The Top Ten Annals of Surgical Oncology Original Articles on Twitter/X: 2020-2023.

Social media has become omnipresent in society, especially given that it enables the rapid and widespread communication of news, events, and information. Social media platforms have become increasingly used by numerous surgical societies to promote meetings and surgical journals to increase the visibility of published content. In September 2020, Annals of Surgical Oncology (ASO) established its Social Media Committee (SMC), which has worked to steadily increase the visibility of published content on social media platforms, namely X (formerly known as Twitter). The purpose of this review is to highlight the 10 ASO original articles with the most engagement on X, based on total number of mentions, since the founding of the SMC. These articles encompass a wide variety of topics from various oncologic disciplines including hepatopancreatobiliary, breast, and gynecologic surgery.

Collagen 1 Fiber Volume Predicts for Recurrence of Stage 1 Non-Small Cell Lung Cancer.

Background: The standard of care for stage 1 NSCLC is upfront surgery followed by surveillance. However, 20-30% of stage 1 NSCLC recur. There is an unmet need to identify individuals likely to recur who would benefit from frequent monitoring and aggressive cancer treatments. Collagen 1 (Col1) fibers detected by second harmonic generation (SHG) microscopy are a major structural component of the extracellular matrix (ECM) of tumors that play a role in cancer progression. Method: We characterized Col1 fibers with SHG microscopy imaging of surgically resected stage 1 NSCLC. Gene expression from RNA sequencing data was used to validate the SHG microscopy findings. Results: We identified a significant (p ≤ 0.05) increase in the Col1 fiber volume in stage 1 NSCLC that recurred. The increase in Col1 fiber volume was supported by significant increases in the gene expression of Col1 in invasive, compared to noninvasive, lung adenocarcinoma. Significant differences were identified in the gene expression of other ECM proteins, as well as CAFs, immune checkpoint markers, immune cytokines, and T-cell markers. Conclusion: Col1 fiber analysis can provide a companion diagnostic test to evaluate the likelihood of tumor recurrence following stage 1 NSCLC. The studies expand our understanding of the role of the ECM in NSCLC recurrence.

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.

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.

Prognostic Significance of Preoperative Tumor Markers in Pseudomyxoma Peritonei from Low-Grade Appendiceal Mucinous Neoplasm: a Study from the US HIPEC Collaborative.

BACKGROUND: Tumor markers are commonly utilized in the diagnostic evaluation, treatment decision making, and surveillance of appendiceal tumors. In this study, we aimed to determine the prognostic significance of elevated preoperative tumor markers in patients with pseudomyxoma peritonei secondary to low-grade appendiceal mucinous neoplasm who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. METHODS: Using a multi-institutional database, eligible patients with measured preoperative tumor markers [carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9), or cancer antigen 125 (CA-125)] were identified. Univariate and multivariate Cox-proportional hazards regression analysis assessed relationships between normal and elevated serum tumor markers with progression-free and overall survival in the context of multiple clinicopathologic variables. RESULTS: zTwo hundred and sixty-four patients met criteria. CEA was the most commonly measured tumor marker (97%). Patients who had any elevated tumor marker had a higher peritoneal carcinomatosis index (PCI) as compared to those with normal range markers. Elevated CEA and CA 19-9 levels were individually associated with longer inpatient length of stay, requirement for intraoperative transfusion, and incomplete cytoreduction. Utilization of neoadjuvant chemotherapy, increased PCI score, elevated CA 19-9 (p = 0.007), and CA-125 levels (p = 0.01) were predictive of decreased progression-free survival on univariate analysis. However, in a multivariate model, only elevated PCI was a statistically significant predictor of progression-free survival. CONCLUSION: Elevated preoperative tumor markers indicate a higher burden of disease but are not independently associated with survival in this retrospective multi-institutional cohort. Further prospective studies are needed to clarify the utility of these markers in this patient population.

A Cost-Effective and Non-Invasive pfeRNA-Based Test Differentiates Benign and Suspicious Pulmonary Nodules from Malignant Ones.

