Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma.

BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin versus ≤2250 mg/m2/≤150 mg/m2, respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m2 cyclophosphamide/>300 mg/m2 doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.

Adrenocortical carcinoma.

Adrenocortical carcinoma is a rare disease with a poor prognosis. Patients can present with a hormonal syndrome or with general symptoms from an abdominal mass. The pathogenesis is unknown. Sometimes the adrenocortical carcinoma is associated with tumour syndromes such as the Beckwith-Wiedemann and Li-Fraumeni syndrome; however, most tumours are sporadic. Using one of the international classification methods, histopathological research can in almost all cases distinguish between adrenocortical adenoma and carcinoma. complete surgical resection is the treatment of choice for adrenocortical carcinoma. Mitotane is given when surgery is not possible, after incomplete resection or for metastatic disease. Frequently used chemotherapeutic combinations are etoposide, doxorubicin, cisplatin and mitotane (EDP/M) and streptozotocin and mitotane (SZ/M). International and national cooperation has resulted in a randomised trial aimed at determining a standard therapy in advanced adrenocortical carcinoma. The Dutch Adrenal Network is a national cooperation of endocrinologists, pathologists and oncologists from all eight academic centres and Máxima Medical centre. The network combines knowledge and expertise and gives patients the opportunity to receive optimal treatment in their own district.

Modelling the effects of (green) antifungals, droplet size distribution and temperature on mould outgrowth in water-in-oil emulsions.

Prevention of fungal spoilage is a key microbiological issue for the shelf life of fat spreads. Our aim was to assess and model the scope of (natural) antimicrobials for extending shelf life of spreads (water-in-oil emulsions). Production conditions were established to make 60% model fat spreads with reproducible droplet size distributions. The mould vulnerabilities ranged from 1 to 20 weeks. The system allowed feasibility testing of lytic enzymes (Novozym 234) and LMW compounds against Penicillium roqueforti, a key-spoilage mould. The action of Novozym 234, carvacrol, undecanol and dihydrocarveol was benchmarked against sorbate and preservative-free controls under ambient and chilled conditions. Novozym 234 was ineffective to prevent outgrowth of P. roqueforti. Carvacrol, undecanol and dihydrocarveol had limited effects on shelf-life extension compared to sorbate. Fungal growth boundaries of (un-)preserved spreads were modelled. The emulsion droplet size distribution (DSD) was first captured in a mechanistic parameter DSD-I (I = Influence). DSD-I was a move away from the mean droplet diameter D3,3 as sole quantitative droplet-size distribution parameter for mould susceptibility of emulsions. DSD-I is a combination of available water droplets and surface area to initiate and sustain fungal outgrowth. Followup experiments showed that modelling D3,3 and distribution width (e(sigma)) instead of DSD-I gave better results for emulsions with high e(sigma). Empirical predictive models were subsequently developed for the effects of D3,3, e(sigma) and undissociated sorbic acid (HSO) on the shelf life of emulsions.