Single dose IOERT versus whole breast irradiation : Cosmetic results in breast-conserving therapy.

BACKGROUND: Scarce data are available about the cosmetic result of single dose intraoperative electron radiotherapy (IOERT) in breast-conserving radiotherapy. METHODS AND MATERIALS: We included 71 breast cancer patients. Breast-conserving surgery and sentinel node procedure had started almost 3 years earlier. Subsequently, 26 patients were treated with IOERT and 45 patients received postoperative whole breast irradiation (WBI). For both groups we determined seven dimensionless asymmetry features. We compared the subjectively and the objectively derived cosmetic scores with each other. RESULTS: For four asymmetry features we noted significantly smaller differences for patients treated with IOERT when compared to those treated with WBI: relative breast contour difference, relative breast area difference and relative breast overlap difference. After correcting for excision volume a significant difference was noticed also for relative lower breast contour. For the IOERT group the cosmetic scores "excellent or good" as determined by each patient and one physician were 88 and 96 %, respectively. When the overall cosmetic scores for patients treated with IOERT and WBI were compared to those of the objectively derived scores, there was a fair level of agreement. CONCLUSION: For patients treated with IOERT we noted less asymmetry and high rates of "good or excellent" subjectively derived cosmetic scores. The level of agreement between the subjectively and the objectively derived cosmetic scores was limited. Due to the small sample size and the design of the study no definitive conclusions can be drawn.

Differences between colon and rectal cancer in complications, short-term survival and recurrences.

PURPOSE: Many apparent differences exist in aetiology, genetics, anatomy and treatment response between colon cancer (CC) and rectal cancer (RC). This study examines the differences in patient characteristics, prevalence of complications and their effect on short-term survival, long-term survival and the rate of recurrence between RC and CC. METHODS: For all stage II-III CC and RC patients who underwent resection with curative intent (2006-2008) in five hospitals in the Netherlands, occurrence of complications, crude survival, relative survival and recurrence rates were compared. RESULTS: A total of 767 CC and 272 RC patients underwent resection. Significant differences were found for age, gender, emergency surgery, T-stage and grade. CC patients experienced fewer complications compared to RC (p = 0.019), but CC patients had worse short-term mortality rates (1.5 versus 6.7 % for 30-day mortality, p = 0.001 and 5.2 versus 9.5 % for 90-day mortality, p = 0.032). The adjusted HR (overall survival) for CC patients with complications was 1.57 (1.23-2.01; p < 0.001) as compared to patients without complications; for RC, the HR was 1.79 (1.12-2.87; p = 0.015). Relative survival analyses showed high excess mortality in the first months after surgery and a sustained, prolonged negative effect on both CC and RC. Complications were associated with a higher recurrence rate for both CC and RC; adjusted analyses showed a trend towards a significant association. CONCLUSION: Large differences exist in patient characteristics and clinical outcomes between CC and RC. CC patients have a significantly higher short-term mortality compared to RC patients due to a more severe effect of complications.

