MRI in addition to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): an international, multicentre, prospective, diagnostic accuracy trial.

BACKGROUND: Guidelines are inconclusive on whether contrast-enhanced MRI using gadoxetic acid and diffusion-weighted imaging should be added routinely to CT in the investigation of patients with colorectal liver metastases who are scheduled for curative liver resection or thermal ablation, or both. Although contrast-enhanced MRI is reportedly superior than contrast-enhanced CT in the detection and characterisation of colorectal liver metastases, its effect on clinical patient management is unknown. We aimed to assess the clinical effect of an additional liver contrast-enhanced MRI on local treatment plan in patients with colorectal liver metastases amenable to local treatment, based on contrast-enhanced CT. METHODS: We did an international, multicentre, prospective, incremental diagnostic accuracy trial in 14 liver surgery centres in the Netherlands, Belgium, Norway, and Italy. Participants were aged 18 years or older with histological proof of colorectal cancer, a WHO performance status score of 0-4, and primary or recurrent colorectal liver metastases, who were scheduled for local therapy based on contrast-enhanced CT. All patients had contrast-enhanced CT and liver contrast-enhanced MRI including diffusion-weighted imaging and gadoxetic acid as a contrast agent before undergoing local therapy. The primary outcome was change in the local clinical treatment plan (decided by the individual clinics) on the basis of liver contrast-enhanced MRI findings, analysed in the intention-to-image population. The minimal clinically important difference in the proportion of patients who would have change in their local treatment plan due to an additional liver contrast-enhanced MRI was 10%. This study is closed and registered in the Netherlands Trial Register, NL8039. FINDINGS: Between Dec 17, 2019, and July 31, 2021, 325 patients with colorectal liver metastases were assessed for eligibility. 298 patients were enrolled and included in the intention-to-treat population, including 177 males (59%) and 121 females (41%) with planned local therapy based on contrast-enhanced CT. A change in the local treatment plan based on liver contrast-enhanced MRI findings was observed in 92 (31%; 95% CI 26-36) of 298 patients. Changes were made for 40 patients (13%) requiring more extensive local therapy, 11 patients (4%) requiring less extensive local therapy, and 34 patients (11%) in whom the indication for curative-intent local therapy was revoked, including 26 patients (9%) with too extensive disease and eight patients (3%) with benign lesions on liver contrast-enhanced MRI (confirmed by a median follow-up of 21·0 months [IQR 17·5-24·0]). INTERPRETATION: Liver contrast-enhanced MRI should be considered in all patients scheduled for local treatment for colorectal liver metastases on the basis of contrast-enhanced CT imaging. FUNDING: The Dutch Cancer Society and Bayer AG - Pharmaceuticals.

Impact of 18FFDG-PET/CT and Laparoscopy in Staging of Locally Advanced Gastric Cancer: A Cost Analysis in the Prospective Multicenter PLASTIC-Study.

BACKGROUND: Unnecessary D2-gastrectomy and associated costs can be prevented after detecting non-curable gastric cancer, but impact of staging on treatment costs is unclear. This study determined the cost impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) and staging laparoscopy (SL) in gastric cancer staging. MATERIALS AND METHODS: In this cost analysis, four staging strategies were modeled in a decision tree: (1) 18FFDG-PET/CT first, then SL, (2) SL only, (3) 18FFDG-PET/CT only, and (4) neither SL nor 18FFDG-PET/CT. Costs were assessed on the basis of the prospective PLASTIC-study, which evaluated adding 18FFDG-PET/CT and SL to staging advanced gastric cancer (cT3-4 and/or cN+) in 18 Dutch hospitals. The Dutch Healthcare Authority provided 18FFDG-PET/CT unit costs. SL unit costs were calculated bottom-up. Gastrectomy-associated costs were collected with hospital claim data until 30 days postoperatively. Uncertainty was assessed in a probabilistic sensitivity analysis (1000 iterations). RESULTS: 18FFDG-PET/CT costs were €1104 including biopsy/cytology. Bottom-up calculations totaled €1537 per SL. D2-gastrectomy costs were €19,308. Total costs per patient were €18,137 for strategy 1, €17,079 for strategy 2, and €19,805 for strategy 3. If all patients undergo gastrectomy, total costs were €18,959 per patient (strategy 4). Performing SL only reduced costs by €1880 per patient. Adding 18FFDG-PET/CT to SL increased costs by €1058 per patient; IQR €870-1253 in the sensitivity analysis. CONCLUSIONS: For advanced gastric cancer, performing SL resulted in substantial cost savings by reducing unnecessary gastrectomies. In contrast, routine 18FFDG-PET/CT increased costs without substantially reducing unnecessary gastrectomies, and is not recommended due to limited impact with major costs. TRIAL REGISTRATION: NCT03208621. This trial was registered prospectively on 30-06-2017.

