Tsvetkova, E.; Sud, S.; Aucoin, N.; Biagi, J.; Burkes, R.; Samson, B.; Brule, S.; Cripps, C.; Colwell, B.; Falkson, C.; Dorreen, M.; Goel, R.; Halwani, F.; Maroun, J.; Michaud, N.; Tehfe, M.; Thirlwell, M.; Vickers, M.; Asmis, T.
The annual Eastern Canadian Colorectal Cancer Consensus Conference was held in Montreal, Quebec, 23–25 October 2014. Expert radiation, medical, and surgical oncologists and pathologists involved in the management of patients with gastrointestinal malignancies participated in presentations and discussions resulting in consensus statements on such hot topics as management of neuroendocrine tumours, advanced and metastatic pancreatic cancer, and metastatic colorectal cancer. PMID:26300681
Bossé, D.; Ng, T.; Ahmad, C.; Alfakeeh, A.; Alruzug, I.; Biagi, J.; Brierley, J.; Chaudhury, P.; Cleary, S.; Colwell, B.; Cripps, C.; Dawson, L.A.; Dorreen, M.; Ferland, E.; Galiatsatos, P.; Girard, S.; Gray, S.; Halwani, F.; Kopek, N.; Mahmud, A.; Martel, G.; Robillard, L.; Samson, B.; Seal, M.; Siddiqui, J.; Sideris, L.; Snow, S.; Thirwell, M.; Vickers, M.; Goodwin, R.; Goel, R.; Hsu, T.; Tsvetkova, E.; Ward, B.; Asmis, T.
The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2016 was held in Montreal, Quebec, 5–7 February. Experts in radiation oncology, medical oncology, surgical oncology, and infectious diseases involved in the management of patients with gastrointestinal malignancies participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses multiple topics: ■ Follow-up and survivorship of patients with resected colorectal cancer■ Indications for liver metastasectomy■ Treatment of oligometastases by stereotactic body radiation therapy■ Treatment of borderline resectable and unresectable pancreatic cancer■ Transarterial chemoembolization in hepatocellular carcinoma■ Infectious complications of antineoplastic agents PMID:28050151
Colombo, Nicoletta; Creutzberg, Carien; Amant, Frederic; Bosse, Tjalling; González-Martín, Antonio; Ledermann, Jonathan; Marth, Christian; Nout, Remi; Querleu, Denis; Mirza, Mansoor Raza; Sessa, Cristiana
Abstract The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11–13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer. Before the conference, the expert panel prepared three clinically-relevant questions about endometrial cancer relating to the following four areas: prevention and screening, surgery, adjuvant treatment and advanced and recurrent disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. Results of this consensus conference, together with a summary of evidence supporting each recommendation, are detailed in this article. All participants have approved this final article. PMID:26645990
Lázár, György; Bursics, Attila; Farsang, Zoltán; Harsányi, László; Kósa, Csaba; Maráz, Róbert; Mátrai, Zoltán; Paszt, Attila; Pavlovics, Gábor; Tamás, Róbert
Therapy for breast cancer today is characterised by ever more precise diagnostic methods and ever more effective oncological treatments, a trend which will certainly continue in the future. Breast preservation and the application of oncoplastic principles are increasingly popular. A sentinel lymph node biopsy in the surgical treatment of the axilla is primary, with the indication for axillary block dissection (ABD) narrowing and radiation therapy becoming an alternative to ABD in certain cases. This publication summarises our recommendations on the surgical treatment of breast cancer based on the content of the 2nd Breast Cancer Consensus Conference and considering the latest international studies and professional recommendations.
Colombo, N; Creutzberg, C; Amant, F; Bosse, T; González-Martín, A; Ledermann, J; Marth, C; Nout, R; Querleu, D; Mirza, M R; Sessa, C
The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11-13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer. Before the conference, the expert panel prepared three clinically relevant questions about endometrial cancer relating to the following four areas: prevention and screening, surgery, adjuvant treatment and advanced and recurrent disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. Results of this consensus conference, together with a summary of evidence supporting each recommendation, are detailed in this article. All participants have approved this final article.
Colombo, Nicoletta; Creutzberg, Carien; Amant, Frederic; Bosse, Tjalling; González-Martín, Antonio; Ledermann, Jonathan; Marth, Christian; Nout, Remi; Querleu, Denis; Mirza, Mansoor Raza; Sessa, Cristiana
The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11-13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer. Before the conference, the expert panel prepared three clinically-relevant questions about endometrial cancer relating to the following four areas: prevention and screening, surgery, adjuvant treatment and advanced and recurrent disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. Results of this consensus conference, together with a summary of evidence supporting each recommendation, are detailed in this article. All participants have approved this final article.
Colombo, Nicoletta; Creutzberg, Carien; Amant, Frederic; Bosse, Tjalling; González-Martín, Antonio; Ledermann, Jonathan; Marth, Christian; Nout, Remi; Querleu, Denis; Mirza, Mansoor Raza; Sessa, Cristiana
The first joint European Society for Medical Oncology (ESMO), European SocieTy for Radiotherapy & Oncology (ESTRO) and European Society of Gynaecological Oncology (ESGO) consensus conference on endometrial cancer was held on 11-13 December 2014 in Milan, Italy, and comprised a multidisciplinary panel of 40 leading experts in the management of endometrial cancer. Before the conference, the expert panel prepared three clinically-relevant questions about endometrial cancer relating to the following four areas: Prevention and screening, surgery, adjuvant treatment and advanced and recurrent disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, the panel developed recommendations for each specific question and a consensus was reached. Results of this consensus conference, together with a summary of evidence supporting each recommendation, are detailed in this article. All participants have approved this final article.
Lázár, György; Bursics, Attila; Farsang, Zoltán; Harsányi, László; Kósa, Csaba; Maráz, Róbert; Mátrai, Zoltán; Paszt, Attila; Pavlovics, Gábor; Tamás, Róbert
Therapy for breast cancer today is characterised by ever more precise diagnostic methods and ever more effective oncological treatments, a trend which will certainly continue into the future. Breast preservation and the application of oncoplastic principles are increasingly popular. A sentinel lymph node biopsy in the surgical treatment of the axilla is primary, with the indication for axillary block dissection (ABD) narrowing and radiation therapy becoming an alternative to ABD in certain cases. This publication summarises our recommendations on the surgical treatment of breast cancer based on the content of the 3rd Breast Cancer Consensus Conference and considering the latest international studies and professional recommendations.
Di Valentin, T; Asmis, T; Asselah, J; Aubin, F; Aucoin, N; Berry, S; Biagi, J; Booth, C M; Burkes, R; Coburn, N; Colwell, B; Cripps, C; Dawson, L A; Dorreen, M; Frechette, D; Goel, R; Gray, S; Hammad, N; Jonker, D; Kavan, P; Maroun, J; Nanji, S; Roberge, D; Samson, B; Seal, M; Shabana, W; Simunovic, M; Snow, S; Tehfe, M; Thirlwell, M; Tsvetkova, E; Vickers, M; Vuong, T; Goodwin, R
The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17-19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer.
Di Valentin, T.; Asmis, T.; Asselah, J.; Aubin, F.; Aucoin, N.; Berry, S.; Biagi, J.; Booth, C.M.; Burkes, R.; Coburn, N.; Colwell, B.; Cripps, C.; Dawson, L.A.; Dorreen, M.; Frechette, D.; Goel, R.; Gray, S.; Hammad, N.; Jonker, D.; Kavan, P.; Maroun, J.; Nanji, S.; Roberge, D.; Samson, B.; Seal, M.; Shabana, W.; Simunovic, M.; Snow, S.; Tehfe, M.; Thirlwell, M.; Tsvetkova, E.; Vickers, M.; Vuong, T.; Goodwin, R.
The annual Eastern Canadian Colorectal Cancer Consensus Conference held in Montreal, Quebec, 17–19 October 2013, marked the 10-year anniversary of this meeting that is attended by leaders in medical, radiation, and surgical oncology. The goal of the attendees is to improve the care of patients affected by gastrointestinal malignancies. Topics discussed during the conference included pancreatic cancer, rectal cancer, and metastatic colorectal cancer. PMID:26966404
Vickers, M M; Pasieka, J; Dixon, E; McEwan, S; McKay, A; Renouf, D; Schellenberg, D; Ruether, D
The 13th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Calgary, Alberta, September 8-10, 2011. Health care professionals involved in the care of patients with gastrointestinal cancers participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management neuroendocrine tumours and locally advanced pancreatic cancer.
McGee, J; Bookman, M; Harter, P; Marth, C; McNeish, I; Moore, K N; Poveda, A; Hilpert, F; Hasegawa, K; Bacon, M; Gatsonis, C; Brand, A; Kridelka, F; Berek, J; Ottevanger, N; Levy, T; Silverberg, S; Kim, B-G; Hirte, H; Okamoto, A; Stuart, G; Ochiai, K
This manuscript reports the consensus statements regarding the design and conduct of clinical trials in patients with newly diagnosed and recurrent epithelial ovarian cancer (EOC), following deliberation at the 5th Ovarian Cancer Consensus Conference (OCCC), held in Tokyo in November 2015. Three important questions were identified for discussion prior to the meeting and achieved consensus during the meeting: 1) What are the most important factors to be evaluated prior to initial therapy? 2) What are the most important factors to be evaluated specifically in recurrent disease? 3) Are there specific considerations for special patient subpopulations? In addition, we report a list of important unmet needs compiled during the consensus process, which is intended to guide future research initiatives.
Eberhardt, W E E; De Ruysscher, D; Weder, W; Le Péchoux, C; De Leyn, P; Hoffmann, H; Westeel, V; Stahel, R; Felip, E; Peters, S
To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.
Vickers, M.M.; Pasieka, J.; Dixon, E.; McEwan, S.; McKay, A.; Renouf, D.; Schellenberg, D.; Ruether, D.
The 13th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Calgary, Alberta, September 8–10, 2011. Health care professionals involved in the care of patients with gastrointestinal cancers participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management neuroendocrine tumours and locally advanced pancreatic cancer. PMID:23300370
Mulder, K.E.; Ahmed, S.; Davies, J.D.; Doll, C.M.; Dowden, S.; Gill, S.; Gordon, V.; Hebbard, P.; Lim, H.; McFadden, A.; McGhie, J.P.; Park, J.; Wong, R.
The 17th annual Western Canadian Gastrointestinal Cancer Consensus Conference (wcgccc) was held in Edmonton, Alberta, 11–12 September 2015. The wcgccc is an interactive multidisciplinary conference attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancer. Surgical, medical, and radiation oncologists; pathologists; radiologists; and allied health care professionals participated in presentation and discussion sessions for the purposes of developing the recommendations presented here. This consensus statement addresses current issues in the management of gastric cancer. PMID:28050139
Toi, Masakazu; Winer, Eric P; Inamoto, Takashi; Benson, John R; Forbes, John F; Mitsumori, Michihide; Robertson, John F R; Sasano, Hironobu; von Minckwitz, Gunter; Yamauchi, Akira; Klimberg, V Suzanne
A consensus conference was held to investigate issues related to the local management of early breast cancer. Here, we highlight the major topics discussed at the conference and propose ideas for future studies. Regarding axillary management, we examined three major issues. First, we discussed whether the use of axillary reverse mapping could clarify the lymphatic system of breast and whether the ipsilateral arm might help avoid lymphedema. Second, the use of an indocyanine green fluorescent navigation system was discussed for intraoperative lymphatic mapping. These new issues should be examined further in practice. Finally, some agreement was reached on the importance of "four-node diagnosis" to aid in the diagnostic accuracy of sentinel nodes. Regarding breast treatment, there was general agreement that the clinical value of surgical margins in predicting local failure was dependent on the tumor's intrinsic biology and subtypes. For patients treated with preoperative chemotherapy, less extensive excision may be feasible in those who respond to systemic therapy in an acceptable manner. Most trials of preoperative chemotherapy lack outcome data on local recurrence. Therefore, there is a need for such data for overview analysis. We also agreed that radiation after mastectomy may be beneficial in node-positive cases where more than four nodes are involved. Throughout the discussions for both invasive and noninvasive disease, the investigation of nomograms was justified for major issues in the decision-making process, such as the presence or absence of microinvasion and the involvement of nonsentinel nodes in sentinel node-positive patients.
Primary Therapy of Patients with Early Breast Cancer: Evidence, Controversies, Consensus: Opinions of German Specialists to the 14th St. Gallen International Breast Cancer Conference 2015 (Vienna 2015).
Untch, M; Harbeck, N; Huober, J; von Minckwitz, G; Gerber, B; Kreipe, H-H; Liedtke, C; Marschner, N; Möbus, V; Scheithauer, H; Schneeweiss, A; Thomssen, C; Jackisch, C; Beckmann, M W; Blohmer, J-U; Costa, S-D; Decker, T; Diel, I; Fasching, P A; Fehm, T; Janni, W; Lück, H-J; Maass, N; Scharl, A; Loibl, S
For the first time, this year's St. Gallen International Consensus Conference on the treatment of patients with primary breast cancer, which takes place every two years, was held not in St. Gallen (Switzerland) but - for logistical reasons - in Vienna (Austria) under its usual name. The 2015 St. Gallen International Consensus Conference was the 14th of its kind. As the international panel of the St. Gallen conference consists of experts from different countries, the consensus mirrors an international cross-section of opinions. From a German perspective, it was considered useful to translate the results of the votes of the St. Gallen conference into practical suggestions, particularly in light of the recently updated treatment guideline of the Gynecologic Oncology Group (AGO-Mamma 2015) in Germany. A German group consisting of 14 breast cancer experts, three of whom are members of the international St. Gallen panel, has therefore provided comments on the results of this year's votes at the 2015 St. Gallen Consensus Conference and their impact on clinical care in Germany. The 14th St. Gallen conference once again focused on surgery of the breast and the axilla, radio-oncologic and systemic treatment options for primary breast cancer depending on tumor biology, and the clinical use of multigene assays. The conference also considered targeted therapies for older and for younger patients, including the diagnosis/treatment of breast cancer during and after pregnancy and the preservation of fertility.
Jackisch, Christian; Harbeck, Nadia; Huober, Jens; von Minckwitz, Gunter; Gerber, Bernd; Kreipe, Hans-Heinrich; Liedtke, Cornelia; Marschner, Norbert; Möbus, Volker; Scheithauer, Heike; Schneeweiss, Andreas; Thomssen, Christoph; Loibl, Sibylle; Beckmann, Matthias W.; Blohmer, Jens-Uwe; Costa, Serban-Dan; Decker, Thomas; Diel, Ingo; Fasching, Peter A.; Fehm, Tanja; Janni, Wolfgang; Lück, Hans-Joachim; Maass, Nicolai; Scharl, Anton; Untch, Michael
Summary The key topics of this year's 14th St. Gallen Consensus Conference on the diagnosis and therapy of primary breast cancer were again questions about breast surgery and axillary surgery, radio-oncology and systemic therapy options in consideration of tumor biology, and the clinical application of multigene assays. This year, the consensus conference took place in Vienna. From a German perspective, it makes sense to substantiate the results of the vote of the international panel representing 19 countries in light of the updated national therapy recommendations of the AGO (Arbeitsgemeinschaft Gynäkologische Onkologie). Therefore, 14 German breast cancer experts, 3 of whom are members of the International St. Gallen Panel, have commented on the voting results of the St. Gallen Consensus Conference 2015 in relation to clinical routine in Germany. PMID:26557827
Gillessen, S.; Omlin, A.; Attard, G.; de Bono, J. S.; Efstathiou, E.; Fizazi, K.; Halabi, S.; Nelson, P. S.; Sartor, O.; Smith, M. R.; Soule, H. R.; Akaza, H.; Beer, T. M.; Beltran, H.; Chinnaiyan, A. M.; Daugaard, G.; Davis, I. D.; De Santis, M.; Drake, C. G.; Eeles, R. A.; Fanti, S.; Gleave, M. E.; Heidenreich, A.; Hussain, M.; James, N. D.; Lecouvet, F. E.; Logothetis, C. J.; Mastris, K.; Nilsson, S.; Oh, W. K.; Olmos, D.; Padhani, A. R.; Parker, C.; Rubin, M. A.; Schalken, J. A.; Scher, H. I.; Sella, A.; Shore, N. D.; Small, E. J.; Sternberg, C. N.; Suzuki, H.; Sweeney, C. J.; Tannock, I. F.; Tombal, B.
The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration-resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged. PMID:26041764
Beyer, J; Albers, P; Altena, R; Aparicio, J; Bokemeyer, C; Busch, J; Cathomas, R; Cavallin-Stahl, E; Clarke, N W; Claßen, J; Cohn-Cedermark, G; Dahl, A A; Daugaard, G; De Giorgi, U; De Santis, M; De Wit, M; De Wit, R; Dieckmann, K P; Fenner, M; Fizazi, K; Flechon, A; Fossa, S D; Germá Lluch, J R; Gietema, J A; Gillessen, S; Giwercman, A; Hartmann, J T; Heidenreich, A; Hentrich, M; Honecker, F; Horwich, A; Huddart, R A; Kliesch, S; Kollmannsberger, C; Krege, S; Laguna, M P; Looijenga, L H J; Lorch, A; Lotz, J P; Mayer, F; Necchi, A; Nicolai, N; Nuver, J; Oechsle, K; Oldenburg, J; Oosterhuis, J W; Powles, T; Rajpert-De Meyts, E; Rick, O; Rosti, G; Salvioni, R; Schrader, M; Schweyer, S; Sedlmayer, F; Sohaib, A; Souchon, R; Tandstad, T; Winter, C; Wittekind, C
In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.
Tudyka, V; Blomqvist, L; Beets-Tan, R G H; Boelens, P G; Valentini, V; van de Velde, C J; Dieguez, A; Brown, G
Some interesting shifts have taken place in the diagnostic approach for detection of colorectal lesions over the past decade. This article accompanies the recent EURECCA consensus group reccomendations for optimal management of colon and rectal cancers. In summary, imaging has a crucial role to play in the diagnosis, staging assessment and follow up of patients with colon and rectal cancer. Recent advances include the use of CT colonography instead of Barium Enema in the diagnosis of colonoic cancer and as an alternative to colonoscopy. Modern mutlidetector CT scanning techniques have also shown improvements in prognostic stratification of patients with colonic cancer and clinical trials are underway testing the selective use of neoadjuvant therapy for imaging identified high risk colon cancers. In rectal cancer, high resolution MRI with a voxel size less or equal to 3 × 1 × 1 mm3 on T2-weighted images has a proven ability to accurately stage patients with rectal cancer. Moreover, preoperative identification of prognostic features allows stratification of patients into different prognostic groups based on assessment of depth of extramural spread, relationship of the tumour edge to the mesorectal fascia (MRF) and extramural venous invasion (EMVI). These poor prognostic features predict an increased risk of local recurrence and/or metastatic disease and should form the basis for preoperative local staging and multidisciplinary preoperative discussion of patient treatment options.
Beyer, J.; Albers, P.; Altena, R.; Aparicio, J.; Bokemeyer, C.; Busch, J.; Cathomas, R.; Cavallin-Stahl, E.; Clarke, N. W.; Claßen, J.; Cohn-Cedermark, G.; Dahl, A. A.; Daugaard, G.; De Giorgi, U.; De Santis, M.; De Wit, M.; De Wit, R.; Dieckmann, K. P.; Fenner, M.; Fizazi, K.; Flechon, A.; Fossa, S. D.; Germá Lluch, J. R.; Gietema, J. A.; Gillessen, S.; Giwercman, A.; Hartmann, J. T.; Heidenreich, A.; Hentrich, M.; Honecker, F.; Horwich, A.; Huddart, R. A.; Kliesch, S.; Kollmannsberger, C.; Krege, S.; Laguna, M. P.; Looijenga, L. H. J.; Lorch, A.; Lotz, J. P.; Mayer, F.; Necchi, A.; Nicolai, N.; Nuver, J.; Oechsle, K.; Oldenburg, J.; Oosterhuis, J. W.; Powles, T.; Rajpert-De Meyts, E.; Rick, O.; Rosti, G.; Salvioni, R.; Schrader, M.; Schweyer, S.; Sedlmayer, F.; Sohaib, A.; Souchon, R.; Tandstad, T.; Winter, C.; Wittekind, C.
In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377–1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478–496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497–513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements. PMID:23152360
Willson, P D
The United Nations-sponsored International Conference on Population held in Mexico City was both a rejection and an affirmation of a new policy of the Reagan administration. The policy denies international family planning funds to nongovernmental organizations that perform or actively promote abortion as a family planning method in other nations. A compromise statement was accepted urging governments to take appropriate measures to discourage abortion as a family planning method and when possible to provide for the humane treatment and counseling of women ho resorted to abortion. The statement on abortion was 1 of 88 reccomendations approved by the conference. The commitment expressed in the 10-year-old World Population Plan of Action to the rights and responsiblity to all people as reaffirmed. The conference also endorsed family life education and sex education as well as suitable family planning, information and services for adolescents, with due consideration given to the role, rights and obligations of parents. Increased support for international population and family planning programs was urged and World Bank President, Clausen, urged a 4-fold increase in international funding by the year 2000. Most of the conference's recommendations re devoted to the broad range of population policy issues, including morbidity and mortality, international and internal migration, the relationship between population and economic development and the status of women. The purpose of the recommendations is to increase the momentum of international support. The Mexico City conference was characterized by a remarkable degree of consensus about population policies with respect to integration with economic development, the need to respect individual rights and the recognition that all nations have sovereign rights to develop and implement their own population policies. Conflict and controversy arose in the areas of the arms race and the Middle East. The US position on abortion funding
van de Velde, C J H; Boelens, P G; Tanis, P J; Espin, E; Mroczkowski, P; Naredi, P; Pahlman, L; Ortiz, H; Rutten, H J; Breugom, A J; Smith, J J; Wibe, A; Wiggers, T; Valentini, V
The first multidisciplinary consensus conference on colon and rectal cancer was held in December 2012, achieving a majority of consensus for diagnostic and treatment decisions using the Delphi Method. This article will give a critical appraisal of the topics discussed during the meeting and in the consensus document by well-known leaders in surgery that were involved in this multidisciplinary consensus process. Scientific evidence, experience and opinions are collected to support multidisciplinary teams (MDT) with arguments for medical decision-making in diagnosis, staging and treatment strategies for patients with colon or rectal cancer. Surgery is the cornerstone of curative treatment for colon and rectal cancer. Standardizing treatment is an effective instrument to improve outcome of multidisciplinary cancer care for patients with colon and rectal cancer. In this article, a review of the following focuses; Perioperative care, age and colorectal surgery, obstructive colorectal cancer, stenting, surgical anatomical considerations, total mesorectal excision (TME) surgery and training, surgical considerations for locally advanced rectal cancer (LARC) and local recurrent rectal cancer (LRRC), surgery in stage IV colorectal cancer, definitions of quality of surgery, transanal endoscopic microsurgery (TEM), laparoscopic colon and rectal surgery, preoperative radiotherapy and chemoradiotherapy, and how about functional outcome after surgery?
van der Kwast, Theo H; Amin, Mahul B; Billis, Athanase; Epstein, Jonathan I; Griffiths, David; Humphrey, Peter A; Montironi, Rodolfo; Wheeler, Thomas M; Srigley, John R; Egevad, Lars; Delahunt, Brett
The 2009 International Society of Urological Pathology consensus conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the substaging of pT2 prostate cancers according to the TNM 2002/2010 system, reporting of tumor size/volume and zonal location of prostate cancers were coordinated by working group 2. A survey circulated before the consensus conference demonstrated that 74% of the 157 participants considered pT2 substaging of prostate cancer to be of clinical and/or academic relevance. The survey also revealed a considerable variation in the frequency of reporting of pT2b substage prostate cancer, which was likely a consequence of the variable methodologies used to distinguish pT2a from pT2b tumors. Overview of the literature indicates that current pT2 substaging criteria lack clinical relevance and the majority (65.5%) of conference attendees wished to discontinue pT2 substaging. Therefore, the consensus was that reporting of pT2 substages should, at present, be optional. Several studies have shown that prostate cancer volume is significantly correlated with other clinicopathological features, including Gleason score and extraprostatic extension of tumor; however, most studies fail to demonstrate this to have prognostic significance on multivariate analysis. Consensus was reached with regard to the reporting of some quantitative measure of the volume of tumor in a prostatectomy specimen, without prescribing a specific methodology. Incorporation of the zonal and/or anterior location of the dominant/index tumor in the pathology report was accepted by most participants, but a formal definition of the identifying features of the dominant/index tumor remained undecided.
Hoffmann, Jürgen; Souchon, Rainer; Lebeau, Annette; Öhlschlegel, Christian; Gruber, Günther; Rageth, Christoph; Weber, Walter; Harbeck, Nadia; Janni, Wolfgang; Kreipe, Hans; Fitzal, Florian; Resch, Alexandra; Bago-Horvath, Zsuzsanna; Peintinger, Florentia
The German, Austrian and Swiss (D.A.CH) Societies of Senology gathered together in 2012 to address dwelling questions regarding axillary clearance in breast cancer patients. The Consensus Panel consisted of 14 members of these societies and included surgical oncologists, gynaecologists, pathologists and radiotherapists. With regard to omitting axillary lymph node dissection in sentinel lymph node macrometastases, the Panel consensually accepted this option for low-risk patients only. A simple majority voted against extending radiotherapy to the axilla after omitting axillary dissection in N1 disease. Consensus was yielded for the use of axillary ultrasound and prospective registers for such patients in the course of follow-up. The questions regarding neoadjuvant therapy and the timing of sentinel lymph node biopsy failed to yield consensus, yet both options (before or after) are possible in clinically node-negative disease.
Leary, A F; Quinn, M; Fujiwara, K; Coleman, R L; Kohn, E; Sugiyama, T; Glasspool, R; Ray-Coquard, I; Colombo, N; Bacon, M; Zeimet, A; Westermann, A; Gomez-Garcia, E; Provencher, D; Welch, S; Small, W; Millan, D; Okamoto, A; Stuart, G; Ochiai, K
This manuscript reports the consensus statements on designing clinical trials in rare ovarian tumours reached at the 5th Ovarian Cancer Consensus Conference (OCCC) held in Tokyo, November 2015. Three important questions were identified concerning rare ovarian tumours (rare epithelial ovarian cancers (eOC), sex-cord stromal tumours (SCST) and germ cell tumours (GCT)): (1) What are the research and trial issues that are unique to rare ovarian tumours? There is a lack of randomised phase III data defining standards of care which makes it difficult to define control arms, but identifies unmet needs that merit investigation. Internationally agreed upon diagnostic criteria, expert pathological review, and translational research are crucial. (2) What should be investigated in rare eOC, GCT and SCST? Trials dedicated to each rare ovarian tumour should be encouraged. Nonetheless, where the question is relevant, rare eOC can be included in eOC trials but with rigorous stratification. Although there is emerging evidence suggesting that rare eOC have different molecular profiles, trials are needed to define new type-specific standards for each rare eOC (clear cell, low grade serous and mucinous). For GCTs, a priority is reducing toxicities from treatment while maintaining cure rates. Both a robust prognostic scoring system and more effective treatments for de novo poor prognosis and relapsed GCTs are needed. For SCSTs, validated prognostic markers as well as alternatives to the current standard of bleomycin/etoposide/cisplatin (BEP) should be identified. (3) Are randomised trials feasible? Randomised controlled trials (RCT) should be feasible in any of the rare tumours through international collaboration. Ongoing trials have already demonstrated the feasibility of RCT in rare eOC and SCST. Mucinous OC may be considered for inclusion, stratified, into RCTs of non-gynaecological mucinous tumours, while RCTs in high risk or relapsed GCT may be performed as a subset of male and
Pellegrini Filho, Alberto; Zurita, Laura
This piece provides an initial assessment of the First Citizen Consensus Conference, an event held in the city of Santiago, Chile, from 22-24 November 2003, on the subject of "The Management of My Medical Record." This conference was the first citizen consensus conference that has been held in Chile as well as the first such conference in Latin America. Consensus conferences were devised by the Danish Board of Technology in 1987 as a way to assess science and technology issues through discussions between experts and a panel of lay persons. At the end of a consensus conference, the lay persons express their opinions and recommendations in a consensus report that is directed at policymakers, decision-makers, and the public in general. The objective of a consensus conference is to bridge the gaps that routinely exist among the general public, experts, and elected officials. So far, the Danish Board of Technology has organized more than 20 of these conferences, using a methodology that has become established as a model. Taking into account the changes that have occurred in the relationship between science and society at large, the Pan American Health Organization has decided to support the holding of consensus conferences in Latin America and the Caribbean. The First Citizen Consensus Conference adapted the Danish methodology to conditions in Chile, and this piece assesses the modifications that were made. In addition, some 6 to 12 months after the conference, there will be an external evaluation of the outcomes and impact of the conference, especially in the communications media, public debate, decision-making, and perceptions of the persons who were involved. Despite the criticisms made in this piece and some shortcomings that are pointed out, the First Citizen Consensus Conference achieved all of its objectives and will serve as an excellent model for similar conferences in other countries of the Americas.
Compérat, Eva; Camparo, Philippe; Srigley, John; Delahunt, Brett; Egevad, Lars
The 2009 International Society of Urological Pathology (ISUP) consensus conference on handling and staging of radical prostatectomy specimens issued recommendations for standardization of pathology reporting of radical prostatectomy specimens. The conference addressed specimen handling, T2 substaging, prostate cancer volume, extraprostatic extension, lymphovascular invasion, seminal vesicle invasion, lymph node metastases and surgical margins. This review summarizes the conclusions and recommendations resulting from the consensus process.
Gisbert, Javier P; Molina-Infante, Javier; Amador, Javier; Bermejo, Fernando; Bujanda, Luis; Calvet, Xavier; Castro-Fernández, Manuel; Cuadrado-Lavín, Antonio; Elizalde, J Ignasi; Gene, Emili; Gomollón, Fernando; Lanas, Ángel; Martín de Argila, Carlos; Mearin, Fermín; Montoro, Miguel; Pérez-Aisa, Ángeles; Pérez-Trallero, Emilio; McNicholl, Adrián G
Helicobacter pylori approximately infect 50% of Spanish population and causes chronic gastritis, peptic ulcer and gastric cancer. Until now, three consensus meetings on H.pylori infection had been performed in Spain (the last in 2012). The changes in the treatment schemes, and the increasing available evidence, have justified organizing the IVSpanish Consensus Conference (March 2016), focused on the treatment of this infection. Nineteen experts participated, who performed a systematic review of the scientific evidence and developed a series of recommendation that were subjected to an anonymous Delphi process of iterative voting. Scientific evidence and the strength of the recommendation were classified using GRADE guidelines. As starting point, this consensus increased the minimum acceptable efficacy of recommended treatments that should reach, or preferably surpass, the 90% cure rate when prescribed empirically. Therefore, only quadruple therapies (with or without bismuth), and generally lasting 14 days, are recommended both for first and second line treatments. Non-bismuth quadruple concomitant regimen, including a proton pump inhibitor, clarithromycin, amoxicillin and metronidazole, is recommended as first line. In the present consensus, other first line alternatives and rescue treatments are also reviewed and recommended.
Jeyarajah, D R; Berman, R S; Doyle, M B; Geevarghese, S K; Posner, M C; Farmer, D; Minter, R M
The findings and recommendations of the North American consensus conference on training in hepatopancreaticobiliary (HPB) surgery held in October 2014 are presented. The conference was hosted by the Society for Surgical Oncology (SSO), the Americas Hepato-Pancreatico-Biliary Association (AHPBA), and the American Society of Transplant Surgeons (ASTS). The current state of training in HPB surgery in North America was defined through three pathways-HPB, surgical oncology, and solid organ transplant fellowships. Consensus regarding programmatic requirements included establishment of minimum case volumes and inclusion of quality metrics. Formative assessment, using milestones as a framework and inclusive of both operative and nonoperative skills, must be present. Specific core HPB cases should be defined and used for evaluation of operative skills. The conference concluded with a focus on the optimal means to perform summative assessment to evaluate the individual fellow completing a fellowship in HPB surgery. Presentations from the hospital perspective and the American Board of Surgery led to consensus that summative assessment was desired by the public and the hospital systems and should occur in a uniform but possibly modular manner for all HPB fellowship pathways. A task force composed of representatives of the SSO, AHPBA, and ASTS are charged with implementation of the consensus statements emanating from this consensus conference.
Jeyarajah, D Rohan; Berman, Russell S; Doyle, Majella; Geevarghese, Sunil K; Posner, Mitchell C; Farmer, Douglas; Minter, Rebecca M
The findings and recommendations of the North American Consensus Conference on Training in HPB Surgery held October 2014 are presented. The conference was hosted by the Society for Surgical Oncology (SSO), Americas Hepatopancreaticobiliary Association (AHPBA), and the American Society of Transplant Surgeons (ASTS). The current state of training in HPB surgery in North America was defined through three pathways-HPB, Surgical Oncology, and Solid Organ Transplant fellowships. Consensus regarding programmatic requirements included establishment of minimum case volumes and inclusion of quality metrics. Formative assessment, using milestones as a framework and inclusive of both operative and non-operative skills, must be present. Specific core HPB cases should be defined and used for evaluation of operative skills. The conference concluded with a focus on the optimal means to perform summative assessment to evaluate the individual fellow completing a fellowship in HPB surgery. Presentations from the hospital perspective and the American Board of Surgery led to consensus that summative assessment was desired by the public and the hospital systems, and should occur in a uniform but possibly modular manner for all HPB fellowship pathways. A task force comprised of representatives of the SSO, AHPBA, and ASTS are charged with implementation of the consensus statements emanating from this consensus conference.Copyright © 2016 The American Society of Transplantation, the American Society of Transplant Surgeons, and the Society of Surgical Oncology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by The American Society of Transplantation, the American Society of Transplant Surgeons, or the Society of Surgical Oncology.
This article starts by reviewing the setbacks that the recent Science and Technology Studies literature has identified in the functioning of technologies of democracy, the different arrangements that look to enact deliberation on technoscientific issues. Putting a focus on the Citizen Consensus Conference, it then proposes that several of these setbacks are related to the kind of "work" that these technologies are expected to do, identifying two kinds of it: performing a laboratory-based experiment and constituting a platform for the dissemination of facts. It then applies this framework to study a Citizen Consensus Conference carried out in Chile in 2003. After a detailed genealogy of the planning, implementation and afterlife of this exercise, the article concludes that several of the limitations experienced are derived from a "successful outcome" conceived as solely running a neat lab-based experiment, arguing for the need to incorporate its functioning as a platform with all the associated transformations and messiness.
Giovannucci, Edward; Harlan, David M; Archer, Michael C; Bergenstal, Richard M; Gapstur, Susan M; Habel, Laurel A; Pollak, Michael; Regensteiner, Judith G; Yee, Douglas
Epidemiologic evidence suggests that cancer incidence is associated with diabetes as well as certain diabetes risk factors and treatments. This consensus statement of experts assembled jointly by the American Diabetes Association and the American Cancer Society reviews the state of science concerning 1) the association between diabetes and cancer incidence or prognosis; 2) risk factors common to both diabetes and cancer; 3) possible biologic links between diabetes and cancer risk; and 4) whether diabetes treatments influence the risk of cancer or cancer prognosis. In addition, key unanswered questions for future research are posed.
Cammarota, Giovanni; Ianiro, Gianluca; Tilg, Herbert; Rajilić-Stojanović, Mirjana; Kump, Patrizia; Satokari, Reetta; Sokol, Harry; Arkkila, Perttu; Pintus, Cristina; Hart, Ailsa; Segal, Jonathan; Aloi, Marina; Masucci, Luca; Molinaro, Antonio; Scaldaferri, Franco; Gasbarrini, Giovanni; Lopez-Sanroman, Antonio; Link, Alexander; de Groot, Pieter; de Vos, Willem M; Högenauer, Christoph; Malfertheiner, Peter; Mattila, Eero; Milosavljević, Tomica; Nieuwdorp, Max; Sanguinetti, Maurizio; Simren, Magnus; Gasbarrini, Antonio
Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridium difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a non-standardised treatment into the clinical practice with safety and proper governance. In view of this, an evidence-based recommendation is needed to drive the practical implementation of FMT. In this European Consensus Conference, 28 experts from 10 countries collaborated, in separate working groups and through an evidence-based process, to provide statements on the following key issues: FMT indications; donor selection; preparation of faecal material; clinical management and faecal delivery and basic requirements for implementing an FMT centre. Statements developed by each working group were evaluated and voted by all members, first through an electronic Delphi process, and then in a plenary consensus conference. The recommendations were released according to best available evidence, in order to act as guidance for physicians who plan to implement FMT, aiming at supporting the broad availability of the procedure, discussing other issues relevant to FMT and promoting future clinical research in the area of gut microbiota manipulation. This consensus report strongly recommends the implementation of FMT centres for the treatment of C. difficile infection as well as traces the guidelines of technicality, regulatory, administrative and laboratory requirements.
Warnock, Garth L.; Tator, Charles H.
Canadian surgical research requires careful nurturing if it is to flourish in tomorrow’s environment. A consensus conference organized by the Research Development Committee of the Canadian Association of Surgical Chairs has addressed a number of issues to promote Canadian surgical research. This synopsis is a summary of the proceedings of that conference. It reflects on the meaning of surgical science, elements of establishing a successful research program, leadership in surgical science, identification of talented trainees, and the means to make the most of opportunities for funding. The information contained in the synopsis should not only assist departments of surgery and surgical specialty societies but should challenge them to set goals and innovative approaches to plan for strong surgical research in a changing environment. PMID:9711162
Untch, M.; Harbeck, N.; Huober, J.; von Minckwitz, G.; Gerber, B.; Kreipe, H.-H.; Liedtke, C.; Marschner, N.; Möbus, V.; Scheithauer, H.; Schneeweiss, A.; Thomssen, C.; Jackisch, C.; Beckmann, M. W.; Blohmer, J.-U.; Costa, S.-D.; Decker, T.; Diel, I.; Fasching, P. A.; Fehm, T.; Janni, W.; Lück, H.-J.; Maass, N.; Scharl, A.; Loibl, S.
For the first time, this yearʼs St. Gallen International Consensus Conference on the treatment of patients with primary breast cancer, which takes place every two years, was held not in St. Gallen (Switzerland) but – for logistical reasons – in Vienna (Austria) under its usual name. The 2015 St. Gallen International Consensus Conference was the 14th of its kind. As the international panel of the St. Gallen conference consists of experts from different countries, the consensus mirrors an international cross-section of opinions. From a German perspective, it was considered useful to translate the results of the votes of the St. Gallen conference into practical suggestions, particularly in light of the recently updated treatment guideline of the Gynecologic Oncology Group (AGO-Mamma 2015) in Germany. A German group consisting of 14 breast cancer experts, three of whom are members of the international St. Gallen panel, has therefore provided comments on the results of this yearʼs votes at the 2015 St. Gallen Consensus Conference and their impact on clinical care in Germany. The 14th St. Gallen conference once again focused on surgery of the breast and the axilla, radio-oncologic and systemic treatment options for primary breast cancer depending on tumor biology, and the clinical use of multigene assays. The conference also considered targeted therapies for older and for younger patients, including the diagnosis/treatment of breast cancer during and after pregnancy and the preservation of fertility. PMID:26166836
On November 9 and 10, 2015, the International Conference on Mesothelioma in Populations Exposed to Naturally Occurring Asbestiform Fibers was held at the University of Hawaii Cancer Center in Honolulu, Hawaii. The meeting was cosponsored by the International Association for the S...
Coelho, Luiz Gonzaga Vaz; Zaterka, Schlioma
Significant progress has been obtained since the First Brazilian Consensus Conference on H. pylori Infection held in 1995, in Belo Horizonte, MG, and justify a second meeting to establish updated guidelines on the current management of H. pylori infection. The Second Brazilian Consensus Conference on H. pylori Infection was organized by the Brazilian Federation of Gastroenterology and Brazilian Nucleus for the Study of Helicobacter and took place on June, 19-20, 2004 in São Paulo, SP. Thirty six delegates coming from 15 different Brazilian states including gastroenterologists, pathologists, microbiologists and pediatricians undertook the meeting. The participants were allocated in one the five main topics of the meeting: H. pylori and dyspepsia, H. pylori and NSAIDs, H. pylori and gastroesophageal reflux disease, H. pylori treatment, and H. pylori retreatment. Seventy per cent and more votes were considered as acceptance for the final statement. The results were presented during a special session on the VI Brazilian Week of Digestive System, in Recife, PE (October 2004), and this publication represents the summary of the main recommendations and conclusions emerged from the meeting.
Egevad, Lars; Srigley, John R; Delahunt, Brett
The 2009 International Society of Urological Pathology consensus conference in Boston, made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. The activities of the conference were coordinated through five workgroups. The results are presented in five separate reports covering (1) specimen handling, (2) T2 substaging and prostate cancer volume, (3) extraprostatic extension, lymphovascular invasion and locally advanced disease, (4) seminal vesicles and lymph node metastases and (5) surgical margins. In this introductory article we describe some novel features of the organization of the consensus process. Following the completion of a pre-meeting survey conference, participants discussed and voted on 43 specific issues of contention relating to the pathological reporting of radical prostatectomy specimens. Consensus, defined as agreement by at least 65% of participants present, was achieved for 30 questions.
Cobb, Charles M; Daubert, Diane M; Davis, Karen; Deming, Jodi; Flemmig, Thomas F; Pattison, Anna; Roulet, Jean-François; Stambaugh, Roger V
A consensus conference was convened to evaluate and address issues of safety and efficacy when using glycine powder in an air-powder jet device for supra- and subgingival applications during dental prophylaxis and periodontal maintenance. The conference reported the following conclusions: 1) Supra- and subgingival air polishing using glycine powder is safe and effective for removal of biofilms from natural tooth structure and restorative materials; 2) there is no evidence of soft-tissue abrasion when using glycine powder in an air-polishing device; 3) in periodontal probing depths of 1 mm to 4 mm, glycine-powder air polishing, using a standard air-polishing nozzle, is more effective at removing subgingival biofilm than manual or ultrasonic instruments; and 4) at probing depths of 5 mm to 9 mm, using a subgingival nozzle, glycine powder air polishing is more effective at removing subgingival biofilm than manual or ultrasonic instrumentation. This conference statement, supported by an industry grant, was drafted by a panel of distinguished dental professionals.
Cuomo, Rosario; Barbara, Giovanni; Pace, Fabio; Annese, Vito; Bassotti, Gabrio; Binda, Gian Andrea; Casetti, Tino; Colecchia, Antonio; Festi, Davide; Fiocca, Roberto; Laghi, Andrea; Maconi, Giovanni; Nascimbeni, Riccardo; Scarpignato, Carmelo; Villanacci, Vincenzo; Annibale, Bruno
The statements produced by the Consensus Conference on Diverticular Disease promoted by GRIMAD (Gruppo Italiano Malattia Diverticolare, Italian Group on Diverticular Diseases) are reported. Topics such as epidemiology, risk factors, diagnosis, medical and surgical treatment of diverticular disease (DD) in patients with uncomplicated and complicated DD were reviewed by a scientific board of experts who proposed 55 statements graded according to level of evidence and strength of recommendation, and approved by an independent jury. Each topic was explored focusing on the more relevant clinical questions. Comparison and discussion of expert opinions, pertinent statements and replies to specific questions, were presented and approved based on a systematic literature search of the available evidence. Comments were added explaining the basis for grading the evidence, particularly for controversial areas.
Barbara, Giovanni; Pace, Fabio; Annese, Vito; Bassotti, Gabrio; Binda, Gian Andrea; Casetti, Tino; Colecchia, Antonio; Festi, Davide; Fiocca, Roberto; Laghi, Andrea; Maconi, Giovanni; Nascimbeni, Riccardo; Scarpignato, Carmelo; Villanacci, Vincenzo; Annibale, Bruno
The statements produced by the Consensus Conference on Diverticular Disease promoted by GRIMAD (Gruppo Italiano Malattia Diverticolare, Italian Group on Diverticular Diseases) are reported. Topics such as epidemiology, risk factors, diagnosis, medical and surgical treatment of diverticular disease (DD) in patients with uncomplicated and complicated DD were reviewed by a scientific board of experts who proposed 55 statements graded according to level of evidence and strength of recommendation, and approved by an independent jury. Each topic was explored focusing on the more relevant clinical questions. Comparison and discussion of expert opinions, pertinent statements and replies to specific questions, were presented and approved based on a systematic literature search of the available evidence. Comments were added explaining the basis for grading the evidence, particularly for controversial areas. PMID:25360320
Kleinman, Daniel Lee; Powell, Maria; Grice, Joshua; Adrian, Judith; Lobes, Carol
A widely touted approach to involving laypeople in science and technology policy-related decisions is the consensus conference. Virtually nothing written on the topic provides detailed discussion of the many steps from citizen recruitment to citizen report. Little attention is paid to how and why the mechanics of the consensus conference process…
Kosecoff, J; Kanouse, D E; Brook, R H
In the last decade, new knowledge has emerged concerning the efficacy of treatment for breast cancer. For that reason, the National Institutes of Health devoted a consensus conference to this topic. To determine whether the consensus conference had influenced practice patterns, and to evaluate the level of quality of care given to women with breast cancer, the medical records of 573 patients treated in ten hospitals throughout the state of Washington were abstracted and analyzed. Results showed no changes with respect to the consensus conference's recommendations for use of a total mastectomy with axillary dissection or the use of a two-step procedure in which the biopsy is performed first and therapeutic options are discussed before a definitive surgery is undertaken. Analyses of quality of care issues not addressed by the consensus conference revealed that 4 percent of the sample were explicitly staged preoperatively and 29 percent postoperatively and that little changed over time in the use of sentinel laboratory tests. These results also show that consensus recommendations will not necessarily change physicians' behavior even where change is possible, and that quality of care in diagnosis and treatment of breast cancer still needs to be addressed. PMID:2254089
McCarthy, Bridget J.; Surawicz, Tanya; Bruner, Janet M.; Kruchko, Carol; Davis, Faith
The Consensus Conference on Brain Tumor Definition was facilitated by the Central Brain Tumor Registry of the United States and held on November 10, 2000, in Chicago, Illinois, to reach multidisciplinary agreement on a standard definition of brain tumors for collecting and comparing data in the U.S. The Brain Tumor Working Group, convened in 1998 to determine the status of brain tumor collection in the U.S., outlined 4 recommendations of which the first 2 guided the discussion for the Consensus Conference: (1) standardization of a definition of primary brain tumors that is based on site alone, rather than on site and behavior, and that can be used by surveillance organizations in collecting these tumors; and (2) development of a reporting scheme that can be used for comparing estimates of primary brain tumors across registries. Consensus was reached on the collection of all primary brain tumor histologies found and reported in the brain or CNS ICD-O site codes (C70.0-C72.9 and C75.1-C75.3), including those coded benign and uncertain as well as those coded malignant. In addition, a comprehensive listing of histologies occurring in the brain and CNS, based on the CBTRUS grouping scheme, was formulated to provide a template for reporting in accordance with the second recommendation of the Brain Tumor Working Group. With consensus achieved on the first 2 recommendations, the stage is set to move forward in estimating additional resources necessary for the collection of these tumors, including funding, training for cancer registrars, identifying quality control measures, and developing computerized edit checks, as outlined in the last 2 recommendations of the Brain Tumor Working Group. PMID:11916506
González de Dios, J; Ochoa Sangrador, C
The recommendations of the Consensus Conference "Diagnostic and Therapeutic Management of Acute Bronchiolitis" are presented. Evidence on the frequency of bronchiolitis in the general population and risk groups, risk factors and markers of severe forms, severity scores and the clinical-etiological profile is summarized. The commonly used diagnostic tests are ineffective in the management of the disease; oxygen saturation measurement is considered necessary only in the initial assessment or to monitor changes in patients with respiratory distress. Other tests such as chest radiograph, rapid diagnostic tests for respiratory virus infection and screening tests for bacterial infection should be used only very selectively. There is sufficient evidence on the lack of effectiveness of most interventions tested in bronchiolitis. Apart from oxygen therapy, fluid therapy, aspiration of secretions and ventilation support, few treatment options will be beneficial. Only in moderate-severe bronchiolitis would it be justified to test a treatment with inhaled bronchodilators (salbutamol or epinephrine) with or without hypertonic saline solution. Heliox and non-invasive ventilation techniques could be used in cases with respiratory failure, methylxanthine in patients with apnea and surfactant in intubated critically ill patients. No treatment has proved effective in preventing persistence or recurrence of post-bronchiolitis symptoms. As for prevention of bronchiolitis, only palivizumab slightly reduces the risk of admissions for lower respiratory infections by respiratory syncytial virus, although its high cost justifies its use only in a small group of high-risk patients.
National Institutes of Health (DHHS), Bethesda, MD.
This report is the product of a National Institutes of Health Consensus Development Conference on Noise and Hearing Loss which addressed the characteristics of noise-induced hearing loss, acoustic parameters of hazardous noise exposure, individual and age-specific susceptibility, and prevention strategies. The report examines the incidence of…
Nishijima, Daniel K.; Dinh, Tu; May, Larissa; Yadav, Kabir; Gaddis, Gary M.; Cone, David C.
Purpose Since 2000, Academic Emergency Medicine (AEM), the journal of the Society for Academic Emergency Medicine, has presented a one-day consensus conference to generate a research agenda for advancement of a scientific topic. One of the 12 annual issues of AEM is reserved for the proceedings of these conferences. The purpose of this study was to measure academic productivity of these conferences by evaluating subsequent federal research funding received by authors of conference manuscripts and calculating citation counts of conference papers. Method This was a cross-sectional study conducted during August and September 2012. NIH RePORTER was searched to identify subsequent federal funding obtained by authors of the consensus conference issues from 2000 to 2010. Funded projects were coded as related or unrelated to conference topic. Citation counts for all conference manuscripts were quantified using Scopus and Google Scholar. Simple descriptive statistics were reported. Results 852 individual authors contributed to 280 papers published in the 11 consensus conference issues. 137 authors (16%) obtained funding for 318 projects. A median of 22 topic-related projects per conference (range 10–97 projects) accounted for a median of $20,488,331 per conference (range $7,779,512–122,918,205). The average (±SD) number of citations per paper was 15.7 ±20.5 in Scopus and 23.7 ±32.6 in Google Scholar. Conclusions The authors of consensus conference manuscripts obtained significant federal grant support for follow-up research related to conference themes. In addition, the manuscripts generated by these conferences were frequently cited. Conferences devoted to research agenda development appear to be an academically worthwhile endeavor. PMID:24280853
Tuttle, Katherine R; Bakris, George L; Bilous, Rudolf W; Chiang, Jane L; de Boer, Ian H; Goldstein-Fuchs, Jordi; Hirsch, Irl B; Kalantar-Zadeh, Kamyar; Narva, Andrew S; Navaneethan, Sankar D; Neumiller, Joshua J; Patel, Uptal D; Ratner, Robert E; Whaley-Connell, Adam T; Molitch, Mark E
The incidence and prevalence of diabetes mellitus have grown significantly throughout the world, due primarily to the increase in type 2 diabetes. This overall increase in the number of people with diabetes has had a major impact on development of diabetic kidney disease (DKD), one of the most frequent complications of both types of diabetes. DKD is the leading cause of end-stage renal disease (ESRD), accounting for approximately 50% of cases in the developed world. Although incidence rates for ESRD attributable to DKD have recently stabilized, these rates continue to rise in high-risk groups such as middle-aged African Americans, Native Americans, and Hispanics. The costs of care for people with DKD are extraordinarily high. In the Medicare population alone, DKD-related expenditures among this mostly older group were nearly $25 billion in 2011. Due to the high human and societal costs, the Consensus Conference on Chronic Kidney Disease and Diabetes was convened by the American Diabetes Association in collaboration with the American Society of Nephrology and the National Kidney Foundation to appraise issues regarding patient management, highlighting current practices and new directions. Major topic areas in DKD included (1) identification and monitoring, (2) cardiovascular disease and management of dyslipidemia, (3) hypertension and use of renin-angiotensin-aldosterone system blockade and mineralocorticoid receptor blockade, (4) glycemia measurement, hypoglycemia, and drug therapies, (5) nutrition and general care in advanced-stage chronic kidney disease, (6) children and adolescents, and (7) multidisciplinary approaches and medical home models for health care delivery. This current state summary and research recommendations are designed to guide advances in care and the generation of new knowledge that will meaningfully improve life for people with DKD.
Guinney, Justin; Dienstmann, Rodrigo; Wang, Xin; de Reyniès, Aurélien; Schlicker, Andreas; Soneson, Charlotte; Marisa, Laetitia; Roepman, Paul; Nyamundanda, Gift; Angelino, Paolo; Bot, Brian M.; Morris, Jeffrey S.; Simon, Iris M.; Gerster, Sarah; Fessler, Evelyn; de Sousa e Melo, Felipe; Missiaglia, Edoardo; Ramay, Hena; Barras, David; Homicsko, Krisztian; Maru, Dipen; Manyam, Ganiraju C.; Broom, Bradley; Boige, Valerie; Perez-Villamil, Beatriz; Laderas, Ted; Salazar, Ramon; Gray, Joe W.; Hanahan, Douglas; Tabernero, Josep; Bernards, Rene; Friend, Stephen H.; Laurent-Puig, Pierre; Medema, Jan Paul; Sadanandam, Anguraj; Wessels, Lodewyk; Delorenzi, Mauro; Kopetz, Scott; Vermeulen, Louis; Tejpar, Sabine
Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression–based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, evident metabolic dysregulation; and CMS4 (Mesenchymal, 23%), prominent transforming growth factor β activation, stromal invasion, and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intra-tumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC – with clear biological interpretability – and the basis for future clinical stratification and subtype–based targeted interventions. PMID:26457759
Mosconi, Paola; Donati, Serena; Colombo, Cinzia; Mele, Alfonso; Liberati, Alessandro; Satolli, Roberto
Background The risks/benefits balance of hormone replacement therapy is controversial. Information can influence consumers' knowledge and behavior; research findings about hormone replacement therapy are uncertain and the messages provided by the media are of poor quality and incomplete, preventing a fully informed decision making process. We therefore felt that an explicit, rigorous and structured assessment of the information needs on this issue was urgent and we opted for the organisation of a national consensus conference (CC) to assess the current status of the quality of information on hormone replacement therapy (HRT) and re-visit recent research findings on its risks/benefits. Methods We chose a structured approach based on the traditional CC method combined with a structured preparatory work supervised by an organising committee (OC) and a scientific board (SB). The OC and SB chose the members of the CC's jury and appointed three multidisciplinary working groups (MWG) which were asked to review clinical issues and different aspects of the quality of information. Before the CC, the three MWGs carried out: a literature review on the risk/benefit profile of HRT and two surveys on the quality of information on lay press and booklets targeted to women. A population survey on women's knowledge, attitude and practice was also carried out. The jury received the documents in advance, listened the presentations during the two-day meeting of the CCs, met immediately after in a closed-door meeting and prepared the final document. Participants were researchers, clinicians, journalists as well as consumers' representatives. Results Key messages in the CC's deliberation were: a) women need to be fully informed about the transient nature of menopausal symptoms, about HRT risks and benefits and about the availability of non-pharmacological interventions; b) HRT is not recommended to prevent menopausal symptoms; c) the term "HRT" is misleading and "post menopausal hormone
This day and a half symposium will bring together experts in blood and marrow transplantation, late effects, and health care delivery to discuss current evidence and knowledge gaps, develop consensus guidelines, and inform future research in the BMT survivor population.
Genetically modified foods have become one of the most popular topics for deliberative exercises involving ordinary citizens worldwide. This paper examines the Taiwanese consensus conference on GM foods held in June 2008, and the implications and limitations of the public deliberations. The consensus conference facilitated multiparty dialogues and enhanced citizens' knowledge, and affected their attitudes. This study demonstrates the ways contextual factors have influenced the outcome of the citizens' deliberative practices, including the government's conventional technocratic decision-making style, the strong influence of the U.S. government, the political and technological culture, the government's framing of economic development concerns, and a lack of pressure from civil society to compel the government to formally respond to their concerns. The consensus conference had a limited effect on policy decision-making, and seemed to serve as a socio-political experiment.
Rioux-Leclercq, Nathalie; Ferran, Algaba; Mahul, Amin; Argani, Pedram; Billis, Athanase; Bonsib, Stephen; Cheng, Liang; Cheville, John; Eble, John; Egevad, Lars; Epstein, Jonathan; Grignon, David; Hes, Ondrej; Humphrey, Peter; Magi-Galluzzi, Cristina; Martignoni, Guido; McKenney, Jesse; Merino, Maria; Moch, Holger; Montironi, Rodolfo; Netto, George; Reuter, Viktor; Samaratunga, Hemamali; Shen, Steven; Srigley, John; Tamboli, Pheroze; Tan, Puay Hoon; Tickoo, Satish; Trpkov, Kiril; Zhou, Ming; Delahunt, Brett; Comperat, Eva
During the last 30 years many advances have been made in kidney tumor pathology. In 1981, 9 entities were recognized in the WHO Classification. In the latest classification of 2004, 50 different types have been recognized. Additional tumor entities have been described since and a wide variety of prognostic parameters have been investigated with variable success; however, much attention has centered upon the importance of features relating to both stage and grade. The International Society of Urological Pathology (ISUP) recommends after consensus conferences the development of reporting guidelines, which have been adopted worldwide ISUP undertook to review all aspects of the pathology of adult renal malignancy through an international consensus conference to be held in 2012. As in the past, participation in this consensus conference was restricted to acknowledged experts in the field.
Kristiansen, G; Egevad, L; Amin, M; Delahunt, B; Srigley, J R; Humphrey, P A; Epstein, J I
In 2005 the International Society of Urological Pathology (ISUP) held a concensus conference on Gleason grading in order to bring this grading system up to the current state of contemporary practice; however, it became clear that further modifications on the grading of prostatic carcinoma were necessary. The International Society of Urological Pathology therefore held a further consensus conference in 2014 to clarify these points. This article presents the essential results of the Chicago grading meeting.
Hughes, Carroll W.; Emslie, Graham J.; Crismon, M. Lynn; Posner, Kelly; Birmaher, Boris; Ryan, Neal; Jensen, Peter; Curry, John; Vitiello, Benedetto; Lopez, Molly; Shon, Steve P.; Pliszka, Steven R.; Trivedi, Madhukar H.
Objective: To revise and update consensus guidelines for medication treatment algorithms for childhood major depressive disorder based on new scientific evidence and expert clinical consensus when evidence is lacking. Method: A consensus conference was held January 13-14, 2005, that included academic clinicians and researchers, practicing…
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT Conference Call Meeting of the Manufactured Housing Consensus Committee AGENCY: Office of the Assistant Secretary for Housing--Federal Housing Commissioner, HUD. ACTION: Notice of...
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HOUSING AND URBAN DEVELOPMENT Conference Call Meeting of the Manufactured Housing Consensus Committee AGENCY: Office of the Assistant Secretary for Housing--Federal Housing Commissioner, HUD. ACTION: Notice of...
White, Patience, Ed.
This report of a consensus conference on pediatric rheumatology deals with the complex nature of rheumatological conditions of children, which require diagnostic, therapeutic, and follow-up services for comprehensive care and demand the cooperation of medical, health, education, mental health, and social service professionals. Conference…
Egevad, Lars; Delahunt, Brett; Srigley, John R; Samaratunga, Hemamali
The International Society of Urological Pathology (ISUP) has issued guidelines for the grading of prostate cancer based on a consensus conference held in 2014. The recommendations resulting from the 2014 consensus conference were a further development of 2005 ISUP modified Gleason grading. In the 2014 system, morphological criteria are clarified, including updated definitions of Gleason pattern 4. In addition to the continued reporting of Gleason scores, we also recommend that Gleason scores ≤6, 3 + 4 = 7, 4 + 3 = 7, 8 and 9-10, respectively, be reported as five groups, i.e. ISUP grades 1-5. This new grading system has the dual benefit of predicting patient outcome as well as facilitating patient communication.
Vlachos, Adrianna; Ball, Sarah; Dahl, Niklas; Alter, Blanche P; Sheth, Sujit; Ramenghi, Ugo; Meerpohl, Joerg; Karlsson, Stefan; Liu, Johnson M; Leblanc, Thierry; Paley, Carole; Kang, Elizabeth M; Leder, Eva Judmann; Atsidaftos, Eva; Shimamura, Akiko; Bessler, Monica; Glader, Bertil; Lipton, Jeffrey M
Diamond Blackfan anaemia (DBA) is a rare, genetically and clinically heterogeneous, inherited red cell aplasia. Classical DBA affects about seven per million live births and presents during the first year of life. However, as mutated genes have been discovered in DBA, non-classical cases with less distinct phenotypes are being described in adults as well as children. In caring for these patients it is often difficult to have a clear understanding of the treatment options and their outcomes because of the lack of complete information on the natural history of the disease. The purpose of this document is to review the criteria for diagnosis, evaluate the available treatment options, including corticosteroid and transfusion therapies and stem cell transplantation, and propose a plan for optimizing patient care. Congenital anomalies, mode of inheritance, cancer predisposition, and pregnancy in DBA are also reviewed. Evidence-based conclusions will be made when possible; however, as in many rare diseases, the data are often anecdotal and the recommendations are based upon the best judgment of experienced clinicians. The recommendations regarding the diagnosis and management described in this report are the result of deliberations and discussions at an international consensus conference. PMID:18671700
Davis, Jennifer C; Verhagen, Evert; Bryan, Stirling; Liu-Ambrose, Teresa; Borland, Jeff; Buchner, David; Hendriks, Marike R C; Weiler, Richard; Morrow, James R; van Mechelen, Willem; Blair, Steven N; Pratt, Mike; Windt, Johann; al-Tunaiji, Hashel; Macri, Erin; Khan, Karim M
This article describes major topics discussed from the 'Economics of Physical Inactivity Consensus Workshop' (EPIC), held in Vancouver, Canada, in April 2011. Specifically, we (1) detail existing evidence on effective physical inactivity prevention strategies; (2) introduce economic evaluation and its role in health policy decisions; (3) discuss key challenges in establishing and building health economic evaluation evidence (including accurate and reliable costs and clinical outcome measurement) and (4) provide insight into interpretation of economic evaluations in this critically important field. We found that most methodological challenges are related to (1) accurately and objectively valuing outcomes; (2) determining meaningful clinically important differences in objective measures of physical inactivity; (3) estimating investment and disinvestment costs and (4) addressing barriers to implementation. We propose that guidelines specific for economic evaluations of physical inactivity intervention studies are developed to ensure that related costs and effects are robustly, consistently and accurately measured. This will also facilitate comparisons among future economic evidence.
Ezzedine, K; Lim, H W; Suzuki, T; Katayama, I; Hamzavi, I; Lan, C C E; Goh, B K; Anbar, T; Silva de Castro, C; Lee, A Y; Parsad, D; van Geel, N; Le Poole, I C; Oiso, N; Benzekri, L; Spritz, R; Gauthier, Y; Hann, S K; Picardo, M; Taieb, A
During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: classification and nomenclature; definition of stable disease; definition of Koebner's phenomenon (KP); and 'autoimmune vitiligo'. These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental vitiligo be classified separately from all other forms of vitiligo and that the term 'vitiligo' be used as an umbrella term for all non-segmental forms of vitiligo, including 'mixed vitiligo' in which segmental and non-segmental vitiligo are combined and which is considered a subgroup of vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of KP for vitiligo as proposed by the VETF (history based, clinical observation based, or experimentally induced). Lastly, the conference agreed that 'autoimmune vitiligo' should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of vitiligo likely involves autoimmune or inflammatory mechanisms.
Ezzedine, K.; Lim, H. W.; Suzuki, T.; Katayama, I.; Hamzavi, I.; Lan, C. C. E.; Goh, B. K.; Anbar, T.; de Castro, C. Silva; Lee, A. Y.; Parsad, D.; van Geel, N.; Le Poole, I. C.; Oiso, N.; Benzekri, L.; Spritz, R.; Gauthier, Y.; Hann, S. K.; Picardo, M.; Taieb, A.
Summary During the 2011 International Pigment Cell Conference (IPCC), the Vitiligo European Taskforce (VETF) convened a consensus conference on issues of global importance for vitiligo clinical research. As suggested by an international panel of experts, the conference focused on four topics: classification and nomenclature; definition of stable disease; definition of Koebner’s phenomenon (KP); and ‘autoimmune vitiligo’. These topics were discussed in seven working groups representing different geographical regions. A consensus emerged that segmental vitiligo be classified separately from all other forms of vitiligo and that the term ‘vitiligo’ be used as an umbrella term for all non-segmental forms of vitiligo, including ‘mixed vitiligo’ in which segmental and non-segmental vitiligo are combined and which is considered a subgroup of vitiligo. Further, the conference recommends that disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably. The conference also endorsed the classification of KP for vitiligo as proposed by the VETF (history based, clinical observation based, or experimentally induced). Lastly, the conference agreed that ‘autoimmune vitiligo’ should not be used as a separate classification as published evidence indicates that the pathophysiology of all forms of vitiligo likely involves autoimmune or inflammatory mechanisms. PMID:22417114
Annibali, S; De Biase, A; Pippi, R; Sfasciotti, G L
During the first Congress of the Italian University Schools of Oral Surgery, held in Rome on 18-20th February, 2010, a task force was convened by the Italian Society of Odontostomatological Surgery (SIdCO) to summarize the data collected from the current literature on selected aspects relating to the mandibular third molar and its removal. The task of the Conference Participants was to review and analyze the pertinent literature and to elaborate conclusive recommendations for the management of the lower third molar. The statements made and the recommendations presented represent the consensus of the Conference, which can be considered the official statement of the SIdCO.
van Golen, Kenneth L; Cristofanilli, Massimo
Inflammatory breast cancer (IBC) is the most aggressive and deadly form of breast cancer. Disease-specific research and conferences have been organized since 2008 with the intent to bring together experts in various disciplines. This report focus on the Third International IBC Conference held in Philadelphia on December 2012.
Bangsbo, Jens; Duda, Joan; Hillman, Charles; Andersen, Lars Bo; Weiss, Maureen; Williams, Craig A; Lintunen, Taru; Green, Ken; Hansen, Peter Riis; Naylor, Patti-Jean; Ericsson, Ingegerd; Nielsen, Glen; Froberg, Karsten; Bugge, Anna; Lundbye-Jensen, Jesper; Dagkas, Symeon; Agergaard, Sine; von Seelen, Jesper; Østergaard, Charlotte; Skovgaard, Thomas; Busch, Henrik; Elbe, Anne-Marie
From 4 to 7 April 2016, 24 researchers from 8 countries and from a variety of academic disciplines gathered in Snekkersten, Denmark, to reach evidence-based consensus about physical activity in children and youth, that is, individuals between 6 and 18 years. Physical activity is an overarching term that consists of many structured and unstructured forms within school and out-of-school-time contexts, including organised sport, physical education, outdoor recreation, motor skill development programmes, recess, and active transportation such as biking and walking. This consensus statement presents the accord on the effects of physical activity on children's and youth's fitness, health, cognitive functioning, engagement, motivation, psychological well-being and social inclusion, as well as presenting educational and physical activity implementation strategies. The consensus was obtained through an iterative process that began with presentation of the state-of-the art in each domain followed by plenary and group discussions. Ultimately, Consensus Conference participants reached agreement on the 21-item consensus statement. PMID:27354718
Bangsbo, Jens; Krustrup, Peter; Duda, Joan; Hillman, Charles; Andersen, Lars Bo; Weiss, Maureen; Williams, Craig A; Lintunen, Taru; Green, Ken; Hansen, Peter Riis; Naylor, Patti-Jean; Ericsson, Ingegerd; Nielsen, Glen; Froberg, Karsten; Bugge, Anna; Lundbye-Jensen, Jesper; Schipperijn, Jasper; Dagkas, Symeon; Agergaard, Sine; von Seelen, Jesper; Østergaard, Charlotte; Skovgaard, Thomas; Busch, Henrik; Elbe, Anne-Marie
From 4 to 7 April 2016, 24 researchers from 8 countries and from a variety of academic disciplines gathered in Snekkersten, Denmark, to reach evidence-based consensus about physical activity in children and youth, that is, individuals between 6 and 18 years. Physical activity is an overarching term that consists of many structured and unstructured forms within school and out-of-school-time contexts, including organised sport, physical education, outdoor recreation, motor skill development programmes, recess, and active transportation such as biking and walking. This consensus statement presents the accord on the effects of physical activity on children's and youth's fitness, health, cognitive functioning, engagement, motivation, psychological well-being and social inclusion, as well as presenting educational and physical activity implementation strategies. The consensus was obtained through an iterative process that began with presentation of the state-of-the art in each domain followed by plenary and group discussions. Ultimately, Consensus Conference participants reached agreement on the 21-item consensus statement.
