Publication date: Available online 4 May 2018
Source:Seminars in Oncology
Author(s): Bello-Rivero Iraldo, Garcia-Vega Yanelda, Duncan-Roberts Yaquelin, Vazquez-Blonquist Dania, Hector Santana Milian, Besada-Perez Vladimir, Rios-Cabrera Margarita
The rational combination of recombinant IFN-α2b and IFN-γ resulted in a new formulation of IFNs (HeberFERON) with improved pharmacodynamics. In basal cell carcinomas HeberFERON produces a more rapid antitumor effect and results in a larger number of complete responses. In patients with glioblastoma multiforme, the administration of HeberFERON after surgery and radiotherapy results in an estimated overall survival of 19 months. Patients with state III or IV renal cell carcinoma also ppear to benefit from the intravenous administration of HeberFERON, with prolongation of survival and a good quality of live. HeberFERON offers a promising alternative formulation of IFNs for the treatment of cancer with a very favorable safety profile.
https://ift.tt/2IQVGSU
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Δευτέρα 28 Μαΐου 2018
HeberFERON, a new formulation of IFNs with improved pharmacodynamics. Perspective for cancer treatment
CIGB-300: A peptide-based drug that impairs the Protein Kinase CK2-mediated phosphorylation
Publication date: Available online 3 May 2018
Source:Seminars in Oncology
Author(s): Silvio E. Perea, Idania Baladrón, Carmen Valenzuela, Yasser Perera
Protein kinase CK2 - formerly referred to as casein kinase II - is a serine/threonine kinase often found overexpressed in solid tumors and hematologic malignancies that phosphorylates many substrates integral to the hallmarks of cancer. CK2 has emerged as a viable oncology target having been experimentally validated with different kinase inhibitors including small molecule ATP-competitors, synthetic peptides and antisense oligonucleotides. To date only two CK2 inhibitors, CIGB-300 and CX-4945, have entered the clinic in Phase 1-2 trials. This review provides information on CIGB-300 a cell-permeable cyclic peptide that inhibits CK2-mediated phosphorylation by targeting the substrate phosphoacceptor domain. We review data that support the concept of CK2 as an anticancer target, address the mechanism of action and summarize preclinical studies showing antiangiogenic and antimetastatic effects as well as synergism with anticancer drugs in preclinical models. We also summarize early clinical research (Phase 1/2 trials) of CIGB-300 in cervical cancer including data in combination with chemoradiotherapy. The clinical data demonstrate the safety, tolerability and clinical effects of intratumoral injections of CIGB-300 and provide the foundation for future Phase 3 clinical trials in locally advanced cervical cancer in combination with standard chemoradiotherapy.
https://ift.tt/2xnXiyp
Nimotuzumab: beyond the EGFR signaling cascade inhibition
Publication date: Available online 2 May 2018
Source:Seminars in Oncology
Author(s): Zaima Mazorra, Lisset Chao, Anabel Lavastida, Belinda Sanchez, Mayra Ramos, Normando Iznaga, Tania Crombet
One of the most known oncogenes is the epidermal growth factor receptor (EGFR) family. It activates multiple signaling cascades which promote carcinogenesis and immune evasion. Therefore, these molecules have been extensively targeted in cancer immunotherapy. Beyond EGFR signaling cascade inhibition, some of these agents are able to induce T cell activation transforming a passive therapy into a vaccine-like effect.Nimotuzumab is an IgG1 humanized MAb directed against the extracellular domain of the EGFR blocking the binding to its ligands. It possesses unique pharmacodynamics properties, which allow treating patients for long–term period and with very low toxicity. Based on its clinical effect, nimotuzumab has been approved in Cuba and abroad for the treatment of different epithelial tumors. Recently, new potential mechanisms of action of nimotuzumab involving the activation of the innate and adaptive immune response have been reported.This review summarizes the main properties of nimotuzumab in comparison with others EGFR specific monoclonal antibodies highlighting its capacity to activate an effective immune response. In addition, differential clinical effect of this antibody and ongoing clinical trials to deeply characterize the biomarkers of clinical benefit are shown.
https://ift.tt/2LCMgsd
CIMAvax-EGF: Toward long-term survival of advanced NSCLC
Publication date: Available online 1 May 2018
Source:Seminars in Oncology
Author(s): Danay Saavedra, Elia Neninger, Camilo Rodriguez, Carmen Viada, Zaima Mazorra, Agustin Lage, Tania Crombet
Lung cancer remains one of the leading causes of cancer related deaths. Non-small cell lung cancer (NSCLC) is the most common histological type of lung cancer. Medical and scientific progress has led to longer survival in an increasing number of patients suffering for cancer. Concerning patients with advanced NSCLC, there is a subgroup with long-term survival. The human Epidermal Growth Factor Receptor (EGFR) family plays a key role in tumor development. This cluster of genes is associated with augmented angiogenesis and enhanced proliferation, survival and migration of tumor cells. The CIMAvax-EGF vaccine consists of a chemical conjugate of the EGF with the P64 protein derived from the Meningitis B bacteria and the Montanide ISA 51, as adjuvant. The vaccine induces antibodies against EGF that results in EGF withdrawal. CIMAvax-EGF has been demonstrated to be safe and immunogenic in advanced NSCLC patients. Here, we summarize the current knowledge of the mechanism of action of CIMAvax-EGF, highlighting the impact of this anti-EGF based vaccine on the long-term survival of advanced NSCLC patients.
https://ift.tt/2xnuhCL
Combining computational and experimental biology to develop therapeutically valuable IL2 muteins
Publication date: Available online 1 May 2018
Source:Seminars in Oncology
Author(s): Kalet León, Karina García-Martínez, Tania Carmenate, Gertrudis Rojas
High-dose IL2, first approved in 1992, has been used in the treatment of advanced renal cell carcinoma and melanoma. In these indications, IL2 induces long lasting objective responses in 5% to 20% of patients. However, toxicity and the unexpected expansion of regulatory T cells (Tregs) have limited its practical use and therapeutic impact, respectively. At the Center of Molecular Immunology in Havana, Cuba, a project was launched in 2005 to rationally design IL2 muteins that could be deployed in the therapy of cancer. The basic goal was to uncouple the pleiotropic effect of IL2 on different immune T cells, to obtain a mutein with a therapeutic index that was better than that achieved with wild type (wt) IL2. Using a combination of computational and experimental biology approaches, we predicted and developed two novel IL2 muteins with therapeutic potential. The first, designated no-alpha mutein, is an agonist of IL2R signaling with a reduced ability to expand Treg in vivo. In mice, the no-alpha mutein IL2 has higher antitumor activity and lower toxicity than wt IL2. It represents a potential best-in-class drug that has begun phase I/II clinical trials in solid tumors. The second, designated no-gamma mutein, is an antagonist of IL2R signaling, with some preferential affinity for Tregs. This mutein has antitumor activity in mice that likely derives from its ability to reduce Treg accumulation in vivo. It represents a first-in-class drug that offers a novel strategy to inhibit Treg activity in vivo.
https://ift.tt/2IVQahV
GM3(Neu5Gc) ganglioside: An evolution fixed neoantigen for cancer immunotherapy
Publication date: Available online 7 May 2018
Source:Seminars in Oncology
Author(s): Mayrel Labrada, Denise Dorvignit, Giselle Hevia, Nely Rodriguez, Ana M. Hernández, Ana M. Vázquez, Luis E. Fernández
Numerous molecules have been considered as target for cancer immunotherapy due to their levels of expression on tumor cells, their putative importance for tumor biology and relative immunogenicity. In this review we focused on the ganglioside GM3(Neu5Gc), a glycosphingolipid present on the outer side of plasma membranes of vertebrate cells. The reasons for selecting GM3(Neu5Gc) as a peculiar tumor specific antigen and its use as target for cancer immunotherapy are discussed, together with the development of antitumor therapies focused on this target by the Center of Molecular Immunology (CIM, Cuba).
