Should Interventional Radiology or Open Surgery Be the First Choice for the Management of Ureteric Stenosis After Transplantation? Dual-Center Study.

BACKGROUND: Ureteric stenosis (US) is the most common urologic complication after kidney transplantation. In this dual-center retrospective study we compared the efficacy and safety of open surgery versus interventional radiology for the management of US. METHODS: From 2009 to January 2016, US was treated by surgical revision in 22 (7.8%) out of 281 recipients at one center (group 1) and managed by percutaneous nephrostomy with antegrade nephroureteral stenting (PNAS) in 22 (14.2%) out of 155 recipients at the other center (group 2). RESULTS: Three patients in group 1 required reintervention and again were treated with open surgery. With a mean follow-up of 42.1 ± 38.7 months, graft function improved in all but one patients (95%). Three patients in group 2 were admitted with relapse of US not amenable to 2nd PNAS, and 2 of them were managed with surgery. These 3 and 2 other cases with improved graft function after PNAS lost their grafts and returned to hemodialysis. The remaining 17 patients (77%) still have functioning grafts. There was no statistically significant difference between the efficacy of PNAS and open surgery for the management of post-transplantation US. However; a benefit in favor of open surgery existed for type 2 urinary tract obstruction in terms of decreased reintervention rate and much better protection of the graft function and survival. CONCLUSIONS: Both interventional radiology and open surgery have acceptable efficacy rates in the management of ureteric complications after renal transplantation. Open surgery is a better treatment option for type 2 obstruction.

Intellectuality and attitudes of clergy about organ donation in Turkey: metasynthesis of observational studies.

INTRODUCTION: In Turkey, donation rates remained low despite the efforts of the Religious Affairs Supreme Council. We sought to determine theological perspectives and behaviors of clergy and theology students toward organ donation. METHODS: We conducted a systematic review and metaanalysis of observational studies. RESULTS: There were 2154 participants. Eighty-two percent stated Islam allows organ donation. Nineteen had organ donation card (<1%). Fifty-four percent were reluctant to donate organs themselves, 56% lacked sufficient knowledge. Twenty percent referred to school education and periodicals as the source of information. Sixty-nine percent were act as opinion leaders for organ donation. In curriculums of the Faculties of Theology, organ donation as a separate topic has not been found. No articles regarding organ donation have been published in theology journals in their 60-year publication history. CONCLUSIONS: A discrepancy exists between the resolutions of the Board of Religious Affairs and attitudes of clergy toward organ donation in Turkey. Theology faculties seem not to pay specific attention to this issue. The Directorate of Religious Affairs and the faculty of theology should meet at a common point immediately in terms of training programs and continuing education with strict audit in context of organ transplantation and donation.

Mass media, online social network, and organ donation: old mistakes and new perspectives.

INTRODUCTION: Contrary to TV programs projecting awareness about organ donation in society, concrete evidence exists about adverse influence of negative broadcasts on organ donation rates. We sought to determine the effect of mass media on public opinion toward organ donation and the efficacy of public campaigns and novel social media attempts on donation rates. METHODS: We conducted a systematic review of relevant literature and national campaign results. RESULTS: Hoaxes about brain death and organ transplantation adversely affect organ donation rates in both Western and Eastern societies. Scientifically controversial and exaggerated press conferences and institutional advertisements create mistrust in doctors, thus reducing organ donation. The overall effect of public education campaigns in promoting organ donation is a temporary 5% gain. Increments in organ donation rates is expected with novel applications of social media (Facebook effect). CONCLUSION: Communication, based on mutual trust, must be established between medicine and the media. Continuing education programs with regard to public awareness on organ donation should be conducted over social media.

En-bloc pelvic resection with concomitant rectosigmoid colectomy and immediate anastomosis as part of primary cytoreductive surgery for patients with advanced ovarian cancer.

