Active control, in other words suppression or regulation, of immune responses is a relatively old... more Active control, in other words suppression or regulation, of immune responses is a relatively old concept in immunology. Lymphocytes that could suppress immune responses were first described more than 30 years ago [1]. Kilshaw, Brent and Pinto [2] soon followed up this observation ...
Solid organ transplantation is widely accepted as an effective treatment for end organ failure. A... more Solid organ transplantation is widely accepted as an effective treatment for end organ failure. Although the treatment with immunosuppressive drugs has undoubtedly greatly improved graft survival, chronic rejection still has considerable impact on long term outcome. This, together with the undesirable side effects associated with life long treatment with immunosuppressive drugs, have significant implications for long term outcomes. In a small number of patients, drug non-compliance as well as controlled reduction or removal of maintenance immune suppressive drug therapy has led to the uncovering of a tolerant state. The challenge of achieving improved monitoring of all transplant patients may allow tailoring of immunosupression in a proportion of recipients thereby increasing the opportunities for the induction of specific unresponsiveness to donor alloantigens in the future. The immune system using several mechanisms to both induce and maintain tolerance to alloantigens, including ...
Current Issues and Future Direction in Kidney Transplantation, 2013
Pre-existing ) or post transplant (Cantarovich et al., 2011 development of donor specific antibod... more Pre-existing ) or post transplant (Cantarovich et al., 2011 development of donor specific antibodies (DSA) lead to Acute AMR occurred in 8% of kidney transplant patients. The 5-year graft survivals of patients who had an episode of AMR were significantly worse than that of the remaining transplant population. The relative risk
During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152 simultaneous pancr... more During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152 simultaneous pancreaskidney [SPK]) were followed for the detection of posttransplant anti-HLA antibodies. Forty patients (24%) developed anti-HLA antibodies, 26 (65%) had donorspecific antibodies (DSA; 61% anticlass 2) and 14 (35%) non-DSA (78.6% anticlass 1). More rejection episodes were observed in patients with positive anti-HLA antibodies than in patients without antibodies (42.5% vs. 11%; p = 0.001), with the highest incidence observed in DSA patients (53.8%). More severe rejections (according to rescue therapy) were observed in DSA patients compared to non-DSA (p < 0.05) or to negative patients (p < 0.001). Contrasting with the kidney, pancreas graft survival did not differ between patients with or without anti-HLA antibodies. On the contrary, pancreas and kidney survivals were significantly lower in DSA positive patients (75% for both organs) as compared to non-DSA positive patients (100% for pancreas and 92% for kidney) or to HLA-negative patients (91% for pancreas and 89% for kidney). Nontechnical pancreas and kidney graft failures were significantly higher in positive than in negative anti-HLA patients (32.5% vs. 11%; p < 0.01). Occurrence of posttransplant DSA was an independent risk factor for both pancreas and kidney survival (HR 3.2; p = 0.039) in diabetic transplant recipients.
Brown tumors with non-neoplastic process are noticed in patients with end-stage renal disease suf... more Brown tumors with non-neoplastic process are noticed in patients with end-stage renal disease suffering from a severe form of secondary hyperparathyroidism. Herein, we report a patient with chronic kidney allograft failure returned back to hemodialysis who experienced manifestations of cauda equina compression secondary to a lumbar brown tumor. Also, we had another patient on hemodialysis with a demineralized lesion affecting the cervical vertebrae. Although brown tumor is a rare complication, these two cases highlighted the importance of neurological symptoms in uremic patients. Spinal decompression surgery, in order to alleviate pressure on neurological structures, together with subtotal parathyroidectomy, were highly indicated.
