Theodore Karatzas

Urological complications: analysis and management of 1525 consecutive renal transplantations.

Urological complications after renal transplantation increase morbidity, delay graft function, and occasionally lead to graft and/or patient loss. The aim of this study was to analyze the causes of and therapeutic approaches to urological complications in renal transplantation as they related to patient outcomes. A series of 1525 consecutive renal transplantations were performed over a 24-year period. Renal grafts were obtained in 814 cases from living-related and in 711 from cadaveric donors. A Lich-Gregoire ureterovesical reimplantation technique with minimal bladder wall dissection was employed in all cases. Ureteral stents were routinely used in cadaveric transplants and exceptionally among living-related grafts. Urological complications were classified according to the mechanism and site of urinary tract involvement: graft ureteropelvic junction obstruction/stenosis (A), ureteral obstruction/stenosis (B), ureterovesical anastomosis obstruction/stenosis (C), urinary leakage (D), and other (E). Overall, we encountered 96 urological complications (6.3%). Group C complications occurred in 29 cases (30.2%), followed by 27 cases (28.1%) for group B patients, 25 cases (26.0%) for group D, 12 cases (12.5%) for group A, and 3 cases (3.1%) for group E patients. Surgical intervention was required in 49 (51.0%) of all urological complications. The others (n = 47, 49.0%) were treated either conservatively or by minimally invasive procedures. A rapid diagnosis of urological complications, assisted by early posttransplant DTPA scans, routine ultrasonography, and especially prompt treatment, resulted in compensation of renal graft dysfunction in the vast majority (n = 90, 93.8%) of cases. Surgical techniques of graft retrieval and reimplantation are of utmost importance to minimize the incidence of urological complications.

Papillary thyroid microcarcinoma: clinicopathological characteristics and implications for treatment in 276 patients

Eur J Clin Invest 2012; 42 (6): 657–664

Rodent models of hepatic ischemia–reperfusion injury: time and percentage-related pathophysiological mechanisms

Ischemia and reperfusion (IR) injury remains one of the major problems in liver surgery and transplantation, which determines the viability of the hepatic tissue after resection and of the grafted organ. This review aims to elucidate the mechanisms involved in IR injury of the liver in rodent experimental studies and the preventative methods and pharmacologic agents that have been applied. Many time- and percentage-related liver IR injury rodent models have been used to examine the pathophysiological mechanisms and the parameters implicated with different morbidity, mortality, and pathology findings. The most preferred experimental rodent model of liver IR is the induction of 70% IR for 45 min, which is associated with almost 100% survival. In this model, plasma levels of several parameters such as alanine transaminase, aspartate aminotransferase, gamma-glutamyltransferase, endothelin-1, malonodialdehyde, tumor necrosis factor α, interleukin 1b, inducible nitric oxide synthase, and caspases are increased. The increase of caspases is associated with the initiation of hepatic cellular apoptosis. The main injuries observed 24 h after reperfusion are nuclear pyknosis, cytoplasmic hypereosinophilia, severe necrosis, and loss of intercellular borders. Both ischemic pre- and post-conditioning preventative methods and pharmacologic agents are successfully applied to alleviate the IR injuries. The selection of the time- and percentage-related liver IR injury rodent model and the potential preventative method should be related to the clinical question being answered.

Pancreatic Islet Cell Transplantation: An Update

Transplantation of pancreatic islets, as a therapeutic modality for type 1 diabetes mellitus (T1DM), at this stage of its development, is reserved for patients with severe glycemic variability, progressive diabetic complications, and life threatening hypoglycemia unawareness, regardless of intensive insulin management. It has not succeeded to become the method of choice for treating T1DM because of limited supply and suboptimal yields of procurement and isolation of islets, graft failure, and relatively high requirements, i.e., at least 10,000 functional Islet Equivalents per kg of patient weight, to achieve prolonged insulin independence and glucose stability. Efforts aimed at making islet transplantation a competitive alternative to exogenous insulin injections for treating T1DM have focused on improving the longevity and functionality of islet cells. In order to succeed, these efforts need to be complemented by others to optimize the rate and efficiency of encapsulation.

