The theory that cancer may arise under conditions of reduced immune capacity is supported by observations of humans with immune deficiencies such as occur following organ transplants. However, no study on humans has been done in which the reference population was the same as that in which the cancer cases arose and in which there was a sufficiently long period of follow-up. Information on 5,692 Nordic recipients of renal transplants in 1964-1982 was linked with the national cancer registries (1964-1986) and population registries. Person-years at risk were calculated from the date of first transplantation until death or the end of the study period and were multiplied by the appropriate age- and calender-specific incidence rates to obtain the expected numbers of cancers. Standardized incidence ratios (SIR) were calculated after stratification by a number of recorded variables. Altogether, 32,392 person-years were accrued, and 471 cancers occurred, yielding overall SIR of 4.6 (95% CI, 4.0 to 5.2) for males and 4.5 (95% CI, 4.0 to 5.2) for females. Significant overall 2- to 5-fold excess risks in both sexes were seen for cancers of the colon, larynx, lung and bladder, and in men also for cancers of the prostate and testis. Notably high risks, 10-fold to 30-fold above expectation, were associated with cancers of the lip, skin (non-melanoma), kidney and endocrine glands, also with non-Hodgkin's lymphoma, and in women also with cancers of the cervix and vulva-vagina. Among a number of donor and recipient variables studied, including tissue types and compatibility (ABO, HLA, DR), age below 45 years at the time of transplantation was the most important determinant for increased risk at most sites. Kidney transplantation increases the risk of cancer in the short and in the long term, consistent with the theory that an impaired immune system allows carcinogenic factors to act. The tumor risk is small in comparison with the benefits of transplants, but patients should be followed up for signs of cancer.

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We found no evidence to implicate any one drug regime preferentially in the development of PTLDs. The risk of developing PTLD seems to be a result of the whole transplantation process, which includes the antigenicity of the foreign graft, the immunosuppression resulting in inadequate cytotoxic T-cell activity, and the result of EBV infection. An important minority of cases are EBV negative.

Despite all efforts to secure a safe organ for transplantation, transmission of donor malignancy and other diseases nevertheless can happen, as is recorded many times in the literature. We have quantified the risk using the population-based cancer registry and found a risk of 8 in 626 (1.3%) for having a donor with undetected malignancy and a risk of 1 in 626 (0.2%) for transmitting a cancer. The risk for getting some transmitted glomerulonephritis is 2 in 626 (0.3%). None of the donors with cerebral malignancies transmitted any tumors to the recipients. Compared with the benefits of organ transplantation, these risks are small; however, if time allows, a search for additional medical information from registries could further minimize the risk of transmission of malignancies or other diseases. However, this requires updated, accurate, and accessible registries and legislation that allows access to personal data and transmission of such data across administrative borders.

The excess cancer rate could be the result of underlying undiagnosed tumors whose antigens have initiated glomerulonephritis, or the immunosuppressive therapy that initiated or energized tumor cells. Based on the findings in our study, there is some support for an association to persistent viruses causing first the glomerulonephritides and then the malignancies, perhaps through a common pathogenesis. This calls for other studies to be done that are specifically designed to investigate this issue, with more data on patient characteristics and confounders.

Our first-line, steroid-free immunosuppressive protocol allows initial graft function, provides a safe level of long-term graft survival and function with a very low rejection rate, gives an acceptable rate of side effects, and possesses the potential for lowering the incidence of chronic rejection over the long-term. Compared with protocols that discontinue steroids after the initial posttransplant period, a steroid-free protocol avoids the increased risk of infection and body disfigurement in the early posttransplant period. It also avoids the long-term risks of steroid use and the increased risks of rejection when the steroids are withdrawn.

Pediatric renal transplant patients present a number of challenges and problems, especially the inhibited post-transplant growth seen in children receiving standard immunosuppressive triple therapy that includes steroids. We report the successful use of steroid-free immunosuppression since 1990 in 14 pediatric renal allograft recipients who received a 10-day initial course of anti-lymphocyte globulin and surface area-adjusted doses of cyclosporine, 7 of whom also received mycophenolate mofetil (MMF) as maintenance immunosuppression. Only 1 patient died (3 months after transplantation as a result of a primary Epstein-Barr virus infection-induced lymphoproliferative disorder), 1 patient's graft never functioned, and another patient lost his graft after 3 years because of chronic rejection. Three patients experienced early acute cellular rejection, which resolved in 2 cases with OKT3, and in the 3rd with MMF. There were no late acute rejections. All patients evidenced growth and a growth spurt under this regimen. We conclude that all the pediatric patients benefited from our steroid-free protocol and that this protocol is superior to conventional triple therapies, which entail the eventual reduction and discontinuation of steroids, a procedure that not only inhibits growth but also carries an additional risk of acute rejection due to a steroid-adapted immune response.

ObjectiveThe risk of being disciplined in connection with a complaint case causes distress to most general practitioners. The present study examined the characteristics of complaint cases resulting in disciplinary action.Material and methodsThe Danish Patients’ Complaints Board's decisions concerning general practice in 2007 were examined. Information on the motives for complaining, as well as patient and general practitioner characteristics, was extracted and the association with case outcome (disciplinary or no disciplinary action) was analysed. Variables included complaint motives, patient gender and age, urgency of illness, cancer diagnosis, healthcare settings (daytime or out-of-hours services), and general practitioner gender and professional seniority.ResultsCases where the complaint motives involved a wish for placement of responsibility (OR = 2.35, p = 0.01) or a wish for a review of the general practitioner's competence (OR = 1.95, p = 0.02) were associated with increased odds of the general practitioner being disciplined. The odds of discipline decreased when the complaint was motivated by a feeling of being devalued (OR = 0.39, p = 0.02) or a request for an explanation (OR = 0.46, p = 0.01). With regard to patient and general practitioner characteristics, higher general practitioner professional seniority was associated with increased odds of discipline (OR = 1.97 per 20 additional years of professional seniority, p = 0.01). None of the other characteristics was statistically significantly associated with discipline in the multiple logistic regression model.ConclusionComplaint motives and professional seniority were associated with decision outcomes. Further research is needed on the impact of professional seniority on performance.