• Low Vitamin D Level Predicts Ulcerative Colitis Relapse
• How the Microbiome Might Promote Metabolic Syndrome and Obesity
• Advising Sinusitis Patients to Use Nasal Irrigation May Help Improve Symptoms
• Antibiotics for Appendicitis: Is Broader Better?
• Metastatic Prostate Cancer on the Rise in the U.S.
• High-Fat Mediterranean Diet Might Cut Risk for CV Events, Breast Cancer, and Diabetes
• Diverticulosis Associated with Diarrhea, Not Constipation
• Near Record for India's Drug Approvals
• Tinnitus Is Common and Often Not Managed According to Guidelines
• Surgery for Meniscal Tears No Better Than Exercise
• Shorter Breast-Feeding Duration among Black Mothers is Linked to Formula in Hospitals
• How Reliable Is Mammographic Assessment of Breast Density?
• Multiple Sclerosis and Trigeminal Neuralgia: A Two-Hit Hypothesis
• Predictors of Long-Term Disability in Multiple Sclerosis
• Modern Breast Surgery: New Techniques, Better Outcomes
Clin Gastroenterol Hepatol 2016 Jun 3
Low Vitamin D Level Predicts Ulcerative Colitis Relapse
Findings support the need for clinical trials of vitamin D supplementation for relapse prevention.
In Crohn disease, low vitamin D level is associated with an increased risk for relapse, and supplementation of vitamin D reduces risk.
To examine the association between vitamin D level and relapse risk in ulcerative colitis, researchers conducted a physician-blinded, prospective study involving 70 patients in clinical remission with ulcerative colitis. Serum levels of vitamin D were measured at the time of a baseline colonoscopy, and patients were followed for 12 months.
Patients who relapsed had a significantly lower mean vitamin D level compared with those who did not relapse (29.5 vs. 50.3 ng/mL).
COMMENT: This study finding supports the need for clinical trials of vitamin D replacement as a method of avoiding relapse in patients with ulcerative colitis. As with Crohn disease, available evidence suggests checking vitamin D levels systematically in patients with ulcerative colitis and replacing vitamin D in those with low levels pending availability of data from such future trials.
Note to readers: At the time NEJM Journal Watch reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S): Gubatan J et al. Low serum vitamin D during remission increases risk of clinical relapse in patients with ulcerative colitis. Clin Gastroenterol Hepatol 2016 Jun 3; [e-pub].
(http://dx.doi.org/10.1016/j.cgh.2016.05.035)
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Nature 2016 Jun 9; 534:213
How the Microbiome Might Promote Metabolic Syndrome and Obesity
Acetate might be the pivotal molecule.
Certain phyla of gut bacteria are more common in patients with metabolic syndrome, obesity, or both (NEJM JW Gen Med Nov 15 2013 and Nature 2013; 500:541). A series of experiments in rats provides strong evidence for metabolic and physiologic mechanisms that explain this correlation.
Consistent with previous study results, relatively large numbers of Firmicutes and small numbers ofBacteroidetes in the rats' feces led to glucose intolerance and obesity. This bacterial milieu was associated with a high concentration of the short-chain fatty acid, acetate, in the gut. High-fat diets promoted this bacterial milieu and increased production of acetate. As acetate travelled through the blood to the brain (or was administered into the ventricular system of the brain), it stimulated the parasympathetic nervous system to increase pancreatic β-cell production of insulin in response to glucose and also to increase production of ghrelin (the “appetite hormone”) in the stomach. Increased caloric intake by the rats, combined with increased circulating insulin, led to weight gain. Eliminating gut bacteria with antibiotics, or interrupting parasympathetic signals to the gut through vagotomy or atropine, eliminated glucose intolerance and weight gain.
COMMENT: If the results of these rat studies prove to be applicable to humans, three new targets for preventing metabolic syndrome and obesity have been identified: modification of the gut microbiome, lowering acetate production in the gut, and parasympathetic blockade.
CITATION(S): Perry RJ et al. Acetate mediates a microbiome–brain–β-cell axis to promote metabolic syndrome. Nature2016 Jun 9; 534:213.
