Learning Harmony: Medical Student Reflections on the Intersection of the Arts & Humanities and Medicine, A Mixed Methods Study.

Background: The arts and humanities form a critical part of medical education. In this study, we explore medical students' reflections following an arts and humanities experience. An intensive day and a half long program focused on music and reflection was designed for first-year students at Harvard Medical School. Methods: Students completed an evaluation of the experience with both open-ended and Likert scale questions. Data were analyzed using a mixed methods approach. Descriptive statistics were used to analyze quantitative data and inductive content analysis for qualitative data. Results: 168 first-year medical and dental students participated in the activity. Survey response rate was 73% (n =122). Quantitatively, the overall quality of the experience was assessed at a mean value of 4.86 points (SD = 0.37 points) out of a maximum of 5, with 5 being excellent. The qualitative evaluation illustrated how the arts and humanities experience encouraged students to reflect on their leadership and doctoring skills, taking a holistic approach to their medical education, and integrating the lessons of the arts and humanities into their medical practice. Conclusion: The arts and humanities program encouraged student reflection on profound questions in medicine related to empathy, vulnerability, and authenticity. This experience broadened students' perspectives regarding the relationship between medicine and the arts and humanities.

Management of Lobular Neoplasia Diagnosed by Core Biopsy.

Lobular neoplasia (LN) involves proliferative changes within the breast lobules. LN is divided into lobular carcinoma in situ (LCIS) and atypical lobular hyperplasia (ALH). LCIS can be further subdivided into three subtypes: classic LCIS, pleomorphic LCIS, and LCIS with necrosis (florid type). Because classic LCIS is now considered as a benign etiology, current guidelines recommend close follow-up with imaging versus surgical excision. The goal of our study was to determine if the diagnosis of classic LN on core needle biopsy (CNB) merits surgical excision. This is a retrospective, observational study conducted at Mount Auburn Hospital, Cambridge, MA, from May 17, 2017, through June 30, 2020. We reviewed the data of breast biopsies conducted at our hospital over this period and included patients who were diagnosed with classic LN (LCIS and/or ALH) and excluded patients having any other atypical lesions on CNB. All known cancer patients were excluded. Of the 2707 CNBs performed during the study period, we identified 68 women who were diagnosed with ALH or LCIS on CNB. CNB was performed for an abnormal mammogram in the majority of patients (60; 88%) while 7(10.3%) had an abnormal breast magnetic resonance imaging study (MRI), and 1 had an abnormal ultrasound (US). A total of 58 patients (85%) underwent excisional biopsy, of which 3 (5.2%) showed malignancy, including 2 cases of DCIS and 1 invasive carcinoma. In addition, there was 1 case (1.7%) with pleomorphic LCIS and 11 cases with ADH (15.5%). The management of LN found on core biopsy is evolving, with some advocating surgical excision and others recommending observation. Our data show a change in diagnosis with excisional biopsy in 13 (22.4%) of patients with 2 cases of DCIS, 1 invasive carcinoma, 1 pleomorphic LCIS, and 9 cases of ADH, diagnosed on excisional biopsy. While ALH and classic LCIS are considered benign, the choice of ongoing surveillance versus excisional biopsy should be made with shared decision making with the patient, with consideration of personal and family history, as well as patient preferences.

Sleepless and Spent in Survivorship: Fatigue and Insomnia in Breast Cancer Survivors.

BACKGROUND: It is estimated that there are 3.8 million breast cancer survivors in the United States. Addressing survivors' post-treatment needs is critical to providing quality healthcare. METHODS: A standardized questionnaire for breast cancer survivors was employed to assess the health status, challenges, and concerns of our breast cancer patients at their survivorship visits, which were conducted 4 months after surgery. All patients were seen in the breast center at one community hospital over a 6-year period. RESULTS: Responses to a standardized questionnaire that was administered to 505 consecutive breast cancer patients at their survivorship visits 4 months after surgery were evaluated. The most striking finding was that 35% reported symptoms of insomnia, 26% had persistent fatigue, and 19% experienced fatigue that interfered with their usual activities. There was a significant association between symptoms of insomnia and radiation treatment (P = .004), pain (P < .001), hormone therapy (P < .01), and side effects of hormone therapy (P < .0001). There was also a significant association between fatigue and pain (P < .001) as well as side effects from hormone treatment (P = .0036). CONCLUSIONS: Over a third (35%) of breast cancer patients suffer from insomnia, while over a quarter (26%) complain of fatigue at their survivorship assessments. Contributing factors include radiation treatment, pain, and hormonal therapy. Careful assessment and treatment of fatigue and symptoms of insomnia in breast cancer patients is needed to improve quality of life for survivors.

Effective Surveillance of High-Risk Women.

