Quality of Life in Patients with Breast Cancer-Related Lymphedema and Reconstructive Breast Surgery.

Background To evaluate the quality of life (QOL) of breast cancer survivors who have undergone breast reconstruction and have breast cancer-related lymphedema (BCRL). Methods Patients with a unilateral mastectomy with or without breast reconstruction were evaluated for BCRL and their QOL. Patients were divided into a non-BCRL and a BCRL group. Patients with subjective complaints of arm swelling and/or an interlimb volume difference of >200 mL, or undergoing treatment for arm lymphedema were defined as having BCRL. QOL was assessed using cancer-specific (EORTC QLQ-C30 and EORTC QLQ-B23) and disease specific (Lymph-ICF) questionnaires. Results In total, 253 patients with a mean follow-up time of 51.7 (standard deviation = 18.5) months since mastectomy completed the QOL questionnaires. Of these patients, 116 (46%) underwent mastectomy alone and 137 (54%) had additional breast reconstruction. A comparison of the QOL scores of 180 patients in the non-BCRL group showed a significantly better physical function (p = 0.004) for patients with reconstructive surgery compared with mastectomy patients. In the 73 patients with BCRL, a comparison of the QOL scores showed no significant differences between patients with mastectomy and reconstructive surgery. After adjusting for potential confounders, multivariate analysis showed a significant impact of BCRL on physical function (ß = - 7.46; p = 0.009), role function (ß = - 15.75; p = 0.003), cognitive function (ß = - 11.56; p = 0.005), body vision (ß = - 11.62; p = 0.007), arm symptoms (ß = 20.78; p = 0.000), and all domains of the Lymph-ICF questionnaire. Conclusions This study implies that BCRL has a negative effect on the QOL of breast cancer survivors, potentially negating the positive effects on QOL reconstructive breast surgery has.

The Human Colon Is More Resistant to Ischemia-reperfusion-induced Tissue Damage Than the Small Intestine: An Observational Study.

OBJECTIVE: Aim of this study was to draw comparisons between human colonic and jejunal ischemia-reperfusion sequelae in a human in vivo experimental model. BACKGROUND: In patients, colonic ischemia-reperfusion generally has a milder course than small intestinal ischemia-reperfusion. It is unclear which pathophysiologic processes are responsible for this difference. METHODS: In 10 patients undergoing colonic surgery and 10 patients undergoing pancreaticoduodenectomy, 6 cm colon or jejunum was isolated and exposed to 60 minutes ischemia followed by various reperfusion periods. Morphology (hematoxylin and eosin), apoptosis (M30), tight junctions (zonula occludens 1), and neutrophil influx (myeloperoxidase) were assessed using immunohistochemistry. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were performed for interleukin-6 and tumor necrosis factor-α. RESULTS: Hematoxylin and eosin staining revealed intact colonic epithelial lining, but extensive damage in jejunal villus tips after 60 minutes ischemia. After reperfusion, the colonic epithelial lining was not affected, whereas the jejunal epithelium was seriously damaged. Colonic apoptosis was limited to scattered cells in surface epithelium, whereas apoptosis was clearly observed in jejunal villi and crypts, (42 times more M30 positivity compared with colon, P < 0.01). Neutrophil influx and increased tumor necrosis factor-α mRNA expression were observed in jejunum after 30 and 120 minutes of reperfusion (P < 0.05). Interleukin-6 mRNA expression was increased in jejunum after 120 minutes of reperfusion (3.6-fold increase, P < 0.05), whereas interleukin-6 protein expression was increased in both colon (1.5-fold increase, P < 0.05) and small intestine (1.5-fold increase, P < 0.05) after 30 and 120 minutes of reperfusion. CONCLUSIONS: Human colon is less susceptible to IR-induced tissue injury than small intestine.

Functional compromise reflected by sarcopenia, frailty, and nutritional depletion predicts adverse postoperative outcome after colorectal cancer surgery.

