Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast Cancer: 10-Year Results of the Randomized Controlled EORTC 10981-22023 AMAROS Trial.

PURPOSE: The European Organisation for Research and Treatment of Cancer 10981-22023 AMAROS trial evaluated axillary lymph node dissection (ALND) versus axillary radiotherapy (ART) in patients with cT1-2, node-negative breast cancer and a positive sentinel node (SN) biopsy. At 5 years, both modalities showed excellent and comparable axillary control, with significantly less morbidity after ART. We now report the preplanned 10-year analysis of the axillary recurrence rate (ARR), overall survival (OS), and disease-free survival (DFS), and an updated 5-year analysis of morbidity and quality of life. METHODS: In this open-label multicenter phase III noninferiority trial, 4,806 patients underwent SN biopsy; 1,425 were node-positive and randomly assigned to either ALND (n = 744) or ART (n = 681). RESULTS: Per intention-to-treat analysis, 10-year ARR cumulative incidence was 0.93% (95% CI, 0.18 to 1.68; seven events) after ALND and 1.82% (95% CI, 0.74 to 2.94; 11 events) after ART (hazard ratio [HR], 1.71; 95% CI, 0.67 to 4.39). There were no differences in OS (HR, 1.17; 95% CI, 0.89 to 1.52) or DFS (HR, 1.19; 95% CI, 0.97 to 1.46). ALND was associated with a higher lymphedema rate in updated 5-year analyses (24.5% v 11.9%; P < .001). Quality-of-life scales did not differ by treatment through 5 years. Exploratory analysis showed a 10-year cumulative incidence of second primary cancers of 12.1% (95% CI, 9.6 to 14.9) after ART and 8.3% (95% CI, 6.3 to 10.7) after ALND. CONCLUSION: This 10-year analysis confirms a low ARR after both ART and ALND with no difference in OS, DFS, and locoregional control. Considering less arm morbidity, ART is preferred over ALND for patients with SN-positive cT1-2 breast cancer.

Ductal Carcinoma in situ after Core Needle Biopsy: In Which Cases Is a Sentinel Node Biopsy Necessary?

INTRODUCTION: In some hospitals it is still common practice to carry out a sentinel node biopsy (SNB) if ductal carcinoma in situ (DCIS) is determined in preoperative staging, although this is against international guidelines. The reason for this is because an infiltrative component can be demonstrated frequently in the final pathohistological examination. In this study, we wanted to investigate possible predictors for infiltrative growth, to select patients to do an SNB or to omit it. MATERIAL AND METHODS: All patients with DCIS in the core needle biopsy (CNB), who were treated with surgery including an SNB, were included in a prospective data registry. Patient characteristics were collected through physical examination, mammography and ultrasonography. All characteristics of the DCIS were noted. After surgery, the pathological results were collected. RESULTS: From the 287 patients, 39 (13.6%) had an infiltrative component in the definitive pathological examination despite only DCIS in preoperative CNB. In total, there were only 14 (4.9%) positive SNBs, of which 11 patients had infiltrative growth in the breast tumor and 3 (1.2% of patients with DCIS alone in the final pathology) did not. In addition, characteristics of the CNB, including microcalcifications and comedonecrosis, did not show a statistically significant higher risk for infiltration. DISCUSSION: Considering the low rates of positive SNBs in our population, we think that an SNB should not be performed in advance when DCIS is diagnosed, because if infiltrative growth is found in the final biopsy, an SNB could always be performed afterwards. Only if an SNB cannot be performed afterwards is an SNB indicated.

Efficacy of Internet-Based Cognitive Behavioral Therapy for Treatment-Induced Menopausal Symptoms in Breast Cancer Survivors: Results of a Randomized Controlled Trial.

