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In patients with limited-stage Hodgkin’s disease, ABVD chemotherapy alone resulted in a higher rate of long-term (12-year) survival than either radiation therapy alone or radiation therapy plus ABVD chemotherapy, with significantly fewer late treatment-related deaths.
- CME
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and V. Deshpande
A number of autoimmune diseases that affect diverse organ systems have recently been noted to be related to IgG4 autoantibodies. The authors review the spectrum of IgG4-related disease and the current status of diagnostic and management approaches.
and Others
Resistance to hormone therapy through activation of cellular pathways involving mTOR can develop in postmenopausal hormone-receptor–positive breast cancer. Adding an mTOR inhibitor to an aromatase inhibitor improved outcomes in patients who had disease progression during hormone therapy.
and A. Darzi
Precision medicine uses clinico-pathological indexes and molecular profiling to create diagnostic, prognostic, and therapeutic strategies tailored to the patient. The ultimate success of precision medicine depends on establishing frameworks for regulating, compiling, and interpreting key information.
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This interactive feature presents the case of a 50-year old woman with a history of breast cancer who presented with fatigue and shortness of breath.
Direct the investigation of the case, test your diagnostic and therapeutic skills, and compare your performance with that of others.
and H.J. Hansen
The results indicate there is a tumor-associated antigenic site on a carcinoembryonic antigen common to both entodermally and nonentodermally-derived tissues.
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Reviewing: Lancet Oncol 2012 Jan
Compared with cytology alone, human papillomavirus DNA testing plus cytology led to fewer high-grade cervical lesions 5 years later.
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Reviewing: Nature 2012 Jan 5
Nature 2012 Jan 12
Cancer stem cells and endothelial signaling might point to novel therapies.
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Original Article
Everolimus in Postmenopausal Hormone-Receptor–Positive Advanced Breast Cancer
Endocrine therapy is the cornerstone of treatment for patients with hormone-receptor (HR)–positive advanced breast cancer. In postmenopausal patients, aromatase inhibitors (e.g. letrozole and anastrozole) have become the treatment of choice in first-line therapy.– Unfortunately, not all…
Perspective
Preparing for Precision Medicine
Ms. H. is a 35-year-old woman from Japan who has had a cough for 3 weeks. Her physician sends her for an x-ray and CT scan that reveal an advanced lesion, which a biopsy confirms to be non–small-cell lung cancer. She has never smoked. Can anything be done for her? Had Ms. H.'s cancer been…
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Review Article
Mechanisms of Disease: IgG4-Related Disease
IgG4-related disease is a newly recognized fibroinflammatory condition characterized by tumefactive lesions, a dense lymphoplasmacytic infiltrate rich in IgG4-positive plasma cells, storiform fibrosis, and, often but not always, elevated serum IgG4 concentrations. The disease was not recognized as…
Correspondence
Ultraviolet A and Photosensitivity during Vemurafenib Therapy
To the Editor: Vemurafenib (PLX4032, Zelboraf) is a selective inhibitor of V600E BRAF. In phase 1, 2, and 3 clinical trials involving patients with tumors that have V600E BRAF mutations, vemurafenib was associated with consistent efficacy and improved survival. These data led to approval of…
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Original Article
ABVD Alone versus Radiation-Based Therapy in Limited-Stage Hodgkin's Lymphoma
Twenty years ago, the standard strategy in the case of patients with stage IA or IIA nonbulky Hodgkin's lymphoma included staging by means of laparotomy and subtotal nodal radiation therapy. With this treatment, 70 to 80% of patients were cured, but they remained at risk for premature death from…
- CME
Editorial
Chemotherapy Alone for Early-Stage Hodgkin's Lymphoma
Extensive radiation therapy was the first therapeutic advance in the treatment of early-stage Hodgkin's lymphoma. More recently, less extensive radiation therapy in combination with chemotherapy has resulted in the lowest reported rates of early relapse. The HD10 trial (ClinicalTrials.gov number,…
Original Article
Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer
Neoadjuvant chemotherapy has become established as a reasonable alternative to adjuvant chemotherapy for operable breast cancer, since it can increase the rates of breast-conserving surgery– and decrease the need for complete axillary lymph-node dissection.– Neoadjuvant chemotherapy also offers…
Review Article
Mechanisms of Disease: Iron Overload in Human Disease
Iron-overload disorders are typically insidious, causing progressive and sometimes irreversible end-organ injury before clinical symptoms develop. With a high index of suspicion, however, the consequences of iron toxicity can be attenuated or prevented. Some iron-overload disorders are quite common…
- CME
Images in Clinical Medicine
Hypertrophic Pulmonary Osteoarthropathy and Tripe Palms
Figure 1.
