A Randomized, Controlled Trial Evaluating Perioperative Risk-Stratification and Risk-Based, Protocol-Driven Management After Elective Major Cancer Surgery.

OBJECTIVE: We evaluated the efficacy of risk-based, protocol-driven management versus (vs) usual management after elective major cancer surgery to reduce 30-day rates of postoperative death or serious complications (DSC) . SUMMARY BACKGROUND DATA: Major cancer surgery is associated with significant perioperative risks which result in worse long-term outcomes. METHODS: Adults scheduled for elective major cancer surgery were stratified/randomized to risk-based escalating levels of care, monitoring, and co-management vs usual management. The primary study outcome was 30-day rate of DSC. Additional outcomes included complications, adverse events, health care utilization, health-related quality of life (HRQOL), and disease-free and overall survival (DFS and OS). RESULTS: Between August 2014 and June 2020, 1529 patients were enrolled and randomly allocated to the study arms; 738 patients in the Intervention Arm and 732 patients in the Control Arm were eligible for analysis. 30-day rate of DSC with the intervention was 15.0% (95% CI, 12.5-17.6%) vs 14.1%, (95% CI, 11.6-16.6%) with usual management (P=0.65). There were no differences in 30-day rates of complications or adverse events (including return to the operating room); postoperative length of stay; rate of discharge to home; or 30, 60, or 90-day HRQOL or rates of hospital readmission or receipt of anti-neoplastic therapy between the study arms. At median follow-up of 48 months, OS (P=0.57) and DFS (P=0.91) were similar. CONCLUSIONS: Risk-based, protocol-driven management did not reduce 30-day rate of DSC after elective major cancer surgery compared to usual management, nor improve postoperative health care utilization, HRQOL, or cancer outcomes. Trials are needed to identify cost-effective, tailored perioperative strategies to optimize outcomes after major cancer surgery.

A phase II clinical trial of neoadjuvant sasanlimab and stereotactic body radiation therapy as an in situ vaccine for cisplatin-ineligible MIBC: the RAD VACCINE MIBC trial.

The utilization of neoadjuvant immune checkpoint inhibitor therapy, specifically anti-PD-1/L1 agents, prior to radical cystectomy is an emerging paradigm in muscle-invasive bladder cancer (MIBC). In situ vaccination represents a strategy to manipulate the tumor in order to augment the immune response toward improved local and distant cancer control. The authors describe the study rationale, design and objectives for RAD VACCINE MIBC, a single-arm, single-institution, phase II trial evaluating the efficacy and safety of combination neoadjuvant sasanlimab (humanized IgG monoclonal antibody that targets PD-1) with stereotactic body radiotherapy as an in situ vaccine in cisplatin-ineligible patients with MIBC. The results from this trial will establish the safety profile of this combination strategy and evaluate pathologic complete response rates.

RAD VACCINE MIBC is a phase II clinical trial that aims to determine the safety and effectiveness of a study drug called sasanlimab (an immune checkpoint inhibitor), combined with radiation therapy (stereotactic body radiation therapy) prior to surgery to remove the bladder (known as radical cystectomy [RC]) in muscle-invasive bladder cancer patients. For this type of cancer, patients typically receive chemotherapy followed by RC as the standard of care. However, many patients who have pre-existing medical conditions such as poor kidney function are unable to receive chemotherapy. These patients undergo RC alone at the risk of less optimal cancer control. Bladder cancer is known to inhibit the immune cells (T cells) from attacking it, which is an important way in which the body controls cancer cells. Sasanlimab allows T cells that are specific to the cancer to potentially reactivate. Ongoing studies have shown that drugs similar to sasanlimab can be used to achieve improvement in cancer control in the bladder (as measured by shrinking the cancer or eradicating it) before surgery. The authors are studying the use of the study drug with the addition of stereotactic body radiotherapy (SBRT) as a combined therapy. The role of SBRT as a combined therapy to immune checkpoint inhibition has been well studied to help improve the process of how immune cells recognize cancer cells. By giving both the study drug and SBRT together before RC, the authors aim to demonstrate the safety of this technique and its effectiveness in eradicating all cancer in the bladder. Clinical Trial Registration: NCT05241340 (ClinicalTrials.gov).

