Doppler-guided goal-directed fluid therapy does not affect intestinal cell damage but increases global gastrointestinal perfusion in colorectal surgery: a randomized controlled trial.

AIM: Individualized, goal-directed fluid therapy (GDFT), based on Doppler measurements of stroke volume, has been proposed as a treatment strategy in terms of reducing complications, mortality and length of hospital stay in major bowel surgery. We studied the effect of Doppler-guided GDFT on intestinal damage as compared with standard postoperative fluid replacement. METHOD: Patients undergoing elective colorectal resection for malignancy were randomized either to standard intra- and postoperative fluid therapy or to standard fluid therapy with additional Doppler-guided GDFT. The primary outcome was intestinal epithelial cell damage measured by plasma levels of intestinal fatty acid-binding protein (I-FABP). Global gastrointestinal perfusion was measured by gastric tonometry, expressed as regional (gastric) minus arterial CO2 -gap (Pr-a CO2 -gap). RESULTS: I-FABP levels were not significantly different between the intervention group and the control group (respectively, 440.8 (251.6) pg/ml and 522.4 (759.9) pg/ml, P = 0.67). Mean areas under the curve (AUCs) of intra-operative Pr-a CO2 -gaps were significantly lower in the intervention group than in the control group (P = 0.01), indicating better global gastrointestinal perfusion in the intervention group. Moreover, the mean intra-operative Pr-a CO2 -gap peak in the intervention group was 0.5 (1.0) kPa, which was significantly lower than the mean peak in the control group, of 1.4 (1.4) kPa (P = 0.03). CONCLUSION: Doppler-guided GDFT during and in the first hours after elective colorectal surgery for malignancy increases global gastrointestinal perfusion, as measured by Pr-a CO2 -gap.

The changing role of axillary treatment in breast cancer: Who will remain at risk for developing arm morbidity in the future?

Primary aim is to give an overview of changes in axillary staging and treatment of breast cancer patients. Secondly, we aim to identify patients with a high arm/shoulder morbidity risk, and describe a strategy to improve early detection and treatment. Recent and initiated studies on axillary staging and treatment were evaluated and clustered for clinically node negative and clinically node positive breast cancer patients, together with studies on pathology, detection and (surgical) prevention and treatment of lymphedema. For clinically node negative patients, the indication for axillary lymph node dissection in sentinel node positive patients is fading. On the contrary, clinically node positive patients are routinely subjected to an axillary lymph node dissection, in combination with other therapies associated with an increased lymphedema risk, such as mastectomy, adjuvant radiation- and (taxane-based) chemotherapy. Techniques for prevention, early detection and (surgical) treatment of lymphedema are being developed. Axillary staging and treatment in breast cancer patients with a clinically node negative status will become less invasive, thereby reducing the incidence of morbidity. Nevertheless, in patients with a clinically node positive status, aggressive treatment will still be required for oncologic control. For these patients, a surveillance program should be implemented in order to apply (curative) surgical treatment for lymphedema.

Sustainability of an enhanced recovery after surgery program (ERAS) in colonic surgery.

BACKGROUND: Between 2006 and 2008 the enhanced recovery after surgery (ERAS) program was implemented in colonic surgery in one-third of all hospitals in the Netherlands (n = 33). This resulted in enhanced recovery and a decrease in hospital length of stay (LOS) from a median of 9 days at baseline to 6 days at one-year follow-up. The present study assessed the sustainability of the ERAS program 3-5 years after its implementation. MATERIALS AND METHODS: From the 33 ERAS hospitals, 10 initially successful hospitals were selected, with success defined as a median LOS of 6 days or lower and protocol adherence rates above 70 %. In 2012 a retrospective audit of 30 consecutive patients was performed in each of these hospitals. Sustainability of the ERAS program was assessed on hospital level, using median hospital LOS, protocol adherence rates and time to functional recovery. Data were compared with the implementation phase data. RESULTS: Overall median LOS in the selected hospitals increased from 5.25 days (interquartile range [IQR] 4.75-6.00; min, 4.00-max, 6.00) to 6 days (IQR 5.00-7.00; min, 5.00-max, 8.00), but this change was not significant (p = 0.052). Time to functional recovery was equal in both phases: median 3.00 days (p = 0.26). Protocol adherence decreased from 75 to 67 % (p = 0.32). Especially adherence to postoperative care elements dropped considerably. CONCLUSIONS: Despite a slight decrease in protocol adherence, the ERAS program was sustained reasonably well in the 10 selected hospitals, although there was quite some variation between the hospitals.

