Effect of centralization and regionalization of pancreatic surgery on resection rates and survival.

BACKGROUND: Centralization of pancreatic surgery in the Netherlands has been ongoing since 2011. The aim of this study was to assess how centralization has affected the likelihood of resection and survival of patients with non-metastatic pancreatic head and periampullary cancer, diagnosed in hospitals with and without pancreatic surgery services. METHODS: An observational cohort study was performed on nationwide data from the Netherlands Cancer Registry (2009-2017), including patients diagnosed with non-metastatic pancreatic head or periampullary cancer. The period of diagnosis was divided into three time intervals: 2009-2011, 2012-2014 and 2015-2017. Hospital of diagnosis was classified as a pancreatic or non-pancreatic surgery centre. Analyses were performed using multivariable logistic and Cox regression models. RESULTS: In total, 10 079 patients were included, of whom 3114 (30.9 per cent) were diagnosed in pancreatic surgery centres. Between 2009-2011 and 2015-2017, the number of patients undergoing resection increased from 1267 of 3169 (40.0 per cent) to 1705 of 3566 (47.8 per cent) (P for trend < 0.001). In multivariable analysis, in 2015-2017, unlike the previous periods, patients diagnosed in pancreatic and non-pancreatic surgery centres had a similar likelihood of resection (odds ratio 1.08, 95 per cent c.i. 0.90 to 1.28; P = 0.422). In this period, however, overall survival was higher in patients diagnosed in pancreatic surgery than in those diagnosed in non-pancreatic surgery centres (hazard ratio 0.92, 95 per cent c.i. 0.85 to 0.99; P = 0.047). CONCLUSION: After centralization of pancreatic surgery, the resection rate for patients with pancreatic head and periampullary cancer diagnosed in non-pancreatic surgery centres increased and became similar to that in pancreatic surgery centres. Overall survival remained higher in patients diagnosed in pancreatic surgery centres.

Differences in Treatment and Outcome of Pancreatic Adenocarcinoma Stage I and II in the EURECCA Pancreas Consortium.

BACKGROUND: The EUropean REgistration of Cancer CAre (EURECCA) consortium aims to investigate differences in treatment and to improve cancer care through Europe. The purpose of this study was to compare neo- and adjuvant chemotherapy (ACT) and outcome after tumor resection for pancreatic adenocarcinoma stage I and II in the EURECCA Pancreas consortium. METHODS: The eight, collaborating national, regional, and single-center partners shared their anonymized dataset. Patients diagnosed in 2012-2013 who underwent tumor resection for pancreatic adenocarcinoma stage I and II were investigated with respect to treatment and survival and compared using uni- and multivariable logistic and Cox regression analyses. All comparisons were performed separately per registry type: national, regional, and single-center registries. RESULTS: In total, 2052 patients were included. Stage II was present in the majority of patients. The use of neo-ACT was limited in most registries (range 2.8-15.5%) and was only different between Belgium and The Netherlands after adjustment for potential confounders. The use of ACT was different between the registries (range 40.5-70.0%), even after adjustment for potential confounders. Ninety-day mortality was also different between the registries (range 0.9-13.6%). In multivariable analyses for overall survival, differences were observed between the national and regional registries. Furthermore, patients in ascending age groups and patients with stage II showed a significant worse overall survival. CONCLUSIONS: This study provides a clear insight in clinical practice in the EURECCA Pancreas consortium. The differences observed in (neo-)ACT and outcome give us the chance to further investigate the best practices and improve outcome of pancreatic adenocarcinoma.

Nationwide outcomes in patients undergoing surgical exploration without resection for pancreatic cancer.

BACKGROUND: Despite improvements in diagnostic imaging and staging, unresectable pancreatic cancer is still encountered during surgical exploration with curative intent. This nationwide study investigated outcomes in patients with unresectable pancreatic cancer found during surgical exploration. METHODS: All patients diagnosed with primary pancreatic (adeno)carcinoma (2009-2013) in the Netherlands Cancer Registry were included. Predictors of unresectability, 30-day mortality and poor survival were evaluated using logistic and Cox proportional hazards regression analysis. RESULTS: There were 10 595 patients with pancreatic cancer during the study interval. The proportion of patients undergoing surgical exploration increased from 19·9 to 27·0 per cent (P < 0·001). Among 2356 patients who underwent surgical exploration, the proportion of patients with tumour resection increased from 61·6 per cent in 2009 to 71·3 per cent in 2013 (P < 0·001), whereas the contribution of M1 disease (18·5 per cent overall) remained stable. Patients who had exploration only had an increased 30-day mortality rate compared with those who underwent tumour resection (7·8 versus 3·8 per cent; P < 0·001). In the non-resected group, among those with M0 (383 patients) and M1 (435) disease at surgical exploration, the 30-day mortality rate was 4·7 and 10·6 per cent (P = 0·002), median survival was 7·2 and 4·4 months (P < 0·001), and 1-year survival rates were 28·0 and 12·9 per cent, respectively. Among other factors, low hospital volume (0-20 resections per year) was an independent predictor for not undergoing tumour resection, but also for 30-day mortality and poor survival among patients without tumour resection. CONCLUSION: Exploration and resection rates increased, but one-third of patients who had surgical exploration for pancreatic cancer did not undergo resection. Non-resectional surgery doubled the 30-day mortality rate compared with that in patients undergoing tumour resection.

