Current Data on Organ Donation and Transplantation in Poland: Poltransplant Activity 2017 to 2022.

BACKGROUND: In this paper, we present organ donation and transplantation activities in Poland from 2017 to 2022. Data came from registries maintained by the Polish Transplant Coordinating Center Poltransplant and consisted of the national waiting list, deceased donor registry, transplant registry, and the live donor registry. Poltransplant is the Competent Authority in Organs, with tasks related to preparing assessments, analyses, information, and reports in transplantation medicine and publishing and disseminating these results in the country and abroad. Poltransplant edits the Poltransplant Bulletin on its web pages and presents its activities at Polish Transplantation Society congresses, published consecutively as professional papers.

Analysis of Complications and Recipients' and Graft Survival in Patients 60 Years of Age and Older in the Long-Term Follow-up Period After Kidney Transplant: A Single-Center, Paired Kidney Analysis.

BACKGROUND: Long-term results of kidney transplant (KTx) in older patients may differ from younger recipients owing to increased cardiovascular comorbidities. The study aimed to analyze surgical and nonsurgical complications that develop in the long-term follow-up period after KTx, and factors that influence results of KTx in recipients aged 60 years and older (≥60) compared with younger recipients (<60). METHODS: One hundred seventy-five patients aged ≥60 years and 175 patients aged <60 years who received a kidney graft from the same deceased donor were enrolled in the study. In the long-term follow-up period (3 months to 5 years after KTx) the incidence of surgical and nonsurgical complications, as well as patient and kidney graft survival, were compared. Additionally, the influence of early complications on patients and kidney graft survival was assessed. RESULTS: There were no differences between recipients aged ≥60 years compared with recipients aged <60 years in occurrence of surgical complications (graft artery stenosis: 0.6% vs 2.3%; ureter stenosis: 3.4% vs 1.1%; lymphocele: 6.9% vs 3.4%) and nonsurgical complications (urinary tract infection: 19.4% vs 23.4%; pneumonia: 8.6% vs 8.6%; cytomegalovirus infection: 6.3% vs 8%; new-onset diabetes after transplant: 16.6% vs 17.1%; cancer incidence: 5.7% vs 4.6%; acute rejection episode: 13.1% vs 17.1%). Five-year recipient survival was lower in a group of patients aged ≥60 years (death, 15.4% vs 8%; death with functioning graft, 12% vs 5.1%). CONCLUSIONS: The incidence of surgical and nonsurgical complications, as well as kidney-graft survival, in recipients aged ≥60 years in a 5-year follow-up period is comparable to younger recipients aged <60 years.

Consequences of Changes in the Liver Allocation System for Transplantation in the Silesian Voivodeship and in the Transplantation Center in Katowice.

BACKGROUND: For a number of years, the system of procured livers for transplantation by transplant centers in a fixed order, regardless of the location of the procurement site, was in force in Poland. In mid-2018, priority was introduced in the collection of livers by a team from a given province. The aim of the study was to evaluate the impact of changing the liver transplantation allocation system at the Katowice Transplant Center (KTW) on the number of transplanted livers and on the selected parameters of donors from which the liver was procured. METHODS: The rates and cold ischemia time (CIT) of procured livers were analyzed. RESULTS: The rate of livers procured by the KTW transplant team increased from 36.6% to 53.3%, and at the same time the rate of livers procured by this team and sent for transplantation in other transplant centers increased. The rate of livers transplanted in the KTW, which were procured in the Silesian Voivodeship, increased from 37.4% to 61.0%, and the rate of livers procured outside the Silesian Voivodeship decreased from 54.8% to 36.4%. The CIT of livers transplanted in the KTW was reduced from 407.5 to 360.0 minutes. The comparative analysis of donor parameters of livers procured by the KTW transplant team and transplanted in Katowice revealed no differences regarding analyzed clinical and biochemical parameters. CONCLUSION: The change in the allocation system increased the number of livers procured by the local team and shortened CIT of livers transplanted at the KTW.

Kidney Graft Failure and Patient Survival Modelling Based on Competing Risks Under Nonproportional Hazards.

