Integration of multiomics data shows down regulation of mismatch repair and tubulin pathways in triple-negative chemotherapy-resistant breast tumors.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Patients with TNBC are primarily treated with neoadjuvant chemotherapy (NAC). The response to NAC is prognostic, with reductions in overall survival and disease-free survival rates in those patients who do not achieve a pathological complete response (pCR). Based on this premise, we hypothesized that paired analysis of primary and residual TNBC tumors following NAC could identify unique biomarkers associated with post-NAC recurrence. METHODS AND RESULTS: We investigated 24 samples from 12 non-LAR TNBC patients with paired pre- and post-NAC data, including four patients with recurrence shortly after surgery (< 24 months) and eight who remained recurrence-free (> 48 months). These tumors were collected from a prospective NAC breast cancer study (BEAUTY) conducted at the Mayo Clinic. Differential expression analysis of pre-NAC biopsies showed minimal gene expression differences between early recurrent and nonrecurrent TNBC tumors; however, post-NAC samples demonstrated significant alterations in expression patterns in response to intervention. Topological-level differences associated with early recurrence were implicated in 251 gene sets, and an independent assessment of microarray gene expression data from the 9 paired non-LAR samples available in the NAC I-SPY1 trial confirmed 56 gene sets. Within these 56 gene sets, 113 genes were observed to be differentially expressed in the I-SPY1 and BEAUTY post-NAC studies. An independent (n = 392) breast cancer dataset with relapse-free survival (RFS) data was used to refine our gene list to a 17-gene signature. A threefold cross-validation analysis of the gene signature with the combined BEAUTY and I-SPY1 data yielded an average AUC of 0.88 for six machine-learning models. Due to the limited number of studies with pre- and post-NAC TNBC tumor data, further validation of the signature is needed. CONCLUSION: Analysis of multiomics data from post-NAC TNBC chemoresistant tumors showed down regulation of mismatch repair and tubulin pathways. Additionally, we identified a 17-gene signature in TNBC associated with post-NAC recurrence enriched with down-regulated immune genes.

Lymph node positivity and association with long-term survival for different histologies of appendiceal cancer.

BACKGROUND: Appendiceal cancers represent a diverse group of malignancies with varying biological behavior. The significance of lymph node metastases in relation to long-term survival and chemotherapy response is poorly defined. METHODS: The National Cancer Database was queried to find patients diagnosed with appendiceal cancer from 1998 to 2012. Kaplan-Meier curves and multivariable Cox regression analyses were used to study the association between lymph node status and overall survival. Stage IV patients were excluded. RESULTS: The rate of nodal positivity of the 9841 patients with known node status was: signet ring 47.4%, carcinoid 42.3%, nonmucinous adenocarcinoma 28.8%, goblet cell 21.9%, and mucinous adenocarcinoma 20.4%. Node-positive patients had worse long-term survival for all subtypes with the exception of carcinoid tumors (p < 0.001). The strongest association was for signet cell and goblet cell. Adjuvant chemotherapy in node-positive patients improved survival for mucinous, nonmucinous, and signet ring cell histology (p < 0.01), but not for goblet cell. CONCLUSIONS: Nodal involvement in patients with appendiceal cancer varies in incidence, association with adverse survival, and response to systemic therapy. Individualized treatment algorithms for the management of the subtypes of appendiceal cancer are needed.

Unplanned implant removal in locally advanced breast cancer.

Study conducted to determine frequency and timing of unplanned breast implant removal after mastectomy, reconstruction, and postmastectomy radiation (PMRT). From 2010-2017, 52 patients underwent mastectomy, reconstruction, and PMRT. With median follow-up of 3.1 years, 23 patients (44%) experienced implant removal. Implant removal occurred in 9 (17%) patients before starting PMRT and 14 (27%) patients after starting PMRT. Implant removal rates were similar for hypofractionated PMRT compared with standard fractionation and for proton compared with photon PMRT. Implant removal is common for women undergoing mastectomy and reconstruction followed by PMRT. The risk is clinically significant even before starting radiation.

Association between subthreshold depression and self-care behaviours in adults with type 2 diabetes: A protocol for a cross-sectional study.

