A randomized trial of laparoscopic versus open surgery for rectal cancer.

BACKGROUND: Laparoscopic resection of colorectal cancer is widely used. However, robust evidence to conclude that laparoscopic surgery and open surgery have similar outcomes in rectal cancer is lacking. A trial was designed to compare 3-year rates of cancer recurrence in the pelvic or perineal area (locoregional recurrence) and survival after laparoscopic and open resection of rectal cancer. METHODS: In this international trial conducted in 30 hospitals, we randomly assigned patients with a solitary adenocarcinoma of the rectum within 15 cm of the anal verge, not invading adjacent tissues, and without distant metastases to undergo either laparoscopic or open surgery in a 2:1 ratio. The primary end point was locoregional recurrence 3 years after the index surgery. Secondary end points included disease-free and overall survival. RESULTS: A total of 1044 patients were included (699 in the laparoscopic-surgery group and 345 in the open-surgery group). At 3 years, the locoregional recurrence rate was 5.0% in the two groups (difference, 0 percentage points; 90% confidence interval [CI], -2.6 to 2.6). Disease-free survival rates were 74.8% in the laparoscopic-surgery group and 70.8% in the open-surgery group (difference, 4.0 percentage points; 95% CI, -1.9 to 9.9). Overall survival rates were 86.7% in the laparoscopic-surgery group and 83.6% in the open-surgery group (difference, 3.1 percentage points; 95% CI, -1.6 to 7.8). CONCLUSIONS: Laparoscopic surgery in patients with rectal cancer was associated with rates of locoregional recurrence and disease-free and overall survival similar to those for open surgery. (Funded by Ethicon Endo-Surgery Europe and others; COLOR II ClinicalTrials.gov number, NCT00297791.).

Conversions in laparoscopic surgery for rectal cancer.

BACKGROUND: Laparoscopic surgery offers patients with rectal cancer short-term benefits and similar survival rates as open surgery. However, selecting patients who are suitable candidates for laparoscopic surgery is essential to prevent intra-operative conversion from laparoscopic to open surgery. Clinical and pathological variables were studied among patients who had converted laparoscopic surgeries within the COLOR II trial to improve patient selection for laparoscopic rectal cancer surgery. METHODS: Between January 20, 2004, and May 4, 2010, 1044 patients with rectal cancer enrolled in the COLOR II trial and were randomized to either laparoscopic or open surgery. Of 693 patients who had laparoscopic surgery, 114 (16 %) were converted to open surgery. Predictive factors were studied using multivariate analyses, and morbidity and mortality rates were determined. RESULTS: Factors correlating with conversion were as follows: age above 65 years (OR 1.9; 95 % CI 1.2-3.0: p = 0.003), BMI greater than 25 (OR 2.7; 95 % CI 1.7-4.3: p < 0.001), and tumor location more than 5 cm from the anal verge (OR 0.5; CI 0.3-0.9). Gender was not significantly related to conversion (p = 0.14). In the converted group, blood loss was greater (p < 0.001) and operating time was longer (p = 0.028) compared with the non-converted laparoscopies. Hospital stay did not differ (p = 0.06). Converted procedures were followed by more postoperative complications compared with laparoscopic or open surgery (p = 0.041 and p = 0.042, respectively). Mortality was similar in the laparoscopic and converted groups. CONCLUSIONS: Age above 65 years, BMI greater than 25, and tumor location between 5 and 15 cm from the anal verge were risk factors for conversion of laparoscopic to open surgery in patients with rectal cancer.

Ten-year outcomes of a randomised trial of laparoscopic versus open surgery for colon cancer.