We analyze data on Silesian patients after kidney transplantation under competing events scenarios where time to death and time to graft failure are considered as absorbing competing events. Our objectives are to use model diagnostics in identifying violations of proportionality assumption under the framework of subdistribution and cause-specific hazards. We use the Fine-Gray proportional hazards model for the subdistribution. Under the cause-specific hazards (CSH) scenario we use the Cox proportional hazards model and Gray's time-varying coefficients model and available model diagnostics. We show that violation of proportional subdistribution hazards assumption may be conveniently identified using residual diagnostics and properly accounted for by involving time interactions with appropriate model predictors. We also show that although the nonproportional effects on cumulative incidence do not necessarily translate in those on cause-specific hazards, they often take place simultaneously, and a violation of the proportionality assumption needs to be checked rigorously. Time-varying effects have a profound impact on clinical inference under competing risks. They do not translate directly between the frameworks of subdistribution and cause-specific hazards because the cumulative incidence is obtained via integrating the cause-specific hazard weighted by the overall survival function. Also, a different definition of the risk set is in place under the cumulative incidence and CSH framework, respectively. However, a simultaneous violation of the proportionality assumption under both frameworks is still possible. Clinical inference may change considerably when such a violation occurs. Nonproportional effects may be properly identified under each framework using available model diagnostics.

Type 1 Diabetic Patients After Simultaneous Pancreas and Kidney Transplantation Have Less Intense Periodontal Inflammation Compared to Kidney Recipients Treated with Insulin.

BACKGROUND Long-term diabetes predisposes to pathological changes in periodontal tissues. Improvement in this respect can be expected in patients after pancreas transplantation. The aim of this study was to assess and compare the intensity of periodontium pathological lesions and inflammation markers concentration in gingival crevicular fluid (GCF) in patients with type 1 diabetes (T1D) after kidney (KTx) or simultaneous pancreas and kidney transplantation (SPK). MATERIAL AND METHODS The study included 20 T1D patients after SPK and 16 after KTx, and 15 non-diabetic kidney recipients (control). Periodontal clinical parameters and concentration of selected biochemical markers of inflammation in GCF were assessed. The following tests were used in statistical data analysis: Shapiro-Wilk test, the t test, the Mann-Whitney U tests, one-way ANOVA with Tukey's post hoc test, and χ² test (also with Yate's correction). Moreover, linear regression and Pearson or Spearman correlation coefficient was used. RESULTS There were no differences in modified Sulcus Bleeding Index (mSBI) and GCF volume between the SPK group and control group, whereas values of these parameters in the KTx group were higher than in the SPK and control groups. Maximal clinical attachment loss and pocket depth and Periotest values were higher in diabetic recipients compared to controls, and did not differ between SPK and KTx. The concentration of IL-1ß, MMP-8, resistin, TNFalpha, and YKL40 in the GCF in the KTx group was higher than in the SPK and control groups. In the combined group of T1D patients, there was a correlation between blood HbA1c and mSBI, GCF volume, and resistin, TNF-alpha and YKL40 concentrations, and between resistin concentration and mSBI. CONCLUSIONS T1D patients after SPK show lower levels of inflammatory markers in GCF and present reduced intensity of periodontitis compared to kidney recipients treated with insulin. The severity of morphological changes in periodontium in T1D patients after KTx or SPK is higher than in non-diabetic kidney recipients.

Beneficial Effect of Successful Simultaneous Pancreas-Kidney Transplantation on Plasma Profile of Metalloproteinases in Type 1 Diabetes Mellitus Patients.

It is not fully elucidated whether the restoring of normal glucose metabolism after successful simultaneous pancreas-kidney transplantation (SPK) improves vascular wall morphology and function in type 1 diabetic (T1D) patients. Therefore, we compared arterial stiffness, assessed by pulse wave velocity (PWV), carotid intima-media thickness (IMT), and biomarkers of arterial wall calcification in T1D patients after SPK or kidney transplantation alone (KTA). In 39 SPK and 39 KTA adult patients of similar age, PWV, IMT, circulating matrix metalloproteinases (MMPs) and calcification biomarkers were assessed at median 83 months post transplantation. Additionally, carotid plaques were visualized and semi-qualitatively classified. Although PWV and IMT values were similar, the occurrence of atherosclerotic plaques (51.3 vs. 70.3%, p < 0.01) and calcified lesions (35.9 vs. 64.9%, p < 0.05) was lower in SPK patients. There were significantly lower concentrations of MMP-1, MMP-2, MMP-3, and osteocalcin in SPK subjects. Among the analyzed biomarkers, only logMMP-1, logMMP-2, and logMMP-3 concentrations were associated with log HbA1c. Multivariate stepwise backward regression analysis revealed that MMP-1 and MMP-3 variability were explained only by log HbA1c. Normal glucose metabolism achieved by SPK is followed by the favorable profile of circulating matrix metalloproteinases, which may reflect the vasoprotective effect of pancreas transplantation.

