Patient-Reported Bowel, Urinary, and Sexual Outcomes After Laparoscopic-Assisted Resection or Open Resection for Rectal Cancer: The Australasian Laparoscopic Cancer of the Rectum Randomized Clinical Trial (ALaCart).

OBJECTIVE: The aim of this study was to compare patient-reported urinary, bowel, and sexual functioning of ALaCaRT Trial participants randomized to open or laparoscopic surgery for rectal cancer. SUMMARY BACKGROUND DATA: The primary endpoint, noninferiority of laparoscopic surgical resection adequacy, was not established. METHODS: Participants completed QLQ-CR29 at baseline, 3, and 12 months post-surgery. Additionally, women completed Rosen's Female Sexual Functioning Index (FSFI). Men completed the International Index of Erectile Function (IIEF) and QLQ-PR25. We compared the proportions of participants in each group who experienced moderate/severe symptoms/dysfunction at each time-point and compared mean difference scores from baseline to 12 months between groups. All analyses were intention-to-treat. Sexual functioning analyses included only the participants who expressed sexual interest at baseline. RESULTS: Baseline PRO compliance of 475 randomized participants was 88%. At 12 months, a lower proportion of open surgery participants experienced moderate-severe fecal incontinence and sore skin, compared to Laparoscopic participants, and a lower proportion of men randomized to open surgery experienced moderate-severe urinary symptoms. There were no differences at 3 months for bowel or urinary symptoms. Sexual functioning among sexually interested participants was similar between groups at 3 and 12 months; however, a lower proportion of women reported moderate to severe sexual dissatisfaction at 3 months in the open as compared to the laparoscopic group, (Rebecca.mercieca@sydney.edu.au., 95% CI 0.03-0.39). DISCUSSION: Despite the slightly lower proportions of open surgery participants self-reporting moderate-severe symptoms for 3 of 16 urinary/bowel domains, and lack of differences in sexual domains, it remains difficult to recommend one surgical approach over another for rectal resection.

Challenging NICE guidelines on parathyroid surgery.

BACKGROUND: National Institute of Clinical Excellence (NICE) recommend against routinely using Intra-Operative Parathyroid Hormone (IOPTH) for first-time parathyroid surgery due to its cost and minimal surgical benefit. The European Society of Endocrine Surgeons differ from this and recommends IOPTH with conflicting pre-operative or single imaging. NICE guidance acknowledged that this may change practice in larger centres. We devised a retrospective single-centre cohort study to analyse the impact of IOPTH on decision-making and cost-effectiveness. METHODOLOGY: First-time parathyroidectomy procedures for primary hyperparathyroidism were assessed between 2017 and 2019. Ultrasound (US) and Sestamibi with parathyroid single-photon emission with computed tomography (SPECT-CT) were compared with IOPTH. The contribution of IOPTH to cure and cost effectiveness ratio was calculated. RESULTS: 114 cases were included, with IOPTH performed in all cases, SPECT-CT in 112 and US in 108 cases. A cure rate of 99.1% (113/114) was achieved. 11.4% (13/114) of the cure rate was influenced by IOPTH (P 0.01), instigating further exploration when its levels didn't decrease. This included 7.1% (4/56) in the concordant-imaging cohort. IOPTH accuracy (96.5%) was significantly superior (P = 0.03) to both US (80%) and SPECT-CT (81%). Comparing the total costs for IOPTH testing over 2 years (£39,721) with 13 potential re-operative procedures in its absence (£63,536), a positive cost-effectiveness ratio of £1832 per re-operative procedure averted was achieved. CONCLUSION: Abandoning IOPTH in first-time parathyroid surgery is too ambitious when weighing the cost of re-operative surgery against cost savings obtained by using routine IOPTH to achieve an improved cure rate, even in concordant imaging.

MONARCC: a randomised phase II study of panitumumab monotherapy and panitumumab plus 5-fluorouracil as first-line therapy for RAS and BRAF wildtype metastatic colorectal cancer: a study by the Australasian Gastrointestinal Trials Group (AGITG).