PURPOSE: We evaluated the effect of Internet-based cognitive behavioral therapy (iCBT), with or without therapist support, on the perceived impact of hot flushes and night sweats (HF/NS) and overall levels of menopausal symptoms (primary outcomes), sleep quality, HF/NS frequency, sexual functioning, psychological distress, and health-related quality of life in breast cancer survivors with treatment-induced menopausal symptoms. PATIENTS AND METHODS: We randomly assigned 254 breast cancer survivors to a therapist-guided or a self-managed iCBT group or to a waiting list control group. The 6-week iCBT program included psycho-education, behavior monitoring, and cognitive restructuring. Questionnaires were administered at baseline and at 10 weeks and 24 weeks postrandomization. We used mixed-effects models to compare the intervention groups with the control group over time. Significance was set at P < .01. An effect size (ES) of .20 was considered small, .50 moderate and clinically significant, and .80 large. RESULTS: Compared with the control group, the guided and self-managed iCBT groups reported a significant decrease in the perceived impact of HF/NS (ES, .63 and .56, respectively; both P < .001) and improvement in sleep quality (ES, .57 and .41; both P < .001). The guided group also reported significant improvement in overall levels of menopausal symptoms (ES, .33; P = .003), and NS frequency (ES, .64; P < .001). At longer-term follow-up (24 weeks), the effects remained significant, with a smaller ES for the guided group on perceived impact of HF/NS and sleep quality and for the self-managed group on overall levels of menopausal symptoms. Additional longer-term effects for both intervention groups were found for hot flush frequency. CONCLUSION: iCBT, with or without therapist support, has clinically significant, salutary effects on the perceived impact and frequency of HF/NS, overall levels of menopausal symptoms, and sleep quality.

Sexual Functioning and Relationship Satisfaction of Partners of Breast Cancer Survivors Who Receive Internet-Based Sex Therapy.

As part of a larger, randomized controlled trial, we evaluated longitudinally the sexual functioning and relationship satisfaction of 69 partners of breast cancer (BC) survivors who received Internet-based cognitive behavioral therapy (CBT) for sexual dysfunction. The findings suggest that Internet-based CBT positively affects the partners' immediate post-CBT and longer-term overall sexual satisfaction, sexual intimacy, and sexual relationship satisfaction. No sustained changes in other areas of sexual functioning were observed. Our CBT program was focused primarily on the sexual health of the BC survivors. We recommend that future programs include more psychoeducational and behavioral elements targeted at the partners.

Internet-Based Cognitive Behavioral Therapy Realizes Long-Term Improvement in the Sexual Functioning and Body Image of Breast Cancer Survivors.

The study aim was to evaluate the long-term efficacy of Internet-based cognitive behavioral therapy (CBT) for sexual dysfunctions in 84 breast cancer survivors. The positive effects of the intervention on overall sexual functioning, sexual desire, sexual arousal, vaginal lubrication, discomfort during sex, sexual distress, and body image observed immediately posttreatment were maintained at three- and nine-month follow-ups. Although sexual pleasure decreased during follow-up, it did not return to baseline levels. Our findings provide evidence that Internet-based CBT has a sustained, positive effect on sexual functioning and body image of breast cancer survivors with a sexual dysfunction.

Rapid genetic counseling and testing in newly diagnosed breast cancer: Patients' and health professionals' attitudes, experiences, and evaluation of effects on treatment decision making.

BACKGROUND: Rapid genetic counseling and testing (RGCT) in newly diagnosed high-risk breast cancer (BC) patients may influence surgical treatment decisions. To successfully integrate RGCT in practice, knowledge of professionals', and patients' attitudes toward RGCT is essential. METHODS: Between 2008 and 2010, we performed a randomized clinical trial evaluating the impact of RGCT. Attitudes toward and experience with RGCT were assessed in 265 patients (at diagnosis, 6- and 12-month follow-up) and 29 medical professionals (before and after the recruitment period). RESULTS: At 6-month follow-up, more patients who had been offered RGCT felt they had been actively involved in treatment decision-making than patients who had been offered usual care (67% vs 48%, P = 0.06). Patients who received DNA-test results before primary surgery reported more often that RGCT influenced treatment decisions than those who received results afterwards (P < 0.01). Eighty-seven percent felt that genetic counseling and testing (GCT) should preferably take place between diagnosis and surgery. Most professionals (72%) agreed that RGCT should be routinely offered to eligible patients. Most patients (74%) and professionals (85%) considered surgeons the most appropriate source for referral. CONCLUSIONS: RGCT is viewed as helpful for newly diagnosed high-risk BC patients in choosing their primary surgery and should be offered routinely by surgeons.

Efficacy of Internet-Based Cognitive Behavioral Therapy in Improving Sexual Functioning of Breast Cancer Survivors: Results of a Randomized Controlled Trial.