(http://dx.doi.org/10.1038/nature18309)
http://www.ncbi.nlm.nih.gov/pubmed/27279214?access_num=
27279214&link_type=MED&dopt=Abstract
Trajkovski M and Wollheim CB.Microbial signals to the brain control weight. Nature 2016 Jun 9;534:185.
(http://dx.doi.org/10.1038/534185a)
http://www.ncbi.nlm.nih.gov/pubmed/27279209?access_num=
27279209&link_type=MED&dopt=Abstract
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Advising Sinusitis Patients to Use Nasal Irrigation May Help
Improve Symptoms
By Kelly Young, Edited by Susan Sadoughi, MD, and André Sofair, MD, MPH
Patients with chronic or recurrent sinusitis who were advised to use nasal irrigation had a modest reduction in symptoms, according to a CMAJ study.
Researchers randomized roughly 900 patients with chronic or recurrent sinusitis to receive brief advice on using one of four approaches:
- Self-administered daily nasal irrigation with a neti pot
- Self-administered daily steam inhalation
- Nasal irrigation plus steam inhalation
- Usual care
At 3 months' follow-up, nasal irrigation groups had greater reductions in self-reported sinusitis symptoms than did other groups. The benefit was retained at 6 months. The authors estimate that about 13 patients would need to be treated with nasal irrigation for one person to benefit. Nasal irrigation was also associated with improvements in headaches, over-the-counter medication use, and the desire to consult a physician the next time.
For most outcomes, steam inhalation had no effect.
http://www.cmaj.ca/content/early/2016/07/18/cmaj.160362
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Pediatrics 2016 Jul;138:e20154547
Antibiotics for Appendicitis: Is Broader Better?
Extended-spectrum antibiotics offer no advantage over narrower-spectrum antibiotics when treating appendicitis.
Acute appendicitis, a common pediatric condition requiring hospitalization, sometimes requires an extended course of antibiotics for complicated disease. Guidelines for antibiotic selection vary, and some recommend broad-spectrum antibiotics to cover resistant gram-negative organisms, includingPseudomonas aeruginosa.
In a retrospective cohort study, investigators compared failure rates of extended-spectrum (e.g., piperacillin-tazobactam) versus narrow-spectrum (e.g., cefoxitin) antibiotic therapy in nearly 25,000 children aged 3–18 years hospitalized for complicated or uncomplicated appendicitis at 23 U.S. children's hospitals. Treatment failure was defined as 30-day readmission for a related condition. Multivariable analysis was used to control for the possibility that sicker children were more likely to receive broader-spectrum antibiotics.
Empiric broad-spectrum antibiotics were administered in 33% of children with uncomplicated appendicitis and 66% of children with complicated appendicitis. Treatment failure was 2.7% overall and was higher, as expected, in complicated versus uncomplicated disease (6.4% vs. 1.1%). Treatment failure was higher overall in children treated with extended-spectrum antibiotics, and this difference was statistically significant in those with complicated appendicitis (absolute risk difference, 1.9%).
COMMENT; Despite the potential for residual confounding in this analysis, the results suggest that use of extended-spectrum antibiotics did not provide any added benefit with respect to preventing treatment failure in children with appendicitis. Broad-spectrum antibiotics, when used widely, lead to increased bacterial resistance in the community and place patients at greater risk for adverse effects such as infection with Clostridium difficile. These study findings suggest that broader is not better, particularly when treating the common pediatric condition of appendicitis.
CITATION(S): Kronman MP et al. Extended- versus narrower-spectrum antibiotics for appendicitis. Pediatrics 2016 Jul;138:e20154547.
(http://dx.doi.org/10.1542/peds.2015-4547)
http://pediatrics.aappublications.org/content/138/1/e20154547?ijkey=
402aece77ccc55219604916deb4a8515e72e2530&keytype2=tf_ipsecsha
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Metastatic Prostate Cancer on the Rise in the U.S.
