Frailty Assessment for Risk Stratification in Pancreatic Surgery

Frailty Assessment for Risk Stratification in Pancreatic Surgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Frailty Assessment for Risk Stratification in Pancreatic Surgery Michael C Frey, Elena Krombholz, Annatina Weber, Silvan Patalong, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7086784/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Sep, 2025 Read the published version in Langenbeck's Archives of Surgery → Version 1 posted 7 You are reading this latest preprint version Abstract Purpose: Pancreatic cancer usually affects the elderly as 70% of new diagnoses are made in patients older than 65 years. A risk factor for postoperative complications is the accumulation of comorbidities and functional decline, which together define “frailty”. The aim of the current study was to assess the impact of frailty on postoperative recovery after pancreatic surgery. Methods: Data of consecutive patients undergoing pancreatic resections between January 2015 and December 2023 were retrospectively analyzed. Postoperative complications were graded according to the Clavien-Dindo Classification (CD), Comprehensive Complication Index (CCI) and complications specific to pancreatic resections as recommended and published by the International Study Group of Pancreatic Surgery. The modified frailty index (mFI) was defined by 11 variables. A mFI score above 0.27 defined frailty according to previous literature. Results: A pancreatic resection was performed in 190 patients of which 27 (14%) were classified as frail. Male gender was associated with frailty (78%, p = 0.003). Frailty was associated with an increased rate of preoperative biliary drainage. Although intensive care stay was increased in the frail group (median 3 vs. 1 day; p = 0.005), total length of hospital stay was not affected. Frailty was associated with an increased rate of severe type C pancreatic fistula (11% vs. 2%, p = 0.038), and a higher comprehensive complication index (26 vs. 12; p = 0.015). Total hospitalization costs were increased for frail patients with 58’022 CHF compared to 44’126 CHF for non-frail patients (p = 0.09). Conclusion: Assessment of frailty should be implemented for preoperative risk stratification, since frailty is associated with higher morbidity after pancreatic resections. Pancreatic Surgery Postoperative outcomes Frailty Risk stratification Introduction Pancreatic cancer ranks as the sixth most commonly diagnosed malignancy in women and the tenth in men. It is the fourth leading cause of cancer-related death and accounts for approximately 8% of all cancer fatalities[ 1 ]. The incidence of pancreatic cancer increases with age, with nearly 70% of cases diagnosed in individuals over 65 years old[ 2 ]. Surgical resection remains the only potentially curative treatment option. However, it is still associated with substantial morbidity and mortality, particularly in elderly and comorbid patients[ 3 ]. These individuals are at increased risk of postoperative complications, which may also lead to significantly higher healthcare costs. The concept of frailty was introduced to characterize a particularly vulnerable subgroup among older adults. Frailty assessment has evolved around two principal models: 1. The deficit accumulation model, which quantifies frailty based on comorbidities and functional impairments derived from medical history or structured questionnaires[ 4 ]. 2. The phenotypic model, which defines frailty through physical characteristics such as weight loss, weakness, and reduced gait speed[ 5 ]. An association between frailty and increased postoperative costs has been demonstrated in previous studies, suggesting an approximate 1.5-fold increase in expenditures among frail patients[ 6 – 8 ]. Nevertheless, specific data on frailty and its economic impact in the context of pancreatic surgery are lacking. Therefore, the present study first aims to stratify a well-characterized cohort of patients undergoing pancreatic resection according to the presence of frailty using a comorbidity-based frailty definition consistent with prior research in this field. Secondly, it seeks to compare postoperative morbidity, mortality and total hospitalization costs between frail and non-frail patient groups. Methods Patient population and outcomes Data of consecutive patients receiving a pancreatic resection for suspected or confirmed pancreatic, bile duct or other neoplasia between January 2015 and December 2023 were collected in a retrospective database. Patient and tumor characteristics including comorbidities, cancer stage, cancer type, preoperative biliary drainage, neoadjuvant and adjuvant chemotherapy regimens, operation type, length of hospital stay and postoperative outcomes were identified. Postoperative complications were graded according to the Clavien-Dindo (CD) classification. The summarized and weighted complications have been assessed with the Comprehensive Complication Index (CCI), which includes all aspects of complications and enables a more thorough assessment of the severity and dimension of postoperative complications. Pancreatectomy specific outcomes were graded according to the International Study Group for Pancreatic Surgery (ISGPS). Total hospitalization costs were assessed as the cumulative sum of all costs generated throughout the hospital stay and compared between groups. Costs were calculated as median costs. Median was used to report total costs. Modified frailty index The modified frailty index (mFI) introduced by Velanovich et. al[ 4 ] in 2013 is based on the concept of “accumulating deficits”. The authors demonstrated that 11 variables – primarily reflecting comorbidities - could effectively predict increased morbidity and mortality across various surgical disciplines, thereby successfully identifying a particularly vulnerable patient population. The modified frailty index includes the following parameters: Myocardial infarction, chronic heart failure, history of stroke or TIA, peripheral vascular disease, Eastern Cooperative Oncology Group Performance Status (ECOG) grade ≥ 2, chronic obstructive pulmonary disease (COPD) or recent pneumonia, hypertension requiring medication, coronary artery disease, impaired sensorium, diabetes, neurologic deficits after stroke. Each positive variable is counted as 1 point. The sum is subsequently divided through the amount of variables (11), resulting in an individual frailty index. Frailty was defined as an mFI score greater than 0.27, consistent with previous studies [ 9 – 11 ]. This threshold was used to stratify patients into frail and non-frail groups for comparative analysis. Surgical procedures All pancreatic resections were performed by one of two hepatopancreatobiliary surgeons. The majority of cases was performed by both surgeons as a team. Before surgery, every patient was discussed in our interdisciplinary tumor board. The type of resection was determined by tumor location and its local extension. Pancreatoduodenectomy (PD), pylorus preserving pancreatoduodenectomy (PPPD), total pancreatectomy (TP) and distal pancreatectomy (DP) with and without splenectomy were performed. In case of venous involvement, portal vein resection and reconstruction was performed by a vascular surgeon. Pancreatectomies involving arterial resection and reconstruction (N = 4) as well as isolated enucleations (N = 2) were excluded from the present analysis to standardize surgical risk for frailty assessment. Statistical Analysis Statistical analysis was performed using SPSS software (Version 24; IBM, Armonk, NY). Categorical variables were compared using the Chi-Square- or Fisher exact test, as applicable. Dichotomous data was expressed as frequencies and percentages. To compare means and standard deviations of normally distributed continuous variables, the unpaired t-test was applied. The Mann-Whitney-U test was used to analyze differences in rank numbers of non-normally distributed variables presented as median values and interquartile range. p-values of < 0.05 were considered statistically significant. Results Patient demographics Pancreatic resection was performed in 190 patients, of whom 27 (14%) were classified as frail. An overview of patient characteristics is given in Table 1 . Male gender was more frequently encountered in the frail group (male gender: 78% vs. 47%, p = 0.003). Furthermore, frail patients were older (74 vs. 70 years; p = 0.002). Body Mass Index (BMI) did not differ between groups, while a higher proportion of patients in the frailty group had an ECOG Score ≥ 2 in (26% vs. 4%, p = 0.001). As expected, frail patients had a higher median age adjusted Charlson Comorbidity Index (8 vs. 6; p < 0.001) and higher American Society of Anesthesiologists (ASA) scores (ASA 3–4: 93% vs. 35%; p < 0.001). More patients in the frail group were active smokers (44% vs. 21%, p = 0.007). Preoperative weight loss was significantly higher in frail patients (7% vs. 1% of body weight, p = 0.014). The median modified frailty index was 0.36 in the frail group, compared to 0.00 in non-frail patients. The most frequently observed frailty components were hypertension, coronary artery disease and myocardial infarction (Table 2 ). Table 1 Patient characteristics. BMI (body mass index), ECOG (Eastern Cooperative Oncology Group), ASA (American Society of Anesthesiologists). Variable Frail N = 27 Non-Frail