BACKGROUND: Doublet chemotherapy in combination with a biologic agent has been a standard of care in patients with metastatic colorectal cancer for over a decade. The evidence for a "lighter" treatment approach is limited to mono-chemotherapy plus bevacizumab in the RAS unselected population. Anti-EGFR antibodies have activity as monotherapy or in combination with chemotherapy in RAS wildtype metastatic colorectal cancer; however their role in first-line treatment in combination with 5-fluorouracil monotherapy or when given alone has not been well studied. MONARCC aims to investigate this approach in an elderly population. METHODS/DESIGN: MONARCC is a prospective, open-label, multicentre, non-comparative randomised phase II trial. Eligible patients aged ≥70 with unresectable metastatic, untreated, RAS/BRAF wildtype metastatic colorectal cancer will be randomised 1:1 to receive panitumumab alone or panitumumab plus infusional 5-fluorouracil. RAS and BRAF analyses will be performed in local laboratories. Comprehensive Health Assessment and Limited Health Assessments will be performed at baseline and at 16 weeks, respectively, to assess frailty. The Patient Symptom Questionnaire and Overall Treatment Utility are to be undertaken at different timepoints to assess the impact of treatment-related toxicities and quality of life. Treatment will be delivered every 2 weeks until disease progression, unacceptable toxicity (as determined by treating clinician or patient), delay of treatment of more than 6 weeks, or withdrawal of consent. The primary end point is 6-month progression-free survival in both arms. Secondary end points include overall survival, time to treatment failure, objective tumour response rate as defined by RECIST v1.1 and safety (adverse events). Tertiary and correlative endpoints include the feasibility and utility of a comprehensive geriatric assessment, quality of life and biological substudies. DISCUSSION: MONARCC investigates the activity and tolerability of first-line panitumumab-based treatments with a view to expand on current treatment options while maximising progression-free and overall survival and quality of life in molecularly selected elderly patients with metastatic colorectal cancer. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry: ACTRN12618000233224 , prospectively registered 14 February 2018.

The Impact of COVID-19 on Surgical Education.

BACKGROUND: At the onset of social distancing, our general surgery residency transitioned its educational curriculum to an entirely virtual format with no gaps in conference offerings. The aim of this study is to examine the feasibility of our evolution to a virtual format and report program attitudes toward the changes. METHODS: On March 15, 2020, due to the coronavirus disease (COVID-19) our institution restricted mass gatherings. We immediately transitioned all lectures to a virtual platform. The cancellation of elective surgeries in April 2020 then created the need for augmented resident education opportunities. We responded by creating additional lectures and implementing a daily conference itinerary. To evaluate the success of the changes and inform the development of future curriculum, we surveyed residents and faculty regarding the changes. Classes and faculty answers were compared for perception of value of the online format. RESULTS: Pre-COVID-19, residency-wide educational offerings were concentrated to one half-day per week. Once restrictions were in place, our educational opportunities were expanded to a daily schedule and averaged 16.5 hours/week during April. Overall, 41/63 residents and 25/94 faculty completed the survey. The majority of residents reported an increased ability (56%) or similar ability (34.1%) to attend virtual conferences while 9.9% indicated a decrease. Faculty responses indicated similar effects (64% increased, 32% similar, 4% decreased). PGY-1 residents rated the changes negatively compared to other trainees and faculty. PGY-2 residents reported neutral views and all other trainees and faculty believed the changes positively affected educational value. Comments from PGY1 and 2 residents revealed they could not focus on virtual conferences as it was not "protected time" in a classroom and that they felt responsible for patient care during virtual lectures. A majority of both residents (61%) and faculty (84%) reported they would prefer to continue virtual conferences in the future. CONCLUSIONS: The necessity for adapting our academic offerings during the COVID-19 era has afforded our program the opportunity to recognize the feasibility of virtual platforms and expand our educational offerings. The majority of participants report stable to improved attendance and educational value. Virtual lectures should still be considered protected time in order to maximize the experience for junior residents.

Potential implications of new information concerning manganese Ohio community health effects studies.

