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Cigarette smoking is associated with pulmonary and cardiovascular disease and confers increased postoperative morbidity and mortality. Smoking cessation in the weeks before surgery can mitigate these risks, and surgeons should screen patients for smoking before a scheduled operation so that appropriate smoking cessation education and resources can be given. Interventions that combine nicotine replacement therapy, pharmacotherapy, and counseling are effective to achieve durable smoking cessation. When trying to stop smoking in the preoperative period, surgical patients experience much higher than average cessation rates compared with the general population, indicating that the time around surgery is ripe for motivating and sustaining behavior change. This chapter summarizes the impact of smoking on postoperative outcomes in abdominal and colorectal surgery, the benefits of smoking cessation, and the impact of interventions aimed to reduce smoking before surgery.

Timely colorectal cancer (CRC) screening has been shown to improve CRC-related morbidity and mortality rates. However, even with this preventative care tool, CRC screening rates remain below 70% among eligible United States (US) adults, with even lower rates among US immigrants. The aim of this scoping review is to describe the barriers to CRC screening faced by this unique and growing immigrant population and discuss possible interventions to improve screening.Four electronic databases were systematically searched for all original research articles related to CRC screening in US immigrants published after 2010. Following a full-text review of articles for inclusion in the final analysis, data extraction was conducted while coding descriptive themes. Thematic analysis led to the organization of this data into five themes.Of the 4637 articles initially identified, 55 met inclusion criteria. Thematic analysis of the barriers to CRC screening identified five unique themes: access, knowledge, culture, trust, health perception, and beliefs. The most cited barriers were in access (financial burden and limited primary care access) and knowledge (CRC/screening knowledge).US immigrants face several barriers to the receipt of CRC screening. When designing interventions to increase screening uptake among immigrants, gaps in physician and screening education, access to care, and trust need to be addressed through culturally sensitive supports. These interventions should be tailored to the specific immigrant group, since a one-size-fits approach fails to consider the heterogeneity within this population.

Rectovaginal fistula (RVF) is an abnormal connection between the rectum and vagina that affects women globally. In low- and middle-income countries (LMIC), RVF is most commonly due to obstetric complications such as prolonged labor or perineal tears, female genital mutilation and trauma such as sexual violence or iatrogenic surgical injuries. Women affected by this condition suffer from debilitating physical symptoms, social isolation, economic disempowerment, psychological trauma, low self-esteem, and loss of role fulfillment. Lack of accessible, high-quality, and effective healthcare is a major barrier to timely and safe obstetric care and to care for subsequent complications such as RVF. Additionally, social, cultural, financial, and systemic barriers put women at risk of acquiring fistula and contribute to delays in seeking and receiving care. Literature evaluating RVF repair in those able to access care offers limited information about management and outcomes. It is difficult to ascertain which surgical techniques are used. To reduce the burden of this often-preventable disease, appropriate investment in healthcare infrastructure to strengthen maternal care in LMICs is paramount. Furthermore, more standardized reporting of severity and treatment approach along with outcome data are critical to improving the quality of care for patients impacted by RVF.

Meaningful reporting of quality metrics relies on detecting a statistical difference when a true difference in performance exists. Larger cohorts and longer time frames can produce higher rates of statistical differences. However, older data are less relevant when attempting to enact change in the clinical setting. The selection of time frames must reflect a balance between being too small (type II errors) and too long (stale data). We explored the use of power analysis to optimize time frame selection for trauma quality reporting.Using data from 22 Level III trauma centers, we tested for differences in 4 outcomes within 4 cohorts of patients. With bootstrapping, we calculated the power for rejecting the null hypothesis that no difference exists amongst the centers for different time frames. From the entire sample for each site, we simulated randomly generated datasets. Each simulated dataset was tested for whether a difference was observed from the average. Power was calculated as the percentage of simulated datasets where a difference was observed. This process was repeated for each outcome.The power calculations for the 4 cohorts revealed that the optimal time frame for Level III trauma centers to assess whether a single site's outcomes are different from the overall average was 2 years based on an 80% cutoff.Power analysis with simulated datasets allows testing of different time frames to assess outcome differences. This type of analysis allows selection of an optimal time frame for benchmarking of Level III trauma center data.

Many rectal cancer survivors experience persistent bowel, urinary, and sexual dysfunction. A better understanding of their lived experience can help guide survivorship care.Multi-modal study of patients who underwent rectal cancer surgery from 2015 to 2019 at a single institution. Surveys and qualitative interviews were used to describe patients' postoperative symptom burden and its impact on their quality of life.The total number of survey respondents was 188 (response rate = 63.5%). Among participants, 41.5% reported their bowel habits, bladder habits (7.8%) and sexual function (36.2%) to be a "moderate" or "big problem" in the past four weeks. The lived experiences varied widely even among patients who report similar symptom burden.Rectal cancer survivors commonly face lasting symptoms that negatively impact their quality of life for years after surgery. Additional support extending beyond the perioperative period is needed for patients with persistent dysfunction.

