Prospective validation of a hospital triage predictive model to decrease undertriage: an EAST multicenter study.

Background: Tiered trauma team activation (TTA) allows systems to optimally allocate resources to an injured patient. Target undertriage and overtriage rates of <5% and <35% are difficult for centers to achieve, and performance variability exists. The objective of this study was to optimize and externally validate a previously developed hospital trauma triage prediction model to predict the need for emergent intervention in 6 hours (NEI-6), an indicator of need for a full TTA. Methods: The model was previously developed and internally validated using data from 31 US trauma centers. Data were collected prospectively at five sites using a mobile application which hosted the NEI-6 model. A weighted multiple logistic regression model was used to retrain and optimize the model using the original data set and a portion of data from one of the prospective sites. The remaining data from the five sites were designated for external validation. The area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC) were used to assess the validation cohort. Subanalyses were performed for age, race, and mechanism of injury. Results: 14 421 patients were included in the training data set and 2476 patients in the external validation data set across five sites. On validation, the model had an overall undertriage rate of 9.1% and overtriage rate of 53.7%, with an AUROC of 0.80 and an AUPRC of 0.63. Blunt injury had an undertriage rate of 8.8%, whereas penetrating injury had 31.2%. For those aged ≥65, the undertriage rate was 8.4%, and for Black or African American patients the undertriage rate was 7.7%. Conclusion: The optimized and externally validated NEI-6 model approaches the recommended undertriage and overtriage rates while significantly reducing variability of TTA across centers for blunt trauma patients. The model performs well for populations that traditionally have high rates of undertriage. Level of evidence: 2.

Physiologic parameters and radiologic findings can predict pulmonary complications and guide management in traumatic rib fractures.

BACKGROUND: Traumatic rib fracture is associated with a high morbidity rate and identifying patients at risk of developing pulmonary complications (PC) can guide management and potentially decrease unnecessary intensive care admissions. Therefore, we sought to assess and compare the utility of a physiologic parameter, vital capacity (VC), with the admission radiologic findings (RibScore) in predicting PC in patients with rib fractures. METHODS: This is a single-center retrospective review (2015-2018) of all adult (≥18 years) patients admitted to a Level I trauma center with traumatic rib fracture. Exclusion criteria included no CT scan and absence of VC within 48 h of admission. The cohort was stratified into two groups based on presence or absence of PC (pneumonia, unplanned intubation, unplanned transfer to the intensive care unit for a respiratory concern, or the need for a tracheostomy). Multivariable logistic regression models were constructed to identify predictors of PC. RESULTS: A total of 654 patients met the inclusion criteria of whom 70 % were males. The median age was 51 years and fall (48 %) was the most common type of injury. A total of 36 patients (5.5 %) developed a pulmonary complication. These patients were more likely to be older, had a higher ISS, and were more likely to require a tube thoracostomy placement. On multivariable logistic regression, first VC ≤30 % (AOR: 4.29), day 1 VC ≤30 % (AOR: 3.61), day 2 VC ≤30 % (AOR: 5.54), Δ(Day2-Day1 VC) (AOR: 0.96), and RibScore ≥2 (AOR: 3.19) were significantly associated with PC. On discrimination analysis, day 2 VC had the highest area under the receiver operating characteristic curve (AuROC), 0.81, and was superior to first VC and day 1 VC in predicting PC. There was no statistically significant difference in predicting PC between day 2 VC and RibScore. On multivariable analysis, first VC ≤30 %, day 1 VC ≤30 %, day 2 VC ≤30 %, and admission RibScore ≥2 were associated with prolonged hospital and ICU LOS. CONCLUSION: VC and RibScore emerged as independent predictors of PC. However, VC was not found to be superior to RibScore in predicting PC. Further prospective research is warranted to validate the findings of this study.

Preoperative CA 19-9 Predicts Disease Progression in Colorectal Peritoneal Metastases Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: An Analysis from the US HIPEC Collaborative.