Kably Ambe, Alberto; Ruiz Moreno, José Antonio; Ponce, Eduardo Lazcano; Vargas Hernández, Victor Manuel; Aguado Pérez, Rogelio A; Alonso de Ruiz, Patricia
Cervical cancer remains a serious public health problem in the world; that is why the Mexican Federation of Schools of Obstetrics and Gynecology convened the elaboration of a consensus that is devoted this number of Ginecologia y Obstetricia de Mexico. In recent years has strengthened perceptions (public and private) in the need for preventive strategies in the medium and long terms. The development of effective vaccines against the human papilloma virus and the application of new methods of detection from viral DNA (completely automated for personal application) allow some degree of optimism. It is proposed a consensus with general recommendations in two consecutive stages: (a) primary prevention consisting of education for the prevention of cervical cancer and universal immunization and (b) secondary prevention by early detection of infections or injuries that could favor carcinogenesis. The consensus reviewed characteristics of available vaccines in detail and proposes strategies for implementation in Mexican population. Also, check out main methods of early detection of infection (or predisposing lesions) and suggests public and private strategies for implementation. Consensus places particular emphasis on early immunization for female population and correct use of methods for detection of infections or injuries that might cause cervical cancer.
Chow, Pierce K. H.; Choo, Su Pin; Ng, David C. E.; Lo, Richard H. G.; Wang, Michael L. C.; Toh, Han Chong; Tai, David W. M.; Goh, Brian K. P.; Wong, Jen San; Tay, Kiang Hiong; Goh, Anthony S. W.; Yan, Sean X.; Loke, Kelvin S. H.; Thang, Sue Ping; Gogna, Apoorva; Too, Chow Wei; Irani, Farah Gillian; Leong, Sum; Lim, Kiat Hon; Thng, Choon Hua
Hepatocellular carcinoma (HCC) is the 6th most common cancer in the world, but the second most common cause of cancer death. There is no universally accepted consensus practice guidelines for HCC owing to rapid developments in new treatment modalities, the heterogeneous epidemiology and clinical presentation of HCC worldwide. However, a number of regional and national guidelines currently exist which reflect practice relevant to the epidemiology and collective experience of the consensus group. In 2014, clinicians at the multidisciplinary Comprehensive Liver Cancer Clinic (CLCC) at the National Cancer Centre Singapore (NCCS) reviewed the latest published scientific data and existing international and regional practice guidelines, such as those of the National Comprehensive Cancer Network, American Association for the Study of Liver Diseases and the Asian Pacific Association for the Study of the Liver, and modified them to reflect local practice. These would serve as a template by which treatment outcomes can be collated and benchmarked against international data. The NCCS Consensus Guidelines for HCC have been successfully implemented in the CLCC since their publication online on 26th September 2014, and the guidelines allow outcomes of treatment to be compared to international data. These guidelines will be reviewed periodically to incorporate new data. PMID:27386428
Trpkov, Kiril; Grignon, David J; Bonsib, Stephen M; Amin, Mahul B; Billis, Athanase; Lopez-Beltran, Antonio; Samaratunga, Hemamali; Tamboli, Pheroze; Delahunt, Brett; Egevad, Lars; Montironi, Rodolfo; Srigley, John R
The International Society of Urologic Pathology 2012 Consensus Conference on renal cancer, through working group 3, focused on the issues of staging and specimen handling of renal tumors. The conference was preceded by an online survey of the International Society of Urologic Pathology members, and the results of this were used to inform the focus of conference discussion. On formal voting a ≥65% majority was considered a consensus agreement. For specimen handling it was agreed that with radical nephrectomy specimens the initial cut should be made along the long axis and that both radical and partial nephrectomy specimens should be inked. It was recommended that sampling of renal tumors should follow a general guideline of sampling 1 block/cm with a minimum of 3 blocks (subject to modification as needed in individual cases). When measuring a renal tumor, the length of a renal vein/caval thrombus should not be part of the measurement of the main tumor mass. In cases with multiple tumors, sampling should include at a minimum the 5 largest tumors. There was a consensus that perinephric fat invasion should be determined by examining multiple perpendicular sections of the tumor/perinephric fat interface and by sampling areas suspicious for invasion. Perinephric fat invasion was defined as either the tumor touching the fat or extending as irregular tongues into the perinephric tissue, with or without desmoplasia. It was agreed upon that renal sinus invasion is present when the tumor is in direct contact with the sinus fat or the loose connective tissue of the sinus, clearly beyond the renal parenchyma, or if there is involvement of any endothelium-lined spaces within the renal sinus, regardless of the size. When invasion of the renal sinus is uncertain, it was recommended that at least 3 blocks of the tumor-renal sinus interface should be submitted. If invasion is grossly evident, or obviously not present (small peripheral tumor), it was agreed that only 1 block was
Lerner, Seth P; McConkey, David J; Hoadley, Katherine A; Chan, Keith S; Kim, William Y; Radvanyi, François; Höglund, Mattias; Real, Francisco X
The advent of Omics technologies has been key to the molecular subclassification of urothelial bladder cancer. Several groups have used different strategies to this aim, with partially overlapping findings. The meeting at the Spanish National Cancer Research Center-CNIO was held to discuss such classifications and reach consensus where appropriate. After updated presentations on the work performed by the teams attending the meeting, a consensus was reached regarding the existence of a group of Basal-Squamous-like tumors - designated BASQ - charaterized the high expression of KRT5/6 and KRT14 and low/undetectable expression of FOXA1 and GATA3. An additional tumor subgroup with urothelial differentiation features was recognized whose optimal molecular definition is required. For other subtypes described, more work is needed to determine how robust they are and how to best define them at the molecular level.
Gan, Emily Y; Eleftheriadou, Viktoria; Esmat, Samia; Hamzavi, Iltefat; Passeron, Thierry; Böhm, Markus; Anbar, Tag; Goh, Boon Kee; Lan, Cheng-Che E; Lui, Harvey; Ramam, M; Raboobee, Noufal; Katayama, Ichiro; Suzuki, Tamio; Parsad, Davinder; Seth, Vaneeta; Lim, Henry W; van Geel, Nanja; Mulekar, Sanjeev; Harris, John; Wittal, Richard; Benzekri, Laila; Gauthier, Yvon; Kumarasinghe, Prasad; Thng, Steven T G; Silva de Castro, Caio Cesar; Abdallah, Marwa; Vrijman, Charlotte; Bekkenk, Marcel; Seneschal, Julien; Pandya, Amit G; Ezzedine, Khaled; Picardo, Mauro; Taïeb, Alain
The Vitiligo Global Issues Consensus Conference (VGICC), through an international e-Delphi consensus, concluded that 'repigmentation' and 'maintenance of gained repigmentation' are essential core outcome measures in future vitiligo trials. This VGICC position paper addresses these core topics in two sections and includes an atlas depicting vitiligo repigmentation patterns and color match. The first section delineates mechanisms and characteristics of vitiligo repigmentation, and the second section summarizes the outcomes of international meeting discussions and two e-surveys on vitiligo repigmentation, which had been carried out over 3 yr. Treatment is defined as successful if repigmentation exceeds 80% and at least 80% of the gained repigmentation is maintained for over 6 months. No agreement was found on the best outcome measure for assessing target or global repigmentation, therefore highlighting the limitations of e-surveys in addressing clinical measurements. Until there is a clear consensus, existing tools should be selected according to the specific needs of each study. A workshop will be conducted to address the remaining issues so as to achieve a consensus.
Isla, D; Majem, M; Viñolas, N; Artal, A; Blasco, A; Felip, E; Garrido, P; Remón, J; Baquedano, M; Borrás, J M; Die Trill, M; García-Campelo, R; Juan, O; León, C; Lianes, P; López-Ríos, F; Molins, L; Planchuelo, M Á; Cobo, M; Paz-Ares, L; Trigo, J M; de Castro, J
Lung cancer is the most common cancer globally and has the highest mortality. Although this disease is not associated with a particular gender, its incidence is rising among women, who are diagnosed at an increasingly younger age compared with men. One of the main reasons for this rise is women taking up smoking. However, many non-smoking women also develop this disease. Other risk factors implicated in the differential development of lung cancer in women are genetic predisposition, tumour histology and molecular profile. Proportionally more women than men with lung cancer have a mutation in the EGFR gene. This consensus statement reviews the available evidence about the epidemiological, biological, diagnostic, therapeutic, social and psychological aspects of lung cancer in women.
Tamburin, Stefano; Paolucci, Stefano; Magrinelli, Francesca; Musicco, Massimo; Sandrini, Giorgio
Pain is very common in the neurorehabilitation setting, where it may not only represent a target for treatment but can also negatively influence rehabilitation procedures directly or through the side effects of painkillers. To date, there are neither guidelines nor consensus on how to assess and treat pain in neurorehabilitation. Because of the very scanty pieces of evidence on this topic, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) was promoted under the auspices of different scientific societies. This article illustrates the rationale, methodology, and topics of the ICCPN. The recommendations of the ICCPN will offer some information on how to deal with pain in neurorehabilitation and may represent the starting point for further studies. PMID:27313474
Dauger, S; Le Bourgeois, F; Guichoux, J; Brissaud, O
Acute respiratory distress syndrome (ARDS) is a rapidly progressive hypoxemic respiratory insufficiency induced by alveolar filling mainly caused by alveolocapillary wall disruption, following direct or indirect pulmonary injury. Much less frequent in children than in adults, pediatric intensivists had long applied adult guidelines to their daily practice. In 2015, experts from the Pediatric Acute Lung Injury Consensus Conference (PALICC) published the first international guidelines specifically dedicated to pediatric ARDS. After a short summary of the history of the ARDS definition since its first report in 1967, we describe the main diagnostic and therapeutic guidelines for PALICC.
During the days August 22–24, 2013 has been held in Harbin (China) an International Consensus Conference aimed to improve the quality and the reporting of the randomized controlled trials (RCTs) in infertility and subfertility field. I, as Italian scientist with experience in clinical infertility trials, was invited to have a speech on the Italian experience in RCTs, with particular regard for the surgical trials. Considerations on this subject were particularly interesting to highlight pitfalls and triumphs of research in Italy. PMID:24257071
Díez, Juan José; Galofré, Juan Carlos; Oleaga, Amelia; Grande, Enrique; Mitjavila, Mercedes; Moreno, Pablo
Thyroid cancer is the leading endocrine system tumor. Great advances have recently been made in understanding of the origin of these tumors and the molecular biology that makes them grow and proliferate, which have been associated to improvements in diagnostic procedures and increased availability of effective local and systemic treatments. All of the above makes thyroid cancer a paradigm of how different specialties should work together to achieve the greatest benefit for the patients. Coordination of all the procedures and patient flows should continue throughout diagnosis, treatment, and follow-up, and is essential for further optimization of resources and time. This manuscript was prepared at the request of the Working Group on Thyroid Cancer of the Spanish Society of Endocrinology and Nutrition, and is aimed to provide a consensus document on the definition, composition, requirements, structure, and operation of a multidisciplinary team for the comprehensive care of patients with thyroid cancer. For this purpose, we have included contributions by several professionals from different specialties with experience in thyroid cancer treatment at centers where multidisciplinary teams have been working for years, with the aim of developing a practical consensus applicable in clinical practice.
Palau, Anna; Perucho, Manuel; Esteller, Manel; Buschbeck, Marcus
The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled “Challenges, opportunities and perspectives” took place November 21–22, 2013 in Barcelona. The 2013 BCEC is the first edition of a series of annual conferences jointly organized by five leading research centers in Barcelona. These centers are the Institute of Predictive and Personalized Medicine of Cancer (IMPPC), the Biomedical Campus Bellvitge with its Program of Epigenetics and Cancer Biology (PEBC), the Centre for Genomic Regulation (CRG), the Institute for Biomedical Research (IRB), and the Molecular Biology Institute of Barcelona (IBMB). Manuel Perucho and Marcus Buschbeck from the Institute of Predictive and Personalized Medicine of Cancer put together the scientific program of the first conference broadly covering all aspects of epigenetic research ranging from fundamental molecular research to drug and biomarker development and clinical application. In one and a half days, 23 talks and 50 posters were presented to a completely booked out audience counting 270 participants. PMID:24413145
Maegele, M; Inaba, K; Rizoli, S; Veigas, P; Callum, J; Davenport, R; Fröhlich, M; Hess, J
Although there is increasing interest in the use of a viscoelastic test procedure (ROTEM/TEG) for diagnostics and therapy guidance of severely injured and bleeding patients, currently no uniformly accepted guidelines exist for how this technology should be integrated into clinical treatment. In September 2014 an international multidisciplinary group of opinion leaders in the field of trauma-induced coagulopathy and other disciplines involved in the treatment of severely injured patients were assembled for a 2-day consensus conference in Philadelphia (USA). This panel included trauma/accident surgeons, general/abdominal surgeons, vascular surgeons, emergency/intensive care surgeons, hematologists, transfusion specialists, anesthesiologists, laboratory physicians, pathobiologists/pathophysiologists and the lay public. A total of nine questions regarding the impact of viscoelastic testing in the early treatment of trauma patients were developed prior to the conference by a panel consensus. Early use was defined as baseline viscoelastic test result thresholds obtained within the first minutes of hospital arrival, when conventional laboratory results are not yet available. The available data for each question were then reviewed in person using standardized presentations by the expert panel. A consensus summary document was then developed and reviewed by the panel in an open forum. Finally, a 2-round Delphi poll was administered to the panel of experts regarding viscoelastic thresholds for triggering the initiation of specific treatments including fibrinogen (concentrates), platelet concentrates, blood plasma products and prothrombin complex concentrates (PCC). This report summarizes the findings and recommendations of this consensus conference, which correspond to a S2k guideline according to the system of the Association of the Scientific Medical Societies in Germany (AWMF) and taking formal consensus findings including Delphi methods into consideration.
Clavien, Pierre-Alain; Lesurtel, Mickael; Bossuyt, Patrick M M; Gores, Gregory J; Langer, Bernard; Perrier, Arnaud
Although liver transplantation is a widely accepted treatment for hepatocellular carcinoma (HCC), much controversy remains and there is no generally accepted set of guidelines. An international consensus conference was held on Dec 2-4, 2010, in Zurich, Switzerland, with the aim of reviewing current practice regarding liver transplantation in patients with HCC and to develop internationally accepted statements and guidelines. The format of the conference was based on the Danish model. 19 working groups of experts prepared evidence-based reviews according to the Oxford classification, and drafted recommendations answering 19 specific questions. An independent jury of nine members was appointed to review these submissions and make final recommendations, after debates with the experts and audience at the conference. This report presents the final 37 statements and recommendations, covering assessment of candidates for liver transplantation, criteria for listing in cirrhotic and non-cirrhotic patients, role of tumour downstaging, management of patients on the waiting list, role of living donation, and post-transplant management.
NIH consensus and state-of-the-science statements are prepared by independent panels of health professionals and public representatives on the basis of (1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality (AHRQ); (2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session; (3) questions and statements from conference attendees during open discussion periods that are part of the public session; and (4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a "snapshot in time" of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research.
Ravi, K; Geno, D M; Katzka, D A
Achalasia is an important but relatively uncommon disorder. While highly effective therapeutic options exist, esophageal cancer remains a long-term potential complication. The risk of esophageal cancer in achalasia remains unclear, with current guidelines recommending against routine endoscopic screening. However, given limited data and conflicting opinion, it is unknown whether consensus regarding screening practices in achalasia among experts exists. A 10-question survey to assess screening practices in achalasia was created and distributed to 28 experts in the area of achalasia. Experts were identified based on publications and meeting presentations in the field. Survey responses were received from 17 of 28 (61%) experts. Wide geographic distribution was seen among respondents, with eight (47%) from Europe or Australia, seven (41%) from the United States, and two (12%) from Asia. Screening for esophageal cancer was inconsistent, with nine (53%) experts endorsing the practice and eight (47%) not. Screening practices did not differ among geographic regions. No consensus regarding the risk for esophageal cancer in achalasia was seen, with three experts reporting no increased risk compared with the general population, eight experts a lifetime risk of 0.1-0.5%, three experts a 0.5-1% risk, two experts a 1-2% risk, and one expert a 3-5% risk. However, these differences in perception of risk did not influence screening practices. Upper endoscopy was utilized among all experts who endorsed screening. However, practices still varied with screening commencing at or within 1 year of diagnosis in two practices compared with 5 and 10 years in three respective practices each. Surveillance intervals also varied, performed every 2 years in four practices, every 3 years in four practices, and every 5 years in one practice. Practice variation in the management of achalasia itself was also seen, with initial treatment with Heller myotomy endorsed by eight experts, pneumatic
Whistance, Robert N.; Forsythe, Rachael O.; Macefield, Rhiannon; Pullyblank, Anne M.; Avery, Kerry N. L.; Brookes, Sara T.; Thomas, Michael G.; Sylvester, Paul A.; Russell, Ann; Oliver, Alfred; Morton, Dion; Kennedy, Robin; Jayne, David G.; Huxtable, Richard; Hackett, Roland; Card, Mia; Brown, Julia; Blazeby, Jane M.
Background Colorectal cancer (CRC) is a major cause of worldwide morbidity and mortality. Surgical treatment is common, and there is a great need to improve the delivery of such care. The gold standard for evaluating surgery is within well-designed randomized controlled trials (RCTs); however, the impact of RCTs is diminished by a lack of coordinated outcome measurement and reporting. A solution to these issues is to develop an agreed standard “core” set of outcomes to be measured in all trials to facilitate cross-study comparisons, meta-analysis, and minimize outcome reporting bias. This study defines a core outcome set for CRC surgery. Methods and Findings The scope of this COS includes clinical effectiveness trials of surgical interventions for colorectal cancer. Excluded were nonsurgical oncological interventions. Potential outcomes of importance to patients and professionals were identified through systematic literature reviews and patient interviews. All outcomes were transcribed verbatim and categorized into domains by two independent researchers. This informed a questionnaire survey that asked stakeholders (patients and professionals) from United Kingdom CRC centers to rate the importance of each domain. Respondents were resurveyed following group feedback (Delphi methods). Outcomes rated as less important were discarded after each survey round according to predefined criteria, and remaining outcomes were considered at three consensus meetings; two involving international professionals and a separate one with patients. A modified nominal group technique was used to gain the final consensus. Data sources identified 1,216 outcomes of CRC surgery that informed a 91 domain questionnaire. First round questionnaires were returned from 63 out of 81 (78%) centers, including 90 professionals, and 97 out of 267 (35%) patients. Second round response rates were high for all stakeholders (>80%). Analysis of responses lead to 45 and 23 outcome domains being retained
Ochoa Sangrador, C
The methodology of the Consensus Conference "Diagnostic and Therapeutic Management of Urinary Tract Infection in Childhood" is presented. The methodology consisted of two phases. In the first phase, a series of documents was drafted, which included an in-depth review of the existing evidence on the diagnosis and treatment of urinary tract infection and of epidemiological data on the etiological and resistance profiles of urinary pathogens in Spain. In the second phase, a multidisciplinary expert panel was convened to evaluate all the documentation and to answer a series of questions and to assign a level of evidence and degree of recommendation to each answer. In this article the search strategies used and their results are described. In addition, the bases for evaluating the efficacy of therapeutic interventions and the validity of the diagnostic tests are presented. Finally, the criteria for hierarchical structuring of the scientific evidence are detailed.
Birch, Daniel W.; Bonjer, H. Jaap; Crossley, Claire; Burnett, Gayle; de Gara, Chris; Gomes, Anthony; Hagen, John; Maciver, Angus G.; Mercer, C. Dale; Panton, O. Neely; Schlachta, Chris M.; Smith, Andy J.; Warnock, Garth L.
Despite the complexities of minimally invasive surgery (MIS), a Canadian approach to training surgeons in this field does not exist. Whereas a limited number of surgeons are fellowship-trained in the specialty, guidelines are still clearly needed to implement advanced MIS. Leaders in the field of gastrointestinal surgery and MIS attended a consensus conference where they proposed a comprehensive mentoring program that may evolve into a framework for a national mentoring and training system. Leadership and commitment from national experts to define the most appropriate template for introducing new surgical techniques into practice is required. This national framework should also provide flexibility for truly novel procedures such as natural orifice translumenal endoscopic surgery. PMID:19680520
Fagiuoli, Stefano; Colli, Agostino; Bruno, Raffaele; Burra, Patrizia; Craxì, Antonio; Gaeta, Giovan Battista; Grossi, Paolo; Mondelli, Mario U; Puoti, Massimo; Sagnelli, Evangelista; Stefani, Stefania; Toniutto, Pierluigi
The statements produced by the consensus conference on infection in end-stage liver disease promoted by the Italian Association for the Study of the Liver, are here reported. The topics of epidemiology, risk factors, diagnosis, prophylaxis, and treatment of infections in patient with compensated and decompensated liver cirrhosis were reviewed by a scientific board of experts who proposed 26 statements that were graded according to level of evidence and strength of recommendation, and approved by an independent jury. Each topic was explored focusing on the more relevant clinical questions. By systematic literature search of available evidence, comparison and discussion of expert opinions, pertinent statements answering specific questions were presented and approved. Short comments were added to explain the basis for grading evidence particularly on case of controversial areas.
Richard, Christian; Argaud, Laurent; Blet, Alice; Boulain, Thierry; Contentin, Laetitia; Dechartres, Agnès; Dejode, Jean-Marc; Donetti, Laurence; Fartoukh, Muriel; Fletcher, Dominique; Kuteifan, Khaldoun; Lasocki, Sigismond; Liet, Jean-Michel; Lukaszewicz, Anne-Claire; Mal, Hervé; Maury, Eric; Osman, David; Outin, Hervé; Richard, Jean-Christophe; Schneider, Francis; Tamion, Fabienne
The influenza H1N1 epidemics in 2009 led a substantial number of people to develop severe acute respiratory distress syndrome and refractory hypoxemia. In these patients, extracorporeal membrane oxygenation was used as rescue oxygenation therapy. Several randomized clinical trials and observational studies suggested that extracorporeal membrane oxygenation associated with protective mechanical ventilation could improve outcome, but its efficacy remains uncertain. Organized by the Société de Réanimation de Langue Française (SRLF) in conjunction with the Société Française d'Anesthésie et de Réanimation (SFAR), the Société de Pneumologie de Langue Française (SPLF), the Groupe Francophone de Réanimation et d'Urgences Pédiatriques (GFRUP), the Société Française de Perfusion (SOFRAPERF), the Société Française de Chirurgie Thoracique et Cardiovasculaire (SFCTV) et the Sociedad Española de Medecina Intensiva Critica y Unidades Coronarias (SEMICYUC), a Consensus Conference was held in December 2013 and a jury of 13 members wrote 65 recommendations to answer the five following questions regarding the place of extracorporeal life support for patients with acute respiratory distress syndrome: 1) What are the available techniques?; 2) Which patients could benefit from extracorporeal life support?; 3) How to perform extracorporeal life support?; 4) How and when to stop extracorporeal life support?; 5) Which organization should be recommended? To write the recommendations, evidence-based medicine (GRADE method), expert panel opinions, and shared decisions taken by all the thirteen members of the jury of the Consensus Conference were taken into account.
The influenza H1N1 epidemics in 2009 led a substantial number of people to develop severe acute respiratory distress syndrome and refractory hypoxemia. In these patients, extracorporeal membrane oxygenation was used as rescue oxygenation therapy. Several randomized clinical trials and observational studies suggested that extracorporeal membrane oxygenation associated with protective mechanical ventilation could improve outcome, but its efficacy remains uncertain. Organized by the Société de Réanimation de Langue Française (SRLF) in conjunction with the Société Française d’Anesthésie et de Réanimation (SFAR), the Société de Pneumologie de Langue Française (SPLF), the Groupe Francophone de Réanimation et d’Urgences Pédiatriques (GFRUP), the Société Française de Perfusion (SOFRAPERF), the Société Française de Chirurgie Thoracique et Cardiovasculaire (SFCTV) et the Sociedad Española de Medecina Intensiva Critica y Unidades Coronarias (SEMICYUC), a Consensus Conference was held in December 2013 and a jury of 13 members wrote 65 recommendations to answer the five following questions regarding the place of extracorporeal life support for patients with acute respiratory distress syndrome: 1) What are the available techniques?; 2) Which patients could benefit from extracorporeal life support?; 3) How to perform extracorporeal life support?; 4) How and when to stop extracorporeal life support?; 5) Which organization should be recommended? To write the recommendations, evidence-based medicine (GRADE method), expert panel opinions, and shared decisions taken by all the thirteen members of the jury of the Consensus Conference were taken into account. PMID:24936342
Delahunt, Brett; Srigley, John R; Montironi, Rodolfo; Egevad, Lars
The International Society of Urological Pathology (ISUP) 2012 Consensus Conference made recommendations regarding the classification, prognostic factors, staging, and immunohistochemical and molecular assessment of adult renal tumors. There was consensus that 5 entities should be recognized as novel tumors: tubulocystic renal cell carcinoma (RCC), acquired cystic disease-associated RCC, clear cell papillary RCC, microphthalmia transcription factor-family translocation RCC [in particular t(6; 11) RCC], and hereditary leiomyomatosis RCC syndrome-associated RCC. In addition, 3 rare epithelial carcinomas were considered emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC, and anaplastic lymphoma kinase translocation RCC. There were also a number of suggested modifications to existing World Health Organization 2004 categories, with the new classification to be known as the ISUP Vancouver Classification. Tumor morphotype, sarcomatoid/rhabdoid differentiation, and tumor necrosis were identified as significant prognostic parameters for RCC. The ISUP Grading System was accepted with grades 1-3 of clear cell and papillary RCC being based on nucleolar prominence, whereas extreme nuclear pleomorphism or sarcomatoid and/or rhabdoid differentiation defined grade 4 tumors. It was agreed that chromophobe RCC should not be graded. Consensus guidelines were formulated for specimen handling, and it was agreed that renal sinus invasion is present when tumor is in direct contact with fat or loose connective tissue of the sinus or if there is involvement of endothelial-lined spaces within the renal sinus, regardless of the size. The role of biomarkers in the diagnosis and assessment of prognosis of renal tumors was considered, and panels of immunohistochemical markers were identified for use in specific differential diagnostic scenarios.
Bruinsma, Sophie M; Roobol, Monique J; Carroll, Peter R; Klotz, Laurence; Pickles, Tom; Moore, Caroline M; Gnanapragasam, Vincent J; Villers, Arnauld; Rannikko, Antti; Valdagni, Riccardo; Frydenberg, Mark; Kakehi, Yoshiyuki; Filson, Christopher P; Bangma, Chris H
Active surveillance (AS) is broadly described as a management option for men with low-risk prostate cancer, but semantic heterogeneity exists in both the literature and in guidelines. To address this issue, a panel of leading prostate cancer specialists in the field of AS participated in a consensus-forming project using a modified Delphi method to reach international consensus on definitions of terms related to this management option. An iterative three-round sequence of online questionnaires designed to address 61 individual items was completed by each panel member. Consensus was considered to be reached if ≥70% of the experts agreed on a definition. To facilitate a common understanding among all experts involved and resolve potential ambiguities, a face-to-face consensus meeting was held between Delphi survey rounds two and three. Convenience sampling was used to construct the panel of experts. In total, 12 experts from Australia, France, Finland, Italy, the Netherlands, Japan, the UK, Canada and the USA participated. By the end of the Delphi process, formal consensus was achieved for 100% (n = 61) of the terms and a glossary was then developed. Agreement between international experts has been reached on relevant terms and subsequent definitions regarding AS for patients with localized prostate cancer. This standard terminology could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making.
Allegrante, John P.; Barry, Margaret M.; Airhihenbuwa, Collins O.; Auld, M. Elaine; Collins, Janet L.; Lamarre, Marie-Claude; Magnusson, Gudjon; McQueen, David V.; Mittelmark, Maurice B.
This paper reports the outcome of the Galway Consensus Conference, an effort undertaken as a first step toward international collaboration on credentialing in health promotion and health education. Twenty-nine leading authorities in health promotion, health education, and public health convened a 2-day meeting in Galway, Ireland, during which the…
National Institutes of Health (DHHS), Bethesda, MD.
This paper reports the results of a Consensus Development Conference on Cochlear Implants sponsored by the National Institutes of Health to improve the hearing of children and adults with hearing impairments. The following questions are addressed: (1) Who is a suitable candidate for a cochlear implant? (2) What are the advantages and disadvantages…
Rosenkranz, S; Lang, I M; Blindt, R; Bonderman, D; Bruch, L; Diller, G P; Felgendreher, R; Gerges, C; Hohenforst-Schmidt, W; Holt, S; Jung, C; Kindermann, I; Kramer, T; Kübler, W M; Mitrovic, V; Riedel, A; Rieth, A; Schmeisser, A; Wachter, R; Weil, J; Opitz, C
The 2015 European Guidelines on Diagnosis and Treatment of Pulmonary Hypertension are also valid for Germany. While the guidelines contain detailed recommendations regarding pulmonary arterial hypertension (PAH), they contain only a relatively short paragraph on other, much more common forms of PH such as PH due to left heart disease. Despite the lack of data, targeted PAH treatments are increasingly being used for PH associated with left heart disease. This development is of concern because of limited ressources and the need to base treatments on scientific evidence. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease, representing an unmet need of targeted PH therapies. It that sense, the practical implementation of the European Guidelines in Germany requires the consideration of several specific issues and already existing novel data. This requires a detailed commentary to the guidelines, and in some aspects an update already appears necessary. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany. This conference aimed to solve practical and controversial issues surrounding the implementation of the European Guidelines in Germany. To this end, several working groups were initiated, one of which was specifically dedicated to PH associated with left heart disease. This article summarizes the results and recommendations of this working group.
International Society of Urological Pathology (ISUP) Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens. Working group 3: extraprostatic extension, lymphovascular invasion and locally advanced disease.
Magi-Galluzzi, Cristina; Evans, Andrew J; Delahunt, Brett; Epstein, Jonathan I; Griffiths, David F; van der Kwast, Theo H; Montironi, Rodolfo; Wheeler, Thomas M; Srigley, John R; Egevad, Lars L; Humphrey, Peter A
The International Society of Urological Pathology Consensus Conference on Handling and Staging of Radical Prostatectomy Specimens in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to extraprostatic extension (pT3a disease), bladder neck invasion, lymphovascular invasion and the definition of pT4 were coordinated by working group 3. It was agreed that prostate cancer can be categorized as pT3a in the absence of adipose tissue involvement when cancer bulges beyond the contour of the gland or beyond the condensed smooth muscle of the prostate at posterior and posterolateral sites. Extraprostatic extension can also be identified anteriorly. It was agreed that the location of extraprostatic extension should be reported. Although there was consensus that the amount of extraprostatic extension should be quantitated, there was no agreement as to which method of quantitation should be employed. There was overwhelming consensus that microscopic urinary bladder neck invasion by carcinoma should be reported as stage pT3a and that lymphovascular invasion by carcinoma should be reported. It is recommended that these elements are considered in the development of practice guidelines and in the daily practice of urological surgical pathology.
Melosky, B.; Ho, C.
Each February, the Canadian Lung Cancer Conference brings together lung cancer researchers, clinicians, and care professionals who are united in their commitment to improve the care of patients with lung cancer. This year’s meeting, held 11–12 February, featured a resident education session, a welcome dinner, networking sessions, lectures, breakout sessions, debates, and a satellite symposium. Key themes from this year’s meeting included innovations across the care spectrum and results of recent clinical trials with targeted agents, immuno-oncology agents, and novel drug combinations.
Inaba, Kenji; Rizoli, Sandro; Veigas, Precilla V; Callum, Jeannie; Davenport, Ross; Hess, John; Maegele, Marc
There has been an increased interest in the use of viscoelastic testing to guide blood product replacement during the acute resuscitation of the injured patient. Currently, no uniformly accepted guidelines exist for how this technology should be integrated into clinical care. In September 2014, an international multidisciplinary group of leaders in the field of trauma coagulopathy and resuscitation was assembled for a 2-day consensus conference in Philadelphia, Pennsylvania. This panel included trauma surgeons, hematologists, blood bank specialists, anesthesiologists, and the lay public.Nine questions regarding the impact of viscoelastic testing in the early resuscitation of trauma patients were developed before the conference by panel consensus. Early use was defined as baseline viscoelastic test result thresholds obtained within the first minutes of hospital arrival-when conventional laboratory results are not available. The available data for each question were then reviewed in person using standardized presentations by the expert panel. A consensus summary document was then developed and reviewed by the panel in an open forum. Finally, a two-round Delphi poll was administered to the panel of experts regarding viscoelastic thresholds for triggering the initiation of specific treatments including fibrinogen, platelets, plasma, and prothrombin complex concentrates. This report summarizes the findings and recommendations of this consensus conference.
Hong, Dae Gy; Shin, So-Jin; Ju, Woong; Cho, Hanbyoul; Lee, Chulmin; Kim, Hyun-Jung; Bae, Duk-Soo
Clinical practice guidelines for gynecologic cancers have been developed by many organizations. Although these guidelines have much in common in terms of the practice of standard of care for uterine corpus cancer, practice guidelines that reflect the characteristics of patients and healthcare and insurance systems are needed for each country. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to produce the third edition of the guidelines as an advanced form based on evidence-based medicine, considering up-to-date clinical trials and abundant qualified Korean data. These guidelines cover screening, surgery, adjuvant treatment, and advanced and recurrent disease with respect to endometrial carcinoma and uterine sarcoma. The committee members and many gynecologic oncologists derived key questions from the discussion, and a number of relevant scientific literatures were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, together with other details. The objective of these practice guidelines is to establish standard policies on issues in clinical areas related to the management of uterine corpus cancer based on the findings in published papers to date and the consensus of experts as a KSGO Consensus Statement. PMID:27894165
Drolet, Beth A; Frommelt, Peter C; Chamlin, Sarah L; Haggstrom, Anita; Bauman, Nancy M; Chiu, Yvonne E; Chun, Robert H; Garzon, Maria C; Holland, Kristen E; Liberman, Leonardo; MacLellan-Tobert, Susan; Mancini, Anthony J; Metry, Denise; Puttgen, Katherine B; Seefeldt, Marcia; Sidbury, Robert; Ward, Kendra M; Blei, Francine; Baselga, Eulalia; Cassidy, Laura; Darrow, David H; Joachim, Shawna; Kwon, Eun-Kyung M; Martin, Kari; Perkins, Jonathan; Siegel, Dawn H; Boucek, Robert J; Frieden, Ilona J
Infantile hemangiomas (IHs) are common neoplasms composed of proliferating endothelial-like cells. Despite the relative frequency of IH and the potential severity of complications, there are currently no uniform guidelines for treatment. Although propranolol has rapidly been adopted, there is significant uncertainty and divergence of opinion regarding safety monitoring, dose escalation, and its use in PHACE syndrome (PHACE = posterior fossa, hemangioma, arterial lesions, cardiac abnormalities, eye abnormalities; a cutaneous neurovascular syndrome characterized by large, segmental hemangiomas of the head and neck along with congenital anomalies of the brain, heart, eyes and/or chest wall). A consensus conference was held on December 9, 2011. The multidisciplinary team reviewed existing data on the pharmacologic properties of propranolol and all published reports pertaining to the use of propranolol in pediatric patients. Workgroups were assigned specific topics to propose protocols on the following subjects: contraindications, special populations, pretreatment evaluation, dose escalation, and monitoring. Consensus protocols were recorded during the meeting and refined after the meeting. When appropriate, protocol clarifications and revision were made and agreed upon by the group via teleconference. Because of the absence of high-quality clinical research data, evidence-based recommendations are not possible at present. However, the team agreed on a number of recommendations that arose from a review of existing evidence, including when to treat complicated IH; contraindications and pretreatment evaluation protocols; propranolol use in PHACE syndrome; formulation, target dose, and frequency of propranolol; initiation of propranolol in infants; cardiovascular monitoring; ongoing monitoring; and prevention of hypoglycemia. Where there was considerable controversy, the more conservative approach was selected. We acknowledge that the recommendations are conservative in
Kobashigawa, Jon; Zuckermann, Andreas; Macdonald, Peter; Leprince, Pascal; Esmailian, Fardad; Luu, Minh; Mancini, Donna; Patel, Jignesh; Razi, Rabia; Reichenspurner, Hermann; Russell, Stuart; Segovia, Javier; Smedira, Nicolas; Stehlik, Josef; Wagner, Florian
Although primary graft dysfunction (PGD) is fairly common early after cardiac transplant, standardized schemes for diagnosis and treatment remain contentious. Most major cardiac transplant centers use different definitions and parameters of cardiac function. Thus, there is difficulty comparing published reports and no agreed protocol for management. A consensus conference was organized to better define, diagnose, and manage PGD. There were 71 participants (transplant cardiologists, surgeons, immunologists and pathologists), with vast clinical and published experience in PGD, representing 42 heart transplant centers worldwide. State-of-the-art PGD presentations occurred with subsequent breakout sessions planned in an attempt to reach consensus on various issues. Graft dysfunction will be classified into primary graft dysfunction (PGD) or secondary graft dysfunction where there is a discernible cause such as hyperacute rejection, pulmonary hypertension, or surgical complications. PGD must be diagnosed within 24 hours of completion of surgery. PGD is divided into PGD-left ventricle and PGD-right ventricle. PGD-left ventricle is categorized into mild, moderate, or severe grades depending on the level of cardiac function and the extent of inotrope and mechanical support required. Agreed risk factors for PGD include donor, recipient, and surgical procedural factors. Recommended management involves minimization of risk factors, gradual increase of inotropes, and use of mechanical circulatory support as needed. Retransplantation may be indicated if risk factors are minimal. With a standardized definition of PGD, there will be more consistent recognition of this phenomenon and treatment modalities will be more comparable. This should lead to better understanding of PGD and prevention/minimization of its adverse outcomes.
Borg, Michael A; Cookson, Barry D; Zarb, Peter; Scicluna, Elizabeth A
Antimicrobial resistance has become a global threat to effective health care delivery. This is particularly the case within the Mediterranean region, where data from recent studies suggests the situation to be particularly acute. A better knowledge base, as well as a collaborative effort, is therefore required to address this ever increasing challenge to effective patient care. Over its four-year period, the Antibiotic Resistance Surveillance and Control in the Mediterranean Region (ARMed) project investigated the epidemiology of antimicrobial resistance, as well as its contributory factors, in a number of countries in the southern and eastern Mediterranean region through the collection of comparable and validated data. The project culminated in a consensus conference held in Malta in November 2006. The conference provided a forum for expert delegates to agree on a number of priority strategic recommendations that would be relevant to resistance containment efforts in the region. There was general agreement on the need for surveillance and audit to underpin any intervention to tackle antimicrobial resistance, both to monitor changing epidemiological trends in critical pathogens as well as to identify antibiotic consumption practices and effectiveness of prevention and control of health care associated infections. In addition, the importance to convey these data to key users was also stressed in all workshops, as was better education and training of health care workers. The recommendations also made it clear that ownership of the problem needs to be improved throughout the region and that resources, both financial as well as human, must be allocated by the respective policy makers in order to combat it.
Maia, Ana Luiza; Ward, Laura S; Carvalho, Gisah A; Graf, Hans; Maciel, Rui M B; Maciel, Léa M Zanini; Rosário, Pedro W; Vaisman, Mario
Thyroid nodules are a common manifestation of thyroid diseases. It is estimated that approximately 10% of adults have palpable thyroid nodules with the frequency increasing throughout life. The major concern on nodule evaluation is the risk of malignancy (5-10%). Differentiated thyroid carcinoma accounts for 90% of all thyroid malignant neoplasias. Although most patients with cancer have a favorable outcome, some individuals present an aggressive form of the disease and poor prognostic despite recent advances in diagnosis and treatment. Here, a set of clinical guidelines for the evaluation and management of patients with thyroid nodules or differentiated thyroid cancer was developed through consensus by 8 member of the Department of Thyroid, Sociedade Brasileira de Endocrinologia e Metabologia. The participants are from different reference medical centers within Brazil, to reflect different practice patterns. Each committee participant was initially assigned to write a section of the document and to submit it to the chairperson, who revised and assembled the sections into a complete draft document, which was then circulated among all committee members for further revision. All committee members further revised and refined the document. The guidelines were developed based on the expert opinion of the committee participants, as well as on previously published information.
Zachor, Ditza A; Curatolo, Paolo
On April 2013 experts in the field of autism from Italy and Israel convened in Jerusalem to discuss and finalize clinical recommendations for early diagnosis and intervention in Autism Spectrum Disorders (ASDs). In this paper, we summarize the results of this Italian-Israeli consensus conference. ASDs constitute a class of severe and heterogeneous neurodevelopmental conditions caused by atypical brain development beginning during early prenatal life, reflecting many genetic, neurobiological and environmental influences. The first clinical signs of ASDs begin to be evident in children between 12 and 18 months of age, often after a period of relatively typical postnatal development. Recent longitudinal studies reveal substantial diversity in developmental trajectories through childhood and adolescence. Some intervention approaches have been demonstrated to be effective in improving core symptoms of ASDs, even if the heterogeneity and developmental nature of the disorder make it implausible that only one specific treatment will be best for all children with ASDs. More randomized control trials (RCTs) on early intervention are needed to identify the most effective strategies and provide the most efficient allocation of resources during the critical early intervention time period. Future research should focus on linking biological phenotypes with specific genotypes, thus establishing a foundation for the development of diagnostic screening tools and individualization of treatments.
Olschewski, H; Behr, J; Bremer, H; Claussen, M; Douschan, P; Halank, M; Held, M; Hoeper, M M; Holt, S; Klose, H; Krüger, S; Lange, T J; Reichenberger, F; Skowasch, D; Ulrich, S; Wilkens, H; Seeger, W
The 2015 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) associated with chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase-5 inhibitors, sGC stimulators) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of PH which may affect quality of life and survival of these patients in a similar manner. To this end, it is crucial to consider the severity of both PH and the underlying lung disease. In June 2016, a Consensus Conference organized by the PH working groups of the German Society of Cardiology (DGK), the German Society of Respiratory Medicine (DGP) and the German Society of Pediatric Cardiology (DGPK) was held in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. Several working groups were initiated, one of which was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.
Sies, Helmut; Hollman, Peter C.H.; Grune, Tilman; Stahl, Wilhelm; Biesalski, Hans K.; Williamson, Gary
Criteria for assessing the purported protection by flavanol-rich foods against vascular dysfunction and oxidative damage to biomolecules was the subject of the 27th Hohenheim Consensus Conference held on July 11, 2011. State-of-the-art evidence was put into perspective, focusing on several questions that were followed by a consensus answer. Among the topics addressed were the major sources of flavanols in the human diet, the bioavailability of flavanols, biomarkers for “health benefit,” and the biological function of flavanols. Consensus was reached on these topics. No conclusion was reached on the design of randomized, controlled trials for substantiation of health claims for flavanol-rich foods as to the necessity of a study arm with an isolated pharmacologically active compound, e.g., (−)-epicatechin. PMID:22516731
Sies, Helmut; Hollman, Peter C H; Grune, Tilman; Stahl, Wilhelm; Biesalski, Hans K; Williamson, Gary
Criteria for assessing the purported protection by flavanol-rich foods against vascular dysfunction and oxidative damage to biomolecules was the subject of the 27th Hohenheim Consensus Conference held on July 11, 2011. State-of-the-art evidence was put into perspective, focusing on several questions that were followed by a consensus answer. Among the topics addressed were the major sources of flavanols in the human diet, the bioavailability of flavanols, biomarkers for "health benefit," and the biological function of flavanols. Consensus was reached on these topics. No conclusion was reached on the design of randomized, controlled trials for substantiation of health claims for flavanol-rich foods as to the necessity of a study arm with an isolated pharmacologically active compound, e.g., (-)-epicatechin.
In an update on recommendations for colorectal cancer screening, an Asia–Pacific consensus group has set a good standard for presenting level of agreement to recommendation levels. However, this update also exposes how consensus groups might concentrate on the less controversial issues—leaving the tricky questions in the dark.
Magnani, C; Bianchi, C; Chellini, E; Consonni, D; Fubini, B; Gennaro, V; Marinaccio, A; Menegozzo, M; Mirabelli, D; Merler, E; Merletti, F; Musti, M; Oddone, E; Romanelli, A; Terracini, B; Zona, A; Zocchetti, C; Alessi, M; Baldassarre, A; Dianzani, I; Maule, M; Mensi, C; Silvestri, S
The III Italian Consensus Conference on Pleural Mesothelioma (MM) convened on January 29th 2015. This report presents the conclusions of the 'Epidemiology, Public Health and Occupational Medicine' section. MM incidence in 2011 in Italy was 3.64 per 100,000 person/years in men and 1.32 in women. Incidence trends are starting to level off. Ten percent of cases are due to non-occupational exposure. Incidence among women is very high in Italy, because of both non-occupational and occupational exposure. The removal of asbestos in place is proceeding slowly, with remaining exposure. Recent literature confirms the causal role of chrysotile. Fibrous fluoro-edenite was classified as carcinogenic by IARC (Group 1) on the basis of MM data. A specific type (MWCNT-7) of Carbon Nanotubes was classified 2B. For pleural MM, after about 45 years since first exposure, the incidence trend slowed down; with more studies needed. Cumulative exposure is a proxy of the relevant exposure, but does not allow to distinguish if duration or intensity may possibly play a prominent role, neither to evaluate the temporal sequence of exposures. Studies showed that duration and intensity are independent determinants of MM. Blood related MM are less than 2.5%. The role of BAP1 germline mutations is limited to the BAP1 cancer syndrome, but negligible for sporadic cases. Correct MM diagnosis is baseline; guidelines agree on the importance of the tumor gross appearance and of the hematoxylin-eosin-based histology. Immunohistochemical markers contribute to diagnostic confirmation: the selection depends on morphology, location, and differential diagnosis. The WG suggested that 1) General Cancer Registries and ReNaM Regional Operational Centres (COR) interact and systematically compare MM cases; 2) ReNaM should report results presenting the diagnostic certainty codes and the diagnostic basis, separately; 3) General Cancer Registries and COR should interact with pathologists to assure the up
Wakabayashi, Go; Cherqui, Daniel; Geller, David A; Han, Ho-Seong; Kaneko, Hironori; Buell, Joseph F
Six years have passed since the first International Consensus Conference on Laparoscopic Liver Resection was held. This comparatively new surgical technique has evolved since then and is rapidly being adopted worldwide. We compared the theoretical differences between open and laparoscopic liver resection, using right hepatectomy as an example. We also searched the Cochrane Library using the keyword "laparoscopic liver resection." The papers retrieved through the search were reviewed, categorized, and applied to the clinical questions that will be discussed at the 2nd Consensus Conference. The laparoscopic hepatectomy procedure is more difficult to master than the open hepatectomy procedure because of the movement restrictions imposed upon us when we operate from outside the body cavity. However, good visibility of the operative field around the liver, which is located beneath the costal arch, and the magnifying provide for neat transection of the hepatic parenchyma. Another theoretical advantage is that pneumoperitoneum pressure reduces hemorrhage from the hepatic vein. The literature search turned up 67 papers, 23 of which we excluded, leaving only 44. Two randomized controlled trials (RCTs) are underway, but their results are yet to be published. Most of the studies (n = 15) concerned short-term results, with some addressing long-term results (n = 7), cost (n = 6), energy devices (n = 4), and so on. Laparoscopic hepatectomy is theoretically superior to open hepatectomy in terms of good visibility of the operative field due to the magnifying effect and reduced hemorrhage from the hepatic vein due to pneumoperitoneum pressure. However, there is as yet no evidence from previous studies to back this up in terms of short-term and long-term results. The 2nd International Consensus Conference on Laparoscopic Liver Resection will arrive at a consensus on the basis of the best available evidence, with video presentations focusing on surgical techniques and the publication
Hu, Xichun; Jiang, Zefei; Li, Huiping; Chen, Jiayi; Cui, Shude; Li, Qing; Liao, Ning; Liu, Donggeng; Liu, Jian; Lu, Jinsong; Shen, Kunwei; Sun, Tao; Teng, Yuee; Tong, Zhongsheng; Wang, Shulian; Wang, Xiang; Wang, Xiaojia; Wang, Yongsheng; Wu, Jiong; Yuan, Peng; Zhang, Pin; Zhang, Qingyuan; Zheng, Hong; Pang, Da; Ren, Guosheng; Shao, Zhimin; Shen, Zhenzhou; Song, Erwei; Song, Santai
The recently available guidelines on the management of advanced breast cancer (ABC) organized by Chinese Anti-Cancer Association, Committee of Breast Cancer Society (CACA-CBCS) do not elucidate ABC in details. To instruct clinicians in treatment of ABC, a Chinese expert consensus meeting on diagnosis and treatment of ABC was held in June 2014 and a consensus is developed. The following consensus provides the level of evidence and supporting documents for each recommendation, and introduces research topics to be urgently addressed. Notably, the consensus on diagnosis and treatment of ABC in China is developed to be applied nationwide. In different areas, multidisciplinary treatment (MDT) tailored to the each patient and the disease itself should be applied based on the basic principles of modern oncology. PMID:26605288
The purpose of this conference is to bring together a community of researchers across the cancer control continuum using geospatial tools, models and approaches to address cancer prevention and control.
Yanamandra, Uday; Khattry, Navin; Kumar, Shaji; Raje, Noopur; Jain, Arihant; Jagannath, Sundar; Menon, Hari; Kumar, Lalit; Varma, Neelam; Varma, Subhash; Saikia, Tapan; Malhotra, Pankaj
The science of multiple myeloma (MM) and related plasma cell disorders is rapidly evolving with increased understanding of the disease biology and recent approval of the newer drugs widening the therapeutic armamentarium. Despite multiple international guidelines regarding the management of this disease, the practice of managing MM is not uniform amongst Indian physicians. There are challenges in management which are unique to the Indian patients. This review discusses these challenges and the consensus of the nation-wide experts in dealing with the same. We also briefly highlighted the perspective of international experts as discussed in the Myeloma State of the Art conference held in September 2016 at PGI, Chandigarh. An Indian Myeloma Academic Groupe (IMAGe) group was formed to strengthen the research, create awareness about myeloma and related disorders and form consensus guidelines/ recommendations that can be adapted to the Indian Scenario.
Frankovich, Jennifer; Cooperstock, Michael; Cunningham, Madeleine W.; Latimer, M. Elizabeth; Murphy, Tanya K.; Pasternack, Mark; Thienemann, Margo; Williams, Kyle; Walter, Jolan; Swedo, Susan E.
Abstract On May 23 and 24, 2013, the First PANS Consensus Conference was convened at Stanford University, calling together a geographically diverse group of clinicians and researchers from complementary fields of pediatrics: General and developmental pediatrics, infectious diseases, immunology, rheumatology, neurology, and child psychiatry. Participants were academicians with clinical and research interests in pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS) in youth, and the larger category of pediatric acute-onset neuropsychiatric syndrome (PANS). The goals were to clarify the diagnostic boundaries of PANS, to develop systematic strategies for evaluation of suspected PANS cases, and to set forth the most urgently needed studies in this field. Presented here is a consensus statement proposing recommendations for the diagnostic evaluation of youth presenting with PANS. PMID:25325534
Epstein, Jonathan I; Egevad, Lars; Amin, Mahul B; Delahunt, Brett; Srigley, John R; Humphrey, Peter A
In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out
Mohan, Vishnu; Woodcock, Deborah; McGrath, Karess; Scholl, Gretchen; Pranaat, Robert; Doberne, Julie W.; Chase, Dian A.; Gold, Jeffrey A.; Ash, Joan S.
A group of informatics experts in simulation, biomedical informatics, patient safety, medical education, and human factors gathered at Corbett, Oregon on April 30 and May 1, 2015. Their objective: to create a consensus statement on best practices for the use of electronic health record (EHR) simulations in education and training, to improve patient safety, and to outline a strategy for future EHR simulation work. A qualitative approach was utilized to analyze data from the conference and generate recommendations in five major categories: (1) Safety, (2) Education and Training, (3) People and Organizations, (4) Usability and Design, and (5) Sociotechnical Aspects. PMID:28269887
Koike, Haruki; Sobue, Gen
Vasculitis can be primarily or secondarily to various underlying diseases. It frequently affects the nervous system, and neurological deficits may remain even after disease remission. Because the progression of vasculitides is usually acute to subacute, early initiation of treatment is important from the viewpoint of patients' functional status. However, early diagnosis may be difficult, particularly in patients with central nervous system vasculitis. Hence, it is important to understand the wide-ranging clinical manifestations of vasculitides. Here, we summarize the 2012 revised International Chapel Hill Consensus Conference nomenclature of vasculitides from the standpoint of central nervous system vasculitis.
Safdar, Basmah; Greenberg, Marna R; Anise, Ayodola; Brown, Jeremy; Conwit, Robin; Filart, Rosemarie; Scott, Jane; Choo, Esther K
As part of the 2014 Academic Emergency Medicine (AEM) consensus conference "Gender-Specific Research in Emergency Care: Investigate, Understand, and Translate How Gender Affects Patient Outcomes," we assembled a diverse panel of representatives from federal and nonfederal funding agencies to discuss future opportunities for sex- and gender-specific research. The discussion revolved around the mission and priorities of each organization, as well as its interest in promoting sex- and gender-specific research. The panelists were asked to provide specific examples of funding lines generated or planned for as pertinent to emergency care. Training opportunities for future researchers in this area were also discussed.
Berney, Daniel M; Wheeler, Thomas M; Grignon, David J; Epstein, Jonathan I; Griffiths, David F; Humphrey, Peter A; van der Kwast, Theo; Montironi, Rodolfo; Delahunt, Brett; Egevad, Lars; Srigley, John R
The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the infiltration of tumor into the seminal vesicles and regional lymph nodes were coordinated by working group 4. There was a consensus that complete blocking of the seminal vesicles was not necessary, although sampling of the junction of the seminal vesicles and prostate was mandatory. There was consensus that sampling of the vas deferens margins was not obligatory. There was also consensus that muscular wall invasion of the extraprostatic seminal vesicle only should be regarded as seminal vesicle invasion. Categorization into types of seminal vesicle spread was agreed by consensus to be not necessary. For examination of lymph nodes, there was consensus that special techniques such as frozen sectioning were of use only in high-risk cases. There was no consensus on the optimal sampling method for pelvic lymph node dissection specimens, although there was consensus that all lymph nodes should be completely blocked as a minimum. There was also a consensus that a count of the number of lymph nodes harvested should be attempted. In view of recent evidence, there was consensus that the diameter of the largest lymph node metastasis should be measured. These consensus decisions will hopefully clarify the difficult areas of pathological assessment in radical prostatectomy evaluation and improve the concordance of research series to allow more accurate assessment of patient prognosis.
The Latin American and Caribbean Population and Development Conference was held in Mexico City from April 29 to May 4, 1993, during which discussions were held on population growth, structure, and distribution in the region; socioeconomic trends and implications; population dynamics and development in the Caribbean subregion; population policies and programs; population growth and distribution and their relation to development and the environment; women and population dynamics; and family planning, health, and family well-being. The conference adopted the Latin American and Caribbean Consensus on Population and Development which is presented in sections on the situation of population and development in Latin America and the Caribbean in the early 1990s, and recommendations on population growth and structure, population distribution, development, the environment, women and population dynamics, population policies and programs, health, family planning and well-being, international migration and development, training, data production, research, and international cooperation in the population field.
... gaps? An impartial, independent panel will be charged with reviewing the available published literature in advance of the ] conference, including a systematic literature review commissioned through...
... charged with reviewing the available published literature in advance of the conference, including a systematic literature review commissioned through the Agency for Healthcare Research and Quality. The...
McNeel, Douglas G; Bander, Neil H; Beer, Tomasz M; Drake, Charles G; Fong, Lawrence; Harrelson, Stacey; Kantoff, Philip W; Madan, Ravi A; Oh, William K; Peace, David J; Petrylak, Daniel P; Porterfield, Hank; Sartor, Oliver; Shore, Neal D; Slovin, Susan F; Stein, Mark N; Vieweg, Johannes; Gulley, James L
Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death among men in the United States. In recent years, several new agents, including cancer immunotherapies, have been approved or are currently being investigated in late-stage clinical trials for the management of advanced prostate cancer. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel, including physicians, nurses, and patient advocates, to develop consensus recommendations for the clinical application of immunotherapy for prostate cancer patients. To do so, a systematic literature search was performed to identify high-impact papers from 2006 until 2014 and was further supplemented with literature provided by the panel. Results from the consensus panel voting and discussion as well as the literature review were used to rate supporting evidence and generate recommendations for the use of immunotherapy in prostate cancer patients. Sipuleucel-T, an autologous dendritic cell vaccine, is the first and currently only immunotherapeutic agent approved for the clinical management of metastatic castrate resistant prostate cancer (mCRPC). The consensus panel utilized this model to discuss immunotherapy in the treatment of prostate cancer, issues related to patient selection, monitoring of patients during and post treatment, and sequence/combination with other anti-cancer treatments. Potential immunotherapies emerging from late-stage clinical trials are also discussed. As immunotherapy evolves as a therapeutic option for the treatment of prostate cancer, these recommendations will be updated accordingly.
Cancer research is a multifaceted endeavour that incorporates not only a myriad of techniques and specialties but also encompasses a huge range of disease types. The National Cancer Research Institute (NCRI) is a UK partnership comprising 21 charity and government funders of cancer research along with the Association of British Pharmaceutical Industry. Each year, the NCRI hosts the largest cancer meeting in the UK; bringing together members of the UK cancer research community, research leaders from around the world, health professionals, service users, research funders, and industry to discuss the latest findings in cancer research from a wide range of disciplines. The 2013 NCRI Conference attracted over 1700 delegates and 150 speakers from 15 different countries. The conference programme covered a large range of topic areas including prevention, screening, model systems, the provision of information, survivorship, and end-of-life care. This conference report gives an overview of the plenary sessions at the conference as well as highlights from the parallel sessions.
Rodrigue, James R.; Kazley, Abby Swanson; Mandelbrot, Didier A.; Hays, Rebecca; LaPointe Rudow, Dianne
Despite its superior outcomes relative to chronic dialysis and deceased donor kidney transplantation, live donor kidney transplantation (LDKT) is less likely to occur in minorities, older adults, and poor patients than in those who are white, younger, and have higher household income. In addition, there is considerable geographic variability in LDKT rates. Concomitantly, in recent years, the rate of living kidney donation (LKD) has stopped increasing and is declining, after decades of consistent growth. Particularly noteworthy is the decline in LKD among black, younger, male, and lower-income adults. The Live Donor Community of Practice within the American Society of Transplantation, with financial support from 10 other organizations, held a Consensus Conference on Best Practices in Live Kidney Donation in June 2014. The purpose of this meeting was to identify LKD best practices and knowledge gaps that might influence LDKT, with a focus on patient and donor education, evaluation efficiencies, disparities, and systemic barriers to LKD. In this article, we discuss trends in LDKT/LKD and emerging novel strategies for attenuating disparities, and we offer specific recommendations for future clinical practice, education, research, and policy from the Consensus Conference Workgroup focused on disparities. PMID:25883072
Sarode, Ravi; Ballas, Samir K; Garcia, Alicia; Kim, Haewon C; King, Karen; Sachais, Bruce; Williams, Lance A
The American Society for Apheresis (ASFA) conducted a one-day consensus conference on red blood cell exchange (RBCx) in sickle cell disease (SCD) during its annual meeting in San Antonio, TX, on May 5, 2015. The authors of this article, a subcommittee of ASFA's Clinical Applications Committee, developed several questions with regard to pathophysiology of SCD and use of RBCx in the management of various complications. These questions were provided to the seven invited speakers who are the experts in the field of SCD. Two experts in the field moderated the proceedings of the conference, which was attended by more than 150 participants. After each presentation, there was a summary of the main points by the moderators and an open discussion with questions from the audience. A video recording of the proceedings, as well as each presentation, was made available to the authors. Each author's summary was reviewed and approved by the respective speaker before submission of this manuscript. The subcommittee also developed several key questions to generate a consensus amongst the speakers on key issues for using RBCx for patients with SCD.
Alderson, Philip O; Bresolin, Linda B; Becker, Gary J; Thrall, James H; Dunnick, N Reed; Hillman, Bruce J; Lee, Joseph K T; Nagy, Edward C
Opportunities for funded radiologic research are greater than ever, and the amount of federal funding coming to academic radiology departments is increasing. Even so, many medical school-based radiology departments have little or no research funding. Accordingly, a consensus panel was convened to discuss ways to enhance research productivity and broaden the base of research strength in as many academic radiology departments as possible. The consensus panel included radiologists who have leadership roles in some of the best-funded research departments, radiologists who direct other funded research programs, and radiologists with related expertise. The goals of the consensus panel were to identify the attributes associated with successful research programs and to develop an action plan for radiology research based on these characteristics.
Gorter, Ramon R; Eker, Hasan H; Gorter-Stam, Marguerite A W; Abis, Gabor S A; Acharya, Amish; Ankersmit, Marjolein; Antoniou, Stavros A; Arolfo, Simone; Babic, Benjamin; Boni, Luigi; Bruntink, Marlieke; van Dam, Dieuwertje A; Defoort, Barbara; Deijen, Charlotte L; DeLacy, F Borja; Go, Peter Mnyh; Harmsen, Annelieke M K; van den Helder, Rick S; Iordache, Florin; Ket, Johannes C F; Muysoms, Filip E; Ozmen, M Mahir; Papoulas, Michail; Rhodes, Michael; Straatman, Jennifer; Tenhagen, Mark; Turrado, Victor; Vereczkei, Andras; Vilallonga, Ramon; Deelder, Jort D; Bonjer, Jaap
Unequivocal international guidelines regarding the diagnosis and management of patients with acute appendicitis are lacking. The aim of the consensus meeting 2015 of the EAES was to generate a European guideline based on best available evidence and expert opinions of a panel of EAES members. After a systematic review of the literature by an international group of surgical research fellows, an expert panel with extensive clinical experience in the management of appendicitis discussed statements and recommendations. Statements and recommendations with more than 70 % agreement by the experts were selected for a web survey and the consensus meeting of the EAES in Bucharest in June 2015. EAES members and attendees at the EAES meeting in Bucharest could vote on these statements and recommendations. In the case of more than 70 % agreement, the statement or recommendation was defined as supported by the scientific community. Results from both the web survey and the consensus meeting in Bucharest are presented as percentages. In total, 46 statements and recommendations were selected for the web survey and consensus meeting. More than 232 members and attendees voted on them. In 41 of 46 statements and recommendations, more than 70 % agreement was reached. All 46 statements and recommendations are presented in this paper. They comprise topics regarding the diagnostic work-up, treatment indications, procedural aspects and post-operative care. The consensus meeting produced 46 statements and recommendations on the diagnostic work-up and management of appendicitis. The majority of the EAES members supported these statements. These consensus proceedings provide additional guidance to surgeons and surgical residents providing care to patients with appendicitis.
Disease management is conceptually recognized as being a significant approach for closing the gaps in care identified by the Institute of Medicine as contributing to poor outcomes from our health care system. That conceptual credibility has been bolstered by the disease management industry through the adoption of an industry-standard definition of disease management and through the development and implementation of disease management accreditation programs by the National Committee for Quality Assurance, Utilization Review Accreditation Commission, and Joint Commission on Accreditation of Healthcare Organizations. The clinical and financial outcomes of disease management programs continue to be suspect, however, due to the lack of an industry standard set of outcomes metrics and a uniform methodology for evaluating those metrics. As a result, the ability to evaluate the effectiveness of any individual program is compromised, and the ability to effectively compare results across programs of different delivery designs is non-existent. To address this issue, American Healthways and Johns Hopkins convened a consensus conference of nearly 150 health care professionals representing health plans, hospitals, practicing physicians (both primary care and specialty), and other health care professionals. The conference purpose was to develop a "first-step" set of metrics and a uniform methodology that could be applied industry-wide to enable meaningful comparisons between programs and to allow evaluation of individual programs whether "homegrown" or "outsourced." The consensus conferees recognized that there were many paths to this objective, but that they had to land on a set of metrics and a methodology that was "doable" in light of today's technology and data availability. The results of their consensus effort follow.
Sheppard, Lisa; Senior, Jane; Park, Chae Hee; Mockenhaupt, Robin; Bazzarre, Terry; Chodzko-Zajko, Wojtek
On May 1, 2001, a coalition of national organizations released a major planning document designed to develop a national strategy for the promotion of physically active lifestyles among the mid-life and older adult population. The National Blueprint: Increasing Physical Activity Among Adults Age 50 and Older was developed with input from 46 organizations with expertise in health, medicine, social and behavioral sciences, epidemiology, gerontology/geriatrics, clinical science, public policy, marketing, medical systems, community organization, and environmental issues. The Blueprint notes that, despite a wealth of evidence about the benefits of physical activity for mid-life and older persons, there has been little success in convincing age 50+ Americans to adopt physically active lifestyles. The Blueprint identifies barriers in the areas of research, home and community programs, medical systems, public policy and advocacy, and marketing and communications. In addition to identifying barriers, the Blueprint proposes a number of concrete strategies that could be employed in order to overcome the barriers to physical activity in society at large. This report summarizes the outcome of the National Blueprint Consensus Conference that was held in October 2002. In this conference, representatives of more than 50 national organizations convened in Washington, D.C. with the goal of identifying high priority and high feasibility strategies which would advance the National Blueprint and which could be initiated within the next 12 to 24 months. Participants in the consensus conference were assigned to one of five breakout groups: home and community, marketing, medical systems, public policy, and research. Each breakout group was charged with identifying the three highest priority strategies within their area for effectively increasing physical activity levels in the mid-life and older adult population. In addition to the 15 strategies identified by the breakout groups, three
Marin, Jennifer R; Mills, Angela M
The 2015 Academic Emergency Medicine consensus conference, "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization" was held on May 12, 2015, with the goal of developing a high-priority research agenda on which to base future research. The specific aims of the conference were to (1) understand the current state of evidence regarding emergency department (ED) diagnostic imaging use and identify key opportunities, limitations, and gaps in knowledge; (2) develop a consensus-driven research agenda emphasizing priorities and opportunities for research in ED diagnostic imaging; and (3) explore specific funding mechanisms available to facilitate research in ED diagnostic imaging. Over a 2-year period, the executive committee and other experts in the field convened regularly to identify specific areas in need of future research. Six content areas within emergency diagnostic imaging were identified before the conference and served as the breakout groups on which consensus was achieved: clinical decision rules; use of administrative data; patient-centered outcomes research; training, education, and competency; knowledge translation and barriers to imaging optimization; and comparative effectiveness research in alternatives to traditional computed tomography use. The executive committee invited key stakeholders to assist with the planning and to participate in the consensus conference to generate a multidisciplinary agenda. There were a total of 164 individuals involved in the conference and spanned various specialties, including general emergency medicine, pediatric emergency medicine, radiology, surgery, medical physics, and the decision sciences.
