Rituximab for recurrence of primary focal segmental glomerulosclerosis after kidney transplantation: Results of a nationwide study

Rituximab (RTX) therapy for primary focal segmental glomerulosclerosis recurrence after kidney transplantation (KT) has been extensively debated. We aimed to assess the benefit of adding RTX to plasmapheresis (PP), corticosteroids, and calcineurin inhibitors (standard of care, SOC). We identified 148 adult patients who received KT in 12/2004–12/2018 at 21 French centers: 109 received SOC (Group 1, G1), and 39 received immediate RTX along with SOC (Group 2, G2). In G1, RTX was introduced after 28 days of SOC in the event of failure (G1a, n = 19) or PP withdrawal (G1b, n = 12). Complete remission (CR) was achieved in 46.6% of patients, and partial remission (PR) was achieved in 33.1%. The 10-year graft survival rates were 64.7% and 17.9% in responders and nonresponders, respectively. Propensity score analysis showed no difference in CR+PR rates between G1 (82.6%) and G2 (71.8%) (p = .08). Following the addition of RTX (G1a), 26.3% of patients had CR, and 31.6% had PR. The incidence of severe infections was similar between patients treated with and without RTX. In multivariable analysis, infection episodes were associated with hypogammaglobulinemia <5 g/L. RTX could be used in cases of SOC failure or remission for early discontinuation of PP without increasing the risk of infection.     

Incidence of thyroid cancer in adults recorded by French cancer registries (1978-1997)

This article analyses time trends and geographical variations of thyroid cancer by histological type. Incidence data were provided by 8 French cancer registries over the period 1978-1997, with 3853 adult cases reported. To assess the effects of age, period, cohort and area on incidence, log-linear Poisson regression models were used. Thyroid cancer increased exponentially from the cohort born in 1925. This increase was essentially due to papillary cancer, which increased by 6.2% per year in men and 8.1% per year in women over the entire period (1978-1997). In women, the recent trends were significantly different between the studied geographical areas. The analysis shows that the increase in thyroid cancer, essentially of the papillary type, is not recent. It may be attributed to a possible screening effect or to an increase in the number of "incidentally" discovered cases linked to the use of modern diagnostic tools.     

Second primary malignancies in thyroid cancer patients

The late health effects associated with radioiodine ((131)I) given as treatment for thyroid cancer are difficult to assess since the number of thyroid cancer patients treated at each centre is limited. The risk of second primary malignancies (SPMs) was evaluated in a European cohort of thyroid cancer patients. A common database was obtained by pooling the 2-year survivors of the three major Swedish, Italian, and French cohorts of papillary and follicular thyroid cancer patients. A time-dependent analysis using external comparison was performed. The study concerned 6841 thyroid cancer patients, diagnosed during the period 1934-1995, at a mean age of 44 years. In all, 17% were treated with external radiotherapy and 62% received (131)I. In total, 576 patients were diagnosed with a SPM. Compared to the general population of each of the three countries, an overall significantly increased risk of SPM of 27% (95% CI: 15-40) was seen in the European cohort. An increased risk of both solid tumours and leukaemias was found with increasing cumulative activity of (131)I administered, with an excess absolute risk of 14.4 solid cancers and of 0.8 leukaemias per GBq of (131)I and 10(5) person-years of follow-up. A relationship was found between (131)I administration and occurrence of bone and soft tissue, colorectal, and salivary gland cancers. These results strongly highlight the necessity to delineate the indications of (131)I treatment in thyroid cancer patients in order to restrict its use to patients in whom clinical benefits are expected.     