BACKGROUND: Laparoscopic surgery for colon cancer is associated with improved recovery and similar cancer outcomes at 3 and 5 years in comparison with open surgery. However, long-term survival rates have rarely been reported. Here, we present survival and recurrence rates of the Dutch patients included in the COlon cancer Laparoscopic or Open Resection (COLOR) trial at 10-year follow-up. METHODS: Between March 1997 and March 2003, patients with non-metastatic colon cancer were recruited by 29 hospitals in eight countries and randomised to either laparoscopic or open surgery. Main inclusion criterion for the COLOR trial was solitary adenocarcinoma of the left or right colon. The primary outcome was disease-free survival at 3 years, and secondary outcomes included overall survival and recurrence. The 10-year follow-up data of all Dutch patients were collected. Analysis was by intention-to-treat. The trial was registered at ClinicalTrials.gov (NCT00387842). RESULTS: In total, 1248 patients were randomised, of which 329 were Dutch. Fifty-eight Dutch patients were excluded and 15 were lost to follow-up, leaving 256 patients for 10-year analysis. Median follow-up was 112 months. Disease-free survival rates were 45.2 % in the laparoscopic group and 43.2 % in the open group (difference 2.0 %; 95 % confidence interval (CI) -10.3 to 14.3; p = 0.96). Overall survival rates were 48.4 and 46.7 %, respectively (difference 1.7 %; 95 % CI -10.6 to 14.0; p = 0.83). Stage-specific analysis revealed similar survival rates for both groups. Sixty-two patients were diagnosed with recurrent disease, accounting for 29.4 % in the laparoscopic group and 28.2 % in the open group (difference 1.2 %; 95 % CI -11.1 to 13.5; p = 0.73). Seven patients had port- or wound-site recurrences (laparoscopic n = 3 vs. open n = 4). CONCLUSIONS: Laparoscopic surgery for non-metastatic colon cancer is associated with similar rates of disease-free survival, overall survival and recurrences as open surgery at 10-year follow-up.

COLOR III: a multicentre randomised clinical trial comparing transanal TME versus laparoscopic TME for mid and low rectal cancer.

INTRODUCTION: Total mesorectal excision (TME) is an essential component of surgical management of rectal cancer. Both open and laparoscopic TME have been proven to be oncologically safe. However, it remains a challenge to achieve complete TME with clear circumferential resections margin (CRM) with the conventional transabdominal approach, particularly in mid and low rectal tumours. Transanal TME (TaTME) was developed to improve oncological and functional outcomes of patients with mid and low rectal cancer. METHODS: An international, multicentre, superiority, randomised trial was designed to compare TaTME and conventional laparoscopic TME as the surgical treatment of mid and low rectal carcinomas. The primary endpoint is involved CRM. Secondary endpoints include completeness of mesorectum, residual mesorectum, morbidity and mortality, local recurrence, disease-free and overall survival, percentage of sphincter-saving procedures, functional outcome and quality of life. A Quality Assurance Protocol including centralised MRI review, histopathology re-evaluation, standardisation of surgical techniques, and monitoring and assessment of surgical quality will be conducted. DISCUSSION: The difference in involvement of CRM between the two treatment strategies is thought to be in favour of the TaTME. TaTME is therefore expected to be superior to laparoscopic TME in terms of oncological outcomes in case of mid and low rectal carcinomas.

Minimally Invasive Versus Open Total Gastrectomy for Gastric Cancer: A Systematic Review and Meta-analysis of Short-Term Outcomes and Completeness of Resection : Surgical Techniques in Gastric Cancer.

Minimally invasive surgical techniques for gastric cancer are gaining more acceptance worldwide as an alternative to open resection. In order to assess the role of minimally invasive and open techniques in total gastrectomy for cancer, a systematic review and meta-analysis was performed. Articles comparing minimally invasive versus open total gastrectomy were reviewed, collected from the Medline, Embase, and Cochrane databases. Two different authors (JS and NW) independently selected and assessed the articles. Outcomes regarding operative results, postoperative recovery, morbidity, mortality, and oncological outcomes were analyzed. Statistical analysis portrayed the weighted mean difference (WMD) with a 95% confidence interval and odds ratio (OR). Out of 1242 papers, 12 studies were selected, including a total of 1360 patients, of which 592 underwent minimally invasive total gastrectomy (MITG). Compared to open total gastrectomy (OTG), MITG showed a longer operation time (WMD: 48.06 min, P < 0.00001), less operative blood loss (WMD: -160.70 mL, P < 0.00001), faster postoperative recovery, measured as shorter time to first flatus (WMD -1.05 days, P < 0.00001), shorter length of hospital stay (WMD: -2.43 days, P = 0.0002), less postoperative complications (OR 0.66, P = 0.02), similar mortality rates (OR 0.60, P = 0.52), and similar rates in lymph node yield (WMD -2.30, P = 0.06). Minimally invasive total gastrectomy showed faster postoperative recovery and less postoperative complications, whereas completeness of the resection was similar in both groups. Duration of surgery was longer in the minimally invasive group. Only comparative non-randomized studies were available, further emphasizing the need for a prospective randomized trial comparing MITG and OTG.

