Adverse effect of splenectomy on growth and survival with murine lymphosarcoma

Recent reports suggest that splenectomy may improve host resistance and inhibit solid tumor growth. The effect of splenectomy on lymphoid tumors in less clear. This study evaluates and compares the effect of splenectomy on tumor growth, therapy and survival in murine lymphosarcoma and mammary tumor. Gardner lymphosarcoma (5 x 10(5) cells) was implanted subcutaneously into 400 6C3HED mice (20 g). Two hundred mice underwent splenectomy 10 days previously. Animals were randomly placed into four groups. Group I (tumor alone) and Group II (splenectomy and tumor) received no further therapy. Group III (tumor) and Group IV (splenectomy and tumor) received cyclophosphamide (50 mg/kg/day x 3 days) beginning 10 days after implantation. The rate of implantation was similar in all groups (greater than 90%). Tumor growth was localized in controls, but was widespread in splenectomized mice. Survival analysis at 30 days showed an increased mortality in untreated mice (Group II) following splenectomy (p less than .02). Survival was (13/102) 12.75% Group I versus (8/103) 7.77% Group II. Survival was similar in mice receiving chemotherapy (36%) and was (p less than .001) greater than the untreated groups (12%). A similar protocol in mice with mammary tumor showed no differences between groups in tumor localization or survival postsplenectomy. These data suggest that splenectomy adversely affects localization and survival in murine lymphosarcoma but not in solid tumor. The variable effect of this operation on the natural history of lymphoid versus solid neoplasia questions the advisability of splenectomy in staging of patients with lymphosarcoma.     

The effect of kidney diseases on survival in liver transplant patients

Background  

Liver transplantation (LTx) is a life-saving procedure for patients with chronic end-stage liver disease or acute liver failure. It is well known that kidney diseases such as acute kidney injury (AKI) and chronic kidney disease (CKD) are highly prevalent in LTx patients. We aimed to assess the effect of kidney disease on survival in LTx patients.     

Dominant effect of histocompatibility on ten-year kidney transplant survival

Using actuarial methods, factors influencing long-term graft survival were examined in 33,594 recent (since 1974) kidney transplants reported to the University of California, Los Angeles, Transplant Registry. One- and 10-year graft-survival rates as well as late (from 3 through 10 years) graft-loss rates (half-lives) were determined. The donor-recipient relationship had the greatest influence on long-term graft survival. Transplants between HLA-identical siblings had graft-survival rates of 89% at 1 year and 68% at 10 years, compared with 76% and 43% for parental donors, and 58% and 26% for cadaver donor transplants, respectively. These differences were also evident from the graft half-lives, which were 22 years for HLA-identical sibling, 12 years for parental, and 8 years for cadaver donor allografts. In cadaver donor transplants, matching for HLA-A,B antigens had the greatest influence on long-term graft survival, with a 15% 10-year graft survival (39% vs. 24%) and 7-year half-life (14 vs. 7 years) advantage seen with the best (zero HLA-A,B mismatches) compared with the worst (4 HLA-A,B) cases, respectively. Some of the factors studied, such as transplant number and pretransplant transfusions, tended to influence the short- rather than long-term graft-survival rates. Others, including HLA-A,B matching, early graft function and the recipient's original disease, influenced both early and late graft survival. Over all, histocompatibility between donor and recipient had by far the greatest influence on the long-term success of renal allografts.     

高危患者肾移植长期存活的临床经验

目的 总结高危肾移植的临床经验,寻找提高长期存活率的方法.方法 将1991年4月至2008年12月我院治疗的921例高危.肾移植病例分为儿童组(34例)、再次移植(再植)组(169例)、高敏组(35例)、高龄组(297例)、糖尿病组(112例)和肝炎病毒感染或携带(肝炎)组(274例),并以807例普通肾移植受者作为对照组,对受者和移植.肾(人/肾)存活率、急性和慢性排斥反应(AR/CR)以及并发症的发生率进行回顾性分析.结果 再植组、高敏组以及肝炎组人/肾存活率均低于对照组(P＜0.05);高龄组仅患者生存率低于对照组(P＜0.05).同对照组相比,儿童组和高敏组等免疫性高危受者AR/CR发生率高(P＜0.05);高龄组、精尿病组以及肝炎组等非免疫性高危受者并发症的种类多,且发病率高.结论 减少AR发生,有利于提高免疫性高危患者的长期存活率;降低并发症发生率,有利于提高非免疫性高危患者的长期存活率.     