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

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

Indocyanine green near-infrared fluorescence bowel perfusion assessment to prevent anastomotic leakage in minimally invasive colorectal surgery (AVOID): a multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Anastomotic leakage is a severe postoperative complication in colorectal surgery and compromised bowel perfusion is considered a major contributing factor. Conventional methods to assess bowel perfusion have a low predictive value for anastomotic leakage. We therefore aimed to evaluate the efficacy of real-time assessment with near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) in the prevention of anastomotic leakage. METHODS: This multicentre, randomised, controlled, phase 3 trial was done in eight hospitals in the Netherlands. We included adults (aged >18 years) who were scheduled for laparoscopic or robotic colorectal surgery (with planned primary anastomosis) for benign and malignant diseases. Preoperatively, patients were randomly assigned (1:1) to fluorescence-guided bowel anastomosis (FGBA) or conventional bowel anastomosis (CBA) by variable block randomisation (block sizes 4, 6, and 8) and stratified by site. The operating surgeon and investigators analysing the data were not masked to group assignment. Patients were unmasked after the surgical procedure or after study end. In the FGBA group, surgeons marked anastomosis levels per conventional perfusion assessment and then administered 5 mg of ICG by 2 mL intravenous bolus. They assessed bowel perfusion using NIR fluorescence imaging and adjusted (or kept) transection lines accordingly. Only conventional methods for bowel perfusion assessment were used in the CBA group. The primary outcome was the difference in the rate of clinically relevant anastomotic leakage (ie, requiring active therapeutic intervention but manageable without reoperation [grade B] or requiring reoperation [grade C], per the International Study Group of Rectal Cancer) between the FGBA group and the CBA group within 90 days post-surgery. The primary outcome and safety were assessed in the intention-to-treat population. This study was registered with ToetsingOnline.nl (NL7502) and ClinicalTrials.gov (NCT04712032) and is complete. FINDINGS: Between July 2, 2020, and Feb 21, 2023, 982 patients were enrolled, of whom 490 were assigned to FGBA and 492 were assigned to CBA. After excluding 51 patients, the intention-to-treat population comprised 931 (463 assigned FGBA and 468 assigned CBA). Patients had a median age of 68·0 years (IQR 59·0-75·0) and 485 (52%) were male and 446 (48%) were female. Ethnicity data were not available. The overall 90-day rate of clinically relevant anastomotic leakage was not significantly different between the FGBA group (32 [7%] of 463 patients) and the CBA group (42 [9%] of 468 patients; relative risk 0·77 [95% CI 0·50-1·20]; p=0·24). No adverse events related to ICG use were observed. 313 serious adverse events in 229 (25%) patients were at 90-day follow-up (159 serious adverse events in 113 [24%] patients in the FGBA group and 154 serious adverse events in 116 [25%] patients in the CBA group). 18 (2%) people died by 90 days (ten in the FGBA group and eight in the CBA group). INTERPRETATION: ICG NIR fluorescence imaging did not reduce 90-day anastomotic leakage rates in this trial across all types of colorectal surgeries. Further research should be done in subgroups, such as rectosigmoid resections, for which evidence suggests ICG NIR might be beneficial. FUNDING: Olympus Medical, Diagnostic Green, and Intuitive Foundation.

Baseline and early digital [ 18 F]FDG PET/CT and multiparametric MRI contain promising features to predict response to neoadjuvant therapy in locally advanced rectal cancer patients: a pilot study.

OBJECTIVE: In this pilot study, we investigated the feasibility of response prediction using digital [ 18 F]FDG PET/computed tomography (CT) and multiparametric MRI before, during, and after neoadjuvant chemoradiation therapy in locally advanced rectal cancer (LARC) patients and aimed to select the most promising imaging modalities and timepoints for further investigation in a larger trial. METHODS: Rectal cancer patients scheduled to undergo neoadjuvant chemoradiation therapy were prospectively included in this trial, and underwent multiparametric MRI and [ 18 F]FDG PET/CT before, 2 weeks into, and 6-8 weeks after chemoradiation therapy. Two groups were created based on pathological tumor regression grade, that is, good responders (TRG1-2) and poor responders (TRG3-5). Using binary logistic regression analysis with a cutoff value of P  ≤ 0.2, promising predictive features for response were selected. RESULTS: Nineteen patients were included. Of these, 5 were good responders, and 14 were poor responders. Patient characteristics of these groups were similar at baseline. Fifty-seven features were extracted, of which 13 were found to be promising predictors of response. Baseline [T2: volume, diffusion-weighted imaging (DWI): apparent diffusion coefficient (ADC) mean, DWI: difference entropy], early response (T2: volume change, DWI: ADC mean change) and end-of-treatment presurgical evaluation MRI (T2: gray level nonuniformity, DWI: inverse difference normalized, DWI: gray level nonuniformity normalized), as well as baseline (metabolic tumor volume, total lesion glycolysis) and early response PET/CT (Δ maximum standardized uptake value, Δ peak standardized uptake value corrected for lean body mass), were promising features. CONCLUSION: Both multiparametric MRI and [ 18 F]FDG PET/CT contain promising imaging features to predict response to neoadjuvant chemoradiotherapy in LARC patients. A future larger trial should investigate baseline, early response, and end-of-treatment presurgical evaluation MRI and baseline and early response PET/CT.

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

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

Improved guideline compliance after a 3-year audit of multidisciplinary colorectal cancer care in the western part of the Netherlands.

