Use of long implants with distal anchorage in the skull base for treatment of extreme maxillary atrophy: the remote bone anchorage concept

The objectives of this study are to present a new concept of the bone anchorage using long implants in remote bone sites and to discuss four cases treated with this method. Our patients were treated with long implants with a distant anchorage in the skull bone. The planning procedure, the construction of the drill guide, and the surgical protocol are described. In the clinical cases described, all four patients were rehabilitated with the remote bone anchorage concept using long implants anchored in the skull base. Patients were followed for 5 - 12 years and the implants remained present and stable in these time periods. The skull base implant is a new concept of bone anchorage using long implants. It can be a solution for complicated clinical situations (often failed bone reconstructions and implant placements) or an alternative for bone grafting and maxillary augmentation procedures. There is effective implant retention in the skull base, an anatomical area that is often overlooked for implant placement.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Rc8HSb
via IFTTT

Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy

DNA methyltransferase 1 (DNMT1) plays a pivotal role in maintaining DNA methylation status. Polymorphisms of DNMT1 may modify the role of DNMT1 in prognosis of gastric cancer (GC). Our aim was to test whether polymorphisms of DNMT1 gene were associated with overall survival of GC. Four hundred and forty-seven GC patients who underwent radical tumorectomy were enrolled in the study. Five tagging SNPs (rs10420321, rs16999593, rs2228612, rs2228611, and rs2288349) of the DNMT1 gene were genotyped by TaqMan assays. Kaplan-Meier survival plots and Cox proportional hazard regression were used to analyze the associations between SNPs of DNMT1 and survival of GC. Patients carrying rs2228611 GA/AA genotype tended to live longer than those bearing the GG genotype (HR 0.68, 95% CI: 0.51–0.91, ). Further multivariate Cox regression analysis showed that rs2228611 was an independent prognostic factor (GA/AA versus GG: OR 0.67, 95% CI 0.49–0.91, ). Nevertheless, other SNPs did not show any significant associations with survival of GC. Polymorphisms of the DNMT1 gene may affect overall survival of GC. The SNP rs2228611 has the potentiality to serve as an independent prognostic marker for GC patients.

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/22rFJ9i
via IFTTT

Personalized therapy for hepatocellular carcinoma: Where are we now?

Personalized therapy for hepatocellular carcinoma: Where are we now?

Cancer Treat Rev. 2016 Mar 2;45:77-86

Authors: Chan SL, Wong AM, Lee K, Wong N, Chan AK

Abstract
Following the approval of sorafenib, a large number of molecular targeted agents have been tested clinically for advanced hepatocellular carcinoma (HCC), but all have failed to demonstrate significant efficacy in clinical trials. Multiple reasons for this phenomenon have been discussed in the literature, with one reason being the lack of patient selection on the basis of molecular profile in clinical trials. The concept of drug testing in selected populations has been recently suggested by retrospective analyses of HCC clinical trials in which a particular subgroup of patients, either enriched by clinical factors or by tissue biomarkers, derived more benefits from the novel drug. In addition, recent advances in genomic medicine have enhanced the understanding of genetic and epigenetic events occurring in HCC, raising the possibility of personalizing targeted agents in accordance with the genetic make-up of the tumors. The development of 'personalized' treatment for HCC is, however, hindered by the lack of fresh biopsy of advanced HCC, the low incidence of genetic driver mutations in HCC and the tumor heterogeneity. These limitations may be overcome by sequencing cell-free DNA in plasma, frequently known as liquid biopsy, and revolution in the concept of the design of clinical trials. In this review article, we aim to: (1) give a summary of the recent sequencing results of HCC and the related implications for drug development; (2) highlight potential individual targeted agents and existing research on biomarker selection in clinical trials; and (3) discuss future directions, including the potential of liquid biopsy and umbrella clinical trials, to enhance personalized drug testing for HCC.