https://ift.tt/2IWQ6KQ
Differential effects of two therapeutic cancer vaccines on short- and long-term survival populations among patients with advanced lung cancer
Publication date: Available online 1 May 2018
Source:Seminars in Oncology
Author(s): Lizet Sanchez, Leacky Muchene, Patricia Lorenzo-Luaces, Carmen Viada, Pedro C. Rodriguez, Sailyn Alfonso, Tania Crombet, Elia Neninger, Ziv Shkedy, Agustin Lage
BackgroundProgress in immunotherapy has revolutionized the treatment landscape for advanced lung cancer, with emerging evidence of patients experiencing long-term survivals. The goal of this study was to explore the existence of short- and long-term survival populations and to assess the effect of immunotherapy on them.MethodsData from two randomized, multicenter, controlled clinical trials was used to evaluate the effect of two therapeutic vaccines (anti-idiotypic vaccine VAXIRA and anti-EGF vaccine CIMAVAX) on survival curves in advanced non–small cell lung cancer patients. Data were fitted to Kaplan-Meier, standard Weibull survival, and two-component Weibull mixture models. Bayesian Information Criterion was used for model selection.ResultsVAXIRA did not modify, neither the fraction of patients with long-term survivals (0.18 in the control group v 0.19 with VAXIRA, P = .88), nor the median overall survival of the patients in the short-term survival subpopulation (6.8 v 7.8 months, P = .24). However, this vaccine showed great benefit for the patients belonging to the subpopulation of patients with long-term survival (33.8 v 76.6 months, P <.0001). CIMAVAX showed impact in the overall survival of both short- and long-term populations (6.8 v 8.8 months, P = .005 and 33.8 v 61.8 months, P = .007). It also increased the proportion of patients with long-term survival (from 0.18 to 0.28, P = .02).ConclusionsThis study shows that therapeutic vaccines produce differential effects on short- and long-term survival populations and illustrates the application of advanced statistical methods to deal with the long-term evolution of patients with advanced lung cancer in the era of immunotherapy.
https://ift.tt/2LCwoG4
Clinical trial participation by adolescents and young adults with cancer: A continued cause for concern?
Publication date: Available online 30 April 2018
Source:Seminars in Oncology
Author(s): Victoria White, Gemma Skaczkowski, Antoinette Anazodo, Helen Bibby, Wayne Nicholls, Ross Pinkerton, Kate Thompson, Lisa M Orme, Rachel Conyers, Michael Osborn, Marianne B Phillips, Rosemary Harrup, Roderick Walker, Michael Coory
International data indicate that rates of clinical trial enrolment for Adolescents and Young Adults (AYAs) with cancer are markedly lower than for any other age group. This paper reviews the recent literature reporting international trends in clinical trial enrolment since 2010. Subsequently, we present the first population-based, national assessment of clinical trial enrolment for AYAs with cancer in Australia. Reported rates of trial enrolment from Australia, Canada, the United States and the United Kingdom were variable, though consistently low, ranging between 2% and 29%. Trial enrolment was higher for younger AYAs (typically 15-19 years) and those attending pediatric hospitals, and this was replicated in the recent Australian data. The findings highlight a lack of substantial improvement in AYA clinical trial enrolment and in particular, a need for improved opportunities to access trials for patients treated at adult centers.
https://ift.tt/2xvNZfZ
Back and forth between cancer treatment and cancer control programs: Insights from the Cuban experience
Publication date: Available online 30 April 2018
Source:Seminars in Oncology
Author(s): Agustin Lage, Teresa Romero
Cancer control is a wider concept than oncology, and includes comprehensive actions for prevention, early diagnosis, treatment, services organization, and education, aiming to modify hard indicators such as incidence, mortality rates, and survival at a population scale. Based on these concepts, organized national cancer programs appeared in several countries in the second half of the 20th century. But at the same time, scientific efforts began to modify the landscape of cancer control. Evidence of mortality reductions began to appear, cancer-driving mutations became measurable, many novel drugs were registered, the methodology of clinical trials spread through health systems, targeted drugs and immunotherapy entered into the mainstream of therapeutics, and treatment goals started to shift from cure to chronic control. The implementation and impact of organized interventions for cancer control show variations according to the context of diverse countries, and scientists and health decision makers can learn from studying these diverse experiences. Among the salient features of cancer control in Cuba are the simultaneous development of a primary care network with abundant human resources and a national biotechnology industry with capacity to provide both generic and innovating drugs and diagnostic systems. The program intentionally assumes the goal of accelerating the transformation of advanced cancer into a chronic disease susceptible of long-term control. The implications of this strategy for population interventions and for scientific research are discussed.
https://ift.tt/2LCj5W0
An evidence-based review on the value of interim FDG-PET in assessing response to therapy in lymphoma
Publication date: Available online 22 April 2018
Source:Seminars in Oncology
Author(s): Hugo J.A. Adams, Thomas C. Kwee
Assessing response to therapy in lymphoma is important for determining patients' prognosis, guiding subsequent treatment, and may be used as an outcome measure of prognostic and therapeutic trials. Traditionally, computed tomography was the mainstay for response assessment and was predominantly performed at the end of treatment, whereas the most recent guidelines propose 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) for this purpose. However, the value of FDG-PET performed during treatment (interim FDG-PET) is still a topic of debate. The purpose of this scientific communication is to provide an evidence-based overview of the value of interim FDG-PET in patients with lymphoma. The article first describes the development of imaging-based response assessment in lymphoma, the rationale and limitations of using FDG-PET for this purpose, and continues with the evidence-based clinical utility of interim FDG-PET in three major lymphoma subtypes (Hodgkin lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma), and finishes with conclusions and recommendations for standard care and future research.
https://ift.tt/2xnufuD
Can surgery be avoided in select breast cancer patients with complete radiological response to neoadjuvant chemotherapy?
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Anuradha Apte, Lesley Pennell, Sankaran Chandrasekahran
https://ift.tt/2J9BWJE
Treatment patterns for unilateral, non-invasive breast cancer in women diagnosed in England: Data from a population-based cohort
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Yasmin Jauhari, Melissa Gannon, Jibby Medina, Karen Clements, Kieran Horgan, David Dodwell, David Cromwell
https://ift.tt/2IYct2q
Optimizing treatment for children and adolescents with papillary thyroid carcinoma in post-Chernobyl exposed region: The roles of lymph node dissections in the central and lateral neck compartments
Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Mikhail Fridman, Olga Krasko, Alfred King-yin Lam
There is lack of data to predict lymph node metastases in pediatric thyroid cancer. The aims are to study (1) the factors affecting the lymph node metastases in children and adolescence with papillary thyroid carcinoma in region exposed to radiation and (2) to evaluate the predictive significance of these factors for lateral compartment lymphadenectomy. Five hundred and nine patients with papillary thyroid carcinoma underwent total thyroidectomy and lymph nodes resection (central and lateral compartments of the neck) surgery during the period of 1991–2010 in Belarus were recruited. The factors related to lymph node metastases were studied in these patients. In the patients with papillary thyroid carcinoma, increase number of cancer-positive lymph nodes in the central neck compartment were associated with a risk to develop lateral nodal disease as well as bilateral nodal disease. Futhermore, positive lateral compartment nodal metastases are associated with age and gender of the patients, tumour size, minimal extra-thyroidal extension, solid architectonic, extensive desmoplasia in carcinoma, presence of psammoma bodies, extensive involvement of the thyroid and metastatic ratio index revealed after examination of the central cervical chain lymph nodes. The presence of nodal disease, degree of lymph node involvement and the distribution of lymph node metastases significantly increase the recurrence rates of patients with papillary thyroid carcinoma. To conclude, the lymph nodes metastases in young patients with papillary thyroid carcinoma in post-Chernobyl exposed region are common and the pattern could be predicted by many clinical and pathological factors.
