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OBJECTIVE: Colorectal cancer poses a significant threat to both psychological and physical health. This study examined relationships between anxiety and depressive symptoms with pain, fatigue, and inflammation among colorectal patients. METHODS: Colorectal cancer patients (n = 88, stages 0-IV) completed a laboratory-based study visit before undergoing adjuvant cancer treatment. Patients completed questionnaires assessing depressive, anxiety, pain, and fatigue symptoms. A blood sample was also collected to measure c-reactive protein (CRP). Analyses controlled for age, sex, cancer stage, body mass index (BMI), and menopause status. RESULTS: Multiple linear regression analyses showed colorectal patients with higher depressive and anxiety symptoms had greater pain, fatigue, and CRP (ps < 0.03). Approximately one-third of patients with clinically significant depressive (CESD >16) and anxiety symptoms (BAI >16) also had clinically-elevated levels of CRP (>3 mg/L) (ps = 0.02). CONCLUSION: These results extend findings from other cancer subgroups showing heightened symptom burden among patients with depression and anxiety. They also highlight the detrimental role that elevated anxiety and depressive symptoms may play in the physical and biological side effects associated with colorectal cancer.

Introduction For early-stage breast cancer, breast-conserving surgery (BCS) plus radiation is standard-of-care. Nationwide, >20% of BCS patients require re-excision for positive margins, resulting in delayed adjuvant therapy, increased complications, emotional and financial stress for patients, and additional cost to the healthcare system. Although several methods may be employed to mitigate positive margins, no technique can fully address the need. MarginProbe® is an adjunctive tool for real-time intraoperative margin assessment and is shown to reduce positive margins by >50%. Areas covered Discussion of the impact of re-excision following BCS, a review of currently available methods for intraoperative margin management, followed by a technology and literature review of the MarginProbe® Radiofrequency Spectroscopy System. Expert opinion Re-excision significantly impacts patients, providers and payers. Limitations in the ability to assess margins at time of surgery warrant more advanced methods of residual disease detection. MarginProbe facilitates the most efficient pathway for breast cancer patients through the surgical phase of treatment. The device is well-suited for adoption as the healthcare focus shifts from volume to value and supports the three pillars of the US Department of Health and Human Services' 'Triple-Aim' strategy: improve population health, improve patient experience of care, and reduce per-capita costs.

Introduction: Percutaneous image-guided biopsy is the procedure of choice for diagnosing suspicious abnormalities on breast imaging. Stereotactic, ultrasound, and magnetic resonance imaging are used for image-guided breast biopsies. Stereotactic guidance uses mammography to localize lesions and facilitate placement of a core biopsy needle. The first systems used a vertical-approach needle insertion. The lateral arm device, which is the most recent advancement in stereotactic biopsies and pre-surgical localization allows procedures to be performed using a needle insertion parallel to the compression plate.Areas covered: The lateral arm device was introduced to the market in 2007 and is the first device of its kind. In this article we review the mechanism of this device, the risks and benefits of the device and other the different other modalities utilized to biopsy and localize the breast. We summarize the current literature on this device along with our own experiences utilizing this device.Expert opinion: The lateral arm device has changed the face of stereotactic-guided breast biopsies and localizations by allowing a new approach to perform these procedures. It has improved care to patients by allowing us to get to areas previously not within the biopsy window, decreased biopsy time and increased patient throughput.

Objective Breast cancer survivors live longer due to more advanced cancer treatments; however, cardiovascular disease (CVD) is the leading non-cancer cause of death in breast cancer survivors. Previous studies have shown that depression is associated with an increased risk of CVD development. This study investigated whether depressive symptoms or mood disorder history, either independently or in combination with cardiotoxic treatments, predicted older cardiopulmonary age using a novel index–the Age Based on Exercise Stress Test (ABEST)–among breast cancer survivors. Methods Breast cancer survivors (N = 80, ages 26–72, stage I-IIIA) were assessed an average of 53 days (SD = 26) post-surgery, but before adjuvant treatment, and again an average of 32 (SD = 6) months thereafter. At both visits, they reported depressive symptoms on the Center for Epidemiologic Studies Depression Scale (CES-D), completed the Structured Clinical Interview for DSM-V, and engaged in an exercise stress test to obtain ABEST scores. Results Controlling for treatment type, age, education, trunk fat, antidepressant use, and time between visits, longitudinal analyses showed that breast cancer survivors with a mood disorder history had worsening ABEST scores over time, compared to their peers without this history (p = .046). Change in physical activity between Visits 1 and 2 did not mediate this relationship (95% CI: -0.16–0.51). Ancillary analyses provided some additional support for the primary finding, such that those with a mood disorder history trended toward greater decreases in Vo2max, although results were marginally non-significant (p = .095). There were no cross-sectional relationships between depressive symptoms or mood disorder history and ABEST scores (ps>.20). Treatment type did not modulate observed relationships (ps>.22). Conclusions Breast cancer survivors with a mood disorder history may experience faster cardiopulmonary aging compared to their peers without such a history, raising risk for CVD.

Leptin influences inflammation and tumor growth and leptin signaling is often dysregulated among obese breast cancer survivors. This leads to a lack of satiety and, ultimately, risk for further weight gain. Breast cancer survivors also experience high rates of depression and anxiety, which are linked to leptin production. This study examined how a woman’s anxiety and depressive symptoms, in combination with their obesity status, were associated with leptin. Breast cancer survivors (n = 200, stages 0–IIIa) completed a baseline visit before treatment and two follow-up visits, 6 and 18 months after treatment ended. Women completed anxiety and depression measures, and blood samples provided leptin data at each visit. This study related fluctuations in a survivor’s own depression and anxiety (i.e., within-person effects), as well as average effects of depression and anxiety (i.e., between-person effects) to changes in leptin depending on BMI. Obese survivors’ leptin was significantly higher at visits when they had higher anxiety and depression symptoms than their own average level of symptoms. In contrast, within-person fluctuations in depression and anxiety were not related to leptin levels among non-obese survivors. No significant between-person effects of depression or anxiety on leptin emerged. Leptin is a critical risk factor for recurrence and further health consequences. Our findings highlight how psychological health influences leptin production among breast cancer survivors. These results highlight a biological pathway that may facilitate further weight gain and health risks among distressed, obese breast cancer survivors.

