Survival of patients with colorectal liver metastases treated with and without preoperative chemotherapy:Nationwide propensity score-matched study

Introduction: Routine treatment with preoperative systemic chemotherapy (CTx) in patients with colorectal liver metastases (CRLM) remains controversial due to lack of consistent evidence demonstrating associated survival benefits. This study aimed to determine the effect of preoperative CTx on overall survival (OS) compared to surgery alone and to assess hospital and oncological network variation in 5-year OS. Methods: This was a population-based study of all patients who underwent liver resection for CRLM between 2014 and 2017 in the Netherlands. After 1:1 propensity score matching (PSM), OS was compared between patients treated with and without preoperative CTx. Hospital and oncological network variation in 5-year OS corrected for case-mix factors was calculated using an observed/expected ratio. Results: Of 2820 patients included, 852 (30.2%) and 1968 (69.8%) patients were treated with preoperative CTx and surgery alone, respectively. After PSM, 537 patients remained in each group, median number of CRLM; 3 [IQR 2–4], median size of CRLM; 28 mm [IQR 18–44], synchronous CLRM (71.1%). Median follow-up was 80.8 months. Five-year OS rates after PSM for patients treated with and without preoperative chemotherapy were 40.2% versus 38.3% (log-rank P = 0.734). After stratification for low, medium, and high tumour burden based on the tumour burden score (TBS) OS was similar for preoperative chemotherapy vs. surgery alone (log-rank P = 0.486, P = 0.914, and P = 0.744, respectively). After correction for non-modifiable patient and tumour characteristics, no relevant hospital or oncological network variation in five-year OS was observed. Conclusion: In patients eligible for surgical resection, preoperative chemotherapy does not provide an overall survival benefit compared to surgery alone.</p

Short-term postoperative outcomes after liver resection in the elderly patient:a nationwide population-based study

BACKGROUND: Liver resection is high-risk surgery in particular in elderly patients. The aim of this study was to explore postoperative outcomes after liver resection in elderly patients. METHODS: In this nationwide study, all patients who underwent liver resection for primary and secondary liver tumours in the Netherlands between 2014 and 2019 were included. Age groups were composed as younger than 70 (70-), between 70 and 80 (septuagenarians), and 80 years or older (octogenarians). Proportion of liver resections per age group and 30-day major morbidity and 30-day mortality were assessed. RESULTS: In total, 6587 patients were included of whom 4023 (58.9%) were younger than 70, 2135 (32.4%) were septuagenarians and 429 (6.5%) were octogenarians. The proportion of septuagenarians increased during the study period (aOR:1.06, CI:1.02-1.09, p < 0.001). Thirty-day major morbidity was higher in septuagenarians (11%) and octogenarians (12%) compared to younger patients (9%, p = 0.049). Thirty-day mortality was higher in septuagenarians (4%) and octogenarians (4%) compared to younger patients (2%, p < 0.001). Cardiopulmonary complications occurred more frequently with higher age, liver-specific complications did not. Higher age was associated with higher 30-day morbidity and 30-day mortality in multivariable logistic regression. CONCLUSION: Thirty-day major morbidity and 30-day mortality are higher after liver resection in elderly patients, attributed mainly to non-surgical cardiopulmonary complications

Population-based study on practice variation regarding preoperative systemic chemotherapy in patients with colorectal liver metastases and impact on short-term outcomes