Sustainability of short stay after breast cancer surgery in early adopter hospitals.

Between 2005 and 2007 a short stay programme for breast cancer surgery was successfully implemented in early adopter hospitals. The current study evaluates the sustainability of this success five years following implementation. A retrospective audit of 160 consecutive patients undergoing breast cancer surgery was performed five years following implementation of short stay. The total proportion of patients treated in short stay was 82% (hospital 1 83%, hospital 2 78%, hospital 3 87%, hospital 4 80%) after five years follow-up, which was comparable to the proportion in short stay directly after implementation (p = 0.938). Overall compliance to the key recommendations to facilitate short stay after breast cancer surgery increased from 65% directly after implementation to 78% five years after implementation. This study shows that short stay after breast cancer surgery was successfully sustained in early adopter hospitals five years following implementation.

The quality of life in long-term breast cancer survivors with breast cancer related lymphedema.

AIM: To compare the health related quality of life (HRQOL) of long-term breast cancer survivors with and without breast cancer related lymphedema (BCRL) treated in the sentinel lymph node biopsy (SLNB) era. METHODS: HRQOL was assessed as subject of a secondary analysis of data gathered for a study evaluating the prevalence of BCRL in long-term breast cancer survivors. The 145 women in this study cohort had undergone SLNB and or axillary lymph node dissection (ALND) according to Dutch Breast cancer treatment guidelines. HRQOL was assessed using two questionnaires : the European Organization for Research and Treatment of Cancer Quality (QLQ-C30) and the Breast Cancer-specific Quality of life questionnaire (QLQ-BR23). RESULTS: Twenty-six women, of whom 5 only underwent SLNB, were identified with objectively measured lymphedema and/or self-perceived arm swelling. Patients with BCRL scored significantly lower on the social (p = 0.000) functioning scale after adjustment for BMI and age compared to women without BCRL. Compared to normative data, women with BCRL scored significantly lower on social- (p < 0.001) and role (p = 0.001) functioning scales. CONCLUSIONS: HRQOL in long-term breast cancer survivors with BCRL is structurally lower than of those without BCRL, even in this small cohort of cancer survivors treated in the SLNB-era.

Activated macrophages containing tumor marker in colon carcinoma: immunohistochemical proof of a concept.

The presence of carcinoembryonic antigen (CEA)-containing activated macrophages has been demonstrated in peripheral blood from patients with colorectal carcinoma. Macrophages migrate from the circulation into the tissue, phagocytose debris, and return to the bloodstream. Hence it seems likely that activated macrophages containing tumor debris, i.e., tumor marker, are present in the stroma of colorectal carcinoma. After phagocytosis, they could follow a hematogenic or lymphogenic route to the peripheral blood. The aim of this study is to assess the presence of tumor marker-containing activated macrophages in the stroma of colon carcinoma and in regional lymph nodes. From 10 cases of colon carcinoma, samples of tumor tissue and metastasis-free lymph nodes were cut in serial sections and stained for CD68 to identify macrophages and for CEA, cytokeratin, or M30 presence. Slides were digitalised and visually inspected using two monitors, comparing the CD68 stain to the tumor marker stain to evaluate the presence of tumor marker-positive macrophages. Macrophages containing tumor marker could be identified in tumor stroma and in metastasis-free regional lymph nodes. The distribution varied for the different markers, CEA-positive macrophages being most abundant. The presence of macrophages containing tumor marker in the tumor stroma and lymph nodes from patients with colon carcinoma could be confirmed in this series using serial immunohistochemistry. This finding supports the concept of activated macrophages, after phagocytosing cell debris, being transported or migrating through the lymphatic system. These results support the potential of tumor marker-containing macrophages to serve as a marker for diagnosis and follow-up of colon cancer patients.

Prevalence of lymphoedema more than five years after breast cancer treatment.