AIMS AND OBJECTIVES: To examine the association between subthreshold depression and self-care behaviours in adults with type 2 diabetes (T2D) attending a tertiary healthcare service. BACKGROUND: Diabetes is a global public health problem. Self-care behaviours are a fundamental element in managing diabetes as adherence to self-care activities is associated with improved glycaemic control. Depression in T2D is associated with decreased adherence to self-care behaviours. Adults with subthreshold depression in diabetes may have difficulties in achieving metabolic control. Further, people with subthreshold depression have an increased risk of developing major depression. Few studies have examined the association between subthreshold depression and self-care behaviours. DESIGN: A cross-sectional study. METHODS: The study will be conducted among 384 adults diagnosed with T2D for at least a year attending their routine outpatient appointment at Tribhuvan University Teaching Hospital in Nepal. Convenience sampling will be used to recruit study participants. Data will be collected via face-to-face interviews and a medical record review. Self-care behaviours will be assessed using the Summary of Diabetes Self-care activities and subthreshold depression will be determined using the Patient Health Questionnaire- 9. Covariates in the study include sociodemographic and clinical factors, diabetes knowledge, perceived social support and self-efficacy. This paper complies with the STROBE reporting guideline for cross-sectional studies. RESULTS: We will use multiple linear regression to examine the association between subthreshold depression and each self-care behaviours (i.e. diet, physical activity, foot care, blood glucose testing and medication) and total self-care behaviour. CONCLUSIONS: Effective management of diabetes requires adherence to self-care behaviours. The findings of the study will help in identifying an effective way to improve diabetes self-care. RELEVANCE TO CLINICAL PRACTICE: Our observations will inform nursing research and practice by providing evidence about how subthreshold depression may influence self-care behaviours.

Implementation of an Enhanced Recovery After Surgery (ERAS) Program is Associated with Improved Outcomes in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has been associated with increased postoperative complications and a prolonged length of stay (LOS). We report on our experience following implementation of an Enhanced Recovery After Surgery (ERAS) program for CRS and HIPEC. METHODS: Patients were divided into pre- and post-ERAS groups. Modifications in the ERAS group included routine use of transversus abdominis plane blocks, intra- and postoperative fluid restriction, and minimizing the use of narcotics, drains, and nasogastric tubes. RESULTS: Of a total of 130 procedures, 49 (38%) were in the pre-ERAS group and 81 (62%) were in the ERAS group. Mean LOS was reduced from 10.3 ± 8.9 days to 6.9 ± 5.0 days (p = 0.007) and the rate of grade III/IV complications was reduced from 24 to 15% (p = 0.243) following ERAS implementation. The ERAS group received less intravenous fluid during hospitalization (19.2 ± 18.7 L vs. 32.8 ± 32.5 L, p = 0.003) and used less opioids than the pre-ERAS group (median of 159.7 mg of oral morphine equivalents vs. 272.6 mg). There were no significant changes in the rates of 30-day readmission or acute kidney injury between the two groups (p = non-significant). On multivariable analyses, ERAS was significantly associated with a reduction in LOS (- 2.89 days, 95% CI - 4.84 to - 0.94) and complication rates (odds ratio 0.22, 95% CI 0.08-0.57). CONCLUSIONS: Implementation of an ERAS program for CRS and HIPEC is associated with a reduction in overall intravenous fluids, postoperative narcotic use, complication rates, and LOS.

Depomedroxyprogesterone acetate therapy for hot flashes in survivors of breast cancer: no unfavorable impact on recurrence and survival.