By Kelly Young, Edited by David G. Fairchild, MD, MPH, and Lorenzo Di Francesco, MD, FACP, FHM
The incidence of metastatic prostate cancer in the U.S. has markedly increased in recent years, reports a study in Prostate Cancer and Prostatic Diseases.
Researchers used a U.S. cancer registry to identify nearly 800,000 cases of prostate cancer diagnosed from 2004 to 2013. During this time, the annual incidence of all prostate cancers didn’t change, but the incidence of metastatic prostate cancer increased 72% from 1685 to 2890. Men aged 55 to 69 years had the largest increase.
In 2008, the U.S. Preventive Services Task Force began recommending against prostate-specific antigen testing in men aged 75 and older. In 2012, the group recommended against all PSA-based screening.
However, the authors note, “these findings cannot be explained completely by reactions to the USPSTF recommendations alone, as increases in metastatic prostate cancer began in the years before its release. Changes in aggregate screening before the USPSTF ... recommendation, alterations in the biological aggressiveness of prostate cancer or increases in the ascertainment of metastatic disease (through increased sensitivity and utilization of imaging) are plausible explanations.”
http://www.nature.com/pcan/journal/vaop/ncurrent/full/pcan201630a.html
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High-Fat Mediterranean Diet Might Cut Risk for CV Events,
Breast Cancer, and Diabetes
By Amy Orciari Herman, Edited by Jaye Elizabeth Hefner, MD
A Mediterranean diet with unlimited fat intake might lower the risk for cardiovascular events, breast cancer, and diabetes, according to a systematic review in the Annals of Internal Medicine. The authors, however, emphasize that the strength of the evidence was low for many outcomes.
The analysis included 56 controlled or cohort studies in which a Mediterranean diet with unrestricted fat intake was compared with any other diet. Among the findings:
- In one randomized trial, a Mediterranean diet was associated with a 29% reduction in risk for CV events, 57% reduction in breast cancer risk, and 30% reduction in diabetes risk.
- In two randomized trials, there was no association between a Mediterranean diet and all-cause mortality.
- Pooled data from cohort studies suggested a link between high adherence to a Mediterranean diet and reduced risk for total and lung cancer, but no association with breast cancer.
http://annals.org/article.aspx?articleid=2534409
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Clin Gastroenterol Hepatol 2016 Jun 21
Diverticulosis Associated with Diarrhea, Not Constipation
This finding is counter to traditional thinking among clinicians.
Traditional syndromes stemming from diverticulosis include diverticulitis, diverticular bleeding, and symptomatic diverticular disease, with the latter now often described as symptomatic, uncomplicated diverticular disease (SUDD), meaning the presence of symptoms without diverticulitis or colitis. Symptoms included in the definition of SUDD have variably included abdominal pain with or without a change in bowel habits.
To identify gastrointestinal symptoms associated with diverticulosis in the general population, researchers conducted a prospective, population-based study in Stockholm. A random sample of residents were mailed questionnaires about gastrointestinal symptoms and then invited by telephone to undergo colonoscopy. Diverticulosis was identified by colonoscopists, and participants underwent routine colonoscopic biopsy to exclude colitis. Results were as follows:
- Participants who accepted colonoscopy were slightly older and more likely to have irritable bowel syndrome (IBS) compared with noncolonoscopy participants.
- Among 742 participants who underwent colonoscopy, 17.5% had diverticulosis, and all had involvement of at least the sigmoid.
- Diverticulosis prevalence increased with age but was similar between genders and not associated with body-mass index.
- Gastrointestinal symptoms were less common in older patients.
- In all participants, diarrhea-like symptoms, including mushy stools, passing mucus, urgency, and abdominal pain were associated with diverticulosis.
- In participants aged ≥60 years, abdominal pain, mushy stools, high-frequency stools, and incomplete bowel movements were associated with diverticulosis, and abdominal pain located in the left lower quadrant was associated with diverticulosis.
COMMENT: In this population-based study, diverticulosis was associated with diarrhea-like symptoms across all age groups and with left-lower-quadrant abdominal pain and diarrhea-predominant IBS in people over 60. These study results do not establish cause and effect but should be of interest to clinicians, who often traditionally expect diverticulosis to be associated with constipation.
