Insight opinion to surgically treated metastatic bone disease: Scandinavian Sarcoma Group Skeletal Metastasis Registry report of 1195 operated skeletal metastasis

The number of cancer patients living with metastatic disease is growing. The increased survival has led to an increase in the number of cancer-induced complications, such as pathologic fractures due to bone metastases. Surgery is most commonly needed for mechanical complications, such as fractures and intractable pain. We determined survival, disease free interval and complications in surgically treated bone metastasis. Data were collected from the Scandinavian Skeletal Metastasis Registry for patients with extremity skeletal metastases surgically treated at eight major Scandinavian referral centres between 1999 and 2009 covering a total of 1195 skeletal metastases in 1107 patients. Primary breast, prostate, renal, lung, and myeloma tumors make up 78% of the tumors. Number of complications is tolerable and is affected by methods of surgery as well as preoperative radiation therapy. Overall 1-year patient survival was 36%; however, mean survival was influenced by the primary tumor type and the presence of additional visceral metastases. Patients with impending fracture had more systemic complications than those with complete fracture. Although surgery is usually only a palliative treatment, patients can survive for years after surgery. We developed a simple, useful and reliable scoring system to predict survival among these patients. This scoring system gives good aid in predicting the prognosis when selecting the surgical method. While it is important to avoid unnecessary operations, operating when necessary can provide benefit.     

Carbon‐14 labeling of hydrochlorothiazide via [14C]formaldehyde production from [14C]carbon dioxide at ambient temperature

[¹⁴C]Formaldehyde was synthesized by reducing ¹⁴CO₂ at ambient temperature with Schwartz's reagent. The [¹⁴C]formaldehyde was then used in the radiosynthesis of high specific activity (2.1 GBq/mmol) [¹⁴C]hydrochlorothiazide via cyclization of 4‐amino‐5‐chloro‐1,3‐benzenedisulfonamide.     

A modeling approach for compounds affecting body composition

Body composition and body mass are pivotal clinical endpoints in studies of welfare diseases. We present a combined effort of established and new mathematical models based on rigorous monitoring of energy intake (EI) and body mass in mice. Specifically, we parameterize a mechanistic turnover model based on the law of energy conservation coupled to a drug mechanism model. Key model variables are fat-free mass (FFM) and fat mass (FM), governed by EI and energy expenditure (EE). An empirical Forbes curve relating FFM to FM was derived experimentally for female C57BL/6 mice. The Forbes curve differs from a previously reported curve for male C57BL/6 mice, and we thoroughly analyse how the choice of Forbes curve impacts model predictions. The drug mechanism function acts on EI or EE, or both. Drug mechanism parameters (two to three parameters) and system parameters (up to six free parameters) could be estimated with good precision (coefficients of variation typically <20 % and not greater than 40 % in our analyses). Model simulations were done to predict the EE and FM change at different drug provocations in mice. In addition, we simulated body mass and FM changes at different drug provocations using a similar model for man. Surprisingly, model simulations indicate that an increase in EI (e.g. 10 %) was more efficient than an equal lowering of EI. Also, the relative change in body mass and FM is greater in man than in mouse at the same relative change in either EI or EE. We acknowledge that this assumes the same drug mechanism impact across the two species. A set of recommendations regarding the Forbes curve, vehicle control groups, dual action on EI and loss, and translational aspects are discussed. This quantitative approach significantly improves data interpretation, disease system understanding, safety assessment and translation across species.