The ability to differentiate between benign, suspicious, and malignant pulmonary nodules is imperative for definitive intervention in patients with early stage lung cancers. Here, we report that plasma protein functional effector sncRNAs (pfeRNAs) serve as non-invasive biomarkers for determining both the existence and the nature of pulmonary nodules in a three-stage study that included the healthy group, patients with benign pulmonary nodules, patients with suspicious nodules, and patients with malignant nodules. Following the standards required for a clinical laboratory improvement amendments (CLIA)-compliant laboratory-developed test (LDT), we identified a pfeRNA classifier containing 8 pfeRNAs in 108 biospecimens from 60 patients by sncRNA deep sequencing, deduced prediction rules using a separate training cohort of 198 plasma specimens, and then applied the prediction rules to another 230 plasma specimens in an independent validation cohort. The pfeRNA classifier could (1) differentiate patients with or without pulmonary nodules with an average sensitivity and specificity of 96.2% and 97.35% and (2) differentiate malignant versus benign pulmonary nodules with an average sensitivity and specificity of 77.1% and 74.25%. Our biomarkers are cost-effective, non-invasive, sensitive, and specific, and the qPCR-based method provides the possibility for automatic testing of robotic applications.

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.

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.

Institutional variation in recovery after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: An opportunity for enhanced recovery pathways.

BACKGROUND: Variations 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. METHODS: Data 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. RESULTS: A 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%. CONCLUSIONS: Significant 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.

Predictors of Non-home Discharge after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Using a national database of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) recipients, we sought to determine risk factors for nonhome discharge (NHD) in a cohort of patients. METHODS: Patients undergoing CRS/HIPEC at any one of 12 participating sites between 2000 and 2017 were identified. Univariate analysis was used to compare the characteristics, operative variables, and postoperative complications of patients discharged home and patients with NHD. Multivariate logistic regression was used to identify independent risk factors of NHD. RESULTS: The cohort included 1593 patients, of which 70 (4.4%) had an NHD. The median [range] peritoneal cancer index in our cohort was 14 [0-39]. Significant predictors of NHD identified in our regression analysis were advanced age (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.05-1.12; P < 0.001), an American Society of Anesthesiologists (ASA) score of 4 (OR, 2.87; 95% CI, 1.21-6.83; P = 0.017), appendiceal histology (OR, 3.14; 95% CI 1.57-6.28; P = 0.001), smoking history (OR, 3.22; 95% CI, 1.70-6.12; P < 0.001), postoperative total parenteral nutrition (OR, 3.14; 95% CI, 1.70-5.81; P < 0.001), respiratory complications (OR, 7.40; 95% CI, 3.36-16.31; P < 0.001), wound site infections (OR, 3.12; 95% CI, 1.58-6.17; P = 0.001), preoperative hemoglobin (OR, 0.81; 95% CI, 0.70-0.94; P = 0.006), and total number of complications (OR, 1.41; 95% CI, 1.16-1.73; P < 0.001). CONCLUSIONS: Early identification of patients at high risk for NHD after CRS/HIPEC is key for preoperative and postoperative counseling and resource allocation, as well as minimizing hospital-acquired conditions and associated health care costs.

The Intersection of Age and Tumor Biology with Postoperative Outcomes in Patients After Cytoreductive Surgery and HIPEC.

BACKGROUND: Patient age is a significant factor in preoperative selection for major abdominal surgery. The association of age, tumor biology, and postoperative outcomes in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) remains ill-defined. METHODS: Retrospective analysis was performed for patients who underwent a CCR0/1 CRS/HIPEC from the US HIPEC Collaborative Database (2000-2017). Age was categorized into < 65 or ≥ 65 years. Primary outcome was postoperative major complications. Secondary outcomes were non-home discharge (NHD) and readmission. Analysis was stratified by disease histology: non-invasive (appendiceal LAMN/HAMN), and invasive (appendiceal/colorectal adenocarcinoma). RESULTS: Of 1090 patients identified, 22% were ≥ 65 (n = 240), 59% were female (n = 646), 25% had non-invasive (n = 276) and 51% had invasive (n = 555) histology. Median PCI was 13 (IQR 7-20). Patients ≥ 65 had a higher rate of major complications (37 vs 26%, p = 0.02), NHD (12 vs 5%, p < 0.01), and readmission (28 vs 22%, p = 0.05), compared to those < 65. For non-invasive histology, age ≥ 65 was not associated with major complications or NHD on multivariable analysis. For invasive histology, when accounting for PCI and CCR, age ≥ 65 was associated with major complications (OR 2.04, 95% CI 1.16-3.59, p = 0.01). When accounting for major complications, age ≥ 65 was associated with NHD (OR 2.54, 95% CI 1.08-5.98, p = 0.03). Age ≥ 65 was not predictive of readmission for any histology when accounting for major complications. CONCLUSIONS: Age ≥ 65 years is an independent predictor for postoperative major complications and non-home discharge for invasive histology, but not non-invasive histology. These data inform preoperative counseling, risk stratification, and early discharge planning.