Overdiagnosis Conference Early Bird Registration Open and Abstract Submission This event will be co-hosted by the National institutes of Health, National Cancer Institute in Washington DC, September 01-03, 2015. |
Safdar, Basmah; Greenberg, Marna R
With the goal of reducing inequalities in patient care, the 2014 Academic Emergency Medicine (AEM) consensus conference, "Gender-Specific Research in Emergency Care: Investigate, Understand, and Translate How Gender Affects Patient Outcomes," convened a diverse group of researchers, clinicians, health care providers, patients, and representatives of federal agencies and policy-makers in Dallas, Texas, in May 2014. The executive and steering committees identified seven clinical domains as key to gender-specific emergency care: cardiovascular, neurological, trauma/injury, substance abuse, pain, mental health, and diagnostic imaging. The main aims of the conference were to: 1) summarize and consolidate current data related to sex- and gender-specific research for acute care and identify critical gender-related gaps in knowledge to inform an EM research agenda; 2) create a consensus-driven research agenda that advances sex- and gender-specific research in the prevention, diagnosis, and management of acute diseases and identify strategies to investigate them; and 3) build a multinational interdisciplinary consortium to disseminate and study the sex and gender medicine of acute conditions. Over a 2-year period, this collaborative network of stakeholders identified key areas where sex- and gender-specific research is most likely to improve clinical care and ultimately patient outcomes. The iterative consensus process culminated in a daylong conference on May 13, 2014, with a total of 133 registrants, with the majority being between ages 31 and 50 years (57%), females (71%), and whites (79%). Content experts led the consensus-building workshops at the conference and used the nominal group technique to consolidate consensus recommendations for priority research. In addition, panel sessions addressed funding mechanisms for gender-specific research as well as gender-specific regulatory challenges to product development and approval. This special issue of AEM reports the
Refugee Policy Group, Washington, DC.
This paper was written in anticipation of the International Conference on Indochinese Refugees (ICIR), held in June 1989 in Geneva (Switzerland). The ICIR was convened to respond to chronic refugee problems in the region, first addressed in the July 1979 Meeting in Geneva on the Situation of Refugees and Displaced Persons in Southeast Asia. It is…
Fujiwara, Hiroyuki; Yokota, Harushige; Monk, Bradley; Treilleux, Isabelle; Devouassoux-Shisheboran, Mojgan; Davis, Alison; Kim, Jae-Weon; Mahner, Sven; Stany, Michael; Pignata, Sandro; Ray-Coquard, Isabelle; Fujiwara, Keiichi
Cervical adenocarcinoma is known to be less common than squamous cell carcinoma of the cervix comprising approximately 25% of all cervical carcinomas. Differences in associated human papillomavirus types, patterns of spread, and prognosis call for treatments that are not always like those for squamous cancers. In this review, we report a consensus developed by the Gynecologic Cancer InterGroup surrounding cervical adenocarcinoma for epidemiology, pathology, treatment, and unanswered questions. Prospective clinical trials are needed to help develop treatment guidelines.
Marin, Jennifer R; Mills, Angela M
The 2015 Academic Emergency Medicine (AEM) consensus conference, "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization," was held on May 12, 2015, with the goal of developing a high-priority research agenda on which to base future research. The specific aims of the conference were to: 1) understand the current state of evidence regarding emergency department (ED) diagnostic imaging utilization and identify key opportunities, limitations, and gaps in knowledge; 2) develop a consensus-driven research agenda emphasizing priorities and opportunities for research in ED diagnostic imaging; and 3) explore specific funding mechanisms available to facilitate research in ED diagnostic imaging. Over a 2-year period, the executive committee and other experts in the field convened regularly to identify specific areas in need of future research. Six content areas within emergency diagnostic imaging were identified prior to the conference and served as the breakout groups on which consensus was achieved: clinical decision rules; use of administrative data; patient-centered outcomes research; training, education, and competency; knowledge translation and barriers to imaging optimization; and comparative effectiveness research in alternatives to traditional computed tomography use. The executive committee invited key stakeholders to assist with planning and to participate in the consensus conference to generate a multidisciplinary agenda. There were 164 individuals involved in the conference spanning various specialties, including emergency medicine (EM), radiology, surgery, medical physics, and the decision sciences. This issue of AEM is dedicated to the proceedings of the 16th annual AEM consensus conference as well as original research related to emergency diagnostic imaging.
Kristiansen, G; Delahunt, B; Srigley, J R; Lüders, C; Lunkenheimer, J-M; Gevensleben, H; Thiesler, T; Montironi, R; Egevad, L
The 2012 consensus conference of the International Society of Urological Pathology (ISUP) has formulated recommendations on classification, prognostic factors and staging as well as immunohistochemistry and molecular pathology of renal tumors. Agreement was reached on the recognition of five new tumor entities: tubulocystic renal cell carcinoma (RCC), acquired cystic kidney disease-associated RCC, clear cell (tubulo) papillary RCC, microphthalmia transcription factor family RCC, in particular t(6;11) RCC and hereditary leiomyomatosis-associated RCC. In addition three rare forms of carcinoma were considered as emerging or provisional entities: thyroid-like follicular RCC, succinate dehydrogenase B deficiency-associated RCC and anaplastic lymphoma kinase (ALK) translocation RCC. In the new ISUP Vancouver classification, modifications to the existing 2004 World Health Organization (WHO) specifications are also suggested. Tumor morphology, a differentiation between sarcomatoid and rhabdoid and tumor necrosis were emphasized as being significant prognostic parameters for RCC. The consensus ISUP grading system assigns clear cell and papillary RCCs to grades 1-3 due to nucleolar prominence and grade 4 is reserved for cases with extreme nuclear pleomorphism, sarcomatoid and/or rhabdoid differentiation. Furthermore, consensus guidelines were established for the preparation of samples. For example, agreement was also reached that renal sinus invasion is diagnosed when the tumor is in direct contact with the fatty tissue or loose connective tissue of the sinus (intrarenal peripelvic fat) or when endothelialized cavities within the renal sinus are invaded by the tumor, independent of the size. The importance of biomarkers for the diagnostics or prognosis of renal tumors was also emphasized and marker profiles were formulated for use in specific differential diagnostics.
Apetoh, Lionel; Smyth, Mark J; Drake, Charles G; Abastado, Jean-Pierre; Apte, Ron N; Ayyoub, Maha; Blay, Jean-Yves; Bonneville, Marc; Butterfield, Lisa H; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Esteban; Chen, Lieping; Colombo, Mario P; Comin-Anduix, Begoña; Coukos, Georges; Dhodapkar, Madhav V; Dranoff, Glenn; Frazer, Ian H; Fridman, Wolf-Hervé; Gabrilovich, Dmitry I; Gilboa, Eli; Gnjatic, Sacha; Jäger, Dirk; Kalinski, Pawel; Kaufman, Howard L; Kiessling, Rolf; Kirkwood, John; Knuth, Alexander; Liblau, Roland; Lotze, Michael T; Lugli, Enrico; Marincola, Francesco; Melero, Ignacio; Melief, Cornelis J; Mempel, Thorsten R; Mittendorf, Elizabeth A; Odun, Kunle; Overwijk, Willem W; Palucka, Anna Karolina; Parmiani, Giorgio; Ribas, Antoni; Romero, Pedro; Schreiber, Robert D; Schuler, Gerold; Srivastava, Pramod K; Tartour, Eric; Valmori, Danila; van der Burg, Sjoerd H; van der Bruggen, Pierre; van den Eynde, Benoît J; Wang, Ena; Zou, Weiping; Whiteside, Theresa L; Speiser, Daniel E; Pardoll, Drew M; Restifo, Nicholas P; Anderson, Ana C
Whereas preclinical investigations and clinical studies have established that CD8(+) T cells can profoundly affect cancer progression, the underlying mechanisms are still elusive. Challenging the prevalent view that the beneficial effect of CD8(+) T cells in cancer is solely attributable to their cytotoxic activity, several reports have indicated that the ability of CD8(+) T cells to promote tumor regression is dependent on their cytokine secretion profile and their ability to self-renew. Evidence has also shown that the tumor microenvironment can disarm CD8(+) T cell immunity, leading to the emergence of dysfunctional CD8(+) T cells. The existence of different types of CD8(+) T cells in cancer calls for a more precise definition of the CD8(+) T cell immune phenotypes in cancer and the abandonment of the generic terms "pro-tumor" and "antitumor." Based on recent studies investigating the functions of CD8(+) T cells in cancer, we here propose some guidelines to precisely define the functional states of CD8(+) T cells in cancer.
Apetoh, Lionel; Smyth, Mark J.; Drake, Charles G.; Abastado, Jean-Pierre; Apte, Ron N.; Ayyoub, Maha; Blay, Jean-Yves; Bonneville, Marc; Butterfield, Lisa H.; Caignard, Anne; Castelli, Chiara; Cavallo, Federica; Celis, Esteban; Chen, Lieping; Colombo, Mario P.; Comin-Anduix, Begoña; Coukos, Georges; Dhodapkar, Madhav V.; Dranoff, Glenn; Frazer, Ian H.; Fridman, Wolf-Hervé; Gabrilovich, Dmitry I.; Gilboa, Eli; Gnjatic, Sacha; Jäger, Dirk; Kalinski, Pawel; Kaufman, Howard L.; Kiessling, Rolf; Kirkwood, John; Knuth, Alexander; Liblau, Roland; Lotze, Michael T.; Lugli, Enrico; Marincola, Francesco; Melero, Ignacio; Melief, Cornelis J.; Mempel, Thorsten R.; Mittendorf, Elizabeth A.; Odun, Kunle; Overwijk, Willem W.; Palucka, Anna Karolina; Parmiani, Giorgio; Ribas, Antoni; Romero, Pedro; Schreiber, Robert D.; Schuler, Gerold; Srivastava, Pramod K.; Tartour, Eric; Valmori, Danila; van der Burg, Sjoerd H.; van der Bruggen, Pierre; van den Eynde, Benoît J.; Wang, Ena; Zou, Weiping; Whiteside, Theresa L.; Speiser, Daniel E.; Pardoll, Drew M.; Restifo, Nicholas P.; Anderson, Ana C.
Whereas preclinical investigations and clinical studies have established that CD8+ T cells can profoundly affect cancer progression, the underlying mechanisms are still elusive. Challenging the prevalent view that the beneficial effect of CD8+ T cells in cancer is solely attributable to their cytotoxic activity, several reports have indicated that the ability of CD8+ T cells to promote tumor regression is dependent on their cytokine secretion profile and their ability to self-renew. Evidence has also shown that the tumor microenvironment can disarm CD8+ T cell immunity, leading to the emergence of dysfunctional CD8+ T cells. The existence of different types of CD8+ T cells in cancer calls for a more precise definition of the CD8+ T cell immune phenotypes in cancer and the abandonment of the generic terms “pro-tumor” and “antitumor.” Based on recent studies investigating the functions of CD8+ T cells in cancer, we here propose some guidelines to precisely define the functional states of CD8+ T cells in cancer. PMID:26137416
National Institutes of Health (DHHS), Bethesda, MD.
A policy statement by a group of experts on screening blood donations for contamination by human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS), is presented in this document. This document provides policy recommendations formed by a consensus conference sponsored by the National Institutes of Health…
National Inst. of Child Health and Human Development (NIH), Bethesda, MD.
This document compiles abstracts of papers that were presented at a 3-day conference of experts which developed a consensus statement on early identification of hearing impairment in infants and young children. Papers addressed taxonomy; epidemiology; developmental consequences of early hearing impairment; methodology, instrumentation, and…
Hu, Jie; Qian, Gui-Sheng; Bai, Chun-Xue
The incidence and mortality of lung cancer in China have rapidly increased. Lung cancer is the leading cause of cancer death in China, possibly because of the inadequate early diagnosis of lung cancer. Reaching a consensus on early diagnostic strategies for lung cancer in China is an unmet needed. Recently, much progress has been made in lung cancer diagnosis, such as screening in high-risk populations, the application of novel imaging technologies, and the use of minimally invasive techniques for diagnosis. However, systemic reviews of disease history, risk assessment, and patients' willingness to undergo invasive diagnostic procedures also need to be considered. A diagnostic strategy for lung cancer should be proposed and developed by a multidisciplinary group. A comprehensive evaluation of patient factors and clinical findings should be completed before treatment.
Arrieta, Oscar; Guzmán-de Alba, Enrique; Alba-López, Luis Felipe; Acosta-Espinoza, Alicia; Alatorre-Alexander, Jorge; Alexander-Meza, José Francisco; Allende-Pérez, Silvia Rosa; Alvarado-Aguilar, Salvador; Araujo-Navarrete, Margarita E; Argote-Greene, Luis Marcelo; Aquino-Mendoza, Cinthia Alejandra; Astorga-Ramos, Alma Magdalena; Austudillo-de la Vega, Horacio; Avilés-Salas, Alejandro; Barajas-Figueroa, Luis Javier; Barroso-Quiroga, Nimbe; Blake-Cerda, Mónica; Cabrera-Galeana, Paula Anel; Calderillo-Ruíz, Germán; Campos-Parra, Alma Delia; Cano-Valdez, Ana María; Capdeville-García, Daniel; Castillo-Ortega, Graciano; Casillas-Suárez, Catalina; Castillo-González, Patricia; Corona-Cruz, José Francisco; Correa-Acevedo, María Elma; Cortez-Ramírez, Séfora Sonciry; de la Cruz-Vargas, Jhony Alberto; de la Garza-Salazar, Jaime G; de la Mata-Moya, María Dolores; Domínguez-Flores, María Eugenia; Domínguez-Malagón, Hugo Ricardo; Domínguez-Parra, Luis Manuel; Domínguez-Peregrina, Alfredo; Durán-Alcocer, Jaime; Enríquez-Aceves, María Isabel; Elizondo-Ríos, Abelardo; Escobedo-Sánchez, Moisés Dante; de Villafranca, Pablo Espinosa-Mireles; Flores-Cantisani, Alberto; Flores-Gutiérrez, Juan Pablo; Franco-Marina, Francisco; Franco-González, Edwin Efraín; Franco-Topete, Ramón Antonio; Fuentes-de la Peña, Homero; Galicia-Amor, Susana; Gallardo-Rincón, Dolores; Gamboa-Domínguez, Armando; García-Andreu, Jorge; García-Cuéllar, Claudia María; García-Sancho-Figueroa, María Cecilia; García-Torrentera, Rogelio; Gerson-Cwilich, Raquel; Gómez-González, Arturo; Green-Schneeweiss, León; Guillén-Núñez, María del Rocío; Gutiérrez-Velázquez, Hilda; Ibarra-Pérez, Carlos; Jiménez-Fuentes, Edgardo; Juárez-Sánchez, Paula; Juárez-Ramiro, Alejandro; Kelly-García, Javier; Kuri-Exsome, Roberto; Lázaro-León, Jesús Miguel; León-Rodríguez, Eucario; Llanos-Osuna, Sara; Llanos-Osuna, Sara; Loyola-García, Ulises; López-González, José Sullivan; López y de Antuñano, Francisco Javier; Loustaunau-Andrade, Marco Antonio; Macedo-Pérez, Eleazar Omar; Machado-Villarroel, Limberth; Magallanes-Maciel, Manuel; Martínez-Barrera, Luis; Martínez-Cedillo, Jorge; Martínez-Martínez, Gloria; Medina-Esparza, Alfredo; Meneses-García, Abelardo; Mohar-Betancourt, Alejandro; Morales Blanhir, Jaime; Morales-Gómez, José; Motola-Kuba, Daniel; Nájera-Cruz, Marcela Patricia; Núñez-Valencia, Carolina del Carmen; Ocampo-Ocampo, María Angélica; Ochoa-Vázquez, María Dolores; Olivares-Torres, Carlos A; Palomar-Lever, Andrés; Patiño-Zarco, Mario; Pérez-Padilla, Rogelio; Peña-Alonso, Yolanda Rocío; Pérez-Romo, Alfredo Rafael; Aquilino Pérez, Mario; Pinaya-Ruíz, Paulo Martín; Pointevin-Chacón, María Adela; Poot-Braga, Juan José; Posadas-Valay, Rodolfo; Ramirez-Márquez, Marcelino; Reyes-Martínez, Ivonne; Robledo-Pascual, Julio; Rodríguez-Cid, Jerónimo; Rojas-Marín, Carlos Enrique; Romero-Bielma, Elizabeth; Rubio-Gutiérrez, Jaime Ernesto; Sáenz-Frías, Julia Angelina; Salazar-Lezama, Miguel Angel; Sánchez-Lara, Karla; Sansores Martínez, Raúl; Santillán-Doherty, Patricio; Alejandro-Silva, Juan; Téllez-Becerra, José Luis; Toledo-Buenrostro, Vinicio; Torre-Bouscoulet, Luis; Torecillas-Torres, Laura; Torres, Marineé; Tovar-Guzmán, Víctor; Turcott-Chaparro, Jenny Georgina; Vázquez-Cortés, Jesús Javier; Vázquez-Manríquez, María Eugenia; Vilches-Cisneros, Natalia; Villegas-Elizondo, José Felipe; Zamboni, Mauro M; Zamora-Moreno, Jesús; Zinser-Sierra, Juan W
Mexican specialists in oncology, oncologic surgery, thoracic surgery, pneumology, pathology, molecular biology, anesthesiology, algology, psychology, nutrition, and rehabilitation (all of them experts in lung cancer treatment) in order to develop the National Consensus on Lung Cancer. The consensus has been developed as an answer to the need of updated Mexican guidelines for the optimal treatment of the disease, as well as to the requirements that such guidelines be established by multidisciplinary panel, depicting the current attention given to cancer lung cases in Mexico. Thus, this paper analyses the epidemiological review, screening, diagnosis, staging, pathology, translational medicine, and the suitable therapies for early, locally advanced, and metastatic disease in the first, second, and third lines of management, as well as rehabilitation and palliative measures.
Barrett-Lee, Peter J.; Gosney, Margot A.; Willett, Alexis M.; Reed, Malcolm W.; Hammond, Pauline J.
This qualitative study investigated the attitudes, perceptions, and practices of breast cancer specialists with reference to the effect of patient age on management decisions in breast cancer, and attempted to identify national consensus on this issue. One hundred thirty-three relevant specialists, including 75 surgeons and 43 oncologists, participated in a virtual consultation using e-mailed questionnaires and open-ended discussion documents, culminating in the development of proposed consensus statements sent to participants for validation. A strong consensus was seen in favor of incorporating minimum standards of diagnostic services, treatment, and care for older patients with breast cancer into relevant national guidance, endorsed by professional bodies. Similarly, an overwhelming majority of participants agreed that simple, evidence-based protocols or guidelines on standardizing assessment of biological and chronological age should be produced by the National Institute for Health and Clinical Excellence and the Scottish Medicines Consortium, developed in collaboration with specialist oncogeriatricians, and endorsed by professional bodies. A further recommendation that all breast cancer patient treatment and diagnostic procedures be undertaken in light of up-to-date, relevant scientific data met with majority support. This study was successful in gauging national specialist opinion regarding the effect of patient age on management decisions in breast cancer in the U.K. PMID:20551430
Small, William Mell, Loren K.; Anderson, Penny; Creutzberg, Carien; De Los Santos, Jennifer; Gaffney, David; Jhingran, Anuja; Portelance, Lorraine; Schefter, Tracey; Iyer, Revathy; Varia, Mahesh; Winter, Kathryn M.S.; Mundt, Arno J.
Purpose: To develop an atlas of the clinical target volume (CTV) definitions for postoperative radiotherapy of endometrial and cervical cancer to be used for planning pelvic intensity-modulated radiotherapy. Methods and Materials: The Radiation Therapy Oncology Group led an international collaberation of cooperative groups in the development of the atlas. The groups included the Radiation Therapy Oncology Group, Gynecologic Oncology Group, National Cancer Institute of Canada, European Society of Therapeutic Radiology and Oncology, and American College of Radiology Imaging Network. The members of the group were asked by questionnaire to define the areas that were to be included in the CTV and to outline theses areas on individual computed tomography images. The initial formulation of the group began in late 2004 and culminated with a formal consensus conference in June 2005. Results: The committee achieved a consensus CTV definition for postoperative therapy for endometrial and cervical cancer. The CTV should include the common, external, and internal iliac lymph node regions. The upper 3.0 cm of the vagina and paravaginal soft tissue lateral to the vagina should also be included. For patients with cervical cancer, or endometrial cancer with cervical stromal invasion, it is also recommended that the CTV include the presacral lymph node region. Conclusion: This report serves as an international template for the definition of the CTV for postoperative intensity-modulated radiotherapy for endometrial and cervical cancer.
Bouchard, Claude; And Others
Presents eight papers: "Physical Activity and Health"; "Exercise and Physical Health"; "Exercise and Physical Health: Cancer and Immune Function"; "Exercise and Psychosocial Health"; "Physical Activity, Health, and Wellbeing at Different Life Stages"; "Descriptive Epidemiology of…
We have spent this first part of the project preparing background material for conference participants and making arrangements for the conference itself. Material regarding state regulatory constraints to the use of bioremediation in the cleanup of radionuclides and heavy metals at DOE sites around the country has been added to the Bioremediation Briefing paper for participants. The Steering Committee has been formulated and will hold their first meeting via phone conference on Monday, September 13, 2005. On the agenda is identification of conference participants, experts, and initial issues likely to be addressed. Human Subjects approval has been secured from the University. The ''pre-test'' has been developed and is ready to implement. The Consensus Conference will be held in Phoenix, AZ during January and February 2005; we are working with the Chamber of Commerce to find an appropriate site.
Kamat, Ashish M; Flaig, Thomas W; Grossman, H Barton; Konety, Badrinath; Lamm, Donald; O'Donnell, Michael A; Uchio, Edward; Efstathiou, Jason A; Taylor, John A
Multiple clinical trials have demonstrated that intravesical Bacillus Calmette-Guérin (BCG) treatment reduces recurrences and progression in patients with non-muscle-invasive bladder cancer (NMIBC). However, although BCG has been in use for almost 40 years, this agent is often underutilized and practice patterns of administration vary. This neglect is most likely caused by uncertainties about the optimal use of BCG, including unawareness of optimal treatment schedules and about patient populations that most benefit from BCG treatment. To address this deficit, a focus group of specialized urologic oncologists (urologists, medical oncologists and radiation oncologists) reviewed the current guidelines and clinical evidence, discussed their experiences and formed a consensus regarding the optimal use of BCG in the management of patients with NIMBC. The experts concluded that continuing therapy with 3-week BCG maintenance is superior to induction treatment only and is the single most important factor in improving outcomes in patients with NMIBC. They also concluded that a reliable alternative to radical cystectomy in truly BCG-refractory disease remains the subject of clinical trials. In addition, definitions for common terms of BCG failure, such as BCG-refractory and BCG-intolerant, have been formulated.
A consensus statement of 100 experts meeting at the Aljoya Conference Center in Seattle, Washington in July 2000 for the First International Conference on Trans-Pacific Transport of Atmospheric Contaminants.
Blecha, Christiane; Wolff, Daniel; Holler, Barbara; Holler, Ernst; Weber, Daniela; Vogt, Regine; Helbig, Horst; Dietrich-Ntoukas, Tina
The purpose of the study was to validate a recently proposed new grading system for ocular manifestations of chronic graft-versus-host disease (cGVHD). Diagnosis of cGVHD was based on the NIH consensus criteria. In addition, a grading scale was applied, which has been developed by the German-Austrian-Swiss Consensus Conference on Clinical Practice in cGVHD. Sixty-six patients (male n = 46, female n = 20, mean age 48 years) with ocular cGVHD were included. Application of the proposed Consensus Conference grading revealed inflammatory activity in all patients with mild (33 %), moderate (44 %), or severe inflammation (23 %). Clinical scoring by the NIH scoring system showed that 6 % of patients had mild symptoms; 59 % of patients had moderate dry eye symptoms partially affecting activities of daily living, without vision impairment; and 35 % of patients had severe dry eye symptoms significantly affecting daily activities. Clinical characterization and grading by the Consensus Conference grading scale revealed that ocular cGVHD (1) frequently leads to severe ocular surface disease based on impaired function of the lacrimal glands and involvement of cornea, conjunctiva, and lids; (2) is mostly associated with ongoing inflammatory activity; (3) often leads to functional impairment and reduced quality of life; and (4) is associated with an increased risk for severe, sight-threatening complications.
Morley, John E.; Morris, John C.; Berg-Weger, Marla; Borson, Soo; Carpenter, Brian D.; del Campo, Natalia; Dubois, Bruno; Fargo, Keith; Fitten, L. Jaime; Flaherty, Joseph H.; Ganguli, Mary; Grossberg, George T.; Malmstrom, Theodore K.; Petersen, Ronald D.; Rodriguez, Carroll; Saykin, Andrew J.; Scheltens, Philip; Tangalos, Eric G.; Verghese, Joe; Wilcock, Gordon; Winblad, Bengt; Woo, Jean; Vellas, Bruno
Cognitive impairment creates significant challenges for patients, their families and friends, and clinicians who provide their health care. Early recognition allows for diagnosis and appropriate treatment, education, psychosocial support, and engagement in shared decision-making regarding life planning, health care, involvement in research, and financial matters. An IAGG-GARN consensus panel examined the importance of early recognition of impaired cognitive health. Their major conclusion was that case-finding by physicians and health professionals is an important step toward enhancing brain health for aging populations throughout the world. This conclusion is in keeping with the position of the United States’ Centers for Medicare and Medicaid Services that reimburses for detection of cognitive impairment as part the of Medicare Annual Wellness Visit and with the international call for early detection of cognitive impairment as a patient’s right. The panel agreed on the following specific findings: (1) validated screening tests are available that take 3 to 7 minutes to administer; (2) a combination of patient- and informant-based screens is the most appropriate approach for identifying early cognitive impairment; (3) early cognitive impairment may have treatable components; and (4) emerging data support a combination of medical and lifestyle interventions as a potential way to delay or reduce cognitive decline. PMID:26315321
Gunn, Martin L; Marin, Jennifer R; Mills, Angela M; Chong, Suzanne T; Froemming, Adam T; Johnson, Jamlik O; Kumaravel, Manickam; Sodickson, Aaron D
In May 2015, the Academic Emergency Medicine consensus conference "Diagnostic imaging in the emergency department: a research agenda to optimize utilization" was held. The goal of the conference was to develop a high-priority research agenda regarding emergency diagnostic imaging on which to base future research. In addition to representatives from the Society of Academic Emergency Medicine, the multidisciplinary conference included members of several radiology organizations: American Society for Emergency Radiology, Radiological Society of North America, the American College of Radiology, and the American Association of Physicists in Medicine. The specific aims of the conference were to (1) understand the current state of evidence regarding emergency department (ED) diagnostic imaging utilization and identify key opportunities, limitations, and gaps in knowledge; (2) develop a consensus-driven research agenda emphasizing priorities and opportunities for research in ED diagnostic imaging; and (3) explore specific funding mechanisms available to facilitate research in ED diagnostic imaging. Through a multistep consensus process, participants developed targeted research questions for future research in six content areas within emergency diagnostic imaging: clinical decision rules; use of administrative data; patient-centered outcomes research; training, education, and competency; knowledge translation and barriers to imaging optimization; and comparative effectiveness research in alternatives to traditional computed tomography use.
Rudow, Dianne LaPointe; Milton, Jennifer; Rodrigue, James R.; Schold, Jesse D.; Hays, Rebecca
Live-donor kidney transplantation (LDKT) is the best treatment for eligible people with late-stage kidney disease. Despite this, living kidney donation rates have declined in the United States in recent years. A potential source of this decline is the financial impact on potential and actual living kidney donors (LKDs). Recent evidence indicates that the economic climate may be associated with the decline in LDKT and that there are nontrivial financial ramifications for some LKDs. In June 2014, the American Society of Transplantation’s Live Donor Community of Practice convened a Consensus Conference on Best Practices in Live Kidney Donation. The conference included transplant professionals, patients, and other key stakeholders (with the financial support of 10 other organizations) and sought to identify best practices, knowledge gaps, and opportunities pertaining to living kidney donation. This workgroup was tasked with exploring systemic and financial barriers to living kidney donation. The workgroup reviewed literature that assessed the financial effect of living kidney donation, analyzed employment and insurance factors, discussed international models for addressing direct and indirect costs faced by LKDs, and summarized current available resources. The workgroup developed the following series of recommendations to reduce financial and systemic barriers and achieve financial neutrality for LKDs: (1) allocate resources for standardized reimbursement of LKDs' lost wages and incidental costs; (2) pass legislation to offer employment and insurability protections to LKDs; (3) create an LKD financial toolkit to provide standardized, vetted education to donors and providers about options to maximize donor coverage and minimize financial effect within the current climate; and (4) promote further research to identify systemic barriers to living donation and LDKT to ensure the creation of mitigation strategies. PMID:26002904
Tushla, Lara; Rudow, Dianne LaPointe; Milton, Jennifer; Rodrigue, James R; Schold, Jesse D; Hays, Rebecca
Live-donor kidney transplantation (LDKT) is the best treatment for eligible people with late-stage kidney disease. Despite this, living kidney donation rates have declined in the United States in recent years. A potential source of this decline is the financial impact on potential and actual living kidney donors (LKDs). Recent evidence indicates that the economic climate may be associated with the decline in LDKT and that there are nontrivial financial ramifications for some LKDs. In June 2014, the American Society of Transplantation's Live Donor Community of Practice convened a Consensus Conference on Best Practices in Live Kidney Donation. The conference included transplant professionals, patients, and other key stakeholders (with the financial support of 10 other organizations) and sought to identify best practices, knowledge gaps, and opportunities pertaining to living kidney donation. This workgroup was tasked with exploring systemic and financial barriers to living kidney donation. The workgroup reviewed literature that assessed the financial effect of living kidney donation, analyzed employment and insurance factors, discussed international models for addressing direct and indirect costs faced by LKDs, and summarized current available resources. The workgroup developed the following series of recommendations to reduce financial and systemic barriers and achieve financial neutrality for LKDs: (1) allocate resources for standardized reimbursement of LKDs' lost wages and incidental costs; (2) pass legislation to offer employment and insurability protections to LKDs; (3) create an LKD financial toolkit to provide standardized, vetted education to donors and providers about options to maximize donor coverage and minimize financial effect within the current climate; and (4) promote further research to identify systemic barriers to living donation and LDKT to ensure the creation of mitigation strategies.
Beutner, K R; Reitano, M V; Richwald, G A; Wiley, D J
A consensus process was undertaken to describe and evaluate current information and practice regarding the diagnosis, treatment, and evaluation of patients with external genital warts (EGWs) and their sex partners. This process developed a number of key statements that were based on strong evidence in the literature or reasonable suppositions and opinions of experts. Key statements included the following. In most cases, EGWs can be diagnosed clinically by visual inspection. No one treatment is ideal for all patients or all warts. Women with EGWs and female sex partners of men with EGWs are at increased risk for human papillomavirus-related cervical disease and, like all women, should be screened for cervical cancer. The diagnosis of EGWs in children requires a sexual abuse evaluation. Clinicians who treat EGWs have a responsibility to counsel patients and to provide information about the infectivity, diagnosis, treatment, and natural history of EGWs and general information about sexual health and other sexually transmitted diseases.
Bourke, Billy; Ceponis, Peter; Chiba, Naoki; Czinn, Steve; Ferraro, Richard; Fischbach, Lori; Gold, Ben; Hyunh, Hien; Jacobson, Kevan; Jones, Nicola L; Koletzko, Sibylle; Lebel, Sylvie; Moayyedi, Paul; Ridell, Robert; Sherman, Philip; van Zanten, Sander; Beck, Ivan; Best, Linda; Boland, Margaret; Bursey, Ford; Chaun, Hugh; Cooper, Geraldine; Craig, Brian; Creuzenet, Carole; Critch, Jeffrey; Govender, Krishnasamy; Hassall, Eric; Kaplan, Alan; Keelan, Monica; Noad, Garth; Robertson, Marli; Smith, Lesley; Stein, Markus; Taylor, Diane; Walters, Thomas; Persaud, Robin; Whitaker, Scott; Woodland, Robert
As an update to previously published recommendations for the management of Helicobacter pylori infection, an evidence-based appraisal of 14 topics was undertaken in a consensus conference sponsored by the Canadian Helicobacter Study Group. The goal was to update guidelines based on the best available evidence using an established and uniform methodology to address and formulate recommendations for each topic. The degree of consensus for each recommendation is also presented. The clinical issues addressed and recommendations made were: population-based screening for H. pylori in asymptomatic children to prevent gastric cancer is not warranted; testing for H. pylori in children should be considered if there is a family history of gastric cancer; the goal of diagnostic interventions should be to determine the cause of presenting gastrointestinal symptoms and not the presence of H. pylori infection; recurrent abdominal pain of childhood is not an indication to test for H. pylori infection; H. pylori testing is not required in patients with newly diagnosed gastroesophageal reflux disease; H. pylori testing may be considered before the use of long-term proton pump inhibitor therapy; testing for H. pylori infection should be considered in children with refractory iron deficiency anemia when no other cause has been found; when investigation of pediatric patients with persistent or severe upper abdominal symptoms is indicated, upper endoscopy with biopsy is the investigation of choice; the 13C-urea breath test is currently the best noninvasive diagnostic test for H. pylori infection in children; there is currently insufficient evidence to recommend stool antigen tests as acceptable diagnostic tools for H. pylori infection; serological antibody tests are not recommended as diagnostic tools for H. pylori infection in children; first-line therapy for H. pylori infection in children is a twice-daily, triple-drug regimen comprised of a proton pump inhibitor plus two antibiotics
Silversides, Candice K; Salehian, Omid; Oechslin, Erwin; Schwerzmann, Markus; Vonder Muhll, Isabelle; Khairy, Paul; Horlick, Eric; Landzberg, Mike; Meijboom, Folkert; Warnes, Carole; Therrien, Judith
With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. They have distinctive forms of heart failure and their cardiac disease can be associated with pulmonary hypertension, thromboemboli, complex arrhythmias and sudden death. Medical aspects that need to be considered relate to the long-term and multisystemic effects of single ventricle physiology, cyanosis, systemic right ventricles, complex intracardiac baffles and failing subpulmonary right ventricles. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. Part III of the guidelines includes recommendations for the care of patients with complete transposition of the great arteries, congenitally corrected transposition of the great arteries, Fontan operations and single ventricles, Eisenmenger's syndrome, and cyanotic heart disease. Topics addressed include genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy risk and follow-up requirements. The complete document consists of four manuscripts, which are published online in the present issue of The Canadian Journal of Cardiology. The complete document and references can also be found at www.ccs.ca or www.cachnet.org.
Silversides, Candice K; Marelli, Ariane; Beauchesne, Luc; Dore, Annie; Kiess, Marla; Salehian, Omid; Bradley, Timothy; Colman, Jack; Connelly, Michael; Harris, Louise; Khairy, Paul; Mital, Seema; Niwa, Koichiro; Oechslin, Erwin; Poirier, Nancy; Schwerzmann, Markus; Taylor, Dylan; Vonder Muhll, Isabelle; Baumgartner, Helmut; Benson, Lee; Celermajer, David; Greutmann, Matthias; Horlick, Eric; Landzberg, Mike; Meijboom, Folkert; Mulder, Barbara; Warnes, Carole; Webb, Gary; Therrien, Judith
With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. They have distinctive forms of heart failure, and their cardiac disease can be associated with pulmonary hypertension, thromboemboli, complex arrhythmias and sudden death.Medical aspects that need to be considered relate to the long-term and multisystemic effects of single-ventricle physiology, cyanosis, systemic right ventricles, complex intracardiac baffles and failing subpulmonary right ventricles. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the understanding of the late outcomes, genetics, medical therapy and interventional approaches in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. The present executive summary is a brief overview of the new guidelines and includes the recommendations for interventions. The complete document consists of four manuscripts that are published online in the present issue of The Canadian Journal of Cardiology, including sections on genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy and contraception risks, and follow-up requirements. The complete document and references can also be found at www.ccs.ca or www.cachnet.org.
North-America and northern European countries exhibit the highest incidence rate of breast cancer, whereas women in southern regions are relatively protected. Immigrants from low cancer incidence regions to high-incidence areas might exhibit similarly higher or excessive cancer risk as compared with the inhabitants of their adoptive country. Additional cancer risk may be conferred by incongruence between their biological characteristics and foreign environment. Many studies established the racial/ethnic disparities in the risk and nature of female breast cancer in United States between African-American and Caucasian women. Mammary tumors in black women are diagnosed at earlier age, and are associated with higher rate of mortality as compared with cancers of white cases. Results of studies on these ethnic/racial differences in breast cancer incidence suggest that excessive pigmentation of dark skinned women results in a relative light-deficiency. Poor light exposure may explain the deleterious metabolic and hormonal alterations; such as insulin resistance, deficiencies of estrogen, thyroxin and vitamin-D conferring excessive cancer risk. The more northern the location of an adoptive country the higher the cancer risk for dark skinned immigrants. Recognition of the deleterious systemic effects of darkness and excessive melatonin synthesis enables cancer protection treatment for people living in light-deficient environment. Recent patents provide new methods for the prevention of hormonal and metabolic abnormities.
Musti, Marina; Bruno, Caterina; Cassano, Filippo; Caputo, Angelo; Cauzillo, Gabriella; Cavone, Domenica; Convertini, Luca; De Blasio, Antonio; De Mei, Barbara; Marra, Mario; Montagano, Giuseppe; Schettino, Biagio; Zona, Amerigo; Comba, Pietro
Herein is reported the health surveillance document agreed upon during the Consensus Conference held in Rome at the Istituto Superiore di Sanità last year. The aim of the consensus conference was to define guidelines for epidemiologic and health surveillance of the resident population in the area of the Basilicata region exposed to tremolite pollution (Local Health Unit 3 territory Lagonegro, PZ). The health surveillance program for residents and the nested epidemiologic study evaluates for each resident willing to participate, individual exposure with a personal dosimeter, as well as the prevalence of obstructive, restrictive or mixed pulmonary functional patterns, searching for fiber and asbestos bodies in induced-sputum, the prevalence of non malignant asbestos disturbances related to pleural anomalies and, last but not least, provides information on risks and sensitization, advising on personal behaviour that could reduce the risks.
Mathieu, Daniel; Marroni, Alessandro; Kot, Jacek
The tenth European Consensus Conference on Hyperbaric Medicine took place in April 2016, attended by a large delegation of experts from Europe and elsewhere. The focus of the meeting was the revision of the European Committee on Hyperbaric Medicine (ECHM) list of accepted indications for hyperbaric oxygen treatment (HBOT), based on a thorough review of the best available research and evidence-based medicine (EBM). For this scope, the modified GRADE system for evidence analysis, together with the DELPHI system for consensus evaluation, were adopted. The indications for HBOT, including those promulgated by the ECHM previously, were analysed by selected experts, based on an extensive review of the literature and of the available EBM studies. The indications were divided as follows: Type 1, where HBOT is strongly indicated as a primary treatment method, as it is supported by sufficiently strong evidence; Type 2, where HBOT is suggested as it is supported by acceptable levels of evidence; Type 3, where HBOT can be considered as a possible/optional measure, but it is not yet supported by sufficiently strong evidence. For each type, three levels of evidence were considered: A, when the number of randomised controlled trials (RCTs) is considered sufficient; B, when there are some RCTs in favour of the indication and there is ample expert consensus; C, when the conditions do not allow for proper RCTs but there is ample and international expert consensus. For the first time, the conference also issued 'negative' recommendations for those conditions where there is Type 1 evidence that HBOT is not indicated. The conference also gave consensus-agreed recommendations for the standard of practice of HBOT.
Carrier, M.; Lazo–Langner, A.; Shivakumar, S.; Tagalakis, V.; Gross, P.L.; Blais, N.; Butts, C.A.; Crowther, M.
Venous thromboembolism is a common complication in cancer patients, and thromboembolism is the second most common cause of death after cancer progression. A number of clinical practice guidelines provide recommendations for the management of cancer-associated thrombosis. However, the guidelines lack recommendations covering commonly encountered clinical challenges (for example, thrombocytopenia, recurrent venous thromboembolism, etc.) for which little or no evidence exists. Accordingly, recommendations were developed to provide expert guidance to medical oncologists and other health care professionals caring for patients with cancer-associated thrombosis. The current expert consensus was developed by a team of 21 clinical experts. For each identified clinical challenge, the literature in medline, embase, and Evidence Based Medicine Reviews was systematically reviewed. The quality of the evidence was assessed, summarized, and graded. Consensus statements were generated, and the experts voted anonymously using a modified Delphi process on their level of agreement with the various statements. Statements were progressively revised through separate voting iterations and were then finalized. Clinicians using these recommendations and suggestions should tailor patient management according to the risks and benefits of the treatment options, patient values and preferences, and local cost and resource allocations. PMID:25684988
Nyquist, Julie G.; And Others
This study investigated the educational process used in tumor boards (cancer case conferences) and whether the process varied based on type of board, frequency of meetings, and presence or absence of residency training programs in the hospital. These data were collected through observation of 715 board sessions of 37 hospitals and 43 tumor boards.…
Contemporary Gleason Grading of Prostatic Carcinoma: An Update With Discussion on Practical Issues to Implement the 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma.
Epstein, Jonathan I; Amin, Mahul B; Reuter, Victor E; Humphrey, Peter A
do not change the Grade Groups, such that in current practice one would, for example, report Gleason score 3+4=7 (Grade Group 2) with minor (tertiary) pattern 5. It was discussed at the 2014 Consensus Conference how minor high-grade patterns would be handled if Grade Groups 1 to 5 eventually were to replace Gleason scores 2 to 10. In the above example, it could be reported as Grade Group 2 with minor high-grade pattern or potentially this could be abbreviated to Grade Group 2+. The recommendation from the 2014 meeting was the same as in the 2005 consensus for grading separate cores with different grades: assign individual Gleason scores to separate cores as long as the cores were submitted in separate containers or the cores were in the same container yet specified by the urologist as to their location (ie, by different color inks). It is the practice of the majority of the authors of this manuscript that if the cores are submitted in a more specific anatomic manner than just left versus right (ie, per sextant site, MRI targets, etc.), that the grade of multiple cores in the same jar from that specific site are averaged together, given they are from the same location within the prostate. In cases with multiple fragmented cores in a jar, there was agreement to give a global Gleason score for that jar. The recommendation from the 2014 meeting was the same as in the 2005 consensus for grading separate nodules of cancer in RP specimens: one should assign a separate Gleason score to each dominant nodule(s). In the unusual occurrence of a nondominant nodule (ie, smaller nodule) that is of higher stage, one should also assign a grade to that nodule. If one of the smaller nodules is the highest grade focus within the prostate, the grade of this smaller nodule should also be recorded. An emerging issue in the studies and those published subsequent to the meeting was that cribriform morphology is associated with a worse prognosis than poorly formed or fused glands and in the
Samaratunga, Hemamali; Montironi, Rodolfo; True, Lawrence; Epstein, Jonathan I; Griffiths, David F; Humphrey, Peter A; van der Kwast, Theo; Wheeler, Thomas M; Srigley, John R; Delahunt, Brett; Egevad, Lars
The 2009 International Society of Urological Pathology Consensus Conference in Boston made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to the handling and processing of radical prostatectomy specimens were coordinated by working group 1. Most uropathologists followed similar procedures for fixation of radical prostatectomy specimens, with 51% of respondents transporting tissue in formalin. There was also consensus that the prostate weight without the seminal vesicles should be recorded. There was consensus that the surface of the prostate should be painted. It was agreed that both the prostate apex and base should be examined by the cone method with sagittal sectioning of the tissue sample. There was consensus that the gland should be fully fixed before sectioning. Both partial and complete embedding of prostates was considered to be acceptable as long as the method of partial embedding is stated. No consensus was determined regarding the necessity of weighing and measuring the length of the seminal vesicles, the preparation of whole mounts rather than standardized blocks and the methodology for sampling of fresh tissue for research purposes, and it was agreed that these should be left to the discretion of the working pathologist.
Wu, Abraham J.; Bosch, Walter R.; Chang, Daniel T.; Hong, Theodore S.; Jabbour, Salma K.; Kleinberg, Lawrence R.; Mamon, Harvey J.; Thomas, Charles R.; Goodman, Karyn A.
Purpose/Objective(s): Current guidelines for esophageal cancer contouring are derived from traditional 2-dimensional fields based on bony landmarks, and they do not provide sufficient anatomic detail to ensure consistent contouring for more conformal radiation therapy techniques such as intensity modulated radiation therapy (IMRT). Therefore, we convened an expert panel with the specific aim to derive contouring guidelines and generate an atlas for the clinical target volume (CTV) in esophageal or gastroesophageal junction (GEJ) cancer. Methods and Materials: Eight expert academically based gastrointestinal radiation oncologists participated. Three sample cases were chosen: a GEJ cancer, a distal esophageal cancer, and a mid-upper esophageal cancer. Uniform computed tomographic (CT) simulation datasets and accompanying diagnostic positron emission tomographic/CT images were distributed to each expert, and the expert was instructed to generate gross tumor volume (GTV) and CTV contours for each case. All contours were aggregated and subjected to quantitative analysis to assess the degree of concordance between experts and to generate draft consensus contours. The panel then refined these contours to generate the contouring atlas. Results: The κ statistics indicated substantial agreement between panelists for each of the 3 test cases. A consensus CTV atlas was generated for the 3 test cases, each representing common anatomic presentations of esophageal cancer. The panel agreed on guidelines and principles to facilitate the generalizability of the atlas to individual cases. Conclusions: This expert panel successfully reached agreement on contouring guidelines for esophageal and GEJ IMRT and generated a reference CTV atlas. This atlas will serve as a reference for IMRT contours for clinical practice and prospective trial design. Subsequent patterns of failure analyses of clinical datasets using these guidelines may require modification in the future.
Féart, Catherine; Mann, Giovanni; Viña, Jose; Chatterji, Somnath; Chodzko-Zajko, Wojtek; Gonzalez-Colaço Harmand, Magali; Bergman, Howard; Carcaillon, Laure; Nicholson, Caroline; Scuteri, Angelo; Sinclair, Alan; Pelaez, Martha; Van der Cammen, Tischa; Beland, François; Bickenbach, Jerome; Delamarche, Paul; Ferrucci, Luigi; Fried, Linda P.; Gutiérrez-Robledo, Luis Miguel; Rockwood, Kenneth; Rodríguez Artalejo, Fernando; Serviddio, Gaetano; Vega, Enrique
Background. There is no consensus regarding the definition of frailty for clinical uses. Methods. A modified Delphi process was used to attempt to achieve consensus definition. Experts were selected from different fields and organized into five Focus Groups. A questionnaire was developed and sent to experts in the area of frailty. Responses and comments were analyzed using a pre-established strategy. Statements with an agreement more than or equal to 80% were accepted. Results. Overall, 44% of the statements regarding the concept of frailty and 18% of the statements regarding diagnostic criteria were accepted. There was consensus on the value of screening for frailty and about the identification of six domains of frailty for inclusion in a clinical definition, but no agreement was reached concerning a specific set of clinical/laboratory biomarkers useful for diagnosis. Conclusions. There is agreement on the usefulness of defining frailty in clinical settings as well as on its main dimensions. However, additional research is needed before an operative definition of frailty can be established. PMID:22511289
Ladetto, M; Buske, C; Hutchings, M; Dreyling, M; Gaidano, G; Le Gouill, S; Luminari, S; Pott, C; Zamò, A; Zucca, E
The European Society for Medical Oncology (ESMO) consensus conference on mature B-cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop recommendations on critical subjects difficult to consider in detail in the ESMO Clinical Practice Guidelines. The following areas were identified: (i) the elderly patient, (ii) prognostic factors suitable for clinical use and (iii) the 'ultra-high-risk' group. Before the conference, the expert panel was divided into three working groups; each group focused on one of these areas in order to address four clinically relevant questions relating to that topic. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the consensus conference, each working group developed recommendations to address each of the four questions assigned to their group. These recommendations were then presented to the entire panel and a consensus was reached. This manuscript presents recommendations dedicated to the second area of interest, i.e. prognostic factors suitable for clinical use. The four topics [i.e. interim positron emission tomography (PET), TP53 mutations, cell of origin (COO) and minimal residual disease (MRD)] were primarily chosen because of the bulk of available data together with the lack of clear guidance regarding their use in clinical practice and within clinical trials. Results, including a summary of evidence supporting each recommendation, are detailed in this manuscript. The panel acknowledged that detection of TP53 inactivation by deletion or mutation in CLL should be implemented in clinical practice (level of evidence I, strength of recommendation A). Due to their potentially high prognostic value, at least in some lymphoma entities, implementation of interim PET, COO and MRD was highly recommended in the context of clinical trials. All
Easaw, J.C.; Shea–Budgell, M.A.; Wu, C.M.J.; Czaykowski, P.M.; Kassis, J.; Kuehl, B.; Lim, H.J.; MacNeil, M.; Martinusen, D.; McFarlane, P.A.; Meek, E.; Moodley, O.; Shivakumar, S.; Tagalakis, V.; Welch, S.; Kavan, P.
Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy has been shown to prevent vte; however, unique clinical circumstances in patients with cancer can often complicate the decisions surrounding the administration of prophylactic anticoagulation. No national Canadian guidelines on the prevention of cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin can be used prophylactically in cancer patients at high risk of developing vte. Direct oral anticoagulants are not recommended for vte prophylaxis at this time. Specific clinical scenarios, including renal insufficiency, thrombocytopenia, liver disease, and obesity can warrant modifications in the administration of prophylactic anticoagulant therapy. There is no evidence to support the monitoring of anti–factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, factor Xa levels could be checked at baseline and periodically in patients with renal insufficiency. The use of anticoagulation therapy to prolong survival in cancer patients without the presence of risk factors for vte is not recommended. PMID:25908912
Lee, Michael S; Menter, David G; Kopetz, Scott
Although clinical management of colon cancer generally has not accounted for the primary tumor site, left-sided and right-sided colon cancers harbor different clinical and biologic characteristics. Right-sided colon cancers are more likely to have genome-wide hypermethylation via the CpG island methylator phenotype (CIMP), hypermutated state via microsatellite instability, and BRAF mutation. There are also differential exposures to potential carcinogenic toxins and microbiota in the right and left colon. Gene expression analyses further shed light on distinct biologic subtypes of colorectal cancers (CRCs), with 4 consensus molecular subtypes (CMSs) identified. Importantly, these subtypes are differentially distributed between right- and left-sided CRCs, with greater proportions of the "microsatellite unstable/immune" CMS1 and the "metabolic" CMS3 subtypes found in right-sided colon cancers. This review summarizes important biologic distinctions between right- and left-sided CRCs that likely impact prognosis and may predict for differential responses to biologic therapy. Given the inferior prognosis of stage III-IV right-sided CRCs and emerging data suggesting that anti-epidermal growth factor receptor antibody therapy is associated with worse survival in right-sided stage IV CRCs compared with left-sided cancers, these biologic differences between right- and left-sided CRCs provide critical context and may provide opportunities to personalize therapy.
Hautmann, Anke Heidewig; Elad, Sharon; Lawitschka, Anita; Greinix, Hildegard; Bertz, Hartmut; Halter, Joerg; Faraci, Maura; Hofbauer, Lorenz Christian; Lee, Stephanie; Wolff, Daniel; Holler, Ernst
With improved outcome of allogeneic stem cell transplantation (allo-SCT) for hematologic malignancies, long-term complications gain greater importance. Skeletal complications such as osteoporosis or avascular necrosis (AVN) occur frequently in allogeneic recipients with a cumulative incidence of diminished bone mineral density of 24-50% between 2 and 12 months after allo-SCT and a cumulative incidence of AVN in as many as 19% of patients 3 years after allo-SCT. Here, we present a review as part of the German, Austrian, and Swiss Consensus Conference on clinical practice in chronic graft-versus-host disease, held 2009 in Regensburg. The Consensus Conference aimed to achieve a consensus on the current evidence of diagnosis, prevention, and therapeutic options of late complications after allo-SCT summarizing and discussing the literature on these topics. In this report, we provide recommendations for metabolic bone diseases agreed upon by the working party. This includes guidelines for diagnosis, prevention, and therapeutic options in patients with low bone mass or AVN.
Malyguine, Anatoli; Umansky, Victor; Kotlan, Beatrix; Aptsiauri, Natalia; Shurin, Michael R
The immune system is a critical element involved in the control of tumor development and progression. While professionals have learned how to manipulate the immune system to generate tumor-specific immune responses, cancer immunotherapy has not yet delivered substantial clinical benefits. It has become increasingly clear that tumor-induced abnormalities in the immune system not only hamper tumor immunosurveillance, but also limit the efficacy of cancer immunotherapy. Meanwhile, the results of recent studies allow the belief that one is on the edge of a real breakthrough in this promising direction in cancer therapy. The 2(nd) International Conference 'Cancer Immunotherapy and Immunomonitoring (CITIM)' was the second meeting in Eastern Europe to specifically focus on the issue of immune regulation in the tumor environment, cancer immunotherapy, and immunomonitoring of immunotherapeutic clinical trials. This CITIM Conference held in Budapest, Hungary, was comprised from 12 plenary sessions, Best Abstract Award session, Poster session, and four Keynote lectures. Outstanding presentations and numerous productive discussions summarized the current place of the field and opened new directions for improving monitoring and therapy for patients with cancer.
Rosário, Pedro Weslley; Ward, Laura S; Carvalho, Gisah A; Graf, Hans; Maciel, Rui M B; Maciel, Léa Maria Z; Maia, Ana Luiza; Vaisman, Mário
Thyroid nodules are frequent findings, especially when sensitive imaging methods are used. Although thyroid cancer is relatively rare, its incidence is increasing, particularly in terms of small tumors, which have an uncertain clinical relevance. Most patients with differentiated thyroid cancer exhibit satisfactory clinical outcomes when treatment is appropriate, and their mortality rate is similar to that of the overall population. However, relapse occurs in a considerable fraction of these patients, and some patients stop responding to conventional treatment and eventually die from their disease. Therefore, the challenge is how to identify the individuals who require more aggressive disease management while sparing the majority of patients from unnecessary treatments and procedures. We have updated the Brazilian Consensus that was published in 2007, emphasizing the diagnostic and therapeutic advances that the participants, representing several Brazilian university centers, consider most relevant in clinical practice. The formulation of the present guidelines was based on the participants' experience and a review of the relevant literature.
Rini, Brian I; McDermott, David F; Hammers, Hans; Bro, William; Bukowski, Ronald M; Faba, Bernard; Faba, Jo; Figlin, Robert A; Hutson, Thomas; Jonasch, Eric; Joseph, Richard W; Leibovich, Bradley C; Olencki, Thomas; Pantuck, Allan J; Quinn, David I; Seery, Virginia; Voss, Martin H; Wood, Christopher G; Wood, Laura S; Atkins, Michael B
Immunotherapy has produced durable clinical benefit in patients with metastatic renal cell cancer (RCC). In the past, patients treated with interferon-alpha (IFN) and interleukin-2 (IL-2) have achieved complete responses, many of which have lasted for multiple decades. More recently, a large number of new agents have been approved for RCC, several of which attack tumor angiogenesis by inhibiting vascular endothelial growth factors (VEGF) and VEGF receptors (VEGFR), as well as tumor metabolism, inhibiting the mammalian target of rapamycin (mTOR). Additionally, a new class of immunotherapy agents, immune checkpoint inhibitors, is emerging and will play a significant role in the treatment of patients with RCC. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a Task Force, which met to consider the current role of approved immunotherapy agents in RCC, to provide guidance to practicing clinicians by developing consensus recommendations and to set the stage for future immunotherapeutic developments in RCC.
Tangjitgamol, Siriwan; Anderson, Benjamin O; See, Hui Ti; Lertbutsayanukul, Chawalit; Sirisabya, Nakarin; Manchana, Tarinee; Ilancheran, Arunachalam; Lee, Khai Mun; Lim, Siew Eng; Chia, Yin-Nin; Domingo, Efren; Kim, Young-Tak; Lai, Chyong-Huey; Dali, Ahmad Zailani Hatta Mohd; Supakapongkul, Wisit; Wilailak, Sarikapan; Tay, Eng-Hseon; Kavanagh, John
Endometrial cancer is one of the gynaecological cancers that carries good overall prognosis because it is often detected at early stages of disease. The International Federation of Gynecology and Obstetrics replaced clinical staging with surgical staging in 1988 and updated the system in 2009. Controversies remain regarding the recommended screening protocol for women with a high risk of endometrial cancer, the role and benefit of retroperitoneal lymph-node dissection, the necessity of ovarian resection, the benefit and type of adjuvant radiation therapy, and the safety of hormone-replacement therapy after treatment. This article reviews the available evidence for optimum management of endometrial cancer and how management strategies can be applied in Asian countries with different levels of health-care resource availability and economic development. An overview of the literature for endometrial-cancer screening, diagnosis, and management is discussed. Consensus statements are formulated on the basis of basic, limited, enhanced, and maximum health-care resource availability, using the framework provided by the Breast Health Global Initiative.
Easaw, J.C.; Shea–Budgell, M.A.; Wu, C.M.J.; Czaykowski, P.M.; Kassis, J.; Kuehl, B.; Lim, H.J.; MacNeil, M.; Martinusen, D.; McFarlane, P.A.; Meek, E.; Moodley, O.; Shivakumar, S.; Tagalakis, V.; Welch, S.; Kavan, P.
Patients with cancer are at increased risk of venous thromboembolism (vte). Anticoagulation therapy is used to treat vte; however, patients with cancer have unique clinical circumstances that can often make decisions surrounding the administration of therapeutic anticoagulation complicated. No national Canadian guidelines on the management of established cancer-associated thrombosis have been published. We therefore aimed to develop a consensus-based, evidence-informed guideline on the topic. PubMed was searched for clinical trials and meta-analyses published between 2002 and 2013. Reference lists of key articles were hand-searched for additional publications. Content experts from across Canada were assembled to review the evidence and make recommendations. Low molecular weight heparin is the treatment of choice for cancer patients with established vte. Direct oral anticoagulants are not recommended for the treatment of vte at this time. Specific clinical scenarios, including the presence of an indwelling venous catheter, renal insufficiency, and thrombocytopenia, warrant modifications in the therapeutic administration of anticoagulation therapy. Patients with recurrent vte should receive extended (>3 months) anticoagulant therapy. Incidental vte should generally be treated in the same manner as symptomatic vte. There is no evidence to support the monitoring of anti–factor Xa levels in clinically stable cancer patients receiving prophylactic anticoagulation; however, levels of anti–factor Xa could be checked at baseline and periodically thereafter in patients with renal insufficiency. Follow-up and education about the signs and symptoms of vte are important components of ongoing patient care. PMID:25908913
Santolaya, María Elena; Rabagliati, Ricardo; Bidart, Teresa; Payá, Ernesto; Guzmán, Ana M; Morales, Ricardo; Braun, Stephanie; Bronfman, Lucía; Ferrés, Marcela; Flores, Claudio; García, Patricia; Letelier, Luz M; Puga, Bárbara; Salgado, Carmen; Thompson, Luis; Tordecilla, Juan; Zubieta, Marcela
The severity and duration of post chemotherapy neutropenia were recognized during the 1960s as main predisposing factors for infections in cancer patients. At the beginning of the 70's a standard management approach for all febrile neutropenia (FN) episodes was proposed, based on hospitalization and intravenous empirical broad spectrum antibiotic therapy. Widespread use of this approach resulted in a significant reduction in mortality attributable to bacterial infections. During the last 10 to 15 years, reappraisal of this standard approach has been done by several research groups who question the benefit of treating all FN patients similarly without taking in to consideration differences in severity of the FN episodes. This reappraisal has led during the 1990s to the development of the concept of high and low risk FN episodes that has been the base for the adoption of selective therapies based on the risk categorization of the individual patient. The Chilean Infectious Diseases Society called upon two government National Programs responsible for the appropriate distribution of chemotherapeutic drugs to all pediatric and adults cancer patients within the public health system, and upon the Chilean Hematology Society for the development of a Consensus on Diagnosis, Treatment and Prevention of Infections during FN Episodes in Cancer patients. The need for this Consensus is based on two main aspects: the new approaches proposed during the past year for management of these episodes, and the increasing population of cancer patients receiving improved chemotherapeutic agents that has increased there survival possibilities as well as there possibility to suffer a FN episode. The topics discussed in this document are based on an updated systematic and analytic review of the medical literature including epidemiology, laboratory diagnostics, risk categorization, treatment and prophylaxis. National data was included when available in order to provide the healthcare personnel
Although physical treatments play a central role in cancer therapy, SI-traceable metrology has only been established for some of them. Several forms of treatment currently used (particularly intensity-modulated radiation therapy (IMRT), hadron therapy, high-intensity therapeutic ultrasound (HITU) and brachytherapy) suffer from the limited metrological support, which restricts the success of these techniques. Recognizing this deficit, the European Union identified metrology for health as one of the first four Targeted Programmes in the framework of the European Metrology Research Programme (EMRP) running from 2008 to 2011. This programme included two EMRP projects addressing metrology for cancer therapy: project T2.J06 dealing with brachytherapy project T2.J07 dealing with external beam cancer therapy using ionizing radiation and high-intensity therapeutic ultrasound. Primary measurement standards applicable to modern treatment conditions were developed under both projects, together with measurement techniques which are meant as a basis for future protocols for dosimetry, treatment planning and monitoring. In order to provide a platform for the presentation of current developments in clinical measurement techniques for cancer therapy, together with the achievements of both projects, an international Conference on Advanced Metrology for Cancer Therapy (CAMCT) was held from 29 November to 1 December 2011 at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. The main sessions of the conference: Primary and secondary standards of absorbed dose to water for IMRT and brachytherapy, 3D dose distributions and treatment planning for IMRT and brachytherapy, Hadron therapy (protons and carbon ions), High-intensity therapeutic ultrasound (HITU), were geared to the main foci of the projects. Metrologists and medical physicists from countries all over the world attended the conference and made it into a forum for the exchange of information and expertise
Amin, Mahul B; Epstein, Jonathan I; Ulbright, Thomas M; Humphrey, Peter A; Egevad, Lars; Montironi, Rodolfo; Grignon, David; Trpkov, Kiril; Lopez-Beltran, Antonio; Zhou, Ming; Argani, Pedram; Delahunt, Brett; Berney, Daniel M; Srigley, John R; Tickoo, Satish K; Reuter, Victor E
Members of the International Society of Urological Pathology (ISUP) participated in a half-day consensus conference to discuss guidelines and recommendations regarding best practice approaches to use of immunohistochemistry (IHC) in differential diagnostic situations in urologic pathology, including bladder, prostate, testis and, kidney lesions. Four working groups, selected by the ISUP leadership, identified several high-interest topics based on common or relevant challenging diagnostic situations and proposed best practice recommendations, which were discussed by the membership. The overall summary of the discussions and the consensus opinion forms the basis of a series of articles, one for each organ site. This Special Article summarizes the overall recommendations made by the four working groups. It is anticipated that this ISUP effort will be valuable to the entire practicing community in the appropriate use of IHC in diagnostic urologic pathology.
Kotlan, Beatrix; Umansky, Viktor; Malyguine, Anatoli M; Marincola, Francesco M; Shurin, Michael R
Biotherapy is widely considered as the fourth treatment modality for patients with cancer, and uses the constantly increasing knowledge in molecular biology, cell biology and immunology. Biotherapy uses naturally occurring biological molecules (e.g., cytokines and antibodies) or works by the manipulation of normal biological mechanisms (controlling or inhibiting tumor growth). Important achievements in anticancer drug development are immunotherapeutic strategies recently approved by the US FDA as well as clinical data of the cancer patients treated in clinical trials. There is a need to expand these novel cancer immunotherapeutic modalities for cancer patients all over the world. To meet that goal, it is essential to spread the information, to summarize the new clinical data and to draw the conclusions from the clinical and preclinical investigations. These frontline tasks can be well advanced by organizing international conferences in this domain in less scientifically developed countries, with a significant tumor burden statistics. Therefore, special efforts were done to organize the 2nd International Cancer Immunotherapy and Immunomonitoring Conference (CITIM-2011) in Hungary.
Investigators from academia and industry gathered on April 4 and 5, 2013, in Washington DC at the Arrowhead’s 2nd Annual Cancer Immunotherapy Conference. Two complementary concepts were discussed: cancer “stem cells” as targets and therapeutic platforms based on stem cells.
Stearns, Lisa; Boortz-Marx, Richard; Du Pen, Stuart; Friehs, Gerhard; Gordon, Michael; Halyard, Michelle; Herbst, Laurel; Kiser, Jennifer
A substantial number of patients with cancer suffer considerable pain at some point during their disease, and approximately 25% of cancer patients die in pain. Providing effective pain management for patients with severe pain that impacts quality of life can present the oncologist or palliative care specialist with complex clinical challenges that often require multifaceted therapeutic measures. This paper presents multidisciplinary consensus-based recommendations for the treatment of intractable cancer pain using intrathecal drug delivery systems, which offer rapid and effective pain relief with less toxicity relative to oral or parenteral administration. Intrathecal drug delivery systems can be highly effective in a variety of patient settings, including cases of refractory pain, diminished performance status, poor tolerability of oral medications, polyanalgesia for complex pain, and inadequate dosing due to addiction concerns. The use of implantable or external systems is discussed, as well as implantation procedures, drug titration recommendations, and management of potential side effects. The authors offer a newly developed algorithm for delivering intraspinal analgesia in patients with cancer. The intent is that increased understanding of available options for truly effective pain management in the oncology and palliative care arena and the benefits of multidisciplinary cooperation will translate into genuine improvements in patient quality of life and a measurable decrease in the number of patients who suffer needlessly in their final days.
A consensus conference on cognitive rehabilitation for mild traumatic brain injury was conducted by the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury and the Defense and Veterans Brain Injury Center. Fifty military and civilian subject matter experts from a broad range of clinical and scientific disciplines developed clinical guidance for the care of Service Members with persistent post-concussion cognitive symptoms three or more months post injury. "Cognitive rehabilitation" was identified to be a broad group of diverse services. Specific services within this rubric were identified as effective or not, and were evaluated both as single-services and as combined integrated cognitive rehabilitation programs. Co-morbidities were acknowledged and addressed, but the conference and ensuing guidance focused primarily upon treatment of cognitive impairment. Guidance regarding effective services addressed the areas of assessment, intervention, outcome measurement, and treatment program implementation.
Berdahl, Carl; Schuur, Jeremiah D.; Fisher, Nancy L.; Burstin, Helen; Pines, Jesse M.