Several epidemiology studies have been conducted in Ohio communities where industrial facilities with manganese emissions are located. New information not addressed in the published papers for this research has been disclosed by U.S. federal agencies pursuant to the Freedom of Information Act. This paper describes the newly available information, presents statistical analyses of the new summary data, and explores how this information potentially impacts the conclusions of the published research. Based on a statistical analysis of the newly available data, we found very few, and no consistent, statistical differences for various illnesses, self-reported symptoms, and neuropsychological/neuromotor test results between one community with a manganese emission source and a control town that were part of the initial research. Further, we determined that the distribution of total suspended particulate manganese air concentrations did not correlate with the distribution of the more biologically relevant respirable manganese concentrations when data from two communities with potential manganese emissions were combined. These results are important, particularly in determining whether the studies should influence regulatory reference values related to manganese. We recommend that the full health effects data set associated with the published research be made available and re-evaluated to address the issues identified in this paper.

Benchmarking the American Society of Breast Surgeon Member Performance for More Than a Million Quality Measure-Patient Encounters.

BACKGROUND: Nine breast cancer quality measures (QM) were selected by the American Society of Breast Surgeons (ASBrS) for the Centers for Medicare and Medicaid Services (CMS) Quality Payment Programs (QPP) and other performance improvement programs. We report member performance. STUDY DESIGN: Surgeons entered QM data into an electronic registry. For each QM, aggregate "performance met" (PM) was reported (median, range and percentiles) and benchmarks (target goals) were calculated by CMS methodology, specifically, the Achievable Benchmark of Care™ (ABC) method. RESULTS: A total of 1,286,011 QM encounters were captured from 2011-2015. For 7 QM, first and last PM rates were as follows: (1) needle biopsy (95.8, 98.5%), (2) specimen imaging (97.9, 98.8%), (3) specimen orientation (98.5, 98.3%), (4) sentinel node use (95.1, 93.4%), (5) antibiotic selection (98.0, 99.4%), (6) antibiotic duration (99.0, 99.8%), and (7) no surgical site infection (98.8, 98.9%); all p values < 0.001 for trends. Variability and reasons for noncompliance by surgeon for each QM were identified. The CMS-calculated target goals (ABC™ benchmarks) for PM for 6 QM were 100%, suggesting that not meeting performance is a "never should occur" event. CONCLUSIONS: Surgeons self-reported a large number of specialty-specific patient-measure encounters into a registry for self-assessment and participation in QPP. Despite high levels of performance demonstrated initially in 2011 with minimal subsequent change, the ASBrS concluded "perfect" performance was not a realistic goal for QPP. Thus, after review of our normative performance data, the ASBrS recommended different benchmarks than CMS for each QM.

Select Choices in Benign Breast Disease: An Initiative of the American Society of Breast Surgeons for the American Board of Internal Medicine Choosing Wisely® Campaign.

BACKGROUND: Up to 50% of all women encounter benign breast problems. In contrast to breast cancer, high-level evidence is not available to guide treatment. Management is therefore largely based on individual physician experience/training. The American board of internal medicine (ABIM) initiated its Choosing Wisely® campaign to promote conversations between patients and physicians about challenging the use of tests or procedures which may not be necessary. The American society of breast surgeons (ASBrS) Patient safety and quality committee (PSQC) chose to participate in this campaign in regard to the management of benign breast disease. METHODS: The PSQC solicited initial candidate measures. PSQC surgeons represent a wide variety of practices. The resulting measures were ranked by modified Delphi appropriateness methodology in two rounds. The final list was approved by ASBrS and endorsed by the ABIM. RESULTS: The final five measures are as follows. (1) Don't routinely excise areas of pseuodoangiomatous stromal hyperplasia (PASH) of the breast in patients who are not having symptoms from it. (2) Don't routinely surgically excise biopsy-proven fibroadenomas that are < 2 cm. (3) Don't routinely operate for a breast abscess without an initial attempt to percutaneously aspirate. (4) Don't perform screening mammography in asymptomatic patients with normal exams who have less than a 5-years life expectancy. (5) Don't routinely drain nonpainful, fluid-filled cysts. CONCLUSIONS: The ASBrS Choosing Wisely® measures that address benign breast disease management are easily accessible to patients via the internet. Consensus was reached by PSQC regarding these recommendations. These measures provide guidance for shared decision-making.

