Management Of Pancreatic Cysts Research Articles

Pancreatic Cysts in the Geriatric Sphere: A Call for Close Consideration of Patient Characteristics in Pancreatic Cyst Management

Pancreatic Cysts in the Geriatric Sphere: A Call for Close Consideration of Patient Characteristics in Pancreatic Cyst Management

Quality of Pancreatic Cyst Clinical Practice Guidelines.

There are various published clinical practice guidelines (CPGs) for the management of pancreatic cystic lesions. However, the quality of these guidelines has not been systematically appraised. This study aimed to evaluate the quality of CPGs published in the last 5 years for the management of pancreatic cysts. A systematic search of the PubMed database for eligible CPGs published between January 1, 2016 and November 17, 2021, using a sensitive filter. The quality of the CPGs was independently evaluated using the Appraisal of Guidelines for Research & Evaluation II instrument, with domain scores considered sufficient quality if >60% and good quality if >80%. The search yielded 4 eligible CPGs out of 426 citations. The scores varied for different domains for each CPG, with the overall median score being 79% for scope and purpose, 26% for stakeholder involvement, 51% for rigor of development, 69% for clarity of presentation, 14% for applicability, and 75% for editorial independence. The study revealed that the quality of the CPGs for pancreatic cyst management in adults remains moderate at best. Patient representatives were not involved in any of the CPG development process. There is a significant scope for improvement in methodological rigor and clarity of presentation.

Using a customized GPT to provide guideline-based recommendations for management of pancreatic cystic lesions.

Background and study aims Rising prevalence of pancreatic cysts and inconsistent management guidelines necessitate innovative approaches. New features of large language models (LLMs), namely custom GPT creation, provided by ChatGPT can be utilized to integrate multiple guidelines and settle inconsistencies. Methods A custom GPT was developed to provide guideline-based management advice for pancreatic cysts. Sixty clinical scenarios were evaluated by both the custom GPT and gastroenterology experts. A consensus was reached between experts and review of guidelines and the accuracy of recommendations provided by the custom GPT was evaluated and compared with experts. Results The custom GPT aligned with expert recommendations in 87% of scenarios. Initial expert recommendations were correct in 97% and 87% of cases, respectively. No significant difference was observed between the accuracy of custom GPT and the experts. Agreement analysis using Cohen's and Fleiss' Kappa coefficients indicated consistency among experts and the custom GPT. Conclusions This proof-of-concept study shows the custom GPT's potential to provide accurate, guideline-based recommendations for pancreatic cyst management, comparable to expert opinions. The study highlights the role of advanced features of LLMs in enhancing clinical decision-making in fields with significant practice variability.

Improving Pancreatic Cyst Management: Artificial Intelligence-Powered Prediction of Advanced Neoplasms through Endoscopic Ultrasound-Guided Confocal Endomicroscopy.

Despite the increasing rate of detection of incidental pancreatic cystic lesions (PCLs), current standard-of-care methods for their diagnosis and risk stratification remain inadequate. Intraductal papillary mucinous neoplasms (IPMNs) are the most prevalent PCLs. The existing modalities, including endoscopic ultrasound and cyst fluid analysis, only achieve accuracy rates of 65-75% in identifying carcinoma or high-grade dysplasia in IPMNs. Furthermore, surgical resection of PCLs reveals that up to half exhibit only low-grade dysplastic changes or benign neoplasms. To reduce unnecessary and high-risk pancreatic surgeries, more precise diagnostic techniques are necessary. A promising approach involves integrating existing data, such as clinical features, cyst morphology, and data from cyst fluid analysis, with confocal endomicroscopy and radiomics to enhance the prediction of advanced neoplasms in PCLs. Artificial intelligence and machine learning modalities can play a crucial role in achieving this goal. In this review, we explore current and future techniques to leverage these advanced technologies to improve diagnostic accuracy in the context of PCLs.

Molecular analysis with pancreaseq® in evaluation and management of pancreatic cysts: A cohort of 28 patients.