Americans living in Health Professional Shortage Areas (HPSA) only have 44% of the required physician workforce to service their residents. We sought to determine whether residents living in HPSA have worse surgical outcomes than those living in non-HPSA.We performed a retrospective review of 1,507,834 Medicare beneficiaries undergoing appendectomy, cholecystectomy, colectomy or hernia repair between 2014 and 2018. Multivariable logistical regression was used to determine the association of living in HPSA with rates of 30-day mortality.Compared with patients living in non-HPSA, patients living in HPSA traveled farther (median distance 35.3 miles vs. 11.7 miles, p 0.001) and longer (median 45 min vs. 20 min, p 0.001) for surgical care. Differences in rates of mortality between patients living in HPSA and non-HPSA (6.0% vs. 6.1%, OR = 0.97, 95% CI 0.97-0.97, p 0.001) were small.Medicare beneficiaries living in HPSA experience more than double the travel time and triple the travel distance to undergo common surgical procedures compared to those living in non-HPSA. For those able to overcome the travel burden, the differences in surgical outcomes were small.

Comprehensive cancer care includes supporting the psychological health of survivors who are at high risk of distress. However, little is known about the emotional experiences of rectal cancer survivors specifically. We sought to explore psychological well-being and coping strategies utilized by rectal cancer survivors.Twenty rectal cancer survivors shared photographs of their post-treatment experiences. In follow-up interviews, participants discussed photographs' meanings and emotional experiences during their cancer journey. Transcribed interviews were analyzed using iterative steps of inductive thematic analysis.Emotions ranged from sadness to anxiety and fear of cancer recurrence. Coping mechanisms were grouped into 3 categories: (1) seeking support and information; (2) focus on attitudes and perspectives; and (3) distancing strategies.Our results highlight the persistent psychological impact of rectal cancer and need for additional support for survivors. Providers may help temper patients' fear of recurrence by explicitly discussing prognosis and risk of recurrence. Although multidisciplinary survivorship clinics are ideal, all cancer care providers and primary care physicians should feel empowered to screen for psychological distress and refer patients to appropriate resources when needed.

Struggling residents are not uncommon in general surgery. Early identification of these residents and effective remediation remain imperfect.We performed a survey of program directors (PD) across all general surgery residencies. Survey questions included the following: demographic information about the program and PD, 10 vignettes about hypothetical residents struggling in various ACGME milestones to assess how PDs would address these deficiencies, and self-reported PD preparedness and availability of resources to support struggling residents.In total, we received 82 responses to our survey. All PDs who participated in our study reported having struggling residents in their program. The three most common ways struggling residents are identified were faculty word-of-mouth, formal evaluations such as milestones and ABSITE performance, and resident word-of-mouth. Over 18% of PDs reported having little to no relevant training in addressing the needs of a struggling resident, and 65.9% of PDs did not feel that their program had 'completely adequate' resources to address these needs. In the majority of cases, PDs offer mentorship with themselves or other faculty as a remediation strategy with infrequent use of other resources.Strategies to identify struggling residents and remediation strategies varied widely across programs. Diversifying remediation approaches should be considered for more effective remediation.

Preoperative staging of clinical stage I rectal cancer can fail to diagnose T3 or nodal disease. Adjuvant treatment of these upstaged patients remains controversial.The objective was to identify predictors of clinical stage I rectal cancer upstaging and quantify rates of local and systemic recurrence.This was a retrospective cohort study.The study was conducted using the data from the United States Rectal Cancer Consortium, a registry of 1,881 rectal cancer resections performed at six academic medical centers.There were a total of 94 clinical stage I rectal cancer patients who underwent proctectomy without preoperative therapy.The primary measures were incidence of pathologic upstaging, recurrence (local and systemic), and overall survival.Among 94 clinical stage I patients who underwent proctectomy without preoperative therapy, 23 (24.5%) were upstaged by surgical pathology. There were 6 pT3N0 patients, 8 pT1-2N+, and 9 pT3N+. There were no significant differences in demographic or clinical characteristics between upstaged and non-upstaged patients. Of the 6 patients who were upstaged to T3N0 disease, none received adjuvant therapy and none recurred. Of the 17 patients who were upstaged to N+ disease, 14 (82%) received adjuvant chemotherapy and 6 (35%) received adjuvant chemoradiation. None developed a local recurrence, but 4 (24%) developed systemic recurrence, and 2 (12%) died of disease over a mean of 36 months follow-up. Among the 9 pT3N+ patients, the systemic recurrence rate was 33%, despite 8 of 9 patients receiving adjuvant fluorouracil, leucovorin, and oxaliplatin.Small sample size hinders ability to draw significant conclusions.One in four patients with stage I rectal cancer had unrecognized T3 or nodal disease found on operative pathology. Occult nodal disease was associated with worse outcomes, despite receiving adjuvant therapy. Systemic recurrence was more common than local recurrence. See Video Abstract at http://links.lww.com/DCR/B885.

