DNA hypermethylation is common in colon cancer. Previously, we have shown that methylation of WNT target genes predicts poor prognosis in stage II colon cancer. The primary objective of this study ...was to assess whether pre-operative treatment with decitabine can decrease methylation and increase the expression of WNT target genes APCDD1, AXIN2 and DKK1 in colon cancer patients. A clinical study was conducted, investigating these potential effects of decitabine in colon cancer patients (DECO). Patients were treated two times with 25 mg/m2 decitabine before surgery. Methylation and expression of LINE1 and WNT target genes (primary outcome) and expression of endogenous retroviral genes (secondary outcome) were analysed in pre- and post-treatment tumour samples using pyrosequencing and rt-PCR. Ten patients were treated with decitabine and eighteen patients were used as controls. Decitabine treatment only marginally decreased LINE1 methylation. More importantly, no differences in methylation or expression of WNT target or endogenous retroviral genes were observed. Due to the lack of an effect on primary and secondary outcomes, the study was prematurely closed. In conclusion, pre-operative treatment with decitabine is safe, but with the current dosing, the primary objective, increased WNT target gene expression, cannot be achieved.
Purpose
Resection of pediatric osteosarcoma in the extremities with soft tissue involvement presents surgical challenges due to difficult visualization and palpation of the tumor. Therefore, an ...adequate image-guided surgery (IGS) system is required for more accurate tumor resection. The use of a 3D model in combination with intraoperative tracked ultrasound (iUS) may enhance surgical decision making. This study evaluates the clinical feasibility of iUS as a surgical tool using a porcine cadaver model.
Methods
First, a 3D model of the porcine lower limb was created based on preoperative scans. Second, the bone surface of the tibia was automatically detected with an iUS by a sweep on the skin. The bone surface of the preoperative 3D model was then matched with the bone surface detected by the iUS. Ten artificial targets were used to calculate the target registration error (TRE). Intraoperative performance of iUS IGS was evaluated by six pediatric surgeons and two pediatric oncologic orthopedists. Finally, user experience was assessed with a post-procedural questionnaire.
Results
Eight registration procedures were performed with a mean TRE of 6.78 ± 1.33 mm. The surgeons agreed about the willingness for clinical implementation in their current clinical practice. They mentioned the additional clinical value of iUS in combination with the 3D model for the localization of the soft tissue components of the tumor. The concept of the proposed IGS system is considered feasible by the clinical panel, but the large TRE and degree of automation need to be addressed in further work.
Conclusion
The participating pediatric surgeons and orthopedists were convinced of the clinical value of the interaction between the iUS and the 3D model. Further research is required to improve the surgical accuracy and degree of automation of iUS-based registration systems for the surgical management of pediatric osteosarcoma.
IntroductionThe efficacy of taurolidine containing lock solutions for the prevention of central line-associated bloodstream infections (CLABSI) in paediatric oncology patients is still unknown. If ...the taurolidine-citrate-heparin lock appears to decrease the incidence of CLABSIs, we hope to increase the quality of life of children with cancer by subsequently reducing the central venous access device (CVAD)-removal rates, dispense of antibiotics, hospital admissions and incidence of severe sepsis resulting in intensive care unit admission.Methods and analysisThis assessor-blinded randomised controlled trial including 462 patients was designed to compare the taurolidine-citrate-heparin lock to the heparin-only lock for the prevention of CLABSIs in paediatric oncology patients. Patients receiving their first CVAD at the Princess Máxima Centre for Paediatric Oncology, Utrecht, the Netherlands, are eligible for inclusion. The primary outcome of this study is the incidence of first CLABSIs from CVAD insertion until the end of the study, maximum follow-up of 90 days. An intention-to-treat and a per-protocol analysis will be performed. An interim analysis will be performed after the inclusion of 50% of the patients. The results of the interim analysis and overall conduct of the trial will be discussed by a data safety monitoring board.Ethics and disseminationThe medical ethics committee NedMec, Utrecht, the Netherlands, has approved this research (number 20/370). Written informed consent for participation in this trial and publication of the trial data is obtained from all patients and/or their parents/guardians. The results of this trial will be published in a peer-reviewed journal and the data will be made available on reasonable request after publication of the main results manuscript.Trial registration numbersNTR6688; NCT05740150.