OBJECTIVE: To determine the association of sarcopenia with postoperative morbidity and mortality after colorectal surgery. BACKGROUND: Functional compromise in elderly colorectal surgical patients is considered as a significant factor of impaired postoperative recovery. Therefore, the predictive value of preoperative functional compromise assessment was investigated. Sarcopenia is a hallmark of functional compromise. METHODS: A total of 310 consecutive patients who underwent oncologic colorectal surgery were included in a prospective digital database. Sarcopenia was assessed using the L3 muscle index utilizing Osirix on preoperative computed tomography. Groningen Frailty Indicator and Short Nutritional Assessment Questionnaire scores were used to assess frailty and nutritional compromise. Predictors for anastomotic leakage, sepsis, and mortality were analyzed by logistic regression analysis. RESULTS: Age was an independent predictor of mortality [P = 0.04; odds ratio, 1.17; 95% confidence interval (CI), 1.01-1.37]. Thirty-day/in-hospital mortality rate in sarcopenic patients was 8.8% versus 0.7% in nonsarcopenic patients (P = 0.001; odds ratio, 15.5; 95% CI, 2.00-120). Sarcopenia was not predictive for anastomotic leakage or sepsis. Combination of high Short Nutritional Assessment Questionnaire score, high Groningen Frailty Indicator score, and sarcopenia strongly predicted sepsis (P = 0.001; odds ratio, 25.1; 95% CI, 5.11-123), sensitivity, 46%; specificity, 97%; positive likelihood ratio, 13 (95% CI, 4.4-38); negative likelihood ratio, 0.57 (95% CI, 0.33-0.97). CONCLUSIONS: Functional compromise in colorectal cancer surgery is associated with adverse postoperative outcome. Assessment of functional compromise by means of a nutritional questionnaire (Short Nutritional Assessment Questionnaire), a frailty questionnaire (Groningen Frailty Indicator), and sarcopenia measurement (L3 muscle index) can accurately predict postoperative sepsis.

Identification of promising strategies to sustain improvements in hospital practice: a qualitative case study.

BACKGROUND: A quality improvement collaborative is an intensive project involving a combination of implementation strategies applied in a limited "breakthrough" time window. After an implementation project, it is generally difficult to sustain its success. In the current study, sustainability was described as maintaining an implemented innovation and its benefits over a longer period of time after the implementation project has ended. The aim of the study was to explore potentially promising strategies for sustaining the Enhanced Recovery After Surgery (ERAS) programme in colonic surgery as perceived by professionals, three to six years after the hospital had successfully finished a quality improvement collaborative. METHODS: A qualitative case study was performed to identify promising strategies to sustain key outcome variables related to the ERAS programme in terms of adherence, time needed for functional recovery and hospital length of stay (LOS), as achieved immediately after implementation. Ten hospitals were selected which had successfully implemented the ERAS programme in colonic surgery (2006-2009), with success defined as a median LOS of 6 days or less and protocol adherence rates above 70%. Fourteen semi-structured interviews were held with eighteen key participants of the care process three to six years after implementation, starting with the project leader in every hospital. The interviews started by confronting them with the level of sustained implementation results. A direct content analysis with an inductive coding approach was used to identify promising strategies. The mean duration of the interviews was 37 minutes (min 26 minutes - max 51 minutes). RESULTS: The current study revealed strategies targeting professionals and the organisation. They comprised internal audit and feedback on outcomes, small-scale educational booster meetings, reminders, changing the physical structure of the organisation, changing the care process, making work agreements and delegating responsibility, and involving a coordinator. A multifaceted self-driven promising strategy was applied in most hospitals, and in most hospitals promising strategies were suggested to sustain the ERAS programme. CONCLUSIONS: Joining a quality improvement collaborative may not be enough to achieve long-term normalisation of transformed care, and additional investments may be needed. The findings suggest that certain post-implementation strategies are valuable in sustaining implementation successes achieved after joining a quality improvement collaborative.

Ischaemia-induced mucus barrier loss and bacterial penetration are rapidly counteracted by increased goblet cell secretory activity in human and rat colon.