PMID: 26995632 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1LABRv8
via IFTTT

Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience.

Modified irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): a single-institution experience.

Med Oncol. 2016 Apr;33(4):37

Authors: Bupathi M, Ahn DH, Wu C, Ciombor KK, Stephens JA, Reardon J, Goldstein DA, Bekaii-Saab T

Abstract
Pancreatic adenocarcinoma is the fourth leading cause of cancer death. Recently, MM-398 (nanoliposomal irinotecan) was shown to be associated with significant improvement in outcome measures with acceptable toxicities when combined with 5-fluorouracil (5-FU)/leucovorin (LV) compared to 5-FU/LV alone in patients failing one line of gemcitabine-based therapy. There is a paucity of data evaluating the role of irinotecan in combination with 5FU in advanced pancreas cancer (APC). We performed a retrospective analysis of all patients who received mFOLFIRI (minus bolus 5FU and LV). All patients with metastatic disease who had failed at least one line of gemcitabine-based therapy prior to receiving mFOLFIRI were included in this study. Descriptive statistics were used to assess the continuous variables and adverse events (AEs), and Kaplan-Meier methods were used to calculate the median progression-free survival (PFS) and overall survival (OS). Forty patients were included in this analysis. Patients received 1-5 lines of prior therapy (25 % with more than 3 lines of prior therapy). The mean age at diagnosis was 60, and 98 % had ECOG of 1. The mean CA 19-9 at the start of therapy was 33,169 U/ml. The median PFS was 2.59 months [95 % confidence interval (CI) (1.90, 3.54)], and OS was 4.75 months [95 % CI (3.14, 8.98)]. The most common AEs included fatigue (98 %), neuropathy (83 %), anorexia (68 %), nausea (60 %) and constipation (55 %). Grade 3 toxicities included fatigue (13 %) and rash (3 %). There were no observed grade 4 toxicities. In this single-institution retrospective analysis, mFOLFIRI was found to be both tolerable and relatively effective in a heavily pretreated patient population with APC. Future prospective studies should consider evaluating the role of mFOLFIRI in refractory APC.

PMID: 26995224 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Rc00Hs
via IFTTT

Tracking metastatic breast cancer: the future of biology in biosensors.

Tracking metastatic breast cancer: the future of biology in biosensors.

Med Oncol. 2016 Apr;33(4):36

Authors: Lim YC, Wiegmans AP

Abstract
Circulating tumour cells associated with breast cancer (brCTCs) represent cells that have the capability to establish aggressive secondary metastatic tumours. The isolation and characterization of CTCs from blood in a single device is the future of oncology diagnosis and treatment. The methods of enrichment of CTCs have primarily utilized simple biological interactions with bimodal reporting with biased high purity and low numbers or low purity and high background. In this review, we will discuss the advances in microfluidics that has allowed the use of more complex selection criteria and biological methods to identify CTC populations. We will also discuss a potential new method of selection based on the response of the oncogenic DNA repair pathways within brCTCs. This method would allow insight into not only the oncogenic signalling at play but the chemoresistance mechanisms that could guide future therapeutic intervention at any stage of disease progression.

PMID: 26995223 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1LABRuY
via IFTTT

Impact of dermatologic adverse events induced by targeted therapies on quality of life.

Impact of dermatologic adverse events induced by targeted therapies on quality of life.

Crit Rev Oncol Hematol. 2016 Mar 5;

Authors: Charles C, Bungener C, Razavi D, Mateus C, Routier E, Lanoy E, Verschoore M, Robert C, Dauchy S

Abstract
BACKGROUND: Investigations about the impact of dermatologic adverse events on quality of life in the context of targeted therapies are quite recent and results vary in some dimensions. This article aims to summarize the existing data and to clarify needs in terms of clinical management and future research.
METHODS: A literature review was done with Pubmed, Medline, Scopus and PsycInfo databases and it combined the empirical studies published in English and in French over the past ten years.
RESULTS AND CONCLUSIONS: Dermatologic adverse events globally have a low to moderate impact on quality of life, mainly in the physical and emotional domains. Reasons for inter-individual variations in adjustment and long-term impact are still not well known. Making quality of life assessments systematic, making early referrals of patients to dermatology consultations and giving more attention to individual experience were identified as measures that could help prevent deterioration in quality of life.

