[show abstract][hide abstract] ABSTRACT: In this retrospective analysis, the clinicopathological features and pattern of metastatic spread of invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and mixed ductal/lobular carcinoma (MDLC), together with the type and outcome of surgical intervention, were comparatively evaluated.
A total of 633 breast cancer patients with histopathological subtype IDC, ILC or MDLC were included in the study. The mean age was 52.6 ± 12.7 years. Follow-up period ranged between 0 and 33 (median 6.0) years. The groups were compared with respect to age, tumor size, nodal involvement, stage, hormonal therapy, multicentricity, multifocality, bilaterality, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2)/neu, p53, and Ki67 expression, disease-free survival (DFS) and overall survival (OS) rates, and surgical approach.
The distribution of patients was as follows: IDC 508 (80.3 %), ILC 78 (12.3 %), MDLC 47 (7.4 %). Among the parameters evaluated, statistically significant differences were observed in mean tumor size (IDC 2.5 ± 1.98 cm, ILC 3.0 ± 1.8 cm, MDLC 3.2 ± 2.4 cm), advanced T stage (T3 + T4) at diagnosis (IDC 14.7 %, ILC 21.4 %, MDLC 25.6 %), N stage (N0 was dominant in IDC and ILC; N3 was dominant in MDLC), tumor-node-metastasis (TNM) stage (stage II was dominant in IDC and ILC; stage III was dominant in MDLC), HER2/neu expression (IDC 23.8 %, ILC 11.8 %, MDLC 21.4 %), and frequency of bone metastasis (IDC 14.3 %, ILC 17.9 %, MDLC 25.5 %).
MDLC-type tumors have different histopathological characteristics and are often diagnosed at advanced stage. However, their survival outcomes do not vary significantly from ILC and IDC.
[show abstract][hide abstract] ABSTRACT: Recurrent episodes of venous thrombosis have been closely correlated with JAK2 V617F mutation. Upto date, JAK2 gene mutation has not been defined as a prothrombic risk factor in renal transplant recipients. Herein; we present a case of portosplenic vein thrombosis in a primary renal transplant recipient with JAK2 V617F mutation who had no history of prior venous thromboembolism or thrombophilia.
A 59 year old female caucasian patient with primary kidney transplant admitted with vague abdominal pain at left upper quadrant. Abdominal doppler ultrasound and magnetic resonance imaging angiography demonstrated splanchnic vein thrombosis (SVT). The final diagnosis was SVT due to MPD (essential thrombocytosis, ET) with JAK2 V617F mutation. After 3 months of treatment with warfarin (>=5 mg/day, to keep target INR values of 1.9-2.5), control MRI angiography and doppler USG demonstrated partial (>%50) resolution of thrombosis with recanalization of hepatopedal venous flow. The patient is still on the same treatment protocol without any complication.
JAK2 V617F mutation analysis should be a routine procedure in the diagnosis and treatment of kidney transplant patients with thrombosis in uncommon sites.
[show abstract][hide abstract] ABSTRACT: The primary objective of this study was to clarify the influence of histotype on the outcome of D1/D2 gastrectomized patients with pathologically proven R0 resection. The secondary objective was to demonstrate overall survival (OS), disease-free survival (DFS), and locoregional recurrence rates following standard curative surgery.
All patients had either pure signet-ring cell carcinoma (SRCC)/poorly differentiated adenocarcinoma (PDC) or moderately differentiated adenocarcinoma (MDC) of the stomach, preoperative radiologic evidence of locoregional disease, and no history of neoadjuvant therapy. Standards of surgical treatment were essentially based on the guidelines of the Japanese Research Society for the Study of Gastric Cancer.
Between October 2003 and August 2010, seventy-eight patients were enrolled. Twenty-three patients underwent D1 dissection and 55 underwent D2 dissection. The OS and DFS rates were 33.2 ± 5.9 months versus 31.5 ± 4.3 months (p = 0.81) and 28.9 ± 5.6 months vs. 29.3 ± 4.4 months (p = 0.96) in the MDC and SRCC/PDC groups, respectively. Neither the extent of the operation (D1 vs. D2, p = 0.79) nor the histopathologic subtype of the primary tumor (MDC vs. SRCC/PDC, p = 0.91) influenced the OS and DFS. Multivariate logistic regression analysis disclosed pathologic stage (pTNM) as the only significant prognostic determinant of OS (p = 0.007) and DFS (p = 0.0003).
Properly performed D1 and D2 dissection in our series resulted in a notable (6.4%) locoregional failure rate. In spite of the satisfactory locoregional control achieved by D1 and D2, there was no improvement in the survival figures of stage IIIA-B and IV gastric cancer patients. The histopathologic subtype of the primary tumor disclosed merely a statistical trend on the outcome measures of gastric cancer after curative surgery.