What is the Optimal Preoperative Imaging Modality for Assessing Peritoneal Cancer Index? An Analysis From the United States HIPEC Collaborative.

BACKGROUND: Radiographic prediction of peritoneal carcinomatosis index (PCI) can improve patient selection for cytoreductive surgery. We aimed to determine the correlation of computed tomography (CT)-predicted PCI (CT-PCI) and magnetic resonance imaging (MRI)-predicted PCI (MRI-PCI) with intraoperative-PCI, and if a preoperative-PCI cutoff is associated with incomplete cytoreduction. PATIENTS AND METHODS: Patients from the US HIPEC Collaborative (2000-2017) with appendiceal, colorectal, or peritoneal mesothelioma (PM) histology who underwent cytoreductive surgery were included. Pearson correlation coefficients were used to determine correlation between preoperative and intraoperative-PCI values. Fisher r-to-z transformation was used to compare correlations. RESULTS: A total of 488 patients were included. Of these, 34% had noninvasive appendiceal, 30% invasive appendiceal, 28% colorectal, and 8% PM histology. CT-PCI was correlated with intraoperative-PCI for patients with noninvasive and invasive appendiceal and colorectal histologies (r = 0.689, 0.554, and 0.571; all P < .001), but not PM (r = 0.188; P = .295). MRI-PCI was correlated with intraoperative-PCI for all histologies (non-invasive appendiceal: r = 0.591; P = .002; invasive appendiceal: r = 0.848; P < .001; colorectal: r = 0.729; P < .001; PM: r = 0.890; P = .007). Comparing CT and MRI, correlations were similar in noninvasive appendiceal and colorectal histologies; MRI was better for invasive appendiceal and PM (P = .005 and P = .021, respectively). Twenty-eight (6%) patients underwent an incomplete cytoreduction (cytoreduction score, 2-3). PCI greater than 15 was associated with cytoreduction score of 2 to 3 for both CT and MRI (CT-PCI: odds ratio, 3.0; P = .033; MRI-PCI: odds ratio, 7.6; P = .071). CONCLUSIONS: In this multi-institutional cohort, CT and MRI-PCI correlate well with intraoperative-PCI. MRI appears to be superior for invasive appendiceal and peritoneal mesothelioma. External validation in a larger population is needed.

Preoperative Risk Score for Predicting Incomplete Cytoreduction: A 12-Institution Study from the US HIPEC Collaborative.

BACKGROUND: For patients with peritoneal carcinomatosis undergoing cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC), incomplete cytoreduction (CCR2/3) confers morbidity without survival benefit. The aim of this study is to identify preoperative factors which predict CCR2/3. METHODS: All patients who underwent curative-intent CRS/HIPEC of low/high-grade appendiceal, colorectal, or peritoneal mesothelioma cancers in the 12-institution US HIPEC Collaborative from 2000 to 2017 were included (n = 2027). The primary aim is to create an incomplete-cytoreduction risk score (ICRS) to predict CCR2/3 CRS utilizing preoperative data. ICRS was created from a randomly selected cohort of 50% of patients (derivation cohort) and verified on the remaining patients (validation cohort). RESULTS: Within our derivation cohort (n = 998), histology was low-grade appendiceal neoplasms in 30%, high-grade appendiceal tumor in 41%, colorectal tumor in 22%, and peritoneal mesothelioma in 8%. CCR0/1 was achieved in 816 patients and CCR 2/3 in 116 patients. On multivariable analysis, preoperative factors associated with incomplete cytoreduction were male gender [odds ratio (OR) 3.4, p = 0.007], presence of ascites (OR 2.8, p = 0.028), cancer antigen (CA)-125 ≥ 40 U/mL (OR 3.4, p = 0.012), and carcinoembryonic antigen (CEA) ≥ 4.2 ng/mL (OR 3.2, p = 0.029). Each preoperative factor was assigned a score of 0 or 1 to form an ICRS from 0 to 4. Scores were grouped as zero (0), low (1-2), or high (3-4). Incidence of CCR2/3 progressively increased by risk group from 1.6% in zero to 13% in low and 39% in high. When ICRS was applied to the validation cohort (n = 1029), this relationship was maintained. CONCLUSION: The incomplete cytoreduction risk score incorporates preoperative factors to accurately stratify the risk of CCR2/3 resection in CRS/HIPEC. This score should not be used in isolation, however, to exclude patients from surgery.

