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Surgery for locally recurrent rectal cancer (LRRC) presents several challenges, which is why the percentage of inadequate resections of these tumors is high. In this exploratory study, we evaluate the use of image-guided surgical navigation during resection of LRRC. Patients who were scheduled to undergo surgical resection of LRRC who were deemed by the multidisciplinary team to be at a high risk of inadequate tumor resection were selected to undergo surgical navigation. The risk of inadequate surgery was further determined by the proximity of the tumor to critical anatomical structures. Workflow characteristics of the surgical navigation procedure were evaluated, while the surgical outcome was determined by the status of the resection margin. In total, 20 patients were analyzed. For all procedures, surgical navigation was completed successfully and demonstrated to be accurate, while no complications related to the surgical navigation were discerned. Radical resection was achieved in 14 cases (70%). In five cases (25%), a tumor-positive resection margin (R1) was anticipated during surgery, as extensive radical resection was determined to be compromised. These patients all received intraoperative brachytherapy. In one case (5%), an unexpected R1 resection was performed. Surgical navigation during resection of LRRC is thus safe and feasible and enables accurate surgical guidance.

In the last decades, laparoscopic surgery has become the gold standard in patients with colorectal cancer. To overcome the drawback of reduced tactile feedback, real-time tissue classification could be of great benefit. In this ex vivo study, hyperspectral imaging (HSI) was used to distinguish tumor tissue from healthy surrounding tissue. A sample of fat, healthy colorectal wall, and tumor tissue was collected per patient and imaged using two hyperspectral cameras, covering the wavelength range from 400 to 1700 nm. The data were randomly divided into a training (75%) and test (25%) set. After feature reduction, a quadratic classifier and support vector machine were used to distinguish the three tissue types. Tissue samples of 32 patients were imaged using both hyperspectral cameras. The accuracy to distinguish the three tissue types using both hyperspectral cameras was 0.88 (STD  =  0.13) on the test dataset. When the accuracy was determined per patient, a mean accuracy of 0.93 (STD  =  0.12) was obtained on the test dataset. This study shows the potential of using HSI in colorectal cancer surgery for fast tissue classification, which could improve clinical outcome. Future research should be focused on imaging entire colon/rectum specimen and the translation of the technique to an intraoperative setting.

Purpose This nationwide study evaluated results of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal metastasis of colorectal origin in the Netherlands following a national protocol. Methods In a multi-institutional study prospective databases of patients with peritoneal carcinomatosis (PC) from colorectal cancer and pseudomyxoma peritonei (PMP) treated according to the Dutch HIPEC protocol, a uniform approach for the CRS and HIPEC treatment, were reviewed. Primary end point was overall survival and secondary end points were surgical outcome and progression-free survival. Results Nine-hundred sixty patients were included; 660 patients (69 %) were affected by PC of colorectal carcinoma and the remaining suffered from PMP (31 %). In 767 procedures (80 %), macroscopic complete cytoreduction was achieved. Three-hundred and thirty one patients had grade III–V complications (34 %). Thirty-two patients died perioperatively (3 %). Median length of hospital stay was 16 days (range 0–166 days). Median follow-up period was 41 months (95 % confidence interval (CI), 36–46 months). Median progression-free survival was 15 months (95 % CI 13–17 months) for CRC patients and 53 months (95 % CI 40–66 months) for PMP patients. Overall median survival was 33 (95 % CI 28–38 months) months for CRC patients and 130 months (95 % CI 98–162 months) for PMP patients. Three- and five-year survival rates were 46 and 31 % respectively in case of CRC patients and 77 and 65 % respectively in case of PMP patients. Conclusions The results underline the safety and efficacy of cytoreduction and HIPEC for PC from CRC and PMP. It is assumed the uniform Dutch HIPEC protocol was beneficial.