Early Complications After Kidney Transplantation in Patients Aged 60 Years and Older: A Single-Center, Paired-Kidney Analysis.

OBJECTIVES: As the population ages, the number of people suffering from cardiovascular diseases (CVD) and diabetes mellitus (DM) increases. The coexistence of these diseases can affect the results of kidney transplantation (KT) in the elderly. The aim of this study was to analyze surgical and nonsurgical complications in the early period after KT and to identify the factors that influence their development in recipients aged ≥ 60 years compared to younger recipients < 60 years. METHODS: One hundred seventy-five recipients of KT ≥ 60 years and 175 recipients of KT < 60 years who received kidneys from the same deceased donor were enrolled into the study. The incidence of surgical and nonsurgical complications, factors that may influence their development, early graft function, and patient and kidney-graft survival were analyzed during a 3-month follow-up period. Donor sources complied with the Helsinki Congress and Istanbul Declaration and organs were not procured from prisoners and individuals who were coerced or paid. RESULTS: Older recipients were characterized by higher body mass index ± SD (26.1 ± 3.5 vs 24.7 ± 3.4 kg/m2) and suffered more often from pretransplant DM (20.6% vs 11.4%) and CVD (34.3% vs 10.3%) and less frequently underwent previous KT (6.3% vs 20.0%). There were no differences between the ≥ 60 year old and < 60 year old groups in reference to surgical (20.6% vs 24%) and nonsurgical complications (28.6% vs 27.4%), early graft function, serum creatinine, and proteinuria. Recipients (95.4% vs 97.1%) and kidney-graft survival (93.1% vs 95.4%) were similar in both groups. The recipient factors that influenced the development of infectious complications were age, dialysis duration, pretransplant DM, and CVD. CONCLUSIONS: Despite higher co-incidence of CVD and DM, the risk of surgical and nonsurgical complications in elderly recipients is comparable to younger recipients in the early period after KT.

Simultaneously Transplanted Pancreas Improves Salivation and Reduces Oral Fungal Infections Incidence in Type 1 Diabetic Renal Transplant Recipients.

BACKGROUND: Long-lasting diabetes mellitus may lead to numerous pathologies in the oral cavity. The aim of the study was to assess the condition of the oral cavity, caries intensity, salivary parameters, and incidence of oral fungal infections in patients with type 1 diabetes (T1D) and end-stage renal disease (ESRD) after kidney transplantation (KTx) or simultaneous kidney and pancreas transplantation (SPK). METHODS: Twenty-one patients after SPK, 18 T1D patients after KTx, and 14 kidney recipients without diabetes (control group) were included in the study. Donor sources complied with Helsinki Congress and the Declaration of Istanbul. RESULTS: Approximal plague index in SPK (80% [68%-90%]) was comparable to KTx (80% [37.5%-92.5%]) but higher than in control group (46% [35%-50%]). All 3 groups did not differ in terms of decayed-missing-filled tooth index: 22.3 ± 4.8 vs 22.5 ± 4.5 vs 19.1 ± 4.9, respectively. Normal saliva resting secretion and consistency were more common in SPK (71.4% and 52%, respectively) than in KTx (27.8% and 50.0%, respectively). Stimulated saliva volume in the SPK, KTx and controls, pH value, and buffering capacity were comparable. In KTx higher incidence of Candida albicans infection (55.6%) compared with SPK (23.8%) and controls (no infection) was observed. CONCLUSIONS: Simultaneously transplanted pancreas improves salivation and reduces the incidence of oral fungal infections in T1D kidney recipients. The severity of caries is higher and oral hygiene is worse in T1D kidney recipients compared with patients after KTx without diabetes.

Comparison of ultrasound therapy and radial shock wave therapy in the treatment of venous leg ulcers - clinical, pilot study.

