Cost-effectiveness analysis of resorbable biosynthetic mesh in contaminated ventral hernia repair.

BACKGROUND: The aim of this study was to compare, in terms of cost and serious complications, the use of biosynthetic resorbable parietal mesh with biologic mesh in patients undergoing contaminated ventral hernia repair (modified Ventral Hernia Working Group grade 3). Poly-4-hydroxy-butyrate (P4HB) biosynthetic mesh has rarely been the subject of comparative studies in the context of contamination. Data are required to confirm the effects of a transition from biological mesh to biosynthetic resorbable mesh. PATIENTS AND METHODS: A cost-effectiveness analysis was conducted. It was based on a decision analysis model built with clinical and economic data issued from a before-after study that included 94 patients hospitalized for ventral hernia repair at the University Hospital of Strasbourg (France) from June 2011 to February 2018. The effectiveness endpoint was the number of patients presenting with a serious specific complication or a general complication at 6 months. Data for surgical hospitalization stays, home hospitalizations and ambulatory care costs were included. RESULTS: We found fewer serious complications with biosynthetic mesh: 21% versus 33% with biologic mesh. A cost savings of US $5146 was determined. Deterministic sensitivity analyses and a probabilistic analysis confirmed our findings and the robustness of the model. CONCLUSION: P4HB biosynthetic resorbable mesh appeared to be the most effective and the least costly option. Additional data will be needed to confirm the superiority of biosynthetic mesh in terms of the recurrence risk reduction over a longer period.

DHA Supplementation Attenuates MI-Induced LV Matrix Remodeling and Dysfunction in Mice.

OBJECTIVE: Myocardial ischemia and reperfusion (I/R) injury is associated with oxidative stress and inflammation, leading to scar development and malfunction. The marine omega-3 fatty acids (ω-3 FA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are mediating cardioprotection and improving clinical outcomes in patients with heart disease. Therefore, we tested the hypothesis that docosahexaenoic acid (DHA) supplementation prior to LAD occlusion-induced myocardial injury (MI) confers cardioprotection in mice. METHODS: C57BL/6N mice were placed on DHA or control diets (CD) beginning 7 d prior to 60 min LAD occlusion-induced MI or sham surgery. The expression of inflammatory mediators was measured via RT-qPCR. Besides FACS analysis for macrophage quantification and subtype evaluation, macrophage accumulation as well as collagen deposition was quantified in histological sections. Cardiac function was assessed using a pressure-volume catheter for up to 14 d. RESULTS: DHA supplementation significantly attenuated the induction of peroxisome proliferator-activated receptor-α (PPAR-α) (2.3 ± 0.4 CD vs. 1.4 ± 0.3 DHA) after LAD occlusion. Furthermore, TNF-α (4.0 ± 0.6 CD vs. 1.5 ± 0.2 DHA), IL-1ß (60.7 ± 7.0 CD vs. 11.6 ± 1.9 DHA), and IL-10 (223.8 ± 62.1 CD vs. 135.5 ± 38.5 DHA) mRNA expression increase was diminished in DHA-supplemented mice after 72 h reperfusion. These changes were accompanied by a less prominent switch in α/ß myosin heavy chain isoforms. Chemokine mRNA expression was stronger initiated (CCL2 6 h: 32.8 ± 11.5 CD vs. 78.8 ± 13.6 DHA) but terminated earlier (CCL2 72 h: 39.5 ± 7.8 CD vs. 8.2 ± 1.9 DHA; CCL3 72 h: 794.3 ± 270.9 CD vs. 258.2 ± 57.8 DHA) in DHA supplementation compared to CD mice after LAD occlusion. Correspondingly, DHA supplementation was associated with a stronger increase of predominantly alternatively activated Ly6C-positive macrophage phenotype, being associated with less collagen deposition and better LV function (EF 14 d: 17.6 ± 2.6 CD vs. 31.4 ± 1.5 DHA). CONCLUSION: Our data indicate that DHA supplementation mediates cardioprotection from MI via modulation of the inflammatory response with timely and attenuated remodeling. DHA seems to attenuate MI-induced cardiomyocyte injury partly by transient PPAR-α downregulation, diminishing the need for antioxidant mechanisms including mitochondrial function, or α- to ß-MHC isoform switch.