INTRODUCTION: Patients with colorectal peritoneal metastases (CRPM) are increasingly treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Unfortunately, data identifying preoperative risk factors for poor oncologic outcomes after this procedure are limited. We aimed to determine the prognostic value of preoperative CEA, CA 125, and CA 19-9 on disease progression after CRS/HIPEC. METHODS: Patients with CRPM treated with curative intent CRS/HIPEC from 12 participating sites in the United States from 2000 to 2017 were identified. Progression-free survival (PFS), defined as disease progression or recurrence, was the primary outcome. RESULTS: In 279 patients who met inclusion criteria, the rate of disease progression was 63.8%, with a median PFS of 11 months (interquartile range [IQR] 5-20). Elevated CA 19-9 was associated with dismal PFS at 2 years (8.9% elevated vs. 30% not elevated, p < 0.01). In 113 patients who underwent upfront CRS/HIPEC, CA 19-9 emerged as the sole tumor marker independently predictive of worse PFS (hazard ratio [HR] 2.88, p = 0.048). In the subgroup of patients who had received neoadjuvant therapy (NAT), no variable was independently predictive of PFS. CA 19-9 levels over 37 U/ml were highly specific for accelerated disease progression after CRS/HIPEC. Lastly, there was no association between PFS and elevated CEA or CA 125. CONCLUSIONS: Elevated CA 19-9 is associated with decreased PFS in patients with CRPM. While traditionally CEA is the main tumor marker assessed in colon cancer, we found that CA 19-9 may better inform preoperative risk stratification for poor oncologic outcomes in patients with CRPM. However, prospective studies are required to confirm this association.

Open versus endovascular repair of penetrating non-aortic arterial injuries: A systematic review and meta analysis.

BACKGROUND: Non-aortic arterial injuries are common and are associated with high morbidity and mortality. Historically, open surgical repair (OSR) was the conventional method of repair. With recent advancements in minimally invasive techniques, endovascular repair (ER) has gained popularity. We sought to compare outcomes in patients undergoing endovascular and open repairs of traumatic non-aortic penetrating arterial injuries. METHODS: A systematic review and meta-analysis was conducted using MEDLINE (OVID), Web of Science, Cochrane Library, and Scopus Database from January 1st, 1990, to March 20th, 2023. Titles and abstracts were screened, followed by full text review. Articles assessing clinically important outcomes between OSR and ER in penetrating arterial injuries were included. Exclusion criteria included blunt injuries, aortic injuries, pediatric populations, review articles, and non-English articles. Odds ratios (OR) and Cohen's d ratios were used to quantify differences in morbidity and mortality. RESULTS: A total of 3770 articles were identified, of which 8 met inclusion criteria and were included in the review. The articles comprised a total of 8369 patients of whom 90 % were male with a median age of 28 years. 85 % of patients were treated with OSR while 15 % underwent ER. With regards to injury characteristics, those who underwent ER were less likely to present with concurrent venous injuries (OR: 0.41; 95 %CI: 0.18, 0.94; p = 0.03). Regarding hospital outcomes, patients who underwent ER had a lower likelihood of in-hospital or 30-day mortality (OR: 0.72; 95 %CI: 0.55, 0.95; p = 0.02) and compartment syndrome (OR: 0.29, 95 %CI: 0.12, 0.71; p = 0.007). The overall risk of bias was moderate. CONCLUSION: Endovascular repair of non-aortic penetrating arterial injuries is increasingly common, however open repair remains the most common approach. Compared to ER, OSR was associated with higher odds of compartment syndrome and mortality. Further prospective research is warranted to determine the patient populations and injury patterns that most significantly benefit from an endovascular approach. LEVEL OF EVIDENCE: Level III, Systematic Reviews & Meta-Analyses.

Predictive Factors for the Application of Pelvic Binders in the Prehospital Setting.