ObjectiveThe aim of this study was to determine whether the extent of peritoneal metastases (PMs) on preoperative diffusion-weighted magnetic resonance imaging (DW-MRI) can be used as a biomarker of disease-free and overall survival in patients with colorectal cancer who are considered for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).MethodsFor this retrospective cohort study, patients with PMs considered for CRS/HIPEC who underwent DW-MRI for preoperative staging in 2016–2017 were included. The DW-MRI protocol consisted of diffusion-weighted, T2-weighted, and pre- and post-gadolinium T1-weighted imaging of the chest, abdomen, and pelvis. DW-MRI images were evaluated by two independent readers to determine the extent of PMs represented by the Peritoneal Cancer Index (MRI-PCI), as well as extraperitoneal metastases. Cox regression and Kaplan–Meier analysis was performed to determine the prognostic value of DW-MRI for overall and disease-free survival.ResultsSeventy-eight patients were included. CRS/HIPEC was planned for 53 patients and completed in 50 patients (60.5%). Median follow-up after DW-MRI was 23 months (interquartile range 13–24). The MRI-PCI of both readers showed prognostic value for overall survival, independently of whether R1 resection was achieved (hazard ratio [HR] 1.06–1.08; p < 0.05). For the patients who received successful CRS/HIPEC, the MRI-PCI also showed independent prognostic value for disease-free survival for both readers (HR 1.09–1.10; p < 0.05).ConclusionThe extent of PMs on preoperative DW-MRI is an independent predictor of overall and disease-free survival and should therefore be considered as a non-invasive prognostic biomarker.

Background Experience with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in a pioneer hospital resulted in a treatment protocol that has become the standard in the Netherlands. Outcome of CRS and HIPEC was reviewed to assure differences between the pioneer phase and the period wherein the Dutch HIPEC protocol was clinically implemented. Methods The first consecutive 100 CRS and HIPEC procedures performed in the Netherlands were included as pioneer cohort (1995–1999). Two-hundred and seventy-two procedures that were performed in three participating HIPEC centres after the implementation of the Dutch HIPEC protocol were included as the implementation cohort (2005–2012). Another 100 recent patients of the first centre were included as a control group (2009–2011). Indications for the CRS and HIPEC treatment were peritoneal carcinomatosis (PC) from colorectal carcinoma and pseudomyxoma peritonei (PMP). Results Of the 472 included procedures, 327 (69 %) procedures were performed for PC from colorectal carcinoma and 145 for PMP (31 %). Compared with the implementation phase, the pioneer phase was characterized by more affected abdominal regions (mean 4.3 vs. 3.5, p  < 0.001), more resections (mean 3.8 vs. 3.4, p  < 0.001), less macroscopic radical cytoreductions (66 vs. 86 %, p  < 0.001) and more patients with major morbidity (grade III–V) (64 vs. 32 %, p  < 0.001). Other determinants of morbidity were high tumour load and multiple organ resections. Outcome of the implementation phase was similar to the control group. Conclusions This study determined that outcome had improved ever since the Dutch HIPEC protocol has been implemented based on completeness of cytoreduction and decreasing morbidity.

PurposeRight-sided colon tumors with peritoneal metastases (PM) are associated with a poorer prognosis than left-sided tumors. We hypothesized that a different pattern of spread could be characterized with abdominopelvic MRI. The objective of this study was to explore the spread of PM in relation to the primary tumor location on MRI.MethodsThis is a retrospective cohort study of patients with PM from colon cancer referred to be considered for CRS-HIPEC at a single tertiary referral center. Patients with colon cancer were eligible if they had undergone an abdominopelvic MRI scan following a clinical diagnosis of PM. The frequency of affected PCI regions on MRI (MRI-PCI) was assessed and compared between tumor sidedness.ResultsOne hundred eighteen patients were included with a median age of 65 (IQR: 56–72). 46% percent were male. The median MRI-PCI was 10 (IQR: 5–16) and 8 (IQR: 4–11) for right- and left-sided tumors, respectively (p = 0.39), and the median number of affected regions was 4 (IQR: 2–7 for right-sided and IQR 2–5 for left-sided tumors). PM was most frequently found close to the primary tumor. The odds ratio of patients with PM of left sided to be affected with PM in the upper abdominal regions was 0.42 (95% CI: 0.20–0.90) and with PM on the small bowels or mesentery was 0.42 (95% CI: 0.19–0.92) over a patient with PM of right-sided colon cancer.ConclusionMRI can help to assess the spread of PM in colonic cancer. In right-sided tumors, the small bowel and upper abdominal regions are more frequently affected.