Objective Breast cancer survivors who experience psychological and physical symptoms after treatment have an increased risk for comorbid disease development, reduced quality of life, and premature mortality. Identifying factors that reduce or exacerbate their symptoms may enhance their long-term health and physical functioning. This study examined how survivors' marital status and marital satisfaction-key health determinants-impacted their psychological and physical health trajectories to understand when, and for whom, marriage offers health benefits. Methods Breast cancer survivors (n=209, stages 0-IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women completed questionnaires assessing their marital status and satisfaction when applicable, as well as their psychological (depressive symptoms, stress) and physical (fatigue, pain) health at each visit. Results Married women-both those in satisfying and dissatisfying marriages-experienced improvements in their depressive symptoms, stress, and fatigue from pretreatment to 6- and 18-months posttreatment. Unmarried (i.e., single, divorced/separated, or widowed) women's depressive symptoms, stress, fatigue, and pain did not change over time, instead remaining elevated 6 and 18 months after treatment ended. Women in satisfying marriages also had fewer psychological and physical symptoms after treatment than those who were unmarried or in dissatisfying marriages. Conclusions Although marriage was associated with improved psychological and physical health, the gains were most notable when survivors' marriages were satisfying. Thus, the quality of survivors' marriages, rather than the marriage itself, provided the most benefits to their psychological and physical health. This article is protected by copyright. All rights reserved.

Background Breast cancer survivors are prone to weakened gut barriers, allowing bacteria to migrate into the blood stream. Gut permeability fuels inflammation, which, among survivors, can elevate risk for comorbid disease development, cancer recurrence, and a poor quality of life; however, survivors’ satisfying relationships can provide health benefits. This longitudinal study used a conceptual model addressing how intimate relationships is associated with health through changes in gut permeability and inflammation. Method Breast cancer survivors (n=139, stages 0–IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women who had an abnormal breast cancer test followed by a benign diagnosis completed visits within a comparable timeframe (noncancer patient controls; n=69). All women completed questionnaires assessing their relationship satisfaction and provided blood samples to assess two bacterial endotoxin biomarkers, lipopolysaccharide-binding protein (LBP) and soluble CD14 (sCD14), as well as C-reactive protein (CRP) and interleukin 6 (IL-6). Results Within-person multilevel mediation analyses showed that when a survivor’s relationship satisfaction was higher than usual, her own LBP and LBP/sCD14 were lower, which was associated with lower than her own average CRP and IL-6 (95% CIs [-0.0104, -0.0002]). IL-6 was also higher when older survivors, but not younger survivors, experienced higher than usual intestinal permeability (p=.001). These effects of satisfying relationships held after accounting for cancer-related and behavioral factors. Post-hoc analyses showed LBP, sCD14, and LBP/sCD14 were associated with CRP for the cancer survivors, but only LBP and LBP/sCD14 were linked to CRP among the noncancer control patients. Conclusion The gut environment is a new promising candidate for understanding a relationship’s long-term health impact, particularly among those with elevated health risks. Survivors may reap multiple physiological benefits from satisfying relationships.

BACKGROUND: Prior to treatment, breast cancer patients are less physically fit compared to peers; during cancer treatment, their fitness typically declines. Depressive symptoms are associated with reduced activity up to 5 years post-treatment, but research has not identified mechanisms linking depression and lower activity. The current study assessed relationships among breast cancer patients’ depression and perceived exertion during exercise as well as heart rate, an objective indicator of exertion. METHODS: Participants were 106 breast cancer patients, stages I–IIIA, who completed surgery but had not started adjuvant treatment. Heart rate and self-rated exertion, measured using the Borg Scale of Perceived Exertion, were assessed every 2 min during a graded exercise test. Depression was assessed using the CES-D and a structured clinical interview. RESULTS: Compared to women below the CES-D clinical cutoff, women with significant depressive symptoms reported steeper increases in exertion during the exercise test (p = .010) but had similar heart rates (p = .224) compared to women below the cutoff. Major depression history was unrelated to perceived exertion (ps > .224) and heart rate (ps > .200) during exercise. CONCLUSIONS: Women with currently elevated depressive symptoms experienced exercise as more difficult compared to women below the CES-D cutoff, but these self-perceptions did not reflect actual heart rate differences. Depression may make exercise feel more demanding, which could ultimately decrease patients’ likelihood of engaging in regular exercise. Results support the use of depression screening tools following breast cancer surgery to identify and intervene on individuals at risk for decreased physical activity during survivorship.

BACKGROUND: Black breast cancer survivors have greater morbidity and mortality than White survivors. However, evidence comparing Black survivors’ psychological symptoms with their White counterparts has been mixed. Prior studies have not compared Black and White survivor’s distress-related symptom trajectories from pre- to post-treatment – the goal of the current study. METHODS: At three annual visits from shortly after diagnosis to 6 and 18 months post-treatment, 195 women (n=163 White; n=32 Black) reported their cancer-related distress (intrusive thoughts and avoidance), perceived stress, anxiety and depressive symptoms, fatigue, and pain. RESULTS: Adjusting for age, educational attainment, income, treatment type, stage at diagnosis, and physical comorbidities, Black and White breast cancer survivors had different trajectories of cancer-related distress (p=.004), intrusive thoughts about cancer diagnosis and treatment (p=.002), perceived stress (p=.04), emotional fatigue (p=.01), and vigor (p=.02). Specifically, among White women, these distress-related symptoms improved from diagnosis to 6 months post-treatment (ps.09). CONCLUSION: Longitudinal assessment of the same breast cancer survivors from diagnosis to early survivorship revealed that Black and White survivors had divergent trajectories of psychological distress symptoms that were not reliably evident at a single timepoint. Overall, White women reported less psychological distress from pre- to post-treatment, but Black women’s distress remained high from diagnosis to 18 months post-treatment. If left untreated, Black women’s high distress levels may contribute to their poorer health throughout survivorship.