Purpose We evaluated the effect of Internet-based cognitive behavioral therapy (CBT) on sexual functioning and relationship intimacy (primary outcomes) and body image, menopausal symptoms, marital functioning, psychological distress, and health-related quality of life (secondary outcomes) in breast cancer survivors (BCSs) with a DSM-IV diagnosis of a sexual dysfunction. Patients and Methods We randomly assigned 169 BCSs to either Internet-based CBT or a waiting-list control group. The CBT consisted of weekly therapist-guided sessions, with a maximum duration of 24 weeks. Self-report questionnaires were completed by the intervention group at baseline (T0), midtherapy (T1), and post-therapy (T2) and at equivalent times by the control group. We used a mixed-effect modeling approach to compare the groups over time. Results Compared with the control group, the intervention group showed a significant improvement over time in overall sexual functioning (effect size for T2 [EST2] = .43; P = .031), which was reflected in an increase in sexual desire (EST1 = .48 and EST2 = .72; P < .001), sexual arousal (EST2 = .50; P = .008), and vaginal lubrication (EST2 = .46; P = .013). The intervention group reported more improvement over time in sexual pleasure (EST1 = .32 and EST2 = .62; P = .001), less discomfort during sex (EST1 = .49 and EST2 = .66; P = .001), and less sexual distress (EST2 = .59; P = .002) compared with the control group. The intervention group reported greater improvement in body image (EST2 = .45; P = .009) and fewer menopausal symptoms (EST1 = .39; P = .007) than the control group. No significant effects were observed for orgasmic function, sexual satisfaction, intercourse frequency, relationship intimacy, marital functioning, psychological distress, or health-related quality of life. Conclusion Internet-based CBT has salutary effects on sexual functioning, body image, and menopausal symptoms in BCSs with a sexual dysfunction.

Prognostic value of pre-operative glucose-corrected maximum standardized uptake value in patients with non-small cell lung cancer after complete surgical resection and 5-year follow-up.

INTRODUCTION: In this study we evaluated the value of pre-operative glucose corrected maximum standard uptake value (GC-SUVmax) as prognostic factor in patients with early stage non-small cell lung cancer (NSCLC) after complete surgical resection. METHODS: This study was designed as a retrospectively evaluated single center study with prospective data registry. Inclusion criteria were: histologically proven stage I NSCLC, 18F-FDG-PET/CT scan prior to surgery, complete resection (R0) and follow up in our outpatient department. Exclusion criteria were: history of malignancy other than NSCLC, diabetes and (neo) adjuvant therapy. Follow up period was 5 years. RESULTS: Between 2006 and 2008 a total of 33 patients (16 males, 17 females) met the inclusion criteria. SUVmax and GC-SUVmax were strongly correlated (Spearman's ρ = 0.97). Five-year overall survival (OS) rate was 70 % (95 % CI = 56-87 %). Patients who died within 5 years of follow up had significantly higher pre-operative GC-SUVmax (median = 10.6, IQR = 8.3-14.4) than patients who were alive at 5-year follow up (median = 6.4, IQR = 3.0-9.8), p = 0.04. SUVmax showed similar differences: 10.4 (8-12.9) vs. 6.6 (3.0-8.8), p = 0.047. The area under the receiver-operating characteristic (ROC) curve at 5 years was 0.70 (95 % CI = 0.50-0.90) for GC-SUVmax and 0.71 (95 % CI = 0.51-0.91) for SUVmax (p = 0.75). CONCLUSION: Pre-operative FDG tumor uptake in patients with NSCLC is predictive for survival after complete surgical resection. GC-SUVmax, as an additional value to SUVmax, may better approach competitive inhibition of FDG and glucose in tumors, however, in this study this potential advantage, if any, was very small.

Jejunal feeding is followed by a greater rise in plasma cholecystokinin, peptide YY, glucagon-like peptide 1, and glucagon-like peptide 2 concentrations compared with gastric feeding in vivo in humans: a randomized trial.