Adoptive transfer of natural killer cells promotes the anti-tumor efficacy of T cells.

The density of NK cells in tumors correlates positively with prognosis in many types of cancers. The average number of infiltrating NK cells is, however, quite modest (approximately 30 NK cells/sq.mm), even in tumors deemed to have a "high" density of infiltrating NK cells. It is unclear how such low numbers of tumor-infiltrating NK cells can influence outcome. Here, we used ovalbumin-expressing tumor cell lines and TCR transgenic, OVA-specific cytotoxic T lymphocytes (OT-I-CTLs) to determine whether the simultaneous attack by anti-tumor CTLs and IL-2-activated NK (A-NK) cells synergistically increases the overall tumor cell kill and whether upregulation of tumor MHC class-I by NK cell-derived interferon-gamma (IFNγ) improves tumor-recognition and kill by anti-tumor CTLs. At equal E:T ratios, A-NK cells killed OVA-expressing tumor cells better than OT-I-CTLs. The cytotoxicity against OVA-expressing tumor cells increased by combining OT-I-CTLs and A-NK cells, but the increase was additive rather than synergistic. A-NK cells adenovirally-transduced to produce IL-12 (A-NKIL-12) produced high amounts of IFNγ. The addition of a low number of A-NKIL-12 cells to OT-I-CTLs resulted in a synergistic, albeit modest, increase in overall cytotoxicity. Pre-treatment of tumor cells with NK cell-conditioned medium increased tumor MHC expression and sensitivity to CTL-mediated killing. Pre-treatment of CTLs with NK cell-conditioned medium had no effect on CTL cytotoxicity. In vivo, MHC class-I expression by OVA-expressing B16 melanoma lung metastases increased significantly within 24-48h after adoptive transfer of A-NKIL-12 cells. OT-I-CTLs and A-NKIL-12 cells localized selectively and equally well into OVA-expressing B16 lung metastases and treatment of mice bearing 7-days-old OVA-B16 lung metastases with both A-NKIL-12 cells and OT-I-CTLs lead to a significant prolongation of survival. Thus, an important function of tumor-infiltrating NK cells may be to increase tumor cell expression of MHC class-I through secretion of IFNγ, to prepare them for recognition by tumor-specific CTLs.

The American Society of Breast Surgeons and Quality Payment Programs: Ranking, Defining, and Benchmarking More Than 1 Million Patient Quality Measure Encounters.

BACKGROUND: To identify and remediate gaps in the quality of surgical care, the American Society of Breast Surgeons (ASBrS) developed surgeon-specific quality measures (QMs), built a patient registry, and nominated itself to become a Center for Medicare and Medicaid Services (CMS) Qualified Clinical Data Registry (QCDR), thereby linking surgical performance to potential reimbursement and public reporting. This report provides a summary of the program development. METHODS: Using a modified Delphi process, more than 100 measures of care quality were ranked. In compliance with CMS rules, selected QMs were specified with inclusion, exclusion, and exception criteria, then incorporated into an electronic patient registry. After surgeons entered QM data into the registry, the ASBrS provided real-time peer performance comparisons. RESULTS: After ranking, 9 of 144 measures of quality were chosen, submitted, and subsequently accepted by CMS as a QCDR in 2014. The measures selected were diagnosis of cancer by needle biopsy, surgical-site infection, mastectomy reoperation rate, and appropriateness of specimen imaging, intraoperative specimen orientation, sentinel node use, hereditary assessment, antibiotic choice, and antibiotic duration. More than 1 million patient-measure encounters were captured from 2010 to 2015. Benchmarking functionality with peer performance comparison was successful. In 2016, the ASBrS provided public transparency on its website for the 2015 performance reported by our surgeon participants. CONCLUSIONS: In an effort to improve quality of care and to participate in CMS quality payment programs, the ASBrS defined QMs, tracked compliance, provided benchmarking, and reported breast-specific QMs to the public.