PURPOSE: Survivors of estrogen receptor-expressing breast cancer generally do not receive estrogen-based therapy for menopausal symptoms due to concern for provoking recurrence of disease. Single-dose depomedroxyprogesterone acetate has been shown to be among the most effective non-estrogen strategies for treatment of menopausal hot flashes, but long-term evidence for safety in survivors is lacking. METHODS: We conducted an institutional review board approved, retrospective, case-control cohort study at a tertiary, academic referral center. Patients with estrogen receptor-expressing early-stage operable breast cancer who received depomedroxyprogesterone acetate for hot flashes between January 2005 and December 2012 were identified. We confirmed 75 patients who met strict inclusion criteria who were matched 1:1 with controls for age, stage of disease, HER2 status, and year of diagnosis. Overall survival, loco-regional recurrence-free survival, and progression-free survival assessments for cases were compared with controls. RESULTS: Median follow-up duration was 68.4 months in cases and 57.6 months in controls. Estimated local-regional recurrence-free survival at 10 years was 97% (95% CI, 92-100%) in cases and 98% (95% CI, 95-100%) in controls. Estimated progression-free survival at 10 years was 89% (95% CI, 80-100%) in cases and 83% (95% CI, 73-95) in controls. The majority (75%) of case patients experienced satisfactory relief of hot flashes from depomedroxyprogesterone injection. DISCUSSION: In this retrospective case-control study, we were unable to identify a detrimental effect of depomedroxyprogesterone acetate therapy for hot flashes in survivors of estrogen receptor-expressing breast cancer. Depomedroxyprogesterone acetate may be acceptable for management of hot flashes in this population.

Pain and opioid prescriptions vary by procedure after breast surgery.

BACKGROUND: With the opioid epidemic in the United States, evaluating opioid prescribing patterns is essential. We evaluated opioids prescribed at discharge following breast surgery and their association with patient factors and pain scores. METHODS: We retrospectively identified adult patients who underwent a mastectomy for cancer at Mayo Clinic sites from January 2010 to December 2016. Pain scores and prescription data were compared across operations and patient factors by univariate and multivariable analyses. RESULTS: Of 4021 patients, 3782 (94.1%) received an opioid prescription. Median oral milligram morphine equivalents (MME) were similar across all site-specific procedure groups (medians ranging from 225 to 375) while pain scores ranged from 1 to 4. Patients undergoing bilateral mastectomy (BM) and immediate breast reconstruction (IBR) reported the greatest pain scores. Pain scores did not vary with age or diagnosis for patients undergoing unilateral mastectomy or BM with lymph node surgery and IBR procedures. On multivariable analysis, variables associated with a MME discharge prescription >Q4 values included age, body mass index, site, year, inpatient status, and pain before discharge >3. CONCLUSION: Patient-reported pain following breast surgery varied by procedure, while MMEs prescribed remained similar. This suggests current opioid prescribing does not reflect intensity of pain and requires further research to optimize discharge opioid prescribing practices.

Cognitive profile and determinants of poor cognition in people without dementia in Parkinson's disease.

Background: The Montreal Cognitive Assessment (MoCA) has been recommended as a cognitive screening tool for clinical practice and research in Parkinson's disease (PD), yet no normative data have been published for MoCA in PD without dementia. Methods: We undertook a pooled secondary analysis of data from two studies (one cross-sectional design and one clinical trial) conducted in the East of England region. All participants were aged 18 years or over, met UK Brain Bank criteria for PD and did not have clinical dementia. Cognitive status was assessed using MoCA at baseline in both studies. The influences of age, gender, disease duration, medication load (LEDD) and mood (HADS) on cognition were examined using regression analysis. Results: Data from 101 people with PD without dementia were available (mean age 71 years, 66% men). Median (IQR) MoCA was 25(22, 27). Age was found as the only predictor of MoCA in this sample. People aged over 71 had poorer MoCA (Beta=0.6 (95%CI 0.44, 0.82)) and an increased odds of MoCA <26 (Beta=0.29 (95%CI 0.12, 0.70)) as well as poorer scores on several MoCA sub-domains. Conclusion: We present the normative data for MoCA in people with PD without clinical dementia. Age appeared to be the only associated factor for lower level of cognition, suggestive of Mild cognitive impairment in PD (PD-MCI) in PD without clinical diagnosis of dementia.

Intraoperative Margin Management in Breast-Conserving Surgery: A Systematic Review of the Literature.