Herein, we present the PancreaSeq® results of 28 patients and emphasize the usefulness of molecular testing in evaluation of pancreatic cysts. A total of 10 (35.7%) non-diagnostic, 6 (21.4%) negative, 5 (17.8%) atypical, and 7 (25%) were positive for mucinous cystic neoplasm (MCN) pancreatic cyst aspirates were analyzed with PancreaSeq® at Mayo Clinic, Jacksonville between September 2021 and February 2023. Three non-diagnostic, two negative, three atypical, and two positive for MCN cysts were positive for KRAS and GNAS mutations. They were interpreted as intraductal papillary mucinous neoplasm (IPMN) with low risk for progression to high-grade dysplasia/adenocarcinoma. One negative case was positive for KRAS and GNAS mutation and RNF43 copy number alteration. It was interpreted as IPMN with a low risk of progression. Two non-diagnostic, one negative, and two positive for MCN cysts were positive for KRAS mutation. All were interpreted as IPMN/MCNs with low risk of progression. One positive for MCN case was positive for GNAS mutation and ALK fusion and one positive for MCN case was positive for GNAS mutation, ALK fusion, and RNF43 copy number alteration. Both were interpreted as IPMN and their risk of progression was interpreted as not well understood. One atypical case was positive for KRAS and TP53 mutation and was interpreted as IPMN/ MCNs with a high risk of progression. VHL mutation was present in one non-diagnostic case. It was interpreted as serous cystadenoma and the risk for progression was low. Molecular analysis of pancreatic cysts with PancreaSeq® is useful in accurate diagnosis, especially when cytologic material is non-diagnostic and helps improve patient management.

The Use of Integrated Molecular Testing in the Assessment and Management of Pancreatic Cysts.

As abdominal imaging becomes more sensitive and regularly used, pancreatic cystic lesions (PCLs) are being diagnosed more frequently. A small but clinically significant minority of these lesions have a predisposition to either harbor malignancy or undergo malignant transformation. This review highlights the current state and performance of cystic fluid biomarkers and how they may be incorporated into management. Among the major domains of molecular testing for PCLs, DNA based analyses have demonstrated the highest accuracy in identifying cyst type and have the most data to support their clinical use. However, epigenetic and protein biomarker based molecular assessments have emerged with the potential to complement DNA based approaches. In addition, recent studies have increasingly demonstrated the value associated with combinations of mutations and other biomarkers in identifying higher grade mucinous cystic lesions. We present the performance of individual biomarkers in cyst fluid analysis with an emphasis on an algorithmic approach to improve the accurate identification of both cyst type and risk of malignant transformation.

Real-Life Management of Pancreatic Cysts: Simplified Review of Current Guidelines.

Pancreatic cysts are becoming a popular diagnostic tool due to the increased availability of high-quality cross-sectional imaging. Pancreatic cystic lesions constitute closed, liquid-containing cavities, which are either neoplastic or non-neoplastic. While serous lesions often follow a benign course, mucinous lesions can hide carcinoma and, therefore, require different management. Moreover, all cysts should be considered mucinous until proven otherwise, thus limiting the errors in managing these entities. Due to the need for high contrast soft tissue imaging, magnetic resonance imaging represents an elective, non-invasive diagnostic tool. Endoscopic ultrasound (EUS) has started gaining more prominence with regard to the proper diagnosis and management of pancreatic cysts, offering quality information with minimal risks. Enabling both the acquisition of endoscopic images of the papilla and the endosonographic high-quality evaluation of septae, mural nodules along with the vascular patterns of the lesion contribute to a definitive diagnosis. Moreover, the possibility of obtaining cytological or histological samples could become mandatory in the foreseeable future, allowing for more precise molecular testing. Future research should focus on detecting methods to quickly diagnose high-grade dysplasia or early cancer for patients with pancreatic cysts, thus allowing time for appropriate treatment and avoiding surgical overtreatment or over surveillance in selected cases.

Diagnosis and Management of Pancreatic Cysts: A Comprehensive Review of the Literature.

The prevalence of pancreatic cysts has been rising due to the widespread use of cross-sectional imaging (CT scan and MRI) of the abdomen. While most pancreatic cysts are benign and do not require treatment or surveillance, a significant minority are premalignant and rarely malignant. The risk stratification of these lesions is not straightforward, and individual risk assessment, cyst size, distribution, and alarming morphologic features (when present) can guide the next steps in management. Neoplastic pancreatic cysts are mucinous or non-mucinous. Endoscopic ultrasound with fine-needle aspiration is often required to classify pancreatic cysts into mucinous and non-mucinous cysts and to assess the malignant potential. Advances in endoscopic techniques (confocal laser endomicroscopy, microforceps biopsy) can provide a definitive diagnosis of pancreatic cysts in some cases; however, the use of these techniques involves a higher risk of adverse events.

Recent advances in detecting premalignant pancreatic cysts

The incidental discovery of pancreatic cysts in asymptomatic patients is on the rise due to the widespread use of cross-sectional imaging. The challenge in the management of pancreatic cysts is in distinguishing those with malignant potentials, like mucinous pancreatic cysts, from non-mucinous cysts that have negligible malignant potentials. Similarly, it can be difficult to identify mucinous cysts that harbour high-grade dysplasia or early cancer. This review focuses on the recent advances in detecting pancreatic cancer and cysts with premalignant potential.