Note to readers: At the time NEJM Journal Watch reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S): Sehgal MEJ et al. Symptomatic diverticulosis is characterized by loose stools. Clin Gastroenterol Hepatol2016 Jun 21; [e-pub]. (http://dx.doi.org/10.1016/j.cgh.2016.06.014)
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Near Record for India's Drug Approvals
FDA has been approving generic drug applications from India's firms at a record pace, with smaller companies like Aurobindo Pharma and Glenmark Pharmaceuticals leading the group. In the last six months of 2015, the FDA approved a record 83 new generic drug applications; in the first half of this year, the pace of approvals slowed to 72 through June, still among the best six-month periods in data going back to 2005. India's increasing importance in the U.S. supply of generic medicines is estimated that it accounted for 31% of all new drug approvals last year.
http://www.bloomberg.com/news/articles/2016-07-20/indian-drug-approvals-near-record-despite-fda-inspection-blitz
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Tinnitus Is Common and Often Not Managed According to Guidelines
By Kelly Young, Edited by William E. Chavey, MD, MS
Roughly 1 in 10 U.S. adults has tinnitus, and physicians aren’t frequently following guidelines in caring for these patients, suggests a study in JAMA Otolaryngology — Head & Neck Surgery.
Of 75,000 surveyed adults, 10% said they experienced tinnitus in the past year. Roughly a quarter of these said their symptoms had lasted longer than 15 years.
Half said they had discussed their tinnitus with their physicians. Of these, 45% said they discussed using medications, despite medication therapy not being recommended for tinnitus. Dietary supplements, such as Ginkgo biloba, were discussed in 8% of cases, despite guidelines recommending against their use.
Neither hearing aids nor cognitive behavioral therapy was commonly discussed (9% and 0.2% respectively); both are recommended treatments.
The authors conclude: “Most patients may not be offered management recommendations consistent with the suggested protocol.”
http://archotol.jamanetwork.com/article.aspx?articleid=2533660
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Surgery for Meniscal Tears No Better Than Exercise
By Kelly Young, Edited by William E. Chavey, MD, MS
For patients with meniscal tears and no osteoarthritis, there is no significant difference between arthroscopic surgery and supervised exercise therapy in terms of knee function, according to a study in The BMJ.
Roughly 140 middle-aged patients with medial degenerative meniscal tear were randomized to receive either arthroscopic partial meniscectomy without postoperative rehabilitation or neuromuscular and strength exercise sessions over 12 weeks.
At 2 years’ follow-up, there was no significant difference between groups in patient-reported pain, symptoms, function, and knee-related quality of life. Roughly 80% of patients in both groups had a clinically meaningful improvement. The exercise group did have greater improvements in muscle strength and in the 6-minute timed hop test at 12 months.
Editorialists call these results, “the latest nail into what should be a sealing coffin” for this surgery.
http://www.bmj.com/content/354/bmj.i3740
http://www.bmj.com/content/354/bmj.i3934
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Pediatrics 2016 Aug; 138:e20152388
Shorter Breast-Feeding Duration among Black Mothers is Linked
to Formula in Hospitals
Compared with white and Hispanic mothers, black mothers had significantly lower breast-feeding intent and initiation rates and shorter breast-feeding duration.
Racial/ethnic disparities in breast-feeding have been described repeatedly, but the factors underlying these disparities are not fully understood.
Researchers analyzed data from 1636 mothers in Baltimore, Maryland, Washington, D.C., and Lake County, Illinois, who were participants in a community-based participatory research study. Factors described as demographic (e.g., maternal age, education, poverty status, relationship status) and non-demographic (e.g., maternal depression, infant prematurity, family history of breast-feeding, formula provided at birth hospital) were tested as potential mediators of the relationship between race/ethnicity (black, white, Hispanic) and breast-feeding intent, initiation, and duration.