Bronchial colonization and complications after lung cancer surgery.

PURPOSE: Infectious complications occur following pulmonary resections preceded or not by induction chemoradiotherapy. We aimed to investigate whether bacterial colonization of the bronchial tree at the time of surgery was associated with postoperative complications. PATIENTS AND METHODS: A retrospective analysis of all patients who underwent open anatomical pulmonary resections for malignancies at a single center was performed. Demographical data of the included patients, intraoperative data, and data on the postoperative course of patients were collected. Outcome of patients with a positive intraoperative bronchial culture was compared to patients with a negative bronchial culture. Relations between the presence of potential bacterial pathogens in the bronchial tree and other possible risk factors for the development of postoperative infectious and non-infectious complications, were analyzed using uni- and multivariate analysis. RESULTS: Between January 2010 and January 2012, a total of 121 consecutive patients underwent open anatomical pulmonary resections for malignancy, of whom 45 were preceded by induction chemoradiotherapy and 5 by induction chemotherapy. Intraoperative bronchial cultures were taken from 58 patients (48 %). Patients with a positive bronchial culture developed significantly more infectious (88 % vs. 20 %, p < 0.001) and non-infectious complications (63 % vs. 12 %, p = 0.001). Positive intraoperative bronchial cultures showed the strongest association with the development of infectious and non-infectious postoperative complications (OR 24.8 and 12.2, respectively). After multivariate analysis, only BMI less than 20 kg/m(2) and the presence of a positive intraoperative bronchial culture were found to be independent risk factors for the development of infectious complications. Chemoradiotherapy was not associated with postoperative complications in the present study. CONCLUSIONS: Bacterial colonization of the bronchial tree assessed intraoperatively, appears to be associated with higher rates of infectious and non-infectious complications after pulmonary resection. Whether early starting of appropriate antibiotics based on intraoperative-taken culture findings will reduce the infectious complication rate in a subcategory of patients needs to be investigated.

Hospital cost-analysis of complications after major abdominal surgery.

BACKGROUND: Complications after major abdominal surgery (MAS) are associated with increased morbidity and mortality. Rising costs in health care are of increasing interest and a major factor affecting hospital costs are postoperative complications. In this study, the costs associated with complications are assessed. METHODS: Retrospective cohort study of 399 consecutive patients that underwent MAS. Analysis of total costs for hospital stay, complications and treatment was performed, including bootstrapping; allowing for subtraction of data with 95% confidence intervals. RESULTS: For a single patient who underwent MAS the average costs, adjusted for ASA-classification and surgery type, adds up to EUR 8,584.81 (95% CI EUR 8,332.51 - EUR 8,860.81) in patients without complications. EUR 15,412.96 (95% CI EUR 14,250.22 - EUR 16,708.82) after minor complications, and EUR 29,198.23 (95% CI EUR 27,187.13 - EUR 31,295.78) after major complications (p < 0.001). CONCLUSION: The results provide an insight into the scope of hospital costs associated with complications. Major complications occur in 20% of patients undergoing MAS and account for 50% of the total costs of care. Implementation of a protocol aimed at early diagnosis and treatment of complications might lead to a decrease in morbidity and mortality, but also prove to be cost effective.