OBJECTIVE: To assess the authors' experiences in en bloc pelvic resection with concomitant rectosigmoid colectomy and primary anastomosis as a part of primary cytoreductive surgery for patients with advanced ovarian cancer. MATERIALS AND METHODS: Atotal of 22 patients with FIGO Stage IIB-IV epithelial ovarian cancer who underwent en bloc pelvic resection with anastomosis were retrospectively reviewed. Data analyses were carried out using SPSS 10.0 and descriptive statistics, Kaplan-Meier survival curves, and Log Rank (Mantel-Cox) test were used for statistical estimations. RESULTS: Median age was 58.8 years. FIGO stage distribution of the patients was; one (4.5%) IIB, three (13.7%) IIC, three (13.7%) IIIA, six (27.3%) IIIB, and nine (40.9%) IIIC. Median peritoneal cancer index (PCI) was 8 (range 5-22) and optimal cytoreduction was achieved in 18 patients (81.8%) of whom 13 (59.1%) had no macroscopic residual disease (complete cytoreduction). There was no perioperative mortality. A total of nine complications occurred in seven (31.8%) patients. Anastomotic leakage was observed in one (4.5%) patient. There was no re-laparotomy. Mean follow-up time was 60 months. There were 15 (68.2%) recurrences of which 12 (80%) presented in extra-pelvic localizations. Mean disease-free survival (DFS) and overall survival (OVS) were estimated as 43.6 and 50.5 months, respectively. Patients with complete cytoreduction had a better DFS (p = 0.006) and OVS (p = 0.003) than those with incomplete cytoreduction. CONCLUSION: En bloc pelvic resection, as a part of surgical cytoreduction, seems to be a safe and effective procedure in many patients with advanced ovarian cancer if required. Despite relatively high general complication rate, anastomosis-related morbidity of this procedure is low as 0.8%. Nevertheless, surgical plan and perioperative care should be personalized according to medical and surgical conditions of the patient.

The outcome effect of double-hormonal therapy in premenopausal breast cancer patients with high nodal-status: Result of a prospective randomized trial.

PURPOSE: The combination of taxanes and anthracyclines has proven efficacy in node-positive (N+) premenopausal primary breast cancer patients. Ovarian ablation is also associated with better survival outcomes in premenopausal hormone-receptor positive (HR+) patients. Therefore, this trial aims to determine the superiority of combined hormonal treatment of ovarian ablation with tamoxifen (TMX) versus TMX alone, in premenopausal N+, HR + patients receiving adjuvant chemotherapy (AC) with taxane and anthracycline. MATERIALS AND METHODS: Premenopausal women who had surgically removed breast cancer with histologically confirmed N + and HR+ were included in the trial. The AC consisted of six cycles of taxotere, adriamycin, cytoxan or taxotere, epirubicin and cytoxan with the completion of radiation therapy. Patients were randomly assigned to receive TMX 20 mg/day for 5 years or up to menopause or TMX 20 mg/day for 5 years plus goserelin (GOS) 3.6 mg injection per month for 2 years. The primary end point was disease-free survival (DFS). RESULTS: Between 2003 and 2011, 101 consecutive patients were allocated to TMX (51 patients) and TMX/GOS (50 patients) groups. The mean follow-up period was 52.4 ± 2.8 months. DFS was 43.0 ± 3.6 months versus 49.9 ± 4.22 months (P = 0.13) and overall survival was 51.1 ± 3.8 months versus 53.1 ± 4.2 months (P = 0.50) in the TMX and TMX/GOS groups, respectively. The results showed 9% absolute risk reduction with respect to DFS in favor of the TMX/GOS group. CONCLUSION: This study group was comprised of stage II and III disease patients with high nodal status. The TMX/GOS combination reduced absolute risk of developing first locoregional or distant relapse by almost 9%. Longer follow-up is required to justify this protocol for routine use.

A prudent algorithm for hyperlipoproteinemia in renal transplant recipients.