N = 163 P value Female, N (%) 6 (22) 87 (53) 0.003 Age, years, mean (SD) 74 (66–77) 70 (62–75) 0.002 BMI, median (interquartile range) 25 (23–27) 24 (22–27) 0.373 ECOG score, N (%) 0 − 1 20 (74) 157 (96) 0.001 >/= 2 7 (26) 6 (4) Age Adjusted Charlson Comorbidity Score, median (interquartile range) 8 (7–9) 6 (5–7) < 0.001 Active smoking, N (%) 12 (44) 33 (21) 0.007 ASA classification, N (%) ASA 1–2 2 (7) 106 (65) < 0.001 ASA 3–4 25 (93) 57 (35) Weight loss before surgery in % body weight, median (interquartile range) 7 (1–13) 1 (0–7) 0.014 Nutrition risk score, median (interquartile range) 4 (3–5) 4 (3–5) 0.128 Table 2 Components of the modified frailty index. ECOG (Eastern Cooperative Oncology Group), COPD (chronic obstructive pulmonary disease). Variable Frail N = 27 Non Frail N = 163 P value Myocardial infarction, N (%) 17 (63) 0 < 0.001 Chronic heart failure, N (%) 2 (7) 1 (1) 0.053 History of stroke or TIA, N (%) 5 (19) 3 (2) 0.002 Peripheral vascular disease, N (%) 10 (37) 3 (2) < 0.001 ECOG Performance Status Garde 2 and higher, N (%) 7 (26) 6 (4) < 0.001 COPD or recent pneumonia, N (%) 6 (22) 3 (2) < 0.001 Hypertension requiring medication, N (%) 26 (96) 63 (39) < 0.001 Coronary artery disease, N (%) 19 (70) 2 (1) < 0.001 Impaired sensorium (clouding), N (%) 0 0 Diabetes, N (%) 9 (33) 19 (12) 0.007 Neurologic deficits after stroke 6 (22) 0 < 0.001 Modified frailty index, median (interquartile range) 0.36 (0.27–0.36) 0.0 (0-0.09) < 0.001 Histopathology and surgical procedures The most frequent cancer type was pancreatic ductal adenocarcinoma which accounted for 59% in the frail- and 56% in the non-frail group (Table 3 ). Distal cholangiocarcinoma was more prevalent in frail patients (22 vs. 6%; p = 0.014). Other malignant diseases were equally distributed. Cystic lesions were more frequently observed in non-frail patients (3 vs. 19%; p = 0.053). Moreover, frailty was associated with a higher rate of preoperative biliary drainage, mostly Endoscopic retrograde cholangiopancreatography (ERCP) (63 vs. 31%; p = 0.001). PD and TP were similarly distributed between both groups (70% and 19% vs. 61% and 9%). DP was significantly less frequent in frail patients (11% vs 30%; p = 0.041). Pathologic tumor staging did not differ significantly between the two groups (Table 3 ). Table 3 Operative and histopathological data CA 19 − 9 (Carbohydrate-Antigen 19 − 9), CEA (Carcinoembryonic Antigen), NET (Neuroendocrine Tumor), Tis (Carcinoma in situ) Variable Frail N = 27 Non Frail N = 163 P value Pancreatic adenocarcinoma, N (%) 16 (59) 92 (56) 0.784 Distal cholangiocarcinoma, N (%) 6 (22) 10 (6) 0.014 Neuroendocrine tumor, N (%) 2 (7) 17 (10) 1.0 Other malignant neoplasia, N (%) 2 (7) 13 (8) 1.0 Benigne neoplasia, N (%) 1 (3) 31 (19) 0.053 Preoperative biliary drainage, N (%) ERCP 17 (63) 50 (31) 0.001 PTCD 0 5 (3) 1.0 Tumor marker CA 19 − 9 level, median (interquartile range) 116 (10–456) 52 (12–261) 0.502 Surgical procedure, N (%) Pancreatoduodenectomy 19 (70) 99 (61) 0.339 Total pancreatectomy 5 (19) 15 (9) 0.171 Distal pancreatectomy 3 (11) 49 (30) 0.041 Operation time, min, median (interquartile range) 303 (270–380) 310 (240–362) 0.640 Blood loss ml, median (interquartile range) 200 (150–500) 200 (100–300) 0.161 Pathologic tumor stage, N (%) (only adenocarcinoma and NET, N = 127) pT0-Tis 8 (8) 0 0.596 pT1-2 3 (19) 20 (20) 1.0 pT3-4 13 (81) 73 (72) 0.554 pNx / N0 6 (35) 41 (41) 0.680 pN1-2 11 (65) 60 (59) Perioperative outcomes There were no differences in operation time and blood loss. In terms of pancreatectomy-specific complications, frail patients exhibited a higher incidence of severe grade C pancreatic fistula (11% vs. 2%, p = 0.038). Similarly, grade A chyle leaks were more frequent in the frail group, whereas no significant differences were observed in delayed gastric emptying, bile leakage and postpancreatectomy hemorrhage (Table 4 ). Minor complications, defined as grade 1 and 2 according to the CD classification, did not differ between the two groups (52% vs. 56%, p = 0.70). However, there was a trend towards increased major complications (CD ≥3) in the frail subgroup (41% vs. 24%, p = 0.07, Table 4 ). When complications were quantified using the Comprehensive Complication Index (CCI), frail patients demonstrated a significantly higher overall burden of complications (median CCI and interquartile range (IQR): 26 (9–64) vs. 12 (9–31); p = 0.015). Furthermore, there was a trend towards an increased 30-day and 90-day mortality in the frail subgroup, which did not reach statistical significance (30-day mortality: 7 vs. 1%, p = 0.053; 90-day mortality: 11% vs. 3%, p = 0.088). Although intensive care unit (ICU) stay was increased in the frail group (3 vs. 1 days; p = 0.005), total length of hospital stay was not affected (18 vs. 16 days, p = 0.301). Total costs per patient were markedly different with 58’022 CHF for frail patients and 44’126 CHF for non-frail patients but did not reach statistical significance (p = 0.09, Table 4 ). Table 4 Postoperative outcomes. ICU (intensive care unit), ECOG (Eastern Cooperative Oncology Group), ASA (American Society of Anesthesiologists, PPAP (post pancreatectomy acute pancreatitis). Variable Frail N = 27 Non Frail N = 163 P value Hospital length of stay (after surgery), days, median (interquartile range) 18 (11–32) 16 (11–25) 0.301 ICU stay, days, median (interquartile range) 3 (0–7) 1 (0–2) 0.005 International study group of pancreatic surgery (ISGPS) complications Postoperative pancreatic fistula (POPF), N (%) Biochemical leak 4 (15) 27 (17) 1.0 Grade B fistula 1 (4) 5 (3) 1.0 Grade C fistula 3 (11) 3 (2) 0.038 Delayed gastric emptying, N (%) Grade A 7 (26) 24 (15) 0.161 Grade B 0 10 (6) 0.362 Grade C 1 (4) 3 (2) 0.461 Bile leakage, N (%) Grade A 0 1 (1) 1.0 Grade B 1 (4) 5 (3) 1.0 Grade C 0 1 (1) 1.0 Postpancreatectomy hemorrhage, N (%) Grade A 0 4 (3) 1.0 Grade B 0 0 Grade C 1 (4) 5 (3) 1.0 Chyle leak, N (%) Grade A 3 (11) 2 (1) 0.021 Grade B 0 0 Grade C 0 0 PPAP, N (%) Grade A 7 (26) 28 (17) 0.288 Grade B 0 0 Grade C 0 0 Complication graded by Clavien Dindo (CD), N (%) CD1-2 14 (52) 91 (56) 0.700 CD3-5 11 (41) 39 (24) 0.070 Comprehensive complication index, median (interquartile range) 26 (9–64) 12 (9–31) 0.015 30-day mortality 2 (7) 1 (1) 0.053 90-day mortality 3 (11) 5 (3) 0.088 Adjuvant chemotherapy N (%) 13 (48) 86 (53) 0.657 Received less chemo cycles than planned, N (%) 5 (31) 32 (38) 0.626 Discharge to nursing home (after rehabilitation), N (%) 1 (4) 6 (4) 1.0 Total costs, CHF, median (interquartile range) 58k (34k-12k) 44k (30k-66k) 0.090 Subgroup analysis stratified by surgical procedure We conducted a subgroup analysis for postoperative outcomes stratified by the surgical procedure (PD, DP and TP). The subgroups for PD and DP did not show any significant differences in terms of hospital- and ICU length of stay, complications, mortality or costs. In the small subgroup of patients who received a TP (5 frail- and 15 non-frail patients), frail patients had a significantly higher CCI (75 vs. 15.6; p = 0.044) and a higher 90-day mortality (60% vs. 6.7%; p = 0.032, Supplementary Table 3). Discussion In the present study, frailty was associated with a significantly higher rate of postoperative complications in patients undergoing pancreatic resection, as well as a clear trend toward increased postoperative mortality. Notably, patients who underwent TP experienced a markedly elevated 90-day mortality rate. Beyond clinical outcomes, cost data were analysed and demonstrated a consistent trend toward increased healthcare expenditures among frail patients. To the best of our knowledge, this is the first study to assess total hospitalization costs for pancreatic resections stratified by frailty status, thereby contributing to the limited body of evidence on the cost implications of frailty in pancreatic surgery. The findings in this study are consistent with previous studies that have established an association between frailty and surgical morbidity across various surgical disciplines, based on data from the National Surgical Quality Improvement Program (NSQIP), a national data collection and quality improvement initiative developed by the American College of Surgeons[ 4 ]. In the present study, the impact of frailty on surgical outcomes was evaluated in a European setting and was found to be consistent with these prior findings. As frailty was not yet an established predictive variable in the surgical community, the authors of the initial NSQIP analysis derived a frailty measure from existing patient demographics and comorbidity data[ 4 ]. Their approach was influenced by the Canadian Study of Health and Aging, which followed 2740 community dwelling elderly over a ten-year period and demonstrated that frailty was a significant predictor of mortality[ 12 ]. The resulting definition of frailty was based on 70 distinct parameters of function and comorbidity, which subsequently served as a model for retrospective studies in the surgical field. An analysis of the NSQIP database demonstrated a marked increase in mortality following pancreatectomy in relation to patients’ frailty status[ 13 ]. Mortality peaked at 22% among frail patients undergoing PD, compared to just 2% in their non-frail counterparts. A different study focusing on outcomes after PD defined frailty using a modified frailty index with a cut-off of 0.27, similar to the approach used in the