BACKGROUND: From 2006 to 2008, an audit of the multidisciplinary diagnosis and treatment of colorectal cancer patients in the western part of the Netherlands was carried out. We evaluated whether compliance with guidelines had improved. METHODS: All patients with newly diagnosed and surgically treated colon (n = 1,667) and rectal cancer (n = 544) stage I-III were evaluated. Nine quality indicators were derived from the evidence-based guidelines. In order to compare hospital performances, hospital results were adjusted for casemix differences between hospitals. RESULTS: Colon cancer patients showed an increase in the examination of 10 or more lymph nodes (from 53% to 78%, P < 0.0001). For rectal cancer patients there was an increase in preoperative visualisation of the total colon (63-74%, P = 0.02), MRI (73-85%, P = 0.003), radiotherapy (from 82% to 93% for patients <75 years, P = 0.01) and examination of at least 10 lymph nodes (40-55%, P = 0.004). In 2006, standardised hospital performances differed widely for all quality indicators. Two years later, hospital performances for some quality indicators were more similar. CONCLUSIONS: After the feedback of benchmark information, compliance with guidelines for diagnosis and treatment of colorectal cancer patients improved, and differences between individual hospitals decreased. Although secular trends cannot be ruled out, it is highly likely that these results can be attributed to the audit.

Colonic stenting versus emergency surgery for acute left-sided malignant colonic obstruction: a multicentre randomised trial.

BACKGROUND: Colonic stenting as a bridge to elective surgery is an alternative for emergency surgery in patients with acute malignant colonic obstruction, but its benefits are uncertain. We aimed to establish whether colonic stenting has better health outcomes than does emergency surgery. METHODS: Patients with acute obstructive left-sided colorectal cancer were enrolled from 25 hospitals in the Netherlands and randomly assigned (1:1 ratio) to receive colonic stenting as a bridge to elective surgery or emergency surgery. The randomisation sequence was computer generated with permuted blocks and was stratified by centre; treatment allocation was concealed by use of a web-based application. Investigators and patients were unmasked to treatment assignment. The primary outcome was mean global health status during a 6-month follow-up, which was assessed with the QL2 subscale of the European Organisation for Research and Treatment of Cancer quality-of-life questionnaire (EORTC QLQ-C30). Analysis was by intention to treat. This study is registered, number ISRCTN46462267. FINDINGS: Between March 9, 2007, and Aug 27, 2009, 98 patients were assigned to receive colonic stenting (n=47 patients) or emergency surgery (n=51). Two successive interim analyses showed increased 30-day morbidity in the colonic stenting group, with an absolute risk increase of 0.19 (95% CI -0.06 to 0.41) in analysis of the first 60 patients (14 of 28 patients receiving colonic stenting vs 10 of 32 receiving emergency surgery), and an absolute risk increase of 0.19 (-0.01 to 0.37) in analysis of the first 90 patients (23 of 47 patients vs 13 of 43). In accordance with the advice of the data safety monitoring committee, the study was suspended on Sept 18, 2009, and ended on March 12, 2010. At the final analysis of 98 patients, mean global health status during follow-up was 63.0 (SD 23.8) in the colonic stenting group and 61.4 (SD 21.9) in the emergency surgery group; after adjustment for baseline values, mean global health status did not differ between treatment groups (-4.7, 95% CI -14.8 to 5.5, p=0.36). No difference was recorded between treatment groups in 30-day mortality (absolute risk difference -0.01, 95% CI -0.14 to 0.12, p=0.89), overall mortality (-0.02, -0.17 to 0.14, p=0.84), morbidity (-0.08, -0.27 to 0.11, p=0.43), and stoma rates at latest follow-up (0.09, -0.10 to 0.27, p=0.35). However, the emergency surgery group had an increased stoma rate directly after initial intervention (0.23, 0.04 to 0.40, p=0.016) and a reduced frequency of stoma-related problems (between-group difference -12.0, -23.7 to -0.2, p=0.046). The most common serious adverse events were abscess (three in the colonic stenting group vs four in the emergency surgery group), perforations (six vs none), and anastomotic leakage (five vs one), and the most common adverse events were pneumonia (three vs one) and wound infection (one vs three). INTERPRETATION: Colonic stenting has no decisive clinical advantages to emergency surgery. It could be used as an alternative treatment in as yet undefined subsets of patients, although with caution because of concerns about tumour spread caused by perforations. FUNDING: None.

Prostate-Specific Membrane Antigen Targeted Pet/CT Imaging in Patients with Colon, Gastric and Pancreatic Cancer.

