741. SEOM clinical guidelines in gestational trophoblastic disease (2017).
作者: A Santaballa.;Y García.;A Herrero.;N Laínez.;J Fuentes.;A De Juan.;V Rodriguez Freixinós.;J Aparicio.;A Casado.;E García-Martinez.
来源: Clin Transl Oncol. 2018年20卷1期38-46页
Gestational trophoblastic disease (GTD) is a rare but curable disease. Recent improvements in diagnosis and molecular biology have resulted in changes in staging and treatment. These guidelines provide evidence-based recommendation on how to manage GTD.
742. SEOM clinical guideline for treatment of kidney cancer (2017).
作者: E Gallardo.;M J Méndez-Vidal.;J L Pérez-Gracia.;J M Sepúlveda-Sánchez.;M Campayo.;I Chirivella-González.;X García-Del-Muro.;A González-Del-Alba.;E Grande.;C Suárez.
来源: Clin Transl Oncol. 2018年20卷1期47-56页
The goal of this article is to provide recommendations about the management of kidney cancer. Based on pathologic and molecular features, several kidney cancer variants were described. Nephron-sparing techniques are the gold standard of localized disease. After a randomized trial, sunitinib could be considered in adjuvant treatment in high-risk patients. Patients with advanced disease constitute a heterogeneous population. Prognostic classification should be considered. Both sunitinib and pazopanib are the standard options for first-line systemic therapy in advanced renal cell carcinoma. Based on the results of two randomized trials, both nivolumab and cabozantinib should be considered the standard for second and further lines of therapy. Response evaluation for present therapies is a challenge.
743. [Primary management of endometrial carcinoma. Joint recommendations of the French society of gynecologic oncology (SFOG) and of the French college of obstetricians and gynecologists (CNGOF)].
作者: D Querleu.;E Darai.;F Lecuru.;A Rafii.;E Chereau.;P Collinet.;P Crochet.;H Marret.;E Mery.;L Thomas.;V Villefranque.;A Floquet.;F Planchamp.
来源: Gynecol Obstet Fertil Senol. 2017年45卷12期715-725页
The management of endometrial carcinoma is constantly evolving. The SFOG and the CNGOF decided to jointly update the previous French recommendations (Institut national du cancer 2011) and to adapt to the French practice the 2015 recommendations elaborated at the time of joint European consensus conference with the participation of the three concerned European societies (ESGO, ESTRO, ESMO).
744. [Chimerism analysis after hematopoietic cell transplantation: Guidelines from the Francophone Society of bone marrow transplantation and cellular therapy (SFGM-TC)].
作者: Valérie Dubois.;Mehdi Alizadeh.;Jean Henri Bourhis.;Pascaline Etancelin.;Olivier Farchi.;Christophe Ferrand.;Laure Goursaud.;Isabelle Mollet.;Virginie Renac.;Pauline Varlet.;Ibrahim Yakoub-Agha.;Jacques-Olivier Bay.
来源: Bull Cancer. 2017年104卷12S期S59-S64页
Chimerism analysis is an important step for the patient follow-up after hematopoietic stem cell transplantation. It is used to quantify the donor and the recipient part of a cell population issued from blood or bone marrow sample. In addition to hemogram, this technique is necessary to appreciate the quality of engraftment. The aim of this article is to propose some recommendation about methods, result analysis and therapeutic decision in hematopoietic stem cell transplantation for malignant or non-malignant diseases.
745. Hairy Cell Leukemia, Version 2.2018, NCCN Clinical Practice Guidelines in Oncology.
作者: William G Wierda.;John C Byrd.;Jeremy S Abramson.;Seema Bhat.;Greg Bociek.;Danielle Brander.;Jennifer Brown.;Asher Chanan-Khan.;Steve E Coutre.;Randall S Davis.;Christopher D Fletcher.;Brian Hill.;Brad S Kahl.;Manali Kamdar.;Lawrence D Kaplan.;Nadia Khan.;Thomas J Kipps.;Jeffrey Lancet.;Shuo Ma.;Sami Malek.;Claudio Mosse.;Mazyar Shadman.;Tanya Siddiqi.;Deborah Stephens.;Nina Wagner.;Andrew D Zelenetz.;Mary A Dwyer.;Hema Sundar.
