The Impact of the Gut Microbiome, Environment, and Diet in Early-Onset Colorectal Cancer Development.

Traditionally considered a disease common in the older population, colorectal cancer is increasing in incidence among younger demographics. Evidence suggests that populational- and generational-level shifts in the composition of the human gut microbiome may be tied to the recent trends in gastrointestinal carcinogenesis. This review provides an overview of current research and putative mechanisms behind the rising incidence of colorectal cancer in the younger population, with insight into future interventions that may prevent or reverse the rate of early-onset colorectal carcinoma.

Immune Microenvironment in Sporadic Early-Onset versus Average-Onset Colorectal Cancer.

The incidence of left-sided colon and rectal cancer in young people are increasing worldwide, but its causes are poorly understood. It is not clear if the tumor microenvironment is dependent on age of onset, and little is known about the composition of tumor-infiltrating T cells in early-onset colorectal cancer (EOCRC). To address this, we investigated T-cell subsets and performed gene expression immune profiling in sporadic EOCRC tumors and matched average-onset colorectal cancer (AOCRC) tumors. Left-sided colon and rectal tumors from 40 cases were analyzed; 20 EOCRC (<45 years) patients were matched 1:1 to AOCRC (70-75 years) patients by gender, tumor location, and stage. Cases with germline pathogenic variants, inflammatory bowel disease or neoadjuvant-treated tumors were excluded. For T cells in tumors and stroma, a multiplex immunofluorescence assay combined with digital image analysis and machine learning algorithms was used. Immunological mediators in the tumor microenvironment were assessed by NanoString gene expression profiling of mRNA. Immunofluorescence revealed no significant difference between EOCRC and AOCRC with regard to infiltration of total T cells, conventional CD4+ and CD8+ T cells, regulatory T cells, or γδ T cells. Most T cells were located in the stroma in both EOCRC and AOCRC. Immune profiling by gene expression revealed higher expression in AOCRC of the immunoregulatory cytokine IL-10, the inhibitory NK cell receptors KIR3DL3 and KLRB1 (CD161), and IFN-a7 (IFNA7). In contrast, the interferon-induced gene IFIT2 was more highly expressed in EOCRC. However, in a global analysis of 770 tumor immunity genes, no significant differences could be detected. T-cell infiltration and expression of inflammatory mediators are similar in EOCRC and AOCRC. This may indicate that the immune response to cancer in left colon and rectum is not related to age of onset and that EOCRC is likely not driven by immune response deficiency.

Prolonged postoperative length of stay may be a valuable marker for susceptibility to relapse beyond established risk factors in patients with stage III colon cancer.

BACKGROUND: Delay from surgery to adjuvant chemotherapy causes impaired survival among patients undergoing radical resection for stage III colon cancer, and the underlying mechanism for this is incompletely clarified. It is established that prolonged postoperative hospital length of stay (LOS) is associated with delayed initiation of the adjuvant treatment driving the assumption that prolonged LOS is prognostically unfavorable due to this fact and case mix factors. We hypothesize that prolonged LOS after surgery is a valuable marker for susceptibility to relapse that is not detected in established prognostic factors and, alone, associated with a shorter disease-free survival (DFS). MATERIALS AND METHODS: A total of 690 consecutive patients undergoing elective radical resection for stage III colon cancer in 2000-2015 were identified in a prospective detailed facility database. Univariate and multivariate analyses were performed using Cox proportional hazards model in the evaluation of LOS as an independent prognostic factor. RESULTS: Short postoperative LOS, low comorbidity, and few complications were associated with longer DFS (p < 0.01). Fewer patients in the short and intermediate LOS groups had a relapse in their disease (28% and 33%, respectively), compared to the patients with longer LOS (40%, p < 0.05). LOS was a prognostic factor for DFS in the unadjusted univariate model (HR 1.04 per unit change) and remained statistically significant in the adjusted multivariate analysis, with a HR of 1.03 per hospital day (p < 0.01). CONCLUSIONS: Postoperative LOS independently correlates with the risk of recurrence and DFS, regardless of if adjuvant chemotherapy is given, along with the factors such as age, comorbidity, complications, and tumor features. We propose a further investigation into the causal mechanisms based on tumor and host biology linking LOS to DFS beyond established risk factors.