AIM: A lack of consistency in the definition of breast cancer related lymphoedema (BCRL) and of uniform measurement criteria contribute to the wide prevalence range found in current literature. This report aims to describe the long-term prevalence of BCRL and secondly, to compare the long-term prevalence of BCRL when assessed by two objective measures and one subjective measure. METHODS: The upper-limbs of 145 post-surgical breast cancer patients were evaluated for the presence of lymphoedema using the water displacement method. Two circumference methods and patient perceived swelling were applied secondarily for comparison. Limb measurements were performed once, more than five years after surgery. RESULTS: The long-term prevalence of BCRL using water displacement was 8%. Prevalence varied when the sum of arm circumference (SOAC), the arm circumference and the self-report methods were used: 16, 31 and 17% [P < 0.001], respectively. Of the women identified with BCRL using the water displacement technique, 82% were detected with the SOAC method, 82% with the arm circumference method and 91% by self-report. Using water displacement as the gold standard the methods with the highest specificities were the SOAC (90%) and self-report method (89%), arm circumference resulted in a low specificity of 73%. CONCLUSION: The prevalence of BCRL more than five years after surgical treatment differs depending on the measuring method used. Our data underlines the necessity for consensus on the diagnostic criteria for BCRL.

A patient-centred instrument for assessment of quality of breast cancer care: results of a pilot questionnaire.

BACKGROUND: In several breast cancer research environments, there was a need to develop a questionnaire that would (1) provide data on how breast cancer patients experience healthcare services, (2) address issues corresponding with patients' needs and expectations and (3) produce useful data for quality assessment and improvement projects aimed at breast cancer care. This article describes the first part of the quantitative process of item selection, instrument construction and optimisation based on the results of a pilot questionnaire. METHODS: Based on qualitative research, a pilot questionnaire with items formulated as "performance" and "importance" statements was developed and sent to all breast cancer patients operated on in the previous 3-15 months in five participating hospitals. Reduction criteria, exploratory factor analysis and reliability analysis were used as part of the process of instrument optimisation. RESULTS: Of the 637 questionnaires sent out, 299 (47%) were returned and 276 (43%) were used for analyses. Out of the 72 quality items included in the pilot questionnaire, 42 items did not meet the inclusion criteria for the revised version. The remaining items refer to the factors patient education regarding aspects related to postoperative treatment, services by the breast nurse, services by the surgeon, patient education regarding activities at home and patient education regarding aspects related to preoperative treatment (Cronbach α = 0.70-0.89). CONCLUSIONS: In this study, the number of items to be included in the self-administered questionnaire was reduced. The resulting set of items that determines patients' perceptions on quality of breast cancer care is easy to complete and enables anonymous responses. Further research can be aimed at establishing the reliability of the current questionnaire.

Patients' opinions on quality of care before and after implementation of a short stay programme following breast cancer surgery.

PURPOSE: To assess breast cancer patients' opinions on quality of care during an implementation study on short hospital stay, and to formulate patient inspired targets for further quality improvement based on results of the QUOTE (Quality of Care Through the Patients' Eyes) breast cancer instrument. RESULTS: Quality of patient education regarding activities at home was in need of improvement in both measurements. Quality of services delivered by the surgeon improved somewhat after implementation. Although quality of waiting and process times improved after implementation, there was still room for further improvement on these aspects. CONCLUSION: A breast cancer care programme in short stay was introduced while, on average, preserving quality of care as perceived by the patient. However, aspects regarding education on drains, prosthesis, exercises after surgery, survival rates, and waiting and process times require continuing attention to enhance patients' assessment of quality of care.

Implementation of a short-stay programme after breast cancer surgery.

BACKGROUND: : Short-stay breast cancer surgery (24 h or day case) is not common practice in Europe. This before-after comparative study was carried out to test the feasibility of systematically implementing a care programme incorporating short-stay admission using strategies tailored to individual hospital needs, and to assess safety and facilitating factors. METHODS: : Patients with breast cancer from four Dutch hospitals participated. The intervention concerned the programme developed by the Maastricht University Medical Centre. This was implemented through local multidisciplinary meetings and educational outreach visits. RESULTS: : Of 421 eligible patients, 324 (77.0 per cent) gave consent to participate. The proportion of patients who had short-stay treatment increased from 45.3 per cent before to 82.2 per cent after implementation of the programme (P < 0.001). No increase was observed in the rate of complications, readmissions, reoperations or number of visits to the emergency department. Factors associated with an increased chance of short-stay treatment were: breast-conserving surgery, having children and being employed. Being aged over 64 years showed a trend towards a decreased chance. CONCLUSION: : Introducing a care programme incorporating short stay following breast cancer surgery in four hospitals was feasible and safe.

