Performance of the QuantiFERON®-TB Gold In-Tube assay in tuberculin skin test converters: a prospective cohort study.

OBJECTIVE: To investigate diagnostic agreement of the QuantiFERON®-TB Gold In-Tube (QFT-GIT) test in adult tuberculin skin test (TST) converters in a high tuberculosis (TB) burden setting. SETTING AND DESIGN: We performed a case-cohort study from 2014 to 2016 in Uganda among residents who were not infected with Mycobacterium tuberculosis. Participants were followed up for 1 year, when they were retested to determine TST conversion. All TST converters and a random sample of participants from baseline were offered QFT-GIT testing. RESULTS: Of 368 enrolled participants, 61 (17%) converted their TST by 1 year. Among 61 converters, 42 were tested using QFT-GIT, 64% of whom were QFT-GIT-positive. Of 307 participants with a persistent negative TST, 48 were tested using QFT-GIT, 83% of whom were QFT-negative. Overall concordance of TST and QFT-GIT was moderate (κ = 0.48, 95%CI 0.30-0.66). Converters with a conversion of 15 mm had a higher proportion of concordant QFT-GIT results (79%) than converters with increments of 10-14.9 mm (52%). CONCLUSION: Concordance between TST and QFT-GIT was moderate among TST converters in this urban African population. These findings call for improved tests that more accurately measure conversion to tuberculous infection.

The role of genomic and antigenomic HCV-RNA strands as predictive factors of response to pegylated interferon plus ribavirin therapy.

BACKGROUND: Hepatitis C virus replicates by the synthesis of an antigenomic HCV-RNA. As the end point of anti-viral therapy is to decrease viral replication, the amount of antigenomic HCV-RNA could influence the response. AIM: To study if amounts of genomic and antigenomic HCV-RNA in the baseline liver biopsy are predictive factors of response to anti-viral therapy. METHODS: Eighty-eight patients with chronic HCV infection (anti-HIV-negative) treated with pegyltaed-interferon-alpha2b plus ribavirin for 12 months were included. Intrahepatic genomic and antigenomic HCV-RNA concentrations were determined by real-time polymerase chain reaction and percentage of infected hepatocytes by in situ hybridization. RESULTS: Of the 88 patients, 31% were responders while 69% were not. Median of antigenomic HCV-RNA in liver of responders and non-responders was 120 000 copies/microg RNA (range: 10,000-775,000) vs. 150,000 copies/microg RNA (range: 100-3,200,000; P = 0.38). Median of genomic HCV-RNA in liver of responders was 1,250,000 copies/microg RNA (range: 5000-9,000,000) and in non-responders 3,180,000 copies/microg RNA (range: 4600-18,000,000; P = 0.0191). Predictive factors of response in the logistic regression were: intrahepatic amount of genomic HCV-RNA, percentage of infected hepatocytes and previous therapy. CONCLUSION: Response to 12 months of therapy with pegylated interferon-alpha2b plus ribavirin depends on the amount of genomic HCV-RNA in the pre-treatment liver biopsy.

Bayesian analysis of a disability model for lung cancer survival.

Bayesian reasoning, survival analysis and multi-state models are used to assess survival times for Stage IV non-small-cell lung cancer patients and the evolution of the disease over time. Bayesian estimation is done using minimum informative priors for the Weibull regression survival model, leading to an automatic inferential procedure. Markov chain Monte Carlo methods have been used for approximating posterior distributions and the Bayesian information criterion has been considered for covariate selection. In particular, the posterior distribution of the transition probabilities, resulting from the multi-state model, constitutes a very interesting tool which could be useful to help oncologists and patients make efficient and effective decisions.

Evaluation of the scatter field for high-energy photon beam attenuators.

Based upon sector integration, a method has been developed to evaluate the scatter from attenuating beam modulators at any point in the field for arbitrarily shaped fields and attenuators with variable thickness. The method requires preliminary measurements of narrow and broad beam transmission fractions as a function of filter thickness and field size. The ratio Sp of the contribution from photons scattered by the attenuator to the non-attenuated primary contribution was derived from these measurements. Sp was determined for x-ray beam energies between 4 and 23 MV with brass and lead attenuators. This quantity was found to be practically independent of beam energy for a given field size and material. The variation of Sp as a function of slab thickness for attenuators covering the entire beam showed a maximum for a thickness of approximately one mean free path. This maximum represents about 6.0% of the transmitted primary dose for an extreme case of a very heavily (1.6 cm thick lead slab) attenuated 15 cm x 15 cm field. The 'scatter field', corresponding to the scatter contribution from the attenuator across the field, was calculated for different partial attenuators and wedges. The results show that this component has a limited influence on calculation of dose distribution, but should be taken into account in absolute dosimetry analysis for large fields and thick wedge filters.