present study[ 11 ]. Consistent with our findings major complications occurred in 40.8%, with a 30-day mortality rate of 6.3% in this group. Between-study comparisons are limited by the use of different frailty scoring systems. The current modified frailty index (mFI), with a cut-off of ≥ 0.27, has been applied in previous studies evaluating outcomes following PD. In one such study, 12% of patients were classified as frail, and surgical outcomes were assessed according to ISGPS definitions. [ 14 ]. Among frail patients, the reported major complication rate and 90-day mortality (31% and 11%, respectively) were comparable to our findings. Similarly, the incidence of type C pancreatic fistulas in frail patients was significantly higher (7.8%), aligning with our observed rate of 11%. In a separate analysis of DPs using the same mFI, major complications (CD-grade ≥ 3) occurred in 26.6% of frail patients, with a notably higher rate of clinically relevant postoperative pancreatic fistula (POPF) (25.3%) in this group[ 15 ]. Regarding potential causes of the increased fistula rates in frail patients, the authors found no difference in pancreatic texture although pancreatic ducts > 3mm were more common in frail patients. Based on these findings, the authors hypothesized that the increased incidence of high-grade fistulas in frail individuals might be due to impaired physiological reserve rather than anatomical factors. The CCI incorporates all postoperative adverse events into a single, weighted score. This approach allows for a more nuanced and quantitative evaluation of both the severity and cumulative burden of complications. In the present study, the CCI was more than twice as high in frail patients compared to their non-frail counterparts. Similarly, previous studies found an increase in CCI for frail patients after gastrointestinal- and hepatopancreatobiliary surgery[ 16 , 17 ]. The cause of the observed increase in complications associated with frailty is multifactorial. An impaired immune response leads to poor wound healing and increased infection risk[ 18 , 19 ]. Sarcopenia, which is typically associated with frailty, promotes immobility and pneumonia. In general the reduced cardiopulmonary function, states of chronic inflammation and an attenuated immune competence are main factors for frail patients which lower their capacity to endure stressors and lead to worse outcomes[ 20 , 21 ]. Since comparable data on the relationship between frailty, costs and pancreatic surgery are lacking, we searched for related cost analyses in similar clinical contexts. In this regard, frailty has been shown to be associated with increased healthcare costs in cases of acute pancreatitis, although a different frailty score was applied in that study[ 22 ]. Similarly, increased costs have been reported after colorectal surgery in association with frailty, and a 1.5-fold rise in expenditures was observed following major elective non-cardiac surgery in frail patients—again based on alternative frailty assessments[ 6 , 7 ]. In our cohort, there was a clear tendency towards increased hospitalization costs in the frail group. Although not directly assessed in the present study, it can be assumed, that an increase in complications would further impact costs beyond the initial hospitalization. In this context, prolonged rehabilitation, increased use of healthcare resources and the potential need for nursing home placement may contribute to additional expenditures. Finally, the present study highlights that surgical outcomes can vary significantly depending on patient-specific factors. Preoperative assessment of frailty may offer an opportunity to align patient expectations with their actual personal risk, as patients often tend to overestimate their resilience to surgical procedures[ 23 ]. In this context, frailty assessment plays a role not only in patient selection but also in shaping patient perception and promoting more realistic expectation regarding surgery. Limitations of the present study include the retrospective nature of the analysis in a single-center setting which is prone to selection bias. Another limitation is the relatively small number of patients assessed. In addition, the wide variety of existing frailty definitions limit the comparability of study results across the literature. Nevertheless, we applied a validated definition that has been previously used to assess various surgical patient populations in retrospective analyses. Using this definition, we identified a frail subgroup characterized by a higher CCI, a trend toward increased mortality, and elevated healthcare costs. Looking ahead, this retrospective study highlights the need for a standardized, prospective frailty assessment before surgery to improve risk stratification and patient counseling. Early identification of frailty opens the door for targeted interventions such as prehabilitation, shared decision-making, and tailored perioperative care. Conclusion Preoperative frailty assessment is an important tool for identifying patients at increased risk of adverse outcomes following pancreatic resection. These high-risk individuals may, in turn, benefit from targeted preoperative interventions and the establishment of realistic expectations regarding major pancreatic surgery. Abbreviations ASA American Society of Anesthesiologists BMI Body Mass Index CA 19-9 Carbohydrate antigen 19-9 CCI Comprehensive Complication Index CD Clavien-Dindo classification COPD Chronic Obstructive Pulmonary Disease DP Distal Pancreatectomy ECOG Eastern Cooperative Oncology Group Performance Status ERCP Endoscopic retrograde cholangiopancreatography ICU Intensive Care Unit ISGPS International Study Group for Pancreatic Surgery IQR Interquartile Range mFI Modified frailty index NSQIP National Surgical Quality Improvement Program PD Pancreatoduodenectomy POPF Postoperative Pancreatic Fistula PPPD Pylorus Preserving Pancreatoduodenectomy TP Total Pancreatectomy Declarations Author contributions MCF, AW and AN contributed to the study conception and design. Data collection and analysis were performed by MCF, EK, ATW, SP and AW. The manuscript was written by MCF, AW and AN. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Acknowledgements Funding : No funding or financial support was provided for the study. Consent for publication : All authors reviewed the final version of the manuscript and approved its submission. Conflict of interest /Competing interests: All authors of this manuscript declare no conflicts of interest. Permissions Ethics approval : The local ethics committee approved the current study.(Project-ID 2022−00665, Ethikkommission Nordwest- und Zentralschweiz) Consent to participate : Patients consent was waived as approved by the local ethics committee. References Siegel RL, Giaquinto AN, Jemal A (2024) Cancer statistics, 2024. CA Cancer J Clin 74:12-49. doi: 10.3322/caac.21820 Howlader N NA, Krapcho M, Garshell J, Miller D,, Altekruse S ea (2015) SEER Cancer Statistics Review, 1975–2012. National Cancer Institute, Bethesda, MD, 2015, pp 1–101, based on November 2014 SEER data submission posted to the SEER website April 2015. 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Supplementary Files Supplementarytables.docx Cite Share Download PDF Status: Published Journal Publication published 03 Sep, 2025 Read the published version in Langenbeck's Archives of Surgery → Version 1 posted Editorial decision: Revision requested 30 Jul, 2025 Reviews received at journal 30 Jul, 2025 Reviewers agreed at journal 21 Jul, 2025 Reviewers invited by journal 13 Jul, 2025 Editor assigned by journal 13 Jul, 2025 Submission checks completed at journal 11 Jul, 2025 First submitted to journal 09 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7086784","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":484842158,"identity":"9605892c-80aa-4f4b-a460-e566e286b11f","order_by":0,"name":"Michael C Frey","email":"","orcid":"","institution":"University Hospital Zurich","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"C","lastName":"Frey","suffix":""},{"id":484842160,"identity":"35c6d469-288b-417a-9d7d-83301c583a8d","order_by":1,"name":"Elena Krombholz","email":"","orcid":"","institution":"Cantonal Hospital Baden","correspondingAuthor":false,"prefix":"","firstName":"Elena","middleName":"","lastName":"Krombholz","suffix":""},{"id":484842161,"identity":"f10c7945-103b-4eb1-99b9-1195c851b128","order_by":2,"name":"Annatina Weber","email":"","orcid":"","institution":"Cantonal Hospital Baden","correspondingAuthor":false,"prefix":"","firstName":"Annatina","middleName":"","lastName":"Weber","suffix":""},{"id":484842162,"identity":"88c6c725-c2a2-4636-9cdf-b39bd90bd1a9","order_by":3,"name":"Silvan Patalong","email":"","orcid":"","institution":"Cantonal Hospital Baden","correspondingAuthor":false,"prefix":"","firstName":"Silvan","middleName":"","lastName":"Patalong","suffix":""},{"id":484842164,"identity":"2e4e67f0-2152-4f6e-aaee-8ae2011ea24f","order_by":4,"name":"Andrea Wirsching","email":"","orcid":"","institution":"Cantonal Hospital Baden","correspondingAuthor":false,"prefix":"","firstName":"Andrea","middleName":"","lastName":"Wirsching","suffix":""},{"id":484842170,"identity":"c4aa8d48-c4c9-4e50-b6f2-e543288240bd","order_by":5,"name":"Antonio Nocito","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIie3PMQuCQBTA8ScHthy0CoJ+hScHRXD0WQrBqcHRURCaglbBoa9yItQitR7oIn4BwbWhIARxOB0b7r+85f14PACd7m/D3xAAHMECIOp1MiICgqVkSEAxT9bZNW/DkMN2lTRFF72Ym8VGHyqIVReEpRjA7nJHIcpqg7Ugdqo6I33TplgAyhOI/FxxtA4moQrhTsiTu+kMwQkRG5AzxJM+YxQDiuX3l7L0GdZ5YquII49NS9/cwUfSdlG0925ZkvcqMjTeMeIFQKfT6XSqPnvJSvCe690zAAAAAElFTkSuQmCC","orcid":"","institution":"Cantonal Hospital Baden","correspondingAuthor":true,"prefix":"","firstName":"Antonio","middleName":"","lastName":"Nocito","suffix":""}],"badges":[],"createdAt":"2025-07-09 18:53:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7086784/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7086784/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00423-025-03849-8","type":"published","date":"2025-09-03T15:56:50+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":90827820,"identity":"c8c18b69-dd8f-4c3d-b66b-578c27cbad0f","added_by":"auto","created_at":"2025-09-08 15:58:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":838712,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7086784/v1/dcf0a9f3-55e4-4b3b-80b7-23e0c12ef781.pdf"},{"id":86791698,"identity":"b2d2feb9-1a81-489f-995d-57d493396d50","added_by":"auto","created_at":"2025-07-15 15:01:44","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":17184,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytables.docx","url":"https://assets-eu.researchsquare.com/files/rs-7086784/v1/836a5d30c6a94de92a96a324.