Complications after laparotomy for trauma: a retrospective analysis in a level I trauma centre.

PURPOSE: Laparotomy is a potential life-saving procedure after traumatic abdominal injury. There is limited literature about morbidity and mortality rates after trauma laparotomy. The primary aim of this study is to describe the complications which may occur due to laparotomy for trauma. METHODS: Retrospective evaluated single-centre study with data registry up to 1 year after initial laparotomy for trauma was performed in a level 1 trauma centre in The Netherlands. Between January 2000 and January 2011, a total of 2390 severely injured trauma patients (ISS ≥ 16) were transported to the VUMC. Patient demographics; mechanism of injury; injury patterns defined by Abbreviated Injury Scale (AIS), Injury Severity Score (ISS) and Revised Trauma Score (RTS); surgical interventions and findings; and morbidity and mortality were documented. RESULTS: A total of 92 trauma patients who underwent a trauma laparotomy met the inclusion criteria. Of these patients, 71 % were male. Median age was 37 years. Median ISS was 27. Mechanisms of injury comprised of car accidents (20 %), fall from height (17 %), motorcycle accidents (12 %), pedestrian/cyclist hit by a vehicle (9 %) and other in three patients (5 %). Penetrating injuries accounted for 37 % of the injuries, consisting of stab wounds (21 %) and gunshot wounds (16 %). Complications classified by the Clavien-Dindo Classification of Surgical Complications showed grade I complications in 21 patients (23 %), grade II in 36 patients (39 %), grade III in 21 patients (23 %), grade IV in 2 patients (2 %) and grade V in 16 patients (17 %). CONCLUSION: Laparotomy for trauma has a high complication rate resulting in significant morbidity and mortality. Most events occur in the early postoperative period. Further prospective research needs to be conducted in order to identify possibilities to improve care in the future.

Intraoperative ultrasound guidance for palpable breast cancer excision (COBALT trial): a multicentre, randomised controlled trial.

BACKGROUND: Breast-conserving surgery for palpable breast cancer is associated with tumour-involved margins in up to 41% of cases and excessively large excision volumes. Ultrasound-guided surgery has the potential to resolve both of these problems, thereby improving surgical accuracy for palpable breast cancer. We aimed to compare ultrasound-guided surgery with the standard for palpable breast cancer-palpation-guided surgery-with respect to margin status and extent of healthy breast tissue resection. METHODS: In this randomised controlled trial, patients with palpable T1-T2 invasive breast cancer were recruited from six medical centres in the Netherlands between October, 2010, and March, 2012. Eligible participants were randomly assigned to either ultrasound-guided surgery or palpation-guided surgery in a 1:1 ratio via a computer-generated random sequence and were stratified by study centre. Patients and investigators were aware of treatment assignments. Primary outcomes were surgical margin involvement, need for additional treatment, and excess healthy tissue resection (defined with a calculated resection ratio derived from excision volume and tumour diameter). Data were analysed by intention to treat. This trial is registered at http://www.TrialRegister.nl, number NTR2579. FINDINGS: 134 patients were eligible for random allocation. Two (3%) of 65 patients allocated ultrasound-guided surgery had tumour-involved margins compared with 12 (17%) of 69 who were assigned palpation-guided surgery (difference 14%, 95% CI 4-25; p=0·0093). Seven (11%) patients who received ultrasound-guided surgery and 19 (28%) of those who received palpation-guided surgery required additional treatment (17%, 3-30; p=0·015). Ultrasound-guided surgery also resulted in smaller excision volumes (38 [SD 26] vs 57 [41] cm(3); difference 19 cm(3), 95% CI 7-31; p=0·002) and a reduced calculated resection ratio (1·0 [SD 0·5] vs 1·7 [1·2]; difference 0·7, 95% CI 0·4-1·0; p=0·0001) compared with palpation-guided surgery. INTERPRETATION: Compared with palpation-guided surgery, ultrasound-guided surgery can significantly lower the proportion of tumour-involved resection margins, thus reducing the need for re-excision, mastectomy, and radiotherapy boost. By achieving optimum resection volumes, ultrasound-guided surgery reduces unnecessary resection of healthy breast tissue and could contribute to improved cosmetic results and quality of life. FUNDING: Dutch Pink Ribbon Foundation, Osinga-Kluis Foundation, Toshiba Medical Systems.