OBJECTIVES: Early pelvic binder placement in the field stabilizes pelvic fractures and tamponades potential hemorrhage within the pelvis. Despite known risk factors for pelvic fracture, it remains challenging to quickly triage and correctly apply a pelvic binder. We aim to develop a prediction model that exclusively uses prehospital criteria to inform the decision to place a pelvic binder. METHODS: The trauma registry was used to identify all trauma patients admitted to an urban Level I trauma center between January 2013 and December 2017. Variables collected included patient demographics, mechanism of injury, prehospital vital signs, and the presence of a pelvic fracture. Participants were randomly assigned to a training group (70%) or a validation group (30%). Univariate analyses were used to identify significant predictors for use in multivariate predictive models. RESULTS: A total of 8,480 (65% male; median age 49; median ISS 9) and 3,676 (65% male; median age 48; median ISS 9) trauma patients were randomly assigned to the training and validation groups, respectively. Univariate analysis showed significant likelihood of pelvic fracture associated with female sex, hemodynamic instability (initial systolic blood pressure < 90 mmHg), blunt injury type, specific mechanisms of injury (motor vehicle collision, motorcycle collision, pedestrian struck by motor vehicle, crushing injury, and riding an animal), impact location, and position in vehicle. Multivariate models adjusting for blunt type injury, hemodynamic instability, impact location, and position in vehicle showed that presence of two or more of these risk factors is significantly associated with presence of pelvic fracture. CONCLUSION: Establishing select prehospital criteria for the empiric application of pelvic binders for patients in the field with blunt injuries, hemodynamic instability, frontal or side motor vehicle collision impact, and non-front seat passenger may improve outcomes among patients with pelvic fractures.

Early career acute care surgeons' priorities and perspectives: A mixed-methods analysis to better understand full-time employment.

BACKGROUND: Understanding the expectations of early career acute care surgeons will help clarify the practice and employment models that will attract and retain high-quality surgeons, thereby sustaining our workforce. This study aimed to outline the clinical and academic preferences and priorities of early career acute care surgeons and to better define full-time employment. METHODS: A survey on clinical responsibilities, employment preferences, work priorities, and compensation was distributed to early career acute care surgeons in the first 5 years of practice. A subset of agreeable respondents underwent virtual semistructured interviews. Both quantitative and thematic analysis were used to describe current responsibilities, expectations, and perspectives. RESULTS: Of 471 surgeons, 167 responded (35%), the majority of whom were assistant professors within the first 3 years of practice (80%). The median desired clinical volume was 24 clinical weeks and 48 call shifts per year, 4 weeks less than their median current clinical volume. Most respondents (61%) preferred a service-based model. The top priorities cited in choosing a job were geography, work schedule, and compensation. Qualitative interviews identified themes related to defining full-time employment, first job expectations and realities, and the often-misaligned system and surgeon. CONCLUSION: Understanding the perspectives of early career surgeons entering the workforce is important particularly in the field of acute care surgery where no standard workload or practice model exists. The wide variety of expectations, practice models, and schedule preferences may lead to a mismatch between surgeon desires and employment expectation. Consistent employment standards across our specialty would provide a framework for sustainability. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.

The Variation of Withdrawal of Life Sustaining Therapy in Older Adults With Traumatic Brain Injury.

INTRODUCTION: The decision to withdraw life sustaining treatment (WDLST) in older adults with traumatic brain injury is subject to wide variability leading to nonbeneficial interventions and unnecessary use of hospital resources. We hypothesized that patient and hospital factors are associated with WDLST and WDLST timing. METHODS: All traumatic brain injury patients ≥65 with Glasgow coma scores (GCS) of 4-11 from 2018 to 2019 at level I and II centers were selected from the National Trauma Data Bank. Patients with head abbreviated injury scores 5-6 or death within 24 h were excluded. Bayesian additive regression tree analysis was performed to identify the cumulative incidence function (CIF) and the relative risks (RR) over time for withdrawal of care, discharge to hospice (DH), and death. Death alone (no WDLST or DH) served as the comparator group for all analyses. A subanalysis of the composite outcome WDLST/DH (defined as end-of-life-care), with death (no WDLST or DH) as a comparator cohort was performed. RESULTS: We included 2126 patients, of whom 1957 (57%) underwent WDLST, 402 (19%) died, and 469 (22%) were DH. 60% of patients were male, and the mean age was 80 y. The majority of patients were injured by fall (76%, n = 1644). Patients who were DH were more often female (51% DH versus 39% WDLST), had a past medical history of dementia (45% DH versus 18% WDLST), and had lower admission injury severity score (14 DH versus 18.6 WDLST) (P < 0.001). Compared to those who DH, those who underwent WDLST had a lower GCS (9.8 versus 8.4, P < 0.001). CIF of WDSLT and DH increased with age, stabilizing by day 3. At day 3, patients ≥90 y had an increased RR of DH compared to WDLST (RR 2.5 versus 1.4). As GCS increased, CIF and RR of WDLST decreased, while CIF and RR of DH increased (RR on day 3 for GCS 12: WDLST 0.42 versus DH 1.31).Patients at nonprofit institutions were more likely to undergo WDLST (RR 1.15) compared to DH (0.68). Compared to patients of White race, patients of Black race had a lower RR of WDLST at all timepoints. CONCLUSIONS: Patient and hospital factors influence the practice of end-of-life-care (WDLST, DH, and death), highlighting the need to better understand variability to target palliative care interventions and standardize care across populations and trauma centers.