[Use of a multileaf collimator for the production of intensity-modulated beams]. / Utilisation d'un collimateur multilames pour la production de faisceaux modulés en intensité.

In external radiotherapy, the use of intensity modulated fields has been proposed for tissue and non-homogeneity compensation or for the generation of conformal dose distributions. Multileaf collimators can be employed dynamically for the modulation of the X-ray field in two dimensions. Efficient dynamic collimation became possible due to advances in computer and linear accelerator technology. It presents a number of advantages over conventional methods such as the use of compensators. We have developed a program which calculates, from a given intensity distribution, the motion of the MLC leaves as a function of monitor units, and we have applied it on a Varian linear accelerator with a 40 pair multileaf collimator. The analysis of the experimental results demonstrates the feasibility and the potential of the method.

[Partial breast irradiation: high dose rate peroperative brachytherapy technique using the MammoSite]. / Irradiation partielle du sein: technique de curiethérapie de haut débit de dose après l'implantation peropératoire du dispositif MammoSite.

In the conservative management of breast cancer, radiation therapy delivering 45 to 50 Gy to the whole breast, in 4.5 to 5 weeks, followed by a booster dose of 10 to 20 Gy is the standard of care. Based on the numerous studies which have reported that the local recurrences occurs within and surrounding the primary tumor site and in order to decrease the treatment duration and its morbidity, partial breast irradiation using several techniques has been developed. Partial irradiation may be considered as an alternative local adjuvant treatment for selected patients with favorable prognostic factors. Using external beam radiation therapy, the 3D-conformal technique is appropriate to deliver the whole dose to a limited volume. In UK, an intraoperative technique using a miniature beam of low energy of x-ray (50 Kv) has been developed (Targit). Milan's team have developed an intraoperative electrons beam radiotherapy using a dedicated linear accelerator in the operative room. In USA and Canada the MammoSite has been advised for clinical use in per-operative brachytherapy of the breast. These two last techniques are currently compared in phase III randomised studies to the standard whole breast irradiation followed by a tumour bed booster dose. In this review we will focus on the MammoSite technique and will describe the per-operative implantation procedure, radiological controls ad dosimetric aspects.

IMP-3 expression in keratoacanthomas and squamous cell carcinomas of the skin: an immunohistochemical study.

The protein insulin-like growth factor II mRNA binding protein 3 (IMP3) is an important factor for cell migration and adhesion in malignancies. Recent studies have shown a remarkable overexpression of IMP3 in different human malignant neoplasms and also revealed it as an important prognostic marker in some tumor entities. The purpose of this study is to compare IMP3 immunostaining in squamous cellular skin tumor and determine whether IMP3 can aid in the differential diagnosis of these lesions. To our knowledge, IMP3 expression has not been investigated in skin squamous cell proliferations thus far. Immunohistochemical staining for IMP3 was performed on slides organized by samples from 67 patients, 34 with keratoacanthoma and 33 with primary squamous cell carcinoma (16 invasive and 17 in situ). The majority of our KAs (25/34) were negative for IMP-3 staining. The majority of SCCs (19/33) are positive for IMP3 staining. The percentage of IMP3 positive cells increases significantly in group SCC (p=0.0111), and in particular in the SCC in situ group (p=0.0021) with respect to the KA group.  IMP3 intensity staining increases significantly in SCCs (p=0.0213), and particularly in SCCs (p=0.008) with respect to KA. Our data show that IMP3 expression is different in keratoacanthomas with respect to squamous cell carcinoma. IMP3 assessment and staining pattern, together with a careful histological study, can be useful in the differential diagnosis between KA e SCC.

The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions.