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Frailty Assessment for Risk Stratification in Pancreatic Surgery","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePancreatic cancer ranks as the sixth most commonly diagnosed malignancy in women and the tenth in men. It is the fourth leading cause of cancer-related death and accounts for approximately 8% of all cancer fatalities[\u003cspan class=\"CitationRef\"\u003e1\u003c/span\u003e]. The incidence of pancreatic cancer increases with age, with nearly 70% of cases diagnosed in individuals over 65 years old[\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e\n\u003cp\u003eSurgical resection remains the only potentially curative treatment option. However, it is still associated with substantial morbidity and mortality, particularly in elderly and comorbid patients[\u003cspan class=\"CitationRef\"\u003e3\u003c/span\u003e]. These individuals are at increased risk of postoperative complications, which may also lead to significantly higher healthcare costs.\u003c/p\u003e\n\u003cp\u003eThe concept of frailty was introduced to characterize a particularly vulnerable subgroup among older adults. Frailty assessment has evolved around two principal models:\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e1. The deficit accumulation model, which quantifies frailty based on comorbidities and functional impairments derived from medical history or structured questionnaires[\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cspan\u003e\n \u003cp\u003e2. The phenotypic model, which defines frailty through physical characteristics such as weight loss, weakness, and reduced gait speed[\u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\n\u003c/span\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eAn association between frailty and increased postoperative costs has been demonstrated in previous studies, suggesting an approximate 1.5-fold increase in expenditures among frail patients[\u003cspan class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]. Nevertheless, specific data on frailty and its economic impact in the context of pancreatic surgery are lacking.\u003c/p\u003e\n\u003cp\u003eTherefore, the present study first aims to stratify a well-characterized cohort of patients undergoing pancreatic resection according to the presence of frailty using a comorbidity-based frailty definition consistent with prior research in this field.\u003c/p\u003e\n\u003cp\u003eSecondly, it seeks to compare postoperative morbidity, mortality and total hospitalization costs between frail and non-frail patient groups.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003ePatient population and outcomes\u003c/p\u003e\u003cp\u003eData of consecutive patients receiving a pancreatic resection for suspected or confirmed pancreatic, bile duct or other neoplasia between January 2015 and December 2023 were collected in a retrospective database. Patient and tumor characteristics including comorbidities, cancer stage, cancer type, preoperative biliary drainage, neoadjuvant and adjuvant chemotherapy regimens, operation type, length of hospital stay and postoperative outcomes were identified. Postoperative complications were graded according to the Clavien-Dindo (CD) classification. The summarized and weighted complications have been assessed with the Comprehensive Complication Index (CCI), which includes all aspects of complications and enables a more thorough assessment of the severity and dimension of postoperative complications. Pancreatectomy specific outcomes were graded according to the International Study Group for Pancreatic Surgery (ISGPS). Total hospitalization costs were assessed as the cumulative sum of all costs generated throughout the hospital stay and compared between groups. Costs were calculated as median costs. Median was used to report total costs.\u003c/p\u003e\u003cp\u003eModified frailty index\u003c/p\u003e\u003cp\u003eThe modified frailty index (mFI) introduced by Velanovich et. al[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] in 2013 is based on the concept of “accumulating deficits”. The authors demonstrated that 11 variables – primarily reflecting comorbidities - could effectively predict increased morbidity and mortality across various surgical disciplines, thereby successfully identifying a particularly vulnerable patient population. The modified frailty index includes the following parameters: Myocardial infarction, chronic heart failure, history of stroke or TIA, peripheral vascular disease, Eastern Cooperative Oncology Group Performance Status (ECOG) grade ≥ 2, chronic obstructive pulmonary disease (COPD) or recent pneumonia, hypertension requiring medication, coronary artery disease, impaired sensorium, diabetes, neurologic deficits after stroke. Each positive variable is counted as 1 point. The sum is subsequently divided through the amount of variables (11), resulting in an individual frailty index. Frailty was defined as an mFI score greater than 0.27, consistent with previous studies [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e–\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This threshold was used to stratify patients into frail and non-frail groups for comparative analysis.\u003c/p\u003e\u003cp\u003eSurgical procedures\u003c/p\u003e\u003cp\u003eAll pancreatic resections were performed by one of two hepatopancreatobiliary surgeons. The majority of cases was performed by both surgeons as a team. Before surgery, every patient was discussed in our interdisciplinary tumor board. The type of resection was determined by tumor location and its local extension. Pancreatoduodenectomy (PD), pylorus preserving pancreatoduodenectomy (PPPD), total pancreatectomy (TP) and distal pancreatectomy (DP) with and without splenectomy were performed. In case of venous involvement, portal vein resection and reconstruction was performed by a vascular surgeon. Pancreatectomies involving arterial resection and reconstruction (N = 4) as well as isolated enucleations (N = 2) were excluded from the present analysis to standardize surgical risk for frailty assessment.\u003c/p\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eStatistical analysis was performed using SPSS software (Version 24; IBM, Armonk, NY). Categorical variables were compared using the Chi-Square- or Fisher exact test, as applicable. Dichotomous data was expressed as frequencies and percentages. To compare means and standard deviations of normally distributed continuous variables, the unpaired t-test was applied. The Mann-Whitney-U test was used to analyze differences in rank numbers of non-normally distributed variables presented as median values and interquartile range. p-values of \u0026lt; 0.05 were considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePatient demographics\u003c/p\u003e\u003cp\u003ePancreatic resection was performed in 190 patients, of whom 27 (14%) were classified as frail. An overview of patient characteristics is given in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Male gender was more frequently encountered in the frail group (male gender: 78% vs. 47%, p\u0026thinsp;=\u0026thinsp;0.003). Furthermore, frail patients were older (74 vs. 70 years; p\u0026thinsp;=\u0026thinsp;0.002). Body Mass Index (BMI) did not differ between groups, while a higher proportion of patients in the frailty group had an ECOG Score \u0026ge; 2 in (26% vs. 4%, p\u0026thinsp;=\u0026thinsp;0.001). As expected, frail patients had a higher median age adjusted Charlson Comorbidity Index (8 vs. 6; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and higher American Society of Anesthesiologists (ASA) scores (ASA 3\u0026ndash;4: 93% vs. 35%; p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). More patients in the frail group were active smokers (44% vs. 21%, p\u0026thinsp;=\u0026thinsp;0.007). Preoperative weight loss was significantly higher in frail patients (7% vs. 1% of body weight, p\u0026thinsp;=\u0026thinsp;0.014). The median modified frailty index was 0.36 in the frail group, compared to 0.00 in non-frail patients. The most frequently observed frailty components were hypertension, coronary artery disease and myocardial infarction (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003ePatient characteristics.