来源: J Natl Compr Canc Netw. 2017年15卷11期1414-1427页
Hairy cell leukemia (HCL) is a rare type of indolent B-cell leukemia, characterized by symptoms of fatigue and weakness, organomegaly, pancytopenia, and recurrent opportunistic infections. Classic HCL should be considered a distinct clinical entity separate from HCLvariant (HCLv), which is associated with a more aggressive disease course and may not respond to standard HCL therapies. Somatic hypermutation in the IGHV gene is present in most patients with HCL. The BRAF V600E mutation has been reported in most patients with classic HCL but not in those with other B-cell leukemias or lymphomas. Therefore, it is necessary to distinguish HCLv from classic HCL. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of classic HCL.
746. NCCN Guidelines Insights: Central Nervous System Cancers, Version 1.2017.
作者: Louis Burt Nabors.;Jana Portnow.;Mario Ammirati.;Joachim Baehring.;Henry Brem.;Nicholas Butowski.;Robert A Fenstermaker.;Peter Forsyth.;Jona Hattangadi-Gluth.;Matthias Holdhoff.;Steven Howard.;Larry Junck.;Thomas Kaley.;Priya Kumthekar.;Jay S Loeffler.;Paul L Moots.;Maciej M Mrugala.;Seema Nagpal.;Manjari Pandey.;Ian Parney.;Katherine Peters.;Vinay K Puduvalli.;John Ragsdale.;Jason Rockhill.;Lisa Rogers.;Chad Rusthoven.;Nicole Shonka.;Dennis C Shrieve.;Allen K Sills.;Lode J Swinnen.;Christina Tsien.;Stephanie Weiss.;Patrick Yung Wen.;Nicole Willmarth.;Mary Anne Bergman.;Anita Engh.
来源: J Natl Compr Canc Netw. 2017年15卷11期1331-1345页
For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options. Research to identify molecular changes that underlie glioma progression has led to the discovery of molecular features that have greater diagnostic and prognostic value than histology. Analyses of these molecular markers across populations from randomized clinical trials have shown that some of these markers are also predictive of response to specific types of treatment, which has prompted significant changes to the recommended treatment options for grade III (anaplastic) gliomas.
747. ACR Appropriateness Criteria® Staging of Pancreatic Ductal Adenocarcinoma.
作者: .;Aliya Qayyum.;Eric P Tamm.;Ihab R Kamel.;Peter J Allen.;Hina Arif-Tiwari.;Victoria Chernyak.;Tamas A Gonda.;Joseph R Grajo.;Nicole M Hindman.;Jeanne M Horowitz.;Harmeet Kaur.;Michelle M McNamara.;Richard B Noto.;Pavan K Srivastava.;Tasneem Lalani.
来源: J Am Coll Radiol. 2017年14卷11S期S560-S569页
Pancreatic adenocarcinoma is associated with poor overall prognosis. Complete surgical resection is the only possible option for cure. As such, increasingly complex surgical techniques including sophisticated vascular reconstruction are being used. Continued advances in surgical techniques, in conjunction with use of combination systemic therapies, and radiation therapy have been suggested to improve outcomes. A key aspect to surgical success is reporting of pivotal findings beyond absence of distant metastases, such as tumor size, location, and degree of tumor involvement of specific vessels associated with potential perineural tumor spread. Multiphase contrast-enhanced multidetector CT and MRI are the imaging modalities of choice for pretreatment staging and presurgical determination of resectability. Imaging modalities such as endoscopic ultrasound and fluorine-18-2-fluoro-2-deoxy-D-glucose imaging with PET/CT are indicated for specific scenarios such as biopsy guidance and confirmation of distant metastases, respectively. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
748. Radiofrequency ablation for hepatic hemangiomas: A consensus from a Chinese panel of experts.
作者: Jun Gao.;Rui-Fang Fan.;Jia-Yin Yang.;Yan Cui.;Jian-Song Ji.;Kuan-Sheng Ma.;Xiao-Long Li.;Long Zhang.;Chong-Liang Xu.;Xin-Liang Kong.;Shan Ke.;Xue-Mei Ding.;Shao-Hong Wang.;Meng-Meng Yang.;Jin-Jin Song.;Bo Zhai.;Chun-Ming Nin.;Shi-Gang Guo.;Zong-Hai Xin.;Jun Lu.;Yong-Hong Dong.;Hua-Qiang Zhu.;Wen-Bing Sun.