To evaluate changes in 30-day postoperative outcomes and individual hospital variation in outcomes from 2012-2019 in a collaborative quality improvement network.Collaborative quality improvement efforts have been shown to improve postoperative outcomes overall, however, heterogeneity in improvement between participating hospitals remains unclear. Understanding the distribution of individual hospital-level changes is necessary to inform resource allocation and policy design.We performed a retrospective cohort study of 51 hospitals in the Michigan Surgical Quality Collaborative (MSQC) from 2012-2019. Risk- and reliability-adjusted hospital rates of 30-day mortality, complications, serious complications, emergency department (ED) visits, readmissions, and reoperations were calculated for each year and compared between the last two years and the first two years of the study period.There was a significant decrease in the rates of all 5 adverse outcomes across MSQC hospitals from 2012-2019. Of the 51 individual hospitals, 31 (61%) hospitals achieved a decrease in mortality (range -1.3 percentage points to +0.6 percentage points), 40 (78%) achieved a decrease in complications (range -8.5 percentage points to +2.9 percentage points), 26 (51%) achieved a decrease in serious complications (range -3.2 percentage points to +3.0 percentage points), 29 (57%) achieved a decrease in ED visits (range 5.0 percentage points to +2.2 percentage points), 46 (90%) achieved a decrease in readmissions (range -3.1 percentage points to +0.4 percentage points) and 39 (76%) achieved a decrease in reoperations (range 3.3 percentage points to +1.0 percentage points).Despite overall improvement in surgical outcomes across hospitals participating in a quality improvement collaborative, there was substantial variation in improvement between hospitals, highlighting opportunities to better understand hospital-level barriers and facilitators to surgical quality improvement.

To compare surgical outcomes and expenditures at hospitals located in Health Professional Shortage Areas to non-shortage area designated hospitals among Medicare beneficiaries.More than a quarter of Americans live in federally designated Health Professional Shortage Areas. While there is growing concern that medical outcomes may be worse, far less is known about hospitals providing surgical care in these areas.Cross sectional retrospective study from 2014-2018 of 842,787 Medicare beneficiary patient admissions to hospitals with and without Health Professional Shortage Area designations for common operations including appendectomy, cholecystectomy, colectomy, and hernia repair. Risk-adjusted outcomes using multivariable logistic regression accounting for patient factors, admission type, and year were compared for each of the four operations. Hospital expenditures were price-standardized, risk-adjusted 30-day surgical episode payments. Primary outcome measures included 30-day mortality, hospital readmissions, and 30-day surgical episode payments.Patients (mean age=75.6 y, males=44.4%) undergoing common surgical procedures in shortage area hospitals were less likely to be white (84.6%vs.88.4%, P0.001) and less likely to have≥2 Elixhauser comorbidities (75.5%vs.78.2%, P0.001). Patients undergoing surgery at Health Professional Shortage Area hospitals had lower risk-adjusted rates of 30-day mortality (6.05%vs.6.69%, OR=0.90, CI0.90-0.91, P0.001) and readmission (14.99%vs.15.74%, OR=0.94, CI=0.94-0.95, P0.001). Medicare expenditures at Health Professional Shortage Area hospitals were also lower than non-shortage designated hospitals ($28,517vs.$29,685, difference= -$1,168, P0.001).Patients presenting to Health Professional Shortage Area hospitals obtain safe care for common surgical procedures without evidence of higher expenditures among Medicare beneficiaries. These findings should be taken into account as current legislative proposals to increase funding for care in these under-served communities are considered.

ImportanceThe health of the US population is decreasing, and novel strategies are needed to reverse the trajectory. The surgical episode may be an opportune time to screen for poor health behaviors and social needs, yet little is known about the feasibility or acceptability of such efforts.ObjectiveTo assess the feasibility and acceptability of a pilot program that engages patients in health behavior change and addresses unmet social needs at the time of surgery.Design, Setting, and, ParticipantsThis quality improvement study was conducted among 10 338 patients seen in a preoperative clinic for elective surgery between February 8 and August 31, 2021. Patients who received a referral for institutional resources were contacted via telephone to complete follow-up surveys 30 to 90 days after surgery and between July 1, 2021, and March 31, 2022.InterventionsImplementation of a tool to screen patients for smoking and food insecurity in a preoperative clinic. Those who screened positive were offered referrals for institutional resources. Telephone surveys were conducted with patients who accepted referrals to understand attitudes toward addressing health behaviors and social needs.Main Outcomes and MeasuresScreening and referral rates, patient-perceived acceptability of addressing health behaviors and social needs at the time of surgery, smoking cessation rates, and resolution of food insecurity.ResultsA total of 10 338 patients (6052 women [58.5%]; mean [SD] age, 56.5 [17.9] years) were evaluated in the preoperative clinic. Of the 10 338 patients, 7825 (75.7%) were successfully screened. Of the 641 identified smokers, 152 (23.7%) accepted a referral for smoking cessation counseling. Of the 181 identified patients with food insecurity, 121 (66.9%) accepted a referral for nonmedical needs assistance. On follow-up surveys, 64 of 78 smokers (82.1%) agreed that the preoperative appointment was an appropriate time to discuss smoking cessation, and 34 of 78 smokers (43.6%) reported quitting smoking. Similarly, 69 of 84 patients with food insecurity (82.1%) agreed it was a good or very good idea for health systems to address nonmedical needs at the time of surgery, and 27 patients (32.1%) reported no longer being insecure about food since their preoperative visit.Conclusions and RelevanceThis study suggests that it is feasible to address patients’ foundational health at the time of surgery. Most patients agreed that these interventions were appropriate during the perioperative period. These results support using the surgical episode as an opportunity to address foundational health.