Results of tailored treatment for breast cancer patients with internal mammary lymph node metastases.

Although the internal mammary (IM) lymph node status is a major prognostic factor in breast cancer, IM nodal staging is not common practice. In order to improve nodal staging, we have routinely performed IM sentinel node (SN) biopsy and have adjusted adjuvant treatment accordingly. We reviewed the outcome of these patients. Data from 764 patients were available for follow-up. A total of 406 patients had no lymph node metastases (group 1), 330 patients had axillary metastases (group 2), 7 patients had IM metastases only (group 3) and 21 patients had both axillary and IM metastases (group 4). Mean follow-up was 46 months. Prognosis did not appear to be worse for patients with IM metastases compared to those with axillary metastases only, which might indicate that they benefit from improved staging and tailored adjuvant treatment algorithms. However, long-term follow-up data, preferably in larger series, are needed to support our findings.

Additional tracer injection to improve the technical success rate of lymphoscintigraphy for sentinel node biopsy in breast cancer.

BACKGROUND: Sentinel node (SN) biopsy has become the standard of care in the treatment of breast cancer. The aim of this study is to determine the value of additional tracer injection to increase the technical success rate of the SN procedure and to identify factors that influence the ability to visualize hotspots. METHODS: From February 1997 to August 2007, 1,208 clinically node-negative breast cancer patients underwent lymphatic mapping for SN biopsy. The technique involved the injection of 370 MBq (10 mCi) Tc-99 m-nanocolloid peritumorally. In case of insufficient or absent visualization of hotspots 37 MBq (1 mCi) of additional tracer was given intracutaneously above the tumor. RESULTS: In 93 patients (7.7%) visualization of hotspots on initial lymphoscintigraphy was insufficient (41 patients) or absent (52 patients). The first 14 patients did not receive additional tracer injection. In five patients, additional tracer did not result in successful lymphoscintigraphy, which is correlated with massive nodal tumor infiltration. In 33 patients with negative initial lymphoscintigraphy, additional tracer injection resulted in secondary SN visualization. In 41 patients with faint hotspots on initial lymphoscintigraphy, additional tracer injection, by increasing nodal uptake, simplified accurate SN biopsy. Decreased radiotracer uptake in this group was associated with older age and high body mass index (BMI). CONCLUSIONS: Additional tracer injection following initial scan failure increases the success rate of lymphoscintigraphy during lymphatic mapping in breast cancer, without compromising accuracy. If additional tracer injection does not result in secondary SN visualization, gross nodal tumor involvement is often present and axillary lymph node dissection (ALND) is mandatory.

Internal mammary lymph drainage and sentinel node biopsy in breast cancer - A study on 1008 patients.

INTRODUCTION: Nowadays, axillary sentinel node (SN) biopsy is a standard procedure in the staging of breast cancer. Although the internal mammary (IM) lymph node status is a major independent prognostic factor in breast cancer patients, sampling of IM sentinel nodes (IMSNs) is not performed routinely. The aim of this study was to determine the likelihood of finding IM lymph node metastases in case of IM hotspots on lymphoscintigraphy and evaluate the relevance of IMSN biopsy as a method to improve staging. PATIENTS AND METHODS: Between April 1997 and May 2006, a total of 1008 consecutive patients with clinically node-negative operable primary breast cancer were enrolled in a prospective study on SN biopsy. Both axillary and IMSNs were sampled, based on lymphoscintigraphy, intraoperative gamma probe detection and blue dye mapping, using 10 mCi (370 MBq) (99m)Tc-nanocolloid injected peritumorally, and 0.5-1.0 ml Patent Blue V injected intradermally. RESULTS: Lymphoscintigraphy showed axillary sentinel nodes in 98% (989/1008) and IMSNs in 20% of the patients (196/1008). Sampling the IM basin, as based on the results of lymphoscintigraphy, was successful in 71% of the patients (139/196) and revealed metastases in 22% (31/139). In 29% of the patients with positive IMSNs (9/31) no axillary metastases were found. CONCLUSION: Evaluation of IMSNs improves nodal staging in breast cancer. Patients with IM hotspots on lymphoscintigraphy have a substantial risk (22%) of metastatic involvement of the IM chain. In addition, true IM node-negative patients can be spared the morbidity associated with adjuvant radiotherapy.

