FOLFIRINOX-based neoadjuvant chemoradiotherapy for borderline and locally advanced pancreatic cancer: A pilot study from a tertiary centre

BackgroundNeoadjuvant chemoradiotherapy, potentially relevant to increase resection rate in pancreatic cancer, is still debated.AimsTo assess tolerance, resection rate and outcomes of patients with non-metastatic pancreatic ductal adenocarcinoma treated by concomitant chemoradiotherapy.MethodsThis monocentric study included all consecutive patients treated from 2010 to 2014 for non-metastatic pancreatic adenocarcinoma. Chemotherapy was followed by chemoradiotherapy in operable patients, surgical resectability being assessed by CT-scan.ResultsSeventy-nine patients were included: 41 patients had borderline and 38 locally advanced tumours. All patients were treated by chemotherapy (FOLFIRINOX), followed by chemoradiotherapy (median dose: 59 Gy, range 45–66 Gy) for 94% of patients. Thirty-seven patients (47%) could subsequently benefit from surgery with a complete R0 resection in 94% of cases, with a postoperative mortality of 5%. Median overall survival was 21.5 months (median follow-up: 48.8 months). Local control, overall and disease-free survival were significantly higher for patients who underwent resection compared to others, with 89.2% vs 59.5% (p = 0.01), 49.7 vs 17.4 months (p < 0.01) and 25.5 vs 9.2 months (p < 0.01), respectively.ConclusionNeoadjuvant treatment consisting of FOLFIRINOX chemotherapy followed by chemoradiotherapy is an efficient strategy for patients with borderline and locally advanced pancreatic cancer, resulting in a 43% rate of secondary complete surgical resection associated with high local control, overall and disease-free survival.     

Colectomy with ileorectal anastomosis preserves female fertility in ulcerative colitis

OBJECTIVES: Restorative proctocolectomy with ileoanal anastomosis (IPAA) is the surgical standard for patients with ulcerative colitis (UC). Significant reduction in female fertility and fecundity after IPAA has been shown in recent studies. In selected cases, colectomy with ileorectal anastomosis (IRA) is another surgical option. The aim of this study was to evaluate fertility in women with UC who underwent IRA. PATIENTS AND METHODS: This study included all women with UC who underwent IRA between 1962 and 1999 and who were 40 years old or younger at the time of surgery, and older than 18 years of age at the time of the interview. Data were collected using a structured telephone interview concerning reproductive behavior and waiting times to pregnancy. RESULTS: Among 40 eligible patients, 37 whose mean age at IRA was 28 years (range 11-39) answered the questionnaire. Twenty-two were unmarried, not wishful of pregnancy and/or already had children. Among 15 females wishing children after IRA, 10 (66%) became pregnant: one had therapeutic abortion, two had a miscarriage, four had 1 child, two had 2 children and one had 4 children. Five patients were sterile after IRA. CONCLUSION: These preliminary results suggest that IRA for UC preserves female fertility. If confirmed in other series this information should be provided to young women with UC before deciding surgical option.     

Assessing the evolution of primary healthcare organizations and their performance (2005-2010) in two regions of Québec province: Montréal and Montérégie

Background

Chronic Kidney Disease is a major cause of morbidity and interventions now exist which can reduce risk. We sought to develop and validate two new risk algorithms (the QKidney^® Scores) for estimating (a) the individual 5 year risk of moderate-severe CKD and (b) the individual 5 year risk of developing End Stage Kidney Failure in a primary care population.

Methods

We conducted a prospective open cohort study using data from 368 QResearch^® general practices to develop the scores. We validated the scores using two separate sets of practices - 188 separate QResearch^® practices and 364 practices contributing to the THIN database. We studied 775,091 women and 799,658 men aged 35-74 years in the QResearch^® derivation cohort, who contributed 4,068,643 and 4,121,926 person-years of observation respectively. We had two main outcomes (a) moderate-severe CKD (defined as the first evidence of CKD based on the earliest of any of the following: kidney transplant; kidney dialysis; diagnosis of nephropathy; persistent proteinuria; or glomerular filtration rate of < 45 mL/min) and (b) End Stage Kidney Failure. We derived separate risk equations for men and women. We calculated measures of calibration and discrimination using the two separate validation cohorts.