BackgroundUrachal adenocarcinoma (UrAC) is a rare malignancy that can cause peritoneal metastases (PM). Analogous to other enteric malignancies, selected patients with limited PM of UrAC can be treated by cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC).ObjectiveThe aim of this study was to address the value of diagnostic laparoscopy (DLS) and abdominal cytology (ACyt) for the detection and evaluation of the extent of PM in patients with UrAC.MethodsA consecutive series of cN0M0 patients with UrAC who underwent DLS with or without ACyt at a tertiary referral center between 2000 and 2018 was assessed. Patients were staged with computed tomography (CT) and/or positron emission tomography (PET)/CT or bone scan. DLS was performed to rule out PM and to evaluate the extent and resectability of PM if seen on imaging. Sensitivity and specificity values were calculated for imaging, DLS, ACyt, and the combination of DLS and ACyt.ResultsThirty-two patients with UrAC underwent DLS. ACyt was obtained in 19 patients. Four patients had suspicion of PM on imaging. In the 28 patients who were PM-negative on imaging, DLS and ACyt revealed PM in 6 (21%) patients, of whom 5 had macroscopically visible PM; 1 patient had positive ACyt without visible PM. Sensitivity of combined DLS/ACyt for the detection of PM was 91%, with a specificity of 100%, whereas sensitivity of imaging was 36%. DLS correctly predicted resectability in all patients.ConclusionCombined DLS/ACyt proved an effective tool to detect occult PM and to evaluate the extent of PM to select UrAC patients for possible treatment with CRS/HIPEC.

In the past decades, image-guided surgery has evolved rapidly. In procedures with a relatively fixed target area, like neurosurgery and orthopedics, this has led to improved patient outcomes. In cancer surgery, intraoperative guidance could be of great benefit to secure radical resection margins since residual disease is associated with local recurrence and poor survival. However, most tumor lesions are mobile with a constantly changing position. Here, we present an innovative technique for real-time tumor tracking in cancer surgery. In this study, we evaluated the feasibility of real-time tumor tracking during rectal cancer surgery. The application of real-time tumor tracking using an intraoperative navigation system is feasible and safe with a high median target registration accuracy of 3 mm. This technique allows oncological surgeons to obtain real-time accurate information on tumor location, as well as critical anatomical information. This study demonstrates that real-time tumor tracking is feasible and could potentially decrease positive resection margins and improve patient outcome.

