Pancreatic Fistula and Delayed Gastric Emptying Are the Highest-Impact Complications After Whipple.

BACKGROUND: Patients undergoing pancreaticoduodenectomy are at risk for a variety of adverse postoperative events, including generic complications such as surgical site infection (SSI) and procedure-specific complications such as postoperative pancreatic fistula (POPF) and delayed gastric emptying (DGE). Knowing which complications have the greatest effect on these patients can help to maximize the value of quality improvement resources. This study aims to quantify the effect of specific postoperative complications on clinical outcomes and resource utilization after pancreaticoduodenectomy. MATERIALS AND METHODS: Patients undergoing pancreaticoduodenectomy between January 2014 and December 2016, who were included in the pancreatectomy-targeted American College of Surgeons National Surgical Quality Improvement Program, were assessed for the development of specific postoperative complications, along with the contributions of these complications toward subsequent clinical outcome and resource utilization. The main outcomes were 30-d end-organ dysfunction, mortality, prolonged hospitalization, nonrounding discharge status, and hospital readmission. Risk-adjusted population attributable fractions were estimated for each complication-outcome pair, with the population attributable fraction representing the anticipated percentage reduction in the outcome where the complication was able to be completely prevented. RESULTS: About 10,922 patients undergoing pancreaticoduodenectomy were included for analysis. The most common postoperative complications were DGE (17.3%), POPF (10.1%), incisional SSI (10.0%), and organ/space SSI (6.2%). POPF and DGE were the only complications that demonstrated sizable effects for all clinical and resource utilization outcomes studied. Other complications had sizable effects for only a few of the outcomes or had small effects for all the outcomes. CONCLUSIONS: Quality initiatives seeking to minimize the burden imposed by postpancreaticoduodenectomy morbidity should focus on POPF and DGE rather than generic complications.

Breast Cancer Survivor Advocacy at a University Hospital: Development of a Peer Support Program with Evaluation by Patients, Advocates, and Clinicians.

Peer-to-peer support programs provide unique psychosocial and educational support for breast cancer patients. A Patient Survivor Advocacy (PSA) program was developed by the University of Wisconsin Breast Center (UWBC) to provide support for newly diagnosed patients from peers who had completed primary treatment. In this study, we evaluated patient, advocate, and clinician experience with the PSA program. A program matching volunteer peer advocates at least 1 year removed from primary treatment with newly diagnosed patients was developed. Peer advocates were recruited from the practices of UWBC clinicians and received in-person training on six dimensions of peer advocacy. Trained advocates were then paired based on demographic and medical history with new patients referred to the program. Survey assessment tools were distributed to assess peer advocate and patient satisfaction, as well as clinician experience. Forty patients have been matched with seven advocates, with contact largely by email (53 %) or phone (36 %). Patients and peer advocates reported satisfaction with the program. The majority of patients (92.9 %) reported that the program was "helpful" and that they would recommend the PSA program to another woman with breast cancer. All peer advocates (100 %) responded with a sense of achievement in their advocate roles. Clinicians noted challenges in referral to the program. Peer advocates can provide key emotional and psychosocial support to newly diagnosed breast cancer patients. The peer advocate, patient, and clinician feedback collected in this study will inform the future development of this program at our and peer institutions.

Reexcision Surgery for Breast Cancer: An Analysis of the American Society of Breast Surgeons (ASBrS) MasterySM Database Following the SSO-ASTRO "No Ink on Tumor" Guidelines.

BACKGROUND: In February 2014 , the Society of Surgical Oncology and the American Society for Radiation Oncology released guidelines standardizing a negative margin after breast-conserving surgery (BCS) as "no ink on tumor" in patients with early-stage invasive cancer. We sought to determine whether reexcision rates after initial BCS decreased after guideline publication, using the ASBrS MasterySM of Breast Surgery Program. METHODS: Between January 2013 and June 2015, data from the ASBrS MasterySM database was analyzed to determine reexcision rates pre and post guideline publication. Reasons for reexcision were evaluated as were the associations with patient and provider characteristics. Chi square test, Fisher's exact test, Student's t test, ANOVA, and multivariable logistic regression were used as appropriate. All analyses were performed using Microsoft Excel and SPSS, with p value <0.05 as significant. RESULTS: Among 252 providers, the overall reexcision rate after initial BCS decreased by 3.7 % from 20.2 to 16.5 % (p < 0.001). Notable was a 13.8 % decrease (p < 0.001) in reexcisions being done for close margins. Of the analyzed physician and patient characteristics the majority of subgroups showed decreases between the two time periods; however, only "Percent Breast Surgery in Practice" was significant. On adjusted analysis, there were no specific patient factors associated with a reduction in reexcision rates. CONCLUSIONS: Following the SSO-ASTRO "no ink on tumor" guideline publication, a reduction in overall reexcision rates and reexcision rates for close margins after initial BCS was observed in the ASBrS MasterySM database. More widespread implementation outside this group of early adopters is anticipated with ongoing dissemination.

