A Preliminary Study on Hepatoprotective, Hypolipidemic and Aortic Morphometric Effects of Omega-3-Rich Fish Oil in Hypercholesterolemic Mice.

This study aims to evaluate the hepatoprotective, hypolipidemic and aortic morphometric effects of fish oil rich in omega-3 in hypercholesterolemic BALB/c mice. This is an experimental model that included 16 male BALB/c mice (Mus musculus) divided into three groups (G1 (standard commercial chow and 0.9% saline solution), G2 (hypercholesterolemic diet and 0.9% saline solution) and G3 (hypercholesterolemic diet and fish oil)) for 8 weeks. There was no significant difference in the treatment with omega-3-rich fish oil in the lipid profile (p > 0.05). In the histological analysis, group G2 detected the presence of hepatitis and liver tissue necrosis, but this was not observed in group G3. As for the morphometry in the light area of the vessel, the G1 group had a higher score (2.62 ± 0.36 mm2) when compared to G2 (2.10 ± 0.16 mm2) and G3 (2.26 ± 0.25 mm2) (p < 0.05). The vessel wall thickness did not differ between the groups (p > 0.05). It is concluded that supplementation with fish oil rich in omega-3 carried out in this study may have a protective effect on liver tissue, but it has not yet improved the lipid and morphometric profile. Despite this research being preliminary, it is a relevant study with future prospects for improving the doses of EPA and DHA in order to better elucidate the benefits of fish oil in models of dyslipidemia.

Minibeam radiation therapy: A micro- and nano-dosimetry Monte Carlo study.

PURPOSE: Minibeam radiation therapy (MBRT) is an innovative strategy based on a distinct dose delivery method that is administered using a series of narrow (submillimetric) parallel beams. To shed light on the biological effects of MBRT irradiation, we explored the micro- and nanodosimetric characteristics of three promising MBRT modalities (photon, electron, and proton) using Monte Carlo (MC) calculations. METHODS: Irradiation with proton (100 MeV), electron (300 MeV), and photon (effective energy of 69 keV) minibeams were simulated using Geant4 MC code and the Geant4-DNA extension, which allows the simulation of energy transfer points with nanometric accuracy. As the target of the simulations, cells containing spherical nuclei with or without a detailed description of the DNA (deoxyribonucleic acid) geometry were placed at different depths in peak and valley regions in a water phantom. The energy deposition and number of events in the cell nuclei were recorded in the microdosimetry study, and the number of DNA breaks and their complexity were determined in the nanodosimetric study, where a multi-scale simulation approach was used for the latter. For DNA damage assessment, an adapted DBSCAN clustering algorithm was used. To compare the photon MBRT (xMBRT), electron MBRT (eMBRT), and proton MBRT (pMBRT) approaches, we considered the treatment of a brain tumor located at a depth of 75 mm. RESULTS: Both mean energy deposition at micrometric scale and DNA damage in the "valley" cell nuclei were very low as compared with these parameters in the peak region at all depths for xMBRT and at depths of 0 to 30 mm and 0 to 50 mm for eMBRT and pMBRT, respectively. Only the charged minibeams were favorable for tumor control by producing similar effects in peak and valley cells after 70 mm. At the micrometer scale, the energy deposited per event pointed to a potential advantage of proton beams for tumor control, as more aggressive events could be expected at the end of their tracks. At the nanometer scale, all three MBRT modalities produced direct clustered DNA breaks, although the majority of damage (>93%) was composed of isolated single strand breaks. The pMBRT led to a significant increase in the proportion of clustered single strand breaks and double-strand breaks at the end of its range as compared to the entrance (7% at 75 mm vs 3% at 10 mm) in contrast to eMBRT and xMBRT. In the latter cases, the proportions of complex breaks remained constant, irrespective of the depth and region (peak or valley). CONCLUSIONS: Enhanced normal tissue sparing can be expected with these three MBRT techniques. Among the three modalities, pMBRT offers an additional gain for radioresistant tumors, as it resulted in a higher number of complex DNA damage clusters in the tumor region. These results can aid understanding of the biological mechanisms of MBRT.

Intermittent dosing of aromatase inhibitors (AI) to improve tolerance in postmenopausal women: a rationale for future clinical studies.