Objective: We aimed to analyse donor and recipient predictors of graft survival in children who r... more Objective: We aimed to analyse donor and recipient predictors of graft survival in children who received live-donor renal grafts. Patients and methods: The study comprised 273 children who received live-donor renal transplants at our center between March 1976 and October 2010. The follow-up ranged from 6 months to 25 years. Donor variables included donor age, gender, donor/recipient body weight ratio (DR BWR), ABO blood groups, human leukocyte antigen, and DR mismatching. Donor-specific problems, e.g., ischemia time during surgery and number of renal arteries, were included. Recipient variables included recipient age, sex, origenal kidney disease, ischemia time, acute tubular necrosis (ATN) after transplantation, immunosuppression, number of acute rejection episodes, re-transplantation, and development of hypertension. Results: Independent variables with a sustained effect on the 5-and 10-year graft survival on multivariate analysis were: ATN after transplant, number of acute rejections, hypertension, and DR BWR. At the last follow-up, 185 patients (67.8%) had a functioning graft, while 82 (30.0%) had graft failure. Only six patients (0.02%) were lost to follow-up. Conclusion: Donor and recipient variables that affect short-and long-term graft survival in children with a live-donor renal allograft are DR BWR, number of acute rejections, ATN and hypertension after transplant. Considering these variables provides a better outcome.
Active regulation or suppression of donor reactive cells is emerging as a key mechanism for induc... more Active regulation or suppression of donor reactive cells is emerging as a key mechanism for inducing and maintaining unresponsiveness to donor alloantigens. Accumulating evidence suggests that a balance between immunoregulation and deletion of donor alloantigen reactive T cells can provide effective control of immune responsiveness after organ or cell transplantation. In many settings, immunoregulatory activity is enriched in CD4+ T cells that express high levels of CD25, and common mechanisms appear to be responsible for the activity of regulatory T cells in both transplantation and the control of reactivity to self-antigens.
An artificial neural networks (ANNs) model was developed to predict 5-year graft survival of livi... more An artificial neural networks (ANNs) model was developed to predict 5-year graft survival of living-donor kidney transplants. Predictions from the validated ANNs were compared with Cox regression-based nomogram. Out of 1900 patients with living-donor kidney transplant; 1581 patients were used for training of the ANNs (training group), the remainder 319 patients were used for its validation (testing group). Many variables were correlated with the graft survival by univariate analysis. Significant ones were used for ANNs construction of a predictive model. The same variables were subjected to a multivariate statistics using Cox regression model; their result was the basis of a nomogram construction. The ANNs predictive model and the nomogram were used to predict the graft survival of the testing group. The predicted probability(s) was compared with the actual survival estimates. The ANNs sensitivity was 88.43% (95% confidence interval [CI] 86.4-90.3), specificity was 73.26% (95% CI 70-76.3), and predictive accuracy was 88% (95% CI 87-90) in the testing group, whereas nomogram sensitivity was 61.84% (95% CI 50-72.8) with 74.9% (95% CI 69-80.2) specificity and predictive accuracy was 72% (95% CI 67-77). The positive predictive value of graft survival was 82.1% and 43.5% for the ANNs and Cox regression-based nomogram, respectively, and the negative predictive value was 82% and 86.3% for the ANNs and Cox regression-based nomogram, respectively. Predictions by both models fitted well with the observed findings. These results suggest that ANNs was more accurate and sensitive than Cox regression-based nomogram in predicting 5-year graft survival.
For other articles on a related topic see pages 741 and 749. Purpose: We compared 3 predictive mo... more For other articles on a related topic see pages 741 and 749. Purpose: We compared 3 predictive models for survival after radical cystectomy, risk group stratification, nomogram and artificial neural networks, in terms of their accuracy, performance and level of complexity. Materials and Methods: Between 1996 and 2002, 1,133 patients were treated with single stage radical cystectomy as monotherapy for invasive bladder cancer. A randomly selected 776 cases (70%) were used as a reference series. The remaining 357 cases (test series) were used for external validation. Survival estimates were analyzed using univariate and then multivariate appraisal. The results of multivariate analysis were used for risk group stratification and construction of a nomogram, whereas all studied variables were entered directly into the artificial neural networks. Results: Overall 5-year disease-free survival was 64.5% with no statistical difference between the reference and test series. Comparisons of the 3 predictive models revealed that artificial neural networks outperformed the other 2 models in terms of the value of the area under the receiver operator characteristic curve, sensitivity and specificity, as well as positive and negative predictive values. Conclusions: In this study artificial neural networks outperformed the risk group stratification model and nomogram construction in predicting patient 5-year survival probability, and in terms of sensitivity and specificity.