Burnout among general surgery residents is prevalent. Guidance on how program directors (PDs) can effectively intervene on general surgery resident wellness is lacking. In this study, we explore how PDs learn about burnout among their residents and support their well-being.Semi-structured interviews were conducted with PDs. Interviews were transcribed and coded by study team dyads who utilized an inductive coding approach, and then reconciled via consensus. Interpretive description was the qualitative analytical method.Program tours to 15 general surgery programs during the exploratory phase of the SECOND Trial.Fifteen general surgery PDs.PDs identified the utility of contextual information in understanding resident wellness and implementing program-specific resident wellness initiatives. Three themes relating to PD awareness of resident burnout and well-being were identified: (1) PDs used conventional and novel methods to collect data from multiple information sources, including residents, faculty, staff, institutional representatives, and anonymous parties. (2) These contextualized data inspired the development of responsive strategies to effect programmatic changes that improved education and wellness. (3) Barriers to acquiring and utilizing information exist, requiring careful analysis, creative problem solving, as well as persistence and dedication to resident wellness.Qualitative analysis of general surgery residency PDs yielded insightful knowledge about gathering and responding to information to support resident wellness, including successful strategies and areas of caution. The experience of these PDs can guide others in evaluating their wellness goals and initiatives for their own residents.

Complication rates after colectomy remain high. Previous work has failed to establish the relative contribution of patient comorbidities, surgeon performance, and hospital systems in the development of complications after elective colectomy.We identified all patients undergoing elective colectomy between 2012 and 2018 at hospitals participating in the Michigan Surgical Quality Collaborative. The primary outcome was development of a postoperative complication. We used risk- and reliability-adjusted generalized linear mixed models to estimate the degree to which variance in patient-, surgeon-, and hospital-level factors contribute to complications.A total of 15,755 patients were included in the study. The mean hospital-level complication rate was 15.8% (range, 8.7% to 30.2%). The proportion of variance attributable to the patient level was 35.0%, 2.4% was attributable to the surgeon level, and 1.8% was attributable to the hospital level. The predicted probability of complication for the least comorbid patient was 1.5% (CI 0.7-3.1%) at the highest performing hospital with the highest performing surgeon, and 6.6% (CI 3.2-12.2%) at the lowest performing hospital with the lowest performing surgeon. By contrast, the most comorbid patient in the cohort had a 66.3% (CI 39.5-85.6%) or 89.4% (CI 73.7-96.2%) risk of complication.This study demonstrated that variance from measured factors at the patient level contributed more than 8-fold more to the development of complications after colectomy compared with variance at the surgeon and hospital level, highlighting the impact of patient comorbidities on postoperative outcomes. These results underscore the importance of initiatives that optimize patient foundational health to improve surgical care.

Background Post-acute care rehabilitation is critically important to recover after trauma but many patients do not have access. A better understanding of the drivers behind inpatient rehabilitation facility (IRF) use has the potential for major cost-savings as well as higher quality, and more equitable patient care. We sought to quantify the variation in hospital rates of trauma patient discharge to inpatient rehabilitation and understand which factors (patient- vs injury- vs hospital-level) contribute the most. Methods We performed a retrospective cohort study of 668,305 adult trauma patients admitted to 900 Level I-IV trauma centers between 2011 and 2015 using the National Trauma Data Bank (NTBD). Participants were included if they met the following criteria: age >18, injury severity score (ISS) >9, identifiable injury type, and who had one of the Centers for Medicare & Medicaid Services (CMS) preferred diagnoses for inpatient rehabilitation under the "60% rule". Results The overall risk- and reliability-adjusted hospital rates of discharge to IRF averaged 18.8% in the non-elderly adult cohort (18-64 years old) and 23.4% in the older adult cohort (65 years or older). Despite controlling for all patient, injury and hospital-level factors, hospital discharge of patients to IRF varied substantially between hospital quintiles and ranged from 9-30% in the non-elderly adult cohort and from 7-46% in the older adult cohort. Proportions of total variance ranged from 2.4% (patient insurance) to 12.1% (injury-level factors) in the non-elderly adult cohort and from 0.3% (patient-level factors) to 26.0% (unmeasured hospital-level factors) in the older adult cohort. Conclusion Among a cohort of injured patients with diagnoses that are associated with significant rehabilitation needs, the hospital at which a patient receives their care may drive a patient's likelihood of recovering at an IRF just as much, if not more, than their clinical attributes. Level of evidence Level III. Epidemiological.

OBJECTIVE Postoperative complications and deaths are unavoidable aspects of a surgical career, but little is known about the impacts of these unwanted outcomes on resident surgeons. The goal of this study was to characterize the impact of complications and deaths on surgery residents in order to facilitate development of improved support systems. DESIGN This qualitative study was designed to explore resident surgeons’ experiences with unwanted outcomes, including postoperative complications and death. Semi-structured interviews explored a range of topics related to personal experiences with unwanted outcomes. Analyses of interview transcripts were performed iteratively and informed by thematic analysis. SETTING An anthropologist at the University of Michigan conducted interviews with general surgery residents from academic, community, and hybrid training programs across the country. PARTICIPANTS Twenty-eight mid-level and senior residents (PGY3 and above) were recruited for participation from 14 different training programs across the United States. RESULTS Resident surgeons described an initial period of emotional response, characterized by feelings of sadness, frustration, or grief. Simultaneously or soon afterward, interviewees described a period of intellectual response aimed at understanding how and why an outcome occurred, with the expressed goal of learning from it. Many residents described impacts to their personal lives. Several factors that influenced the duration and intensity of these responses were identified, including a sense of ownership, which was a powerful driver for improvement. CONCLUSIONS This qualitative study provides a nuanced description of resident surgeons’ responses to unwanted outcomes. While emotional responses were characterized by strong feelings, such as sadness and grief, intellectual responses were focused on learning from the events. These data may help inform the development of structured support systems by residency programs. Structured Abstract Facing post-operative complications and deaths is an unavoidable aspect of surgical training, but the impacts on surgery residents has not been well characterized. Through semi-structured interviews with general surgery residents from programs across the United States, this qualitative study explored the ways that residents respond to unwanted outcomes. Residents described an initial period of emotional response, characterized by strong feelings, often of sadness or grief. There was a subsequent or concomitant period of intellectual response, in which residents examined how and why this outcome occurred, with the goal of learning from it. A feeling of ownership was strengthened by involvement in patient care and length of rotation. In light of this detailed description of resident experiences, residency programs can foster the development of improved support for trainees as they navigate these profoundly impactful events.