Results

Our final model for moderate-severe CKD included: age, ethnicity, deprivation, smoking, BMI, systolic blood pressure, diabetes, rheumatoid arthritis, cardiovascular disease, treated hypertension, congestive cardiac failure; peripheral vascular disease, NSAID use and family history of kidney disease. In addition, it included SLE and kidney stones in women. The final model for End Stage Kidney Failure was similar except it did not include NSAID use. Each risk prediction algorithms performed well across all measures in both validation cohorts. For the THIN cohort, the model to predict moderate-severe CKD explained 56.38% of the total variation in women and 57.49% for men. The D statistic values were high with values of 2.33 for women and 2.38 for men. The ROC statistic was 0.875 for women and 0.876 for men.

Conclusions

These new algorithms have the potential to identify high risk patients who might benefit from more detailed assessment, closer monitoring or interventions to reduce their risk.     

Hemorheological disturbances correlate with the lipid profile but not with the NCEP-ATPIII score of the metabolic syndrome

The metabolic syndrome, which is associated with an high risk for diabetes and atherothrombosis, is associated with hemorheologic abnormalities. These abnormalities seem more and more to be explained by its various symptoms than by insulin resistance which represents theoretically the core of the syndrome. In this study we aimed at defining the specific hemorheologic profile of insulin resistance and hyperinsulinemia by separating a sample of 90 subjects into 4 subgroups according to the clinical score "NCEP-ATPIII" which is the best recognized standardized definition of the syndrome. Results show no significant changes of blood rheology across classes of NCEP score despite a borderline rank correlation between RBC aggregability "M1" and the score. Whole blood viscosity was mostly correlated to HDL-cholesterol (r = -0.353, p = 0.007) and triglycerides (r = 0.574, p = 0.0001). Plasma viscosity was correlated with total cholesterol (r = 0.3359, p = 0.02) and with LDL-cholesterol (r = 0.357, p = 0.03). Red blood cell rigidity "Tk" was negatively correlated to HDL-cholesterol (r = -0.430, p = 0.007). Aggregability "M" was correlated to total cholesterol (r = 0.356, p = 0.01) and "M1" to HDL-cholesterol (r = -0.406, p = 0.006). Thus, despite previously described correlations with glucose disposal parameters, the hyperviscosity syndrome of the metabolic syndrome is not proportional to its clinical scoring and is strongly dependent upon the lipid profile.     

The hemorheological aspects of the metabolic syndrome are a combination of separate effects of insulin resistance, hyperinsulinemia and adiposity

The metabolic syndrome which is at high risk for diabetes and atherothrombosis is associated with hemorheologic abnormalities. Initially, insulin resistance was considered as the core of the syndrome. However, it becomes clear that the syndrome is a cluster in which the combined effects of obesity, insulin resistance, and hyperinsulinemia can be inconstantly associated, contributing to a various extent to a global impairment of blood rheology. We previously reported in 157 nondiabetic subjects that both obesity and insulin resistance increase red cell rigidity (Dintenfass's Tk) and plasma viscosity (eta p), and that whole blood viscosity at high shear rate (eta b 1000 s(-1)) reflects rather obesity than insulin resistance. In this study we aimed at defining the specific hemorheologic profile of insulin resistance and hyperinsulinemia by separating a sample of 81 subjects into 4 subgroups according to quartiles of insulin sensitivity (SI) (measured with the minimal model of an intravenous glucose tolerance test) and baseline insulin. Results show that (1) values of SI within the upper quartile are associated with low eta b due to low eta p; (2) low SI regardless insulinemia is associated with increased aggregation indexes; (3) when low SI is associated with hyperinsulinemia (insulin the upper quartile and SI in the lower) there is a further increase in eta b due to an increase in eta p; (4) neither SI nor insulinemia modify Hct. Thus hyperinsulinemia and insulin resistance induce hyperviscosity syndromes which are somewhat different, although they are associated most of the time. Low SI increases RBC aggregation while hyperinsulinemia increases eta p.     