Current imaging modalities frequently misjudge disease stage in colorectal, gastric and pancreatic cancer. As treatment decisions are dependent on disease stage, incorrect staging has serious consequences. Previous preclinical research and case reports indicate that prostate-specific membrane antigen (PSMA)-targeted PET/CT imaging might provide a solution to some of these challenges. This prospective clinical study aims to assess the feasibility of [18F]DCFPyL PET/CT imaging to target and visualize primary colon, gastric and pancreatic cancer. In this prospective clinical trial, patients with colon, gastric and pancreatic cancer were included and underwent both [18F]DCFPyL and [18F]FDG PET/CT scans prior to surgical resection or (for gastric cancer) neoadjuvant therapy. Semiquantitative analysis of immunohistochemical PSMA staining was performed on the surgical resection specimens, and the results were correlated to imaging parameters. The results of this study demonstrate detection of the primary tumor by [18F]DCFPyL PET/CT in 7 out of 10 patients with colon, gastric and pancreatic cancer, with a mean tumor-to-blood pool ratio (TBR) of 3.3 and mean SUVmax of 3.6. However, due to the high surrounding uptake, visual distinction of these tumors was difficult, and the SUVmax and TBR on [18F]FDG PET/CT were significantly higher than on [18F]DCFPyL PET/CT. In addition, no correlation between PSMA expression in the resection specimen and SUVmax on [18F]DCFPyL PET/CT was found. In conclusion, the detection of several gastrointestinal cancers using [18F]DCFPyL PET/CT is feasible. However, low tumor expression and high uptake physiologically in organs/background hamper the clear distinction of the tumor. As a result, [18F]FDG PET/CT was superior in detecting colon, gastric and pancreatic cancers.

Clinical Challenges in Resection and Reconstruction of a Verrucous Carcinoma of the Right Calcaneus With a Medial Plantar Artery Perforator Flap: A Case Report.

A verrucous carcinoma is a rare, low-grade variant of a well-differentiated squamous cell carcinoma (SCC). It frequently occurs in Caucasian males aged 50 to 60. The tumour is locally destructive, grows into muscle, nerves and bones, but rarely metastasizes. Here we report a patient with verrucous carcinoma on the right calcaneus with the uncommon symptom of a haemorrhagic plaque at the centre and also an exophytic component. A 52-year-old man presented with a 10-year-old, progressive, painful, pruritic, exophytic growing, hyperkeratotic and haemorrhagic plaque of 5.2 x 3.5cm on the right calcaneus. The lesion emerged after extensive burns after blast trauma as a child. Excisional biopsy with 2mm margin in combination with clinical presentation favoured a verrucous carcinoma. The pathology report showed that the tumour was not excised radically; therefore, re-excision with 5mm margin was required and was performed two months later. The wound was closed with a medial plantar artery perforator (MPAP) flap. The donor site was closed with a full-thickness skin graft (FTSG) from the medial side of the right upper leg and was covered by a tie-over bandage. Verrucous carcinoma is a rare tumour and can be adequately surgically treated by excision with clear margins. In this case, the verrucous carcinoma of the right calcaneus was excised and reconstructed with an MPAP flap with decent results, despite a challenging postoperative course.

Importance of patient reported and clinical outcomes for patients with locally advanced rectal cancer and their treating physicians. Do clinicians know what patients want?

INTRODUCTION: Several factors are included in decision making for treatment of patients with locally advanced rectal cancer, including a trade-off between risks and gains of both clinical and functional outcomes. However, it is largely unknown which outcomes are most important to patients and whether this differs between patients and clinicians. METHODS: Both clinicians and patients treated for locally advanced rectal cancer were invited to fill out an online questionnaire, including a choice-based conjoint experiment. Participants were presented 14 comparisons of two hypothetical case presentations, characterized by different treatments and outcomes of care (6 attributes) and were asked to select the case with the best outcome at that moment. Hierarchical Bayes Estimation was used to calculate the relative importance (RI) of each of the six attributes. RESULTS: In total, 94 patients and 128 clinicians completed the questionnaire. For patients, avoiding surgery with permanent stoma was most important (RI 24.4, 95%CI 21.88-26.87) and a 2-year difference in disease-free survival was least important (RI 5.6, 95%CI 4.9-6.2). Clinicians assigned highest importance to avoiding severe and daily worries about cancer recurrence (RI 30.7, 95%CI 29.1-32.4), while this was ranked 4th by patients (RI 17.9, 95%CI 16.5-19.4, p < 0.001). CONCLUSION: When confronted with different outcomes within one case description, patients find the duration of disease free survival the least important. In addition, considerable differences were found between the importance assigned by patients and clinicians to clinical and functional outcomes, most notably in avoiding surgery with permanent stoma and worries about recurrence.