Trends in the indications for and short-term outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is an increasingly utilized strategy for patients with peritoneal surface malignancies (PSM). METHODS: The US HIPEC Collaborative was retrospectively reviewed to compare the indications and perioperative outcomes of patients who underwent CRS ±â€¯HIPEC between 2000 and 2012 (P1) versus 2013-2017 (P2). RESULTS: Among 2,364 patients, 39% were from P1 and 61% from P2. The most common primary site was appendiceal (64%) while the median PCI was 13 and most patients had CCR 0 (60%) or 1 (25%). Over time, median estimated blood loss, need for transfusion, and length of hospital stay decreased. While the incidence of any (55% vs. 57%; p = 0.426) and Clavien III/IV complications did not change over time, there was a decrease in 90-day mortality (5% vs. 3%; p = 0.045). CONCLUSION: CRS-HIPEC is increasingly performed for PSM at high-volume centers. Despite improvements in some perioperative outcomes and a reduction in postoperative mortality, morbidity rates remain high.

Predictors of Anastomotic Failure After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Does Technique Matter?

BACKGROUND: Anastomotic failure (AF) after cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) remains a dreaded complication. Whether specific factors, including anastomotic technique, are associated with AF is poorly understood. METHODS: Patients who underwent CRS-HIPEC including at least one bowel resection between 2000 and 2017 from 12 academic institutions were reviewed to determine factors associated with AF (anastomotic leak or enteric fistula). RESULTS: Among 1020 patients who met the inclusion criteria, the median age was 55 years, 43.9% were male, and the most common histology was appendiceal neoplasm (62.3%). The median Peritoneal Cancer Index was 14, and 93.2% of the patients underwent CC0/1 resection. Overall, 82 of the patients (8%) experienced an AF, whereas 938 (92.0%) did not. In the multivariable analysis, the factors associated with AF included male gender (odds ratio [OR], 2.2; p < 0.01), left-sided colorectal resection (OR 10.0; p = 0.03), and preoperative albumin (OR 1.8 per g/dL; p = 0.02).Technical factors such as method (stapled vs hand-sewn), timing of anastomosis, and chemotherapy regimen used were not associated with AF (all p > 0.05). Anastomotic failure was associated with longer hospital stay (23 vs 10 days; p < 0.01), higher complication rate (90% vs 59%; p < 0.01), higher reoperation rate (41% vs 9%; p < 0.01), more 30-day readmissions (59% vs 22%; p < 0.01), greater 30-day mortality (9% vs 1%; p < 0.01), and greater 90-day mortality (16% vs 8%; p = 0.02) as well as shorter median overall survival (25.6 vs 66.0 months; p < 0.01). CONCLUSIONS: Among patients undergoing CRS-HIPEC, AF is independently associated with postoperative morbidity and worse long-term outcomes. Because patient- and tumor-related, but not technical, factors are associated with AF, operative technique may be individualized based on patient considerations and surgeon preference.

Primary Tumor Sidedness is Predictive of Survival in Colon Cancer Patients Treated with Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy: A US HIPEC Collaborative Study.

INTRODUCTION: The clinical relevance of primary tumor sidedness is not fully understood in colon cancer patients with peritoneal metastasis treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: This was a retrospective cohort study of a multi-institutional database of patients with peritoneal surface malignancy at 12 participating high-volume academic centers from the US HIPEC Collaborative. RESULTS: Overall, 336 patients with colon primary tumors who underwent curative-intent CRS with or without HIPEC were identified; 179 (53.3%) patients had right-sided primary tumors and 157 (46.7%) had left-sided primary tumors. Patients with right-sided tumors were more likely to be older, male, have higher Peritoneal Cancer Index (PCI), and have a perforated primary tumor, but were less likely to have extraperitoneal disease. Patients with complete cytoreduction (CC-0/1) had a median disease-free survival (DFS) of 11.5 months (95% confidence interval [CI] 7.6-15.3) versus 13.1 months (95% CI 9.5-16.8) [p = 0.158] and median overall survival (OS) of 30 months (95% CI 23.5-36.6) versus 45.4 months (95% CI 35.9-54.8) [p = 0.028] for right- and left-sided tumors; respectively. Multivariate analysis revealed that right-sided primary tumor was an independent predictor of worse DFS (hazard ratio [HR] 1.75, 95% CI 1.19-2.56; p =0.004) and OS (HR 1.72, 95% CI 1.09-2.73; p = 0.020). CONCLUSION: Right-sided primary tumor was an independent predictor of worse DFS and OS. Relevant clinicopathologic criteria, such as tumor sidedness and PCI, should be considered in patient selection for CRS with or without HIPEC, and guide stratification for clinical trials.