Measures of Appropriateness and Value for Breast Surgeons and Their Patients: The American Society of Breast Surgeons Choosing Wisely (®) Initiative.

BACKGROUND: Current breast cancer care is based on high-level evidence from randomized, controlled trials. Despite these data, there continues to be variability of breast cancer care, including overutilization of some tests and operations. To reduce overutilization, the American Board of Internal Medicine Choosing Wisely (®) Campaign recommends that professional organizations provide patients and providers with a list of care practices that may not be necessary. Shared decision making regarding these services is encouraged. METHODS: The Patient Safety and Quality Committee of the American Society of Breast Surgeons (ASBrS) solicited candidate measures for the Choosing Wisely (®) Campaign. The resulting list of "appropriateness" measures of care was ranked by a modified Delphi appropriateness methodology. The highest-ranked measures were submitted to and later approved by the ASBrS Board of Directors. They are listed below. RESULTS: (1) Don't routinely order breast magnetic resonance imaging in new breast cancer patients. (2) Don't routinely excise all the lymph nodes beneath the arm in patients having lumpectomy for breast cancer. (3) Don't routinely order specialized tumor gene testing in all new breast cancer patients. (4) Don't routinely reoperate on patients with invasive cancer if the cancer is close to the edge of the excised lumpectomy tissue. (5) Don't routinely perform a double mastectomy in patients who have a single breast with cancer. CONCLUSIONS: The ASBrS list for the Choosing Wisely (®) campaign is easily accessible to breast cancer patients online. These measures provide surgeons and their patients with a starting point for shared decision making regarding potentially unnecessary testing and operations.

TARGIT-R (Retrospective): North American Experience with Intraoperative Radiation Using Low-Kilovoltage X-Rays for Breast Cancer.

BACKGROUND: Single-dose intraoperative radiotherapy (IORT) is an emerging treatment for women with early stage breast cancer. The objective of this study was to define the frequency of IORT use, patient selection, and outcomes of patients treated in North America. METHODS: A multi-institutional retrospective registry was created, and 19 institutions using low-kilovoltage IORT for the treatment of breast cancer entered data on patients treated at their institution before July 31, 2013. Patient selection, IORT treatment details, complications, and recurrences were analyzed. RESULTS: From 2007 to July 31, 2013, a total of 935 women were identified and treated with lumpectomy and IORT. A total of 822 patients had at least 6 months' follow-up documented and were included in the analysis. The number of IORT cases performed increased significantly over time (p < 0.001). The median patient age was 66.8 years. Most patients had disease that was <2 cm in size (90 %) and was estrogen positive (91 %); most patients had invasive ductal cancer (68 %). Of those who had a sentinel lymph node procedure performed, 89 % had negative sentinel lymph nodes. The types of IORT performed were primary IORT in 79 %, secondary IORT in 7 %, or planned boost in 14 %. Complications were low. At a median follow-up of 23.3 months, crude in-breast recurrence was 2.3 % for all patients treated. CONCLUSIONS: IORT use for the treatment of breast cancer is significantly increasing in North America, and physicians are selecting low-risk patients for this treatment option. Low complication and local recurrence rates support IORT as a treatment option for selected women with early stage breast cancer.

Hypothesis-based weight-of-evidence evaluation and risk assessment for naphthalene carcinogenesis.