INTRODUCTION: Venous insufficiency and venous leg ulcers each year affect more and more people, especially in developed countries. The challenge of our time is to find an effective method of treating venous leg ulcers, which will further shorten treatment time and reduce the cost of treatment. AIM: To compare the effects of treating venous leg ulcers using ultrasound therapy, radial shock wave therapy and standard care. MATERIAL AND METHODS: Group A consisted of 17 patients. Patients were treated with ultrasound therapy US power density 0.5 W/cm2, pulsed wave with a duty cycle of 1/5, and 1 MHz frequency. Group B consisted of 17 patients. Patients were treated with the radial shock wave R-ESWT using surface energy density 0.17 mJ/mm2, 100 impulses/cm2, frequency of 5 Hz and a pressure of 0.2 MPa. Group C (control group) consisted of 17 patients. Patients in this group received standard care: gauze dressing saturated in 0.9% sodium chloride and elastic bandages changed daily for 4 weeks. RESULTS: Ultrasound therapy with 1 MHz and energy power density 0.5 W/cm2 for 4 weeks resulted in an average reduction of 68% of the area of ulceration. We used for venous leg ulcers 4-week treatment with radial shock wave therapy resulting in a 38% mean percentage reduction of the ulceration area. Standard care reduces the area of ulceration by only 16%. CONCLUSIONS: The use of ultrasound therapy for the treatment of venous leg ulcers is more effective than the use of radial shock wave therapy or standard care alone.

Randomized, controlled clinical pilot study of venous leg ulcers treated with using two types of shockwave therapy.

Background. Venous leg ulcers are difficult to heal wounds. The basis of their physiotherapeutic treatment is compression therapy. However, for many years, the search for additional or other methods to supplement the treatment of venous ulcers, which would shorten the duration of treatment, is underway. One of such methods is the shockwave therapy. Methods. The purpose of our study was to compare radial shockwave therapy (R-ESWT) with focused shockwave therapy (F-ESWT) in venous leg ulcers treatment. Patients were randomly assigned to tree groups. In the first group the radial shockwave therapy (0.17mJ/mm2, 100 impulses/cm2, 5 Hz), in the second group the focused shockwave therapy (0.173mJ/mm2, 100 impulses/cm2, 5 Hz) was used and in third group standard care was used. Patients in shockwave therapy groups were given 6 treatments at five-day intervals. Total area, circumference, Gilman index, maximum length and maximum width of ulcers were measured. The patients from the third group wet gauze dressing with saline and gently compressing elastic bandages were used (standard wound care SWC). Results. Analysis of the results shows that a complete cure of ulcers was achieved in 35% of patients who were treated with radial shockwave, 26% of patients with focused shockwave used. There is statistically significant difference between the standard care and radial shockwave therapy as well as between the standard care and focused shockwave therapy. There is no statistically significant difference between the use of radial and focused shockwave in the treatment of venous leg ulcers (p> 0.05). Conclusion. There is no statistically significant difference between the use of radial and focused shockwave in the treatment of venous leg ulcers. Treatment of venous leg ulcers with shockwaves is more effective than the standard wound care.

Usefulness of Pancreas Donor Risk Index and Pre-Procurement Pancreas Allocation Suitability Score: Results of the Polish National Study.

BACKGROUND Pre-procurement pancreas suitability score (P-PASS) and pancreas donor risk (PDRI) index are scoring systems believed to predict suitability of pancreatic grafts. Most European countries and the United States apply PDRI, while Poltransplant keeps using P-PASS: more than 16 points raises a red flag for graft use. Recent data discourage use of PDRI to predict pancreas graft survival. The aim of the present study was to assess PDRI and P-PASS as predictors of transplanted pancreas survival in a Polish population. MATERIAL AND METHODS From February 1998 to September 2015, 407 pancreas transplantations were performed in Poland: 370 (90.9%) simultaneous pancreas-kidney transplantation and 37 (9.1%) pancreas transplantation alone or pancreas after kidney. The endpoint was death-uncensored 12-month graft survival with satisfactory glycemic control without insulin. RESULTS Average P-PASS was 15.9±2.66 and PDRI was 0.96±0.37. Recipients who survived 12 months with good graft function had an average P-PASS score of 15.7 and PDRI of 0.95. Recipients with death-uncensored graft loss had a mean P-PASS of 16.4 and PDRI of 0.99. Univariate analysis revealed donor age, body mass index (BMI), and P-PASS to be significant risk factors for 1-year pancreas graft survival. CONCLUSIONS P-PASS, but not PDRI, is a reliable tool to predict pancreas graft survival in the Polish population.

