External validation of a lung cancer-based prediction model for two-year mortality in esophageal cancer patient cohorts.

PURPOSE/OBJECTIVE: Chemo-radiotherapy can improve the oncological outcome of esophageal cancer (EC) patients, but may cause long term radiation-induced toxicity, including an increased risk of non-cancer related death. For lung cancer patients, a model to predict 2-year total mortality using mean heart dose (MHD) and gross tumor volume (GTV) has previously been developed and validated. This project aimed to externally validate this model in EC patients. METHODS: Five EC patient cohorts from 3 different Dutch centres were used for model validation. External validity of the model was assessed separately in definitive (n = 170) and neo-adjuvant (n = 568) chemoradiotherapy (dCRT and nCRT) patients. External validity was assessed in terms of calibration by calibration plots, calibration-in-the-large (CITL) and calibration slope (CS), and discrimination by assessment of the c-statistic. If suboptimal model performance was observed, the model was further updated accordingly. RESULTS: For the dCRT patients, good calibration was found after adjustment of the intercept (CITL 0.00; CS 1.08). The c-statistic of the adjusted model was 0.67 (95%CI: 0.58 to 0.75). For nCRT patients the model needed adjustment of both the slope and the intercept because of initial miscalibration in the validation population (CITL 0.00; CS 1.72). After recalibration, the model showed perfect calibration (i.e., CITL 0, CS 1), as is common after recalibration. The c-statistic of the recalibrated model equaled 0.62 (95%CI: 0.57 to 0.67). CONCLUSION: The existing model for 2-year mortality prediction in lung cancer patients, based on the predictive factors MHD and GTV, showed good performance in EC patients after updating the intercept and/or slope of the original model.

Priorities and preferences of advanced soft tissue sarcoma patients starting palliative chemotherapy: baseline results from the HOLISTIC study.

INTRODUCTION: Palliative chemotherapy is the principal treatment of patients with advanced soft tissue sarcomas (STS); however prognosis is limited (median overall survival 12-19 months). In this setting, patient values and priorities are central to personalised treatment decisions. PATIENTS AND METHODS: The prospective HOLISTIC study was conducted in the UK and the Netherlands assessing health-related quality of life in STS patients receiving palliative chemotherapy. Participants completed a questionnaire before starting chemotherapy, including attitudes towards quality of life (QoL) versus length of life (LoL), decisional control preferences, and decisional conflict. Chi-square and Fisher's exact tests were used to evaluate associations between patient characteristics and preferences. RESULTS: One hundred and thirty-seven patients with advanced STS participated (UK: n = 72, the Netherlands: n = 65). Median age was 62 (27-79) years. Preference for extended LoL (n = 66, 48%) was slightly more common than preference for QoL (n = 56, 41%); 12 patients (9%) valued LoL and QoL equally (missing: n = 3). Younger patients (age <40 years) prioritised LoL, whereas two-thirds of older patients (aged ≥65 years) felt that QoL was equally or more important than LoL (P = 0.020). Decisional conflict was most common in patients who prioritised QoL (P = 0.024). Most patients preferred an active (n = 45, 33%) or collaborative (n = 59, 44%) role in treatment decisions. Gender, performance status, and country were significantly associated with preferred role. Concordance between preferred and actual role in chemotherapy decision was high (n = 104, 76%). CONCLUSIONS: Heterogeneous priorities and preferences among advanced STS patients support personalised decisions about palliative treatment. Considering individual differences during treatment discussions may enhance communication and optimise patient-centred care.

Colorectal anastomotic leak: transcriptomic profile analysis.

BACKGROUND: Anastomotic leakage in patients undergoing colorectal surgery is associated with morbidity and mortality. Although multiple risk factors have been identified, the underlying mechanisms are mainly unknown. The aim of this study was to perform a transcriptome analysis of genes underlying the development of anastomotic leakage. METHODS: A set of human samples from the anastomotic site collected during stapled colorectal anastomosis were used in the study. Transcriptomic profiles were generated for patients who developing anastomotic leakage and case-matched controls with normal anastomotic healing to identify genes and biological processes associated with the development of anastomotic leakage. RESULTS: The analysis included 22 patients with and 69 without anastomotic leakage. Differential expression analysis showed that 44 genes had adjusted P < 0.050, consisting of two upregulated and 42 downregulated genes. Co-functionality analysis of the 150 most upregulated and 150 most downregulated genes using the GenetICA framework showed formation of clusters of genes with different enrichment for biological pathways. The enriched pathways for the downregulated genes are involved in immune response, angiogenesis, protein metabolism, and collagen cross-linking. The enriched pathways for upregulated genes are involved in cell division. CONCLUSION: These data indicate that patients who develop anastomotic leakage start the healing process with an error at the level of gene regulation at the time of surgery. Despite normal macroscopic appearance during surgery, the transcriptome data identified several differences in gene expression between patients who developed anastomotic leakage and those who did not. The expressed genes and enriched processes are involved in the different stages of wound healing. These provide therapeutic and diagnostic targets for patients at risk of anastomotic leakage.