Comparative Effectiveness and Risks of Bowel Preparation Before Elective Colorectal Surgery.

OBJECTIVE: The objective of this study was to determine the relationship between bowel preparation and surgical site infections (SSIs), and also other postoperative complications, after elective colorectal surgery. BACKGROUND: SSI is a major source of postoperative morbidity/costs after colorectal surgery. The value of preoperative bowel preparation to prevent SSI remains controversial. METHODS: We analyzed 32,359 patients who underwent elective colorectal resections in the American College of Surgeons National Surgery Quality Improvement Program database from 2012 to 2014. Univariable and multivariable analyses were performed; propensity adjustment using patient/procedure characteristics was used to account for nonrandom receipt of bowel preparation. RESULTS: 26.7%, 36.6%, 3.8%, and 32.9% of patients received no bowel preparation, mechanical bowel preparation (MBP), oral antibiotics (OA), and MBP + OA, respectively. After propensity adjustment, MBP was not associated with decreased risk of SSI compared with no bowel preparation. In contrast, both OA and OA + MBP were associated with decreased risk of any SSI (adjusted odds ratio 0.49, 95% confidence interval 0.38-0.64; and adjusted odds ratio 0.45, 95% confidence interval 0.40-0.50, respectively) compared with no bowel preparation. OA and MBP + OA were associated with decreased risks of anastomotic leak, postoperative ileus, readmission, and also shorter length of stay (all P < 0.05). Bowel preparation was not associated with increased risk of cardiac/renal complications compared with no preparation. CONCLUSIONS: The use of MBP alone before elective colorectal resection to prevent SSI is ineffective and should be abandoned. In contrast, OA and MBP + OA are associated with decreased risks of SSI and are not associated with increased risks of other adverse outcomes compared with no preparation. Prospective studies to determine the efficacy of OA are warranted; in the interim, MBP + OA should be used routinely before elective colorectal resection to prevent SSI.

Granular cell tumor experience at a comprehensive cancer center.

BACKGROUND: Granular cell tumors (GCTs) are rare lesions occurring almost anywhere in the body. Multiple case reports have been published. However, there are very few large-scale studies regarding GCT. The aim of this study was to define characteristics, treatment patterns and outcomes of patients with GCT. METHODS: An institutional review board-approved retrospective chart review was performed. Descriptive statistics, chi-square analyses, and Kaplan-Meier survival estimates were produced. RESULTS: Fifty patients were treated for GCT at our institution between 1992 and 2015. The median age was 47 y; 62% of patients were female and 64% were whites. Median tumor size was 0.8 cm. Four percent of patients had malignant tumors, 10.0% had atypical tumors, and 86.0% had benign tumors. The most frequent location of tumors was the gastrointestinal tract (n = 30; 60%), followed by skin/subcutaneous tissues (n = 19; 38%), then respiratory tract (n = 1; 2%). Most patients underwent surgical excision or endoscopic removal of their tumors without prior biopsy. Three patients (6%) had multifocal tumors; they were more likely to experience recurrence than patients with unifocal tumors (33.3% versus 10.6%, respectively; P = 0.05). Six patients (12.0%) experienced recurrence, with a median time to recurrence of 13.5 mo. Overall cancer-specific 5-y survival was 98.0%. Overall recurrence-free 5-y survival was 86.4%. Patients with atypical tumors had a lower recurrence-free 5-y survival rate than those with benign tumors (75.0% versus 89.7%, respectively; P = 0.04). CONCLUSIONS: Patients with GCT fair well, particularly when tumors are benign. Patients with multifocal tumors are more likely to experience recurrence and should be closely monitored.

Does the Surgical Apgar Score predict serious complications after elective major cancer surgery?

