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.

Recovery of Patient-reported Quality of Life After Esophagectomy.

BACKGROUND: Esophagectomy is an important, but potentially morbid, operation used to treat benign and malignant conditions that may significantly impact patient quality of life (QOL). Patient-reported outcomes (PROs) are measures of QOL that come directly from patient self-report. This study characterizes patterns of change and recovery in PROs in the first year after esophagectomy. METHODS: Longitudinal QOL scores measuring physical function, pain, and dyspnea were obtained from esophagectomy patients during all clinic visits. PRO scores were obtained using the National Institutes of Health-sponsored Patient-Reported Outcomes Measurement Information System from April 2018 to February 2021. Mean PRO scores over 100 days after surgery were compared with baseline PRO scores using mixed-effects modeling with compound symmetry correlational structure. RESULTS: One hundred three patients with PRO results were identified. Reasons for esophagectomy were malignancy (87.4%), achalasia (5.8%), stricture (5.8%), and dysplasia (1.0%). When comparing mean PRO scores at visits ≤ 50 days after surgery with preoperative PRO scores, physical function scores declined by 27.3% (P < .001), whereas dyspnea severity and pain interference scores had increased by 24.5% (P < .001) and 17.1% (P < .001), respectively. Although recovery occurred over the course of the 100 days after surgery, mean physical function scores and dyspnea scores were still 12.7% (P = .02) and 26.4% (P = .001) worse, respectively, than mean preoperative levels. CONCLUSIONS: Despite declines in QOL scores immediately after esophagectomy, recovery back toward baseline was observed during the first 100 days. These findings are of considerable importance when counseling patients regarding esophagectomy, tracking recovery, and implementing quality improvement initiatives. Further long-term follow-up is needed to determine recovery beyond 100 days.

Do Lymph Node Metastases Matter in Appendiceal Cancer with Peritoneal Carcinomatosis? A US HIPEC Collaborative Study.

BACKGROUND: Whether formal regional lymph node (LN) evaluation is necessary for patients with appendiceal adenocarcinoma (AA) who have peritoneal metastases is unclear. The aim of this study was to evaluate the prognostic value of LN metastases on survival in patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). METHODS: A retrospective analysis of the US HIPEC collaborative, a multi-institutional consortium comprising 12 high-volume centers, was performed to identify patients with AA who underwent CRS-HIPEC with adequate LN sampling (≥ 12 LNs). RESULTS: Two hundred-fifty patients with AA who underwent CRS-HIPEC were included. Outcomes were compared between LN - and LN + disease. Baseline patient characteristics between groups were similar, with most patients undergoing complete cytoreduction (0/1: 86.0% vs. 76.8%, p = 0.08), respectively. More adverse tumor factors were found in patients with LN + disease, including poor differentiation, signet ring cells, and lymphovascular invasion. Multivariate analysis of overall survival (OS) found LN + disease was independently associated with worse OS (HR: 2.82 95%CI: 1.25-6.34, p = 0.01), even after correction for receipt of systemic therapy. On Kaplan-Meier analysis, median OS was lower in patients with LN + disease (25.9 months vs. 91.4 months, p < 0.01). LN + disease remained associated with poor OS following propensity score matching (HR: 4.98 95%CI: 1.72-14.40, p < 0.01) and in patients with PCI ≥ 20 (HR: 3.68 95%CI: 1.54-8.80, p < 0.01). CONCLUSIONS: In this large multi-institutional study of patients with AA undergoing CRS-HIPEC, LN status remained associated with worse OS even in the setting of advanced peritoneal carcinomatosis. Formal LN evaluation should be performed for most patients with AA undergoing CRS-HIPEC.

The Impact of Carbohydrate Antigen 19-9 on Survival in Patients with Clinical Stage I and II Pancreatic Cancer.