The Affordable Care Act (ACA) of 2010 is expanding the use of quality measurement and promulgating new payment models that place downward pressure on health care utilization and costs. As emergency department (ED) computed tomography utilization has tripled in the past decade, stakeholders have identified advanced imaging as an area where quality and efficiency measures should expand. On May 12, 2015, Academic Emergency Medicine convened a consensus conference titled “Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization.” As part of the conference, a panel of health care policy leaders and emergency physicians discussed the effect of the ACA and other quality programs on ED diagnostic imaging, specifically the way that quality metrics may affect ED care and how ED diagnostic imaging fits in the broader strategy of the U.S. government. This article discusses the content of the panel’s presentations. PMID:26568025
Gupta, Sumit; Aitken, Joanne F; Bartels, Ute; Brierley, James; Dolendo, Mae; Friedrich, Paola; Fuentes-Alabi, Soad; Garrido, Claudia P; Gatta, Gemma; Gospodarowicz, Mary; Gross, Thomas; Howard, Scott C; Molyneux, Elizabeth; Moreno, Florencia; Pole, Jason D; Pritchard-Jones, Kathy; Ramirez, Oscar; Ries, Lynn A G; Rodriguez-Galindo, Carlos; Shin, Hee Young; Steliarova-Foucher, Eva; Sung, Lillian; Supriyadi, Eddy; Swaminathan, Rajaraman; Torode, Julie; Vora, Tushar; Kutluk, Tezer; Frazier, A Lindsay
Population-based cancer registries generate estimates of incidence and survival that are essential for cancer surveillance, research, and control strategies. Although data on cancer stage allow meaningful assessments of changes in cancer incidence and outcomes, stage is not recorded by most population-based cancer registries. The main method of staging adult cancers is the TNM classification. The criteria for staging paediatric cancers, however, vary by diagnosis, have evolved over time, and sometimes vary by cooperative trial group. Consistency in the collection of staging data has therefore been challenging for population-based cancer registries. We assembled key experts and stakeholders (oncologists, cancer registrars, epidemiologists) and used a modified Delphi approach to establish principles for paediatric cancer stage collection. In this Review, we make recommendations on which staging systems should be adopted by population-based cancer registries for the major childhood cancers, including adaptations for low-income countries. Wide adoption of these guidelines in registries will ease international comparative incidence and outcome studies.
The 1st Baltic Osseointegration Academy and Lithuanian University of Health Sciences Consensus Conference 2016. Summary and Consensus Statements: Group II - Peri-Implantitis Diagnostics and Decision Tree
Dursun, Erhan; Galindo-Moreno, Pablo; Juodzbalys, Gintaras; López-Martínez, Jesús; O'Valle, Francisco; Padial-Molina, Miguel; Ramanauskaite, Ausra
ABSTRACT Introduction The task of Group 2 was to review and update the existing data concerning clinical and genetic methods of diagnostics of peri-implantitis. Special interest was paid to the peri-implant crevicular fluid (PICF) overview including analysis of enzymes and biomarkers and microbial profiles from implants. Material and Methods The main areas of interest were as follows: effect of smoking and history of periodontitis, prosthetic treatment mistakes, excess cement, overloading, general diseases influence on peri-implantitis development. The systematic review and/or meta-analysis were registered in PROSPERO, an international prospective register of systematic reviews: http://www.crd.york.ac.uk/PROSPERO/. The literature in the corresponding areas of interest was searched and reported using the PRISMA (Preferred Reporting Item for Systematic Review and Meta-Analysis) Statement: http://www.prisma-statement.org/. The method of preparation of systematic reviews of the literature based on comprehensive search strategies was discussed and standardized. The summary of the materials and methods employed by the authors in preparing the systematic review and/or meta-analysis is presented in Preface chapter. Results The results and conclusions of the review process are presented in the respective papers. The group′s general commentaries, consensus statements, clinical recommendations and implications for research are presented in this article. PMID:27833736
Faria e Almeida, Ricardo; Cicciù, Marco; Daugela, Povilas; Ramanauskaite, Ausra; Saulacic, Nikola; Tervonen, Tellervo; Wang, Hom-Lay; Yu, Shan-Huey
ABSTRACT Introduction The task of Group 3 was to review and update the existing data concerning non-surgical, surgical non-regenerative and surgical regenerative treatment of peri-implantitis. Special interest was paid to the preventive and supporting therapy in case of peri-implantitis. Material and Methods The main areas of interest were as follows: effect of smoking and history of periodontitis, prosthetic treatment mistakes, excess cement, overloading, general diseases influence on peri-implantitis development. The systematic review and/or meta-analysis were registered in PROSPERO, an international prospective register of systematic reviews: http://www.crd.york.ac.uk/PROSPERO/. The literature in the corresponding areas of interest was searched and reported using the PRISMA (Preferred Reporting Item for Systematic Review and Meta-Analysis) Statement: http://www.prisma-statement.org/. The method of preparation of systematic reviews of the literature based on comprehensive search strategies was discussed and standardized. The summary of the materials and methods employed by the authors in preparing the systematic review and/or meta-analysis is presented in Preface chapter. Results The results and conclusions of the review process are presented in the respective papers. The group′s general commentaries, consensus statements, clinical recommendations and implications for research are presented in this article. PMID:27833741
D’Cruz, Anil K.; Sharma, Shilpi; Agarwal, Jaiprakash P.; Thakar, Alok; Teli, Ashraf; Arya, Supreeta; Desai, Chirag; Chaturvedi, Pankaj; Sebastian, Paul; Verghese, Bipin T.; Kane, Shubhada; Sucharita, V; Kaur, Tanvir; Shukla, D. K.; Rath, Goura Kishor
EXECUTIVE SUMMARY The document is based on consensus among the experts and best available evidence pertaining to Indian population and is meant for practice in India.Early diagnosis is imperative in improving outcomes and preserving quality of life. High index of suspicion is to be maintained for leukoplakia (high risk site).Evaluation of a patient with newly diagnosed tongue cancer should include essential tests: Magnetic resonance imaging (MRI) is investigative modality of choice when indicated. Computed tomography (CT) scan is an option when MRI is unavailable. In early lesions when imaging is not warranted ultrasound may help guide management of the neck.Early stage cancers (stage I & II) require single modality treatment – either surgery or radiotherapy. Surgery is preferred. Adjuvant radiotherapy is indicated for T3/T4 cancers, presence of high risk features [lymphovascular emboli (LVE), perineural invasion (PNI), poorly differentiated, node +, close margins). Adjuvant chemoradiation (CTRT) is indicated for positive margins and extranodal disease.Locally advanced operable cancers (stage III & IVA) require combined multimodality treatment - surgery + adjuvant treatment. Adjuvant treatment is indicated in all and in the presence of high risk features as described above.Locally advanced inoperable cancers (stage IVB) are treated with palliative chemo-radiotherapy, chemotherapy, radiotherapy, or symptomatic treatment depending upon the performance status. Select cases may be considered for neoadjuvant chemotherapy followed by surgical salvage.Metastatic disease (stage IVC) should be treated with a goal for palliation. Chemotherapy may be offered to patients with good performance status. Local treatment in the form of radiotherapy may be added for palliation of symptoms.Intense follow-up every 3 months is required for initial 2 years as most recurrences occur in the first 24 months. After 2nd year follow up is done at 4-6 months interval. At each follow up
Haase, Michael; Müller, Christian; Damman, Kevin; Murray, Patrick T; Kellum, John A; Ronco, Claudio; McCullough, Peter A
Pathophysiological mechanisms of cardiorenal syndromes (CRS) types 1-5 are still sparsely characterized. In an attempt to address this issue, a consensus conference on CRS was held in Venice, Italy, in November 2012 under the auspices of the Acute Dialysis Quality Initiative (ADQI). Working group 1 discussed monodirectional mechanisms of CRS type 1 which is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). Pre-conference we performed a systematic search and review of the available literature using a modified Delphi analysis. Hereby identified and in this review discussed questions were: (i) What are the predominant pathophysiologic mechanisms of CRS type 1 in acute decompensated heart failure? (ii) Could biomarker profiling identify pathomechanisms or hemodynamic phenotype of patients with CRS type 1? Could predictive biomarkers improve renal safety of therapy in CRS type 1? (iii) How do the timing, severity and duration relate to the mechanisms and outcomes of CRS type 1? In summary, after discussion and appraisal of the best available evidence, working group 1 makes consensus recommendations for future research on pathologic mechanisms of CRS type 1 and recommendations for clinical practice where treatment is in either proof or disproof of a mechanism.
Patel, Prabhudas; Vora, Hemangini; Aggarwal, Bharat B; Gandhi, Varsha; Mehta, Kapil; Pathak, Sen
Cancer is primarily an "old-age" disease that has an "age-old" history. The overall incidence of cancer is much higher in Western countries, but is rapidly growing in Eastern countries perhaps due to change in life-style. Almost three million studies published to date indicate that cancer is a hyperproliferative disorder that arises from dysregulation of multiple cell signaling pathways. The cancer genome landscape indicates that approximately 140 genes and 12 cell signaling pathways drive almost all cancers. "Targeted therapy," a buzz word in cancer treatment for the past two decades, has provided antibodies, as well as small-molecule inhibitors. These therapies have been successful only in few instances. However, in most cases, minor increase in overall survival has been reported at the cost of huge expense. An alternative strategy is to prevent cancer or to diagnose and treat the disease at an early stage to gain survival benefits. Such interventions are also cost-effective. To address some of these issues, the 6th International Translational Cancer Research Conference was held during February 4-7th, 2016, in Ahmedabad, Gujarat, India; the homeland of Mahatma Gandhi. This conference was focused on utilizing multidisciplinary approaches for prevention and early treatment that would likely simultaneously or sequentially target many key pathways. Several distinguished speakers were invited from around the world. This article highlights primary features of this conference.
Tan, Puay Hoon; Cheng, Liang; Srigley, John R; Griffiths, David; Humphrey, Peter A; van der Kwast, Theodore H; Montironi, Rodolfo; Wheeler, Thomas M; Delahunt, Brett; Egevad, Lars; Epstein, Jonathan I
The 2009 International Society of Urological Pathology Consensus Conference in Boston, made recommendations regarding the standardization of pathology reporting of radical prostatectomy specimens. Issues relating to surgical margin assessment were coordinated by working group 5. Pathologists agreed that tumor extending close to the 'capsular' margin, yet not to it, should be reported as a negative margin, and that locations of positive margins should be indicated as either posterior, posterolateral, lateral, anterior at the prostatic apex, mid-prostate or base. Other items of consensus included specifying the extent of any positive margin as millimeters of involvement; tumor in skeletal muscle at the apical perpendicular margin section, in the absence of accompanying benign glands, to be considered organ confined; and that proximal and distal margins be uniformly referred to as bladder neck and prostatic apex, respectively. Grading of tumor at positive margins was to be left to the discretion of the reporting pathologists. There was no consensus as to how the surgical margin should be regarded when tumor is present at the inked edge of the tissue, in the absence of transected benign glands at the apical margin. Pathologists also did not achieve agreement on the reporting approach to benign prostatic glands at an inked surgical margin in which no carcinoma is present.
Zaghloul, Mohamed S
A wide gathering of scientists, clinicians, pharmacists and nurses specialized in pediatric oncology practice met to celebrate the second anniversary of Children's Cancer Hospital, Egypt (CCHE). The celebration was in the form of high-brow teaching lectures and reports presented by international experts in the fields of pediatric CNS tumors, solid tumors (neuroblastoma, nephroblastoma, soft tissue and bone tumors, lymphoma, leukemia and pediatric oncology nursing. The conference extends its activities to hospital management, clinical pharmacy and telemedicine. Furthermore, CCHE experts presented the efforts performed to establish a state-of-the-art pediatric oncology hospital equipped with all needed facilities to raise the standard of care to the highest levels.
Musey, Paul I; Linnstaedt, Sarah D; Platts-Mills, Timothy F; Miner, James R; Bortsov, Andrey V; Safdar, Basmah; Bijur, Polly; Rosenau, Alex; Tsze, Daniel S; Chang, Andrew K; Dorai, Suprina; Engel, Kirsten G; Feldman, James A; Fusaro, Angela M; Lee, David C; Rosenberg, Mark; Keefe, Francis J; Peak, David A; Nam, Catherine S; Patel, Roma G; Fillingim, Roger B; McLean, Samuel A
Pain is a leading public health problem in the United States, with an annual economic burden of more than $630 billion, and is one of the most common reasons that individuals seek emergency department (ED) care. There is a paucity of data regarding sex differences in the assessment and treatment of acute and chronic pain conditions in the ED. The Academic Emergency Medicine consensus conference convened in Dallas, Texas, in May 2014 to develop a research agenda to address this issue among others related to sex differences in the ED. Prior to the conference, experts and stakeholders from emergency medicine and the pain research field reviewed the current literature and identified eight candidate priority areas. At the conference, these eight areas were reviewed and all eight were ratified using a nominal group technique to build consensus. These priority areas were: 1) gender differences in the pharmacological and nonpharmacological interventions for pain, including differences in opioid tolerance, side effects, or misuse; 2) gender differences in pain severity perceptions, clinically meaningful differences in acute pain, and pain treatment preferences; 3) gender differences in pain outcomes of ED patients across the life span; 4) gender differences in the relationship between acute pain and acute psychological responses; 5) the influence of physician-patient gender differences and characteristics on the assessment and treatment of pain; 6) gender differences in the influence of acute stress and chronic stress on acute pain responses; 7) gender differences in biological mechanisms and molecular pathways mediating acute pain in ED populations; and 8) gender differences in biological mechanisms and molecular pathways mediating chronic pain development after trauma, stress, or acute illness exposure. These areas represent priority areas for future scientific inquiry, and gaining understanding in these will be essential to improving our understanding of sex and gender
Huguet, Florence; Goodman, Karyn A.; Azria, David; Racadot, Severine; Abrams, Ross A.
Summary: Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose
Hubbard-Lucey, Vanessa M; Tontonoz, Matthew J
The inaugural International Cancer Immunotherapy Conference, cohosted by the Cancer Research Institute (CRI), the American Association for Cancer Research (AACR), the Association for Cancer Immunotherapy (CIMT), and the European Academy of Tumor Immunology (EATI), was held in New York City on September 16–19, 2015. The conference brought together nearly 1,400 scientists, clinicians, regulators, patient advocates, and other stakeholders to discuss the latest scientific developments in cancer immunology and immunotherapy, as well as the regulatory hurdles facing new drug development. This conference report summarizes the main themes that emerged during the 4-day meeting.
Fischer, Peter M
The topics discussed at the conference covered many aspects of cancer research, from the genetic search for new targets, target validation and drug discovery, all the way to preclinical and clinical development of oncology drugs. Here the presentations on new metabolic, angiogenic, cell cycle and other molecular targets, as well as recent developments with experimental drugs with action on some of these targets, are summarised. Particular emphasis is placed on the emerging realisation that changes in the metabolic phenotype lie at the heart of cellular transformation. New insights into the biological links between cancer cell metabolism and the balance between survival and death signalling are likely to lead to the identification of a new category of anticancer targets.
This is a conference committee report of the House and Senate to amend the Public Health Service Act to improve the national cancer program and to authorize appropriations for such programs. Title 1, Extension of Cancer Program, deals with administrative, budgetary, and personnel matters; programs of routine exfoliative cytology tests; and requirements of peer review of grant applications and contract projects. Title 2, Biomedical Research, establishes a President's Biomedical Research Panel to study and make recommendations concerning the subject, content, organization, and operation of biomedical and behavioral reserach conducted and supported under programs of the National Institutes of Health and the National Institutes of Mental Health. After 15 months, the panel will submit to the President and Congress a comprehensive report of its findings and recomendations. The 7-member panel shall expire after 18 months.
Thomssen, Christoph; Augustin, Doris; Ettl, Johannes; Haidinger, Renate; Lück, Hans-Joachim; Lüftner, Diana; Marmé, Frederik; Marschner, Norbert; Müller, Lothar; Overkamp, Friedrich; Ruckhäberle, Eugen; Thill, Marc; Untch, Michael; Wuerstlein, Rachel; Harbeck, Nadia
Summary The Advanced Breast Cancer Third International Consensus Conference on the diagnosis and treatment of advanced breast cancer took place in Lisbon, Portugal, on November 5-7, 2015. This year's conference (ABC3) was focused on the treatment of metastatic breast cancer (stage IV), as it was 4 years ago at the first consensus meeting (ABC1). A matter of particular interest was the patients’ perspective. Thus, patient-relevant issues were addressed by the consensus discussions, such as those on treatment goals, quality of life, care of long-term survivors (‘survivorship issues’), and coping with disease-related symptoms and the side effects of treatment. Further important issues on the agenda were the use of standardized instruments for the assessment of individual treatment success (‘patient-reported outcome measures’) and the evaluation of the benefit of novel drugs (e.g. the European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale). Diagnosis and treatment of inoperable locally advanced breast cancer had already been discussed 2 years earlier at the ABC2 Consensus and were not dealt with in the framework of this year's ABC3 Consensus. With regard to country-specific peculiarities, which unavoidably found their way into the ABC Consensus, a working group of German breast cancer experts commented on the voting results of the ABC panelists. As for the past consensus, the group specially considered the German guidelines for the diagnosis and treatment of breast cancer (AGO (Gyneco-Oncology Working Group), S3, DGHO (German Society of Hematology and Medical Oncology)) in order to adapt the ABC3 consensus for everyday therapy in Germany. PMID:27051399
Sarkar, Debalina; Shields, Brian; Davies, Melanie L; Müller, Jürgen; Wakeman, Jane A
Cancer stem cells (CSCs) are initiating cells in colorectal cancer (CRC). Colorectal tumours undergo epithelial to mesenchymal transition (EMT)-like processes at the invasive front, enabling invasion and metastasis, and recent studies have linked this process to the acquisition of stem cell-like properties. It is of fundamental importance to understand the molecular events leading to the establishment of cancer initiating cells and how these mechanisms relate to cellular transitions during tumourigenesis. We use an in vitro system to recapitulate changes in CRC cells at the invasive front (mesenchymal-like cells) and central mass (epithelial-like cells) of tumours. We show that the mesoderm inducer BRACHYURY is expressed in a subpopulation of CRC cells that resemble invasive front mesenchymal-like cells, where it acts to impose characteristics of CSCs in a fully reversible manner, suggesting reversible formation and modulation of such cells. BRACHYURY, itself regulated by the oncogene β-catenin, influences NANOG and other 'stemness' markers including a panel of markers defining CRC-CSC whose presence has been linked to poor patient prognosis. Similar regulation of NANOG through BRACHYURY was observed in other cells lines, suggesting this might be a pathway common to cancer cells undergoing mesenchymal transition. We suggest that BRACHYURY may regulate NANOG in mesenchymal-like CRC cells to impose a 'plastic-state', allowing competence of cells to respond to signals prompting invasion or metastasis.
Implementation of novel biomarkers in the diagnosis, prognosis, and management of acute kidney injury: executive summary from the tenth consensus conference of the Acute Dialysis Quality Initiative (ADQI).
McCullough, Peter A; Bouchard, Josee; Waikar, Sushrut S; Siew, Edward D; Endre, Zoltan H; Goldstein, Stuart L; Koyner, Jay L; Macedo, Etienne; Doi, Kent; Di Somma, Salvatore; Lewington, Andrew; Thadhani, Ravi; Chakravarthi, Raj; Ice, Can; Okusa, Mark D; Duranteau, Jacques; Doran, Peter; Yang, Li; Jaber, Bertrand L; Meehan, Shane; Kellum, John A; Haase, Michael; Murray, Patrick T; Cruz, Dinna; Maisel, Alan; Bagshaw, Sean M; Chawla, Lakhmir S; Mehta, Ravindra L; Shaw, Andrew D; Ronco, Claudio
Detection of acute kidney injury is undergoing a dynamic revolution of biomarker technology allowing greater, earlier, and more accurate determination of diagnosis, prognosis, and with powerful implication for management. Biomarkers can be broadly considered as any measurable biologic entity or process that allows differentiation between normal function and injury or disease. The ADQI (Acute Dialysis Quality Initiative) had its Ninth Consensus Conference dedicated to synthesis and formulation of the existing literature on biomarkers for the detection of acute kidney injury in a variety of settings. In the papers that accompany this summary, ADQI workgroups fully develop key concepts from a summary of the literature in the domains of early diagnosis, differential diagnosis, prognosis and management, and concurrent physiologic and imaging measures.
Implementation of Novel Biomarkers in the Diagnosis, Prognosis, and Management of Acute Kidney Injury: Executive Summary from the Tenth Consensus Conference of the Acute Dialysis Quality Initiative (ADQI)
McCullough, Peter A.; Bouchard, Josee; Waikar, Sushrut S.; Siew, Edward D.; Endre, Zoltan H.; Goldstein, Stuart L.; Koyner, Jay L.; Macedo, Etienne; Doi, Kent; Di Somma, Salvatore; Lewington, Andrew; Thadhani, Ravi; Chakravarthi, Raj; Ice, Can; Okusa, Mark D.; Duranteau, Jacques; Doran, Peter; Yang, Li; Jaber, Bertrand L.; Meehan, Shane; Kellum, John A.; Haase, Michael; Murray, Patrick T.; Cruz, Dinna; Maisel, Alan; Bagshaw, Sean M.; Chawla, Lakhmir S.; Mehta, Ravindra L.; Shaw, Andrew D.; Ronco, Claudio
Detection of acute kidney injury is undergoing a dynamic revolution of biomarker technology allowing greater, earlier, and more accurate determination of diagnosis, prognosis, and with powerful implication for management. Biomarkers can be broadly considered as any measurable biologic entity or process that allows differentiation between normal function and injury or disease. The ADQI (Acute Dialysis Quality Initiative) had its Ninth Consensus Conference dedicated to synthesis and formulation of the existing literature on biomarkers for the detection of acute kidney injury in a variety of settings. In the papers that accompany this summary, ADQI workgroups fully develop key concepts from a summary of the literature in the domains of early diagnosis, differential diagnosis, prognosis and management, and concurrent physiologic and imaging measures. PMID:23689652
'Progress In Vaccination Against Cancer' (PIVAC) examines the latest advances in tumour immunology and their clinical applications. Previous conferences were held in Blaubeuren, London, Cambridge, Oxford, Copenhagen, Stockholm, Nottingham and Freudenstadt-Lauterbad in the Black Forest. The residential format of these conferences encourages interactions between participants and permits a focussed discussion on the new data and concepts. The main topic of the 5th European PIVAC was the induction and maintenance of an active immune memory against cancer. The results of clinical trials with different cancer vaccines were presented. The correlations between tumour regression and immune response, the role of innate and specific immunity, and ways of enhancing these two arms of the antitumour response were explored. Particular attention was devoted to the presence and function of regulatory T cells as a prelude to improving the design of these trials and understanding why they have produced unimpressive results. A consensus was reached on the need to combine vaccination with strategies for suppressing regulatory T cell function. The immune-escape mechanisms of tumours and the emerging importance of some newly discovered mutations were also fully discussed.
National Institutes of Health (DHHS), Bethesda, MD.
The paper presents a summary of the findings from a 1982 conference held by the National Institutes of Health on the issue of diets and hyperactivity. Six questions are addressed, touching on the nature of hyperactivity and its quantifiable measurement, defined diets, empirical evidence regarding the effects of these diets on hyperactivity,…
The clinical indications and guidelines for low-density lipoprotein (LDL)-apheresis set by the 1st Italian Consensus Conference held in Ostuni in 1990 and completed in 1992, but never published, are reported schematically. In 1994, within the Project “Prevention and control of the factors of the disease (FATMA)” by the Italian National Research Council, subproject 8 “Control of cardiovascular disease”, a “Hearing on therapeutic apheresis: need for a target-oriented project” was organised. The meeting was the last scientific initiative on LDL-apheresis supported by public funds in Italy. After roughly two decades of use of LDL-apheresis, new guidelines were required based on the latest scientific evidence. In 2006, the Italian multicentre study on LDL-apheresis Working Group (IMSLDLa-WP), a scientific initiative at national level, was developed. It initially gathered together 19 Italian centres qualified for the application of lipid apheresis and LDL-apheresis (2007–2008), then 23 in 2010, located in the north, south, centre of Italy and in Sicily and Sardinia. The multicentre study aimed to validate the protocol for selecting patients and to create a network between the Italian centres. A secondary objective was the creation of a database of patients with familial hypercholesterolaemia and other severe forms of dyslipidaemia undergoing treatment with LDL-apheresis using the available techniques. Since LDL-apheresis has multidisciplinary treatment indications, the agreement on the new guidelines was reached through a panel of experts, of different medical and surgical specialties, with scientific and medical interest in the treatment indications, application and development of LDL-apheresis. The initiatives of the IMSLDLa-WP led to the 2nd Italian Consensus Conference on LDL-apheresis held in Rome in 2009. The previous and most recent guidelines are reported here synoptically. PMID:27416576
Diagnosis and treatment of pain in plexopathy, radiculopathy, peripheral neuropathy and phantom limb pain. Evidence and recommendations from the Italian Consensus Conference on Pain on Neurorehabilitation.
Ferraro, Francesco; Jacopetti, Marco; Spallone, Vincenza; Padua, Luca; Traballesi, Marco; Brunelli, Stefano; Cantarella, Cristina; Ciotti, Cristina; Coraci, Daniele; Dalla Toffola, Elena; Mandrini, Silvia; Morone, Giovanni; Pazzaglia, Costanza; Romano, Marcello; Schenone, Angelo; Togni, Rossella; Tamburin, Stefano
Pain may affect all aspects of social life and reduce the quality of life. Neuropathic pain (NP) is common in patients affected by plexopathy, radiculopathy, mononeuropathy, peripheral neuropathy. Phantom limb pain (PLP) is a painful sensation that is common after amputation, and its pathophysiological mechanisms involve changes in the peripheral and central nervous system. Given the lack of conclusive evidence and specific guidelines on these topics, the aim of the Italian Consensus Conference on Pain on Neurorehabilitation (ICCPN) was to collect evidence and offer recommendations to answer currently open questions on the assessment and treatment of NP associated with the above conditions and PLP. When no evidence was available, recommendations were based on consensus between expert opinions. Current guidelines on the assessment and pharmacological treatment of NP can be applied to plexopathy, radiculopathy, mononeuropathy, peripheral neuropathy, while evidence for invasive treatments and physical therapy is generally poor because of the low quality of studies. Treatment of PLP is still unsatisfactory. Data on the functional outcome and impact of pain on neurorehabilitation outcome in these conditions are lacking. In most cases, a multidisciplinary approach is recommended to offer a better outcome and reduce side effects. High quality studies are requested to address the unmet needs in this field.
Adam, René; de Gramont, Aimery; Figueras, Joan; Kokudo, Norihiro; Kunstlinger, Francis; Loyer, Evelyne; Poston, Graeme; Rougier, Philippe; Rubbia-Brandt, Laura; Sobrero, Alberto; Teh, Catherine; Tejpar, Sabine; Van Cutsem, Eric; Vauthey, Jean-Nicolas; Påhlman, Lars
An international panel of multidisciplinary experts convened to develop recommendations for managing patients with colorectal cancer (CRC) and synchronous liver metastases (CRCLM). A modified Delphi method was used. CRCLM is defined as liver metastases detected at or before diagnosis of the primary CRC. Early and late metachronous metastases are defined as those detected ⩽12months and >12months after surgery, respectively. To provide information on potential curability, use of high-quality contrast-enhanced computed tomography (CT) before chemotherapy is recommended. Magnetic resonance imaging is increasingly being used preoperatively to aid detection of subcentimetric metastases, and alongside CT in difficult situations. To evaluate operability, radiology should provide information on: nodule size and number, segmental localization and relationship with major vessels, response after neoadjuvant chemotherapy, non-tumoral liver condition and anticipated remnant liver volume. Pathological evaluation should assess response to preoperative chemotherapy for both the primary tumour and metastases, and provide information on the tumour, margin size and micrometastases. Although the treatment strategy depends on the clinical scenario, the consensus was for chemotherapy before surgery in most cases. When the primary CRC is asymptomatic, liver surgery may be performed first (reverse approach). When CRCLM are unresectable, the goal of preoperative chemotherapy is to downsize tumours to allow resection. Hepatic resection should not be denied to patients with stable disease after optimal chemotherapy, provided an adequate liver remnant with inflow and outflow preservation remains. All patients with synchronous CRCLM should be evaluated by a hepatobiliary multidisciplinary team.
Wildiers, Hans; Heeren, Pieter; Puts, Martine; Topinkova, Eva; Janssen-Heijnen, Maryska L.G.; Extermann, Martine; Falandry, Claire; Artz, Andrew; Brain, Etienne; Colloca, Giuseppe; Flamaing, Johan; Karnakis, Theodora; Kenis, Cindy; Audisio, Riccardo A.; Mohile, Supriya; Repetto, Lazzaro; Van Leeuwen, Barbara; Milisen, Koen; Hurria, Arti
Purpose To update the International Society of Geriatric Oncology (SIOG) 2005 recommendations on geriatric assessment (GA) in older patients with cancer. Methods SIOG composed a panel with expertise in geriatric oncology to develop consensus statements after literature review of key evidence on the following topics: rationale for performing GA; findings from a GA performed in geriatric oncology patients; ability of GA to predict oncology treatment–related complications; association between GA findings and overall survival (OS); impact of GA findings on oncology treatment decisions; composition of a GA, including domains and tools; and methods for implementing GA in clinical care. Results GA can be valuable in oncology practice for following reasons: detection of impairment not identified in routine history or physical examination, ability to predict severe treatment-related toxicity, ability to predict OS in a variety of tumors and treatment settings, and ability to influence treatment choice and intensity. The panel recommended that the following domains be evaluated in a GA: functional status, comorbidity, cognition, mental health status, fatigue, social status and support, nutrition, and presence of geriatric syndromes. Although several combinations of tools and various models are available for implementation of GA in oncology practice, the expert panel could not endorse one over another. Conclusion There is mounting data regarding the utility of GA in oncology practice; however, additional research is needed to continue to strengthen the evidence base. PMID:25071125
Melosky, B.; Agulnik, J.; Albadine, R.; Banerji, S.; Bebb, D.G.; Bethune, D.; Blais, N.; Butts, C.; Cheema, P.; Cheung, P.; Cohen, V.; Deschenes, J.; Ionescu, D.N.; Juergens, R.; Kamel-Reid, S.; Laurie, S.A.; Liu, G.; Morzycki, W.; Tsao, M.S.; Xu, Z.; Hirsh, V.
Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered. PMID:27330348
Black, Joyce M; Edsberg, Laura E; Baharestani, Mona M; Langemo, Diane; Goldberg, Margaret; McNichol, Laurie; Cuddigan, Janet
Although pressure ulcer (PrU) development is now generally considered an indicator for quality of care, questions and concerns about situations in which they are unavoidable remain. Considering the importance of this issue and the lack of available research data, in 2010 the National Pressure Ulcer Advisory Panel (NPUAP) hosted a multidisciplinary conference to establish consensus on whether there are individuals in whom pressure ulcer development may be unavoidable and whether a difference exists between end-of-life skin changes and pressure ulcers. Thirty-four stakeholder organizations from various disciplines were identified and invited to send a voting representative. Of those, 24 accepted the invitation. Before the conference, existing literature was identified and shared via a webinar. A NPUAP task force developed standardized consensus questions for items with none or limited evidence and an interactive protocol was used to develop consensus among conference delegates and attendees. Consensus was established to be 80% agreement among conference delegates. Unanimous consensus was achieved for the following statements: most PrUs are avoidable; not all PrUs are avoidable; there are situations that render PrU development unavoidable, including hemodynamic instability that is worsened with physical movement and inability to maintain nutrition and hydration status and the presence of an advanced directive prohibiting artificial nutrition/hydration; pressure redistribution surfaces cannot replace turning and repositioning; and if enough pressure was removed from the external body the skin cannot always survive. Consensus was not obtained on the practicality or standard of turning patients every 2 hours nor on concerns surrounding the use of medical devices vis-à-vis their potential to cause skin damage. Research is needed to examine these issues, refine preventive practices in challenging situations, and identify the limits
Kulawiec, Mariola; Owens, Kjerstin M; Singh, Keshav K
Mutations in mtDNA are found in most cancers. In this study, we studied the role of cancer cell mutant mtDNA in tumorigenesis. We sequenced the entire mitochondrial genome of three different breast cancer cell lines and found that all three, MCF7, MDA-MB-231 and MDA-MB-435, contained mutations in mtDNA. MDA-MB-435 cells contained a mutation in the tRNA(Leu(CUN)) gene known to be involved in pathogenesis of mitochondrial diseases. We generated a mutant cybrid (cytoplasmic hybrid) by repopulating the recipient rho(0) (completely devoid of mtDNA) cells with donor mtDNA derived from an enucleated MDA-MB-435 breast cancer cell line. An isogenic wild-type cybrid was produced by transfer of normal mtDNA from a healthy donor. When compared to the wild type, we found that mutant mtDNA increases mitochondrial membrane potential. However, this increase in mitochondrial membrane potential was not associated with increase in reactive oxygen species (ROS) production. MtDNA mutations conferred resistance to apoptosis triggered by etoposide. Our study also revealed that mutations in mtDNA increase metastatic potential. Using a tail-vein model of metastasis in a mouse model, we show that the mutant cybrid metastatizes to the lungs and forms macrometastic foci. Additionally we found that mutations in mtDNA constitutively activate the PI3/Akt pathway that contributes to increased metastatis. Together our study demonstrates that mutant mtDNA promotes apoptotic resistance and metastasis in a mouse model.
Salem, Ahmed F; Whitaker-Menezes, Diana; Howell, Anthony; Sotgia, Federica; Lisanti, Michael P
Here, we set out to test the novel hypothesis that increased mitochondrial biogenesis in epithelial cancer cells would "fuel" enhanced tumor growth. For this purpose, we generated MDA-MB-231 cells (a triple-negative human breast cancer cell line) overexpressing PGC-1α and MitoNEET, which are established molecules that drive mitochondrial biogenesis and increased mitochondrial oxidative phosphorylation (OXPHOS). Interestingly, both PGC-1α and MitoNEET increased the abundance of OXPHOS protein complexes, conferred autophagy resistance under conditions of starvation and increased tumor growth by up to ~3-fold. However, this increase in tumor growth was independent of neo-angiogenesis, as assessed by immunostaining and quantitation of vessel density using CD31 antibodies. Quantitatively similar increases in tumor growth were also observed by overexpression of PGC-1β and POLRMT in MDA-MB-231 cells, which are also responsible for mediating increased mitochondrial biogenesis. Thus, we propose that increased mitochondrial "power" in epithelial cancer cells oncogenically promotes tumor growth by conferring autophagy resistance. As such, PGC-1α, PGC-1β, mitoNEET and POLRMT should all be considered as tumor promoters or "metabolic oncogenes." Our results are consistent with numerous previous clinical studies showing that metformin (a weak mitochondrial "poison") prevents the onset of nearly all types of human cancers in diabetic patients. Therefore, metformin (a complex I inhibitor) and other mitochondrial inhibitors should be developed as novel anticancer therapies, targeting mitochondrial metabolism in cancer cells.
Rex, Douglas K; Kahi, Charles J; Levin, Bernard; Smith, Robert A; Bond, John H; Brooks, Durado; Burt, Randall W; Byers, Tim; Fletcher, Robert H; Hyman, Neil; Johnson, David; Kirk, Lynne; Lieberman, David A; Levin, Theodore R; O'Brien, Michael J; Simmang, Clifford; Thorson, Alan G; Winawer, Sidney J
Patients with resected colorectal cancer are at risk for recurrent cancer and metachronous neoplasms in the colon. This joint update of guidelines by the American Cancer Society and the US Multi-Society Task Force on Colorectal Cancer addresses only the use of endoscopy in the surveillance of these patients. Patients with endoscopically resected Stage I colorectal cancer, surgically resected Stages II and III cancers, and Stage IV cancer resected for cure (isolated hepatic or pulmonary metastasis) are candidates for endoscopic surveillance. The colorectum should be carefully cleared of synchronous neoplasia in the perioperative period. In nonobstructed colons, colonoscopy should be performed preoperatively. In obstructed colons, double-contrast barium enema or computed tomography colonography should be performed preoperatively, and colonoscopy should be performed 3 to 6 months after surgery. These steps complete the process of clearing synchronous disease. After clearing for synchronous disease, another colonoscopy should be performed in 1 year to look for metachronous lesions. This recommendation is based on reports of a high incidence of apparently metachronous second cancers in the first 2 years after resection. If the examination at 1 year is normal, then the interval before the next subsequent examination should be 3 years. If that examination is normal, then the interval before the next subsequent examination should be 5 years. Shorter intervals may be indicated by associated adenoma findings (see "Guidelines for Colonoscopy Surveillance After Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society"). Shorter intervals also are indicated if the patient's age, family history, or tumor testing indicate definite or probable hereditary nonpolyposis colorectal cancer. Patients undergoing low anterior resection of rectal cancer generally have higher rates of local cancer recurrence compared with those
Castelnuovo, Gianluca; Giusti, Emanuele M.; Manzoni, Gian Mauro; Saviola, Donatella; Gatti, Arianna; Gabrielli, Samantha; Lacerenza, Marco; Pietrabissa, Giada; Cattivelli, Roberto; Spatola, Chiara A. M.; Corti, Stefania; Novelli, Margherita; Villa, Valentina; Cottini, Andrea; Lai, Carlo; Pagnini, Francesco; Castelli, Lorys; Tavola, Mario; Torta, Riccardo; Arreghini, Marco; Zanini, Loredana; Brunani, Amelia; Capodaglio, Paolo; D'Aniello, Guido E.; Scarpina, Federica; Brioschi, Andrea; Priano, Lorenzo; Mauro, Alessandro; Riva, Giuseppe; Repetto, Claudia; Regalia, Camillo; Molinari, Enrico; Notaro, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Simpson, Susan G.; Wiederhold, Brenda; Tamburin, Stefano
Background: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams. Objectives: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases. Methods: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions. Results: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive—Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post—Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes
Gender-specific research for emergency diagnosis and management of ischemic heart disease: proceedings from the 2014 Academic Emergency Medicine Consensus Conference Cardiovascular Research Workgroup.
Safdar, Basmah; Nagurney, John T; Anise, Ayodola; DeVon, Holli A; D'Onofrio, Gail; Hess, Erik P; Hollander, Judd E; Legato, Mariane J; McGregor, Alyson J; Scott, Jane; Tewelde, Semhar; Diercks, Deborah B
Coronary artery disease (CAD) is the most common cause of death for both men and women. However, over the years, emergency physicians, cardiologists, and other health care practitioners have observed varying outcomes in men and women with symptomatic CAD. Women in general are 10 to 15 years older than men when they develop CAD, but suffer worse postinfarction outcomes compared to age-matched men. This article was developed by the cardiovascular workgroup at the 2014 Academic Emergency Medicine (AEM) consensus conference to identify sex- and gender-specific gaps in the key themes and research questions related to emergency cardiac ischemia care. The workgroup had diverse stakeholder representation from emergency medicine, cardiology, critical care, nursing, emergency medical services, patients, and major policy-makers in government, academia, and patient care. We implemented the nominal group technique to identify and prioritize themes and research questions using electronic mail, monthly conference calls, in-person meetings, and Web-based surveys between June 2013 and May 2014. Through three rounds of nomination and refinement, followed by an in-person meeting on May 13, 2014, we achieved consensus on five priority themes and 30 research questions. The overarching themes were as follows: 1) the full spectrum of sex-specific risk as well as presentation of cardiac ischemia may not be captured by our standard definition of CAD and needs to incorporate other forms of ischemic heart disease (IHD); 2) diagnosis is further challenged by sex/gender differences in presentation and variable sensitivity of cardiac biomarkers, imaging, and risk scores; 3) sex-specific pathophysiology of cardiac ischemia extends beyond conventional obstructive CAD to include other causes such as microvascular dysfunction, takotsubo, and coronary artery dissection, better recognized as IHD; 4) treatment and prognosis are influenced by sex-specific variations in biology, as well as patient
Itazawa, Tomoko; Tamaki, Yukihisa; Komiyama, Takafumi; Nishimura, Yasumasa; Nakayama, Yuko; Ito, Hiroyuki; Ohde, Yasuhisa; Kusumoto, Masahiko; Sakai, Shuji; Suzuki, Kenji; Watanabe, Hirokazu; Asamura, Hisao
The purpose of this study was to develop a consensus-based computed tomographic (CT) atlas that defines lymph node stations in radiotherapy for lung cancer based on the lymph node map of the International Association for the Study of Lung Cancer (IASLC). A project group in the Japanese Radiation Oncology Study Group (JROSG) initially prepared a draft of the atlas in which lymph node Stations 1-11 were illustrated on axial CT images. Subsequently, a joint committee of the Japan Lung Cancer Society (JLCS) and the Japanese Society for Radiation Oncology (JASTRO) was formulated to revise this draft. The committee consisted of four radiation oncologists, four thoracic surgeons and three thoracic radiologists. The draft prepared by the JROSG project group was intensively reviewed and discussed at four meetings of the committee over several months. Finally, we proposed definitions for the regional lymph node stations and the consensus-based CT atlas. This atlas was approved by the Board of Directors of JLCS and JASTRO. This resulted in the first official CT atlas for defining regional lymph node stations in radiotherapy for lung cancer authorized by the JLCS and JASTRO. In conclusion, the JLCS-JASTRO consensus-based CT atlas, which conforms to the IASLC lymph node map, was established.
Itazawa, Tomoko; Tamaki, Yukihisa; Komiyama, Takafumi; Nishimura, Yasumasa; Nakayama, Yuko; Ito, Hiroyuki; Ohde, Yasuhisa; Kusumoto, Masahiko; Sakai, Shuji; Suzuki, Kenji; Watanabe, Hirokazu; Asamura, Hisao
The purpose of this study was to develop a consensus-based computed tomographic (CT) atlas that defines lymph node stations in radiotherapy for lung cancer based on the lymph node map of the International Association for the Study of Lung Cancer (IASLC). A project group in the Japanese Radiation Oncology Study Group (JROSG) initially prepared a draft of the atlas in which lymph node Stations 1–11 were illustrated on axial CT images. Subsequently, a joint committee of the Japan Lung Cancer Society (JLCS) and the Japanese Society for Radiation Oncology (JASTRO) was formulated to revise this draft. The committee consisted of four radiation oncologists, four thoracic surgeons and three thoracic radiologists. The draft prepared by the JROSG project group was intensively reviewed and discussed at four meetings of the committee over several months. Finally, we proposed definitions for the regional lymph node stations and the consensus-based CT atlas. This atlas was approved by the Board of Directors of JLCS and JASTRO. This resulted in the first official CT atlas for defining regional lymph node stations in radiotherapy for lung cancer authorized by the JLCS and JASTRO. In conclusion, the JLCS–JASTRO consensus-based CT atlas, which conforms to the IASLC lymph node map, was established. PMID:27609192
Coelho, Luiz Gonzaga; Maguinilk, Ismael; Zaterka, Schlioma; Parente, José Miguel; do Carmo Friche Passos, Maria; Moraes-Filho, Joaquim Prado P
Signicant progress has been obtained since the Second Brazilian Consensus Conference on Helicobacter pylori Infection held in 2004, in São Paulo, SP, Brazil, and justify a third meeting to establish updated guidelines on the current management of H. pylori infection. The Third Brazilian Consensus Conference on H pylori Infection was organized by the Brazilian Nucleus for the Study of Helicobacter, a Department of the Brazilian Federation of Gastroenterology and took place on April 12-15, 2011, in Bento Gonçalves, RS, Brazil. Thirty-one delegates coming from the five Brazilian regions and one international guest, including gastroenterologists, pathologists, epidemiologists, and pediatricians undertook the meeting. The participants were allocated in one of the five main topics of the meeting: H pylori, functional dyspepsia and diagnosis; H pylori and gastric cancer; H pylori and other associated disorders; H pylori treatment and retreatment; and, epidemiology of H pylori infection in Brazil. The results of each subgroup were submitted to a final consensus voting to all participants. Relevant data were presented, and the quality of evidence, strength of recommendation, and level of consensus were graded. Seventy per cent and more votes were considered as acceptance for the final statement. This article presents the main recommendations and conclusions to guide Brazilian doctors involved in the management of H pylori infection.
NIH Consensus Statements are prepared by a nonadvocate, non-Federal panel of experts, based on (1) presentations by investigators working in areas relevant to the consensus questions during a 2 day public session; (2) questions and statements from conference attendees during open discussion periods that are part of the public session; and (3) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. The statement reflects the panel's assessment of medical knowledge available at the time the statement was written. Thus, it provides a "snapshot in time" of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research.
Pulsipher, Michael A.; Skinner, Roderick; McDonald, George B.; Hingorani, Sangeeta; Armenian, Saro H.; Cooke, Kenneth R.; Gracia, Clarisa; Petryk, Anna; Bhatia, Smita; Bunin, Nancy; Nieder, Michael L.; Dvorak, Christopher C.; Sung, Lillian; Sanders, Jean E.; Kurtzberg, Joanne; Baker, K. Scott
Existing standards for screening and management of late effects occurring in children who have undergone hematopoietic cell transplantation (HCT) include recommendations from pediatric cancer networks and consensus guidelines from adult-oriented transplantation societies applicable to all recipients of HCT. While these approaches have significant merit, they are not pediatric-HCT focused and they do not address post-HCT challenges faced by children with complex non-malignant disorders. In this article we discuss the strengths and weaknesses of current published recommendations and conclude that pediatric-specific guidelines for post-HCT screening and management would be beneficial to the long-term health of these patients and would promote late-effects research in this field. Our panel of late effects experts also provides recommendations for follow up and therapy of selected post-HCT organ and endocrine complications in pediatric patients. PMID:22248713
Tamaki, Kentaro; Tamaki, Nobumitsu; Kamada, Yoshihiko; Uehara, Kano; Zaha, Hisamitsu; Onomura, Mai; Gushimiyagi, Masanori; Kurashita, Kaname; Miyazato, Keiko; Tengan, Hiromu; Miyara, Kyuichiro; Ishida, Takanori
Breast cancer mortality is gradually increasing in Okinawa. The 1st Okinawa Breast Oncology Meeting was held on 6 July 2012 and discussions on how to curb the rising trend were focused on breast cancer screening, adjuvant treatment, socioeconomic and geographic issues, and the problem of complementary and alternative medicine. The consensus of the 1st Okinawa Breast Oncology Meeting was that ultrasonography screening is an acceptable screening system for Okinawan women because of the geographic disadvantage of having many small islands and rural areas. Educational and economic support is needed for women in rural areas to get correct information, for access to urban areas and to be treated by evidence-based optimal therapy for breast cancer. In addition, new approaches are needed for Okinawan people to successfully educate patients to correctly interpret evidence-based information.
López Torrecilla, José; Hervás, Asunción; Zapatero, Almudena; Gómez Caamaño, Antonio; Macías, Victor; Herruzo, Ismael; Maldonado, Xavier; Gómez Iturriaga, Alfonso; Casas, Francesc; González San Segundo, Carmen
Management of patients who experience biochemical failure after radical radiotherapy with or without hormonal therapy is highly challenging. The clinician must not only choose the type of treatment, but also the timing and optimal sequence of treatment administration. When biochemical failure occurs, numerous treatment scenarios are possible, thus making it more difficult to select the optimal approach. Moreover, rapid and ongoing advances in treatment options require that physicians make decisions that could impact both survival and quality of life. The aim of the present consensus statement, developed by the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR), is to provide cancer specialists with the latest, evidence-based information needed to make the best decisions for the patient under all possible treatment scenarios. The structure of this consensus statement follows the typical development of disease progression after biochemical failure, with the most appropriate treatment recommendations given for each stage. The consensus statement is organized into three separate chapters, as follows: biochemical failure with or without local recurrence and/or metastasis; progression after salvage therapy; and treatment of castration-resistant patients.
López Torrecilla, José; Hervás, Asunción; Zapatero, Almudena; Gómez Caamaño, Antonio; Macías, Victor; Herruzo, Ismael; Maldonado, Xavier; Gómez Iturriaga, Alfonso; Casas, Francesc; González San Segundo, Carmen
Management of patients who experience biochemical failure after radical radiotherapy with or without hormonal therapy is highly challenging. The clinician must not only choose the type of treatment, but also the timing and optimal sequence of treatment administration. When biochemical failure occurs, numerous treatment scenarios are possible, thus making it more difficult to select the optimal approach. Moreover, rapid and ongoing advances in treatment options require that physicians make decisions that could impact both survival and quality of life. The aim of the present consensus statement, developed by the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR), is to provide cancer specialists with the latest, evidence-based information needed to make the best decisions for the patient under all possible treatment scenarios. The structure of this consensus statement follows the typical development of disease progression after biochemical failure, with the most appropriate treatment recommendations given for each stage. The consensus statement is organized into three separate chapters, as follows: biochemical failure with or without local recurrence and/or metastasis; progression after salvage therapy; and treatment of castration-resistant patients. PMID:26109913
Management of acute coronary syndromes, particularly unstable angina, acute myocardial infarction and non-Q-wave myocardial infarction, is one of the most common and costly problems facing modern medicine. Furthermore, the increasing availability of new research and clinical information relevant to the treatment of these conditions means that continuing reappraisal of management strategies is necessary. Accordingly, the Ushuaia conference, Tierra Del Fuego, Argentina, was convened to discuss current approaches and future treatment prospects for patients with these conditions. The conference was comprised of leading Argentinian cardiologists whose primary aim was to formulate consensus recommendations regarding the management of patients with acute coronary syndromes. The first of the major recommendations for the pharmacological management of acute coronary syndromes arising from the Ushuaia Consensus Conference was that aspirin (200 to 500mg initially, then 100 to 325 mg/day) should be administered to all patients except those for whom aspirin is absolutely (or relatively, depending on the clinician's discretion) contraindicated. In such cases, ticlopidine is a suitable alternative. Intravenous nitrates are indicated for patients with angina pain (24 to 48 hours' duration), ECG changes, recurrence of angina, or signs of heart failure; in other cases, oral, transdermal or sublingual nitrates may be administered. Use of beta-blockers is recommended except when absolutely contraindicated or when there is a strong suspicion of vasospasm as a dominant mechanism in angina. Intravenous administration of these agents is preferred in patients with tachycardia, arterial hypertension or angina. Calcium antagonists are generally not recommended as first choice therapy, but can be indicated (preferably using agents that decrease heart rate) when beta-blockers are contraindicated or when there is a strong suspicion of vasospasm as a dominant mechanism in angina. Calcium
[2008 update of the 8th Consensus Development Conference of the Francophone Society of Medical Emergencies of 1999. The treatment of adult renal colic by the emergency services and in emergency rooms].
El Khebir, M; Fougeras, O; Le Gall, C; Santin, A; Perrier, C; Sureau, C; Miranda, J; Ecollan, P; Bagou, G; Trinh-Duc, A; Traxer, O
The care in the emergencies of the renal colic at the adult was the object in 1999 of a conference of consensus of the French Society of Emergency (SFMU) in association with the French Association of Urology and the Society of Nephrology. This already former text was the object of an update in 2008 by the subcommittee of scientific monitoring of the SFMU and was presented to the congress 2008. This public presentation in the presence of an expert urologist allowed to confront this new text with the practices and to publish an updating of the conference of consensus of 1999. A survey of practice was led with the emergency physicians, whose results are presented.
Valdagni, Riccardo; Scardino, Peter T; Denis, Louis
The European School of Oncology (ESO) Inside Track Conference, "Predictive Modeling in Prostate Cancer," the first event ever dedicated to prediction in prostate cancer, was organized in collaboration with the Prostate Program of Milan National Cancer Institute and the American Italian Cancer Foundation in the wonderful scenario of the Excelsior Lido Hotel in Venice on April 17 through 19, 2008. More than 240 participants from 23 countries attended this 3-day conference, which convened an exceptional group of experts from all over the world whose presentations provided a framework for understanding the state of the art in predictive modeling of prostate cancer and displayed future research trends in the uro-oncologic community. Cancer 2009;115(13 suppl):3035-8. (c) 2009 American Cancer Society.
Schmoll, H J; Souchon, R; Krege, S; Albers, P; Beyer, J; Kollmannsberger, C; Fossa, S D; Skakkebaek, N E; de Wit, R; Fizazi, K; Droz, J P; Pizzocaro, G; Daugaard, G; de Mulder, P H M; Horwich, A; Oliver, T; Huddart, R; Rosti, G; Paz Ares, L; Pont, O; Hartmann, J T; Aass, N; Algaba, F; Bamberg, M; Bodrogi, I; Bokemeyer, C; Classen, J; Clemm, S; Culine, S; de Wit, M; Derigs, H G; Dieckmann, K P; Flasshove, M; Garcia del Muro, X; Gerl, A; Germa-Lluch, J R; Hartmann, M; Heidenreich, A; Hoeltl, W; Joffe, J; Jones, W; Kaiser, G; Klepp, O; Kliesch, S; Kisbenedek, L; Koehrmann, K U; Kuczyk, M; Laguna, M P; Leiva, O; Loy, V; Mason, M D; Mead, G M; Mueller, R P; Nicolai, N; Oosterhof, G O N; Pottek, T; Rick, O; Schmidberger, H; Sedlmayer, F; Siegert, W; Studer, U; Tjulandin, S; von der Maase, H; Walz, P; Weinknecht, S; Weissbach, L; Winter, E; Wittekind, C
Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based chemotherapy, together with radiation and surgical measures, leads to the high cure rate of > or = 99% in early stages and 90%, 75-80% and 50% in advanced disease with 'good', 'intermediate' and 'poor' prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to the presence or absence of vascular invasion. Thus, different treatment options according to prognostic factors including histology, stage and patient factors and possibilities of the treating centre as well may be used to define the treatment strategy which is definitively chosen for an individual patient. However, this strategy of reduction of treatment load as well as the treatment itself require very high expertise of the treating physician with careful management and follow-up and thorough cooperation by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the available evidence which has been the basis for this consensus guideline delivering a clear proposal for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour and individual clinical situations. Since this guideline is based on the highest evidence level available today, a deviation from these proposals should be a rare and justified exception.
Muller, Berrend G.; Fütterer, Jurgen J.; Gupta, Rajan T.; Katz, Aaron; Kirkham, Alexander; Kurhanewicz, John; Moul, Judd W.; Pinto, Peter A.; Rastinehad, Ardeshir R.; Robertson, Cary; de la Rosette, Jean; Sanchez-Salas, Rafael; Jones, J. Stephen; Ukimura, Osamu; Verma, Sadhna; Wijkstra, Hessel; Marberger, Michael
Objective To establish a consensus on the utility of multiparametric magnetic resonance imaging (mpMRI) to identify patients for focal therapy. Methods Urological surgeons, radiologists, and basic researchers, from Europe and North America participated in a consensus meeting about the use of mpMRI in focal therapy of prostate cancer.The consensus process was face-to-face and specific clinical issues were raised and discussed with agreement sought when possible. All participants are listed among the authors.Topics specifically did not include staging of prostate cancer, but rather identifying the optimal requirements for performing MRI, and the current status of optimally performed mpMRI to (i) determine focality of prostate cancer (e.g. localising small target lesions of ≥0.5 mL), (ii) to monitor and assess the outcome of focal ablation therapies, and (iii) to identify the diagnostic advantages of new MRI methods.In addition, the need for transperineal template saturation biopsies in selecting patients for focal therapy was discussed, if a high quality mpMRI is available. In other words, can mpMRI replace the role of transperineal saturation biopsies in patient selection for focal therapy? Results Consensus was reached on most key aspects of the meeting; however, on definition of the optimal requirements for mpMRI, there was one dissenting voice.mpMRI is the optimum approach to achieve the objectives needed for focal therapy, if made on a high quality machine (3T with/without endorectal coil or 1.5T with endorectal coil) and judged by an experienced radiologist.Structured and standardised reporting of prostate MRI is paramount.State of the art mpMRI is capable of localising small tumours for focal therapy.State of the art mpMRI is the technique of choice for follow-up of focal ablation. Conclusions The present evidence for MRI in focal therapy is limited.mpMRI is not accurate enough to consistently grade tumour aggressiveness.Template-guided saturation biopsies
International Survey on Technical Aspects of Laparoscopic Liver Resection: a web-based study on the global diffusion of laparoscopic liver surgery prior to the 2nd International Consensus Conference on Laparoscopic Liver Resection in Iwate, Japan.
Hibi, Taizo; Cherqui, Daniel; Geller, David A; Itano, Osamu; Kitagawa, Yuko; Wakabayashi, Go
The technique of laparoscopic liver resection (LLR) has been greatly improved since the first international consensus conference. Our aim was to evaluate the worldwide spread of LLR prior to the 2nd International Consensus Conference on Laparoscopic Liver Resection in Iwate, Japan (4-6 October 2014). The International Survey on Technical Aspects of Laparoscopic Liver resection was designed to assess dissemination of LLR, indications, and the surgical techniques. The anonymous questionnaire was e-mailed to liver surgeons worldwide. A total of 448 liver surgeons responded to the survey. The peak age range of surgeons performing LLR was 41-50 years. Japan had by far the largest number of respondents (n = 223), followed by the US (n = 38) and France (n = 20). In Japan, the majority of surgeons performing LLR belonged to community hospitals, where LLR has been increasingly used since its implementation in 2009 or later, comprising up to 40% of all liver resection cases. In contrast, in North America and Europe, LLR was mostly performed at academic medical centers. LLR has undergone global dissemination after the first international consensus conference in 2008. Japan has experienced unparalleled, explosive diffusion characterized by the adoption of LLR at middle-tier, regional institutions.
Evidence is growing that there may be a connection between certain chemicals in the environment and the rising incidence of breast cancer in North America. Two recent Canadian conferences have been held to disseminate information and another is planned for 1996. "We have a situation that is similar to global warming, " Devra Lee Davis, founder of the US Breast Cancer Prevention Collaborative Research Group, warned people attending a conference in Niagara Falls, Ont. "Breast cancer continues to increase. The increase is greatest among older women who have fewer of the known risk factors. It makes sense to try to limit exposure to things that could be promoting the disease."
refilling phase after complete microbubble destruction. There are not enough data in the literature showing the additional role of quantitative analysis for clinical purposes. Thus, at present, quantitative softwares should be considered as research tools. Conversely, there is a general consensus based on experimental and clinical studies on the use of myocardial contrast echo in patients with acute myocardial infarction by means of qualitative or semi-quantitative analysis. Important information on the infarct area extension, on the efficacy of reperfusion therapy, on the presence and extension of the no-reflow phenomenon and on the extent of residual tissue viability may be derived from the routine use of myocardial contrast echo. The reference technique still remains myocardial scintigraphy even though many theoretical problems are being discussed. Part 8: Implementing ultrasound contrast in the echocardiography laboratory. Contrast echocardiography should be considered an extension of the existing echocardiographic examination. Standard laboratory equipment is sufficient to run a contrast echocardiography program. However, cultural and technological upgrading is mandatory to obtain good results in contrast echocardiography. Intravenous infusion is easier during stress echocardiography than during rest study, because the time and cost for the venous line are comprised. In this setting, the cost-effectiveness for the addition of contrast agent is optimal, but patient selection is a critical point. The economic issue (contrast agent and personnel costs, and time needed) of contrast echocardiography determines the fact that without adequate reimbursement there is no incentive to perform the procedure.
Fitzgibbons, P L; Henson, D E; Hutter, R V
The Cancer Committee of the College of American Pathologists has prepared an update of the consensus statement on premalignant breast lesions and breast cancer risk that was originally published in the Archives of Pathology & Laboratory Medicine in 1986. The objective of this publication is to better define the relative breast cancer risk associated with specific histologic abnormalities by incorporating data derived from recent case-control studies. Explanatory notes are used to document and explain specific risk classifications. In addition to refining the degree of risk associated with individual lesions, such as fibroadenoma and atypical hyperplasia, this update includes a discussion of age-specific breast cancer risk and provides examples that can be used when counseling patients.
High-resolution rectal MRI plays a crucial role in evaluating rectal cancer by providing multiple prognostic findings and imaging features that guide proper patient management. Quality reporting is critical for accurate effective communication of the information among multiple disciplines, for which a systematic structured approach is beneficial. Existing guides on reporting of rectal MRI are divergent on some issues, largely reflecting the differences in overall management of rectal cancer patients between the United States and Europe. The Korean Society of Abdominal Radiology (KSAR) study group for rectal cancer has developed an expert consensus recommendation regarding essential items for structured reporting of rectal cancer MRI using a modified Delphi method. This recommendation aims at presenting an up-to-date, evidence-based, practical, structured reporting template that can be readily adopted in daily clinical practice. In addition, a thorough explanation of the clinical and scientific rationale underlying the reporting items and their formats is provided. This KSAR recommendation may serve as a useful tool to help achieve more standardized optimal care for rectal cancer patients using rectal MRI.
High-resolution rectal MRI plays a crucial role in evaluating rectal cancer by providing multiple prognostic findings and imaging features that guide proper patient management. Quality reporting is critical for accurate effective communication of the information among multiple disciplines, for which a systematic structured approach is beneficial. Existing guides on reporting of rectal MRI are divergent on some issues, largely reflecting the differences in overall management of rectal cancer patients between the United States and Europe. The Korean Society of Abdominal Radiology (KSAR) study group for rectal cancer has developed an expert consensus recommendation regarding essential items for structured reporting of rectal cancer MRI using a modified Delphi method. This recommendation aims at presenting an up-to-date, evidence-based, practical, structured reporting template that can be readily adopted in daily clinical practice. In addition, a thorough explanation of the clinical and scientific rationale underlying the reporting items and their formats is provided. This KSAR recommendation may serve as a useful tool to help achieve more standardized optimal care for rectal cancer patients using rectal MRI. PMID:28096724
The Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4) was held 3 to 4 May 2012 in Montreal, Quebec, Canada. A group of neuroimaging experts were assigned the task of reviewing and summarizing the literature on clinical and research applications of different neuroimaging modalities in cognitive disorders. This paper summarizes the literature and recommendations made to the conference regarding the role of several emerging neuroimaging modalities in cognitive disorders. Functional magnetic resonance imaging (MRI), magnetic resonance spectroscopy, and diffusion tensor imaging are discussed in detail within this paper. Other emergent neuroimaging modalities such as positron emission tomography with novel ligands, high-field MRI, arterial spin labeling MRI and noncerebral blood flow single-photon emission computerized tomography are only discussed briefly. Neuroimaging modalities that were recommended at the CCCDTD4 for both clinical and research applications such as amyloid and flurodeoxyglucose positron emission tomography, computerized tomography and structural MRI are discussed in a separate paper by the same authors. A literature search was conducted using the PubMed database including articles in English that involved human subjects and covered the period from the last CCCDTD publication (CCCDTD3; January 2006) until April 2012. Search terms included the name of the specific modality, dementia, Alzheimer's disease, and mild cognitive impairment. A separate search used the same parameters but was restricted to review articles to identify recent evidence-based reviews. Case studies and small case series were not included. Papers representing current evidence were selected, reviewed, and summarized, and the results were presented at the CCCDTD4 meeting with recommendations regarding the utility of various neuroimaging modalities in cognitive disorders. The evidence was graded according to the Oxford Centre for Evidence Based
Burhan, Amer M; Bartha, Robert; Bocti, Christian; Borrie, Michael; Laforce, Robert; Rosa-Neto, Pedro; Soucy, Jean-Paul
The Fourth Canadian Consensus Conference on the Diagnosis and Treatment of Dementia (CCCDTD4) was held 3 to 4 May 2012 in Montreal, Quebec, Canada. A group of neuroimaging experts were assigned the task of reviewing and summarizing the literature on clinical and research applications of different neuroimaging modalities in cognitive disorders. This paper summarizes the literature and recommendations made to the conference regarding the role of several emerging neuroimaging modalities in cognitive disorders. Functional magnetic resonance imaging (MRI), magnetic resonance spectroscopy, and diffusion tensor imaging are discussed in detail within this paper. Other emergent neuroimaging modalities such as positron emission tomography with novel ligands, high-field MRI, arterial spin labeling MRI and noncerebral blood flow single-photon emission computerized tomography are only discussed briefly. Neuroimaging modalities that were recommended at the CCCDTD4 for both clinical and research applications such as amyloid and flurodeoxyglucose positron emission tomography, computerized tomography and structural MRI are discussed in a separate paper by the same authors. A literature search was conducted using the PubMed database including articles in English that involved human subjects and covered the period from the last CCCDTD publication (CCCDTD3; January 2006) until April 2012. Search terms included the name of the specific modality, dementia, Alzheimer's disease, and mild cognitive impairment. A separate search used the same parameters but was restricted to review articles to identify recent evidence-based reviews. Case studies and small case series were not included. Papers representing current evidence were selected, reviewed, and summarized, and the results were presented at the CCCDTD4 meeting with recommendations regarding the utility of various neuroimaging modalities in cognitive disorders. The evidence was graded according to the Oxford Centre for Evidence Based
The discovery of cancer dependencies has the potential to inform therapeutic strategies and to identify putative drug targets. Integrating data from comprehensive genomic profiling of cancer cell lines and from functional characterization of cancer cell dependencies, we discovered that loss of the enzyme methylthioadenosine phosphorylase (MTAP) confers a selective dependence on protein arginine methyltransferase 5 (PRMT5) and its binding partner WDR77. MTAP is frequently lost due to its proximity to the commonly deleted tumor suppressor gene, CDKN2A.
Xynos, Evaghelos; Tekkis, Paris; Gouvas, Nikolaos; Vini, Louiza; Chrysou, Evangelia; Tzardi, Maria; Vassiliou, Vassilis; Boukovinas, Ioannis; Agalianos, Christos; Androulakis, Nikolaos; Athanasiadis, Athanasios; Christodoulou, Christos; Dervenis, Christos; Emmanouilidis, Christos; Georgiou, Panagiotis; Katopodi, Ourania; Kountourakis, Panteleimon; Makatsoris, Thomas; Papakostas, Pavlos; Papamichael, Demetris; Pechlivanides, George; Pentheroudakis, Georgios; Pilpilidis, Ioannis; Sgouros, Joseph; Triantopoulou, Charina; Xynogalos, Spyridon; Karachaliou, Niki; Ziras, Nikolaos; Zoras, Odysseas; Souglakos, John
In rectal cancer management, accurate staging by magnetic resonance imaging, neo-adjuvant treatment with the use of radiotherapy, and total mesorectal excision have resulted in remarkable improvement in the oncological outcomes. However, there is substantial discrepancy in the therapeutic approach and failure to adhere to international guidelines among different Greek-Cypriot hospitals. The present guidelines aim to aid the multidisciplinary management of rectal cancer, considering both the local special characteristics of our healthcare system and the international relevant agreements (ESMO, EURECCA). Following background discussion and online communication sessions for feedback among the members of an executive team, a consensus rectal cancer management was obtained. Statements were subjected to the Delphi methodology voting system on two rounds to achieve further consensus by invited multidisciplinary international experts on colorectal cancer. Statements were considered of high, moderate or low consensus if they were voted by ≥80%, 60-80%, or <60%, respectively; those obtaining a low consensus level after both voting rounds were rejected. One hundred and two statements were developed and voted by 100 experts. The mean rate of abstention per statement was 12.5% (range: 2-45%). In the end of the process, all statements achieved a high consensus. Guidelines and algorithms of diagnosis and treatment were proposed. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. PMID:27064746
Current state of the art, multimodality research and future visions for the treatment of patients with prostate cancer: consensus results from "Challenges and Chances in Prostate Cancer Research Meeting 2013".
Combs, Stephanie E; Debus, Jürgen; Feick, Günter; Hadaschik, Boris; Hohenfellner, Markus; Schüle, Roland; Zacharias, Jens-Peter; Schwardt, Malte
A brainstorming and consensus meeting organized by the German Cancer Aid focused on modern treatment of prostate cancer and promising innovative techniques and research areas. Besides optimization of screening algorithms, molecular-based stratification and individually tailored treatment regimens will be the future of multimodal prostate cancer management. Effective interdisciplinary structures, including biobanking and data collection mechanisms are the basis for such developments.