https://ift.tt/2sh8isd
Enhanced pre-operative assessment of the axilla with grey-scale and contrast enhanced ultrasound (CEUS) may characterise a group of patients who can safely omit axillary surgery
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Karina Cox, Jenny Weeks, Pippa Mills, Ali Sever, Deborah Allen, Nick Wakeham, Neal Chhaya, Ruxandra Pietrosanu
https://ift.tt/2ITQIRu
Complete cytoreduction after five or more cycles of neo-adjuvant chemotherapy confers a survival benefit in advanced ovarian cancer
Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Andrew Phillips, Sudha Sundar, Kavita Singh, James Nevin, Ahmed Elattar, Sean Kehoe, Janos Balega
ObjectivesTo assess the impact of 5 or more cycles of neoadjuvant chemotherapy (NACT) and cytoreductive outcomes on overall survival (OS) in patients undergoing interval debulking surgery (IDS) for advanced ovarian cancer.MethodsA retrospective review of patients receiving NACT followed by IDS between 2007 and 2017. Patients were analysed according to number of NACT cycles received: group 1 consisted of patients receiving ≤4 cycles and group 2 consisted of those receiving ≥5 cycles. Outcomes were stratified by cytoreductive outcome, surgical complexity, stage and chemotherapy exposure.Results231 patients in group 1 and 167 in group 2 were identified. In group 1, the OS for those achieving Complete (R0), Optimal<1 cm (R1) and Suboptimal (R2) was 51.1, 36.1, and 34.3 months respectively. Statistically significant differences in survival were seen in patients achieving R0vR2 (p < 0.019) but not in R0vR1 (p = 0.125) or R1vR2 (p = 0.358). In group 2, the OS for those achieving R0, R1 and R2 was 53.0, 24.7, and 22.1 months respectively. Statistically significant differences were seen between R0vR1 and R0vR2 (p < 0.00001) but not between R1vR2 (p = 0.917). No difference in OS was seen between groups 1 and 2. In patients achieving R1, there was a trend towards decreasing OS with increasing exposure to NACT from 36.1 (95%CI 32.0–40.2)months with 3 cycles to 24.3 (95%CI 14.4–34.2)months with ≥6 cycles.ConclusionsSurgery with utilisation of cytoreductive procedures to achieve complete clearance should be offered to all patients even after ≥5 cycles if R0 can be achieved. R1 cytoreduction has questionable value in those receiving ≤4 cycles and no value in those receiving ≥5 cycles.
https://ift.tt/2si2iPW
Antidepressants appear safe in patients with carcinoid tumor: Results of a restrospective review
Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Elie Isenberg-Grzeda, Meredith MacGregor, Afton Bergel, Stacy Eagle, Fernando Espi Forcen, Reema Mehta, Konstantina Matsoukas, Jonathan Wills, Diane Reidy-Lagunes, Yesne Alici
IntroductionPatients living with neuroendocrine tumors have high rates of depression, often necessitating antidepressants, including selective serotonin reuptake inhibitors (SSRI). Neuroendocrine tumors (NETs) secrete vasoactive substances, including serotonin, which contribute to the cluster of symptoms known as carcinoid syndrome (flushing and diarrhea). Controversy exists over whether or not antidepressants are safe in NET. We aimed to study the safety of antidepressant use in NET patients.MethodsWe conducted a retrospective chart review of patients with well differentiated NET who were also prescribed antidepressants from January 2008 through April 2015. The study took place at Memorial Sloan Kettering Cancer Center and was approved by the hospital's institutional review board.ResultsNinety-two patients were included. There were 16 (17.4%) patients with carcinoid syndrome (10 ileum, 1 duodenum, 1 jejunum and 4 unknown primary); and 76 (82.6%) patients without (41 lung, 9 pancreas, 8 ileal, 5 duodenum, 5 appendix, 2 unknown primary, 1 jejunum and 5 other). Median duration of antidepressant prescription was 11.6 months (range, 0–121) among those with carcinoid syndrome (N = 16) and 14.3 months (range, 0–172) among those without carcinoid syndrome (n = 76). Antidepressants were stopped in 31 cases (33.7%), though the reason was not specified in the majority of cases (n = 18; 58%). None of the patients developed carcinoid syndrome while being prescribed antidepressants. No patients developed carcinoid crisis.ConclusionOur findings do not support previous authors' recommendations that SSRIs must be avoided in NET patients. Several classes of antidepressants appeared safe in NET patients with and without carcinoid syndrome.
https://ift.tt/2sgd5dt
A ‘best-practice’ pathway for the acute management of mastitis and breast abscess enables non-specialists to “get it right first time”
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Neill Patani, Findlay MacAskill, Sarah Eshelby, Asha Omar, Anika Kaura, Kayo Contractor, Paul Thiruchelvam, Sally Curtis, Janice Main, Deborah Cunningham, Katy Hogben, Ragheed Al-Mufti, Dimitri Hadjiminas, Daniel Leff
https://ift.tt/2xoNVhK
Morbidity of rectosigmoid resection in cytoreductive surgery for ovarian cancer. Risk factor analysis
Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): M. Fournier, C. Huchon, C. Ngo, C. Bensaid, A.S. Bats, P. Combe, M.A. le FrèreBelda, L. Fournier, A. Berger, F. Lecuru
AimRectosigmoid resection is often performed during cytoreductive surgery for ovarian cancer, to achieve the goal of no residual tumour. Here, we evaluated the morbidity associated with rectosigmoid resection and the underlying risk factors.MethodsWe retrospectively assessed consecutive patients managed with rectosigmoid resection during cytoreductive surgery for ovarian cancer at our centre in Paris, France, between 2005 and 2013. All previously identified risk factors were analysed. Major complications were defined as grade III-IV in the Clavien-Dindo classification.ResultsOf 228 patients, 116 had primary and 112 interval surgery; 43/228 [18.9%]; experienced major complications, and these were more common after primary surgery [24.1% vs. 13.4%, p = .04]. The 69 patients who had rectosigmoid resection [33 primary vs. 36 interval surgery, p = .32] had a higher morbidity rate compared to the other patients [30.4% vs. 14.6%, p = .006]. The anastomotic leakage rate was 2.89%. By multivariate logistic regression, independent risk factors for morbidity were postmenopausal status [adjusted odds ratio (aOR), 13.7; 95% confidence interval (95%CI), 1.2;161.9], surgery after neoadjuvant chemotherapy [aOR, 4.4; 95%CI, 1.1;18.8], and peritoneal stripping of the left; paracolic gutter [aOR, 11.3; 95%CI, 2.3;54.3].ConclusionThe morbidity of rectosigmoid resection during cytoreductive surgery for ovarian cancer seems acceptable. Ileostomy does not seem associated with a lower risk of major complications or adjuvant bevacizumab with a higher complication rate.
https://ift.tt/2si27UM
Indocyanine green (ICG) fluorescence mapping for sentinel lymph node (SLN) localisation in early breast cancer
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Sujit Gnanakumar, Dorin Dumitru, Elena Provenzano, John Benson
https://ift.tt/2ITQKJ6
Robotic versus laparoscopic radical hysterectomy in early cervical cancer: A case matched control study
Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Valerio Gallotta, Carmine Conte, Alex Federico, Giuseppe Vizzielli, Salvatore Gueli Alletti, Lucia Tortorella, Luigi Pedone Anchora, Francesco Cosentino, Vito Chiantera, Anna Fagotti, Marco D'Indinosante, Silvia Pelligra, Giovanni Scambia, Gabriella Ferrandina
BackgroundThis study aims at evaluating the feasibility, surgical outcome and oncological results observed after robotic radical hysterectomy (RH) compared to laparoscopy for patients with early stage cervical cancer (ECC) patients.MethodsBetween January 2010 and October 2016, 210 patients underwent RH for treatment of ECC: 70 underwent robotic approach (Cases), and 140 underwent laparoscopic approach (Controls).ResultsThere was no statistically significant difference between the two approaches with regard to clinical patient characteristics and in terms of extent of RH and rate of pelvic and aortic lymphadenectomy. Operative time was significantly longer in the robotic versus laparoscopic group (median = 243 min, range 90–612 versus median = 210 min, range 80–660; p value = 0.008). Conversion to laparotomy was necessary in 4 patients (1.9%) in the whole series.No difference was found in terms of intraoperative and postoperative complications between the two groups. Overall, during the observation period, 34 (16.2%) patients experienced any grade postoperative complications, and 21 (10.0%) had >G2 complications.The 3-yr DFS was 88.0% versus 84.0% in robotic and laparoscopic group, respectively (p value = 0.866). Central and/or lateral pelvic disease represented the most common site of relapse. The 3-yr OS was 90.8% in patients underwent robotic RH versus 94.0% in patients underwent laparoscopic RH (p value = 0.924).ConclusionsThe present study shows the equivalence of robotic and laparoscopic approaches to radical surgery of ECC patients, in terms of perioperative and postoperative outcomes with equivalent survival figures, and thus the choice of approach can be tailored to the choice of patient and surgeon.