BACKGROUND: Major cancer surgery is associated with significant risks of perioperative morbidity and mortality, resulting in delayed adjuvant therapy, higher recurrence rates, and worse overall survival. Previous retrospective studies have used the Surgical Apgar Score (SAS) for perioperative risk assessment. This study prospectively evaluated the predictive value of SAS to predict serious complication (SC) after elective major cancer surgery. METHODS: Demographic, comorbidity, procedure, and intraoperative data were collected prospectively for 405 patients undergoing elective major cancer surgery between 2014-17. The SAS was calculated immediately postoperative and outcome data were collected prospectively. Rates of SC according to SAS risk category were compared using Cochran-Armitage trend test. Receiver operating characteristic curves and area under the receiver operating characteristic curves were generated and 95% confidence intervals were calculated. RESULTS: Eighty percent, 17.3%, and 2.7% of patients were low (SAS 7-10), intermediate (SAS 5-6), and high risk (SAS 0-4), respectively, for SC based on their SAS. Forty-six (11.4%) had an SC within 30 days; 3.7% returned to the operating room, 3.7% experienced a urinary tract infection, 3.2% experienced a respiratory complication, 2.7% experienced a wound complication, and 1.2% experienced a cardiac complication. Overall, 9.3%, 18.6%, and 27.3% of patients with SAS 7-10, 5-6, and 0-4 experienced an SC, respectively (P = 0.005). The overall discriminatory ability of the SAS was modest (area under the receiver operating characteristic curves 0.661; 95% confidence intervals, 0.582-0.740). CONCLUSIONS: Although there was an overall association between SAS and higher risk of subsequent postoperative SC in our cohort, the ability of the SAS to accurately predict risk of postoperative SC at the patient level was limited.

Evaluation and management of intrahepatic and extrahepatic cholangiocarcinoma.

Cholangiocarcinomas are rare biliary tract tumors that are often challenging to diagnose and treat. Cholangiocarcinomas are generally categorized as intrahepatic or extrahepatic depending on their anatomic location. The majority of patients with cholangiocarcinoma do not have any of the known or suspected risk factors and present with advanced disease. The optimal evaluation and management of patients with cholangiocarcinoma requires thoughtful integration of clinical information, imaging studies, cytology and/or histology, as well as prompt multidisciplinary evaluation. The current review focuses on recent advances in the diagnosis and treatment of patients with cholangiocarcinoma and, in particular, on the role of endoscopy, surgery, transplantation, radiotherapy, systemic therapy, and liver-directed therapies in the curative or palliative treatment of these individuals. Cancer 2016;122:1349-1369. © 2016 American Cancer Society.

Surgical management of pancreatic neoplasms: what's new?

Pancreatic cancer is the fourth leading cause of cancer deaths in the USA. Although some patients will present with premalignant pancreatic lesions (i.e., intraductal papillary mucinous neoplasms) or localized tumors amenable to curative resection, the majority of patients will unfortunately present with technically unresectable or metastatic disease. This review of the recent medical literature will discuss the optimal work-up and management of premalignant pancreatic lesions and the surgical management of localized, borderline resectable, and locally advanced (i.e., unresectable) pancreatic tumors. It will focus on new criteria used to define surgical "resectability," the significance and clinical impact of surgical margins, the role of multimodality therapy in the management of patients with borderline resectable or locally advanced tumors, the role of surgery for local or distant recurrence, and minimally invasive surgical approaches.

Extracellular Vesicles, Circadian Rhythms, and Cancer: A Comprehensive Review with Emphasis on Hepatocellular Carcinoma.

This review comprehensively explores the complex interplay between extracellular vesicles (ECVs)/exosomes and circadian rhythms, with a focus on the role of this interaction in hepatocellular carcinoma (HCC). Exosomes are nanovesicles derived from cells that facilitate intercellular communication by transporting bioactive molecules such as proteins, lipids, and RNA/DNA species. ECVs are implicated in a range of diseases, where they play crucial roles in signaling between cells and their surrounding environment. In the setting of cancer, ECVs are known to influence cancer initiation and progression. The scope of this review extends to all cancer types, synthesizing existing knowledge on the various roles of ECVs. A unique aspect of this review is the emphasis on the circadian-controlled release and composition of exosomes, highlighting their potential as biomarkers for early cancer detection and monitoring metastasis. We also discuss how circadian rhythms affect multiple cancer-related pathways, proposing that disruptions in the circadian clock can alter tumor development and treatment response. Additionally, this review delves into the influence of circadian clock components on ECV biogenesis and their impact on reshaping the tumor microenvironment, a key component driving HCC progression. Finally, we address the potential clinical applications of ECVs, particularly their use as diagnostic tools and drug delivery vehicles, while considering the challenges associated with clinical implementation.