Nationwide standardization of minimally invasive right hemicolectomy for colon cancer and development and validation of a video-based competency assessment tool (the Right study).

BACKGROUND: 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. METHOD: 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). RESULTS: 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. CONCLUSION: 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).

Trends and overall survival after combined liver resection and thermal ablation of colorectal liver metastases: a nationwide population-based propensity score-matched study.

BACKGROUND: In colorectal liver metastases (CRLM) patients, combination of liver resection and ablation permit a more parenchymal-sparing approach. This study assessed trends in use of combined resection and ablation, outcomes, and overall survival (OS). METHODS: This population-based study included all CRLM patients who underwent liver resection between 2014 and 2022. To assess OS, data was linked to two databases containing date of death for patients treated between 2014 and 2018. Hospital variation in the use of combined minor liver resection and ablation versus major liver resection alone in patients with 2-3 CRLM and ≤3 cm was assessed. Propensity score matching (PSM) was applied to evaluate outcomes. RESULTS: This study included 3593 patients, of whom 1336 (37.2%) underwent combined resection and ablation. Combined resection increased from 31.7% in 2014 to 47.9% in 2022. Significant hospital variation (range 5.9-53.8%) was observed in the use of combined minor liver resection and ablation. PSM resulted in 1005 patients in each group. Major morbidity was not different (11.6% vs. 5%, P = 1.00). Liver failure occurred less often after combined resection and ablation (1.9% vs. 0.6%, P = 0.017). Five-year OS rates were not different (39.3% vs. 33.9%, P = 0.145). CONCLUSION: Combined resection and ablation should be available and considered as an alternative to resection alone in any patient with multiple metastases.

Hospital variation and outcomes after repeat hepatic resection for colorectal liver metastases: a nationwide cohort study.

BACKGROUND: Approximately 70% of patients with colorectal liver metastases (CRLM) experiences intrahepatic recurrence after initial liver resection. This study assessed outcomes and hospital variation in repeat liver resections (R-LR). METHODS: This population-based study included all patients who underwent liver resection for CRLM between 2014 and 2022 in the Netherlands. Overall survival (OS) was collected for patients operated on between 2014 and 2018 by linkage to the insurance database. RESULTS: Data of 7479 liver resections (1391 (18.6%) repeat and 6088 (81.4%) primary) were analysed. Major morbidity and mortality were not different. Factors associated with major morbidity included ASA 3+, major liver resection, extrahepatic disease, and open surgery. Five-year OS after repeat versus primary liver resection was 42.3% versus 44.8%, P = 0.37. Factors associated with worse OS included largest CRLM >5 cm (aHR 1.58, 95% CI: 1.07-2.34, P = 0.023), >3 CRLM (aHR 1.33, 95% CI: 1.00-1.75, P = 0.046), extrahepatic disease (aHR 1.60, 95% CI: 1.25-2.04, P = 0.001), positive tumour margins (aHR 1.42, 95% CI: 1.09-1.85, P = 0.009). Significant hospital variation in performance of R-LR was observed, median 18.9% (8.2% to 33.3%). CONCLUSION: Significant hospital variation was observed in performance of R-LR in the Netherlands reflecting different treatment decisions upon recurrence. On a population-based level R-LR leads to satisfactory survival.