Palatini, Paolo; Rosei, Enrico Agabiti; Casiglia, Edoardo; Chalmers, John; Ferrari, Roberto; Grassi, Guido; Inoue, Teruo; Jelakovic, Bojan; Jensen, Magnus T; Julius, Stevo; Kjeldsen, Sverre E; Mancia, Giuseppe; Parati, Gianfranco; Pauletto, Paolo; Stella, Andrea; Zanchetti, Alberto
In June 2015, a panel of experts gathered in a consensus conference to plan updating recommendations on the management of the hypertensive patient with elevated heart rate (HR), previously released in 2006. The issues examined during that meeting and further discussed by the participants during the following months involved the assessment of HR, the relevance of HR as a cardiovascular risk factor, the definition of tachycardia and the treatment of the hypertensive patient with high HR. For the measurement of resting HR the panel experts recommended that scientific investigations focusing on HR should report information on length of resting period before measurement, information about temperature and environment, method of measurement, duration of measurement, number of readings, time interval between measurements, body position and type of observer. According to the panellists there is convincing evidence that HR is an important risk factor for cardiovascular disease and they suggest to routinely include HR measurement in the assessment of the hypertensive patient. Regarding the definition of tachycardia, the panellists acknowledged that in the absence of convincing data any threshold used to define tachycardia is arbitrary. Similarly, as there are no outcome studies of HR lowering in tachycardia hypertension, the panellists could not make practical therapeutic suggestions for the management of such patients. However, the experts remarked that absence of evidence does not mean evidence against the importance of tachycardia as a risk factor for cardiovascular disease and that long-term exposure to a potentially important risk factor may impair the patient's prognosis. The main aims of the present document are to alert researchers and physicians about the importance of measuring HR in hypertensive patients, and to stimulate research to clarify unresolved issues.
Facchinetti, Fabio; Bizzarri, Mariano; Benvenga, Salvatore; D'Anna, Rosario; Lanzone, Antonio; Soulage, Christophe; Di Renzo, Gian Carlo; Hod, Moshe; Cavalli, Pietro; Chiu, Tony T; Kamenov, Zdravko A; Bevilacqua, Arturo; Carlomagno, Gianfranco; Gerli, Sandro; Oliva, Mario Montanino; Devroey, Paul
In recent years, interest has been focused to the study of the two major inositol stereoisomers: myo-inositol (MI) and d-chiro-inositol (DCI), because of their involvement, as second messengers of insulin, in several insulin-dependent processes, such as metabolic syndrome and polycystic ovary syndrome. Although these molecules have different functions, very often their roles have been confused, while the meaning of several observations still needs to be interpreted under a more rigorous physiological framework. With the aim of clarifying this issue, the 2013 International Consensus Conference on MI and DCI in Obstetrics and Gynecology identified opinion leaders in all fields related to this area of research. They examined seminal experimental papers and randomized clinical trials reporting the role and the use of inositol(s) in clinical practice. The main topics were the relation between inositol(s) and metabolic syndrome, polycystic ovary syndrome (with a focus on both metabolic and reproductive aspects), congenital anomalies, gestational diabetes. Clinical trials demonstrated that inositol(s) supplementation could fruitfully affect different pathophysiological aspects of disorders pertaining Obstetrics and Gynecology. The treatment of PCOS women as well as the prevention of GDM seem those clinical conditions which take more advantages from MI supplementation, when used at a dose of 2g twice/day. The clinical experience with MI is largely superior to the one with DCI. However, the existence of tissue-specific ratios, namely in the ovary, has prompted researchers to recently develop a treatment based on both molecules in the proportion of 40 (MI) to 1 (DCI).
Kirchhof, Paulus; Bax, Jeroen; Blomstrom-Lundquist, Carina; Calkins, Hugh; Camm, A John; Cappato, Ricardo; Cosio, Francisco; Crijns, Harry; Diener, Hans-Christian; Goette, Andreas; Israel, Carsten W; Kuck, Karl-Heinz; Lip, Gregory Y H; Nattel, Stanley; Page, Richard L; Ravens, Ursula; Schotten, Ulrich; Steinbeck, Gerhard; Vardas, Panos; Waldo, Albert; Wegscheider, Karl; Willems, Stephan; Breithardt, Günter
Atrial fibrillation (AF) causes important mortality and morbidity on a population-level. So far, we do not have the means to prevent AF or AF-related complications adequately. Therefore, over 70 experts on atrial fibrillation convened for the 2nd AFNET/EHRA consensus conference to suggest directions for research to improve management of AF patients (Appendix 1). The group defined three main areas in need for research in AF: 1. better understanding of the mechanisms of AF; 2. Improving rhythm control monitoring and management; and 3. comprehensive cardiovascular risk management in AF patients. The group put forward the hypothesis that successful therapy of AF and its associated complications will require comprehensive therapy. This applies e.g. to the "old" debate of "rate versus rhythm control", since rhythm control is generally added to underlying (continued) rate control therapy, but also to the emerging debate of "antiarrhythmic drugs versus catheter ablation", of which both may be needed in most patients to maintain sinus rhythm, but also to therapy of conditions that predispose to AF and contribute to cardiovascular complications such as stroke, cognitive decline, heart failure, and acute coronary syndromes. We call for research initiatives aiming at a better understanding of the different causes of AF and its complications, and at development and validation of mechanism-based therapies. The future of AF therapy may require a combination of management of underlying and concomitant conditions, early and comprehensive rhythm control therapy, adequate control of ventricular rate and cardiac function, and continuous therapy to prevent AF-associated complications (e.g. antithrombotic therapy). The reasons for these suggestions are detailed in this paper.
Kennedy, Andrew; Bester, Lourens; Salem, Riad; Sharma, Ricky A; Parks, Rowan W; Ruszniewski, Philippe
Objectives Liver metastasis from a neuroendocrine tumour (NET) represents a significant clinical entity. A multidisciplinary group of experts was convened to develop state-of-the-art recommendations for its management. Methods Peer-reviewed published reports on intra-arterial therapies for NET hepatic metastases were reviewed and the findings presented to a jury of peers. The therapies reviewed included transarterial embolization (TAE), transarterial chemoembolization (TACE) and radioembolization (RE). Two systems were used to evaluate the level of evidence in each publication: (i) the US National Cancer Institute (NCI) system, and (ii) the GRADE system. Results Eighteen publications were reviewed. These comprised 11 reports on TAE or TACE and seven on RE. Four questions posed to the panel were answered and recommendations offered. Conclusions Studies of moderate quality support the use of TAE, TACE and RE in hepatic metastases of NETs. The quality and strength of the reports available do not allow any modality to be determined as superior in terms of imaging response, symptomatic response or impact on survival. Radioembolization may have advantages over TAE and TACE because it causes fewer side-effects and requires fewer treatments. Based on current European Neuroendocrine Tumor Society (ENETS) Consensus Guidelines, RE can be substituted for TAE or TACE in patients with either liver-only disease or those with limited extrahepatic metastases. PMID:25186181
Brewster, Abenaa M; Patterson, Sherri L; Forman, Michele R; Hughes-Halbert, Chanita; Limburg, Paul J; Ondrey, Frank G; Paskett, Electra D; Wetter, David W; Hawk, Ernest T
The Eighth Annual Frontiers in Cancer Prevention Research meeting was held in Houston, Texas, in November 2009. This report highlights significant presentations that advance the fields of chemoprevention, clinical trial recruitment and retention, cancer screening including optical imaging, energy balance, and nutritional epidemiology, and health communications and decision making. In findings from the randomized Reduction by Dutasteride of Prostate Cancer Events trial, dutasteride reduced the risk of biopsy-detectable prostate cancer in high-risk men by 23% compared with placebo. Important clues about the dosing and window of susceptibility for supplementation with choline, vitamin D, and folate were revealed from epigenetic research that has implications for future nutritional epidemiology research. Noninvasive optical imaging techniques using endoscopic ultrasound and autofluorescence for the early detection of cancers in the lung, pancreas, and oral cavity are being studied. The report also addresses the challenges of promoting cancer prevention. Understanding how individuals process risk information and make sustained behavior changes and the effect of socioeconomic status on health disparities were identified as critical areas of research. This multidisciplinary research meeting of basic, clinical, and behavioral scientists and epidemiologists continues to play a major role in identifying the research priority areas of cancer prevention, elucidating new mechanisms of carcinogenesis for targeted chemoprevention therapies and delivering a comprehensive strategy for engaging individuals in the unifying goal to reduce cancer incidence.
The International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: a list of recommendations and additional conclusions: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.
Le Roux, Peter; Menon, David K; Citerio, Giuseppe; Vespa, Paul; Bader, Mary Kay; Brophy, Gretchen; Diringer, Michael N; Stocchetti, Nino; Videtta, Walter; Armonda, Rocco; Badjatia, Neeraj; Bösel, Julian; Chesnut, Randall; Chou, Sherry; Claassen, Jan; Czosnyka, Marek; De Georgia, Michael; Figaji, Anthony; Fugate, Jennifer; Helbok, Raimund; Horowitz, David; Hutchinson, Peter; Kumar, Monisha; McNett, Molly; Miller, Chad; Naidech, Andrew; Oddo, Mauro; Olson, DaiWai; O'Phelan, Kristine; Provencio, J Javier; Puppo, Corinna; Riker, Richard; Roberson, Claudia; Schmidt, Michael; Taccone, Fabio
Careful patient monitoring using a variety of techniques including clinical and laboratory evaluation, bedside physiological monitoring with continuous or non-continuous techniques and imaging is fundamental to the care of patients who require neurocritical care. How best to perform and use bedside monitoring is still being elucidated. To create a basic platform for care and a foundation for further research the Neurocritical Care Society in collaboration with the European Society of Intensive Care Medicine, the Society for Critical Care Medicine and the Latin America Brain Injury Consortium organized an international, multidisciplinary consensus conference to develop recommendations about physiologic bedside monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews as a background to the recommendations. In this article, we highlight the recommendations and provide additional conclusions as an aid to the reader and to facilitate bedside care.
Di Gangi, Iole Maria; Mazza, Tommaso; Fontana, Andrea; Copetti, Massimiliano; Fusilli, Caterina; Ippolito, Antonio; Mattivi, Fulvio; Latiano, Anna; Andriulli, Angelo
Purpose pancreatic adenocarcinoma is the fourth leading cause of cancer related deaths due to its aggressive behavior and poor clinical outcome. There is a considerable variability in the frequency of serum tumor markers in cancer' patients. We performed a metabolomics screening in patients diagnosed with pancreatic cancer. Experimental Design Two targeted metabolomic assays were conducted on 40 serum samples of patients diagnosed with pancreatic cancer and 40 healthy controls. Multivariate methods and classification trees were performed. Materials and Methods Sparse partial least squares discriminant analysis (SPLS-DA) was used to reduce the high dimensionality of a pancreatic cancer metabolomic dataset, differentiating between pancreatic cancer (PC) patients and healthy subjects. Using Random Forest analysis palmitic acid, 1,2-dioleoyl-sn-glycero-3-phospho-rac-glycerol, lanosterol, lignoceric acid, 1-monooleoyl-rac-glycerol, cholesterol 5α,6α epoxide, erucic acid and taurolithocholic acid (T-LCA), oleoyl-L-carnitine, oleanolic acid were identified among 206 metabolites as highly discriminating between disease states. Comparison between Receiver Operating Characteristic (ROC) curves for palmitic acid and CA 19-9 showed that the area under the ROC curve (AUC) of palmitic acid (AUC=1.000; 95% confidence interval) is significantly higher than CA 19-9 (AUC=0.963; 95% confidence interval: 0.896-1.000). Conclusion Mass spectrometry-based metabolomic profiling of sera from pancreatic cancer patients and normal subjects showed significant alterations in the profiles of the metabolome of PC patients as compared to controls. These findings offer an information-rich matrix for discovering novel candidate biomarkers with diagnostic or prognostic potentials. PMID:26735340
Hurria, Arti; Dale, William; Mooney, Margaret; Rowland, Julia H.; Ballman, Karla V.; Cohen, Harvey J.; Muss, Hyman B.; Schilsky, Richard L.; Ferrell, Betty; Extermann, Martine; Schmader, Kenneth E.; Mohile, Supriya G.
A majority of cancer diagnoses and deaths occur in patients age ≥ 65 years. With the aging of the US population, the number of older adults with cancer will grow. Although the coming wave of older patients with cancer was anticipated in the early 1980s, when the need for more research on the cancer-aging interface was recognized, many knowledge gaps remain when it comes to treating older and/or frailer patients with cancer. Relatively little is known about the best way to balance the risks and benefits of existing cancer therapies in older patients; however, these patients continue to be underrepresented in clinical trials. Furthermore, the available clinical trials often do not include end points pertinent to the older adult population, such as preservation of function, cognition, and independence. As part of its ongoing effort to advance research in the field of geriatric oncology, the Cancer and Aging Research Group held a conference in November 2012 in collaboration with the National Cancer Institute, the National Institute on Aging, and the Alliance for Clinical Trials in Oncology. The goal was to develop recommendations and establish research guidelines for the design and implementation of therapeutic clinical trials for older and/or frail adults. The conference sought to identify knowledge gaps in cancer clinical trials for older adults and propose clinical trial designs to fill these gaps. The ultimate goal of this conference series is to develop research that will lead to evidence-based care for older and/or frail adults with cancer. PMID:25071116
Reis, Leonardo O; Billis, Athanase; Zequi, Stenio C; Tobias-Machado, Marcos; Viana, Publio; Cerqueira, Michael; Ward, John F
Prostate cancer is a common malignancy among men, and the current screening, imaging and sampling approaches aim to detect early-stage, organ-confined disease. In such scenario, focal prostate cancer therapy currently relies on the index lesion concept as the dominant lesion that drives the disease natural history. Focal therapy demands the essential imaging and sampling techniques to strategically locate and qualify the disease, but, despite advances in technology, prostate imaging and biopsy have several limitations that need to be overcome if focal therapy is to be developed further. The I Prostate Cancer Focal Treatment International Symposium was convened to foster discussion on this topic that sits at the crossroads of multiple disciplines (Urology, Pathology, Radiology, Radiation Oncology and Medical Oncology) all of which were represented for this comprehensive multidisciplinary review of the current literature.
Kotecha, Rishi S; Kees, Ursula R; Cole, Catherine H; Gottardo, Nicholas G
Rare childhood cancers have not benefited to the same extent from the gains that have been made for their frequently occurring counterparts. In recent years, this gap has been recognized and a number of vehicles now exist to improve outcome, including rare tumor groups, disease-specific registries, and clinics. The multitude of approaches has allowed significant progress, however, this framework is limited by patient number and is not inclusive for every type of rare childhood cancer. These shortcomings can be overcome by a single global unified approach to the study of rare childhood tumors.
Will screening colonoscopy disappear and transform gastroenterology practice? Threats to clinical practice and recommendations to reduce their impact: report of a consensus conference conducted by the AGA Institute Future Trends Committee.
Regueiro, Carol R
The AGA Institute Future Trends Committee (FTC) developed this report based on a consensus conference it convened on April 1-2, 2006, in Washington, DC. The report was prepared for the FTC by Carol Regueiro, MD, a medical writer under contract to the AGA Institute, and Michael Stolar, PhD, staff liaison to the FTC. It was approved by the FTC on July 12, 2006, and accepted by the AGA Institute Governing Board on July 22, 2006. This report reflects the panel's assessment of information available at the time of the conference. Readers should view this report in the context of data that will continue to accumulate and facts that may change after its creation.
This research note presents a preliminary study of the structure of consensus statements (CSs). The consensus statement is released by a medical association after calling a consensus development conference on a pertinent medical issue. Using a very small corpus, this note attempts to characterize consensus statements by identifying the sequence of…
Fitzgerald, Rebecca C; Hardwick, Richard; Huntsman, David; Carneiro, Fatima; Guilford, Parry; Blair, Vanessa; Chung, Daniel C; Norton, Jeff; Ragunath, Krishnadath; Van Krieken, J Han; Dwerryhouse, Sarah; Caldas, Carlos
25-30% of families fulfilling the criteria for hereditary diffuse gastric cancer have germline mutations of the CDH1 (E-cadherin) gene. In light of new data and advancement of technologies, a multidisciplinary workshop was convened to discuss genetic testing, surgery, endoscopy and pathology reporting. The updated recommendations include broadening of CDH1 testing criteria such that: histological confirmation of diffuse gastric criteria is only required for one family member; inclusion of individuals with diffuse gastric cancer before the age of 40 years without a family history; and inclusion of individuals and families with diagnoses of both diffuse gastric cancer (including one before the age of 50 years) and lobular breast cancer. Testing is considered appropriate from the age of consent following counselling and discussion with a multidisciplinary team. In addition to direct sequencing, large genomic rearrangements should be sought. Annual mammography and breast MRI from the age of 35 years is recommended for women due to the increased risk for lobular breast cancer. In mutation positive individuals prophylactic total gastrectomy at a centre of excellence should be strongly considered. Protocolised endoscopic surveillance in centres with endoscopists and pathologists experienced with these patients is recommended for: those opting not to have gastrectomy, those with mutations of undetermined significance, and in those families for whom no germline mutation is yet identified. The systematic histological study of prophylactic gastrectomies almost universally shows pre-invasive lesions including in situ signet ring carcinoma with pagetoid spread of signet ring cells. Expert histopathological confirmation of these early lesions is recommended.
The 2016 Academic Emergency Medicine Consensus Conference, Shared Decision Making in the Emergency Department: Development of a Policy-relevant Patient-centered Research Agenda May 10, 2016, New Orleans, LA.
Grudzen, Corita R; Anderson, Jana R; Carpenter, Christopher R; Hess, Erik P
Shared decision making in emergency medicine has the potential to improve the quality, safety, and outcomes of emergency department (ED) patients. Given that the ED is the gateway to care for patients with a variety of illnesses and injuries and the safety net for patients otherwise unable to access care, shared decision making in the ED is relevant to numerous disciplines and the interests of the United States (U.S.) public. On May 10, 2016 the 16th annual Academic Emergency Medicine (AEM) consensus conference, "Shared Decision Making: Development of a Policy-Relevant Patient-Centered Research Agenda" was held in New Orleans, Louisiana. During this one-day conference clinicians, researchers, policy-makers, patient and caregiver representatives, funding agency representatives, trainees, and content experts across many areas of medicine interacted to define high priority areas for research in 1 of 6 domains: 1) diagnostic testing; 2) policy, 3) dissemination/implementation and education, 4) development and testing of shared decision making approaches and tools in practice, 5) palliative care and geriatrics, and 6) vulnerable populations and limited health literacy. This manuscript describes the current state of shared decision making in the ED context, provides an overview of the conference planning process, the aims of the conference, the focus of each respective breakout session, the roles of patient and caregiver representatives and an overview of the conference agenda. The results of this conference published in this issue of AEM provide an essential summary of the future research priorities for shared decision making to increase quality of care and patient-centered outcomes.
Papamichael, D; Audisio, R A; Glimelius, B; de Gramont, A; Glynne-Jones, R; Haller, D; Köhne, C-H; Rostoft, S; Lemmens, V; Mitry, E; Rutten, H; Sargent, D; Sastre, J; Seymour, M; Starling, N; Van Cutsem, E; Aapro, M
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in Europe and worldwide, with the peak incidence in patients >70 years of age. However, as the treatment algorithms for the treatment of patients with CRC become ever more complex, it is clear that a significant percentage of older CRC patients (>70 years) are being less than optimally treated. This document provides a summary of an International Society of Geriatric Oncology (SIOG) task force meeting convened in Paris in 2013 to update the existing expert recommendations for the treatment of older (geriatric) CRC patients published in 2009 and includes overviews of the recent data on epidemiology, geriatric assessment as it relates to surgery and oncology, and the ability of older CRC patients to tolerate surgery, adjuvant chemotherapy, treatment of their metastatic disease including palliative chemotherapy with and without the use of the biologics, and finally the use of adjuvant and palliative radiotherapy in the treatment of older rectal cancer patients. An overview of each area was presented by one of the task force experts and comments invited from other task force members.
The mile-high city of Denver was the site of this year's World Conference on Lung Cancer, which reached its 16th event. The conference scheduled 3 days of intensive scientific research presentations and discussions arranged in oral, mini-oral and poster sessions, plus an array of additional educational sessions. Being the largest international gathering of lung cancer and thoracic malignancy clinicians and researchers, important new research on prevention, screening and treatment of lung cancer and other malignancies of the thorax, with special emphasis on thymoma and mesothelioma, was presented during the conference.
Dervenis, Christos; Xynos, Evaghelos; Sotiropoulos, George; Gouvas, Nikolaos; Boukovinas, Ioannis; Agalianos, Christos; Androulakis, Nikolaos; Athanasiadis, Athanasios; Christodoulou, Christos; Chrysou, Evangelia; Emmanouilidis, Christos; Georgiou, Panagiotis; Karachaliou, Niki; Katopodi, Ourania; Kountourakis, Panteleimon; Kyriazanos, Ioannis; Makatsoris, Thomas; Papakostas, Pavlos; Papamichael, Demetris; Pechlivanides, George; Pentheroudakis, Georgios; Pilpilidis, Ioannis; Sgouros, Joseph; Tekkis, Paris; Triantopoulou, Charina; Tzardi, Maria; Vassiliou, Vassilis; Vini, Louiza; Xynogalos, Spyridon; Ziras, Nikolaos; Souglakos, John
There is discrepancy and failure to adhere to current international guidelines for the management of metastatic colorectal cancer (CRC) in hospitals in Greece and Cyprus. The aim of the present document is to provide a consensus on the multidisciplinary management of metastastic CRC, considering both special characteristics of our Healthcare System and international guidelines. Following discussion and online communication among the members of an executive team chosen by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic CRC disease was developed. Statements were subjected to the Delphi methodology on two voting rounds by invited multidisciplinary international experts on CRC. Statements reaching level of agreement by ≥80% were considered as having achieved large consensus, whereas statements reaching 60-80% moderate consensus. One hundred and nine statements were developed. Ninety experts voted for those statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In the end of the process, all statements achieved a large consensus. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. R0 resection is the only intervention that may offer substantial improvement in the oncological outcomes. PMID:27708505
Casali, P. G.; Bruzzi, P.; Bogaerts, J.; Blay, J.-Y.; Aapro, M.; Adamous, A.; Berruti, A.; Blay, J.-Y.; Bogaerts, J.; Bressington, J.; Bruzzi, B.; Capocaccia, R.; Cardoso, F.; Casali, P. G.; Celis, J. E.; Cervantes, A.; Ciardiello, F.; Claussen, C.; Coleman, M.; Comis, S.; Craine, S.; De Boltz, D.; De Lorenzo, F.; Dei Tos, A. P.; Gatta, G.; Geissler, J.; Giuliani, R.; Grande, E.; Gronchi, A.; Jezdic, S.; Jonsson, B.; Jost, L.; Keulen, H.; Lacombe, D.; Lamory, G.; Le Cam, Y.; Leto di Priolo, S.; Licitra, L.; Macchia, F.; Margulies, A.; Marreaud, S.; McVie, G.; Narbutas, S.; Oliver, K.; Pavlidis, N.; Pelouchova, J.; Pentheroudakis, G.; Piccart, M.; Pierotti, M. A.; Pravettoni, G.; Redmond, K.; Riegman, P.; Ruffilli, M. P.; Ryner, D.; Sandrucci, S.; Seymour, M.; Torri, V.; Trama, A.; Van Belle, S.; Vassal, G.; Wartenberg, M.; Watts, C.; Wilson, A.; Yared, W.
While they account for one-fifth of new cancer cases, rare cancers are difficult to study. A higher than average degree of uncertainty should be accommodated for clinical as well as for population-based decision making. Rules of rational decision making in conditions of uncertainty should be rigorously followed and would need widely informative clinical trials. In principle, any piece of new evidence would need to be exploited in rare cancers. Methodologies to explicitly weigh and combine all the available evidence should be refined, and the Bayesian logic can be instrumental to this end. Likewise, Bayesian-design trials may help optimize the low number of patients liable to be enrolled in clinical studies on rare cancers, as well as adaptive trials in general, with their inherent potential of flexibility when properly applied. While clinical studies are the mainstay to test hypotheses, the potential of electronic patient records should be exploited to generate new hypotheses, to create external controls for future studies (when internal controls are unpractical), to study effectiveness of new treatments in real conditions. Framework study protocols in specific rare cancers to sequentially test sets of new agents, as from the early post-phase I development stage, should be encouraged. Also the compassionate and the off-label settings should be exploited to generate new evidence, and flexible regulatory innovations such as adaptive licensing could convey new agents early to rare cancer patients, while generating evidence. Though validation of surrogate end points is problematic in rare cancers, the use of an updated notion of tumor response may be of great value in the single patient to optimize the use of therapies, all the more the new ones. Disease-based communities, involving clinicians and patients, should be regularly consulted by regulatory bodies when setting their policies on drug approval and reimbursement in specific rare cancers. PMID:25274616
Imaging technologies are being increasingly employed to guide the delivery of cancer therapies with the intent to increase their performance and efficacy. To date, many patients have benefited from image-guided treatments through prolonged survival and improvements in quality of life. Advances in nanomedicine have enabled the development of multifunctional imaging agents that can further increase the performance of image-guided cancer therapy. Specifically, this talk will focus on examples that demonstrate the benefits and application of nanomedicine in the context of image-guide surgery, personalized drug delivery, tracking of cell therapies and high precision radiotherapy delivery.
Hidalgo, M; Álvarez, R; Gallego, J; Guillén-Ponce, C; Laquente, B; Macarulla, T; Muñoz, A; Salgado, M; Vera, R; Adeva, J; Alés, I; Arévalo, S; Blázquez, J; Calsina, A; Carmona, A; de Madaria, E; Díaz, R; Díez, L; Fernández, T; de Paredes, B G; Gallardo, M E; González, I; Hernando, O; Jiménez, P; López, A; López, C; López-Ríos, F; Martín, E; Martínez, J; Martínez, A; Montans, J; Pazo, R; Plaza, J C; Peiró, I; Reina, J J; Sanjuanbenito, A; Yaya, R; Carrato, Alfredo
The management of patients with pancreatic cancer has advanced over the last few years. We convey a multidisciplinary group of experts in an attempt to stablish practical guidelines for the diagnoses, staging and management of these patients. This paper summarizes the main conclusions of the working group. Patients with suspected pancreatic ductal adenocarcinoma should be rapidly evaluated and referred to high-volume centers. Multidisciplinary supervision is critical for proper diagnoses, staging and to frame a treatment plan. Surgical resection together with chemotherapy offers the highest chance for cure in early stage disease. Patients with advanced disease should be classified in treatment groups to guide systemic treatment. New chemotherapeutic regimens have resulted in improved survival. Symptomatic management is critical in this disease. Enrollment in a clinical trial is, in general, recommended.
Denise Lach; Stephanie Sanford
A consensus workshop was developed and convened with ten state regulators to characterize concerns regarding emerging bioremediation technology to be used to clean-up radionuclides and heavy metals in mixed wastes at US DOE sites. Two questions were explored: integrated questions: (1) What impact does participation in a consensus workshop have on the knowledge, attitudes, and practices of state regulators regarding bioremediation technology? (2) How effective is a consensus workshop as a strategy for eliciting and articulating regulators’ concerns regarding the use of bioremediation to clean up radionuclides and heavy metals in mixed wastes at U.S. Department of Energy Sites around the county? State regulators met together for five days over two months to learn about bioremediation technology and develop a consensus report of their recommendations regarding state regulatory concerns. In summary we found that panel members: - quickly grasped the science related to bioremediation and were able to effectively interact with scientists working on complicated issues related to the development and implementation of the technology; - are generally accepting of in situ bioremediation, but concerned about costs, implementation (e.g., institutional controls), and long-term effectiveness of the technology; - are concerned equally about technological and implementation issues; and - believed that the consensus workshop approach to learning about bioremediation was appropriate and useful. Finally, regulators wanted decision makers at US DOE to know they are willing to work with DOE regarding innovative approaches to clean-up at their sites, and consider a strong relationship between states and the DOE as critical to any effective clean-up. They do not want perceive themselves to be and do not want others to perceive them as barriers to successful clean-up at their sites.
Tavtigian, Sean V.; Oefner, Peter J.; Babikyan, Davit; Hartmann, Anne; Healey, Sue; Le Calvez-Kelm, Florence; Lesueur, Fabienne; Byrnes, Graham B.; Chuang, Shu-Chun; Forey, Nathalie; Feuchtinger, Corinna; Gioia, Lydie; Hall, Janet; Hashibe, Mia; Herte, Barbara; McKay-Chopin, Sandrine; Thomas, Alun; Vallée, Maxime P.; Voegele, Catherine; Webb, Penelope M.; Whiteman, David C.; Sangrajrang, Suleeporn; Hopper, John L.; Southey, Melissa C.; Andrulis, Irene L.; John, Esther M.; Chenevix-Trench, Georgia
The susceptibility gene for ataxia telangiectasia, ATM, is also an intermediate-risk breast-cancer-susceptibility gene. However, the spectrum and frequency distribution of ATM mutations that confer increased risk of breast cancer have been controversial. To assess the contribution of rare variants in this gene to risk of breast cancer, we pooled data from seven published ATM case-control mutation-screening studies, including a total of 1544 breast cancer cases and 1224 controls, with data from our own mutation screening of an additional 987 breast cancer cases and 1021 controls. Using an in silico missense-substitution analysis that provides a ranking of missense substitutions from evolutionarily most likely to least likely, we carried out analyses of protein-truncating variants, splice-junction variants, and rare missense variants. We found marginal evidence that the combination of ATM protein-truncating and splice-junction variants contribute to breast cancer risk. There was stronger evidence that a subset of rare, evolutionarily unlikely missense substitutions confer increased risk. On the basis of subset analyses, we hypothesize that rare missense substitutions falling in and around the FAT, kinase, and FATC domains of the protein may be disproportionately responsible for that risk and that a subset of these may confer higher risk than do protein-truncating variants. We conclude that a comparison between the graded distributions of missense substitutions in cases versus controls can complement analyses of truncating variants and help identify susceptibility genes and that this approach will aid interpretation of the data emerging from new sequencing technologies. PMID:19781682
Singh, Anju; Bodas, Manish; Wakabayashi, Nobunao; Bunz, Fred; Biswal, Shyam
Nuclear factor erythroid-2 related factor 2 (Nrf2), a redox-sensitive transcription factor, regulates the expression of antioxidant enzymes and several anti-apoptotic proteins, which confer cytoprotection against oxidative stress and apoptosis. Constitutive activation of Nrf2 in lung cancer cells promotes tumorigenicity and contributes to chemoresistance by upregulation of glutathione, thioredoxin, and the drug efflux pathways involved in detoxification of electrophiles and broad spectrum of drugs. In this study, we show that RNAi-mediated lowering of Nrf2 levels in non-small-cell lung cancer (NSCLC) cell lines (A549 and H460) led to a dramatic increase in endogenous reactive oxygen species (ROS) levels. Similarly, γ-irradiation-induced formation of protein carbonyls were significantly higher in Nrf2-depleted lung cancer cells, suggesting increased lethality of ionizing radiation in the absence of Nrf2. Radiation-induced protein oxidation in Nrf2shRNA cells correlated with reduced survival as measured by clonogenic assay. Radiation-induced cell death was abrogated by pretreatment with antioxidants such as N-acetyl-L-cysteine, glutathione, and vitamin-E, highlighting the importance of antioxidants in conferring protection against radiation injury. Using genetically-modified gain and loss of function models of Nrf2, in mouse embryonic fibroblasts, we establish that constitutive activation of Nrf2 protects against ionizing radiation toxicity and confers radioresistance. Thus, targeting Nrf2 activity in radioresistant tumors could be a promising strategy to circumvent radioresistance.
Singh, Anju; Bodas, Manish; Wakabayashi, Nobunao; Bunz, Fred
Abstract Nuclear factor erythroid-2 related factor 2 (Nrf2), a redox-sensitive transcription factor, regulates the expression of antioxidant enzymes and several anti-apoptotic proteins, which confer cytoprotection against oxidative stress and apoptosis. Constitutive activation of Nrf2 in lung cancer cells promotes tumorigenicity and contributes to chemoresistance by upregulation of glutathione, thioredoxin, and the drug efflux pathways involved in detoxification of electrophiles and broad spectrum of drugs. In this study, we show that RNAi-mediated lowering of Nrf2 levels in non-small-cell lung cancer (NSCLC) cell lines (A549 and H460) led to a dramatic increase in endogenous reactive oxygen species (ROS) levels. Similarly, γ-irradiation-induced formation of protein carbonyls were significantly higher in Nrf2-depleted lung cancer cells, suggesting increased lethality of ionizing radiation in the absence of Nrf2. Radiation-induced protein oxidation in Nrf2shRNA cells correlated with reduced survival as measured by clonogenic assay. Radiation-induced cell death was abrogated by pretreatment with antioxidants such as N-acetyl-L-cysteine, glutathione, and vitamin-E, highlighting the importance of antioxidants in conferring protection against radiation injury. Using genetically-modified gain and loss of function models of Nrf2, in mouse embryonic fibroblasts, we establish that constitutive activation of Nrf2 protects against ionizing radiation toxicity and confers radioresistance. Thus, targeting Nrf2 activity in radioresistant tumors could be a promising strategy to circumvent radioresistance. Antioxid. Redox Signal. 13, 1627–1637. PMID:20446773
Ribeiro, Joana; Cardoso, Maria João
The Tenth European Breast Cancer Conference, EBCC 10, was held in Amsterdam in March 2016 with a total of 3061 participants from 95 different countries spread over five continents. The EBCC council is a joint venture of ESO, EORTC Breast Cancer Group, EUSOMA, and Europa Donna. The Scientific Programme for EBCC-10 tried to bring to the stage all the active participants in the diagnostic and treatment of breast cancer along with patients themselves. The need to achieve 'patient's access to high quality treatment' through breast units that have been accredited through a European certification process was the basis of the EBCC 10 manifesto. The congress scientific programme allowed participants to review the most up-to-date knowledge in the breast cancer field presented by experts having in mind its application to every day practice. The purpose of this summary is to describe to the readers the results of the late-breaking and best abstracts presented at EBCC10.
Mellman, Ira; Hubbard-Lucey, Vanessa M; Tontonoz, Matthew J; Kalos, Michael D; Chen, Daniel S; Allison, James P; Drake, Charles G; Levitsky, Hy; Lonberg, Nils; van der Burg, Sjoerd H; Fearon, Douglas T; Wherry, E John; Lowy, Israel; Vonderheide, Robert H; Hwu, Patrick
With the recent FDA approvals of pembrolizumab and nivolumab, and a host of additional immunomodulatory agents entering clinical development each year, the field of cancer immunotherapy is changing rapidly. Strategies that can assist researchers in choosing the most promising drugs and drug combinations to move forward through clinical development are badly needed in order to reduce the likelihood of late-stage clinical trial failures. On October 5, 2014, the Cancer Immunotherapy Consortium of the Cancer Research Institute, a collaborative think tank composed of stakeholders from academia, industry, regulatory agencies, and patient interest groups, met to discuss strategies for de-risking immunotherapy development, with a focus on integrating preclinical and clinical studies, and conducting smarter early-phase trials, particularly for combination therapies. Several recommendations were made, including making better use of clinical data to inform preclinical research, obtaining adequate tissues for biomarker studies, and choosing appropriate clinical trial endpoints to identify promising drug candidates and combinations in nonrandomized early-phase trials.
Johnson, Rachelle W.; Finger, Elizabeth C.; Olcina, Monica M.; Vilalta, Marta; Aguilera, Todd; Miao, Yu; Merkel, Alyssa R.; Johnson, Joshua R.; Sterling, Julie A.; Wu, Joy Y.; Giaccia, Amato J.
Breast cancer cells frequently home to the bone marrow, where they may enter a dormant state before forming a bone metastasis. Several members of the interleukin-6 (IL-6) cytokine family are implicated in breast cancer bone colonization, but the role for the IL-6 cytokine leukemia inhibitory factor (LIF) in this process is unknown. We tested the hypothesis that LIF provides a pro-dormancy signal to breast cancer cells in the bone. In breast cancer patients, LIF receptor (LIFR) levels are lower with bone metastases and are significantly and inversely correlated with patient outcome and hypoxia gene activity. Hypoxia also reduces the LIFR:STAT3:SOCS3 signaling pathway in breast cancer cells. Loss of the LIFR or STAT3 enables otherwise dormant breast cancer cells to down-regulate dormancy, quiescence, and cancer stem cell-associated genes, and to proliferate in and specifically colonize the bone, suggesting LIFR:STAT3 signaling confers a dormancy phenotype in breast cancer cells disseminated to bone. PMID:27642788
Tan, Daniel S W; Yom, Sue S; Tsao, Ming S; Pass, Harvey I; Kelly, Karen; Peled, Nir; Yung, Rex C; Wistuba, Ignacio I; Yatabe, Yasushi; Unger, Michael; Mack, Philip C; Wynes, Murry W; Mitsudomi, Tetsuya; Weder, Walter; Yankelevitz, David; Herbst, Roy S; Gandara, David R; Carbone, David P; Bunn, Paul A; Mok, Tony S K; Hirsch, Fred R
Mutations in the epidermal growth factor receptor gene (EGFR) represent one of the most frequent "actionable" alterations in non-small cell lung cancer (NSCLC). Typified by high response rates to targeted therapies, EGFR tyrosine kinase inhibitors (TKIs) are now established first-line treatment options and have transformed the treatment paradigm for NSCLC. With the recent breakthrough designation and approval of the third-generation EGFR TKI osimertinib, available systemic and local treatment options have expanded, requiring new clinical algorithms that take into account individual patient molecular and clinical profiles. In this International Association for the Study of Lung Cancer commissioned consensus statement, key pathologic, diagnostic, and therapeutic considerations, such as optimal choice of EGFR TKI and management of brain metastasis, are discussed. In addition, recommendations are made for clinical guidelines and research priorities, such as the role of repeat biopsies and use of circulating free DNA for molecular studies. With the rapid pace of progress in treating EGFR-mutant NSCLC, this statement provides a state-of-the-art review of the contemporary issues in managing this unique subgroup of patients.
Hariri, Lida P.; Niederst, Matthew J.; Mulvey, Hillary; Adams, David C.; Hu, Haichuan; Chico Calero, Isabel; Szabari, Margit V.; Vakoc, Benjamin J.; Hasan, Tayyaba; Bouma, Brett E.; Engelman, Jeffrey A.; Suter, Melissa J.
Despite significant advances in targeted therapies for lung cancer, nearly all patients develop drug resistance within 6-12 months and prognosis remains poor. Developing drug resistance is a progressive process that involves tumor cells and their microenvironment. We hypothesize that microenvironment factors alter tumor growth and response to targeted therapy. We conducted in vitro studies in human EGFR-mutant lung carcinoma cells, and demonstrated that factors secreted from lung fibroblasts results in increased tumor cell survival during targeted therapy with EGFR inhibitor, gefitinib. We also demonstrated that increased environment stiffness results in increased tumor survival during gefitinib therapy. In order to test our hypothesis in vivo, we developed a multimodal optical imaging protocol for preclinical intravital imaging in mouse models to assess tumor and its microenvironment over time. We have successfully conducted multimodal imaging of dorsal skinfold chamber (DSC) window mice implanted with GFP-labeled human EGFR mutant lung carcinoma cells and visualized changes in tumor development and microenvironment facets over time. Multimodal imaging included structural OCT to assess tumor viability and necrosis, polarization-sensitive OCT to measure tissue birefringence for collagen/fibroblast detection, and Doppler OCT to assess tumor vasculature. Confocal imaging was also performed for high-resolution visualization of EGFR-mutant lung cancer cells labeled with GFP, and was coregistered with OCT. Our results demonstrated that stromal support and vascular growth are essential to tumor progression. Multimodal imaging is a useful tool to assess tumor and its microenvironment over time.
We constructed a multifunction nano system SWNT-GC and investigated the synergize photothermal and immunological effects. Here, we improve the SWNT-GC nano system and design a new synergistic nano-particle, both have the photothermal effects and immunological effects. We investigate the therapeutic effects and detect the immune response with metastatic mouse tumor models. We also study the therapeutic mechanism after treatment in vitro and in vivo. With the enhancement of nano-materials on photothermal effects, laser treatment could destroy primary tumor and protect normal tissue with low dose laser irradiation. With the immunological effects of nano-materials, the treatment could trigger specific antitumor immune response, to eliminate the metastasis tumor. It is providing a promising treatment modality for the metastatic cancers.
Kristiansen, G; Roth, W; Helpap, B
The current grading of prostate cancer is based on the classification system of the International Society of Urological Pathology (ISUP) following a consensus conference in Chicago in 2014. The foundations are based on the frequently modified grading system of Gleason. This article presents a brief description of the development to the current ISUP grading system.
Background Most currently known breast cancer predisposition genes play a role in DNA repair by homologous recombination. Recent studies conducted on RAD51 paralogs, involved in the same DNA repair pathway, have identified rare germline mutations conferring breast and/or ovarian cancer predisposition in the RAD51C, RAD51D and XRCC2 genes. The present study analysed the five RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, XRCC3) to estimate their contribution to breast and ovarian cancer predisposition. Methods The study was conducted on 142 unrelated patients with breast and/or ovarian cancer either with early onset or with a breast/ovarian cancer family history. Patients were referred to a French family cancer clinic and had been previously tested negative for a BRCA1/2 mutation. Coding sequences of the five genes were analysed by EMMA (Enhanced Mismatch Mutation Analysis). Detected variants were characterized by Sanger sequencing analysis. Results Three splicing mutations and two likely deleterious missense variants were identified: RAD51B c.452 + 3A > G, RAD51C c.706-2A > G, RAD51C c.1026 + 5_1026 + 7del, RAD51B c.475C > T/p.Arg159Cys and XRCC3 c.448C > T/p.Arg150Cys. No RAD51D and XRCC2 gene mutations were detected. These mutations and variants were detected in families with both breast and ovarian cancers, except for the RAD51B c.475C > T/p.Arg159Cys variant that occurred in a family with 3 breast cancer cases. Conclusions This study identified the first RAD51B mutation in a breast and ovarian cancer family and is the first report of XRCC3 mutation analysis in breast and ovarian cancer. It confirms that RAD51 paralog mutations confer breast and ovarian cancer predisposition and are rare events. In view of the low frequency of RAD51 paralog mutations, international collaboration of family cancer clinics will be required to more accurately estimate their penetrance and establish clinical guidelines in carrier individuals. PMID
The role of gender, psycho-social factors and anthropological-cultural dimensions on pain in neurorehabilitation. Evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation.
Aloisi, Anna M; Berlincioni, Vanna; Torta, Riccardo; Nappi, Rossella E; Tassorelli, Cristina; Barale, Francesco; Ieraci, Valentina; Giusti, Emanuele M; Pietrabissa, Giada; Tamburin, Stefano; Manzoni, Gian M; Castelnuovo, Gianluca
Pain is frequent in patients undergoing neurorehabilitation, but there is a number of still unanswered questions on this topic. The Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) was constituted with the purpose to identify the best practices that can be used in this context. In this article we summarize the existing evidence and recommendations provided by the ICCPN about the role of gender, psycho-social factors and anthropological-cultural dimensions on pain in neurorehabilitation. Sex, gender, psycho-social variables, anthropological and cultural features may influence pain expression, and its pharmacological and non-pharmacological outcome, but the role of these factors has not been consistently explored in neurorehabilitation. There is a number of psychological factors that can be correlated with or represent a predictor for pain, or may influence the treatment and outcome of neurorehabilitation programs. All these factors should be considered when designing these programs, and future studies should incorporate them as potential covariates that may influence outcome.
Liu, Liang; Xiang, Jinfeng; Chen, Rufu; Fu, Deliang; Hong, Defei; Hao, Jihui; Li, Yixiong; Li, Jiangtao; Li, Shengping; Mou, Yiping; Mai, Gang; Ni, Quanxing; Peng, Li; Qin, Renyi; Qian, Honggang; Shao, Chenghao; Sun, Bei; Sun, Yongwei; Tao, Min; Tian, Bole; Wang, Hongxia; Wang, Jian; Wang, Liwei; Wang, Wei; Wang, Weilin; Zhang, Jun; Zhao, Gang; Zhou, Jun; Yu, Xianjun
The prognosis for pancreatic cancer (PC) is poor; however, the timely and accurate treatment of this disease will significantly improve prognosis. Serum biomarkers involve non-invasive tests that facilitate the early detection of tumors, predict outcomes and assess responses to therapy, so that the patient can be continuously monitored and receive the most appropriate therapy. Studies have reported that cancer antigen (CA)125 [also known as mucin 16 (MUC16)] has functional significance in the tumorigenic, metastatic and drug resistant properties of PC. Our aim was to use this biomarker in the diagnosis, detection of metastasis, prognosis and in the monitoring of the treatment effects of PC. Members of the Chinese Study Group for Pancreatic Cancer (CSPAC) reviewed the literature on CA125/MUC16 and developed an objective consensus on the clinical utility of CA125/MUC16 for PC. They confirmed the role of CA125/MUC16 in tumorigenesis and the progression of PC, and recommended monitoring CA125/MUC16 levels in all aspects of the diagnosis and treatment of PC, particularly those that involve the monitoring of treatments. In addition, they suggested that the combination of other biomarkers and imaging techniques, together with CA125/MUC16, would improve the accuracy of the clinical decision-making process, thereby facilitating the optimization of treatment strategies. Periodic clinical updates of the use of CA125/MUC16 have been established, which are important for further analyses and comparisons of clinical results from affiliates and countries, particularly as regards the in-depth biological function and clinical translational research of this biomarker.
Shenoy, Anitha K.; Jin, Yue; Luo, Huacheng; Pampo, Christine; Shao, Rong; Siemann, Dietmar W.; Heldermon, Coy D.; Law, Brian K.; Chang, Lung-Ji
Carcinoma cells can acquire increased motility and invasiveness through epithelial-to-mesenchymal transition (EMT). However, the significance of EMT in cancer metastasis has been controversial, and the exact fates and functions of EMT cancer cells in vivo remain inadequately understood. Here, we tracked epithelial cancer cells that underwent inducible or spontaneous EMT in various tumor transplantation models. Unlike epithelial cells, the majority of EMT cancer cells were specifically located in the perivascular space and closely associated with blood vessels. EMT markedly activated multiple pericyte markers in carcinoma cells, in particular PDGFR-β and N-cadherin, which enabled EMT cells to be chemoattracted towards and physically interact with endothelium. In tumor xenografts generated from carcinoma cells that were prone to spontaneous EMT, a substantial fraction of the pericytes associated with tumor vasculature were derived from EMT cancer cells. Depletion of such EMT cells in transplanted tumors diminished pericyte coverage, impaired vascular integrity, and attenuated tumor growth. These findings suggest that EMT confers key pericyte attributes on cancer cells. The resulting EMT cells phenotypically and functionally resemble pericytes and are indispensable for vascular stabilization and sustained tumor growth. This study thus proposes a previously unrecognized role for EMT in cancer. PMID:27721239
Liu, Zhenyu; Shi, Aiping; Song, Dong; Han, Bing; Zhang, Zhiru; Ma, Le; Liu, Dongxu; Fan, Zhimin
Clear evidence has linked obesity to a high risk of incidence as well as poor clinical outcome of breast cancer. It has been proven that changes in the levels of adipokines caused by obesity are associated with the initiation and progression of breast cancer. Resistin is a novel adipokine that is upregulated in breast cancer patients and promotes breast cancer cell growth, invasion, and migration. The aim of the study was to investigate whether resistin affected the efficacy of doxorubicin (Dox), one of the most effective anthracycline chemotherapeutic agents in the treatment of breast cancer. Treatment with resistin significantly attenuated Dox-induced apoptosis in a dose- and time-dependent manner, resulting in an increase in breast cancer cells survival. Moreover, resistin significantly induced autophagy flux and inhibition of autophagy abrogated the pro-survival effect of resistin in doxorubicin-treated cells. Furthermore, the AMPK/mTOR/ULK1 and JNK signaling pathways were activated by resistin treatment. Inhibition of these two pathways markedly reduced the ratio of LC3B-II/LC3B-I and increased cell apoptosis induced by Dox. For the first time, our findings indicate that resistin confers resistance to doxorubicin-induced apoptosis through autophagy induction and that this process involves the activation of AMPK/mTOR/ULK1 and JNK signaling pathways. Our findings suggest that resistin antagonism may be a novel strategy to overcome resistance to doxorubicin-based chemotherapy in breast cancer patients.
The International Multidisciplinary Consensus Conference on Multimodality Monitoring in Neurocritical Care: evidentiary tables: a statement for healthcare professionals from the Neurocritical Care Society and the European Society of Intensive Care Medicine.
Le Roux, Peter; Menon, David K; Citerio, Giuseppe; Vespa, Paul; Bader, Mary Kay; Brophy, Gretchen; Diringer, Michael N; Stocchetti, Nino; Videtta, Walter; Armonda, Rocco; Badjatia, Neeraj; Bösel, Julian; Chesnut, Randall; Chou, Sherry; Claassen, Jan; Czosnyka, Marek; De Georgia, Michael; Figaji, Anthony; Fugate, Jennifer; Helbok, Raimund; Horowitz, David; Hutchinson, Peter; Kumar, Monisha; McNett, Molly; Miller, Chad; Naidech, Andrew; Oddo, Mauro; Olson, DaiWai; O'Phelan, Kristine; Provencio, J Javier; Puppo, Corinna; Riker, Richard; Roberson, Claudia; Schmidt, Michael; Taccone, Fabio
A variety of technologies have been developed to assist decision-making during the management of patients with acute brain injury who require intensive care. A large body of research has been generated describing these various technologies. The Neurocritical Care Society (NCS) in collaboration with the European Society of Intensive Care Medicine (ESICM), the Society for Critical Care Medicine (SCCM), and the Latin America Brain Injury Consortium (LABIC) organized an international, multidisciplinary consensus conference to perform a systematic review of the published literature to help develop evidence-based practice recommendations on bedside physiologic monitoring. This supplement contains a Consensus Summary Statement with recommendations and individual topic reviews on physiologic processes important in the care of acute brain injury. In this article we provide the evidentiary tables for select topics including systemic hemodynamics, intracranial pressure, brain and systemic oxygenation, EEG, brain metabolism, biomarkers, processes of care and monitoring in emerging economies to provide the clinician ready access to evidence that supports recommendations about neuromonitoring.
Segal, Brahm H; Herbrecht, Raoul; Stevens, David A; Ostrosky-Zeichner, Luis; Sobel, Jack; Viscoli, Claudio; Walsh, Thomas J; Maertens, Johan; Patterson, Thomas F; Perfect, John R; Dupont, Bertrand; Wingard, John R; Calandra, Thierry; Kauffman, Carol A; Graybill, John R; Baden, Lindsey R; Pappas, Peter G; Bennett, John E; Kontoyiannis, Dimitrios P; Cordonnier, Catherine; Viviani, Maria Anna; Bille, Jacques; Almyroudis, Nikolaos G; Wheat, L Joseph; Graninger, Wolfgang; Bow, Eric J; Holland, Steven M; Kullberg, Bart-Jan; Dismukes, William E; De Pauw, Ben E
Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.
Lacal, Juan-Carlos; Carnero, Amancio
The Spanish National Cancer Center has launched a new series of cancer conferences devoted to timely themes in oncology. These meetings aim to bring together a maximum of 50 participants, including 20 to 25 speakers along with 25 to 30 participants for in-depth discussion of new results and ideas in frontline cancer research. There is no registration fee to attend, but participants must organize their own travel and accommodation expenses; free communications are presented as posters, but a few may be selected for short (15 min) oral presentations. This particular meeting was organized by Amancio Carnero and David H Beach, and was mostly devoted to state of the art methodologies for the identification of new targets for anticancer drug design, although the development of novel drugs was also discussed.
The 1st Baltic Osseointegration Academy and Lithuanian University of Health Sciences Consensus Conference 2016. Summary and Consensus Statements: Group I - Peri-Implantitis Aetiology, Risk Factors and Pathogenesis
Andolsek, Francesca; Astramskaite, Inesa; Berton, Federico; Di Lenarda, Roberto; Fernandes, Maria Helena; Frassetto, Andrea; Gomes, Pedro de Sousa; Guobis, Zygimantas; Jimbo, Ryo; Juodzbalys, Gintaras; Khoury, Aiman; Kubilius, Ricardas; Kuoppala, Ritva; Lombardi, Teresa; Maminskas, Julius; Pacauskiene, Ingrida; Perinetti, Giuseppe; Poskevicius, Lukas; Pranskunas, Mindaugas; Puisys, Algirdas; Raustia, Aune
ABSTRACT Introduction The task of Group 1 was to review and update the existing data concerning aetiology, risk factors and pathogenesis of peri-implantitis. Previous history of periodontitis, poor oral hygiene, smoking and presence of general diseases have been considered among the aetiological risk factors for the onset of peri-implant pathologies, while late dental implant failures are commonly associated with peri-implantitis and/or with the application of incorrect biomechanical forces. Special interest was paid to the bone cells dynamics as part of the pathogenesis of peri-implantitis. Material and Methods The main areas indagated by this group were as follows: influence of smoking, history of periodontitis and general diseases on peri-implantitis development, bio-mechanics of implant loading and its influence on peri-implant bone and cellular dynamics related to the pathogenesis of peri-implantitis. The systematic reviews and/or meta-analyses were registered in PROSPERO, an international prospective register of systematic reviews: http://www.crd.york.ac.uk/PROSPERO/. The literature in the corresponding areas of interest was screened and reported following the PRISMA (Preferred Reporting Item for Systematic Review and Meta-Analysis) Statement: http://www.prisma-statement.org/. Method of preparation of the systematic reviews, based on comprehensive search strategies, was discussed and standardized. The summary of the materials and methods employed by the authors in preparing the systematic reviews and/or meta-analyses is presented in Preface chapter. Results The results and conclusions of the review process are presented in the respective papers. One systematic review with meta-analysis, three systematic reviews and one theoretical analysis were performed. The group′s general commentaries, consensus statements, clinical recommendations and implications for research are presented in this article. PMID:27833732
Winawer, Sidney J; Zauber, Ann G; Fletcher, Robert H; Stillman, Jonathon S; O'brien, Michael J; Levin, Bernard; Smith, Robert A; Lieberman, David A; Burt, Randall W; Levin, Theodore R; Bond, John H; Brooks, Durado; Byers, Tim; Hyman, Neil; Kirk, Lynne; Thorson, Alan; Simmang, Clifford; Johnson, David; Rex, Douglas K
, whereas people with hyperplastic polyps only should have a 10-year follow-up as average-risk people. Recent papers have reported a significant number of missed cancers by colonoscopy. However, high-quality baseline colonoscopy with excellent patient preparation and adequate withdrawal time should minimize this and reduce clinicians' concerns. These guidelines were developed jointly by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society to provide a broader consensus and thereby increase utilization of the recommendations by endoscopists. Adoption of these guidelines nationally can have a dramatic impact on shifting available resources from intensive surveillance to screening. It has been shown that the first screening colonoscopy and polypectomy produces the greatest effects on reducing the incidence of colorectal cancer in patients with adenomatous polyps.
Shimelis, Hermela; Mesman, Romy L S; Von Nicolai, Catharina; Ehlen, Asa; Guidugli, Lucia; Martin, Charlotte; Calleja, Fabienne Mgr; Meeks, Huong; Hallberg, Emily; Hinton, Jamie; Lilyquist, Jenna; Hu, Chunling; Aalfs, Cora M; Aittomaki, Kristiina; Andrulis, Irene L; Anton-Culver, Hoda; Arndt, Volker; Beckmann, Matthias W; Benitez, Javier J; Bogdanova, Natalia; Bojesen, Stig E; Bolla, Manjeet K; Borresen-Dale, Anne-Lise; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Broeks, Annegien; Brouwers, Barbara; Bruning, Thomas; Burwinkel, Barbara; Chang-Claude, Jenny; Chenevix-Trench, Georgia; Cheng, Ching-Yu; Choi, Ji-Yeob; Collée, J Margriet; Cox, Angela; Cross, Simon S; Czene, Kamila; Darabi, Hatef; Dennis, Joe; Dork, Thilo; Dos Santos Silva, Isabel; Dunning, Alison M; Fasching, Peter A; Figueroa, Jonine D; Flyger, Henrik; Garcia-Closas, Montserrat; Giles, Graham G; Glendon, Gord; Guenel, Pascal; Haiman, Christopher A; Hall, Per; Hamann, Ute; Hartman, Mikael; Hogervorst, Frans B L; Hollestelle, Antoinette; Hopper, John L; Ito, Hidemi; Jakubowska, Anna; Kang, Daehee; Kosma, Veli-Matti; Kristensen, Vessela; Lai, Kah-Nyin; Lambrechts, Diether; Le Marchand, Loic; Li, Jingmei; Lindblom, Annika; Lophatananon, Artitaya; Lubinski, Jan; Machackova, Eva; Mannermaa, Arto; Margolin, Sara; Marme, Frederik; Matsuo, Keitaro; Miao, Hui; Michailidou, Kyriaki; Milne, Roger L; Muir, Kenneth; Neuhausen, Susan L; Nevanlinna, Heli; Olson, Janet E; Olswold, Curtis; Oosterwijk, Jan C; Osorio, Ana; Peterlongo, Paolo; Peto, Julian; Pharoah, Paul D P; Pylkäs, Katri; Radice, Paolo; Rashid, Muhammad U; Rhenius, Valerie; Rudolph, Anja; Sangrajrang, Suleeporn; Sawyer, Elinor J; Schmidt, Marjanka K; Schoemaker, Minouk J; Seynaeve, Caroline M; Shah, Mitul; Shen, Chen-Yang; Shrubsole, Martha J; Shu, Xiao-Ou; Slager, Susan L; Southey, Melissa C; Stram, Daniel O; Swerdlow, Anthony J; Teo, Soo Hwang; Tomlinson, Ian; Torres, Diana; Truong, Therese; van Asperen, Christi J; van der Kolk, Lizet E; Wang, Qin; Winqvist, Robert; Wu, Anna H; Yu, Jyh-Cherng; Zheng, Wei; Zheng, Ying; Leary, Jennifer; Walker, Logan C; Foretova, Lenka; Fostira, Florentia; Claes, Kathleen; Varesco, Liliana; Moghadasi, Setareh; Easton, Douglas F; Spurdle, Amanda B; Devilee, Peter; Vrieling, Harry; Monteiro, Alvaro N; Goldgar, David E; Carreira, Aura; Vreeswijk, Maaike P G; Couch, Fergus J
Breast cancer risks conferred by many germline missense variants in the BRCA1 and BRCA2 genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR=2.52, p=0.04) and BRCA1 c.5096G>A, p.Arg1699Gln (OR=4.29, p=0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR=2.68, p=0.004) and c.8187G>T, p.Lys2729Asn (OR=1.4, p=0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared to wildtype. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants.
Corujo, David; Mas, Gloria; Malinverni, Roberto; Di Croce, Luciano; Buschbeck, Marcus
ABSTRACT The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled “Coding and Non-Coding functions of the Genome” took place October 29–30, 2015 in Barcelona. The 2015 BCEC was the third edition of a series of annual conferences jointly organized by 5 leading research centers in Barcelona together with B-Debate, an initiative of BioCat. Luciano Di Croce from the Center for Genomic Regulation and Marcus Buschbeck from the Josep Carreras Leukemia Research Institute put together the scientific program with a particular focus on the role of non-coding RNAs in enhancer regulation, epigenetic control by Polycomb complexes, histone variants, and nuclear organization. In one and a half days, 22 talks and 56 posters were presented to an audience of 215 participants. PMID:26996885
Caglevic, Christian; Gallardo, Jorge; de la Torre, Marcela; Mahave, Mauricio; Müller, Bettina; Solé, Sebastián; Moscoso, Yuri; De La Fuente, Hernán; Roa, Juan Carlos; Hoefler, Sebastián; Butte, Jean M; González M, Pablo; O'Connor, Juan Manuel; Torres, Javiera; Pérez Encalada, Verónica; Alarcón Cano, Daniel; Ubillos, Luis; Rolfo, Christian; Lingua, Alejo; Díaz Romero, Consuelo; Padilla Rosciano, Alejandro; Cuartero, Viviana; Calderillo Ruiz, Germán; Schwartsmann, Gilberto; Kon Jara, Xavier; Andrade G, Andrés; Mas López, Luis; Barajas, Olga; Carballido, Marcela; Lembach, Hanns; Morillas G, Lena; Roca, Enrique; Lobatón, José; Montenegro B, Paola; Yepes, Andrés; Marsiglia, Hugo
Pancreatic cancer is a malignancy of great impact in developed countries and is having an increasing impact in Latin America. Incidence and mortality rates are similar for this cancer. This is an important reason to offer to the patients the best treatments available. During the Latin American Symposium of Gastroenterology Oncology (SLAGO) held in Viña del Mar, Chile, in April 2015, a multidisciplinary group of specialists in the field met to discuss about this disease. The main conclusions of this meeting, where practitioners from most of Latin American countries participated, are listed in this consensus that seek to serve as a guide for better decision making for patients with pancreatic cancer in Latin America.
Cox, Angela; Bernard, Philip; Camp, Nicola J.
Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cellular processes and diseases such as cancer; however, their functions remain poorly characterised. Several studies have demonstrated that lncRNAs are typically disease and tumour subtype specific, particularly in breast cancer where lncRNA expression alone is sufficient to discriminate samples based on hormone status and molecular intrinsic subtype. However, little attempt has been made to assess the reproducibility of lncRNA signatures across more than one dataset. In this work, we derive consensus lncRNA signatures indicative of breast cancer subtype based on two clinical RNA-Seq datasets: the Utah Breast Cancer Study and The Cancer Genome Atlas, through integration of differential expression and hypothesis-free clustering analyses. The most consistent signature is associated with breast cancers of the basal-like subtype, leading us to generate a putative set of six lncRNA basal-like breast cancer markers, at least two of which may have a role in cis-regulation of known poor prognosis markers. Through in silico functional characterization of individual signatures and integration of expression data from pre-clinical cancer models, we discover that discordance between signatures derived from different clinical cohorts can arise from the strong influence of non-cancerous cells in tumour samples. As a consequence, we identify nine lncRNAs putatively associated with breast cancer associated fibroblasts, or the immune response. Overall, our study establishes the confounding effects of tumour purity on lncRNA signature derivation, and generates several novel hypotheses on the role of lncRNAs in basal-like breast cancers and the tumour microenvironment. PMID:27685983
Bradford, James R; Cox, Angela; Bernard, Philip; Camp, Nicola J
Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cellular processes and diseases such as cancer; however, their functions remain poorly characterised. Several studies have demonstrated that lncRNAs are typically disease and tumour subtype specific, particularly in breast cancer where lncRNA expression alone is sufficient to discriminate samples based on hormone status and molecular intrinsic subtype. However, little attempt has been made to assess the reproducibility of lncRNA signatures across more than one dataset. In this work, we derive consensus lncRNA signatures indicative of breast cancer subtype based on two clinical RNA-Seq datasets: the Utah Breast Cancer Study and The Cancer Genome Atlas, through integration of differential expression and hypothesis-free clustering analyses. The most consistent signature is associated with breast cancers of the basal-like subtype, leading us to generate a putative set of six lncRNA basal-like breast cancer markers, at least two of which may have a role in cis-regulation of known poor prognosis markers. Through in silico functional characterization of individual signatures and integration of expression data from pre-clinical cancer models, we discover that discordance between signatures derived from different clinical cohorts can arise from the strong influence of non-cancerous cells in tumour samples. As a consequence, we identify nine lncRNAs putatively associated with breast cancer associated fibroblasts, or the immune response. Overall, our study establishes the confounding effects of tumour purity on lncRNA signature derivation, and generates several novel hypotheses on the role of lncRNAs in basal-like breast cancers and the tumour microenvironment.
Cardoso, Fatima; Bese, Nuran; Distelhorst, Sandra R; Bevilacqua, Jose Luiz B; Ginsburg, Ophira; Grunberg, Steven M; Gralla, Richard J; Steyn, Ann; Pagani, Olivia; Partridge, Ann H; Knaul, Felicia Marie; Aapro, Matti S; Andersen, Barbara L; Thompson, Beti; Gralow, Julie R; Anderson, Benjamin O
Breast cancer patients may have unmet supportive care needs during treatment, including symptom management of treatment-related toxicities, and educational, psychosocial, and spiritual needs. Delivery of supportive care is often a low priority in low- and middle-income settings, and is also dependent on resources available. This consensus statement describes twelve key recommendations for supportive care during treatment in low- and middle-income countries, identified by an expert international panel as part of the 5th Breast Health Global Initiative (BHGI) Global Summit for Supportive Care, which was held in October 2012, in Vienna, Austria. Panel recommendations are presented in a 4-tier resource-stratified table to illustrate how health systems can provide supportive care services during treatment to breast cancer patients, starting at a basic level of resource allocation and incrementally adding program resources as they become available. These recommendations include: health professional and patient and family education; management of treatment related toxicities, management of treatment-related symptoms of fatigue, insomnia and non-specific pain, and management of psychosocial and spiritual issues related to breast cancer treatment. Establishing supportive care during breast cancer treatment will help ensure that breast cancer patients receive comprehensive care that can help 1) improve adherence to treatment recommendations, 2) manage treatment-related toxicities and other treatment related symptoms, and 3) address the psychosocial and spiritual aspects of breast cancer and breast cancer treatments.
2014 Female Athlete Triad Coalition consensus statement on treatment and return to play of the female athlete triad: 1st International Conference held in San Francisco, CA, May 2012, and 2nd International Conference held in Indianapolis, IN, May 2013.
De Souza, Mary Jane; Nattiv, Aurelia; Joy, Elizabeth; Misra, Madhusmita; Williams, Nancy I; Mallinson, Rebecca J; Gibbs, Jenna C; Olmsted, Marion; Goolsby, Marci; Matheson, Gordon
The Female Athlete Triad is a medical condition often observed in physically active girls and women, and involves 3 components: (1) low energy availability with or without disordered eating, (2) menstrual dysfunction, and (3) low bone mineral density. Female athletes often present with 1 or more of the 3 Triad components, and an early intervention is essential to prevent its progression to serious endpoints that include clinical eating disorders, amenorrhea, and osteoporosis. This consensus statement represents a set of recommendations developed following the first (San Francisco, California) and second (Indianapolis, Indianna) International Symposia on the Female Athlete Triad. It is intended to provide clinical guidelines for physicians, athletic trainers, and other health care providers for the screening, diagnosis, and treatment of the Female Athlete Triad and to provide clear recommendations for return to play. The 2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return to Play of the Female Athlete Triad Expert Panel has proposed a risk stratification point system that takes into account magnitude of risk to assist the physician in decision-making regarding sport participation, clearance, and return to play. Guidelines are offered for clearance categories, management by a multidisciplinary team, and implementation of treatment contracts. This consensus paper has been endorsed by The Female Athlete Triad Coalition, an International Consortium of leading Triad researchers, physicians, and other health care professionals, the American College of Sports Medicine, and the American Medical Society for Sports Medicine.
2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return to Play of the Female Athlete Triad: 1st International Conference held in San Francisco, California, May 2012 and 2nd International Conference held in Indianapolis, Indiana, May 2013.
De Souza, Mary Jane; Nattiv, Aurelia; Joy, Elizabeth; Misra, Madhusmita; Williams, Nancy I; Mallinson, Rebecca J; Gibbs, Jenna C; Olmsted, Marion; Goolsby, Marci; Matheson, Gordon
The Female Athlete Triad is a medical condition often observed in physically active girls and women, and involves three components: (1) low energy availability with or without disordered eating, (2) menstrual dysfunction and (3) low bone mineral density. Female athletes often present with one or more of the three Triad components, and an early intervention is essential to prevent its progression to serious endpoints that include clinical eating disorders, amenorrhoea and osteoporosis. This consensus statement represents a set of recommendations developed following the 1st (San Francisco, California, USA) and 2nd (Indianapolis, Indiana, USA) International Symposia on the Female Athlete Triad. It is intended to provide clinical guidelines for physicians, athletic trainers and other healthcare providers for the screening, diagnosis and treatment of the Female Athlete Triad and to provide clear recommendations for return to play. The 2014 Female Athlete Triad Coalition Consensus Statement on Treatment and Return to Play of the Female Athlete Triad expert panel has proposed a risk stratification point system that takes into account magnitude of risk to assist the physician in decision-making regarding sport participation, clearance and return to play. Guidelines are offered for clearance categories, management by a multidisciplinary team and implementation of treatment contracts. This consensus paper has been endorsed by the Female Athlete Triad Coalition, an International Consortium of leading Triad researchers, physicians and other healthcare professionals, the American College of Sports Medicine and the American Medical Society for Sports Medicine.