Lymphedema has traditionally been managed through noninvasive means with complete decongestive therapy. However, complete decongestive therapy is an intensive program that requires lifelong adherence by patients with lymphedema. More recently, reconstructive surgical procedures have shown promise in improving lymphedema by physiologically restoring lymphatic function. One of these types of procedures, lymphaticovenular anastomosis, relies on technological advances in imaging, particularly indocyanine green lymphangiography.This article reviews indocyanine green and near-infrared fluorescence imaging. In addition, this article discusses the application of this imaging to the preoperative, intraoperative, and postoperative assessment of the lymphatic system in the setting of lymphaticovenular anastomosis surgery.Indocyanine green lymphangiography offers significant advantages over other types of imaging of the lymphatic system. In the future, it is hopeful that additional options for these imaging devices will become available which may increase their accessibility by centers interested in performing reconstructive lymphatic surgery, including in relation to cost. Finally, more studies with higher levels of evidence are needed to better define the long-term outcomes associated with lymphatic surgery including LVA. In this regard, practitioners should fully harness the information conferred by ICG lymphangiography as both a clinical and research tool.

Introduction: Negative pressure wound therapy (NPWT) has become a mainstay in the armamentarium for wound care. Since the initial commercial vacuum-assisted closure device became available in 1995,...

Objective: Percutaneous breast and axillary core biopsy followed by marker placement are integral parts of a breast imager’s practice benefiting both patients and clinicians. Marker placement is th...

Leptin influences inflammation and tumor growth and leptin signaling is often dysregulated among obese breast cancer survivors. This leads to a lack of satiety and, ultimately, risk for further weight gain. Breast cancer survivors also experience high rates of depression and anxiety, which are linked to leptin production. This study examined how a woman's anxiety and depressive symptoms, in combination with their obesity status, were associated with leptin.Breast cancer survivors (n = 200, stages 0-IIIa) completed a baseline visit before treatment and two follow-up visits, 6 and 18 months after treatment ended. Women completed anxiety and depression measures, and blood samples provided leptin data at each visit. This study related fluctuations in a survivor's own depression and anxiety (i.e., within-person effects), as well as average effects of depression and anxiety (i.e., between-person effects) to changes in leptin depending on BMI.Obese survivors' leptin was significantly higher at visits when they had higher anxiety and depression symptoms than their own average level of symptoms. In contrast, within-person fluctuations in depression and anxiety were not related to leptin levels among non-obese survivors. No significant between-person effects of depression or anxiety on leptin emerged.Leptin is a critical risk factor for recurrence and further health consequences. Our findings highlight how psychological health influences leptin production among breast cancer survivors.These results highlight a biological pathway that may facilitate further weight gain and health risks among distressed, obese breast cancer survivors.

Background The Center for Disease Control (CDC) recently named childhood abuse histories as a public health risk. Clear links between abuse histories and inflammation exist. However, it remains unknown how abuse histories impact inflammatory trajectories throughout adulthood. Accordingly, this study assessed inflammatory trajectories across three visits among healthy adults with and without abuse histories. Method In this secondary analysis of data from a longitudinal observational study of cancer survivors and noncancer controls, 157 noncancer controls (Mage = 55.8, range = 32–83) completed the Childhood Experiences Questionnaire (CTQ), providing data on physical, emotional, and sexual abuse prior to age 18. Cytokines interleukin-6 (IL-6), interleukin 1-beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were collected at the baseline visit and two follow-up visits approximately one (M months = 11.52, SD = 4.10) and two years (M months = 23.79, SD = 4.40) later. To represent inflammatory changes, cytokine data at each visit were combined into a composite z-score. Covariates in all analyses included age, biological sex, race, income, body mass index, menopause status, psychological diagnosis history, and medical comorbidities. Results Compared to their nonabused peers, those who had experienced any type of abuse in childhood demonstrated steeper rises in inflammation across time. Inflammation rose more steeply for individuals with physical and emotional abuse histories compared to those without such histories. Conclusion Overall, these data suggest that childhood abuse histories may quicken age-related increases in inflammation, contributing to accelerated aging, morbidity, and early mortality. These findings provide mechanistic insight into why child abuse is a public health risk.

Background Among breast cancer survivors, elevated inflammation has been linked to greater recurrence risk. Psychological processes, such as cancer-related distress, can pose threats to a survivor’s longevity and wellbeing. Although distress can heighten inflammation, little is known about how fluctuations in distress during and after treatment impact a woman’s own inflammation – the primary question of this study. Methods Breast cancer survivors (n = 165, stages 0-III) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after. At each visit, women completed the Impact of Events Scale to assess cancer-related distress, and a blood sample was collected to measure proinflammatory cytokines IL-6, TNF-α, IL-1β, and IL-8. This longitudinal study related fluctuations in survivor’s own cancer-related distress (i.e., within-person effects), as well as average effects of cancer-related distress between survivors (i.e., between-person effects) to inflammatory changes across visits. Results Women had elevated inflammation at visits where they expressed more cancer-related distress than what was typical. In contrast, the average cancer-related distress was not associated with inflammation. Conclusion Larger increases in a women’s cancer-related distress was linked with higher inflammation across visits. Comparing a survivor’s own cancer-related distress to her average levels may prove useful in identifying links between distress and inflammation.

PURPOSE: A number of studies have shown that self-rated health reliably predicts mortality. This study assessed the impact of perseveration on self-rated health, physical functioning, and physical symptoms (pain, fatigue, breast cancer symptoms) among breast cancer patients. We hypothesized that cancer-related distress would serve as an intervening variable between both worry and rumination and self-rated health, physical functioning, and physical symptoms. METHODS: Women (N=124) who were approximately seven weeks post-surgery but pre adjuvant treatment completed the Impact of Events Scale, the Penn State Worry Questionnaire, and the Rumination Scale. They also rated their pain, fatigue, physical functioning, and self-rated health using the RAND-36 and breast cancer symptoms with the Breast Cancer Prevention Trial Symptom Checklist (BCPT). Covariates included body mass index, age, cancer stage, menopause status, and physical comorbidities. RESULTS: Worry was associated with higher cancer-related distress, which in turn predicted greater pain and breast cancer symptoms, poorer physical functioning, and lower self-rated health. Rumination also predicted greater cancer-related distress, which ultimately contributed to greater pain along with poorer physical functioning and self-rated health. Models with fatigue as an outcome were not significant. CONCLUSIONS: These findings suggest that perseveration can heighten cancer-related distress and subsequent perceptions of physical symptoms and health among breast cancer patients prior to adjuvant treatment. Perseveration early in the cancer trajectory can adversely increase the impact of a cancer diagnosis and treatment on functioning and quality of life.