The Development and Inclusion of Questions on Surgery in the 2018 Zambia Demographic and Health Survey.

BACKGROUND: While primary data on the unmet need for surgery in low- and middle-income countries is lacking, household surveys could provide an entry point to collect such data. We describe the first development and inclusion of questions on surgery in a nationally representative Demographic and Health Survey (DHS) in Zambia. METHOD: Questions regarding surgical conditions were developed through an iterative consultative process and integrated into the rollout of the DHS survey in Zambia in 2018 and administered to a nationwide sample survey of eligible women aged 15-49 years and men aged 15-59 years. RESULTS: In total, 7 questions covering 4 themes of service delivery, diagnosed burden of surgical disease, access to care, and quality of care were added. The questions were administered across 12,831 households (13,683 women aged 15-49 years and 12,132 men aged 15-59 years). Results showed that approximately 5% of women and 2% of men had undergone an operation in the past 5 years. Among women, cesarean delivery was the most common surgery; circumcision was the most common procedure among men. In the past 5 years, an estimated 0.61% of the population had been told by a health care worker that they might need surgery, and of this group, 35% had undergone the relevant procedure. CONCLUSION: For the first time, questions on surgery have been included in a nationwide DHS. We have shown that it is feasible to integrate these questions into a large-scale survey to provide insight into surgical needs at a national level. Based on the DHS design and implementation mechanisms, a country interested in including a set of questions like the one included in Zambia, could replicate this data collection in other settings, which provides an opportunity for systematic collection of comparable surgical data, a vital role in surgical health care system strengthening.

Global surgery, obstetric, and anaesthesia indicator definitions and reporting: An Utstein consensus report.

BACKGROUND: Indicators to evaluate progress towards timely access to safe surgical, anaesthesia, and obstetric (SAO) care were proposed in 2015 by the Lancet Commission on Global Surgery. These aimed to capture access to surgery, surgical workforce, surgical volume, perioperative mortality rate, and catastrophic and impoverishing financial consequences of surgery. Despite being rapidly taken up by practitioners, data points from which to derive the indicators were not defined, limiting comparability across time or settings. We convened global experts to evaluate and explicitly define-for the first time-the indicators to improve comparability and support achievement of 2030 goals to improve access to safe affordable surgical and anaesthesia care globally. METHODS AND FINDINGS: The Utstein process for developing and reporting guidelines through a consensus building process was followed. In-person discussions at a 2-day meeting were followed by an iterative process conducted by email and virtual group meetings until consensus was reached. The meeting was held between June 16 to 18, 2019; discussions continued until August 2020. Participants consisted of experts in surgery, anaesthesia, and obstetric care, data science, and health indicators from high-, middle-, and low-income countries. Considering each of the 6 indicators in turn, we refined overarching descriptions and agreed upon data points needed for construction of each indicator at current time (basic data points), and as each evolves over 2 to 5 (intermediate) and >5 year (full) time frames. We removed one of the original 6 indicators (one of 2 financial risk protection indicators was eliminated) and refined descriptions and defined data points required to construct the 5 remaining indicators: geospatial access, workforce, surgical volume, perioperative mortality, and catastrophic expenditure. A strength of the process was the number of people from global institutes and multilateral agencies involved in the collection and reporting of global health metrics; a limitation was the limited number of participants from low- or middle-income countries-who only made up 21% of the total attendees. CONCLUSIONS: To track global progress towards timely access to quality SAO care, these indicators-at the basic level-should be implemented universally as soon as possible. Intermediate and full indicator sets should be achieved by all countries over time. Meanwhile, these evolutions can assist in the short term in developing national surgical plans and collecting more detailed data for research studies.

Simulation capacity building in rural Indian hospitals: a 1-year follow-up qualitative analysis.