Isolated hypoxic hepatic perfusion with retrograde outflow in patients with irresectable liver metastases; a new simplified technique in isolated hepatic perfusion.

BACKGROUND: Isolated hepatic perfusion with high-dose chemotherapy is a treatment option for patients with irresectable metastases confined to the liver. Prolonged local control and impact on survival have been claimed. Major drawbacks are magnitude and costs of the procedure. We developed an isolated hypoxic hepatic perfusion (IHHP) with retrograde outflow without the need for a heart-lung machine. PATIENTS AND METHODS: Twenty-four consecutive patients with irresectable metastases of various origins were treated. IHHP inflow was via the hepatic artery, outflow via the portal vein with occlusion of the retrohepatic caval vein. Radiolabeled albumine was used for leakage monitoring. Melphalan was used at 1-2 mg/kg. A 25-minute perfusion period was followed by a complete washout. Local and systemic melphalan concentrations were determined. RESULTS: Compared with oxygenated classical IHP, the IHPP procedure reduced operation time from >8 h to 4 hours, blood loss from >4000 to 900 cc and saved material and personnel costs. Leakage was 0% with negligible systemic toxicity and 0% perioperative mortality. Tumor response: complete response (CR) in 4%, partial response (PR) in 58%, and stable disease (SD) in 13%. Median time to progression was 9 months (2-24 months); pharmacokinetics demonstrated intrahepatic melphalan concentrations more than 9 fold higher than postperfusion systemic concentrations. CONCLUSIONS: IHPP is a relatively simple procedure with reduced costs, reduced blood loss, no mortality, limited toxicity, and response rates comparable to classic IHP. The median duration of 9 months of tumor control should be improved. Hereto, vasoactive drugs, will be explored in further studies.

Laparoscopic ileocolic resection versus infliximab treatment of distal ileitis in Crohn's disease: a randomized multicenter trial (LIR!C-trial).

BACKGROUND: With the availability of infliximab, nowadays recurrent Crohn's disease, defined as disease refractory to immunomodulatory agents that has been treated with steroids, is generally treated with infliximab. Infliximab is an effective but expensive treatment and once started it is unclear when therapy can be discontinued. Surgical resection has been the golden standard in recurrent Crohn's disease. Laparoscopic ileocolic resection proved to be safe and is characterized by a quick symptom reduction. The objective of this study is to compare infliximab treatment with laparoscopic ileocolic resection in patients with recurrent Crohn's disease of the distal ileum with respect to quality of life and costs. METHODS/DESIGN: The study is designed as a multicenter randomized clinical trial including patients with Crohn's disease located in the terminal ileum that require infliximab treatment following recent consensus statements on inflammatory bowel disease treatment: moderate to severe disease activity in patients that fail to respond to steroid therapy or immunomodulatory therapy. Patients will be randomized to receive either infliximab or undergo a laparoscopic ileocolic resection. Primary outcomes are quality of life and costs. Secondary outcomes are hospital stay, early and late morbidity, sick leave and surgical recurrence. In order to detect an effect size of 0.5 on the Inflammatory Bowel Disease Questionnaire at a 5% two sided significance level with a power of 80%, a sample size of 65 patients per treatment group can be calculated. An economic evaluation will be performed by assessing the marginal direct medical, non-medical and time costs and the costs per Quality Adjusted Life Year (QALY) will be calculated. For both treatment strategies a cost-utility ratio will be calculated. Patients will be included from December 2007. DISCUSSION: The LIR!C-trial is a randomized multicenter trial that will provide evidence whether infliximab treatment or surgery is the best treatment for recurrent distal ileitis in Crohn's disease. TRIAL REGISTRATION: Nederlands Trial Register NTR1150.

Colonic stenting as bridge to surgery versus emergency surgery for management of acute left-sided malignant colonic obstruction: a multicenter randomized trial (Stent-in 2 study).