A significant proportion of post-menopausal, patients treated with AI reports side-effects, especially bone pain. In such patients, the difficulties to treat pain and to clearly identify its causes may lead to treatment discontinuation. Ageing is associated with physiological modifications that may impair drug pharmacokinetics (PKs). The elimination can be altered, with decreased drug clearance (CL), resulting in an increased exposure to the drug, reflected by increased AUCs. The reported increases in AI exposure being around 50 %, an intermittent dosing schedule of 1 administration every other day could result in a similar drug exposure as compared to the usual daily schedule.

Liver metastases from breast cancer: Surgical resection or not? A case-matched control study in highly selected patients.

AIM: To determine whether, in a highly selected patient population, medical treatment combined with surgical resection of liver metastases from breast cancer is associated with improved survival compared with medical treatment alone. PATIENTS AND METHODS: Between 1988 and 2007, 100 liver resections for metastatic breast cancer were performed at Institut Curie, 51 of which met the criteria for inclusion in this case-control study. With the exception of bone metastases, patients with other distant metastasis sites were excluded. Surgery was only performed in patients with stable disease or disease responding to medical treatment evaluated by imaging evaluation. Surgical cases were individually matched with 51 patients receiving medical treatment only. All patients had 4 or fewer resectable liver metastases. The study group was matched with the control group for age, year of breast cancer diagnosis, time to metastasis, TNM stage, hormone receptor status and breast cancer tumour pathology. RESULTS: Univariate analysis confirmed a survival advantage for patients lacking bone metastases and axillary lymphadenopathy at the time of breast cancer diagnosis and for surgically treated patients. Multivariate analysis indicated that surgery and the absence of bone metastases were associated with a better prognosis. A multivariate Cox model adapted for paired data showed a RR = 3.04 (CI: 1.87-4.92) (p < 0.0001) in favour of surgical treatment. CONCLUSION: Surgical resection of liver metastases from primary breast cancer appears to provide a survival benefit for highly selected patients.

Subclinical infection and asymptomatic carriage of gastrointestinal zoonoses: occupational exposure, environmental pathways, and the anonymous spread of disease.

Asymptomatic carriage of gastrointestinal zoonoses is more common in people whose profession involves them working directly with domesticated animals. Subclinical infections (defined as an infection in which symptoms are either asymptomatic or sufficiently mild to escape diagnosis) are important within a community as unknowing (asymptomatic) carriers of pathogens do not change their behaviour to prevent the spread of disease; therefore the public health significance of asymptomatic human excretion of zoonoses should not be underestimated. However, optimal strategies for managing diseases where asymptomatic carriage instigates further infection remain unresolved, and the impact on disease management is unclear. In this review we consider the environmental pathways associated with prolonged antigenic exposure and critically assess the significance of asymptomatic carriage in disease outbreaks. Although screening high-risk groups for occupationally acquired diseases would be logistically problematical, there may be an economic case for identifying and treating asymptomatic carriage if the costs of screening and treatment are less than the costs of identifying and treating those individuals infected by asymptomatic hosts.

The standard tangential fields used for breast irradiation do not allow optimal coverage and dose distribution in axillary levels I-II and the sentinel node area.

BACKGROUND: Recent data from ACOSOG Z0011 and NSABP B32 trials suggested no need for axillary lymph node dissection (ALND) in patients with micrometastatic involvement of the sentinel lymph node (SLN). The low rate of axillary recurrence was attributed to the axilla coverage by the tangential fields (TgFs) irradiation and systemic therapy. This study aimed to evaluate dose distribution and coverage of the axilla levels I-II and the SLN area. PATIENTS AND METHODS: One hundred and nine patients were analyzed according to three groups: group 1 (50 Gy; n = 18), group 2 (60 Gy; n = 34) and group 3 (66 Gy; n = 57). Patients were treated using the standard (STgF; n = 22) or high (HTgF; n = 87) TgF. RESULTS: The median doses delivered to level I using HTgF versus STgF were 33 and 20 Gy (P = 0.0001). The mean dose delivered to the SLN area was only 28 Gy. Additionally, the SLN area was totally included in the HTgF in 1 out of 12 patients who had intraoperative clip placement in the SNL area. CONCLUSIONS: TgFs provide a limited coverage of the axilla and the SNLB area. This information should be considered when only TgFs are planned to target the axilla in patients with a positive SLN without ALND. Standardization of locoregional radiotherapy in this situation is urgently needed.

Outcome in early cervical cancer following pre-operative low dose rate brachytherapy: a ten-year follow up of 257 patients treated at a single institution.

