-infected patients, but cumulative data seem to contradict these findings. The aim of the study was to analyze post-LTx survival in HCV-positive patients in comparison with non-HCV-positive recipients and impact of antiviral treatment on survival in patients with recurrent HCV hepatitis. MATERIAL AND METHODS: Using data from the Polish national transplant registry, a retrospective cohort study of 327 patients who underwent LTx between 2000 and 2012 was performed. Cumulative 5-year mortality for HCV-positive patients vs. HCV-negative recipients and HCV-positive recipients treated with pegylated interferon/ribavirin vs. non-treated subjects was calculated using Kaplan-Meyer methodology. Mortality hazard rates were estimated using univariate proportional Cox models. RESULTS: Liver transplantation in HCV-positive vs. HCV-negative recipients was associated with significantly lower survival rate (cumulative 5-year survival 89.8 vs. 80.26%, respectively, p=0.04276) with a 5-year mortality HR of 1.99. Antiviral treatment improved survival irrespective of virological response (84.06% treated vs. 51.22% non-treated, p=0.00003). Univariate Cox HR for HCV treated vs. untreated patients is 0.18. Further improvement of survival was significantly associated with sustained virological response (100% vs. 77.67%, p=0.042). CONCLUSIONS: Our study confirms higher mortality risk among HCV-infected transplant recipients, improved survival related to the HCV treatment following graft reinfection, and positive association between the HCV treatment success and better survival.

Laparoscopic live-donor nephrectomy with retroperitoneoscopic access - first case experience.

BACKGROUND: Despite observed huge progress in understanding the immunological basis of transplantation and the development of new immunosuppressive agents that have significantly improved both -- the patient and graft survival, still the kidney donation from live volunteers remains the most consistent factor which affects the long-term survival. The conventional, open method of donor nephrectomy is associated with significant surgical trauma. The laparoscopic live-donor nephrectomy (LDN) is the alternative for open approach. CASE REPORT: We present our experience of the case of laparoscopic removal of the kidney from a living donor. We applied retroperitoneoscopic access, the operation time was 210 minutes. Kidney was implanted shortly after LDN and its immediate function was observed. We have observed no serious postoperative complications either in donor or recipient. CONCLUSIONS: We hope that this successful initial case of LDN will have a positive effect on cooperation between transplantologists and urologists, and on rate of kidney donation in Poland.

[Current status of liver transplantation]. / Stan przeszczepiania watroby w Polsce.

The authors present current status of liver transplantation (LTx) in Poland. Till 2004, 845 LTx were performed: 604 in adults and 241 in children; 71 of them were the living donor LTx. Post-inflammatory cirrhosis in adults and biliary atresia in children were the most common indications for LTx. The results of LTx in Poland are good and comparable with the results published by other centers. The number of available cadaveric grafts is growing and in 2004 achieved an index of harvesting as high as 14,7 per million people.

Biliary complications following adult liver transplantation with routine use of external biliary drainage.

OBJECTIVES: Biliary complications are still common and often related to the use of biliary drains in liver transplant setting. We analyzed the incidence, treatment and outcome of biliary complications following adult orthotopic liver transplantation (OLTx) performed between February 2002 and October 2004. METHODS: Overall there were 46 OLTx performed in 44 patients. Two cases of primary graft-non-function (one re-graft) and 2 early postoperative deaths were excluded from the study resulting in 42 OLTx performed in 41 patients included in the final analysis. Biliary reconstruction was by duct-to-duct choledochocholedochostomy (DD, n = 37) and Roux-en-Y hepaticojejunostomy (RYHJ, n = 5) performed over an external Levin type biliary drain in all cases. RESULTS: The overall incidence of biliary complications was 28.6% (12/42). Bile leak was the commonest and occurred in 16.6% (7/42) of transplants, whereas biliary strictures were found in 3 (7.2%) patients. Eight (19%) patients required surgical treatment and one patient died due to a biliary complication (2.4% mortality rate). Majority (7/12) of complications were bile drain related and all of these occurred in patients with DD anastomosis. CONCLUSION: Biliary complications continue to cause significant morbidity after OLTx but rarely result in mortality if early diagnosis and prompt therapy is applied. Majority of biliary complications following DD anastomosis have been related to the use of biliary drains. In view of this and endoscopic expertise available, duct to duct anastomosis without a biliary drain may reduce complication rates and improve outcome.

Early results of a new liver transplant program in Szczecin, Poland.

New liver transplant programs have usually been associated with a significant learning curve. This learning curve, however, can be minimized or avoided if certain conditions are met. In this paper we describe the establishment of a new liver transplant program in Szczecin, Poland and present its early results. Four members of the team underwent training in clinical liver transplantation in major centers in Europe. Transplant protocols were then adopted, all the necessary facilities set up, and multidisciplinary team created. Between February 2002 and August 2003, 22 adult orthotopic liver transplantations (OLT) were performed in 21 patients (13 male; mean age 46.3 years; range 33-62), including I retransplant for early hepatic artery thrombosis. Eighteen (86%) patients are alive between 4 and 22 (median 11) months after OLT. Seventeen patients have normal liver function and 14 of them have resumed full life activity. Three patients died: one of bacterial peritonitis (day 6), one of chronic rejection with allograft failure (month 4) and one following massive stroke (month 10). Surgical complications occurred in 7 patients (33%). We believe that proper training of vital team members at established transplant centers with good results, availability of adequate equipment and all the facilities required with strict adherence to transplant protocols are all paramount for a successful start of a liver transplant program.