Three-year Patient Survival Research Articles

Short- and Long-Term Outcomes with the Use of Kidneys and Livers Donated after Cardiac Death

The shortage of deceased donor kidneys and livers for transplantation has prompted the use of organs from donors deceased after cardiac death (DCD). We used the UNOS database to examine patient and graft survival following transplantation of DCD organs compared to those following grafts from donors deceased after brain death (DBD; for livers, grafts from donors < 60 years old were labeled '< 60 yrs'). Of 44035 deceased donor kidney transplant recipients, 1177 (3%) received a DCD kidney. There was no difference in patient or graft survival at 5 years (DCD vs. DBD: 81.3% vs. 80.8% and 66.9% vs. 66.5%; p = 0.70 and p = 0.52 respectively). Of 24688-deceased donor liver transplant recipients, 345 (1.4%) were from DCD donors and 20289 (82%) were from '< 60 yrs' DBD donors. Three-year patient and graft survival were inferior in the DCD group (DCD vs. '< 60 yrs' DBD: 77% vs. 80% and 65% vs. 75%; p = 0.016 and p < 0.0001 respectively) but were comparable to current alternatives, '>/= 60 yrs' DBD livers (donor age >/= 60) and split livers. DCD livers are a reasonable option when death is imminent. Our study demonstrates good outcomes using DCD kidneys and livers and encourages their use.

Successful Transplantation of Kidneys from Deceased Donors with Acute Renal Failure: Three-Year Results

Kidneys from deceased donors with acute renal failure (ARF) are generally not accepted for transplantation because of the expected poor outcome. This prospective study examined the utilization of kidneys from donors with ARF for transplantation and the outcomes. Fifty-five kidneys from donors with ARF were transplanted. The outcome was compared with concurrent and matched 55 recipients of standard criteria donor (SCD) kidneys and 55 expanded criteria donor (ECD) kidneys. ARF kidneys were accepted from donors aged <50 years, a negative history for kidney disease, and a negative pretransplant biopsy for chronic structural changes. The immunosuppression was similar in all three groups. The outcome measurements included three-year patient and graft survival, biopsy-proven acute rejection (BPAR), subclinical acute rejection (SCAR), and chronic allograft nephropathy (CAN), serum creatinine, and creatinine clearance. Three-year patient and graft survival was 90% and 90% in ARF group, 100% and 89% in SCD group and 83% and 66% in ECD group. BPAR and SCAR were comparable in the groups but CAN was significantly higher in ECD group. Mean serum creatinine levels were 1.9+/-1.1, 1.9+/-0.9, and 2.2+/-1.3 mg/dl and mean creatinine clearances were 66+/-15, 68+/-14, and 58+/-10 mls/minute in ARF, SCD, and ECD groups, respectively (SCD and ARF vs. ECD P = 0.04). Transplantation of kidneys from selected deceased donors with ARF provides comparable survival and function compared to kidneys from non-ARF donors and may be considered for transplantation to expand the donor pool to overcome the current acute shortage of kidneys.

Long-Term Survival in Patients Presenting With Type B Acute Aortic Dissection

Follow-up survival studies in patients with acute type B aortic dissection have been restricted to a small number of patients in single centers. We used data from a contemporary registry of acute type B aortic dissection to better understand factors associated with adverse long-term survival. We examined 242 consecutive patients discharged alive with acute type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2003. Kaplan-Meier survival curves were constructed, and Cox proportional hazards analysis was performed to identify independent predictors of follow-up mortality. Three-year survival for patients treated medically, surgically, or with endovascular therapy was 77.6+/-6.6%, 82.8+/-18.9%, and 76.2+/-25.2%, respectively (median follow-up 2.3 years, log-rank P=0.61). Independent predictors of follow-up mortality included female gender (hazard ratio [HR],1.99; 95% confidence interval [CI], 1.07 to 3.71; P=0.03), a history of prior aortic aneurysm (HR, 2.17; 95% CI, 1.03 to 4.59; P=0.04), a history of atherosclerosis (HR, 2.48; 95% CI, 1.32 to 4.66; P<0.01), in-hospital renal failure (HR, 2.55; 95% CI, 1.15 to 5.63; P=0.02), pleural effusion on chest radiograph (HR, 2.56; 95% CI, 1.18 to 5.58; P=0.02), and in-hospital hypotension/shock (HR, 12.5; 95% CI, 3.24 to 48.21; P<0.01). Contemporary follow-up mortality in patients who survive to hospital discharge with acute type B aortic dissection is high, approaching 1 in every 4 patients at 3 years. Current treatment and follow-up surveillance require further study to better understand and optimize care for patients with this complex disease.

