Grotz, Travis E

Abstract Objectives Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is associated with significant postoperative complications. Early detection of at-risk patients may lead to improved outcomes. The role of C-reactive protein (CRP) in predicting postoperative complications has only been recently investigated. Methods Postoperative complications were categorized according to Clavien-Dindo classification and further divided into minor (Grade <3) and major complications (Grade ≥3A). Absolute CRP counts (mg/L) on postoperative days (POD) 1–7, and proportional change in CRP was compared and the area under (AUC) receiver operating characteristics (ROC) curve was calculated. Univariate and multivariate analysis was performed. Significant findings were externally validated. Results Twenty-five percent of patients experienced one or more major complications. A CRP level of ≥106 mg/L on POD 2 and 65.5 mg/L on POD 4 were significantly associated with an increased risk of major complications with an AUC of 0.658 and 0.672, respectively. The proportional increase in CRP between POD 1 and 4 (ΔCRP POD 1/4) at a cut-off of 30 % had the best AUC of 0.744 and was the only independent risk factor for major complications (p<0.0001) on multivariate analysis. ∆CRP had an AUC of 0.716 (p=0.002) when validated in an independent database. Conclusions CRP can be used in a variety of ways to predict major complications after CRS and HIPEC. However, the ∆CRP POD 1/4>30 % is the best indicator of major complications. Serial CRP measurements in the early postoperative period may lead to early detection of patients at risk of major complications allowing for alternative management strategies to improve outcomes.

AbstractBackgroundCytoreductive 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.MethodsPatients 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.ResultsAmong 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.ConclusionWhile 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.

Background. Early-onset gastric cancer (EOGC,age≤60years at diagnosis) now comprises >30% of new gastric cancers in the United States. It is hypothesized that chronic acid suppression with proton-pump inhibitors (PPIs) may promote tumorigenesis, while other medications including statins, nonsteroidal anti-inflammatory drugs (NSAIDs), metformin, and cyclooxygenase-2 (COX-2) inhibitors have been proposed as protective. We aimed to assess for an association between use of the aforementioned commonly prescribed medications and EOGC development. Methods. We used a population-based medical record linkage system, to identify cases of EOGC in Olmsted County, Minnesota, between January 1, 1995, and December 31, 2020. Patients were matched 1 : 1 with controls based on age at diagnosis, sex, smoking status, and body mass index (BMI). Conditional logistic regression was used to examine associations with the odds of EOGC development. Results. Ninety-six cases of EOGC were identified during the study period. On both univariate and multivariate regression analysis, there was no significant association between use of PPIs, statins, NSAIDs, or metformin and EOGC development. In a final multivariable model, there was a significant reduction in odds of EOGC with COX-2 inhibitor use for six months or more prior to cancer diagnosis (OR=0.39, 95% CI 0.16-0.94). Conclusion. In this retrospective, population-based study of individuals in Olmsted County, MN, we found significantly reduced odds of EOGC development associated with COX-2 inhibitor use for six months or more prior to diagnosis, but no association between EOGC development and use of PPIs and other commonly prescribed medications.

AbstractBackgroundWhile 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.MethodsPatients 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).ResultsA 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%).ConclusionsAs 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.

AbstractBackgroundVariations in care have been demonstrated both within and among institutions in many clinical settings. By standardizing perioperative practices, Enhanced Recovery After Surgery (ERAS) pathways reduce variation in perioperative care. We sought to characterize the variation in cytoreductive surgery (CRS)/heated intraperitoneal chemotherapy (HIPEC) perioperative practices among experienced US medical centers.MethodsData from the US HIPEC Collaborative represents a retrospective multi‐institutional cohort study of CRS and CRS/HIPEC procedures performed from 12 major academic institutions. Patient characteristics and perioperative practices were reported and compared. Institutional variation was analyzed using hierarchical mixed‐effects linear (continuous outcomes) or logistic (binary outcomes) regression models.ResultsA total of 2372 operations were included. CRS/HIPEC was performed most commonly for appendiceal histologies (64.2%). The rate of complications (overall 56.3%, range: 31.8‐70.9) and readmissions (overall 20.6%, range: 8.9‐33.3) varied by institution (P < .001). Institution‐level variation in perioperative practice patterns existed among measured ERAS pathway process/outcomes (P < .001). The percentages of variation with each process/outcome measure attributable solely to institutional practices ranged from 0.6% to 66.6%.ConclusionsSignificant variation exists in the perioperative care of patients undergoing CRS/HIPEC at major US academic institutions. These findings provide a strong rationale for the investigation of best practices in CRS/HIPEC patients.

Cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with improved survival for patients with colorectal peritoneal metastases (CR-PM). However, the role of neoadjuvant chemotherapy (NAC) prior to CRS-HIPEC is poorly understood. A retrospective review of adult patients with CR-PM who underwent CRS+/-HIPEC from 2000–2017 was performed. Among 298 patients who underwent CRS+/-HIPEC, 196 (65.8%) received NAC while 102 (34.2%) underwent surgery first (SF). Patients who received NAC had lower peritoneal cancer index score (12.1 + 7.9 vs. 14.3 + 8.5, p = 0.034). There was no significant difference in grade III/IV complications (22.4% vs. 16.7%, p = 0.650), readmission (32.3% vs. 23.5%, p = 0.114), or 30-day mortality (1.5% vs. 2.9%, p = 0.411) between groups. NAC patients experienced longer overall survival (OS) (median 32.7 vs. 22.0 months, p = 0.044) but similar recurrence-free survival (RFS) (median 13.8 vs. 13.0 months, p = 0.456). After controlling for confounding factors, NAC was not independently associated with improved OS (OR 0.80) or RFS (OR 1.04). Among patients who underwent CRS+/-HIPEC for CR-PM, the use of NAC was associated with improved OS that did not persist on multivariable analysis. However, NAC prior to CRS+/-HIPEC was a safe and feasible strategy for CR-PM, which may aid in the appropriate selection of patients for aggressive cytoreductive surgery.

Background National Comprehensive Cancer Network (NCCN) guidelines recommend accurate clinical staging, perioperative therapy, and complete lymphadenectomy for patients with stage II to III gastric cancer. However, national compliance remains low. It was hypothesized that integrated cancer networks might improve compliance and outcomes within the community. Methods Patients with stage II to III gastric adenocarcinoma undergoing curative‐intent resection (National Cancer Data Base, 2006‐2015) were examined. Guideline compliance was defined as any perioperative adjunctive therapy, complete lymphadenectomy, complete clinical staging, and complete compliance (all measures). Univariate comparisons and multivariable regression were used to assess factors associated with compliance, and Kaplan‐Meier analysis was used to assess survival. Results There were 27,210 patients identified: 7235 (26.6%) underwent surgery alone, whereas 19,975 (73.4%) received additional therapy. Half (53.1%) had complete lymphadenectomies, whereas complete clinical staging was available for 65.5%. Overall compliance with all 3 measures was 30.1%. Compliance improved by approximately 20% for each measure across the 10‐year study period. Although patients treated at academic programs were most likely to receive concordant care in an adjusted analysis, those treated at integrated care networks were more likely to receive guideline‐concordant care (odds ratio [OR], 0.69) than those treated at comprehensive community programs (OR, 0.48) or community programs (OR, 0.45; all P values <.001). The median overall survival was 45.5 months for patients who received guideline‐concordant care and 32.0 months for those who did not ( P < .001, reference for all ORs: academic programs). Conclusions Compliance with guidelines was associated with improved outcomes. Although the rate of compliance with NCCN guidelines is improving, integrated care networks may be an important way of improving the quality of gastric cancer care within the community.

Perioperative radiation therapy (RT) has been associated with reduced local recurrence in patients with retroperitoneal sarcomas (RPS); however, selection criteria remain unclear. We hypothesized that perioperative RT would improve survival in patients with RPS and would be associated with pathological factors. The National Cancer Database (NCDB) from 2004 to 2012 was reviewed for patients with nonmetastatic RPS undergoing curative intent resection. Tumor size was dichotomized at 15 cm based on 8th edition American Joint Committee on Cancer (AJCC) staging. Patients with the highest comorbidity score were excluded. Unadjusted Kaplan–Meier and adjusted Cox proportional hazards modeling analyzed overall survival (OS). Multivariable logistic regression modeled margin positivity. A total of 2,264 patients were included; 727 patients (32.1%) had perioperative radiation in whom 203 (9.0%) had radiation preoperatively. Median (IQR) RPS size was 17.5 [11.0–27.0] cm. Histopathology was high grade in 1048 patients (43.7%). Multivariable analysis revealed that perioperative radiation was independently associated with decreased mortality (HR 0.72, 95% confidence intervals (CIs) 0.62–0.84,p<0.001), and preoperative RT was associated with reduced margin positivity (HR 0.72, 95% CI 0.53–0.97,p=0.032). Stratified survival analysis showed that radiation was associated with prolonged median OS for RPS that were high-grade (64.3 vs. 43.6 months,p<0.001), less than 15 cm (104.1 vs. 84.2 months,p=0.007), and leiomyosarcomatous (104.8 vs. 61.8 months,p<0.001). Perioperative radiation is independently associated with decreased mortality in patients with high-grade, less than 15 cm, and leiomyosarcomatous tumors. Preoperative radiation is independently associated with margin-negative resection. These data support the selective use of perioperative radiation in the multidisciplinary management of RPS.