https://ift.tt/2JaGNdv
Sentinel lymph node biopsy (SLNB) in clinically node negative early breast cancer: a publication-level meta-analysis
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Gurdeep Mannu, Carolyn Taylor, Paul McGale, David Dodwell
https://ift.tt/2IWmmhh
Editorial Board
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
https://ift.tt/2IWMd8I
No difference in oncological outcomes after immediate or delayed reconstruction following mastectomy for breast cancer
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Elizabeth Morrow, Ross Dolan, Eva Weiler-Mithoff, Vivienne Blackhall, Laszlo Romics
https://ift.tt/2JaGFL3
Neo-adjuvant versus adjuvant chemotherapy in early breast cancer: EBCTCG patient-level meta-analysis of long-term outcomes among 4756 women in 10 randomised trials
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Paul McGale, Carolyn Taylor, Gurdeep Mannu, Jeremy Braybrooke, Rosie Bradley, Hongchao Pan, Yaochen Wang, Zhe Wang, David Dodwell
https://ift.tt/2xmSMQt
Chemotherapy utilisation in patients aged 50 years and over, diagnosed with invasive early breast cancer in England: Data from a population-based cohort
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Melissa Gannon, Yasmin Jauhari, Kieran Horgan, Jibby Medina, Karen Clements, David Cromwell, David Dodwell
https://ift.tt/2JaGoaZ
Hepatectomy increases metastatic graft and growth in an immunocompetent murine model of peritoneal metastases
Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Rea Lo Dico, Annemilai Tijeras-Raballand, Philippe Bonnin, Jean Marie Launay, Rachid Kaci, Cynthia Pimpie, Brice Malgras, Anthony Dohan, Gianluigi Maria Lo Dico, Marc Pocard
BackgroundCurative surgery of synchronous peritoneal metastases (PM) and colorectal liver metastases (LM) has been recently investigated as feasible option. When synchronous peritoneal and liver resection is not achievable, the sequence of the surgery remains unknown. Our hypothesis was that liver resection (LR) promotes peritoneal growth resulting in a non-resectable PM. We sought to analyse the effects of major LR and liver regeneration after hepatectomy in a murine model of PM and the associated angiogenesis.MethodsMurine model of colorectal PM in Balb/C mice was developed by intraperitoneal injection of different CT-26 tumour cell concentrations. Five days after the injection, mice were randomized into three groups: 68% hepatectomy group, sham laparotomy and control group without surgery. On post-operative days 1, 5 and 20, PM was evaluated macroscopically, tumour growth and liver regeneration by immunohistochemistry, and angiogenesis by immunofluorescence. Circulating progenitor cells, plasmatic cytokines and digestive arterial blood flow velocity measurements were also analysed.ResultsReproducible murine model of limited colorectal PM was obtained. Surgery induced PM increases and promoted neo-angiogenesis. Major hepatectomy influence the tumour growth in the late phase after surgery, the extent of extra-peritoneal metastasis and the increase of Ki-67 expression in the remnant liver.ConclusionsThis animal model confirms the pro-tumoural and pro-angiogenic role of surgery, laparotomy and major LR, which promotes the increase of angiogenic factors and their participation in PM growth. These results suggest that peritoneal resection should be first step in the case of two-step liver and peritoneal surgery for patients with colorectal PM and LM.
https://ift.tt/2IYcrHQ
International validation of the European organisation for research and treatment of cancer QLQ-BRECON23 quality-of-life questionnaire for women undergoing breast reconstruction
Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Zoe Winters, Maryam Afzal, Claudia Rutherford, Bernhard Holzner, Gerald Rumpold, Renee A. da Costa Vieira, Sue Hartup, Kathy Flitcroft, Vesna Bjelic-Radisic, Anne Oberguggenburger, Marie Panouilleres, Maria Mani, Guiseppe Catanuto, Michael Douek, Jalal Kokan, Madeleine Trudy King
https://ift.tt/2J9BM50
Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study
Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Federica Bruno, Dario Baratti, Antonia Martinetti, Daniele Morelli, Elisa Sottotetti, Chiara Bonini, Marcello Guaglio, Shigeki Kusamura, Marcello Deraco
BackgroundThe differential diagnosis between diffuse malignant peritoneal mesothelioma (DMPM) and other peritoneal surface malignancies (PSM) is still challenging. Serum mesothelin and osteopontin are increasingly used as markers of pleural mesothelioma, but their role in DMPM is unclear. We assessed the diagnostic and prognostic values of mesothelin, osteopontin, CEA, CA19.9, CA125, and CA15.3 in DMPM patients.MethodsMarkers were dosed before cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) by enzyme-linked immunosorbent assay (ELISA) in 30 DMPM patients and 14 controls with other PSMs. Receiver-operating characteristics (ROC) curve were plotted. The performance of each marker was assessed by the area under the ROC curve (AUC-ROC).ResultsMean mesothelin levels were 7.84 ng/dl (SD = 5.14) in DMPM group and 3.00 ng/dl (SD = 1.25) in controls (P = 0.001). Mean CEA levels were 5.3 ng/dl (SD = 4.7), and 61.96 ng/dl (SD = 112.5) in the two groups (P = 0.008). No statistical difference was seen for osteopontin (P = 0.738), CA19.9 (P = 0.081), CA125 (P = 0.600), and CA15.3 (P = 0.365). AUC-ROC was 0.836 for CA19.9, 0.812 for mesothelin, 0.793 for CEA, and lower for CA125 (0.652), osteopontin (0.531), and CA15.3 (0.481). Using diagnostic cut-offs selected by ROC methodology, sensitivity, specificity, positive and negative predictive values were 70.0%, 100.0%, 100.0%, and 60.9% for mesothelin >5.21 ng/dl, and 90.0%, 85.7%, 93.1%, and 80.0% for CA19.9 < 8.8 U/dl. At multivariate analysis, osteopontin correlated with survival (hazard rate 6.46; 95%CI 1.81–23.05; P = 0.004).ConclusionWhen assessing PSMs of unknown origin, elevated mesothelin with low CA19.9 may increase the suspicion index for DMPM. Ospeopontin warrants further investigations as a prognostic marker for DMPM.