BACKGROUND Postmastectomy radiation therapy often impacts decision-making and outcomes of breast reconstruction. However, plastic surgeons typically have limited information regarding the likelihood of radiation therapy when decisions about immediate breast reconstruction are made. The study objective was to examine whether commonly available information can be used to predict the probability of radiation therapy. METHODS A retrospective review was performed of patients undergoing mastectomy and sentinel lymph node biopsy. Multivariate logistic regression analysis of variables available in greater than 95 percent of patients was performed in relation to predicting radiation therapy. RESULTS A total of 322 patients were reviewed, of whom 55 (17.1 percent) received radiation therapy, which was indicated for patients having four or more positive axillary lymph nodes in all cases. Multivariate logistic regression identified the intraoperative sentinel lymph node frozen section results (OR, 27.3), tumor size (OR, 1.7), and age (OR, 0.96) as significant predictors. The sentinel lymph node frozen section exhibited negative and positive predictive values for radiation therapy of 95.4 percent and 54.3 percent, respectively. When sentinel lymph node frozen section was combined with tumor size greater than or equal to 2.0 cm, the positive predictive value increased to 80.5 percent. CONCLUSION Immediate breast reconstruction patients who have negative intraoperative sentinel lymph node frozen section results have a less than 5 percent chance of radiation therapy, whereas patients with positive intraoperative sentinel lymph node frozen section results and tumor size greater than or equal to 2.0 cm have a greater than 80 percent chance of radiation therapy. CLINICAL QUESTION/LEVEL OF EVIDENCE Risk, III.

Objective Cross-sectional data have linked gut barrier abnormalities and endotoxemia with depression, even among those without gastrointestinal symptoms. This study examined longitudinal associations between endotoxemia markers and depressive symptoms, as well as the role of inflammation in this relationship. Design At three annual visits, 315 women (n=209 breast cancer survivors, n = 106 non-cancer patient controls, M=55 years old) completed the Center for Epidemiological Studies Depression questionnaire (CES-D) and provided blood samples to assess inflammatory markers – interleukin-6, tumor necrosis factor-alpha, and C-reactive protein – and endotoxemia markers – lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), and their ratio. Results Adjusting for key demographic variables, health behaviors, visit 1 depressive symptoms, and cancer status and treatment, women with higher visit 1 LBP and LBP/sCD14 had more depressive symptoms at the two subsequent annual visits. Illustrating the notable impact, a woman at the 75th percentile for LBP or LBP/sCD14 at visit 1 was 18 % more likely to report clinically significant depressive symptoms (CES-D ≥16) at follow-up than a woman in the lowest quartile. Cancer status and treatment type did not modulate this relationship. In contrast, visit 1 depressive symptoms did not predict endotoxemia at follow-up. A significant interaction between LBP/sCD14 and inflammatory burden suggested that visit 1 endotoxemia fueled depressive symptoms only in the context of elevated inflammation. Conclusion These results suggest that endotoxemia, combined with systemic inflammation, can drive depressive symptoms. These findings may implicate bacterial endotoxin translocation from the gut to the bloodstream in depression etiology. Interventions that reduce endotoxemia and inflammation may lessen the risk of depression.

Background Breast cancer survivors with elevated inflammation have a greater risk for cancer recurrence, premature mortality, and comorbid disease development. The psychological stress survivors experience when confronted with a breast cancer diagnosis and cancer treatment can heighten inflammation. Identifying factors that reduce stress and inflammation could lead to improvements in survivors’ long-term health. Accordingly, this study examined the health-enhancing effects of romantic relationships—a key health determinant—on breast cancer survivors’ stress and inflammation. Methods Breast cancer survivors (n = 139, stages 0–IIIC) completed a baseline visit before treatment and two follow-up visits 6 and 18 months after treatment ended. Women completed self-report questionnaires assessing their romantic relationship satisfaction and perceived stress, and they provided a blood sample for serum markers of inflammation at each visit. The longitudinal design allowed for examination within and between survivors. We conducted multilevel mediation analyses to assess how changes in survivors’ relationship satisfaction were related to changes in stress and inflammation from visit to visit (i.e., within-person effects), as well as how the average effects of relationship satisfaction were associated with average stress and inflammation levels throughout the study (i.e., between-person effects). Results At the within-person level, at visits in which survivors were more satisfied with their relationships, they also perceived less stress, which in turn was related to lower than their own average levels of serum C-reactive protein and proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β). At the between-person level, survivors who had greater relationship satisfaction throughout the study had lower perceived stress, which was linked to lower levels of inflammation. Conclusion Breast cancer survivors in satisfying romantic relationships felt less stressed and in turn had lower inflammation throughout cancer treatment. This study illustrates the utility of a within-person approach to not only consider the average effects of relationship satisfaction, but also how changes in their own relationship satisfaction impact stress and inflammation over time. Our findings demonstrate important psychological and immunological pathways through which satisfying relationships may promote breast cancer survivors’ long-term health.

