PTSD symptoms as a consequence of breast cancer diagnosis : clinical implications

It is a well-established multidisciplinary practice at the European Institute of Oncology, that nurses and physicians often report their difficulties to clinical psychologists regarding adherence to hospital scheduling and procedures, when faced with women who, having been diagnosed with cancer, may be too overwhelmed to understand medical advice. We thus undertook an observational-prospective-cohort study, to investigate the prevalence and variation of PTSD symptomatology in women awaiting a mastectomy at a mean of 30 days after diagnosis and up to 2 years after discharge from hospital. The presence of any correlations between PTSD symptoms and medical and psycho-social variables was also investigated. Between March 2011 and June 2012, 150 women entered the study and were evaluated at four points in time: pre-hospital admission, admission for surgery, hospital discharge and two years later. The prevalence of distress at pre-hospital admission was 20% for intrusion symptoms, 19.1% for avoidance symptoms and 70.7% for state anxiety. Intrusion was negatively correlated with time from diagnosis independently of tumor dimensions, i.e. independently of the perceived seriousness of the illness. Even though at two-year follow up the prevalence of intrusion and avoidance is similar to that in the general population, patients with high levels of intrusion and avoidance at pre-hospital admission will maintain these levels, showing difficulties in adjusting to illness even two years later. As for psycho-social factors, the presence of a positive cancer family and relational history is associated with high levels of distress, in particular with intrusive thinking. Proper interventions aimed at the management of these issues and at their implications in clinical practice is clearly warranted

Intramammary administration of platelet concentrate as an unconventional therapy in bovine mastitis: first clinical application

Bovine udder infections induce a variety of changes in gene expression of different growth factors that may suggest their possible role in glandular tissue protection or repair processes. Growth factors and also chemokines and cytokines may act synergistically to increase the infiltration of neutrophils and macrophages to promote angiogenesis, fibroplasia, matrix deposition, and, ultimately, re-epithelialization. Considering the vast applications, typically in human medicine, of platelet concentrate (PC) and its ease of preparation, the aim of our study was to evaluate an alternative therapy to stimulate the regeneration of glandular tissue, administering a concentration in excess of the growth factors contained in the PC. In each one of the 3 farms examined in the trial, PC was prepared from donor cows in good health, free from infections, and with no records of medications administered during the previous 2 mo. The platelet produced in one farm was used only for treating the cows of the same farm in a heterologous way. A total of 229 mastitic quarters were divided in 3 groups: antibiotic group (treated with intramammary antibiotic), antibiotic and PC group (treated intramammarily with antibiotics in association with PC), and PC group (treated with intramammary PC alone). The diagnosis of mastitis was based on somatic cell count and bacteriological evaluation of the milk from the affected quarter. Platelet concentrate, alone or in association with antibiotic, was used for 3 consecutive days as an unconventional therapy in bovine acute and chronic mastitis. Our data show that the associated action of antibiotic and PC performed significantly better than the antibiotic alone, either for the recovery of the affected mammary quarters or for somatic cell count reduction. In the same way, the association antibiotic plus PC showed significantly fewer relapses compared with the antibiotic alone, either for acute or chronic mastitis. The treatment with only PC did not show statistically significant differences compared with both antibiotic alone or associated treatment for acute mastitis, and it was better than the use of only antibiotic for chronic mastitis. Our results show that PC alone may be useful for a quick resolution of the inflammatory response, playing a role in limiting the tissue damage to the mammary gland parenchyma and reducing the recurrence rates

IART® (Intra-Operative Avidination for Radionuclide Therapy) for accelerated radiotherapy in breast cancer patients. Technical aspects and preliminary results of a phase II study with 90Y-labelled biotin