Comparative molecular profiling of pancreatic ductal adenocarcinoma of the head versus body and tail.

Pancreatic ductal adenocarcinoma (PDAC) of the head (H) and body/tail (B/T) differ in embryonic origin, cell composition, blood supply, lymphatic and venous drainage, and innervation. We aimed to compare the molecular and tumor immune microenvironment (TIME) profiles of PDAC of the H vs. B/T. A total of 3499 PDAC samples were analyzed via next-generation sequencing (NGS) of RNA (whole transcriptome, NovaSeq), DNA (NextSeq, 592 genes or NovaSeq, whole exome sequencing), and immunohistochemistry (Caris Life Sciences, Phoenix, AZ). Significance was determined as p values adjusted for multiple corrections (q) of <0.05. Anatomic subsites of PDAC tumors were grouped by primary tumor sites into H (N = 2058) or B/T (N = 1384). There were significantly more metastatic tumors profiled from B/T vs. H (57% vs. 44%, p < 0.001). KRAS mutations (93.8% vs. 90.2%), genomic loss of heterozygosity (12.7% vs. 9.1%), and several copy number alterations (FGF3, FGF4, FGF19, CCND1, ZNF703, FLT4, MUTYH, TNFRS14) trended higher in B/T when compared to H (p < 0.05 but q > 0.05). Expression analysis of immuno-oncology (IO)-related genes showed significantly higher expression of CTLA4 and PDCD1 in H (q < 0.05, fold change 1.2 and 1.3) and IDO1 and PDCD1LG2 expression trended higher in B/T (p < 0.05, fold change 0.95). To our knowledge, this is one of the largest cohorts of PDAC tumors subjected to broad molecular profiling. Differences in IO-related gene expression and TIME cell distribution suggest that response to IO therapies may differ in PDAC arising from H vs. B/T. Subtle differences in the genomic profiles of H vs. B/T tumors were observed.

Effect of metabolic syndrome and its components on recurrence and survival in colon cancer patients.

BACKGROUND: Although epidemiologic studies suggest that metabolic syndrome (MetS) increases the risk of colorectal cancer, its effect on cancer mortality remains controversial. METHODS: The authors used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database (1998-2006) to conduct a retrospective cohort study of 36,079 patients with colon cancer to determine the independent effect of MetS and its components on overall survival (OS) and recurrence-free rates (RFRs). Data on MetS and its components were ascertained from Medicare claims. OS and RFRs in patients with and without MetS and its components were compared using multivariate Cox models. RESULTS: MetS had no apparent effect on OS or RFR. Both elevated glucose/diabetes mellitus (DM) and elevated hypertension were associated with worse OS (adjusted hazard ratio [aHR], 1.17 [95% confidence interval, 1.13-1.21] and 1.08 [95% confidence interval, 1.03-1.12], respectively) and worse RFRs (aHR, 1.25 [95% confidence interval, 1.16-1.34] and 1.22 [95% confidence interval, 1.12-1.33], respectively). In contrast, dyslipidemia was associated with improved survival (aHR, 0.77; 95% confidence interval, 0.75-0.80) and reduced recurrence (aHR, 0.71; 95% confidence interval, 0.66-0.75). These effects were consistent for both men and women and were more pronounced in patients with early stage disease. CONCLUSIONS: MetS had no apparent effect on colon cancer outcomes, probably because of the combined adverse effects of elevated glucose/DM and hypertension and the protective effect of dyslipidemia in patients with nonmetastatic disease. The authors concluded that patients who have early stage colon cancer with elevated glucose/DM and/or hypertension may benefit from more intensive surveillance and/or broader use of adjuvant therapy and that trials to define the benefits of low-fat diets, insulin-lowering agents, and statins on recurrence/survival in patients with nonmetastatic colon cancer are warranted.