OBJECTIVE: Colonic ischaemia is frequently observed in clinical practice. This study provides a novel insight into the pathophysiology of colon ischaemia/reperfusion (IR) using a newly developed human and rat experimental model. DESIGN: In 10 patients a small part of colon that had to be removed for surgical reasons was isolated and exposed to 60 min of ischaemia (60I) with/without different periods of reperfusion (30R and 60R). Tissue not exposed to IR served as control. In rats, colon was exposed to 60I, 60I/30R, 60I/120R or 60I/240R (n=7 per group). The tissue was snap-frozen or fixed in glutaraldehyde, formalin or methacarn fixative. Mucins were stained with Periodic Acid Schiff/Alcian Blue (PAS/AB) and MUC2/Dolichos biflorus agglutinin (DBA). Bacteria were studied using electron microscopy (EM) and fluorescent in situ hybridisation (FISH). Neutrophils were studied using myeloperoxidase staining. qPCR was performed for MUC2, interleukin (IL)-6, IL-1ß and tumour necrosis factor α. RESULTS: In rats, PAS/AB and MUC2/DBA staining revealed mucus layer detachment at ischaemia which was accompanied by bacterial penetration (in EM and FISH). Human and rat studies showed that, simultaneously, goblet cell secretory activity increased. This was associated with expulsion of bacteria from the crypts and restoration of the mucus layer at 240 min of reperfusion. Inflammation was limited to minor influx of neutrophils and increased expression of proinflammatory cytokines during reperfusion. CONCLUSIONS: Colonic ischaemia leads to disruption of the mucus layer facilitating bacterial penetration. This is rapidly counteracted by increased secretory activity of goblet cells, leading to expulsion of bacteria from the crypts as well as restoration of the mucus barrier.

Structured synchronous implementation of an enhanced recovery program in elective colonic surgery in 33 hospitals in The Netherlands.

BACKGROUND: It has been clearly shown that after elective colorectal surgery patients benefit from multimodal perioperative care programs. The Dutch Institute for Health Care Improvement started a breakthrough project to implement a multimodal perioperative care program of enhanced recovery after surgery (ERAS). This pre/post noncontrolled study evaluated the success of large-scale implementation of the ERAS program for elective colonic surgery using the breakthrough series. METHODS: A total of 33 hospitals participated in this breakthrough project during 2005-2009. Each hospital performed a retrospective chart review to gather information on traditionally treated patients (pre-ERAS group, n = 1,451). During the subsequent year patients were treated according to the ERAS program (ERAS group, n = 1 034). Outcomes were length of stay (LOS), functional recovery, adherence to the protocol, and determinants of reduced LOS. RESULTS: Median LOS decreased significantly from 9 to 6 days (p < 0.001). In the ERAS group, functional recovery was reached within 3 days. Adherence to the protocol elements was high during the preoperative and perioperative phases but slightly lower during the postoperative phase. Younger age, female sex, American Society of Anesthesiologists grades I/II, and laparoscopic surgery were associated with decreased LOS. Care elements that positively influenced LOS were cessation of intravenous fluids and mobilization on postoperative day 1 and administration of laxatives postoperatively. CONCLUSIONS: The ERAS program was successfully implemented in one-third of all Dutch hospitals using the breakthrough series. Participating hospitals reduced the LOS by a median 3 days and were able to improve their standard of care in elective colonic surgery.

Microsurgical techniques for the treatment of breast cancer-related lymphedema: a systematic review.

BACKGROUND: Upper limb lymphedema is one of the most underestimated and debilitating complications of breast cancer treatment. The aim of this review is to summarize the recent literature for evidence of the effectiveness of lymphatic microsurgery for the treatment of breast cancer-related lymphedema (BCRL). METHODS: A search was conducted for articles published from January 2000 until January 2012. Only studies on secondary lymphedema after breast cancer treatment and those examining the effectiveness of microsurgery were included. RESULTS: No randomized clinical trials or comparative studies were available. Ten case-series met inclusion criteria: (composite) tissue transfer (n = 4), lymphatic vessel transfer (n = 2), and derivative microlymphatic surgery (n = 4). Limb volume/circumference reduction varied from 2 to 50% over a follow-up time ranging from 1 to 132 months. Postoperative discontinuation rates of conservative therapy were only reported after composite tissue transfer, ranging from 33 to 100% after 3 to 24 months. Clear selection criteria for lymphatic surgery and lymphatic flow assessment were absent in most studies. CONCLUSION: We identified important methodological shortcomings of the available literature. Evidence acquired through comparative studies with uniform patient selection is lacking. Consistent positive findings with regards to limb volume reduction and limited complications are reasons to further explore these techniques in methodologically superior studies.

Sarcopenia negatively affects preoperative total functional liver volume in patients undergoing liver resection.