Introduction: Definitions regarding resectability and hence indications for preoperative chemotherapy vary. Use of preoperative chemotherapy may influence postoperative outcomes. This study aimed to assess the variation in use of preoperative chemotherapy for CRLM and related postoperative outcomes in the Netherlands. Materials and methods: All patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were included from a national database. Case-mix factors contributing to the use of preoperative chemotherapy, hospital variation and postoperative outcomes were assessed using multivariable logistic regression. Postoperative outcomes were postoperative complicated course (PCC), 30-day morbidity and 30-day mortality. Results: In total, 4469 patients were included of whom 1314 patients received preoperative chemotherapy and 3155 patients did not. Patients receiving chemotherapy were significantly younger (mean age (+SD) 66.3 (10.4) versus 63.2 (10.2) p < 0.001) and had less comorbidity (Charlson scores 2+ (24% versus 29%, p = 0.010). Unadjusted hospital variation concerning administration of preoperative chemotherapy ranged between 2% and 55%. After adjusting for case-mix factors, three hospitals administered significantly more preoperative chemotherapy than expected and six administered significantly less preoperative chemotherapy than expected. PCC was 12.1%, 30-day morbidity was 8.8% and 30-day mortality was 1.5%. No association between preoperative chemotherapy and PCC (OR 1.24, 0.98–1.55, p = 0.065), 30-day morbidity (OR 1.05, 0.81–1.39, p = 0.703) or with 30-day mortality (OR 1.22, 0.75–2.09, p = 0.467) was found. Conclusion: Significant hospital variation in the use of preoperative chemotherapy for CRLM was present in the Netherlands. No association between postoperative outcomes and use of preoperative chemotherapy was found

Case-mix adjustment to compare nationwide hospital performances after resection of colorectal liver metastases

Background: Differences in patient demographics and disease burden can influence comparison of hospital performances. This study aimed to provide a case-mix model to compare short-term postoperative outcomes for patients undergoing liver resection for colorectal liver metastases (CRLM). Methods: This retrospective, population-based study included all patients who underwent liver resection for CRLM between 2014 and 2018 in the Netherlands. Variation in case-mix variables between hospitals and influence on postoperative outcomes was assessed using multivariable logistic regression. Primary outcomes were 30-day major morbidity and 30-day mortality. Validation of results was performed on the data from 2019. Results: In total, 4639 patients were included in 28 hospitals. Major morbidity was 6.2% and mortality was 1.4%. Uncorrected major morbidity ranged from 3.3% to 13.7% and mortality ranged from 0.0% to 5.0%. between hospitals. Significant differences between hospitals were observed for age higher than 80 (0.0%-17.1%, p <0.001), ASA 3 or higher (3.3%-36.3%, p <0.001), histopathological parenchymal liver disease (0.0%-47.1%, p <0.001), history of liver resection (8.1%-36.3%, p <0.001), major liver resection (6.7%-38.0%, p <0.001) and synchronous metastases (35.5%-62.1%, p <0.001). Expected 30-day major morbidity between hospitals ranged from 6.4% to 11.9% and expected 30-day mortality ranged from 0.6% to 2.9%. After case-mix correction no significant outliers concerning major morbidity and mortality remained. Validation on patients who underwent liver resection for CRLM in 2019 affirmed these outcomes. Conclusion: Case-mix adjustment is a prerequisite to allow for institutional comparison of short-term postoperative outcomes after liver resection for CRLM. (C) 2020 University Medical Center Groningen. Published by Elsevier Ltd

Nationwide Outcome after Pancreatoduodenectomy in Patients at very High Risk (ISGPS-D) for Postoperative Pancreatic Fistula

OBJECTIVE: To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), categorized as ISGPS-D.SUMMARY BACKGROUND DATA: Morbidity and mortality after ISGPS-D PD is perceived so high that a recent randomized trial advocated prophylactic total pancreatectomy (TP) as alternative aiming to lower this risk. However, current outcomes of ISGPS-D PD remain unknown as large nationwide series are lacking.METHODS: Nationwide retrospective analysis including consecutive patients undergoing ISGPS-D PD (i.e., soft texture and pancreatic duct ≤3 mm), using the mandatory Dutch Pancreatic Cancer Audit (2014-2021). Primary outcome was in-hospital mortality and secondary outcomes included major morbidity (i.e., Clavien-Dindo grade ≥IIIa) and POPF (ISGPS grade B/C). The use of prophylactic TP to avoid POPF during the study period was assessed.RESULTS: Overall, 1402 patients were included. In-hospital mortality was 4.1% (n=57), which decreased to 3.7% (n=20/536) in the last 2 years. Major morbidity occurred in 642 patients (45.9%) and POPF in 410 (30.0%), which corresponded with failure to rescue in 8.9% (n=57/642). Patients with POPF had increased rates of major morbidity (88.0% vs. 28.3%; P&lt;0.001) and mortality (6.3% vs. 3.5%; P=0.016), compared to patients without POPF. Among 190 patients undergoing TP, prophylactic TP to prevent POPF was performed in 4 (2.1%).CONCLUSION: This nationwide series found a 4.1% in-hospital mortality after ISGPS-D PD with 45.9% major morbidity, leaving little room for improvement through prophylactic TP. Nevertheless, given the outcomes in 30% of patients who develop POPF, future randomized trials should aim to prevent and mitigate POPF in this high-risk category.</p

