FOLFIRINOX in patients with peritoneal carcinomatosis from pancreatic adenocarcinoma: a retrospective study.

Background: Peritoneal carcinomatosis (pcm) in metastatic pancreatic ductal adenocarcinomas (mpdac) is frequently encountered in day-to-day practice, but rarely addressed in the literature. The objective of the present study was to describe the management and outcome of patients diagnosed with pcm. Methods: Data for all consecutive patients with mpdac treated in our centre between 1 January 2014 and 31 August 2015 were analyzed retrospectively. Computed tomography imaging was centrally reviewed by a dedicated radiologist to determine the date of pcm diagnosis. Results: The analysis included 48 patients. Median age in the group was 61 years, and 41 patients had an Eastern Cooperative Oncology Group performance status (ecog ps) of 0-1. All patients presented with pcm either synchronously (group 1) or metachronously (group 2). Those groups differed significantly by baseline ecog ps and neutrophil-to-lymphocyte ratio (nlr), with ecog ps being poorer and nlr being higher in group 1. In addition to pcm, the main sites of metastasis were liver (62.5%) and lungs (31.3%). First-line chemotherapy in 36 patients (75%) was folfirinox (fluorouracil-irinotecan-leucovorin-oxaliplatin). The median overall survival for the entire population was 10.81 months [95% confidence interval (ci): 7.16 months to 14.16 months]; it was 13.17 months (95% ci: 5.9 months to 15.4 months) for patients treated with folfirinox. Median overall survival was 7.13 months (95% ci: 4.24 months to 10.41 months) for patients in group 1 and 14.34 months (95% ci: 9.79 months to 19.91 months) for patients in group 2, p = 0.1296. Conclusions: Compared with other metastatic sites, synchronous pcm seems to be a poor prognostic factor. It could be more frequently associated with a poor ecog ps and a nlr greater than 5 in this group of patients. In patients with mpdac and pcm, either synchronous or metachronous, folfirinox remains an efficient regimen.

Molecular screening program to select molecular-based recommended therapies for metastatic cancer patients: analysis from the ProfiLER trial.

BACKGROUND: Antitumor activity of molecular-targeted agents is guided by the presence of documented genomic alteration in specific histological subtypes. We aim to explore the feasibility, efficacy and therapeutic impact of molecular profiling in routine setting. PATIENTS AND METHODS: This multicentric prospective study enrolled adult or pediatric patients with solid or hematological advanced cancer previously treated in advanced/metastatic setting and noneligible to curative treatment. Each molecular profile was established on tumor, relapse or biopsies, and reviewed by a molecular tumor board (MTB) to identify molecular-based recommended therapies (MBRT). The main outcome was to assess the incidence rate of genomic mutations in routine setting, across specific histological types. Secondary objectives included a description of patients with actionable alterations and for whom MBRT was initiated, and overall response rate. RESULTS: Four centers included 2579 patients from February 2013 to February 2017, and the MTB reviewed the molecular profiles achieved for 1980 (76.8%) patients. The most frequently altered genes were CDKN2A (N = 181, 7%), KRAS (N = 177, 7%), PIK3CA (N = 185, 7%), and CCND1 (N = 104, 4%). An MBRT was recommended for 699/2579 patients (27%), and only 163/2579 patients (6%) received at least one MBRT. Out of the 182 lines of MBRT initiated, 23 (13%) partial responses were observed. However, only 0.9% of the whole cohort experienced an objective response. CONCLUSION: An MBRT was provided for 27% of patients in our study, but only 6% of patients actually received matched therapy with an overall response rate of 0.9%. Molecular screening should not be used at present to guide decision-making in routine clinical practice outside of clinical trials.This trial is registered with ClinicalTrials.gov, number NCT01774409.

Environmental gamma dosimetry with OSL of alpha-Al(2)O(3):C for in situ sediment measurements.

The physical properties of alpha-Al(2)O(3):C are very similar to that of quartz, which make it an attractive dosimetric material for geological and archaeological dating applications. Storage experiments in an ultra-low-radiation underground environment (UDO at PTB) and gamma-ray spectrometry show that the optically stimulated luminescence (OSL) signal of this material does neither suffer from a significant inherent background caused by traces of radionuclides (<6 microGy a(-1)) nor from fading. After having performed a simple calibration procedure, gamma dosimetry based on alpha-Al(2)O(3):C detectors, which were exposed in a brick block and a lead castle for different periods of time, provided concordant results with dose values derived from independent gamma-ray spectrometric measurements using high-purity germanium and NaI:Tl detectors. These investigations indirectly confirm both the absence of a significant inherent background and fading of the detector material. Small doses of a few micro gray accumulated in short exposure times to environmental radiation can be accurately measured, even when doses (i.e. transport dose) much larger than the actual environmental dose have to be subtracted. It is shown that the OSL signal caused by small transport doses can be easily and reproducibly reset even under difficult field conditions by illuminating the dosemeters with the blue light from Luxeon LEDs. Summarised, alpha-Al(2)O(3):C appears to be the material of choice for dosimetric dating applications of quartz or related materials, when analysed by using OSL.