Purpose
The aim of this study was to evaluate whether implementation of a comprehensive quality improvement program was associated with improved outcomes in patients undergoing oncological colorectal ...surgery in a non-academic, non-referral community hospital.
Methods
The quality improvement program (QIP) was introduced in January 2011 and consisted of the following interventions: (1) avoidance of postoperative nonsteriodal anti-inflammatory drugs; (2) normovolemia was pursued pre- and postoperatively; (3) non-resectional surgery if possible, in patients over 80 with ASA 3 or 4 classification; and (4) a standardized, postoperative surveillance protocol was introduced, with CRP determination day 2 and 4, and if necessary subsequent abdominal CT with rectal contrast to reduce delay in diagnosis of complications. From a prospectively maintained database of 488 patients undergoing colorectal surgery between 2009 and 2014, postoperative outcomes of patients operated before and after implementation of the program were compared.
Results
The severe complication rate (Clavien-Dindo >3b) decreased significantly (25.0 vs. 13.7 %;
p
< .001) after implementation of the QIP program. The mortality rate dropped from 8.7 to 2.6 % (
p
= .003). The percentage of anastomotic leakage was 9.6% before QIP implementation and 4.2% after (
p
= .013). Median length of hospital stay decreased from 9 (IQR 5–19) to 7 days (IQR 4–12) (
p
< .001). Multivariate analyses showed that surgery after implementation of the program was a strong independent predictor for less major complications (OR 0.54, 95 % CI 0.32–0.88).
Conclusions
A significant decrease in major complications and mortality was observed after introduction of a relative simple quality improvement program.
Nephron-sparing surgery can be considered in well-defined cases of unilateral and bilateral Wilms tumors, but the surgical procedure can be very challenging for the pediatric surgeon to perform.
To ...assess the added value of personalized 3-dimensional (3-D) kidney models derived from conventional imaging data to enhance preoperative surgical planning.
In a survey study, the conventional imaging data of 10 Dutch children with Wilms tumors were converted to 3-D prints and augmented reality (AR) holograms and a panel of pediatric oncology surgeons (n = 7) assessed the quality of the different imaging methods during preoperative evaluation. Kidney models were created with 3-D printing and AR using a mixed reality headset for visualization.
Differences in the assessment of 4 anatomical structures (tumor, arteries, veins, and urinary collecting structures) using questionnaires. A Likert scale measured differences between the imaging methods, with scores ranging from 1 (completely disagree) to 5 (completely agree).
Of the 10 patients, 7 were girls, and the mean (SD) age was 3.7 (1.7) years. Compared with conventional imaging, the 3-D print and the AR hologram models were evaluated by the surgeons to be superior for all anatomical structures: tumor (median scores for conventional imaging, 4.07; interquartile range IQR, 3.62-4.15 vs 3-D print, 4.67; IQR, 4.14-4.71; P = .008 and AR hologram, 4.71; IQR, 4.26-4.75; P = .002); arteries (conventional imaging, 3.62; IQR, 3.43-3.93 vs 3-D print, 4.54; IQR, 4.32-4.71; P = .002 and AR hologram, 4.83; IQR, 4.64-4.86; P < .001), veins (conventional imaging, 3.46; IQR 3.39-3.62 vs 3-D print, 4.50; IQR, 4.39-4.68; P < .001 and AR hologram, 4.83; IQR, 4.71-4.86; P < .001), and urinary collecting structures (conventional imaging, 2.76; IQR, 2.42-3.00 vs 3-D print, 3.86; IQR, 3.64-4.39; P < .001 and AR hologram, 4.00; IQR, 3.93-4.58; P < .001). There were no differences in anatomical assessment between the two 3-D techniques (the 3-D print and AR hologram).