[show abstract][hide abstract] ABSTRACT: Neurologic problems have a major effect on the survival and quality of life in renal transplant recipients. This study sought to review the incidence and character of neurologic complications after renal transplant.
Medical records of 319 renal transplant recipients admitted to the Transplant Outpatient Clinic were reviewed retrospectively for neurologic complications.
Of the 319 transplant recipient patients reviewed, 124 patients (39%) were women and 193 patients (61%) were men. The mean patient age was 41 ± 11 years, and the transplanted kidney was received from deceased donors in 161 patients (51%) and living donors in 158 patients (49%). There were 50 patients (16%) who had neurologic complications, most commonly herpes zoster infection associated with immunosuppressive medication. Only 1 patient, who had glioblastoma multiforme, died. Treatment included corticosteroids in 296 patients (93%) and calcineurin inhibitors (including tacrolimus) in 111 patients (35%).
Neurologic complications are common after renal transplant. Most complications are associated with immunosuppressive medications.
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation. 06/2012; 10(3):243-6.
[show abstract][hide abstract] ABSTRACT: The primary objective of this review was to clarify the efficacy of commercially available and tested agents for the treatment of first acute rejection episode (ARE) and particularly a steroid-resistant rejection (SRR) seeking to provide generalizable level I evidence for clinical practice. The inclusion criteria were restricted to prospective randomized trials (PRT) that (1) reported outcomes of first, biopsy-proven ARE based on Banff 97 diagnostic criteria; (2) excluded borderline changes that were not considered to be acute rejection; (3) included protocol biopsies confirming reversal or recurrence of rejection; (4) utilized calcineurin inhibitor-based double or triple baseline immunosuppression prior to and after the reversal of ARE and possessed Jadad scores at least 3 upon final assessment by both reviewers. Two PRTs compared rabbit-anti-thymocyte globulin (ATG) to low-dose corticosteroids or OKT3, following a first rejection episode in renal transplantation patients. The analysis of pooled data revealed 25% and 31% absolute risk reduction (ARR), in regard to initial treatment failure and recurrence of ARE, respectively, in favor of ATG treatment. Treatment morbidity showed similar long-term graft and patient survival rates in both arms. Three optimal trials compared the efficacy of various polyclonal or polyclonal versus monoclonal (OKT3) antibodies for the treatment of SRR. The estimated efficacy potential of rabbit-ATG appeared to be 11,4% greater than horse-ATG with particularly Banff grade II but also grade III patients demonstrating the greatest benefit. Among two PRTs comparing ATG to OKT3, ATG tended to show better graft function, fewer recurrent rejections (9% ARR), fewer graft losses due to immunologic failure (7% ARR), and better tolerance. The incidence of malignant tumors was similar in both treatment arms. In conclusion, thymoglobulins, especially those of rabbit origin, displayed greater efficacy for the treatment of ARE and SRR. Application of CD3 monitoring using flow-cytometry provided a reliable guid to prevented excessive immunosuppressive administration.
[show abstract][hide abstract] ABSTRACT: A prospective study in 82 consecutive patients with mid- and distal rectal adenocarcinomas having specific histology and tumor stage was conducted to asses impact of curative surgery.
Patients with moderately differentiated adenocarcinoma (MDAC) with or without mucinous differentiation underwent curative resection. Forty patients were in Stage B1-B2 and 42 patients were in Stage C1-C2. Surgery options were: (1) Abdominoperineal resection (APR) for tumors located within 6cm of the anal verge and (2) Tumor specific mesorectal excision (TSME) and low anterior anastomosis (LAA) for those located between 6 to 12cm from the anal verge. The primary endpoints were overall (OS) and disease-free survival (DFS).
Patients in Stage B1-B2 had a local failure rate of 15% compared with 31% of patients in stage C1-C2 (p=0.18). Satellite tumor nodule formation (STN) was observed in one patient in B group and in 13/42 (31%) of Stage C tumors. LR did not vary with mucinous differentiation. Only lymph node involvement (N1-3) (p=0.028) had an impact on locoregional recurrence and both lymph node involvement and STN formation influenced disease-free survival (p=0.008).
Preoperative precise detection of Stage C rectal adenocarcinomas is of utmost importance to facilitate the implementation of therapies for downstaging and for better local and distant control following surgery.