10 INVITED RECIST version 2.0

For the first time in decades, patients with difficult-to-treat cancers such as advanced stage metastatic melanoma are being offered a glimpse of hope in the form of immunotherapies. By targeting factors that foster the development and maintenance of an immunosuppressive microenvironment within tumors, these therapies release the brakes on the host’s own immune system; allowing cure of disease. Indeed, phase III clinical trials have revealed that therapies such as ipilimumab and pembrolizumab which target the CTLA4 and PD-1 immune checkpoints, respectively, have raised the three-year survival of patients with melanoma to ∼70%, and overall survival (>5 years) to ∼30%. Despite this unprecedented efficacy, many patients fail to respond, and more concerning, some patients who demonstrate encouraging initial responses to immunotherapy, can acquire resistance over time. There is now an urgent need to identify mechanisms of resistance, to predict outcome and to identify targets for combination therapy. Here, with the aim of guiding future combination trials that target specific resistance mechanisms to immunotherapies, we have summarised and discussed the current understanding of mechanisms promoting resistance to anti-PD1/PDL1 therapies, and how combination strategies which target these pathways might yield better outcomes for patients.

Drug-Eluting Stents Versus Coronary Artery Bypass Grafting in Patients with Diabetes Mellitus

Reduction of restenosis and reinterventions was recently reported with percutaneous interventions (PCI) with drug-eluting stents (Cypher). This study compares results of Cypher (Cordis, Miami Lakes, FL) stenting and surgical revascularization in diabetic patients. From January 2002 to January 2005, 518 consecutive diabetic patients underwent myocardial revascularization; 176 by PCI incorporating Cyphers and 342 treated surgically. Single-vessel patients in the surgical group were treated with the left internal thoracic artery (ITA) and most multivessel patients were treated with two ITAs. After matching for age, sex, right system revascularization, and extent of coronary disease, two groups (86 patients each) were used to compare the two revascularization modalities. Both groups were similar; however, left main, poor ejection fraction, total occlusion, and bifurcation lesions were more prevalent in the surgical group, and in-stent restenosis in the PCI group. The mean number of coronary vessels treated was higher in the surgical group (2.05 vs 1.6, p < 0.001). Mean follow-up was 18 months. Overall mortality (early and late) was 2.3% and 3.5% in the Cypher and surgical groups, respectively (p = 0.65). Angina returned in 39.5% of the Cypher group and 15.1% of the surgical group, p < 0.001. There were 25 reinterventions in the Cypher group compared with five in the surgical group (p = 0.010). The Cox proportional hazard model revealed assignment to the Cypher group to be the only independent predictor of reangina (odds ratio [OR] 3.26, 95% confidence interval [CI] 1.63 to 6.53) and reintervention (OR 4.17, 95% CI 1.92 to 20.83). Despite improved results of PCI with Cyphers, midterm clinical outcome of diabetic patients treated surgically is better.

Liver Transplantation: Experience With Our First 100 Cases

Objectives Our goal was to evaluate the results of the first 100 liver transplants performed in our institution. Methods We retrospectively analyzed the first 100 liver transplants undertaken in adults from November 2001 to August 2005. Results The mean age of the recipients was 50 years (20 to 69) and 73% were men. The mean waiting time was 35 days. The mean age of the donors was 60 years (15 to 87), and 60% were men. One-year patient and graft survival rates were 93% and 90%, respectively. Three-year patient and graft survival rates were 85% and 82%, respectively. The need for retransplantation was 3%. Surgical complications included hepatic artery stenoses, 2%; hepatic artery thromboses, 2%; biliary leaks, 6%; and biliary stenoses, 14%. Conclusions These results are no different from the overall results for liver transplantation in Spain during the same period.

