Wuthering heights: Outcomes from pancreatic surgery and trends in treatment of pancreatic ductal adenocarcinoma in Norway in a post-centralization era

Aim: The main aim of this thesis was to explore the contemporary outcomes of pancreatic surgery and treatment of pancreatic ductal adenocarcinoma in Norway seen in light of the centralization process and the volume-outcome relationship. Methods: We analysed three complete national patient cohorts using prospectively gathered data from national medical quality registries. The inclusion criteria were either having a pancreatoduodenectomy (Paper I and II) or being diagnosed with pancreatic ductal adenocarcinoma (Paper III). The main studied outcomes were short-term morbidity and mortality, and for paper III provision of tumour-directed treatment and survival. Results: In paper I we found that the national in-hospital mortality and 90-day mortality after pancreatoduodenectomy were 2% and 4%, respectively, and 14% of patients had a relaparotomy within 30 days. High age, male gender and relaparotomy were independent predictors of 90-day mortality, whereas Regional Health Authority where treated was not. In paper II we showed that patients who had a pancreatoduodenectomy at the medium/low-volume units had similar short-term outcomes to patients treated at the sole high-volume unit (>40 PDs a year). For patients diagnosed with pancreatic ductal adenocarcinoma between 2004-2018 (paper III), resection rates (p<0.001) and use of perioperative chemotherapy (p<0.001) increased over time, and survival after resection improved with a HR (95% CI) for death of 0.65 (0.57-0.76) between late and early study period. For non-resected patients, provision of palliative chemotherapy increased over time (p<0.001). Still, four in ten patients did not receive any tumour-directed treatment. Conclusions: The postoperative outcomes after pancreatoduodenectomy in Norway are beneficial and the current level of centralization of surgery seems just. Although more patients with pancreatic ductal adenocarcinoma currently reach resection and the survival prospects for this subgroup are slightly improving, no sizeable improvement was seen for this patient group when viewed as a whole

Diverting stomas reduce reoperation rates for anastomotic leak but not overall reoperation rates within 30 days after anterior rectal resection: a national cohort study

Purpose A diverting stoma is commonly formed to reduce the rate of anastomotic leak following anterior resection with anastomosis, although some studies question this strategy. The aim of this study was to assess the leak rates and overall complication burden after anterior resection with and without a diverting stoma. Methods A 5-year national cohort with prospectively registered data of patients who underwent elective anterior resection for rectal cancer located<15 cm from the anal verge. Data were retrieved from the Norwegian Registry for Gastrointestinal Surgery and the Norwegian Colorectal Cancer Registry. Primary end point was relaparotomy or relaparoscopy for anastomotic leak within 30 days from index surgery. Secondary endpoints were postoperative complications including reoperation for any cause. Results Some 1018 patients were included of whom 567 had a diverting stoma and 451 had not. Rate of reoperation for anastomotic leak was 13 out of 567 (2.3%) for patients with diverting stoma and 35 out of 451 (7.8%) (p>0.001) for patients without. In multivariable analyses not having a diverting stoma (aOR 3.77, c.i 1.97–7.24, p<0.001) was associated with increased risk for anastomotic leak. However, there were no diferences in overall reoperation rates following anterior resection with or without diverting stoma (9.3% vs 10.9%, p=0.423), and overall complication rates were similar. Reoperation was associated with increased mortality irrespective of the main intraoperative fnding. Conclusion Diverting stoma formation after anterior resection is protective against reoperation for anastomotic leak but does not afect overall rates of reoperation or complications within 30 days

Treatment and survival of patients with pancreatic ductal adenocarcinoma: 15-year national cohort

Background - Improvement in survival from pancreatic ductal adenocarcinoma (PDAC) has been reported in trial settings but is less explored in unselected cohorts. The aim of this study was to assess trends in provision of treatments and survival in Norway over a 15-year period following the implementation of hepato-pancreato-biliary (HPB) multidisciplinary teams, centralization of surgery, and implementation of modern chemotherapy (CTx) regimens. Methods - A population-based observational study was conducted by analysing all patients diagnosed with PDAC between 2004 and 2018 using coupled data from the Cancer Registry of Norway and the National Patient Registry. Results - A total of 10 630 patients were identified, of whom 1492 (14.0 per cent) underwent surgical resection. The resection rate, median age of those resected, and provision of perioperative CTx all increased over time. Median overall survival after resection improved from 16.0 months in the period 2004 to 2008 to 25.1 months in the period 2014 to 2018 (P  Conclusion - Survival after resection increased substantially, as did national resection rates. Little development in the provision of CTx or survival was observed for non-resected patients