Background The regulatory focus theory (RFT) posits that people can pursue goals with a promotion or prevention focus. Greater alignment of RFT motivational styles between faculty and residents may enhance resident operative autonomy. This study establishes a set of faculty behaviors residents can identify to infer faculty motivational styles. Methods 10 behaviors associated with promotion and prevention motivational styles were identified. General surgery residents rated faculty on how strongly they exhibit these behaviors. Faculty conducted a self-assessment of how strongly they exhibit these behaviors. Results There is a positive correlation between resident and faculty ratings for the promotion-associated behaviors of “works quickly,” “high energy,” and “mostly provides broad oversight,” and for the prevention-associated behaviors of “works slowly and deliberately,” “quiet and calm,” and “preference for vigilant strategies.” Conclusion Residents can observe faculty operative behaviors to infer faculty motivational styles. Residents may use this knowledge to adjust to faculty motivational styles and enhance operative interactions.

Introduction Ghana has seen a rise in the incidence of colorectal cancer (CRC) over the past decade. In 2011, the Ghana National Cancer Steering Committee created a guideline recommending fecal occult blood testing (FOBT) for CRC screening in individuals over the age of 50. There is limited data available on current Ghanaian CRC screening trends and adherence to the established guidelines. Methods We conducted a survey of 39 physicians working at the Komfo Anokye Teaching Hospital in Kumasi, Ghana. The survey evaluates physician knowledge, practice patterns, and perceived personal-, patient- and system-level barriers pertaining to CRC screening. Results Almost 10% of physicians would not recommend colorectal cancer screening for asymptomatic, average risk patients who met the age inclusion criteria set forth in the national guidelines. Only 1 physician would recommend FOBT as an initial screening test for CRC. The top reasons for not recommending CRC screening with FOBT were the lack of equipment/facilities for the test (28.1%) and lack of training (18.8%). The two most commonly identified barriers to screening identified by >85% of physicians, were lack of awareness of screening/not perceiving colorectal cancer as a serious health threat (patient-level) and high screening costs/lack of insurance coverage (system-level). Conclusion Despite creation of national guidelines for CRC screening, there has been low uptake and implementation. This is due to several barriers at the physician-, patient- and system-levels including lack of resources and physician training to follow-up on positive screening results, limited monetary support and substantial gaps in knowledge at the patient level.

This Surgical Perspective presents the case for leveraging the surgical episode to impact population health. We describe a novel screening and referral pilot and propose several policy changes aimed at delivering population-health focused surgical care.

MenaINV, an actin-regulatory protein known to promote metastasis, has roles in driving cross-talk between extracellular matrix, growth factor cues, and their downstream pathways during tumor cell invasion. MenaINV is a shared component of the signaling pathway driving both EGF chemotaxis and fibronectin haptotaxis., Directed cell migration, a key process in metastasis, arises from the combined influence of multiple processes, including chemotaxis—the directional movement of cells to soluble cues—and haptotaxis—the migration of cells on gradients of substrate-bound factors. However, it is unclear how chemotactic and haptotactic pathways integrate with each other to drive overall cell behavior. MenaINV has been implicated in metastasis by driving chemotaxis via dysregulation of phosphatase PTP1B and more recently in haptotaxis via interaction with integrin α5β1. Here we find that MenaINV-driven haptotaxis on fibronectin (FN) gradients requires intact signaling between α5β1 integrin and the epidermal growth factor receptor (EGFR), which is influenced by PTP1B. Furthermore, we show that MenaINV-driven haptotaxis and ECM reorganization both require the Rab-coupling protein RCP, which mediates α5β1 and EGFR recycling. Finally, MenaINV promotes synergistic migratory response to combined EGF and FN in vitro and in vivo, leading to hyperinvasive phenotypes. Together our data demonstrate that MenaINV is a shared component of multiple prometastatic pathways that amplifies their combined effects, promoting synergistic cross-talk between RTKs and integrins.

The Michigan Journal of Medicine (MJM) is a peer-reviewed, student-run medical journal. It serves as a unique learning opportunity for those involved including the Editor-in-Chief (EiC), Editors, Reviewers, and authors. In its second year, there was one EiC (fourth-year medical student), 12 Editors (fourth-year medical students), and 42 Reviewers (second- and third-year medical students). Manuscripts were reviewed and edited by Editorial Teams made up of the EiC, one Editor, and three to four Reviewers. This infrastructure allowed for senior to junior student mentoring as well as multiple rounds of manuscript review, which generated high quality, thorough feedback for authors. No manuscripts were rejected without providing thorough feedback to authors. Struggles from the second year of this initiative included low submission volume and hierarchy hardships leading to difficulty leading peers and tough decisions related to delegation.