PGC-1 expression level in human colorectal cancer: A predictor of lymph node metastasis

3616 Background: Previous study showed that the expression of peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ coactivator-1 (PGC-1) was correlated with clinical outcome in breast cancer. However, no published data are available about the biological and clinical significance of PGC-1 in colorectal cancer. Thus, our aim was to explore the expression of PPARγ and PGC-1 in colorectal cancer as well as their association with other clinicopathological features, and to evaluate the role of PPARγ and PGC-1 as a prognostic indicator of colorectal cancer. Methods: We have investigated the presence of PPARγ and PGC-1 in human colorectal cancer tissues and adjacent normal tissues from 108 primary colorectal cancer patients by immunohistochemistry. The correlation between their expression and clinicopathologic features was investigated. Three-year overall survival of patients with different expression of PPARγ and PGC-1 were analyzed by the Kaplan-Meier method. Results: No significant correlation was found between PPARγ expression and age at surgery, gender, histopathologic differentiation, depth of infiltration, relapse, and Dukes’ stage. No significant correlation was found between PGC-1 expression and age at surgery, the histopathologic differentiation, the depth of infiltration, and relapse. However, PGC-1 expression was closely related to Duke’s stage and nodal metastasis (p=0.024 and p=0.020, respectively). Survival analysis showed that the PGC-1-positive group has a reduced overall survival (p=0.0367). Conclusions: Based on our results, PGC-1 may be valuable marker of nodal metastasis and represent a biomarker of poor prognosis in colorectal cancer. No significant financial relationships to disclose.

Safety and Efficacy of Steroid Withdrawal Two Days after Kidney Transplantation: Analysis of Results at Three Years

Chronic steroid therapy in spite of myriad side effects is widely used in kidney transplantation. This prospective controlled study evaluated safety and efficacy of steroid withdrawal at 2 days in kidney recipients monitored by surveillance biopsy. In all, 300 kidney recipients were studied; 150 in second-day steroid withdrawal group and 150 in steroid treated group (control group). Immunosuppression was basiliximab induction and maintenance was a calcineurin inhibitor and mycophenolate mofetil or sirolimus. Biopsy-proven acute rejection (BPAR) was treated by methylpredisolone. Surveillance biopsies were completed to evaluate subclinical acute rejection (SCAR) and chronic allograft nephropathy (CAN). Primary end point was acute rejection. Three-year patient and graft survival, new onset diabetes mellitus (NODM), serum creatinine and creatinine clearance were evaluated. Acute rejection was diagnosed in 14% in control group and 16% in steroid withdrawal group. Three-year patient and graft survival was 89% and 79% in control and 91% and 78% in steroid withdrawal group. Serum creatinine and creatinine clearance was 1.9+/-0.8 and 59+/-11 in control group and 1.8+/-0.9 mg/dl and 61+/-10 mls/minute in steroid withdrawal group. Incidence of SCAR and progression of CAN were comparable in the 2 groups. At 3-years NODM was diagnosed in 21% in control group and 4% in steroid withdrawal group (P<0.01). Two-day steroid withdrawal in kidney transplant recipients did not affect BPAR, SCAR, CAN, graft function and patient and graft survival compared to control group up to 3 years. NODM was significantly less in steroid withdrawal group. Two-day steroid withdrawal is safe and beneficial in kidney transplant recipients.

Pancreas transplantation: advantages of both enteric and bladder drainage combined in a two‐step approach

Although there is a tendency to perform enteric drainage of pancreas transplants in simultaneous pancreas-kidney (SPK) transplantation, bladder drainage is still preferable in pancreas transplantation alone (PTA) or after a previous kidney transplantation (PAK). Our hypothesis was that enteric conversion of a bladder drained pancreas is an effective and safe procedure. We studied the complication rate and physiological effects of enteric conversion in patients with primary bladder-drained SPK transplantation. We performed 51 enteric conversions in bladder-drained SPK transplant recipients. As we observed a low complication rate, with time enteric conversions were also performed for less strict and severe indications. The main indications for conversion were urological problems, metabolic complications and reflux-pancreatitis. The median transplantation-conversion interval was 12 months (range 2-40 months). Post-operative complications consisted of seven urinary tract infections, two low-grade superficial wound infections, one minor bleeding, one phlebitis and one paralytic ileus. In two patients, a relaparotomy was necessary. No graft rejection following enteric conversion was found. Long-term renal and pancreatic function were not affected by the enteric conversion. Three-year patient, kidney and pancreas survival rates after enteric conversion were 93, 97 and 93%, respectively (censored data). Enteric conversion after pancreas transplantation is an effective and safe procedure. Therefore, we suggest a policy of a two-step approach of primary bladder drainage followed by an enteric conversion of the pancreas in a selected group of SPK patients.