The Role of Preoperative Inflammatory Markers in Pancreatectomy: a Norwegian Nationwide Cohort Study

Background and purpose Preoperative infammatory markers, such as Glasgow prognostic score, modifed Glasgow prognostic score and C-reactive protein to albumin ratio, were shown to be associated with prognosis in patients undergoing pancreatectomy for cancer. However, little is known about their predictive role in a Western population. Methods The Norwegian National Registry for Gastrointestinal Surgery (NORGAST) was used to capture all pancreatectomies performed within the study period (November 2015—April 2021). The association between the preoperative infammatory markers and postoperative outcomes was studied. Their impact on survival was examined in patients operated for pancreatic ductal adenocarcinoma. Results A total of 1554 patients underwent pancreatectomy in this period. Glasgow prognostic score, modifed Glasgow prognostic score and C-reactive protein to albumin ratio were associated with severe complications (Accordion grade≥III) in the univariable but not in the multivariable analysis. C-reactive protein to albumin ratio, but not Glasgow prognostic score and modifed Glasgow prognostic score, was linked to survival following pancreatectomy for ductal adenocarcinoma. In the multivariable model, age, neoadjuvant chemotherapy, ECOG score, C-reactive protein to albumin ratio and total pancreatectomy correlated with survival. Also, preoperative C-reactive protein to albumin ratio was signifcantly associated with survival after pancreatoduodenectomy. Conclusions Preoperative Glasgow prognostic score, modifed Glasgow prognostic score and C-reactive protein to albumin ratio have no role in predicting the complications after pancreatectomy. C-reactive protein to albumin ratio is a signifcant predictor for survival in ductal adenocarcinoma, yet its clinical relevance should be explored in conjunction with the pathology parameters and adjuvant therapy

Centralizing a national pancreatoduodenectomy service: striking the right balance

Background - Centralization of pancreatic surgery is currently called for owing to superior outcomes in higher‐volume centres. Conversely, organizational and patient concerns speak for a moderation in centralization. Consensus on the optimal balance has not yet been reached. This observational study presents a volume–outcome analysis of a complete national cohort in a health system with long‐standing centralization. Methods - Data for all pancreatoduodenectomies in Norway in 2015 and 2016 were identified through a national quality registry and completed through electronic patient journals. Hospitals were dichotomized (high‐volume (40 or more procedures/year) or medium–low‐volume). Results - Some 394 procedures were performed (201 in high‐volume and 193 in medium–low‐volume units). Major postoperative complications occurred in 125 patients (31·7 per cent). A clinically relevant postoperative pancreatic fistula occurred in 66 patients (16·8 per cent). Some 17 patients (4·3 per cent) died within 90 days, and the failure‐to‐rescue rate was 13·6 per cent (17 of 125 patients). In multivariable comparison with the high‐volume centre, medium–low‐volume units had similar overall complication rates, lower 90‐day mortality (odds ratio 0·24, 95 per cent c.i. 0·07 to 0·82) and no tendency for a higher failure‐to‐rescue rate. Conclusion - Centralization beyond medium volume will probably not improve on 90‐day mortality or failure‐to‐rescue rates after pancreatoduodenectomy

Preoperative Inflammatory Markers in Liver Resection for Colorectal Liver Metastases: A National Registry-Based Study