Trends in Distal Esophageal and Gastroesophageal Junction Cancer Care: The Dutch Nationwide Ivory Study.

OBJECTIVE: This study evaluated the nationwide trends in care and accompanied postoperative outcomes for patients with distal esophageal and gastro-esophageal junction cancer. SUMMARY OF BACKGROUND DATA: The introduction of transthoracic esophagectomy, minimally invasive surgery, and neo-adjuvant chemo(radio)therapy changed care for patients with esophageal cancer. METHODS: Patients after elective transthoracic and transhiatal esophagectomy for distal esophageal or gastroesophageal junction carcinoma in the Netherlands between 2007-2016 were included. The primary aim was to evaluate trends in both care and postoperative outcomes for the included patients. Additionally, postoperative outcomes after transthoracic and tran-shiatal esophagectomy were compared, stratified by time periods. RESULTS: Among 4712 patients included, 74% had distal esophageal tumors and 87% had adenocarcinomas. Between 2007 and 2016, the proportion of transthoracic esophagectomy increased from 41% to 81%, and neo-adjuvant treatment and minimally invasive esophagectomy increased from 31% to 96%, and from 7% to 80%, respectively. Over this 10-year period, postoperative outcomes improved: postoperative morbidity decreased from 66.6% to 61.8% ( P = 0.001), R0 resection rate increased from 90.0% to 96.5% (P <0.001), median lymph node harvest increased from 15 to 19 ( P <0.001), and median survival increased from 35 to 41 months ( P = 0.027). CONCLUSION: In this nationwide cohort, a transition towards more neo-adju-vant treatment, transthoracic esophagectomy and minimally invasive surgery was observed over a 10-year period, accompanied by decreased postoperative morbidity, improved surgical radicality and lymph node harvest, and improved survival.

Practice variation and outcomes of minimally invasive minor liver resections in patients with colorectal liver metastases: a population-based study.

INTRODUCTION: In 2017, the Southampton guideline stated that minimally invasive liver resections (MILR) should considered standard practice for minor liver resections. This study aimed to assess recent implementation rates of minor MILR, factors associated with performing MILR, hospital variation, and outcomes in patients with colorectal liver metastases (CRLM). METHODS: This population-based study included all patients who underwent minor liver resection for CRLM in the Netherlands between 2014 and 2021. Factors associated with MILR and nationwide hospital variation were assessed using multilevel multivariable logistic regression. Propensity-score matching (PSM) was applied to compare outcomes between minor MILR and minor open liver resections. Overall survival (OS) was assessed with Kaplan-Meier analysis on patients operated until 2018. RESULTS: Of 4,488 patients included, 1,695 (37.8%) underwent MILR. PSM resulted in 1,338 patients in each group. Implementation of MILR increased to 51.2% in 2021. Factors associated with not performing MILR included treatment with preoperative chemotherapy (aOR 0.61 CI:0.50-0.75, p < 0.001), treatment in a tertiary referral hospital (aOR 0.57 CI:0.50-0.67, p < 0.001), and larger diameter and number of CRLM. Significant hospital variation was observed in use of MILR (7.5% to 93.0%). After case-mix correction, six hospitals performed fewer, and six hospitals performed more MILRs than expected. In the PSM cohort, MILR was associated with a decrease in blood loss (aOR 0.99 CI:0.99-0.99, p < 0.01), cardiac complications (aOR 0.29, CI:0.10-0.70, p = 0.009), IC admissions (aOR 0.66, CI:0.50-0.89, p = 0.005), and shorter hospital stay (aOR CI:0.94-0.99, p < 0.01). Five-year OS rates for MILR and OLR were 53.7% versus 48.6%, p = 0.21. CONCLUSION: Although uptake of MILR is increasing in the Netherlands, significant hospital variation remains. MILR benefits short-term outcomes, while overall survival is comparable to open liver surgery.

Recurrent Disease After Esophageal Cancer Surgery: A Substudy of The Dutch Nationwide Ivory Study.