Immunosuppression for liver transplantation in HCV-infected patients: Mechanism-based principles

We retrospectively analyzed 42 hepatitis C virus (HCV)-infected patients who underwent cadaveric liver transplantation under two strategies of immunosuppression: (1) daily tacrolimus (TAC) throughout and an initial cycle of high-dose prednisone (PRED) with subsequent gradual steroid weaning, or (2) intraoperative antithymocyte globulin (ATG) and daily TAC that was later space weaned. After 36 +/- 4 months, patient and graft survival in the first group was 18/19 (94.7%) with no examples of clinically serious HCV recurrence. In the second group, the three-year patient survival was 12/23 (52%), and graft survival was 9/23 (39%); accelerated recurrent hepatitis was the principal cause of the poor results. The data were interpreted in the context of a recently proposed immunologic paradigm that is equally applicable to transplantation and viral immunity. In the framework of this paradigm, the disparate hepatitis outcomes reflected different equilibria reached under the two immunosuppression regimens between the relative kinetics of viral distribution (systemically and in the liver) and the slowly recovering HCV-specific T-cell response. As a corollary, the aims of treatment of the HCV-infected liver recipients should be to predict, monitor, and equilibrate beneficial balances between virus distribution and the absence of an immunopathologic antiviral T-cell response. In this view, favorable equilibria were accomplished in the nonweaned group of patients but not in the weaned group. In conclusion, since the anti-HCV response is unleashed when immunosuppression is weaned, treatment protocols that minimize disease recurrence in HCV-infected allograft recipients must balance the desire to reduce immunosuppression or induce allotolerance with the need to prevent antiviral immunopathology.

Infectious Enteritis After Intestinal Transplantation: Incidence, Timing, and Outcome

The study reviews the incidence, timing, and outcome of infectious enteritis (IE) after intestinal transplantation (ITx). A retrospective review of all patients who underwent ITx at a single institution between 1991 and 2003 was undertaken using database and medical records. Standard statistical analyses were performed. Of 33 ITx recipients, 13 (39%) developed 20 culture- or biopsy-proven episodes of IE. Recipient demographics included the following: 10 males, median age 34 (10-585) months, 11 liver + intestine grafts, and two isolated intestine grafts. Infections were diagnosed a median of 76 days (32-1,800 days) after ITx. There were 14 viral (one cytomegalovirus, eight rotavirus, four adenovirus, one Epstein-Barr virus), three bacterial (Clostridium difficile), and three protozoal (one Giardia lamblia, two Cryptosporidium) infections. The bacterial infections tended to present earlier than the viral infections, and the most frequent presenting symptom was diarrhea. Complete resolution was achieved in 17 (94%) incidences with the appropriate antimicrobial or conservative therapy. It was interesting that there were seven rejection episodes documented by biopsy at the approximate time of diagnosis of IE. There were two graft losses: one because of adenoviral enteritis and one because of rejection after rotavirus enteritis. Three-year patient survival is 74% with no deaths directly attributable to IE. IE can occur in 39% of recipients after ITx. Viral agents are the cause in two thirds of the cases. With supportive care and appropriate treatment, resolution is possible in the majority of cases. Differentiating rejection and infection on histopathology can be difficult and relies on cultures and immunostaining.

Primary focal segmental glomerulosclerosis – Long‐term outcome after pediatric renal transplantation*