The efficacy of various Enoxaparin dosing regimens in general surgery patients: A systematic review.

BACKGROUND: Patients undergoing surgical procedures are at an increased risk of venous thromboembolism events. A fixed Enoxaparin dosing regimen is the standard of care for chemoprophylaxis in most institutions; however, breakthrough venous thromboembolism events are still reported. We aimed to systematically review the literature to determine the ability of various Enoxaparin dosing regimens to achieve adequate prophylactic anti-Xa levels for venous thromboembolism prevention in hospitalized general surgery patients. Additionally, we aimed to assess the correlation between subprophylactic anti-Xa levels and the development of clinically significant venous thromboembolism events. METHODS: A systematic review was conducted using major databases from January 1, 1993, to February 17, 2023. Two independent researchers screened titles and abstracts, followed by a full-text review. Articles were included if Enoxaparin dosing regimens were evaluated by anti-Xa levels. Exclusion criteria included systematic reviews, pediatric population, nongeneral surgery (defined as trauma, orthopedics, plastics, and neurosurgery), and non-Enoxaparin chemoprophylaxis. The primary outcome was peak Anti-Xa level measured at steady state concentration. The risk of bias was assessed using the Risk of Bias in Nonrandomized studies-of Intervention tool. RESULTS: A total of 6,760 articles were extracted, of which 19 were included in the scoping review. Nine studies included bariatric patients, whereas 5 studies explored abdominal surgical oncology patients. Three studies assessed thoracic surgery patients, and 2 studies included patients undergoing "general surgery" procedures. A total of 1,502 patients were included. The mean age was 47 years, and 38% were males. The percentages of patients reaching adequate prophylactic anti-Xa levels were 39%, 61%, 15%, 50%, and 78% across the 40 mg daily, 40 mg twice daily, 30 mg twice daily, and weight-tiered, and body mass index-based groups, respectively. The overall risk of bias was low to moderate. CONCLUSION: Fixed Enoxaparin dosing regimens are not correlated with adequate anti-Xa levels in general surgery patients. Additional research is warranted to assess the efficacy of dosing regimens based on novel physiologic parameters (such as estimated blood volume).

Anti-Factor Xa Monitoring of Enoxaparin Thromboembolism Prophylaxis in Emergency General Surgery Patients.

BACKGROUND: Rates of venous thromboembolism (VTE) remain high in emergency general surgery (EGS) patients despite chemical VTE prophylaxis. Emerging literature supports anti-factor Xa (AFXa) monitoring for patients on enoxaparin (LMWH), although a significant knowledge gap remains regarding the optimal dosing and monitoring in EGS patients. We hypothesize that standard dose VTE prophylaxis regimens provide inadequate VTE prophylaxis in EGS patients. STUDY DESIGN: A prospective cohort study of all adult EGS patients at a single institution between August 2021 and February 2022 receiving standard dose LMWH for VTE prophylaxis was performed. AFXa levels were obtained 4 hours after the third dose of enoxaparin with a target range of 0.3 to 0.5 IU/mL. Adjustment to dosing and repeat AFXa measurement after the adjusted third dose was obtained. RESULTS: A total of 81 patients underwent AFXa monitoring, the majority (75%) of whom were started on 40 mg LMWH daily. Initial peak AFXa measurement was low in 87.7% of patients (mean 0.16 IU/mL). Of patients who had an initial low AFXa, remained admitted, and underwent dosing adjustment and AFXa reassessment (27%), the majority were adjusted to either 30 or 40 mg of LMWH twice daily (23.7% and 55%, respectively), with 82% of patients remaining low. There were no significant differences in demographics or BMI between those with low vs adequate AFXa levels at either initial or subsequent measurement. CONCLUSIONS: Standard LMWH dosing provides inadequate AFXa inhibition for adequate VTE prophylaxis. These findings highlight the importance of ongoing AFXa monitoring and the need to establish clinical protocols to improve VTE prophylaxis in EGS patients.