BACKGROUND: Carbohydrate antigen (CA) 19-9 is a biomarker to monitor treatment effect. A threshold to predict prognostic significance remains undefined. We evaluated the impact of CA19-9 on overall survival (OS) in patients with early-stage pancreatic cancer (PC) utilizing the National Cancer Database (NCDB). METHODS: The NCDB was queried from 2010 to 2014 to identify patients with clinical stage I-II PC. Patients who had undocumented pretreatment CA19-9 were excluded. Patients were stratified into two cohorts: CA19-9 < 98 U/mL and CA19-9 ≥ 98 U/mL, and further categorized into surgery versus no surgery. Twelve- and 24-month OS rates are reported. RESULTS: Overall, 32,382 patients (stage I: 12,173; stage II: 20,209) were included. The majority of stage I (52.1%) and II (60%) patients had CA19-9 ≥ 98 U/mL. Stage I-II patients with CA19-9 < 98 U/mL had improved OS rates (stage I: 67.5%, 42.6%; stage II: 59.8%, 32.8%) compared with stage I and II patients with CA19-9 ≥ 98 U/mL (stage I: 50.7%, 26.9%; stage II: 48.1%, 22%). Among resected stage I patients, CA19-9 <98 U/mL was associated with improved OS (< 98: 80.5%, 56%; ≥ 98: 70.2%, 42.8%), and a similar trend was seen in resected stage II patients (< 98: 77.6%, 49.9%; ≥ 98: 71%, 39.2%). Unresected stage I patients with lower CA19-9 had improved OS (< 98: 42.1%, 17.5; ≥ 98: 29.9%, 10%), with similar findings in unresected stage II patients (< 98: 41.1%, 15.3%; ≥ 98: 33.4%, 10.6%). CONCLUSIONS: Our study demonstrated the prognostic value of CA19-9 in patients with clinical stage I-II PC, with a value < 98 U/mL demonstrating improved survival. Surgery significantly improved survival at 12 and 24 months irrespective of CA19-9.

Implementation of a Hepatocellular Carcinoma Screening Program for At-risk Patients Safety-Net Hospital: A Model for National Dissemination.

OBJECTIVE: This study aimed to enhance hepatocellular carcinoma (HCC) screening to achieve earlier diagnosis of patients with hepatitis C (HCV) cirrhosis in our Safety-Net population. BACKGROUND: Adherence to HCC screening guidelines at Safety-Net hospitals is poor. Only 23% of patients with HCC at our health system had a screening exam within 1-year of diagnosis and 46% presented with stage IV disease. HCV-induced cirrhosis remains the most common etiology of HCC (75%) in our patients. METHODS: In the setting of an established HCV treatment clinic, an HCC screening quality improvement initiative was initiated for patients with stage 3 fibrosis or cirrhosis by transient elastography. The program consisted of semiannual imaging. Navigators scheduled imaging appointments and tracked compliance. RESULTS: From April 2018 to April 2021, 318 patients were enrolled (mean age 61 years, 81% Black race, 38% uninsured). Adherence to screening was higher than previously reported: 94%, 75%, and 74% of patients completed their first, second, and third imaging tests. Twenty-two patients (7%) were diagnosed with HCC; 55% stage I and 14% stage IV. All patients were referred and 13 (59%) received treatment. Median time to receipt of treatment was 77 days (range, 32-282). Median overall survival for treated patients was 32 months. CONCLUSIONS: Implementation of an HCC screening program at a safety-net hospital is feasible and facilitated earlier diagnosis in this study. Patient navigation and tracking completion of imaging tests were key components of the program's success. Next steps include expanding the program to additional at-risk populations.

Implications of leukocytosis following distal pancreatectomy splenectomy (DPS) and association with postoperative complications.

BACKGROUND: Early identification of complications after distal pancreatectomy splenectomy (DPS) poses challenges, as white blood cell count (WBC) is confounded by physiologic leukocytosis. We examined WBC patterns associated with complications after DPS. METHODS: Clinicopathologic data were collected for patients who underwent DPS in our system from 2009 to 2016. We examined WBC, temperature, platelet count (PC), and ratios of these variables as potential early indicators of patients at risk of infections or major complications (MCs). RESULTS: 348 patients met study inclusion, of whom 206 (59%) were women and the median patient age was 59 ± 15 years. Infectious and MC rates were 11% and 16%, respectively, with <1% 30-day mortality. Postoperative WBC peaks were higher in patients with infections and MCs compared with no complication (23 vs. 17, p < 0.0001). WBC peak timing occurred postoperative day (POD) 2-3 for uncomplicated cases while peaks occurred POD9 for patients with infections and MCs. DISCUSSION: These data define patterns of leukocytosis following DPS. Although differences in infection markers were identified for patients with and without complications, no obvious thresholds were identified. Clinical suspicion for complications after DPS remains our best tool for early identification.