BACKGROUND: Breast surgeons have a wide variety of intraoperative techniques available to help achieve low rates for positive margins of excision, with variable levels of evidence. METHODS: A systematic review of the medical literature from 1995 to July 2016 was conducted, with 434 abstracts identified and evaluated. The analysis included 106 papers focused on intraoperative management of breast cancer margins and contained actionable data. RESULTS: Ultrasound-guided lumpectomy for palpable tumors, as an alternative to palpation guidance, can lower positive margin rates, but the effect when used as an alternative to wire localization (WL) for nonpalpable tumors is less certain. Localization techniques such as radioactive seed localization and radioguided occult lesion localization were found potentially to lower positive margin rates as alternatives to WL depending on baseline positive margin rates. Intraoperative pathologic methods including gross histology, frozen section analysis, and imprint cytology all have the potential to lower the rates of positive margins. Cavity-shave margins and the Marginprobe device both lower rates of positive margins, with some potential for negative cosmetic effects. Specimen radiography and multiple miscellaneous techniques did not affect positive margin rates or provided too little evidence for formation of a conclusion. CONCLUSIONS: A systematic review of the literature showed evidence that several intraoperative techniques and actions can lower the rates of positive margins. These results are presented together with graded recommendations.

Racial and Socioeconomic Differences in the Use of High-Volume Commission on Cancer-Accredited Hospitals for Cancer Surgery in the United States.

BACKGROUND: Although major cancer surgery at a high-volume hospital is associated with lower postoperative mortality, the use of such hospitals may not be equally distributed. OBJECTIVE: Our aim was to study socioeconomic and racial differences in cancer surgery at Commission on Cancer (CoC)-accredited high-volume hospitals. METHODS: The National Cancer Database (NCDB) was used to identify patients undergoing surgery for colon, esophageal, liver, and pancreatic cancer from 2003 to 2012. Annual hospital volume for each cancer was categorized using quartiles of patient volume. Patient-level predictors of surgery at a high-volume hospital, trends in the use of a high-volume hospital, and adjusted likelihood of surgery at a high-volume hospital in 2012 versus 2003 were analyzed. RESULTS: African American patients were less likely to undergo surgery at a high-volume hospital for esophageal (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.49-0.73) and pancreatic cancer (OR 0.83, 95% CI 0.74-0.92), while uninsured patients and those residing in low educational attainment zip codes were less likely to undergo surgery at a high-volume hospital for esophageal, liver, and pancreatic cancer. In 2012, African Americans, uninsured patients, and those from low educational attainment zip codes were no more likely to undergo surgery at a high-volume hospital than in 2003 for any cancer type. These differences were not seen in colon cancer patients, for whom significant regionalization was not seen. CONCLUSIONS: Differences in the use of CoC-accredited high-volume hospitals for major cancer surgery were seen nationwide and persisted over the duration of the study. Strategies to increase referrals and/or access to high-volume hospitals for African American and socioeconomically disadvantaged patients should be explored.

Nipple Discharge: Imaging Variability Among U.S. Radiologists.

OBJECTIVE: The purpose of this study was to assess radiologists' choice of imaging modality for the evaluation of clinical symptoms of physiologic nipple discharge (e.g., bilateral discharge, multiple-duct orifices, and yellow, green, or white color) and pathologic nipple discharge (e.g., unilateral discharge, single-duct orifices, spontaneous and serous discharge, and clear or bloodstained color). MATERIALS AND METHODS: An online survey was sent to lead interpreting physicians at mammography facilities accredited by the American College of Radiology (ACR). Statistical analysis was performed using chi-square tests for frequency data and multinomial logistic regression. RESULTS: A total of 849 responses to 8170 distributed surveys were received, for a response rate of 10.4%. For the workup of physiologic nipple discharge, 30% of respondents recommended screening mammography (SM); 24%, diagnostic mammography (DM) only; and 46%, both DM and targeted ultrasound (US) (DM plus US). For the workup of physiologic nipple discharge, practitioners in nonacademic settings and those who read breast images during less than 50% of their practice were significantly more likely to recommend DM (with or without US), compared with SM (the standard recommended by the ACR). Those reading breast images less than 50% of the time were also more likely to recommend MRI after conventional imaging revealed negative results. For the workup of pathologic nipple discharge, 91.0% of respondents recommended DM plus US; 8.5%, DM only; and fewer than 1.0%, SM. Nonacademic providers and those who read breast images less than 50% of the time were significantly less likely to recommend DM plus US (the standard recommended by the ACR), compared with DM only. CONCLUSION: The present study shows variability in imaging modality selection among U.S. radiologists handling the imaging workflow for benign and pathologic nipple discharge. Radiologists do not uniformly follow ACR practice guidelines, which potentially leads to unnecessary workups and extra health care costs.