Preoperative chemoradiotherapy but not chemotherapy is associated with reduced risk of postoperative pancreatic fistula after pancreatoduodenectomy for pancreatic ductal adenocarcinoma:a nationwide analysis

Background: Postoperative pancreatic fistula remains the leading cause of significant morbidity after pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Preoperative chemoradiotherapy has been described to reduce the risk of postoperative pancreatic fistula, but randomized trials on neoadjuvant treatment in pancreatic ductal adenocarcinoma focus increasingly on preoperative chemotherapy rather than preoperative chemoradiotherapy. This study aimed to investigate the impact of preoperative chemotherapy and preoperative chemoradiotherapy on postoperative pancreatic fistula and other pancreatic-specific surgery related complications on a nationwide level. Methods: All patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included in the mandatory nationwide prospective Dutch Pancreatic Cancer Audit (2014–2020). Baseline and treatment characteristics were compared between immediate surgery, preoperative chemotherapy, and preoperative chemoradiotherapy. The relationship between preoperative chemotherapy, chemoradiotherapy, and clinically relevant postoperative pancreatic fistula (International Study Group of Pancreatic Surgery grade B/C) was investigated using multivariable logistic regression analyses. Results: Overall, 2,019 patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included, of whom 1,678 underwent immediate surgery (83.1%), 192 (9.5%) received preoperative chemotherapy, and 149 (7.4%) received preoperative chemoradiotherapy. Postoperative pancreatic fistula occurred in 8.3% of patients after immediate surgery, 4.2% after preoperative chemotherapy, and 2.0% after preoperative chemoradiotherapy (P = .004). In multivariable analysis, the use of preoperative chemoradiotherapy was associated with reduced risk of postoperative pancreatic fistula (odds ratio, 0.21; 95% confidence interval, 0.03–0.69; P = .033) compared with immediate surgery, whereas preoperative chemotherapy was not (odds ratio, 0.59; 95% confidence interval, 0.25–1.25; P = .199). Intraoperatively hard, or fibrotic pancreatic texture was most frequently observed after preoperative chemoradiotherapy (53% immediate surgery, 62% preoperative chemotherapy, 77% preoperative chemoradiotherapy, P &lt; .001). Conclusion: This nationwide analysis demonstrated that in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma, only preoperative chemoradiotherapy, but not preoperative chemotherapy, was associated with a reduced risk of postoperative pancreatic fistula.</p

Preoperative chemoradiotherapy but not chemotherapy is associated with reduced risk of postoperative pancreatic fistula after pancreatoduodenectomy for pancreatic ductal adenocarcinoma:a nationwide analysis