Development and Validation of an Explainable Machine Learning Model for Major Complications After Cytoreductive Surgery.

Importance: Cytoreductive surgery (CRS) is one of the most complex operations in surgical oncology with significant morbidity, and improved risk prediction tools are critically needed. Machine learning models can potentially overcome the limitations of traditional multiple logistic regression (MLR) models and provide accurate risk estimates. Objective: To develop and validate an explainable machine learning model for predicting major postoperative complications in patients undergoing CRS. Design, Setting, and Participants: This prognostic study used patient data from tertiary care hospitals with expertise in CRS included in the US Hyperthermic Intraperitoneal Chemotherapy Collaborative Database between 1998 and 2018. Information from 147 variables was extracted to predict the risk of a major complication. An ensemble-based machine learning (gradient-boosting) model was optimized on 80% of the sample with subsequent validation on a 20% holdout data set. The machine learning model was compared with traditional MLR models. The artificial intelligence SHAP (Shapley additive explanations) method was used for interpretation of patient- and cohort-level risk estimates and interactions to define novel surgical risk phenotypes. Data were analyzed between November 2019 and August 2021. Exposures: Cytoreductive surgery. Main Outcomes and Measures: Area under the receiver operating characteristics (AUROC); area under the precision recall curve (AUPRC). Results: Data from a total 2372 patients were included in model development (mean age, 55 years [range, 11-95 years]; 1366 [57.6%] women). The optimized machine learning model achieved high discrimination (AUROC: mean cross-validation, 0.75 [range, 0.73-0.81]; test, 0.74) and precision (AUPRC: mean cross-validation, 0.50 [range, 0.46-0.58]; test, 0.42). Compared with the optimized machine learning model, the published MLR model performed worse (test AUROC and AUPRC: 0.54 and 0.18, respectively). Higher volume of estimated blood loss, having pelvic peritonectomy, and longer operative time were the top 3 contributors to the high likelihood of major complications. SHAP dependence plots demonstrated insightful nonlinear interactive associations between predictors and major complications. For instance, high estimated blood loss (ie, above 500 mL) was only detrimental when operative time exceeded 9 hours. Unsupervised clustering of patients based on similarity of sources of risk allowed identification of 6 distinct surgical risk phenotypes. Conclusions and Relevance: In this prognostic study using data from patients undergoing CRS, an optimized machine learning model demonstrated a superior ability to predict individual- and cohort-level risk of major complications vs traditional methods. Using the SHAP method, 6 distinct surgical phenotypes were identified based on sources of risk of major complications.

Elderly Patients Benefit From Enhanced Recovery Protocols After Colorectal Surgery.

BACKGROUND: Enhanced recovery protocols (ERAS) aim to decrease physiological stress response to surgery and maintain postoperative physiological function. Proponents of ERAS state these protocols decrease lengths of stay (LOS) and complication rates. Our aim was to assess whether elderly patients receive the same benefit as younger patients using ERAS protocols. METHODS: We queried patients from 2015 to 2017 at our institution with Enhanced Recovery in Surgery (ERIN) variables from the targeted colectomy NSQIP database. The patients were divided into sextiles and analyzed for readmission, LOS, return of bowel function, tolerating diet, mobilization, and multimodal pain management comparing the youngest sextile to the oldest sextile. RESULTS: Two hundred sixty-two patients (73% colectomies) were enrolled in ERAS. When compared with the youngest sextile (age 19-43.8), the oldest sextile (age 71.4-92.5) had similar readmission rates at 9.8% versus 9.5% (P-value = 0.87), quicker return of bowel function, average 1.9 d versus 3.7 d (P-value < 0.01), and tolerated diet quicker, average POD 2.4 d versus 5.1 d (P-value < 0.01). There was a slight decrease in the use of multimodal pain management 88% versus 100% (P-value = 0.07), but mobilization on POD1 was slightly better in the elderly at 80% versus 78% (P-value = 0.76). Elderly patients enrolled in ERAS had an average LOS of 4.9 days versus 7.8 in the younger patients (P-value = 0.08). Among elderly non-ERAS patients average LOS was 14.6 days. CONCLUSION: Overall, elderly patients fared better or the same on the ERIN variables analyzed than the younger cohort. ERAS protocols are beneficial and applicable to elderly patients undergoing colorectal surgery.

