Research Spotlight

Posted March 15th 2016

Improving Treatment of Uncomplicated Diverticulitis: The Old Appendicitis.

James W. Fleshman M.D.

James W. Fleshman, M.D.

Fleshman, J. (2016). “Improving Treatment of Uncomplicated Diverticulitis: The Old Appendicitis.” JAMA Surg. Feb 10. [Epub ahead of print]

Full text of this article.

We continue to struggle with the perfect definition of the indication for an elective operation in the patient with diverticulitis. Simianu et al,1 in their review of the MarketScan Commercial Claims and Encounters Database, have attempted to determine the influences that drive early and late operation on patients with diverticulitis. The group from University of Washington, Swedish Hospital of Seattle, and Virginia Mason Clinic hypothesized that patients commonly undergo early (<3 episodes) elective resection for diverticulitis, especially when the patient is young and responsible for the cost of the operation, which is done laparoscopically, and the preceding episodes have been frequent over a short period. Simianu et al concluded that none of these factors influenced the decision to operate and at least 50% of patients had early operations. The database is a commercial insurance administrative database with all of the limitations of an administrative database. Since these are insured, non–immune-compromised patients with uncomplicated disease, there is an element of selection and bias. The clinical data that normally influence the timing of an operation are not available (computed tomography, white blood cell count, vital signs). In an interesting twist, the definition of an incident of diverticulitis included the use of antibiotics as an outpatient or an inpatient in combination with the code for diverticulitis or the prescription of ciprofloxacin and metronidazole, in combination, in a patient with a previous episode of diverticulitis. This should have increased the number of episodes beyond the 2 cases that have historically been used as an indication for an operation. It did not. There are, therefore, surgeons who persist in operating immediately for more than 1 episode of diverticulitis. This is reminiscent of the way we treated diverticulitis in past years. Why have we not seen an improvement in the consistency of patterns of elective operation? Can we have surgeons who hold fiercely onto autonomy? Why have surgeons in the southern part of the United States continued to operate early on patients with uncomplicated diverticulitis when the patients are not noticeably different from the patients elsewhere? If capitated patients are the least likely to have early operation of the insured patients from the multiple insurance plans represented in this database, it would seem that protocols and peer review are working to reduce unnecessary operations in these patients. There was also an association between open operations and early operation. Could this indicate that resistance to change is contributing to the problem? Older surgeons who have not adopted laparoscopic techniques may also be holding on to the outdated thoughts toward diverticulitis. Assuming that not all patients who underwent operation for early diverticulitis would have eventually have required operation, there is a possibility that we, as surgeons concerned with population health, could reduce the cost of care for these patients by prescribing bulk fiber and encouraging a healthy diet high in vegetables, all of which may help to avoid another episode of diverticulitis. There should never be a financial reason for operating on an early case of diverticulitis. Chronic malignant smoldering diverticulitis, that has caused stricturing and resulted in a difficult operation to remove the disease, usually develops after many more than 3 episodes of diverticulitis. It is my opinion that this should not be considered an excuse for early operation on uncomplicated diverticulitis. Patients usually have symptoms that point to the development of severe disease, such as chronic rather than intermittent pain, incomplete resolution of fever and leukocytosis, and partial obstructive symptoms with each episode. As Simianu et al mentioned in their article,1 time between episodes may be a significant influence on this progression as well. The concerned, informed, and ethical surgeon will adhere to the recommendations proposed by almost all of the national surgical societies to improve the care for patients with diverticulitis and avoid operation on early uncomplicated diverticulitis. This review did not indicate whether there is a difference between academic, major metropolitan community, and small community hospitals in their treatment of diverticulitis. The mobility of patients in search of health care should allow the appropriate care of uncomplicated diverticulitis as the public is better educated in the modern method of treating diverticulitis. As with all interesting studies, there are always more questions than answers at the end of the study. The authors acknowledge that the next step should be a focused prospective approach to answering the number of questions raised from their article. (Excerpt from text.)


Posted March 15th 2016

Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.

Robert G. Mennel M.D.

Robert G. Mennel, M.D.

Harris, L. N., N. Ismaila, L. M. McShane, F. Andre, D. E. Collyar, A. M. Gonzalez-Angulo, E. H. Hammond, N. M. Kuderer, M. C. Liu, R. G. Mennel, C. van Poznak, R. C. Bast and D. F. Hayes (2016). “Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline.” J Clin Oncol. Feb 8. [Epub ahead of print]

Full text of this article.

PURPOSE: To provide recommendations on appropriate use of breast tumor biomarker assay results to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. METHODS: A literature search and prospectively defined study selection sought systematic reviews, meta-analyses, randomized controlled trials, prospective-retrospective studies, and prospective comparative observational studies published from 2006 through 2014. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert panel members used informal consensus to develop evidence-based guideline recommendations. RESULTS: The literature search identified 50 relevant studies. One randomized clinical trial and 18 prospective-retrospective studies were found to have evaluated the clinical utility, as defined by the guideline, of specific biomarkers for guiding decisions on the need for adjuvant systemic therapy. No studies that met guideline criteria for clinical utility were found to guide choice of specific treatments or regimens. RECOMMENDATIONS: In addition to estrogen and progesterone receptors and human epidermal growth factor receptor 2, the panel found sufficient evidence of clinical utility for the biomarker assays Oncotype DX, EndoPredict, PAM50, Breast Cancer Index, and urokinase plasminogen activator and plasminogen activator inhibitor type 1 in specific subgroups of breast cancer. No biomarker except for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was found to guide choices of specific treatment regimens. Treatment decisions should also consider disease stage, comorbidities, and patient preferences.