Sutherland, Scott M; Chawla, Lakhmir S; Kane-Gill, Sandra L; Hsu, Raymond K; Kramer, Andrew A; Goldstein, Stuart L; Kellum, John A; Ronco, Claudio; Bagshaw, Sean M
The data contained within the electronic health record (EHR) is "big" from the standpoint of volume, velocity, and variety. These circumstances and the pervasive trend towards EHR adoption have sparked interest in applying big data predictive analytic techniques to EHR data. Acute kidney injury (AKI) is a condition well suited to prediction and risk forecasting; not only does the consensus definition for AKI allow temporal anchoring of events, but no treatments exist once AKI develops, underscoring the importance of early identification and prevention. The Acute Dialysis Quality Initiative (ADQI) convened a group of key opinion leaders and stakeholders to consider how best to approach AKI research and care in the "Big Data" era. This manuscript addresses the core elements of AKI risk prediction and outlines potential pathways and processes. We describe AKI prediction targets, feature selection, model development, and data display.
Coates, A S; Winer, E P; Goldhirsch, A; Gelber, R D; Gnant, M; Piccart-Gebhart, M; Thürlimann, B; Senn, H-J
The 14th St Gallen International Breast Cancer Conference (2015) reviewed substantial new evidence on locoregional and systemic therapies for early breast cancer. Further experience has supported the adequacy of tumor margins defined as 'no ink on invasive tumor or DCIS' and the safety of omitting axillary dissection in specific cohorts. Radiotherapy trials support irradiation of regional nodes in node-positive disease. Considering subdivisions within luminal disease, the Panel was more concerned with indications for the use of specific therapies, rather than surrogate identification of intrinsic subtypes as measured by multiparameter molecular tests. For the treatment of HER2-positive disease in patients with node-negative cancers up to 1 cm, the Panel endorsed a simplified regimen comprising paclitaxel and trastuzumab without anthracycline as adjuvant therapy. For premenopausal patients with endocrine responsive disease, the Panel endorsed the role of ovarian function suppression with either tamoxifen or exemestane for patients at higher risk. The Panel noted the value of an LHRH agonist given during chemotherapy for premenopausal women with ER-negative disease in protecting against premature ovarian failure and preserving fertility. The Panel noted increasing evidence for the prognostic value of commonly used multiparameter molecular markers, some of which also carried prognostic information for late relapse. The Panel noted that the results of such tests, where available, were frequently used to assist decisions about the inclusion of cytotoxic chemotherapy in the treatment of patients with luminal disease, but noted that threshold values had not been established for this purpose for any of these tests. Multiparameter molecular assays are expensive and therefore unavailable in much of the world. The majority of new breast cancer cases and breast cancer deaths now occur in less developed regions of the world. In these areas, less expensive pathology tests may
Senff, Nancy J; Noordijk, Evert M; Kim, Youn H; Bagot, Martine; Berti, Emilio; Cerroni, Lorenzo; Dummer, Reinhard; Duvic, Madeleine; Hoppe, Richard T; Pimpinelli, Nicola; Rosen, Steven T; Vermeer, Maarten H; Whittaker, Sean; Willemze, Rein
Primary cutaneous B-cell lymphomas (CBCL) represent approximately 20% to 25% of all primary cutaneous lymphomas. With the advent of the World Health Organization-European Organization for Research and Treatment of Cancer (EORTC) Consensus Classification for Cutaneous Lymphomas in 2005, uniform terminology and classification for this rare group of neoplasms were introduced. However, staging procedures and treatment strategies still vary between different cutaneous lymphoma centers, which may be because consensus recommendations for the management of CBCL have never been published. Based on an extensive literature search and discussions within the EORTC Cutaneous Lymphoma Group and the International Society for Cutaneous Lymphomas, the present report aims to provide uniform recommendations for the management of the 3 main groups of CBCL. Because no systematic reviews or (randomized) controlled trials were available, these recommendations are mainly based on retrospective studies and small cohort studies. Despite these limitations, there was consensus among the members of the multidisciplinary expert panel that these recommendations reflect the state-of-the-art management as currently practiced in major cutaneous lymphoma centers. They may therefore contribute to uniform staging and treatment and form the basis for future clinical trials in patients with a CBCL.
Zhang, Yang; Geng, Liying; Talmon, Geoffrey; Wang, Jing
Development of drug resistance is one of the major causes of colorectal cancer recurrence, yet mechanistic understanding and therapeutic options remain limited. Here, we show that expression of microRNA (miR)-520g is correlated with drug resistance of colon cancer cells. Ectopic expression of miR-520g conferred resistance to 5-fluorouracil (5-FU)- or oxaliplatin-induced apoptosis in vitro and reduced the effectiveness of 5-FU in the inhibition of tumor growth in a mouse xenograft model in vivo. Further studies indicated that miR-520g mediated drug resistance through down-regulation of p21 expression. Moreover, p53 suppressed miR-520g expression, and deletion of p53 up-regulated miR-520g expression. Inhibition of miR-520g in p53−/− cells increased their sensitivity to 5-FU treatment. Importantly, studies of patient samples indicated that expression of miR-520g correlated with chemoresistance in colorectal cancer. These findings indicate that the p53/miR-520g/p21 signaling axis plays an important role in the response of colorectal cancer to chemotherapy. A major implication of our studies is that inhibition of miR-520g or restoration of p21 expression may have considerable therapeutic potential to overcome drug resistance in colorectal cancer patients, especially in those with mutant p53. PMID:25616665
Oudin, Madeleine J; Barbier, Lucie; Schäfer, Claudia; Kosciuk, Tatsiana; Miller, Miles A; Han, Sangyoon; Jonas, Oliver; Lauffenburger, Douglas A; Gertler, Frank B
Taxane therapy remains the standard of care for triple-negative breast cancer. However, high frequencies of recurrence and progression in treated patients indicate that metastatic breast cancer cells can acquire resistance to this drug. The actin regulatory protein MENA and particularly its invasive isoform, MENA(INV), are established drivers of metastasis. MENA(INV) expression is significantly correlated with metastasis and poor outcome in human patients with breast cancer. We investigated whether MENA isoforms might play a role in driving resistance to chemotherapeutics. We find that both MENA and MENA(INV) confer resistance to the taxane paclitaxel, but not to the widely used DNA-damaging agents doxorubicin or cisplatin. Furthermore, paclitaxel treatment does not attenuate growth of MENA(INV)-driven metastatic lesions. Mechanistically, MENA isoform expression alters the ratio of dynamic and stable microtubule populations in paclitaxel-treated cells. MENA expression also increases MAPK signaling in response to paclitaxel treatment. Decreasing ERK phosphorylation by co-treatment with MEK inhibitor restored paclitaxel sensitivity by driving microtubule stabilization in MENA isoform-expressing cells. Our results reveal a novel mechanism of taxane resistance in highly metastatic breast cancer cells and identify a combination therapy to overcome such resistance. Mol Cancer Ther; 16(1); 143-55. ©2016 AACR.
Rex, Douglas K; Kahi, Charles J; Levin, Bernard; Smith, Robert A; Bond, John H; Brooks, Durado; Burt, Randall W; Byers, Tim; Fletcher, Robert H; Hyman, Neil; Johnson, David; Kirk, Lynne; Lieberman, David A; Levin, Theodore R; O'Brien, Michael J; Simmang, Clifford; Thorson, Alan G; Winawer, Sidney J
Patients with resected colorectal cancer are at risk for recurrent cancer and metachronous neoplasms in the colon. This joint update of guidelines by the American Cancer Society (ACS) and US Multi-Society Task Force on Colorectal Cancer addresses only the use of endoscopy in the surveillance of these patients. Patients with endoscopically resected Stage I colorectal cancer, surgically resected Stage II and III cancers, and Stage IV cancer resected for cure (isolated hepatic or pulmonary metastasis) are candidates for endoscopic surveillance. The colorectum should be carefully cleared of synchronous neoplasia in the perioperative period. In nonobstructed colons, colonoscopy should be performed preoperatively. In obstructed colons, double contrast barium enema or computed tomography colonography should be done preoperatively, and colonoscopy should be performed 3 to 6 months after surgery. These steps complete the process of clearing synchronous disease. After clearing for synchronous disease, another colonoscopy should be performed in 1 year to look for metachronous lesions. This recommendation is based on reports of a high incidence of apparently metachronous second cancers in the first 2 years after resection. If the examination at 1 year is normal, then the interval before the next subsequent examination should be 3 years. If that colonoscopy is normal, then the interval before the next subsequent examination should be 5 years. Shorter intervals may be indicated by associated adenoma findings (see Postpolypectomy Surveillance Guideline). Shorter intervals are also indicated if the patient's age, family history, or tumor testing indicate definite or probable hereditary nonpolyposis colorectal cancer. Patients undergoing low anterior resection of rectal cancer generally have higher rates of local cancer recurrence, compared with those with colon cancer. Although effectiveness is not proven, performance of endoscopic ultrasound or flexible sigmoidoscopy at 3- to 6
Liu, Chengfei; Lou, Wei; Zhu, Yezi; Yang, Joy C.; Nadiminty, Nagalakshmi; Gaikwad, Nilesh W.; Evans, Christopher P.; Gao, Allen C.
The introduction of enzalutamide and abiraterone has led to improvement in the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, acquired resistance to enzalutamide and abiraterone therapies frequently develops within a short period in many patients. In the present study, we developed enzalutamide resistant prostate cancer cells in an effort to understand the mechanisms of resistance. Global gene expression analysis showed that steroid biosynthesis pathway is activated in enzalutamide resistant prostate cancer cells. One of the crucial steroidogenic enzymes, AKR1C3, was significantly elevated in enzalutamide resistant cells. In addition, AKR1C3 is highly expressed in metastatic and recurrent prostate cancer and in enzalutamide resistant prostate xenograft tumors. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis of the steroid metabolites revealed that androgen precursors such as cholesterol, DHEA and progesterone, as well as androgens are highly up regulated in enzalutamide resistant prostate cancer cells compared to the parental cells. Knock down of AKR1C3 expression by shRNA or inhibition of AKR1C3 enzymatic activity by indomethacin resensitized enzalutamide resistant prostate cancer cells to enzalutamide treatment both in vitro and in vivo. In contrast, overexpression of AKR1C3 confers resistance to enzalutamide. Furthermore, the combination of indomethacin and enzalutamide resulted in significant inhibition of enzalutamide-resistant tumor growth. These results suggest that AKR1C3 activation is a critical resistance mechanism associated with enzalutamide resistance, targeting intracrine androgens and AKR1C3 will overcome enzalutamide resistance and improve survival of advanced prostate cancer patients. PMID:25649766
Bagshaw, Sean M; Goldstein, Stuart L; Ronco, Claudio; Kellum, John A
The world is immersed in "big data". Big data has brought about radical innovations in the methods used to capture, transfer, store and analyze the vast quantities of data generated every minute of every day. At the same time; however, it has also become far easier and relatively inexpensive to do so. Rapidly transforming, integrating and applying this large volume and variety of data are what underlie the future of big data. The application of big data and predictive analytics in healthcare holds great promise to drive innovation, reduce cost and improve patient outcomes, health services operations and value. Acute kidney injury (AKI) may be an ideal syndrome from which various dimensions and applications built within the context of big data may influence the structure of services delivery, care processes and outcomes for patients. The use of innovative forms of "information technology" was originally identified by the Acute Dialysis Quality Initiative (ADQI) in 2002 as a core concept in need of attention to improve the care and outcomes for patients with AKI. For this 15(th) ADQI consensus meeting held on September 6-8, 2015 in Banff, Canada, five topics focused on AKI and acute renal replacement therapy were developed where extensive applications for use of big data were recognized and/or foreseen. In this series of articles in the Canadian Journal of Kidney Health and Disease, we describe the output from these discussions.
Fuller, Clifton D.; Nijkamp, Jasper; Duppen, Joop C.; Rasch, Coen R.N.; Thomas, Charles R.; Wang, Samuel J.; Okunieff, Paul; Jones, William E.; Baseman, Daniel; Patel, Shilpen; Demandante, Carlo G.N.; Harris, Anna M.; Smith, Benjamin D.; Katz, Alan W.; McGann, Camille
Purpose: Variations in target volume delineation represent a significant hurdle in clinical trials involving conformal radiotherapy. We sought to determine the effect of a consensus guideline-based visual atlas on contouring the target volumes. Methods and Materials: A representative case was contoured (Scan 1) by 14 physician observers and a reference expert with and without target volume delineation instructions derived from a proposed rectal cancer clinical trial involving conformal radiotherapy. The gross tumor volume (GTV), and two clinical target volumes (CTVA, including the internal iliac, presacral, and perirectal nodes, and CTVB, which included the external iliac nodes) were contoured. The observers were randomly assigned to receipt (Group A) or nonreceipt (Group B) of a consensus guideline and atlas for anorectal cancers and then instructed to recontour the same case/images (Scan 2). Observer variation was analyzed volumetrically using the conformation number (CN, where CN = 1 equals total agreement). Results: Of 14 evaluable contour sets (1 expert and 7 Group A and 6 Group B observers), greater agreement was found for the GTV (mean CN, 0.75) than for the CTVs (mean CN, 0.46-0.65). Atlas exposure for Group A led to significantly increased interobserver agreement for CTVA (mean initial CN, 0.68, after atlas use, 0.76; p = .03) and increased agreement with the expert reference (initial mean CN, 0.58; after atlas use, 0.69; p = .02). For the GTV and CTVB, neither the interobserver nor the expert agreement was altered after atlas exposure. Conclusion: Consensus guideline atlas implementation resulted in a detectable difference in interobserver agreement and a greater approximation of expert volumes for the CTVA but not for the GTV or CTVB in the specified case. Visual atlas inclusion should be considered as a feature in future clinical trials incorporating conformal RT.
Russi, Elvio G; Moretto, Francesco; Rampino, Monica; Benasso, Marco; Bacigalupo, Almalina; De Sanctis, Vitaliana; Numico, Gianmauro; Bossi, Paolo; Buglione, Michela; Lombardo, Antonino; Airoldi, Mario; Merlano, Marco C; Licitra, Lisa; Denaro, Nerina; Pergolizzi, Stefano; Pinto, Carmine; Bensadoun, Renè-Jean; Girolomoni, Giampiero; Langendijk, Johannes A
The adverse effects of radiation therapy, often integrated with chemotherapy and/or targeted therapies, on the skin include severe acute and chronic dermatitis associated with pain, discomfort, itching, and burning, and may heavily affect patients' quality of life. The management of these skin adverse effects in head and neck cancer patients (HNCPs) are very heterogeneous due to the lack of shared rigorous classification systems and evidence based treatments. A multidisciplinary group of head and neck cancer specialists from Italy met with the aim of reaching a consensus on a clinical definition and management of dermatitis in HNCPs treated with radiotherapy with or without systemic therapies in order to improve skin toxicity management. The Delphi Appropriateness Method was used. External expert reviewers then evaluated the conclusions carefully according to their area of expertise. This paper offers contains seven clusters of statements about the management of dermatitis in HNCPs and a review of recent literature on these topics.
Winawer, Sidney J; Zauber, Ann G; Fletcher, Robert H; Stillman, Jonathon S; O'Brien, Michael J; Levin, Bernard; Smith, Robert A; Lieberman, David A; Burt, Randall W; Levin, Theodore R; Bond, John H; Brooks, Durado; Byers, Tim; Hyman, Neil; Kirk, Lynne; Thorson, Alan; Simmang, Clifford; Johnson, David; Rex, Douglas K
people with hyperplastic polyps only should have a 10-year follow-up evaluation, as for average-risk people. There have been recent studies that have reported a significant number of missed cancers by colonoscopy. However, high-quality baseline colonoscopy with excellent patient preparation and adequate withdrawal time should minimize this and reduce clinicians concerns. These guidelines were developed jointly by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society to provide a broader consensus and thereby increase the use of the recommendations by endoscopists. The adoption of these guidelines nationally can have a dramatic impact on shifting available resources from intensive surveillance to screening. It has been shown that the first screening colonoscopy and polypectomy produces the greatest effects on reducing the incidence of colorectal cancer in patients with adenomatous polyps.
Consensus on the management of advanced radioactive iodine-refractory differentiated thyroid cancer on behalf of the Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and Spanish Rare Cancer Working Group (GETHI).
Capdevila, J; Galofré, J C; Grande, E; Zafón Llopis, C; Ramón Y Cajal Asensio, T; Navarro González, E; Jiménez-Fonseca, P; Santamaría Sandi, J; Gómez Sáez, J M; Riesco Eizaguirre, G
Thyroid cancer is the single most prevalent endocrine malignancy; differentiated thyroid cancer (DTC) accounts for more than 90 % of all malignancies and its incidence has been rising steadily. For more patients, surgical treatment, radioactive iodine (RAI) ablation, and thyroid-stimulating hormone (TSH) suppressive therapy achieve an overall survival (OS) rate of 97.7 % at 5 years. Nevertheless, locoregional recurrence occurs in up to 20 % and distant metastases in approximately 10 % at 10 years. Two-thirds of these patients will never be cured with radioactive iodine therapy and will become RAI-refractory, with a 3-year OS rate of less than 50 %. Over the last decade, substantial progress has been made in the management of RAI-refractory DTC. Given the controversy in some areas, the Spanish Task Force for Thyroid Cancer on behalf of Spanish Society of Endocrinology Thyroid Cancer Working Group (GTSEEN) and the Spanish Rare Cancer Working Group (GETHI) have created a national joint task force to reach a consensus addressing the most challenging aspects of management in these patients. In this way, multidisciplinary management should be mandatory and nuclear medicine targeted therapy, novel molecular targeted agents, and combinations are currently changing the natural history of RAI-refractory DTC.
Goldhirsch, A.; Winer, E. P.; Coates, A. S.; Gelber, R. D.; Piccart-Gebhart, M.; Thürlimann, B.; Senn, H.-J.; Albain, Kathy S.; André, Fabrice; Bergh, Jonas; Bonnefoi, Hervé; Bretel-Morales, Denisse; Burstein, Harold; Cardoso, Fatima; Castiglione-Gertsch, Monica; Coates, Alan S.; Colleoni, Marco; Costa, Alberto; Curigliano, Giuseppe; Davidson, Nancy E.; Di Leo, Angelo; Ejlertsen, Bent; Forbes, John F.; Gelber, Richard D.; Gnant, Michael; Goldhirsch, Aron; Goodwin, Pamela; Goss, Paul E.; Harris, Jay R.; Hayes, Daniel F.; Hudis, Clifford A.; Ingle, James N.; Jassem, Jacek; Jiang, Zefei; Karlsson, Per; Loibl, Sibylle; Morrow, Monica; Namer, Moise; Kent Osborne, C.; Partridge, Ann H.; Penault-Llorca, Frédérique; Perou, Charles M.; Piccart-Gebhart, Martine J.; Pritchard, Kathleen I.; Rutgers, Emiel J.T.; Sedlmayer, Felix; Semiglazov, Vladimir; Shao, Zhi-Ming; Smith, Ian; Thürlimann, Beat; Toi, Masakazu; Tutt, Andrew; Untch, Michael; Viale, Giuseppe; Watanabe, Toru; Wilcken, Nicholas; Winer, Eric P.; Wood, William C.
The 13th St Gallen International Breast Cancer Conference (2013) Expert Panel reviewed and endorsed substantial new evidence on aspects of the local and regional therapies for early breast cancer, supporting less extensive surgery to the axilla and shorter durations of radiation therapy. It refined its earlier approach to the classification and management of luminal disease in the absence of amplification or overexpression of the Human Epidermal growth factor Receptor 2 (HER2) oncogene, while retaining essentially unchanged recommendations for the systemic adjuvant therapy of HER2-positive and ‘triple-negative’ disease. The Panel again accepted that conventional clinico-pathological factors provided a surrogate subtype classification, while noting that in those areas of the world where multi-gene molecular assays are readily available many clinicians prefer to base chemotherapy decisions for patients with luminal disease on these genomic results rather than the surrogate subtype definitions. Several multi-gene molecular assays were recognized as providing accurate and reproducible prognostic information, and in some cases prediction of response to chemotherapy. Cost and availability preclude their application in many environments at the present time. Broad treatment recommendations are presented. Such recommendations do not imply that each Panel member agrees: indeed, among more than 100 questions, only one (trastuzumab duration) commanded 100% agreement. The various recommendations in fact carried differing degrees of support, as reflected in the nuanced wording of the text below and in the votes recorded in supplementary Appendix S1, available at Annals of Oncology online. Detailed decisions on treatment will as always involve clinical consideration of disease extent, host factors, patient preferences and social and economic constraints. PMID:23917950
Lim, Karen; Portelance, Lorraine; Creutzberg, Carien; Juergenliemk-Schulz, Ina M.; Mundt, Arno; Mell, Loren K.; Mayr, Nina; Viswanathan, Akila; Jhingran, Anuja; Erickson, Beth; De Los Santos, Jennifer; Gaffney, David; Yashar, Catheryn; Beriwal, Sushil; Wolfson, Aaron
Purpose: Accurate target definition is vitally important for definitive treatment of cervix cancer with intensity-modulated radiotherapy (IMRT), yet a definition of clinical target volume (CTV) remains variable within the literature. The aim of this study was to develop a consensus CTV definition in preparation for a Phase 2 clinical trial being planned by the Radiation Therapy Oncology Group. Methods and Materials: A guidelines consensus working group meeting was convened in June 2008 for the purposes of developing target definition guidelines for IMRT for the intact cervix. A draft document of recommendations for CTV definition was created and used to aid in contouring a clinical case. The clinical case was then analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants. Results: Nineteen experts in gynecological radiation oncology generated contours on axial magnetic resonance images of the pelvis. Substantial STAPLE agreement sensitivity and specificity values were seen for gross tumor volume (GTV) delineation (0.84 and 0.96, respectively) with a kappa statistic of 0.68 (p < 0.0001). Agreement for delineation of cervix, uterus, vagina, and parametria was moderate. Conclusions: This report provides guidelines for CTV definition in the definitive cervix cancer setting for the purposes of IMRT, building on previously published guidelines for IMRT in the postoperative setting.
Zhang, Chunyu; Elkahloun, Abdel G.; Robertson, Matthew; Gills, Joell J.; Tsurutani, Junji; Shih, Joanna H.; Fukuoka, Junya; Hollander, M. Christine; Harris, Curtis C.; Travis, William D.; Jen, Jin; Dennis, Phillip A.
The dismal lethality of lung cancer is due to late stage at diagnosis and inherent therapeutic resistance. The incorporation of targeted therapies has modestly improved clinical outcomes, but the identification of new targets could further improve clinical outcomes by guiding stratification of poor-risk early stage patients and individualizing therapeutic choices. We hypothesized that a sequential, combined microarray approach would be valuable to identify and validate new targets in lung cancer. We profiled gene expression signatures during lung epithelial cell immortalization and transformation, and showed that genes involved in mitosis were progressively enhanced in carcinogenesis. 28 genes were validated by immunoblotting and 4 genes were further evaluated in non-small cell lung cancer tissue microarrays. Although CDK1 was highly expressed in tumor tissues, its loss from the cytoplasm unexpectedly predicted poor survival and conferred resistance to chemotherapy in multiple cell lines, especially microtubule-directed agents. An analysis of expression of CDK1 and CDK1-associated genes in the NCI60 cell line database confirmed the broad association of these genes with chemotherapeutic responsiveness. These results have implications for personalizing lung cancer therapy and highlight the potential of combined approaches for biomarker discovery. PMID:21887332
Valind, Anders; Jin, Yuesheng; Baldetorp, Bo; Gisselsson, David
Constitutional aneuploidy is typically caused by a single-event meiotic or early mitotic error. In contrast, somatic aneuploidy, found mainly in neoplastic tissue, is attributed to continuous chromosomal instability. More debated as a cause of aneuploidy is aneuploidy itself; that is, whether aneuploidy per se causes chromosomal instability, for example, in patients with inborn aneuploidy. We have addressed this issue by quantifying the level of somatic mosaicism, a proxy marker of chromosomal instability, in patients with constitutional aneuploidy by precise background-filtered dual-color FISH. In contrast to previous studies that used less precise methods, we find that constitutional trisomy, even for large chromosomes that are often trisomic in cancer, does not confer a significantly elevated rate of somatic chromosomal mosaicism in individual cases. Constitutional triploidy was associated with an increased level of somatic mosaicism, but this consisted mostly of reversion from trisomy to disomy and did not correspond to a proportionally elevated level of chromosome mis-segregation in triploids, indicating that the observed mosaicism resulted from a specific accumulation of cells with a hypotriploid chromosome number. In no case did the rate of somatic mosaicism in constitutional aneuploidy exceed that of "chromosomally stable" cancer cells. Our findings show that even though constitutional aneuploidy was in some cases associated with low-level somatic mosaicism, it was insufficient to generate the cancer-like levels expected if aneuploidy single-handedly triggered cancer-like chromosomal instability.
Ribeiro, Joana; Cardoso, Maria João
The Tenth European Breast Cancer Conference, EBCC 10, was held in Amsterdam in March 2016 with a total of 3061 participants from 95 different countries spread over five continents. The EBCC council is a joint venture of ESO, EORTC Breast Cancer Group, EUSOMA, and Europa Donna. The Scientific Programme for EBCC-10 tried to bring to the stage all the active participants in the diagnostic and treatment of breast cancer along with patients themselves. The need to achieve ‘patient’s access to high quality treatment’ through breast units that have been accredited through a European certification process was the basis of the EBCC 10 manifesto. The congress scientific programme allowed participants to review the most up-to-date knowledge in the breast cancer field presented by experts having in mind its application to every day practice. The purpose of this summary is to describe to the readers the results of the late-breaking and best abstracts presented at EBCC10. PMID:27350789
Kea, Bory; Sun, Benjamin Chih-An
Consensus development sprang from a desire to synthesize clinician and expert opinions on clinical practice and research agendas in the 1950s. And since the American Institute of Medicine formally defined "guidelines" in 1990, there has been a proliferation of clinical practice guidelines (CPG) both formally and informally. This modern decision-making tool used by both physicians and patients, requires extensive planning to overcome the challenges of consensus development while reaping its rewards. Consensus allows for a group approach of multiple experts sharing ideas to form consensus on topics ranging from appropriateness of procedures to research agenda development. Disagreements can shed light on areas of controversy and launch further discussions. It has five main components: three inputs (defining the task, participant identification and recruitment, and information synthesis), the approach (consensus development by explicit or implicit means), and the output (dissemination of results). Each aspect requires extensive planning a priori as they influence the entire process, from how information will be interpreted, the interaction of participants, the resulting judgment, to whether there will be uptake of results. Implicit approaches utilize qualitative methods and/or a simple voting structure of majority wins, and are used in informal consensus development methods and consensus development conferences. Explicit approaches aggregate results or judgments using explicit rules set a priori with definitions of "agreement" or consensus. Because the implicit process can be more opaque, unforeseen challenges can emerge such as the undue influence of a minority. And yet, the logistics of explicit approaches may be more time consuming and not appropriate when speed is a priority. In determining which method to use, it is important to understand the pros and cons of different approaches and how it will affect the overall input, approach, and outcome.
Kea, Bory; Sun, Benjamin C.
Consensus development sprang from a desire to synthesize clinician and expert opinions on clinical practice and research agendas in the 1950s. And since the American Institute of Medicine formally defined “guidelines” in 1990, there has been a proliferation of clinical practice guidelines (CPG) both formally and informally. This modern decision making tool used by both physicians and patients, requires extensive planning to meet the challenges of consensus development while reaping its rewards. Consensus allows for a group approach with multiple experts sharing ideas to form consensus on topics ranging from appropriateness of procedures to research agenda development. Disagreements can shed light on areas of controversy and launch further discussions. It has five main components: three inputs (defining the task, participant identification and recruitment, and information synthesis), the approach (consensus development by explicit or implicit means), and the output (dissemination of results). Each aspect requires extensive planning a priori as they influence the entire process, from how information will be interpreted, the interaction of participants, the resulting judgment, to whether there will be uptake of results. Implicit approaches utilize qualitative methods and/or a simple voting structure of majority wins, and are used in informal consensus development methods and consensus development conferences. Explicit approaches aggregate results or judgments using explicit rules set a priori with definitions of “agreement” or consensus. Because the implicit process can be more opaque, unforeseen challenges can emerge such as the undue influence of a minority. And yet, the logistics of explicit approaches may be more time consuming and not appropriate when speed is a priority. In determining which method to use, it is important to understand the pros and cons of the different approaches and how it will affect the overall input, approach, and outcome. PMID
Luker, Gary D
The AACR Special Conference on Molecular Imaging in Cancer: Linking Biology, Function, and Clinical Applications In Vivo, was held January 23-27, 2002, at the Contemporary Hotel, Walt Disney World, Orlando, FL. Co-Chairs David Piwnica-Worms, Patricia Price and Thomas Meade brought together researchers with diverse expertise in molecular biology, gene therapy, chemistry, engineering, pharmacology, and imaging to accelerate progress in developing and applying technologies for imaging specific cellular and molecular signals in living animals and humans. The format of the conference was the presentation of research that focused on basic and translational biology of cancer and current state-of-the-art techniques for molecular imaging in animal models and humans. This report summarizes the special conference on molecular imaging, highlighting the interfaces of molecular biology with animal models, instrumentation, chemistry, and pharmacology that are essential to convert the dreams and promise of molecular imaging into improved understanding, diagnosis, and management of cancer.
Fitamant, Julien; Guenebeaud, Céline; Coissieux, Marie-May; Guix, Catherine; Treilleux, Isabelle; Scoazec, Jean-Yves; Bachelot, Thomas; Bernet, Agnès; Mehlen, Patrick
Netrin-1, an axon navigation cue was proposed to play a crucial role during colorectal tumorigenesis by regulating apoptosis. The netrin-1 receptors DCC and UNC5H were shown to belong to the family of dependence receptors that share the ability to induce apoptosis in the absence of their ligands. Such a trait confers on these receptors a tumor suppressor activity. Expression of one of these dependence receptors at the surface of a tumor cell is indeed speculated to render this cell dependent on ligand availability for its survival, hence inhibiting uncontrolled cell proliferation or metastasis. Consequently, it is a selective advantage for a tumor cell to lose this dependence receptor activity, as previously described with losses of DCC and UNC5H expression in human cancers. However, the model predicts that a similar advantage may be obtained by gaining autocrine expression of the ligand. We describe here that, unlike human nonmetastatic breast tumors, a large fraction of metastatic breast cancers overexpress netrin-1. Moreover, we show that netrin-1-expressing mammary metastatic tumor cell lines undergo apoptosis when netrin-1 expression is experimentally decreased or when decoy soluble receptor ectodomains are added. Such treatments prevent metastasis formation both in a syngenic mouse model of lung colonization of a mammary cancer cell line and in a model of spontaneous lung metastasis of xenografted human breast tumor. Thus, netrin-1 expression observed in a large fraction of human metastatic breast tumors confers a selective advantage for tumor cell survival and potentially represents a promising target for alternative anticancer therapeutic strategies. PMID:18353983
Anderson, Benjamin O; Cazap, Eduardo; El Saghir, Nagi S; Yip, Cheng-Har; Khaled, Hussein M; Otero, Isabel V; Adebamowo, Clement A; Badwe, Rajendra A; Harford, Joe B
The purpose of the Breast Health Global Initiative (BHGI) 2010 summit was to provide a consensus analysis of breast cancer control issues and implementation strategies for low-income and middle-income countries (LMCs), where advanced stages at presentation and poor diagnostic and treatment capacities contribute to lower breast cancer survival rates than in high-income countries. Health system and patient-related barriers were identified that create common clinical scenarios in which women do not present for diagnosis until their cancer has progressed to locally advanced or metastatic stages. As countries progress to higher economic status, the rate of late presentation is expected to decrease, and diagnostic and treatment resources are expected to improve. Health-care systems in LMCs share many challenges including national or regional data collection, programme infrastructure and capacity (including appropriate equipment and drug acquisitions, and professional training and accreditation), the need for qualitative and quantitative research to support decision making, and strategies to improve patient access and compliance as well as public, health-care professional, and policy-maker awareness that breast cancer is a cost-effective, treatable disease. The biggest challenges identified for low-income countries were little community awareness that breast cancer is treatable, inadequate advanced pathology services for diagnosis and staging, and fragmented treatment options, especially for the administration of radiotherapy and the full range of systemic treatments. The biggest challenges identified for middle-resource countries were the establishment and maintenance of data registries, the coordination of multidisciplinary centres of excellence with broad outreach programmes to provide community access to cancer diagnosis and treatment, and the resource-appropriate prioritisation of breast cancer control programmes within the framework of existing, functional health
cause of adult death in the world. For men in developed countries, the full effects of smoking can already be seen. Tobacco now causes one-third of all male deaths in middle age (plus one fifth in old age). Tobacco is a cause of about half of all male cancer deaths in middle age (plus one-third in old age). Of those who start smoking in their teenage years and keep on smoking, about half will be killed by tobacco. Half of these deaths will be in middle age (35-69) and each will lose an average of 20-25 years of non-smoker life expectancy. In non-smokers in many countries, cancer mortality is decreasing slowly and total mortality rapidly. The war against cancer is being won slowly: the effects of cigarette smoking are holding back this victory. Lung cancer now kills more women in the United States each year than breast cancer. For women in developed countries, the peak of the tobacco epidemic has not yet arrived. Tobacco now causes almost one-third of all deaths in women in middle age in the United States. Although it has only 5% of the world's female population, the United States has 50% of the world's deaths from smoking in women. Tobacco smoking is a major cause of premature death. Throughout Europe, in 1990 tobacco smoking caused three quarters of a million deaths in middle age (between 35 and 69). In the Member States of the European Union in 1990 there were over one quarter of a million deaths in middle age directly caused by tobacco smoking: there were 219700 in men and 31900 in women. There were many more deaths caused by tobacco at older ages. In countries of central and eastern Europe, including the former USSR, there were 441200 deaths in middle age in men and 42100 deaths in women. There is a need for urgent action to help contain this important and unnecessary loss of life. In formulating Recommendations, the European Cancer Experts Consensus Committee recognised that Tobacco Control depends on various parts of society and not only on the individual.
Canadian Cardiovascular Society 2009 Consensus Conference on the management of adults with congenital heart disease: Outflow tract obstruction, coarctation of the aorta, tetralogy of Fallot, Ebstein anomaly and Marfan’s syndrome
Silversides, Candice K; Beauchesne, Luc; Bradley, Timothy; Connelly, Michael; Niwa, Koichiro; Mulder, Barbara; Webb, Gary; Colman, Jack; Therrien, Judith
With advances in pediatric cardiology and cardiac surgery, the population of adults with congenital heart disease (CHD) has increased. In the current era, there are more adults with CHD than children. This population has many unique issues and needs. Since the 2001 Canadian Cardiovascular Society Consensus Conference report on the management of adults with CHD, there have been significant advances in the field of adult CHD. Therefore, new clinical guidelines have been written by Canadian adult CHD physicians in collaboration with an international panel of experts in the field. Part II of the guidelines includes recommendations for the care of patients with left ventricular outflow tract obstruction and bicuspid aortic valve disease, coarctation of the aorta, right ventricular outflow tract obstruction, tetralogy of Fallot, Ebstein anomaly and Marfan’s syndrome. Topics addressed include genetics, clinical outcomes, recommended diagnostic workup, surgical and interventional options, treatment of arrhythmias, assessment of pregnancy risk and follow-up requirements. The complete document consists of four manuscripts that are published online in the present issue of The Canadian Journal of Cardiology. The complete document and references can also be found at www.ccs.ca or www.cachnet.org. PMID:20352138
Schnur, Julie B.; Montgomery, Guy H.
The effects of four empirically supported therapeutic relationship factors (therapeutic alliance, empathy, goal consensus/collaboration, and group cohesion) on the outcome of psychotherapeutic interventions conducted with individuals living with cancer were systematically reviewed. PubMed, PsycINFO, and CINAHL were searched from their inception through November 13, 2008. Studies of psychotherapeutic interventions targeted to individuals living with cancer, which also empirically assessed the association between any of these therapeutic relationship factors and psychotherapy outcome were included in the review (8 of 742 papers initially reviewed). Information on study methodology and results were abstracted independently by the authors using a standardized form. Results indicated that therapist-rated rapport and group cohesion were significantly related to positive psychotherapeutic outcomes. No studies examined empathy. The literature on collaboration was mixed, but showed some support for increased collaboration being related to positive therapeutic outcomes. Overall the current literature on the role of therapeutic relationship factors in the context of individuals living with cancer is scant, and much more research is needed to determine the overall contribution of these four relationship elements to the outcomes of psychotherapeutic interventions for individuals living with cancer. Results of such studies could have important clinical and research implications. PMID:20006414
... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health NIH State-of-the-Science Conference: Enhancing Use and Quality of Colorectal Cancer Screening Notice is hereby given by the National Institutes of Health (NIH) of the ``NIH State-of-the-Science...
Shen, He; Blijlevens, Maxime; Yang, Nuo; Frangou, Costakis; Wilson, Kayla E.; Xu, Bo; Zhang, Yinglong; Zhang, Lirui; Morrison, Carl D.; Shepherd, Lori; Hu, Qiang; Zhu, Qianqian; Wang, Jianmin; Liu, Song; Zhang, Jianmin
Genetic and epigenetic alterations have been identified as to contribute directly or indirectly to the generation of transitional cell carcinoma of the urinary bladder (TCC-UB). We have previously found that amplification of chromosome 6p22 is significantly associated with the muscle-invasive rather than superficial TCC-UB. Here, we demonstrated that Sox4, one of the candidate oncogenes located within the chromosome 6p22 amplicon, confers bladder cancer stem cell (CSC) properties. Down-regulation of Sox4 led to the inhibition of cell migration, colony formation as well as mesenchymal-to-epithelial transition (MET). Interestingly, knockdown of Sox4 also reduced the sphere formation, enriched cell population with high levels of aldehyde dehydrogenase (ALDH high) and tumor formation potential. Using gene expression profiling, we further identified novel Sox4 target genes. Last, immunohistochemistry analysis of human bladder tumor tissue microarrays (TMAs) indicated that high Sox4 expression was correlated with advanced cancer stages and poor survival rate. In summary, our data show that Sox4 is an important regulator of the bladder CSC properties and it may serve as a biomarker of the aggressive phenotype in bladder cancer. PMID:26681916
Rabaglio, Manuela; Aebi, Stefan; Castiglione-Gertsch, Monica
Endocrine treatment for breast cancer was introduced more than a century ago. The discovery of hormone receptors has allowed targeting of endocrine treatment to patients whose primary tumours express these receptors. In the adjuvant setting, different approaches are used in premenopausal or postmenopausal women. In premenopausal patients, suppression of ovarian function and the use of tamoxifen are the most important therapeutic options, even though questions on timing, duration, and combination of these compounds remain unanswered. The use of aromatase inhibitors in combination with ovarian-function suppression is currently under investigation in the premenopausal setting. In postmenopausal patients, aromatase inhibitors given after 2-3 years or 5 years of tamoxifen have shown a significant benefit over tamoxifen alone. However, questions on this treatment also remain unanswered. For example, whether all patients should receive an aromatase inhibitor or whether some subgroups of patients might be optimally treated by tamoxifen alone is yet to be established. In this paper we review the published work on adjuvant endocrine treatment in breast cancer and provide recommendations from the 2007 St Gallen International Conference on Primary Therapy of Early Breast Cancer.
LaPensee, Elizabeth W; Schwemberger, Sandy J; LaPensee, Christopher R; Bahassi, El Mustapha; Afton, Scott E; Ben-Jonathan, Nira
Resistance to chemotherapy is a major obstacle for successful treatment of breast cancer patients. Given that prolactin (PRL) acts as an anti-apoptotic/survival factor in the breast, we postulated that it antagonizes cytotoxicity by chemotherapeutic drugs. Treatment of breast cancer cells with PRL caused variable resistance to taxol, vinblastine, doxorubicin and cisplatin. PRL prevented cisplatin-induced G(2)/M cell cycle arrest and apoptosis. In the presence of PRL, significantly less cisplatin was bound to DNA, as determined by mass spectroscopy, and little DNA damage was seen by gamma-H2AX staining. PRL dramatically increased the activity of glutathione-S-transferase (GST), which sequesters cisplatin in the cytoplasm; this increase was abrogated by Jak and mitogen-activated protein kinase inhibitors. PRL upregulated the expression of the GSTmu, but not the pi, isozyme. A GST inhibitor abrogated antagonism of cisplatin cytotoxicity by PRL. In conclusion, PRL confers resistance against cisplatin by activating a detoxification enzyme, thereby reducing drug entry into the nucleus. These data provide a rational explanation for the ineffectiveness of cisplatin in breast cancer, which is characterized by high expression of both PRL and its receptor. Suppression of PRL production or blockade of its actions should benefit patients undergoing chemotherapy by allowing for lower drug doses and expanded drug options.
Cardenas, Carlos; Montagna, Michele K; Pitruzzello, Mary; Lima, Eydis; Mor, Gil; Alvero, Ayesha B
Resistance to mitochondria-initiated apoptosis is a hallmark of chemoresistant cancer stem cells including CD44+/MyD88+ epithelial ovarian cancer (EOC) stem cells. This is controlled by members of the Bcl2 family of proteins, which function as rheostats of mitochondrial stability. We observed a differential expression profile of Bcl2 family members comparing the chemoresistant EOC stem cells and the chemosensitive CD44-/MyD88- EOC cells. Chemoresistant EOC stem cells surprisingly express higher levels of the pro-apoptotic members Bak and Bax compared to the chemosensitive EOC cells. In addition, whereas chemosensitive EOC cells preferentially express Bcl2, chemoresistant EOC stem cells preferentially express Bclxl. In the EOC stem cells, 40% knock-down of Bclxl expression was sufficient to induce the full activation of caspases and this can be reversed by concurrent knock-down of Puma. More importantly, we demonstrate that Bclxl expression levels in EOC cells is dynamic and can be regulated by microenvironments that are enriched with the pro-inflammatory cytokine IL-6 such as the cancer stem cell and adipocyte niches. Adipocyte-induced upregulation of Bclxl correlated with acquisition of chemoresistance and thus demonstrates how a specific microenvironment can regulate the expression of apoptotic proteins and confer chemoresistance.
Song, K-H; Cho, H; Kim, S; Lee, H-J; Oh, S J; Woo, S R; Hong, S-O; Jang, H S; Noh, K H; Choi, C H; Chung, J-Y; Hewitt, S M; Kim, J-H; Son, M; Kim, S-H; Lee, B I; Park, H-C; Bae, Y-K; Kim, T W
Immune selection drives the evolution of tumor cells toward an immune-resistant and cancer stem cell (CSC)-like phenotype. We reported that apoptosis inhibitor-5 (API5) acts as an immune escape factor, which has a significant role in controlling immune resistance to antigen-specific T cells, but its functional association with CSC-like properties remains largely unknown. In this study, we demonstrated for the first time that API5 confers CSC-like properties, including NANOG expression, the frequency of CD44-positive cells and sphere-forming capacity. Critically, these CSC-like properties mediated by API5 are dependent on FGFR1 signaling, which is triggered by E2F1-dependent FGF2 expression. Furthermore, we uncovered the FGF2-NANOG molecular axis as a downstream component of API5 signaling that is conserved in cervical cancer patients. Finally, we found that the blockade of FGFR signaling is an effective strategy to control API5high human cancer. Thus, our findings reveal a crucial role of API5 in linking immune resistance and CSC-like properties, and provide the rationale for its therapeutic application for the treatment of API5+ refractory tumors. PMID:28092370
Using the approaches of history of the present, this article recovers the discussions surrounding the 12th International Conference on Cancer carried out in Buenos Aires in 1978, in reaction to which Georges Périès organized a "counter-conference" in Paris. In order to understand this discussion, the political situation of the time is described, as is the state of human rights at the time in Argentina, the role of the media - in particular the newspapers La Nación and Clarín and the magazine Gente - and the institutional position adopted by the National Academy of Medicine, as expressed in a letter sent to the presidents of the primary scientific societies of the world. The letter is reprinted in this text as a documentary source, taken from Memoria: Año 1978 (Presidencia de Dr. José E. Rivarola) [Acta: Year 1978 (Presidency of Dr. José E. Rivarola)]. The framework of the discussion makes reference to science's social policy versus science's supposed neutrality and the role of scientific societies.
Winkler, Katrin; Ramer, Robert; Dithmer, Sophie; Ivanov, Igor; Merkord, Jutta; Hinz, Burkhard
Inhibition of endocannabinoid degradation has been suggested as tool for activation of endogenous tumor defense. One of these strategies lies in blockade of fatty acid amide hydrolase (FAAH) which catalyzes the degradation of endocannabinoids (anandamide [AEA], 2-arachidonoylglycerol [2-AG]) and endocannabinoid-like substances (N-oleoylethanolamine [OEA], N-palmitoylethanolamine [PEA]). This study addressed the impact of two FAAH inhibitors (arachidonoyl serotonin [AA-5HT], URB597) on A549 lung cancer cell metastasis and invasion. LC-MS analyses revealed increased levels of FAAH substrates (AEA, 2-AG, OEA, PEA) in cells incubated with either FAAH inhibitor. In athymic nude mice FAAH inhibitors were shown to elicit a dose-dependent antimetastatic action yielding a 67% and 62% inhibition of metastatic lung nodules following repeated administration of 15 mg/kg AA-5HT and 5 mg/kg URB597, respectively. In vitro, a concentration-dependent anti-invasive action of either FAAH inhibitor was demonstrated, accompanied with upregulation of tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). Using siRNA approaches, a causal link between the TIMP-1-upregulating and anti-invasive action of FAAH inhibitors was confirmed. Moreover, knockdown of FAAH by siRNA was shown to confer decreased cancer cell invasiveness and increased TIMP-1 expression. Inhibitor experiments point toward a role of CB2 and transient receptor potential vanilloid 1 in conferring anti-invasive effects of FAAH inhibitors and FAAH siRNA. Finally, antimetastatic and anti-invasive effects were confirmed for all FAAH substrates with AEA and OEA causing a TIMP-1-dependent anti-invasive action. Collectively, the present study provides first-time proof for an antimetastatic action of FAAH inhibitors. As mechanism of its anti-invasive properties an upregulation of TIMP-1 was identified. PMID:26930716
Park, Hee Chul; Yu, Jeong Il; Cheng, Jason Chia-Hsien; Zeng, Zhao Chong; Hong, Ji Hong; Wang, Michael Lian Chek; Kim, Mi Sook; Chi, Kwan Hwa; Liang, Po-Ching; Lee, Rheun-Chuan; Lau, Wan-Yee; Han, Kwang Hyub; Chow, Pierce Kah-Hoe; Seong, Jinsil
A consensus meeting to develop practice guidelines and to recommend future clinical trials for radiation therapy (RT), including external beam RT (EBRT), and selective internal RT (SIRT) in hepatocellular carcinoma (HCC) was held at the 5th annual meeting of the Asia-Pacific Primary Liver Cancer Expert consortium. Although there is no randomized phase III trial evidence, the efficacy and safety of RT in HCC has been shown by prospective and retrospective studies using modern RT techniques. Based on these results, the committee came to a consensus on the utility and efficacy of RT in the management of HCC according to each disease stage as follows: in early and intermediate stage HCC, if standard treatment is not compatible, RT, including EBRT and SIRT can be considered. In locally advanced stage HCC, combined EBRT with transarterial chemoembolization or hepatic arterial infusion chemotherapy, and SIRT can be considered. In terminal stage HCC, EBRT can be considered for palliation of symptoms and reduction of morbidity caused by the primary tumor or its metastases. Despite the currently reported benefits of RT in HCC, the committee agreed that there is a compelling need for large prospective studies, including randomized phase III trial evidence evaluating the role of RT. Specifically studies evaluating the efficacy and safety of sequential combination of EBRT and SIRT are strongly recommended. PMID:27493892
Tamaki, Kentaro; Tamaki, Nobumitsu; Kamada, Yoshihiko; Uehara, Kano; Zaha, Hisamitsu; Onomura, Mai; Ueda, Makoto; Kurashita, Kaname; Miyazato, Keiko; Higa, Junko; Miyara, Kyuichiro; Shiraishi, Makiko; Murayama, Shigemi; Ishida, Takanori
The rate of breast cancer mortality in Okinawa has gradually been increasing up to 2010. Now Okinawa has the second worst mortality rate in Japan, in part due to the enormous dietary changes resulting from the post-World War II US military occupation, high incidence of obesity, high non-optimal treatment rate, and low breast-cancer screening rate. To reduce breast cancer mortality in Okinawa, we established the Okinawa Breast Oncology Meeting (OBOM) in 2012. At the 7th OBOM held on January 10th, 2014, we discussed the breast cancer mortality in Okinawa focusing on lifestyle, breast cancer screening and optimal treatments. The Okinawan women who were overweight and/or obese during premenopausal and postmenopausal ages had a statistically significant higher risk of breast cancer development compared to those with non-overweight and/or obese women. The traditional diet of Okinawa consists of foods low in calories but rich in nutritional value. Therefore, we recommend Okinawan people not to forget the Okinawan traditional lifestyle, and to reduce their bodyweight to prevent breast cancer. One of the main goals of the OBOM is to raise breast cancer screening attendance rates to 50% (29.2% in 2010). We should standardize the quality control for breast cancer screening in Okinawa. It is important to continue enlightening the Okinawan population to receive optimal treatment. In addition, we are striving to establish systematic medical cooperation between the hospitals specializing in breast cancer treatment with rural hospitals. The OBOM group endeavors to contribute to the improvement of breast cancer mortality in Okinawa.
Campbell, Thomas M; Castro, Mauro A A; de Santiago, Ines; Fletcher, Michael N C; Halim, Silvia; Prathalingam, Radhika; Ponder, Bruce A J; Meyer, Kerstin B
The fibroblast growth factor receptor 2 (FGFR2) locus is consistently the top hit in genome-wide association studies for oestrogen receptor-positive (ER(+)) breast cancer. Yet, its mode of action continues to be controversial. Here, we employ a systems biology approach to demonstrate that signalling via FGFR2 counteracts cell activation by oestrogen. In the presence of oestrogen, the oestrogen receptor (ESR1) regulon (set of ESR1 target genes) is in an active state. However, signalling by FGFR2 is able to reverse the activity of the ESR1 regulon. This effect is seen in multiple distinct FGFR2 signalling model systems, across multiple cells lines and is dependent on the presence of FGFR2. Increased oestrogen exposure has long been associated with an increased risk of breast cancer. We therefore hypothesized that risk variants should reduce FGFR2 expression and subsequent signalling. Indeed, transient transfection experiments assaying the three independent variants of the FGFR2 risk locus (rs2981578, rs35054928 and rs45631563) in their normal chromosomal context show that these single-nucleotide polymorphisms (SNPs) map to transcriptional silencer elements and that, compared with wild type, the risk alleles augment silencer activity. The presence of risk variants results in lower FGFR2 expression and increased oestrogen responsiveness. We thus propose a molecular mechanism by which FGFR2 can confer increased breast cancer risk that is consistent with oestrogen exposure as a major driver of breast cancer risk. Our findings may have implications for the clinical use of FGFR2 inhibitors.
Rao, X; Di Leva, G; Li, M; Fang, F; Devlin, C; Hartman-Frey, C; Burow, M E; Ivan, M; Croce, C M; Nephew, K P
Fulvestrant is a selective estrogen receptor downregulator (SERD) and highly effective antagonist to hormone-sensitive breast cancers following failure of previous tamoxifen or aromatase inhibitor therapies. However, after prolonged fulvestrant therapy, acquired resistance eventually occurs in the majority of breast cancer patients, due to poorly understood mechanisms. To examine a possible role(s) of aberrantly expressed microRNAs (miRNAs) in acquired fulvestrant resistance, we compared antiestrogen-resistant and -sensitive breast cancer cells, revealing the overexpression of miR-221/222 in the SERD-resistant cell lines. Fulvestrant treatment of estradiol (E2)- and fulvestrant-sensitive MCF7 cells resulted in increased expression of endogenous miR-221/222. Ectopic upregulation of miR-221/222 in estrogen receptor-α (ERα)-positive cell lines counteracted the effects of E2 depletion or fulvestrant-induced cell death, thus also conferring hormone-independent growth and fulvestrant resistance. In cells with acquired resistance to fulvestrant, miR-221/222 expression was essential for cell growth and cell cycle progression. To identify possible miR-221/222 targets, miR-221- or miR-222- induced alterations in global gene expression profiles and target gene expression at distinct time points were determined, revealing that miR-221/222 overexpression resulted in deregulation of multiple oncogenic signaling pathways previously associated with drug resistance. Activation of β-catenin by miR-221/222 contributed to estrogen-independent growth and fulvestrant resistance, whereas TGF-β-mediated growth inhibition was repressed by the two miRNAs. This first in-depth investigation into the role of miR-221/222 in acquired fulvestrant resistance, a clinically important problem, demonstrates that these two 'oncomirs' may represent promising therapeutic targets for treating hormone-independent, SERD-resistant breast cancer.
Rao, X; Di Leva, G; Li, M; Fang, F; Devlin, C; Hartman-Frey, C; Burow, ME; Ivan, M; Croce, CM; Nephew, KP
Fulvestrant is a selective estrogen receptor downregulator (SERD) and highly effective antagonist to hormone-sensitive breast cancers following failure of previous tamoxifen or aromatase inhibitor therapies. However, after prolonged fulvestrant therapy, acquired resistance eventually occurs in the majority of breast cancer patients, due to poorly understood mechanisms. To examine a possible role(s) of aberrantly expressed microRNAs (miRNAs) in acquired fulvestrant resistance, we compared antiestrogen-resistant and -sensitive breast cancer cells, revealing the over-expression of miR-221/222 in the SERD-resistant cell lines. Fulvestrant treatment of estradiol (E2)- and fulvestrant-sensitive MCF7 cells resulted in increased expression of endogenous miR-221/222. Ectopic upregulation of miR-221/222 in estrogen receptor-α (ERα)-positive cell lines counteracted the effects of E2 depletion or fulvestrant-induced cell death, thus also conferring hormone-independent growth and fulvestrant resistance. In cells with acquired resistance to fulvestrant, miR-221/222 expression was essential for cell growth and cell cycle progression. To identify possible miR-221/222 targets, miR-221- or miR-222- induced alterations in global gene expression profiles and target gene expression at distinct time points were determined, revealing that miR-221/222 overexpression resulted in deregulation of multiple oncogenic signaling pathways previously associated with drug resistance. Activation of β-catenin by miR-221/222 contributed to estrogen-independent growth and fulvestrant resistance, whereas TGF-β-mediated growth inhibition was repressed by the two miRNAs. This first in-depth investigation into the role of miR-221/222 in acquired fulvestrant resistance, a clinically important problem, demonstrates that these two ‘oncomirs’ may represent promising therapeutic targets for treating hormone-independent, SERD-resistant breast cancer. PMID:21057537
The 4th International PhD Student Cancer Conference was held at the IFOM-IEO-Campus in Milan from 19-21 May 2010 http://www.semm.it/events_researchPast.phpThe Conference covered many topics related to cancer, from basic biology to clinical aspects of the disease. All attendees presented their research, by either giving a talk or presenting a poster. This conference is an opportunity to introduce PhD students to top cancer research institutes across Europe.THE CORE PARTICIPANTING INSTITUTES INCLUDED: European School of Molecular Medicine (SEMM)-IFOM-IEO Campus, MilanBeatson Institute for Cancer Research (BICR), GlasgowCambridge Research Institute (CRI), Cambridge, UKMRC Gray Institute of Radiation Biology (GIROB), OxfordLondon Research Institute (LRI), LondonPaterson Institute for Cancer Research (PICR), ManchesterThe Netherlands Cancer Institute (NKI), Amsterdam'You organizers have crushed all my prejudices towards Italians. Congratulations, I enjoyed the conference immensely!' Even if it might have sounded like rudeness for sure this was supposed to be a genuine compliment (at least, that's how we took it), also considering that it was told by a guy who himself was the fusion of two usually antithetical concepts: fashion style and English nationality.The year 2010 has marked an important event for Italian research in the international scientific panorama: the European School of Molecular Medicine (SEMM) had the honour to host the 4th International PhD Student Cancer Conference, which was held from 19-21 May 2010 at the IFOM-IEO-Campus (http://www.semm.it/events_researchPast.php) in Milan.The conference was attended by more than one hundred students, coming from a selection of cutting edge European institutes devoted to cancer research. The rationale behind it is the promotion of cooperation among young scientists across Europe to debate about science and to exchange ideas and experiences. But that is not all, it is also designed for PhD students to get in touch
Viswanathan, Akila N.; Erickson, Beth; Gaffney, David K.; Bosch, Walter
Purpose/Objective To create and compare consensus clinical target volume (CTV) contours for computed tomography (CT) and 3 Tesla (3T) magnetic resonance (MR) image-based cervical-cancer brachytherapy Materials/Methods Twenty-three gynecologic radiation oncology experts contoured the same 3 cervical-cancer brachytherapy cases: one Stage IIB near-complete response (CR) case with a tandem and ovoid, one Stage IIB partial response (PR) case with ovoid with needles and one Stage IB2 CR case with a ring applicator. CT contours were completed before MRI contours. These were analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with kappa statistics as a measure of agreement between participants. The conformity index (CI) was calculated for each of the six data sets. Dice coefficients were generated to compare CT and MR contours of the same case. Results For all 3 cases, the mean tumor volume was smaller on MR than on CT (p<0.001). Kappa and CI estimates were slightly higher for CT, indicating a higher level of agreement on CT. DICE coefficients were 89% for the Stage IB2 case with a CR, 74% for the Stage IIB case with a PR, and 57% for the Stage IIB case with a CR. Conclusion When comparing MR- to CT-contoured CTV volumes, the higher level of agreement on CT may be due to the more distinct contrast visible on the images at the time of brachytherapy. The largest difference at the time of brachytherapy was in the case with parametrial extension at diagnosis that had a near-complete response, due to the appearance of the parametria on CT but not on MR. Based on these results, a 95% consensus volume was generated for CT and for MR. Online contouring atlases are available for instruction at http://www.nrgoncology.org/Resources/ContouringAtlases.aspx. PMID:25304792
In many countries of the Association of Southeast Asian Nations (ASEAN), cancer is an increasing problem due to ageing and a transition to Western lifestyles. Governments have been slow to react to the health consequences of these socioeconomic changes, leading to the risk of a cancer epidemic overwhelming the region. A major limitation to motivating change is the paucity of high-quality data on cancer, and its socioeconomic repercussions, in ASEAN. Two initiatives have been launched to address these issues. First, a study of over 9000 new cancer patients in ASEAN - the ACTION study - which records information on financial difficulties, as well as clinical outcomes, subsequent to the diagnosis. Second, a series of roundtable meetings of key stakeholders and experts, with the broad aim of producing advice for governments in ASEAN to take appropriate account of issues relating to cancer, as well as to generate knowledge and interest through engagement with the media. An important product of these roundtables has been the Jakarta Call to Action on Cancer Control. The growth and ageing of populations is a global challenge for cancer services. In the less developed parts of Asia, and elsewhere, these problems are compounded by the epidemiological transition to Western lifestyles and lack of awareness of cancer at the government level. For many years, health services in less developed countries have concentrated on infectious diseases and mother-and-child health; despite a recent wake-up call (United Nations, 2010), these health services have so far failed to allow for the huge increase in cancer cases to come. It has been estimated that, in Asia, the number of new cancer cases per year will grow from 6.1 million in 2008 to 10.6 million in 2030 (Sankaranarayanan et al., 2014). In the countries of the Association of Southeast Asian Nations (ASEAN), corresponding figures are 770 thousand in 2012 (Figure 1), rising to 1.3 million in 2030 (Ferlay et al., 2012). ASEAN
Dunne, Philip D.; O'Reilly, Paul G.; Coleman, Helen G.; Gray, Ronan T.; Longley, Daniel B.; Johnston, Patrick G.; Salto-Tellez, Manuel
The Colorectal Cancer (CRC) Subtyping Consortium (CRCSC) recently published four consensus molecular subtypes (CMS's) representing the underlying biology in CRC. The Microsatellite Instable (MSI) immune group, CMS1, has a favorable prognosis in early stage disease, but paradoxically has the worst prognosis following relapse, suggesting the presence of factors enabling neoplastic cells to circumvent this immune response. To identify the genes influencing subsequent poor prognosis in CMS1, we analyzed this subtype, centered on risk of relapse. In a cohort of early stage colon cancer (n=460), we examined, in silico, changes in gene expression within the CMS1 subtype and demonstrated for the first time the favorable prognostic value of chemokine-like factor (CKLF) gene expression in the adjuvant disease setting [HR=0.18, CI=0.04-0.89]. In addition, using transcription profiles originating from cell sorted CRC tumors, we delineated the source of CKLF transcription within the colorectal tumor microenvironment to the leukocyte component of these tumors. Further to this, we confirmed that CKLF gene expression is confined to distinct immune subsets in whole blood samples and primary cell lines, highlighting CKLF as a potential immune cell-derived factor promoting tumor immune-surveillance of nascent neoplastic cells, particularly in CMS1 tumors. Building on the recently reported CRCSC data, we provide compelling evidence that leukocyte-infiltrate derived CKLF expression is a candidate biomarker of favorable prognosis, specifically in MSI-immune stage II/III disease. PMID:27153559
Goodman, Karyn A.; Regine, William F.; Dawson, Laura A.; Ben-Josef, Edgar; Haustermans, Karin; Bosch, Walter R.; Turian, Julius; Abrams, Ross A.
Purpose: To develop contouring guidelines to be used in the Radiation Therapy Oncology Group protocol 0848, a Phase III randomized trial evaluating the benefit of adjuvant chemoradiation in patients with resected head of pancreas cancer. Methods and Materials: A consensus committee of six radiation oncologists with expertise in gastrointestinal radiotherapy developed stepwise contouring guidelines and an atlas for the delineation of the clinical target volume (CTV) in the postoperative treatment of pancreas cancer, based on identifiable regions of interest and margin expansions. Areas at risk for subclinical disease to be included in the CTV were defined, including nodal regions, anastomoses, and the preoperative primary tumor location. Regions of interest that could be reproducibly contoured on postoperative imaging after a pancreaticoduodenectomy were identified. Standardized expansion margins to encompass areas at risk were developed after multiple iterations to determine the optimal margin expansions. Results: New contouring recommendations based on CT anatomy were established. Written guidelines for the delineation of the postoperative CTV and normal tissues, as well as a Web-based atlas, were developed. Conclusions: The postoperative abdomen has been a difficult area for effective radiotherapy. These new guidelines will help physicians create fields that better encompass areas at risk and minimize dose to normal tissues.
Rockefeller Foundation, New York, NY.
These papers by four social scientists were prepared for a conference to analyze the current absence of a value consensus in American life and to examine grounds for a consensus. Further, the contribution of education and the media to the shaping and dissemination of values is explored. Kenneth Boulding contends that underlying moral diversity is…
Martin, George M
The 2008 Research Conference of the American Federation for Aging Research took place in New York City on October 6-7 and had, as its theme, the interface between the biology of cancer and the biology of aging. The first day was devoted to a series of 5-year progress reports by grantees of an innovative program jointly sponsored by the National Cancer Institute and the National Institute on Aging aimed at fostering both basic and clinical interactions and integrations among investigators with primary research interests in either the biology of aging or the biology of cancer. This was followed by a series of presentations on cell biology (Judith Campisi), evolutionary biology (Steven N. Austad), mitochondrial damage (Lawrence A. Loeb), stem cell functionality (Thomas A. Rando), oxidative stress and cancer resistance (Rochelle Buffenstein), signal transduction and replicative senescence in cancer and aging (Norman E. Sharpless), and telomere biology (Jack D. Griffith). Overview presentations were given by John W. Rowe and Harvey Jay Cohen. The conference closed with a roundtable discussion with representatives of industry in an effort to enhance communications with academicians.
Dey, Prasenjit; Baddour, Joelle; Muller, Florian; Wu, Chia Chin; Wang, Huamin; Liao, Wen-Ting; Lan, Zangdao; Chen, Alina; Gutschner, Tony; Kang, Yaan; Fleming, Jason; Satani, Nikunj; Zhao, Di; Achreja, Abhinav; Yang, Lifeng; Lee, Jiyoon; Chang, Edward; Genovese, Giannicola; Viale, Andrea; Ying, Haoqiang; Draetta, Giulio; Maitra, Anirban; Wang, Y Alan; Nagrath, Deepak; DePinho, Ronald A
The genome of pancreatic ductal adenocarcinoma (PDAC) frequently contains deletions of tumour suppressor gene loci, most notably SMAD4, which is homozygously deleted in nearly one-third of cases. As loss of neighbouring housekeeping genes can confer collateral lethality, we sought to determine whether loss of the metabolic gene malic enzyme 2 (ME2) in the SMAD4 locus would create cancer-specific metabolic vulnerability upon targeting of its paralogous isoform ME3. The mitochondrial malic enzymes (ME2 and ME3) are oxidative decarboxylases that catalyse the conversion of malate to pyruvate and are essential for NADPH regeneration and reactive oxygen species homeostasis. Here we show that ME3 depletion selectively kills ME2-null PDAC cells in a manner consistent with an essential function for ME3 in ME2-null cancer cells. Mechanistically, integrated metabolomic and molecular investigation of cells deficient in mitochondrial malic enzymes revealed diminished NADPH production and consequent high levels of reactive oxygen species. These changes activate AMP activated protein kinase (AMPK), which in turn directly suppresses sterol regulatory element-binding protein 1 (SREBP1)-directed transcription of its direct targets including the BCAT2 branched-chain amino acid transaminase 2) gene. BCAT2 catalyses the transfer of the amino group from branched-chain amino acids to α-ketoglutarate (α-KG) thereby regenerating glutamate, which functions in part to support de novo nucleotide synthesis. Thus, mitochondrial malic enzyme deficiency, which results in impaired NADPH production, provides a prime 'collateral lethality' therapeutic strategy for the treatment of a substantial fraction of patients diagnosed with this intractable disease.
Song, Shumei; Honjo, Soichiro; Jin, Jiankang; Chang, Shih-Shin; Scott, Ailing W; Chen, Qiongrong; Kalhor, Neda; Correa, Arlene M.; Hofstetter, Wayne L.; Albarracin, Constance T.; Wu, Tsung-Teh; Johnson, Randy L.; Hung, Mien-Chie; Ajani, Jaffer A.