Recurrence of the primary disease is a significant issue in pediatric renal transplantation (RTx). According to data reported by the North American Pediatric Renal Transplantation Cooperative Study, patients with focal segmental glomerulosclerosis (FSGS) as primary renal disease have a recurrence rate of 30% after the first RTx. The relative risk of an early graft loss because of recurrent disease is increased to 1.6-3.1 in pediatric patients with FSGS. In a German open multicenter study, which was initiated to investigate mycophenolate mofetil (MMF) after pediatric RTx [Transplantation 2001:71:638, Transplantation 2003:75:454], patients with FSGS were evaluated for recurrence rate, risk factors for recurrence, long-term graft function, glomerular filtration rate and transplant survival. All patients received immunosuppression with MMF, cyclosporine A and prednisone without induction therapy. Renal function and survival data for FSGS patients were compared with the results of patients with other primary renal diseases within the same study population. Among 86 patients transplanted between 1996 and 1999 eight patients suffered from FSGS as primary disease. Recurrence was diagnosed in two of the eight patients. One out of these two patients lost his graft as a result of recurrence. Risk factors such as time between diagnosis and end stage renal disease (ESRD) and age at onset did not predict recurrence. A three-year patient survival in the FSGS group was 100%, graft survival 87% vs. 97% in the non-FSGS group. Acute rejections occurred in three out of eight FSGS patients and in 37 out of 78 among the non-FSGS group. Long-term renal function, calculated using mathematical modeling based on glomerular filtration rate (GFR) data during 3 yr after RTx, was similar in FSGS patients - including a patient who had recurrence with a functioning graft - and those without FSGS. In patients with FSGS, recurring disease after RTx remains an important cause of graft loss (one of two patients in this population) even under modern immunosuppressants. Nevertheless, the immunosuppressive regimen used was associated with a similar graft survival rate and long-term renal function of FSGS patients compared with patients with other primary diseases.

Posttransplant Lymphoproliferative Disorder: Significance of Central Nervous System Involvement

Background Few data exist regarding central nervous system (CNS) involvement in patients with posttransplant lymphoproliferative disorder (PTLD). The purpose of this study was to review the Israel Penn International Transplant Tumor Registry (IPITTR) experience with CNS involvement by PTLD. Methods Nine hundred ten PTLD cases from the United States were reported to the IPITTR and reviewed for CNS involvement. Results One hundred thirty-six transplant recipients with PTLD (15%) had CNS involvement. The highest incidence of CNS involvement occurred in pancreas (3 of 11; 27%) and kidney transplant recipients (76 of 429; 18%). Fifteen cases occurred in children and 121 cases in adults. For both children and adults, isolated CNS disease was associated with better survival when compared with multiple-site involvement (children: 29% vs 0%; adults: 12% vs 6%; P < .05). Three-year survival in PTLD patients with CNS involvement was 9.4% and without CNS involvement was 49.4% ( P < .01). Radiation therapy alone appeared to provide the best survival rates (25%). Conclusions CNS involvement in transplant recipients with PTLD carries an ominous prognosis; however, isolated CNS involvement has a better prognosis than CNS plus extracranial involvement. Radiation therapy alone provides the best results, but this may be a reflection of isolated CNS disease.

Living donor kidney transplantation in a Veterans Administration medical center

Background A shortage of organ donors remains the major limiting factor in kidney transplantation. Living donor renal transplantation, especially living-unrelated donors, may expand the donor pool by providing another source of excellent grafts. Methods Between 1983 and 2003, 109 living donor kidney transplants were performed. Potential donors were assessed with a standardized routine. Antithymocyte serum (N-ATS) and Basiliximab were used as induction agents. Sandimmune, Gengraf, Neoral, and Prograf were the main immunosuppressants with Immuran, Mycophenolate Mofetil, and steroids. Eighty-two percent of the recipients were from out of state. Results Seventy-eight percent of the living donors were from living-related donors and 22% were from living-unrelated donors. One- and three-year patient survival rates were 97.6% and 93.2% with 1- and 3-year graft survival rates of 93.2% and 88.3%, respectively. There were 6 delayed graft functions (5.5%), 16 acute cellular rejections (10%), and 10 chronic rejections (9%). Twelve patients died, 7 of them with a functioning graft. In the past 6 years (1997–2003), the number of living donor kidney transplants surpassed deceased donor kidney transplants. Conclusions Because of the limited number of cadaveric kidneys available for transplant, living donors represent a valuable source, and the use of living-unrelated donors has produced an additional supply of organs. In our program, the proportion of living donors used for kidney transplant is comparable with other non–Veterans Administration programs and the survival of these allografts appears to be superior to deceased donor kidney transplants.