Clinical and pathological characteristics of incidental and nonincidental papillary thyroid microcarcinoma in 339 patients

We analyzed the incidence and the clinicopathological characteristics of papillary thyroid microcarcinoma (PTMC) in a high prevalence region of goiter with the purpose to investigate differences between incidental and nonincidental PTMC.

Association of Intraoperative Neuromonitoring With Reduced Recurrent Laryngeal Nerve Injury in Patients Undergoing Total Thyroidectomy

Importance Injury of the recurrent laryngeal nerve (RLN) is one of the most serious complications of thyroid surgery. Intraoperative neuromonitoring (IONM) has been introduced to verify RLN function integrity and may be a helpful adjunct in nerve dissection. Objective To determine whether the use of IONM can reduce the incidence of RLN injury in patients undergoing total thyroidectomy. Design, Setting, and Participants This cohort study included 2556 patients who underwent total thyroidectomy between January 2002 and December 2012 in the Department of Otolaryngology-Head and Neck Surgery of Venizeleio General Hospital, Heraklion, Greece. Patients who had IONM during the procedure (n = 1481) were compared with patients who underwent surgery with nerve visualization alone (n = 1075). All patients underwent indirect laryngoscopy-fiberoptic nasopharyngoscopy both preoperatively and on day 2 after surgery to assess vocal cord motility. Main Outcomes and Measures Use of IONM and incidence of RLN injury. Results A total of 2556 patients (2028 women and 528 men [5112 RLNs at risk]; mean [SD] age, 51.35 [14.18] years; age range, 18-89 years) underwent total thyroidectomy. Univariate analysis showed that the use of IONM resulted in a significant reduction in RLN injury incidence (3.3% vs 0.7%) with a relative risk reduction of 2.6% (odds ratio [OR], 5.15; 95% CI, 3.12-8.49; number needed to treat, 19). Multivariate logistic regression showed that no use of IONM was an independent risk factor for RLN injury in patients who underwent total thyroidectomy (adjusted OR [AOR], 5.44; 95% CI, 3.26-9.09). Additional risk factors for RLN injury were operative time (AOR, 12.91; 95% CI, 6.66-25.06), maximum diameter greater than 45 mm of right thyroid lobe (AOR, 4.91; 95% CI, 3.12-8.56) and left thyroid lobe (AOR, 2.24; 95% CI, 1.39-4.32), extrathyroid extension (AOR, 3.26; 95% CI, 1.62-6.59), incidental parathyroidectomy (AOR, 3.30; 95% CI, 2.13-5.09), and tumor size larger than 10 mm (AOR, 3.24; 95% CI, 1.59-6.62). Conclusions and Relevance Our findings showed that the use of IONM decreased significantly both temporary and permanent RLN injuries. The technology of IONM is safe and reliable, and this technique is an important adjunct in nerve dissection and functional neural integrity. The routine use of IONM reduced pitfalls and provided guidance for our surgeons in difficult cases, reoperations, and high-risk patients.

Gastrointestinal Stromal Tumors (GISTs): An Updated Experience

BackgroundGastrointestinal stromal tumors (GISTs) are relatively common mesenchymal tumors of the digestive tract characterized by c-KIT mutations. This is a comprehensive review of the current data of the literature on the various aspects of the diagnosis and treatment of these tumors.MethodsThe stomach is the most commonly involved site for these tumors in the digestive tract. Computed tomography and endoscopy can usually establish the diagnosis. The study of certain specific immunohistochemical markers may contribute to better characterization of these tumors.ResultsSurgical resection of GISTs has been the most effective therapy. In addition, targeted therapy with tyrosine kinase inhibitors may reduce the development of recurrence or decrease the disease progression in patients with metastatic disease.ConclusionsThe introduction of tyrosine kinase inhibitors has resulted in significant improvement in the overall prognosis of these patients. Furthermore, preoperative imatinib can decrease tumor volume and is associated with complete surgical resection in locally advanced primary GISTs.