[Taste and smell changes resulting from cancer therapies]. / Smaak- en reukverandering na oncologische behandeling.

Cancer therapies often cause changes in taste and smell. In this article, three patients treated with immunotherapy, chemotherapy and targeted therapy who experience changes in taste or smell are presented. These patients report lower quality of life and altered eating habits due to these changes. The prevalence and type of taste and smell changes is diverse among different cancer treatments and individual patients. In clinical practice, diagnosis is supported by questionnaires, taste strips or smell sticks. It is important to acknowledge the changes in taste and smell and inform the patient about these changes. More tools become available to provide patients with personalized advise to adjust their meals to their new sense of taste and smell at home. Furthermore, hospital cooks are implementing new strategies to adjust meals to taste and smell alterations and individual preferences. Smell training is an option for patients with severe smell disorders.

Danger signals in the initiation of the inflammatory response after myocardial infarction.

During myocardial infarction, sterile inflammation occurs. The danger model is a solid theoretic framework that explains this inflammation as danger associated molecular patterns activate the immune system. The innate immune system can sense danger signals through different pathogen recognition receptors (PRR) such as toll-like receptors, nod-like receptors and receptors for advanced glycation endproducts. Activation of a PRR results in the production of cytokines and the recruitment of leukocytes to the site of injury. Due to tissue damage and necrosis of cardiac cells, danger signals such as extracellular matrix (ECM) breakdown products, mitochondrial DNA, heat shock proteins and high mobility box 1 are released. Matricellular proteins are non-structural proteins expressed in the ECM and are upregulated upon injury. Some members of the matricellular protein family (like tenascin-C, osteopontin, CCN1 and the galectins) have been implicated in the inflammatory and reparative responses following myocardial infarction and may function as danger signals. In a clinical setting, danger signals can function as prognostic and/or diagnostic biomarkers and for drug targeting. In this review we will provide an overview of the established knowledge on the role of danger signals in myocardial infarction and we will discuss areas of interest for future research.

Evaluation of polysulfated glycosaminoglycan for the treatment of hip dysplasia in dogs.

A double-blinded, controlled clinical study was performed to compare the response of adult dogs affected with hip dysplasia to a placebo and three different dosages of polysulfated glycosaminoglycan (PSGAG): 2.2 mg/kg, 4.4 mg/kg, and 8.8 mg/kg. Dogs were randomly assigned to treatment groups. The drug was administered intramuscularly every 3 to 5 days for a total of eight injections. Response to treatment was analyzed based on changes in lameness, range of motion (ROM), and pain on manipulation of the hip joints. Evaluation for adverse reactions included complete blood cell (CBC) count, blood urea nitrogen (BUN), creatinine, and physical examination. Data were collected on a total of 111 dogs. Eighty-four met all criteria for inclusion in the study. Dogs that were given 4.4 mg/kg of PSGAG showed the greatest improvement in orthopedic scores, whereas dogs in the placebo group showed the smallest improvement; however, the differences in clinical improvement between the four treatment groups were not statistically significant. No local or systemic adverse reactions related to the drug were observed.

Magnetic resonance imaging in the diagnosis of degenerative lumbosacral stenosis in four dogs.

Magnetic resonance imaging was used to diagnose degenerative lumbosacral stenosis in four dogs that had physical and neurologic signs consistent with a cauda equina lesion. Nerve root displacement by protruding disc material and loss of epidural fat were identified. In all dogs, the diagnosis was confirmed by dorsal laminectomy of the lumbosacral area.

Calcium crystal-associated arthropathy (pseudogout) in a dog.

Calcium pyrophosphate dihydrate (Ca2P2O7.2H2O) crystal-associated arthropathy (pseudogout) was diagnosed in a dog. Clinical signs included non-weightbearing lameness, signs of pain on joint manipulation, and high rectal temperature. Arthrocentesis of carpal joints revealed extra- and intracellular crystals containing calcium. The suspected cause was polyarthritis secondary to chronic Ehrlichia infection. Results of joint tap performed after resolution of the clinical signs were negative for calcium pyrophosphate dihydrate crystals.