Background Surgical management of Zollinger-Ellison syndrome (ZES) relies on localization and resection of all tumor foci. We describe the benefit of combined intraoperative use of a portable large field of view gamma camera (LFOVGC) and a handheld gamma detection probe (HGDP) for indium-111 ( 111 In)-pentetreotide radioguided localization and confirmation of gastrinoma resection in ZES. Study Design Five patients (6 cases) with 111 In-pentetreotide-avid ZES were evaluated. Patients were injected with 111 In-pentetreotide for diagnostic imaging the day before surgery. Intraoperatively, an HGDP and LFOVGC were used to localize 111 In-pentetreotide-avid lesions, guide resection, assess specimens for 111 In-pentetreotide activity, and to verify lack of abnormal post-resection surgical field activity. Results Large field of view gamma camera imaging and HGDP-assisted detection were helpful for localization and guided resection of tumor and removal of 111 In-pentetreotide-avid tumor foci in all cases. In 3 of 5 patients (3 of 6 cases), these techniques led to detection and resection of additional tumor foci beyond those detected by standard surgical techniques. The 111 In-pentetreotide–positive or–negative specimens correlated with neuroendocrine tumors or benign pathology, respectively. In one patient with mild residual focal activity on post-resection portable LFOVGC imaging, thought to be artifact, had recurrence of disease in the same area 5 months after surgery. Conclusions Real-time LFOVGC imaging and HGDP use for surgical management of gastrinoma improve success of localizing and resecting all neuroendocrine tumor–positive tumor foci, providing instantaneous navigational feedback. This approach holds potential for improving long-term patient outcomes in patients with ZES.

Early cancer detection is the central and most important factor for allowing successful treatment and resultant positive longterm patient outcomes. Recently, optical techniques have been applied to this purpose, although each has inherent limitations. In particular, Raman spectroscopy applied in the pathological diagnosis of cancerous tissues has received increasing attention, with the merit of being highly sensitive to the biochemical alterations in tissue compositions and applicable in vivo. Nevertheless, its application has been impeded by the high background intensity, which masks the Raman signal of biological molecules. In this work, the influence of laser excitation wavelength (785 vs. 830nm) and optical mode (single mode vs. multimode) on the background intensity of fresh human tissues was studied. Based on the results, laser with 830nm excitation demonstrated better background reduction than that with 785nm excitation for the same optical mode, but the Raman signal intensity was conversely reduced, and the signal-to-noise ratio (SNR) not improved. In contrast, by comparing single-mode and multimode 785nm excitations, it was shown that the single-mode laser with its smaller beam waist and beam propagation factor had better background reduction ability and an improvement of the SNRs. It is speculated that this decrease in background intensity comes from the effect of the optical mode on the Mie scattering from the biological tissue. High-quality spectra based on a careful selection of both laser excitation wavelength and optical mode will benefit Raman measurements in further research focusing on spectral interpretation and histopathological correlation ultimately aimed toward intraoperative applications. Copyright © 2014 John Wiley & Sons, Ltd. Additional supporting information may be found in the online version of this article at the publisher’s web site.

Background: Cancer survivors often experience cognitive difficulties after treatment completion. Although chemotherapy enhances risk for cognitive problems, it is likely only one piece of a complex puzzle that explains survivors’ cognitive functioning. Loneliness may be one psychosocial risk factor. The current studies included both subjective and objective cognitive measures and tested whether lonelier breast cancer survivors would have more concentration and memory complaints and experience more concentration difficulties than their less lonely counterparts. Methods: The relationship between loneliness and cognitive function was tested among three samples of breast cancer survivors. Study 1 was a sample of breast cancer survivors (n=200) who reported their concentration and memory problems. Study 2a was a sample of breast cancer survivors (n=185) and noncancer controls (n=93) who reported their concentration and memory problems. Study 2b was a subsample of Study 2a breast cancer survivors (n=22) and noncancer controls (n=21) who completed a standardized neuropsychological test assessing concentration. Results: Studies 1 and 2a revealed that lonelier women reported more concentration and memory problems than less lonely women. Study 2b utilized a standardized neuropsychological continuous performance test and demonstrated that lonelier women experienced more concentration problems than their less lonely counterparts. Conclusions: These studies demonstrated that loneliness is linked to concentration and memory complaints and the experience of concentration problems among breast cancer survivors. The results were also highly consistent across three samples of breast cancer survivors. These data suggest that loneliness may be a risk factor for cognitive difficulties among cancer survivors. Copyright © 2014 John Wiley & Sons, Ltd.

Purpose To retrospectively compare 2 methods of pre-resection, image-guided tumor localization—preoperative needle-wire localization (PNWL) and intraoperative ultrasonography-guided localization and tissue fixation (IUGLTF)—for patients with invasive breast cancer at the time of breast-conserving surgery (BCS). Patients and Methods We identified 118 cases in which image-guided localization was required for nonpalpable and questionably palpable tumors from a series of 204 consecutive invasive breast cancers treated by BCS. We defined a positive margin as tumor at the inked surface. We defined a close margin as tumor within 1 mm or less of the inked surface. Results Of those 118 cases requiring pre-resection, image-guided localization, 54 patients underwent PNWL and 64 underwent IUGLTF placement. A positive margin was identified in 6 of 54 (11.1%) undergoing PNWL compared with 1 of 64 (1.6%) undergoing IUGLTF (P = .046). A positive or close margin was identified in 9 of 54 (16.7%) undergoing PNWL compared with 3 of 64 (4.7%) undergoing IUGLTF (P = .032). The mean volume and mean weight of the BCS specimens were not different in the 2 groups. Conclusion Based on the finding of less margin positivity associated with the IUGLTF technique than the PNWL technique, we believe that the use of an IUGLTF device by surgeons during BCS could be highly advantageous in the surgical management of nonpalpable and questionably palpable invasive breast cancers.

Infrared (IR) spectroscopic imaging of human liver tissue slices has been used to identify and characterize liver tumors. Liver tissue, containing a liver metastasis of breast origin (mucinous carcinoma) was surgically removed from a consenting patient and frozen without formalin fixation or dehydration procedures, so that lipids and water remain in the tissues. A set of IR metrics (ratios of various IR peaks) was determined for tumors in fixation-free liver tissues. K-means cluster analysis was used to tell tumor from nontumor. In this case, there was a large reduction in lipid content on going from nontumor to tumor tissue and a well resolved IR spectrum of nontumor liver lipid has been obtained and analyzed. These IR metrics may someday guide work on IR spectroscopic diagnostics on live patients in the operating room. This work also suggests utility for these methods beyond the identification of liver tumors, perhaps in the study of liver lipids.