Type 1 diabetic patients have better endothelial function after simultaneous pancreas-kidney transplantation than after kidney transplantation with continued insulin therapy.

The purpose of this study was to analyse the influence of simultaneous pancreas-kidney or kidney transplantation on endothelial function and systemic inflammation in type 1 diabetic patients with end-stage renal disease. In 39 simultaneous pancreas-kidney, 39 type 1 diabetic kidney and 52 non-diabetic kidney recipients, flow-mediated dilatation was measured. Additionally, blood glycated haemoglobin, serum creatinine and lipids, plasma nitrites [Formula: see text] and nitrates, asymmetric dimethylarginine, soluble vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin, high-sensitivity C-reactive protein, tumour necrosis factor-α, interleukin 1ß and interleukin 6 concentrations were assessed. During 58 ± 31 months follow-up period, flow-mediated dilatation and [Formula: see text] were greater in simultaneous pancreas-kidney than in type 1 diabetic kidney recipients [10.4% ± 4.7% vs 7.7% ± 4.2%, p < 0.05 and 0.94 (0.74-1.34) vs 0.24 (0.20-0.43) µmol/L, p < 0.01, respectively]. In type 1 diabetic patients after simultaneous pancreas-kidney or kidney transplantation, [Formula: see text] correlated with flow-mediated dilatation (r = 0.306, p < 0.05) and with blood glycated haemoglobin (r = -0.570, p < 0.001). The difference in [Formula: see text] was linked to blood glycated haemoglobin and estimated glomerular filtration rate, whereas the difference in flow-mediated dilatation was linked to [Formula: see text]. The levels of inflammatory markers (except soluble vascular cell adhesion molecule-1) were similar in simultaneous pancreas-kidney and type 1 diabetic kidney recipients. Improved endothelial function in type 1 diabetic patients with end-stage renal disease after simultaneous pancreas-kidney compared to kidney transplantation is associated with normalisation of glucose metabolism but not with improvement in plasma pro-inflammatory cytokines.

Histopathological Examination may be Useful for Assessment of Fibrosis and Lipomatosis of Pancreas Allograft Prior to Solid Organ Transplantation.

BACKGROUND: The results of pancreas transplantation depend in a large degree on appropriate pancreas allograft donor selection. Several risk factors of early surgical complications or pancreas allograft loss following transplantation have been identified, but the final decision on pancreas harvesting for transplantation belongs to the surgeon. In the present study we aimed to assess whether histopathological examination may be utilized for detection of fibrosis and lipomatosis in tissue from a potential pancreas allograft. Additionally, we aimed to test whether presence of pancreatic fibrosis and lipomatosis may be explained solely by donor age and/or body mass index (BMI). MATERIAL AND METHODS: Pancreata retrieved from 50 deceased organ donors referred to our institution and not transplanted between 2010 and 2013 were used for the present study. Tissue samples were excised from pancreata, fixed in formalin, and embedded in paraffin. Presence and intensity of pancreatic fibrosis and lipomatosis were assessed semi-quantitatively. RESULTS: Fibrosis was found in the majority of study samples (72%), but it was usually mild or moderate. Lipomatosis was present in 34% of the study cases. Presence of fibrosis was more frequent in older donors, but was still not rare in donors under 40 years old. Presence of lipomatosis did not seem to be significantly related to donor age. Neither pancreatic fibrosis nor lipomatosis was related to donor BMI. CONCLUSIONS: There is no clear relationship between histological parenchymal changes in potential pancreas allograft and donor age and BMI. Histopathological assessment of pancreatic fibrosis and/or lipomatosis can potentially facilitate decision making on pancreas allograft acceptance for solid organ transplantation.

A comparative clinical study on five types of compression therapy in patients with venous leg ulcers.