With trends toward increasing patient involvement in medical decision-making, decreasing clinic times, and the availability of the Internet, patients and their caregivers are increasingly researching cancer diagnoses online. It is essential for physicians to understand patient Internet usage as it relates to their own health education. Internet usage trends have been studied in various areas, but not in thoracic diseases. This prospective cohort study surveyed 337 thoracic surgery patients and their caregivers with both cancer and non-cancer diagnoses to examine their Internet usage trends. Cancer subjects were more likely to research their condition online if they were younger, had a higher income, had a higher education level, and were currently employed. Only age and income level were predictive for non-cancer subjects. Separately, cancer subjects were more likely to trust information found on the Internet if they had a higher education. Subjects were most likely to conduct research on a hospital website than other websites. These data will be helpful to thoracic surgeons who want to appropriately educate patients and their caregivers and direct them to reliable Internet sources. These data also illustrate the importance of developing trustworthy hospital websites with disease-specific information.

After major upper extremity traumatic amputation, replantation is attempted based upon the assumption that outcomes for a replanted limb exceed those for revision amputation with prosthetic rehabilitation. While some reports have examined functional differences between these patients, it is increasingly apparent that patient perceptions are also critical determinants of success. Currently, little patient-reported outcomes data exists to support surgical decision-making in the setting of major upper extremity traumatic amputation. Therefore, the purpose of this study is to directly compare patient-reported outcomes after replantation versus prosthetic rehabilitation.At three tertiary care centers, patients with a history of traumatic unilateral upper extremity amputation at or between the radiocarpal and elbow joints were identified. Patients who underwent either successful replantation or revision amputation with prosthetic rehabilitation were contacted. Patient-reported health status was evaluated with both DASH and MHQ instruments. Intergroup comparisons were performed for aggregate DASH score, aggregate MHQ score on the injured side, and each MHQ domain.Nine patients with successful replantation and 22 amputees who underwent prosthetic rehabilitation were enrolled. Aggregate MHQ score for the affected extremity was significantly higher for the Replantation group compared to the Prosthetic Rehabilitation group (47.2 vs. 35.1, p0.05). Among the MHQ domains, significant advantages to replantation were demonstrated with respect to overall function (41.1 vs. 19.7, p=0.03), ADLs (28.3 vs. 6.0, p=0.03), and patient satisfaction (46.0 vs. 24.4, p=0.03). Additionally, Replantation patients had a lower mean DASH score (24.6 vs. 39.8, p=0.08).Patients in this study who experienced major upper extremity traumatic amputation reported more favorable patient-reported outcomes after successful replantation compared to revision amputation with prosthetic rehabilitation.

During breast cancer progression, alternative mRNA splicing produces functionally distinct isoforms of Mena, an actin regulator with roles in cell migration and metastasis. Aggressive tumor cell subpopulations express Mena[superscript INV], which promotes tumor cell invasion by potentiating EGF responses. However, the mechanism by which this occurs is unknown. Here we report that Mena associates constitutively with the tyrosine phosphatase PTP1B and mediates a novel negative feedback mechanism that attenuates receptor tyrosine kinase signaling. On EGF stimulation, complexes containing Mena and PTP1B are recruited to the EGFR, causing receptor dephosphorylation and leading to decreased motility responses. Mena also interacts with the 5′ inositol phosphatase SHIP2, which is important for the recruitment of the Mena-PTP1B complex to the EGFR. When Mena[superscript INV] is expressed, PTP1B recruitment to the EGFR is impaired, providing a mechanism for growth factor sensitization to EGF, as well as HGF and IGF, and increased resistance to EGFR and Met inhibitors in signaling and motility assays. In sum, we demonstrate that Mena plays an important role in regulating growth factor–induced signaling. Disruption of this attenuation by Mena[superscript INV] sensitizes tumor cells to low–growth factor concentrations, thereby increasing the migration and invasion responses that contribute to aggressive, malignant cell phenotypes., Breast Cancer Research Program (U.S.) (Grant W81XWH-10-1-0040), Breast Cancer Research Program (U.S.) (Grant W81XWH-13-1-0031), National Institutes of Health (U.S.) (Grant U54-CA112967), National Institutes of Health (U.S.) (Grant GM58801), Virginia and D.K. Ludwig Fund for Cancer Research

General surgery residents' exposure to cardiothoracic (CT) surgery rotations has decreased, which may affect resident satisfaction. We surveyed general surgery graduates to assess the relationships among rotation satisfaction, CT disease exposure, rotation length, mentorship, and mistreatment.A survey assessing CT curriculum, exposure, mentorship, and satisfaction was forwarded to general surgery graduates from 17 residency programs. A Wilcoxon rank-sum test was used to assess statistical significance of ordinal level data. Statistical significance was defined as p0.05.This study was conducted at the University of Michigan Health System in Ann Arbor, MI, a tertiary care center.The survey was sent to approximately 1300 graduates of general surgery residency programs who graduated between the years of 1999 to 2014. A total of 94 responses were completed and received.Receiving adequate exposure to CT procedures and disease management was significantly associated with higher satisfaction ratings for all procedures, particularly thoracotomy incisions (p0.001), empyemas and pleural effusions (p0.001), and lung cancer care (p0.001). The absence of mistreatment and good/very good mentorship were both positively associated with higher reported satisfaction (p = 0.018 and p0.001, respectively). Increased length of time on CT rotation was neither associated with improved levels of satisfaction nor with an improvement in the quality of mentorship.Rotation satisfaction is positively associated with procedure exposure, better mentorship, and the absence of mistreatment. Longer rotation length was not associated with satisfaction. Shorter rotations are not detrimental to training if they have focused clinical exposure and invested mentors to maximize resident satisfaction. These specific markers of rotation quality are useful in curricular design.