Advanced Donor Age Alone Is Not a Risk Factor for Graft Survival in Kidney Transplantation

BACKGROUND The use of kidneys from elderly deceased donors has substantially increased organ supply, although it is associated with worse graft function and survival rates. The risk of kidneys from elderly donors as well as expanded criteria donors (ECDs) on kidney transplant outcome was investigated. PATIENTS AND METHODS Seventy-five kidney transplants from ECDs over a 5-year period were reviewed retrospectively. Old age and increased donor risk variables were analyzed separately in relation to graft function and survival. RESULTS Sixty-four of 75 (85.3%) recipients had functioning grafts 5 years posttransplant. The overall actuarial graft survivals from 1 to 5 years were 87.5%, 68.1%, 57.3%, 55.4%, and 47.3%, respectively. Early graft function gave 47 (62.7%) kidneys remarkable actuarial survivals of 100.0%, 88.3%, 75.8%, 75.8%, and 68.4% at 1 to 5 years posttransplant, and 28 (37.3%) kidneys had delayed graft function with substantially decreased actuarial survival rates, ranging from 66.7% to 23.2%. Kidneys from elderly donors had considerable actuarial graft survival rates of 100.0%, 83.3%, 76.9%, 76.9%, and 67.0% from 1 to 5 years, respectively; these were the best graft survival rates compared with kidneys from the other donor categories. The other donor risk variables when associated with advanced age of any had an adverse effect on recipient graft function and survival, but no single risk variable alone, or a combination of any two, showed any statistically significant variability. CONCLUSION Elderly kidney donors provided a substantial organ pool expansion without affecting patient and graft survival in many patients. ECDs can be utilized safely if adequate measures are taken.

Changes of blood biochemistry in the rabbit animal model in atherosclerosis research; a time- or stress-effect

BackgroundRabbits are widely used in biomedical research and especially as animal models in atherosclerosis studies. Blood biochemistry is used to monitor progression of disease, before final evaluation including pathology of arteries and organs. The aim of the present study was to assess the consistency of the biochemical profile of New Zealand White rabbits on standard diet from 3 to 6 months of age, during which they are often used experimentally.Methods and resultsEight conventional male 3-month-old New Zealand White rabbits were used. Blood samples were taken at baseline, 1, 2 and 3 months later. Plasma glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerol concentrations, and alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase activities and malondialdehyde were measured. Statistically significant time-related changes were observed in glucose, total cholesterol and triacylglycerol, which were not correlated with aortic lesions at 6 months of age. Similarly, hepatic enzyme activity had significant time-related changes, without a corresponding liver pathology.ConclusionsAge progression and stress due to single housing may be the underlying reasons for these biochemistry changes. These early changes, indicative of metabolic alterations, should be taken into account even in short-term lipid/atherosclerosis studies, where age and standard diet are not expected to have an effect on the control group of a study.

Temperature profiles of different cooling methods in porcine pancreas procurement.

Porcine islet xenotransplantation is a promising alternative to human islet allotransplantation. Porcine pancreas cooling needs to be optimized to reduce the warm ischemia time (WIT) following donation after cardiac death, which is associated with poorer islet isolation outcomes. This study examines the effect of four different cooling Methods on core porcine pancreas temperature (n = 24) and histopathology (n = 16). All Methods involved surface cooling with crushed ice and chilled irrigation. Method A, which is the standard for porcine pancreas procurement, used only surface cooling. Method B involved an intravascular flush with cold solution through the pancreas arterial system. Method C involved an intraductal infusion with cold solution through the major pancreatic duct, and Method D combined all three cooling Methods. Surface cooling alone (Method A) gradually decreased core pancreas temperature to <10 °C after 30 min. Using an intravascular flush (Method B) improved cooling during the entire duration of procurement, but incorporating an intraductal infusion (Method C) rapidly reduced core temperature 15–20 °C within the first 2 min of cooling. Combining all methods (Method D) was the most effective at rapidly reducing temperature and providing sustained cooling throughout the duration of procurement, although the recorded WIT was not different between Methods (P = 0.36). Histological scores were different between the cooling Methods (P = 0.02) and the worst with Method A. There were differences in histological scores between Methods A and C (P = 0.02) and Methods A and D (P = 0.02), but not between Methods C and D (P = 0.95), which may highlight the importance of early cooling using an intraductal infusion. In conclusion, surface cooling alone cannot rapidly cool large (porcine or human) pancreata. Additional cooling with an intravascular flush and intraductal infusion results in improved core porcine pancreas temperature profiles during procurement and histopathology scores. These data may also have implications on human pancreas procurement as use of an intraductal infusion is not common practice.