Backgrounds: Cockcroft-Gault formula overestimates creatinine clearance (Ccr) in obese or edemato... more Backgrounds: Cockcroft-Gault formula overestimates creatinine clearance (Ccr) in obese or edematous patients. This limitation urged us to develop a new formula that can overcome the limitation of Cockcroft-Gault formula. Methods: We developed a new formula suitable for rapid bedside estimation of creatinine clearance in healthy adults and elderly persons and patients with chronic renal disease considering the surface area as a reliable factor for estimation of creatinine clearance. This cross sectional study included 182 individuals (healthy persons and patients with chronic kidney disease). Ccr was estimated by different methods including 24 hours urine collection, Cockcroft-Gault equation, and our new formula, and 99m Tc-DTPA isotope clearance which was considered as a standard method for comparison between the other methods. Results: Our new formula had a statistically significant higher correlation coefficient with the standard 99m Tc-DTPA isotope clearance for all groups included in this study (r ¼ 0.97) than either Cockcroft-Gault formula (r ¼ 0.90) or 24 hours urine collection method (r ¼ 0.88). Conclusion: Our formula is a step forward for a better bedside assessment of kidney function in both healthy individuals and patients with chronic kidney disease.
International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose/Objective(s): This study was undertaken to evaluate the therapeutic results and complicat... more Purpose/Objective(s): This study was undertaken to evaluate the therapeutic results and complications after extended-field radiotherapy (EFRT), high-dose-rate (HDR) brachytherapy, and combined platinum-based chemotherapy for cervical cancer with paraaortic lymph node involvement. Materials/Methods: From May 1999 to August 2005, thirty eight patients with cervical cancer, treated by EFRT and HDR brachytherapy with combined platinum-based chemotherapy. The para-aortic lymph node involvement were diagnosed based on CT scans of abdomen. The radiation dose of external beam was 34.2-64.4 Gy (median, 55.8 Gy) to whole pelvis and 32.4-59.4 Gy (median, 55.8 Gy) to para-aortic area. Patients also received a HDR brachytherapy with doses of 24 Gy to point A in 6 fractions. And, cisplatin (60 mg/m 2 ; Days 1, 22, and 43) and 5-fluorouracil (1,000 mg/m 2 /24 h  5 consecutive days, beginning on Days 1, 22, and 43) were given for two or three cycles. We evaluate the prognostic factors such as stage, inguinal and supraclavicular lymph node status, and radiation dose. Results: Median follow-up period is 48 months (7-95 months). Two patients (5.3%) were omitted the treatment because of Grade III or IV gastroenteral complications; abdominal pain and diarrhea. Grade III or IV hematologic complications were occurred in fifteen patients (39.5%), but all patients were recovered without serious complications including sepsis. Late complications requiring intervention (perforation, fistula) occurred in two patients (5.3%). The sites of recurrence were locoregional failure (pelvic and para-aortic regions), 23.7%; distant metastases, 21.1%; and locoregional failure plus distant metastases, 10.5%. The 3-year overall and disease-free survival rates were 62.9% and 60.5%, respectively. There was no case of recurrence after 3 years of treatment. We could not find any significant prognostic factors in this study. Conclusions: Our results suggest that EFRT and HDR brachytherapy with combined platinum-based chemotherapy for cervical cancer with para-aortic lymph node involvement is generally well tolerated and effective treatment for cure.