Are comorbidities associated with long-term survival of lung cancer? A population-based cohort study from French cancer registries.

BACKGROUND: Survival rates of lung cancer remains poor and the impact of comorbidities on the prognosis is discussed. The objective of this study was to assess if the Charlson Comorbidity Index (CCI) was associated with 8-year survival rates by histological type. METHODS: A cohort study was conducted using randomly selected cases from 10 French cancer registries. Net survival rates were computed using the Pohar-Perme estimator of the net cumulative rate. Three Cox models were independently built for adenocarcinomas, squamous cell and small cell cancers to estimate prognostic factors including CCI grade. RESULTS: A total of 646 adenocarcinomas, 524 squamous cell and 233 small cell cancers were included in the analysis. The net 8-year survival rate ranged from 12.6% (95% CI: 9.8-15.4%) for adenocarcinomas and 13.4% (95% CI: 10.1-16.7%) for squamous cell carcinomas, to 3.7% (95% CI: 1.1-6.3%) for small cell cancers. Observed and net survival rates decreased for CCI grades ≥3 for all histological group considered. After adjustment for sex, age group, stage and diagnostic mode, CCI grades 1 (HR = 1.6 [95% CI: 1.1-2.3]), 2 (HR = 1.7 [95% CI: 1.1-2.7]) and ≥ 3 (HR = 2.7 [95% CI: 1.7-4.4]) were associated with lower survival rates only for small cell cancers. CONCLUSION: After adjustment for age, sex, stage and diagnostic mode, the presence of comorbidity based on CCI grades 1-2 and ≥ 3 was associated with lower survival rates for small cell cancers whereas no differences were observed for adenocarcinomas and squamous cell cancers.

Merkel cell carcinoma in France: a registries-based, comprehensive epidemiological survey.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine carcinoma. Owing to its low incidence, epidemiological data are scarce and have never been analysed in France to identify the main epidemiological trends. METHODS: Data from MCC patients diagnosed between 1998 and 2010 were obtained from 11 French cancer registries in the FRANCIM network. The main epidemiological characteristics of MCC were investigated between 2006 and 2010 because comprehensive data were only available for this period. The main focus was tumour incidence and mortality over time. RESULTS: Between 1998 and 2010, 562 cases of MCC were reported in the registries. From 2006 to 2010 (290 cases), European- and world-standardized incidence rates were 0.26 and 0.43 per 100,000 person-years in men and 0.24 and 0.38 per 100,000 person-years in women. MCC is more frequent in females in France (56.9%) with male/female ratio 1.1. Relative survival rates were 84%, 56% and 42% at one, three and 5 years, respectively. CONCLUSIONS: The incidence of MCC clearly increased over time in all areas under focus. The standardized incidence in France was comparable to the incidence observed in other countries for the same period, but French data are too recent to conclude on an increase in MCC incidence. Prognosis remains poor in all countries in which data are available.

Are dietary reports in a case-control study on thyroid cancer biased by risk perception of Chernobyl fallout?