Objective A cancer diagnosis provokes significant levels of emotional distress, with intrusive thoughts being the most common manifestation among breast cancer survivors. Cancer-related intrusive thoughts can take the form of emotional memories, flashbacks, nightmares, and intrusive images. Emotional arousal after a severe life stressor prolongs adrenergic activation, which in turn may increase risk for post-traumatic symptomatology. However, antihypertensive beta-blockers block adrenergic activation and are known to reduce traumatic memories and related psychological distress. Thus, the current study examined the association between beta-blocker use and the severity of cancer-related intrusive thoughts and related symptoms following a cancer diagnosis. Methods The 174 breast and 36 female colorectal cancer patients who had recently undergone diagnostic screening or biopsy included 39 beta-blocker users and 171 non-users. Prior to any cancer treatment including surgery, participants completed questionnaires that included the Impact of Events Scale and the Center for Epidemiological Studies Depression Scale. Analyses controlled for age, education, cancer stage, cancer type, days since diagnosis, marital status, depression, and comorbidities. Results Although the high rates of cancer-related distress in this sample were similar to those of other studies with recently diagnosed patients, beta-blocker users endorsed 32% fewer cancer-related intrusive thoughts than non-users. Conclusions Recently diagnosed cancer patients using beta-blockers reported less cancer-related psychological distress. These results suggest that beta-blocker use may benefit cancer patients' psychological adjustment following diagnosis, and provide a promising direction for future investigations on the pharmacological benefits of beta-blockers for cancer-related distress. Copyright © 2012 John Wiley & Sons, Ltd.

Purpose The sequelae of cancer treatment may increase systemic inflammation and create a phenotype at increased risk of functional decline and comorbidities, leading to premature mortality. Little is known about how this trajectory compares with natural aging among peers of the same age without cancer. This longitudinal study investigated proinflammatory cytokines and comorbidity development over time among breast cancer survivors and a noncancer control group. Methods Women (N = 315; 209 with breast cancer and 106 in the control group) were recruited at the time of their work-up for breast cancer; they completed the baseline questionnaire, interview, and blood draw (lipopolysaccharide-stimulated production of interleukin [IL] -6, tumor necrosis factor-α, and IL-1β). Measures were repeated 6 and 18 months after primary cancer treatment (cancer survivors) or within a comparable time frame (control group). Results There were no baseline differences in comorbidities or cytokines between survivors and the control group. Over time, breast cancer survivors had significantly higher tumor necrosis factor-α and IL-6 compared with the control group. Survivors treated with surgery, radiation, and chemotherapy accumulated a significantly greater burden of comorbid conditions and suffered greater pain associated with inflammation over time after cancer treatment than did the control group. Conclusion Survivors who had multimodal treatment had higher cytokines and comorbidities, suggestive of accelerated aging. Comorbidities were related to inflammation in this sample, which could increase the likelihood of premature mortality. Given that many comorbidities take years to develop, future research with extended follow-up beyond 18 months is necessary to examine the evidence of accelerated aging in cancer survivors and to determine the responsible mechanisms.

Background Nipple adenoma is a very uncommon, benign proliferative process of lactiferous ducts of the nipple. Clinically, it often presents as a palpable nipple nodule, a visible nipple skin erosive lesion, and/or with discharge from the surface of the nipple skin, and is primarily seen in middle-aged women. Resultantly, nipple adenoma can clinically mimic the presentation of mammary Paget’s disease of the nipple. The purpose of our current case report is to present a comprehensive review of the available data on nipple adenoma, as well as provide useful information to health care providers (including dermatologists, breast health specialists, and other health care providers) who evaluate patients with dermatologic conditions of the breast skin for appropriately clinically recognizing, diagnosing, and treating patients with nipple adenoma. Case presentation Fifty-three year old Caucasian female presented with a one year history of erythema and induration of the skin of the inferior aspect of the right nipple/areolar region. Skin punch biopsies showed subareolar duct papillomatosis. The patient elected to undergo complete surgical excision with right central breast resection. Final histopathologic evaluation confirmed nipple adenoma. The patient is doing well 31 months after her definitive surgical therapy. Conclusions Since nipple adenoma represents a benign proliferative process of the nipple, complete surgical excision is curative. However, the coexistence of nipple adenoma and ipsilateral or contralateral breast cancer is well reported in the literature. The potential for a direct causal link or association of nipple adenoma and breast cancer cannot be fully excluded.

Surgical resection remains the primary curative intervention for cancer treatment. However, the occurrence of a residual tumor after resection is very common, leading to the recurrence of the disease and the need for re-resection. We develop a surgical Google Glass navigation system that combines near infrared fluorescent imaging and ultrasonography for intraoperative detection of sites of tumor and assessment of surgical resection boundaries, well as for guiding sentinel lymph node (SLN) mapping and biopsy. The system consists of a monochromatic CCD camera, a computer, a Google Glass wearable headset, an ultrasonic machine and an array of LED light sources. All the above components, except the Google Glass, are connected to a host computer by a USB or HDMI port. Wireless connection is established between the glass and the host computer for image acquisition and data transport tasks. A control program is written in C++ to call OpenCV functions for image calibration, processing and display. The technical feasibility of the system is tested in both tumor simulating phantoms and in a human subject. When the system is used for simulated phantom resection tasks, the tumor boundaries, invisible to the naked eye, can be clearly visualized with the surgical Google Glass navigation system. This system has also been used in an IRB approved protocol in a single patient during SLN mapping and biopsy in the First Affiliated Hospital of Anhui Medical University, demonstrating the ability to successfully localize and resect all apparent SLNs. In summary, our tumor simulating phantom and human subject studies have demonstrated the technical feasibility of successfully using the proposed goggle navigation system during cancer surgery.

Freehand SPECT (fhSPECT) is a technology platform for providing 3-dimensional (3D) navigation for radioguided surgical procedures, such as sentinel lymph node (SLN) biopsy (SLNB). In addition to the information provided by conventional handheld gamma detection probes, fhSPECT allows for direct visualization of the distribution of radioactivity in any given region of interest, allowing for improved navigation to radioactive target lesions and providing accurate lesion depth measurements. Herein, we will review the currently available clinical data on the use of fhSPECT: (i) for SLNB of various malignancies, including difficult-to-detect SLNs, and (ii) for radioguided localization of solid tumors. Moreover, the combination of fhSPECT with other technologies (e.g., small field-of-view gamma cameras, and diagnostic ultrasound) is discussed. These technical advances have the potential to greatly expand the clinical application of radioguided surgery in the future.