Introduction: The benefits of simulation-based medical training are well described. The most effective way to plant and scale simulation training in rural locations remains undescribed. We sought to plant simulation training programmes for anaesthesia emergencies in two rural Indian hospitals. Methods: Two Indian consultant anaesthetists without experience in medical simulation underwent a 3-day course at the Boston Children's Hospital's (BCH) Simulator Program. They returned to their institutions and launched simulation programmes with an airway manikin and mock patient monitor. The 1-year experience was evaluated using individual, in-depth interviews of simulation facilitators. Three staff members (responsible for facilitating medical simulations over the prior year) at two rural hospitals in India were interviewed. None attended the BCH training; instead, they received on-the-job training from the BCH-trained, consultant anaesthetist colleagues. Results: Successes included organisational adoption of simulation training with exercises 1 year after the initial BCH-training, increased interdisciplinary teamwork and improved clinical competency in managing emergencies. Barriers to effective, local implementation of simulation programmes fell into three categories: time required to run simulations, fixed and rigid roles, and variable resources. Thematic improvement requests were for standardised resources to help train simulation facilitators and demonstrate to participants a well-run simulation, in addition to context-sensitive scenarios. Conclusion: An in-person training of simulation facilitators to promote medical simulation programmes in rural hospitals produced ongoing simulation programmes 1 year later. In order to make these programmes sustainable, however, increased investment in developing simulation facilitators is required. In particular, simulation facilitators must be prepared to formally train other simulation facilitators, too.

Association of DNA repair gene variants with colorectal cancer: risk, toxicity, and survival.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in DNA repair genes have a potential clinical value in predicting treatment outcomes. In the current study, we examined the association of SNPs in the genes XRCC1-rs25487, ERCC1-rs11615, ERCC2-rs238406, and ERCC2-rs13181 with colorectal cancer (CRC) risk, relapse-free survival (RFS), overall survival (OS), and toxicity during chemotherapy. METHODS: SNPs were analysed in 590 CRC cases and 300 controls using TaqMan technology. The association of SNPs with CRC risk and toxicity during chemotherapy was analysed using Chi2 test. The Kaplan-Meier method and log-rank test was used to measure the effects of the SNPs on RFS and OS. RESULTS: The CC genotype of ERCC2-rs238406 and the ERCC2-rs13181 C allele were associated with a significantly increased risk of CRC. The ERCC1-rs11615 genotype T/T was associated with stomatitis in adjuvant chemotherapy (p = 0.03). Also, more patients with the ERCC2-rs13181 C allele needed dose reduction compared to patients with the A/A genotype (p = 0.02). In first line chemotherapy, more patients with the ERCC1-rs11615 C allele suffered from nausea compared to those with the T/T genotype (p = 0.04) and eye reactions and thrombocytopenia were more common in patients with the ERCC2-rs13181 C allele compared to the A/A genotype (p = 0.006 and p = 0.004, respectively). ERCC2- rs238406 C/C was also associated with a higher frequency of thrombocytopenia (p = 0.03). A shorter 5-year OS was detected in stage I & II CRC patients with the ERCC2- rs238406 C allele (p = 0.02). However, there was no significant association between the SNPs and 5-year RFS. CONCLUSIONS: Both SNPs in ERCC2 were associated with risk of CRC as well as toxicity during first line treatment. In addition, ERCC2- rs238406 was linked to OS in early stage CRC. The ERCC1-rs11615 variant was associated with toxicity during adjuvant chemotherapy. The results add support to previous findings that SNPs in ERCC1 and ERCC2 have a prognostic and predictive value in clinical management of CRC.

Safety and efficiency of gasless laparoscopy: a systematic review protocol.