Adverse effect of splenectomy on recurrence in total gastrectomy cancer patients with perioperative transfusion

BACKGROUND: To investigate the interactions between splenectomy and perioperative transfusion in gastric cancer patients. METHODS: Medical records of 449 gastric cancer patients who had undergone total gastrectomies for curative intent between 1991 and 1995 were reviewed. The influence of splenectomy on tumor recurrence and survival both in the transfused and nontransfused patients were evaluated by univariate and multivariate analysis. RESULTS: The recurrence rate in the splenectomy group was 48.1% as compared with 22.6% in the spleen-preserved group among transfused patients (P=.001); it was 40.7% compared with 26.5% among nontransfused patients (P=.086). There was no significant difference in the mean survival between the splenectomy group and the spleen-preserved group in a subgroup analysis by stage. Multivariate analysis identified splenectomy as an independent risk factor for recurrence but not as a predictor for survival among transfused patients. CONCLUSIONS: Splenectomy does not appear to abrogate the adverse effect of perioperative transfusion on prognosis in gastric cancer patients. Moreover, it may increase postoperative recurrence in transfused patients.     

Initial survival data of kidney transplant patients with pre-transplant monoclonal gammopathy

Soltero L, Carbajal H, Xu J, McCarthy J, Suki WN, Gaber AO, Adrogué HE. Initial survival data of kidney transplant patients with pre‐transplant monoclonal gammopathy.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01539.x.
© 2011 John Wiley & Sons A/S. Abstract: Background: Monoclonal gammopathy of undetermined significance (MGUS) is the presence of a serum monoclonal protein at a concentration of <3 g/dL without evidence of lymphoproliferative disease or organ damage. The prevalence of MGUS in kidney transplantation (KT) candidates is unknown. The present is a retrospective report of patients who underwent evaluation for a KT and were found to have MGUS at our center. Methods: All transplant candidates found to have MGUS between the years 2000 and 2007 were included. Variables were collected. Patients with MGUS that received a KT were compared with patients with MGUS that were not transplanted. Results: Of a total of 1215 KT candidates, 34 were found to have MGUS during the KT evaluation. Nine patients with MGUS were transplanted. Myeloma or lymphoproliferative disease was not observed. Following transplantation, the MGUS group had a lower survival than the non‐transplanted group. However, survival from the time of MGUS diagnosis was not different between the transplanted and non‐transplanted MGUS groups. Conclusions: In this group, transplantation did not confer a survival benefit. It is our hope that these initial data will serve as a platform for future studies. We suggest MGUS screening in all patients older than 50 yr of age undergoing evaluation for transplantation.     

The influence of HLA mismatches and immunosuppression on kidney graft survival: an analysis of more than 1300 patients

New immunosuppressive drugs used in kidney transplantation decreased the incidence of acute rejection. It was hypothesized that, with their power, the importance of HLA matching was decreased. To evaluate the influence of HLA matching, immunosuppression, and other possible risk factors, we analyzed data of 1314 consecutive deceased donor kidney transplantation. We divided the patient population into 4 cohorts, according to the era of transplantation: era 1, before 1990, azathioprine (Aza) and cyclosporine (Csa) no microemulsion; era 2, between 1990 and 1995, Csa microemulsion; era 3, between 1996 and 2000, wide use of mycophenolate mofetil (MMF) and anti-thymocyte globulin (ATG); and era 4, after 2000, marked by sirolimus and tacrolimus (TAC) use. Multivariate analysis compared death-censored graft survival. Using as reference the results obtained with 0 HLA mismatches, we verified, during era 1 and era 2, an increased risk of graft loss for all of the subgroups with HLA mismatch >0. However, during era 3 and era 4, the number of HLA mismatches did not influence graft survival. Although acute rejection and delayed graft function, which decreased in the later periods, remained as prognostic factors for graft loss. Considering the immunosuppressive protocol with Csa+Aza+Pred as reference, protocols used after 1995 with Pred+Csa+ATG, with Pred+Csa+MMF, and with Pred+Tac+MMF presented better survival results. Results showed that the significance of HLA matching decreased while the results improved with the new immunosuppressant drugs. These observations support the hypothesis that the weakened importance of HLA matching may be a consequence of the increasing efficacy of the immunosuppression.     