Validation of the Amsterdam IADL Questionnaire©, a new tool to measure instrumental activities of daily living in dementia.

BACKGROUND: This study describes the validation of a new instrument measuring instrumental activities of daily living (IADL), the Amsterdam IADL Questionnaire© (a registered copyright of the Alzheimer Center of the VU University Medical Center). This informant-based tool aimed at detecting IADL problems in incipient dementia was previously found to have a high internal consistency and test-retest reliability. METHODS: Patients and their informants who visited the Alzheimer Center of the VU University Medical Center were included in this study. Item response theory was used to estimate the individuals' trait levels as a measure of IADL disability. Construct validity was tested by correlating estimated trait levels with clinical and demographic measures using Pearson's or Kendall's τ correlation coefficients. Additionally, estimated trait levels between patients with and without dementia and between patients with early- and late-onset dementia were compared using independent t tests. RESULTS: A total of 206 informants of patients completed the Amsterdam IADL Questionnaire. The correlations between estimated trait levels and other measures were in concordance with previously formed hypotheses. Patients diagnosed with dementia (n = 93) had higher estimated trait levels than patients without dementia (n = 96), Cohen's effect size, d = 1.04, t(187) = 7.1, p < 0.001. We found no differences between early- and late-onset dementia patients. CONCLUSIONS: Results suggest that the Amsterdam IADL Questionnaire is a reliable and valid instrument in the evaluation of dementia.

Assessment of instrumental activities of daily living in dementia: diagnostic value of the Amsterdam Instrumental Activities of Daily Living Questionnaire.

BACKGROUND: Measuring impairments in "instrumental activities of daily living" (IADL) is important in dementia, but challenging due to the lack of reliable and valid instruments. We recently developed the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q; note 1). We aim to investigate the diagnostic accuracy of the A-IADL-Q for dementia in a memory clinic setting. METHODS: Patients visiting the Alzheimer Center of the VU University Medical Center with their informants between 2009 and 2011 were included (N = 278). Diagnoses were established in a multidisciplinary consensus meeting, independent of the A-IADL-Q scores. An optimal A-IADL-Q cutoff point was determined, and sensitivity and specificity were calculated. Area under the curves (AUCs) were compared between A-IADL-Q and "disability assessment of dementia" (DAD). The additional diagnostic value of the A-IADL-Q to Mini-Mental State Examination (MMSE) was examined using logistic regression analyses. RESULTS: Dementia prevalence was 50.5%. Overall diagnostic accuracy based on the AUC was 0.75 (95% confidence interval [CI]: 0.70-0.81) for the A-IADL-Q and 0.70 (95% CI: 0.63-0.77) for the DAD, which did not differ significantly. The optimal cutoff score for the A-IADL-Q was 51.4, resulting in sensitivity of 0.74 and specificity of 0.64. Combining the A-IADL-Q with the MMSE improved specificity (0.94), with a decline in sensitivity (0.55). Logistic regression models showed that adding A-IADL-Q improved the diagnostic accuracy (Z = 2.55, P = .011), whereas the DAD did not. CONCLUSIONS: In this study, we showed a fair diagnostic accuracy for A-IADL-Q and an additional value in the diagnosis of dementia. These results support the role of A-IADL-Q as a valuable diagnostic tool.

Diagnostic accuracy and reproducibility of the Ottawa Knee Rule vs the Pittsburgh Decision Rule.