BACKGROUND: Jejunal feeding is preferred instead of gastric feeding in patients who are intolerant to gastric feeding or at risk of aspiration. However, the impact of gastric feeding compared with that of jejunal feeding on postprandial circulating plasma glucose and amino acid concentrations and the associated endocrine response in vivo in humans remains largely unexplored. OBJECTIVE: We compared the impact of administering enteral nutrition as either gastric feeding or jejunal feeding on endocrine responses in vivo in humans. DESIGN: In a randomized, crossover study design, 12 healthy young men (mean ± SD age: 21 ± 2 y) received continuous enteral nutrition that contained noncoagulating proteins for 12 h via a nasogastric tube or a nasojejunal tube placed 30-40 cm distal to the ligament of Treitz. Blood samples were collected during the 12-h postprandial period to assess the rise in plasma glucose, amino acid, and gastrointestinal hormone concentrations. RESULTS: No differences were observed in the postprandial rise in circulating plasma amino acid and glucose concentrations between regimens. Jejunal feeding resulted in higher peak plasma insulin concentrations than did gastric feeding (392 ± 53 compared with 326 ± 54 pmol/L, respectively; P < 0.05). The postprandial rise in plasma cholecystokinin, peptide YY (PYY), glucagon-like peptide 1 (GLP-1), and glucagon-like peptide 2 (GLP-2) concentrations was greater after jejunal feeding than after gastric feeding, with higher peak concentrations and a greater postprandial incremental AUC for GLP-1 and cholecystokinin (all P < 0.05). Plasma ghrelin concentrations did not differ between regimens. CONCLUSIONS: Enteral nutrition with gastric or jejunal feeding in healthy young men results in similar postprandial plasma amino acid and glucose concentrations. However, the endocrine response differs substantially, with higher peak plasma cholecystokinin, PYY, GLP-1, and GLP-2 concentrations being attained after jejunal feeding. This effect may result in an improved anabolic response, greater insulin sensitivity, and an improved intestinotropic effect. Nevertheless, it may also lead to delayed gastric emptying. This trial was registered at trialregister.nl as NTR2801.

Intraoperative Ultrasound Guidance in Breast-Conserving Surgery Improves Cosmetic Outcomes and Patient Satisfaction: Results of a Multicenter Randomized Controlled Trial (COBALT).

BACKGROUND: Ultrasound-guided breast-conserving surgery (USS) results in a significant reduction in both margin involvement and excision volumes (COBALT trial). Objective. The aim of the present study was to determine whether USS also leads to improvements in cosmetic outcome and patient satisfaction when compared with standard palpation-guided surgery (PGS). METHODS: A total of 134 patients with T1­T2 invasive breast cancer were included in the COBALT trial (NTR2579) and randomized to either USS (65 patients) or PGS (69 patients). Cosmetic outcomes were assessed by a three-member panel using computerized software Breast Cancer Conservative Treatment cosmetic results (BCCT.- core) and by patient self-evaluation, including patient satisfaction. Time points for follow-up were 3, 6, and 12 months after surgery. Overall cosmetic outcome and patient satisfaction were scored on a 4-point Likert scale (excellent, good, fair, or poor), and outcomes were analyzed using a multilevel, mixed effect, proportional odds model for ordinal responses. RESULTS: Ultrasound-guided breast-conserving surgery achieved better cosmetic outcomes, with 20 % excellence overall and only 6 % rated as poor, whereas 14 % of PGS outcomes were rated excellent and 13 % as poor. USS also had consistently lower odds for worse cosmetic outcomes (odds ratio 0.55, p = 0.067) than PGS. The chance of having a worse outcome was significantly increased by a larger lumpectomy volume (ptrend = 0.002); a volume [40 cc showed odds 2.78-fold higher for a worse outcome than a volume B40 cc. USS resulted in higher patient satisfaction compared with PGS. CONCLUSION: Ultrasound-guided breast-conserving surgery achieved better overall cosmetic outcomes and patient satisfaction than PGS. Lumpectomy volumes[40 cc resulted in significantly worse cosmetic outcomes.

Does rapid genetic counseling and testing in newly diagnosed breast cancer patients cause additional psychosocial distress? results from a randomized clinical trial.

PURPOSE: Female breast cancer patients carrying a BRCA1/2 mutation have an increased risk of second primary breast cancer. Rapid genetic counseling and testing (RGCT) before surgery may influence choice of primary surgical treatment. In this article, we report on the psychosocial impact of RGCT. METHODS: Newly diagnosed breast cancer patients at risk for carrying a BRCA1/2 mutation were randomized to an intervention group (offer of RGCT) or a usual care control group (ratio 2:1). Psychosocial impact and quality of life were assessed with the Impact of Events Scale, Hospital Anxiety and Depression Scale, Cancer Worry Scale, and the EORTC QLQ-C30 and QLQ-BR23. Assessments took place at study entry and at 6- and 12-month follow-up visits. RESULTS: Between 2008 and 2010, 265 patients were recruited into the study. Completeness of follow-up data was more than 90%. Of the 178 women in the intervention group, 177 had genetic counseling, of whom 71 (40%) had rapid DNA testing and 59 (33%) received test results before surgery. Intention-to-treat and per-protocol analyses showed no statistically significant differences between groups over time in any of the psychosocial outcomes. CONCLUSIONS: In this study, RGCT in newly diagnosed breast cancer patients did not have any measurable adverse psychosocial effects.