Conditional Survival Following Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies: An Analysis from the US HIPEC Collaborative.

INTRODUCTION: The long-term prognosis of patients who undergo cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies (PSM) varies considerably on the basis of histological and operative factors. While overall survival (OS) estimates are used to inform adjuvant therapy and surveillance strategies, conditional survival may provide more clinically relevant estimates of prognosis by accounting for disease-free time elapsed. PATIENTS AND METHODS: All patients from 12 academic institutions who underwent CRS ± HIPEC for PSM from 2000 to 2017 were retrospectively analyzed. OS and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method while conditional overall (COS) and conditional disease-free survival (CDFS) rates were calculated at 1, 2, or 3 years from surgery for different tumor histologies. RESULTS: Overall, 1610 patients underwent CRS ± HIPEC. Among patients with benign appendiceal mucinous tumors (N = 460), 5-year OS and COS at 3 years were 92.1% and 96.3% (Δ4.2%), respectively. For patients with well-differentiated appendiceal cancers (N = 400), 5-year OS and COS at 3 years were 76.3% and 88.3% (Δ12.0%), respectively. For patients with high-grade appendiceal cancers (N = 258), 5-year OS and COS at 3 years were 43.8% and 75.4% (Δ31.6%), respectively. For patients with colorectal cancers (N = 362), 5-year OS and COS at 3 years were 31.8% and 67.3% (Δ35.5%), respectively. For patients with peritoneal mesothelioma (N = 130), 5-year OS and COS at 3 years were 67.6% and 89.7% (Δ22.1%), respectively. Similar trends were observed for DFS/CDFS. CONCLUSION: The conditional survival of patients undergoing CRS ± HIPEC for PSM is associated with tumor histology. COS and CDFS provide a more accurate, dynamic estimate of survival than OS and DFS, especially for patients with more aggressive histologies.

Influence of insurance status on the postoperative outcomes of cytoreductive surgery and HIPEC.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is increasingly performed for peritoneal surface malignancies but remains associated with significant morbidity. Scant research is available regarding the impact of insurance status on postoperative outcomes. METHODS: Patients undergoing CRS/HIPEC between 2000 and 2017 at 12 participating sites in the US HIPEC Collaborative were identified. Univariate and multivariate analyses were used to compare the baseline characteristics, operative variables, and postoperative outcomes of patients with government, private, or no insurance. RESULTS: Among 2268 patients, 699 (30.8%) had government insurance, 1453 (64.0%) had private, and 116 (5.1%) were uninsured. Patients with government insurance were older, more likely to be non-white, and comorbid (p < 0.05). Patients with government (OR: 2.25, CI: 1.50-3.36, p < 0.001) and private (OR: 1.69, CI: 1.15-2.49, p = 0.008) insurance had an increased risk of complications on univariate analysis. There was no independent relationship on multivariate analysis. An American Society of Anesthesiologists score of 3 or 4, peritoneal carcinomatosis index score >15, completeness of cytoreduction score >1, and nonhome discharge were factors independently associated with a postoperative complication. CONCLUSION: While there were differences in postoperative outcomes between the three insurance groups on univariate analysis, there was no independent association between insurance status and postoperative complications after CRS/HIPEC.

Mechanical Ventilation Does Not Predict Pneumothorax Observation Failure in the Severely Injured.