Establishing and characterizing patient-derived xenografts using pre-chemotherapy percutaneous biopsy and post-chemotherapy surgical samples from a prospective neoadjuvant breast cancer study.

BACKGROUND: Patient-derived xenografts (PDXs) are increasingly used in cancer research as a tool to inform cancer biology and drug response. Most available breast cancer PDXs have been generated in the metastatic setting. However, in the setting of operable breast cancer, PDX models both sensitive and resistant to chemotherapy are needed for drug development and prospective data are lacking regarding the clinical and molecular characteristics associated with PDX take rate in this setting. METHODS: The Breast Cancer Genome Guided Therapy Study (BEAUTY) is a prospective neoadjuvant chemotherapy (NAC) trial of stage I-III breast cancer patients treated with neoadjuvant weekly taxane+/-trastuzumab followed by anthracycline-based chemotherapy. Using percutaneous tumor biopsies (PTB), we established and characterized PDXs from both primary (untreated) and residual (treated) tumors. Tumor take rate was defined as percent of patients with the development of at least one stably transplantable (passed at least for four generations) xenograft that was pathologically confirmed as breast cancer. RESULTS: Baseline PTB samples from 113 women were implanted with an overall take rate of 27.4% (31/113). By clinical subtype, the take rate was 51.3% (20/39) in triple negative (TN) breast cancer, 26.5% (9/34) in HER2+, 5.0% (2/40) in luminal B and 0% (0/3) in luminal A. The take rate for those with pCR did not differ from those with residual disease in TN (p = 0.999) and HER2+ (p = 0.2401) tumors. The xenografts from 28 of these 31 patients were such that at least one of the xenografts generated had the same molecular subtype as the patient. Among the 35 patients with residual tumor after NAC adequate for implantation, the take rate was 17.1%. PDX response to paclitaxel mirrored the patients' clinical response in all eight PDX tested. CONCLUSIONS: The generation of PDX models both sensitive and resistant to standard NAC is feasible and these models exhibit similar biological and drug response characteristics as the patients' primary tumors. Taken together, these models may be useful for biomarker discovery and future drug development.

Wide Variation and Overprescription of Opioids After Elective Surgery.

OBJECTIVE: We aimed to identify opioid prescribing practices across surgical specialties and institutions. BACKGROUND: In an effort to minimize the contribution of prescription narcotics to the nationwide opioid epidemic, reductions in postoperative opioid prescribing have been proposed. It has been suggested that a maximum of 7 days, or 200 mg oral morphine equivalents (OME), should be prescribed at discharge in opioid-naïve patients. METHODS: Adults undergoing 25 common elective procedures from 2013 to 2015 were identified from American College of Surgeons National Surgical Quality Improvement Program data from 3 academic centers in Minnesota, Arizona, and Florida. Opioids prescribed at discharge were abstracted from pharmacy data and converted into OME. Wilcoxon Rank-Sum and Kruskal-Wallis tests assessed variations. RESULTS: Of 7651 patients, 93.9% received opioid prescriptions at discharge. Of 7181 patients who received opioid prescriptions, a median of 375 OME (interquartile range 225-750) were prescribed. Median OME varied by sex (375 men vs 390 women, P = 0.002) and increased with age (375 age 18-39 to 425 age 80+, P < 0.001). Patients with obesity and patients with non-cancer diagnoses received more opioids (both P < 0.001). Subset analysis of the 5756 (75.2%) opioid-naïve patients showed the majority received >200 OME (80.9%). Significant variations in opioid prescribing practices were seen within each procedure and between the 3 medical centers. CONCLUSIONS: The majority of patients were overprescribed opioids. Significant prescribing variation exists that was not explained by patient factors. These data will guide practices to optimize opioid prescribing after surgery.

Outcomes of Concurrent Breast and Gynecologic Risk Reduction Surgery.