OBJECTIVES: Sarcopenia may negatively affect short-term outcomes after liver resection. The present study aimed to explore whether total functional liver volume (TFLV) is related to sarcopenia in patients undergoing partial liver resection. METHODS: Analysis of total liver volume and tumour volume and measurements of muscle surface were performed in patients undergoing liver resection using OsiriX(®) and preoperative computed tomography. The ratio of TFLV to bodyweight was calculated as: [TFLV (ml)/bodyweight (g)]*100%. The L3 muscle index (cm(2) /m(2) ) was then calculated by normalizing muscle areas (at the third lumbar vertebral level) for height. RESULTS: Of 40 patients, 27 (67.5%) were classified as sarcopenic. There was a significant correlation between the L3 skeletal muscle index and TFLV (r= 0.64, P < 0.001). Median TFLV was significantly lower in the sarcopenia group than in the non-sarcopenia group [1396 ml (range: 1129-2625 ml) and 1840 ml (range: 867-2404 ml), respectively; P < 0.05]. Median TFLV : bodyweight ratio was significantly lower in the sarcopenia group than in the non-sarcopenia group [2.0% (range: 1.4-2.5%) and 2.3% (range: 1.5-2.5%), respectively; P < 0.05]. CONCLUSIONS: Sarcopenic patients had a disproportionally small preoperative TFLV compared with non-sarcopenic patients undergoing liver resection. The preoperative hepatic physiologic reserve may therefore be smaller in sarcopenic patients.

Sustainability of healthcare innovations (SUSHI): long term effects of two implemented surgical care programmes (protocol).

BACKGROUND: Two healthcare innovations were successfully implemented using different implementation strategies. First, a Short Stay Programme for breast cancer surgery (MaDO) was implemented in four early adopter hospitals, using a hospital-tailored implementation strategy. Second, the Enhanced Recovery After Surgery (ERAS) programme for colonic surgery was implemented in 33 Dutch hospitals, using a generic breakthrough implementation strategy. Both strategies resulted in a shorter hospital length of stay without a decrease in quality of care. Currently, it is unclear to what extent these innovative programmes and their results have been sustained three to five years following implementation. The aim of the sustainability of healthcare innovations (SUSHI) study is to analyse sustainability and its determinants using two implementation cases. METHODS: This observational study uses a mixed methods approach. The study will be performed in 14 hospitals in the Netherlands, from November 2010. For both implementation cases, the programme aspects and the effects will be evaluated by means of a follow-up measurement in 160 patients who underwent breast cancer surgery and 300 patients who underwent colonic surgery. A policy cost-effectiveness analysis from a societal perspective will be performed prospectively for the Short Stay Programme for breast cancer surgery in 160 patients. To study determinants of sustainability key professionals in the multidisciplinary care processes and implementation change agents will be interviewed using semi-structured interviews. DISCUSSION: The concept of sustainability is not commonly studied in implementation science. The SUSHI study will provide insight in to what extent the short-term implementation benefits have been maintained and in the determinants of long-term continuation of programme activities.

Hyperbaric oxygen treatment for skin flap necrosis after a mastectomy: a case study.

The rate of complications in immediate breast reconstruction is in 15% to 20% due to partial loss of the mastectomy skin flaps. In the case of skin necrosis or ischemia, a therapy that reduces skin loss could be of additional benefit. Hyperbaric oxygen has been used to treat compromised flaps and grafts, an indication recognized and reimbursed according to the Undersea and Hyperbaric Medical Society (UHMS). So far, hyperbaric oxygen has not been previously reported as therapy for full-thickness breast skin flap necrosis on patients with a direct reconstruction with silicone implants after a skin-sparing mastectomy. This report presents such a case, in which a 52-year-old woman carrier of the BRCA2 mutation gene was successfully treated with hyperbaric oxygen therapy.

Cost-effectiveness of a short stay admission programme for breast cancer surgery.

BACKGROUND: Short stay (admission, surgery, and discharge the same day or within 24 hours) following breast cancer surgery is part of an established care protocol but as yet not well implemented in Europe. Alongside a before-after multi-centre implementation study, an economic evaluation was performed exploring the cost-effectiveness of a short stay programme (SSP) versus care as usual (CAU). MATERIAL AND METHODS: In the implementation study, 324 patients were included. In the economic evaluation a societal perspective was applied with a six week time horizon. Cost data were obtained from Case Record Forms and cost diaries. Effectiveness was assessed by calculating Quality Adjusted Life Years (QALYs), using the EuroQol-5D. Cost-effectiveness was expressed as the incremental costs per QALY. RESULTS: Mean societal costs decreased by euro955,- (95% CI euro - 2104,- to euro157,-) for patients in SSP (n=127) compared with CAU (n=135). Mean healthcare costs differed euro883,- (95% CI euro - 1560,- to euro870,-) in favour of SSP. The incremental cost-effectiveness ratio could not be calculated due to similar effectiveness for both groups, i.e. the difference in QALYs was zero. The cost-effectiveness acceptability curves showed that the probability that SSP was more cost-effective than CAU was over 90% in the base-case analysis. DISCUSSION: A short stay programme as implemented is cost-effective compared with care as usual. In achieving good and more efficient quality of care, larger scale implementation is warranted.