Entomological survey and report of a knockdown resistance mutation in the malaria vector Anopheles gambiae from the Republic of Guinea.

The purpose of our entomological survey was to estimate mosquito biodiversity, infectivity rates and insecticide resistance levels in Anopheles species in four study sites in a mining area with high malaria transmission in southeastern Guinea. Anopheles gambiae s.l. (77%) was the most common Anopheles collected followed by An. funestus (20%). The specimens of the An. gambiae complex were predominantly An. gambiae S form (97.6%) with 1.4% of An. gambiae M form found in Kérouané only, and 1% of An. arabiensis which was present in all four study sites. Anopheles gambiae S form and An. funestus were found to be infected with Plasmodium falciparum, with infectivity rates of 4.1% and 4.4% and inoculation rates of 0.60 and 0.19 infected bite/person/night, respectively. In addition, a high level (79%) of the knockdown resistance (kdr) L1014F mutation was reported in the populations of An. gambiae S form. The high malaria transmission that occurs in the prospected area of Guinea requires a long-term vector control programme. However, such a control programme will have to consider the presence of the kdr gene at a surprisingly high level within the dominant vector, which could reduce the expected impact of vector control.

Malaria risk perception, knowledge and prophylaxis practices among travellers of African ethnicity living in Paris and visiting their country of origin in sub-Saharan Africa.

An observational prospective cohort study assessed malaria risk perception, knowledge and prophylaxis practices among individuals of African ethnicity living in Paris and travelling to their country of origin to visit friends or relatives (VFR). The study compared two groups of VFR who had visited a travel clinic (TC; n=122) or a travel agency (TA; n=69) before departure. Of the 47% of VFR citing malaria as a health concern, 75% knew that malaria is mosquito-borne and that bed nets are an effective preventive measure. Perception of high malaria risk was greater in the TA group (33%) than in the TC group (7%). The availability of a malaria vaccine was mentioned by 35% of VFR, with frequent confusion between yellow fever vaccine and malaria prevention. Twenty-nine percent took adequate chemoprophylaxis with complete adherence, which was higher among the TC group (41%) than the TA group (12%). Effective antivector protection measures used were bed nets (16%), wearing long clothes at night (14%) and air conditioning (8%), with no differences between the study groups except in the use of impregnated bed nets (11% of the TC group and none of the TA group). Media coverage, malaria chemoprophylaxis repayment and cultural adaptation of preventive messages should be improved to reduce the high rate of inadequate malaria prophylaxis in VFR.

Influence of meteorological parameters on the clinical presentation of cutaneous leishmaniasis in French Guiana and on the efficacy of pentamidine treatment of the disease.

In French Guiana, marked seasonal fluctuations have been observed in the numbers of individuals who present with cutaneous leishmaniasis (CL). To investigate the seasonal trends further, the clinical characteristics and responses to treatment of 455 cases of CL, who presented over a 3-year period (1995-1998), were compared against data on the weather for the calendar month of presentation (month 0) and for the month before presentation (month-1). Several statistically significant associations were observed. The number of sunlight hours in month -1 was lower for the treatment successes than for the treatment failures [adjusted odds ratio (AOR) for successful treatment=0.28; 95% confidence interval (CI)=0.13-0.6; P=0.001] and for those with long incubation periods than for those with relatively short incubation periods (multiple-regression coefficient=-0.003; P=0.002). However, the radiation intensity for month-1 was higher for the treatment successes than for the treatment failures (AOR=2.1; CI=1.1-3.8; P=0.02). Relatively high numbers of hours of sunlight on month-1 were associated with relatively high numbers of parasites on the skin smears (AOR=1.03; CI=1.01-1.04; P<0.001). Relatively high numbers of hours of sunlight during month 0 were associated with lymphangitis (AOR=0.4; CI=0.19-0.8; P=0.01). These results indicate that meteorological parameters may influence the evolution of CL, at least in French Guiana.

Influence of clinical presentation on the efficacy of a short course of pentamidine in the treatment of cutaneous leishmaniasis in French Guiana.