Role of artificial intelligence in pancreatic cystic neoplasms: modernizing the identification and longitudinal management of pancreatic cysts

Mucinous cysts of the pancreas represent the most common identifiable precursor to pancreatic cancer. Evidence-based guidelines for screening and surveillance exist, but many patients are either not properly identified or lost to follow-up. Artificial Intelligence, specifically computational linguistics models, can dramatically improve patient identification and mitigate risk through modernizing pancreatic cyst longitudinal surveillance. Herein we discuss the risk associated with mucinous cysts of the pancreas and modern approaches to patient identification and follow-up.

Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts

Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.

The Role of Confocal Endomicroscopy in the Diagnosis and Management of Pancreatic Cysts

Pancreatic cystic lesions are an increasingly common clinical finding. Current diagnostic techniques cannot reliably differentiate patients with high-risk lesions requiring surgical resection from those that can be safely surveyed or discharged. As a result, some patients may undergo unnecessary surgery with associated morbidity while others enter long-term surveillance with associated healthcare costs. Needle-based confocal laser endomicroscopy enables real time microscopic examination of the epithelial lining of a cyst wall at the time of a standard endoscopic ultrasound examination. The procedure is associated with low rates of adverse events, especially when the probe is loaded into the fine-needle aspiration needle before the procedure and examination times are limited. Needle-based confocal laser endomicroscopy has consistently been shown to have better diagnostic accuracy than cytology, which is often paucicellular and non-diagnostic in pancreatic cystic lesions. Studies have shown that diagnostic accuracy in needle-based confocal laser endomicroscopy is 84–95% in mucinous lesions and 39–99% in serous lesions. However, this technology is expensive and its place in diagnostic algorithms remains uncertain. Despite this, health economic analyses in certain health systems have been favourable, largely because of its potential to be able to discharge patients with benign lesions, such as serous cystic neoplasms, from long-term surveillance. Widespread adoption of this technology is unlikely but it has the potential to have an important role in indeterminate pancreatic cystic lesions.

Updates in diagnosis and management of pancreatic cysts.

Incidental pancreatic cysts are commonly encountered with some cysts having malignant potential. The most common pancreatic cystic neoplasms include serous cystadenoma, mucinous cystic neoplasm and intraductal papillary mucinous neoplasm. Risk stratifying pancreatic cysts is important in deciding whether patients may benefit from endoscopic ultrasound (EUS) or surgical resection. Surgery should be reserved for patients with malignant cysts or cysts at high risk for developing malignancy as suggested by various risk features including solid mass, nodule and dilated main pancreatic duct. EUS may supplement magnetic resonance imaging findings for cysts that remain indeterminate or have concerning features on imaging. Various cyst fluid markers including carcinoembryonic antigen, glucose, amylase, cytology, and DNA markers help distinguish mucinous from nonmucinous cysts. This review will guide the practicing gastroenterologist in how to evaluate incidental pancreatic cysts and when to consider referral for EUS or surgery. For presumed low risk cysts, surveillance strategies will be discussed. Managing pancreatic cysts requires an individualized approach that is directed by the various guidelines.

ID: 3522273 ASSESSING KRAS/GNAS AND BIOLOGIC BEHAVIOR USING MOLECULAR DNA ANALYSIS IN CHARACTERIZING PRE-MALIGNANT PANCREATIC CYSTS

The prevalence of pancreatic cysts, estimated at 2.5%, has increased due to improved imaging modalities. Intraductal papillary mucinous neoplasm (IPMN) and mucinous cystic neoplasm (MCN) are the most prevalent pancreatic cystic neoplasms with malignant potential. Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) has become useful in identifying pancreatic cysts, but diagnostic yield of cytology is reported to be 31%. The role for DNA molecular analysis, including KRAS/GNAS mutations and assessment of cyst biologic behavior in the management of pancreatic cysts has yet to be determined.

Society of Abdominal Radiology Disease Focused Panel Survey on Clinical Utilization of Incidental Pancreatic Cyst Management Recommendations and Template Reporting.