OBJECTIVE: To report the outcome of preoperative low dose rate uterovaginal brachytherapy (LDR-UVBT) followed by radical surgery in the treatment of early cervical carcinoma. METHODS: 257 patients treated at Institut Curie from 1985 to 2008 for cervical carcinoma less than 4cm (FIGO stages Ib1, IIA and IIB) were studied. Patients received preoperative LDR-UVBT followed by hysterectomy Piver II type, with pelvic lymph nodes dissection (PLND). Predictive factors for pathological response to brachytherapy were analyzed with logistic regression, as well as survival rates. RESULTS: 44% of patients had residual tumor, 4.3% of patients had parametrial invasion and 17.9% of patients had lymph node involvement. Predictive factors for an incomplete pathological response were: initial clinical tumor size 20mm (OR 2.1), pN1 (OR 2.77), glandular carcinoma (OR 2.51) and lymphovascular invasion (OR 4.35). 7.4% and 2.7% of patients had respectively grade 2 and grade 3 post-therapeutic late complications. Median follow up was 122 months [1-282]. Five-year actuarial overall survival and disease free survival were respectively 83% CI [78.3-87.5] and 80.9% CI [76.3-85.7]. In multivariate analysis, factors affecting significantly the overall survival and disease free survival rates were: lymph node involvement (RR 4.53 and 8.96 respectively), parametrial involvement (RR 5.69 and 5.62 respectively), smoking (RR 3.07 and 2.63 respectively). CONCLUSIONS: Preoperative LDR-UVBT results in good disease control with a low complications rate. Its accuracy could be improved by a better selection of patients. Lymph nodes and parametrial evaluation remains a challenging issue that should be achieved with imaging and minimal invasive surgery.

Management of exposed, infected implant-based breast reconstruction and strategies for salvage.

INTRODUCTION: Complications of implant-based breast reconstruction are rare but mastectomy flap necrosis and peri-implant infection are the most frequent and remain an important cause of early implant failure. This study aimed to compare the results of three different management strategies employed to deal with these complications at our institution. PATIENTS AND METHODS: A consecutive series of 71 infected/exposed prostheses in 68 patients over a 20-year period were analysed. Management strategies included explantation and delayed reconstruction, implant salvage and explantation and immediate autologous reconstruction. RESULTS: Only 19 of 45 (42%), managed with implant removal, went on to delayed reconstruction. Methods of delayed reconstruction were distributed equally between implant-only, implant and autologous tissue and autologous-only reconstructions. The implant was successfully salvaged in nine cases, but reducing the implant size or introducing new tissue as a flap increased the success from 45% to 53%. Three patients with infected implant-only breast reconstruction underwent explantation and immediate conversion to autologous-only reconstructions. CONCLUSIONS: All the three interventions reviewed here have their place in the management of infected implant-based breast reconstructions. It is noteworthy that following implant removal, the likelihood of the patient proceeding to delayed reconstruction of any kind is similar to the likelihood of successful salvage (42% vs. 45%). This study population had high numbers of exposed implants in irradiated fields. Reducing implant size or introducing new tissue in the form of a flap increases the chances of successful implant salvage. In the presence of mild infection, removal of exposed/infected implants and immediate conversion to an autologous-only reconstruction can prove to be successful.

Risk of invasive breast cancer after lobular intra-epithelial neoplasia: review of the literature.

OBJECTIVE: Lobular intra-epithelial neoplasia (LIN) is a rare breast disease that has been regarded alternately as a risk factor for invasive breast cancer in both breasts or a true breast cancer precursor. The controversy is largely dependent on the estimation of the IBC (Invasive Breast Cancer) risk after LIN; however a systematic review of the published data has not been previously performed. We aimed to review the IBC after LIN and the characteristics of those cancers. METHODS: A PubMed search was performed to identify the published articles in English addressing the breast cancer risk after LIN. RESULTS: There was a wide range in the figures estimating the risk of the breast cancer among the 22 studies that form the basis of this review. The cumulative average risk of invasive breast cancer (IBC) was 8.7% (range 0-33). It was 4.7% (range 0-25) for the ipsilateral and 4.2% (range 0-16) for the contralateral breast. 52% of the breast cancers occurred more than 10 years after the initial LIN. A lobular histotype was present in 30% (range 0-67%) of all IBC. CONCLUSIONS: LIN should be considered both as a risk factor (low and similar level of IBC risk for both breasts, long delay between LIN and IBC) and a precursor for IBC (over-representation of lobular histotype).