BACKGROUND: Hyperlipidemia and particularly low-density lipoprotein cholesterol (LDL-C) have been proposed as independent risk factors predisposing to chronic allograft nephropathy. OBJECTIVE: The primary objective of this prospective randomized study was to evaluate the efficacy of the modified National Cholesterol Education Program (NCEP) Step I Diet to prevent posttransplantation hyperlipidemia. The secondary objective was to assess the impact of fluvastatin on the lipid profile of patients unresponsive to dietary measures. METHODS: The study population consisted of 143 consecutive patients who underwent transplantation between October 1998 and January 2005. Patients who failed to demonstrate total and LDL-C levels below the optimal values of 200 mg/dL and 130 mg/dL respectively, were recruited for fluvastatin treatment. The remaining patients who achieved and maintained the target lipid levels continued on the same dietary regimen. RESULTS: Baseline demographic characteristics were not different among the fluvastatin and modified Step I Diet groups. Mean total cholesterol (231.2 vs 187.3 mg/dL; P < .000), LDL-C (134.5 vs 99.2 mg/dL; P < .000), high-density lipoprotein cholesterol (HDL-C; 62.9 vs 55.7 mg/dL; P = .012), and triglyceride (170.3 vs 138.7 mg/dL; P = .011) levels following the dietary run-in period were significantly different between the patients assigned to fluvastatin treatment and those left on the diet, respectively. Fluvastatin achieved reductions ranging from 12% to 14% in the concentrations of total cholesterol (231.2 +/- 4.29 mg/dL to 202.7 +/- 3.89 mg/dL; P < .000) and LDL-C (134.5 +/- 3.53 mg/dL to 115.6 +/- 3.18 mg/dL; P < .000) among 91% of patients after 1 year of treatment. A substantial decrease in all lipoprotein concentrations occurred in 53 patients in the modified Step I Diet group with significant reductions in total cholesterol (187.3 +/- 4.98 mg/dL to 172.7 +/- 3.8 mg/dL; P < .000) and LDL-C (99.2 +/- 4.0 mg/dL to 96.2 +/- 3.44 mg/dL; P < .000). CONCLUSION: Initiation and education of the Step I Diet should be provided during hospitalization. The 3-month dietary run-in period was deemed sufficient to determine the effect of diet on lipid abnormalities. Reduction of lipoprotein levels by a 40-mg daily fluvastatin dose was sufficient, safe, and tolerable.

Late conversion from calcineurin inhibitor-based to sirolimus-based immunosuppression due to chronic toxicity: a prospective study with protocol biopsy amendment.

BACKGROUND: There is an emerging consensus on conversion from calcineurin inhibitor (CNI)-based regimens to proliferation signal inhibitor (PSI)-based protocols for the prevention of a progressive decline in graft function due to CNI toxicity. METHODS: Thirty-one primary renal transplant recipients within 17-48 years of age (mean, 32.2 +/- 1.6) were enrolled in this dual-center study. Eligible patients had a baseline (pre-engraftment) biopsy and completed at least 12 months of follow-up with deteriorating graft function indicative of chronic CNI toxicity with or without nonspecific interstitial fibrosis/tubular atrophy (IF/TA) on a biopsy specimen. A fast conversion protocol, being defined as a 50% initial reduction followed by complete withdrawal of CNI drug within 2 weeks of introducing rapamycin was performed in all patients. A sirolimus (SRL) loading dose was not prescribed; all subjects directly received maintenance (2-5 mg/d) doses of the drug. The primary endpoint of this study was assessement of renal function using cGFR and renal histology by protocol biopsy at 1 year after conversion. RESULTS: The mean follow-up after conversion was 21.6 months. The difference between cGFR before compared with cGFR after 12 months after conversion (40.8 +/- 2.36 mL/min vs 55.7 +/- 3.6 mL/min; P < .000) and at the last follow-up (40.8 +/- 2.36 mL/min vs 53.8 +/- 2.96 mL/min; P < .000) was significant. The mean IF/TA with glomerulosclerosis and chronic vasculopathy scores of biopsy specimens at baseline, during conversion, and at 12 months of the study were 2.25 +/- 0.3, 3.30 +/- 0.24, and 3.0 +/- 0.30, respectively. The change in scores was indicative of mild progression; however, the difference was not significant. IF/TA, glomerulosclerosis, and chronic vasculopathy scores improved in 8 (30%) subjects, remained unchanged in 11 (42%) and worsened in 7 (28%) after 1 year of SRL therapy. After conversion there was no patient or graft loss in this group. Moreover, SCr and GFR improved in 21 or 29 patients (72%), remained stable in 4 (14%), and decreased in 4 (14%) patients. The predictors of successful conversion in our study were GFR > or = 40.6 mL/min, SCr < or = 2.34 mg/dL, and histological allograft damage score < or =3. CONCLUSION: SRL-MPA/MMF-ST combination may be a good therapeutic strategy against chronic CNI toxicity, particularly for patients whose conversion biopsy specimens demonstrated mild IF/TA, glomerulosclerosis, and chronic vasculopathy scores (< or =3.1 +/- 0.3).

Impact of calcineurin inhibitors on bone metabolism in primary kidney transplant patients.