https://ift.tt/2xoNPGU
The effect of clinical and tumour factors on prognosis after contralateral breast cancer (CBC) in Northern Ireland (NI)
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Colin McIlmunn, Finian Bannon, Deirdre Fitzpatrick, Kienan Savage, Stuart McIntosh
https://ift.tt/2sdzLv8
Targeted axillary lymph node dissection improves the accuracy of axillary assessment
Publication date: June 2018
Source:European Journal of Surgical Oncology, Volume 44, Issue 6
Author(s): Deyana Oweis, Rachel Howitt, Nidhi Sibal, Loraine Kalra, Adam Critchley, Henry Cain
https://ift.tt/2IV08Ms
Cancers, Vol. 10, Pages 166: Zinc Metallochaperones as Mutant p53 Reactivators: A New Paradigm in Cancer Therapeutics
Cancers, Vol. 10, Pages 166: Zinc Metallochaperones as Mutant p53 Reactivators: A New Paradigm in Cancer Therapeutics
Cancers doi: 10.3390/cancers10060166
Authors: Samuel Kogan Darren R. Carpizo
Restoration of wild-type structure and function to mutant p53 with a small molecule (hereafter referred to as “reactivating” mutant p53) is one of the holy grails in cancer therapeutics. The majority of TP53 mutations are missense which generate a defective protein that is targetable. We are currently developing a new class of mutant p53 reactivators called zinc metallochaperones (ZMCs) and, here, we review our current understanding of them. The p53 protein requires the binding of a single zinc ion, coordinated by four amino acids in the DNA binding domain, for proper structure and function. Loss of the wild-type structure by impairing zinc binding is a common mechanism of inactivating p53. ZMCs reactivate mutant p53 using a novel two-part mechanism that involves restoring the wild-type structure by reestablishing zinc binding and activating p53 through post-translational modifications induced by cellular reactive oxygen species (ROS). The former causes a wild-type conformation change, the later induces a p53-mediated apoptotic program to kill the cancer cell. ZMCs are small molecule metal ion chelators that bind zinc and other divalent metal ions strong enough to remove zinc from serum albumin, but weak enough to donate it to mutant p53. Recently we have extended our understanding of the mechanism of ZMCs to the role of cells’ response to this zinc surge. We found that cellular zinc homeostatic mechanisms, which normally function to maintain free intracellular zinc levels in the picomolar range, are induced by ZMCs. By normalizing zinc levels, they function as an OFF switch to ZMCs because zinc levels are no longer sufficiently high to maintain a wild-type structure. This on/off switch leads to a transient nature to the mechanism of ZMCs in which mutant p53 activity comes on in a few hours and then is turned off. This finding has important implications for the translation of ZMCs to the clinic because it indicates that ZMC concentrations need not be maintained at high levels for their activity. Indeed, we found that short exposures (as little as 15 min) were adequate to observe the mutant p53 reactivating activity. This switch mechanism imparts an advantage over other targeted therapeutics in that efficacy can be accomplished with minimal exposure which minimizes toxicity and maximizes the therapeutic window. This on/off switch mechanism is unique in targeted cancer therapeutics and will impact the design of human clinical trials.
https://ift.tt/2smRMpO
Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study
Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study
Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter study, Published online: 29 May 2018; doi:10.1038/s41416-018-0079-9
Author Correction: Chemotherapy with radiotherapy influences time-to-development of radiation-induced sarcomas: a multicenter studyhttps://ift.tt/2JcUcBL
Checkpoint blockade in the treatment of breast cancer: current status and future directions
Checkpoint blockade in the treatment of breast cancer: current status and future directions
Checkpoint blockade in the treatment of breast cancer: current status and future directions, Published online: 29 May 2018; doi:10.1038/s41416-018-0126-6
Checkpoint blockade in the treatment of breast cancer: current status and future directionshttps://ift.tt/2JgMln7
High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancer
High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancer
High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancer, Published online: 29 May 2018; doi:10.1038/s41416-018-0136-4
High-serum MMP-8 levels are associated with decreased survival and systemic inflammation in colorectal cancerhttps://ift.tt/2ITnySn
Proximity to overhead power lines and childhood leukaemia: an international pooled analysis
Proximity to overhead power lines and childhood leukaemia: an international pooled analysis
Proximity to overhead power lines and childhood leukaemia: an international pooled analysis, Published online: 29 May 2018; doi:10.1038/s41416-018-0097-7
Proximity to overhead power lines and childhood leukaemia: an international pooled analysishttps://ift.tt/2sfiBNz
Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study
Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study
Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study, Published online: 29 May 2018; doi:10.1038/s41416-018-0103-0
Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH studyhttps://ift.tt/2IX6c7o
Hepatic Abscess in a Returning Traveler with Crohn’s Disease: Differentiating Amebic from Pyogenic Liver Abscess
Liver abscess is a rare but serious complication of Crohn's disease. Patients with Crohn's disease are at risk for pyogenic liver abscesses due to immunosuppressive therapy, fistulous disease, and intraabdominal abscesses. Inflammatory bowel disease patients are also known to have a greater prevalence of amebiasis compared to the rest of the population; however, a higher incidence of amebic liver abscess has not been reported. We describe a case of a liver abscess in a patient with Crohn's disease that was initially presumed pyogenic but later determined to be amebic in origin. Epidemiology, clinical presentation, diagnosis, and treatment of amebic and pyogenic liver abscesses are discussed.
https://ift.tt/2kvWk9P
Giant intrascrotal embryonal rhabdomyosarcoma in an adult: a case report and review of the literature
Intrascrotal embryonal rhabdomyosarcoma in adults is a rare tumor with high aggression and a poor prognosis. We report our patient's case and review the relevant literature to improve the understanding of this...
https://ift.tt/2xkGMiz
Management of Resistance to First-Line Anaplastic Lymphoma Kinase Tyrosine Kinase Inhibitor Therapy
Opinion statement
A decade after the discovery of echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (EML4-ALK) rearrangements in non-small cell lung cancer (NSCLC), several inhibitors have gained regulatory approval, and their sequential use has deferred platinum-based chemotherapy to later lines of therapy. Nevertheless, although most ALK-driven tumors dramatically respond to ALK TKIs , all patients ultimately develop drug-resistant disease. Analysis of post-progression biopsy samples has provided invaluable insight into the mechanisms of resistance, now informing on subsequent therapeutic strategies. In particular, the identification of secondary ALK mutations, which are a common mechanism of resistance to both first-generation and to an even larger extent to second-generation ALK TKIs, may shape a personalized optimal treatment strategy beyond the current first-line choice. Alectinib has now become a preferred treatment option in the first line of therapy, and extrapolation of data obtained from post-progression samples after second-line next-generation ALK TKIs suggests that acquired resistance is likely to be mediated in more than half of patients by ALK resistance mutations. Nevertheless, clinical and preclinical evidence suggests that multiple resistance mechanisms may co-exist at different levels in the same TKI-resistant patient. Newer ALK tyrosine kinase inhibitors (TKIs) overcome some resistance mutations through higher exposure and potency, and generally present greater CNS activity, but are unlikely to overcome resistance mediated through separate oncogenic pathway activations, or epithelial to mesenchymal transition (EMT) and small cell lung cancer (SCLC) transformation. Furthermore, while resistance mutations can be detected through commonly available sequencing methods, the identification of other mechanisms of resistance is much less straightforward in the clinic. We hypothesize that the ALK resistance mutation status will likely be crucially important in the choice of second-line therapy after a second-generation TKI. Emerging clinical data also refines the optimal placing of PD-1- and PD-L1-directed immunotherapy in the treatment sequence.
https://ift.tt/2s9PZoX
Overview of Current and Future Adjuvant Therapy for Muscle-Invasive Urothelial Carcinoma
Opinion statement
Muscle-invasive bladder cancer (MIBC) has high metastatic potential at diagnosis but is still often curable with aggressive management, which may give patients the best odds for a favorable clinical outcome. The standard-of-care management of MIBC includes a radical cystectomy and pelvic lymph node dissection. If the patient is cisplatin-eligible, neoadjuvant cisplatin-based combination chemotherapy should also be given. Post-surgery adjuvant treatments include observation, chemotherapy, radiation, or enrollment in a clinical trial. Several adjuvant immunotherapy trials with checkpoint inhibitors, which block the interaction between PD-1 and PD-L1, as monotherapy or in combinations with chemotherapy, radiation, or other immunotherapy agents are currently ongoing. Given the lack of level 1 evidence for the survival benefit of adjuvant therapies post-cystectomy, the standard of care remains observation with radiologic and clinical surveillance. However, in patients who did not receive neoadjuvant cisplatin-based combination chemotherapy and are cisplatin-eligible, adjuvant cisplatin-based chemotherapy should be considered and discussed. Genomic alterations and gene expression profiles may eventually help to identify patient subgroups for more effective adjuvant therapy. Genetic abnormalities in the DNA repair genes and basal intrinsic tumor subtype appear to predict response to neoadjuvant cisplatin-based chemotherapy in MIBC. In the coming years, validating these genetic markers will be key to individualizing perioperative chemotherapy.