BACKGROUND: Gasless laparoscopy, developed in the early 1990s, was a means to minimize the clinical and financial challenges of pneumoperitoneum and general anaesthesia. It has been used in a variety of procedures such as in general surgery and gynecology procedures including diagnostic laparoscopy. There has been increasing evidence of the utility of gasless laparoscopy in resource limited settings where diagnostic imaging is not available. In addition, it may help save costs for hospitals. The aim of this study is to conduct a systematic review of the available evidence surrounding the safety and efficiency of gasless laparoscopy compared to conventional laparoscopy and open techniques and to analyze the benefits that gasless laparoscopy has for low resource setting hospitals. METHODS: This protocol is developed by following the Preferred Reporting Items for Systematic review and Meta-Analysis-Protocols (PRISMA-P). The PRISMA statement guidelines and flowchart will be used to conduct the study itself. MEDLINE (Ovid), Embase, Web of Science, Cochrane Central, and Global Index Medicus (WHO) will be searched and the National Institutes of Health Clinical Trials database. The articles that will be found will be pooled into Covidence article manager software where all the records will be screened for eligibility and duplicates removed. A data extraction spreadsheet will be developed based on variables of interest set a priori. Reviewers will then screen all included studies based on the eligibility criteria. The GRADE tool will be used to assess the quality of the studies and the risk of bias in all the studies will be assessed using the Cochrane Risk assessment tool. The RoB II tool will assed the risk of bias in randomized control studies and the ROBINS I will be used for the non-randomized studies. DISCUSSION: This study will be a comprehensive review on all published articles found using this search strategy on the safety and efficiency of the use of gasless laparoscopy. The systematic review outcomes will include safety and efficiency of gasless laparoscopy compared to the use of conventional laparoscopy or laparotomy. TRIAL REGISTRATION: The study has been registered in PROSPERO under registration number: CRD42017078338.

Implementation of an international standardized set of outcome indicators in pregnancy and childbirth in Kenya: Utilizing mobile technology to collect patient-reported outcomes.

BACKGROUND: Limited data exist on health outcomes during pregnancy and childbirth in low- and middle-income countries. This is a pilot of an innovative data collection tool using mobile technology to collect patient-reported outcome measures (PROMs) selected from the International Consortium of Health Outcomes Measurement (ICHOM) Pregnancy and Childbirth Standard Set in Nairobi, Kenya. METHODS: Pregnant women in the third trimester were recruited at three primary care facilities in Nairobi and followed prospectively throughout delivery and until six weeks postpartum. PROMs were collected via mobile surveys at three antenatal and two postnatal time points. Outcomes included incontinence, dyspareunia, mental health, breastfeeding and satisfaction with care. Hospitals reported morbidity and mortality. Descriptive statistics on maternal and child outcomes, survey completion and follow-up rates were calculated. RESULTS: In six months, 204 women were recruited: 50% of women returned for a second ante-natal care visit, 50% delivered at referral hospitals and 51% completed the postnatal visit. The completion rates for the five PROM surveys were highest at the first antenatal care visit (92%) and lowest in the postnatal care visit (38%). Data on depression, dyspareunia, fecal and urinary incontinence were successfully collected during the antenatal and postnatal period. At six weeks postpartum, 86% of women breastfeed exclusively. Most women that completed the survey were very satisfied with antenatal care (66%), delivery care (51%), and post-natal care (60%). CONCLUSION: We have demonstrated that it is feasible to use mobile technology to follow women throughout pregnancy, track their attendance to pre-natal and post-natal care visits and obtain data on PROM. This study demonstrates the potential of mobile technology to collect PROM in a low-resource setting. The data provide insight into the quality of maternal care services provided and will be used to identify and address gaps in access and provision of high quality care to pregnant women.

EGFR, but not COX-2, protein in resected pancreatic ductal adenocarcinoma is associated with poor survival.

The effects of EGFR and COX-2 protein overexpression on clinical outcomes in pancreatic ductal adenocarcinoma (PDAC) patients remains unclear. Therefore, the aim of the present study was to evaluate the protein expression of epithelial growth factor receptor (EGFR) and cyclooxygenase-2 (COX-2) in tumor cells in surgically resected PDAC, in comparison with clinicopathological characteristics and clinical outcomes. Immunohistochemical staining of formalin-fixed paraffin-embedded tissue derived from surgically resected tumors was performed. Tissue slides were evaluated for membrane wild-type EGFR and cytoplasmic COX-2 staining using a histoscore system. Statistical associations between EGFR and COX-2 staining and clinicopathological characteristics were examined to predict survival. In a cohort of 32 resected PDAC patients, high EGFR protein expression in tumor cells was significantly associated with shorter median overall survival (7.9 vs. 39.2 months, P=0.0038). The corresponding hazard ratio (HR) for patients with high EGFR protein expression in tumor cells was 3.12 [95% confidence interval (CI): 1.39-7.00, P=0.006]. COX-2 protein expression was not associated with survival (22.6 vs. 24.5 months P=0.60; HR 1.22 95% CI: 0.59-2.51, P=0.60). Following multivariate Cox regression analysis, high EGFR protein expression in tumor cells (P=0.043) remained as significant independent prognostic factor for survival. In conclusion, high wild-type EGFR protein expression, but not COX-2 protein expression, in tumor cells is a prognostic factor for reduced overall survival following pancreatic tumor resection, supporting a role for EGFR in identifying resected patients that may benefit from EGFR-targeted therapy.