\u003c/b\u003e BMI (body mass index), ECOG (Eastern Cooperative Oncology Group), ASA (American Society of Anesthesiologists).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFrail\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;27\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon-Frail\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;163\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e87 (53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, years, mean (SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74 (66\u0026ndash;77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70 (62\u0026ndash;75)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI, median (interquartile range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25 (23\u0026ndash;27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24 (22\u0026ndash;27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.373\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eECOG score, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0 \u0026minus;\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e157 (96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;/= 2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge Adjusted Charlson Comorbidity Score, median (interquartile range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (7\u0026ndash;9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (5\u0026ndash;7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eActive smoking, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33 (21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eASA classification, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eASA 1\u0026ndash;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e106 (65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eASA 3\u0026ndash;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e25 (93)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e57 (35)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight loss before surgery in % body weight, median (interquartile range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (1\u0026ndash;13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0\u0026ndash;7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNutrition risk score, median (interquartile range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (3\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (3\u0026ndash;5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.128\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eComponents of the modified frailty index.\u003c/b\u003e ECOG (Eastern Cooperative Oncology Group), COPD (chronic obstructive pulmonary disease).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFrail\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;27\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon Frail\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;163\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMyocardial infarction, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic heart failure, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory of stroke or TIA, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePeripheral vascular disease, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eECOG Performance Status Garde 2 and higher, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOPD or recent pneumonia, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension requiring medication, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e63 (39)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCoronary artery disease, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eImpaired sensorium (clouding), N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeurologic deficits after stroke\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eModified frailty index,\u003c/p\u003e\u003cp\u003emedian (interquartile range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.36 (0.27\u0026ndash;0.36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.0 (0-0.09)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eHistopathology and surgical procedures\u003c/p\u003e\u003cp\u003eThe most frequent cancer type was pancreatic ductal adenocarcinoma which accounted for 59% in the frail- and 56% in the non-frail group (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Distal cholangiocarcinoma was more prevalent in frail patients (22 vs. 6%; p\u0026thinsp;=\u0026thinsp;0.014). Other malignant diseases were equally distributed. Cystic lesions were more frequently observed in non-frail patients (3 vs. 19%; p\u0026thinsp;=\u0026thinsp;0.053). Moreover, frailty was associated with a higher rate of preoperative biliary drainage, mostly Endoscopic retrograde cholangiopancreatography (ERCP) (63 vs. 31%; p\u0026thinsp;=\u0026thinsp;0.001). PD and TP were similarly distributed between both groups (70% and 19% vs. 61% and 9%). DP was significantly less frequent in frail patients (11% vs 30%; p\u0026thinsp;=\u0026thinsp;0.041). Pathologic tumor staging did not differ significantly between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eOperative and histopathological data\u003c/b\u003e CA 19\u0026thinsp;\u0026minus;\u0026thinsp;9 (Carbohydrate-Antigen 19\u0026thinsp;\u0026minus;\u0026thinsp;9), CEA (Carcinoembryonic Antigen), NET (Neuroendocrine Tumor), Tis (Carcinoma in situ)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFrail\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;27\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon Frail\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;163\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePancreatic adenocarcinoma, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e92 (56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.784\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDistal cholangiocarcinoma, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeuroendocrine tumor, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOther malignant neoplasia, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBenigne neoplasia, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePreoperative biliary drainage, N (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eERCP\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50 (31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePTCD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTumor marker\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCA 19\u0026thinsp;\u0026minus;\u0026thinsp;9 level, median (interquartile range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e116 (10\u0026ndash;456)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52 (12\u0026ndash;261)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.502\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSurgical procedure, N (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePancreatoduodenectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (70)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e99 (61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.339\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal pancreatectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15 (9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.171\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDistal pancreatectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.041\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOperation time, min,\u003c/p\u003e\u003cp\u003emedian (interquartile range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e303 (270\u0026ndash;380)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e310 (240\u0026ndash;362)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.640\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlood loss ml, median (interquartile range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e200 (150\u0026ndash;500)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e200 (100\u0026ndash;300)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.161\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePathologic tumor stage, N (%)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(only adenocarcinoma and NET, N\u0026thinsp;=\u0026thinsp;127)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT0-Tis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.596\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT1-2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT3-4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e73 (72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.554\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epNx / N0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41 (41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.680\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epN1-2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60 (59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003ePerioperative outcomes\u003c/p\u003e\u003cp\u003eThere were no differences in operation time and blood loss. In terms of pancreatectomy-specific complications, frail patients exhibited a higher incidence of severe grade C pancreatic fistula (11% vs. 