The aim of this study was to compare five types of compression therapy in venous leg ulcers (intermittent pneumatic vs. stockings vs. multi layer vs. two layer short stretch bandages vs. Unna boots). Primary study endpoints were analysis of changes of the total ulcer surface area, volume and linear dimensions inside observed groups. The secondary end points were comparisons between all groups the number of completely healed wounds (ulcer healing rates), Gilman index and percentage change of ulcer surface area. In total, 147 patients with unilateral venous leg ulcers were included to this study. Participants were randomly allocated to the groups: A, B, C, D and E. After two months the healing rate was the highest in group A (intermittent pneumatic compression) - 57.14%, 16/28 patients, B (ulcer stocking system) - 56.66%, 17/30 patients and C (multi layer short stretch bandage) - 58.62%, 17/29 patients. Significantly much worse rate found in group D (two layer short stretch bandages) - only 16.66%, 5/30 patients and E (Unna boots) - 20%, 6/30 patients. The analysis of changes of the percentage of Gilman index and wound total surface area confirmed that intermittent pneumatic compression, stockings and multi layer bandages are the most efficient. The two layer short - stretch bandages and Unna boots appeared again much less effective.

A randomized, controlled clinical pilot study comparing three types of compression therapy to treat venous leg ulcers in patients with superficial and/or segmental deep venous reflux .

Compression therapy--including inelastic, elastic, and intermittent pneumatic compression--is the standard of care for venous ulcers (VLUs) and chronic venous insufficiency, but there is no consensus in the literature regarding the most effective type of compression therapy. A prospective, randomized, clinical pilot study was conducted among 70 patients with unilateral VLUs treated in a hospital dermatology department in Poland to compare three types of compression therapy (intermittent pneumatic compression, stockings, and short-stretch bandages) in persons with superficial deep venous reflux alone or combined with the segmental variety. Study endpoints were change in ulcer dimensions and proportions healed. Patients with superficial or combined superficial and deep vein insufficiency were randomly allocated to receive one of the three therapies (one of each vein type for each treatment option, six groups total). All patients received saline-soaked gauze dressings along with micronized purified flavonoid fraction, diosmin, hesperidin, and Daflon 500 once daily. Compression treatments were changed or pneumatic compression provided daily for 15 days. Wound size reduction and percentage of wounds healed were significantly higher in groups receiving intermittent pneumatic compression or stockings than in groups using short-stretch bandages (for percentage change of ulcer surface area, P = 0.02; for healing rates P = 0.01). These results warrant additional randomized controlled clinical studies with a larger sample size and longer patient follow-up.

Apoptosis of tubular epithelial cells in preimplantation biopsies of kidney grafts with immediate, slow and delayed function.

BACKGROUND: Apoptosis is a form of cell death observed in kidney grafts as a result of ischemia/reperfusion injury. The aim of our prospective study was to analyze the intensity of apoptosis in kidney tubules after cold storage in respect to early and 12-month post-transplant graft function. MATERIAL/METHODS: The intensity of renal tubular apoptosis was estimated by TUNEL method in proximal and distal tubules in 72 pre-implantation kidney biopsies. Sixteen patients with biopsies that did not fulfill Banff 97 classification, with early acute rejection or early graft loss, were excluded. Early graft function was defined as IGF (N=17) when serum creatinine (sCr) was <264 µmol/l at 3(rd) postoperative day (POD); as SGF (N=20) when sCr >264 µmol/l and not more than 1 dialysis was performed; and as DGF (N=19) when more than 1 dialysis was done. RESULTS: The percentage of apoptotic cells was markedly higher in distal than in proximal tubules in all 3 groups. The percentage of apoptotic cells in distal tubules found was: 3.02% (1.03-5.00%) in IGF, 1.66% (0.92-2.39%) in SGF, and 1.76% (0.84-2.68%) in DGF; these differences were not significant. In the IGF group the mean percentage of apoptotic cells in distal tubule was higher than in the other groups (not statistically significant). The subgroups of patients with higher and lower than median (1.35%) apoptotic cell range in distal tubules had similar graft function at the 12-month follow-up. CONCLUSIONS: The enhancement of tubular epithelial cells apoptosis in kidney grafts after cold storage does not determine its early and later excretory function.

Intra-abdominal infections after simultaneous pancreas - kidney transplantation.