The need to collect, aggregate, and analyze global anesthesia and surgery data.

In the Sustainable Development Goals era, there is a new awareness of the need for an integrated approach to healthcare interventions and a strong commitment to Universal Health Coverage. To achieve the goal of strengthening entire health systems, surgery, as a crosscutting treatment modality, is indispensable. For any health system strengthening exercise, baseline data and longitudinal monitoring of progress are necessary. With improved data capabilities, there are unparalleled possibilities to map out and understand systems, integrating data from many sources and sectors. Nevertheless, there is also a need to prioritize among indicators to avoid information overload and data collection fatigue. There is a similar need to define indicators and collection methodology to create standardized and comparable data. Finally, there is a need to establish data pathways to ensure clear responsibilities amongst national and international institutions and integrate surgical metrics into existing mechanisms for sustainable data collection. This is a call to collect, aggregate, and analyze global anesthesia and surgery data, with an account of existing data sources and a proposed way forward.

RéSUMé: À l'époque des objectifs du développement durable, on constate une nouvelle sensibilisation au besoin d'une approche intégrée dans les interventions en soins de santé et un fort engagement en faveur d'une couverture médicale universelle. Pour atteindre l'objectif du renforcement de systèmes entiers de santé, la chirurgie en tant que modalité thérapeutique transversale est indispensable. Pour toute activité de renforcement du système de santé, des données de référence et un suivi longitudinal des progrès sont nécessaires. Avec de meilleures données, il existe des possibilités sans équivalent de cartographier et de comprendre les systèmes, en intégrant des données provenant de multiples sources et secteurs. Néanmoins, il est également nécessaire de prioriser les indicateurs pour éviter une surcharge d'informations et une fatigue dans la collecte des données. Il existe un besoin similaire de définition des indicateurs et de la méthodologie de collecte afin de créer des données standardisées et comparables. Enfin, il est nécessaire d'établir des cheminements de données pour garantir des responsabilités claires entre les institutions nationales et internationales et intégrer les paramètres chirurgicaux dans les mécanismes existants pour une collecte durable des données. Ceci est un appel à la collecte, au regroupement et à l'analyse de données globales en anesthésie et en chirurgie avec un compte rendu des sources de données existantes et une proposition d'avancée.

Surgical quality indicators in low-resource settings: A new evidence-based tool.

BACKGROUND: Worldwide efforts to improve access to surgical care must be accompanied by improvements in the quality of surgical care; however, these efforts are contingent on the ability to measure quality. This report describes a novel, evidence-based tool to measure quality of surgical care in low-resource settings. METHODS: We defined a widely applicable, multidimensional conceptual framework for quality. The suitability of currently available quality metrics to low-resource settings was evaluated. Then we developed new indicators with sufficient supportive evidence to complete the framework. The complete set of metrics was condensed into four collection sources and tools. RESULTS: The following 15 final evidence-based indicators were defined: (1) Safe structure: morbidity and mortality conference; (2) safe process: use of the safe surgery checklist; (3) (4) safe outcomes: perioperative mortality rate and proportion of cases with complications graded >2 on the Clavien-Dindo scale; (5) effective structure: provider density; (6) effective process: procedure rate; (7) effective outcome: rate of caesarean sections; (8) patient-centered process: use of informed consent; (9) patient-centered outcome: patient hospital satisfaction questionnaire; (10) timely structure: travel time to hospital; (11) timely process: time from emergency department presentation to non-elective abdominal surgery; (12) timely outcome: patient follow-up plan; (13) efficient process: daily operating room usage; (14) equitable outcome: comparative income of patients compared with population; and (15) proportion of patients facing catastrophic expenditure because of surgical care. CONCLUSION: This tool provides an evidence-based conceptual tool to assess the quality of surgical care in diverse low-resource settings.