来源: World J Gastroenterol. 2017年23卷39期7077-7086页
Recent studies have shown that radiofrequency (RF) ablation therapy is a safe, feasible, and effective procedure for hepatic hemangiomas, even huge hepatic hemangiomas. RF ablation has the following advantages in the treatment of hepatic hemangiomas: minimal invasiveness, definite efficacy, high safety, fast recovery, relatively simple operation, and wide applicability. It is necessary to formulate a widely accepted consensus among the experts in China who have extensive expertise and experience in the treatment of hepatic hemangiomas using RF ablation, which is important to standardize the application of RF ablation for the management of hepatic hemangiomas, regarding the selection of patients with suitable indications to receive RF ablation treatment, the technical details of the techniques, therapeutic effect evaluations, management of complications, etc. A final consensus by a Chinese panel of experts who have the expertise of using RF ablation to treat hepatic hemangiomas was reached by means of literature review, comprehensive discussion, and draft approval.
749. The 2017 Bethesda System for Reporting Thyroid Cytopathology.
The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) established a standardized, category-based reporting system for thyroid fine-needle aspiration (FNA) specimens. The 2017 revision reaffirms that every thyroid FNA report should begin with one of six diagnostic categories, the names of which remain unchanged since they were first introduced: (i) nondiagnostic or unsatisfactory; (ii) benign; (iii) atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS); (iv) follicular neoplasm or suspicious for a follicular neoplasm; (v) suspicious for malignancy; and (vi) malignant. There is a choice of two different names for some of the categories. A laboratory should choose the one it prefers and use it exclusively for that category. Synonymous terms (e.g., AUS and FLUS) should not be used to denote two distinct interpretations. Each category has an implied cancer risk that ranges from 0% to 3% for the "benign" category to virtually 100% for the "malignant" category, and, in the 2017 revision, the malignancy risks have been updated based on new (post 2010) data. As a function of their risk associations, each category is linked to updated, evidence-based clinical management recommendations. The recent reclassification of some thyroid neoplasms as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has implications for the risk of malignancy, and this is accounted for with regard to diagnostic criteria and optional notes. Such notes can be useful in helping guide surgical management.
750. The American Brachytherapy Society consensus statement for accelerated partial-breast irradiation.
作者: Chirag Shah.;Frank Vicini.;Simona F Shaitelman.;Jaroslaw Hepel.;Martin Keisch.;Douglas Arthur.;Atif J Khan.;Robert Kuske.;Rakesh Patel.;David E Wazer.
来源: Brachytherapy. 2018年17卷1期154-170页
Adjuvant radiation after breast-conserving surgery remains the standard-of-care treatment for patients with ductal carcinoma in situ and early-stage invasive breast cancer. Multiple alternatives to standard whole-breast irradiation exist including accelerated partial-breast irradiation (APBI). Therefore, the purpose of this APBI guideline is to provide updated data for clinicians as well as recommendations regarding appropriate patient selection and techniques to deliver APBI.
751. Clinical relevance of molecular diagnostics in gastrointestinal (GI) cancer: European Society of Digestive Oncology (ESDO) expert discussion and recommendations from the 17th European Society for Medical Oncology (ESMO)/World Congress on Gastrointestinal Cancer, Barcelona.
作者: Alexander Baraniskin.;Jean-Luc Van Laethem.;Lucjan Wyrwicz.;Ulrich Guller.;Harpreet S Wasan.;Tamara Matysiak-Budnik.;Thomas Gruenberger.;Michel Ducreux.;Fatima Carneiro.;Eric Van Cutsem.;Thomas Seufferlein.;Wolff Schmiegel.