BACKGROUND: This study addresses the effectiveness of risk models and screening breast magnetic resonance imaging (MRI) in women who have atypical hyperplasia (AH), lobular carcinoma in situ (LCIS), or a family history of breast cancer, but not a genetic mutation. PATIENTS AND METHODS: A retrospective review of 444 women who had 458 breast screening MRIs at a community teaching hospital over a 12-month period between March 25, 2014 and March 31, 2015 was performed. The patients underwent high risk screening with breast MRIs alternating with mammograms every 6 months. After excluding patients with prior breast or ovarian cancer, genetic mutations, and chest wall radiation, 200 remaining patients constituted the study cohort. Over the following 5 years, the patients were screened with MRIs alternating with mammograms every 6 months. A total of 961 total MRI screenings were performed over the entire 5-year period of the study. RESULTS: A total of 200 women fit the study criteria. Of these 103 had a prior history of AH or LCIS. Over the 5-year period, 60 women dropped out of the screening regimen, 6 patients were diagnosed with breast cancer on screening MRIs, and 2 additional patients were diagnosed with breast cancer on screening mammograms. Surprisingly, the highest Tyrer-Cuzick (T-C) scores did not correlate with increased development of breast cancers in our population. CONCLUSIONS: This study shows that there is wide variation in the results of risk assessment models. Risk models may overestimate breast cancer risk, suggesting that re-evaluation of current risk assessment and screening protocols is warranted.

Acceptability of a patient decision aid for women aged 70 and older with stage I, estrogen receptor-positive, HER2-negative breast cancer.

OBJECTIVES: A comprehensive decision aid (DA) for women ≥70 years with Stage I ER+/HER2-negative breast cancer was developed to support locoregional and systemic treatment decision-making. We aimed to test the acceptability of this novel DA in women newly-diagnosed with breast cancer. MATERIALS AND METHODS: Women ≥70 diagnosed with Stage I, ER+/HER2- breast cancer were recruited from three Boston-area hospitals. They underwent baseline interviews after initial surgical consultation, reviewed the DA, and were surveyed <2 weeks later to determine DA acceptability (e.g., was it helpful?), changes in decisional conflict, stage of decision-making, and knowledge. Participants could optionally complete a three-month follow-up. Paired t-tests and McNemar's tests were used for statistical comparisons, and thematic analyses were conducted to identify themes in participants' open-ended comments. RESULTS: Thirty-three of 56 eligible patients approached completed the baseline and acceptability surveys, and 25 completed the three-month follow-up. Participants' mean age was 74.7 years (±3.8). Nearly all participants (n = 31, 94%) strongly agreed that the DA was helpful and felt that the DA prepared them for treatment decision-making, with a mean decision preparation score of 4.1 (out of 5.0); 6% (n = 2) found it very anxiety provoking. Knowledge improved with a mean of 9.0 out of 14 questions correct at baseline to 10.6 correct on the acceptability survey (p < 0.0001). CONCLUSIONS: A DA tailored to women ≥70 with Stage I, ER+, HER2- breast cancer increased knowledge and was perceived to be helpful by older women. A randomized controlled trial is needed to evaluate its efficacy.

Longitudinal study of breast cancer risk markers.

Atypical hyperplasia (AH) and lobular carcinoma in situ (LCIS) are markers for an increased risk of breast cancer, yet outcomes for these diagnoses are not well-documented. In this study, all breast biopsies performed for radiologic abnormalities over a 10-year period were reviewed. Patients with AH or LCIS were followed for an additional 10 years to assess subsequent rates of cancer diagnosis. Long-term follow-up showed that 25 (7.8%) patients with AH and 5 patients with LCIS (5.7%) developed breast cancer over the follow-up period, a lower rate of breast cancer development than predicted by risk models.

Developing a patient decision aid for women aged 70 and older with early stage, estrogen receptor positive, HER2 negative, breast cancer.

OBJECTIVES: Since women ≥70 years with early stage, estrogen receptor positive (ER+), HER2 negative breast cancer face several preference-sensitive treatment decisions, the investigative team aimed to develop a pamphlet decision aid (DA) for such women. MATERIALS AND METHODS: The content of the DA was informed by literature review, international criteria, and expert feedback, and includes information on benefits and risks of lumpectomy versus mastectomy, lymph node surgery, radiotherapy after lumpectomy, and endocrine therapy. It considers women's overall health and was written using low literacy principles. Women from two Boston-based hospitals who were diagnosed in the past 6-24 months were recruited to provide feedback on the DA and its acceptability. The DA was iteratively revised based on their qualitative input. RESULTS: Of 48 eligible women contacted, 35 (73%) agreed to participate. Their mean age was 74.3 years; 33 (94%) were non-Hispanic white; and 24 (67%) were college graduates. Overall, 26 (74%) thought the length of the DA was just right, 29 (83%) thought all or most of the information was clear, 32 (91%) found the DA helpful, and 33 (94%) would recommend it. In open ended comments, participants noted that the DA was clear, well-organized, and would help women prepare for and participate in treatment decision-making. CONCLUSIONS: The investigative team developed a novel breast cancer treatment DA that is acceptable to women ≥70 years with a history of ER+, HER2-, early stage breast cancer. Next, the DA's efficacy needs to be tested with diverse older women newly diagnosed with breast cancer.