Impact of Perioperative Blood Transfusions on Outcomes After Hyperthermic Intraperitoneal Chemotherapy: A Propensity-Matched Analysis.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a major operation frequently necessitating red blood cell transfusion. Using multi-institutional data from the U.S. HIPEC Collaborative, this study sought to determine the association of perioperative allogenic blood transfusion (PABT) with perioperative outcomes after CRS/HIPEC. METHODS: This retrospective cohort study analyzed patients who underwent CRS/HIPEC for peritoneal surface malignancy between 2000 and 2017. Propensity score-matching was performed to mitigate bias. Univariate analysis was used to compare demographic, preoperative, intraoperative, and postoperative variables. Factors independently associated with PABT were identified using multivariate analysis. RESULTS: The inclusion criteria were met by 1717 patients, 510 (29.7%) of whom required PABT. The mean Peritoneal Cancer Index (PCI) of our cohort was 14.8 ± 9.3. Propensity score-matching showed an independent association between PABT and postoperative risk of pleural effusion, hemorrhage, pulmonary embolism, enteric fistula formation, Clavien-Dindo grades 3 and 4 morbidity, longer hospital stay, and reoperation (all P < 0.05 in the multivariate analysis). Compared with the patients who received 1 to 5 red blood cell (RBC) units, the patients who received more than 5 units had a greater risk of renal impairment, a longer intensive care unit (ICU) stay, and more postoperative infections. Finally, PABT was an independent predictor of worse survival for patients with appendiceal and colorectal primaries. CONCLUSION: Even low levels of PABT for patients undergoing CRS/HIPEC are independently associated with a greater risk of infectious and non-infectious postoperative complications, and this risk is increased for patients receiving more than 5 RBC units. Worse survival was independently predicted by PABT for patients with peritoneal carcinomatosis of an appendiceal or colorectal origin.

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.

Comparing Activity Trackers With vs. Without Alarms to Increase Postoperative Ambulation: A Randomized Control Trial.

Early ambulation is a key component to postoperative recovery; however, measuring steps taken is often inconsistent and nonstandardized. This study aimed to determine whether an activity tracker with alarms would increase postoperative ambulation in patients after elective colorectal procedures. Forty-eight patients were randomly assigned to either trackers with 5 daily alarms or activity trackers alone. Over 223 total patient days, the trackers recorded a complete data set for 216 patient days (96.9%). Increasing the postoperative day significantly affected the number of steps taken, while age, sex, Risk Analysis Index score, and approach (laparoscopic versus open) did not show a significant effect. The mean steps per day in the intervention group were 1468 (median 495; interquartile range (IQR) 1345) and in the control group was 1645 (median 1014; IQR 2498). The use of trackers with alarms did not significantly affect the number of daily steps compared to trackers alone (ANOVA, P = .93). Although activity trackers with alarms did not increase postoperative ambulation compared with trackers with no alarms, we demonstrated a strategy to operationalize the use of trackers into postoperative care to provide a quantitative value for ambulation. This enables quantification of a key component in the Enhanced Recovery After Surgery protocol.

Should Signet Ring Cell Histology Alter the Treatment Approach for Clinical Stage I Gastric Cancer?