Sarcopenia, defined as a decrease in skeletal muscle mass and strength, is an important risk factor in clinical medicine associated with frailty, mortality, and worse surgical and nonsurgical outcomes. Conventional measures of sarcopenia rely on the subjective "eyeball test" and do not adequately describe risk. Computed tomography (CT) imaging studies may be used to objectively measure sarcopenia and may be used for surgical risk stratification and identification of patients for inclusion in a novel clinical remediation program.We describe results observed in the general, vascular, and liver transplant surgery populations determined by analytic morphomics--an analysis of CT scans in a semiautomated process using MATLAB v13.0. A perioperative optimization program has been implemented with the objective of remediating sarcopenia through improvement of patient mental and physical status prior to surgery.Using analytic morphomics, we have noted significantly higher cost and increased rates of mortality and surgical complications among sarcopenic patients. The training program shows initial success, and among participating patients, we have observed reductions in payer and hospital costs and a decrease in length of hospital stay for patients following surgery.Through analytic morphomics, we are able to quantify markers of sarcopenia and identify patients at risk for increased mortality and poor surgical outcomes. Early identification of patients offers us the opportunity to remediate sarcopenia through perioperative training and support. Participating patients spend less time in the hospital and have lower healthcare costs. This program has the potential to improve the perioperative patient experience and ease financial burdens.

Directed-cell migration is key step in the metastatic cascade, and multiple cues can promote local invasion. The most well studied mode of cell motility for metastasizing tumor cells is chemotaxis, the directional movement of cells attracted to a source of soluble cues. In contrast, haptotaxis, migration of cells on gradients of substrate-bound factors, remains poorly understood. Mena, an actin regulatory protein, plays an important role in cell motility and is upregulated in various cancers, driving migration in response to chemotactic and haptotactic cues. We have recently shown expression of the pro-metastatic isoform of Mena, MenaINV, increases sensitivity to growth factors (EGF, HGF and IGF) via dysregulation of the phosphatase PTP1B, as well as high concentrations of fibronectin (FN) via its interaction with the integrin α5β1. We hypothesized that MenaINV may also promote crosstalk between these two pathways to drive metastasis. First, we show that MenaINV-driven haptotaxis on FN gradients and FN-driven invasion requires crosstalk between α5β1 and EGFR. Indeed, we show evidence that MenaINV expression is associated high phosphorylation of EGFR in high FN environments in vitro and in human breast cancer databases. Second, we find that MenaINV promotes synergy between EGF and FN in vitro and in vivo, leading to hyper-invasive phenotypes that drive more invasion than which each cue alone. Finally, we show that MenaINV-driven haptotaxis, ECM reorganization and 3D invasion requires RCP-dependent recycling of α5β1 and EGFR. Together, our data demonstrate that MenaINV is a shared component of the machinery that mediates both haptotactic responses to FN and chemotactic responses to EGF, two pathways that promote tumor progression. Citation Format: Madeleine J. Oudin, Miles A. Miller, Tatsiana Kosciuk, Joelle Klazen, Alisha Lussiez, Douglas Lauffenburger, James E. Bear, Frank B. Gertler. Mena at the nexus of chemotaxis and haptotaxis during tumor progression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5057.

Brain metastases are a serious obstacle in the treatment of patients with human epidermal growth factor receptor-2 ( HER2 )–amplified breast cancer. Although extracranial disease is controlled with HER2 inhibitors in the majority of patients, brain metastases often develop. Because these brain metastases do not respond to therapy, they are frequently the reason for treatment failure. We developed a mouse model of HER2 -amplified breast cancer brain metastasis using an orthotopic xenograft of BT474 cells. As seen in patients, the HER2 inhibitors trastuzumab and lapatinib controlled tumor progression in the breast but failed to contain tumor growth in the brain. We observed that the combination of a HER2 inhibitor with an anti–VEGF receptor-2 (VEGFR2) antibody significantly slows tumor growth in the brain, resulting in a striking survival benefit. This benefit appears largely due to an enhanced antiangiogenic effect: Combination therapy reduced both the total and functional microvascular density in the brain xenografts. In addition, the combination therapy led to a marked increase in necrosis of the brain lesions. Moreover, we observed even better antitumor activity after combining both trastuzumab and lapatinib with the anti-VEGFR2 antibody. This triple-drug combination prolonged the median overall survival fivefold compared with the control-treated group and twofold compared with either two-drug regimen. These findings support the clinical development of this three-drug regimen for the treatment of HER2 -amplified breast cancer brain metastases.