2%, p\u0026thinsp;=\u0026thinsp;0.038). Similarly, grade A chyle leaks were more frequent in the frail group, whereas no significant differences were observed in delayed gastric emptying, bile leakage and postpancreatectomy hemorrhage (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Minor complications, defined as grade 1 and 2 according to the CD classification, did not differ between the two groups (52% vs. 56%, p\u0026thinsp;=\u0026thinsp;0.70). However, there was a trend towards increased major complications (CD \u0026ge;3) in the frail subgroup (41% vs. 24%, p\u0026thinsp;=\u0026thinsp;0.07, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). When complications were quantified using the Comprehensive Complication Index (CCI), frail patients demonstrated a significantly higher overall burden of complications (median CCI and interquartile range (IQR): 26 (9\u0026ndash;64) vs. 12 (9\u0026ndash;31); p\u0026thinsp;=\u0026thinsp;0.015). Furthermore, there was a trend towards an increased 30-day and 90-day mortality in the frail subgroup, which did not reach statistical significance (30-day mortality: 7 vs. 1%, p\u0026thinsp;=\u0026thinsp;0.053; 90-day mortality: 11% vs. 3%, p\u0026thinsp;=\u0026thinsp;0.088). Although intensive care unit (ICU) stay was increased in the frail group (3 vs. 1 days; p\u0026thinsp;=\u0026thinsp;0.005), total length of hospital stay was not affected (18 vs. 16 days, p\u0026thinsp;=\u0026thinsp;0.301). Total costs per patient were markedly different with 58\u0026rsquo;022 CHF for frail patients and 44\u0026rsquo;126 CHF for non-frail patients but did not reach statistical significance (p\u0026thinsp;=\u0026thinsp;0.09, Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003ePostoperative outcomes.\u003c/b\u003e ICU (intensive care unit), ECOG (Eastern Cooperative Oncology Group), ASA (American Society of Anesthesiologists, PPAP (post pancreatectomy acute pancreatitis).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFrail\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;27\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNon Frail\u003c/p\u003e\u003cp\u003eN\u0026thinsp;=\u0026thinsp;163\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHospital length of stay (after surgery), days, median (interquartile range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (11\u0026ndash;32)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (11\u0026ndash;25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.301\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eICU stay, days, median (interquartile range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (0\u0026ndash;7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (0\u0026ndash;2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInternational study group of pancreatic surgery (ISGPS) complications\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePostoperative pancreatic fistula (POPF), N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBiochemical leak\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27 (17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade B fistula\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade C fistula\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.038\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDelayed gastric emptying, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24 (15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.161\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.362\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade C\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.461\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBile leakage, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade C\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePostpancreatectomy hemorrhage, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade C\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChyle leak, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.021\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade C\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePPAP, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade A\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28 (17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.288\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade B\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGrade C\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComplication graded by Clavien Dindo (CD), N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD1-2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (52)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e91 (56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.700\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCD3-5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39 (24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.070\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComprehensive complication index,\u003c/p\u003e\u003cp\u003emedian (interquartile range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26 (9\u0026ndash;64)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (9\u0026ndash;31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.015\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e30-day mortality\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e90-day mortality\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.088\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdjuvant chemotherapy N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e86 (53)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.657\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReceived less chemo cycles than planned, N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (31)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32 (38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.626\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDischarge to nursing home\u003c/p\u003e\u003cp\u003e(after rehabilitation), N (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal costs, CHF,\u003c/p\u003e\u003cp\u003emedian (interquartile range)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58k\u003c/p\u003e\u003cp\u003e(34k-12k)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44k\u003c/p\u003e\u003cp\u003e(30k-66k)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.090\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eSubgroup analysis stratified by surgical procedure\u003c/p\u003e\u003cp\u003eWe conducted a subgroup analysis for postoperative outcomes stratified by the surgical procedure (PD, DP and TP). The subgroups for PD and DP did not show any significant differences in terms of hospital- and ICU length of stay, complications, mortality or costs. In the small subgroup of patients who received a TP (5 frail- and 15 non-frail patients), frail patients had a significantly higher CCI (75 vs. 15.6; p\u0026thinsp;=\u0026thinsp;0.044) and a higher 90-day mortality (60% vs. 6.7%; p\u0026thinsp;=\u0026thinsp;0.032, Supplementary Table\u0026nbsp;3).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, frailty was associated with a significantly higher rate of postoperative complications in patients undergoing pancreatic resection, as well as a clear trend toward increased postoperative mortality. Notably, patients who underwent TP experienced a markedly elevated 90-day mortality rate. Beyond clinical outcomes, cost data were analysed and demonstrated a consistent trend toward increased healthcare expenditures among frail patients. To the best of our knowledge, this is the first study to assess total hospitalization costs for pancreatic resections stratified by frailty status, thereby contributing to the limited body of evidence on the cost implications of frailty in pancreatic surgery.\u003c/p\u003e\u003cp\u003eThe findings in this study are consistent with previous studies that have established an association between frailty and surgical morbidity across various surgical disciplines, based on data from the National Surgical Quality Improvement Program (NSQIP), a national data collection and quality improvement initiative developed by the American College of Surgeons[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In the present study, the impact of frailty on surgical outcomes was evaluated in a European setting and was found to be consistent with these prior findings. As frailty was not yet an established predictive variable in the surgical community, the authors of the initial NSQIP analysis derived a frailty measure from existing patient demographics and comorbidity data[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Their approach was influenced by the Canadian Study of Health and Aging, which followed 2740 community dwelling elderly over a ten-year period and demonstrated that frailty was a significant predictor of mortality[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The resulting definition of frailty was based on 70 distinct parameters of function and comorbidity, which subsequently served as a model for retrospective studies in the surgical field.