Background: Breast conserving surgery (BCS) plus external beam radiotherapy (EBRT) is considered the standard treatment for early breast cancer. We have investigated the possibility of irradiating the residual gland, using an innovative nuclear medicine approach named IART® (Intra-operative Avidination for Radionuclide Therapy). Aim: The objective of this study was to determine the optimal dose of avidin with a fixed activity (3.7 GBq) of 90Y-biotin, in order to provide a boost of 20 Gy, followed by EBRT to the whole breast (WB) at the reduced dose of 40 Gy. Local and systemic toxicity, patient's quality of life, including the cosmetic results after the combined treatment with IART® and EBRT, were assessed. Methods: After tumour excision, the surgeon injected native avidin diluted in 30 ml of saline solution into and around the tumour bed (see video). Patients received one of three avidin dose levels: 50 mg (10 pts), 100 mg (15 pts) and 150 mg (10 pts). Between 12 to 24 h after surgery, 3.7 GBq 90Y-biotin spiked with 185 MBq 111In-biotin was administered intravenously (i.v.). Whole body scans and SPECT images were performed up to 30 h post-injection for dosimetric purposes. WB-EBRT was administered four weeks after the IART® boost. Local toxicity and quality of life were evaluated. Results: Thirty-five patients were evaluated. No side effects were observed after avidin administration and 90Y-biotin infusion. An avidin dose level of 100 mg resulted the most appropriate in order to deliver the required radiation dose (19.5 + 4.0 Gy) to the surgical bed. At the end of IART®, no local toxicity occurred and the overall cosmetic result was good. The tolerance to the reduced EBRT was also good. The highest grade of transient local toxicity was G3, which occurred in 3/32 pts following the completion of WB-EBRT. The combination of IART® +EBRT was well accepted by the patients, without any changes to their quality of life. Conclusions: These preliminary results support the hypothesis that IART® may represent a valid approach to accelerated WB irradiation after BCS. We hope that this nuclear medicine technique will contribute to a better management of breast cancer patients. © the authors; licensee ecancermedicalscience

Prevalence in bulk tank milk and epidemiology of Campylobacter jejuni in dairy herds in Northern Italy

Thermotolerant Campylobacter spp. are frequently the cause of human gastroenteritis and have assumed more importance in Italy following the increased consumption of raw milk. Our objectives were to determine the prevalence and genotypes of Campylobacter spp. in dairy herds and to investigate the possible sources of bulk milk contamination. Bulk milk from dairy herds (n = 282) was cultured for Campylobacter spp. and Enterobacteriaceae. At three Campylobacter jejuni-positive farms, bovine feces, pigeon intestines, milk, and water points were also investigated. Isolates were identified by PCR and genotyped using multilocus sequence typing (MLST). C. jejuni was detected in 34 (12%) bulk milk samples. The strains belonged to 14 sequence types, and the most common clonal complexes were CC-21, CC-48, and CC-403. No association was demonstrated between the presence of C. jejuni and high levels of Enterobacteriaceae in bulk milk. At the three farms examined, C. jejuni was isolated from bovine feces (25/82 [30.5%]), pigeon intestines (13/60 [21.7%]), bulk milk (10/24 [41.7%]), and water points (4/16 [25%]). MLST revealed lineages that were common between milk and bovine feces but distinct between cattle and pigeons. In one herd, C. jejuni with the same genotype was isolated repeatedly from bulk milk and a cow with an udder infection. Our results showed a high prevalence of C. jejuni in bulk milk and suggested that udder excretion, in addition to fecal matter, may be a route of bulk milk contamination. MLST analysis indicated that pigeons are probably not relevant for the transmission of C. jejuni to cattle and for milk contamination

Disease-relevant proteostasis regulation of cystic fibrosis transmembrane conductance regulator

Mismanaged protein trafficking by the proteostasis network contributes to several conformational diseases, including cystic fibrosis, the most frequent lethal inherited disease in Caucasians. Proteostasis regulators, as cystamine, enable the beneficial action of cystic fibrosis transmembrane conductance regulator (CFTR) potentiators in \u394F508-CFTR airways beyond drug washout. Here we tested the hypothesis that functional CFTR protein can sustain its own plasma membrane (PM) stability. Depletion or inhibition of wild-type CFTR present in bronchial epithelial cells reduced the availability of the small GTPase Rab5 by causing Rab5 sequestration within the detergent-insoluble protein fraction together with its accumulation in aggresomes. CFTR depletion decreased the recruitment of the Rab5 effector early endosome antigen 1 to endosomes, thus reducing the local generation of phosphatidylinositol-3-phosphate. This diverts recycling of surface proteins, including transferrin receptor and CFTR itself. Inhibiting CFTR function also resulted in its ubiquitination and interaction with SQSTM1/p62 at the PM, favoring its disposal. Addition of cystamine prevented the recycling defect of CFTR by enhancing BECN1 expression and reducing SQSTM1 accumulation. Our results unravel an unexpected link between CFTR protein and function, the latter regulating the levels of CFTR surface expression in a positive feed-forward loop, and highlight CFTR as a pivot of proteostasis in bronchial epithelial cells