De-Escalating the Management of In Situ and Invasive Breast Cancer.

It is necessary to identify appropriate areas of de-escalation in breast cancer treatment to minimize morbidity and maximize patients' quality of life. Less radical treatment modalities, or even no treatment, have been reconsidered if they offer the same oncologic outcomes as standard therapies. Identifying which patients benefit from de-escalation requires particular care, as standard therapies will continue to offer adequate cancer outcomes. We provide an overview of the literature on the de-escalation of treatment of ductal carcinoma in situ (DCIS), local treatment of breast cancer, and surgery after neoadjuvant systemic therapy. De-escalation of breast cancer treatment is a key area of investigation that will continue to remain a priority. Improvements in understanding the natural history and biology of breast cancer, imaging modalities, and adjuvant treatments will expand this even further. Future efforts will continue to challenge us to consider the true role of various treatment modalities.

Association of Surgeon-Patient Sex Concordance With Postoperative Outcomes.

Importance: Surgeon sex is associated with differential postoperative outcomes, though the mechanism remains unclear. Sex concordance of surgeons and patients may represent a potential mechanism, given prior associations with physician-patient relationships. Objective: To examine the association between surgeon-patient sex discordance and postoperative outcomes. Design, Setting, and Participants: In this population-based, retrospective cohort study, adult patients 18 years and older undergoing one of 21 common elective or emergent surgical procedures in Ontario, Canada, from 2007 to 2019 were analyzed. Data were analyzed from November 2020 to March 2021. Exposures: Surgeon-patient sex concordance (male surgeon with male patient, female surgeon with female patient) or discordance (male surgeon with female patient, female surgeon with male patient), operationalized as a binary (discordant vs concordant) and 4-level categorical variable. Main Outcomes and Measures: Adverse postoperative outcome, defined as death, readmission, or complication within 30-day following surgery. Secondary outcomes assessed each of these metrics individually. Generalized estimating equations with clustering at the level of the surgical procedure were used to account for differences between procedures, and subgroup analyses were performed according to procedure, patient, surgeon, and hospital characteristics. Results: Among 1 320 108 patients treated by 2937 surgeons, 602 560 patients were sex concordant with their surgeon (male surgeon with male patient, 509 634; female surgeon with female patient, 92 926) while 717 548 were sex discordant (male surgeon with female patient, 667 279; female surgeon with male patient, 50 269). A total of 189 390 patients (14.9%) experienced 1 or more adverse postoperative outcomes. Sex discordance between surgeon and patient was associated with a significant increased likelihood of composite adverse postoperative outcomes (adjusted odds ratio [aOR], 1.07; 95% CI, 1.04-1.09), as well as death (aOR, 1.07; 95% CI, 1.02-1.13), and complications (aOR, 1.09; 95% CI, 1.07-1.11) but not readmission (aOR, 1.02; 95% CI, 0.98-1.07). While associations were consistent across most subgroups, patient sex significantly modified this association, with worse outcomes for female patients treated by male surgeons (compared with female patients treated by female surgeons: aOR, 1.15; 95% CI, 1.10-1.20) but not male patients treated by female surgeons (compared with male patients treated by male surgeons: aOR, 0.99; 95% CI, 0.95-1.03) (P for interaction = .004). Conclusions and Relevance: In this study, sex discordance between surgeons and patients negatively affected outcomes following common procedures. Subgroup analyses demonstrate that this is driven by worse outcomes among female patients treated by male surgeons. Further work should seek to understand the underlying mechanism.

Perioperative normothermia during major surgery: is it important?