Leadership in American Surgery: Women are Rising to the Top.

OBJECTIVE: To celebrate the increasing representation of women as leaders in American surgery and provide suggestions for increasing diversity in leadership. BACKGROUND: Women were barred from entering the practice of medicine or surgery until the mid 1800's when Elizabeth Blackwell led the way as the first woman admitted to medical school. Although the numbers of women practicing medicine and surgery have increased exponentially since Dr Blackwell graduated, the number of women in leadership positions has remained low until recently. METHODS: An analysis of the literature on the history of women in surgery and the websites of the major surgical societies. RESULTS: More women are now rising to leadership positions in surgery, both in academics and within surgical organizations. The American College of Surgeons and many other surgical societies, as well as an increasing number of academic departments of surgery have realized that women can be inspiring and capable leaders. However, increasing the number of under-represented minority women in leadership positions remains an opportunity for improvement. CONCLUSIONS: Great progress has been made in the advancement of women into leadership positions in surgery. To continue this trend and increase the number of under-represented minority women in surgery will require attention to recruitment, mentorship, and sponsorship.

What is the Role of the Arts in Medical Education and Patient Care? A Survey-based Qualitative Study.

To inform medical education reform efforts, we systematically collected information on the level of arts and humanities engagement in our medical school community. Attitudes regarding incorporating arts and humanities-based teaching methods into medical education and patient care were also assessed. An IRB-approved survey was electronically distributed to all faculty, residents, fellows, and students at our medical school. Questions focused on personal practice of the arts and/or humanities, as well as perceptions of, and experience with formally incorporating these into medical teaching. Of 13,512 community members surveyed, 2,775 responded (21% overall response rate). A majority of respondents agreed or strongly agreed that medical education and patient care could be "enhanced" by the integration of the arts (67% and 74% respectively). There was enthusiastic support for the creation of a formal program in the arts at our medical school (72 %). Integration of the arts into medical education may have a role in improving the quality of medical training and would likely be well received by teachers and learners.

Evidence for the role of bevacizumab in the treatment of advanced metastatic breast cancer: a review.

Angiogenesis inhibitors may provide a new approach to the treatment of metastatic breast cancer. Bevacizumab is a monoclonal antibody against pathologic angiogenesis. A pivotal study (ECOG 2100) showed that bevacizumab in combination with paclitaxel increased progression-free survival for patients with metastatic breast cancer by 6 months. Subsequently, several clinical trials have shown that the combination of bevacizumab with a taxane can improve disease-free survival but does not prolong overall survival. While generally well tolerated, bevacizumab is potentially toxic for some patients who develop hypertension, proteinuria, bleeding, impaired wound healing, bowel perforation or thromboembolic events. Here, we review the current evidence for the use of bevacizumab in breast cancer and ongoing studies that address the questions of how to optimize regimens and schedules for the use of anti-angiogenic agents and the identification of those patients who would benefit the most from treatment with regimens that include antiangiogenic therapy.

Nipple-sparing mastectomy: evaluation of patient satisfaction, aesthetic results, and sensation.

The purpose of this study is to describe our experience with nipple-sparing mastectomy and immediate reconstruction, with particular attention to patient satisfaction, aesthetic results, and nipple sensation. Immediate reconstruction was performed on 17 breasts in 10 patients, using either implants or autologous tissue flaps. Assessment of outcomes was performed through patient interviews, a self-reported patient satisfaction survey and review of postoperative photographs. Short-term complications included partial loss of the nipple-areolar complex requiring debridement (n = 3) and removal of the nipple-areolar complex (n = 2) for occult ductal carcinoma in situ. While all patients with completed breast reconstructions were satisfied with their general reconstructive experience, 6 of 9 patients were aesthetically satisfied with their breast reconstruction. Postoperative nipple sensation was reported in 75% of patients, although sensation was low (mean of 2.8 of 10). As nipple-sparing mastectomy is becoming an increasing patient preference, preoperative discussion needs to address expectations, aesthetic satisfaction, and long-term cancer control.

Urinary metalloproteinases: noninvasive biomarkers for breast cancer risk assessment.