BACKGROUND: Surgery alone is standard-of-care for stage I gastric adenocarcinoma; however, clinicians can offer preoperative therapy for clinical stage I disease with signet ring cell histology, given its presumed aggressive biology. We aimed to assess the validity of this practice. METHODS: The National Cancer Database (2004-2015) was reviewed for patients with clinical stage I signet ring cell gastric adenocarcinoma who underwent treatment with surgery alone, perioperative chemotherapy, neoadjuvant therapy, or adjuvant therapy. Analysis was stratified by preoperative clinical/pathologic stage. Primary outcome was overall survival (OS). RESULTS: Of 1018 patients, median age was 60 years (±14); 53% received surgery alone (n = 542), 5% received perioperative chemotherapy (n = 47), 12% received neoadjuvant therapy (n = 125), and 30% received adjuvant therapy (n = 304). For clinical stage I disease, surgery alone was associated with an improved 5-year OS rate (71%) versus perioperative chemotherapy (58%), neoadjuvant therapy (38%), or adjuvant therapy (52%) [overall p < 0.01]. For pathologic stage I, surgery alone had equivalent or improved survival compared with perioperative, neoadjuvant, and adjuvant therapy (5-year OS: 78% vs. 89% [p = 0.77] vs. 64% [p = 0.04] vs. 84% [p = 0.99]). Adjuvant therapy was associated with improved 5-year OS compared with pretreatment for those patients upstaged (37%) to pathologic stage II/III (55% vs. 36% and 34% vs. 7%; all p < 0.01). CONCLUSIONS: This stage-specific study demonstrates improved survival with surgery alone for clinical stage I signet ring cell gastric adenocarcinoma. Despite 37% of clinical stage I patients being upstaged to pathologic stage II/III, adjuvant therapy offers a favorable rescue strategy, with improved outcomes compared with those treated preoperatively. Surgery alone also affords similar or improved survival for pathologic stage I disease versus multimodality therapy. This study challenges the bias to overtreat stage I signet ring cell gastric adenocarcinoma.

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.

HSP90 expression and early recurrence in gastroenteropancreatic neuroendocrine tumors: Potential for a novel therapeutic target.

BACKGROUND: Heat shock protein (HSP)-90 promotes tumor growth and is overexpressed in many malignancies. HSP90 expression profile and its potential as a therapeutic target in primary and metastatic neuroendocrine tumors (NETs) are not known. METHODS: HSP90 cytoplasmic expression and Ki-67 index were re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables for patients who underwent resection of primary and metastatic gastroenteropancreatic (GEP) neuroendocrine tumors at a single institution (2000-2013). Primary outcome was recurrence-free survival (RFS). RESULTS: Of 263 tumors reviewed, 73% (n = 191) were primary GEP NETs, and 12% (n = 31) were NET liver metastases. Of the primary GEP-NETs, mean age was 56 years, 42% were male; 53% (n = 103) were pancreatic and 23% (n = 44) were small bowel. HSP90 expression was high in 34% (n = 64) and low in 66% (n = 127). Compared to low expression, high HSP90 was associated with advanced T-stage (T3/T4) (47 vs 27%; p = 0.02). Among patients who underwent curative-intent resections for primary, non-metastatic NETs (n = 145), high HSP90 was independently associated with worse RFS (HR 5.09, 95% CI 1.65-15.74; p = 0.005), after accounting for positive margin, LN involvement, increased tumor size, site of primary tumor, and Ki-67. When assessing NET liver metastases, 13% (n = 4) had high HSP90 expression and 87% (n = 26) had low expression. Patients with liver metastases with high HSP90 tended to have worse 1- and 3-year progression-free survival (25%, 25%) compared to those with low HSP90 (69%, 49%; p = 0.059). CONCLUSION: HSP90 exhibits differential expression in resected GEP-NETs and liver metastases. High cytoplasmic expression is associated with early disease recurrence, even after accounting for other adverse pathologic factors. HSP90 inhibition may be a potential therapeutic target for neuroendocrine tumors.

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.

Differences in outcome for patients with cholangiocarcinoma: Racial/ethnic disparity or socioeconomic factors?