OBJECTIVE: This study investigated the patterns, predictors, and survival of recurrent disease following esophageal cancer surgery. BACKGROUND: Survival of recurrent esophageal cancer is usually poor, with limited prospects of remission. METHODS: This nationwide cohort study included patients with distal esophageal and gastroesophageal junction adenocarcinoma and squamous cell carcinoma after curatively intended esophagectomy in 2007 to 2016 (follow-up until January 2020). Patients with distant metastases detected during surgery were excluded. Univariable and multivariable logistic regression were used to identify predictors of recurrent disease. Multivariable Cox regression was used to determine the association of recurrence site and treatment intent with postrecurrence survival. RESULTS: Among 4626 patients, 45.1% developed recurrent disease a median of 11 months postoperative, of whom most had solely distant metastases (59.8%). Disease recurrences were most frequently hepatic (26.2%) or pulmonary (25.1%). Factors significantly associated with disease recurrence included young age (≤65 y), male sex, adenocarcinoma, open surgery, transthoracic esophagectomy, nonradical resection, higher T-stage, and tumor positive lymph nodes. Overall, median postrecurrence survival was 4 months [95% confidence interval (95% CI): 3.6-4.4]. After curatively intended recurrence treatment, median survival was 20 months (95% CI: 16.4-23.7). Survival was more favorable after locoregional compared with distant recurrence (hazard ratio: 0.74, 95% CI: 0.65-0.84). CONCLUSIONS: This study provides important prognostic information assisting in the surveillance and counseling of patients after curatively intended esophageal cancer surgery. Nearly half the patients developed recurrent disease, with limited prospects of survival. The risk of recurrence was higher in patients with a higher tumor stage, nonradical resection and positive lymph node harvest.

The learning curve of transanal total mesorectal excision for rectal cancer is associated with local recurrence: results from a multicentre external audit.

AIM: Transanal total mesorectal excision (TaTME) has been suggested as a potential solution for the resection of challenging mid and low rectal cancer. This relatively complex procedure has been implemented in many centres over the last years, despite the absence of long-term safety data. Recently, concern has arisen because of an increase in local recurrence in the implementation phase. The aim of this study was to assess the correlation between accumulated experience and local recurrences. METHOD: An independent clinical researcher performed an external audit of consecutive series of all TaTME procedures in six centres in the Netherlands. Kaplan-Meier estimated local recurrence rates were calculated and multivariate Cox proportional hazards regression analysis performed to assess risk factors for local recurrence. Primary outcome was the local recurrence rate in the initial implementation (cases 1-10), continued adoption (cases 11-40) and prolonged experience (case 41 onward). RESULTS: Six hundred and twenty-four consecutive patients underwent TaTME for rectal cancer with a median follow-up of 27 months (range 1-82 months). The estimated 2- and 3-year local recurrence rates were 4.6% and 6.6%, respectively. Cox proportional hazards regression revealed procedural experience to be an independent factor in multivariate analysis next to advanced stage (ycMRF+, pT3-4, pN+) and pelvic sepsis. Corrected analysis projected the 3-year local recurrence rates to be 9.7%, 3.3% and 3.5% for the implementation, continued adoption and prolonged experience cohorts, respectively. CONCLUSION: This multicentre study shows a high local recurrence rate (12.5%) after implementation of TaTME which lowers to an acceptable rate (3.4%) when experience increases. Therefore, intensified proctoring and further precautions must be implemented to reduce the unacceptably high risk of local recurrence at units starting this technique.

Zinc-Impregnated Mesh for Abdominal Wall Repair Reduces Infection in a Rat Model of Peritonitis.