The most well studied mode of cell motility for metastasizing tumor cells is chemotaxis, the directional movement of cells attracted to a source of soluble cues. In contrast, haptotaxis, migration of cells on gradients of substrate-bound factors, remains poorly understood. Due to the high expression of extracellular matrix (ECM) proteins such as collagen and fibronectin (FN) in metastatic tumors, it is possible that haptotaxis along ECM gradients could also be driving invasion. Mena, an actin regulatory protein, plays an important role in cell motility and is upregulated in various cancers, where Mena, and in particular the MenaINV isoform, potentiates chemotactic and invasive responses to EGF. All Mena isoforms bind directly to the α5 subunit of the α5β1 integrin, a FN receptor. We hypothesized that the pro-metastatic effect of MenaINV arises from increases in tumor cell responses to specific chemotactic and haptotactic cues, including EGF and FN. To study haptotaxis, MDA-MB231 breast adenocarcinoma cells were plated on gradients of fluorescently-labeled FN in 2D or in 3D collagen gels, generated within a PDMS microfluidic device. Wild type cells expressing low levels of endogenous Mena failed to respond to a FN gradient, but migrated equally well in all directions irrespective of the FN gradient. Surprisingly, ectopic expression of Mena in these cells conferred the ability to respond to FN gradients, with cells exhibiting haptotactic response towards higher concentrations of FN in 2D and 3D. Interestingly, cells expressing MenaINV were able to haptotax towards FN concentrations 4 times higher then cells expressing Mena, while reorganizing and recruiting both collagen and FN surrounding them. MenaINV-dependent haptotaxis was ablated by deletion of the α5 binding site within Mena or treatment with an α5 function blocking antibody, but was unaffected by inhibition of another FN receptor, αVβ3. Using intravital imaging of mouse mammary tumors, we visualized haptotaxis of MenaINV-expressing cells towards gradients of fluorescently labelled FN released locally from implanted microsccale devices. Tumor cells expressing MenaINV lacking the α5 binding site did not haptotax, displayed decreased motility and metastasis to the lung. This was also accompanied by a striking change in the organization of the ECM surrounding the tumor. While investigating the mechanism of haptotaxis, we found that MenaINV-driven invasive responses to FN were also dependent on EGFR signalling and mediated by the phosphatase PTP1B. Finally, using a combination of in vitro and in vivo invasion assays, we show that MenaINV expression promoted synergistic invasive responses to combinations of EGF and FN and also caused increased phosphorylation of Paxilin and FAK at focal adhesions. Together, our data demonstrate that MenaINV is a shared component of the machinery that mediates both haptotactic responses to FN and chemotactic responses to EGF, two pathways that promote tumor progression. Citation Format: Madeleine J. Oudin, Oliver Jonas, Tatiana Kosciuk, Liliane C. Broye, Jeff Wyckoff, Miles A. Miller, Alisha Lussiez, Sreeja Asokan, Robert Langer, Douglas Lauffenburger, James E. Bear, Frank B. Gertler. Mena at the nexus of chemotaxis and haptotaxis during tumor progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 437. doi:10.1158/1538-7445.AM2015-437

To metastasize and disseminate, carcinoma cells must invade the surrounding extracellular matrix (ECM) and migrate to reach blood or lymphatic vessels. Collagen (CN) and fibronectin (FN), two components of the ECM surrounding tumors, are highly expressed in metastatic tumors and their patterns of expression can correlate with metastatic outcome in patient samples. Mena, an actin regulatory protein, is upregulated in breast cancer and is alternatively spliced to produce protein isoforms with distinct functions during tumor progression. The invasion-specific MenaINV isoform increases metastasis by potentiating tumor cell motility and invasion responses to various growth factors. All Mena isoforms bind directly to the α5 subunit of the α5β1 integrin, an FN receptor. We hypothesized that the interaction between MenaINV and α5β1 plays an important role in integrating signals from the ECM as well as growth factors to drive invasion. MDA-MB-231 breast cancer cells expressing MenaINV showed increased adhesion to FN alone as well as mixture of FN and CN, compared to control cells. MenaINV cells also had an increased number of α5-positive adhesions as well as increased signalling at focal adhesions as measured by phospho-Paxilin, compared to control. In 3D invasion assays, addition of FN to a CN gel drove invasion of MenaINV-expressing cells even in the absence of any growth factor ligand, an effect driven by its interaction with α5 and dependent on signalling via EGFR and Met. Furthermore, addition of FN caused an even greater potentiation of EGF-induced invasion by MenaINV, an effect that was dependent upon its interaction with α5. Next, we examined how MenaINV affects tumor cell responses to a gradient of FN within a 3D collagen gel. Control cells failed to respond to an FN gradient, while cells expressing MenaINV migrated preferentially towards FN and significantly reorganized both the collagen and FN surrounding them. Deletion of the α5 binding site or treatment with an α5 function blocking antibody ablated the effects MenaINV on movement towards a FN gradient as well ECM reorganization. Overall, these results suggest that some aspects of the pro-metastatic effects of MenaINV involve its ability to bind α5 and regulate bidirectional signaling with FN and growth factors in the tumor microenvironment. Citation Format: Madeleine J. Oudin, Liliane C. Broye, Alisha Lussiez, Sreeja B. Asokan, Miles A. Miller, Douglas A. Lauffenburger, James E. Bear, Frank B. Gertler. MenaINV interaction with α5β1 promotes tumor cell invasion in response to gradients of growth factors and fibronectin. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1988. doi:10.1158/1538-7445.AM2014-1988