Impact of the new rectal cancer definition on multimodality treatment and interhospital variability:Results from a nationwide cross-sectional study

Aim: This study aimed to determine the consequences of the new definition of rectal cancer for decision-making in multidisciplinary team meetings (MDT). The new definition of rectal cancer, the lower border of the tumour is located below the sigmoid take-off (STO), was implemented in the Dutch guideline in 2019 after an international Delphi consensus meeting to reduce interhospital variations. Method: All patients with rectal cancer according to the local MDT, who underwent resection in 2016 in the Netherlands were eligible for this nationwide collaborative cross-sectional study. MRI-images were rereviewed, and the tumours were classified as above or on/below the STO. Results: This study registered 3107 of the eligible 3178 patients (98%), of which 2784 patients had an evaluable MRI. In 314 patients, the tumour was located above the STO (11%), with interhospital variation between 0% and 36%. Based on TN-stage, 175 reclassified patients with colon cancer (6%) would have received different treatment (e.g., omitting neoadjuvant radiotherapy, candidate for adjuvant chemotherapy). Tumour location above the STO was independently associated with lower risk of 4-year locoregional recurrence (HR 0.529; p = 0.030) and higher 4-year overall survival (HR 0.732; p = 0.037) compared to location under the STO. Conclusion: By using the STO, 11% of the prior MDT-based diagnosis of rectal cancer were redefined as sigmoid cancer, with potential implications for multimodality treatment and prognostic value. Given the substantial interhospital variation in proportion of redefined cancers, the use of the STO will contribute to standardisation and comparability of outcomes in both daily practice and trial settings.</p

Evaluation of National Surgical Practice for Lateral Lymph Nodes in Rectal Cancer in an Untrained Setting

Background: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. Methods: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either ‘node-picking’ (the removal of an individual LLN) or ‘partial regional node dissection’ (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those undergoing only rectal resection. Results: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7–3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2–2.5, p = 0.874). Conclusion: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.</p

Prognostic Implications of Lateral Lymph Nodes in Rectal Cancer:A Population-Based Cross-sectional Study with Standardized Radiological Evaluation after Dedicated Training

BACKGROUND: There is an ongoing discussion regarding the prognostic implications of the presence, short-axis diameter, and location of lateral lymph nodes. OBJECTIVE: To analyze lateral lymph node characteristics, the role of downsizing on restaging MRI, and associated local recurrence rates for patients with cT3-4 rectal cancer after MRI re-review and training. DESIGN: Retrospective population-based cross-sectional study. SETTINGS: This collaborative project was led by local investigators from surgery and radiology departments in 60 Dutch hospitals. PATIENTS: A total of 3057 patients underwent rectal cancer surgery in 2016: 1109 had a cT3-4 tumor located ≤8 cm from the anorectal junction, of whom 891 received neoadjuvant therapy. MAIN OUTCOME MEASURES: Local recurrence and (ipsi) lateral local recurrence rates. RESULTS: Re-review identified 314 patients (35%) with visible lateral lymph nodes. Of these, 30 patients had either only long-stretched obturator (n = 13) or external iliac (n = 17) nodes, and both did not lead to any lateral local recurrences. The presence of internal iliac/obturator lateral lymph nodes (n = 284) resulted in 4-year local recurrence and lateral local recurrence rates of 16.4% and 8.8%, respectively. Enlarged (≥7 mm) lateral lymph nodes (n = 122) resulted in higher 4-year local recurrence (20.8%, 13.1%, 0%; p &lt;.001) and lateral local recurrence (14.7%, 4.4%, 0%; p &lt; 0.001) rates compared to smaller and no lateral lymph nodes, respectively. Visible lateral lymph nodes (HR 1.8 [1.1-2.8]) and enlarged lateral lymph nodes (HR 1.9 [1.1-3.5]) were independently associated with local recurrence in multivariable analysis. Enlarged lateral lymph nodes with malignant features had higher 4-year lateral local recurrence rates of 17.0%. Downsizing had no impact on lateral local recurrence rates. Enlarged lateral lymph nodes were found to be associated with higher univariate 4-year distant metastasis rates (36.4% vs 24.4%; p = 0.021), but this was not significant in multivariable analyses (HR 1.3 [0.9-1.]) and did not worsen overall survival. LIMITATIONS: This study was limited by the retrospective design and total number of patients with lateral lymph nodes. CONCLUSIONS: The risk of lateral local recurrence due to (enlarged) lateral lymph nodes was confirmed, but without the prognostic impact of downsizing after neoadjuvant therapy. These results point toward the incorporation of primary lateral lymph node size into treatment planning. See Video Abstract.</p

