Is locally advanced head and neck cancer 'increasing' in the Netherlands? The paradox of absolute numbers, standardized incidence rates and proportional share.

BACKGROUND: Several reports have indicated that locally advanced head and neck cancer (LAHNC) has increased in the past decade. However, incidence trends cannot be easily compared because slightly different definitions of LAHNC were used. AIM: To investigate if the incidence of locally advanced disease (LAD) in the oral cavity, oropharynx, hypopharynx and larynx is indeed increasing over time, considering the growing and ageing population in the Netherlands. PATIENTS AND METHODS: Data were obtained from the Netherlands Cancer Registry (NCR). Primary head and neck squamous cell carcinomas of the oral cavity, oropharynx, hypopharynx and larynx diagnosed between 1989 and 2017 were included. Yearly numbers and European standardized incidence rates (ESRs) were reported by extent of disease. The annual percentage change (APC) over time in ESRs was calculated to assess trends. RESULTS: Absolute numbers and ESRs of LAD increased over time for oral cavity and most prominently for oropharynx carcinomas (before 1996, APC: 0.4, 95%CI: 0.1; 0.8 and APC: 5.7 (95%CI: 3.1; 8.4) after 1996: 1.5 (1.0; 2.0) respectively. For hypopharynx cancer the absolute number and ESR of LAD increased until 1997 and declined with 0.8% per year since 1997. Absolute numbers of patients with larynx cancer stayed stable over time, while ESR decreased (APC: -0.8 (95%CI: -1.1; -0.6)). CONCLUSION: The perception of an increasing trend in LAD in the Netherlands can be attributed to the increasing incidence of oral cavity and oropharynx carcinomas. For LAD of the hypopharynx a decreasing trend was observed. In larynx cancer, the proportional share of LAD of the larynx increased, even though incidence rates declined.

Determination of the Porosity of PLGA Microparticles by Tracking Their Sedimentation Velocity Using a Flow Imaging Microscope (FlowCAM).

PURPOSE: To investigate whether particle sedimentation velocity tracking using a flow imaging microscope (FlowCAM) can be used to determine microparticle porosity. METHODS: Two different methods were explored. In the first method the sedimentation rate of microparticles was tracked in suspending media with different densities. The porosity was calculated from the average apparent density of the particles derived by inter- or extrapolation to the density of a suspending medium in which the sedimentation velocity was zero. In the second method, the microparticle size and sedimentation velocity in one suspending fluid were used to calculate the density and porosity of individual particles by using the Stokes' law of sedimentation. RESULTS: Polystyrene beads of different sizes were used for the development, optimization and validation of the methods. For both methods we found porosity values that were in excellent agreement with the expected values. Both methods were applied to determine the porosity of three PLGA microparticle batches with different porosities (between about 4 and 52%). With both methods we obtained microparticle porosity values similar to those obtained by mercury intrusion porosimetry. CONCLUSIONS: We developed two methods to determine average microparticle density and porosity by sedimentation velocity tracking, using only a few milligrams of powder.

Developing and testing an intervention to prevent homelessness among individuals discharged from psychiatric wards to shelters and 'No Fixed Address'.

Shelter data in a recent study revealed discharges from psychiatric facilities to shelters or the street occurred at least 194 times in 2002 in London, Ontario, Canada. This problem must be addressed to reduce the disastrous effects of such discharge, including re-hospitalization and prolonged homelessness. An intervention was developed and tested to prevent homelessness associated with discharge directly to no fixed address. A total of 14 participants at-risk of being discharged without housing were enrolled, with half randomized into the intervention group. The intervention group was provided with immediate assistance in accessing housing and assistance in paying their first and last month's rent. The control group received usual care. Data was collected from participants prior to discharge, at 31 and 6-months post-discharge. All the individuals in the intervention group maintained housing after 3 and 6 months. All but one individual in the control group remained homeless after 3 and 6 months. The exception joined the sex trade to avoid homelessness. The results of this pilot were so dramatic that randomizing to the control group was discontinued. Discussions are underway to routinely implement the intervention. Systemic improvements can prevent homelessness for individuals being discharged from psychiatric wards.

Determination of threshold values for determining the size of the fraction of steroid hormone receptor-positive tumor cells in paraffin-embedded breast carcinomas.

BACKGROUND: For 4 years we used a multiparameter DNA flow cytometric (MP-FCM) technique to assess steroid hormone receptor expression in the diagnostic workup of routinely processed formalin-fixed, paraffin-embedded breast carcinomas as an alternative to immunohistochemistry (IHC) for the quantification of hormone receptor-positive cells. In all cases a positive fraction of hormone receptor-expressing epithelial cells was detected. This observation raised the question of what the cutoff value might be to distinguish receptor-negative from receptor-positive tumors. METHODS: In our search for a possible threshold value of positivity for estrogen receptor (ER) and progesterone receptor (PR) in MP-FCM, we developed four steps. First, we compared IHC results in our own laboratory with the results obtained by MP-FCM on a small series of breast tumors (n = 42). Second, after collecting our first 843 tumors, we made a comparison with the literature of the distribution of receptor positivity according to age classes. Third, using the most likely threshold that resulted from this comparison, we compared a subset of 340 node-negative tumors for their combined ER/PR profiles with the data from a similar group of node-negative tumor cases from the National Cancer Institute's Surveillance, Epidemiology and End-Result (SEER) study. Fourth, with the results of these comparisons, we prospectively collected IHC data and MP-FCM results of the same tumor samples for a period of 1 year. In this way, we collected data for an additional 180 tumors. RESULTS: The first step in this process resulted in an previous publication where 20% of steroid hormone receptor-positive cells seemed to be an acceptable cutoff point for positivity. However, the second step provided the best correlation at approximately 35% of ER reactive cells in the cytokeratin-positive cell population. With this cutoff, the distribution of combined ER/PR profiles in our patient population of node-negative breast cancers also showed a distribution similar to the data from the SEER study. The fourth step, using the 35% threshold value, resulted in a good correlation (r = 0.85, P < 0.0001) for ER and PR between IHC and MP-FCM in the 180 tumors investigated. CONCLUSION: By comparing in-house data with those from large external data collections in the literature, a threshold percentage can be defined that distinguishes steroid hormone receptor-negative from hormone receptor-positive tumors. As a result, information about DNA content and cell cycle distribution can be obtained. This observational study provides additional support to our opinion that MP-FCM is an alternative for IHC determination of ER and PR positivity. It is more objective and quantification can be done more appropriately. The additional value of this approach is that we generate continuous variables of ER/PR content instead of categorical classes, which can be used at different threshold levels for evaluation of clinical relevance.