High-dose-rate Brachytherapy as Adjuvant Local rEirradiation for Salvage Treatment of Recurrent breAst cancer (BALESTRA): a retrospective mono-institutional study

Purpose: To evaluate clinical results of catheter-based interstitial high-dose-rate (HDR) brachytherapy (BT) as adjuvant treatment in previously irradiated recurrent breast cancer. Material and methods: Between January 2011 and September 2015, 31 consecutive patients with histologically confirmed recurrent breast cancer after conservative surgery and conventional whole breast radiotherapy, were retreated with a second conservative surgical resection and reirradiated with adjuvant interstitial HDR-BT. None of the brachytherapy implant was performed during the quadrantectomy procedure. A dose of 34 Gy in 10 fractions, 2 fractions per day, with a minimal interval of 6 hours was delivered. Results: At the time of the implant, the median age of patients was 59.7 years (range, 39.3-74.9 years). The median time from first treatment until BT for local recurrence was 11.9 years (range, 2.5-27.8 years). The median interval between salvage surgery and BT was 3.6 months (range, 1-8.2 months). No acute epidermitis or soft tissue side effects higher than grade 2 were recorded, with good cosmetic results in all patients. Most of the patients presented grade 1-2 late side effects. Only one patient developed grade 3 liponecrosis. After a median follow-up of 73.7 months (range, 28.8-102.4 months), the overall survival and cancer specific survival were 87.1% and 90.3%, respectively; 5-year local control and 5-year progression-free survival rate were 90.3% and 83.9%, respectively. Conclusions: Our preliminary analysis showed that HDR-BT is a feasible treatment for partial breast reirradiation offering very low complications rate and fast procedure. Higher patients' cohort is warranted in order to define the role of this treatment modality in the breast conservative management of local recurrence

The efficacy of 'Radio guided Occult Lesion Localization' (ROLL) versus 'Wire-guided Localization' (WGL) in breast conserving surgery for non-palpable breast cancer: A randomized clinical trial – ROLL study

<p>Abstract</p> <p>Background</p> <p>With the increasing number of non palpable breast carcinomas, the need of a good and reliable localization method increases. Currently the wire guided localization (WGL) is the standard of care in most countries. Radio guided occult lesion localization (ROLL) is a new technique that may improve the oncological outcome, cost effectiveness, patient comfort and cosmetic outcome. However, the studies published hitherto are of poor quality providing less than convincing evidence to change the current standard of care.</p> <p>The aim of this study is to compare the ROLL technique with the standard of care (WGL) regarding the percentage of tumour free margins, cost effectiveness, patient comfort and cosmetic outcome.</p> <p>Methods/design</p> <p>The ROLL trial is a multi center randomized clinical trial. Over a period of 2–3 years 316 patients will be randomized between the ROLL and the WGL technique. With this number, the expected 15% difference in tumour free margins can be detected with a power of 80%. Other endpoints include cosmetic outcome, cost effectiveness, patient (dis)comfort, degree of difficulty of the procedures and the success rate of the sentinel node procedure.</p> <p>The rationale, study design and planned analyses are described.</p> <p>Trial Registration</p> <p>(<url>http://www.clinicaltrials.gov</url>, study protocol number NCT00539474)</p

Multiple sclerosis and celiac disease : is there an increased risk?

Multiple sclerosis and celiac disease are both considered immune-mediated diseases. Recently, improved serological screening methods provided a higher prevalence of celiac disease (CD) in the general population worldwide and also demonstrated gastrointestinal symptoms may be lacking. The aim of this study was to determine the prevalence of (CD) in an unselected group of 95 adults with multiple sclerosis using transglutaminase antibodies. No patients showed pathological values. Different immune and genetic basis between the two diseases may represent crucial insights to explain our results