BACKGROUND: In retrospective case-control studies performed following nuclear tests or nuclear accidents, individual thyroid radiation dose reconstructions are based on fallout and meteorological data from the residential area, demographic characteristics, and lifestyle as well as dietary information. Collecting the latter is a controversial step, as dietary declarations may be affected by the subjects' beliefs about their risk behavior. This report analyses the potential for such bias in a case-control study performed in eastern France. METHODS: The study included 765 cases of differentiated thyroid carcinoma matched with 831 controls. Risk perceptions and beliefs of cases and controls were compared using Chi2 tests and differences in dietary reports were analyzed using a two-way ANOVA. RESULTS: In general, atmospheric pollution and living near a nuclear power plant were the two major risks that may influence thyroid cancer occurrence cited by cases and controls. When focusing in particular on the consequences of the Chernobyl accident, cases were more likely to think that the consequences were responsible for thyroid cancer occurrence than controls. Vegetable consumption during the two months after the Chernobyl accident was correlated with the status of subjects, but not to their beliefs. Conversely, consumption of fresh dairy products was not correlated with the status or beliefs of subjects. CONCLUSION: We found no evidence of systematic bias in dietary reports according to the status or beliefs held by subjects about the link between thyroid cancer occurrence and Chernobyl fallout. As such, these dietary reports may be used in further studies involving individual dosimetric reconstructions.

Oral cancer characteristics in France: Descriptive epidemiology for early detection.

Despite the frequency and lethality of oral cancers in France, there are no detailed general population data regarding the characteristics of these patients to fuel the public health authorities' reflections about early detection policies. Thus, the objective of this study was to determine, in the general population, the characteristics of both patients and tumours at the time of the diagnosis. A high-resolution, population-based study using 13 French registries was conducted on 1089 tumours diagnosed in 2010. Men accounted for 75% of cases. The most frequent sites were tonsil (28.4%) and oral tongue (21.1%). The median age varied from 56.7 years for floor of mouth to 66.4 years for gum. The lesions were mainly diagnosed on pain and those diagnosed after routine clinical examination were scarce (2.6%). There were 65.5% stage III and IV at diagnosis. Oral tongue, floor of mouth and palate presented tumours less than 2cm only in 34 to 40% of cases. Advanced stage was associated with the presence of comorbidities, and tonsil or base of tongue topography. Stage was not associated with Département, deprivation index or gender. This study provided a picture of the characteristics of oral cancer patients and their tumours and showed that diagnoses are often made late, even for those tumours most easily accessible to direct visual and tactile examination. Nevertheless, it remains to define the target population of an early detection and to evaluate the benefit of such detection on the mortality rate.

[Prostate cancer incidence and mortality trends in France from 1980 to 2011]. / Le cancer de la prostate, évolution de l'incidence et de la mortalité en France entre 1980 et 2011.

UNLABELLED: The prostate cancer became for two decades the most frequent cancer in men. We describe the evolution of its incidence and mortality from 1980 to 2011 for France. METHODS: Incidence data were collected from registries and national incidence estimates were based on the use of mortality as a correlate of incidence. RESULTS: After a very strong increase of incidence between 1980 (24.8/100,000) and 2005 (124.5/100,000), we observe a net decline since (97.7/100,000, in 2011). The reduction began earlier for the old patients. The evolution of mortality is very different. We observe a regular reduction since the end of 1990s (from 18.0/100,000 in 1990 to 10.5/100,000 in 2011). The reduction began earlier for the young patients. CONCLUSION: This pattern of evolution is observed in all the countries where the use of the PSA had caused an important increase of the diagnosis of prostate cancer. LEVEL OF EVIDENCE: 3.

Trends in breast cancer incidence and mortality in France 1990-2008.

The objective of this work was to detail the incidence and mortality trends of invasive and in situ breast cancer (BC) in France, especially regarding the development of screening, over the 1990-2008 period. Data issued from nine population-based cancer registries were studied. The incidence of invasive BC increased annually by 0.8 % from 1990 to 1996 and more markedly by 3.2 % from 1996 to 2003, and then sharply decreased until 2006 (-2.3 % per year), especially among women aged 50-69 years (-4.9 % per year). This trend was similar whatever the introduction date of the organized screening (OS) program in the different areas. The incidence of ductal carcinoma in situ steadily increased between 1990 and 2005, particularly among women aged 50-69 years and 70 and older. At the same time, the mortality from BC decreased annually by 1.1 % over the entire study period. This decrease was more pronounced in women aged 40-49 and 50-69 and, during the 1990-1999 period, in the areas where OS began in 1989-1991. The similarity in the incidence trends for all periods of implementation of OS in the different areas was striking. This suggests that OS alone does not explain the changes observed in incidence rate. Our study highlights the importance of closely monitoring the changes in incidence and mortality indicators, and of better understanding the factors causing variation.