BACKGROUND: Women considering risk reduction surgery after a diagnosis of breast/ovarian cancer and/or inherited cancer gene mutation face difficult decisions. The safety of combined breast and gynecologic surgery has not been well studied; therefore, we evaluated the outcomes for patients who have undergone coordinated multispecialty surgery. METHODS: We conducted a retrospective review of patients undergoing simultaneous breast and gynecologic surgery for newly or previously diagnosed breast cancer and/or an inherited cancer gene mutation during the same anesthetic at a single institution from 1999 to 2013. RESULTS: Seventy-three patients with a mean age of 50 years (range 27-88) were identified. Most patients had newly diagnosed breast cancer or ductal carcinoma in situ (62 %) and 28 patients (38 %) had an identified BRCA mutation. Almost all gynecologic procedures were for risk reduction or benign gynecologic conditions (97 %). Mastectomy was performed in 39 patients (53 %), the majority of whom (79 %) underwent immediate reconstruction. The most common gynecologic procedure involved bilateral salpingo-oophorectomy, which was performed alone in 18 patients (25 %) and combined with hysterectomy in 40 patients (55 %). A total of 32 patients (44 %) developed postoperative complications, most of which were minor and did not require surgical intervention or hospitalization. Two of the 19 patients who underwent implant reconstruction (11 %; 3 % of the entire cohort) had major infectious complications requiring explantation. CONCLUSION: Combined breast and gynecologic procedures for a breast cancer diagnosis and/or risk reduction in patients can be accomplished with acceptable morbidity. Concurrent operations, including reconstruction, can be offered to patients without negatively impacting their outcome.

Potential Cost Savings of Contrast-Enhanced Digital Mammography.

OBJECTIVE: The purpose of this article is to discuss whether the sensitivity and specificity of contrast-enhanced digital mammography (CEDM) render it a viable diagnostic alternative to breast MRI. CONCLUSION: That CEDM couples low-energy images (comparable to the diagnostic quality of standard mammography) and subtracted contrast-enhanced mammograms make it a cost-effective modality and a realistic substitute for the more costly breast MRI.

Religious and Spiritual Beliefs of Physicians.

The aim of this study is to describe religious and spiritual beliefs of physicians and examine their influence on the decision to pursue medicine and daily medical practice. An anonymous survey was e-mailed to physicians at a large, multidisciplinary tertiary referral center with satellite clinics. Data were collected from January 2014 through February 2014. There were 2097 respondents (69.1 % men), and number of practicing years ranged from ≤1 to ≥30. Primary care physicians or medical specialists represented 74.1 %, 23.6 % were in surgical specialties, and 2.3 % were psychiatrists. The majority of physicians believe in God (65.2 %), and 51.2 % reported themselves as religious, 24.8 % spiritual, 12.4 % agnostic, and 11.6 % atheist. This self-designation was largely independent of specialty except for psychiatrists, who were more likely report agnosticism (P = 0.003). In total, 29.0 % reported that religious or spiritual beliefs influenced their decision to become a physician. Frequent prayer was reported by 44.7 % of physicians, but only 20.7 % reported having prayed with patients. Most physicians consider themselves religious or spiritual, but the rates of agnosticism and atheism are higher than the general population. Psychiatrists are the least religious group. Despite the influence of religion on physicians' lives and medical practice, the majority have not incorporated prayer into patient encounters.

Association of Distance Traveled for Surgery with Short- and Long-Term Cancer Outcomes.