Discrete choice experiments for complex health-care decisions: does hierarchical information integration offer a solution?

This paper describes an application of hierarchical information integration (HII) discrete choice experiments. We assessed theoretical and construct validity, as well as internal consistency, to investigate whether HII can be used to investigate complex multi-faceted health-care decisions (objective 1). In addition, we incorporated recent advances in mixed logit modelling (objective 2). Finally, we determined the response rate and predictive ability to study the feasibility of HII to support health-care management (objective 3). The clinical subject was the implementation of the guideline for breast cancer surgery in day care, which is a complex process that involves changes at the organizational and management levels, as well as the level of health-care professionals and that of patients.We found good theoretical and construct validity and satisfactory internal consistency. The proposed mixed logit model, which included repeated measures corrections and subexperiment error scale variations, also performed well. We found a poor response, but the model had satisfactory predictive ability. Therefore, we conclude that HII can be used successfully to study complex multi-faceted health-care decisions (objectives 1 and 2), but that the feasibility of HII to support health-care management, in particular in challenging implementation projects, seems less favourable (objective 3).

USPIO-enhanced MR imaging for nodal staging in patients with primary rectal cancer: predictive criteria.

PURPOSE: To prospectively determine diagnostic performance of predictive criteria for nodal staging with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging in primary rectal cancer patients, with histopathologic findings as reference standard. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained. Twenty-eight rectal cancer patients (18 men, 10 women; mean age, 68 years) underwent USPIO-enhanced MR. Two observers with different experience evaluated each node on three-dimensional T2*-weighted images for border irregularity, short- and long-axis diameter, and estimated percentage (<30%, 30%-50%, or >50%) of white region within the node. Ratio of measured surface area of white region within the node to measured surface area of total node (ratio(A)) was calculated. Signal intensity (SI) of gluteus muscle (SI(GM)), total node (SI(TN)), and white (SI(WR)) and dark (SI(DR)) regions within the node were used to calculate SI(TN)/SI(GM) and SI(WR)/SI(DR) ratios. Lesion-by-lesion, receiver operating characteristic curve, and interobserver agreement analyses were performed. The most accurate and practical criterion was evaluated by observer 3. RESULTS: In 28 patients, 236 lymph nodes were examined. Area under the receiver operating characteristic curve (AUC) of estimated percentage of white region and ratio(A) were 0.96 and 0.99 (observer 1) and 0.95 and 0.97 (observer 2), respectively. AUC of estimated percentage criterion for observer 3 was 0.96. AUC of border, short- and long-axis diameter, and SI(TN)/SI(GM) and SI(WR)/SI(DR) ratios were 0.65, 0.75, 0.79, 0.85, and 0.75 (observer 1) and 0.58, 0.75, 0.79, 0.89, and 0.79 (observer 2), respectively. Interobserver agreement (kappa value) for estimated white region between observers 1 and 2, 1 and 3, and 2 and 3 were 0.77, 0.79, and 0.84, respectively. For observers 1 and 2, kappa value for border was 0.28. For observers 1 and 2, intraclass correlation coefficient for short- and long-axis diameters, ratio(A), and SI(TN)/SI(GM) and SI(WR)/SI(DR) ratios were 0.91, 0.96, 0.91, 0.72, and 0.92, respectively. CONCLUSION: Estimated percentage of white region and measured ratio(A) are the most accurate criteria for predicting malignant nodes with USPIO-enhanced MR imaging; the first criterion is the most practical.

Interorgan synthesis of arginine is down-regulated in tumor-bearing mice undergoing surgical trauma.