Association Between the Most Frequent Complications After Surgery for Stage I-III Colon Cancer and Short-Term Survival, Long-Term Survival, and Recurrences.

BACKGROUND: The purpose of this study was to identify the ten most frequent complications after surgery for stage I-III colon cancer and to assess the association between these complications and overall survival, conditional overall survival, and recurrences. METHODS: All patients who underwent surgery for stage I-III colon cancer in five hospitals in the Western region of the Netherlands were identified. Crude and adjusted Cox proportional hazards models were used to study the association between complications and 1-year overall survival, 5-year overall survival, 5-year conditional overall survival, and 5-year disease-free period. RESULTS: Data from 761 patients were used for the analyses. Complications were associated with decreased 1-year overall survival (hazard ratio (HR) 2.87, 95 % confidence interval (CI) 1.82-4.51; p < 0.001), 5-year overall survival (HR 1.59, 95 % CI 1.25-2.04; p < 0.001), and 5-year conditional overall survival (HR 1.34, 95 % CI 1.06-1.69; p = 0.016), whereas an increasing number of complications had no additional impact. Anastomotic leakage, excessive blood loss, and (abdominal) sepsis were associated with reduced 1-year overall survival, anastomotic leakage, delirium, abscess, and (abdominal) sepsis with reduced 5-year overall survival, and anastomotic leakage, delirium, and abscess with reduced 5-year conditional overall survival. Anastomotic leakage, electrolyte disorders, and abscess were risk factors for recurrence within five years. CONCLUSIONS: Our results demonstrate the serious impact of the most frequent complications after surgery for colon cancer on short-term and long-term outcomes. This study confirms the prolonged impact of surgery and demonstrates that complications result not only in reduced 1-year survival, but also in reduced long-term outcomes.

Differences in outcomes of oesophageal and gastric cancer surgery across Europe.

BACKGROUND: In several European countries, centralization of oesophagogastric cancer surgery has been realized and clinical audits initiated. The present study was designed to evaluate differences in resection rates, outcomes and annual hospital volumes between these countries, and to analyse the relationship between hospital volume and outcomes. METHODS: National data were obtained from cancer registries or clinical audits in the Netherlands, Sweden, Denmark and England. Differences in outcomes were analysed between countries and between hospital volume categories, adjusting for available case-mix factors. RESULTS: Between 2004 and 2009, 10 854 oesophagectomies and 9010 gastrectomies were registered. Resection rates in England were 18·2 and 21·6 per cent for oesophageal and gastric cancer respectively, compared with 28·5-29·9 and 41·4-41·9 per cent in the Netherlands and Denmark (P < 0·001). The adjusted 30-day mortality rate after oesophagectomy was lowest in Sweden (1·9 per cent). After gastrectomy, the adjusted 30-day mortality rate was significantly higher in the Netherlands (6·9 per cent) than in Sweden (3·5 per cent; P = 0·017) and Denmark (4·3 per cent; P = 0·029). Increasing hospital volume was associated with a lower 30-day mortality rate after oesophagectomy (odds ratio 0·55 (95 per cent confidence interval 0·42 to 0·72) for at least 41 versus 1-10 procedures per year) and gastrectomy (odds ratio 0·64 (0·41 to 0·99) for at least 21 versus 1-10 procedures per year). CONCLUSION: Hospitals performing larger numbers of oesophagogastric cancer resections had a lower 30-day mortality rate. Differences in outcomes between several European countries could not be explained by differences in hospital volumes. To understand these differences in outcomes and resection rates, with reliable case-mix adjustments, a uniform European upper gastrointestinal cancer audit with recording of standardized data is warranted.

Complicated postoperative recovery increases omission, delay and discontinuation of adjuvant chemotherapy in patients with Stage III colon cancer.