The PRECious trial PREdiction of Complications, a step-up approach, CRP first followed by CT-scan imaging to ensure quality control after major abdominal surgery: study protocol for a stepped-wedge trial.

BACKGROUND: After major abdominal surgery (MAS), 20% of patients endure major complications, which require invasive treatment and are associated with increased morbidity and mortality. A quality control algorithm after major abdominal surgery aimed at early identification of patients at risk of developing major complications can decrease associated morbidity and mortality. Literature studies show promising results for C-reactive protein (CRP) as an early marker for postoperative complications, however clinical significance has yet to be determined. METHODS: A multicenter, stepped wedge, prospective clinical trial including all adult patients planned to undergo elective MAS. The first period consists of standard postoperative monitoring, which entails on demand additional examinations. This is followed by a period with implementation of postoperative control according to the PRECious protocol, which implicates standardized measurement of CRP levels. If CRP levels exceed 140 mg/L on postoperative day 3,4 or 5, an enhanced CT-scan is performed. Primary outcome in this study is a combined primary outcome, entailing all morbidity and mortality due to postoperative complications. Complications are graded according to the Clavien-Dindo classification. Secondary outcomes are hospital length of stay, patients reported outcome measures (PROMs) and cost-effectiveness. Data will be collected during admission, three months and one year postoperatively. Approval by the medical ethics committee of the VU University Medical Center was obtained (ID 2015.114). DISCUSSION: the PRECious trial is a stepped-wedge, multicenter, open label, prospective clinical trial to determine the effect of a standardized postoperative quality control algorithm on postoperative morbidity and mortality, and cost-effectiveness. TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT02102217. Registered 5 February 2015.

Jejunal Casein Feeding Is Followed by More Rapid Protein Digestion and Amino Acid Absorption When Compared with Gastric Feeding in Healthy Young Men.

BACKGROUND: Dietary protein is required to attenuate the loss of muscle mass and to support recovery during a period of hospitalization. Jejunal feeding is preferred over gastric feeding in patients who are intolerant of gastric feeding. However, the impact of gastric vs. jejunal feeding on postprandial dietary protein digestion and absorption kinetics in vivo in humans remains largely unexplored. OBJECTIVE: We compared the impact of gastric vs. jejunal feeding on subsequent dietary protein digestion and amino acid (AA) absorption in vivo in healthy young men. METHODS: In a randomized crossover study design, 11 healthy young men (aged 21 ± 2 y) were administered 25 g specifically produced intrinsically l-[1-(13)C]phenylalanine-labeled intact casein via a nasogastric and a nasojejunal tube placed ~30 cm distal to the ligament of Treitz. Protein was provided in a 240-mL solution administered over a 65-min period in both feeding regimens. Blood samples were collected during the 7-h postprandial period to assess the increase in plasma AA concentrations and dietary protein-derived plasma l-[1-(13)C]phenylalanine enrichment. RESULTS: Jejunal feeding compared with gastric feeding resulted in higher peak plasma phenylalanine, leucine, total essential AA (EAA), and total AA concentrations (all P < 0.05). This was attributed to a more rapid release of dietary protein-derived AAs into the circulation, as evidenced by a higher peak plasma l-[1-(13)C]phenylalanine enrichment concentration (2.9 ± 0.2 vs. 2.2 ± 0.2 mole percent excess; P < 0.05). The total postprandial plasma AA incremental area under the curve and time to peak did not differ after jejunal vs. gastric feeding. Plasma insulin concentrations increased to a greater extent after jejunal feeding when compared with gastric feeding (275 ± 38 vs. 178 ± 38 pmol/L; P < 0.05). CONCLUSIONS: Jejunal feeding of intact casein is followed by more rapid protein digestion and AA absorption when compared with gastric feeding in healthy young men. The greater postprandial increase in circulating EAA concentrations may allow a more robust increase in muscle protein synthesis rate after jejunal vs. gastric casein feeding. This trial was registered at trialregister.nl as NTR2801.

Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer (EORTC 10981-22023 AMAROS): a randomised, multicentre, open-label, phase 3 non-inferiority trial.