PMID: 26995080 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1Rc02yX
via IFTTT

Analysis of nodal coverage utilizing image guided radiation therapy for primary gynecologic tumor volumes.

Analysis of nodal coverage utilizing image guided radiation therapy for primary gynecologic tumor volumes.

Med Dosim. 2016 Mar 16;

Authors: Ahmed F, Sarkar V, Gaffney DK, Salter B, Poppe MM

Abstract
PURPOSE: To evaluate radiation dose delivered to pelvic lymph nodes, if daily Image Guided Radiation Therapy (IGRT) was implemented with treatment shifts based on the primary site (primary clinical target volume [CTV]). Our secondary goal was to compare dosimetric coverage with patient outcomes.
MATERIALS AND METHODS: A total of 10 female patients with gynecologic malignancies were evaluated retrospectively after completion of definitive intensity-modulated radiation therapy (IMRT) to their pelvic lymph nodes and primary tumor site. IGRT consisted of daily kilovoltage computed tomography (CT)-on-rails imaging fused with initial planning scans for position verification. The initial plan was created using Varian׳s Eclipse treatment planning software. Patients were treated with a median radiation dose of 45Gy (range: 37.5 to 50Gy) to the primary volume and 45Gy (range: 45 to 64.8Gy) to nodal structures. One IGRT scan per week was randomly selected from each patient׳s treatment course and re-planned on the Eclipse treatment planning station. CTVs were recreated by fusion on the IGRT image series, and the patient׳s treatment plan was applied to the new image set to calculate delivered dose. We evaluated the minimum, maximum, and 95% dose coverage for primary and nodal structures. Reconstructed primary tumor volumes were recreated within 4.7% of initial planning volume (0.9% to 8.6%), and reconstructed nodal volumes were recreated to within 2.9% of initial planning volume (0.01% to 5.5%).
RESULTS: Dosimetric parameters averaged less than 10% (range: 1% to 9%) of the original planned dose (45Gy) for primary and nodal volumes on all patients (n = 10). For all patients, ≥99.3% of the primary tumor volume received ≥ 95% the prescribed dose (V95%) and the average minimum dose was 96.1% of the prescribed dose. In evaluating nodal CTV coverage, ≥ 99.8% of the volume received ≥ 95% the prescribed dose and the average minimum dose was 93%. In evaluating individual IGRT sessions, we found that 6 patients had an estimated minimal nodal CTV dose less than 90% (range: 78 to 99%) of that planned. With a median follow-up of 42.5 months, 2 patients experienced systemic disease progression at an average of 19.6 months. One patient was found to have a local or regional failure with an average follow-up of 42 months.
CONCLUSION: Using only 3 dimensional IGRT corrections in gynecological radiation allows excellent coverage of the primary target volume and good average nodal CTV coverage. If IGRT corrections are based on alignment to the primary tumor volume, and is only able to be corrected in 3 degrees, this can create situations in which nodal volumes may be under dosed. Utilizing multiple IGRT sessions appears to average out dose discrepancies over the course of treatment. The implication of underdosing in a single IGRT session needs further evaluation in future studies. Based on the concern of minimum dose to a nodal target volume, these findings may signal caution when using IGRT and IMRT in gynecological radiation patients. Possible techniques to overcome this situation may include averaging shifts between tumor and nodal volume, use of a treatment couch with 6° of freedom, deformable registration, or adaptive planning.

PMID: 26994828 [PubMed - as supplied by publisher]

from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1LABTDc
via IFTTT