Adverse effect of splenectomy in experimental peritonitis

Patients undergoing splenectomy have increased operative morbidity and mortality, especially when associated with gastrointestinal surgery or injury. This present study was designed to assess the effect of splenectomy on mortality in a polymicrobial fecal peritonitis model and evaluate therapy with antibiotic (cefoxitin) or immunomodulation (glucan). Human stool-barium (0.15 cc) was placed in the peritoneum of Sprague-Dawley rats at the time of splenectomy or sham surgery. Splenectomy animals were then treated with 5% dextrose, cefoxitin (60 mg im q 6 hr), glucan (7.5 mg ip prior to surgery), or cefoxitin plus glucan. Splenectomy resulted in decreased survival (5% vs 30%, P less than 0.05). Treatment with cefoxitin (90%) or glucan (47%) significantly improved survival. Combined glucan-cefoxitin therapy had no improvement over cefoxitin alone. Peritoneal and blood cultures were performed 12 hr postoperatively. There were no significant differences in growth of bacteria between sham and splenectomy animals. Cefoxitin treatment resulted in lower growth of bacteria from both blood and peritoneum (P less than 0.05). Glucan treatment caused a significant decrease in the number of bloodborne bacteria (P less than 0.05). Intravascular colloidal carbon clearance and leucocyte counts were performed at 12 hr postoperatively. Presence of peritonitis significantly enhanced intravascular clearance, while splenectomy had no effect. Addition of glucan or cefoxitin therapy to splenectomy animals did not enhance intravascular clearance. Leucocyte counts were significantly lower (P less than 0.05) when splenectomy was added to peritonitis animals. Glucan and cefoxitin therapy did not increase leucocyte counts. Based on these studies we conclude that (1) splenectomy increases mortality in fecal peritonitis, (2) antibiotic and immunomodulator afford some protection, and (3) exact mechanism of protection remains unclear.     

Quality of life in adult transplant recipients more than 15 years after kidney transplantation

BACKGROUND: With continuously rising survival rates following renal transplantation, health-related quality of life (HQOL) of long-term transplant survivors becomes increasingly important. METHODS: Recipients more than 15 years after successful renal transplantation were studied retrospectively. HQOL in 139 long-term transplant recipients was assessed using the SF-36 and the disease-specific kidney transplant questionnaire (KTQ-25). RESULTS: Long-term transplant recipients revealed satisfactory HQOL that was comparable to the healthy population in four of eight SF-36 categories (role physical, social functioning, role emotional and mental health). Other SF-36 categories such as physical functioning, physical pain, general health, and vitality were reduced. Among the study population, disease-specific HQOL was comparable or even improved to that of patients awaiting transplantation. In contrast to retired or unemployed patients, employed recipients revealed a highly significant improved HQOL in numerous SF-36 categories such as physical functioning (P<0.001), physical pain (P<0.001), general health (P<0.001), vitality (P<0.001), social functioning (P<0.005), and mental health (P<0.001), as well as for the KTQ-dimensions physical symptoms (P<0.001), fatigue (P>0.001), uncertainty/fear (P<0.01), and emotions (P<0.05). Other factors positively correlating with improved HQOL in certain dimensions were living situation, systolic blood pressure, and recipient age. CONCLUSIONS: More than 15 years after renal transplantation, recipients present satisfactory HQOL comparable to the general healthy population or at least to pretransplant patients. Vocational rehabilitation following renal transplantation is of highest importance among long-term survivors and is associated with improved HQOL.     

Cadaver kidney transplantation in patients more than 65 years old

Summary Elderly patients with end-stage renal disease often remain on dialytic therapy because they are at increased risk for mortality and morbidity. We placed 24 cadaver kidney transplants into 24 patients aged 65–74 years between September 1, 1985, and August 31, 1995. Rates of patient and graft survival were compared with those of 404 concurrent first cadaver-kidney transplant recipients between the ages of 20 and 44 years. The 5-year rates of patient and graft survival were not significantly different (86% versus 92% and 77% versus 63%, respectively; study group presented first). Primary cadaver kidney transplantation can be successfully performed in patients older than 65 years when a selection algorithm is applied to exclude active infection, active malignancy, unsuitable anatomy for technical success, high probability of operative mortality, and noncompliance. Pelvic arteriosclerosis and lower urinary tract abnormalities can cause intraoperative technical problems.     

An investigation of the primary immunosuppressive therapy's influence on kidney transplant survival at one month after transplantation

Immunosuppressive therapy is complex and challenging to do correctly due to on-target and off-target side effects. However, it is vital to successful allotransplantation. In this article, we analyzed the critical classes of immunosuppressants used in renal transplantation, highlighting the mechanisms of action and typical clinical applications used to develop predictive models for the diagnosis of various diseases, including the prediction of survival after kidney transplantation. In patients, the authors used a dataset with two immunosuppressants (tacrolimus and cyclosporin). The primary task was investigating critical risk factors associated with early transplant rejection. For this, the censored Kaplan-Meier survival estimation method was used. Our study shows a pairwise correlation between taking and not using a particular immunosuppressant. Therefore, the correct choice of immunosuppressive drugs is necessary to improve the prognosis of transplant survival.     