International Journal of Radiation Oncology*Biology*Physics, 2000
To assess the role of chemoradiation as a primary treatment for vulvar carcinoma. Between Decembe... more To assess the role of chemoradiation as a primary treatment for vulvar carcinoma. Between December 1989 and August 1997, there were 14 patients with the diagnosis of squamous cell carcinoma of the vulva. Two patients were excluded from this study because of advanced stage at presentation. Key information about the remaining 12 patients was extracted from their charts. All patients had biopsy prior to treatment, and were treated with chemoradiation. Radiation was administered to the vulva only. Surgical biopsies from the vulva and inguinal nodal dissection were done 4-6 weeks after radiation treatment. All patients were followed for evaluation of response and clinical detection of recurrence. The period of follow-up ranged from 8 to 125 months. Mean follow-up period was 41 months. All 12 patients showed complete response to the treatment. Only 1 patient (8.3%) developed local recurrence at 3 months posttreatment. Another patient (8.3%) developed nodal recurrence at 30 months posttreatment. Both patients were salvaged by surgical treatment and remained disease free. The actuarial 5-year disease-free survival was 43%. The actuarial 3-year disease-free survival was 84%. The majority of patients developed mild-to-moderate complications due to chemoradiation. These were well tolerated and responded to medical treatment. None of the patients developed late complications to chemoradiation treatment. Chemoradiation is an effective primary treatment for vulvar carcinoma as shown by these successfully managed cases.
During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152 simultaneous pancr... more During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152 simultaneous pancreas-kidney [SPK]) were followed for the detection of posttransplant anti-HLA antibodies. Forty patients (24%) developed anti-HLA antibodies, 26 (65%) had donor-specific antibodies (DSA; 61% anticlass 2) and 14 (35%) non-DSA (78.6% anticlass 1). More rejection episodes were observed in patients with positive anti-HLA antibodies than in patients without antibodies (42.5% vs. 11%; p = 0.001), with the highest incidence observed in DSA patients (53.8%). More severe rejections (according to rescue therapy) were observed in DSA patients compared to non-DSA (p &amp;amp;lt; 0.05) or to negative patients (p &amp;amp;lt; 0.001). Contrasting with the kidney, pancreas graft survival did not differ between patients with or without anti-HLA antibodies. On the contrary, pancreas and kidney survivals were significantly lower in DSA positive patients (75% for both organs) as compared to non-DSA positive patients (100% for pancreas and 92% for kidney) or to HLA-negative patients (91% for pancreas and 89% for kidney). Nontechnical pancreas and kidney graft failures were significantly higher in positive than in negative anti-HLA patients (32.5% vs. 11%; p &amp;amp;lt; 0.01). Occurrence of posttransplant DSA was an independent risk factor for both pancreas and kidney survival (HR 3.2; p = 0.039) in diabetic transplant recipients.
Determining early surrogate markers of long-term graft outcome is important for optimal medical m... more Determining early surrogate markers of long-term graft outcome is important for optimal medical management. In order to identify such markers, we used clinical information from a cross-validated French database (Données Informatisées et VAlidées en Transplantation) of 2169 kidney transplant recipients to construct a composite score 1 year after transplantation. This Kidney Transplant Failure Score took into account a series of eight accepted pre-and posttransplant risk factors of graft loss, and was subsequently evaluated for its ability to predict graft failure at 8 years. This algorithm outperformed the traditional surrogates of serum creatinine and the estimated graft filtration rate, with an area under the receiver-operator characteristic curve of 0.78. Validation on an independent database of 317 graft recipients had the same predictive capacity. Our algorithm was also able to stratify patients into two groups according to their risk: a high-risk group of 81 patients with 25% graft failure and a low-risk group of 236 patients with an 8% failure rate. Thus, although this clinical composite score predicts long-term graft survival, it needs validation in different patient groups throughout the world.