Spanish-speaking Hispanic mothers had the highest rates of intent and initiation and longest mean duration of breast-feeding (92%, 91%, 17.1 weeks), followed by English-speaking Hispanic mothers (88%, 90%, 10.4 weeks), white mothers (77%, 78%, 16.5 weeks), and black mothers (57%, 61%, 6.4 weeks). Disparities were mediated by multiple demographic and nondemographic factors, notably: formula given in the birth hospital (mediating shorter breast-feeding duration among black mothers) and a family history of breast-feeding (mediating higher breast-feeding rates for Hispanic mothers).
COMMENT: This study offers an unusually broad look at both demographic and nondemographic factors related to racial/ethnic breast-feeding disparities. The finding that the very short breast-feeding duration among black mothers is mediated largely by formula being offered in birth hospitals inspires me to redouble advocacy efforts for “baby-friendly” (no routine formula given) hospitals in my city. It also reminds me that discussing family traditions can be a way to reinforce breast-feeding for some and encourage the beginning of a new family tradition for others.
CITATION(S): McKinney CO et al. Racial and ethnic differences in breastfeeding. Pediatrics 2016 Aug; 138:e20152388.
(http://dx.doi.org/10.1542/peds.2015-2388)
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Ann Intern Med 2016 Jul 18
How Reliable Is Mammographic Assessment of Breast Density?
Observational analysis of large data set finds wide variation in density assessment by radiologists.
Having mammographically dense breasts impedes performance of screening mammography and has been associated with excess risk for breast cancer. Radiological categories of breast density are: almost entirely fat, scattered fibroglandular densities, heterogeneously dense, or extremely dense (the first two categories defined as “nondense” and the latter two as “dense”). Many states have mandated that information on breast density be communicated to women, focusing attention on supplemental breast imaging. Investigators analyzed prospectively collected observational data from screening mammograms performed between 2011 and 2013 (145,123 women, 216,783 screens; mean age, 58; 80% non-Hispanic white) from 30 U.S. radiology centers (83 radiologists). Data on consecutive screens were available for 45,313 women.
Overall, 37% of mammograms were assessed as dense. Radiologists varied substantially in assigning the four breast density categories. Based on the “dense versus nondense” classification, 25% of radiologists rated <29% of mammograms as dense, while 25% indicated ≥51% were dense. The least variation among ratings occurred for the “extremely dense” category. Among women with consecutive mammograms read by different radiologists, differing density categories between readings were noted in 33%. When stratified as dense versus nondense, consecutive readings were discordant 17% of the time for different radiologists and 10% of the time for the same radiologist.
COMMENT: The substantial variation among radiologists regarding breast density assessment supports previous guidance from the American College of Obstetricians and Gynecologists and others that a screening mammography report of dense breasts should not routinely trigger a recommendation for supplemental breast imaging (NEJM JW Womens Health May 2014 and Obstet Gynecol 2014; 123:910; NEJM JW Womens Health Jun 2015 and Ann Intern Med 2015 May 18; [e-pub]). However, when radiologists report extremely dense breast tissue, clinicians may consider recommending that the subsequent screen include concomitant breast tomosynthesis (NEJM JW Womens Health Jun 2016 and JAMA 2016 Apr 26; [e-pub]).
CITATION(S): Sprague BL et al. Variation in mammographic breast density assessments among radiologists in clinical practice: Findings from a multicenter observational study. Ann Intern Med 2016 Jul 18; [e-pub].
(http://dx.doi.org/10.7326/M15-2934)
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Neurology 2016 May 4
Multiple Sclerosis and Trigeminal Neuralgia: A Two-Hit Hypothesis
Neurovascular compression was observed in a large proportion of patients with MS and TN.
Trigeminal neuralgia (TN) occurs in 2% to 5% of patients with multiple sclerosis (MS). The cause is thought to be a demyelinating plaque within the root entry zone of the pons. Investigators used magnetic resonance imaging (MRI) to determine what proportion of patients with MS-associated TN had neurovascular compression of the nerve.