PURPOSE: The aim of this present study was to compare the diagnostic accuracy and reproducibility of 2 clinical decision rules (the Ottawa Knee Rules [OKR] and Pittsburgh Decision Rules [PDR]) developed for selective use of x-rays in the evaluation of isolated knee trauma. Application of a decision rule leads to a more efficient evaluation of knee injuries and a reduction in health care costs. The diagnostic accuracy and reproducibility are compared in this study. METHODS: A cross-sectional interobserver study was conducted in the emergency department of an urban teaching hospital from October 2008 to July 2009. Two observer groups collected data on standardized case-report forms: emergency medicine residents and surgical residents. Standard knee radiographs were performed in each patient. Participants were patients 18 years and older with isolated knee injuries. Pooled sensitivity and specificity were compared using χ(2) statistics, and interobserver agreement was calculated by using κ statistics. RESULTS: Ninety injuries were assessed. Seven injuries concerned fractures (7.8%). For the OKR, the pooled sensitivity and specificity were 0.86 (95% confidence interval [CI], 0.57-0.96) and 0.27 (95% CI, 0.21-0.35), respectively. The PDR had a pooled sensitivity and specificity of 0.86 (95% CI, 0.57-0.96) and 0.51 (95% CI, 0.44-0.59). The PDR was significantly (P = .002) more specific. The κ values for the OKR and PDR were 0.51 (95% CI, 0.32-0.71) and 0.71 (95% CI, 0.57-0.86), respectively. CONCLUSION: The PDR was found to be more specific than the OKR, with equal sensitivity. Interobserver agreement was moderate for the OKR and substantial for the PDR.

Criteria for cancelling helicopter emergency medical services (HEMS) dispatches.

INTRODUCTION: In The Netherlands there is no consensus about criteria for cancelling helicopter emergency medical services (HEMS) dispatches. This study assessed the ability of the primary HEMS dispatch criteria to identify major trauma patients. The predictive power of other early prehospital parameters was evaluated to design a safe triage model for HEMS dispatch cancellations. METHODS: All trauma-related dispatches of HEMS during a period of 6 months were included. Data concerning prehospital information and inhospital treatment were collected. Patients were divided into two groups (major and minor trauma) according to the following criteria: injury severity score 16 or greater, emergency intervention, intensive care unit admission, or inhospital death. Logistic regression analysis was used to design a prediction model for the early identification of major trauma patients. RESULTS: In total, 420 trauma-related dispatches were evaluated, of which 155 concerned major trauma patients. HEMS was more often cancelled for minor trauma patients than for major trauma patients (57.7% vs 20.6%). Overall, HEMS dispatch criteria had a sensitivity of 87.7% and a specificity of 45.3% for identifying major trauma patients. Significant differences were found for vital sign abnormalities, anatomical components and several parameters of the mechanism of injury. A triage model designed for cancelling HEMS correctly identified major trauma patients (sensitivity 99.4%). CONCLUSION: The accuracy of the current HEMS dispatch criteria is relatively low, resulting in high cancellation rates and low predictability for major trauma. The new HEMS cancellation triage model identified all major trauma patients with an acceptable overtriage and will probably reduce unjustified HEMS dispatches.

A new informant-based questionnaire for instrumental activities of daily living in dementia.

BACKGROUND: Interference in everyday functioning is part of the diagnostic criteria for dementia. Questionnaires measuring "instrumental activities of daily living" (IADL) are used to measure this interference, but the psychometric quality of these questionnaires is often questioned. In addition, these questionnaires are less suited for early-onset patients. This is problematic, given the high frequency of relatively young patients in memory clinics. In this article, we describe the development and psychometric properties of a new informant-based IADL questionnaire aimed at detecting incipient dementia and appropriate for a broad age range. METHODS: We defined IADL in consensus with experts and constructed items based on existing items and suggestions from experts and informants. Informants of subjects (n = 206) who visited the Alzheimer Center of the VU University Medical Center completed the questionnaire. Factor structure was investigated using classical exploratory factor analysis and item response theory. We assessed test-retest reliability in 73 informants using weighted κ values. RESULTS: The questionnaire consisted of 75 items and was computerized to enhance ease of administration. Exploratory factor analysis supported a single-factor model, with 48.3% of the variance being explained by the first factor. We removed five items, as they did not fit the model. High internal consistency was demonstrated. Test-retest reliability showed that the majority of items (87.9%) had substantial-to-almost perfect κ values. CONCLUSION: The Amsterdam IADL Questionnaire (Amsterdam IADL questionnaire is a registered trademark of Alzheimer Center VU University Medical Center, Amsterdam, The Netherlands) is a 70-item informant-based computerized questionnaire aimed at detecting early dementia and early-onset dementia. Initial results show that this questionnaire is a promising new tool.