BACKGROUND: Observative management of small traumatic pneumothoraces (PTX) has been shown to decrease chest tube utilization in non-mechanically ventilated patients without compromising outcomes. This approach could be used in mechanically ventilated (MV) patients, though many feel these patients are at increased risk of observation failure. METHODS: A single center retrospective study of all adults undergoing observation of a computed tomography (CT) diagnosed PTX from 2015-2019. Patients with chest tube placement within 4-hours of arrival, concurrent hemothorax, or death within 24-hours were excluded. Observation failure was defined as chest tube placement. RESULTS: Of 340 patients, 64 were on MV. The groups were of similar age, BMI, underlying pulmonary comorbidities, and PTX size (10.1 mm vs 8.8 mm, P = .20). The MV group was more severely injured (ISS [25+] [60.9% vs 11.2%, P < .001]). There was no difference in observation failure rates by MV status overall (6.3% vs 5.1%, P = .75) or by PTX size (<15 mm [5% vs 2.2%, P = .37], <20 mm [4.8% vs 3.1%, P = .45], <25 mm [4.8% vs 4.1%, P = .73], <30 mm [4.8% vs 4.1%, P = .73], <35 mm [4.8% vs 4.7%, P = 1.00]). MV was not an independent predictor of observation failure on multivariable analysis (OR .64, 95% CI .18-2.20), though PTX size was (OR 1.11, 95% CI 1.05-1.17). When comparing those who failed vs those who did not, the only difference was PTX size (9.34 mm vs 19.41 mm, P < .001). CONCLUSION: MV is not an independent predictor of PTX observation failure. While PTX size appears to play a role, further studies are needed to outline safe parameters for observation in those undergoing MV.

Predicting outcomes after traumatic brain injury: A novel hospital prediction model for a patient reported outcome.

BACKGROUND: Estimation of long-term quality of life in patients sustaining Traumatic brain injuries is a difficult but important task during the early hospitalization. There are very limited tools to assess these outcomes, therefore we aimed to develop a predictive model for quality-of-life that could be used in hospitalized adults with TBIs. METHODS: The TRACK-TBI dataset was used to identify adult patients with TBI from 2014 to 2018. Multiple variables were assessed to predict favorable versus unfavorable scores on the Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS). RESULTS: We included 1549 subjects. 57% had a favorable outcome, and were more likely to have private insurance, higher GCS scores, and fewer comorbidities. A model (TBI-PRO) for 3, 6, and 12-month QOLIBRI score was created. The AUROCs for predicting 3, 6 and 12-month favorable QOLIBRI scores were 0.81, 0.79, and 0.76, respectively. CONCLUSION: The TBI-PRO model adequately estimates long-term outcomes in patients with TBI.

The Utility of Preoperative Tumor Markers in Peritoneal Carcinomatosis from Primary Appendiceal Adenocarcinoma: an Analysis from the US HIPEC Collaborative.

BACKGROUND: Prognostication based on preoperative clinical factors is lacking in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). This study aims to determine the value of preoperative tumor markers as predictors of progression-free survival (PFS) and overall survival (OS) for patients with peritoneal carcinomatosis from a primary mucinous adenocarcinoma of the appendix (MACA). METHODS: We queried the United States HIPEC Collaborative, a database of patients with peritoneal carcinomatosis treated with CRS/HIPEC at twelve institutions between 2000 and 2017, identifying 409 patients with MACA. Multivariate analysis was used to identify independent predictors of disease progression. Subgroup analysis was conducted to evaluate the impact of tumor grade on the predictive value of tumor markers. RESULTS: CA19-9 [HR 2.44, CI 1.2-3.4] emerged as an independent predictor of PFS while CEA [HR 4.98, CI 1.06-23.46] was independently predictive of OS (p <0.01). Tumor differentiation was the most potent predictor of both PFS (poorly differentiated vs well, [HR 4.5 CI 2.01-9.94]) and OS ([poorly differentiated vs well-differentiated: [HR 13.5, CI 3.16-57.78]), p <0.05. Among patients with combined CA19-9 elevation and poorly differentiated histology, 86% recurred within a year of CRS/HIPEC (p < 0.01). Similarly, the coexistence of CEA elevation and unfavorable histology led to the lowest survival rate at two years [36%, p < 0.01]. CA-125 was not predictive of PFS or OS. CONCLUSION: Elevated preoperative CA19-9 portends worse PFS, while elevated CEA predicts worse OS after CRS/HIPEC in patients with MACA. This study provides additional evidence that CA19-9 and CEA levels should be collected during standard preoperative bloodwork, while CA-125 can likely be omitted. Tumor differentiation, when added to preoperative tumor marker levels, provides powerful prognostic information. Prospective studies are required to confirm this association.