BACKGROUND: Intra-abdominal infections (IAI) are among the most common causes of pancreatic graft loss and recipient death in the early period after simultaneous pancreas - kidney transplantation (SPK). The aim of the study was to analyze risk factors and clinical consequences of IAI in SPK patients. MATERIAL/METHODS: Forty-six consecutive SPK performed from 2004 to 2010 were subjected to analysis. RESULTS: IAI developed in 10 recipients (21.7%). The group of recipients with IAI had a higher rate of patients that required transfusion of more than 2 blood units (90% vs. 47%, p=0.028) or relaparotomy (80% vs. 14%, p<0.001), in comparison with patients without IAI. Additionally, in patients with IAI, both delayed kidney graft function or primary kidney graft nonfunction (40% vs. 11%, p=0.001) and recipient death (40% vs. 3%, p=0.006) were more frequently observed. Logistic regression analysis revealed an increased risk of IAI development in patients who required early relaparotomy (OR=24.8, p<0.001), transfusion of more than 2 blood units (OR=12.6, p=0.02), or postoperative dialysis therapy (OR=14.1, p=0.003). CONCLUSIONS: Perioperative blood loss requiring transfusion and necessity of relaparotomy increase the risk of IAI after SPK. Development of IAI after SPK may result in impaired kidney graft function and increases patient mortality in the early postoperative period.

Pheochromocytoma in rats with multiple endocrine neoplasia (MENX) shares gene expression patterns with human pheochromocytoma.

Pheochromocytomas are rare neoplasias of neural crest origin arising from chromaffin cells of the adrenal medulla and sympathetic ganglia (extra-adrenal pheochromocytoma). Pheochromocytoma that develop in rats homozygous for a loss-of-function mutation in p27Kip1 (MENX syndrome) show a clear progression from hyperplasia to tumor, offering the possibility to gain insight into tumor pathobiology. We compared the gene-expression signatures of both adrenomedullary hyperplasia and pheochromocytoma with normal rat adrenal medulla. Hyperplasia and tumor show very similar transcriptome profiles, indicating early determination of the tumorigenic signature. Overrepresentation of developmentally regulated neural genes was a feature of the rat lesions. Quantitative RT-PCR validated the up-regulation of 11 genes, including some involved in neural development: Cdkn2a, Cdkn2c, Neurod1, Gal, Bmp7, and Phox2a. Overexpression of these genes precedes histological changes in affected adrenal glands. Their presence at early stages of tumorigenesis indicates they are not acquired during progression and may be a result of the lack of functional p27Kip1. Adrenal and extra-adrenal pheochromocytoma development clearly follows diverged molecular pathways in MENX rats. To correlate these findings to human pheochromocytoma, we studied nine genes overexpressed in the rat lesions in 46 sporadic and familial human pheochromocytomas. The expression of GAL, DGKH, BMP7, PHOX2A, L1CAM, TCTE1, EBF3, SOX4, and HASH1 was up-regulated, although with different frequencies. Immunohistochemical staining detected high L1CAM expression selectively in 27 human pheochromocytomas but not in 140 nonchromaffin neuroendocrine tumors. These studies reveal clues to the molecular pathways involved in rat and human pheochromocytoma and identify previously unexplored biomarkers for clinical use.

Germinal mutations of RET, SDHB, SDHD, and VHL genes in patients with apparently sporadic pheochromocytomas and paragangliomas.

INTRODUCTION: Pheochromocytomas and paragangliomas are derived from neural crest cells and are localized mainly in adrenal medulla and sympathetic or parasympathetic ganglia. They can be inherited (25%) and be part of multi-endocrine syndromes such as MEN2 syndrome, von Hippel-Lindau syndrome, pheochromocytoma/paraganglioma syndrome, neurofibromatosis type 1, and Sturge-Weber syndrome. Clinical presentation can sometimes be atypical and does not always allow proper diagnosis. In such situations, DNA analysis can be helpful, especially when the pheochromocytoma is the first and only symptom. MATERIAL AND METHODS: We analyzed DNA from 60 patients diagnosed and treated in the Centre of Oncology with a diagnosis of pheochromocytoma or paraganglioma. DNA analysis was carried out for RET (exons 10, 11, 13, and 16), SDHB, SDHD, and VHL genes. Techniques used for the analysis were direct sequence analysis, MSSCP, and RFLP. RESULTS: Germinal mutations were found in 16 patients (26,7%). Most frequent were mutations in RET proto-oncogene, followed by VHL gene, one mutation in SDHB, and one in SDHD genes. A comparison of some of the clinical features of both groups (with and without mutation) showed statistically significant differences. CONCLUSIONS: The results of our study show that genetic predisposition is frequent in chromaffin tissue tumours, which indicates that DNA analysis is necessary in every case, also because of possible atypical clinical presentation. (Pol J Endocrinol 2010; 61 (1): 43-48).