The use of positron-emitting and high-energy gamma photon-emitting radiopharmaceuticals, like fluorine-18 fluorodeoxyglucose (18F-FDG), for real-time cancer detection and surgical guidance within the operating room and for real-time guidance of diagnostic and therapeutic interventional procedures within the interventional radiology suite, has great clinical potential. This technology may allow for (1) real-time intraoperative staging of the extent of disease; (2) real-time intraoperative surgical planning and execution of the necessary and most appropriate operation, determination of the extent of surgical resection, and determination of the completeness of surgical resection; (3) real-time pathologic evaluation of intact surgical resected specimens for the confirmation of completeness of surgical resection and for surgical margin assessment; (4) real-time pathologic evaluation of diagnostically biopsied tissues for confirmation of correctness of tissue diagnosis; and (5) real-time guidance of diagnostic and therapeutic interventional procedures within the interventional radiology suite. This chapter discusses (1) the history and development of positron imaging and detection, (2) the fundamental basis for the use of 18F-FDG in positron imaging and detection strategies, (3) the inherent limitations of 18F-FDG in positron imaging and detection strategies, (4) radiation detection devices utilized during 18F-FDG-directed surgery, (5) the clinical applications of real-time 18F-FDG-directed surgery and real-time 18F-FDG-directed interventional procedures, (6) timing issues related to 18F-FDG-directed surgery, (7) the inherent challenge of in situ detection of 18F-FDG with a gamma photon detection device, and (8) occupational radiation exposure during 18F-FDG radioguided surgical procedures.

Radioguided surgery involves utilizing a radiation detection device within the operating room in a real-time fashion to identify a radioisotope that has been administered to a patient prior to the time of attempted detection and for the sole purpose of guiding the successful performance of the surgical procedure. Since its first description in the late 1940s, radioguided surgery has expanded tremendously and has become a well-established discipline within the practice of surgery. It has been investigated and applied to the surgical management of numerous solid malignancies and has most significantly impacted upon the surgical management of breast cancer, melanoma, and parathyroid disease. Radioguided surgery provides the surgeon with critical and real-time information regarding the exact location of the disease and the overall extent of disease burden, as well as allows the surgeon to minimize the degree of surgical invasiveness associated with many commonplace diagnostic and therapeutic surgical procedures, while still maintaining maximum treatment-directed benefits to the patient. As we move forward through the twenty-first century, we envision further growth of the current technological platforms of radioguided surgery, with a continued emphasis upon promoting integration of handheld radiation detection devices and advanced nuclear medicine molecular imaging for guiding and optimizing the intraoperative detection and resection of conditions affecting both cancer and noncancer patients.

Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms, but the incidence is rising. Surgery plays a central role in its management, as it is the only potentially curative treatment option for limited primary and recurrent disease and is critical in the surgical debulking and cytoreduction of advanced recurrent and metastatic disease. For preoperative detection of disease, gamma-emitting radiopharmaceuticals are available which can also be intraoperatively used for radioguided surgery. Most experience exists for 111In-octreotide, a radiopharmaceutical targeting agent specifically binding to somatostatin receptors expressed on the tumor cell surface. In comparison to traditional intraoperative inspection and palpation techniques, intraoperative localization using 111In-octreotide has demonstrated high sensitivity and detection rates. Recently, first promising results have been reported for utilization of intraoperative scintigraphic imaging in GEP-NETs in addition to more commonplace gamma probe localization.

Radioimmunoguided surgery is a specific application of radioguided surgery which involves intraoperative radioimmunodetection, using a handheld radiation detection device within the operating room in a real-time fashion, for the identification of a radiolabeled antibody or antibody fragment/derivative that has been administered to a patient prior to the time of attempted intraoperative detection and for the sole purpose of guiding the successful performance of the surgical procedure. This chapter discusses (1) the history and development of radioimmunoguided surgery, (2) tumor-associated antigens, (3) monoclonal antibodies, (4) clinical applications of radioimmunoguided surgery, and (5) the future clinical relevance of radioimmunoguided surgery in cancer diagnostics and cancer therapeutics (i.e., oncologic theranostics) as a potential powerful form of antigen-directed cancer surgery.

Surgical resection remains the primary curative treatment for many early-stage cancers, including breast cancer. The development of intraoperative guidance systems for identifying all sites of disease and improving the likelihood of complete surgical resection is an area of active ongoing research, as this can lead to a decrease in the need of subsequent additional surgical procedures. We develop a wearable goggle navigation system for dual-mode optical and ultrasound imaging of suspicious lesions. The system consists of a light source module, a monochromatic CCD camera, an ultrasound system, a Google Glass, and a host computer. It is tested in tissue-simulating phantoms and an ex vivo human breast tissue model. Our experiments demonstrate that the surgical navigation system provides useful guidance for localization and core needle biopsy of simulated tumor within the tissue-simulating phantom, as well as a core needle biopsy and subsequent excision of Indocyanine Green (ICG)-fluorescing sentinel lymph nodes. Our experiments support the contention that this wearable goggle navigation system can be potentially very useful and fully integrated by the surgeon for optimizing many aspects of oncologic surgery. Further engineering optimization and additional in vivo clinical validation work is necessary before such a surgical navigation system can be fully realized in the everyday clinical setting.