BACKGROUND: Inequities in cancer survival are well documented. Whether disparities in overall survival (OS) result from inherent racial differences in underlying disease biology or socioeconomic factors (SEF) is not known. Our aim was to define the association of race/ethnicity and SEF with OS in pts with cholangiocarcinoma (CCA). METHODS: Patients with CCA of all sites and stages in the National Cancer Data Base (2004-13) were included. Racial/ethnic groups were defined as non-Hispanic White (NH-W), non-Hispanic Black (NH-B), Asian, and Hispanic. Income and education were based on census data for patients' zip code. Income was defined as high (≥$63,000) vs low (<$63,000). Primary outcome was OS. RESULTS: 27,151 patients were included with a mean age of 68 yrs; 51% were male. 78% were NH-W, 8% NH-B, 8% Hispanic, and 6% Asian. 56% had Medicare, 33% private insurance, 7% Medicaid, and 4% were uninsured. 67% had low income. 19% lived in an area where >20% of adults did not finish high school. NH-B and Hispanic patients had more unfavorable SEF including uninsured status, low income, and less formal education than NH-W and Asian pts (all p < 0.001). They were also younger, more likely to be female and to have metastatic disease (all p < 0.001). Despite this, NH-B race and Hispanic ethnicity were not associated with decreased OS. Male sex, older age, non-private insurance, low income, lower education, non-academic facility, location outside the Northeast, higher Charlson-Deyo score, worse grade, larger tumor size, and higher stage were all associated with decreased OS (all p < 0.001). On MV analysis, along with adverse pathologic factors, type of insurance (p = 0.003), low income (p < 0.001), and facility type and location of treatment (p < 0.001) remained associated with decreased OS; non-white race/ethnicity was not. CONCLUSIONS: Disparities in survival exist in CCA, however they are not driven by race/ethnicity. Non-privately insured and low-income patients had decreased OS, as did patients treated at non-academic centers and outside the Northeast. This suggests that decreased ability to access and afford care results in worse outcomes, rather than biological differences amongst racial/ethnic groups.

Implications of Postoperative Complications for Survival After Cytoreductive Surgery and HIPEC: A Multi-Institutional Analysis of the US HIPEC Collaborative.

BACKGROUND: Postoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on the survival of patients with appendiceal or colorectal cancer after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is unknown. METHODS: The US HIPEC Collaborative (2000-2017) was reviewed for patients who underwent CCR0/1 CRS/HIPEC for appendiceal/colorectal cancer. The analysis was stratified by noninvasive appendiceal neoplasm versus invasive appendiceal/colorectal adenocarcinoma. The POCs were grouped into infectious, cardiopulmonary, thromboembolic, and intestinal dysmotility. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS). RESULTS: Of the 1304 patients, 33% had noninvasive appendiceal neoplasm (n = 426), and 67% had invasive appendiceal/colorectal adenocarcinoma (n = 878). In the noninvasive appendiceal cohort, POCs were identified in 55% of the patients (n = 233). The 3-year OS and RFS did not differ between the patients who experienced a complication and those who did not (OS, 94% vs 94%, p = 0.26; RFS, 68% vs 60%, p = 0.15). In the invasive appendiceal/colorectal adenocarcinoma cohort, however, POCs (63%; n = 555) were associated with decreased 3-year OS (59% vs 74%; p < 0.001) and RFS (32% vs 42%; p < 0.001). Infectious POCs were the most common (35%; n = 196). In Multivariable analysis accounting for gender, peritoneal cancer index (PCI), and incomplete resection (CCR1), infectious POCs in particular were associated with decreased OS compared with no complication (hazard ratio [HR] 2.08; p < 0.01) or other types of complications (HR, 1.6; p < 0.01). Similarly, infectious POCs were independently associated with worse RFS (HR 1.61; p < 0.01). CONCLUSION: Postoperative complications are associated with decreased OS and RFS after CRS/HIPEC for invasive histology, but not for an indolent disease such as noninvasive appendiceal neoplasm, and this association is largely driven by infectious complications. The exact mechanism is unknown, but may be immunologic. Efforts must target best practices and standardized prevention strategies to minimize infectious postoperative complications.