Analysis of Immune Cells from Human Mammary Ductal Epithelial Organoids Reveals Vδ2+ T Cells That Efficiently Target Breast Carcinoma Cells in the Presence of Bisphosphonate.

Developing strategies to enhance cancer prevention is a paramount goal, particularly given recent concerns about surgical treatment of preinvasive states such as ductal carcinoma in situ. Promoting effective immunosurveillance by leukocytes that scan for nascent neoplastic transformations represents a potential means to achieve this goal. Because most breast cancers arise within the ductal epithelium, enhancing protective immunosurveillance will likely necessitate targeting one or more of the distinctive lymphocyte types found in these sites under normal conditions. Here, we have characterized the intraepithelial lymphocyte compartment of non-cancerous human breast tissue and identified a subset of T lymphocytes that can be pharmacologically targeted to enhance their responses to breast cancer cells. Specifically, Vδ2(+) γδ T cells were consistently present in preparations of mammary ductal epithelial organoids and they proliferated in response to zoledronic acid, an aminobisphosphonate drug. Vδ2(+) T cells from breast ductal organoids produced the antitumor cytokine IFNγ and efficiently killed bisphosphonate-pulsed breast carcinoma cells. These findings demonstrate the potential for exploiting the ability of Vδ2(+) γδ T cells to respond to FDA-approved bisphosphonate drugs as a novel immunotherapeutic approach to inhibit the outgrowth of breast cancers.

Differential CARM1 Isoform Expression in Subcellular Compartments and among Malignant and Benign Breast Tumors.

PURPOSE: Coactivator-associated arginine methyltransferase 1 (CARM1) is a coactivator for ERα and cancer-relevant transcription factors, and can methylate diverse cellular targets including histones. CARM1 is expressed in one of two alternative splice isoforms, full-length CARM1 (CARM1FL) and truncated CARM1 (CARM1ΔE15). CARM1FL and CARM1ΔE15 function differently in transcriptional regulation, protein methylation, and mediation of pre-mRNA splicing in cellular models. METHODS: To investigate the functional roles and the prognosis potential of CARM1 alternative spliced isoforms in breast cancer, we used recently developed antibodies to detect differential CARM1 isoform expression in subcellular compartments and among malignant and benign breast tumors. RESULTS: Immunofluorescence in MDA-MB-231 and BG-1 cell lines demonstrated that CARM1ΔE15 is the dominant isoform expressed in the cytoplasm, and CARM1FL is more nuclear localized. CARM1ΔE15 was found to be more sensitive to Hsp90 inhibition than CARM1FL, indicating that the truncated isoform may be the oncogenic form. Clinical cancer samples did not have significantly higher expression of CARM1FL or CARM1ΔE15 than benign breast samples at the level of mRNA or histology. Furthermore neither CARM1FL nor CARM1ΔE15 expression correlated with breast cancer molecular subtypes, tumor size, or lymph node involvement. CONCLUSIONS: The analysis presented here lends new insights into the possible oncogenic role of CARM1ΔE15. This study also demonstrates no obvious association of CARM1 isoform expression and clinical correlates in breast cancer. Recent studies, however, have shown that CARM1 expression correlates with poor prognosis, indicating a need for further studies of both CARM1 isoforms in a large cohort of breast cancer specimens.

Metastasis of primary lung carcinoma to the breast: a systematic review of the literature.

BACKGROUND: The purpose of this systematic review was to summarize previously published case reports of primary lung carcinoma metastasis to the breast to assess common clinical and pathologic features and management strategies. MATERIALS AND METHODS: Case reports describing breast metastasis of primary lung carcinoma were systematically evaluated in MEDLINE and EMBASE. RESULTS: Thirty-one reported cases of non-small-cell lung carcinoma (NSCLC) metastasized to the breast were identified, along with eight cases of small-cell lung carcinoma. Sixty-seven percent of reported NSCLC metastases to the breast were detected metachronously with the primary lung abnormality, whereas 80% of small-cell lung carcinoma breast metastases appeared synchronously. Thyroid transcription factor 1 was found to be expressed in 58% of total NSCLC breast metastases, including 83% of those of adenocarcinoma origin. Therapeutic strategies among NSCLC cases varied widely, and only 36% of NSCLC breast metastasis patients were administered chemotherapy. Additional sites of metastasis in these cases are summarized as well. CONCLUSIONS: It is recommended to include metastatic lung cancer in the differential diagnosis of patients presenting with a breast abnormality in the context of a suspected lung cancer. Thyroid transcription factor 1 expression should be examined in these cases. The metachronous versus synchronous nature of lung carcinoma metastasis to the breast has consequences for both detection of the primary and secondary lesions and patient outlook. Clinical correlation is vital to effective management of the care of patients harboring these atypical secondary lesions.