BACKGROUND: The objective of this study was to assess whether a zinc-impregnated polypropylene mesh (ZnMesh) has better antibacterial properties in a contaminated environment compared with a regular polypropylene mesh. MATERIALS AND METHODS: Thirty-eight Wistar Han rats underwent cecal ligation and puncture to induce peritonitis 24 h before implantation of an intraperitoneal ZnMesh or a regular polypropylene mesh. Primary outcome was the number of colony forming units (CFU) per sample (mesh and abdominal wall). Secondary outcomes were macroscopic (incorporation of mesh, abscesses, and adhesions on mesh surface) and histological (inflammatory cell reaction, mesh-specific parameters, and collagen deposition) parameters. All outcomes were evaluated after 30 and 90 d. RESULTS: After 30 d, no significant difference in CFU per sample was present between the ZnMesh and control groups. After 90 d, a lower number of CFU per sample was present in the ZnMesh group compared with the control group (trypticase soy agar with 5% sheep blood: 0 log10 CFU/sample IQR: 0-1.40 versus 1.58 log10 CFU/sample IQR: 0-4.30, P = 0.012; MacConkey: 0 log10 CFU/sample IQR: 0-2.65 versus 1.18 log10 CFU/sample IQR: 0-4.04, P = 0.438). After 90 d, the percentage of adhesions on mesh surface was significantly higher in the ZnMesh group (95% IQR: 60%-100% versus 50% IQR: 23%-75%, P = 0.029). No differences were seen in other macroscopic outcomes or histology. CONCLUSIONS: A significantly lower number of CFU per sample was found in the ZnMesh group after 90 d. After 30 d, no statistically significant differences in CFU per sample were seen. This result suggests that the ZnMesh group has better antibacterial properties in a contaminated environment. However, this is at the cost of a significantly higher percentage of adhesions.

Transanal minimally invasive surgery (TAMIS) versus endoscopic submucosal dissection (ESD) for resection of non-pedunculated rectal lesions (TRIASSIC study): study protocol of a European multicenter randomised controlled trial.

BACKGROUND: In the recent years two innovative approaches have become available for minimally invasive en bloc resections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. METHODS: Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. DISCUSSION: This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for the en bloc resection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. TRIAL REGISTRATION: Netherlands Trial Register, NL7083 , 06 July 2018.

Population-Based Study on Risk Factors for Tumor-Positive Resection Margins in Patients with Gastric Cancer.

BACKGROUND: Radical gastrectomy is the cornerstone of the treatment of locally advanced gastric cancer. This study was designed to evaluate factors associated with a tumor-positive resection margin after gastrectomy and to evaluate the influence of hospital volume. METHODS: In this Dutch cohort study, patients with junctional or gastric cancer who underwent curative gastrectomy between 2011 and 2017 were included. The primary outcome was incomplete tumor removal after the operation defined as the microscopic presence of tumor cells at the resection margin. The association of patient and disease characteristics with incomplete tumor removal was tested with multivariable regression analysis. The association of annual hospital volume with incomplete tumor removal was tested and adjusted for the patient- and disease characteristics. RESULTS: In total, 2799 patients were included. Incomplete tumor removal was seen in 265 (9.5%) patients. Factors associated with incomplete tumor removal were: tumor located in the entire stomach (odds ratio (OR) [95% confidence interval (CI): 3.38 [1.91-5.96] reference: gastroesophageal junction), cT3, cT4, cTx (1.75 [1.20-2.56], 2.63 [1.47-4.70], 1.60 [1.03-2.48], reference: cT0-2), pN+ (2.73 [1.96-3.80], reference: pN-), and diffuse and unknown histological subtype (3.15 [2.14-4.46] and 2.05 [1.34-3.13], reference: intestinal). Unknown differentiation grade was associated with complete tumor removal (0.50 [0.30-0.83], reference: poor/undifferentiated). Compared with a hospital volume of < 20 resections/year, 20-39, and > 39 resections were associated with lower probability for incomplete tumor removal (OR 0.56 [0.42-0.76] and 0.34 [0.18-0.64]). CONCLUSIONS: Tumor location, cT, pN, histological subtype, and tumor differentiation are associated with incomplete tumor removal. The association of incomplete tumor removal with an annual hospital volume of < 20 resections may underline the need for further centralization of gastric cancer care in the Netherlands.

Prognostic value of microvessel density in stage II and III colon cancer patients: a retrospective cohort study.