The OVHIPEC-1 trial previously showed that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval cytoreductive surgery resulted in improved progression-free and overall survival compared with cytoreductive surgery alone at 4·7 years of follow-up in patients with stage III epithelial ovarian cancer who were ineligible for primary cytoreduction. We report the final survival outcomes after 10 years of follow-up. In this open-label, randomised, controlled, phase 3 trial, patients with primary epithelial stage III ovarian cancer were recruited at eight HIPEC centres in the Netherlands and Belgium. Patients were eligible if they were aged 18–76 years, had not progressed during at least three cycles of neoadjuvant carboplatin plus paclitaxel, had a WHO performance status score of 0–2, normal blood counts, and adequate renal function. Patients were randomly assigned (1:1) to undergo interval cytoreductive surgery without HIPEC (surgery group) or with HIPEC (100 mg/m2 cisplatin; surgery-plus-HIPEC group). Randomisation was done centrally by minimisation with a masked web-based allocation procedure at the time of surgery when residual disease smaller than 10 mm diameter was anticipated, and was stratified by institution, previous suboptimal cytoreductive surgery, and number of abdominal regions involved. The primary endpoint was progression-free survival and a secondary endpoint was overall survival, analysed in the intention-to-treat population (ie, all randomly assigned patients). This study is registered with ClinicalTrials.gov, NCT00426257, and is closed. Between April 1, 2007, and April 30, 2016, 245 patients were enrolled and followed up for a median of 10·1 years (95% CI 8·4–12·9) in the surgery group (n=123) and 10·4 years (95% CI 9·5–13·3) in the surgery-plus-HIPEC group (n=122). Recurrence, progression, or death occurred in 114 (93%) patients in the surgery group (median progression-free survival 10·7 months [95% CI 9·6–12·0]) and 109 (89%) patients in the surgery-plus-HIPEC group (14·3 months [12·0–18·5]; hazard ratio [HR] 0·63 [95% CI 0·48–0·83], stratified log-rank p=0·0008). Death occurred in 108 (88%) patients in the surgery group (median overall survival 33·3 months [95% CI 29·0–39·1]) and 100 (82%) patients in the surgery-plus-HIPEC group (44·9 months [95% CI 38·6–55·1]; HR 0·70 [95% CI 0·53–0·92], stratified log-rank p=0·011). These updated survival results confirm the long-term survival benefit of HIPEC in patients with primary stage III epithelial ovarian cancer undergoing interval cytoreductive surgery. Dutch Cancer Foundation (KWF Kankerbestrijding).

The percentage of tumor-positive surgical resection margin rates in patients treated for locally advanced primary or recurrent rectal cancer is high. Image-guided navigation may improve complete resection rates. To ascertain whether image-guided navigation during rectal cancer resection improves complete resection rates compared with surgical procedures without navigation. This prospective single-center nonrandomized controlled trial was conducted at the Netherlands Cancer Institute-Antoni van Leeuwenhoek in Amsterdam, the Netherlands. The prospective or navigation cohort included adult patients with locally advanced primary or recurrent rectal cancer who underwent resection with image-guided navigation between February 1, 2016, and September 30, 2019, at the tertiary referral hospital. Clinical results of this cohort were compared with results of the historical cohort, which was composed of adult patients who received rectal cancer resection without image-guided navigation between January 1, 2009, and December 31, 2015. Rectal cancer resection with image-guided navigation. The primary end point was the complete resection rate, measured by the amount of tumor-negative resection margin rates. Secondary outcomes were safety and usability of the system. Safety was evaluated by the number of navigation system-associated surgical adverse events. Usability was assessed from responses to a questionnaire completed by the participating surgeons after each procedure. In total, 33 patients with locally advanced or recurrent rectal cancer were included (23 men [69.7%]; median [interquartile range] age at start of treatment, 61 [55.0-69.0] years). With image-guided navigation, a radical resection (R0) was achieved in 13 of 14 patients (92.9%; 95% CI, 66.1%-99.8%) after primary resection of locally advanced tumors and in 15 of 19 patients (78.9%; 95% CI, 54.4%-94.0%) after resection of recurrent rectal cancer. No navigation system-associated complications occurred before or during surgical procedures. In the historical cohort, 142 patients who underwent resection without image-guided navigation were included (95 men [66.9%]; median [interquartile range] age at start of treatment, 64 [55.0-70.0] years). In these patients, an R0 resection was accomplished in 85 of 101 patients (84.2%) with locally advanced rectal cancer and in 20 of 41 patients (48.8%) with recurrent rectal cancer. A significant difference was found between the navigation and historical cohorts after recurrent rectal cancer resection (21.1% vs 51.2%; P = .047). For locally advanced primary tumor resection, the difference was not significant (7.1% vs 15.8%; P = .69). Surgeons stated in completed questionnaires that the navigation system improved decisiveness and helped with tumor localization. Findings of this study suggest that image-guided navigation used during rectal cancer resection is safe and intuitive and may improve tumor-free resection margin rates in recurrent rectal cancer. Netherlands Trial Register Identifier: NTR7184.