AIM: The study included investigation of factors determining suboptimal adjuvant chemotherapy of patients diagnosed with Stage III colon cancer. METHOD: All 606 patients diagnosed with Stage III colon cancer between 2006 and 2008 in the western part of the Netherlands were included. Patient [gender, age, comorbidity and socio-economic status (SES)], tumour (location, stage and grade) and treatment (emergency surgery, laparoscopic surgery, reoperation, hospital stay and multidisciplinary meeting) factors were examined in logistic regression analyses predicting a complicated postoperative period and omission, delay and discontinuation of adjuvant chemotherapy. RESULTS: Overall, 27% of all patients experienced a complicated postoperative period, which was independently associated with emergency surgery, older age, multiple comorbidity, male gender and poor tumour grade. Of patients who survived this period, 60% received chemotherapy. Chemotherapy was omitted more often in women, the elderly and in patients with Stage IIIB, reoperation, prolonged hospital stay and (borderline) after open surgery. Of patients who received chemotherapy, 86% started within 8 weeks after surgery. Patients with a higher SES, reoperation and prolonged hospital stay had a higher probability of a delayed start. Sixty-seven per cent of patients completed their chemotherapy. For women, elderly patients and patients with prolonged hospital stay a higher probability of discontinuation was noted. CONCLUSION: Age was the most important predictive factor for receiving adjuvant chemotherapy. However, at all ages, complicated postoperative recovery negatively influenced the administration of chemotherapy to Stage III colon cancer patients, as well as a timely start and completion of chemotherapy.

Influence of hospital type on outcomes after oesophageal and gastric cancer surgery.

BACKGROUND: Outcomes after oesophagectomy and gastrectomy vary considerably between hospitals. Possible explanations include differences in case mix, hospital volume and hospital type. The present study examined the distribution of oesophagectomies and gastrectomies between hospital types in the Netherlands, and the relationship between hospital type and outcome. METHODS: Data were obtained from the nationwide Netherlands Cancer Registry. Hospitals were categorized as university hospitals (UH), non-university teaching hospitals (NUTH) and non-university non-teaching hospitals (NUNTH). Hospital type-outcome relationships were analysed by Cox regression, adjusting for case mix, hospital volume, year of diagnosis and use of multimodal therapies. RESULTS: Between 1989 and 2009, 10 025 oesophagectomies and 14 221 gastrectomies for cancer were performed in the Netherlands. The percentage of oesophagectomies and gastrectomies performed in UH increased from 17·6 and 6·4 per cent respectively in 1989 to 44·1 and 12·9 per cent in 2009. After oesophagectomy, the 3-month mortality rate was 2·5 per cent in UH, 4·4 per cent in NUTH and 4·1 per cent in NUNTH (P = 0·006 for UH versus NUTH). After gastrectomy, the 3-month mortality rate was 4·9 per cent in UH, 8·9 per cent in NUTH and 8·7 per cent in NUNTH (P < 0·001 for UH versus NUTH). Three-year survival was also higher in UH than in NUTH and NUNTH. CONCLUSION: Oesophagogastric resections performed in UH were associated with better outcomes but, owing to variation in outcomes within hospital types, centres of excellence cannot be designated solely on hospital type. Detailed information on case mix and outcomes is needed to identify centres of excellence.

Socioeconomic differences in survival among breast cancer patients in the Netherlands not explained by tumor size.

There seem to be socioeconomically differences in survival for females with breast cancer, usually associated with a higher stage of disease. However, differences within tumor size have not been studied. Aim of this study is to assess differences in survival according to socioeconomic status (SES), stratified for tumor size and stage at diagnosis, for females with breast cancer in the Netherlands. All females diagnosed with breast cancer (1995-2005) were selected from the Netherlands Cancer Registry. Patients were linked to a SES database according to postal code. A multivariable logistic regression was used to assess factors associated with SES. Overall survival (OS) and relative survival (RS) were calculated. Overall, 127,599 patients were included. Higher SES was associated with lower T-stage (P < 0.0001). A decreased survival (OS and RS) was found for patients with a lower SES. Also within different size groups, RS was different. Overall, 10-year OS for the high SES group was 65 and 58% for the low SES group (hazard ratio 1.1, P < 0.001) and RS was 79 versus 74% (relative excess risk, RER 1.2; P < 0.001). The socioeconomic differences remained statistically significant (P < 0.001) after adjustment for age, year of diagnosis, grade, TNM stage, and treatment. For the lowest SES group 777 deaths could be avoided. Socioeconomic differences in survival of breast cancer patients were observed in the Netherlands. Higher stage at diagnosis of patients with a lower SES only partly explains the decreased survival. Policies aimed at the reduction of socioeconomic health inequalities might be important to improve survival of breast cancer.