BACKGROUND: Microvessel density (MVD), as a derived marker for angiogenesis, has been associated with poor outcome in several types of cancer. This study aimed to evaluate the prognostic value of MVD in stage II and III colon cancer and its relation to tumour-stroma-percentage (TSP) and expression of HIF1A and VEGFA. METHODS: Formalin-fixed paraffin-embedded (FFPE) colon cancer tissues were collected from 53 stage II and 54 (5-fluorouracil-treated) stage III patients. MVD was scored by digital morphometric analysis of CD31-stained whole tumour sections. TSP was scored using haematoxylin-eosin stained slides. Protein expression of HIF1A and VEGFA was determined by immunohistochemical evaluation of tissue microarrays. RESULTS: Median MVD was higher in stage III compared to stage II colon cancers (11.1% versus 5.6% CD31-positive tissue area, p < 0.001). High MVD in stage II patients tended to be associated with poor disease free survival (DFS) in univariate analysis (p = 0.056). In contrast, high MVD in 5FU-treated stage III patients was associated with better DFS (p = 0.006). Prognostic value for MVD was observed in multivariate analyses for both cancer stages. CONCLUSIONS: MVD is an independent prognostic factor associated with poor DFS in stage II colon cancer patients, and with better DFS in stage III colon cancer patients treated with adjuvant chemotherapy.

A preoperative prognostic model to predict surgical success in patients with perihilar cholangiocarcinoma.

BACKGROUND: Patients with resectable perihilar cholangiocarcinoma (PHC) on imaging have a substantial risk of metastatic or locally advanced disease, incomplete (R1) resection, and 90-day mortality. Our aim was to develop a preoperative prognostic model to predict surgical success, defined as a complete (R0) resection without 90-day mortality, in patients with resectable PHC on imaging. STUDY DESIGN: Patients with PHC who underwent exploratory laparotomy in three tertiary referral centers were identified. Multivariable logistic regression was performed to identify preoperatively available prognostic factors. A prognostic model was developed using data from two European centers and validated in one American center. RESULTS: In total, 671 patients with PHC underwent exploratory laparotomy. In the derivation cohort, surgical success was achieved in 102 of 331 patients (30.8%). No resection was performed in 176 patients (53.2%) because of metastatic or locally advanced disease. Of the 155 patients (46.8%) who underwent a resection, 38 (24.5%) had an R1-resection. Of the remaining 117 (35.3%), 15 (12.8%) had 90-day mortality. Independent poor prognostic factors for surgical success were identified, and a preoperative prognostic model was developed with a concordance index of 0.71. External validation showed good concordance (0.70). CONCLUSION: Surgical success was achieved in only 30% of patients with PHC undergoing exploratory laparotomy and could be predicted by age, cholangitis, hepatic artery involvement, lymph node metastases, and Blumgart stage.

Conditional survival in patients with unresectable perihilar cholangiocarcinoma.

BACKGROUND: Conditional survival is the life expectancy from a point in time for a patient who has survived a specific period after presentation. The aim of the study was to estimate conditional survival for patients with unresectable perihilar cholangiocarcinoma. METHODS: Patients with unresectable perihilar cholangiocarcinoma from two academic hospitals in the Netherlands between 2002 and 2012 were assessed. A multivariable Cox proportional hazards analysis was performed to identify risk factors associated with overall survival. Survival was estimated using the Kaplan-Meier method to evaluate factors associated with overall survival. RESULTS: In total, 572 patients were included. Overall survival was 42% at one year and 6% at three years. The conditional chance of surviving three years was 15% at 1 year and increased to 38% at 2 years. Independent poor prognostic factors for overall survival were age ≥65 years, tumor size >3 cm on imaging, bilirubin levels (>250 µmol/L), CA19-9 level at presentation (>1000 U/ml), and suspected distant metastases on imaging. The conditional survival of patients with and without these prognostic factors was comparable after patients survived the first two or more years. CONCLUSION: The conditional chance of surviving for patients with unresectable perihilar cholangiocarcinoma increases with time. Poor prognostic factors become less relevant once patients have survived two years.