来源: Eur J Cancer. 2017年86卷305-317页
In the epoch of precision medicine and personalised oncology, which aims to deliver the right treatment to the right patient, molecular genetic biomarkers are a topic of growing interest. The aim of this expert discussion and position paper is to review the current status of various molecular tests for gastrointestinal (GI) cancers and especially considering their significance for the clinical routine use.
752. European Society of Endocrinology Clinical Practice Guidelines for the management of aggressive pituitary tumours and carcinomas.
作者: Gerald Raverot.;Pia Burman.;Ann McCormack.;Anthony Heaney.;Stephan Petersenn.;Vera Popovic.;Jacqueline Trouillas.;Olaf M Dekkers.; .
来源: Eur J Endocrinol. 2018年178卷1期G1-G24页
Pituitary tumours are common and easily treated by surgery or medical treatment in most cases. However, a small subset of pituitary tumours does not respond to standard medical treatment and presents with multiple local recurrences (aggressive pituitary tumours) and in rare occasion with metastases (pituitary carcinoma). The present European Society of Endocrinology (ESE) guideline aims to provide clinical guidance on diagnosis, treatment and follow-up in aggressive pituitary tumours and carcinomas.
753. JLCS medical practice guidelines for thymic tumors: summary of recommendations.
作者: Kohei Yokoi.;Kazuya Kondo.;Kiminori Fujimoto.;Masaki Hara.;Yoshihisa Kadota.;Koji Kawaguchi.;Hideo Kunitoh.;Yoshihiro Matsuno.;Jun Nakajima.;Makoto Nishio.;Kazuhiko Ogawa.;Mitsugu Omasa.
来源: Jpn J Clin Oncol. 2017年47卷12期1119-1122页
The Guideline Committee of the Japan Lung Cancer Society (JLCS) for Thymic Tumors published the Medical Practice Guideline for Thymic Tumors in Japanese as Chapter 3 of the Medical Practice Guidelines for Lung Cancers according to evidence-based medicine in December 2016. This medical practice guideline is the first for thymic epithelial tumors in Japan, and comprises a set of recommendations covering clinical diagnosis, treatment and pathological diagnosis. Thymic epithelial tumors include thymoma, thymic carcinoma and thymic neuroendocrine tumor. The recommendations for clinical diagnosis concern detection of the symptoms, blood and serum tests according to clinical presentation, essential imaging for differential diagnosis and staging, and the necessity and methods of definitive diagnosis. The recommendations for treatment are dependent on tumor stage and recurrence status, and the treatment modalities included surgery, radiation therapy, chemotherapy and multimodality therapy. Those for pathological diagnosis deal with the handing methods of resected specimen and essential reporting contents for pathological diagnosis. Since data from large-scale analyses or clinical studies of thymic epithelial tumor are limited due to its low prevalence, the relevant recommendations and grading were based on available reported evidence and expert opinions as well as diagnostic methods and treatments commonly used in Japan. This report summarizes the recommendations concerning each topic addressed by this JLCS guideline for thymic tumors.
754. Role of Bone-Modifying Agents in Metastatic Breast Cancer: An American Society of Clinical Oncology-Cancer Care Ontario Focused Guideline Update.
作者: Catherine Van Poznak.;Mark R Somerfield.;William E Barlow.;J Sybil Biermann.;Linda D Bosserman.;Mark J Clemons.;Sukhbinder K Dhesy-Thind.;Melissa S Dillmon.;Andrea Eisen.;Elizabeth S Frank.;Reshma Jagsi.;Rachel Jimenez.;Richard L Theriault.;Theodore A Vandenberg.;Gary C Yee.;Beverly Moy.