Background Preoperative inflammatory markers were shown to be associated with prognosis following surgery for hepato-pancreato-biliary cancer. Yet little evidence exists about their role in patients with colorectal liver metastases (CRLM). This study aimed to examine the association between selected preoperative inflammatory markers and outcomes of liver resection for CRLM. Methods Data from the Norwegian National Registry for Gastrointestinal Surgery (NORGAST) was used to capture all liver resections performed in Norway within the study period (November 2015–April 2021). Preoperative inflammatory markers were Glasgow prognostic score (GPS), modified Glasgow prognostic score (mGPS) and C-reactive protein to albumin ratio (CAR). The impact of these on postoperative outcomes, as well as on survival were studied. Results Liver resections for CRLM were performed in 1442 patients. Preoperative GPS C 1 and mGPS C 1 were present in 170 (11.8%) and 147 (10.2%) patients, respectively. Both were associated with severe complications but became non-significant in the multivariable model. GPS, mGPS, CAR were significant predictors for overall survival in the univariable analysis, but only CAR remained such in the multivariable model. When stratified by the type of surgical approach, CAR was a significant predictor for survival after open but not laparoscopic liver resections. Conclusions GPS, mGPS and CAR have no impact on severe complications after liver resection for CRLM. CAR outperforms GPS and mGPS in predicting overall survival in these patients, especially following open resections. The prognostic significance of CAR in CRLM should be tested against other clinical and pathology parameters relevant for prognosis

Translation and validation of the Norwegian version of the postoperative quality of recovery score QoR-15

Background As patient-centered care gains more attention, assessing the patient's perspective on their recovery has become increasingly important. In response to the need for a reliable and valid patient reported outcome measurement tool for major surgical resections in Norway. The Norwegian Registry for Gastrointestinal Surgery (NORGAST) initiated a project to translate and evaluate QoR-15's psychometric properties for patients going through general, gastrointestinal (GI), and hepato-pancreato-biliary (HPB) resectional surgery. Methods After a translation and adaption of the original version of QoR–15 into Norwegian, the QoR–15NO was psychometrically evaluated including a confirmatory factor analysis to test for unidimensionality, as well as tests for content validity, internal consistency, measurement error, construct validity, feasibility, and responsiveness. This process included cognitive interviews using a structured interview guide. Further, patients who underwent various types of GI/HPB surgery at five hospitals in different parts of Norway completed the QoR-15NO before surgery and on the first or second day after surgery. The impact of surgery was classified according to Surgical Outcome Risk Tool v2 (SORT), in extra major/complex, major, intermediate, and minor. Results This study included 324 patients with 83% return rate with both pre- and postoperative forms. There were negative correlations between duration of surgery and postoperative QoR-15 score and the difference between post- and preoperative score (change score). Individuals who had gone through surgery with major impact had a lower postoperative mean QoR-15 score (97) than their counterparts who had experienced either medium (QoR-15: 110) or minor (QoR15: 119) impact surgery. Cronbach's alpha (0.88) and Omega Alpha Total (ωt = 0.90) indicate that the scale has good to very good internal consistency. Test–retest reliability was measured by Intra-class Correlation Coefficient to ICC = 0.70. Confirmatory factor analyses supported that a one-factor model with correlated residuals had a good fit to data. Conclusion This study supports QoR-15NO as a valid, essentially unidimensional, feasible, and responsive instrument among patients undergoing general, GI, and HPB resectional surgery in Norway. The total QoR-15NO score provides important information that can be used in an everyday clinical setting and integrated into NORGAST

Benchmarking of aggregated length of stay after open and laparoscopic surgery for cancers of the digestive system

Background: Length of hospital stay (LOS) may serve as a surrogate measure of healthcare quality and resource use, particularly when transfers of care and readmissions are accounted for. This study aimed to benchmark true hospital stay by measuring index, transfer and readmission stays across the range of digestive cancer surgery. Methods: A cohort study of all patients undergoing resection for cancer of the oesophagus, stomach, liver, pancreas, colon or rectum in 2012–2016 was undertaken. Index LOS, transfer and readmission stays were merged into an ‘aggregated’ length of stay (a‐LOS), and compared between organ sites and between open and minimal‐access approaches. Results: In total, 24 354 resections were reported (mean age of patients 68·3 years; 51·3 per cent were men). Resections were reported as laparoscopic for 9151 procedures (37·6 per cent), with a further 283 (3·0 per cent) described as converted to open surgery. Use of a‐LOS compared with standard LOS added a median of 5 days for pancreatoduodenectomy, 4 days for major liver resections, 3 days for oesophageal and gastric resections, and 2 days for minor liver, distal pancreatic and rectal resections. Conclusion: Overall hospital stay across organ sites and procedures is better described by a‐LOS. The study benchmarks the use of total hospital days during the first 30 days in a universal healthcare system