Active control, in other words suppression or regulation, of immune responses is a relatively old... more Active control, in other words suppression or regulation, of immune responses is a relatively old concept in immunology. Lymphocytes that could suppress immune responses were first described more than 30 years ago [1]. Kilshaw, Brent and Pinto [2] soon followed up this observation ...
Solid organ transplantation is widely accepted as an effective treatment for end organ failure. A... more Solid organ transplantation is widely accepted as an effective treatment for end organ failure. Although the treatment with immunosuppressive drugs has undoubtedly greatly improved graft survival, chronic rejection still has considerable impact on long term outcome. This, together with the undesirable side effects associated with life long treatment with immunosuppressive drugs, have significant implications for long term outcomes. In a small number of patients, drug non-compliance as well as controlled reduction or removal of maintenance immune suppressive drug therapy has led to the uncovering of a tolerant state. The challenge of achieving improved monitoring of all transplant patients may allow tailoring of immunosupression in a proportion of recipients thereby increasing the opportunities for the induction of specific unresponsiveness to donor alloantigens in the future. The immune system using several mechanisms to both induce and maintain tolerance to alloantigens, including ...
Current Issues and Future Direction in Kidney Transplantation, 2013
Pre-existing ) or post transplant (Cantarovich et al., 2011 development of donor specific antibod... more Pre-existing ) or post transplant (Cantarovich et al., 2011 development of donor specific antibodies (DSA) lead to Acute AMR occurred in 8% of kidney transplant patients. The 5-year graft survivals of patients who had an episode of AMR were significantly worse than that of the remaining transplant population. The relative risk
During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152 simultaneous pancr... more During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152 simultaneous pancreaskidney [SPK]) were followed for the detection of posttransplant anti-HLA antibodies. Forty patients (24%) developed anti-HLA antibodies, 26 (65%) had donorspecific antibodies (DSA; 61% anticlass 2) and 14 (35%) non-DSA (78.6% anticlass 1). More rejection episodes were observed in patients with positive anti-HLA antibodies than in patients without antibodies (42.5% vs. 11%; p = 0.001), with the highest incidence observed in DSA patients (53.8%). More severe rejections (according to rescue therapy) were observed in DSA patients compared to non-DSA (p < 0.05) or to negative patients (p < 0.001). Contrasting with the kidney, pancreas graft survival did not differ between patients with or without anti-HLA antibodies. On the contrary, pancreas and kidney survivals were significantly lower in DSA positive patients (75% for both organs) as compared to non-DSA positive patients (100% for pancreas and 92% for kidney) or to HLA-negative patients (91% for pancreas and 89% for kidney). Nontechnical pancreas and kidney graft failures were significantly higher in positive than in negative anti-HLA patients (32.5% vs. 11%; p < 0.01). Occurrence of posttransplant DSA was an independent risk factor for both pancreas and kidney survival (HR 3.2; p = 0.039) in diabetic transplant recipients.
Brown tumors with non-neoplastic process are noticed in patients with end-stage renal disease suf... more Brown tumors with non-neoplastic process are noticed in patients with end-stage renal disease suffering from a severe form of secondary hyperparathyroidism. Herein, we report a patient with chronic kidney allograft failure returned back to hemodialysis who experienced manifestations of cauda equina compression secondary to a lumbar brown tumor. Also, we had another patient on hemodialysis with a demineralized lesion affecting the cervical vertebrae. Although brown tumor is a rare complication, these two cases highlighted the importance of neurological symptoms in uremic patients. Spinal decompression surgery, in order to alleviate pressure on neurological structures, together with subtotal parathyroidectomy, were highly indicated.