Prognostic significance of lymph node metastasis found during pulmonary metastasectomy for extrapulmonary carcinoma

Background The prognostic significance of lymph node metastasis in cancer patients is well documented. Pulmonary metastasectomy in selected patients is associated with improved survival. Little is known about the prognostic significance of lymph node metastases found during pulmonary metastasectomy for extrapulmonary carcinoma metastatic to the lung. Methods The records of all patients who underwent pulmonary metastasectomy and complete mediastinal lymph node dissection for extrapulmonary carcinomas at our institution from November 1985 through July 1999 were reviewed. Results Eight hundred eighty-three patients underwent pulmonary metastasectomy. Of these, 70 patients (7.9%) (44 men, 26 women) had concomitant complete lymphadenectomy. Median age was 64 years (range, 33 to 83 years). Median time interval between primary tumor resection and metastasectomy was 34 months (range, 0 to 188 months). Wedge excision was performed in 46 patients, lobectomy in 16, both in 7, and pneumonectomy in 1. Lymph node metastases were found in 20 patients (28.6%) and were classified as intrapulmonary or hilar (N1) in 9, mediastinal (N2) in 8, and both in 3. There were no operative deaths. Median follow-up was 6.6 years (range, 1.1 to 14.6 years). Three-year survival for patients with negative lymph nodes was 69% as compared with only 38% for those with positive lymph nodes ( p < 0.001). Conclusions The presence of lymph node metastases at the time of pulmonary metastasectomy for extrapulmonary carcinoma has an adverse effect on prognosis. Complete mediastinal lymph node dissection should be considered at the time of pulmonary metastasectomy for carcinoma to improve staging and guide treatment.

Induction therapy with interleukin-2 receptor antagonist after intestinal transplantation is associated with reduced acute cellular rejection and improved renal function

Purpose To determine the effectiveness of induction immunotherapy with interleukin-2 receptor antagonists (IL2RA) after intestinal transplantation (IT). Methods A single-center, retrospective study was undertaken of all patients undergoing IT using existing medical records and database. Immunotherapy was either triple (standard maintenance triple therapy [SMTT]) or IL2RA [induction IL2RA plus SMTTx] or OKT3 [induction antilymphocyte preparations plus SMTTx]). Data was collected for the first 175 postoperative days. Outcomes included pretransplant renal function, posttransplant serum creatinine normalized to age (nl-sCR), rejection (ACR), and survival. Standard statistical analysis was undertaken. Results There were no significant differences in the groups: triple ( n = 10, median age 3.5 years, cGFR 106 ± 44 mL/min), IL2RA ( n = 13, median age 3.2 years, cGFR 101 ± 61 mL/min), OKT3 ( n = 4, median age 7.7 years, cGFR 104 ± 27 mL/min). nl-sCR was significantly ( P < .01) lower in IL2RA at most postoperative weeks. IL2RA had significantly fewer rejection and infectious episodes than the other two groups. Three-year patient survival was 92% in IL2RA versus 50% triple and OKT3. Conclusions IL2RA immunotherapy after IT is associated with a lower incidence of renal dysfunction as compared with historical controls. Furthermore, IL2RA therapy resulted in a lower incidence of rejection and improved survival. IL2RA should be considered in select patients undergoing IT.

Treatment Options for Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) or neuroendocrine carcinoma of the skin is uncommon, often aggressive, and has a poor prognosis. Complete surgical excision with histologic documentation of clear resection margins is recommended for the primary cancer. Retrospective analysis of clinical data strongly suggests that adjuvant radiotherapy improves local control of MCC, but no evidence has been published that it prolongs survival. Sentinel lymph node biopsy is a useful method of determining the need for regional lymph node dissection in stage I patients. Chemotherapy regimens similar to those employed for small cell carcinoma of the lung have been recommended for advanced MCC. Patients often show an initial response to therapy, but it is usually short-lived. The three-year overall survival for patients with MCC is 31%. Before an improvement in long-term survival can be realized, early detection, appropriate use of surgery and radiation therapy, and the development of effective systemic chemotherapy are required.