To assess current practice patterns with respect to protocols used for incidental pancreatic cyst follow-up, management guidelines, and template reporting. The Society of Abdominal Radiology Disease Focused Panel on intraductal pancreatic neoplasms distributed an anonymous 14-question survey to its members in June 2018 that focused on current utilization of incidental pancreatic cyst guidelines, protocols, and template reporting. Among the 1,390 email invitations, 323 responded, and 94.7% (306 of 323) completed all questions. Respondents were mainly radiologists (93.8%, 303 of 323) from academic institutions (74.7%, 227 of 304) in North America (93.7%, 286 of 305). Of respondents, 42.5% (136 of 320) preferred 2017 ACR recommendations, 17.8% (57 of 320) homegrown systems, 15.0% (48 of 320) Fukuoka guidelines, and 7.8% (25 of 320) American Gastroenterological Association guidelines. The majority (68.7%, 222 of 323) agreed or strongly agreed that developing a single international consensus recommendation for management was important, and most radiologists preferred to include them in reports (231 of 322, 71.7%); yet only half included recommendations in >75% of reports (161 of 321). MR cholangiopancreatography was the modality of choice for follow-up of <2.5 cm cysts. Intravenous contrast was routinely used by 69.7% (212 of 304). Standardized reporting templates were rarely used in practice (12.8% 39 of306). Nearly 7 of 10 radiologists desire a unified international consensus recommendation for management of incidental cystic pancreatic lesions; ACR 2017 recommendations are most commonly used, followed by homegrown systems and Fukuoka guidelines. The majority of radiologists routinely use MR cholangiopancreatography with intravenous contrast for follow-up of incidental cystic lesions, but template reporting is rarely used.

Guidelines on management of pancreatic cysts detected in high-risk individuals: An evaluation of the 2017 Fukuoka guidelines and the 2020 International Cancer of the Pancreas Screening (CAPS) consortium statements

BackgroundObjectives: Pancreatic cysts are frequently detected in high-risk individuals (HRI) undergoing surveillance for pancreatic cancer. The International Cancer of the Pancreas Screening (CAPS) Consortium developed consensus recommendations for surgical resection of pancreatic cysts in HRI that are similar to the Fukuoka guidelines used for the management of sporadic cysts. We compared the performance characteristics of CAPS criteria for pancreatic cyst management in HRI with the Fukuoka guidelines originally designed for the management of cysts in non-HRI. MethodsUsing prospectively collected data from CAPS studies, we determined for each patient with resected screen-detected cyst(s) whether Fukuoka guidelines or CAPS consensus statements would have recommended surgery. We compared sensitivity, specificity, PPV, NPV, and Receiver Operator Characteristics (ROC) curves of these guidelines at predicting the presence of high-grade dysplasia or invasive cancer in pancreatic cysts. Results356/732 HRI had ≥ one pancreatic cyst detected; 24 had surgery for concerning cystic lesions. The sensitivity, specificity, PPV, and NPV for the Fukuoka criteria were 40%, 85%, 40%, and 85%, while those of the CAPS criteria were 60%, 85%, 50%, 89%, respectively. ROC curve analyses showed no significant difference between the Fukuoka and CAPS criteria. ConclusionsIn HRI, the CAPS and Fukuoka criteria are moderately specific, but not sufficiently sensitive for detecting advanced neoplasia in cystic lesions. New approaches are needed to guide the surgical management of cystic lesions in HRI.

Management of pancreatic cysts and guidelines: what the gastroenterologist needs to know.

The prevalence of pancreatic cysts has increased significantly over the last decade, partly secondary to increased quality and frequency of cross-sectional imaging. While the majority never progress to cancer, a small number will and need to be followed. The management of pancreatic cysts can be both confusing and intimidating due to the multiple guidelines with varying recommendations. Despite the differences in the specifics of the guidelines, they all agree on several high-risk features that should get the attention of any clinician when assessing a pancreatic cyst: presence of a mural nodule or solid component, dilation of the main pancreatic duct (or presence of main duct intraductal papillary mucinous neoplasm), pancreatic cyst size ⩾3–4 cm, or positive cytology on pancreatic cyst fluid aspiration. Other important criteria to consider include rapid cyst growth (⩾5 mm/year), elevated serum carbohydrate antigen 19-9 levels, new-onset diabetes mellitus, or acute pancreatitis thought to be related to the cystic lesion.