In this study, the 3-D kidney models were associated with improved anatomical understanding among the surgeons and can be helpful in future preoperative planning of nephron-sparing surgery for Wilms tumors. These models may be considered as a supplementary visualization in clinical care.
Background
The aim of this study was to compare perineal wound healing between gluteal turnover flap and primary closure in patients undergoing abdominoperineal resection (APR) for rectal cancer.
...Methods
Patients who underwent APR for primary or recurrent rectal cancer with gluteal turnover flap in two university hospitals (2016–2021) were compared to a multicentre cohort of primary closure (2000–2017). The primary endpoint was uncomplicated perineal wound healing within 30 days. Secondary endpoints were long-term wound healing, related re-interventions, and perineal herniation. The perineal hernia rate was assessed using Kaplan Meier analysis.
Results
Twenty–five patients had a gluteal turnover flap and 194 had primary closure. The uncomplicated perineal wound-healing rate within 30 days was 68% (17/25) after gluteal turnover flap versus 64% (124/194) after primary closure, OR 2.246; 95% CI 0.734–6.876;
p
= 0.156 in multivariable analysis. No major wound complications requiring surgical re-intervention occurred after flap closure. Eighteen patients with gluteal turnover flap completed 12-month follow-up, and none of them had chronic perineal sinus, compared to 6% (11/173) after primary closure (
p
= 0.604). The symptomatic 18-month perineal hernia rate after flap closure was 0%, compared to 9% after primary closure (
p
= 0.184).
Conclusions
The uncomplicated perineal wound-healing rate after the gluteal turnover flap and primary closure after APR is similar, and no chronic perineal sinus or perineal hernia occurred after flap closure. Future studies have to confirm potential benefits of the gluteal turnover flap.
Surgical treatment of pediatric chest wall tumors requires accurate surgical planning and tumor localization to achieve radical resections while sparing as much healthy tissue as possible. Augmented ...Reality (AR) could facilitate surgical decision making by improving anatomical understanding and intraoperative tumor localization.
We present our clinical experience with the use of an AR system for intraoperative tumor localization during chest wall resections. Furthermore, we present the pre-clinical results of a new registration method to improve our conventional AR system.
From January 2021, we used the HoloLens 2 for pre-incisional tumor localization during all chest wall resections inside our center. A patient-specific 3D model was projected onto the patient by use of a five-point registration method based on anatomical landmarks. Furthermore, we developed and pre-clinically tested a surface matching method to allow post-incisional AR guidance by performing registration on the exposed surface of the ribs.
Successful registration and holographic overlay were achieved in eight patients. The projection seemed most accurate when landmarks were positioned in a non-symmetric configuration in proximity to the tumor. Disagreements between the overlay and expected tumor location were mainly due to user-dependent registration errors. The pre-clinical tests of the surface matching method proved the feasibility of registration on the exposed ribs.
Our results prove the applicability of AR guidance for the pre- and post-incisional localization of pediatric chest wall tumors during surgery. The system has the potential to enable intraoperative 3D visualization, hereby facilitating surgical planning and management of chest wall resections.
IV
Treatment Study
•What is currently known about this topic?
Augmented Reality is a visualization technique that can give a direct impression of the patient's anatomy in 3D and therefore has great potential within surgical applications.•What new information is contained in this article?
This article presents the clinical application and further development of an AR system for intraoperative tumor localization during pediatric chest wall resections.
Substantial variation exists when performing a minimally invasive right hemicolectomy (MIRH) due to disparities in training, expertise and differences in implementation of innovations. This study ...aimed to achieve national consensus on an optimal and standardized MIRH technique for colon cancer and to develop and validate a video-based competency assessment tool (CAT) for MIRH.
Statements covering all elements of MIRH were formulated. Subsequently, the Delphi technique was used to reach consensus on a standardized MIRH among 76 colorectal surgeons from 43 different centres. A CAT was developed based on the Delphi results. Nine surgeons assessed the same 12 unedited full-length videos using the CAT, allowing evaluation of the intraclass correlation coefficient (ICC).