BACKGROUND: If treatment of the axilla is indicated in patients with breast cancer who have a positive sentinel node, axillary lymph node dissection is the present standard. Although axillary lymph node dissection provides excellent regional control, it is associated with harmful side-effects. We aimed to assess whether axillary radiotherapy provides comparable regional control with fewer side-effects. METHODS: Patients with T1-2 primary breast cancer and no palpable lymphadenopathy were enrolled in the randomised, multicentre, open-label, phase 3 non-inferiority EORTC 10981-22023 AMAROS trial. Patients were randomly assigned (1:1) by a computer-generated allocation schedule to receive either axillary lymph node dissection or axillary radiotherapy in case of a positive sentinel node, stratified by institution. The primary endpoint was non-inferiority of 5-year axillary recurrence, considered to be not more than 4% for the axillary radiotherapy group compared with an expected 2% in the axillary lymph node dissection group. Analyses were by intention to treat and per protocol. The AMAROS trial is registered with ClinicalTrials.gov, number NCT00014612. FINDINGS: Between Feb 19, 2001, and April 29, 2010, 4823 patients were enrolled at 34 centres from nine European countries, of whom 4806 were eligible for randomisation. 2402 patients were randomly assigned to receive axillary lymph node dissection and 2404 to receive axillary radiotherapy. Of the 1425 patients with a positive sentinel node, 744 had been randomly assigned to axillary lymph node dissection and 681 to axillary radiotherapy; these patients constituted the intention-to-treat population. Median follow-up was 6·1 years (IQR 4·1-8·0) for the patients with positive sentinel lymph nodes. In the axillary lymph node dissection group, 220 (33%) of 672 patients who underwent axillary lymph node dissection had additional positive nodes. Axillary recurrence occurred in four of 744 patients in the axillary lymph node dissection group and seven of 681 in the axillary radiotherapy group. 5-year axillary recurrence was 0·43% (95% CI 0·00-0·92) after axillary lymph node dissection versus 1·19% (0·31-2·08) after axillary radiotherapy. The planned non-inferiority test was underpowered because of the low number of events. The one-sided 95% CI for the underpowered non-inferiority test on the hazard ratio was 0·00-5·27, with a non-inferiority margin of 2. Lymphoedema in the ipsilateral arm was noted significantly more often after axillary lymph node dissection than after axillary radiotherapy at 1 year, 3 years, and 5 years. INTERPRETATION: Axillary lymph node dissection and axillary radiotherapy after a positive sentinel node provide excellent and comparable axillary control for patients with T1-2 primary breast cancer and no palpable lymphadenopathy. Axillary radiotherapy results in significantly less morbidity. FUNDING: EORTC Charitable Trust.

The effect of fibers on coagulation of casein-based enteral nutrition in an artificial gastric digestion model.

A serious complication seen in critically ill patients is the solidification of enteral nutrition causing gastrointestinal obstruction. It has been suggested that enteral nutrition enriched with insoluble fibers may increase the risk of this complication. Therefore, we investigate the effect of soluble and insoluble dietary fibers on the coagulation of a casein-based enteral nutrition in an artificial gastric digestion model. A 100% casein-based enteral nutrition was enriched with increasing concentrations of soluble fibers (acacia fiber, oligofructose and inulin) and insoluble fibers (soy polysaccharide, resistant starch and alpha cellulose). After digestion in an artificial gastric model, the chyme was poured over sequentially placed sieves, separating the coagulate into size fractions of larger than 2 mm, between 1 and 2 mm, and between 0.25 and 1 mm. Of these fractions we measured wet weight, dry weight and protein content. A significant effect on the fraction larger than 2 mm was considered to be clinically relevant. Addition of high concentrations soy polysaccharide and resistant starch to a casein-based enteral nutrition, did not alter the wet weight, whereas dry weight and protein content of the coagulate was significantly reduced. When high concentrations of soy polysaccharide and resistant starch are added to a 100% casein-based enteral nutrition, the coagulate consist of more water and less proteins, which may lead to an increased protein digestion and absorption in a clinical setting. The suggestion that insoluble fibers increase the risk of gastrointestinal obstruction in critically ill patients is not supported by these data.

(18)F-fluorodeoxyglucose positron emission tomography versus computed tomography in predicting histopathological response to epidermal growth factor receptor-tyrosine kinase inhibitor treatment in resectable non-small cell lung cancer.