The Outcome of Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Patients with Pancreatic Cystic Neoplasms: A Systematic Review

Introduction: Pancreatic cancer is the sixth most common cause of death from cancer in the UK. Cystic pancreatic neoplasms are being recognized more with the increase in the use of the CT scan. EUS has been increasingly used to asses and identify lesions in the pancreas, however, it can’t differentiate between benign and malignant tumors alone. The role of EUS guided FNA cytology (EUS FNAC) is still controversial in the management of pancreatic cysts where neoplastic process is questioned. Aim: This systematic review is aiming to explore the currently available evidence assessing the role of EUS guided FNA cytology (EUS FNAC) in the management of pancreatic cystic neoplasms. Methods: A total of five studies with 597 patient EUS FNAC episodes were included in this systematic review. Results: The sensitivity of the EUS FNAC in the papers was variable between 46.7% to 91.7% while the sensitivity of the test was 100% for all the papers except for 1 paper which was 82.1%. CEA level was assessed in 3 papers, however, the cut off level was different. Conclusion: The high specificity of EUS FNAC qualify it as a useful adjunct to ascertain or exclude malignancy in the pancreatic cystic lesions. EUS FNAC cannot be used alone as a method of screening, given low sensitivity. Measuring CEA in the cyst fluid can be a good aide to increase the sensitivity and an identifiable cut off level should be proposed. Well-conducted and powered studies are needed to further explore the role of EUS FNAC in patients with pancreatic cystic neoplastic lesions.

Cost-effectiveness of consensus guideline based management of pancreatic cysts: The sensitivity and specificity required for guidelines to be cost-effective

BackgroundDetection of cystic lesions of the pancreas has outpaced our ability to stratify low-grade cystic lesions from those at greater risk for pancreatic cancer, raising a concern for overtreatment. MethodsWe developed a Markov decision model to determine the cost-effectiveness of guideline-based management for asymptomatic pancreatic cysts. Incremental costs per quality-adjusted life year gained and survival were calculated for current management guidelines. A sensitivity analysis estimated the effect on cost-effectiveness and mortality if overtreatment of low-grade cysts is avoided, and the sensitivity and specificity thresholds required of methods of cyst stratification to improve costs expended. Results“Surveillance” using current management guidelines had an incremental cost-effectiveness ratio of $171,143/quality adjusted life year compared with no surveillance or operative treatment (“do nothing”). An incremental cost-effectiveness ratio for surveillance decreases to $80,707/quality adjusted life year if the operative overtreatment of low-grade cysts was avoided. Assuming a societal willingness-to-pay of $100,000/quality adjusted life year, the diagnostic specificity for high-risk cysts must be >67% for surveillance to be preferred over surgery and “do nothing.” Changes in sensitivity alone cannot make surveillance cost-effective. Most importantly, survival in surveillance is worse than “do nothing” for 3 years after cyst diagnosis, although long-term survival is improved. The disadvantage is eliminated when overtreatment of low-grade cysts is avoided. ConclusionCurrent management of pancreatic cystic lesions is not cost-effective and may increase mortality owing to overtreatment of low-grade cysts. The specificity for risk stratification for high-risk cysts must be greater than 67% to make surveillance cost-effective.

Clinical and Economic Outcomes of Patients Undergoing Guideline-Directed Management of Pancreatic Cysts.

Numerous guidelines exist for the management of pancreatic cysts. We sought to compare the guideline-directed management strategies for pancreatic cysts by comparing 2 approaches (2017 International Consensus Guidelines and 2015 American Gastroenterological Association Guidelines) that differ significantly in their thresholds for imaging, surveillance, and surgery. We developed a Monte Carlo model to evaluate the outcomes for a cohort of 10,000 patients managed per each guideline. The primary outcome was mortality related to pancreatic cyst management. Secondary outcomes included all-cause mortality, missed cancers, number of surgeries, number of imaging studies, cumulative cost, and quality-adjusted life years. Deaths because of pancreatic cyst management and quality-adjusted life years were similar in both guidelines at a significantly higher cost of $3.6 million per additional cancer detected in the Consensus Guidelines. Deaths from "unrelated" causes (1,422) vastly outnumbered deaths related to pancreatic cysts (125). Secondary outcomes included more missed cancers in the American Gastroenterological Association guideline (71 vs 49), more surgeries and imaging studies in the Consensus guideline (711 vs 163; 116,997 vs 68,912), and higher cost in the Consensus guideline ($168.3 million vs $89.4 million). As the rate of malignant transformation increases, a more-intensive guideline resulted in fewer deaths related to pancreatic cyst management. Our study demonstrates trade-offs between more- and less-intensive management strategies for pancreatic cysts. Although deaths related to pancreatic cyst management were similar in each strategy, fewer missed cancers in the more-intensive surveillance strategy is offset by a greater number of surgical deaths and higher cost. In conclusion, our study identifies that if the rate malignant transformation of pancreatic cysts is low (0.12% annually), a less-intensive guideline will result in similar deaths to a more-intensive guideline at a much lower cost.