After three Delphi rounds, consensus (≥80% agreement) was achieved on 23 of the 24 statements. Consensus statements included the use of low intra-abdominal pressure, detailed anatomical outline how to perform complete mesocolic excision with central vascular ligation, the creation of an intracorporeal anastomosis, and specimen extraction through a Pfannenstiel incision using a wound protector. The CAT included seven consecutive steps to measure competency of the MIRH and showed high consistency among surgeons with an overall ICC of 0.923.
Nationwide consensus on a standardized and optimized technique of MIRH was reached. The CAT developed showed excellent interrater reliability. These achievements are crucial steps to an ongoing nationwide quality improvement project (the Right study).
Abstract
Background
Abdominoperineal resection (APR) for rectal cancer is associated with high morbidity of the perineal wound, and controversy exists about the optimal closure technique. Primary ...perineal wound closure is still the standard of care in the Netherlands. Biological mesh closure did not improve wound healing in our previous randomised controlled trial (BIOPEX-study). It is suggested, based on meta-analysis of cohort studies, that filling of the perineal defect with well-vascularised tissue improves perineal wound healing. A gluteal turnover flap seems to be a promising method for this purpose, and with the advantage of not having a donor site scar. The aim of this study is to investigate whether a gluteal turnover flap improves the uncomplicated perineal wound healing after APR for rectal cancer.
Methods
Patients with primary or recurrent rectal cancer who are planned for APR will be considered eligible in this multicentre randomised controlled trial. Exclusion criteria are total exenteration, sacral resection above S4/S5, intersphincteric APR, biological mesh closure of the pelvic floor, collagen disorders, and severe systemic diseases. A total of 160 patients will be randomised between gluteal turnover flap (experimental arm) and primary closure (control arm). The total follow-up duration is 12 months, and outcome assessors and patients will be blinded for type of perineal wound closure. The primary outcome is the percentage of uncomplicated perineal wound healing on day 30, defined as a Southampton wound score of less than two. Secondary outcomes include time to perineal wound closure, incidence of perineal hernia, the number, duration and nature of the complications, re-interventions, quality of life and urogenital function.
Discussion
The uncomplicated perineal wound healing rate is expected to increase from 65 to 85% by using the gluteal turnover flap. With proven effectiveness, a quick implementation of this relatively simple surgical technique is expected to take place.
Trial registration
The trial was retrospectively registered at Clinicaltrials.gov
NCT04004650
on July 2, 2019.
The role of zoledronic acid (ZA) when added to the neoadjuvant treatment of breast cancer (BC) in enhancing the clinical and pathological response of tumors is unclear. The effect of ZA on the ...antitumor effect of neoadjuvant chemotherapy has not prospectively been studied before.
NEOZOTAC is a national, multicenter, randomized study comparing the efficacy of TAC (docetaxel, adriamycin and cyclophosphamide i.v.) followed by granulocyte colony-stimulating factor on day 2 with or without ZA 4mg i.v. q 3 weeks inpatients withstage II/III, HER2-negative BC. We present data on the pathological complete response (pCR in breast and axilla), on clinical response using MRI, and toxicity. Post hoc subgroup analyses were undertaken to address the predictive value of menopausal status.
Addition of ZA to chemotherapy did not improve pCR rates (13.2% for TAC+ZA versus 13.3% for TAC). Postmenopausal women (N = 96) had a numerical benefit from ZA treatment (pCR 14.0% for TAC+ZA versus 8.7% for TAC, P = 0.42). Clinical objective response did not differ between treatment arms (72.9% versus 73.7%). There was no difference in grade III/IV toxicity between treatment arms.
Addition of ZA to neoadjuvant chemotherapy did not improve pathological or clinical response to chemotherapy. Further investigations are warranted in postmenopausal women with BC, since this subgroup might benefit from ZA treatment.
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