来源: J Clin Oncol. 2017年35卷35期3978-3986页
Purpose To update, in collaboration with Cancer Care Ontario (CCO), key recommendations of the American Society of Clinical Oncology (ASCO) guideline on the role of bone-modifying agents (BMAs) in metastatic breast cancer. This focused update addressed the new data on intervals between dosing and the role of BMAs in control of bone pain. Methods A joint ASCO-CCO Update Committee conducted targeted systematic literature reviews to identify relevant studies. Results The Update Committee reviewed three phase III noninferiority trials of dosing intervals, one systematic review and meta-analysis of studies of de-escalation of BMAs, and two randomized trials of BMAs in control of pain secondary to bone metastases. Recommendations Patients with breast cancer who have evidence of bone metastases should be treated with BMAs. Options include denosumab, 120 mg subcutaneously, every 4 weeks; pamidronate, 90 mg intravenously, every 3 to 4 weeks; or zoledronic acid, 4 mg intravenously every 12 weeks or every 3 to 4 weeks. The analgesic effects of BMAs are modest, and they should not be used alone for bone pain. The Update Committee recommends that the current standard of care for supportive care and pain management-analgesia, adjunct therapies, radiotherapy, surgery, systemic anticancer therapy, and referral to supportive care and pain management-be applied. Evidence is insufficient to support the use of one BMA over another. Additional information is available at www.asco.org/breast-cancer-guidelines and www.asco.org/guidelineswiki .
755. Role of Bone-Modifying Agents in Metastatic Breast Cancer: An American Society of Clinical Oncology-Cancer Care Ontario Focused Guideline Update Summary.756. Clinical practice guidelines for the diagnosis and management of melanoma: melanomas that lack classical clinical features.
作者: Victoria J Mar.;Alex J Chamberlain.;John W Kelly.;William K Murray.;John F Thompson.
来源: Med J Aust. 2017年207卷8期348-350页
A Cancer Council Australia multidisciplinary working group is currently revising and updating the 2008 evidence-based clinical practice guidelines for the management of cutaneous melanoma. While there have been many recent improvements in treatment options for metastatic melanoma, early diagnosis remains critical to reducing mortality from the disease. Improved awareness of the atypical presentations of this common malignancy is required to achieve this. A chapter of the new guidelines was therefore developed to aid recognition of atypical melanomas. Main recommendations: Because thick, life-threatening melanomas may lack the more classical ABCD (asymmetry, border irregularity, colour variegation, diameter > 6 mm) features of melanoma, a thorough history of the lesion with regard to change in morphology and growth over time is essential. Any lesion that is changing in morphology or growing over a period of more than one month should be excised or referred for prompt expert opinion. Changes in management as a result of the guidelines: These guidelines provide greater emphasis on improved recognition of the atypical presentations of melanoma, in particular nodular, desmoplastic and acral lentiginous subtypes, with particular awareness of hypomelanotic and amelanotic lesions.
757. International consensus guidelines for scoring the histopathological growth patterns of liver metastasis.
作者: Pieter-Jan van Dam.;Eric P van der Stok.;Laure-Anne Teuwen.;Gert G Van den Eynden.;Martin Illemann.;Sophia Frentzas.;Ali W Majeed.;Rikke L Eefsen.;Robert R J Coebergh van den Braak.;Anthoula Lazaris.;Maria Celia Fernandez.;Boris Galjart.;Ole Didrik Laerum.;Roni Rayes.;Dirk J Grünhagen.;Michelle Van de Paer.;Yves Sucaet.;Hardeep Singh Mudhar.;Michael Schvimer.;Hanna Nyström.;Mark Kockx.;Nigel C Bird.;Fernando Vidal-Vanaclocha.;Peter Metrakos.;Eve Simoneau.;Cornelis Verhoef.;Luc Y Dirix.;Steven Van Laere.;Zu-Hua Gao.;Pnina Brodt.;Andrew R Reynolds.;Peter B Vermeulen.
来源: Br J Cancer. 2017年117卷10期1427-1441页
Liver metastases present with distinct histopathological growth patterns (HGPs), including the desmoplastic, pushing and replacement HGPs and two rarer HGPs. The HGPs are defined owing to the distinct interface between the cancer cells and the adjacent normal liver parenchyma that is present in each pattern and can be scored from standard haematoxylin-and-eosin-stained (H&E) tissue sections. The current study provides consensus guidelines for scoring these HGPs.
759. Evidence-based clinical practice guideline for the evaluation of potentially malignant disorders in the oral cavity: A report of the American Dental Association.