Loss of KCNQ1 expression in stage II and stage III colon cancer is a strong prognostic factor for disease recurrence.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. Accurately identifying stage II CRC patients at risk for recurrence is an unmet clinical need. KCNQ1 was previously identified as a tumour suppressor gene and loss of expression was associated with poor survival in patients with CRC liver metastases. In this study the prognostic value of KCNQ1 in stage II and stage III colon cancer patients was examined. METHODS: KCNQ1 mRNA expression was assessed in 90 stage II colon cancer patients (AMC-AJCCII-90) using microarray gene expression data. Subsequently, KCNQ1 protein expression was evaluated in an independent cohort of 386 stage II and stage III colon cancer patients by immunohistochemistry of tissue microarrays. RESULTS: Low KCNQ1 mRNA expression in stage II microsatellite stable (MSS) colon cancers was associated with poor disease-free survival (DFS) (P=0.025). Loss of KCNQ1 protein expression from epithelial cells was strongly associated with poor DFS in stage II MSS (P<0.0001), stage III MSS (P=0.0001) and stage III microsatellite instable colon cancers (P=0.041). KCNQ1 seemed an independent prognostic value in addition to other high-risk parameters like angio-invasion, nodal stage and microsatellite instability-status. CONCLUSIONS: We conclude that KCNQ1 is a promising biomarker for prediction of disease recurrence and may aid stratification of patients with stage II MSS colon cancer for adjuvant chemotherapy.

Expression of apoptosis regulating proteins identifies stage II and III colon cancer patients with high risk of recurrence.

BACKGROUND AND OBJECTIVES: Deregulation of apoptosis related genes may be associated with poor outcome in cancer. Aim of the present study was to investigate the prognostic role of expression levels of apoptosis related proteins in stage II and III colon cancer. METHODS: From tumor samples of 386 stage II and III colon cancer patients, DNA was isolated and tissue microarrays were constructed. Expression of Bcl-2, Bcl-X, BAX, XIAP, Fas, FasL and c-FLIP was evaluated and PCR-based microsatellite instability analysis was performed. RESULTS: High FasL expressing tumors were associated with high disease recurrence rates in stage II colon cancer patients overall, as was low Bcl-X expression in microsatellite stable stage II patients. In stage II patients, a multivariable model based on FasL and Bcl-XL expression revealed a significant association with disease free survival (DFS). In stage III colon cancer patients, low Bcl-2, low BAX and low Fas expression levels were associated with worse outcome. In these patients a multivariable model based on angioinvasion and Bcl-2, Fas and FasL expression was significantly associated with DFS. CONCLUSIONS: Stage II patients with low Bcl-X and high FasL protein expression levels and stage III patients with low Fas, high FasL and low Bcl-2 expression could be considered as high risk for disease recurrence.

Association of modified textbook outcome and overall survival after surgery for colorectal liver metastases: A nationwide analysis.

BACKGROUND: Textbook outcome (TO) represents a multidimensional quality measurement, encompassing the desirable short-term outcomes following surgery. This study aimed to investigate whether achieving TO after resection of colorectal liver metastases (CRLM) surgery is related to better overall survival (OS) in a national cohort. METHOD: Data was retrieved from the Dutch Hepato Biliary Audit. A modified definition of TO (mTO) was used because readmissions were only recorded from 2019. mTO was achieved when no severe postoperative complications, mortality, prolonged length of hospital stay, occurred and when adequate surgical resection margins were obtained. To compare outcomes of patients with and without mTO and reduce baseline differences between both groups propensity score matching (PSM) was used for patients operated on between 2014 and 2018. RESULTS: Out of 6525 eligible patients, 81 % achieved mTO. For the cohort between 2014 and 2018, those achieving mTO had a 5-year OS of 46.7 % (CI 44.8-48.6) while non-mTO patients had a 5-year OS of 33.7 % (CI 29.8-38.2), p < 0.001. Not achieving mTO was associated with a worse OS (aHR 1.34 (95 % CI 1.17-1.53), p < 0.001. Median follow-up was 76 months., PSM assigned 519 patients to each group. In the PSM cohort patients achieving mTO, 5-year OS was 43.6 % (95 % CI 39.2-48.5) compared to 36.4 % (95 % CI 31.9-41.2) in patients who did not achieve mTO, p = 0.006. CONCLUSION: Achieving mTO is associated with improved long-term survival. This emphasizes the importance of optimising perioperative care and reducing postoperative complications in surgical treatment of CRLM.