Renal de novo arginine production has been suggested to be crucial for regulation of arginine production in disease. We investigated how the interorgan pathway for de novo arginine production is affected by the presence of malignant tumor and/or surgical trauma. Controls and methylcholanthrene-sarcoma-bearing mice were studied, both with and without undergoing laparotomy (n = 9-13 per group). One day after laparotomy, amino acid fluxes across the hindquarter, intestine, liver, and kidney were studied. In contrast to healthy mice, the liver of tumor-bearing mice took up citrulline (9 +/- 3 vs 1 +/- 2 nmol/[10 g min], P < .05), simultaneous with attenuated renal arginine output (4 +/- 3 vs 12 +/- 2 nmol/[10 g min], P < .05), despite increased intestinal conversion of glutamine to citrulline (15 +/- 3 vs 8 +/- 1 nmol/[10 g min], P < .05). In tumor-bearing mice undergoing surgery, intestinal citrulline output decreased (from 15 +/- 3 to 8 +/- 2 nmol/[10 g min], P < .05) and renal arginine output remained close to zero despite increased renal citrulline uptake (from 6 +/- 2 to 12 +/- 2 nmol/[10 g min], P < .05). In conclusion, the interorgan pathway for de novo arginine production was differently regulated depending on the pathophysiological situation. In methylcholanthrene-sarcoma-bearing mice, decreased de novo arginine production was accompanied by the presence of hepatic citrulline uptake, whereas tumor-bearing mice subjected to surgical trauma showed concomitant decreased intestinal citrulline output.

The patient's perspective of the quality of breast cancer care. The development of an instrument to measure quality of care through focus groups and concept mapping with breast cancer patients.

Quality of care is often described by professionals. However, in this study breast cancer patients participated in developing an instrument that reflects quality of care from the patient's perspective. Through focus groups and concept mapping patients' ideas on determinants of good quality of care were generated and categorised according to similarity and importance. Information from eight focus group interviews with a total of 72 participants yielded 221 quality of care aspects. Following reduction, 81 aspects were used for categorisation during six concept mapping sessions with 67 participants. After analysis, 55 aspects remained grouped into six clusters. This study was conducted with a large number of breast cancer patients, undergoing the full range of treatment modalities, in different hospitals, in different areas in the Netherlands. Therefore, this set of quality of care indicators can be considered valid and suitable for the evaluation of breast cancer care as experienced by patients.

Introduction of a breast cancer care programme including ultra short hospital stay in 4 early adopter centres: framework for an implementation study.

BACKGROUND: Whereas ultra-short stay (day care or 24 hour hospitalisation) following breast cancer surgery was introduced in the US and Canada in the 1990s, it is not yet common practice in Europe. This paper describes the design of the MaDO study, which involves the implementation of ultra short stay admission for patients after breast cancer surgery, and evaluates whether the targets of the implementation strategy are reached. The ultra short stay programme and the applied implementation strategy will be evaluated from the economic perspective. METHODS/DESIGN: The MaDO study is a pre-post-controlled multi-centre study, that is performed in four hospitals in the Netherlands. It includes a pre and post measuring period of six months each with six months of implementation in between in at least 40 patients per hospital per measurement period. Primary outcome measure is the percentage of patients treated in ultra short stay. Secondary endpoints are the percentage of patients treated according to protocol, degree of involvement of home care nursing, quality of care from the patient's perspective, cost-effectiveness of the ultra short stay programme and cost-effectiveness of the implementation strategy. Quality of care will be measured by the QUOTE-breast cancer instrument, cost-effectiveness of the ultra short stay programme will be measured by means of the EuroQol (administered at four time-points) and a cost book for patients. Cost-effectiveness analysis will be performed from a societal perspective. Cost-effectiveness of the implementation strategy will be measured by determination of the costs of implementation activities. DISCUSSION: This study will reveal barriers and facilitators for implementation of the ultra short stay programme. Moreover, the results of the study will provide information about the cost-effectiveness of the ultra short stay programme and the implementation strategy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77253391.

Presence of tumour inhibits the normal post-operative response in arginine and NO production in non-cachectic mice.