[show abstract][hide abstract] ABSTRACT: Cholemia and bacterial translocation with portal endotoxemia are integral in the pathogenesis of obstructive jaundice (OJ). There is sufficient experimental data about hemodynamic and histopathological consequences of OJ. In contrast, pathological information of renal changes in patients with OJ is still lacking. Therefore; the primary objective of this prospective study is to show the specific histopathological changes in kidneys of patients with short-term biliary tract obstruction receiving a standard perioperative medical treatment protocol.
Twenty consecutive patients with biliary obstruction were included in the study. Fluid replacement, prevention of biliary sepsis, and portal endotoxemia were mainstays of the perioperative treatment protocol. Fluid and electrolyte balance was maintained by twice daily body weight calculations, central venous pressure, and mean arterial pressure monitoring. Renal function was assessed by glomerular filtration rate estimation by modification of diet in renal disease-7 formula. Kidney biopsy evaluation was focused on tubular changes, thrombotic microangiopathy, endothelial damage, and peritubular capillary (PTC) dilatation with or without C4d staining. Fresh frozen sections were evaluated with immunofluorescence microscopy for glomerular IgG, IgA, IgM, C3, and C1q staining.
The mean duration of OJ was 15.5 ± 1.4 days. Body weight increased before surgery through volume expansion (P = 0.001). All patients have shown mean arterial pressure ≥ 70 and ≤ 120 mmHg and renal function was very well preserved in all but one subject during the perioperative period. Despite those favorable figures, dilatation of peritubular venules and acute tubular necrosis were shown synchronously in all cases. C4d staining in PTC and arterioles and thrombotic microangiopathy were entirely absent in the study group. Immune complex deposits in PTCs and in glomeruli were not detected. Three patients had isolated glomerular C4d deposition without accompanying thrombotic microangiopathy and IgG, IgA, IgM, C3, and C1q staining of glomerular capillaries in I immunofluorescence microscopy.
This study is the first in the literature to address the histopathological changes that occur in humans with short-term biliary obstruction. Acute tubular necrosis and venous dilatation was observed in all biopsies, without exception, despite the maintenance of strict volume control in all patients. The adequacy of volume control may not be implicated in those results; rather a possible mechanism related to untrapped endotoxin in the gut lumen or systemic circulation might lead to prolonged PTC dilatation and hypoperfusion with synchronous acute tubular necrosis. Absolute recovery of renal function in all patients and the demonstration of solitary acute tubular necrosis with no microvascular-glomerular-interstitial inflammation or injury, suggests that the perioperative treatment regime in this study is fairly efficacious in short-term OJ.
European journal of gastroenterology & hepatology 09/2010; 22(12):1458-65. · 1.66 Impact Factor
[show abstract][hide abstract] ABSTRACT: Nephrotoxic potential of mammalian target of rapamycin inhibitors (mTORi) is different from calcineurin inhibitors (CNI). The aim of this study is to investigate the interstitial fibrosis (ci) and tubular atrophy (ct) progression from the baseline to first year under a mTORi-based, CNI-free regimen.
Thirty-five kidney transplant recipients who had to have adequate baseline and first year protocol biopsy were enrolled. Exclusion criteria were: the replacement of CNI at any time; acute deterioration in allograft functions; and serum creatinine level above 3 mg/dL at 12 months. Banff criteria were used for histopathological classification. Progression was defined as delta ci + ct ≥ 2 (difference between 12th month and baseline).
Mean age of patients and donors were 34 ± 11 and 49 ± 10 years. Twelve patients had delayed graft function (DGF). The maintenance regimen consisted of sirolimus (n = 24) and everolimus (n = 11) with mycophenolate mofetil and steroids. Incidence of acute rejection was 25.7%. At baseline, the incidence of nil and mild fibrosis were 80% and 20%, respectively. At 12 months, 17.1% of patients had moderate, 40% had mild and 42.9% had nil fibrosis. Histological progression from baseline to first year was present in 34% of patients. In multivariate analysis the presence of DGF (P = 0.018) and deceased donor type (P = 0.011) were the most important predictors for fibrosis progression.
Progression of graft fibrosis may be seen in one-third of patients under a mTORi-based regimen particularly manifested in deceased donor recipients with subsequent DGF.