Role of thyroid surgery in the obstructive sleep apnea syndrome.

OBJECTIVES: To study the impact of thyroid surgery on obstructive sleep apnea syndrome (OSAS) evaluated by the apnea/hypopnea index (AHI) was studied. Secondary objectives were to evaluate the impact on the positional component of OSAS and to highlight possible predictors of improvement of OSAS after thyroidectomy. METHODS: Twenty-eight patients with OSAS are included in this monocentric study: they underwent total thyroidectomy (n = 26) or left loboisthmectomy. Postoperative assessment involves a nocturnal control polysomnography as of 60 days after surgery. RESULTS: The mean age at the time of surgery is 61.3 years (standard deviation ±7.3) and average body mass index is 29.6 kg/m2 (±7.3). Continuous positive airway pressure (CPAP) treatment is introduced preoperatively in 82% of patients. The statistical analysis shows a significant decrease of 33% in postoperative AHI for the total population (p = 0.001), 77% in patients under CPAP (p = 0.05), and 27% in patients without CPAP (p = 0.02). CPAP therapy could be released in four patients. Given the limited number of subjects studied, the surgery did not impact on the positional component of the OSAS. Statistical analysis failed to link a predictive factor to AHI reduction. CONCLUSIONS: We propose thyroid surgery as an alternative or as a complement to CPAP treatment for the patients with goitre: it allows a significant decrease in postoperative AHI, allowing adaptation of the CPAP treatment downward, or even a release in some cases. These results need to be confirmed on a larger series of patients in a prospective study with standardized criteria for polysomnography and multivariate analysis.

Waiting time disparities in breast cancer diagnosis and treatment: a population-based study in France.

Waiting times are key indicators of a health's system performance, but are not routinely available in France. We studied waiting times for diagnosis and treatment according to patients' characteristics, tumours' characteristics and medical management options in a sample of 1494 breast cancers recorded in population-based registries. The median waiting time from the first imaging detection to the treatment initiation was 34 days. Older age, co-morbidity, smaller size of tumour, detection by organised screening, biopsy, increasing number of specimens removed, multidisciplinary consulting meetings and surgery as initial treatment were related to increased waiting times in multivariate models. Many of these factors were related to good practices guidelines. However, the strong influence of organised screening programme and the disparity of waiting times according to geographical areas were of concern. Better scheduling of diagnostic tests and treatment propositions should improve waiting times in the management of breast cancer in France.

[Incidence and mortality of urological cancers in 2012 in France]. / Projection de l'incidence et de la mortalité par cancer urologique en France en 2012.

OBJECTIVES: Present national estimations of the incidence and mortality trends in urological cancers in France between 1980 and 2012. MATERIAL AND METHODS: Francim database and French Register of Cancers. RESULTS: Analysis of the current data shows a regular increase of the incidence of renal cancer in men and women (7,781 cases in men and 3,792 in women in 2012). For bladder cancer, trends are divergent. There is a small reduction in incidence for men and an increase for women (9,549 cases in men and 2,416 in women in 2012). Testicular cancer is still increasing slightly (2,317 incidental cases in 2012). The incidence of prostate cancer experienced a huge increase up until 2005, and thereafter it decreased sharply, though it is difficult to discern whether this drop (which was observed up until 2008) continued at the same rate after that point (56,841 incidences in 2012 based on the rates calculated for 2009). CONCLUSION: The analyses by organ database show that there are significant variations in the incidence of urological cancers, particularly for prostate cancer, which shows that both the natural history of urological tumours and the methods of detection have an impact on incidence.