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Editorial
Fighting Fire with Fire: Rekindling the Bevacizumab Debate
The results of the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-40 trial and the GeparQuinto (GBG44) trial, both of which are reported in this issue of the Journal, are particularly timely given the definitive announcement by the Food and Drug Administration (FDA) on November 18,…
Perspective
Selling Bone Marrow — Flynn v. Holder
On December 1, 2011, in Flynn v. Holder, the U.S. Court of Appeals for the Ninth Circuit held that the ban on selling "bone marrow" that is part of the National Organ Transplant Act (NOTA) of 1984 does not encompass "peripheral blood stem cells" obtained through apheresis. This ruling means that…
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Clinical Implications of Basic Research
Closing the Iron Gate
Genetic hemochromatosis is a prevalent iron-overload disease resulting from inadequate production of the iron-regulatory hormone hepcidin. Recently, Preza and colleagues developed an oral, biologically active hepcidin mimic that offers a new experimental approach to treating hemochromatosis and…
Original Article
Neoadjuvant Chemotherapy and Bevacizumab for HER2-Negative Breast Cancer
The efficacy of neoadjuvant chemotherapy, as measured by the rate of pathological complete response (the absence of invasive and intraductal disease in the breast and the axillary lymph nodes), varies according to breast-cancer subtype. When anthracyclines, taxanes, and agents directed against…
- CME
Editorial
RAF around the Edges — The Paradox of BRAF Inhibitors
The recent success of BRAF inhibitors represents a great stride forward for melanoma research. When used to treat patients with melanoma who harbor the BRAF V600E mutation, these inhibitors lead to the remission of even advanced lesions. However, resistance to BRAF inhibitors emerges within months.…
Original Article
Recurrent Somatic DICER1 Mutations in Nonepithelial Ovarian Cancers
Sex cord–stromal tumors and germ-cell tumors account for less than 10% of ovarian cancers. Unlike epithelial ovarian cancers, both sex cord–stromal tumors and germ-cell tumors can also occur in the testicle; testicular germ-cell tumors are the most common cancer in boys and men of European…
Perspective
Painful Inequities — Palliative Care in Developing Countries
When Artur, a former KGB agent in Ukraine, developed prostate cancer that metastasized to his bones, his pain grew so intense that he moved hours away from his family so they would not witness his suffering. "I don't want them to see me cry," he said. Lacking access to the opioid regimens that we…
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Case Records of the Massachusetts General Hospital
Case 2-2012 — A 63-Year-Old Woman with Dyspnea and Rapidly Progressive Respiratory Failure
Presentation of Case. Dr. Susan K. Mathai (Internal Medicine): A 63-year-old woman was admitted to this hospital because of rapidly progressive respiratory failure. The patient had a history of Poland syndrome (agenesis of the right breast, pectoralis muscle, and the third and fourth costal…
A 63-year-old woman was admitted to the hospital because of respiratory failure. She had a history of granulomatous polyangiitis and a breast implant that had recently become painful. Imaging revealed bilateral pulmonary infiltrates and a soft-tissue mass extending from the implant through the chest wall.
Original Article
RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors
The T→A transversion at position 1799 of BRAF (BRAF V600E) is present in approximately 50% of patients with metastatic melanoma. BRAF V600E induces constitutive signaling through the mitogen-activated protein kinase (MAPK) pathway, stimulating cancer-cell proliferation and survival. The clinical…
Patients with melanoma who are treated with a BRAF inhibitor have a high incidence of keratoacanthomas. Most of the tumors have oncogenic mutations in HRAS that probably preceded the use of the BRAF inhibitor. In animal models, second tumors are blocked when a MEK inhibitor is added to the BRAF inhibitor.
Correspondence
Factor XIII in the Treatment of Hemophilia A
To the Editor: Patients with hemophilia A (a deficiency of factor VIII [FVIII]) have spontaneous bleeding because of abnormal thrombin generation, which results in the formation of weak, unstable clots. The formation of these weak clots is also the result of delayed and reduced activation of…
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Correspondence
Generalizing Lung-Cancer Screening Results
To the Editor: The results of the National Lung Screening Trial (NLST) (ClinicalTrials.gov number, NCT00047385) (Aug. 4 issue) showed that screening of high-risk persons is very effective in reducing mortality from lung cancer. Persons with a history of cigarette smoking of at least 30 pack-years…
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Investigators in the Rotterdam Study note that only about 30% of their study population met the entry criteria for the National Lung Screening Trial (NLST). Others at some risk were excluded; whether the 20% reduction in mortality seen in the NLST will transfer to other risk groups is unclear.