We have described recently that cancer patients have low plasma arginine concentrations, even without weight loss being present, suggesting that decreased arginine availability may be a specific feature of the presence of tumour. As arginine is important in post-operative repair, we hypothesized that abnormalities in arginine metabolism in cancer lead to an aberrant post-operative response in arginine and NO metabolism. To investigate this, we studied post-operative alterations in arginine and NO production and the acute-phase response in MCA (methylcholanthrene) sarcoma-bearing mice. Controls, mice with small MCA tumours (<15% of carcass weight) and large MCA tumours (>15% of carcass weight) were studied, either with or without undergoing laparotomy. The stable isotopes L-[guanidino-(15)N(2)-(2)H(2)]arginine and L-[ureido-(15)N]citrulline were used to study whole-body arginine and NO production rates. SAP (serum amyloid P component) concentrations were measured to assess the acute-phase response. Significance was tested using Mann-Whitney U test. In healthy FVB mice, laparotomy significantly increased whole-body arginine production (from 42+/-3 to 54+/-3 nmol x 10 g(-1) of carcass weight x min(-1)), NO production (from 1.1+/-0.1 to 1.4+/-0.2 nmol x 10 g(-1) of carcass weight x min(-1)) and levels of SAP (from 4+/-1 to 115+/-23 ng/ml), whereas in all MCA tumour-bearing mice baseline values of arginine metabolism and SAP concentration were already elevated and the response to laparotomy was absent. In conclusion, MCA tumour-bearing mice had a disturbed post-operative metabolic response, as evidenced by attenuated post-operative arginine and NO production, concomitant with an attenuated acute-phase response. This indicates that altered arginine metabolism may be an important characteristic of the metabolic changes in cancer.

Protein breakdown on whole-body and organ level in non-cachectic tumour-bearing mice undergoing surgery.

BACKGROUND & AIMS: Since both cancer and surgery are known to alter protein turnover, we investigated how the presence of tumour affects post-operative protein breakdown. METHODS: Controls and tumour-bearing non-cachectic mice were studied, both with and without laparotomy (n=8 per group). One day after laparotomy, stable isotopes of phenylalanine and 3-methylhistidine were used in a steady-state protocol to assess total protein breakdown on whole-body level and in muscle, intestines, liver and kidney, in addition to whole-body myofibrillar protein breakdown and body composition. Proteasomal chymotrypsin-like activity was measured to determine activity of the ATP-dependent ubiquitin pathway. RESULTS: On whole-body level, the presence of tumour increased total protein breakdown from 47+/-6 to 58+/-4 nmol/10 g/min (p<0.05) and myofibrillar protein breakdown from 0.70+/-0.04 to 1.22+/-0.14 nmol/10 g/min (p<0.05) without affecting protein breakdown in organs, body composition or proteasomal activity. Laparotomy increased myofibrillar protein breakdown in controls (from 0.70+/-0.04 to 0.98+/-0.12 nmol/10 g/min, p<0.05) and tumour-bearing mice (from 1.22+/-0.14 to 1.54+/-0.22 nmol/10 g/min, p=0.15) to a similar extent. CONCLUSIONS: Whole-body total protein breakdown, total protein breakdown across organs, body composition or proteasomal activity were not affected by laparotomy. Tumour-bearing mice had increased total and myofibrillar protein breakdown on whole-body level even before weight loss was obvious. However, this did not affect the post-operative response in protein breakdown or body composition.

Factors associated with sustainability of 2 quality improvement programs after achieving early implementation success. A qualitative case study.

RATIONALE, AIMS, AND OBJECTIVES: Sustainability of innovations is a relatively new concept in health care research and has become an issue of growing interest. The current study explored factors related to the sustainability of 2 multidisciplinary hospital-based programs 3 to 6 years after achieving early implementation success. METHOD: An exploratory qualitative study was conducted into 2 implementation cases, an Enhanced Recovery After Surgery program for colorectal surgery and a short-stay program for breast cancer surgery. Semistructured interviews were held with key persons involved in the care process in 14 hospitals from both cases minimally 3 years after the implementation, between March 2012 and May 2013. The Consolidated Framework for Implementation Research was used to direct the development of the interview guide, during data collection and during analysis. A directed content analysis was performed. RESULTS: A total of 21 interviews with 26 individuals were held, 18 regarding the Enhanced Recovery After Surgery case and 8 regarding the short-stay program case. Respondents mentioned the following factors associated with sustainability of the programs: modification and adaptability of the program, cost-effectiveness, institutionalization into existing systems, short communication lines within the multidisciplinary team, an innovative culture, benefits for patients, cosmopolitanism, the existence of external policies and incentives, trust and belief in the program, and spread of the program to other settings. Two factors are not covered by the Consolidated Framework for Implementation Research, ie, modification of the program over the years and spread of the program to other contexts. CONCLUSIONS: The factors associated with sustainability put forward in both cases were largely the same. Leadership and the implementation project were not mentioned as having influenced the long-term sustainability of the benefits achieved. Sustainability of the innovations is influenced by determinants stemming from all ecological levels of the health care system and demands continuous effort in the postimplementation phase.