[show abstract][hide abstract] ABSTRACT: The purpose of the study was to describe the imaging findings of male breast disease. One hundred and sixty-four male patients, who underwent mammography and ultrasonography (US) between January 1999 and December 2008, were retrospectively evaluated. Seventy-five patients (46%) underwent biopsy, and 89 patients (54%) were diagnosed radiologically. The radiologic and pathologic diagnoses in 164 cases of this series were 13 cancers (8%), including one ipsilateral and one contralateral breast cancers, 147 cases of gynecomastia (90%), one fibroadenoma (0.6%), two cases of fibrocystic disease of the breast (1.2%), and one epidermoid inclusion cyst (0.6%). Three mammographic patterns were adequate to describe all 147 cases of gynecomastia in our series: 53 patients (36%) had nodular gynecomastia, 46 patients (31%) had dendritic gynecomastia, and 48 patients (33%) had diffuse gynecomastia. Gynecomastia was unilateral in 65% of cases (n=95), and bilateral in 35% of cases (n=52). On physical examination, two of the malignant lesions had no clinic features of malignancy (15%). On mammography, 11 of 13 malignant masses were demonstrated (85%). A mass with microcalcifications was seen on mammograms in one case (9%). The contours of the masses were irregular in nine cases (82%), well-circumscribed in two cases (18%). The location of the masses was retroareolar in seven cases (64%) and eccentric to the nipple in four cases (36%). The size of the masses varied between 0.5 cm and 5 cm (mean 2.4 cm). Nipple retraction was evident in five cases (45%), and skin thickening in four cases (36%). All of the malignant masses were demonstrated on ultrasound; however, one of them was seen retrospectively after mammography. All of the masses were hypoechoic and solid, the contours were well-defined and smooth in two masses (15%), and irregular in 11 masses (85%), and five masses (39%) had posterior prominent shadowing. Axillary lymphadenopathia was detected in two cases (15%). One patient had a previous contralateral breast cancer, and one had an ipsilateral. On mammography, breast cancer characteristically exhibits an irregular subareolar mass, nipple retraction, and skin ulceration or thickening, but sometimes breast cancer has a well-circumscribed contour and punctuated microcalcifications. Ultrasonography is essential and useful for further characterization and helpful for demonstrating lymphadenopathies of the axillary region.
The Breast Journal 01/2010; 16(5):510-8. · 1.83 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of this study was to determine the prevalence of impairments relevant to upper extremity following breast cancer surgery and its impact on disability and health-related quality of life.
Sixty-seven female patients being treated with modified radical mastectomy or breast conserving surgery were included. They were evaluated for impairments (arm edema, loss of handgrip strength, limited shoulder joint range of motion, and pain), physical disability using the disabilities of the arm, shoulder, and hand (DASH) questionnaire, and for health related quality of life by means of the functional assessment of cancer therapy-breast+4 (FACT-B+4).
The most common impairment observed was arm pain on motion; the cause of 20% variance in disability score (r = 0.203, P = 0.000). Arm pain on motion, anterior chest wall pain, loss of grip strength, and shoulder flexion were significant factors in different domains of quality of life according to the FACT-B+4 questionnaire.
Pain relief should be the priority of treatment along with the prevention of joint movement restriction to ensure a sufficient quality of life for surgically treated breast cancer patients.
Southern medical journal 12/2009; 103(1):37-41. · 0.92 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hyperlipidemia and particularly low-density lipoprotein cholesterol (LDL-C) have been proposed as independent risk factors predisposing to chronic allograft nephropathy.
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.
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.
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).
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.
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
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).
[show abstract][hide abstract] ABSTRACT: SUMMARY: BACKGROUND: The purpose of this study was to define the diagnostic accuracy of mammography and ultrasound in the evaluation of male breast disease, and to suggest a diagnostic protocol for male breast disease. MATERIAL AND METHODS: We retrospectively reviewed clinical, radiographic, and pathologic records of 75 patients. Breast Imaging Reporting and Data System (BI-RADS) category 4-5 mammograms and ultrasonograms were suggested as suspicious for malignancy. RESULTS: Of the 75 patients, 23 (31%) were considered to have suspicious lesions by mammography and/or ultrasonography. 13 of the patients were shown to have breast cancer. The remaining 52 (69%) were referred for biopsy by clinicians; all of the biopsy specimens were benign (gynecomastia). The accuracy data of mammography and ultrasonography are: sensitivity, 69 and 100%; specificity, 87 and 97%; positive predictive value, 53 and 87%; negative predictive value, 93 and 100%; and accuracy, 84 and 97%, respectively. CONCLUSION: We suggest a new diagnostic algorithm for the evaluation of male breast disease in which ultrasonography may be used to evaluate palpable abnormalities as the first diagnostic tool of choice. To use and to trust imaging would decrease the number of false-positive biopsies that would be generated by physical examination alone.
Breast Care 01/2009; 4(4):255-259. · 0.68 Impact Factor
[show abstract][hide abstract] ABSTRACT: To determine the outcome of recurrent Graves' disease with ophthalmopathy (GO) following bilateral total thyroidectomy (TT) in patients with no history of anti-inflammatory treatment with steroids or radioactive iodine treatment.