Purpose Esophageal cancer (EC) is an aggressive malignancy and often resistant to therapy. Overexpression of EGFR has been associated with poor prognosis of EC patients. However, clinical trials using EGFR inhibitors have not provided benefit for EC patients. Failure of EGFR inhibition may be due to crosstalk with other oncogenic pathways. Experimental Design In this study, expression of YAP1 and EGFR were examined in EAC resistant tumor tissues vs sensitive tissues by immunohistochemistry. Western blot, immunofluorescence, real-time PCR, promoter analysis, site-directed mutagenesis and in vitro and in vivo functional assays were performed to elucidate the YAP1 mediate EGFR expression and transcription and the relationship with chemoresistance in esophageal cancer. Results We demonstrate that Hippo pathway coactivator YAP1 can induce EGFR expression and transcription in multiple cell systems. Both YAP1 and EGFR are overexpressed in resistant EC tissues compared to sensitive EC tissues. Further, we found that YAP1 increases EGFR expression at the level of transcription requiring an intact TEAD binding site in the EGFR promoter. Most importantly, exogenous induction of YAP1 induces resistance to 5-FU and docetaxcel, while knockdown of YAP sensitizes EC cells to these cytotoxics. Verteporfin, a YAP1 inhibitor, effectively inhibits both YAP1 and EGFR expression and sensitizes cells to cytotoxics. Conclusions Our data provide evidence that YAP1 up-regulation of EGFR plays an important role in conferring therapy resistance in EC cells. Targeting YAP1-EGFR axis may be more efficacious than targeting EGFR alone in EC. PMID:25739674
Bacon, Monica; Kitchener, Henry; Stuart, Gavin C E; Vermorken, Jan B
The Gynecologic Cancer InterGroup (GCIG) has developed from a small network of ovarian cancer researchers to a large international forum addressing multiple issues related to research in gynecologic cancers. Member groups of the GCIG have collaboratively conducted pivotal clinical trials in cancers of the ovary, endometrium, and cervix. The participation of operational and statistical personnel from the GCIG member groups has facilitated a collegial approach to international differences and restrictions.One of the powerful initiatives of the GCIG is the facilitation of the Ovarian Cancer Consensus Conference every few years. The 4th Ovarian Cancer Consensus Conference was held in Vancouver, Canada, in June 2010, and the resulting publications (herein) provide an invaluable resource to researchers in the field of gynecologic oncology.
Viswanathan, Akila N.; Gaffney, David K.; Beriwal, Sushil; Bhatia, Sudershan K.; Lee Burnett, Omer; D'Souza, David P.; Patil, Nikhilesh; Haddock, Michael G.; Jhingran, Anuja; Jones, Ellen L.; Kunos, Charles A.; Lee, Larissa J.; Mayr, Nina A.; Petersen, Ivy; Petric, Primoz; Portelance, Lorraine; Small, William; Strauss, Jonathan B.; and others
Objective: To create and compare consensus clinical target volume (CTV) contours for computed tomography (CT) and 3-Tesla (3-T) magnetic resonance (MR) image-based cervical-cancer brachytherapy. Methods and Materials: Twenty-three experts in gynecologic radiation oncology contoured the same 3 cervical cancer brachytherapy cases: 1 stage IIB near-complete response (CR) case with a tandem and ovoid, 1 stage IIB partial response (PR) case with tandem and ovoid with needles, and 1 stage IB2 CR case with a tandem and ring applicator. The CT contours were completed before the MRI contours. These were analyzed for consistency and clarity of target delineation using an expectation maximization algorithm for simultaneous truth and performance level estimation (STAPLE), with κ statistics as a measure of agreement between participants. The conformity index was calculated for each of the 6 data sets. Dice coefficients were generated to compare the CT and MR contours of the same case. Results: For all 3 cases, the mean tumor volume was smaller on MR than on CT (P<.001). The κ and conformity index estimates were slightly higher for CT, indicating a higher level of agreement on CT. The Dice coefficients were 89% for the stage IB2 case with a CR, 74% for the stage IIB case with a PR, and 57% for the stage IIB case with a CR. Conclusion: In a comparison of MR-contoured with CT-contoured CTV volumes, the higher level of agreement on CT may be due to the more distinct contrast medium visible on the images at the time of brachytherapy. MR at the time of brachytherapy may be of greatest benefit in patients with large tumors with parametrial extension that have a partial or complete response to external beam. On the basis of these results, a 95% consensus volume was generated for CT and for MR. Online contouring atlases are available for instruction at (http://www.nrgoncology.org/Resources/ContouringAtlases/GYNCervicalBrachytherapy.aspx)
Breast cancer and primary systemic therapy. Results of the Consensus Meeting on the recommendations for pathological examination and histological report of breast cancer specimens in the Marche Region.
Santinelli, A; De Nictolis, M; Mambelli, V; Ranaldi, R; Bearzi, I; Battellpi, N; Mariotti, C; Fabbietti, L; Baldassarre, S; Giuseppetti, G M; Fabris, G
Primary systemic therapy (PST) adds some practical problems to the pathologic examination of neoplastic breast tissue obtained from patients before and after chemotherapy. Pathologists, oncologists, breast surgeons, radiotherapists and radiologists in the Marche Region held a Consensus Meeting in Ancona on May 13, 2010, in which 15 statements dealing with neoadjuvant chemotherapy were approved by all participants. The first two statements are related to the pre-PST phase and concern the technical procedures and the histological report of the core biopsy. The other statements deal with similar issues of the post-PST surgical specimen.
Psychological Considerations in the Assessment and Treatment of Pain in Neurorehabilitation and Psychological Factors Predictive of Therapeutic Response: Evidence and Recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation
Castelnuovo, Gianluca; Giusti, Emanuele M.; Manzoni, Gian Mauro; Saviola, Donatella; Gatti, Arianna; Gabrielli, Samantha; Lacerenza, Marco; Pietrabissa, Giada; Cattivelli, Roberto; Spatola, Chiara A. M.; Corti, Stefania; Novelli, Margherita; Villa, Valentina; Cottini, Andrea; Lai, Carlo; Pagnini, Francesco; Castelli, Lorys; Tavola, Mario; Torta, Riccardo; Arreghini, Marco; Zanini, Loredana; Brunani, Amelia; Capodaglio, Paolo; D'Aniello, Guido E.; Scarpina, Federica; Brioschi, Andrea; Priano, Lorenzo; Mauro, Alessandro; Riva, Giuseppe; Repetto, Claudia; Regalia, Camillo; Molinari, Enrico; Notaro, Paolo; Paolucci, Stefano; Sandrini, Giorgio; Simpson, Susan G.; Wiederhold, Brenda; Tamburin, Stefano
Background: In order to provide effective care to patients suffering from chronic pain secondary to neurological diseases, health professionals must appraise the role of the psychosocial factors in the genesis and maintenance of this condition whilst considering how emotions and cognitions influence the course of treatment. Furthermore, it is important not only to recognize the psychological reactions to pain that are common to the various conditions, but also to evaluate how these syndromes differ with regards to the psychological factors that may be involved. As an extensive evaluation of these factors is still lacking, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCPN) aimed to collate the evidence available across these topics. Objectives: To determine the psychological factors which are associated with or predictive of pain secondary to neurological conditions and to assess the influence of these aspects on the outcome of neurorehabilitation. Methods: Two reviews were performed. In the first, a PUBMED search of the studies assessing the association between psychological factors and pain or the predictive value of these aspects with respect to chronic pain was conducted. The included papers were then rated with regards to their methodological quality and recommendations were made accordingly. In the second study, the same methodology was used to collect the available evidence on the predictive role of psychological factors on the therapeutic response to pain treatments in the setting of neurorehabilitation. Results: The first literature search identified 1170 results and the final database included 189 articles. Factors such as depression, anxiety, pain catastrophizing, coping strategies, and cognitive functions were found to be associated with pain across the various conditions. However, there are differences between chronic musculoskeletal pain, migraine, neuropathy, and conditions associated with complex disability with regards to the
Garland, S; Park, S N; Ngan, H Y S; Frazer, I; Tay, E H; Chen, C J; Bhatla, N; Pitts, M; Shin, H R; Konno, R; Smith, J; Pagliusi, S; Park, J S
Asia accounts for more than half of all cases of cervical cancer registered globally and improving prevention is urgently needed. A range of tools and strategies is now available to effectively prevent this disease, including two new prophylactic HPV vaccines approved and recommended for adolescents and young women. However, without communication these tools may have little impact on disease burden. The conferences of the Asia Oceania Research Organisation in Genital Infection and Neoplasia (AOGIN) bring together clinicians and scientists whose work is related to genital infections, particularly HPV, cervical dysplasia and neoplasia, as well as other anogenital cancers, with the aim of improving communication on prevention through human papillomavirus (HPV) vaccination and screening in Asian countries. The scope of this year's AOGIN conference was to extend education to include health workers, family doctors, paediatricians, governmental health agencies, and the general public through patients' testimonials that can reach out to women raising awareness of this silent disease. Community based initiatives and awareness campaigns were also reported, and can empower the people to engage in a dialog with local governments towards prioritization of cancer prevention programs, achieving more for the public than isolated actions. Parents and teachers are encouraged to communicate about these issues within families and schools. Evidence was discussed that males can participate in cervical cancer control as well, and prevention programs involving men should not be neglected as they may reduce genital disease burden in women. Opinion leaders proposed prevention measures to be considered for governmental decisions. While each country develops a locally appropriate policy for cervical cancer control there is a need to revise these programs regularly, as knowledge increases in response to public need, as well as to gather evidence about disease burden and the effectiveness of
Middleton, Fiona K.; Patterson, Miranda J.; Elstob, Claire J.; Fordham, Sarah; Herriott, Ashleigh; Wade, Mark A.; McCormick, Aiste; Edmondson, Richard; May, Felicity E.B.; Allan, James M.; Pollard, John R.; Curtin, Nicola J.
ATRis an attractive target in cancer therapy because it signals replication stress and DNA lesions for repair and to S/G2 checkpoints. Cancer-specific defects in the DNA damage response (DDR) may render cancer cells vulnerable to ATR inhibition alone. We determined the cytotoxicity of the ATR inhibitor VE-821 in isogenically matched cells with DDR imbalance. Cell cycle arrest, DNA damage accumulation and repair were determined following VE-821 exposure. Defectsin homologous recombination repair (HRR: ATM, BRCA2 and XRCC3) and baseexcision repair (BER: XRCC1) conferred sensitivity to VE-821. Surprisingly, the loss of different components of the trimeric non-homologous end-joining (NHEJ) protein DNA-PK had opposing effects. Loss of the DNA-binding component, Ku80, caused hypersensitivity to VE-821, but loss of its partner catalytic subunit, DNA-PKcs, did not. Unexpectedly, VE-821 was particularly cytotoxic to human and hamster cells expressing high levels of DNA-PKcs. High DNA-PKcs was associated with replicative stress and activation of the DDR. VE-821 suppressed HRR, determined by RAD51 focus formation, to a greater extent in cells with high DNA-PKcs. Defects in HRR and BER and high DNA-PKcs expression, that are common in cancer, confer sensitivity to ATR inhibitor monotherapy and may be developed as predictive biomarkers for personalised medicine. PMID:26486089
Untch, M.; Augustin, D.; Ettl, J.; Haidinger, R.; Harbeck, N.; Lück, H.-J.; Lüftner, D.; Marmé, F.; Müller, L.; Overkamp, F.; Ruckhäberle, E.; Thill, M.; Thomssen, C.; Wuerstlein, R.; Marschner, N.
The Third International Consensus Conference for Advanced Breast Cancer ABC3 on the diagnosis and treatment of advanced breast cancer was held in Lisbon from 5 to 7 November 2015. This year the focus was the treatment of metastatic breast cancer (stage IV) – including the patient perspectives. Important topics were questions relating to quality of life, the care for long-term survivors as well as the management of disease-related symptoms and treatment-based side effects. The use of standardised tools to assess individual treatment success and the benefits of new substances were important points for discussion. The diagnosis and treatment of inoperable locally advanced breast cancer were discussed two years ago during the ABC2 consensus 1. A working group of German breast cancer experts commented on the results of the ABC panellists, paying particular attention to the German guidelines (AGO, S3, DGHO) on the diagnosis and treatment of breast cancer 2, 3, 4, 5 in Germany. PMID:26941448
Nalluri, Joseph J.; Barh, Debmalya; Azevedo, Vasco; Ghosh, Preetam
Decoding the patterns of miRNA regulation in diseases are important to properly realize its potential in diagnostic, prog- nostic, and therapeutic applications. Only a handful of studies computationally predict possible miRNA-miRNA interactions; hence, such interactions require a thorough investigation to understand their role in disease progression. In this paper, we design a novel computational pipeline to predict the common signature/core sets of miRNA-miRNA interactions for different diseases using network inference algorithms on the miRNA-disease expression profiles; the individual predictions of these algorithms were then merged using a consensus-based approach to predict miRNA-miRNA associations. We next selected the miRNA-miRNA associations across particular diseases to generate the corresponding disease-specific miRNA-interaction networks. Next, graph intersection analysis was performed on these networks for multiple diseases to identify the common signature/core sets of miRNA interactions. We applied this pipeline to identify the common signature of miRNA-miRNA inter- actions for cancers. The identified signatures when validated using a manual literature search from PubMed Central and the PhenomiR database, show strong relevance with the respective cancers, providing an indirect proof of the high accuracy of our methodology. We developed miRsig, an online tool for analysis and visualization of the disease-specific signature/core miRNA-miRNA interactions, available at: http://bnet.egr.vcu.edu/miRsig. PMID:28045122
AORTIC (OAREC), the Pan – African organization aiming to unite African scientists in the fight against cancer on the continent, held its 2015 conference in November, in Marrakesh. It was an opportunity to evaluate the progress made, to strengthen scientific collaborations and to draw the future battle lines against cancer on the continent. PMID:26913074
National Cancer Inst. (NIH), Bethesda, MD.
Twenty presentations from a 1978 conference for parents of children with cancer focus on the teenager and cancer, long term survival of children, the parents and treatment, and practical problems involved. The following papers and authors are represented: "The Role of the Patient Family" (Clark, Fox-Kolenda); "How the Child Perceives Illness and…
Chen, Herbert; Sippel, Rebecca S.; Pacak, Karel
Pheochromocytomas, intra-adrenal paraganglioma, and extra-adrenal sympathetic and parasympathetic paragangliomas are neuroendocrine tumors derived from adrenal chromaffin cells or similar cells in extra-adrenal sympathetic and parasympathetic paraganglia, respectively. Serious morbidity and mortality rates associated with these tumors are related to the potent effects of catecholamines on various organs, especially those of the cardiovascular system. Before any surgical procedure is done, pre-operative blockade is necessary to protect the patient against significant release of catecholamines due to anesthesia and surgical manipulation of the tumor. Treatment options vary with the extent of the disease with laparoscopic surgery being the preferred treatment for removal of primary tumors. Medullary thyroid cancer (MTC) is a malignancy of the thyroid C-cells or parafollicular cells. Thyroid c-cells elaborate a number of peptides and hormones, such as calcitonin, CEA, and chromogranin A. Some or all of these markers are elevated in patients with MTC and can be used to confirm the diagnosis as well as to follow patients longitudinally for recurrence. MTC consists of a spectrum of disease that ranges from extremely indolent tumors that are stable for many years to aggressive types associated with a high mortality rate. Genetic testing for RET mutations has allowed identification of familial cases and prophylactic thyroidectomy for cure. The only curative treatment is complete surgical resection. PMID:20664475
Wilson, B. W.
The EPA Draft Document on EMF and Cancers grew out of an earlier effort by EPA to track biological effects literature relative to radio-frequency (RF) exposure. Scope of the document was broadened to include extremely low frequency electric and magnetic fields prior to an announcement in 1986 that EPA would formally review the whole area of non-ionizing radiation. An extensive survey of the relevant bioeffects and epidemiologic literature was carried out, and writing on the document began in earnest on the document sometime in 1989. In its draft form, the document reviewed the literature on mechanisms of Interaction between electromagnetic fields and biological tissue, EMF epidemiologic studies, supporting evidence for carcinogenicity and research needs. In the early summer of 1990, a draft of the document was reviewed by some 22 individuals within the EPA and other government agencies. It was also sent out for external review to an additional 9 qualified scientists who had worked in the area and were familiar with EMF-related literature in epidemiology, biology, and physics. Many of the comments sent to EPA from this first review, prior to release of the draft for public comment, were strikingly similar to those resulting from the second (public) review process. Thus, it appears that much of the controversy that was later associated with the document could have been avoided had the authors been diligent in following the recommendations of the initial set of reviewers.
Kim, S-M; Kim, H; Yun, M R; Kang, H N; Pyo, K-H; Park, H J; Lee, J M; Choi, H M; Ellinghaus, P; Ocker, M; Paik, S; Kim, H R; Cho, B C
Aberrant fibroblast growth factor receptor (FGFR) activation/expression is a common feature in lung cancer (LC). In this study, we evaluated the antitumor activity of and the mechanisms underlying acquired resistance to two potent selective FGFR inhibitors, AZD4547 and BAY116387, in LC cell lines. The antitumor activity of AZD4547 and BAY1163877 was screened in 24 LC cell lines, including 5 with FGFR1 amplification. Two cell lines containing FGFR1 amplifications, H1581 and DMS114, were sensitive to FGFR inhibitors (IC50<250 nm). Clones of FGFR1-amplified H1581 cells resistant to AZD4547 or BAY116387 (H1581AR and H1581BR cells, respectively) were established. Receptor tyrosine kinase (RTK) array and immunoblotting analyses showed strong overexpression and activation of Met in H1581AR/BR cells, compared with that in the parental cells. Gene set enrichment analysis against the Kyoto Encyclopedia of Genes and Genomes (KEGG) database showed that cytokine-cytokine receptor interaction pathways were significantly enriched in H1581AR/BR cells, with Met contributing significantly to the core enrichment. Genomic DNA quantitative PCR and fluorescent in situ hybridization analyses showed MET amplification in H1581AR, but not in H1581BR, cells. Met amplification drives acquired resistance to AZD4547 in H1581AR cells by activating ErbB3. Combination treatment with FGFR inhibitors and an anaplastic lymphoma kinase (ALK)/Met inhibitor, crizotinib, or Met-specific short interfering RNA (siRNA) synergistically inhibited cell proliferation in both H1581AR and H1581BR cells. Conversely, ectopic expression of Met in H1581 cells conferred resistance to AZD4547 and BAY1163877. Acquired resistance to FGFR inhibitors not only altered cellular morphology, but also promoted migration and invasion of resistant clones, in part by inducing epithelial-to-mesenchymal transition. Taken together, our data suggest that Met activation is sufficient to bypass dependency on FGFR signaling. Concurrent
Schalka, Sérgio; Steiner, Denise; Ravelli, Flávia Naranjo; Steiner, Tatiana; Terena, Aripuanã Cobério; Marçon, Carolina Reato; Ayres, Eloisa Leis; Addor, Flávia Alvim Sant'anna; Miot, Helio Amante; Ponzio, Humberto; Duarte, Ida; Neffá, Jane; Cunha, José Antônio Jabur da; Boza, Juliana Catucci; Samorano, Luciana de Paula; Corrêa, Marcelo de Paula; Maia, Marcus; Nasser, Nilton; Leite, Olga Maria Rodrigues Ribeiro; Lopes, Otávio Sergio; Oliveira, Pedro Dantas; Meyer, Renata Leal Bregunci; Cestari, Tânia; Reis, Vitor Manoel Silva dos; Rego, Vitória Regina Pedreira de Almeida
Brazil is a country of continental dimensions with a large heterogeneity of climates and massive mixing of the population. Almost the entire national territory is located between the Equator and the Tropic of Capricorn, and the Earth axial tilt to the south certainly makes Brazil one of the countries of the world with greater extent of land in proximity to the sun. The Brazilian coastline, where most of its population lives, is more than 8,500 km long. Due to geographic characteristics and cultural trends, Brazilians are among the peoples with the highest annual exposure to the sun. Epidemiological data show a continuing increase in the incidence of non-melanoma and melanoma skin cancers. Photoprotection can be understood as a set of measures aimed at reducing sun exposure and at preventing the development of acute and chronic actinic damage. Due to the peculiarities of Brazilian territory and culture, it would not be advisable to replicate the concepts of photoprotection from other developed countries, places with completely different climates and populations. Thus the Brazilian Society of Dermatology has developed the Brazilian Consensus on Photoprotection, the first official document on photoprotection developed in Brazil for Brazilians, with recommendations on matters involving photoprotection.
Schalka, Sérgio; Steiner, Denise; Ravelli, Flávia Naranjo; Steiner, Tatiana; Terena, Aripuanã Cobério; Marçon, Carolina Reato; Ayres, Eloisa Leis; Addor, Flávia Alvim Sant'anna; Miot, Helio Amante; Ponzio, Humberto; Duarte, Ida; Neffá, Jane; da Cunha, José Antônio Jabur; Boza, Juliana Catucci; Samorano, Luciana de Paula; Corrêa, Marcelo de Paula; Maia, Marcus; Nasser, Nilton; Leite, Olga Maria Rodrigues Ribeiro; Lopes, Otávio Sergio; Oliveira, Pedro Dantas; Meyer, Renata Leal Bregunci; Cestari, Tânia; dos Reis, Vitor Manoel Silva; Rego, Vitória Regina Pedreira de Almeida
Brazil is a country of continental dimensions with a large heterogeneity of climates and massive mixing of the population. Almost the entire national territory is located between the Equator and the Tropic of Capricorn, and the Earth axial tilt to the south certainly makes Brazil one of the countries of the world with greater extent of land in proximity to the sun. The Brazilian coastline, where most of its population lives, is more than 8,500 km long. Due to geographic characteristics and cultural trends, Brazilians are among the peoples with the highest annual exposure to the sun. Epidemiological data show a continuing increase in the incidence of non-melanoma and melanoma skin cancers. Photoprotection can be understood as a set of measures aimed at reducing sun exposure and at preventing the development of acute and chronic actinic damage. Due to the peculiarities of Brazilian territory and culture, it would not be advisable to replicate the concepts of photoprotection from other developed countries, places with completely different climates and populations. Thus the Brazilian Society of Dermatology has developed the Brazilian Consensus on Photoprotection, the first official document on photoprotection developed in Brazil for Brazilians, with recommendations on matters involving photoprotection. PMID:25761256
Huber, Bernd A.; Malot, Christiane; Domaracka, Alicja; Solov'yov, Andrey V.
The 1st Nano-IBCT Conference entitled 'Radiation Damage in Biomolecular Systems: Nanoscale Insights into Ion Beam Cancer Therapy' was held in Caen, France, in October 2011. The Meeting was organised in the framework of the COST Action MP1002 (Nano-IBCT) which was launched in December 2010 (http://fias.uni-frankfurt.de/nano-ibct). This action aims to promote the understanding of mechanisms and processes underlying the radiation damage of biomolecular systems at the molecular and nanoscopic level and to use the findings to improve the strategy of Ion Beam Cancer Therapy. In the hope of achieving this, participants from different disciplines were invited to represent the fields of physics, biology, medicine and chemistry, and also included those from industry and the operators of hadron therapy centres. Ion beam therapy offers the possibility of excellent dose localization for treatment of malignant tumours, minimizing radiation damage in normal healthy tissue, while maximizing cell killing within the tumour. Several ion beam cancer therapy clinical centres are now operating in Europe and elsewhere. However, the full potential of such therapy can only be exploited by better understanding the physical, chemical and biological mechanisms that lead to cell death under ion irradiation. Considering a range of spatio-temporal scales, the proposed action therefore aims to combine the unique experimental and theoretical expertise available within Europe to acquire greater insight at the nanoscopic and molecular level into radiation damage induced by ion impact. Success in this endeavour will be both an important scientific breakthrough and give great impetus to the practical improvement of this innovative therapeutic technique. Ion therapy potentially provides an important advance in cancer therapy and the COST action MP1002 will be very significant in ensuring Europe's leadership in this field, providing the scientific background, required data and mechanistic insight which
Management of sporadic desmoid-type fibromatosis: a European consensus approach based on patients' and professionals' expertise - a sarcoma patients EuroNet and European Organisation for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group initiative.
Kasper, B; Baumgarten, C; Bonvalot, S; Haas, R; Haller, F; Hohenberger, P; Moreau, G; van der Graaf, W T A; Gronchi, A
Desmoid-type fibromatosis (DF) is a rare monoclonal, fibroblastic proliferation characterised by a variable and often unpredictable clinical course. It may affect nearly all parts of the body including extremities, trunk and abdomen. Considering the variable clinical presentations, anatomic locations and biological behaviours, an individualised treatment approach is required. No established or evidence-based approach for the treatment of this neoplasm is available as of today. Therefore, we propose a consensus treatment algorithm based on a round table meeting bringing together sarcoma experts from the European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) with patient advocates from Sarcoma Patients EuroNet (SPAEN). The aim of the meeting was to develop - for the first time ever - a consensus approach based on professionals' AND patients' expertise. As a fundamental prerequisite, all patients should be discussed in a multidisciplinary setting in centres or professional networks with a specific expertise in the disease.
International Expert Consensus on Primary Systemic Therapy in the Management of Early Breast Cancer: Highlights of the Fifth Symposium on Primary Systemic Therapy in the Management of Operable Breast Cancer, Cremona, Italy (2013)
Amoroso, Vito; Generali, Daniele; Buchholz, Thomas; Cristofanilli, Massimo; Pedersini, Rebecca; Curigliano, Giuseppe; Daidone, Maria Grazia; Di Cosimo, Serena; Dowsett, Mitchell; Fox, Stephen; Harris, Adrian L.; Makris, Andreas; Vassalli, Lucia; Ravelli, Andrea; Cappelletti, Maria Rosa; Hatzis, Christos; Hudis, Clifford A.; Pedrazzoli, Paolo; Sapino, Anna; Semiglazov, Vladimir; Von Minckwitz, Gunter; Simoncini, Edda L.; Jacobs, Michael A.; Barry, Peter; Kühn, Thorsten; Darby, Sarah; Hermelink, Kerstin; Symmans, Fraser; Gennari, Alessandra; Schiavon, Gaia; Dogliotti, Luigi; Berruti, Alfredo
Expert consensus-based recommendations regarding key issues in the use of primary (or neoadjuvant) systemic treatment (PST) in patients with early breast cancer are a valuable resource for practising oncologists. PST remains a valuable therapeutic approach for the assessment of biological antitumor activity and clinical efficacy of new treatments in clinical trials. Neoadjuvant trials provide endpoints, such as pathological complete response (pCR) to treatment, that potentially translate into meaningful improvements in overall survival and disease-free survival. Neoadjuvant trials need fewer patients and are less expensive than adjuvant trial, and the endpoint of pCR is achieved in months, rather than years. For these reasons, the neoadjuvant setting is ideal for testing emerging targeted therapies in early breast cancer. Although pCR is an early clinical endpoint, its role as a surrogate for long-term outcomes is the key issue. New and better predictors of treatment efficacy are needed to improve treatment and outcomes. After PST, accurate management of post-treatment residual disease is mandatory. The surgery of the sentinel lymph-node could be an acceptable option to spare the axillary dissection in case of clinical negativity (N0) of the axilla at the diagnosis and/or after PST. No data exists yet to support the modulation of the extent of locoregional radiation therapy on the basis of the response attained after PST although trials are underway. PMID:26063896
Basu, Partha; Chandna, Puneet; Bamezai, R N K; Siddiqi, Maqsood; Saranath, Dhananjaya; Lear, Adrian; Ratnam, Sam
Type-specific detection of human papillomavirus (HPV) is indicated for better risk stratification and clinical management of women testing positive for HPV and for epidemiologic surveillance. MassARRAY spectrometry (MassARRAY; Sequenom) is a novel method for type-specific detection of 15 high-risk oncogenic HPV types: HPV-16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, -68, and -73. PreTect HPV-Proofer (Proofer; Norchip) is a type-specific assay that detects E6/E7 mRNA from five high-risk oncogenic HPV types: HPV-16, -18, -31, -33, and -45. The performance of these tests for type-specific identification of HPV was assessed with cervical specimens from 192 cases of cervical cancer in comparison with consensus MY09/MY11 PCR followed by nucleotide sequencing (consensus PCR). The overall HPV detection rates were 94.8% (95% confidence interval [CI], 91.7, 97.9), 83.3% (95% CI, 78.1, 88.5), and 86.5% (95% CI, 81.7, 91.3) for MassARRAY, Proofer, and consensus PCR, respectively. All tests were negative in six (3.1%) of the 192 cases. Considering only the specimens that contained at least one of the five types targeted by Proofer, the detection rates were 96.6%, 91.4%, and 86.9% for MassARRAY, Proofer, and consensus PCR, respectively. MassARRAY detected multiple infections in 14.1%, Proofer detected multiple infections in 3.6%, and consensus PCR failed to detect any multiple infections. The agreement was highest at 86.0% (kappa = 0.76) between MassARRAY and Proofer and lowest at 81.8% (kappa = 0.69) between Proofer and consensus PCR. In conclusion, MassARRAY is a highly sensitive and accurate method for type-specific detection of oncogenic HPV in cervical cancer, with Proofer showing impressive performance.
Nogales, Vanesa; Reinhold, William C.; Varma, Sudhir; Martinez-Cardus, Anna; Moutinho, Catia; Moran, Sebastian; Heyn, Holger; Sebio, Ana; Barnadas, Agusti; Pommier, Yves; Esteller, Manel
Platinum-derived drugs such as cisplatin and carboplatin are among the most commonly used cancer chemotherapy drugs, but very few specific molecular and cellular markers predicting differential sensitivity to these agents in a given tumor type have been clearly identified. Epigenetic gene silencing is increasingly being recognized as a factor conferring distinct tumoral drug sensitivity, so we have used a comprehensive DNA methylation microarray platform to interrogate the widely characterized NCI60 panel of human cancer cell lines with respect to CpG methylation status and cisplatin/carboplatin sensitivity. Using this approach, we have found promoter CpG island hypermethylation-associated silencing of the putative DNA/RNA helicase Schlafen-11 (SLFN11) to be associated with increased resistance to platinum compounds. We have also experimentally validated these findings in vitro. In this setting, we also identified the BRCA1 interacting DHX9 RNA helicase (also known as RHA) as a protein partner for SLFN11, suggesting a mechanistic pathway for the observed chemoresistance effect. Most importantly, we have been able to extend these findings clinically, following the observation that those patients with ovarian and non-small cell lung cancer carrying SLFN11 hypermethylation had a poor response to both cisplatin and carboplatin treatments. Overall, these results identify SLFN11 epigenetic inactivation as a predictor of resistance to platinum drugs in human cancer. PMID:26625211
Yi, S; La Count, S; Liu, J; Bai, X; Lu, L
Purpose: To study the role of activation-induced cytidine deaminase (AID) in malignant cell resistance to radiation therapy. Methods: We first developed several small devices that could be used to adopt radiation beams from clinical high dose rate brachy therapy (HDR) or linac-based megavoltage machines to perform pre-clinical cell and mouse experiments. Then we used these devices to deliver radiation to AID-positive and AID-silenced cancer cells or tumors formed by these cells in mice. Cells and mice bearing tumors received the same dose under the same experimental conditions. For cells, we observed the apoptosis and the cell survival rate over time. For mice bearing tumors, we measured and recorded the tumor sizes every other day for 4 weeks. Results: For cell experiments, we found that the AID-positive cells underwent much less apoptosis compared with AID-silenced cells upon radiation. And for mouse experiments, we found that AID-positive tumors grew significantly faster than the AID-silenced tumors despite of receiving the same doses of radiation. Conclusion: Our study suggests that AID may confer cancer resistance to radiation therapy, and AID may be a significant biomarker predicting cancer resistance to radiation therapy for certain cancer types.
Beauchamp, Ellen M; Woods, Brittany A; Dulak, Austin M; Tan, Li; Xu, Chunxiao; Gray, Nathanael S; Bass, Adam J; Wong, Kwok-kin; Meyerson, Matthew; Hammerman, Peter S
The treatment of non-small cell lung cancer has evolved dramatically over the past decade with the adoption of widespread use of effective targeted therapies in patients with distinct molecular alterations. In lung squamous cell carcinoma (lung SqCC), recent studies have suggested that DDR2 mutations are a biomarker for therapeutic response to dasatinib and clinical trials are underway testing this hypothesis. Although targeted therapeutics are typically quite effective as initial therapy for patients with lung cancer, nearly all patients develop resistance with long-term exposure to targeted drugs. Here, we use DDR2-dependent lung cancer cell lines to model acquired resistance to dasatinib therapy. We perform targeted exome sequencing to identify two distinct mechanisms of acquired resistance: acquisition of the T654I gatekeeper mutation in DDR2 and loss of NF1. We show that NF1 loss activates a bypass pathway, which confers ERK dependency downstream of RAS activation. These results indicate that acquired resistance to dasatinib can occur via both second-site mutations in DDR2 and by activation of bypass pathways. These data may help to anticipate mechanisms of resistance that may be identified in upcoming clinical trials of anti-DDR2 therapy in lung cancer and suggest strategies to overcome resistance.
Naidu, R; Har, Y C; Taib, N A
The genotype analysis of the Gly and Arg allele at codon 388 of fibroblast growth factor receptor-4 (FGFR4) gene was evaluated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in a hospital-based Malaysian population. Peripheral blood samples were collected from 387 breast cancer patients and 252 normal and healthy women who had no history of any malignancy. The aim of the present study was to evaluate the association between the FGFR4 Gly388Arg polymorphism and breast cancer risk as well as clinicopathological parameters of the patients. The Gly/Gly, Gly/Arg, Arg/Arg, and Arg allele genotypes were detected in 46.3%, 44.4%, 9.3%, and 53.7% of breast cancer cases, respectively. The distribution of genotype (p = 0.204) and allele (p = 0.086) frequencies of FGFR4 polymorphism were not significantly different between the breast cancer cases and normal individuals. Women who were Arg/ Arg homozygotes (OR = 1.714, 95% CI 0.896-3.278), Gly/Arg heterozygotes (OR = 1.205, 95% CI 0.863-1.683), carriers of Arg allele genotype (OR = 1.269, 95% CI 0.921-1.750), or Arg allele (OR = 1.246, 95% CI 0.970-1.602) were not associated with breast cancer risk. The Arg allele genotype was significantly associated with lymph node metastases (p = 0.001) but not with other clinicopathological parameters. Our findings suggest that the polymorphic variant at codon 388 of FGFR4 gene does not confer increased risk to breast cancer development but it may be a potential genetic marker for tumor prognosis.
The design of phase II clinical trials testing cancer therapeutics: consensus recommendations from the clinical trial design task force of the national cancer institute investigational drug steering committee.
Seymour, Lesley; Ivy, S Percy; Sargent, Daniel; Spriggs, David; Baker, Laurence; Rubinstein, Larry; Ratain, Mark J; Le Blanc, Michael; Stewart, David; Crowley, John; Groshen, Susan; Humphrey, Jeffrey S; West, Pamela; Berry, Donald
The optimal design of phase II studies continues to be the subject of vigorous debate, especially studies of newer molecularly targeted agents. The observations that many new therapeutics "fail" in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials, further emphasize the critical importance of robust and efficient phase II design. The Clinical Trial Design Task Force (CTD-TF) of the National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) has published a series of discussion papers on phase II trial design in Clinical Cancer Research. The IDSC has developed formal recommendations about aspects of phase II trial design that are the subject of frequent debate, such as endpoints (response versus progression-free survival), randomization (single-arm designs versus randomization), inclusion of biomarkers, biomarker-based patient enrichment strategies, and statistical design (e.g., two-stage designs versus multiple-group adaptive designs). Although these recommendations in general encourage the use of progression-free survival as the primary endpoint, randomization, inclusion of biomarkers, and incorporation of newer designs, we acknowledge that objective response as an endpoint and single-arm designs remain relevant in certain situations. The design of any clinical trial should always be carefully evaluated and justified based on characteristic specific to the situation.
Society of Surgical Oncology–American Society for Radiation Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Stages I and II Invasive Breast Cancer
Moran, Meena S.; Schnitt, Stuart J.; Giuliano, Armando E.; Harris, Jay R.; Khan, Seema A.; Horton, Janet; Klimberg, Suzanne; Chavez-MacGregor, Mariana; Freedman, Gary; Houssami, Nehmat; Johnson, Peggy L.; Morrow, Monica
Purpose: To convene a multidisciplinary panel of breast experts to examine the relationship between margin width and ipsilateral breast tumor recurrence (IBTR) and develop a guideline for defining adequate margins in the setting of breast conserving surgery and adjuvant radiation therapy. Methods and Materials: A multidisciplinary consensus panel used a meta-analysis of margin width and IBTR from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus. Results: Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a 2-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component. Conclusions: The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.
Fujita-Yamaguchi, Yoko; Lin, Ren-Jang; Jove, Richard
The conference was held to facilitate research collaborations between US and Japan scientists, and to commemorate the rich history of the Beckman Research Institute of City of Hope (COH) research contributed by many Japanese doctors. Most noticeable is Dr. Ryojun Kinoshita, an internationally renowned oncologist who built the first research team at the campus of COH Medical Center in 1952. The conference received enthusiastic support from Junichi Ihara, Consul General of Japan, Los Angeles. During the two day conference, seven scientists from Japan, six scientists from Southern California, and six scientists from COH presented various aspects of cancer and diabetes research which included nuclear receptor regulation, DNA base and chromatin modifications, cancer glycosylation, circadian clock, cell polarity, tumorigenesis, micro and small RNA therapies, genomics, epigenetics, and signaling.
Rajendiran, Smrithi; Kashyap, Meghana V; Vishwanatha, Jamboor K
The Texas Center for Health Disparities, a National Institute on Minority Health and Health Disparities Center of Excellence, presents an annual conference to discuss prevention, awareness education and ongoing research about health disparities both in Texas and among the national population. The 2013 Texas Conference on Health Disparities brought together experts, in research, patient care and community outreach, on the "Intersection of Smoking, Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and Cancer". Smoking, HIV/AIDS and cancer are three individual areas of public health concern, each with its own set of disparities and risk factors based on race, ethnicity, gender, geography and socio-economic status. Disparities among patient populations, in which these issues are found to be comorbid, provide valuable information on goals for patient care. The conference consisted of three sessions addressing "Comorbidities and Treatment", "Public Health Perspectives", and "Best Practices". This article summarizes the basic science, clinical correlates and public health data presented by the speakers.
The Immunochemotherapy: Correcting Immune Escape in Cancer meeting was co-organized by George Prendergast (Lankenau Institute for Medical Research, PA, USA), Guido Kroemer (Gustave Roussy Cancer Institute, Paris, France) and Laurence Zitvogel (Gustave Roussy Cancer Institute) in partnership with Abcam. It brought together investigators with a diverse background in immunology, oncology and cancer biology, and offered a forum for discussion of a new vision that acknowledges the role of the host immune system not only in cancer development and progression, but also as a major determinant of response to treatment. An important implication of this vision is that synergy between conventional cytocidal modalities and immune response modifiers is not only possible, but holds the promise to revolutionize cancer treatment. The emerging evidence that was presented in support of this new concept will be summarized in this article.
Koh, Jaemoon; Chung, Doo Hyun
Pellino-1 is an E3 ubiquitin ligase that mediates immune receptor signaling pathways. The role of Pellino-1 in oncogenesis of lung cancer was investigated in this study. Pellino-1 expression was increased in human lung cancer cell lines compared with non-neoplastic lung cell lines. Pellino-1 overexpression in human lung cancer cells, A549 and H1299 cells, increased the survival and colony forming ability. Pellino-1 overexpression in these cells also conferred resistance to cisplatin- or paclitaxel-induced apoptosis. In contrast, depletion of Pellino-1 decreased the survival of A549 and H1299 cells and sensitized these cells to cisplatin- and paclitaxel-induced apoptosis. Pellino-1 overexpression in A549 and H1299 cells upregulated the expression of inhibitor of apoptosis (IAP) proteins, including cIAP1 and cIAP2, while Pellino-1 depletion downregulated these molecules. Notably, Pellino-1 directly interacted with cIAP2 and stabilized cIAP2 through lysine63-mediated polyubiquitination via its E3 ligase activity. Pellino-1-mediated chemoresistance in lung cancer cells was dependent on the induction of cIAP2. Moreover, a strong positive correlation between Pellino-1 and the cIAP2 expression was observed in human lung adenocarcinoma tissues. Taken together, these results demonstrate that Pellino-1 contributes to lung oncogenesis through the overexpression of cIAP2 and promotion of cell survival and chemoresistance. Pellino-1 might be a novel oncogene and potential therapeutic target in lung cancer. PMID:27248820
Porebski, Benjamin T.; Buckle, Ashley M.
A popular and successful strategy in semi-rational design of protein stability is the use of evolutionary information encapsulated in homologous protein sequences. Consensus design is based on the hypothesis that at a given position, the respective consensus amino acid contributes more than average to the stability of the protein than non-conserved amino acids. Here, we review the consensus design approach, its theoretical underpinnings, successes, limitations and challenges, as well as providing a detailed guide to its application in protein engineering. PMID:27274091
The African Organisation for Research and Training in Cancer and its conferences: a historical perspective and highlights of the Ninth International Conference, Durban, South Africa, 21–24 November 2013
Williams, Christopher KO; Cristina Stefan, D; Rawlinson, Fiona; Simbiri, Kenneth; Mbulaiteye, Sam M
The objectives of the African Organisation for Research and Training in Cancer (AORTIC), both at its inception in the early 1980s, and at its reactivation in 2000 following a decade of inactivity, included bringing the products of decades of advances in cancer research to African populations through international collaboration. The historical perspective provided in this report illustrates progress in achieving these objectives through successive continent-wide activities over a period of 30 years, culminating in the organisation’s most recent conference held in Durban, South Africa, 21–24 November 2013. The constant growth in the number of attendants and increasing diversity of the nations of their origin are consistent with advances, whereby the number of participants and the nations of their origin have grown from 24 in 1983 to almost 1000 in 2013, and from 14 to 70, respectively. While earlier AORTIC conferences used to assume the atmosphere of ‘jamborees’, more recent ones have morphed to problem-solving events, with the concerted collaboration of international organisations, including the World Health Organisation (WHO), International Union Against Cancer (UICC), the Africa Union (AU), the US National Cancer Institute (NCI), the International Psycho-Oncology Society (IPOS), and others. The topics of discussion at the Ninth AORTIC International Conference on Cancer in Africa in Durban were those of paramount importance for low- and middle-income countries: childhood cancers, cancers of the cervix, breast, and prostate, as well as cancer care challenges resulting from ignorance, neglect, and economic deprivation. The role of environmental factors that underlie Burkitt’s lymphoma was the subject of the Epidemiology of Burkitt Lymphoma in East-African Children and Minors Workshop, highlighting the NCI research programme in East Africa, while the Workshop on Cost Effectiveness of Treatment of Cancer in Africa surmised that treating childhood cancers is
Sorokin, Alexey V; Nair, Binoj C; Wei, Yongkun; Aziz, Kathryn E; Evdokimova, Valentina; Hung, Mien-Chie; Chen, Junjie
The protein tyrosine phosphatase receptor PTPRN2 is expressed predominantly in endocrine and neuronal cells, where it functions in exocytosis. We found that its immature isoform proPTPRN2 is overexpressed in various cancers, including breast cancer. High proPTPRN2 expression was associated strongly with lymph node-positive breast cancer and poor clinical outcome. Loss of proPTPRN2 in breast cancer cells promoted apoptosis and blocked tumor formation in mice, whereas enforced expression of proPTPRN2 in nontransformed human mammary epithelial cells exerted a converse effect. Mechanistic investigations suggested that ProPTPRN2 elicited these effects through direct interaction with TRAF2, a hub scaffold protein for multiple kinase cascades, including ones that activate NF-κB. Overall, our results suggest PTPRN2 as a novel candidate biomarker and therapeutic target in breast cancer.
Huang, Shih-Wei; Chen, Shih-Hua; Chen, Weichung; Wu, I.-Chen; Wu, Ming Tsang; Kuo, Chie-Tong; Wang, Hsiang-Chen
This study presents a method to identify early esophageal cancer within endoscope using hyperspectral imaging technology. The research samples are three kinds of endoscopic images including white light endoscopic, chromoendoscopic, and narrow-band endoscopic images with different stages of pathological changes (normal, dysplasia, dysplasia - esophageal cancer, and esophageal cancer). Research is divided into two parts: first, we analysis the reflectance spectra of endoscopic images with different stages to know the spectral responses by pathological changes. Second, we identified early cancerous lesion of esophagus by principal component analysis (PCA) of the reflectance spectra of endoscopic images. The results of this study show that the identification of early cancerous lesion is possible achieve from three kinds of images. In which the spectral characteristics of NBI endoscopy images of a gray area than those without the existence of the problem the first two, and the trend is very clear. Therefore, if simply to reflect differences in the degree of spectral identification, chromoendoscopic images are suitable samples. The best identification of early esophageal cancer is using the NBI endoscopic images. Based on the results, the use of hyperspectral imaging technology in the early endoscopic esophageal cancer lesion image recognition helps clinicians quickly diagnose. We hope for the future to have a relatively large amount of endoscopic image by establishing a hyperspectral imaging database system developed in this study, so the clinician can take this repository more efficiently preliminary diagnosis.
Kim, Minji; Quan, Yuhua; Choi, Byeong Hyun; Choi, Yeonho; Kim, Hyun Koo; Kim, Beop-Min
Pulmonary nodule could be identified by intraoperative fluorescence imaging system from systemic injection of indocyanine green (ICG) which achieves enhanced permeability and retention (EPR) effects. This study was performed to evaluate optimal injection time of ICG for detecting cancer during surgery in rabbit lung cancer model. VX2 carcinoma cell was injected in rabbit lung under fluoroscopic computed tomography-guidance. Solitary lung cancer was confirmed on positron emitting tomography with CT (PET/CT) 2 weeks after inoculation. ICG was administered intravenously and fluorescent intensity of lung tumor was measured using the custom-built intraoperative color and fluorescence merged imaging system (ICFIS) for 15 hours. Solitary lung cancer was resected through thoracoscopic version of ICFIS. ICG was observed in all animals. Because Lung has fast blood pulmonary circulation, Fluorescent signal showed maximum intensity earlier than previous studies in other organs. Fluorescent intensity showed maximum intensity within 6-9 hours in rabbit lung cancer. Overall, Fluorescent intensity decreased with increasing time, however, all tumors were detectable using fluorescent images until 12 hours. In conclusion, while there had been studies in other organs showed that optimal injection time was at least 24 hours before operation, this study showed shorter optimal injection time at lung cancer. Since fluorescent signal showed the maximum intensity within 6-9 hours, cancer resection could be performed during this time. This data informed us that optimal injection time of ICG should be evaluated in each different solid organ tumor for fluorescent image guided surgery.
Current Knowledge and Priorities for Future Research in Late Effects after Hematopoietic Cell Transplantation for Inherited Bone Marrow Failure Syndromes: Consensus Statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric Hematopoietic Cell Transplantation.
Dietz, Andrew C; Mehta, Parinda A; Vlachos, Adrianna; Savage, Sharon A; Bresters, Dorine; Tolar, Jakub; Boulad, Farid; Dalle, Jean Hugues; Bonfim, Carmem; de la Fuente, Josu; Duncan, Christine N; Baker, K Scott; Pulsipher, Michael A; Lipton, Jeffrey M; Wagner, John E; Alter, Blanche P
Fanconi anemia (FA), dyskeratosis congenita (DC), and Diamond Blackfan anemia (DBA) are 3 of the most common inherited bone marrow failure syndromes (IBMFS), in which the hematologic manifestations can be cured with hematopoietic cell transplantation (HCT). Later in life, these patients face a variety of medical conditions, which may be a manifestation of underlying disease or due to pre-HCT therapy, the HCT, or a combination of all these elements. Very limited long-term follow-up data exist in these populations, with FA the only IBMFS that has specific published data. During the international consensus conference sponsored by the Pediatric Blood and Marrow Transplant Consortium entitled "Late Effects Screening and Recommendations following Allogeneic Hematopoietic Cell Transplant (HCT) for Immune Deficiency and Nonmalignant Hematologic Disease" held in Minneapolis, Minnesota in May of 2016, a half-day session was focused specifically on the unmet needs for these patients with IBMFS. A multidisciplinary group of experts discussed what is currently known, outlined an agenda for future research, and laid out long-term follow-up guidelines based on a combination of evidence in the literature as well as expert opinion. This article addresses the state of science in that area as well as consensus regarding the agenda for future research, with specific screening guidelines to follow in the next article from this group.
Kim, Youngmi; Kim, Hyuna; Park, Deokbum; Jeoung, Dooil
We previously reported the role of histone deacetylase 3 (HDAC3) in response to anti-cancer drugs. The decreased expression of HDAC3 in anti-cancer drug-resistant cancer cell line is responsible for the resistance to anti-cancer drugs. In this study, we investigated molecular mechanisms associated with regulation of HDAC3 expression. MG132, an inhibitor of proteasomal degradation, induced the expression of HDAC3 in various anti-cancer drug-resistant cancer cell lines. Ubiquitination of HDAC3 was observed in various anti-cancer drug-resistant cancer cell lines. HDAC3 showed an interaction with SIAH2, an ubiquitin E3 ligase, that has increased expression in various anti-cancer drug-resistant cancer cell lines. miRNA array analysis showed the decreased expression of miR-335 in these cells. Targetscan analysis predicted the binding of miR-335 to the 3′-UTR of SIAH2. miR-335-mediated increased sensitivity to anti-cancer drugs was associated with its effect on HDAC3 and SIAH2 expression. miR-335 exerted apoptotic effects and inhibited ubiquitination of HDAC3 in anti-cancer drug-resistant cancer cell lines. miR-335 negatively regulated the invasion, migration, and growth rate of cancer cells. The mouse xenograft model showed that miR-335 negatively regulated the tumorigenic potential of cancer cells. The down-regulation of SIAH2 conferred sensitivity to anti-cancer drugs. The results of the study indicated that the miR-335/SIAH2/HDAC3 axis regulates the response to anti-cancer drugs. PMID:25997740
Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC).
Zwald, F; Leitenberger, J; Zeitouni, N; Soon, S; Brewer, J; Arron, S; Bordeaux, J; Chung, C; Abdelmalek, M; Billingsley, E; Vidimos, A; Stasko, T
Advancements in solid organ transplantation successfully extend the lives of thousands of patients annually. The tenet of organ stewardship aims to prevent the futile expenditure of scarce donor organs in patient populations with high mortality risk, to the detriment of potential recipients with greater predicted life expectancy. The development of skin cancer posttransplantation portends tremendous morbidity, adversely affecting quality of life for many transplant recipients. This special article, provided by of members of the International Transplant Skin Cancer Collaborative (ITSCC), will provide the transplant professional with a consensus opinion and recommendations as to an appropriate wait period pretransplantation for transplant candidates with a history of either cutaneous squamous cell carcinoma, malignant melanoma, or Merkel cell carcinoma.
[Recommendations for radiological diagnosis and assessment of treatment response in lung cancer: a national consensus statement by the Spanish Society of Medical Radiology and the Spanish Society of Medical Oncology].
Ferreirós, J; Cabeza, B; Gayete, Á; Sánchez, M; Torres, M I; Cobo, M; Isla, D; Puente, J; Reguart, N; de Castro, J
The last decade has seen substantial progress in the diagnostic and therapeutic approach to lung cancer, thus meaning that its prognosis has improved. The Spanish Society of Medical Radiology (SERAM) and the Spanish Society of Medical Oncology (SEOM) have therefore produced a national consensus statement in order to make recommendations for radiological diagnosis and assessment of treatment response in patients with lung cancer. This expert group recommends multi-detector computed tomography (MDCT) as the technique of choice for investigating this disease. The radiology report should include a full assessment by the TNM staging system. Lastly, when the patient is on immunotherapy, response evaluation should employ not only Response Evaluation Criteria in Solid Tumours (RECIST 1.1) but also Immune-Related Response Criteria (irRC).
Pan, Amy; Zhang, Hongyong; Li, Yuanpei; Lin, Tzu-yin; Wang, Fuli; Lee, Joyce; Cheng, Mingshan; Dall'Era, Marc; Li, Tianhong; deVere White, Ralph; Pan, Chong-Xian; Lam, Kit S.
Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus. To synthesize disulfide-crosslinked PLZ4 nanomicelles (DC-PNM), cysteine was introduced between the cholic acid and PEG. DC-PNM-PTX was synthesized through the evaporation method by loading PTX in the core. The loading capacity of PTX in DC-PNM was 25% (W/W). The loading efficiency was over 99%. DC-PNM-PTX was spherical with the median size of 25 nm. The stability of DC-PNM-PTX was determined in a solution containing sodium docecyl sulfate (SDS). It was stable in a SDS solution, but dissolved within 5 min after the addition of glutathione at the physiological intracellular concentration of 10 mM. In vivo targeting and anti-tumor activity were determined in immunodeficient mice carrying patient-derived bladder cancer xenografts (PDXs). After intravenous administration, DC-PNM specifically targeted the bladder cancer PDXs, but very little to the lung cancer xenografts in the same mice (p < 0.001). DC-PNM loaded with PTX overcame cisplatin resistance, and improved the median survival from 55 d with free PTX to 69.5 d (p = 0.03) of mice carrying PDXs. In conclusion, DC-PNM remained stable in the SDS solution, specifically targeted the bladder cancer xenografts in vivo, and improved the anti-cancer efficacy of PTX.
Taylor, Michael D; Northcott, Paul A; Korshunov, Andrey; Remke, Marc; Cho, Yoon-Jae; Clifford, Steven C; Eberhart, Charles G; Parsons, D Williams; Rutkowski, Stefan; Gajjar, Amar; Ellison, David W; Lichter, Peter; Gilbertson, Richard J; Pomeroy, Scott L; Kool, Marcel; Pfister, Stefan M
Medulloblastoma, a small blue cell malignancy of the cerebellum, is a major cause of morbidity and mortality in pediatric oncology. Current mechanisms for clinical prognostication and stratification include clinical factors (age, presence of metastases, and extent of resection) as well as histological subgrouping (classic, desmoplastic, and large cell/anaplastic histology). Transcriptional profiling studies of medulloblastoma cohorts from several research groups around the globe have suggested the existence of multiple distinct molecular subgroups that differ in their demographics, transcriptomes, somatic genetic events, and clinical outcomes. Variations in the number, composition, and nature of the subgroups between studies brought about a consensus conference in Boston in the fall of 2010. Discussants at the conference came to a consensus that the evidence supported the existence of four main subgroups of medulloblastoma (Wnt, Shh, Group 3, and Group 4). Participants outlined the demographic, transcriptional, genetic, and clinical differences between the four subgroups. While it is anticipated that the molecular classification of medulloblastoma will continue to evolve and diversify in the future as larger cohorts are studied at greater depth, herein we outline the current consensus nomenclature, and the differences between the medulloblastoma subgroups.
Wang, Yongqiang; Huang, Yi; Liu, Huan; Li, Feida; He, Luyun; Sun, Da; Yu, Yuan; Li, Qiaoling; Huang, Peide; Zhang, Meng; Zhao, Xin; Bi, Tengteng; Zhuang, Xuehan; Zhang, Liyan; Lu, Jingxiao; Sun, Xiaojuan; Zhou, Fangjian; Liu, Chunxiao; Yang, Guosheng; Hou, Yong; Fan, Zusen; Cai, Zhiming
Bladder cancer (BC) is distinguished by high rate of recurrence after surgery, but the underlying mechanisms remain poorly understood. Here we performed the whole-exome sequencing of 37 BC individuals including 20 primary and 17 recurrent samples in which the primary and recurrent samples were not from the same patient. We uncovered that MLL, EP400, PRDM2, ANK3 and CHD5 exclusively altered in recurrent BCs. Specifically, the recurrent BCs and bladder cancer cells with MLL mutation displayed increased histone H3 tri-methyl K4 (H3K4me3) modification in tissue and cell levels and showed enhanced expression of GATA4 and ETS1 downstream. What's more, MLL mutated bladder cancer cells obtained with CRISPR/Cas9 showed increased ability of drug-resistance to epirubicin (a chemotherapy drug for bladder cancer) than wild type cells. Additionally, the BC patients with high expression of GATA4 and ETS1 significantly displayed shorter lifespan than patients with low expression. Our study provided an overview of the genetic basis of recrudescent bladder cancer and discovered that genetic alterations of MLL were involved in BC relapse. The increased modification of H3K4me3 and expression of GATA4 and ETS1 would be the promising targets for the diagnosis and therapy of relapsed bladder cancer. PMID:26625313
Wu, Song; Yang, Zhao; Ye, Rui; An, Dan; Li, Chong; Wang, Yitian; Wang, Yongqiang; Huang, Yi; Liu, Huan; Li, Feida; He, Luyun; Sun, Da; Yu, Yuan; Li, Qiaoling; Huang, Peide; Zhang, Meng; Zhao, Xin; Bi, Tengteng; Zhuang, Xuehan; Zhang, Liyan; Lu, Jingxiao; Sun, Xiaojuan; Zhou, Fangjian; Liu, Chunxiao; Yang, Guosheng; Hou, Yong; Fan, Zusen; Cai, Zhiming
Bladder cancer (BC) is distinguished by high rate of recurrence after surgery, but the underlying mechanisms remain poorly understood. Here we performed the whole-exome sequencing of 37 BC individuals including 20 primary and 17 recurrent samples in which the primary and recurrent samples were not from the same patient. We uncovered that MLL, EP400, PRDM2, ANK3 and CHD5 exclusively altered in recurrent BCs. Specifically, the recurrent BCs and bladder cancer cells with MLL mutation displayed increased histone H3 tri-methyl K4 (H3K4me3) modification in tissue and cell levels and showed enhanced expression of GATA4 and ETS1 downstream. What's more, MLL mutated bladder cancer cells obtained with CRISPR/Cas9 showed increased ability of drug-resistance to epirubicin (a chemotherapy drug for bladder cancer) than wild type cells. Additionally, the BC patients with high expression of GATA4 and ETS1 significantly displayed shorter lifespan than patients with low expression. Our study provided an overview of the genetic basis of recrudescent bladder cancer and discovered that genetic alterations of MLL were involved in BC relapse. The increased modification of H3K4me3 and expression of GATA4 and ETS1 would be the promising targets for the diagnosis and therapy of relapsed bladder cancer.
Liu, Joyce; Huang, Huang-Chiao; Rizvi, Imran; Hasan, Tayyaba
Given the consistently poor prognoses for some of the most difficult-to-treat cancers, rapidly translatable treatment regimens that offer improvements in outcomes are much needed. The repurposing of FDA approved non-cancer drugs presents an opportunity to design clinically feasible, novel combinations of therapies with a mechanistic rationale, to overcome resistance and survival pathways that render many current treatments ineffective. Tetracyclines are a class of antibiotics that demonstrate potential for such repurposing, as they have also been shown by others to affect a wide range of targets in cancer. Notably, the unique structure of tetracyclines allows them to act through both light activated and non-light mediated mechanisms. While light activation of tetracyclines can result in singlet oxygen production, their non-light mediated targets include inhibition of DNA repair enzymes and modulation of hypoxia-inducible markers, among others. With these mechanisms in mind, we seek to elucidate the benefit of including tetracyclines as part of an already promising, mechanistically cooperative photochemotherapy combination for ovarian cancer. In ovarian cancer, the dismal rates of recurrence and survival associated with the aggressive disease further emphasize the need to mechanistically reinforce treatments regimens. Thus, the results will highlight insights into the cooperative effect of repurposed tetracyclines on treatment response and molecular markers, both in vitro and in a challenging mouse model of disseminated ovarian cancer.
Hill, Richard; Madureira, Patricia A.; Ferreira, Bibiana; Baptista, Inês; Machado, Susana; Colaço, Laura; dos Santos, Marta; Liu, Ningshu; Dopazo, Ana; Ugurel, Selma; Adrienn, Angyal; Kiss-Toth, Endre; Isbilen, Murat; Gure, Ali O.; Link, Wolfgang
Intrinsic and acquired resistance to chemotherapy is the fundamental reason for treatment failure for many cancer patients. The identification of molecular mechanisms involved in drug resistance or sensitization is imperative. Here we report that tribbles homologue 2 (TRIB2) ablates forkhead box O activation and disrupts the p53/MDM2 regulatory axis, conferring resistance to various chemotherapeutics. TRIB2 suppression is exerted via direct interaction with AKT a key signalling protein in cell proliferation, survival and metabolism pathways. Ectopic or intrinsic high expression of TRIB2 induces drug resistance by promoting phospho-AKT (at Ser473) via its COP1 domain. TRIB2 expression is significantly increased in tumour tissues from patients correlating with an increased phosphorylation of AKT, FOXO3a, MDM2 and an impaired therapeutic response. This culminates in an extremely poor clinical outcome. Our study reveals a novel regulatory mechanism underlying drug resistance and suggests that TRIB2 functions as a regulatory component of the PI3K network, activating AKT in cancer cells. PMID:28276427
Huang, C-Y; Kuo, W-T; Huang, Y-C; Lee, T-C; Yu, L C H
Cancer cells may survive under oxygen and nutrient deprivation by metabolic reprogramming for high levels of anaerobic glycolysis, which contributes to tumor growth and drug resistance. Abnormally expressed glucose transporters (GLUTs) are colocalized with hypoxia (Hx) inducible factor (HIF)1α in peri-necrotic regions in human colorectal carcinoma. However, the underlying mechanisms of anti-necrotic resistance conferred by glucose metabolism in hypoxic cancer cells remain poorly understood. Our aim was to investigate signaling pathways of Hx-induced necroptosis and explore the role of glucose pyruvate metabolite in mechanisms of death resistance. Human colorectal carcinoma cells were Hx exposed with or without glucose, and cell necroptosis was examined by receptor-interacting protein (RIP)1/3 kinase immunoprecipitation and 32P kinase assays. Our results showed increased RIP1/3 complex formation and phosphorylation in hypoxic, but not normoxic cells in glucose-free media. Blocking RIP1 signaling, by necrostatin-1 or gene silencing, decreased lactodehydrogenase (LDH) leakage and plasma membrane disintegration. Generation of mitochondrial superoxide was noted after hypoxic challenge; its reduction by antioxidants inhibited RIP signaling and cell necrosis. Supplementation of glucose diminished the RIP-dependent LDH leakage and morphological damage in hypoxic cells, whereas non-metabolizable sugar analogs did not. Hypoxic cells given glucose showed nuclear translocation of HIF1α associated with upregulation of GLUT-1 and GLUT-4 expression, as well as increase of intracellular ATP, pyruvate and lactate levels. The glucose-mediated death resistance was ablated by iodoacetate (an inhibitor to glyceraldehyde-3-phosphate dehydrogenase), but not by UK5099 (an inhibitor to mitochondrial pyruvate carrier), suggesting that glycolytic pathway was involved in anti-necrotic mechanism. Lastly, replacing glucose with cell-permeable pyruvate derivative also led to decrease of Hx
Mahachai, Varocha; Vilaichone, Ratha-Korn; Pittayanon, Rapat; Rojborwonwitaya, Jarin; Leelakusolvong, Somchai; Kositchaiwat, Chomsri; Mairiang, Pisaln; Praisontarangkul, Ong-Ard; Ovartlarnporn, Buncha; Sottisuporn, Jaksin; Pisespongsa, Pises; Maneerattanaporn, Monthira; Sony, Ravin; Sirinthornpunya, Siam; Chaiyamahapurk, Orawan; Wiwattanachang, Olarn; Sansak, Inchaya; Harnsomboon, Piyathida; Chitapanarux, Taned; Chuenrattanakul, Surapon
Management of Helicobacter pylori infection is an important aspect of many upper gastrointestinal tract diseases, such as chronic gastritis, peptic ulcer disease, gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. The Thailand Consensus on H. pylori treatment 2015 consisted of 22 national experts who took active roles, discussed all important clinical information and investigated clinical aspects in four workshops, focuising on: (1) Diagnosis (2) Treatment (3) Follow-up after eradication and (4) H. pylori infection and special conditions. Experts were invited to participate on the basis of their expertise and contribution to H. pylori works and/or consensus methodology. The results of each workshop were taken to a final consensus vote by all experts. Recommendations were developed from the best evidence and availability to guide clinicians in management of this specific infection associated with variety of clinical outcomes.
Treado, Patrick J.; Stewart, Shona D.; Smith, Aaron; Kirschner, Heather; Post, Christopher; Overholt, Bergein F.
Colorectal cancer (CRC) is the third most common cancer in men and women in the United States. Raman Molecular Imaging (RMI) is an effective technique to evaluate human tissue, cells and bodily fluids, including blood serum for disease diagnosis. ChemImage Corporation, in collaboration with clinicians, has been engaged in development of an in vitro diagnostic Raman assay focused on CRC detection. The Raman Assay for Colorectal Cancer (RACC) exploits the high specificity of Raman imaging to distinguish diseased from normal dried blood serum droplets without additional reagents. Pilot Study results from testing of hundreds of biobank patient samples have demonstrated that RACC detects CRC with high sensitivity and specificity. However, expanded clinical trials, which are ongoing, are revealing a host of important preanalytical considerations associated with sample collection, sample storage and stability, sample shipping, sample preparation and sample interferents, which impact detection performance. Results from recent clinical studies will be presented.
Kaowinn, Sirichat; Cho, Il-Rae; Moon, Jeong; Jun, Seung Won; Kim, Chang Seok; Kang, Ho Young; Kim, Manbok; Koh, Sang Seok; Chung, Young-Hwa
Pancreatic adenocarcinoma upregulated factor (PAUF), a novel oncogene, plays a crucial role in the development of pancreatic cancer, including its metastasis and proliferation. Therefore, PAUF-expressing pancreatic cancer cells could be important targets for oncolytic virus-mediated treatment. Panc-1 cells expressing PAUF (Panc-PAUF) showed relative resistance to parvovirus H-1 infection compared with Panc-1 cells expressing an empty vector (Panc-Vec). Of interest, expression of type I IFN-α receptor (IFNAR) was higher in Panc-PAUF cells than in Panc-Vec cells. Increased expression of IFNAR in turn increased the activation of Stat1 and Tyk2 in Panc-PAUF cells compared with that in Panc-Vec cells. Suppression of Tyk2 and Stat1, which are important downstream molecules for IFN-α signaling, sensitized pancreatic cancer cells to parvovirus H-1-mediated apoptosis. Further, constitutive suppression of PAUF sensitized Bxpc3 pancreatic cancer cells to parvovirus H-1 infection. Taken together, these results suggested that PAUF conferred resistance to pancreatic cancer cells against oncolytic parvovirus H-1 infection through IFNAR-mediated signaling. - Highlights: • PAUF confers resistance against oncolytic parvovirus H-1 infection. • PAUF enhances the expression of IFNAR in Panc-1 cells. • Increased activation of Tyk2 or Stat1 by PAUF provides resistance to parvovirus H-1-mediated apoptosis. • Constitutive inhibition of PAUF enhances parvovirus H-1-mediated oncolysis of Bxpc3 pancreatic cancer cells.
A paradox in cancer research is that the majority of patients enrolled in clinical trials are relatively young and fit while typical patients in daily practice are elderly and have comorbidities and impaired organ function. Given these differences, many major studies provide an imperfect guide to optimizing the treatment of the majority of patients. Since cancer incidence is highly correlated with age, and since the world's population is rapidly ageing, this problem can only increase. For this reason, oncologists and geriatricians need to collaborate in developing tools to systematically assess the health status of elderly patients and their fitness to receive cancer therapies of various intensity. Tailoring anti-cancer treatments and supportive care to individual needs should be seen as part of the move towards personalized medicine. Achieving this goal is as much of a challenge to developing and middle-income countries as it is to western nations. The 2015 annual conference of the International Society of Geriatric Oncology (SIOG) held in Prague, Czech Republic, November 2015 and had a global focus on advancing the science of geriatric oncology and supportive care. Central to this approach is the systematic assessment of life expectancy, independent functioning, and the physical and psychological health of older cancer patients. The assumption behind comprehensive geriatric assessment is that elderly cancer patients have complex needs. The implication is that effective intervention will require a multidisciplinary team. Examples of effective geriatric assessment, multidisciplinary working and supportive care were presented at the SIOG conference.