Matrix metalloproteinases (MMP) and a disintegrin and metalloprotease 12 (ADAM 12) can be detected in the urine of breast cancer patients and provide independent prediction of disease status. To evaluate the potential of urinary metalloproteinases as biomarkers to predict breast cancer risk status, urine samples from women with known risk marker lesions, atypical hyperplasia and lobular carcinoma in situ (LCIS), were analyzed. Urine samples were obtained from 148 women: 44 women with atypical hyperplasia, 24 women with LCIS, and 80 healthy controls. MMP analysis was done using gelatin zymography and ADAM 12 analysis was done via immunoblotting with monospecific antibodies and subsequent densitometric measurement. Positive urinary MMP-9 levels indicated a 5-fold risk of atypical hyperplasia and >13-fold risk of LCIS compared with normal controls. Urinary ADAM 12 levels were significantly elevated in women with atypical hyperplasia and LCIS from normal controls, with receiver operating characteristic curve analysis showing an area under the curve of 0.914 and 0.950, respectively. To assess clinical applicability, a predictive index was developed using ADAM 12 in conjunction with Gail risk scores for women with atypia. Scores above 2.8 on this ADAM 12-Gail risk prediction index score are predictive of atypical hyperplasia (sensitivity, 0.976; specificity, 0.977). Our data suggest that the noninvasive detection and analysis of urinary ADAM 12 and MMP-9 provide important clinical information for use as biomarkers in the identification of women at increased risk of developing breast cancer.

ADAM 12 cleaves extracellular matrix proteins and correlates with cancer status and stage.

ADAM 12 is a member of a family of disintegrin-containing metalloproteases that have been implicated in a variety of diseases including Alzheimer's disease, arthritis, and cancer. We purified ADAM 12 from the urine of breast cancer patients via Q-Sepharose anion exchange and gelatin-Sepharose affinity chromatography followed by protein identification by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Four peptides were identified that spanned the amino acid sequence of ADAM 12. Immunoblot analysis using ADAM 12-specific antibodies detected an approximately 68-kDa band identified as the mature form of ADAM 12. To characterize catalytic properties of ADAM 12, full-length ADAM 12-S was expressed in COS-7 cells and purified. Substrate specificity studies demonstrated that ADAM 12-S degrades gelatin, type IV collagen, and fibronectin but not type I collagen or casein. Gelatinase activity of ADAM 12 was completely abrogated by zinc chelators 1,10-phenanthroline and EDTA and was partially inhibited by the hydroxamate inhibitor Marimastat. Endogenous matrix metalloprotease inhibitor TIMP-3 inhibited activity. To validate our initial identification of this enzyme in human urine, 117 urine samples from breast cancer patients and controls were analyzed by immunoblot. The majority of samples from cancer patients were positive for ADAM 12 (67 of 71, sensitivity 0.94) compared with urine from controls in which ADAM 12 was detected with significantly lower frequency. Densitometric analyses of immunoblots demonstrated that ADAM 12 protein levels were higher in urine from breast cancer patients than in control urine. In addition, median levels of ADAM 12 in urine significantly increased with disease progression. These data demonstrate for the first time that ADAM 12 is a gelatinase, that it can be detected in breast cancer patient urine, and that increased urinary levels of this protein correlate with breast cancer progression. They further support the possibility that detection of urinary ADAM 12 may prove useful in the development of noninvasive diagnostic and prognostic tests for breast and perhaps other cancers.

K+ channel inhibition accelerates intestinal epithelial cell wound healing.

Restitution is the process by which superficial interruptions in the gastrointestinal mucosa are repaired by the flattening and spreading of epithelial cells surrounding the damage. During this process, mucosal epithelial cells undergo extensive reshaping and cytoskeletal remodeling. K(+) channels, located primarily on the basolateral surface of gut epithelial cells, are central to both actin polymerization, via their control of membrane potential, and cell volume regulation. We questioned whether K(+) channels are involved in restitution using an in vitro model of intestinal epithelium, monolayers of the human colon carcinoma cell line T84. We report that pharmacologic K(+) channel inhibition accelerates wound healing in T84 cell monolayers. Both Ca(++)-dependent and constitutively active channels are involved, as indicated by the sensitivity to clotrimazole, charybdotoxin, and barium. The ability of clotrimazole to accelerate wound resealing was also observed in Caco-2 cell sheets. Pharmacologic stimulation of K(+) channel activity had no effect on the repair rate. Analysis of the resealing process by time lapse and confocal microscopy revealed that K(+) channel inhibitors abolished the initial wound retraction, briefly accelerated the repair rate, and altered the shape of the cell sheet abutting the injury during the early phase of resealing. We hypothesize that K(+) channel inactivation interrupts the coregulation of f-actin polymerization and volume control that is initiated by the healing process.