Preoperative staging of liver metastases from uveal melanoma by magnetic resonance imaging (MRI) and fluorodeoxyglucose-positron emission tomography (FDG-PET).

BACKGROUND: Microscopically complete (R0) resection of metastases from uveal melanoma prolongs median overall survival compared to incomplete surgery. The aim of this study was to compare the sensitivity of dynamic-enhanced magnetic resonance imaging (MRI) with fluorodeoxyglucose-positron emission tomography (FDG-PET) in the preoperative diagnosis of liver metastases from uveal melanoma. PATIENTS AND METHODS: Fifteen consecutive patients (mean age: 56 years) underwent FDG-PET and liver MRI. Extrahepatic metastatic disease was excluded by whole body computed tomography and bone scintigraphy. MRI and FDG-PET were performed with a mean of 19 days (range: 1-30) before surgery. Imaging findings were compared with surgical (including intraoperative ultrasonography) and histological findings on a lesion by lesion analysis. RESULTS: R0 resection was performed in 12 patients. A total of 28 lesions were resected with 27 histologically proven metastases. Nine lesions were smaller than 5mm, 7 measured 5-10mm and 11 were larger than 10mm. Sensitivity and positive predictive value were 67% and 95% for MRI compared to 41% and 100% for FDG-PET. The difference between the two modalities was statistically significant (p=0.01; McNemar test). In remaining 3 patients, diffuse miliary disease (>10 capsular lesions) was discovered intraoperatively, and was suspected on preoperative MRI in 2 cases. Only one extrahepatic lesion identified by FDG-PET was falsely positive. CONCLUSIONS: In this preliminary study, MRI was superior to FDG-PET for staging of liver metastases from uveal melanoma. Although miliary disease was suggested by MRI in some cases, preoperative confirmation remains imperfect.

Oncoplastic breast surgery: a review and systematic approach.

Oncoplastic breast surgery (OBS) is relatively new, but has made rapid progress from its tentative steps of infancy in the 1990s. The recent Milanese Consensus Conference on Breast Conservation concluded that, firstly, oncoplastic techniques are warranted to allow wide excision and clear margins without compromising cosmesis. Secondly, such surgery is ideally performed at the same time as oncological excision. Whilst technically more challenging than standard breast conserving therapy (BCT), OBS is well proven, if not yet widely practised, both oncologically and aesthetically and a review of the available techniques is perhaps timely. The roots of breast conserving therapy can be traced to the 1930s, actually due to advances made in radiotherapy, and the last 20 years have seen it become firmly established. This review aims to summarise the key historical developments and latest innovations in OBS. Not only are our patients, who expect not only safe cancer treatment but a satisfactory aesthetic outcome, increasingly informed and demanding, but longer follow up has stimulated surgeons to improve outcomes. In many cases, particularly with ptosis and macromastia, the cancer can be treated, usually with wider excision margins, simultaneously improving the aesthetic appearance. Present at the birth of OBS, the Institut Curie has continued to introduce innovative techniques over the last two decades and a systematic approach, comprising nine basic techniques, has evolved to allow high quality treatment of any and all breast cancers suitable for OBS.

Lateral mammaplasty reconstruction after surgery for breast cancer.

BACKGROUND: Up to 60 per cent of cancers develop laterally in the breast and breast-conserving surgery frequently produces superolateral nipple-areolar complex (NAC) distortion aggravated by postoperative irradiation. Correction is technically demanding and the outcomes are variable. Lateral mammaplasty may allow wider excision margins and prevent such deformities. METHODS: This was a review of 86 consecutive patients who had lateral mammaplasty: combined wide tumour excision with NAC repositioning on a reliable dermoglandular pedicle. Simultaneous axillary surgery was performed via a separate or combined incision. Aesthetic outcomes were assessed. RESULTS: The median age of the women was 54 (range 29-75) years; 55 (64 per cent) had palpable tumours and 73 (85 per cent) underwent simultaneous axillary surgery. Median radiological and histological tumour sizes were 29.8 and 33.6 mm, respectively, and median weight of excised tumour was 150 g. Two patients required haematoma evacuation. Eleven women required revisional surgery for involved or close margins. Aesthetic outcomes were excellent or good in 93 per cent. CONCLUSION: Lateral mammaplasty produced clear margins in 87 per cent of women. It is an option when a deformity is anticipated after breast-conserving surgery, and is particularly valuable when neoadjuvant chemotherapy has downgraded a large tumour.