The inhibitory effect of ¹¹¹In-DTPA⁰-octreotide on intrahepatic tumor growth after partial hepatectomy

The aim of this animal study was to evaluate whether peptide receptor radionuclide therapy with 111In -diethylenetriaminepentaacetic acid (DTPA)0-octreotide was able to reduce tumor growth even under tumor growth-stimulating conditions induced by partial hepatectomy (PHx). Methods: Rats underwent 70% PHx or sham operation. The development of hepatic metastases was determined 21 d after direct injection of somatostatin receptor (SS-R)-positive or SS-R-negative tumor cells into the portal vein. Groups of 8 or 9 animals that underwent PHx or sham operation were treated with octreotide 50 μg/kg subcutaneously twice daily or with 370 MBq 111In-DTPA0-octreotide intravenously on days 1 and 8. Both treatments were compared with control treatment. Forty non-tumor-bearing rats were used to determine the influence of 111In-DTPA0-octreotide therapy on liver regeneration after PHx. Results: PHx induced an increase in tumor growth in all experiments (P &lt; 0.01). Octreotide treatment did not influence tumor growth after PHx or sham operation. 111In-DTPA0-octreotide could effectively reduce tumor growth in the liver of SS-R-positive tumors also under conditions of increased tumor growth as generated by PHx (P &lt; 0.01). 111In-DTPA0-octreotide was also effective on SS-R-negative tumors after PHx (P = 0.01) but not after sham operation. Furthermore, 111In-DTPA0-octreotide therapy did not influence liver regeneration or liver function after PHx. Conclusion: Peptide receptor radionuclide therapy with 111In-DTPA0octreotide is effective in SS-R-positive tumors. During liver regeneration, the growth of SS-R-negative tumors is also reduced. This effect is not induced by impairment of liver regeneration or liver function. Radionuclide therapy could therefore be a promising treatment modality for patients with symptomatic liver metastases of neuroendocrine tumors in combination with liver resection.</p

The inhibitory effect of ¹¹¹In-DTPA⁰-octreotide on intrahepatic tumor growth after partial hepatectomy

The aim of this animal study was to evaluate whether peptide receptor radionuclide therapy with 111In -diethylenetriaminepentaacetic acid (DTPA)0-octreotide was able to reduce tumor growth even under tumor growth-stimulating conditions induced by partial hepatectomy (PHx). Methods: Rats underwent 70% PHx or sham operation. The development of hepatic metastases was determined 21 d after direct injection of somatostatin receptor (SS-R)-positive or SS-R-negative tumor cells into the portal vein. Groups of 8 or 9 animals that underwent PHx or sham operation were treated with octreotide 50 μg/kg subcutaneously twice daily or with 370 MBq 111In-DTPA0-octreotide intravenously on days 1 and 8. Both treatments were compared with control treatment. Forty non-tumor-bearing rats were used to determine the influence of 111In-DTPA0-octreotide therapy on liver regeneration after PHx. Results: PHx induced an increase in tumor growth in all experiments (P &lt; 0.01). Octreotide treatment did not influence tumor growth after PHx or sham operation. 111In-DTPA0-octreotide could effectively reduce tumor growth in the liver of SS-R-positive tumors also under conditions of increased tumor growth as generated by PHx (P &lt; 0.01). 111In-DTPA0-octreotide was also effective on SS-R-negative tumors after PHx (P = 0.01) but not after sham operation. Furthermore, 111In-DTPA0-octreotide therapy did not influence liver regeneration or liver function after PHx. Conclusion: Peptide receptor radionuclide therapy with 111In-DTPA0octreotide is effective in SS-R-positive tumors. During liver regeneration, the growth of SS-R-negative tumors is also reduced. This effect is not induced by impairment of liver regeneration or liver function. Radionuclide therapy could therefore be a promising treatment modality for patients with symptomatic liver metastases of neuroendocrine tumors in combination with liver resection.</p

Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): a multicentre, open-label, randomised trial

Item does not contain fulltex

Prospective study on image-guided navigation surgery for pelvic malignancies

Background and objectives: Surgery of advanced tumors and lymph nodes in the pelvis can be challenging due to the narrow pelvic space and vital surrounding structures. This study explores the application of a novel electromagnetic navigation system to guide pelvic surgery. Methods: This was a prospective study on surgery for malignancies in the pelvis. Preoperatively obtained imaging was used to create a patient-specific three-dimensional (3D) roadmap. In the operating room, the 3D roadmap was registered to an intraoperative computed tomography scan. A tracked pointer was used during surgery for guidance. Primary endpoint was safety and feasibility, secondary endpoints were accuracy and usability. Results: Twenty-eight colorectal, four liposarcomas, and one gynecological patient were included. There were no safety issues. Navigation was feasible in 31 patients. The mean target registration errors of 4.0 and 6.3 mm were achieved for straight and French position, respectively. In seven of seven patients with a locally advanced rectal tumor and in seven of eight patients with recurrences, negative margins were achieved. Thirty-three of 36 target lymph nodes were successfully removed. Surgeons using the system indicated faster localization of the tumor and improved decisiveness. Conclusion: This novel surgical navigation system was safe and feasible during pelvic surgery and can facilitate its users

Incidence, treatment and survival of malignant pleural and peritoneal mesothelioma: a population-based study

Introduction: Malignant mesothelioma (MM) is an aggressive cancer that primarily arises from the pleura (MPM) or peritoneum (MPeM), mostly due to asbestos exposure.This study reviewed the Dutch population-based incidence, treatment and survival since the national ban on asbestos in 1993.Materials and methods: Patients with MPM or MPeM diagnosed from 1993 to 2018 were selected from the Dutch cancer registry.Annual percentage change (APC) was calculated for (age-specific and sex-specific) revised European standardised incidence rates (RESR).Treatment pattern and Kaplan-Meier overall survival analyses were performed.Results: In total, 12 168 patients were included in the study.For male patients younger than 80 years, the MM incidence significantly decreased in the last decade (APC ranging between -9.4% and -1.8%, p<0.01).Among both male and female patients aged over 80 years, the incidence significantly increased during the entire study period (APC 3.3% and 4.6%, respectively, p<0.01).From 2003 onwards, the use of systemic chemotherapy increased especially for MPM (from 9.3% to 39.4%).Overall, 62.2% of patients received no antitumour treatment.The most common reasons for not undergoing antitumour treatment were patient preference (42%) and performance status (25.6%).The median overall survival improved from 7.3 (1993-2003) to 8.9 (2004-2011) and 9.3 months from 2012 to 2018 (p<0.001).Conclusion: The peak of MM incidence was reached around 2010 in the Netherlands, and currently the incidence is declining in most age groups.The use of systemic chemotherapy increased from 2003, which likely resulted in improved overall survival over time.The majority of patients do not receive treatment though and prognosis is still poor

Diffuse reflectance spectroscopy as a tool for real-time tissue assessment during colorectal cancer surgery

Colorectal surgery is the standard treatment for patients with colorectal cancer. To overcome two of the main challenges, the circumferential resection margin and postoperative complications, real-time tissue assessment could be of great benefit during surgery. In this ex vivo study, diffuse reflectance spectroscopy (DRS) was used to differentiate tumor tissue from healthy surrounding tissues in patients with colorectal neoplasia. DRS spectra were obtained from tumor tissue, healthy colon, or rectal wall and fat tissue, for every patient. Data were randomly divided into training (80%) and test (20%) sets. After spectral band selection, the spectra were classified using a quadratic classifier and a linear support vector machine. Of the 38 included patients, 36 had colorectal cancer and 2 had an adenoma. When the classifiers were applied to the test set, colorectal cancer could be discriminated from healthy tissue with an overall accuracy of 0.95 (±0.03). This study demonstrates the possibility to separate colorectal cancer from healthy surrounding tissue by applying DRS. High classification accuracies were obtained both in homogeneous and inhomogeneous tissues. This is a fundamental step toward the development of a tool for real-time in vivo tissue assessment during colorectal surgery.Medical Instruments & Bio-Inspired Technolog