More than 1500 MS patients were screened to find 37 with TN, with 28 included in the study. Participants underwent 3T MRI with fine cuts through the brainstem and time-of-flight MR angiography. MRI scans detected a demyelinating plaque in the pons on the TN-affected side within 26 of 28 patients. However, 17 of the 28 patients (15 of the 26 with pontine plaque) appeared to have neurovascular compression of the trigeminal nerve with structural changes to the nerve.
COMMENT: TN is an extremely painful condition that can be medically refractory. MS patients are at increased risk for TN. These findings suggest that MS-associated TN may be caused by a double-hit phenomenon, with an MS plaque in the pons and neurovascular compression. The authors present no outcome data for different treatment approaches, but raise the question of whether neurosurgical decompression might be considered. Surgical treatment might be reasonable for patients with evidence of nerve compression who have failed more-conservative measures, such as medical therapy or gamma-knife ablation.
CITATION(S): Truini A et al. A dual concurrent mechanism explains trigeminal neuralgia in patients with multiple sclerosis. Neurology 2016 May 4; [e-pub].
(http://dx.doi.org/10.1212/WNL.0000000000002720)
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Ann Neurol 2016 Jun 1
Predictors of Long-Term Disability in Multiple Sclerosis
A large registry data analysis evaluated baseline elements and treatment effects at 10 years.
The MSBase registry is an international collaboration with data from more than 35,000 multiple sclerosis (MS) patients. Investigators evaluated 2466 of these patients who were prescribed interferon or glatiramer acetate as first-line disease-modifying treatment for relapsing MS and who had expanded disability status scale (EDSS) scores within 12 months of starting the treatment and again about 10 years later.
During the 10 years, the annualized relapse rate (ARR) was 0.36 and EDSS scores increased a median 1.0 steps. There were 39 deaths after follow-up. Drug discontinuations occurred in 58% at a median 4 years and drug switches in 38%; 19% of follow-up was spent untreated.
Predictors of disability included older age at onset, longer disease duration at baseline, and higher ARR. Longer cumulative treatment was associated with lower EDSS at 10 years, with a median 1-point difference per 12 years of treatment versus nontreatment. Pregnancy also had a protective effect (EDSS score reduction by 0.36 with ≥1 pregnancy). Disability was minimal (EDSS, 0–3.0) in 49%, mild (EDSS, 3.0–3.5) in 13%, moderate (EDSS, 4.0–5.5) in 21%, and severe (EDSS, 6.0 and above) in 18%.
COMMENT: These findings confirm that over a 10-year period in the injectable therapy era, about half of MS patients do well with minimal to no physical disability (not considering fatigue, mood, pain, and cognition). However, the other half are likely experiencing MS symptoms and difficulties on a regular basis, and more than a third are experiencing moderate to severe problems. Patients who present at older age and with more-frequent relapses are at heightened risk for worsening disability. Based on this real world dataset, MS therapies do appear to reduce risk for worsening, if patients continue to take their medication long-term.
CITATION(S): Jokubaitis VG et al. Predictors of long-term disability accrual in relapse-onset multiple sclerosis. Ann Neurol 2016 Jun 1; [e-pub].
(http://dx.doi.org/10.1002/ana.24682)
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Modern Breast Surgery: New Techniques, Better Outcomes
Laila Samiian, MD
Individualized approaches feature innovative surgical procedures and improved cosmetic results.
Management of breast cancer has changed dramatically over the past several decades. More women undergoing initial diagnosis and treatment for breast cancer are surviving longer thanks to early detection, targeted therapies, and individualized approaches featuring less-aggressive surgery; moreover, quality of care has benefited from multidisciplinary, team-oriented efforts emphasizing minimally invasive biopsies and better cosmetic outcomes.1,2
IMAGE-GUIDED CORE NEEDLE BIOPSY
In contrast to surgical excision of a breast lesion, image-guided core needle biopsy (CNB) allows definitive preoperative diagnosis and is therefore the most appropriate first step. Although lesions close to the skin, chest wall, or an implant may require surgical excision for diagnosis, most breast lesions are amenable to CNB. If the result is benign, women can avoid potentially deforming surgery. If a malignancy is diagnosed, CNB allows time for evaluation of the extent of disease as well as informed decision making about additional diagnostic and therapeutic options (e.g., genetic testing, plastic surgery consultation, neoadjuvant therapy).