OBJECTIVE: Posttransplant bone disease and bone metabolism markers were investigated in primary kidney transplant recipients receiving calcineurin inhibitor (CNI) based triple immunosuppression. We examined the safety profile and independent potential of CNIs on bone formation and bone resorption. The study also attempted to correct for modifiable and nonmodifiable factors that impact on posttransplantation bone metabolism, such as age, renal function, rejection, steroid dosage, and secondary hyperparathyroidism. MATERIALS AND METHODS: Serum alkaline phosphatase and osteocalcin were used as indices of bone formation and urinary deoxypyridinoline as a marker for bone resorption. Bone mineral density (BMD) data were assessed in all patients. Osteocalcin and deoxypyridinoline data were correlated with BMD scores to predict the clinical utility and sensitivity of these tests. Sixty-six patients among 300 kidney transplant recipients were enrolled as eligible candidates based upon more than 12 months' posttransplantation follow-up excellent graft function (GFR values >60 mL/min), and intact parathormone levels <100 pg/mL. RESULTS: Mean follow-up was 1395.3 +/- 179.3 days and 1488.9 +/- 225.1 days for cyclosporine (CsA) and FK506 groups, respectively. Mean values for alkaline phosphatase and osteocalcin were 108.8 +/- 6.0 versus 98.4 +/- 9.7 U/L and 10.1 +/- 1.2 versus 9.8 +/- 1.5 ng/mL for the CsA and FK506 groups, respectively. Both CsA and FK506 caused mild osteoblastic proliferation and matrix mineralization activity, as reflected by increased osteocalcin and alkaline phosphatase levels in 22.6% and 12.5% of patients, respectively. This bone formation activity was counterbalanced by a three-fold increase in urine deoxypyridinoline levels in both groups. Mean deoxypyridinoline levels were, respectively, 13.8 +/- 4.4 versus 11.3 +/- 2.1 nM/mMCr in the CsA and FK506 groups. Thirty-four (68%) patients in the CsA and 10 (62.5%) in the FK506 groups had elevated deoxypyridinoline levels. A strong correlation existed between deoxypyridinoline levels and BMD scores for the CsA group (P < .0001). Despite the presence of relatively greater elevations in deoxypyridinoline and BMD values among CsA-treated patients, there was no significant difference in terms of bone resorption potential of both groups. No correlation existed between iPTH values (<65 pg/mL or among 65 to 98.2 pg/mL) at any time versus osteocalcin, alkaline phosphatase, deoxypyridinoline, or BMD levels. The symptomatic bone disease and fracture rates were 0% in this series. CONCLUSION: Calcineurin inhibitor-based immunosuppression with low maintenance doses of glucocorticoids induces slight bone formation but relatively potent, clinically relevant bone resorption.

Efficacy and safety of enteric-coated mycophenolate sodium in de novo and maintenance renal transplant patients.

Enteric-coated mycophenolate sodium (ECMPS) has been developed as an alternative agent to mycophenolate mofetil (MMF), with the aim to provide reduction in gastrointestinal side effects. This open-label, single-arm, two-center prospective study sought to investigate the efficacy and safety of ECMPS used in combination with steroid and cyclosporine (CyA) in de novo and maintenance renal transplant patients with 12 months' follow-up. Twenty-one patients were recruited (mean age, 39 +/- 8 years) into the de novo group. Of these patients, 66% were male and 76.2% underwent living related kidney donation. The induction immunosuppression was ATG in 10 and basiliximab in 6 patients. At 12 months' posttransplantation, there was no graft or patient loss and two (10%) acute rejection episodes. None of the patients in this group discontinued the study medication due to drug-induced adverse events. One patient was excluded from the study because of recurrent oxalosis. Serum creatinine (SCr) levels at 3, 6, and 12 months after renal transplant were 1.30 +/- 0.3, 1.40 +/- 0.3, and 1.40 +/- 0.3 mg/dL, respectively. The maintenance group included 20 patients. Time posttransplantation (mean +/- SD) was 27 +/- 25 months. All patients in this group had been on maintenance azathioprine or MMF in combination with steroid and CyA. These patients were switched to ECMPS. They mean age was 36 +/- 8 years. Sixty-six percent of the patients were male and 57% received living donor kidneys. Acute rejection was nil, whereas two patients lost their grafts owing to chronic rejection in this group. Three patients were excluded from the study, one to discontinuation of the drug because of intractable diarrhea, the second to loss to follow-up, and the last case due to withdrawal of informed consent. Leukopenia was not observed in this group. The SCr levels prior to and at 3, 6, and 12 months after conversion to ECMPS were 1.80 +/- 1.0, 1.95 +/- 1.5, 1.50 +/- 0.8, and 1.60 +/- 0.8 mg/dL, respectively. This is the first phase IV study with ECMPS in the Turkish population. Renal function was preserved in both groups. Only 2.5% of patients were excluded because of side effects. Use of ECMPS in combination with prednisolone and CyA is an effective and safe therapeutic choice for both de novo and maintenance renal transplant patients.