The cure 'rates' achieved using intramuscular pentamidine isethionate (two injections of 4 mg/kg separated by an interval of 48 h) were investigated in French Guiana, in 198 consecutive patients with cutaneous leishmaniasis caused by Leishmania braziliensis guyanensis. One aim was to see if initial clinical presentation could be used to predict treatment failure. The cure rate after one course of pentamidine isethionate was 87% and almost all (80%) of the treatment failures responded to an identical second course. Although many of the patients complained of adverse effects, most commonly of pain at the injection site (54%), none of these effects was severe. Although frequently associated with discomfort, the two-injection course, giving a total of 8 mg pentamidine isethionate/kg, appears to be an effective treatment for cutaneous leishmaniasis in French Guiana. The observation of satellite papules on presentation was associated with a significantly increased risk of failure of the first course of treatment (P = 0.01), with an odds ratio (and 95% confidence interval) estimated at 3.5 (1.3-11.1), after adjusting for other clinical presentations and lesion size and number. The presence of satellite papules perhaps indicates that the patient's immune system is unable to control the progression of the parasite. Patients with more than three lesions were also less likely to be cured after one course of pentamidine than those with fewer lesions (P = 0.01).

Seasonal fluctuations of incubation, healing delays, and clinical presentation of cutaneous leishmaniasis in French Guiana.

An investigation was conducted to determine whether seasonal variations affected the development of cutaneous leishmaniasis. Data from 499 cases treated between July 1994 and December 1998 were analyzed. The interval between infection and consultation and between treatment and clinical cure varied significantly between cases with an incubation period during the dry season compared with the rainy season (P < 0.001). When the incubation period occurred during the dry season, the standard pentamidine isethionate treatment seemed to be less effective (i.e.. the odds ratio for failure was 1.9 [1.1-3.4], P = 0.01). The presence of lymphangitis was more frequent during the dry season (i.e., the odds ratio was 0.26 [0.15-0.45], P < 0.001). These results suggested that the observed seasonal variations were due to variations in the host/parasite balance. Converging indirect elements that suggest a role for variations in solar ultraviolet radiation are discussed.

EPR and TL correlation in some powdered Greek white marbles.

Thermoluminescence of white powdered marble samples, chosen to display different EPR spectra, were studied. Two peaks at 280 degrees C and 360 degrees C can be observed among the TL glow curves while the EPR spectra exhibit two signals: the A signal with g perpendicular = 2.0038 and g parallel = 2.0024 due to the SO3- centre and the B one with g1 = 2.0005; g2 = 2.0001; g3 = 1.9998 due to mechanical powder reduction (drilling). Owing to heating and simultaneous experiments, a correlation have been established: the 280 degrees C TL peak is associated to the A signal and thus to the SO3- centre and the 360 degrees C TL peak is caused by mechanical treatment corresponding to the B EPR signal.

Melanoma screening: report of a survey in occupational medicine.

BACKGROUND: Epidemiological studies concerning melanoma are most often performed by general practitioners and dermatologists in patients previously aware of the risk of nevi. OBJECTIVE: To determine the efficiency of early detection of melanoma by occupational medicine specialists trained in the use of ABCDE criteria during annual systematic examination of workers. METHODS: A total of 370 subjects with suspect lesions that demonstrated at least 2 of 5 ABCDE criteria were selected from 65000 employees examined; these subjects were requested to see their physician about possible excision. Of the 370 subjects, 273 (73.8%) were seen at a second-year follow-up visit to determine their outcome. RESULTS: Among the 273 subjects who were seen again, 172 (63.0%) had consulted a physician. For the 101 subjects who had not seen a physician, the main reason was the negligence (86.1%). A total of 353 atypical nevi were observed. The mean number of ABCDE criteria noted per lesion was 2.6. Lesion diameter greater than 6 mm was the most frequent (80.5%) and enlargement the least frequent criteria seen; heterochromous coloration and diameter greater than 6 mm was the most common association (54.5%). Five histologically confirmed melanomas were found among nevi excised in 78 subjects. CONCLUSION: This screening approach seems efficient for the early detection of melanoma, demonstrating an incidence of 7.7 per 100000 vs. 9 per 100000 in the general French population.

Variable clinical presentation of cutis laxa.

We present 2 families with 4 individuals suffering from congenital cutis laxa. Family A has a single affected male child with developmental delay and ligamentous laxity, making this only the second male of the total 15 patients so far reported with this particular syndrome. Family B has 3 affected males, 2 of whom have significant involvement of other systems. Only one of the 4 affected children had very obvious loose skin folds and dependency on this clinical feature alone could result in under-diagnosis of this disease. The clinical features and family pedigree information suggests recessive inheritance in Family B but the mode of inheritance in Family A is inconclusive.