Affording what's free and paying for choice: comparing the cost of public and private hospitalizations in urban Kerala

OBJECTIVE: To assess the cost of public and private hospitalizations in urban Kerala and discuss policy implications of social disparities in the economic burden of hospital care. METHODS: The NSSO survey on health care (1995-1996) for urban Kerala was analysed with regards to expenditure incurred by hospital episodes. Multilevel linear models were built to assess factors associated with levels of health expenditure. FINDINGS: Hospital care involves paying admission fees in 68% of cases of hospitalizations (98% in private and 20% in public sector) in urban Kerala. Poor households and those headed by casual workers show significantly lower levels of health expenditure and a higher proportion of health-related loss of income than other social groups. Although there is significant expenditure in both sectors for these groups, hospitalization on free public wards is associated with lower expenditure than other options. Factors linked with higher expenditure are: duration of stay; hospitalizations on paying public wards and in the private sector; hospitalizations for above poverty line households and hospitalizations for chronic illnesses. Expenditure for services bought from outside the hospital is important in the public sector. CONCLUSION: Hospitalization incurs significant expenditure in urban Kerala. Greater availability of free medical services in the public sector and financial protection against the cost of hospitalization are warranted.     

Innovative and diverse strategies toward primary health care reform: lessons learned from the Canadian experience

INTRODUCTION: In the last decade, Canadian provincial and territorial health systems have taken diverse approaches to strengthening primary care delivery. Although the Canadian and US systems differ in significant ways, important commonalities include the organization of care delivery, core principles guiding primary care reform, and some degree of provincial/state autonomy. This suggests that Canadian experiences, which employed a variety of tools, strategies, and policies, may be informative for US efforts to improve primary care. INNOVATIONS: The range of primary care reform initiatives implemented across Canada target organizational infrastructure, provider payment, health care workforce, and quality and safety. Primary care teams and networks in which multiple physicians work in concert with other providers have become widespread in some provinces; they vary on a number of dimensions, including physician payment, incorporation of other providers, and formal enrolment of patients. Family medicine is attracting more recent medical school graduates, a trend likely affected by new physician payment models, increases in the number of primary care providers, and efforts to better integrate nonphysician providers into clinical practice. Efforts to integrate electronic medical records into practice and pursue quality improvement strategies are gaining ground in some provinces. CONCLUSIONS: Canadian primary care reform initiatives rely on voluntary participation, incremental change, and diverse models, encouraging engagement and collaboration from a range of stakeholders including patients, providers, and policymakers. Cross-country collaboration in evaluating and translating Canada's primary care reform efforts are likely to yield important lessons for the US experience.     

Selective internal radiation therapy compared with sorafenib for hepatocellular carcinoma with portal vein thrombosis

Purpose

Tumoural portal vein thrombosis (PVT) is a major prognostic factor in hepatocellular carcinoma (HCC). The efficacy of sorafenib, the only treatment approved at an advanced stage, is limited. Based on previous data, selective internal radiation therapy (SIRT), or ⁹⁰Y radioembolization, seems an interesting option. We aimed to compare both treatments in this population.

Methods

We retrospectively compared patients treated in two centres for HCC with tumoural PVT. We compared overall survival (OS) between patients treated with SIRT and patients treated with sorafenib. Analyses were performed before and after 1:1 matching with a propensity score for controlling indication bias, using a Cox proportional hazards model.

Results

A total of 151 patients were analysed, 34 patients treated with SIRT and 117 patients treated with sorafenib only. In the whole population, SIRT was associated with a higher median OS as compared with sorafenib: 18.8 vs 6.5 months (log-rank p?<?0.001). There was an imbalance of baseline characteristics between patients treated by SIRT and sorafenib, which justified patient matching with use of a propensity score: 24 patients treated with SIRT could be matched with 24 patients treated with sorafenib. OS was estimated with a median of 26.2 vs 8.7 months in patients treated with SIRT vs sorafenib, respectively (log-rank p?=?0.054). Before and after patient matching, the adjusted hazard ratio related to treatment by SIRT was estimated at 0.62 [95 % confidence interval (CI) 0.39–0.97] (p?=?0.037) and 0.40 (95 % CI 0.19–0.82) (p?=?0.013), respectively.

Conclusion

SIRT seems more effective than sorafenib in patients presenting with HCC and tumoural PVT. This hypothesis is being tested in prospective randomized trials.