From May 2002 to August 2005, 35 patients (27 female, 8 male) with different stages of Graves' disease underwent TT. The degree of ophthalmopathy was assessed by the NOSPECS scoring system and thyrotropin receptor antibody (TRAb) levels were measured for the detection of thyroidal and retro-orbital inflammatory activity before and after surgery.
The mean duration of thyroid disease was 21.4 months and mean follow-up was 422 days. Significant improvement, which was defined as complete regression of periorbital oedema accompanied by a > 1 point decrease in NOSPECS, was observed in 30 (85%) patients. The remaining five patients had stable eye disease. The mean TRAb value and NOSPECS score before and after TT were 33.8 U/L versus 3.4 U/L and 3.0 versus 1.52, respectively, and the differences were statistically significant (p < 0.0000). A major reduction in TRAb values achieved after TT was clearly indicative of undetectable inflammatory activity and all the patients demonstrated negative TRAb values within 6 months of the operation. TT was accomplished with very low morbidity (3%) and provided a significant reduction in TRAb levels with attendant improvement in GO in the vast majority of patients in this study.
TT resulted in a significant reduction in TRAb levels with concomitant regression of recurrent GO in all patients. The operative morbidity was very low and mortality was nil. However, the long-term consequences of permanent hypothyroidism, which is the ultimate result of TT, are of major concern.
Asian Journal of Surgery 07/2008; 31(3):115-8. · 0.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: Target of rapamycin inhibitors have presented similar graft and patient outcomes with no evidence of drug-induced nephrotoxicity when compared with calcineurin inhibitors. The principal aim of this study is to demonstrate the efficacy of sirolimus-based triple immunosuppression with antithymocyte globulin induction in expanded donor kidney transplantation.
Twenty-seven primary expanded criteria donor kidney transplant recipients were recruited. The severity of kidney damage was qualified by zero-hour biopsies. Protocol biopsies were performed at 1 year to assess the chronic allograft damage. Death, graft function, proteinuria and adverse events were systematically analysed during the study period.
The mean follow up was 20.2 months. Patient and graft survival was 100% with a mean glomerular filtration rate (GFR) of 53.1+/-4.9 mL/min at last follow up. The cumulative incidence of acute rejection was 11% at the last follow up. At 1 year, mean creatinine, GFR and proteinuria were 1.84 mg/dL, 52.3 mL/min, 651.5 mg/day, respectively. Four patients required surgical intervention due to urinary complications and recovered successfully. Two patients developed acute graft dysfunction due to acute tubular necrosis which was presumably drug related. Ten patients developed relapsing urinary tract infections and three patients had pneumonia. No infectious death occurred throughout the study period. Baseline renal structure was preserved in 13 biopsies at 1 year post transplant. Five patients demonstrated progressive but mild tubular atrophy or interstitial fibrosis in their protocol biopsies. The mean chronic allograft damage index scores at baseline and at 1 year from biopsy were 2.57+/-0.23 and 2.83+/-0.23, respectively (P=0.046).
Low-dose sirolimus-based triple immunosuppression with antibody induction offered a safe clinical outcome in expanded criteria donor kidneys with the achievement of stable renal function and favourable recipient outcomes throughout the short term. However, mild progression of histological damage and increased risk of bacterial infection are a major concern. Additionally, the benefit (if any) of the low acute rejection rate on long-term graft outcome is still undetermined.
[show abstract][hide abstract] ABSTRACT: 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.
[show abstract][hide abstract] ABSTRACT: 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.
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.
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.
Calcineurin inhibitor-based immunosuppression with low maintenance doses of glucocorticoids induces slight bone formation but relatively potent, clinically relevant bone resorption.
[show abstract][hide abstract] ABSTRACT: ABSTRACT
The frequency and variety of solid organ transplantation in reproductive-age women increases each year.
Although most transplant-related pregnancies have been reported in women with kidney allografts,
pregnancy is also possible in young women with other solid organ transplants including liver, pancreaskidney, heart, lung and heart-lung transplants. Most of these pregnancies have resulted in a successfull
outcome; however, for optimal maternal and neonatal outcomes, a multidisciplinary approach including
careful follow-ups of the obstetrician and transplant team is essential. This article reviews and discusses
preconceptional counselling, graft rejection and dysfunction during pregnancy, safety of immunosuppressive
medications with regard to fetus, and perinatal risks and pregnancy management for women with various
solid organ transplants, taking into consideration previous published reports, especially The National
Transplantation Pregnancy Registry (NTPR)’s.
Keywords: Solid Organ Transplantation, Pregnancy, Complications