PURPOSE: To prospectively evaluate diagnostic computed tomography (CT) and (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for identification of histopathologic response to neoadjuvant erlotinib, an epidermal growth factor receptor-tyrosine kinase inhibitor in patients with resectable non-small cell lung cancer (NSCLC). METHODS: This study was designed as an open-label phase 2 trial, performed in four hospitals in the Netherlands. Patients received preoperative erlotinib 150 mg once daily for 3 weeks. CT and FDG-PET/CT were performed at baseline and after 3 weeks of treatment. CT was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. FDG-PET/CT, tumor FDG uptake, and changes were measured by standardized uptake values (SUV). Radiologic and metabolic responses were compared to the histopathological response. RESULTS: Sixty patients were enrolled onto this study. In 53 patients (22 men, 31 women), the combination of CT, FDG-PET/CT, and histopathological evaluation was available for analysis. Three patients (6 %) had radiologic response. According to European Organisation for Research and Treatment of Cancer (EORTC) criteria, 15 patients (28 %) showed metabolic response. In 11 patients, histopathologic response (≥50 % necrosis) was seen. In predicting histopathologic response, relative FDG change in SUVmax showed more SUVmax decrease in the histopathologic response group (-32 %) versus the group with no pathologic response (-4 %) (p = 0.0132). Relative change in tumor size on diagnostic CT was similar in these groups with means close to 0. CONCLUSIONS: FDG-PET/CT has an advantage over CT as a predictive tool to identify histopathologic response after 3 weeks of EGFR-TKI treatment in NSCLC patients.

Timing of metabolic response monitoring during erlotinib treatment in non-small cell lung cancer.

UNLABELLED: The purpose of this study was to prospectively evaluate the timing of metabolic response monitoring with (18)F-FDG PET of (neoadjuvant) erlotinib treatment in patients with early-stage non-small cell lung cancer. METHODS: This study was designed as an open-label phase II trial performed in 4 hospitals in The Netherlands. Patients received preoperative erlotinib (150 mg) once daily for 3 wk. Response evaluation was performed after 4-7 d and at 3 wk with (18)F-FDG PET/CT scans. Tumor (18)F-FDG uptake and changes were measured as standardized uptake values (SUVs). The metabolic response was classified on the basis of European Organization for Research and Treatment of Cancer criteria (>25% decrease in the maximum SUV) and was compared with histopathologic regression as observed in the resection specimen. RESULTS: From December 2006 to November 2010, 60 patients with non-small cell lung cancer eligible for surgical resection were enrolled in this study. For 43 patients (18 men and 25 women), baseline (18)F-FDG PET/CT scans as well as both monitoring scans and histopathologic response monitoring were available. A partial metabolic response on (18)F-FDG PET/CT scans was observed for 10 patients (23%) after 1 wk and for 14 patients (33%) after 3 wk. Histopathologic examination revealed regression (necrosis of >50%) in 11 patients (26%). In these patients, the maximum SUV decreased by a mean of 17% within 1 wk and a mean of 31% at 3 wk. Seven patients were identified as responders within 1 wk. CONCLUSION: Response monitoring with (18)F-FDG PET/CT within 1 wk after the start of erlotinib treatment identified approximately 64% of histopathologic responders on the basis of European Organization for Research and Treatment of Cancer criteria.

Preservation of the gut by preoperative carbohydrate loading improves postoperative food intake.

BACKGROUND & AIMS: A carbohydrate (CHO) drink given preoperatively changes the fasted state into a fed state. The ESPEN guidelines for perioperative care include preoperative CHO loading and re-establishment of oral feeding as early as possible after surgery. An intestinal ischaemia reperfusion (IR) animal model was used to investigate whether preoperative CHO loading increases spontaneous postoperative food intake, intestinal barrier function and the catabolic response. METHODS: Male Wistar rats (n = 65) were subjected to 16 h fasting with ad libitum water and: A) sham laparotomy (Sham fasted, n = 24); B) intestinal ischaemia (IR fasted, n = 27); and C) intestinal ischaemia with preoperatively access to a CHO drink (IR CHO, n = 14). Spontaneous food intake, intestinal barrier function, insulin sensitivity, intestinal motility and plasma amino acids were measured after surgery. RESULTS: The IR CHO animals started eating significantly earlier and also ate significantly more than the IR fasted animals. Furthermore, preoperative CHO loading improved the intestinal barrier function, functional enterocyte metabolic mass measured by citrulline and reduced muscle protein catabolism, as indicated by normalization of the biomarker 3-methylhistidine. CONCLUSIONS: Preoperative CHO loading improves food intake, preserves the GI function and reduces the catabolic response in an IR animal model. These findings suggest that preoperative CHO loading preserves the intestinal function in order to accelerate recovery and food intake. If this effect is caused by overcoming the fasted state or CHO loading remains unclear.