To eat or not to eat: facilitating early oral intake after elective colonic surgery in the Netherlands.

BACKGROUND & AIMS: It was shown that patients in the Netherlands remain exposed to unnecessarily prolonged starvation after abdominal surgery. The present study examined whether a structured collaborative effort would help to implement the early start of oral nutrition after colorectal surgery. METHODS: In 2006, twenty-six Dutch hospitals signed up to a "breakthrough project" concerning the implementation of the enhanced recovery after surgery (ERAS) programme with early oral feeding as one of the key elements. Each hospital determined the usual start of food intake by analyzing 50 patients who underwent a colorectal resection in 2004 (n=1126). Subsequently, over the course of one year 861 colorectal surgery patients were treated according to the ERAS programme. The first day that patients were eating before and after the breakthrough project was compared using Kaplan-Meier analyses and Cox regression models. RESULTS: Patients treated according to the ERAS programme were eating 3 days earlier than the patients traditionally treated (p<0.000). Two days after surgery 65% of the ERAS patients were eating normal food versus 7% of the pre-ERAS patients. CONCLUSIONS: The present nationwide collaborative effort was successful in implementing a change towards an early start of oral nutrition after abdominal surgery.

Length of stay: an inappropriate readout of the success of enhanced recovery programs.

BACKGROUND: Enhanced recovery after surgery (ERAS) programs are designed to reduce hospital length of stay by shortening the postoperative recovery period. The intended effect of an accelerated recovery on the length of stay may be frustrated by a delayed discharge. This study was designed to assess the influence of an ERAS program on the proportion, appropriateness, and extent of delay in discharge. METHODS: Patients who enrolled in the ERAS program (n = 121) between 2003 and 2006 were compared with 52 patients who were managed traditionally in 2001. RESULTS: Ninety percent of the pre-ERAS patients and 87% of the ERAS patients were not discharged on the day that discharge criteria were fulfilled. The additional stay of 59% of the pre-ERAS patients and 69% of the ERAS patients was inappropriate. Wound care (15% in the pre-ERAS and 3% of the ERAS group) and observation of any symptoms pointing to an anastomotic leakage (10% in both groups) were the most important reasons for a medical appropriate delay of discharge. The extent of delay in discharge decreased significantly from a median of two days in the pre-ERAS group to a median of 1 day in the ERAS group (p = 0.004). CONCLUSIONS: Reductions in length of stay up to a median of 2 days after start of an enhanced recovery program may relate to changes in organization of care and not to a shorter recovery period. Recovery statistics should replace or at least be added to the length of stay as outcome of enhanced recovery programs.

A protocol is not enough to implement an enhanced recovery programme for colorectal resection.

BACKGROUND: Single-centre studies have suggested that enhanced recovery can be achieved with multimodal perioperative care protocols. This international observational study evaluated the implementation of an enhanced recovery programme in five European centres and examined the determinants affecting recovery and length of hospital stay. METHODS: Four hundred and twenty-five consecutive patients undergoing elective open colorectal resection above the peritoneal reflection between January 2001 and January 2004 were enrolled in a protocol that defined multiple perioperative care elements. One centre had been developing multimodal perioperative care for 10 years, whereas the other four had previously undertaken traditional care. RESULTS: The case mix was similar between centres. Protocol compliance before and during the surgical procedure was high, but it was low in the immediate postoperative phase. Patients fulfilled predetermined recovery criteria a median of 3 days after operation but were actually discharged a median of 5 days after surgery. Delay in discharge and the development of major complications prolonged length of stay. Previous experience with fast-track surgery was associated with a shorter hospital stay. CONCLUSION: Functional recovery in 3 days after colorectal resection could be achieved in daily practice. A protocol is not enough to enable discharge of patients on the day of functional recovery; more experience and better organization of care may be required.