https://ift.tt/2siXfhu
Merkel cell carcinoma and cellular cytotoxicity: sensitivity to cellular lysis and screening for potential target antigens suitable for antibody-dependent cellular cytotoxicity
Abstract
The recent success of checkpoint inhibitors in the treatment of Merkel cell carcinoma (MCC) confirms that MCC tumors can be immunogenic. However, no treatment directly targeting the tumor is available for use in combination with these checkpoint inhibitors to enhance their efficacity. This study was carried out to characterize MCC line sensitivity to cellular lysis and to identify cell surface antigens that could be used for direct targeting of this tumor. For five representative MCC lines, the absence or low expression of MICA, MICB, HLA-I, and ICAM-1 was associated with low level of recognition by NK cells and T lymphocytes. However, expression of HLA-I and ICAM-1 and sensitivity to cellular lysis could be restored or increased after exposure to INFγ. We tested 41 antibodies specific for 41 different antigens using a novel antibody-dependent cellular cytotoxicity (ADCC) screening system for target antigens. Anti-CD326 (EpCAM) was the only antibody capable of inducing ADCC on the five MCC lines tested. Because MCC tumors are often directly accessible, local pharmacologic manipulation to restore HLA class-I and ICAM-1 cell surface expression (and thus sensitivity to cell lysis) can potentially benefit immune therapeutic intervention. In line with this, our observation that ADCC against EpCAM can induce lysis of MCC lines and suggests that therapeutic targeting of this antigen deserves to be explored further.
https://ift.tt/2LCOIi5
Intratumoral Heterogeneity of Frameshift Mutations of GLI1 Encoding a Hedgehog Signaling Protein in Colorectal Cancers
Abstract
GLI1 is a transcription factor for hedgehog signaling that plays a crucial role in signaling pathways for controlling cell proliferation, alterations of which are known to contribute to tumorigenesis. Aim of this study was to explore whether GLI1 gene is mutated in gastric (GC) and colorectal cancers (CRC). In a public database, we found that GLI1 had a G7 mononucleotide repeat in the coding sequences that could be a mutation target in the cancers with microsatellite instability (MSI). In this study, we analyzed frameshift mutation of GLI1 in 79 GCs and 129 CRCs (high MSI (MSI-H) or microsatellite stable (MSS)) by single-strand conformation polymorphism analysis and DNA sequencing. We found 10 frameshift mutations in the repeat, nine for CRCs and one for GC. All of the mutations were detected in cancers with MSI-H and there was a statistical difference in the frameshift mutation frequencies between the cancers with MSI-H (10/113) and MSS (0/90). We also analyzed intratumoral heterogeneity (ITH) of the frameshift mutation in 16 CRCs and found that the mutations exhibited regional ITH in three of the CRCs (18.8%). Our data indicate GLI1 harbored not only frameshift mutation but also its mutational ITH, which together could be a feature of GC and CRC with MSI-H.
https://ift.tt/2L1vvFH
Breast Cancer Risk Associated with Genotype Polymorphisms of the Aurora Kinase a Gene (AURKA): a Case-Control Study in a High Altitude Ecuadorian Mestizo Population
Abstract
Breast cancer (BC) is the leading cause of cancer related death among women in 2014. The AURKA gene that encodes the protein called Aurora kinase A plays an important role in the progression of the cell cycle, by controlling and promoting the entry into the phase of mitosis. The single nucleotide polymorphism AURKA T91A (rs2273535) (Phe21Ile) has been identified as functional alternator of this kinase, the Ile allele is associated with the occurrence of chromosome segregation errors and tumor progression. Therefore, it is essential to know how BC risk is associated with histopathological characteristics, immunohistochemical characteristics, and genotype polymorphism in a high altitude Ecuadorian mestizo population. In this retrospective case-control study 200 individuals were analyzed. DNA was extracted from 100 healthy and 100 affected women. Genotypes were determined by genomic sequencing. We found significant association between the AURKA T91A (rs2273535) (Phe21Ile) genotype and an increased risk of BC development: Phe/Ile (odds ratio [OR] = 2.6; 95% confidence interval [CI] = 1.4–4.9; P = 0.004), Ile/Ile (OR = 3.8; 95% CI = 1.6–9.0; P = 0.002), and Phe/Ile + Ile/Ile (OR = 2.9; 95% CI = 1.6–5.2; P = 0.001). Additionally, the rs2273535 variant was associated with the tumor grade SBR III (OR = 9.6; 95% CI = 1.0–91.9; P = 0.048) and the Ki-67 ≥ 20 (OR = 16.5; 95% CI = 2.7–101.3; P = 0.002). In brief, this study provides the first evidence where the Ile allele of the AURKA gene could act as potentially predictive biomarker of BC in the high altitude Ecuadorian mestizo population that lives at 2800 m above sea level (masl).
https://ift.tt/2L2ILtQ
Single-Nucleotide Polymorphisms of the MSH2 and MLH1 Genes, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population
Abstract
Basal cell carcinoma - BCC is considered a multifactorial neoplasm involving genetic, epigenetic and environmental factors. Where UVB radiation is considered the main physical agent involved in BCC carcinogenesis. The Brazil and state of Paraíba are exposed to high levels of UVB rays. The mismatch repair - MMR is important DNA repair mechanisms to maintain replication fidelity. Therefore, single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in MMR may be potential molecular markers of susceptibility to BCC. The objective of this study was to evaluate and describe for the first time the SNPs rs560246973, rs2303425 and rs565410865 and risk of developing BCC. The present study analyzed 100 samples of paraffin-embedded tissue from patients with histopathological diagnosis of BCC and 100 control samples. The results were obtained by genotyping method, Dideoxy Unique Allele Specific – PCR (DSASP). The SNPs rs2303425 were not associated with Basal Cell Carcinoma. However, the SNPs rs560246973 and rs565410865 was shown to be associated with the development of BCC when compared to control samples (P < 0.0001). The SNPs rs565410865 was also statistical significance between the genotypes of and the age group (p = 0.0027) and tumor location (p = 0,0191). The result suggests that SNPs rs2303425 and rs565410865 are associated with susceptibility to the development of BCC in the Brazilian population and may be considered as potential molecular markers for BCC.
https://ift.tt/2slvhS2
Trends in thyroid cancer: Retrospective analysis of incidence and survival in Denmark 1980–2014
Source:Cancer Epidemiology, Volume 55
Author(s): Christian Mirian, Christian Grønhøj, David Hebbelstrup Jensen, Kathrine Kronberg Jakobsen, Kirstine Karnov, Jakob Schmidt Jensen, Christoffer Holst Hahn, Tina Agander Klitmøller, Jens Bentzen, Christian von Buchwald
BackgroundThyroid cancer incidence has been reported to be increasing since the 1970 s. The aim of this study was to investigate the change in incidence and survival from 1980 to 2014 in Denmark.MethodsWe identified patients registered with thyroid cancer in the period 1980–2014. We evaluated the age-adjusted incidence rate (AAIR) and the average annual percentage change (AAPC), constructed age–period–cohort models (APCs), and evaluated relative survival (RS).ResultsWe included 5139 patients. The AAIR was 1.6 cases per 100,000 in 1980 and 4.5 cases in 2014 with an AAPC of 3.4%. The AAIR for papillary carcinomas (n = 2864) quintupled in the study period, and accounts for most of the observed increase in incidence with an AAPC of 4.9%. Follicular carcinomas (n = 920) nearly tripled in AAIR and had the second greatest increase in AAPC. Papillary carcinomas had the best prognosis with 1-year and 5-year RSs of 95% and 91%, followed by the follicular carcinomas with 1-year and 5-year RSs of 90% and 80%, respectively. Anaplastic carcinomas (n = 320) had the worst prognosis with 1-year and 5-year RSs of 18% and 12%. We found a significant age effect in the APC model for the incidence of thyroid cancer but no significant cohort or period effects.ConclusionThe incidence of thyroid cancer is rising. This is primarily attributable to an increase in papillary carcinomas. The relative survival has improved significantly in Denmark since 1980. The cause of the increasing incidence remains to be established, but enhanced diagnostic scrutiny and increased iodine intake may be influential.