Outcomes of liver surgery: A decade of mandatory nationwide auditing in the Netherlands.

BACKGROUND: In 2013, the nationwide Dutch Hepato Biliary Audit (DHBA) was initiated. The aim of this study was to evaluate changes in indications for and outcomes of liver surgery in the last decade. METHODS: This nationwide study included all patients who underwent liver surgery for four indications, including colorectal liver metastases (CRLM), hepatocellular carcinoma (HCC), and intrahepatic- and perihilar cholangiocarcinoma (iCCA - pCCA) between 2014 and 2022. Trends in postoperative outcomes were evaluated separately for each indication using multilevel multivariable logistic regression analyses. RESULTS: This study included 8057 procedures for CRLM, 838 for HCC, 290 for iCCA, and 300 for pCCA. Over time, these patients had higher risk profiles (more ASA-III patients and more comorbidities). Adjusted mortality decreased over time for CRLM, HCC and iCCA, respectively aOR 0.83, 95%CI 0.75-0.92, P < 0.001; aOR 0.86, 95%CI 0.75-0.99, P = 0.045; aOR 0.40, 95%CI 0.20-0.73, P < 0.001. Failure to rescue (FTR) also decreased for these groups, respectively aOR 0.84, 95%CI 0.76-0.93, P = 0.001; aOR 0.81, 95%CI 0.68-0.97, P = 0.024; aOR 0.29, 95%CI 0.08-0.84, P = 0.021). For iCCA severe complications (aOR 0.65 95%CI 0.43-0.99, P = 0.043) also decreased. No significant outcome differences were observed in pCCA. The number of centres performing liver resections decreased from 26 to 22 between 2014 and 2022, while median annual volumes did not change (40-49, P = 0.66). CONCLUSION: Over time, postoperative mortality and FTR decreased after liver surgery, despite treating higher-risk patients. The DHBA continues its focus on providing feedback and benchmark results to further enhance outcomes.

Determinants of Physical Activity among Patients with Colorectal Cancer: From Diagnosis to 5 Years after Diagnosis.

INTRODUCTION: Physical activity (PA) is associated with higher quality of life and probably better prognosis among colorectal cancer (CRC) patients. This study focuses on determinants of PA among CRC patients from diagnosis until 5 yr postdiagnosis. METHODS: Sociodemographic and disease-related factors of participants of two large CRC cohort studies were combined. Moderate-to-vigorous PA during sport and leisure time (MVPA-SL) was measured at diagnosis (T0) and 6, 12, 24, and 60 months (T6 to T60) postdiagnosis, using the SQUASH questionnaire. Mixed-effects models were performed to identify sociodemographic and disease-related determinants of MVPA-SL, separately for stage I-III colon (CC), stage I-III rectal cancer (RC), and stage IV CRC (T0 and T6 only). Associations were defined as consistently present when significant at ≥4 timepoints for the stage I-III subsets. MVPA-SL levels were compared with an age- and sex-matched sample of the general Dutch population. RESULTS: In total, 2905 CC, 1459 RC and 436 stage IV CRC patients were included. Patients with higher fatigue scores, and women compared with men had consistently lower MVPA-SL levels over time, regardless of tumor type and stage. At T6, having a stoma was significantly associated with lower MVPA-SL among stage I-III RC patients. Systemic therapy and radiotherapy were not significantly associated with MVPA-SL changes at T6. Compared with the general population, MVPA-SL levels of CRC patients were lower at all timepoints, most notably at T6. CONCLUSIONS: Female sex and higher fatigue scores were consistent determinants of lower MVPA-SL levels among all CRC patients, and MVPA-SL levels were lowest at 6 months postdiagnosis. Our results can inform the design of intervention studies aimed at improving PA, and guide healthcare professionals in optimizing individualized support.