Patterns in current anaesthesiological peri-operative practice for colonic resections: a survey in five northern-European countries.

BACKGROUND: For colorectal surgery, evidence suggests that optimal management includes: no pre-operative fasting, a thoracic epidural analgesia continued for 2 days post-operatively, and avoidance of fluid overload. In addition, no long-acting benzodiazepines on the day of surgery and use of short-acting anaesthetic medication may be beneficial. We examined whether these strategies have been adopted in five northern-European countries. METHODS: In 2003, a questionnaire concerning peri-operative anaesthetic routines in elective, open colonic cancer resection was sent to the chief anaesthesiologist in 258 digestive surgical centres in Scotland, the Netherlands, Denmark, Sweden and Norway. RESULTS: The response rate was 74% (n = 191). Although periods of pre-operative fasting up to 48 h were reported, most (> 85%) responders in all countries declared to adhere to guidelines for pre-operative fasting and oral clear liquids were permitted until 2-3 h before anaesthesia. Solid food was permitted up to 6-8 h prior to anaesthesia. In all countries more than 85% of the responders indicated that epidural anaesthesia was routinely used. Except for Denmark, long-acting benzodiazepines were still widely used. Short-acting anaesthetics were used in all countries except Scotland where isoflurane is the anaesthetic of choice. With the exception of Denmark, intravenous fluids were used unrestrictedly. CONCLUSION: In northern Europe, most anaesthesiologists adhere to evidence-based optimal management strategies on pre-operative fasting, thoracic epidurals and short-acting anaesthetics. However, premedication with longer-acting agents is still common. Avoidance of fluid overload has not yet found its way into daily practice. This may leave patients undergoing elective colonic surgery at risk of oversedation and excessive fluid administration with potential adverse effects on surgical outcome.

Systematic review of enhanced recovery programmes in colonic surgery.

BACKGROUND: Fast track (FT) programmes optimize perioperative care in an attempt to accelerate recovery, reduce morbidity and shorten hospital stay. The aim of this review was to assess FT programmes for elective segmental colonic resections. METHODS: A systematic review was performed of all randomized controlled trials and controlled clinical trials on FT colonic surgery. The main endpoints were number of applied FT elements, hospital stay, readmission rate, morbidity and mortality. Quality assessment and data extraction were performed independently by three observers. RESULTS: Six papers were eligible for analysis (three randomized controlled and three controlled clinical trials), including 512 patients. FT programmes contained a mean of nine (range four to 12) of the 17 FT elements as defined in the literature. Primary hospital stay (weighted mean difference - 1.56 days, 95 per cent confidence interval (c.i.) - 2.61 to - 0.50 days) and morbidity (relative risk 0.54, 95 per cent c.i. 0.42 to 0.69) were significantly lower for FT programmes. Readmission rates were not significantly different (relative risk 1.17, 95 per cent c.i. 0.73 to 1.86). No increase in mortality was found. CONCLUSIONS: FT appears to be safe and shortens hospital stay after elective colorectal surgery. However, as the evidence is limited, a multicentre randomized trial seems justified.

ESPEN Guidelines on Enteral Nutrition: Non-surgical oncology.

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility of increasing or ensuring nutrient intake in cases where normal food intake is inadequate. These guidelines are intended to give evidence-based recommendations for the use of ONS and TF in cancer patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards, are based on all relevant publications since 1985 and were discussed and accepted in a consensus conference. Undernutrition and cachexia occur frequently in cancer patients and are indicators of poor prognosis. EN should be started if undernutrition already exists or if food intake is markedly reduced for more than 7-10 days. Standard formulae are recommended for EN. Nutritional needs generally are comparable to non-cancer subjects. In cachectic patients metabolic modulators such as progestins, steroids and possibly eicosapentaenoic acid may help to improve nutritional status. EN is indicated preoperatively for 5-7 days in cancer patients undergoing major abdominal surgery. During radiotherapy of head/neck and gastrointestinal regions dietary counselling and ONS prevent weight loss and interruption of radiotherapy. Routine EN is not indicated during (high-dose) chemotherapy.