https://ift.tt/2xir1sg
Intratumoral Heterogeneity of Frameshift Mutations of GLI1 Encoding a Hedgehog Signaling Protein in Colorectal Cancers
Abstract
GLI1 is a transcription factor for hedgehog signaling that plays a crucial role in signaling pathways for controlling cell proliferation, alterations of which are known to contribute to tumorigenesis. Aim of this study was to explore whether GLI1 gene is mutated in gastric (GC) and colorectal cancers (CRC). In a public database, we found that GLI1 had a G7 mononucleotide repeat in the coding sequences that could be a mutation target in the cancers with microsatellite instability (MSI). In this study, we analyzed frameshift mutation of GLI1 in 79 GCs and 129 CRCs (high MSI (MSI-H) or microsatellite stable (MSS)) by single-strand conformation polymorphism analysis and DNA sequencing. We found 10 frameshift mutations in the repeat, nine for CRCs and one for GC. All of the mutations were detected in cancers with MSI-H and there was a statistical difference in the frameshift mutation frequencies between the cancers with MSI-H (10/113) and MSS (0/90). We also analyzed intratumoral heterogeneity (ITH) of the frameshift mutation in 16 CRCs and found that the mutations exhibited regional ITH in three of the CRCs (18.8%). Our data indicate GLI1 harbored not only frameshift mutation but also its mutational ITH, which together could be a feature of GC and CRC with MSI-H.
https://ift.tt/2L1vvFH
Breast Cancer Risk Associated with Genotype Polymorphisms of the Aurora Kinase a Gene (AURKA): a Case-Control Study in a High Altitude Ecuadorian Mestizo Population
Abstract
Breast cancer (BC) is the leading cause of cancer related death among women in 2014. The AURKA gene that encodes the protein called Aurora kinase A plays an important role in the progression of the cell cycle, by controlling and promoting the entry into the phase of mitosis. The single nucleotide polymorphism AURKA T91A (rs2273535) (Phe21Ile) has been identified as functional alternator of this kinase, the Ile allele is associated with the occurrence of chromosome segregation errors and tumor progression. Therefore, it is essential to know how BC risk is associated with histopathological characteristics, immunohistochemical characteristics, and genotype polymorphism in a high altitude Ecuadorian mestizo population. In this retrospective case-control study 200 individuals were analyzed. DNA was extracted from 100 healthy and 100 affected women. Genotypes were determined by genomic sequencing. We found significant association between the AURKA T91A (rs2273535) (Phe21Ile) genotype and an increased risk of BC development: Phe/Ile (odds ratio [OR] = 2.6; 95% confidence interval [CI] = 1.4–4.9; P = 0.004), Ile/Ile (OR = 3.8; 95% CI = 1.6–9.0; P = 0.002), and Phe/Ile + Ile/Ile (OR = 2.9; 95% CI = 1.6–5.2; P = 0.001). Additionally, the rs2273535 variant was associated with the tumor grade SBR III (OR = 9.6; 95% CI = 1.0–91.9; P = 0.048) and the Ki-67 ≥ 20 (OR = 16.5; 95% CI = 2.7–101.3; P = 0.002). In brief, this study provides the first evidence where the Ile allele of the AURKA gene could act as potentially predictive biomarker of BC in the high altitude Ecuadorian mestizo population that lives at 2800 m above sea level (masl).
https://ift.tt/2L2ILtQ
Single-Nucleotide Polymorphisms of the MSH2 and MLH1 Genes, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population
Abstract
Basal cell carcinoma - BCC is considered a multifactorial neoplasm involving genetic, epigenetic and environmental factors. Where UVB radiation is considered the main physical agent involved in BCC carcinogenesis. The Brazil and state of Paraíba are exposed to high levels of UVB rays. The mismatch repair - MMR is important DNA repair mechanisms to maintain replication fidelity. Therefore, single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in MMR may be potential molecular markers of susceptibility to BCC. The objective of this study was to evaluate and describe for the first time the SNPs rs560246973, rs2303425 and rs565410865 and risk of developing BCC. The present study analyzed 100 samples of paraffin-embedded tissue from patients with histopathological diagnosis of BCC and 100 control samples. The results were obtained by genotyping method, Dideoxy Unique Allele Specific – PCR (DSASP). The SNPs rs2303425 were not associated with Basal Cell Carcinoma. However, the SNPs rs560246973 and rs565410865 was shown to be associated with the development of BCC when compared to control samples (P < 0.0001). The SNPs rs565410865 was also statistical significance between the genotypes of and the age group (p = 0.0027) and tumor location (p = 0,0191). The result suggests that SNPs rs2303425 and rs565410865 are associated with susceptibility to the development of BCC in the Brazilian population and may be considered as potential molecular markers for BCC.
https://ift.tt/2slvhS2
Formation of a protein corona influences the biological identity of nanomaterials
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Daniel Nierenberg, Annette R. Khaled, Orielyz Flores
The development and testing of nanomaterials is an area of interest due to promising diagnostic and therapeutic applications in the treatment of diseases like cancer or cardiovascular disease. While extensive studies of the physicochemical properties of nanoparticles (NPs) are available, the investigation of the protein corona (PC) that is formed on NPs in biofluids is a relatively new area of research. The fact that few NPs are in clinical use indicates that the biological identity of NPs, which is in large part due to the PC formed in blood or other bodily fluids, may be altered in ways yet to be fully understood. Herein, we review the recent advances in PC research with the intent to highlight the current state of the field. We discuss the dynamic processes that control the formation of the PC on NPs, which involve the transient soft corona and more stable hard corona. Critical factors, like the environment and disease-state that affect the composition and stability of the PC are presented, with the intent of showcasing promising applications for utilizing the PC for disease diagnosis and the identification of disease-related biomarkers. This review summarizes the unique challenges presented by the nanoparticle corona and indicates future directions for investigation.
https://ift.tt/2xkUhPd
Pitfalls of Combining Novel Agents in Lymphoma
Opinion statement
As our knowledge of lymphoma and its intricate signaling pathways has grown, so has the development of novel agents. While their mechanisms of action vary considerably, these therapies supplement and in some cases offer alternatives to standard chemotherapy. Initial studies have highlighted tolerable side effects though in the majority of instances limited efficacy when used as monotherapy. Research has focused on combining these novel agents to improve outcomes and perhaps offer refined treatment options. Novel combinations represent new territory, inherently dissimilar to combination chemotherapy with new pitfalls and challenges given their unique mechanisms of action. Though promising, it is crucial to consider the complex interplay that can occur. While there is potential for improved outcomes, there is also the possibility of unexpected toxicities. For this reason, it is critical that novel combinations be carefully considered and tested in clinical trials before widespread use. Thus far, research has shown that combination therapies are successful when not only avoiding overlapping toxicity but also capitalizing on synergy. We believe that more specific targets and an improved understanding of their off-/on-target effects will further successful novel combinations.
https://ift.tt/2sjReRx
2018 consensus statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology on the diagnosis and treatment of cancer of unknown primary
Abstract
Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2–9% of all cancer patients, mostly 60–75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.
https://ift.tt/2sm0ipf
Correction to: Molecular detection of viruses in Kenyan bats and discovery of novel astroviruses, caliciviruses and rotaviruses
The affiliation listed for Cecilia Waruhiu is incorrect. The byline and affiliation line should appear as shown above.
https://ift.tt/2xkBBiz
Occurrence of type 1 and type 2 diabetes in patients treated with immunotherapy (anti-PD-1 and/or anti-CTLA-4) for metastatic melanoma: a retrospective study
Abstract
Anti-PD-1 and anti-CTLA-4 antibodies cause immune-related side effects such as autoimmune type 1 diabetes (T1D). It has also been suggested that by increasing TNF-α, IL-2 and IFN-γ production, anti-PD-1 and/or anti-CTLA-4 treatment could affect pancreatic beta cell function and insulin sensitivity. This study was based on a retrospective observational analysis from 2 July 2014 to 27 June 2016, which evaluated the occurrence of T1D and changes in glycemia and C-reactive protein (CRP) plasma concentrations in patients undergoing anti-PD-1 and/or anti-CTLA-4 treatment for melanoma at the Saint Louis Hospital. All cases of T1D that developed during immunotherapy registered in the French Pharmacovigilance Database (FPVD) were also considered. Among the 132 patients included, 3 cases of T1D occurred. For the remaining subjects, blood glucose was not significantly affected by anti-PD-1 treatment, but CRP levels (mg/l) significantly increased during anti-PD-1 treatment (p = 0.017). However, 1 case of type 2 diabetes (T2D) occurred (associated with a longer therapy duration). Moreover, glycemia of patients pretreated (n = 44) or concomitantly treated (n = 8) with anti-CTLA-4 tended to increase during anti-PD-1 therapy (p = 0.068). From the FPVD, we obtained 14 cases of T1D that occurred during immunotherapy and were primarily characterized by the rapidity and severity of onset. In conclusion, in addition to inducing this rare immune-related diabetes condition, anti-PD-1 treatment appears to increase CRP levels, a potential inflammatory trigger of insulin resistance, but without any short-term impact on blood glucose level.
https://ift.tt/2siOcNv
Completion pneumonectomy: a valuable option for lung cancer recurrence or new primaries
Abstract
Background
The preoperative selection of patients with lung cancer recurrence remains a major clinical challenge. Several aspects of this kind of surgery are still insufficiently evidence-based, with only a few series with more than 50 patients.