Posted March 15th 2016

Atrophy of the Heart After Insertion of a Left Ventricular Assist Device and Closure of the Aortic Valve.

William C. Roberts M.D.

William C. Roberts, M.D.

Roberts, W. C., S. A. Hall, J. M. Ko, P. A. McCullough and B. Lima (2016). “Atrophy of the Heart After Insertion of a Left Ventricular Assist Device and Closure of the Aortic Valve.” Am J Cardiol 117(5): 878-879.

Full text of this article.

Described are findings in a 70-year-old man who had heart transplantation 4 years after treatment with a left ventricular assist device, and surgical closure of his previously replaced aortic valve. The result was a totally nonfunctioning left ventricle resulting in severe atrophy.


Posted March 15th 2016

Proliferation of Online Medical Journals.

William C. Roberts M.D.

William C. Roberts, M.D.

Roberts, W. C. (2016). “Proliferation of Online Medical Journals.” Am J Cardiol 117(4): 699-700.

Full text of this article.

Almost daily on my emails there is a new open access (online) medical journal requesting a manuscript from me, or asking that I review a manuscript received by them. During a recent 2-month period, I counted at least 26 heart-related journals (Table 1) and at least 75 non-heart related journals (Table 2). Most do not have a physician as editor and few are included on PubMed. Medicine went from a physician editor of international distinction to a non-physician editor of unknown qualifications. Most of the online journals charge authors to publish their manuscripts and not the readers for reading them, the reverse of hundreds of years of publishing. Some of these online journals not only request reviews from physicians of the submitted manuscripts but also request that physicians recommend names of appropriate reviewers, and some request that physicians actually manage groups of manuscripts as visiting editors. A young investigator might be tempted to submit his/her manuscript to one of the open-access journals after receiving a gracious invitation to do so rather than submit the manuscript to an established journal. I realize that online publishing without print publishing will probably be the future for most present-day print journals but that change has not occurred yet so I recommend staying with the print journals as long as they use that medium. Academic careers will not be built by publishing in the open access journals with non-physician editors.


Posted March 15th 2016

Incidence and Predictive Factors for Recovery of Ovarian Function in Amenorrheic Women in Their 40s Treated With Letrozole.

Joyce O'Shaughnessy M.D.

Joyce O’Shaughnessy, M.D.

Krekow, L. K., B. A. Hellerstedt, R. P. Collea, S. Papish, S. M. Diggikar, R. Resta, S. J. Vukelja, F. A. Holmes, P. K. Reddy, L. Asmar, Y. Wang, P. S. Fox, S. R. Peck and J. O’Shaughnessy (2016). “Incidence and Predictive Factors for Recovery of Ovarian Function in Amenorrheic Women in Their 40s Treated With Letrozole.” J Clin Oncol. Feb 16. [Epub ahead of print]

Full text of this article.

PURPOSE: This prospective study assessed the impact of 2 years of aromatase inhibitor (AI) therapy on the incidence of ovarian function recovery (OFR) in women age 40 to 49 with estrogen receptor-positive breast cancer who were premenopausal at diagnosis and who underwent chemotherapy-induced amenorrhea during adjuvant treatment. PATIENTS AND METHODS: Women age 40 to 49 with estrogen receptor-positive breast cancer who had ceased menstruating with adjuvant cyclophosphamide-based chemotherapy, had postmenopausal serum estradiol (E2), and had received tamoxifen for >/= 1 year were treated with letrozole (2.5 mg) daily for >/= 2 years. Serum follicle-stimulating hormone (FSH) and E2 were measured at baseline and over 2 years. A general linear model was used to assess serial FSH by OFR. Logistic regression was used to assess baseline predictors and OFR. RESULTS: The study enrolled 177 women (145 women age 45 to 49 years and 32 women age 40 to 44 years). Of 173 evaluable patients, 67 (39%; 95% CI, 31% to 46%) regained ovarian function; 11 of these patients (6%; 95% CI, 3% to 10%) resumed menses, and 56 of these patients (32%; 95% CI, 25% to 39%) developed premenopausal E2 without menses. Among AI-naive patients, serial FSH significantly increased over time (P < .001), did not vary significantly by OFR status (P = .55), but showed mild evidence of a decrease after month 12 for those who resumed menses (P = .0989). Age less than 45 years and inhibin B were significant multivariable baseline predictors of OFR. CONCLUSION: These results emphasize the challenge in determining definitive menopause in women with chemotherapy-induced amenorrhea. The risk of OFR during treatment with AIs in amenorrheic women in their 40s is high, and AI therapy should be avoided in these patients.