Inhalation of naphthalene causes olfactory epithelial nasal tumors in rats (but not in mice) and benign lung adenomas in mice (but not in rats). The limited available human data have not identified an association between naphthalene exposure and increased respiratory cancer risk. Assessing naphthalene's carcinogenicity in humans, therefore, depends entirely on experimental evidence from rodents. We evaluated the respiratory carcinogenicity of naphthalene in rodents, and its potential relevance to humans, using our Hypothesis-Based Weight-of-Evidence (HBWoE) approach. We systematically and comparatively reviewed data relevant to key elements in the hypothesized modes of action (MoA) to determine which is best supported by the available data, allowing all of the data from each realm of investigation to inform interpretation of one another. Our analysis supports a mechanism that involves initial metabolism of naphthalene to the epoxide, followed by GSH depletion, cytotoxicity, chronic inflammation, regenerative hyperplasia, and tumor formation, with possible weak genotoxicity from downstream metabolites occurring only at high cytotoxic doses, strongly supporting a non-mutagenic threshold MoA in the rat nose. We also conducted a dose-response analysis, based on the likely MoA, which suggests that the rat nasal MoA is not relevant in human respiratory tissues at typical environmental exposures. Our analysis illustrates how a thorough WoE evaluation can be used to support a MoA, even when a mechanism of action cannot be fully elucidated. A non-mutagenic threshold MoA for naphthalene-induced rat nasal tumors should be considered as a basis to determine human relevance and to guide regulatory and risk-management decisions.

Prostate cancer polar localization on core biopsy predicts pathologic stage.

INTRODUCTION: This study investigated the polar sub-localization of prostate cancer on needle core biopsy ('polar' defined as tumor = 1 mm from the tissue polar edge) as a predictor of extraprostatic extension. MATERIALS AND METHODS: Histologic sections from 58 patients who underwent preoperative prostate biopsy and radical prostatectomy at the University of Kentucky from 2006 to 2013 were evaluated. Patients were retrospectively case matched based on pathologic stage (pT2 versus pT3/4) using biopsy Gleason grade and prostate-specific antigen. Histologic sections of needle core biopsies were analyzed for polar involvement. The location of polar involvement was correlated to the presence of extraprostatic extension on final prostatectomy pathology. RESULTS: Average percentage of total polar cores was predictive of extraprostatic extension on final prostatectomy, particularly in the prostatic apex and base (p = 0.029 and 0.006, respectively). Higher grade tumors were identified at the pole in the high stage cohort (p = 0.032). Total percent polar involvement had the greatest sensitivity and specificity for predicting extraprostatic extension when directly compared to previously described histologic parameters (percent greatest involvement of a single core, length of greatest involvement of a single core, presence of perineural invasion, presence of bilateral gland involvement, and percent total positive core involvement). The location of polar involvement on needle core biopsy was also predictive of the precise location of extraprostatic extension on final prostatectomy pathology (Chi-square p < .001, negative predictive value > 70% in all prostate sextants). CONCLUSIONS: These data suggest the use of biopsy polar core involvement as a valuable histologic predictor of increased pathologic stage.

ACR Appropriateness Criteria® Ductal Carcinoma in Situ.

Ductal carcinoma in situ (DCIS) is a breast neoplasm with potential for progression to invasive cancer. Management commonly involves excision, radiotherapy, and hormonal therapy. Surgical assessment of regional lymph nodes is rarely indicated except in cases of microinvasion or mastectomy. Radiotherapy is employed for local control in breast conservation, although it may be omitted for select low-risk situations. Several radiotherapy techniques exist beyond standard whole-breast irradiation (ie, partial-breast irradiation [PBI], hypofractionated whole-breast radiation); evidence for these is evolving. We present an update of the American College of Radiology (ACR) Appropriateness Criteria® for the management of DCIS. The ACR Appropriateness Criteria® are evidence-based guidelines for specific clinical conditions, which are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review includes an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi technique) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Meta-Analysis of Soybean-based Biodiesel.