Response shift effects on measuring post-operative quality of life among breast cancer patients: a multicenter cohort study.

PURPOSE: To characterize response shift effects in patients with breast cancer (BC). METHODS: The QLQ-C30, BR23, and EurQOL-EQ-5D were assessed at baseline and at the end of the first hospitalization. We used the then-test approach to characterize changes in internal standards by calculating the mean difference between the then-test (retrospective measure) and pre-test baseline QoL assessments. The Ideal Scale Approach was also used to assess changes in standards by comparing health and QoL expectancies between baseline and the end of the first hospitalization. Successive Comparison Approach was used to assess changes in values through the longitudinal assessment of the relative importance of EuroQOL dimensions. RESULTS: The results of this study showed that recalibration RS effects occurred early after the first hospitalization for 6/15 dimensions of QLQ-C30 (emotional, cognitive, fatigue, insomnia, appetite loss, diarrhea) and 2/8 of BR-23 (future perspective, systemic therapy side effects). Moreover, health and QoL expectancies changed between the baseline and the end of the first hospitalization, and changes in values were seen for the self-care and usual activities dimensions of the EuroQOL-EQ-5D. CONCLUSIONS: The occurrence of RS early after the first hospitalization suggests that it needs to be taken into account to interpret QoL changes in BC.

Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva.

Alternative therapies have been sought to alleviate mutilation and morbidity associated with surgery for vulvar neoplasms. Our prime objective was to assess tumor absence in pathological vulvar and nodal specimens following neoadjuvant chemoradiotherapy in locally advanced vulvar neoplasms. Data were retrospectively collected from January 2001 to May 2009 from 22 patients treated with neoadjuvant therapy for locally advanced squamous cell carcinoma of the vulva. Neoadjuvant treatment consisted of inguino-pelvic radiotherapy (50 Gy) in association with chemotherapy when possible. Surgery occurred at intervals of between 5 to 8 weeks. The median age of patients at diagnosis was 74.1 years. All patients were primarily treated with radiotherapy and 15 received a concomitant chemotherapy. Additionally, all patients underwent radical vulvectomy and bilateral inguino-femoral lymphadenectomy. Tumor absence in the vulvar and nodal pathological specimens was achieved for 6 (27%) patients, while absence in the vulvar pathological specimens was only achieved for 10 (45.4%) patients. Postoperative follow-up revealed breakdown of groin wounds, vulvar wounds and chronic lymphedema in 3 (14.3%), 7 (31.8%) and 14 cases (63.6%), respectively. Within a median follow-up time of 2.3 years [interquartile range (IQR), 0.6-4.6], 12 (54.6%) patients experienced complete remission and 6 cases succumbed to metastatic evolution within a median of 2.2 years (IQR, 0.6-4.6), with 1 case also experiencing perineal recurrence. Median survival time, estimated using the Kaplan-Meier method, was 5.1 years (IQR, 1.0-6.8). We suggest that neoadjuvant chemoradiotherapy may represent a reliable and promising strategy in locally advanced squamous cell carcinoma of the vulva.

The role of general practitioners in diagnosis of cutaneous melanoma: a population-based study in France.