Predictors of mortality and morbidity in acute obstructive jaundice: implication of preventive measures.

BACKGROUND/AIMS: The afferent events in acute obstructive jaundice (AOJ) are characterized by endotoxemia-induced decrease in systemic vascular resistance and bile salt mediated natriuresis and diuresis leading to diminished effective plasma volume. METHODOLOGY: A prospective protocol aimed at preventing those alterations was carried out in 104 consecutive patients with AOJ. The preoperative risk factors that predict postoperative mortality and morbidity were reevaluated and correctable factors were identified. RESULTS: The average duration between the initiation of jaundice and surgery was 9.3 days. The perioperative mortality was 0%. The essentials of the treatment protocol were lactulose and cefazolin administration respectively for the prevention of portal endotoxemia and biliary sepsis and maintenance of body weight with adequately replaced fluid and electrolytes. Clinically relevant nutritional deficit was not observed in any of the patients during the perioperative period. The unique factor that predicted late mortality was the preoperative alanine transaminase value. Renal hemodynamics and hematologic parameters were completely correctable before the operation and patients with malignant or benign biliary strictures benefited and responded to the treatment similarly. CONCLUSIONS: Measures taken to prevent the activation and progression of the afferent events in AOJ, have resulted in excellent clinical outcomes.

Adjuvant chemotherapy in a unique population of patients with gastric cancer undergoing surgery.

BACKGROUND/AIMS: Total gastrectomy with D2 dissection theoretically removes the gross primary tumor with its potential route of dissemination, that is locoregional lymph nodes. Complementary therapy for the control of systemic microscopic disease should be taken into consideration in patients whom surgery with curative intent was performed. METHODOLOGY: Twenty-eight patients with moderately differentiated, locally advanced gastric carcinoma underwent total gastrectomy with D2 lymph node dissection. The operative mortality rate was 0% in this series. Fifteen patients received six courses of adjuvant 5-FU + leucovorin in doses of 425 mg/m2/d and 20 mg/m2/d respectively in five-day cycles month ly. The remaining 13 patients constituted the control (surgery only) group. RESULTS: The mean disease-free and overall survival rates were 41 and 48 months (p: 0.78) and 42 and 53 months (p: 0.43) in the control and chemotherapy groups, respectively. The odds ratio for crude mortality was 0.7. CONCLUSIONS: Although statistical significance has not been achieved in this study, a trend toward adjuvant chemotherapy has emerged in that unique group of patients with moderately differentiated (intestinal type) adenocarcinoma of the stomach undergoing curative surgery.

Two-day induction with thymoglobulin in kidney transplantation: risks and benefits.

INTRODUCTION: The aim of this study was to develop an induction protocol to reduce allograft rejection with fewer posttransplant infections and malignancies. METHODS: In this prospective randomized study, a T- and B-cell depletion protocol, consisting of IV thymoglobulin (ATG 5 mg/kg/d) plus methylprednisolone (500 mg/d) plus azathiopurine (2 mg/kg/d), was on days 0 and 1 after renal transplantation. CyA was introduced at day 3.39 among patients undergoing either primary living related (n = 16) or cadaveric (n = 23) transplants excluding recipients of full-HLA-matched sibling, or five- and six-HLA-matched cadaveric donor kidneys. The adequacy of immunosuppression was evaluated by flow cytometric analysis for total, CD3+ (T-cell), and CD19+ (B-cell) lymphocytes. RESULTS: The acute rejection rate was 6% and 37/39 patients are alive with functioning grafts at an average follow-up of 14.5 months. The overall patient and graft survival rate was 95%. Their mean creatinine value was 1.27 mg/dL. Six patients (16%) required hospitalization due to serious infections. The two deaths were attributed to septicemia and brain abcess caused by unusual agents, namely, Rhodococcus equi and Sporobolomyces. One patient presented with a cutaneous Kaposi sarcoma in the 11th month posttransplant. CONCLUSION: A Two-day induction protocol with thymoglobulin yields acceptable acute rejection rates among renal transplants. However, caution is necessary for adverse events, particularly atypical bacterial and fungal infections.