Background: Postoperative pancreatic fistula remains the leading cause of significant morbidity after pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Preoperative chemoradiotherapy has been described to reduce the risk of postoperative pancreatic fistula, but randomized trials on neoadjuvant treatment in pancreatic ductal adenocarcinoma focus increasingly on preoperative chemotherapy rather than preoperative chemoradiotherapy. This study aimed to investigate the impact of preoperative chemotherapy and preoperative chemoradiotherapy on postoperative pancreatic fistula and other pancreatic-specific surgery related complications on a nationwide level. Methods: All patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included in the mandatory nationwide prospective Dutch Pancreatic Cancer Audit (2014–2020). Baseline and treatment characteristics were compared between immediate surgery, preoperative chemotherapy, and preoperative chemoradiotherapy. The relationship between preoperative chemotherapy, chemoradiotherapy, and clinically relevant postoperative pancreatic fistula (International Study Group of Pancreatic Surgery grade B/C) was investigated using multivariable logistic regression analyses. Results: Overall, 2,019 patients after pancreatoduodenectomy for pancreatic ductal adenocarcinoma were included, of whom 1,678 underwent immediate surgery (83.1%), 192 (9.5%) received preoperative chemotherapy, and 149 (7.4%) received preoperative chemoradiotherapy. Postoperative pancreatic fistula occurred in 8.3% of patients after immediate surgery, 4.2% after preoperative chemotherapy, and 2.0% after preoperative chemoradiotherapy (P = .004). In multivariable analysis, the use of preoperative chemoradiotherapy was associated with reduced risk of postoperative pancreatic fistula (odds ratio, 0.21; 95% confidence interval, 0.03–0.69; P = .033) compared with immediate surgery, whereas preoperative chemotherapy was not (odds ratio, 0.59; 95% confidence interval, 0.25–1.25; P = .199). Intraoperatively hard, or fibrotic pancreatic texture was most frequently observed after preoperative chemoradiotherapy (53% immediate surgery, 62% preoperative chemotherapy, 77% preoperative chemoradiotherapy, P &lt; .001). Conclusion: This nationwide analysis demonstrated that in patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma, only preoperative chemoradiotherapy, but not preoperative chemotherapy, was associated with a reduced risk of postoperative pancreatic fistula.</p

Nationwide oncological networks for resection of colorectal liver metastases in the Netherlands:Differences and postoperative outcomes

INTRODUCTION: Widespread differences in patient demographics and disease burden between hospitals for resection of colorectal liver metastases (CRLM) have been described. In the Netherlands, networks consisting of at least one tertiary referral centre and several regional hospitals have been established to optimize treatment and outcomes. The aim of this study was to assess variation in case-mix, and outcomes between these networks. METHODS: This was a population-based study including all patients who underwent CRLM resection in the Netherlands between 2014 and 2019. Variation in case-mix and outcomes between seven networks covering the whole country was evaluated. Differences in case-mix, expected 30-day major morbidity (Clavien-Dindo ≥3a) and 30-day mortality between networks were assessed. RESULTS: In total 5383 patients were included. Thirty-day major morbidity was 5.7% and 30-day mortality was 1.5%. Significant differences between networks were observed for Charlson Comorbidity Index, ASA 3+, previous liver resection, liver disease, preoperative MRI, preoperative chemotherapy, ≥3 CRLM, diameter of largest CRLM ≥55 mm, major resection, combined resection and ablation, rectal primary tumour, bilobar and extrahepatic disease. Uncorrected 30-day major morbidity ranged between 3.3% and 13.1% for hospitals, 30-day mortality ranged between 0.0% and 4.5%. Uncorrected 30-day major morbidity ranged between 4.4% and 6.0% for networks, 30-day mortality ranged between 0.0% and 2.5%. No negative outliers were observed after case-mix correction. CONCLUSION: Variation in case-mix and outcomes are considerably smaller on a network level as compared to a hospital level. Therefore, auditing is more meaningful at a network level and collaboration of hospitals within networks should be pursued

Nationwide Outcome after Pancreatoduodenectomy in Patients at very High Risk (ISGPS-D) for Postoperative Pancreatic Fistula