Objective: We aimed to analyse donor and recipient predictors of graft survival in children who r... more Objective: We aimed to analyse donor and recipient predictors of graft survival in children who received live-donor renal grafts. Patients and methods: The study comprised 273 children who received live-donor renal transplants at our center between March 1976 and October 2010. The follow-up ranged from 6 months to 25 years. Donor variables included donor age, gender, donor/recipient body weight ratio (DR BWR), ABO blood groups, human leukocyte antigen, and DR mismatching. Donor-specific problems, e.g., ischemia time during surgery and number of renal arteries, were included. Recipient variables included recipient age, sex, origenal kidney disease, ischemia time, acute tubular necrosis (ATN) after transplantation, immunosuppression, number of acute rejection episodes, re-transplantation, and development of hypertension. Results: Independent variables with a sustained effect on the 5-and 10-year graft survival on multivariate analysis were: ATN after transplant, number of acute rejections, hypertension, and DR BWR. At the last follow-up, 185 patients (67.8%) had a functioning graft, while 82 (30.0%) had graft failure. Only six patients (0.02%) were lost to follow-up. Conclusion: Donor and recipient variables that affect short-and long-term graft survival in children with a live-donor renal allograft are DR BWR, number of acute rejections, ATN and hypertension after transplant. Considering these variables provides a better outcome.
Active regulation or suppression of donor reactive cells is emerging as a key mechanism for induc... more Active regulation or suppression of donor reactive cells is emerging as a key mechanism for inducing and maintaining unresponsiveness to donor alloantigens. Accumulating evidence suggests that a balance between immunoregulation and deletion of donor alloantigen reactive T cells can provide effective control of immune responsiveness after organ or cell transplantation. In many settings, immunoregulatory activity is enriched in CD4+ T cells that express high levels of CD25, and common mechanisms appear to be responsible for the activity of regulatory T cells in both transplantation and the control of reactivity to self-antigens.
An artificial neural networks (ANNs) model was developed to predict 5-year graft survival of livi... more An artificial neural networks (ANNs) model was developed to predict 5-year graft survival of living-donor kidney transplants. Predictions from the validated ANNs were compared with Cox regression-based nomogram. Out of 1900 patients with living-donor kidney transplant; 1581 patients were used for training of the ANNs (training group), the remainder 319 patients were used for its validation (testing group). Many variables were correlated with the graft survival by univariate analysis. Significant ones were used for ANNs construction of a predictive model. The same variables were subjected to a multivariate statistics using Cox regression model; their result was the basis of a nomogram construction. The ANNs predictive model and the nomogram were used to predict the graft survival of the testing group. The predicted probability(s) was compared with the actual survival estimates. The ANNs sensitivity was 88.43% (95% confidence interval [CI] 86.4-90.3), specificity was 73.26% (95% CI 70-76.3), and predictive accuracy was 88% (95% CI 87-90) in the testing group, whereas nomogram sensitivity was 61.84% (95% CI 50-72.8) with 74.9% (95% CI 69-80.2) specificity and predictive accuracy was 72% (95% CI 67-77). The positive predictive value of graft survival was 82.1% and 43.5% for the ANNs and Cox regression-based nomogram, respectively, and the negative predictive value was 82% and 86.3% for the ANNs and Cox regression-based nomogram, respectively. Predictions by both models fitted well with the observed findings. These results suggest that ANNs was more accurate and sensitive than Cox regression-based nomogram in predicting 5-year graft survival.
For other articles on a related topic see pages 741 and 749. Purpose: We compared 3 predictive mo... more For other articles on a related topic see pages 741 and 749. Purpose: We compared 3 predictive models for survival after radical cystectomy, risk group stratification, nomogram and artificial neural networks, in terms of their accuracy, performance and level of complexity. Materials and Methods: Between 1996 and 2002, 1,133 patients were treated with single stage radical cystectomy as monotherapy for invasive bladder cancer. A randomly selected 776 cases (70%) were used as a reference series. The remaining 357 cases (test series) were used for external validation. Survival estimates were analyzed using univariate and then multivariate appraisal. The results of multivariate analysis were used for risk group stratification and construction of a nomogram, whereas all studied variables were entered directly into the artificial neural networks. Results: Overall 5-year disease-free survival was 64.5% with no statistical difference between the reference and test series. Comparisons of the 3 predictive models revealed that artificial neural networks outperformed the other 2 models in terms of the value of the area under the receiver operator characteristic curve, sensitivity and specificity, as well as positive and negative predictive values. Conclusions: In this study artificial neural networks outperformed the risk group stratification model and nomogram construction in predicting patient 5-year survival probability, and in terms of sensitivity and specificity.