\u003c/p\u003e\u003cp\u003eAn analysis of the NSQIP database demonstrated a marked increase in mortality following pancreatectomy in relation to patients\u0026rsquo; frailty status[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Mortality peaked at 22% among frail patients undergoing PD, compared to just 2% in their non-frail counterparts. A different study focusing on outcomes after PD defined frailty using a modified frailty index with a cut-off of 0.27, similar to the approach used in the present study[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Consistent with our findings major complications occurred in 40.8%, with a 30-day mortality rate of 6.3% in this group.\u003c/p\u003e\u003cp\u003eBetween-study comparisons are limited by the use of different frailty scoring systems. The current modified frailty index (mFI), with a cut-off of \u0026ge;\u0026thinsp;0.27, has been applied in previous studies evaluating outcomes following PD. In one such study, 12% of patients were classified as frail, and surgical outcomes were assessed according to ISGPS definitions. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Among frail patients, the reported major complication rate and 90-day mortality (31% and 11%, respectively) were comparable to our findings. Similarly, the incidence of type C pancreatic fistulas in frail patients was significantly higher (7.8%), aligning with our observed rate of 11%. In a separate analysis of DPs using the same mFI, major complications (CD-grade\u0026thinsp;\u0026ge;\u0026thinsp;3) occurred in 26.6% of frail patients, with a notably higher rate of clinically relevant postoperative pancreatic fistula (POPF) (25.3%) in this group[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Regarding potential causes of the increased fistula rates in frail patients, the authors found no difference in pancreatic texture although pancreatic ducts\u0026thinsp;\u0026gt;\u0026thinsp;3mm were more common in frail patients. Based on these findings, the authors hypothesized that the increased incidence of high-grade fistulas in frail individuals might be due to impaired physiological reserve rather than anatomical factors.\u003c/p\u003e\u003cp\u003eThe CCI incorporates all postoperative adverse events into a single, weighted score. This approach allows for a more nuanced and quantitative evaluation of both the severity and cumulative burden of complications. In the present study, the CCI was more than twice as high in frail patients compared to their non-frail counterparts. Similarly, previous studies found an increase in CCI for frail patients after gastrointestinal- and hepatopancreatobiliary surgery[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe cause of the observed increase in complications associated with frailty is multifactorial. An impaired immune response leads to poor wound healing and increased infection risk[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Sarcopenia, which is typically associated with frailty, promotes immobility and pneumonia. In general the reduced cardiopulmonary function, states of chronic inflammation and an attenuated immune competence are main factors for frail patients which lower their capacity to endure stressors and lead to worse outcomes[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSince comparable data on the relationship between frailty, costs and pancreatic surgery are lacking, we searched for related cost analyses in similar clinical contexts. In this regard, frailty has been shown to be associated with increased healthcare costs in cases of acute pancreatitis, although a different frailty score was applied in that study[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Similarly, increased costs have been reported after colorectal surgery in association with frailty, and a 1.5-fold rise in expenditures was observed following major elective non-cardiac surgery in frail patients\u0026mdash;again based on alternative frailty assessments[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. In our cohort, there was a clear tendency towards increased hospitalization costs in the frail group. Although not directly assessed in the present study, it can be assumed, that an increase in complications would further impact costs beyond the initial hospitalization. In this context, prolonged rehabilitation, increased use of healthcare resources and the potential need for nursing home placement may contribute to additional expenditures.\u003c/p\u003e\u003cp\u003eFinally, the present study highlights that surgical outcomes can vary significantly depending on patient-specific factors. Preoperative assessment of frailty may offer an opportunity to align patient expectations with their actual personal risk, as patients often tend to overestimate their resilience to surgical procedures[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In this context, frailty assessment plays a role not only in patient selection but also in shaping patient perception and promoting more realistic expectation regarding surgery.\u003c/p\u003e\u003cp\u003eLimitations of the present study include the retrospective nature of the analysis in a single-center setting which is prone to selection bias. Another limitation is the relatively small number of patients assessed. In addition, the wide variety of existing frailty definitions limit the comparability of study results across the literature. Nevertheless, we applied a validated definition that has been previously used to assess various surgical patient populations in retrospective analyses. Using this definition, we identified a frail subgroup characterized by a higher CCI, a trend toward increased mortality, and elevated healthcare costs.\u003c/p\u003e\u003cp\u003eLooking ahead, this retrospective study highlights the need for a standardized, prospective frailty assessment before surgery to improve risk stratification and patient counseling. Early identification of frailty opens the door for targeted interventions such as prehabilitation, shared decision-making, and tailored perioperative care.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePreoperative frailty assessment is an important tool for identifying patients at increased risk of adverse outcomes following pancreatic resection. These high-risk individuals may, in turn, benefit from targeted preoperative interventions and the establishment of realistic expectations regarding major pancreatic surgery.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eASA American Society of Anesthesiologists\u003c/p\u003e\n\u003cp\u003eBMI Body Mass Index\u003c/p\u003e\n\u003cp\u003eCA 19-9 Carbohydrate antigen 19-9\u003c/p\u003e\n\u003cp\u003eCCI Comprehensive Complication Index\u003c/p\u003e\n\u003cp\u003eCD Clavien-Dindo classification\u003c/p\u003e\n\u003cp\u003eCOPD Chronic Obstructive Pulmonary Disease\u003c/p\u003e\n\u003cp\u003eDP Distal Pancreatectomy\u003c/p\u003e\n\u003cp\u003eECOG Eastern Cooperative Oncology Group Performance Status\u003c/p\u003e\n\u003cp\u003eERCP Endoscopic retrograde cholangiopancreatography\u003c/p\u003e\n\u003cp\u003eICU Intensive Care Unit\u003c/p\u003e\n\u003cp\u003eISGPS International Study Group for Pancreatic Surgery\u003c/p\u003e\n\u003cp\u003eIQR Interquartile Range\u003c/p\u003e\n\u003cp\u003emFI Modified frailty index\u003c/p\u003e\n\u003cp\u003eNSQIP National Surgical Quality Improvement Program\u003c/p\u003e\n\u003cp\u003ePD Pancreatoduodenectomy\u003c/p\u003e\n\u003cp\u003ePOPF Postoperative Pancreatic Fistula\u003c/p\u003e\n\u003cp\u003ePPPD Pylorus Preserving Pancreatoduodenectomy\u003c/p\u003e\n\u003cp\u003eTP Total Pancreatectomy\u003c/p\u003e\n\n"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMCF, AW and AN contributed to the study conception and design. Data collection and analysis were performed by MCF, EK, ATW, SP and AW. The manuscript was written by MCF, AW and AN. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eNo funding or financial support was provided for the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors reviewed the final version of the manuscript and approved its submission.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;/Competing interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors of this manuscript declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePermissions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe local ethics committee approved the current study.(Project-ID 2022\u0026minus;00665, Ethikkommission Nordwest- und Zentralschweiz)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e:\n\u003cp\u003ePatients consent was waived as approved by the local ethics committee.