BACKGROUND: Acute left-sided colonic obstruction is most often caused by malignancy and the surgical treatment is associated with a high mortality and morbidity rate. Moreover, these operated patients end up with a temporary or permanent stoma. Initial insertion of an enteral stent to decompress the obstructed colon, allowing for surgery to be performed electively, is gaining popularity. In uncontrolled studies stent placement before elective surgery has been suggested to decrease mortality, morbidity and number of colostomies. However stent perforation can lead to peritoneal tumor spill, changing a potentially curable disease in an incurable one. Therefore it is of paramount importance to compare the outcomes of colonic stenting followed by elective surgery with emergency surgery for the management of acute left-sided malignant colonic obstruction in a randomized multicenter fashion. METHODS/DESIGN: Patients with acute left-sided malignant colonic obstruction eligible for this study will be randomized to either emergency surgery (current standard treatment) or colonic stenting as bridge to elective surgery. Outcome measurements are effectiveness and costs of both strategies. Effectiveness will be evaluated in terms of quality of life, morbidity and mortality. Quality of life will be measured with standardized questionnaires (EORTC QLQ-C30, EORTC QLQ-CR38, EQ-5D and EQ-VAS). Morbidity is defined as every event leading to hospital admission or prolonging hospital stay. Mortality will be analyzed as total mortality as well as procedure-related mortality. The total costs of treatment will be evaluated by counting volumes and calculating unit prices. Including 120 patients on a 1:1 basis will have 80% power to detect an effect size of 0.5 on the EORTC QLQ-C30 global health scale, using a two group t-test with a 0.05 two-sided significance level. Differences in quality of life and morbidity will be analyzed using mixed-models repeated measures analysis of variance. Mortality will be compared using Kaplan-Meier curves and log-rank statistics. DISCUSSION: The Stent-in 2 study is a randomized controlled multicenter trial that will provide evidence whether or not colonic stenting as bridge to surgery is to be performed in patients with acute left-sided colonic obstruction. TRIAL REGISTRATION: Current Controlled Trials ISRCTN46462267.

In vivo dosimetry with MOSFETs and GAFCHROMIC films during electron IORT for Accelerated Partial Breast Irradiation.

PURPOSE: The purpose of this study was to compare the delivered dose to the expected intraoperative radiation therapy (IORT) dose with in vivo dosimetry. For IORT using electrons in accelerated partial breast irradiation, this is especially relevant since a high dose is delivered in a single fraction. METHODS: For 47 of breast cancer patients, in vivo dosimetry was performed with MOSFETs and/or GAFCHROMIC EBT2 films. A total dose of 23.33 Gy at dmax was given directly after completing the lumpectomy procedure with electron beams generated with an IORT dedicated mobile accelerator. A protection disk was used to shield the thoracic wall. RESULTS: The results of in vivo MOSFET dosimetry for 27 patients and GAFROMIC film dosimetry for 20 patients were analysed. The entry dose for the breast tissue, measured with MOSFETs, (mean value 22.3 Gy, SD 3.4%) agreed within 1.7% with the expected dose (mean value 21.9 Gy). The dose in breast tissue, measured with GAFCHROMIC films (mean value 23.50 Gy) was on average within 0.7% (SD = 3.7%, range -5.5% to 5.6%) of the prescribed dose of 23.33 Gy. CONCLUSIONS: The dose measured with MOSFETs and GAFROMIC EBT2 films agreed well with the expected dose. For both methods, the dose to the thoracic wall, lungs and heart for left sided patents was lower than 2.5 Gy even when 12 MeV was applied. The positioning time of GAFCHROMIC films is negligible and based on our results we recommend its use as a standard tool for patient quality assurance during breast cancer IORT.

Long-Term Health-Related Quality of Life in Patients With Rectal Cancer After Preoperative Short-Course and Long-Course (Chemo) Radiotherapy.