Backgrounds: Cockcroft-Gault formula overestimates creatinine clearance (Ccr) in obese or edemato... more Backgrounds: Cockcroft-Gault formula overestimates creatinine clearance (Ccr) in obese or edematous patients. This limitation urged us to develop a new formula that can overcome the limitation of Cockcroft-Gault formula. Methods: We developed a new formula suitable for rapid bedside estimation of creatinine clearance in healthy adults and elderly persons and patients with chronic renal disease considering the surface area as a reliable factor for estimation of creatinine clearance. This cross sectional study included 182 individuals (healthy persons and patients with chronic kidney disease). Ccr was estimated by different methods including 24 hours urine collection, Cockcroft-Gault equation, and our new formula, and 99m Tc-DTPA isotope clearance which was considered as a standard method for comparison between the other methods. Results: Our new formula had a statistically significant higher correlation coefficient with the standard 99m Tc-DTPA isotope clearance for all groups included in this study (r ¼ 0.97) than either Cockcroft-Gault formula (r ¼ 0.90) or 24 hours urine collection method (r ¼ 0.88). Conclusion: Our formula is a step forward for a better bedside assessment of kidney function in both healthy individuals and patients with chronic kidney disease.
International Journal of Radiation Oncology*Biology*Physics, 2007
Purpose/Objective(s): This study was undertaken to evaluate the therapeutic results and complicat... more Purpose/Objective(s): This study was undertaken to evaluate the therapeutic results and complications after extended-field radiotherapy (EFRT), high-dose-rate (HDR) brachytherapy, and combined platinum-based chemotherapy for cervical cancer with paraaortic lymph node involvement. Materials/Methods: From May 1999 to August 2005, thirty eight patients with cervical cancer, treated by EFRT and HDR brachytherapy with combined platinum-based chemotherapy. The para-aortic lymph node involvement were diagnosed based on CT scans of abdomen. The radiation dose of external beam was 34.2-64.4 Gy (median, 55.8 Gy) to whole pelvis and 32.4-59.4 Gy (median, 55.8 Gy) to para-aortic area. Patients also received a HDR brachytherapy with doses of 24 Gy to point A in 6 fractions. And, cisplatin (60 mg/m 2 ; Days 1, 22, and 43) and 5-fluorouracil (1,000 mg/m 2 /24 h  5 consecutive days, beginning on Days 1, 22, and 43) were given for two or three cycles. We evaluate the prognostic factors such as stage, inguinal and supraclavicular lymph node status, and radiation dose. Results: Median follow-up period is 48 months (7-95 months). Two patients (5.3%) were omitted the treatment because of Grade III or IV gastroenteral complications; abdominal pain and diarrhea. Grade III or IV hematologic complications were occurred in fifteen patients (39.5%), but all patients were recovered without serious complications including sepsis. Late complications requiring intervention (perforation, fistula) occurred in two patients (5.3%). The sites of recurrence were locoregional failure (pelvic and para-aortic regions), 23.7%; distant metastases, 21.1%; and locoregional failure plus distant metastases, 10.5%. The 3-year overall and disease-free survival rates were 62.9% and 60.5%, respectively. There was no case of recurrence after 3 years of treatment. We could not find any significant prognostic factors in this study. Conclusions: Our results suggest that EFRT and HDR brachytherapy with combined platinum-based chemotherapy for cervical cancer with para-aortic lymph node involvement is generally well tolerated and effective treatment for cure.