OBJECTIVE: To assess nationwide surgical outcome after pancreatoduodenectomy (PD) in patients at very high risk for postoperative pancreatic fistula (POPF), categorized as ISGPS-D.SUMMARY BACKGROUND DATA: Morbidity and mortality after ISGPS-D PD is perceived so high that a recent randomized trial advocated prophylactic total pancreatectomy (TP) as alternative aiming to lower this risk. However, current outcomes of ISGPS-D PD remain unknown as large nationwide series are lacking.METHODS: Nationwide retrospective analysis including consecutive patients undergoing ISGPS-D PD (i.e., soft texture and pancreatic duct ≤3 mm), using the mandatory Dutch Pancreatic Cancer Audit (2014-2021). Primary outcome was in-hospital mortality and secondary outcomes included major morbidity (i.e., Clavien-Dindo grade ≥IIIa) and POPF (ISGPS grade B/C). The use of prophylactic TP to avoid POPF during the study period was assessed.RESULTS: Overall, 1402 patients were included. In-hospital mortality was 4.1% (n=57), which decreased to 3.7% (n=20/536) in the last 2 years. Major morbidity occurred in 642 patients (45.9%) and POPF in 410 (30.0%), which corresponded with failure to rescue in 8.9% (n=57/642). Patients with POPF had increased rates of major morbidity (88.0% vs. 28.3%; P&lt;0.001) and mortality (6.3% vs. 3.5%; P=0.016), compared to patients without POPF. Among 190 patients undergoing TP, prophylactic TP to prevent POPF was performed in 4 (2.1%).CONCLUSION: This nationwide series found a 4.1% in-hospital mortality after ISGPS-D PD with 45.9% major morbidity, leaving little room for improvement through prophylactic TP. Nevertheless, given the outcomes in 30% of patients who develop POPF, future randomized trials should aim to prevent and mitigate POPF in this high-risk category.</p

Early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy:nationwide propensity-score-matched analysis

Background: Although robotic pancreatoduodenectomy has shown promising outcomes in experienced high-volume centres, it is unclear whether implementation on a nationwide scale is safe and beneficial. The aim of this study was to compare the outcomes of the early experience with robotic pancreatoduodenectomy versus open pancreatoduodenectomy in the Netherlands. Methods: This was a nationwide retrospective cohort study of all consecutive patients who underwent robotic pancreatoduodenectomy or open pancreatoduodenectomy who were registered in the mandatory Dutch Pancreatic Cancer Audit (18 centres, 2014-2021), starting from the first robotic pancreatoduodenectomy procedure per centre. The main endpoints were major complications (Clavien-Dindo grade greater than or equal to III) and in-hospital/30-day mortality. Propensity-score matching (1 : 1) was used to minimize selection bias. Results: Overall, 701 patients who underwent robotic pancreatoduodenectomy and 4447 patients who underwent open pancreatoduodenectomy were included. Among the eight centres that performed robotic pancreatoduodenectomy, the median robotic pancreatoduodenectomy experience was 86 (range 48-149), with a 7.3% conversion rate. After matching (698 robotic pancreatoduodenectomy patients versus 698 open pancreatoduodenectomy control patients), no significant differences were found in major complications (40.3% versus 36.2% respectively; P = 0.186), in-hospital/30-day mortality (4.0% versus 3.1% respectively; P = 0.326), and postoperative pancreatic fistula grade B/C (24.9% versus 23.5% respectively; P = 0.578). Robotic pancreatoduodenectomy was associated with a longer operating time (359 min versus 301 min; P &lt; 0.001), less intraoperative blood loss (200 ml versus 500 ml; P &lt; 0.001), fewer wound infections (7.4% versus 12.2%; P = 0.008), and a shorter hospital stay (11 days versus 12 days; P &lt; 0.001). Centres performing greater than or equal to 20 robotic pancreatoduodenectomies annually had a lower mortality rate (2.9% versus 7.3%; P = 0.009) and a lower conversion rate (6.3% versus 11.2%; P = 0.032). Conclusion: This study indicates that robotic pancreatoduodenectomy was safely implemented nationwide, without significant differences in major morbidity and mortality compared with matched open pancreatoduodenectomy patients. Randomized trials should be carried out to verify these findings and confirm the observed benefits of robotic pancreatoduodenectomy versus open pancreatoduodenectomy.</p