BACKGROUND: Both preoperative short-course radiotherapy (SC-PRT) and preoperative long-course chemo radiotherapy (CRT) have shown to reduce local recurrence rates after total mesorectal excision (TME), but neither resulted in improved survival. This study compared the long-term health-related quality of life (HRQL) and symptoms between CRT and SC-PRT. METHODS: Patients who were preoperatively treated with a total dose of 50.0 to 50.4 Gy for locally advanced rectal cancers were identified from 2 hospital registries. Starting from 2011, all patients who were disease-free in the study population (n = 105) were sent a HRQL-questionnaire composed of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and questions on bowel and urinary function. Patients who underwent SC-PRT in the TME trial were used as a reference group. RESULTS: HRQL results from 85 patients receiving CRT (81.0%), with a median follow-up time of 58 months, were compared with the results of patients who underwent SC-PRT (n = 306). Apart from more nausea and vomiting reported by patients receiving CRT (mean score for CRT 5.9 vs. 1.3 for SC-PRT; P < .01; not clinically relevant) and less satisfaction with urinary function indicated by patients who received CRT (mean score for CRT 71.2 vs. 81.2 for SC-PRT; P < .01), no significant differences were found in HRQL and symptoms between patients who received CRT and SC-PRT. CONCLUSIONS: This analysis of HRQL in patients who received CRT shows no clinically relevant differences in long-term HRQL and symptoms between patients who received CRT and SC-PRT, apart from less satisfaction with urinary function reported by patients who received CRT. These results indicate that both approaches have a comparable impact on long-term HRQL.

Acute toxicity after a diverting stoma and spacer prior to chemoradiation in locally advanced rectal cancer.

BACKGROUND AND PURPOSE: Chemoradiotherapy (CRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC). For grade ⩾3 acute diarrhea there is a relationship between dose and irradiated small bowel volume. The aim of this study was to evaluate whether combined placement of a diverting stoma and sigmoid spacer (DSSS) led to reduced irradiated small bowel volume and less grade ⩾3 acute diarrhea in the treatment of LARC. MATERIALS/METHODS: Between 2003 and 2010, 54 of 189 LARC patients treated with CRT in two institutions had a DSSS prior to CRT. Data on patient and treatment characteristics and outcomes were collected retrospectively. Delineation of small bowel was performed with planning CT-scans. CTCAE version 4.0 was used for acute toxicity. RESULTS: Patients with a DSSS had significantly less small bowel volume irradiated up to doses of 20Gy. This difference was not observed for the higher dose levels. CRT induced grade ⩾3 acute diarrhea was not different between the two groups (8.3% vs. 12.8%; p=0.41). CONCLUSION: DSSS is not clearly beneficial to reduce grade ⩾3 acute diarrhea, and it must be considered whether placement of a DSSS is justified for this purpose.

[Breast-conserving surgery and radiotherapy as a one-day procedure]. / Borstsparende ingreep en bestraling in dagbehandeling.

A single dose of irradiation to the lumpectomy cavity alone after breast-conserving surgery in breast cancer patients has been available in the Netherlands since 2011. This new treatment modality is used in the Haaglanden Medical Centre in The Hague and in the Catharina Hospital in Eindhoven. The goal of intraoperative radiation therapy is to limit the patient burden caused by whole breast irradiation, while maintaining excellent local tumour control. The technique is used only in patients with a low probability of recurrent disease in the breast. Approximately 150 patients receive intraoperative radiation therapy each year In the Netherlands, an estimated 4,000 breast cancer patients were eligible in 2013 for this new treatment technique or another method of partial breast irradiation. In both hospitals the results are closely monitored. Only 15 of the first 200 patients experienced a side effect within a period of 3 months after intraoperative radiation therapy. These side effects were successfully treated either with antibiotics or with surgery.

The role of allopurinol in human liver ischemia/reperfusion injury: a prospective randomized clinical trial.

BACKGROUND/AIMS: To investigate the effect of pretreatment with allopurinol on oxidative stress during reperfusion and the role in liver tissue protection in partial liver resections for colorectal cancer metastases confined to the liver. METHODOLOGY: Prospective, randomized, clinical trial, single center, Leiden University Medical Center, The Netherlands. SUBJECTS: Curative partial liver resection of colorectal metastases in 16 patients with or without allopurinol pretreatment, between June 1992 and February 1994. INTERVENTIONS: Partial liver resections with Pringle maneuver, intravenous allopurinol versus no allopurinol. OUTCOME MEASURES: The effect of allopurinol on liver cell damage caused by ischemia/reperfusion studied by measuring malondialdehyde, glutathione, glutathione disulfide, vitamin C, liver enzymes and blood clotting factors in blood samples. Morbidity and mortality were also evaluated. RESULTS: Pretreatment with allopurinol had no significant effect on any of our study parameters. CONCLUSIONS: Because ischemia/reperfusion damage is little in our study, pretreatment with allopurinol is of no value.