Perioperative mortality rates in low-income and middle-income countries: a systematic review and meta-analysis.

INTRODUCTION: The Lancet Commission on Global Surgery proposed the perioperative mortality rate (POMR) as one of the six key indicators of the strength of a country's surgical system. Despite its widespread use in high-income settings, few studies have described procedure-specific POMR across low-income and middle-income countries (LMICs). We aimed to estimate POMR across a wide range of surgical procedures in LMICs. We also describe how POMR is defined and reported in the LMIC literature to provide recommendations for future monitoring in resource-constrained settings. METHODS: We did a systematic review of studies from LMICs published from 2009 to 2014 reporting POMR for any surgical procedure. We extracted select variables in duplicate from each included study and pooled estimates of POMR by type of procedure using random-effects meta-analysis of proportions and the Freeman-Tukey double arcsine transformation to stabilise variances. RESULTS: We included 985 studies conducted across 83 LMICs, covering 191 types of surgical procedures performed on 1 020 869 patients. Pooled POMR ranged from less than 0.1% for appendectomy, cholecystectomy and caesarean delivery to 20%-27% for typhoid intestinal perforation, intracranial haemorrhage and operative head injury. We found no consistent associations between procedure-specific POMR and Human Development Index (HDI) or income-group apart from emergency peripartum hysterectomy POMR, which appeared higher in low-income countries. Inpatient mortality was the most commonly used definition, though only 46.2% of studies explicitly defined the time frame during which deaths accrued. CONCLUSIONS: Efforts to improve access to surgical care in LMICs should be accompanied by investment in improving the quality and safety of care. To improve the usefulness of POMR as a safety benchmark, standard reporting items should be included with any POMR estimate. Choosing a basket of procedures for which POMR is tracked may offer institutions and countries the standardisation required to meaningfully compare surgical outcomes across contexts and improve population health outcomes.

Alterations in Tumor DNA Are Related to Short Postoperative Survival in Patients Resected for Pancreatic Carcinoma Aimed at Cure.

OBJECTIVES: Pancreatic ductal adenocarcinomas (PDACs) are found in more than 85% of patients with pancreatic cancer and with 5-year survival of less than 10%. Effective treatment may be radical surgery, which is hampered by rapid relapse. Therefore, our aim was to compare DNA sequence alterations in patients with short and long survival to evaluate if confirmed DNA alterations predict short postoperative survival. METHODS: DNA was extracted from tumor tissue from 59 PDAC patients, analyzed for KRAS mutations, and hybridized to 180 K CGH + SNP microarrays and 450 K methylation arrays. Analyses were based on postoperative survival where less than 12 months was considered to be short survival and more than 18 months was considered long survival. RESULTS: Ninety-three percent of the patients had KRAS mutations in tumor DNA. Great heterogeneity of whole genome DNA sequence alterations were observed among chromosomes within the patient materials. Specific DNA sequence alterations did not directly predict postoperative survival, although short survivors had significantly more and larger DNA amplifications (P < 0.006). Amplifications on chromosome 11 and 21 and deletions on chromosome 2 predicted short postoperative survival (P < 0.03). DNA methylation was not related to survival. CONCLUSIONS: Highly variable genetic differences among DNA regions in PDAC tumors were demonstrated. Postoperative short survival was related to tumor sequence DNA alterations on chromosome 2, 11, and 21.

Case Mix Difference Can Affect Evaluation of Outcome of Treatment for Colorectal Cancer.