A multi-institutional analysis of Textbook Outcomes among patients undergoing cytoreductive surgery for peritoneal surface malignancies.

BACKGROUND: While recent studies have introduced the composite measure of a textbook outcome (TO) for measuring postoperative outcomes, the incidence of a TO has not been characterized among patients undergoing cytoreductive surgery (CRS) for peritoneal surface malignancies (PSM). STUDY DESIGN: All patients who underwent CRS ± hyperthermic intraperitoneal chemotherapy (HIPEC) between 1999 and 2017 from 12 institutions were included. A TO was defined as the absence of any of the following criteria: completeness of cytoreduction >1, reoperation within 90-days, readmission within 90-days, mortality within 90-days, any grade ≥2 complication, hospital stay >75th percentile, and non-home discharge. RESULTS: Among 1904 patients who underwent CRS, only 30.9% achieved a TO while 69.1% failed to achieve a TO most commonly because of postoperative complications. On multivariable analysis, factors associated with achieving a TO were age <65 years (OR: 1.5), albumin ≥3.5 g/dl (OR: 5.7), receipt of HIPEC (OR: 4.5), PCI ≤14 (OR: 2.2), intravenous fluid volume ≤10,000 ml (OR: 2.1), blood loss ≤1000 ml (OR: 4.2) and operative time <7 h (OR: 1.9); while receipt of neoadjuvant therapy (OR: 0.7) and liver resection (OR: 0.4) were associated with not achieving a TO (all p < 0.05). TO was associated with improved overall survival (median 159 months vs 56 months, p < 0.01) even after controlling for confounders on Cox regression (hazard ratio: 2.5, p < 0.01). CONCLUSION: Among patients undergoing CRS ± HIPEC for PSM, failure to achieve a TO is common and independently associated with worse overall survival.

A novel preoperative risk score to optimize patient selection for performing concomitant liver resection with cytoreductive surgery/HIPEC.

BACKGROUND: While parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), liver resection (LR) is increasingly performed with CRS/HIPEC. METHODS: Patients from the US HIPEC Collaborative (2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival (OS). RESULTS: A total of 658 patients were included. About 83 (15%) underwent LR of colorectal (58%) or invasive appendiceal (42%) metastases. LR patients had more complications (81% vs. 60%; p = .001), greater number of complications (2.3 vs. 1.5; p < .001) per patient and required more reoperations (22% vs. 11%; p = .007) and readmissions (39% vs. 25%; p = .014) than non-LR patients. LR patients had decreased OS (2-year OS 62% vs. 79%, p < .001), even when accounting for peritoneal carcinomatosis index and histology type. Preoperative factors associated with decreased OS on multivariable analysis in LR patients included age < 60 years (HR, 3.61; 95% CI, 1.10-11.81), colorectal histology (HR, 3.84; 95% CI, 1.69-12.65), and multiple liver tumors (HR, 3.45; 95% CI, 1.21-9.85) (all p < .05). When assigning one point for each factor, there was an incremental decrease in 2-year survival as the risk score increased from 0 to 3 (0: 100%; 1: 91%; 2: 58%; 3: 0%). CONCLUSIONS: As CRS/HIPEC + LR has become more common, we created a simple risk score to stratify patients considered for CRS/HIPEC + LR. These data aid in striking the balance between an increased perioperative complication profile with the potential for improvement in OS.

CRS/HIPEC with Major Organ Resection in Peritoneal Mesothelioma Does not Impact Major Complications or Overall Survival: A Retrospective Cohort Study of the US HIPEC Collaborative.