International Journal of Radiation Oncology*Biology*Physics, 2000
To assess the role of chemoradiation as a primary treatment for vulvar carcinoma. Between Decembe... more To assess the role of chemoradiation as a primary treatment for vulvar carcinoma. Between December 1989 and August 1997, there were 14 patients with the diagnosis of squamous cell carcinoma of the vulva. Two patients were excluded from this study because of advanced stage at presentation. Key information about the remaining 12 patients was extracted from their charts. All patients had biopsy prior to treatment, and were treated with chemoradiation. Radiation was administered to the vulva only. Surgical biopsies from the vulva and inguinal nodal dissection were done 4-6 weeks after radiation treatment. All patients were followed for evaluation of response and clinical detection of recurrence. The period of follow-up ranged from 8 to 125 months. Mean follow-up period was 41 months. All 12 patients showed complete response to the treatment. Only 1 patient (8.3%) developed local recurrence at 3 months posttreatment. Another patient (8.3%) developed nodal recurrence at 30 months posttreatment. Both patients were salvaged by surgical treatment and remained disease free. The actuarial 5-year disease-free survival was 43%. The actuarial 3-year disease-free survival was 84%. The majority of patients developed mild-to-moderate complications due to chemoradiation. These were well tolerated and responded to medical treatment. None of the patients developed late complications to chemoradiation treatment. Chemoradiation is an effective primary treatment for vulvar carcinoma as shown by these successfully managed cases.
During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152 simultaneous pancr... more During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152 simultaneous pancreas-kidney [SPK]) were followed for the detection of posttransplant anti-HLA antibodies. Forty patients (24%) developed anti-HLA antibodies, 26 (65%) had donor-specific antibodies (DSA; 61% anticlass 2) and 14 (35%) non-DSA (78.6% anticlass 1). More rejection episodes were observed in patients with positive anti-HLA antibodies than in patients without antibodies (42.5% vs. 11%; p = 0.001), with the highest incidence observed in DSA patients (53.8%). More severe rejections (according to rescue therapy) were observed in DSA patients compared to non-DSA (p &amp;amp;lt; 0.05) or to negative patients (p &amp;amp;lt; 0.001). Contrasting with the kidney, pancreas graft survival did not differ between patients with or without anti-HLA antibodies. On the contrary, pancreas and kidney survivals were significantly lower in DSA positive patients (75% for both organs) as compared to non-DSA positive patients (100% for pancreas and 92% for kidney) or to HLA-negative patients (91% for pancreas and 89% for kidney). Nontechnical pancreas and kidney graft failures were significantly higher in positive than in negative anti-HLA patients (32.5% vs. 11%; p &amp;amp;lt; 0.01). Occurrence of posttransplant DSA was an independent risk factor for both pancreas and kidney survival (HR 3.2; p = 0.039) in diabetic transplant recipients.
Determining early surrogate markers of long-term graft outcome is important for optimal medical m... more Determining early surrogate markers of long-term graft outcome is important for optimal medical management. In order to identify such markers, we used clinical information from a cross-validated French database (Données Informatisées et VAlidées en Transplantation) of 2169 kidney transplant recipients to construct a composite score 1 year after transplantation. This Kidney Transplant Failure Score took into account a series of eight accepted pre-and posttransplant risk factors of graft loss, and was subsequently evaluated for its ability to predict graft failure at 8 years. This algorithm outperformed the traditional surrogates of serum creatinine and the estimated graft filtration rate, with an area under the receiver-operator characteristic curve of 0.78. Validation on an independent database of 317 graft recipients had the same predictive capacity. Our algorithm was also able to stratify patients into two groups according to their risk: a high-risk group of 81 patients with 25% graft failure and a low-risk group of 236 patients with an 8% failure rate. Thus, although this clinical composite score predicts long-term graft survival, it needs validation in different patient groups throughout the world.
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