An informant questionnaire for detecting Alzheimer's disease: are some items better than others?

A decline in everyday cognitive functioning is important for diagnosing dementia. Informant questionnaires, such as the informant questionnaire on cognitive decline in the elderly (IQCODE), are used to measure this. Previously, conflicting results on the IQCODEs ability to discriminate between Alzheimer's disease (AD), mild cognitive impairment (MCI), and cognitively healthy elderly were found. We aim to investigate whether specific groups of items are more useful than others in discriminating between these patient groups. Informants of 180 AD, 59 MCI, and 89 patients with subjective memory complaints (SMC) completed the IQCODE. To investigate the grouping of questionnaire items, we used a two-dimensional graded response model (GRM).The association between IQCODE, age, gender, education, and diagnosis was modeled using structural equation modeling. The GRM with two groups of items fitted better than the unidimensional model. However, the high correlation between the dimensions (r=.90) suggested unidimensionality. The structural model showed that the IQCODE was able to differentiate between all patient groups. The IQCODE can be considered as unidimensional and as a useful addition to diagnostic screening in a memory clinic setting, as it was able to distinguish between AD, MCI, and SMC and was not influenced by gender or education.

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.

Open surgical repair of ruptured juxtarenal aortic aneurysms with and without renal cooling: observations regarding morbidity and mortality.

OBJECTIVES: Little is known about the outcome of ruptured juxtarenal aortic aneurysm (RJAA) repair. Surgical treatment of RJAAs requires suprarenal aortic cross-clamping, which causes additional renal ischemia-reperfusion injury on top of the pre-existing hypovolemic shock syndrome. As endovascular alternatives rarely exist in this situation, open repair continues to be the gold standard. We analyzed our results of open RJAA repair during an 11-year period. DESIGN: Retrospective observational study. MATERIALS AND METHODS: Between July 1997 and December 2008, all consecutive patients with RJAAs were included in the study. Part of these patients received cold perfusion of the kidneys during suprarenal aortic cross-clamping. Perioperative variables, morbidity, and 30-day or in-hospital mortality were assessed. Renal insufficiency was defined as an acute rise of >or=0.5 mg/dL in serum creatinine level. Multiple organ failure (MOF) was scored using the sequential organ failure assessment score (SOFA score). RESULTS: A total of 29 consecutive patients with an RJAA, confirmed by computed tomography-scanning, presented to our hospital. In eight patients, the operation was aborted before the start of aortic repair, because no blood pressure could be regained in spite of maximal resuscitation measures. They were excluded from further analysis. Of the remaining 21 patients, 10 died during hospital stay. Renal insufficiency occurred in 11 out of 21 of the patients. Eleven out of 21 patients developed MOF postoperatively. In a subgroup of patients who received renal cooling during suprarenal aortic clamping, the 30-day or in-hospital mortality was two of 10 vs eight of 11 in patients who did not receive renal cooling (P = .03); renal insufficiency occurred in one out of 10 patients in the subgroup with renal cooling vs 10 out of 11 without renal cooling (P < .001) and MOF in two of 10 vs nine of 11, respectively (P = .009). CONCLUSIONS: Open surgical repair of RJAAs is still associated with high mortality and morbidity. To our knowledge, this is the first report of cold perfusion of the kidneys during RJAA repair. Although numbers are small, a beneficial effect of renal cooling on the outcome of RJAA repair is suggested, warranting further research with this technique.