Breast cancer in elderly compared to younger patients in the Netherlands: stage at diagnosis, treatment and survival in 127,805 unselected patients.

Breast cancer is the most common type of cancer in several parts of the world and the number of elderly patients is increasing. The aim of this study was to describe stage at diagnosis, treatment, and relative survival of elderly patients compared to younger patients in the Netherlands. Adult female patients with their first primary breast cancer diagnosed between 1995 and 2005 were selected. Stage, treatment, and relative survival were described for young and elderly (≥ 65 years) patients and within the cohort of elderly patients according to 5-year age groups. Overall, 127,805 patients were included. Elderly breast cancer patients were diagnosed with a higher stage of disease. Moreover, within the elderly differences in stage were observed. Elderly underwent less surgery (99.2-41.2%); elderly received hormonal treatment as monotherapy more frequently (0.8-47.3%); and less adjuvant systemic treatment (79-53%). Elderly breast cancer patients with breast cancer had a decreased relative survival. Although relative survival was lower in the elderly, the percentage of patients who die of their breast cancer less than 50% above age 75. In conclusion, the relative survival for the elderly is lower as compared to their younger counterparts while the percentage of deaths due to other causes increases with age. This could indicate that the patient selection is poor and fit patients could suffer from "under treatment". In the future, specific geriatric screening tools are necessary to identify fit elderly patients who could receive more "aggressive" treatment while best supportive care should be given to frail elderly patients.

Underestimation of pancreatic cancer in the national cancer registry - Reconsidering the incidence and survival rates.

BACKGROUND: In the Netherlands, like in many other European countries, pancreatic cancer mortality was found to be systematically higher than the incidence. This suggests that there is an underestimation of the reported incidence of pancreatic cancer. AIM: We aimed to study the incidence of pancreatic cancer in the Rotterdam area and to compare this with the national level. METHODS: This study is embedded in the Rotterdam Study (RS), an ongoing population-based prospective cohort study of people aged 45 years and above, enrolled between 1989 till 2006. Details on incident pancreatic cancer cases were available until 2013. Age-specific incidence rates were calculated and compared with data available in the Netherlands Cancer Registry. RESULTS: At baseline 14,922 participants were at risk of developing pancreatic cancer. Median follow-up time was 16.4 person years per person. In total, 113 participants developed pancreatic cancer. Rates increased with age with an incidence rate of 109.9 (95% confidence interval [CI]; 85.7-138.8) per 100,000 person years for people older than 75. This is higher than the currently reported 55.9-89.2 per 100,000 person year. Of the 113 cases identified in the RS, only 67.3% was reported as pancreatic cancer in the Netherlands Cancer Registry. Cases that were not registered were significantly older and had significantly poorer survival. CONCLUSION: The incidence of pancreatic cancer, as registered by the Netherlands Cancer Registry, is an underestimation. Patients, not registered by the cancer registry, have a significantly poorer survival. Consequently, we probably overestimate the already poor survival of pancreatic cancer.

Cause of death the first year after curative colorectal cancer surgery; a prolonged impact of the surgery in elderly colorectal cancer patients.

BACKGROUND: The 1-year mortality after colorectal cancer surgery is high and explains age related differences in colorectal cancer survival. To gain better insight in its etiology, cause of death for these patients was studied. METHODS: All 1924 patients who had a resection for stage I-III colorectal cancer from 2006 to 2008 in the Western region of the Netherlands were identified. Data were merged with cause of death data from the Central Bureau of Statistics Netherlands. To calculate excess mortality as compared to the general population, national data were used. RESULTS: Overall 13.2% of patients died within the first postoperative year. One-year mortality increased with age. It was as high as 43% in elderly patients that underwent emergency surgery. In 75% of patients, death was attributed to the colorectal cancer. In 25% of all patients, registered deaths were attributed to postoperative complications. Elderly patients with comorbidity more frequently died due to complications (p < 0.01). Death of other causes was similar to background mortality according to age group. CONCLUSION: In the presently studied cohort of patients that died within one year of surgery, cause of death was predominantly attributed to colorectal cancer. However, because it is not to be expected that in this cohort the number of deaths from recurrences is very high, the excess 1-year mortality indicates a prolonged impact of the surgery, especially in elderly patients. Therefore, in these patients we should focus on limiting the physiological impact of the surgery and be more involved in the post-hospital period.