Efficacy of cognitive behavioral therapy and physical exercise in alleviating treatment-induced menopausal symptoms in patients with breast cancer: results of a randomized, controlled, multicenter trial.

PURPOSE: The purpose of our study was to evaluate the effect of cognitive behavioral therapy (CBT), physical exercise (PE), and of these two interventions combined (CBT/PE) on menopausal symptoms (primary outcome), body image, sexual functioning, psychological well-being, and health-related quality of life (secondary outcomes) in patients with breast cancer experiencing treatment-induced menopause. PATIENTS AND METHODS: Patients with breast cancer reporting treatment-induced menopausal symptoms (N=422) were randomly assigned to CBT (n=109), PE (n=104), CBT/PE (n=106), or to a waiting list control group (n=103). Self-report questionnaires were completed at baseline, 12 weeks, and 6 months. Multilevel procedures were used to compare the intervention groups with the control group over time. RESULTS: Compared with the control group, the intervention groups had a significant decrease in levels of endocrine symptoms (Functional Assessment of Cancer Therapy-Endocrine Symptoms; P<.001; effect size, 0.31-0.52) and urinary symptoms (Bristol Female Lower Urinary Tract Symptoms Questionnaire; P=.002; effect size, 0.29-0.33), and they showed an improvement in physical functioning (36-Item Short Form Health Survey physical functioning subscale; P=.002; effect size, 0.37-0.46). The groups that included CBT also showed a significant decrease in the perceived burden of hot flashes and night sweats (problem rating scale of the Hot Flush Rating Scale; P<.001; effect size, 0.39-0.56) and an increase in sexual activity (Sexual Activity Questionnaire habit subscale; P=.027; effect size, 0.65). Most of these effects were observed at both the 12-week and 6-month follow-ups. CONCLUSION: CBT and PE can have salutary effects on endocrine symptoms and, to a lesser degree, on sexuality and physical functioning of patients with breast cancer experiencing treatment-induced menopause. Future work is needed to improve the design and the planning of these interventions to improve program adherence.

Ultrasound-guided breast-sparing surgery to improve cosmetic outcomes and quality of life. A prospective multicentre randomised controlled clinical trial comparing ultrasound-guided surgery to traditional palpation-guided surgery (COBALT trial).

BACKGROUND: Breast-conserving surgery for breast cancer was developed as a method to preserve healthy breast tissue, thereby improving cosmetic outcomes. Thus far, the primary aim of breast-conserving surgery has been the achievement of tumour-free resection margins and prevention of local recurrence, whereas the cosmetic outcome has been considered less important. Large studies have reported poor cosmetic outcomes in 20-40% of patients after breast-conserving surgery, with the volume of the resected breast tissue being the major determinant. There is clear evidence for the efficacy of ultrasonography in the resection of nonpalpable tumours. Surgical resection of palpable breast cancer is performed with guidance by intra-operative palpation. These palpation-guided excisions often result in an unnecessarily wide resection of adjacent healthy breast tissue, while the rate of tumour-involved resection margins is still high. It is hypothesised that the use of intra-operative ultrasonography in the excision of palpable breast cancer will improve the ability to spare healthy breast tissue while maintaining or even improving the oncological margin status. The aim of this study is to compare ultrasound-guided surgery for palpable tumours with the standard palpation-guided surgery in terms of the extent of healthy breast tissue resection, the percentage of tumour-free margins, cosmetic outcomes and quality of life. METHODS/DESIGN: In this prospective multicentre randomised controlled clinical trial, 120 women who have been diagnosed with palpable early-stage (T1-2N0-1) primary invasive breast cancer and deemed suitable for breast-conserving surgery will be randomised between ultrasound-guided surgery and palpation-guided surgery. With this sample size, an expected 20% reduction of resected breast tissue and an 18% difference in tumour-free margins can be detected with a power of 80%. Secondary endpoints include cosmetic outcomes and quality of life. The rationale, study design and planned analyses are described. CONCLUSION: The COBALT trial is a prospective, multicentre, randomised controlled study to assess the efficacy of ultrasound-guided breast-conserving surgery in patients with palpable early-stage primary invasive breast cancer in terms of the sparing of breast tissue, oncological margin status, cosmetic outcomes and quality of life. TRIAL REGISTRATION NUMBER: Netherlands Trial Register (NTR): NTR2579.