How useful is the IQCODE for discriminating between Alzheimer's disease, mild cognitive impairment and subjective memory complaints?

BACKGROUND: Informant questionnaires may be useful in diagnosing early dementia. Conflicting results were found when these questionnaires were used to differentiate patients with mild cognitive impairment (MCI) from healthy elderly subjects. We evaluated the ability of the most commonly used informant questionnaire, the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), to discriminate between Alzheimer's disease (AD), MCI and subjective memory complaints (SMC). METHODS: Informants of 180 AD patients, 59 MCI patients and 89 SMC subjects who visited the Alzheimer Center of the VU University Medical Center between 2004 and 2007 completed the short Dutch version of the IQCODE. Logistic regression and receiver operating characteristic curves were used to evaluate the diagnostic ability of the IQCODE. RESULTS: The IQCODE was able to differentiate AD from MCI and SMC, but was not able to differentiate SMC from MCI. CONCLUSIONS: The IQCODE may be helpful in diagnosing AD but is of limited use in differentiating MCI from SMC.

Sports activity in adolescents in the Netherlands with a pectus excavatum; the impact of surgery.

PURPOSE: Pectus excavatum (PE) is the most common chest wall deformity in adolescents. The main complaint is cosmetic, but many patients also complain about exertional dyspnea. This may lead to the patient seeking surgery of the thoracic wall deformity (TWD). The assumption is that both, appearance and physical complaints will have a negative effect on being able or wanting to engage in sport activity. METHODS: In December 2011 a prospective registration of sport activity in pectus excavatum patients started. Sport activity was assessed using questionnaires (CHQ, SF-36 and PEEQ). Measurements were taken before corrective surgery (preoperatively) and 12 months postoperatively. RESULTS: 127 patients have been included. The number of patients who were active in sports preoperatively and after 12 months remained steady. The type of sport activity, individual sport or team sport showed no significant change. The CHQ showed that physical activity caused fewer complaints (p < 0.001). The PEEQ showed a decrease in difficulties with sports activity performance after 12 months (p < 0.001). CONCLUSIONS: Twelve months after surgical correction of PE there was no significant increase in the number of patients performing sport activities. However there was a significant decrease of complaints or difficulties during sport compared to preoperatively. LEVEL OF EVIDENCE: Level IV.

Effect of Bilateral Prefrontal rTMS on Left Prefrontal NAA and Glx Levels in Schizophrenia Patients with Predominant Negative Symptoms: An Exploratory Study.

BACKGROUND: Prefrontal repetitive Transcranial Magnetic Stimulation (rTMS) may improve negative symptoms in patients with schizophrenia, but few studies have investigated the underlying neural mechanism. OBJECTIVE: This study aims to investigate changes in the levels of glutamate and glutamine (Glx, neurotransmitter and precursor) and N-Acetyl Aspartate (NAA) in the left dorsolateral prefrontal cortex of patients with schizophrenia treated with active bilateral prefrontal rTMS as compared to sham-rTMS, as measured with 1H-Magnetic Resonance Spectroscopy (1H-MRS). METHODS: Patients were randomized to a 3-week course of active or sham high-frequency rTMS. Pre-treatment and post-treatment 1H-MRS data were available for 24 patients with schizophrenia with moderate to severe negative symptoms (Positive and Negative Syndrome Scale (PANSS) negative subscale ≥ 15). Absolute metabolite concentrations were calculated using LCModel with the water peak as reference. To explore the association between treatment condition and changes in concentration of Glx and NAA, we applied a linear regression model. RESULTS: We observed an increase of Glx concentration in the active treatment group and a decrease of Glx concentration in the group receiving sham treatment. The association between changes in Glx concentration and treatment condition was significant. No significant associations between changes in NAA and treatment condition were found. CONCLUSIONS: Noninvasive neurostimulation with high-frequency bilateral prefrontal rTMS may influence Glx concentration in the prefrontal cortex of patients with schizophrenia. Larger studies are needed to confirm these findings and further elucidate the underlying neural working mechanism of rTMS.