Methods
A retrospective study on 29 patients who underwent a completion pneumonectomy for postoperative lung cancer recurrence or new primary was done in the period between October 2004 and December 2015. Inclusion criteria include complete (R0) first and second resections, histologically proven recurrent or new malignancy, complete pathohistological report after both operations, and exact data about the treatment outcome at the time of the last contact with patients or their families.
Results
There were 25 (86.2%) males and 4 (13.8%) females (M:F 6.2:1). In 13/29 patients, the interval between the first and second operations was less than 2 years, while in the remaining 16 patients, it was longer than 2 years. Concerning the operative stage distribution, stage I was more frequent after the first operation (44.8 vs. 22%), while stage III was dominant after the second operation (40.7 vs. 10.3%). The same tumor histology after the first and second operations existed in 24 (82.8%) patients. Adjuvant treatment was given to 53.6% of patients after the first and to 45.5% of patients after the second operation. The overall 5-year survival was 30%, median survival being 35 ± 16.9 months (1.896, 68.104 95% CI). A median survival of patients in post-surgery stage I after re-do surgery was better in comparison with that in higher stages (35 ± 22.6 vs.17.2 ± 15.1 vs. 21 ± 6.7 months, p > 0.05). Patients with the same tumor type at both operations lived significantly longer (median survival 48 ± 21.5 vs. 7.7 ± 1.9 months) than patients with different tumor histology after the second operation. Patients under 60 years (42.9%) lived longer than patients older than 60 years (median survival 69 ± 4.5 vs. 17.2 ± 14.3 months). The Cox regression analysis revealed only the disease stage at first operation and the same/different tumor histology as significant prognostic factors. One patient died from cardiac insufficiency caused by bronchopleural fistula (3.4% operative mortality). Operative morbidity was 34.4%.
Conclusion
Completion pneumonectomy may be a reasonable option for postoperative lung cancer recurrence or new primaries only in carefully selected patients, in whom the potential oncological benefits overweigh the surgical risk.
https://ift.tt/2kuIh4o
Nalbuphine as an adjuvant to 0.25% levobupivacaine in ultrasound-guided supraclavicular block provided prolonged sensory block and similar motor block durations (RCT)
Abstract
Purpose
Prolonged postoperative analgesia with early motor recovery for early rehabilitation is a challenge in regional block. The purpose of this study is to evaluate the effect of adding 20 mg nalbuphine to 25 ml of 0.25% levobupivacaine in supraclavicular brachial plexus block.
Methods
One hundred thirty-five (135) patients scheduled for hand and forearm surgeries with supraclavicular block were randomly allocated into three equal groups. Group L received 25 ml of 0.5% levobupivacaine + 1 ml normal saline; group H received 25 ml of 0.25% levobupivacaine + 1 ml normal saline; and group N received 25 ml of 0.25% levobupivacaine + 1 ml (20 mg) nalbuphine. Onset time and duration of sensory and motor block, and time to first analgesic dose were recorded.
Results
Sensory block onset was comparable between the three groups. Motor block onset in group L and group N was comparable (13.16 ± 3.07 and 13.84 ± 3.05 min, respectively) and was shorter than that in group H (15.71 ± 2 0.91 min). Sensory block duration in group L and group N was comparable (522.22 ± 69.57 and 533.78 ± 66.03 min, respectively) and was longer than that in group H (342.67 ± 92.80 min). Motor block duration in group N and group H was comparable (272.00 ± 59.45 and 249.78 ± 66.01 min, respectively) and was shorter than that in group L (334.67 ± 57.90 min). Time to first analgesic dose was significantly longer in group N (649.78 ± 114.76 min) than that of group L and group H (575.56 ± 96.85 and 375.56 ± 84.49 min, respectively) and longer in group L when compared to group H.
Conclusions
Adding 20 mg nalbuphine to 25 ml of 0.25% levobupivacaine in supraclavicular block provided prolonged duration of sensory block with similar duration of motor block.
https://ift.tt/2LybVlz
Spinal anesthesia for surgery longer than 60 min in infants: experience from the first 2 years of a spinal anesthesia program
Abstract
Purpose
Spinal anesthesia (SA) is being increasingly used in infants to avoid the potential negative neurocognitive effects of general anesthesia (GA). However, SA has been reported to provide a relatively short duration of surgical anesthesia.
Methods
We retrospectively reviewed SA cases for surgical procedures lasting more than 60 min in children up to 3 years old. All patients received bupivacaine 0.5% (1 mg/kg up to 7 mg) with clonidine 1 µg/kg ± epinephrine. The primary outcome was success of SA without subsequent conversion to GA.
Results
Thirty-five patients met inclusion criteria (all males, age 7 ± 5 months, weight 8 ± 2 kg). Procedures included male genital, groin and multiple site surgeries. Average surgical duration was 71 ± 12 min (range 60–111 min). SA was successful in 31 of 35 patients (89%; 95% confidence interval 78, 99%). The cause of failure was rarely due to the duration of surgery (1 of 4 patients). Six patients with successful SA required sedation with dexmedetomidine ± fentanyl. Differences in procedure duration and patient characteristics were not statistically significant between successful and failed SA.
Conclusions
SA is a highly successful technique and may offer an alternative to GA in children undergoing appropriate surgery expected to last as long as 60–100 min.
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Dependent functional status is associated with unplanned postoperative intubation after elective cervical spine surgery: a national registry analysis
Abstract
Purpose
The impact of preoperative functional status on 30-day unplanned postoperative intubation and clinical outcomes among patients who underwent cervical spine surgery is not well-described. We hypothesized that functional dependence is associated with 30-day unplanned postoperative intubation and that among the reintubated cohort, functional dependence is associated with adverse postoperative clinical outcomes after cervical spine surgery.
Methods
Utilizing the 2007–2016 American College of Surgeons National Surgical Quality Improvement Program database, we identified adult elective anterior and posterior cervical spine surgery patients by Current Procedural Terminology codes. We performed (1) a Cox Proportional Hazard analysis for the following outcomes: reintubation, prolonged ventilator use, and pneumonia and (2) an adjusted logistic regression analysis among patients that required postoperative reintubation to evaluate the association of functional status with adverse postoperative outcomes.
Results
The sample size was 26,263, of which 550 (2.1%) were functionally dependent. The adjusted model suggested that when compared with functionally independent patients, dependent patients were at increased risk of unplanned 30-day intubation (HR 2.05, 95% CI 1.26–3.34; P = 0.003). The adjusted risk of 30-day postoperative pneumonia was significantly higher in patients with functional dependence (HR 1.61, 95% CI 1.02–2.54, P = 0.036). Among patients that required postoperative reintubation, the odds of 30-day mortality was significantly higher in patients with functional dependence (OR 5.82, 95% CI 1.59–23.4, P < 0.001).
Conclusion
Preoperative functional dependence is a good marker for estimating postoperative unplanned intubation following cervical spine surgery.
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