Prognostic value of geriatric assessment in older patients with advanced breast cancer receiving chemotherapy.

INTRODUCTION: The prognostic value of geriatric assessment in older patients with breast cancer treated with chemotherapy is largely unknown. METHODS: Fifty-five patients with advanced breast cancer aged 70 years or older were assessed by Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Levels of albumin, hemoglobin, creatinine and lactate dehydrogenase were measured. Patients completing at least four cycles of chemotherapy were reassessed by GFI and MMSE and mortality was evaluated using Cox regression analysis. RESULTS: The mean age was 76 year (SD 4.8). Inferior MNA and GFI scores were associated with increased hazard ratios for mortality: 3.05 (95% confidence interval [CI]: 1.44-6.45; p = 0.004) and 3.40 (95% CI: 1.62-7.10; p = 0.001), respectively. Physical aspects of frailty worsened during the course of chemotherapy. Laboratory values were not associated with assessment scores nor were they predictive for mortality. CONCLUSIONS: Malnutrition and frailty, rather than cognitive impairment and laboratory values, were associated with an increased mortality risk in these elderly breast cancer patients with advanced breast cancer.

Use of different comorbidity scores for risk-adjustment in the evaluation of quality of colorectal cancer surgery: does it matter?

AIMS: Comorbidity affects outcomes after colorectal cancer surgery. However, it's importance in risk adjustment is unclear and different measures are being used. This study aims to assess its impact on post-operative outcomes. METHODS: All 2204 patients who were operated on for stage I-III colorectal cancer in the Midwestern region of the Netherlands between January 1, 2006 and December 31, 2008 were analyzed. A multivariate two-step enter-model was used to evaluate the effect of the American Society of Anaesthesiologists Physical Status classification (ASA) score, the sum of diseased organ systems (SDOS), the Charlson Comorbidity Index (CCI) and a combination of specific comorbidities on 30-day mortality, surgical complications and a prolonged length of stay (LOS). For each retrieved model, and for a model without comorbidity, a ROC curve was made. RESULTS: High ASA score, SDOS, CCI, pulmonary disease and previous malignancy were all strongly associated with 30-day mortality and a prolonged LOS. High ASA score and gastro-intestinal comorbidity were risk factors for surgical complications. Predictive values for all comorbidity measures were similar with regard to all adverse post-operative outcomes. Omitting comorbidity only had a marginal effect on the predictive value of the model. CONCLUSION: Irrespective of the measure used, comorbidity is an independent risk factor for adverse outcome after colorectal surgery. However, the importance of comorbidity in risk-adjustment models is limited. Probably the work and costs of data collection for auditing can be reduced, without compromising risk-adjustment.

Predictive value of geriatric assessment for patients older than 70 years, treated with chemotherapy.

INTRODUCTION: Comprehensive geriatric assessment (CGA) gives useful information on the functional status of older cancer patients. However, its meaning for a proper selection of elderly patients before chemotherapy and, even more important, the influence of chemotherapy on the outcome of geriatric assessment is unknown. METHODS: 202 cancer patients, for whom an indication for chemotherapy was made by the medical oncologist, underwent a GA before start of chemotherapy by Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Index (GFI) and Mini Mental State Examination (MMSE). After completion of a minimum of four cycles of chemotherapy or at 6 months after the start of chemotherapy the GFI and MMSE assessment was repeated. RESULTS: Frailty was shown in 10% of patients by means of MMSE, 32% by MNA, 37% by GFI and in 15% by IQCODE. Compared to patients who received 4 or more cycles of chemotherapy, the MNA and MMSE scores were significantly lower for patients treated with less than 4 cycles (p = 0.001 and p = 0.04 respectively). The mortality rate after start of chemotherapy was increased for patients with low MNA and high GFI scores with hazard ratios of 2.19 (95% confidence interval [CI]: 1.42-3.39; p < 0.001) and 1.80 (95% CI: 1.17-2.78; p = 0.007), respectively. After adjusting for sex, age, purpose of chemotherapy and type of malignancy these hazard ratios remained significant (p < 0.001 and p = 0.004), respectively. Finally, for the 51 patients who underwent repeated post-chemotherapy evaluation by GFI and MMSE, a statistically significant deterioration for the MMSE (p = 0.041) was found but not for the GFI. CONCLUSIONS: Both inferior MNA and MMSE scores increased the probability not to complete chemotherapy. Also, an inferior score for MNA and GFI showed an increased mortality risk after the start of chemotherapy. The mean MMSE score worsened significantly during chemotherapy.