Biofuel policy changes in the United States have renewed interest in soybean [ (L.) Merr.] biodiesel. Past studies with varying methodologies and functional units can provide valuable information for future work. A meta-analysis of nine peer-reviewed soybean life cycle analysis (LCA) biodiesel studies was conducted on the northern Great Plains in the United States. Results of LCA studies were assimilated into a standardized system boundary and functional units for global warming (GWP), eutrophication (EP), and acidification (AP) potentials using biodiesel conversions from peer-reviewed and government documents. Factors not fully standardized included variations in NO accounting, mid- or end-point impacts, land use change, allocation, and statistical sampling pools. A state-by-state comparison of GWP lower and higher heating values (LHV, HHV) showed differences attributable to variations in spatial sampling and agricultural practices (e.g., tillage, irrigation). The mean GWP of LHV was 21.1 g·CO-eq MJ including outliers, and median EP LHV and AP LHV was 0.019 g·PO-eq MJ and 0.17 g·SO-eq MJ, respectively, using the limited data available. An LCA case study of South Dakota soybean-based biodiesel production resulted in GWP estimates (29 or 31 g·CO-eq MJ; 100% mono alkyl esters [first generation] biodiesel or 100% fatty acid methyl ester [second generation] biodiesel) similar to meta-analysis results (30.1 g·CO-eq MJ). Meta-analysis mean results, including outliers, resemble the California Low Carbon Fuel Standard for soybean biodiesel default value without land use change of 21.25 g·CO-eq MJ. Results were influenced by resource investment differences in water, fertilizer (e.g., type, application), and tillage. Future biofuel LCA studies should include these important factors to better define reasonable energy variations in regional agricultural management practices.

ACR Appropriateness Criteria local-regional recurrence (LRR) and salvage surgery-breast cancer.

Although both breast-conserving surgery and mastectomy generally provide excellent local-regional control of breast cancer, local-regional recurrence (LRR) does occur. Predictors for LRR include patient, tumor, and treatment-related factors. Salvage after LRR includes coordination of available modalities, including surgery, radiation, chemotherapy, and hormonal therapy, depending on the clinical scenario. Management recommendations for breast cancer LRR, including patient scenarios, are reviewed, and represent evidence-based data and expert opinion of the American College of Radiology Appropriateness Criteria Expert Panel on LRR.The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel.The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In instances in which evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Electricians' chrysotile asbestos exposure from electrical products and risks of mesothelioma and lung cancer.

Both mechanistic and epidemiology studies indicate chrysotile asbestos has a threshold below which it does not cause mesothelioma or lung cancer. We conducted a critical review to determine whether electricians are at increased risk for these cancers and, if so, whether their exposure to chrysotile in electrical products could be responsible. We found that most, but not all, epidemiology studies indicate electricians are at increased risk for both cancers. Studies that evaluated electricians' exposure to asbestos during normal work tasks have generally reported low concentrations in air; an experimental study showed that grinding or drilling products containing encapsulated chrysotile resulted in exposures to chrysotile fibers far below the OSHA permissible exposure limit and the cancer no observed adverse effect level. Studies of other craftsmen who often work in the vicinity of electricians, such as insulators, reported asbestos (including amphibole) exposures that were relatively high. Overall, the evidence does not indicate that exposure to chrysotile in electrical products causes mesothelioma or lung cancer in electricians. Rather, the most likely cause of lung cancer in electricians is smoking, and the most likely cause of mesothelioma is exposure to amphibole asbestos as a result of renovation/demolition work or working in the proximity of other skilled craftsmen.

The Impact of Chemotherapy-Related Cognitive Impairment on Social Roles and Well-Being in Breast Cancer Survivors.

PURPOSE: To explore the impact of disruptions in information processing (DIPs) on social roles, well-being, and quality of life (QOL) in breast cancer survivors after chemotherapy. PARTICIPANTS & SETTING: Experiences of DIPs were explored in eight breast cancer survivors aged 53-70 years, 12-60 months post-treatment, referred from a National Cancer Institute-designated cancer center and a nonprofit breast cancer support organization from January 6 to August 31, 2020. METHODOLOGIC APPROACH: This study used a mixed-methods approach. Participants journaled and answered questionnaires sent via mail that asked them about changes in their cognition, QOL, and social roles. Qualitative data were thematically analyzed using constant comparative analysis, and questionnaire scores were compared with qualitative data. FINDINGS: Journals revealed problems with functioning in occupational roles and increased stress, anxiety, and frustration. Women with more DIPs tended to have lower role satisfaction and QOL. Greater role satisfaction was associated with higher QOL and social role participation. IMPLICATIONS FOR NURSING: Mitigating the effects of DIPs on social function may allow women to continue in important roles, which has the potential to affect QOL.