作者: Mark W Lingen.;Elliot Abt.;Nishant Agrawal.;Anil K Chaturvedi.;Ezra Cohen.;Gypsyamber D'Souza.;JoAnn Gurenlian.;John R Kalmar.;Alexander R Kerr.;Paul M Lambert.;Lauren L Patton.;Thomas P Sollecito.;Edmond Truelove.;Malavika P Tampi.;Olivia Urquhart.;Laura Banfield.;Alonso Carrasco-Labra.
来源: J Am Dent Assoc. 2017年148卷10期712-727.e10页
An expert panel convened by the American Dental Association (ADA) Council on Scientific Affairs and the Center for Evidence-Based Dentistry conducted a systematic review and formulated clinical recommendations to inform primary care clinicians about the potential use of adjuncts as triage tools for the evaluation of lesions, including potentially malignant disorders (PMDs), in the oral cavity.
760. Technical aspects of endoscopic ultrasound (EUS)-guided sampling in gastroenterology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Guideline - March 2017.
作者: Marcin Polkowski.;Christian Jenssen.;Philip Kaye.;Silvia Carrara.;Pierre Deprez.;Angels Gines.;Gloria Fernández-Esparrach.;Pierre Eisendrath.;Guruprasad P Aithal.;Paolo Arcidiacono.;Marc Barthet.;Pedro Bastos.;Adele Fornelli.;Bertrand Napoleon.;Julio Iglesias-Garcia.;Andrada Seicean.;Alberto Larghi.;Cesare Hassan.;Jeanin E van Hooft.;Jean-Marc Dumonceau.
来源: Endoscopy. 2017年49卷10期989-1006页
For routine EUS-guided sampling of solid masses and lymph nodes (LNs) ESGE recommends 25G or 22G needles (high quality evidence, strong recommendation); fine needle aspiration (FNA) and fine needle biopsy (FNB) needles are equally recommended (high quality evidence, strong recommendation).When the primary aim of sampling is to obtain a core tissue specimen, ESGE suggests using 19G FNA or FNB needles or 22G FNB needles (low quality evidence, weak recommendation).ESGE recommends using 10-mL syringe suction for EUS-guided sampling of solid masses and LNs with 25G or 22G FNA needles (high quality evidence, strong recommendation) and other types of needles (low quality evidence, weak recommendation). ESGE suggests neutralizing residual negative pressure in the needle before withdrawing the needle from the target lesion (moderate quality evidence, weak recommendation).ESGE does not recommend for or against using the needle stylet for EUS-guided sampling of solid masses and LNs with FNA needles (high quality evidence, strong recommendation) and suggests using the needle stylet for EUS-guided sampling with FNB needles (low quality evidence, weak recommendation).ESGE suggests fanning the needle throughout the lesion when sampling solid masses and LNs (moderate quality evidence, weak recommendation).ESGE equally recommends EUS-guided sampling with or without on-site cytologic evaluation (moderate quality evidence, strong recommendation). When on-site cytologic evaluation is unavailable, ESGE suggests performance of three to four needle passes with an FNA needle or two to three passes with an FNB needle (low quality evidence, weak recommendation).For diagnostic sampling of pancreatic cystic lesions without a solid component, ESGE suggests emptying the cyst with a single pass of a 22G or 19G needle (low quality evidence, weak recommendation). For pancreatic cystic lesions with a solid component, ESGE suggests sampling of the solid component using the same technique as in the case of other solid lesions (low quality evidence, weak recommendation).ESGE does not recommend antibiotic prophylaxis for EUS-guided sampling of solid masses or LNs (low quality evidence, strong recommendation), and suggests antibiotic prophylaxis with fluoroquinolones or beta-lactam antibiotics for EUS-guided sampling of cystic lesions (low quality evidence, weak recommendation). ESGE suggests that evaluation of tissue obtained by EUS-guided sampling should include histologic preparations (e. g., cell blocks and/or formalin-fixed and paraffin-embedded tissue fragments) and should not be limited to smear cytology (low quality evidence, weak recommendation).
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