Renal cell carcinoma (RCC) accounts for approximately 85% to 90% of all primary kidney malignancies, with clear cell RCC (ccRCC) constituting approximately 70% to 85% of all RCCs. This study describes an innovative multimodal imaging and detection strategy that uses 124I-labeled chimeric monoclonal antibody G250 (124I-cG250) for accurate preoperative and intraoperative localization and confirmation of extent of disease for both laparoscopic and open surgical resection of ccRCC. Two cases presented herein highlight how this technology can potentially guide complete surgical resection and confirm complete removal of all diseased tissues. This innovative 124I-cG250 (ie, 124I-girentuximab) multimodal imaging and detection approach, which would be clinically very useful to urologic surgeons, urologic medical oncologists, nuclear medicine physicians, radiologists, and pathologists who are involved in the care of ccRCC patients, holds great potential for improving the diagnostic accuracy, operative planning and approach, verification of disease resection, and monitoring for evidence of disease recurrence in ccRCC patients.

Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important. The current study sought to determine biomarkers of fatigue that exist before cancer treatment. Relationships between the expression of latent Epstein–Barr virus (EBV) and cytomegalovirus (CMV) and fatigue were examined in 158 women newly diagnosed with breast cancer or awaiting a positive diagnostic result. Higher CMV antibody titers, but not EBV antibody titers, were associated with a greater likelihood of being fatigued. Associations between fatigue and higher CMV antibody titers remained after controlling for alcohol use, smoking, comorbidities, depressive symptoms, age, BMI, cancer stage, and sleep problems. More sleep problems and higher levels of depressive symptoms were also associated with a greater likelihood of being fatigued. CMV antibody titers, but not EBV antibody titers, were associated with higher levels of C-reactive protein (CRP), but CRP was not associated with fatigue. When the cellular immune system is compromised, reactivation of latent herpesviruses may fuel chronic inflammatory responses. Prior work has suggested that fatigue may be related to inflammation and its associated sickness behaviors; accordingly, our findings may be tapping into this same physiological substrate.

Breast implant surgery is one of the most commonly performed procedures in the field of plastic surgery. While silicone implants are now routinely used in breast surgery, they have previously been the subject of controversy. This was particularly true in the U.S., where there was a moratorium on their use from 1992 to 2006. Following subsequent scientific validation of their safety, silicone implants have re-gained widespread acceptance for clinical use. Modern implant design has aimed to optimize aesthetic outcomes while minimizing implant-related complications, such as capsular contracture and device rupture. One of the most significant advances has been the use of highly cohesive silicone which, through extensive cross-linking, maintains its shape within the body in the presence of physiologic forces. Overall, silicone breast implants are associated with a high degree of patient satisfaction and low rates of complications. Further independent research is necessary to better establish long-term outcomes.

Within breast tissue, aromatase expression and activity is increased by prostaglandin E2, providing a rationale for combining the COX-2 inhibitor celecoxib with an aromatase inhibitor. To evaluate the effect of these drugs on aromatase and other biomarkers, a phase II trial of neoadjuvant exemestane followed sequentially by celecoxib plus exemestane was performed.Postmenopausal women with estrogen receptor (ER) and/or progesterone (PR) positive stages II-III breast cancers received 8 weeks of exemestane 25 mg daily, followed by 8 weeks of exemestane 25 mg daily and celecoxib 400 mg twice daily. Core biopsies were collected pretreatment, after 8 weeks of exemestane, and at definitive breast cancer surgery. A tissue microarray was constructed and immunohistochemistry (IHC) for aromatase, ER, PR, HER-2, Ki-67, and COX-2 was performed.Twenty-two women were enrolled. Celecoxib was discontinued in 4 (18%) women for toxicity (all grade 1 and 2) and 2 (9%) developed serious cardiac events occurring at 1 and 4 months after completing treatment. By US, there were 8 (36%)-partial responses and 12 (55%)-stable disease. There were no pathological complete responses (pCR). There were statistically significant decreases in ER (P = .003), PR (P = .002), Ki-67 (P.001), and COX-2 (P = .004) expression. No significant differences in aromatase or HER-2 expression were observed (P = .13 and P = .39, respectively).The addition of celecoxib to exemestane was tolerated by the majority of women and anti-tumor response was observed. Additional studies, including gene expression, are required to more fully understand the basis for the decreased expression of ER, PR, Ki-67, and COX-2.

Anti-TAG-72 monoclonal antibodies target the tumor-associated glycoprotein (TAG)-72 in various solid tumors. This study evaluated the use of anti-TAG-72 monoclonal antibodies, both murine CC49 and humanized CC49 (HuCC49deltaCH2), for near-infrared fluorescent (NIR) tumor imaging in colorectal cancer xenograft models. The murine CC49 and HuCC49deltaCH2 were conjugated with Cy7 monofunctional N-hydroxysuccinimide ester (Cy7-NHS). Both in vitro and in vivo anti-TAG-72 antibody binding studies were performed. The in vitro study utilized the human colon adenocarcinoma cell line LS174T that was incubated with Cy7, antibody-Cy7 conjugates, or excessive murine CC49 followed by the antibody-Cy7 conjugates and was imaged by fluorescence microscopy. The in vivo study utilized xenograft mice, bearing LS174T subcutaneous tumor implants, that received tail vein injections of Cy7, murine CC49-Cy7, HuCC49deltaCH2-Cy7, or nonspecific IgG-Cy7 and were imaged by the Xenogen IVIS 100 system from 15 min to 288 h. The biodistribution of the fluorescence labeled antibodies was determined by imaging the dissected tissues. The in vitro study revealed that the antibody-Cy7 conjugates bound to LS174T cells and were blocked by excessive murine CC49. The in vivo study demonstrated that murine CC49 achieved a tumor/blood ratio of 15 at 96 h postinjection. In comparison, HuCC49deltaCH2-Cy7 cleared much faster than murine CC49-Cy7 from the xenograft mice, and HuCC49deltaCH2-Cy7 achieved a tumor/blood ratio of 12 at 18 h postinjection. In contrast, Cy7 and Cy7 labeled nonspecific IgG resulted in no demonstrable tumor accumulation. When mice were injected with excessive unlabeled murine CC49 at 6 h before the injection of murine CC49-Cy7 or HuCC49deltaCH2-Cy7, both the intensity and retention time of the fluorescence from the tumor were reduced. In summary, the Cy7 labeled murine CC49 and HuCC49deltaCH2 demonstrate tumor-targeting capabilities in living colorectal cancer xenograft mice and provide an alternative modality for tumor imaging.