Non-small cell lung cancer cells survived ionizing radiation treatment display cancer stem cell and epithelial-mesenchymal transition phenotypes.

Ionizing radiation (IR) is used for patients diagnosed with unresectable non small cell lung cancer (NSCLC), however radiotherapy remains largely palliative due to radioresistance. Cancer stem cells (CSCs), as well as epithelial-mesenchymal transition (EMT), may contribute to drug and radiation resistance mechanisms in solid tumors. Here we investigated the molecular phenotype of A549 and H460 NSCLC cells that survived treatment with IR (5Gy) and are growing as floating tumor spheres and cells that are maintained in a monolayer after irradiation.Non-irradiated and irradiated cells were collected after one week, seeded onto ultra low attachment plates and propagated as tumor spheres. Bulk NSCLC cells which survived radiation and grew in spheres express cancer stem cell surface and embryonic stem cell markers and are able to self-renew, and generate differentiated progeny. These cells also have a mesenchymal phenotype. Particularly, the radiation survived sphere cells express significantly higher levels of CSC markers (CD24 and CD44), nuclear ß-catenin and EMT markers (Snail1, Vimentin, and N-cadherin) than non-irradiated lung tumor sphere cells. Upregulated levels of Oct-4, Sox2 and beta-catenin were detected in H460 cells maintained in a monolayer after irradiation, but not in radiation survived adherent A459 cells.PDGFR-beta was upregulated in radiation survived sphere cells and in radiation survived adherent cells in both A549 and H460 cell lines. Combining IR treatment with axitinib or dasatinib, inhibitors with anti-PDFGR activity, potentiates the efficacy of NSCLC radiotherapy in vitro.Our findings suggest that radiation survived cells have a complex phenotype combining the properties of CSCs and EMT. CD44, SNAIL and PDGFR-beta are dramatically upregulated in radiation survived cells and might be considered as markers of radiotherapy response in NSCLC.

Rare breast cancer: 933 adenoid cystic carcinomas from the National Cancer Data Base.

BACKGROUND: Adenoid cystic carcinoma (ACC) is a rare subtype of breast malignancy. METHODS: Patients with ACC and infiltrating ductal carcinoma (IDC) reported to the National Cancer Data Base from 1998 to 2008 were reviewed for patient age, ethnicity, tumor size, nodal status, American Joint Committee on Cancer TNM Stage, tumor grade, initial treatment, hormone receptor status (for patients from 2004 to 2008), and survival (for patients from 1998 to 2003). RESULTS: A total of 933 patients with ACC and 729,938 with IDC were identified. No differences were found for incidence by race/ethnicity (p = 0.97). The group with ACC was older (median 60 vs. 58 years), had larger tumors (median 18 vs. 16 mm), had more grade 1 tumors (46 vs. 18 %), was less likely to undergo axillary lymph node evaluation (75.9 vs. 96.3 %), had fewer node-positive patients (5.1 vs. 35.5 %), had fewer estrogen receptor-positive tumors (15.4 vs. 75.6 %), had fewer progesterone receptor-positive tumors (13.3 vs. 65.2 %), and underwent breast-conserving surgery more often (69.8 vs. 59.8 %). Chemotherapy was provided less often for ACC (11.3 vs. 46.4 %), as was hormone therapy (9.1 vs. 42.3 %). All of these differences were statistically significant (p < 0.0001). With a median follow-up of 65.7 months (ACC) and 64.9 months (IDC), 5-year overall survival (OS) was 88 % for ACC vs. 84 % for IDC (p = 0.02). Grade 1 OS (ACC, 91 % vs. IDC, 92 %; p = 0.50) and stage I OS (ACC, 90 % vs. IDC, 91 %; p = 0.93) were equal. CONCLUSIONS: Compared with IDC, ACC has different characteristics (lower grade, hormone receptor negative, node negative), is treated differently (less axillary surgery, fewer mastectomies, less chemotherapy, less hormone therapy), and has an improved prognosis, with 88 % 5-year survival.