IMAGE-GUIDED BREAST SURGERY
With greater use of breast imaging, more nonpalpable breast cancers are being diagnosed. A variety of techniques can guide the surgical excision of such lesions.
Wire-guided localization (WGL) involves image-guided placement of a hooked wire and is usually performed under local anesthesia in the radiology department on the day of surgery. This procedure can be complicated by wires becoming dislodged or transected or migrating; it also limits the surgeon's ability to conceal the scar in relation to the wire's position.1 In addition to potential scheduling conflicts between radiology and surgery, WGL can be uncomfortable for the patient, who must be transported to the operating room with a wire extruding from her breast.
Radioactive Seed Localization (RSL) entails placement of a 4-mm titanium 125iodine (I) radiolabeled seed into the breast lesion under local anesthesia with mammographic or ultrasound guidance. RSL can be performed in the radiology department a few days before surgery, allowing the seed to stay in place prior to detection by the surgeon with a gamma probe. By facilitating schedule flexibility, RSL reduces the likelihood of delays on the day of surgery. In the operating room, the surgeon uses the gamma probe to localize the lesion and tailor the incision cosmetically. After lumpectomy, the excised specimen is probed and radiographed to visually confirm that it contains the seed and that the resection margins are adequate. Limitations of RSL include possible loss of the seed during surgery and safety issues regarding handling and disposal of the radioactive isotope. Once the seed has been placed in the patient's body, it should be removed within a few days; it will remain radioactive for a relatively long time, as the half-life of125I is 60 days,1 underscoring the importance of medical clearance prior to seed placement to avoid surgery cancellation.
Intraoperative ultrasound (IOUS) allows the surgeon to tailor the incision in a cosmetic manner while performing the lumpectomy with real-time visualization of the tumor. This approach circumvents the need for preoperative localization of a seed or wire. However, IOUS can only be used for lesions (or clips) visible by ultrasound. The excised specimen is evaluated sonographically to confirm that the tumor has been removed and the surgical margins are sufficient. Reexcision of close margins can be accomplished immediately. Compared with intraoperative palpation or WGL, IOUS lessens the likelihood of positive surgical margins.2,3 IOUS requires advanced training and accreditation in breast ultrasound through a certification process offered by the American Society of Breast Surgeons.
ONCOPLASTIC LUMPECTOMY
Breast-conserving surgery using techniques to maintain the normal contour of the breast while completely resecting the tumor is known as oncoplastic lumpectomy (OL). The cavity created by the lumpectomy is repaired by mobilizing the patient's own breast tissue. This approach allows women with larger tumors to undergo breast conservation with better cosmetic results; moreover, OL reduces the likelihood of mastectomy without compromising local control, while minimizing the need for implants and extensive reconstruction. Special attention is required to ensure adequate margins (confirmed with intraoperative radiographic and pathologic evaluation of the specimen). Surgeons performing OL must acquire specialized skills and knowledge of oncologic and plastic surgery techniques in collaboration with a multidisciplinary team.
NIPPLE-SPARING MASTECTOMY
The aim of nipple-sparing mastectomy (NSM) is to preserve the skin envelope overlying the breast, including the skin of the nipple and areola, while removing the breast's glandular elements and the majority of ductal tissue beneath the nipple-areola complex. This surgery can be performed via inconspicuous incisions at the inframammary crease or the periareolar border; combined with immediate reconstruction, it yields excellent cosmetic results. To minimize risk for necrosis or recurrence, the surgeon must remove glandular breast tissue within its anatomic boundaries while maintaining the blood supply to the skin and nipple-areola complex. For cancer cases, intraoperative pathologic evaluation of frozen sections from the nipple margin is recommended. NSM is oncologically safe in selected patients whose cancer is not near or within the skin or nipple (thus, Paget disease is a contraindication).4 This surgical approach is safe for prophylaxis in patients with BRCA mutations.5 However, the procedure may not be appropriate for women who smoke or have large, drooping breasts.