Tunicamycin and neuraminidase effects on luteinizing hormone (LH)-releasing hormone binding and LH release from rat pituitary cells in culture

We have studied the effects of tunicamycin (TM) and neuraminidase on the binding of 125I-labeled Buserelin, a GnRH agonist, and on GnRH-stimulated LH release in cultured rat pituitary cells. Treatment with TM, an antibiotic which inhibits protein glycosylation, abolished the development of elongated cell processes without any effect on cell viability. Concomitantly, TM caused a time- and dose-dependent inhibition of specific binding of Buserelin and of GnRH-stimulated LH release. The inhibition of binding was due to a decrease in the number of GnRH receptors without any significant effect on binding affinity. Protein synthesis was not affected under these experimental conditions, suggesting that the aglycosylated GnRH receptors are probably intracellularly accumulated and are not expressed on the cell surface. Treatment with neuraminidase inhibited only 50% of GnRH agonist binding and did not affect GnRH-stimulated LH release. These results indicate that the oligosaccharide portion is essential for the functional properties of the GnRH receptor.     

Cancer prevalence in France: time trend, situation in 2002 and extrapolation to 2012

BackgroundCancer prevalence is a basic indicator of the cancer burden in a population and essential to estimate the resources needed for care of cancer patients. This paper provides a prevalence estimate for 2002 and 2012 in France and an assessment of the trend in prevalence over the period 1993–2002.MethodIncidence and survival data from French cancer registries were used to estimate specific 5-year partial prevalence rates that were then applied to the whole French population.ResultsIn 2002, the 5-year partial prevalence was over 427,000 in men and 409,000 in women. The most frequent cancer site among men was prostate (35% of the cases) and breast in women (45% of the cases). In 2002, in France, more than 3.5% of men over 74 years old are alive with a prostatic cancer diagnosed within 5 years. The increase in the number of cases between 1993 and 2002 was about 40% and was mainly due to prostate and breast cancers. The demographic variations alone induce an increase of the number of prevalent cases of 75,000 among men and 54,500 among women if both incidence and survival are considered as stable during the period 2002–2012.ConclusionThis study uses a large amount of information from cancer registries which makes it possible to assess the cancer burden. Five-year prevalence is very sensitive to changes in incidence and demographic changes. Prevalence has to be estimated regularly in order to ensure accurate medical care meets demand.     

Cancer incidence and mortality in France over the period 1980-2005

BACKGROUND: The objective of this study was to provide updated estimates of national trends in cancer incidence and mortality for France for 1980-2005. METHODS: Twenty-five cancer sites were analysed. Incidence data over the 1975-2003 period were collected from 17 registries working at the department level, covering 16% of the French population. Mortality data for 1975-2004 were provided by the Inserm. National incidence estimates were based on the use of mortality as a correlate of incidence, mortality being available at both department and national levels. Observed incidence and mortality data were modelled using an age-cohort approach, including an interaction term. Short-term predictions from that model gave estimates of new cancer cases and cancer deaths in 2005 for France. RESULTS: The number of new cancer cases in 2005 was approximately 320,000. This corresponds to an 89% increase since 1980. Demographic changes were responsible for almost half of that increase. The remainder was largely explained by increases in prostate cancer incidence in men and breast cancer incidence in women. The relative increase in the world age-standardised incidence rate was 39%. The number of deaths from cancer increased from 130,000 to 146,000. This 13% increase was much lower than anticipated on the basis of demographic changes (37%). The relative decrease in the age-standardised mortality rate was 22%. This decrease was steeper over the 2000-2005 period in both men and women. Alcohol-related cancer incidence and mortality continued to decrease in men. The increasing trend of lung cancer incidence and mortality among women continued; this cancer was the second cause of cancer death among women. Breast cancer incidence increased regularly, whereas mortality has decreased slowly since the end of the 1990s. CONCLUSION: This study confirmed the divergence of cancer incidence and mortality trends in France over the 1980-2005 period. This divergence can be explained by the combined effects of a decrease in the incidence of the most aggressive cancers and an increase in the incidence of less aggressive cancers, partly due to changes in medical practices leading to earlier diagnoses.     

Malignant lymphoplasmacytic lymphoma with prominent splenomegaly (primary lymphoma of the spleen)

Eleven patients (age range 51-65 years) presenting with primary splenic lymphoma of lymphoplasmacytic type are described, together with detailed histological, immunohistochemical, and ultrastructural findings. The subclassification of this type of lymphoma is considered, and the prognosis discussed.