Survival after liver transplantation for hepatocellular carcinoma

Background Selection criteria for patients with hepatocellular carcinoma (HCC) suitable for liver transplantation (LT) include tumor size and number and vascular invasion. There has been a recent trend to expand the transplant criteria for HCC. We reviewed our experience to determine survival following LT based on tumor characteristics. Methods A retrospective analysis was performed on 72 patients with HCC who underwent LT between 1985 and July 2002. The Milan criteria were applied for LT candidacy for HCCs that were deemed unresectable from anatomical considerations and/or the severity of underlying cirrhosis. Patients were divided into four groups: group 1: patients with known HCC who satisfied the selection criteria ( n = 22); group 2: patients with known HCC that exceeded the criteria ( n = 17); group 3: patients with incidental HCC found at pathological examination of the explant ( n = 33); group 4: contemporary LT recipients without HCC ( n = 935). Results In the known HCC group, the interval between listing as status 2 and transplantation was 72.2 ± 133.6 days (median 23 days). Three-year patient survival was 80.2% in group 1, 35.8% in group 2, 63.2% in group 3, and 81.5% in group 4. In group 2 patients, the tumors were significantly larger, had more nodules, and were more often bilobar. In group 3, five (15%) exceeded the criteria mainly because of tumor size and four patients died within 3 years post-LT (three from tumor recurrence). Conclusion Liver transplantation for HCC yields acceptable survival in early-stage tumors, particularly if transplanted soon after listing. Long-term survival was inferior in patients with multiple tumors and tumors that were greater than 5 cm in diameter.

Controlling treatment allocation bias in a registry analysis when comparing calcineurin inhibitors

Previous analyses of outcomes between immunosuppressive regimens included data from the early years of tacrolimus use and frequently included all Tacrolimus- or cyclosporine-based regimens. We now evaluate clinical outcomes associated with only the two most commonly prescribed regimens—Tacrolimus (Tac)-mycophenylate mofetil (MMF) and cyclosporine (CsA)-MMF—using recent data reported to the UNOS Scientific Renal Transplant Registry. Data from living donor kidney transplants was chosen to minimize selection bias between treatment groups. Outcomes are reported only for recent years (1998 to 1999 with 3-year follow-up) because acute rejection rates were markedly higher in 1995 to 1997 compared to 1998 to 2000 (38% to 68% vs 21% to 32%) and clinical practice has evolved since 1995, which would have biased results in favor of more recent immunosuppressive regimens. Three-year graft survival for patients transplanted from 1998 to 1999 was significantly higher in living donor kidney transplant patients receiving CsA-MMF (91.1%, n = 4686) versus Tac-MMF (88.1%, n = 2393) ( P = .0006). After adjustment for potential confounding variables, risk of graft failure at 3 years was significantly higher in patients receiving Tac-MMF versus CsA-MMF for both all-cause graft failure (hazard ratio 1.28, 95%CI 1.09 to 1.49, P = .002) and death-censored graft failure (hazard ratio 1.25, 95%CI 1.05 to 1.49, P = .013). In view of the reduced rejection rate that has been reported using Tac-MMF versus CsA-MMF in clinical trials, it is possible that the nonimmunologic effects of calcineurin inhibitors may now play an increasingly important role in determining graft survival rates. In conclusion, this large-scale registry analysis demonstrates that graft survival in living donor kidney transplant patients is significantly improved using CsA-MMF compared to Tac-MMF.

Tumor response to induction chemoradiation: influence on survival after esophagectomy.

Preoperative chemoradiation is becoming standard of care for locally advanced esophageal cancer. The objective of this study was to determine if the degree of pathologic response to preoperative chemoradiation could predict survival and recurrence after resection in patients with adenocarcinoma of the distal esophagus. Between January 1998 and December 2001, 366 patients underwent esophagectomy for adenocarcinoma of the esophagus; 108 (30%) had induction chemoradiation prior to surgery. The records of these 108 patients were reviewed. Histologic examination of the resected specimens documented complete pathologic response (CR) in 24 patients (22%) and residual tumor (RT) in 84 (78%). Operative mortality was 3.7%. Follow-up was complete in all patients and ranged from 1 to 46 months (median, 11 months). Three-year survival for patients with CR was 64% as compared to 34% for patients with RT (P=0.17). Median survival for patients with CR has not yet been reached; however, median survival for patients with RT was 19 months. Three-year cancer free survival for patients with CR was 57% compared to 30% for patients with RT (P=0.03). While median survival free of recurrence for patients with CR has not yet been reached, median survival free of recurrence for patients with RT was 9 months. Complete pathologic response to induction chemoradiation is associated with improved early overall and disease-free survival following esophagectomy for adenocarcinoma of the distal esophagus. Because recurrent cancer still develops in many of these patients, even after complete pathologic response, the search for the optimal treatment continues.