INTRODUCTION: CRS/HIPEC is thought to confer a survival advantage for patients with malignant peritoneal mesothelioma (MPM). However, the impact of nonperitoneal organ resection is not clearly defined. We evaluated the impact of major organ resection (MOR) on postoperative outcomes and overall survival (OS). PATIENTS AND METHODS: The US HIPEC collaborative database (2000-2017) was reviewed for MPM patients who underwent CRS/HIPEC. MOR was defined as total or partial resection of diaphragm, stomach, spleen, pancreas, small bowel, colon, rectum, kidney, ureter, bladder, and/or uterus. MOR was categorized as 0, 1, or 2+ organs. RESULTS: A total of 174 patients were identified. Median PCI was 16 (3-39). The distribution of patients with MOR-0, MOR-1, and MOR-2+ was 94, 45, and 35 patients, respectively. MOR-1 and MOR-2+ groups had a higher frequency of any complication compared with MOR-0 (57.8%, 74.3%, and 48.9%, respectively, p = 0.035), but Clavien 3/4 complications were similar. Median length of stay was slightly higher in the MOR-1 and MOR-2+ groups (10 and 11 days) compared with the MOR-0 cohort (9 days, p = 0.005). Incomplete cytoreduction, ASA class 4, and male gender were associated with increased mortality on unadjusted analysis; however, their impact on OS was attenuated on multivariable analysis. MOR was not associated with OS based on these data (MOR-1: HR 1.67, 95% CI 0.59-4.74; MOR-2+ : HR 0.77, 95% CI 0.22-2.69). CONCLUSIONS: MOR was not associated with an increase in major complications or worse OS in patients undergoing CRS/HIPEC for MPM and should be considered, if necessary, to achieve complete cytoreduction for MPM patients.

The impact of HIPEC vs. EPIC for the treatment of mucinous appendiceal carcinoma: a study from the US HIPEC collaborative.

INTRODUCTION: Mucinous appendiceal carcinoma is a rare malignancy that commonly spreads to the peritoneum leading to peritoneal metastases. Complete cytoreduction with perioperative intraperitoneal chemotherapy (PIC) is the mainstay of treatment, administered as either hyperthermic intra peritoneal chemotherapy (HIPEC) or early post-operative intraperitoneal chemotherapy (EPIC). Our goal was to assess the perioperative and long term survival outcomes associated with these two PIC methods. MATERIALS AND METHODS: Patients with mucinous appendiceal carcinoma were identified in the US HIPEC Collaborative database from 12 academic institutions. Patient demographics, clinical characteristics, and survival outcomes were compared among patients who underwent HIPEC vs. EPIC with inverse probability weighting (IPW) used for adjustment. RESULTS: Among 921 patients with mucinous appendiceal carcinoma, 9% underwent EPIC while 91% underwent HIPEC. There was no difference in Grade III-V complications between the two groups (18.5% for HIPEC vs. 15.0% for EPIC, p=.43) though patients who underwent HIPEC had higher rates of readmissions (21.2% vs. 8.8%, p<.01). Additionally, PIC method was not an independent predictor for overall survival (OS) or recurrence-free survival (RFS) after adjustment on multivariable analysis. CONCLUSIONS: Among patients with mucinous appendiceal carcinoma, both EPIC and HIPEC appear to be associated with similar perioperative and long-term outcomes.

Comparison of open and closed hyperthermic intraperitoneal chemotherapy: Results from the United States hyperthermic intraperitoneal chemotherapy collaborative.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis can be performed in two ways: Open or closed abdominal technique. AIM: To evaluate the impact of HIPEC method on post-operative and long-term survival outcomes. METHODS: Patients undergoing CRS with HIPEC from 2000-2017 were identified in the United States HIPEC collaborative database. Post-operative, recurrence, and overall survival outcomes were compared between those who received open vs closed HIPEC. RESULTS: Of the 1812 patients undergoing curative-intent CRS and HIPEC, 372 (21%) patients underwent open HIPEC and 1440 (79%) underwent closed HIPEC. There was no difference in re-operation or severe complications between the two groups. Closed HIPEC had higher rates of 90-d readmission while open HIPEC had a higher rate of 90-d mortalities. On multi-variable analysis, closed HIPEC technique was not a significant predictor for overall survival (hazards ratio: 0.75, 95% confidence interval: 0.51-1.10, P = 0.14) or recurrence-free survival (hazards ratio: 1.39, 95% confidence interval: 1.00-1.93, P = 0.05) in the entire cohort. These findings remained consistent in the appendiceal and the colorectal subgroups. CONCLUSION: In this multi-institutional analysis, the HIPEC method was not independently associated with relevant post-operative or long-term outcomes. HIPEC technique may be left to the discretion of the operating surgeon.