C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migration and proliferation, has shown differential immunostaining in various benign and malignant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was performed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intradermal nevi, 3 junctional nevi, 15 cases of primary compound nevus, 11 cases of Spitz nevus), 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were positive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007) in both groups. The patient's age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other variables (P=0.014). The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008) compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi). Immunostaning for c-Kit in metastatic melanomas was negative. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplasmatic and membranous positivity for c-kit, in contrast with the absence of any immunoreactivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immunohistochemical marker for distinguishing melanoma from melanocytic nevi, if we consider c-Kit expression in intraepidermal proliferating cells. The c-Kit expression in proliferating melanocytes in the dermis could help in the differential diagnosis between a superficial spreading melanoma (with dermis invasion) and a compound nevus or an intradermal nevus. Finally, c-Kit could be a good diagnostic tool for distinguishing benign compound nevi from malignant melanocytic lesions with dermis invasion and to differentiate metastatic melanoma from primary melanoma.

[Persistence of the omphalomesenteric duct. Childhood differential diagnosis of umbilical granuloma]. / Persistencia del conducto onfalomesentérico. Diagnóstico diferencial de granuloma umbilical en la infancia.

The omphalomesenteric duct is an embryonic structure which communicates the vitelline duct with the midgut. It normally disappears between the fifth and ninth weeks of intrauterine life. Anomalies related with the total or partial absence of this involution are show in 2 % of the population. We report a case of persistence of the omphalomesenteric duct and review the bibliography to establish the differences between this anomaly and umbilical granuloma, which is the main differential diagnosis.

[Impact of medical counselling on giving up smoking during pregnancy]. / Impacto del consejo médico para dejar de fumar durante la gestación.

OBJECTIVE: Women s tobacco consumption has increased in Spain in recent years, especially among women of reproductive age. This study aims to evaluate the impact of medical counselling integrated into pre-natal care on tobacco consumption during pregnancy and the period after delivery. DESIGN: Quasi-experimental intervention study.Setting. Hospital del Mar, Barcelona. PATIENTS: 219 patients who attended the Hospital del Mar for delivery during 1996 (control group) and 169 patients seen during their pregnancies at the same hospital in 1997 (intervention group). INTERVENTIONS: The control group patients had received normal care. The pregnant women in the intervention group received systematic structured counselling on giving up smoking, backed up by a special brochure composed for this purpose. MEASUREMENTS AND RESULTS: The intervention and control groups showed no statistically significant differences either in their social or demographic variables or in their tobacco consumption. In both groups the evolution of their smoking during pregnancy was determined during their pre-natal visits and six months after delivery through a telephone interview. 44 of the women in the control group (20.1%) gave up smoking before their first pre-natal visit, and 11 (5%) gave up during pregnancy. In the intervention group 26 (17.7%) had given up spontaneously and 16 (10.9%) gave up during pregnancy. Of those who gave up completely during pregnancy, 36.4% of women in the control group and 64.3% in the intervention group remained abstinent at six months (P=.002). CONCLUSIONS: Counselling at pre-natal check-ups to give up smoking lightly increases the number of women who give up and reduces significantly the number of post-delivery backsliders.

[Validity of the declared tobacco consumption in pregnancy]. / Validez del consumo declarado de tabaco en el embarazo.

OBJECTIVES: To analyse the relationship between the stated consumption of tobacco by pregnant women who say they smoked before pregnancy and the levels of cotinine in their urine at the start and end of pregnancy. DESIGN: Observational, longitudinal study. PARTICIPANTS: During 1997. STUDY GROUP: 147 pregnant women at their first pre-natal visit to outclinics of the Hospital del Mar. CONTROL GROUP: 50 non-smoker pregnant women monitored during their pregnancy. MEASUREMENTS AND MAIN RESULTS: The numbers of cigarettes per day that they said they smoked on their first monitoring visit to our centre and at the last attendance before giving birth were recorded. Cotinine levels in the urine samples taken on these visits were measured. Mean cotinine in pregnant women who said they had given up smoking was higher than in non-smokers. There was a statistically significant linear relationship between the number of cigarettes stated and cotinine levels at the first and last pregnancy monitoring visits, as well as between the variation in the number of cigarettes and cotinine levels at these two visits. The negative predictive value of what they said about their tobacco habit was 82.9%. CONCLUSIONS: There was a certain under-declaration by pregnant smokers, although their statements of consumption and cotinine levels correlated closely. The under-declaration did not increase despite reiterated advice to stop smoking, which means that, despite its limitations, it could be a useful indicator for evaluating the effect of interventions aimed at stopping women smoking during pregnancy.