CONTRALATERAL PROPHYLACTIC MASTECTOMY
Rates of contralateral prophylactic mastectomy (CPM) continue to rise among U.S. women. CPM is medically appropriate for patients with high-risk genetic mutations, strong family histories, and high-risk breast disease such as lobular carcinoma in situ. However, many women choose CPM out of fear and anxiety about cancer recurrence or perceived risk for contralateral breast cancer. In survivors of first breast cancers without genetic mutations, 10-year risk for contralateral breast cancer is only 3% to 5%.6 CPM does not prevent the development of metastatic disease and has no survival benefit over breast-conserving surgery or unilateral mastectomy.7 Furthermore, compared with unilateral therapeutic mastectomy, the addition of CPM substantially raises risk for a major surgical complication.8
CONCLUSION:Mounting complexities in the treatment of patients with breast cancer have prompted the development of formal fellowship training in breast surgical oncology. Patients treated by high-volume breast surgeons have better cancer outcomes and greater satisfaction with their care.9,10 A multidisciplinary team-based approach involving procedures performed by well-trained, up-to-date surgeons combined with effective targeted therapies pave the future of this discipline.
Dr. Samiian is Assistant Professor of Surgery and Chief, Section of Breast Surgery at University of Florida College of Medicine–Jacksonville.
CITATION(S):
- Ahmed M et al. Surgical treatment of nonpalpable primary invasive and in situ breast cancer. Nat Rev Clin Oncol 2015 Nov; 12:645. (http://dx.doi.org/10.1038/nrclinonc.2015.161)
PubMed abstract (Free) - Ahmed M and Douek M.Intra-operative ultrasound versus wire-guided localization in the surgical management of non-palpable breast cancers: Systematic review and meta-analysis. Breast Cancer Res Treat 2013 Aug; 140:435.
(http://dx.doi.org/10.1007/s10549-013-2639-2)
PubMed abstract (Free) - Krekel NMA et al. Intraoperative ultrasound guidance for palpable breast cancer excision (COBALT trial): A multicentre, randomised controlled trial. Lancet Oncol 2013 Jan; 14:48.
(http://dx.doi.org/10.1016/S1470-2045(12)70527-2)
PubMed abstract (Free) - De La Cruz L et al. Overall survival, disease-free survival, local recurrence, and nipple–areolar recurrence in the setting of nipple-sparing mastectomy: A meta-analysis and systematic review. Ann Surg Oncol 2015 Oct; 22:3241. (http://dx.doi.org/10.1245/s10434-015-4739-1)
PubMed abstract (Free) - Yao K et al. Nipple-sparing mastectomy in BRCA1/2 mutation carriers: An interim analysis and review of the literature. Ann Surg Oncol 2015 Feb; 22:370. (http://dx.doi.org/10.1245/s10434-014-3883-3)
PubMed abstract (Free) - Nichols HB et al. Declining incidence of contralateral breast cancer in the United States from 1975 to 2006. J Clin Oncol 2011 Apr; 29:1564. (http://dx.doi.org/10.1200/JCO.2010.32.7395)
- Wong SM et al. Growing use of contralateral prophylactic mastectomy despite no improvement in long-term survival for invasive breast cancer. Ann Surg 2016 Apr 12; [e-pub].
(http://dx.doi.org/10.1097/SLA.0000000000001698) - Miller ME et al. Operative risks associated with contralateral prophylactic mastectomy: A single institution experience. Ann Surg Oncol 2013 Dec; 20:4113. (http://dx.doi.org/10.1245/s10434-013-3108-1)
PubMed abstract (Free)Web of Science - Skinner KA et al. Breast cancer: Do specialists make a difference? Ann Surg Oncol 2003 Jul; 10:606.
(http://dx.doi.org/10.1245/ASO.2003.06.017)
PubMed abstract (Free)Web of Science - Waljee JF et al. Patient satisfaction with treatment of breast cancer: Does surgeon specialization matter? J Clin Oncol 2007 Aug 20; 25:3694. (http://dx.doi.org/10.1200/JCO.2007.10.9272)
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