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSiegel RL, Giaquinto AN, Jemal A (2024) Cancer statistics, 2024. CA Cancer J Clin 74:12-49. doi: 10.3322/caac.21820\u003c/li\u003e\n\u003cli\u003eHowlader N NA, Krapcho M, Garshell J, Miller D,, Altekruse S ea (2015) SEER Cancer Statistics Review, 1975\u0026ndash;2012. National Cancer Institute, Bethesda, MD, 2015, pp 1\u0026ndash;101, based on November 2014 SEER data submission posted to the SEER website April 2015. SEER Cancer Statistics Review \u003c/li\u003e\n\u003cli\u003eHartwig W, Werner J, Jager D, Debus J, Buchler MW (2013) Improvement of surgical results for pancreatic cancer. Lancet Oncol 14:e476-e485. doi: 10.1016/S1470-2045(13)70172-4\u003c/li\u003e\n\u003cli\u003eVelanovich V, Antoine H, Swartz A, Peters D, Rubinfeld I (2013) Accumulating deficits model of frailty and postoperative mortality and morbidity: its application to a national database. J Surg Res 183:104-110. doi: 10.1016/j.jss.2013.01.021\u003c/li\u003e\n\u003cli\u003eFried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, et al. (2001) Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 56:M146-156. doi: 10.1093/gerona/56.3.m146\u003c/li\u003e\n\u003cli\u003eMcGinn R, Agung Y, Grudzinski AL, Talarico R, Hallet J, McIsaac DI (2023) Attributable Perioperative Cost of Frailty after Major, Elective Noncardiac Surgery: A Population-based Cohort Study. Anesthesiology 139:143-152. doi: 10.1097/ALN.0000000000004601\u003c/li\u003e\n\u003cli\u003eRobinson TN, Wu DS, Stiegmann GV, Moss M (2011) Frailty predicts increased hospital and six-month healthcare cost following colorectal surgery in older adults. Am J Surg 202:511-514. doi: 10.1016/j.amjsurg.2011.06.017\u003c/li\u003e\n\u003cli\u003eLakra A, Kyaw NR, Puleo JM, Kuna MC, Tram M, Zimmerman JP (2025) Frailty Is Associated With Increased 30-day Readmissions and Costs After Total Shoulder Arthroplasty. Clin Orthop Relat Res doi: 10.1097/CORR.0000000000003461\u003c/li\u003e\n\u003cli\u003eTsiouris A, Hammoud ZT, Velanovich V, Hodari A, Borgi J, Rubinfeld I (2013) A modified frailty index to assess morbidity and mortality after lobectomy. J Surg Res 183:40-46. doi: 10.1016/j.jss.2012.11.059\u003c/li\u003e\n\u003cli\u003eRockwood K, Andrew M, Mitnitski A (2007) A comparison of two approaches to measuring frailty in elderly people. J Gerontol A Biol Sci Med Sci 62:738-743. doi: 10.1093/gerona/62.7.738\u003c/li\u003e\n\u003cli\u003eMogal H, Vermilion SA, Dodson R, Hsu FC, Howerton R, Shen P, et al. (2017) Modified Frailty Index Predicts Morbidity and Mortality After Pancreaticoduodenectomy. Ann Surg Oncol 24:1714-1721. doi: 10.1245/s10434-016-5715-0\u003c/li\u003e\n\u003cli\u003eSong X, Mitnitski A, Rockwood K (2010) Prevalence and 10-year outcomes of frailty in older adults in relation to deficit accumulation. J Am Geriatr Soc 58:681-687. doi: 10.1111/j.1532-5415.2010.02764.x\u003c/li\u003e\n\u003cli\u003eAugustin T, Burstein MD, Schneider EB, Morris-Stiff G, Wey J, Chalikonda S, et al. (2016) Frailty predicts risk of life-threatening complications and mortality after pancreatic resections. Surgery 160:987-996. doi: 10.1016/j.surg.2016.07.010\u003c/li\u003e\n\u003cli\u003eLi V, Awan A, Serrano PE (2022) Frailty Predicts Postoperative Complications following Pancreaticoduodenectomy. Eur Surg Res 63:232-240. doi: 10.1159/000522576\u003c/li\u003e\n\u003cli\u003ePark Y, Hwang DW, Lee JH, Song KB, Jun E, Lee W, et al. (2023) Evaluation of postoperative outcomes of minimally invasive distal pancreatectomy for left-sided pancreatic tumors based on the modified frailty index: a retrospective cohort study. Int J Surg 109:3497-3505. doi: 10.1097/JS9.0000000000000670\u003c/li\u003e\n\u003cli\u003evan der Windt DJ, Bou-Samra P, Dadashzadeh ER, Chen X, Varley PR, Tsung A (2018) Preoperative risk analysis index for frailty predicts short-term outcomes after hepatopancreatobiliary surgery. HPB (Oxford) 20:1181-1188. doi: 10.1016/j.hpb.2018.05.016\u003c/li\u003e\n\u003cli\u003eArtiles-Armas M, Roque-Castellano C, Conde-Martel A, Marchena-Gomez J (2019) The Comprehensive Complication Index is Related to Frailty in Elderly Surgical Patients. J Surg Res 244:218-224. doi: 10.1016/j.jss.2019.06.011\u003c/li\u003e\n\u003cli\u003ePanayi AC, Orkaby AR, Sakthivel D, Endo Y, Varon D, Roh D, et al. (2019) Impact of frailty on outcomes in surgical patients: A systematic review and meta-analysis. Am J Surg 218:393-400. doi: 10.1016/j.amjsurg.2018.11.020\u003c/li\u003e\n\u003cli\u003eRocha V, Marmelo F, Leite-Moreira A, Moreira-Goncalves D (2017) Clinical Utility of Frailty Scales for the Prediction of Postoperative Complications: Systematic Review and Meta-Analysis. Rev Port Cir Cardiotorac Vasc 24:132. \u003c/li\u003e\n\u003cli\u003eWagner D, DeMarco MM, Amini N, Buttner S, Segev D, Gani F, et al. (2016) Role of frailty and sarcopenia in predicting outcomes among patients undergoing gastrointestinal surgery. World J Gastrointest Surg 8:27-40. doi: 10.4240/wjgs.v8.i1.27\u003c/li\u003e\n\u003cli\u003eMcIsaac DI, Taljaard M, Bryson GL, Beaule PE, Gagne S, Hamilton G, et al. (2020) Frailty and long-term postoperative disability trajectories: a prospective multicentre cohort study. Br J Anaesth 125:704-711. doi: 10.1016/j.bja.2020.07.003\u003c/li\u003e\n\u003cli\u003ePatel N, Bahirwani J, Bodrya K, Patel D, Schneider Y (2024) Hidden Dangers of Frailty: Higher Mortality, Complications and Costs in Acute Pancreatitis. Dig Dis Sci 69:3188-3194. doi: 10.1007/s10620-024-08480-z\u003c/li\u003e\n\u003cli\u003eRevenig LM, Canter DJ, Henderson MA, Ogan K, Kooby DA, Maithel SK, et al. (2015) Preoperative quantification of perceptions of surgical frailty. J Surg Res 193:583-589. doi: 10.1016/j.jss.2014.07.069\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"langenbecks-archives-of-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"laos","sideBox":"Learn more about [Langenbeck's Archives of Surgery](http://link.springer.com/journal/423)","snPcode":"423","submissionUrl":"https://submission.nature.com/new-submission/423/3","title":"Langenbeck's Archives of Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Pancreatic Surgery, Postoperative outcomes, Frailty, Risk stratification","lastPublishedDoi":"10.21203/rs.3.rs-7086784/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7086784/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose:\u003c/h2\u003e\u003cp\u003ePancreatic cancer usually affects the elderly as 70% of new diagnoses are made in patients older than 65 years. A risk factor for postoperative complications is the accumulation of comorbidities and functional decline, which together define \u0026ldquo;frailty\u0026rdquo;. The aim of the current study was to assess the impact of frailty on postoperative recovery after pancreatic surgery.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003eData of consecutive patients undergoing pancreatic resections between January 2015 and December 2023 were retrospectively analyzed. Postoperative complications were graded according to the Clavien-Dindo Classification (CD), Comprehensive Complication Index (CCI) and complications specific to pancreatic resections as recommended and published by the International Study Group of Pancreatic Surgery. The modified frailty index (mFI) was defined by 11 variables. A mFI score above 0.27 defined frailty according to previous literature.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eA pancreatic resection was performed in 190 patients of which 27 (14%) were classified as frail. Male gender was associated with frailty (78%, p\u0026thinsp;=\u0026thinsp;0.003). Frailty was associated with an increased rate of preoperative biliary drainage. Although intensive care stay was increased in the frail group (median 3 vs. 1 day; p\u0026thinsp;=\u0026thinsp;0.005), total length of hospital stay was not affected. Frailty was associated with an increased rate of severe type C pancreatic fistula (11% vs. 2%, p\u0026thinsp;=\u0026thinsp;0.038), and a higher comprehensive complication index (26 vs. 12; p\u0026thinsp;=\u0026thinsp;0.015). Total hospitalization costs were increased for frail patients with 58\u0026rsquo;022 CHF compared to 44\u0026rsquo;126 CHF for non-frail patients (p\u0026thinsp;=\u0026thinsp;0.09).\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eAssessment of frailty should be implemented for preoperative risk stratification, since frailty is associated with higher morbidity after pancreatic resections.\u003c/p\u003e","manuscriptTitle":"Frailty Assessment for Risk Stratification in Pancreatic Surgery","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-15 15:01:39","doi":"10.21203/rs.3.rs-7086784/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-07-30T18:00:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-07-30T17:34:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"144659018937693829040247597546706879912","date":"2025-07-21T20:53:27+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-13T13:57:21+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-13T13:55:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-11T06:49:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"Langenbeck's Archives of Surgery","date":"2025-07-09T18:51:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"langenbecks-archives-of-surgery","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"laos","sideBox":"Learn more about [Langenbeck's Archives of Surgery](http://link.springer.com/journal/423)","snPcode":"423","submissionUrl":"https://submission.nature.com/new-submission/423/3","title":"Langenbeck's Archives of Surgery","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"dc6203e0-578a-426f-beae-b216c149c66a","owner":[],"postedDate":"July 15th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-09-08T15:58:11+00:00","versionOfRecord":{"articleIdentity":"rs-7086784","link":"https://doi.org/10.1007/s00423-025-03849-8","journal":{"identity":"langenbecks-archives-of-surgery","isVorOnly":false,"title":"Langenbeck's Archives of Surgery"},"publishedOn":"2025-09-03 15:56:50","publishedOnDateReadable":"September 3rd, 2025"},"versionCreatedAt":"2025-07-15 15:01:39","video":"","vorDoi":"10.1007/s00423-025-03849-8","vorDoiUrl":"https://doi.org/10.1007/s00423-025-03849-8","workflowStages":[]},"version":"v1","identity":"rs-7086784","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7086784","identity":"rs-7086784","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}