BACKGROUND: The influence of distance traveled for treatment on short- and long-term cancer outcomes is unclear. METHODS: Patients with colon, esophageal, liver, and pancreas cancer from 2003 to 2006 were identified from the National Cancer Data Base (NCDB). Distance traveled for surgical treatment was estimated using zip code centroids. Propensity scores were generated for probability of traveling farther for treatment. Mixed effects logistic regression for 90-day mortality and Cox regression for 5-year mortality were compared between patients treated regionally and those traveling from farther away. RESULTS: The mean distance traveled for all patients for surgical resection was 30.0 ± 227 miles, with a median distance of 7.5 (interquartile range 14.4) miles. Patients who were aged ≥80 years, on Medicaid, or African American were less likely to be in the fourth quartile of distance (Q4) traveled for surgery. Patients who were in Q4 had a lower risk-adjusted 90-day mortality compared to Q1 for colon [odds ratio (OR) 0.89, 95 % confidence interval (CI) 0.82-0.96], liver (OR 0.49, 95 % CI 0.3-0.78), and pancreatic (OR 0.74, 95 % CI 0.56-0.98) cancer. Similarly, patients in Q4 for all tumor types had a lower risk-adjusted 5-year mortality compared to patients in Q1; colon (hazard ratio (HR) 0.96, 95 % CI 0.93-0.99), esophagus (HR 0.84, 95 % CI 0.75-0.94), liver (HR 0.75, 95 % CI 0.62-0.89), and pancreas (HR 0.87, 95 % CI 0.80-0.95). CONCLUSIONS: Greater travel distance for surgical resection of gastrointestinal cancers is associated with lower 90-day and 5-year mortality outcomes. This distance bias has implications for regionalization and reporting of cancer outcomes.

Isolated limb perfusion in Merkel cell carcinoma offers high rate of complete response and durable local-regional control: Systematic review and institutional experience.

INTRODUCTION: Hyperthermic isolated limb perfusion (HILP) has an established role in the management of melanoma, but its role for Merkel cell carcinoma (MCC) is less well defined. METHODS: Retrospective review of our institutional experience with HILP for MCC was conducted (2009-2015). Literature search was performed through 04/2015 and 10 studies met inclusion criteria. RESULTS: Four patients underwent HILP for MCC at our institution. There were no major complications and complete response was achieved in all patients. Early metastatic recurrence developed in two patients. The remaining two had no evidence of disease at last follow-up (36 months) or death (39 months). Systematic review identified an additional 12 pts that underwent HILP for MCC, for a total of 16 cases. Median age was 73 [IQR 69-78] years and 56% were men. Of the patients with reported follow-up, 12 (86%) had complete response, 1 had stable disease, and 1 partial response. Four patients developed local-regional recurrence and six distant metastases, all within 6 months. Overall median follow-up time was 15 [7-36] months. CONCLUSION: Among a highly selective group of patients, regional perfusion for MCC is safe and has a high complete response rate. HILP is an acceptable therapeutic modality for obtaining durable loco-regional control but early distant metastatic disease remains a significant cause of mortality. J. Surg. Oncol. 2016;114:187-192. © 2016 Wiley Periodicals, Inc.

Exome sequencing reveals frequent deleterious germline variants in cancer susceptibility genes in women with invasive breast cancer undergoing neoadjuvant chemotherapy.

When sequencing blood and tumor samples to identify targetable somatic variants for cancer therapy, clinically relevant germline variants may be uncovered. We evaluated the prevalence of deleterious germline variants in cancer susceptibility genes in women with breast cancer referred for neoadjuvant chemotherapy and returned clinically actionable results to patients. Exome sequencing was performed on blood samples from women with invasive breast cancer referred for neoadjuvant chemotherapy. Germline variants within 142 hereditary cancer susceptibility genes were filtered and reviewed for pathogenicity. Return of results was offered to patients with deleterious variants in actionable genes if they were not aware of their result through clinical testing. 124 patients were enrolled (median age 51) with the following subtypes: triple negative (n = 43, 34.7%), HER2+ (n = 37, 29.8%), luminal B (n = 31, 25%), and luminal A (n = 13, 10.5%). Twenty-eight deleterious variants were identified in 26/124 (21.0%) patients in the following genes: ATM (n = 3), BLM (n = 1), BRCA1 (n = 4), BRCA2 (n = 8), CHEK2 (n = 2), FANCA (n = 1), FANCI (n = 1), FANCL (n = 1), FANCM (n = 1), FH (n = 1), MLH3 (n = 1), MUTYH (n = 2), PALB2 (n = 1), and WRN (n = 1). 121/124 (97.6%) patients consented to return of research results. Thirteen (10.5%) had actionable variants, including four that were returned to patients and led to changes in medical management. Deleterious variants in cancer susceptibility genes are highly prevalent in patients with invasive breast cancer referred for neoadjuvant chemotherapy undergoing exome sequencing. Detection of these variants impacts medical management.