AIM: To explore the potential effects of patient selection, for example by organization, on survival as outcome parameter in colorectal cancer treatment. PATIENTS AND METHODS: The main cohort was identified in a Hospital-based registry and outcome data of all 2,717 patients operated on for colorectal cancer between 2000-2011 were evaluated. A simulation of different center settings was performed using several potential selection criteria, including emergency cases, referral surgery and palliative resection, and used for comparison of outcome data. RESULTS: Overall survival and cancer-specific survival can be significantly affected in both short-term (30-/90-day) mortality and long-term survival by factors of organizational level. CONCLUSION: Survival data as an outcome parameter can be affected by the composition of the patient cohort and thus reflect possible selection bias for example due to organization, referral patterns and practice customs. This potential bias should be acknowledged when making inter-hospital comparisons of outcome.

Cost-utility estimations of palliative care in patients with pancreatic adenocarcinoma: a retrospective analysis.

BACKGROUND: We earlier reported cost-utility estimates in patients who undergo resection aimed at cure for pancreatic carcinoma. The present study describes similar information on patients with unresectable tumors who experienced palliative care only. METHODS: A population-based cohort of patients with exocrine pancreatic adenocarcinoma during 1998-2005 was evaluated retrospectively (n = 444). Total direct health care costs at departments of surgery and oncology, for primary health care, and at hospice were achieved. Self-estimated health-related quality of life (HRQL) was assessed by the SF-36. A single preference-based utility index, SF-6D, was derived from SF-36 items to estimate quality-adjusted life years (QALYs). Results were compared to similar findings in a previously reported group of patients with pancreatic carcinoma resected for cure (n = 31). RESULTS: Palliative care patients (n = 305) had impaired HRQL particularly related to physical domains. The mean preference-based health utility index at diagnosis was 0.65 ± 0.02 [95 % confidence interval (CI) 0.61-0.69] compared to 0.77 ± 0.02 (95 % CI 0.75-0.79) in healthy reference individuals. Total direct health care costs were 50 % in patients on palliative care compared to costs for surgical R0 resections (23,701 and 50,950, respectively). QALYs for 1 year from diagnosis were 0.2 (95 % CI 0.17-0.23) in patients on palliative care and 0.48 (95 % CI 0.44-0.54) in resection patients. Costs per QALY were 118,418 and 106,146, respectively (95 % CI 103,048-139,418 and 94,352-115,795). CONCLUSIONS: Optimized palliative care of patients with exocrine pancreatic carcinoma had costs per achieved utility similar to those for surgical resections aimed at cure.

Cost-utility estimation of surgical treatment of pancreatic carcinoma aimed at cure.

BACKGROUND: Little is reported on costs for radical tumor resections of pancreatic carcinoma in relationship to adjusted quality of life survival postoperatively. Therefore, the aim of the present study was to estimate the cost utility of surgical treatment aimed at cure. METHODS: A population-based cohort of patients with exocrine or ampullary pancreatic adenocarcinoma resected for cure in Gothenburg University Hospitals during 1998-2005 were evaluated retrospectively (n = 139). Total inpatient and outpatient healthcare costs were available for 103 patients, and health-related quality of life (HRQL) (based on the SF-36 Health Survey) were assessed preoperatively and postoperataively in 119 patients. Survival and utility index (SF-36-6D) across 5 years of postoperative follow-up were used to achieve quality adjusted life years. RESULTS: Mean survival after resection was 977 days for patients with exocrine pancreatic carcinoma, with expected differences among subgroups as related to disease stage (p < 0.01), in agreement with international reports. The HRQL index was 0.65 ± 0.06 preoperatively, 0.63 ± 0.04 early postoperatively (<1 year) and 0.69 ± 0.06 at long-term follow-up (1-5 years) compared to 0.77 ± 0.02 in age-matched healthy reference individuals from the Swedish population (p < 0.05). Total lifetime costs for treatments including surgery and adjuvant chemotherapy were 39,000 euro per patient, with a mean of 1.13 (95% Confidence Interval [CI] 0.93-1.40) QALYs across 5 years follow-up. The cost per QALY was 35,000 euro (95% CI 28,026 euro-41,947 euro). CONCLUSIONS: Resection aimed at cure of pancreatic exocrine ductal carcinoma provided costs for one quality adjusted year of survival comparable to other complex surgical treatments within cost limits regarded as reasonable to bear by the Swedish health care system, as well as in several other Western countries.