Revisiting double kidney transplantation: two kidneys provide better graft survival than one

Double kidney transplantation is an accepted strategy to increase the donor pool. Regarding older donor kidneys, protocols for deciding to perform a dual or a single transplantation are mainly based on preimplantation biopsies. The aim of our study was to evaluate the long-term graft and patient survivals of our “Dual Kidney Transplant program.” Patients who lost one of their grafts peritransplantation were used as controls. A total of 203 patients underwent kidney transplantation from December 1996 to January 2008 in our “old for old” renal transplantation program. We excluded 21 patients because of a nonfunctioning kidney, hyperacute rejection, or patient death with a functioning graft within the first month. Seventy-nine among 182 kidney transplantation the “old for old” program were dual kidney transplantation (DKT). Fifteen of 79 patients lost one of their kidney grafts (the uninephrectomized (UNX) UNX group). At 1 year, renal function was lower and proteinuria greater among the UNX than the DKT group. Patient survival was similar in both groups. However, death-censored graft survival was lower in UNX than DKT patients. The 5-year graft survival rate was 70% in UNX versus 93% in DKT cohorts (P = .04). In conclusion, taking into account the kidney shortage, our results may question whether the excellent transplant outcomes with DKT counter balance the reduced donor pool obviating acceptable transplant outcomes for more patients with single kidney transplantation.     

Adverse effect of splenectomy in renal transplantation.

Between January 1968 and June 1974 at Newcastle upon Tyne, 63 patients underwent splenectomy in association with transplantation; 45 of these had splenectomy with bilateral nephrectomy before (20) or at the time of (25) transplantation; 18 had post-transplant splenectomy for leucopenia. Mortality was significantly higher in splenectomized patients than in 136 non-splenectomized controls. Of the 63 splenectomized patients, 25 died within 1 year of transplantation, 12 of severe infection associated with leucopenia. Although splenectomy produced a temporary rise in white cell count, leucopenia during the first year of immunosuppressive therapy was not significantly less frequent in splenectomized patients than in controls. There was no significant difference in graft loss between the splenectomy and control groups. It is concluded that splenectomy is contra-indicated in patients who are to undergo renal transplantation and confers no benefit when carried out because of leucopenia developing after renal transplantation.     

Impaired kidney transplant survival in patients with antibodies to hepatitis C virus.

BACKGROUND: With a few exceptions, most published studies do not show an influence of antibodies to the hepatitis C virus (HCV) on the success of a kidney transplant. METHODS: We studied all our renal transplant recipients who had received kidneys from cadaver donors (n = 335) and had been treated with quadruple immunosuppression (steroids, azathioprine, and antilymphocyte antibodies, followed by cyclosporin). We had information on the status of the hepatitis C antibodies before and/or after the transplant in 320 cases (95.5%; in 300, pre-transplant). Patients with HCV antibodies before and/or after the transplant were considered to be HCV positive (HCV+). RESULTS: The HCV+ patients had more time in dialysis and a greater number of transfusions, hyperimmunized cases, and re-transplants. The evolution in the first post-transplant year was similar in both groups, but afterwards, the HCV+ patients had proteinuria more often as well as worse kidney function. The survival rate of the graft was significantly less in the HCV+ cases: 90.6, 68.3 and 51.0% at respectively 1, 5 and 10 years, compared with 91.5, 84.7 and 66.5% in HCV-patients (P<0.01). The patient survival rate was: 96.4, 87.0, and 71.9% in the HCV+ patients at 1, 5, and 10 years, compared with 98.2, 96.0 and 90.0% in the HCV- cases respectively (P<0.01). The differences remained the same in stratified studies according to time spent in dialysis or pre/post-transplant evolution of HCV antibodies, even when immunologically high-risk patients were excluded. In multivariant analysis, the presence of HCV antibodies acted as a independent prognostic factor for the survival of the kidney and the patient: 3.0 (1.8-5.0) and 3.1 (1.2-7.8) odds-ratio (95% of the confidence interval), respectively. The main cause of death among HCV+ patients was cardiovascular; there was no apparent increase in mortality rate due to infections or chronic liver disease. The loss of organs was mainly due to chronic nephropathy or death with a functioning kidney. CONCLUSION: The presence of hepatitis C antibodies, before or after transplantation, is associated with a worse long-term survival rate for both the patient and the transplanted kidney in our patients treated with quadruple therapy.