BACKGROUND: Little data are available concerning the role of general practitioners (GPs) in the diagnosis of melanoma. OBJECTIVES: To evaluate the actual role of GPs in a population-based study covering five regions of France and 8·2 million inhabitants. MATERIALS AND METHODS: A survey of cancer registries and pathology laboratories, and questionnaires to practitioners were used to identify incident melanomas in 2008, and evaluate characteristics of patients (age, sex, area of residence, social isolation), tumours (Breslow, ulceration, location, histological type), and GPs (training, conditions of practice), and their influence on patterns of diagnosis and Breslow thickness. RESULTS: Among 898 melanomas, 376 (42%) were first diagnosed in a general practice setting (GP group). Breslow thickness was much higher in the GP group than in other melanomas (median: 0·95 vs. 0·61 mm, P < 0·0001). Multivariate analysis identified an older age, lower limb location, nodular subtype and Breslow thickness as factors associated with the GP group. Within this group, 52·5% of melanomas were detected by patients (median Breslow thickness: 1·30 mm) and 47·5% by GPs (median Breslow thickness: 0·80 mm, P = 0·0009), including 8% during a systematic full-body skin examination. Previous GP training on melanoma was associated with active detection by GPs. Male sex and social isolation of patients were associated with thicker melanomas, whereas active detection by GPs was associated with thinner CMs. CONCLUSIONS: GPs play a key role in melanoma diagnosis in France, but still frequently detect thick tumours. Increasing awareness and training of GPs and focusing attention on male and/or socially isolated patients should help to improve early detection of melanoma.

Epidemiology of posttransplant lymphoproliferative disorders in adult kidney and kidney pancreas recipients: report of the French registry and analysis of subgroups of lymphomas.

A registry of posttransplant lymphoproliferative disorders (PTLD) was set up for the entire population of adult kidney transplant recipients in France. Cases of PTLD were prospectively enrolled between January 1, 1998, and December 31, 2007. Ten-year cumulative incidence was analyzed in patients transplanted after January 1, 1989. PTLD risk factors were analyzed in patients transplanted after January 1, 1998 by Cox analysis. Cumulative incidence was 1% after 5 years, 2.1% after 10 years. Multivariate analysis showed that PTLD was significantly associated with: older age of the recipient 47-60 years and >60 years (vs. 33-46 years, adjusted hazard ratio (AHR) = 1.87, CI = 1.22-2.86 and AHR = 2.80, CI = 1.73-4.55, respectively, p < 0.0001), simultaneous kidney-pancreas transplantation (AHR = 2.52, CI = 1.27-5.01 p = 0.008), year of transplant 1998-1999 and 2000-2001 (vs. 2006-2007, AHR = 3.36, CI = 1.64-6.87 and AHR = 3.08, CI = 1.55-6.15, respectively, p = 0.003), EBV mismatch (HR = 5.31, CI = 3.36-8.39, p < 0.001), 5 or 6 HLA mismatches (vs. 0-4, AHR = 1.54, CI = 1.12-2.12, p = 0.008), and induction therapy (AHR = 1.42, CI = 1-2.02, p = 0.05). Analyses of subgroups of PTLD provided new information about PTLD risk factors for early, late, EBV positive and negative, polymorphic, monomorphic, graft and cerebral lymphomas. This nationwide study highlights the increased risk of PTLD as long as 10 years after transplantation and the role of cofactors in modifying PTLD risk, particularly in specific PTLD subgroups.

A prospective randomized study of two reminding strategies: telephone versus mail in the screening of cervical cancer in women who did not initially respond.

OBJECTIVE: To compare the efficacy and cost-effectiveness of two reminding strategies addressed to women who did not respond to a first invitation to undergo cervical cancer screening. STUDY DESIGN: A randomized study was carried out by a programme created in Alsace to organize cervical cancer screening. In total, 10,662 women who did not have a smear test 1 year after a first notice was sent, were randomly allocated to receive either a new letter with a reply coupon or a telephone call. The uptake of screening was measured using routine data. Efficacy and direct costs of the two methods were compared. RESULTS: Uptake at 8 months was 6.3% [95% confidence interval (CI) 5.6-7.0%] for telephone calls and 5.8% (95% CI 5.2-6.4%) for letters. The difference was not significant. More information was collected through telephone calls than by letters, but with less reliability. Furthermore, telephone calls were more costly. CONCLUSIONS: We found that in our region, a mail reminder was as effective as, and less expensive than, a telephone call; moreover, it was applicable to the whole population, including patients without a telephone.