Brugmans, M.J.P.; Leenhouts, H.P.
The Proceedings of the 20th LH Gray Conference on Radiation Cancer Analysis and Low Dose Risk Estimation: New Developments and Perspectives (17-21 February 2002, Ede, the Netherlands) comprises 32 peer-reviewed papers on invited and proffered contributions to the conference with a preface by the guest editors. The on-going discussion of low dose radiation risk; the issue of the linear, non-threshold extrapolation; and the anticipated new recommendations, e.g. from BEIR and ICRP, provided the back-drop for the conference. The meeting dealt with topics such as basic mechanisms and bystander effects, cancer modeling, cancer genetics, radon exposure and lung cancer risk, cancer after medical exposure, cancer risk estimation, dose-effect relationships, and application to radiation protection.
Schiffman, Mark; Katki, Hormuzd A.; Castle, Philip E.; Fetterman, Barbara; Wentzensen, Nicolas; Poitras, Nancy E.; Lorey, Thomas; Cheung, Li C.; Kinney, Walter K.
Primary human papillomavirus (HPV) testing (without concurrent Pap tests) every 3 years is under consideration in the United States as an alternative to the two recommended cervical cancer screening strategies: primary Pap testing every 3 years, or concurrent Pap and HPV testing (“cotesting”) every 5 years. Using logistic regression and Weibull survival models, we estimated and compared risks of cancer and cervical intraepithelial neoplasia grade 3 or worse (CIN3+) for the three strategies among 1011092 women aged 30 to 64 years testing HPV-negative and/or Pap-negative in routine screening at Kaiser Permanente Northern California since 2003. All statistical tests were two sided. Three-year risks following an HPV-negative result were lower than 3-year risks following a Pap-negative result (CIN3+ = 0.069% vs 0.19%, P < .0001; Cancer = 0.011% vs 0.020%, P < .0001) and 5-year risks following an HPV-negative/Pap-negative cotest (CIN3+ = 0.069% vs 0.11%, P < .0001; Cancer = 0.011% vs 0.014%, P = .21). These findings suggest that primary HPV testing merits consideration as another alternative for cervical screening. PMID:25038467
Kang, Benedict J.; Jang, Gun Hyuk; Park, Sungwook; Lee, Kwan Hyi
Prostate cancer causes one of the leading cancer-related deaths among the Caucasian adult males in Europe and the United State of America. However, it has a high recovery rate indicating when a proper treatment is delivered to a patient. There are cases of over- or under-treatments which exacerbate the disease states indicating the importance of proper therapeutic approach depending on stage of the disease. Recognition of the unmet needs has raised a need for stratification of the disease. There have been attempts to stratify based on biomarker expression patterns in the course of disease progression. To closely observe the biomarker expression patterns, we propose the use of quantitative imaging method by using fabricated quantum dot-based nanoprobe to quantify biomarker expression on the surface of prostate cancer cells. To characterize the cell line and analyze the biomarker levels, cluster of differentiation 44 (CD 44), prostate specific membrane antigen (PSMA), and epithelial cell adhesion molecule (EpCAM) are used. Each selected biomarker per cell line has been quantified from which we established a signature of biomarkers of a prostate cancer cell line.
Hsu, Chao-Hsin; Chu, Cheng-Hsun; Chen, Weichung; Wu, I.-Chen; Wu, Ming Tsang; Kuo, Chie-Tong; Tsiang, Raymond Chien-Chao; Wang, Hsiang-Chen
We have demonstrated a Cu2O/ZnO nanorods (NRs) array p-n heterostructures photoelectrochemical biosensor. The electrodeposition of Cu2O at pH 12 acquired the preferably (111) lattice planes, resulting in the largest interfacial electric field between Cu2O and ZnO, which finally led to the highest separation efficiency of photogenerated charge carriers. High verticality ZnO nanorods by seed layer and thermal annealing assist the hydrothermal growth. The optimized Cu2O/ZnO NRs array p-n heterostructures exhibited enhanced PEC performance, such as elevated photocurrent and photoconversion efficiency, as well as excellent sensing performance for the sensitive detection of four strains of different races and different degree of cancer cell which made the device self-powered. We got spectral response characteristics and operating wavelength range of biosensor, and to verify the biological characteristics of cancer cells wafer react with different stages of cancer characterized by a cancer measured reaction experiment.
Toi, Masakazu; Winer, Eric P; Benson, John R; Inamoto, Takashi; Forbes, John F; von Minckwitz, Gunter; Robertson, John F R; Grobmyer, Stephen R; Jatoi, Ismail; Sasano, Hironobu; Kunkler, Ian; Ho, Alice Y; Yamauchi, Chikako; Chow, Louis W C; Huang, Chiun-Sheng; Han, Wonshik; Noguchi, Shinzaburo; Pegram, Mark D; Yamauchi, Hideko; Lee, Eun-Sook; Larionov, Alexey A; Bevilacqua, Jose L B; Yoshimura, Michio; Sugie, Tomoharu; Yamauchi, Akira; Krop, Ian E; Noh, Dong Young; Klimberg, V Suzanne
Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the second of a two part conference scene, consensus recommendations for radiation treatment, primary systemic therapies and management of genetic predisposition are reported and focus on the following topics: influence of both clinical response to PST and stage at presentation on recommendations for postmastectomy radiotherapy; use of regional nodal irradiation in selected node-positive patients and those with adverse pathological factors; extent of surgical resection following downstaging of tumors with PST; use of preoperative hormonal therapy in premenopausal women with larger, node-negative luminal A-like tumors and managing increasing demands for contralateral prophylactic mastectomy in patients with a unilateral sporadic breast cancer.
In an epistemology of contextualism, how robust does consensus need to be for critique to be practically effective? In 'Relativism and the Critical Potential of Philosophy of Education,' Frieda Heyting proposes a form of contextualism, but her argument raises a number of problems. The kinds of criteria that her version of contextualism will…
Vidal, Samuel J.; Rodriguez-Bravo, Veronica; Quinn, S. Aidan; Rodriguez-Barrueco, Ruth; Lujambio, Amaia; Williams, Estrelania; Sun, Xiaochen; de la Iglesia-Vicente, Janis; Lee, Albert; Readhead, Ben; Chen, Xintong; Galsky, Matthew; Esteve, Berta; Petrylak, Daniel P.; Dudley, Joel T.; Rabadan, Raul; Silva, Jose M.; Hoshida, Yujin; Lowe, Scott W.; Cordon-Cardo, Carlos; Domingo-Domenech, Josep
SUMMARY Elucidating the determinants of aggressiveness in lethal prostate cancer may stimulate therapeutic strategies that improve clinical outcomes. We used experimental models and clinical databases to identify GATA2 as a regulator of chemotherapy resistance and tumorigenicity in this context. Mechanistically, direct upregulation of the growth hormone IGF2 emerged as a mediator of the aggressive properties regulated by GATA2. IGF2 in turn activated IGF1R and INSR as well as a downstream polykinase program. The characterization of this axis prompted a combination strategy whereby dual IGF1R/INSR inhibition restored the efficacy of chemotherapy and improved survival in preclinical models. These studies reveal a GATA2-IGF2 aggressiveness axis in lethal prostate cancer and identify a therapeutic opportunity in this challenging disease. PMID:25670080
Anbil, Sriram R.; Rizvi, Imran; Khan, Amjad P.; Celli, Jonathan P.; Maytin, Edward V.; Hasan, Tayyaba
Biomodulation of cancer cell metabolism represents a promising approach to overcome tumor heterogeneity and poor selectivity, which contribute significantly to treatment resistance. To date, several studies have demonstrated that modulation of cell metabolism including the heme synthesis pathway serves as an elegant approach to improve the efficacy of aminolevulinic acid (ALA) based photodynamic therapy (PDT). However, the ability of biomodulation-enhanced PDT to improve outcomes in low resource settings and to address challenges in treating lethal tumors with exogenous photosensitizers remains underexplored. The ability of vitamin D or methotrexate to enhance PDT efficacy in a carcinogen-induced hamster cheek pouch model of oral squamous cell carcinoma and in 3D cell-based models for pancreatic ductal adenocarcinoma is evaluated. Challenges associated with adapting PDT regimens to low resource settings, understanding the effects of biomodulatory agents on the metabolism of cancer cells, and the differential effects of biomodulatory agents on tumor and stromal cells will be discussed.
Zhang, Di; Graff, Taylor; Crawford, Susan; Subramanian, Hariharan; Thompson, Sebastian; Derbas, Justin R.; Lyengar, Radha; Roy, Hemant K.; Brendler, Charles B.; Backman, Vadim
Prostate Cancer (PC) is the second leading cause of cancer deaths in American men. While prostate specific antigen (PSA) test has been widely used for screening PC, >60% of the PSA detected cancers are indolent, leading to unnecessary clinical interventions. An alternative approach, active surveillance (AS), also suffer from high expense, discomfort and complications associated with repeat biopsies (every 1-3 years), limiting its acceptance. Hence, a technique that can differentiate indolent from aggressive PC would attenuate the harms from over-treatment. Combining microscopy with spectroscopy, our group has developed partial wave spectroscopic (PWS) microscopy, which can quantify intracellular nanoscale organizations (e.g. chromatin structures) that are not accessible by conventional microscopy. PWS microscopy has previously been shown to predict the risk of cancer in seven different organs (N ~ 800 patients). Herein we use PWS measurement of label-free histologically-normal prostatic epithelium to distinguish indolent from aggressive PC and predict PC risk. Our results from 38 men with low-grade PC indicated that there is a significant increase in progressors compared to non-progressors (p=0.002, effect size=110%, AUC=0.80, sensitivity=88% and specificity=72%), while the baseline clinical characteristics were not significantly different. We further improved the diagnostic power by performing nuclei-specific measurements using an automated system that separates in real-time the cell nuclei from the remaining prostate epithelium. In the long term, we envision that the PWS based prognostication can be coupled with AS without any change to the current procedure to mitigate the harms caused by over-treatment.
Shah, Amy T.; Cannon, Taylor M.; Higginbotham, Jim N.; Skala, Melissa C.
Tumor heterogeneity poses challenges for devising optimal treatment regimens for cancer patients. In particular, subpopulations of cells can escape treatment and cause relapse. There is a need for methods to characterize tumor heterogeneity of treatment response. Cell metabolism is altered in cancer (Warburg effect), and cells use the autofluorescent cofactor NADH in numerous metabolic reactions. Previous studies have shown that microscopy measurements of NADH autofluorescence are sensitive to treatment response in breast cancer, and these techniques typically assess hundreds of cells per group. An alternative approach is flow cytometry, which measures fluorescence on a single-cell level and is attractive for characterizing tumor heterogeneity because it achieves high-throughput analysis and cell sorting in millions of cells per group. Current applications for flow cytometry rely on staining with fluorophores. This study characterizes flow cytometry measurements of NADH autofluorescence in breast cancer cells. Preliminary results indicate flow cytometry of NADH is sensitive to cyanide perturbation, which inhibits oxidative phosphorylation, in nonmalignant MCF10A cells. Additionally, flow cytometry is sensitive to higher NADH intensity for HER2-positive SKBr3 cells compared with triple-negative MDA-MB-231 cells. These results agree with previous microscopy studies. Finally, a mixture of SKBr3 and MDA-MB-231 cells were sorted into each cell type using NADH intensity. Sorted cells were cultured, and microscopy validation showed the expected morphology for each cell type. Ultimately, flow cytometry could be applied to characterize tumor heterogeneity based on treatment response and sort cell subpopulations based on metabolic profile. These achievements could enable individualized treatment strategies and improved patient outcomes.
Koh, Frederick Hong-Xiang; Shi, Wang
The biliary duct is an extremely rare site for colon cancer metastasis. It often leads to a diagnostic dilemma, since primary cholangiocarcinoma (potentially treatable with surgery) has a similar presentation. This paper highlights our experience with 5 consecutive patients who had colon malignancy with biliary metastasis, and prognosis of their disease. Five patients, with a history of primary colon cancer since 2010, were identified to have biliary metastasis. Of these, 4 (80.0%) patients were male. The median time to diagnosis of biliary metastasis from diagnosis of colon cancer was 59.2 months (0-70.1 months), and all exhibited symptoms of biliary obstruction or its associated complications. Evaluation of the tumour samples revealed all specimens to be negative for CK7 but positive for CK20, suggestive of a colorectal primary. The median survival of the 5 patients was 23.5 months (1.8-44.5 months) from the diagnosis of biliary metastasis. However, none of their death was related to the direct complication of biliary obstruction. Biliary metastasis is a rare entity for metastatic colon malignancy. Diagnosis may be difficult radiologically, and immunohistochemical staining may help in identification. The overall survival for these patients is dismal. PMID:28317047
Melosky, B.; Ho, C.
The Canadian Lung Cancer Conference 2014, held in Vancouver, British Columbia, was an opportunity for Canadian lung cancer researchers and treatment experts to meet and discuss current breakthroughs and paradigm shifts in the field. The full-day program featured lectures, discussion, and debates, with ample time for informal networking. We are already looking forward to next year’s meeting (scheduled for February 6, 2015), where we expect to discuss and reflect on some of the latest results and breakthroughs from both the American Society of Clinical Oncology and the European Society for Medical Oncology.
In a recent publication in Cancer Cell, CTD2 investigators discovered that a known cancer-associated gain-of-function alteration in phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) results in novel protein activity that confers sensitivity to mitogen-activated protein kinase (MAPK) inhibitors. The PIK3R1 gene encodes the p85α regulatory subunit of PIK3. Under normal conditions, p85α suppresses PIK3 mediated activation of downstream pathways that promote cell growth and survival.
Spender, Lindsay C.; Ferguson, G. John; Liu, Sijia; Cui, Chao; Girotti, Maria Romina; Sibbet, Gary; Higgs, Ellen B.; Shuttleworth, Morven K.; Hamilton, Tom; Lorigan, Paul; Weller, Michael; Vincent, David F.; Sansom, Owen J.; Frame, Margaret; Dijke, Peter ten; Marais, Richard; Inman, Gareth J.
Recent data implicate elevated transforming growth factor-β (TGFβ) signalling in BRAF inhibitor drug-resistance mechanisms, but the potential for targeting TGFβ signalling in cases of advanced melanoma has not been investigated. We show that mutant BRAFV600E confers an intrinsic dependence on TGFβ/TGFβ receptor 1 (TGFBR1) signalling for clonogenicity of murine melanocytes. Pharmacological inhibition of the TGFBR1 blocked the clonogenicity of human mutant BRAF melanoma cells through SMAD4-independent inhibition of mitosis, and also inhibited metastasis in xenografted zebrafish. When investigating the therapeutic potential of combining inhibitors of mutant BRAF and TGFBR1, we noted that unexpectedly, low-dose PLX-4720 (a vemurafenib analogue) promoted proliferation of drug-naïve melanoma cells. Pharmacological or pharmacogenetic inhibition of TGFBR1 blocked growth promotion and phosphorylation of SRC, which is frequently associated with vemurafenib-resistance mechanisms. Importantly, vemurafenib-resistant patient derived cells retained sensitivity to TGFBR1 inhibition, suggesting that TGFBR1 could be targeted therapeutically to combat the development of vemurafenib drug-resistance. PMID:27835901
Zhuang, X B; Xing, N; Zhang, Q; Yuan, S J; Chen, W; Qiao, T K
Immunotherapy is a hot issue in cancer research over the years and tumor cell vaccine is one of the increasing number of studies. Although the whole tumor cell vaccine can provide the best source of immunizing antigens, there is still a limitation that most tumors are not naturally immunogenic. CpG Oligodeoxynucleotides (CpG ODNs), synthetic oligonucleotides containing a cytosine-phosphate-guanine(CpG) motif, was shown to enhance immune responses to a wide variety of antigens. In this study, we generated the radioresistant Lewis lung cancer cell by repeated X-ray radiation and inactivated it as a whole tumor cell vaccine to enhance the immunogenicity of tumor cell vaccine. Mice were subcutaneously immunized with this inactivated vaccine combined with CpG ODN1826 and then inoculated with autologous Lewis lung cancer (LLC) to estimate the antitumor efficacy. The results showed that the radioresistant tumor cell vaccine combined with CpG ODN1826 could significantly inhibit tumor growth, increased survival of the mice and with 20% of the mice surviving tumor free in vivo compared with the unimmunized mice bearing LLC tumor. A significant increase of apoptosis was also observed in the tumor prophylactically immunized with vaccine of inactivated radioresistant tumor cell plus CpG ODN1826. The potent antitumor effect correlated with higher secretion levels of tumor necrosis factor-alpha(TNF-α) and lower levels of interleukin-10(IL-10) concentration in serum. Furthermore, the results suggested that the antitumor mechanism was probably depended on the decreased level of programmed death ligand-1(PD-L1) which plays an important role in the negative regulation of immune response by the inhibition of tumor antigen-specific T cell activation. These findings clearly demonstrated that the radioresistant tumor cell vaccine combined with CpG ODN1826 as an appropriate adjuvant could induce effective antitumor immunity in vivo.
This talk will introduce a new nanotechnology platform for cancer combination therapy that utilizes near infrared light activation not only for photodynamic damage but also as an extrinsic mechanism to initiate release of complimentary drugs to suppress dynamic bursts in molecular signaling networks that promote tumor cell survival and treatment escape. The goal is to achieve co-delivery with concomitant activity of photodynamic, molecular inhibitor and chemotherapeutic agents, selectively within the tumor. This approach overcomes challenges in achieving synergistic interactions using sequential drug delivery. Conventional drug delivery is compromised by the differential pharmacokinetics of individual agents and potentially antagonistic effects—such as vascular shutdown by one agent that limits delivery of the second. Here, photodynamic damage—which efficiently kills drug-resistant cells via damage of common proteins involved in drug-resistance (such as anti-apoptosis factors and drug-efflux transporters)—is synchronized spatially and temporally with the photo-initiated release of complimentary agents—to enable full interaction amongst the individual therapies. This spatiotemporal synchronization offers new prospects for exploiting time-sensitive synergistic interactions. Specific implementations of these concepts will be presented in preclinical models of cancer. Strategies to enable molecular-targeting of cancer cells via site-specific attachment of targeting moieties to the outer lipid shell of these nanovehicles will also be discussed. If successful in humans, this new paradigm for synchronized, tumor-focused combination therapy will ultimately supersede the present use of chronic drug injection by increasing efficacy per cycle whilst reducing systemic exposure to toxic drugs.
Walsh, Kyle M; Whitehead, Todd P; de Smith, Adam J; Smirnov, Ivan V; Park, Minsun; Endicott, Alyson A; Francis, Stephen S; Codd, Veryan; Samani, Nilesh J; Metayer, Catherine; Wiemels, Joseph L
Aberrant telomere lengthening is an important feature of cancer cells in adults and children. In addition to somatic mutations, germline polymorphisms in telomere maintenance genes impact telomere length. Whether these telomere-associated polymorphisms affect risk of childhood malignancies remains largely unexplored. We collected genome-wide data from three groups with pediatric malignancies [neuroblastoma (N = 1516), acute lymphoblastic leukemia (ALL) (N = 958) and osteosarcoma (N = 660)] and three control populations (N = 6892). Using case-control comparisons, we analyzed eight single nucleotide polymorphisms (SNPs) in genes definitively associated with interindividual variation in leukocyte telomere length (LTL) in prior genome-wide association studies: ACYP2, TERC, NAF1, TERT, OBFC1, CTC1, ZNF208 and RTEL1 Six of these SNPs were associated (P < 0.05) with neuroblastoma risk, one with leukemia risk and one with osteosarcoma risk. The allele associated with longer LTL increased cancer risk for all these significantly associated SNPs. Using a weighted linear combination of the eight LTL-associated SNPs, we observed that neuroblastoma patients were predisposed to longer LTL than controls, with each standard deviation increase in genotypically estimated LTL associated with a 1.15-fold increased odds of neuroblastoma (95%CI = 1.09-1.22; P = 7.9×10(-7)). This effect was more pronounced in adolescent-onset neuroblastoma patients (OR = 1.46; 95%CI = 1.03-2.08). A one standard deviation increase in genotypically estimated LTL was more weakly associated with osteosarcoma risk (OR = 1.10; 95%CI = 1.01-1.19; P = 0.017) and leukemia risk (OR = 1.07; 95%CI = 1.00-1.14; P = 0.044), specifically for leukemia patients who relapsed (OR = 1.19; 95%CI = 1.01-1.40; P = 0.043). These results indicate that genetic predisposition to longer LTL is a newly identified risk factor for neuroblastoma and potentially for other cancers of childhood.
More than 400 leading experts in cancer survivorship convened today for a conference, Cancer Survivorship Research: Translating Science to Care, to focus on such current concerns as how obesity might not have the same effects on all cancer survivors, and
Yamada, Daisuke; Watanabe, Satoshi; Kawahara, Kohichi; Maeda, Takehiko
Aberrant changes to several signaling pathways because of genetic mutations or increased cytokine production are critical for tumor cells to become malignant. Semaphorin 3A (SEMA3A) acts as a bivalent factor that suppresses or promotes tumor development in different pathological backgrounds. Previously, we showed that SEMA3A positively regulated the proliferative and glycolytic activities of mouse-derived Lewis lung carcinoma (LLC) cells. Plexins A1-A4 (PLXNA1-PLXNA4) are SEMA3A receptors; however, it is not known which subtype is critical for oncogenic SEMA3A signaling. We used LLC cells to investigate the role of PLXNA1 in oncogenic SEMA3A signaling. Using short hairpin RNA-mediated knockdown, we investigated the effects of constitutive inhibition of Plxna1 on cell proliferation, metabolic dependency, and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sensitivity. We found that Plxna1 knockdown did not affect apoptosis but resulted in decreased cell proliferation and reductions in mRNA expression levels of proliferation-marker genes, such as Ccnd1, Pcna, and Myc. In addition, we found decreased mRNA expression levels of glycolysis-associated genes, such as Pkm2 and Ldha, and decreased lactate production. In contrast, we found no changes in the mRNA expression levels of oxidative phosphorylation-associated genes, such as Cycs, Cox5a, and Atp5g1. We found that Plxna1 knockdown conferred resistance to glucose starvation but increased cytotoxicity to oligomycin. Plxna1 or Sema3a knockdown caused an increased sensitivity to the EGFR-TKIs gefitinib and erlotinib, in Lewis lung carcinoma (LLC) cells. These findings demonstrate that PLXNA1 mediates the acquisition of malignant phenotypes induced by autocrine SEMA3A signaling.
Cheng, Joseph C.; Bai, Aiping; Beckham, Thomas H.; Marrison, S. Tucker; Yount, Caroline L.; Young, Katherine; Lu, Ping; Bartlett, Anne M.; Wu, Bill X.; Keane, Barry J.; Armeson, Kent E.; Marshall, David T.; Keane, Thomas E.; Smith, Michael T.; Jones, E. Ellen; Drake, Richard R.; Bielawska, Alicja; Norris, James S.; Liu, Xiang
Escape of prostate cancer (PCa) cells from ionizing radiation–induced (IR-induced) killing leads to disease progression and cancer relapse. The influence of sphingolipids, such as ceramide and its metabolite sphingosine 1-phosphate, on signal transduction pathways under cell stress is important to survival adaptation responses. In this study, we demonstrate that ceramide-deacylating enzyme acid ceramidase (AC) was preferentially upregulated in irradiated PCa cells. Radiation-induced AC gene transactivation by activator protein 1 (AP-1) binding on the proximal promoter was sensitive to inhibition of de novo ceramide biosynthesis, as demonstrated by promoter reporter and ChIP-qPCR analyses. Our data indicate that a protective feedback mechanism mitigates the apoptotic effect of IR-induced ceramide generation. We found that deregulation of c-Jun induced marked radiosensitization in vivo and in vitro, which was rescued by ectopic AC overexpression. AC overexpression in PCa clonogens that survived a fractionated 80-Gy IR course was associated with increased radioresistance and proliferation, suggesting a role for AC in radiotherapy failure and relapse. Immunohistochemical analysis of human PCa tissues revealed higher levels of AC after radiotherapy failure than those in therapy-naive PCa, prostatic intraepithelial neoplasia, or benign tissues. Addition of an AC inhibitor to an animal model of xenograft irradiation produced radiosensitization and prevention of relapse. These data indicate that AC is a potentially tractable target for adjuvant radiotherapy. PMID:24091326
Aminkeng, Folefac; Bhavsar, Amit P; Visscher, Henk; Rassekh, Shahrad R; Li, Yuling; Lee, Jong W; Brunham, Liam R; Caron, Huib N; van Dalen, Elvira C; Kremer, Leontien C; van der Pal, Helena J; Amstutz, Ursula; Rieder, Michael J; Bernstein, Daniel; Carleton, Bruce C; Hayden, Michael R; Ross, Colin J D
Anthracyclines are used in over 50% of childhood cancer treatment protocols, but their clinical usefulness is limited by anthracycline-induced cardiotoxicity (ACT) manifesting as asymptomatic cardiac dysfunction and congestive heart failure in up to 57% and 16% of patients, respectively. Candidate gene studies have reported genetic associations with ACT, but these studies have in general lacked robust patient numbers, independent replication or functional validation. Thus, the individual variability in ACT susceptibility remains largely unexplained. We performed a genome-wide association study in 280 patients of European ancestry treated for childhood cancer, with independent replication in similarly treated cohorts of 96 European and 80 non-European patients. We identified a nonsynonymous variant (rs2229774, p.Ser427Leu) in RARG highly associated with ACT (P = 5.9 × 10(-8), odds ratio (95% confidence interval) = 4.7 (2.7-8.3)). This variant alters RARG function, leading to derepression of the key ACT genetic determinant Top2b, and provides new insight into the pathophysiology of this severe adverse drug reaction.
Ramer, Robert; Heinemann, Katharina; Merkord, Jutta; Rohde, Helga; Salamon, Achim; Linnebacher, Michael; Hinz, Burkhard
The antitumorigenic mechanism of cannabidiol is still controversial. This study investigates the role of COX-2 and PPAR-γ in cannabidiol's proapoptotic and tumor-regressive action. In lung cancer cell lines (A549, H460) and primary cells from a patient with lung cancer, cannabidiol elicited decreased viability associated with apoptosis. Apoptotic cell death by cannabidiol was suppressed by NS-398 (COX-2 inhibitor), GW9662 (PPAR-γ antagonist), and siRNA targeting COX-2 and PPAR-γ. Cannabidiol-induced apoptosis was paralleled by upregulation of COX-2 and PPAR-γ mRNA and protein expression with a maximum induction of COX-2 mRNA after 8 hours and continuous increases of PPAR-γ mRNA when compared with vehicle. In response to cannabidiol, tumor cell lines exhibited increased levels of COX-2-dependent prostaglandins (PG) among which PGD(2) and 15-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) caused a translocation of PPAR-γ to the nucleus and induced a PPAR-γ-dependent apoptotic cell death. Moreover, in A549-xenografted nude mice, cannabidiol caused upregulation of COX-2 and PPAR-γ in tumor tissue and tumor regression that was reversible by GW9662. Together, our data show a novel proapoptotic mechanism of cannabidiol involving initial upregulation of COX-2 and PPAR-γ and a subsequent nuclear translocation of PPAR-γ by COX-2-dependent PGs.
Bermon, Stephane; Castell, Lindy M; Calder, Philip C; Bishop, Nicolette C; Blomstrand, Eva; Mooren, Frank C; Krüger, Karsten; Kavazis, Andreas N; Quindry, John C; Senchina, David S; Nieman, David C; Gleeson, Michael; Pyne, David B; Kitic, Cecilia M; Close, Graeme L; Larson-Meyer, D Enette; Marcos, Ascension; Meydani, Simin N; Walsh, Neil P; Nagatomi, Ryochi
In this consensus statement on immunonutrition and exercise, a panel of knowledgeable contributors from across the globe provides a consensus of updated science, including the background, the aspects for which a consensus actually exists, the controversies and, when possible, suggested directions for future research.
Finkle, Bryan S., Ed.; And Others
The Division of Applied Research of the National Institute on Drug Abuse sponsored a Consensus Conference at which key technical, scientific, and procedural issues of employee drug testing could be discussed. The conference, which included politicians and government officials; representatives of business, industry, and labor; and laboratory…
Liebeskind, Benjamin J.; McWhite, Claire D.; Marcotte, Edward M.
Correctly estimating the age of a gene or gene family is important for a variety of fields, including molecular evolution, comparative genomics, and phylogenetics, and increasingly for systems biology and disease genetics. However, most studies use only a point estimate of a gene’s age, neglecting the substantial uncertainty involved in this estimation. Here, we characterize this uncertainty by investigating the effect of algorithm choice on gene-age inference and calculate consensus gene ages with attendant error distributions for a variety of model eukaryotes. We use 13 orthology inference algorithms to create gene-age datasets and then characterize the error around each age-call on a per-gene and per-algorithm basis. Systematic error was found to be a large factor in estimating gene age, suggesting that simple consensus algorithms are not enough to give a reliable point estimate. We also found that different sources of error can affect downstream analyses, such as gene ontology enrichment. Our consensus gene-age datasets, with associated error terms, are made fully available at so that researchers can propagate this uncertainty through their analyses (geneages.org). PMID:27259914
Rey, Guillermo Álvarez; Cuesta, Jordi Ardevol; Loureda, Rafael Arriaza; España, Fernando Ávila; Matas, Ramón Balius; Pazos, Fernando Baró; de Dios Beas Jiménez, Juan; Rosell, Jorge Candel; Fernandez, César Cobián; Ros, Francisco Esparza; Colmenero, Josefina Espejo; de Prado, Jorge Fernández; Cota, Juan José García; González, Jose Ignacio Garrido; Santander, Manuela González; Munilla, Miguel Ángel Herrador; Ruiz, Francisco Ivorra; Díaz, Fernando Jiménez; Marqueta, Pedro Manonelles; Fernandez, Antonio Maestro; Benito, Juan José Muñoz; Vilás, Ramón Olivé; Teres, Xavier Peirau; Amaro, José Peña; Roque, Juan Pérez San; Parenteu, Christophe Ramírez; Serna, Juan Ribas; Álvarez, Mikel Sánchez; Marchori, Carlos Sanchez; Soto, Miguel del Valle; Alonso, José María Villalón; García, Pedro Guillen; de la Iglesia, Nicolas Hugo; Alcorocho, Juan Manuel Lopez
On the 21st of March, 2015, experts met at Clínica CEMTRO in Madrid, Spain, under the patronage of The Spanish Society for Sports Traumatology (SETRADE), The Spanish Federation of Sports Medicine (FEMEDE), The Spanish Association of Medical Services for Football Clubs (AEMEF), and The Spanish Association of Medical Services for Basketball Clubs (AEMB) with the aim of establishing a round table that would allow specialists to consider the most appropriate current general actions to be taken when treating muscle tears in sport, based on proven scientific data described in the medical literature. Each expert received a questionnaire prior to the aforementioned meeting comprising a set of questions concerning therapeutic indications generally applied in the different stages present during muscle repair. The present Consensus Document is the result of the answers to the questionnaire and resulting discussion and consensus over which are the best current indications in the treatment of muscle tears in sport. Avoiding immobilization, not taking nonsteroidal anti-inflammatory drugs (NSAIDs) randomly, fostering early mobilization, increasing vascularization of injured, site and regulating inflammatory mechanisms—without inhibiting these from the early stages of the recovery period—all stood out as main points of the Consensus Document. Additionally, there is controversy concerning cell stimulation techniques and the use of growth factors or cell inhibitors. The decision concerning discharge was unanimous, as was the criteria considered when it came to performing sport techniques without pain. PMID:27213161
Huang, Huang-Chiao; Mallidi, Srivalleesha; Liu, Joyce; Chiang, Chun-Te; Mai, Zhiming; Goldschmidt, Ruth; Rizvi, Imran; Ebrahim-Zadeh, Neema; Hasan, Tayyaba
It is increasingly evident that the most effective cancer treatments will involve interactive regimens that target multiple non-overlapping pathways, preferably such that each component enhances the others to improve outcomes while minimizing systemic toxicities. Toward this goal, we developed a combination of photodynamic therapy and irinotecan, which mechanistically cooperate with each other, beyond their individual tumor destruction pathways, to cause synergistic reduction in orthotopic pancreatic tumor burden. A three-way mechanistic basis of the observed the synergism will be discussed: (i) PDT downregulates drug efflux transporters to increase intracellular irinotecan levels. (ii) Irinotecan reduces the expression of hypoxia-induced marker, which is upregulated by PDT. (iii) PDT downregulates irinotecan-induced survivin expression to amplify the apoptotic and anti-proliferative effects. The clinical translation potential of the combination will also be highlighted.
Esophageal squamous cell neoplasia (ESCN) is the sixth leading cause of cancer death worldwide. Most deaths due to ESCN occur in developing countries, with highest risk areas in northern China. Lugol's chromoendoscopy (LCE) is the gold-standard for ESCN screening; while the sensitivity of LCE for ESCN is >95%, LCE suffers poor specificity (< 65%) due to false positive findings from inflammatory lesions. High resolution microendoscopy (HRME) uses a low-cost, fiber-optic fluorescence microscope to image morphology of the surface epithelium without need for biopsy. We developed a tablet-interfaced HRME with automated, real-time image analysis. In an in vivo study of 177 patients referred for endoscopy in China, use of the algorithm identified neoplasia with a sensitivity and specificity of 95% and 91% compared to the gold standard of histology.
Yang, Chunhua; Gundala, Sushma Reddy; Mukkavilli, Rao; Vangala, Subrahmanyam; Reid, Michelle D; Aneja, Ritu
Phytochemical complexity of plant extracts may offer health-promoting benefits including chemotherapeutic and chemopreventive effects. Isolation of 'most-active fraction' or single constituents from whole extracts may not only compromise the therapeutic efficacy but also render toxicity, thus emphasizing the importance of preserving the natural composition of whole extracts. The leaves of Annona muricata, commonly known as Graviola, are known to be rich in flavonoids, isoquinoline alkaloids and annonaceous acetogenins. Here, we demonstrate phytochemical synergy among the constituents of Graviola leaf extract (GLE) compared to its flavonoid-enriched (FEF) and acetogenin-enriched (AEF) fractions. Comparative quantitation of flavonoids revealed enrichment of rutin (~7-fold) and quercetin-3-glucoside (Q-3-G, ~3-fold) in FEF compared to GLE. In vivo pharmacokinetics and in vitro absorption kinetics of flavonoids revealed enhanced bioavailability of rutin in FEF compared to GLE. However, GLE was more effective in inhibiting in vitro prostate cancer proliferation, viability and clonogenic capacity compared to FEF. Oral administration of 100mg/kg bw GLE showed ~1.2-fold higher tumor growth-inhibitory efficacy than FEF in human prostate tumor xenografts although the concentration of rutin and Q-3-G was more in FEF. Contrarily, AEF, despite its superior in vitro and in vivo efficacy, resulted in death of the mice due to toxicity. Our data indicate that despite lower absorption and bioavailability of rutin, maximum efficacy was achieved in the case of GLE, which also comprises of other phytochemical groups including acetogenins that make up its natural complex environment. Hence, our study emphasizes on evaluating the nature of interactions among Graviola leaf phytochemcials for developing favorable dose regimen for prostate cancer management to achieve optimal therapeutic benefits.
Yang, Chunhua; Gundala, Sushma Reddy; Mukkavilli, Rao; Vangala, Subrahmanyam; Reid, Michelle D.; Aneja, Ritu
Phytochemical complexity of plant extracts may offer health-promoting benefits including chemotherapeutic and chemopreventive effects. Isolation of ‘most-active fraction’ or single constituents from whole extracts may not only compromise the therapeutic efficacy but also render toxicity, thus emphasizing the importance of preserving the natural composition of whole extracts. The leaves of Annona muricata, commonly known as Graviola, are known to be rich in flavonoids, isoquinoline alkaloids and annonaceous acetogenins. Here, we demonstrate phytochemical synergy among the constituents of Graviola leaf extract (GLE) compared to its flavonoid-enriched (FEF) and acetogenin-enriched (AEF) fractions. Comparative quantitation of flavonoids revealed enrichment of rutin (~7-fold) and quercetin-3-glucoside (Q-3-G, ~3-fold) in FEF compared to GLE. In vivo pharmacokinetics and in vitro absorption kinetics of flavonoids revealed enhanced bioavailability of rutin in FEF compared to GLE. However, GLE was more effective in inhibiting in vitro prostate cancer proliferation, viability and clonogenic capacity compared to FEF. Oral administration of 100mg/kg bw GLE showed ~1.2-fold higher tumor growth-inhibitory efficacy than FEF in human prostate tumor xenografts although the concentration of rutin and Q-3-G was more in FEF. Contrarily, AEF, despite its superior in vitro and in vivo efficacy, resulted in death of the mice due to toxicity. Our data indicate that despite lower absorption and bioavailability of rutin, maximum efficacy was achieved in the case of GLE, which also comprises of other phytochemical groups including acetogenins that make up its natural complex environment. Hence, our study emphasizes on evaluating the nature of interactions among Graviola leaf phytochemcials for developing favorable dose regimen for prostate cancer management to achieve optimal therapeutic benefits. PMID:25863125
Spicer, Graham; Young, Scott T.; Yi, Ji; Shea, Lonnie D.; Backman, Vadim
The role of extracellular matrix modification and signaling in cancer progression is an increasingly recognized avenue for the progression of the disease. Previous study of field effect carcinogenesis with Inverse Spectroscopic Optical Coherence Tomography (ISOCT) has revealed pronounced changes in the nanoscale-sensitive mass fractal dimension D measured from field effect tissue when compared to healthy tissue. However, the origin of this difference in tissue ultrastructure in field effect carcinogenesis has remained poorly understood. Here, we present findings supporting the idea that enzymatic crosslinking of the extracellular matrix is an effect that presents at the earliest stages of carcinogenesis. We use a model of collagen gel with crosslinking induced by lysyl oxidase (LOXL4) to recapitulate the difference in D previously reported from healthy and cancerous tissue biopsies. Furthermore, STORM imaging of this collagen gel model verifies the morphologic effects of enzymatic crosslinking at length scales as small as 40 nm, close to the previously reported lower length scale sensitivity threshold of 35 nm for ISOCT. Analysis of the autocorrelation function from STORM images of collagen gels and subsequent fitting to the Whittle-Matérn correlation function shows a similar effect of LOXL4 on D from collagen measured with ISOCT and STORM. We extend this to mass spectrometric study of tissue to directly measure concentrations of collagen crosslink residues. The validation of ISOCT as a viable tool for non-invasive rapid quantification of collagen ultrastructure lends it to study other physiological phenomena involving ECM restructuring such as atherosclerotic plaque screening or cervical ripening during pregnancy.
Toi, Masakazu; Winer, Eric P; Benson, John R; Inamoto, Takashi; Forbes, John F; von Minckwitz, Gunter; Robertson, John F R; Grobmyer, Stephen R; Jatoi, Ismail; Sasano, Hironobu; Kunkler, Ian; Ho, Alice Y; Yamauchi, Chikako; Chow, Louis W C; Huang, Chiun-Sheng; Han, Wonshik; Noguchi, Shinzaburo; Pegram, Mark D; Yamauchi, Hideko; Lee, Eun-Sook; Larionov, Alexey A; Bevilacqua, Jose L B; Yoshimura, Michio; Sugie, Tomoharu; Yamauchi, Akira; Krop, Ian E; Noh, Dong Young; Klimberg, V Suzanne
ABSTRACT Kyoto Breast Cancer Consensus Conference, Kyoto, Japan, 18-20 February 2014 The loco-regional management of breast cancer is increasingly complex with application of primary systemic therapies, oncoplastic techniques and genetic testing for breast cancer susceptibility. Personalization of loco-regional treatment is integral to optimization of breast cancer care. Clinical and pathological tumor stage, biological features and host factors influence loco-regional treatment strategies and extent of surgical procedures. Key issues including axillary staging, axillary treatment, radiation therapy, primary systemic therapy (PST), preoperative hormonal therapy and genetic predisposition were identified and discussed at the Kyoto Breast Cancer Consensus Conference (KBCCC2014). In the first of a two part conference scene, consensus recommendations for axillary management are presented and focus on the following topics: indications for completion axillary lymph node dissection in primary surgical patients with ≤2 macrometastases or any sentinel nodal deposits after PST; the timing of sentinel lymph node biopsy in the context of PST; use of axillary irradiation as a component of primary treatment plans and the role of intraoperative node assessment in the post-Z0011 era.
Liu, Wanqing; He, Lijun; Ramírez, Jacqueline; Krishnaswamy, Soundararajan; Kanteti, Rajani; Wang, Yi-Ching; Salgia, Ravi; Ratain, Mark J
Somatic mutations in the EGFR tyrosine kinase (TK) domain play a critical role in the development and treatment of non-small cell lung cancer (NSCLC). Strong genetic influence on susceptibility to these mutations has been suggested. To identify the genetic factors conferring risk for the EGFR TK mutations in NSCLC, a case-control study was conducted in 141 Taiwanese NSCLC patients by focusing on three functional polymorphisms in the EGFR gene [-216G/T, intron 1(CA)n and R497K]. Allelic imbalance (AI) of the EGFR -216G/T polymorphism was also tested in the heterozygous patients as well as in the NCI-60 cancer cell lines to further verify its function. We found that the frequencies of the alleles -216T and CA-19 are significantly higher in the patients with any mutation (p=0.032 and 0.01, respectively), in particular in those with exon 19 microdeletions (p=0.006 and 0.033, respectively), but not in the patients with L858R mutation. The -216T allele is favored to be amplified in both tumor DNA of lung cancer patients and cancer cell lines. We conclude that the local haplotype structures across the EGFR gene may favor the development of cellular malignancies and thus significantly confer risk to the occurrence of EGFR mutations in NSCLC, particularly the exon 19 microdeletions. PMID:21292812
Kurstedt, Jr., H. A.; Jones, R. M.; Walker, J. A.; Middleman, L. I.
In this paper, we describe a new research effort on consensus tied to the Environmental Restoration Program (ERP) within the US Department of Energy's Office of Defense Waste and Transportation Management (DWTM). We define consensus and explain why consensus decisions are not merely desirable but necessary in furthering ERP activities. As examples of our planned applied research, we first discuss Nominal Group Technique as a representative consensus-generating tool, and we conclude by describing the consensus-related mission of the Waste Management Review Group, established at Virginia Tech to conduct independent, third-party review of DWTM/ERP plans and activities. 10 refs.
Huang, Yi; Liu, Dan; Chen, Bojiang; Zeng, Jing; Wang, Lei; Zhang, Shangfu; Mo, Xianming; Li, Weimin
Proapoptotic BH-3-only protein Bad (Bcl-Xl/Bcl-2-associated death promoter homolog, Bad) initiates apoptosis in human cells, and contributes to tumorigenesis and chemotherapy resistant in malignancies. This study explored association between the Bad expression level and prognosis in patients with non-small cell lung cancer (NSCLC). In our study, a cohort of 88 resected primary NSCLC cases were collected and analyzed. Bad expression level was determined via immunohistochemical staining assay. The prognostic significances of Bad expression were evaluated with univariate and multivariate survival analysis. The results showed that compared with normal lung tissues, Bad expression level significantly decreased in NSCLC (P < 0.05). Bad expression was associated with adjuvant therapy status. Loss of Bad independently predicted poor prognosis in whole NSCLC cohort and early stage subjects (T1 + T2 and N0 + N1) (all P < 0.05). Overall survival time was also drastically shortened for Bad negative phenotype in NSCLC patients with smoking history, especially lung squamous cell carcinoma (all P < 0.05). In conclusion, this study provided clinical evidence that loss of Bad is an independent and powerful predictor of adverse prognosis in NSCLC. Bad protein could be a new biomarker for selecting individual therapy strategies and predicting therapeutic response in subjects with NSCLC.
A one-day workshop on Burkitt lymphoma (BL) was held at the 9th African Organization for Research and Training in Cancer (AORTIC) conference in 2013 in Durban, South Africa. The workshop featured 15 plenary talks by delegates representing 13 institutions that either fund or implement research on BL targeting AORTIC delegates primarily interested in pediatric oncology. The main outcomes of the meeting were improved sharing of knowledge and experience about ongoing epidemiologic BL research, BL treatment in different settings, the role of cancer registries in cancer research, and opportunities for African scientists to publish in scientific journals. The idea of forming a consortium of BL to improve coordination, information sharing, accelerate discovery, dissemination, and translation of knowledge and to build capacity, while reducing redundant efforts was discussed. Here, we summarize the presentations and discussions from the workshop. PMID:25686906
Layfield, Lester J; Abrams, Jacki; Cochand-Priollet, Beatrix; Evans, Doug; Gharib, Hossein; Greenspan, Frank; Henry, Michael; LiVolsi, Virginia; Merino, Maria; Michael, Claire W; Wang, Helen; Wells, Samuel A
The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine Needle Aspiration (FNA) State of the Science Conference on October 22-23, 2007 in Bethesda, MD. The 2-day meeting was accompanied by a permanent informational Web site and several on-line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document addresses follow-up procedures and therapeutic options for suggested diagnostic categories. Follow-up options for "nondiagnostic" and "benign" thyroid aspirates are given. The value of ultrasound examination in the follow-up of "nondiagnostic" and "benign" thyroid aspirates is discussed. Ultrasound findings requiring reaspiration or surgical resection are described as are the timing and length of clinical and ultrasonographic surveillance for cytologically "benign" nodules. Options for surgical intervention are given for the diagnostic categories of "atypical/borderline," "follicular neoplasm," "suspicious for malignancy" and "malignant" (http://thyroidfna.cancer.gov/pages/info/agenda/).
Antczak, Andrzej; Wokołorczyk, Dominika; Kluźniak, Wojciech; Kashyap, Aniruddh; Jakubowska, Anna; Gronwald, Jacek; Huzarski, Tomasz; Byrski, Tomasz; Dębniak, Tadeusz; Masojć, Bartłomiej; Górski, Bohdan; Gromowski, Tomasz; Gołąb, Adam; Sikorski, Andrzej; Słojewski, Marcin; Gliniewicz, Bartłomiej; Borkowski, Tomasz; Borkowski, Andrzej; Przybyła, Jacek; Sosnowski, Marek; Małkiewicz, Bartosz; Zdrojowy, Romuald; Sikorska-Radek, Paulina; Matych, Józef; Wilkosz, Jacek; Różański, Waldemar; Kiś, Jacek; Bar, Krzysztof; Janiszewska, Hanna; Stawicka, Małgorzata; Milecki, Piotr; Lubiński, Jan; Narod, Steven A; Cybulski, Cezary
A number of single nucleotide polymorphisms (SNPs) in the human genome have been associated with increased risk of prostate cancer. Recently, a single SNP in the region of chromosome 8q24 (rs188140481) has been associated with a three-fold increased risk of prostate cancer in Europe and North America. To establish whether rs188140481 is associated with the risk of prostate cancer in Poland, we genotyped 3467 men with prostate cancer and 1958 controls. The A allele of rs188140481 was detected in 44 of 3467 (1.3%) men with prostate cancer and in seven of 1958 (0.4%) controls (odds ratio=3.6; 95% confidence interval 1.6-7.9; P=0.0006). The allele was present in eight of 390 (2.1%) men with familial prostate cancer (odds ratio=5.8; 95% confidence interval 2.1-16.2; P=0.001). A positive family history of cancers at sites other than the prostate was observed in 27% of men who carried the rs188140481 risk allele and in 44% of noncarriers (P=0.04). No cancer at a site other than the prostate was more common in first-degree or second-degree relatives of carriers of the rs188140481 risk allele than relatives of noncarriers. The rs188140481 polymorphism in the 8q24 region confers a moderate increase in the risk of prostate cancer in Polish men. The SNP does not appear to be associated with susceptibility to cancers of other types.
Rostami, Kamran; Aldulaimi, David; Holmes, Geoffrey; Johnson, Matt W; Robert, Marie; Srivastava, Amitabh; Fléjou, Jean-François; Sanders, David S; Volta, Umberto; Derakhshan, Mohammad H; Going, James J; Becheanu, Gabriel; Catassi, Carlo; Danciu, Mihai; Materacki, Luke; Ghafarzadegan, Kamran; Ishaq, Sauid; Rostami-Nejad, Mohammad; Peña, A Salvador; Bassotti, Gabrio; Marsh, Michael N; Villanacci, Vincenzo
Microscopic enteritis (ME) is an inflammatory condition of the small bowel that leads to gastrointestinal symptoms, nutrient and micronutrient deficiency. It is characterised by microscopic or sub-microscopic abnormalities such as microvillus changes and enterocytic alterations in the absence of definite macroscopic changes using standard modern endoscopy. This work recognises a need to characterize disorders with microscopic and submicroscopic features, currently regarded as functional or non-specific entities, to obtain further understanding of their clinical relevance. The consensus working party reviewed statements about the aetiology, diagnosis and symptoms associated with ME and proposes an algorithm for its investigation and treatment. Following the 5(th) International Course in Digestive Pathology in Bucharest in November 2012, an international group of 21 interested pathologists and gastroenterologists formed a working party with a view to formulating a consensus statement on ME. A five-step agreement scale (from strong agreement to strong disagreement) was used to score 21 statements, independently. There was strong agreement on all statements about ME histology (95%-100%). Statements concerning diagnosis achieved 85% to 100% agreement. A statement on the management of ME elicited agreement from the lowest rate (60%) up to 100%. The remaining two categories showed general agreement between experts on clinical presentation (75%-95%) and pathogenesis (80%-90%) of ME. There was strong agreement on the histological definition of ME. Weaker agreement on management indicates a need for further investigations, better definitions and clinical trials to produce quality guidelines for management. This ME consensus is a step toward greater recognition of a significant entity affecting symptomatic patients previously labelled as non-specific or functional enteropathy.
The tumor suppressor gene HIC1 (hypermethylated in cancer 1) is a sequence-specific transcriptional repressor: definition of its consensus binding sequence and analysis of its DNA binding and repressive properties.
Pinte, Sébastien; Stankovic-Valentin, Nicolas; Deltour, Sophie; Rood, Brian R; Guérardel, Cateline; Leprince, Dominique
HIC1 (hypermethylated in cancer 1) is a tumor suppressor gene located at chromosome 17p13.3, a region frequently hypermethylated or deleted in human tumors and in a contiguous-gene syndrome, the Miller-Dieker syndrome. HIC1 is a transcriptional repressor containing five Krüppel-like C(2)H(2) zinc fingers and an N-terminal dimerization and autonomous repression domain called BTB/POZ. Although some of the HIC1 transcriptional repression mechanisms have been recently deciphered, target genes are still to be discovered. In this study, we determined the consensus binding sequence for HIC1 and investigated its DNA binding properties. Using a selection and amplification of binding sites technique, we identified the sequence 5'-(C)/(G)NG(C)/(G)GGGCA(C)/(A) CC-3' as an optimal binding site. In silico and functional analyses fully validated this consensus and highlighted a GGCA core motif bound by zinc fingers 3 and 4. The BTB/POZ domain inhibits the binding of HIC1 to a single site but mediates cooperative binding to a probe containing five concatemerized binding sites, a property shared by other BTB/POZ proteins. Finally, full-length HIC1 proteins transiently expressed in RK13 cells and more importantly, endogenous HIC1 proteins from the DAOY medulloblastoma cell line, repress the transcription of a reporter gene through their direct binding to these sites, as confirmed by chromatin immunoprecipitation experiments. The definition of the HIC1-specific DNA binding sequence as well as the requirement for multiple sites for optimal binding of the full-length protein are mandatory prerequisites for the identification and analyses of bona fide HIC1 target genes.
Su, Shishuai; Ding, Yanping; Li, Yiye; Wu, Yan; Nie, Guangjun
Triple-negative breast cancer is a malignant cancer type with a high risk of early recurrence and distant metastasis. Unlike other breast cancers, triple-negative breast cancer is lack of targetable receptors and, therefore, patients largely receive systemic chemotherapy. However, inevitable adverse effects and acquired drug resistance severely constrain the therapeutic outcome. Here we tailor-designed a porphyrin-based micelle that was self-assembled from a hybrid amphiphilic polymer comprising polyethylene glycol, poly (d, l-lactide-co-glycolide) and porphyrin. The bilayer micelles can be simultaneously loaded with two chemotherapeutic drugs with synergistic cytotoxicity and distinct physiochemical properties, forming a uniform and spherical nanostructure. The drug-loaded micelles showed a tendency to accumulate in the tumor and can be internalized by tumor cells for drug release in acidic organelles. Under near-infrared laser irradiation, high density of self-quenched porphyrins in the hydrophobic layer absorbed light efficiently and converted into an excited state, leading to the release of sufficient heat for photothermal therapy. The integration of localized photothermal effect and synergistic chemotherapy conferred great chemosensitivity to cancer cells and achieved tumor regression using about 1/10 of traditional drug dosage. As a result, chemotherapy-associated adverse effects were successfully avoided. Our present study established a novel porphyrin-based nanoplatform with photothermal activity and expanded drug loading capacity, providing new opportunities for challenging conventional chemotherapy and fighting against stubborn triple-negative breast cancer.
Ganz, Patricia A; Yip, Cheng Har; Gralow, Julie R; Distelhorst, Sandra R; Albain, Kathy S; Andersen, Barbara L; Bevilacqua, Jose Luiz B; de Azambuja, Evandro; El Saghir, Nagi S; Kaur, Ranjit; McTiernan, Anne; Partridge, Ann H; Rowland, Julia H; Singh-Carlson, Savitri; Vargo, Mary M; Thompson, Beti; Anderson, Benjamin O
Breast cancer survivors may experience long-term treatment complications, must live with the risk of cancer recurrence, and often experience psychosocial complications that require supportive care services. In low- and middle-income settings, supportive care services are frequently limited, and program development for survivorship care and long-term follow-up has not been well addressed. As part of the 5th Breast Health Global Initiative (BHGI) Global Summit, an expert panel identified nine key resources recommended for appropriate survivorship care, and developed resource-stratified recommendations to illustrate how health systems can provide supportive care services for breast cancer survivors after curative treatment, using available resources. Key recommendations include health professional education that focuses on the management of physical and psychosocial long-term treatment complications. Patient education can help survivors transition from a provider-intense cancer treatment program to a post-treatment provider partnership and self-management program, and should include: education on recognizing disease recurrence or metastases; management of treatment-related sequelae, and psychosocial complications; and the importance of maintaining a healthy lifestyle. Increasing community awareness of survivorship issues was also identified as an important part of supportive care programs. Other recommendations include screening and management of psychosocial distress; management of long-term treatment-related complications including lymphedema, fatigue, insomnia, pain, and women's health issues; and monitoring survivors for recurrences or development of second primary malignancies. Where possible, breast cancer survivors should implement healthy lifestyle modifications, including physical activity, and maintain a healthy weight. Health professionals should provide well-documented patient care records that can follow a patient as they transition from active treatment
Legree, 1995) .74 .88 MSCEIT ( Mayer Caruso & Salovey , 1999) .90 .98 TKML (Legree, Psotka, Tremble & Bourne, in press) .96 1.00...Conference of the APA, Washington, DC. Mayer , J. D., Caruso, D. R., & Salovey , P. (1999). Emotional intelligence meets traditional standards for an...center technologies have been utilized for industrial and scientific purposes to develop models of performance and evaluate theories of cognition ( Mayer
Giardiello, Francis M; Allen, John I; Axilbund, Jennifer E; Boland, C Richard; Burke, Carol A; Burt, Randall W; Church, James M; Dominitz, Jason A; Johnson, David A; Kaltenbach, Tonya; Levin, Theodore R; Lieberman, David A; Robertson, Douglas J; Syngal, Sapna; Rex, Douglas K
The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; Figure 2 illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; Figures 3-6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; Table 10 provides guidelines for screening at-risk and affected persons with Lynch syndrome; and Table 12 lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.
Giardiello, Francis M; Allen, John I; Axilbund, Jennifer E; Boland, C Richard; Burke, Carol A; Burt, Randall W; Church, James M; Dominitz, Jason A; Johnson, David A; Kaltenbach, Tonya; Levin, Theodore R; Lieberman, David A; Robertson, Douglas J; Syngal, Sapna; Rex, Douglas K
The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool to screen individuals in the office or endoscopy setting; Figure 2 illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; Figures 3,4,5,6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; Table 10 provides guidelines for screening at-risk and affected persons with Lynch syndrome; and Table 12 lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.
Lu, Renquan; Hu, Xiaobo; Zhou, Junmei; Sun, Jiajun; Zhu, Alan Z.; Xu, Xiaofeng; Zheng, Hui; Gao, Xiang; Wang, Xian; Jin, Hongchuan; Zhu, Ping; Guo, Lin
Oestrogen receptor α (ERα) antagonists are used in endocrine therapies for ERα-positive (ERα+) breast cancer patients. Unfortunately the clinical benefit is limited due to intrinsic and acquired drug resistance. Here using integrated genomic and functional studies, we report that amplification and/or overexpression of COPS5 (CSN5/JAB1) confers resistance to tamoxifen. Amplification and overexpression of COPS5, a catalytic subunit of the COP9 complex, is present in about 9% of the ERα+ primary breast cancer and more frequently (86.7%, 26/30) in tamoxifen-refractory tumours. Overexpression of COPS5, through its isopeptidase activity, leads to ubiquitination and proteasome-mediated degradation of NCoR, a key corepressor for ERα and tamoxifen-mediated suppression of ERα target genes. Importantly, COPS5 overexpression causes tamoxifen-resistance in preclinical breast cancer models in vitro and in vivo. We also demonstrate that genetic inhibition of the isopeptidase activity of COPS5 is sufficient to re-sensitize the resistant breast cancer cells to tamoxifen-treatment, offering a potential therapeutic approach for endocrine-resistant breast cancer patients. PMID:27375289
Rajendiran, Smrithi; Kashyap, Meghana V.; Vishwanatha, Jamboor K.
The Texas Center for Health Disparities, a National Institute on Minority Health and Health Disparities Center of Excellence, presents an annual conference to discuss prevention, awareness education and ongoing research about health disparities both in Texas and among the national population. The 2013 Texas Conference on Health Disparities brought together experts, in research, patient care and community outreach, on the “Intersection of Smoking, Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and Cancer”. Smoking, HIV/AIDS and cancer are three individual areas of public health concern, each with its own set of disparities and risk factors based on race, ethnicity, gender, geography and socio-economic status. Disparities among patient populations, in which these issues are found to be comorbid, provide valuable information on goals for patient care. The conference consisted of three sessions addressing “Comorbidities and Treatment”, “Public Health Perspectives”, and “Best Practices”. This article summarizes the basic science, clinical correlates and public health data presented by the speakers. PMID:24227993
Śmiałek, Małgorzata A.; Limão-Vieira, Paulo; Mason, Nigel J.; Solov'yov, Andrey V.
The second Nano-IBCT conference of the COST Action MP1002: Nanoscale Insights into Ion Beam Cancer Therapy was held in Sopot, Poland, from May 20th to May 24th, 2013. The Nano-IBCT action had been launched in December 2010 and brings together experts from different disciplines (physics, chemistry, biology, hadron-therapy centres, medical institutions), with specialisms in the radiation damage of biological matter. This meeting follows up the first one that was held in October, 2011 in Caen, France and we were pleased to see again so many of the participants of the previous meeting as well as to welcome some new colleagues joining and sharing their knowledge and expertise in this field. Contribution to the Topical Issue "Nano-scale Insights into Ion-beam Cancer Therapy", edited by Andrey V. Solov'yov, Nigel Mason, Paulo Limão-Vieira and Malgorzata Smialek-Telega.
Denise Lach, Principle Investigator; Stephanie Sanford, Co-P.I.
During the summer of 2002, we developed and implemented a ''consensus workshop'' with Idaho citizens to elicit their concerns and issues regarding the use of bioremediation as a cleanup technology for radioactive nuclides and heavy metals at Department of Energy (DOE) sites. The consensus workshop is a derivation of a technology assessment method designed to ensure dialogue between experts and lay people. It has its origins in the United States in the form of ''consensus development conferences'' used by the National Institutes of Health (NIH) to elicit professional knowledge and concerns about new medical treatments. Over the last 25 years, NIH has conducted over 100 consensus development conferences. (Jorgensen 1995). The consensus conference is grounded in the idea that technology assessment and policy needs to be socially negotiated among many different stakeholders and groups rather than narrowly defined by a group of experts. To successfully implement new technology, the public requires access to information that addresses a full complement of issues including understanding the organization proposing the technology. The consensus conference method creates an informed dialogue, making technology understandable to the general public and sets it within perspectives and priorities that may differ radically from those of the expert community. While specific outcomes differ depending on the overall context of a conference, one expected outcome is that citizen panel members develop greater knowledge of the technology during the conference process and, sometimes, the entire panel experiences a change in attitude toward the technology and/or the organization proposing its use (Kluver 1995). The purpose of this research project was to explore the efficacy of the consensus conference model as a way to elicit the input of the general public about bioremediation of radionuclides and heavy metals at Department of Energy sites. Objectives of the research included: (1
Prostate pathology of genetically engineered mice: definitions and classification. The consensus report from the Bar Harbor meeting of the Mouse Models of Human Cancer Consortium Prostate Pathology Committee.
Shappell, Scott B; Thomas, George V; Roberts, Richard L; Herbert, Ron; Ittmann, Michael M; Rubin, Mark A; Humphrey, Peter A; Sundberg, John P; Rozengurt, Nora; Barrios, Roberto; Ward, Jerrold M; Cardiff, Robert D
The Pathological Classification of Prostate Lesions in Genetically Engineered Mice (GEM) is the result of a directive from the National Cancer Institute Mouse Models of Human Cancer Consortium Prostate Steering Committee to provide a hierarchical taxonomy of disorders of the mouse prostate to facilitate classification of existing and newly created mouse models and the translation to human prostate pathology. The proposed Bar Harbor Classification system is the culmination of three meetings and workshops attended by various members of the Prostate Pathology Committee of the Mouse Models of Human Cancer Consortium. A 2-day Pathology Workshop was held at The Jackson Laboratory in Bar Harbor, Maine, in October 2001, in which study sets of 93 slides from 22 GEM models were provided to individual panel members. The comparison of mouse and human prostate anatomy and disease demonstrates significant differences and considerable similarities that bear on the interpretation of the origin and natural history of their diseases. The recommended classification of mouse prostate pathology is hierarchical, and includes developmental, inflammatory, benign proliferative, and neoplastic disorders. Among the neoplastic disorders, preinvasive, microinvasive, and poorly differentiated neoplasms received the most attention. Specific criteria were recommended and will be discussed. Transitions between neoplastic states were of particular concern. Preinvasive neoplasias of the mouse prostate were recognized as focal, atypical, and progressive lesions. These lesions were designated as mouse prostatic intraepithelial neoplasia (mPIN). Some atypical lesions were identified in mouse models without evidence of progression to malignancy. The panel recommended that mPIN lesions not be given histological grades, but that mPIN be further classified as to the absence or presence of documented associated progression to invasive carcinoma. Criteria for recognizing microinvasion, for classification of
Engelbarts, Matthias; Schuster, Vanessa; Kisser, Ulrich; Sabariego, Carla; Stier-Jarmer, Marita; Coenen, Michaela; Ernst, Benjamin Philipp; Strieth, Sebastian; Harréus, Ulrich; Becker, Sven
The "Comprehensive ICF Core Set for Head and Neck Cancer" (ICF-HNC) is an application of the "International Classification of Functioning, Disability and Health" (ICF), representing the characteristic spectrum of issues in patients with head and neck cancer (HNC). Our primary aim was to evaluate which categories of the ICF-HNC are dealt with by speech and language therapists (SLTs) in Germany, Austria, and Switzerland. The secondary aim was to identify outcome measures used by SLTs to measure the categories of the ICF-HNC in clinical practice. SLTs experienced in the treatment of HNC patients evaluated the categories of the ICF-HNC in a three-round Delphi survey. They were asked whether the listed categories represented issues treated by SLTs in HNC patients, and what outcome measures were used to assess them. Altogether, 31 SLTs completed the survey. 47 of 108 previously selected categories of the ICF-HNC achieved the cut-off value. Out of these, 40.4% were derived from the component "Body Functions", 36.2% from "Body Structures", 12.8% from "Environmental Factors", and 10.6% from "Activities and Participation". Altogether, 82 of the mentioned outcome measures were considered as reasonable from the perspective of SLTs. Of these, only 37 achieved more than 50% approval. This study emphasises the importance of "Body Structures" and "Body Functions" for SLTs in Germany and Switzerland in treating patients with HNC. Moreover, the results highlighted the need to agree on evidence-based outcome measures in speech and language therapy.
Yu, Xinfeng; Shi, Wenna; Zhang, Yuhang; Wang, Xiaohui; Sun, Shiyue; Song, Zhiyu; Liu, Man; Zeng, Qiao; Cui, Shuxiang; Qu, Xianjun
The activation of CXCL12/CXCR4 axis is associated with potential progression of cancer, such as invasion, metastasis and chemoresistance. However, the underlying mechanisms of CXCL12/CXCR4 axis and cancer progression have been poorly explored. We hypothesized that miRNAs might be critical downstream mediators of CXCL12/CXCR4 axis involved in cancer invasion and chemoresistance in CRC. In human CRC cells, we found that the activation of CXCL12/CXCR4 axis promoted epithelial-mesenchymal transition (EMT) and concurrent upregulation of miR-125b. Overexpression of miR-125b robustly triggered EMT and cancer invasion, which in turn enhanced the expression of CXCR4. Importantly, the reciprocal positive feedback loop between CXCR4 and miR-125b further activated the Wnt/β-catenin signaling by targeting Adenomatous polyposis coli (APC) gene. There was a negative correlation of the expression of miR-125b with APC mRNA in paired human colorectal tissue specimens. Further experiments indicated a role of miR-125b in conferring 5-fluorouracil (5-FU) resistance in CRC probably through increasing autophagy both in vitro and in vivo. MiR-125b functions as an important downstream mediator upon the activation of CXCL12/CXCR4 axis that involved in EMT, invasion and 5-FU resistance of CRC. These findings shed a new insight into the role of miR-125b and provide a potential therapeutic target in CRC. PMID:28176874
Cook, John; Oreskes, Naomi; Doran, Peter T.; Anderegg, William R. L.; Verheggen, Bart; Maibach, Ed W.; Carlton, J. Stuart; Lewandowsky, Stephan; Skuce, Andrew G.; Green, Sarah A.; Nuccitelli, Dana; Jacobs, Peter; Richardson, Mark; Winkler, Bärbel; Painting, Rob; Rice, Ken
The consensus that humans are causing recent global warming is shared by 90%-100% of publishing climate scientists according to six independent studies by co-authors of this paper. Those results are consistent with the 97% consensus reported by Cook et al (Environ. Res. Lett. 8 024024) based on 11 944 abstracts of research papers, of which 4014 took a position on the cause of recent global warming. A survey of authors of those papers (N = 2412 papers) also supported a 97% consensus. Tol (2016 Environ. Res. Lett. 11 048001) comes to a different conclusion using results from surveys of non-experts such as economic geologists and a self-selected group of those who reject the consensus. We demonstrate that this outcome is not unexpected because the level of consensus correlates with expertise in climate science. At one point, Tol also reduces the apparent consensus by assuming that abstracts that do not explicitly state the cause of global warming (‘no position’) represent non-endorsement, an approach that if applied elsewhere would reject consensus on well-established theories such as plate tectonics. We examine the available studies and conclude that the finding of 97% consensus in published climate research is robust and consistent with other surveys of climate scientists and peer-reviewed studies.
Purpose - Noting that discussions of public participation and priority setting typically presuppose certain political theories of democracy, the purpose of this paper is to discuss two theories: the consensual and the agonistic. The distinction is illuminating when considering the difference between institutionalized public participation an