PH caused by anesthesia-induced thermoregulatory inhibition and exposure to cold operating room environments still occurs in a significant proportion of patients undergoing major surgery. Although the association between specific perioperative temperatures (in and of themselves) and postoperative morbidity remains unclear, there is fair evidence to suggest that perioperative active warming may reduce the risk of postoperative cardiac events, bleeding, and SSIs. As such, proactive efforts by surgical teams to prevent PH are warranted and have become the standard of care at many institutions. Continued intraoperative monitoring of core temperature (ideally using esophageal probes) is recommended in all cases lasting more than 30 minutes, both to detect malignant hyperthermia and to maintain normothermia. Preoperative and/or intraoperative use of warmed forced-air devices is an effective way to minimize redistribution hypothermia following induction, whereas intraoperative use of warmed i.v. fluids helps reduce the potential for fluid-induced hypothermia and, in turn, optimizes rates of perioperative normothermia.

Modified frailty index predicts complications and death after non-bariatric gastrectomies.

BACKGROUND: The modified frailty index (mFI) has been shown to predict mortality and morbidity after major operations. The aim of the present study was to assess the mFI as a preoperative predictor of short-term postoperative complications and 30-day mortality in patients undergoing gastrectomy for non-bariatric diseases. METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database was queried for patients who underwent total or partial gastrectomy from 2005 to 2011. A mFI was calculated based on 11 variables as previously described. The population divided into the following four categories based on the mFI score: the non-frail (mFI 0), the low frail (mFI 1), the intermediate frail (mFI 2) and frail (mFI ≥3). Thirty-day mortality and postoperative complications were evaluated. RESULTS: Overall, 5,711 patients underwent a gastrectomy for non-bariatric diseases. Higher mFI score was associated with higher rates of mortality (from 1.2% in the non-frail group to 10.7% in frail group, P<0.001), overall morbidity (26.7% vs. 51.1%, P<0.001), postoperative Clavien IV complication (6% vs. 24.6%, P<0.001), serious complications (19.3% vs. 42.6%, P<0.001), sepsis-related complications (8.4% vs. 16.4%, P<0.001), cardiopulmonary complications (5% vs. 20.7%, P<0.001) and failure to rescue (5.7% vs. 21.8%, P<0.001). CONCLUSIONS: Higher mFI score in patients undergoing non-bariatric gastrectomy, is associated with a stepwise greater risk of postoperative morbidity and mortality. MFI Score can be easily calculated preoperatively, from the patient's history, and it can be used as an exceptionally useful criterion for treatment planning.

Atherosclerotic Cardiovascular Disease, Cancer, and Financial Toxicity Among Adults in the United States.

BACKGROUND: Financial toxicity (FT) is a well-established side-effect of the high costs associated with cancer care. In recent years, studies have suggested that a significant proportion of those with atherosclerotic cardiovascular disease (ASCVD) experience FT and its consequences. OBJECTIVES: This study aimed to compare FT for individuals with neither ASCVD nor cancer, ASCVD only, cancer only, and both ASCVD and cancer. METHODS: From the National Health Interview Survey, we identified adults with self-reported ASCVD and/or cancer between 2013 and 2018, stratifying results by nonelderly (age <65 years) and elderly (age ≥65 years). We defined FT if any of the following were present: any difficulty paying medical bills, high financial distress, cost-related medication nonadherence, food insecurity, and/or foregone/delayed care due to cost. RESULTS: The prevalence of FT was higher among those with ASCVD when compared with cancer (54% vs. 41%; p < 0.001). When studying the individual components of FT, in adjusted analyses, those with ASCVD had higher odds of any difficulty paying medical bills (odds ratio [OR]: 1.22; 95% confidence interval [CI]: 1.09 to 1.36), inability to pay bills (OR: 1.25; 95% CI: 1.04 to 1.50), cost-related medication nonadherence (OR: 1.28; 95% CI: 1.08 to 1.51), food insecurity (OR: 1.39; 95% CI: 1.17 to 1.64), and foregone/delayed care due to cost (OR: 1.17; 95% CI: 1.01 to 1.36). The presence of ≥3 of these factors was significantly higher among those with ASCVD and those with both ASCVD and cancer when compared with those with cancer (23% vs. 30% vs. 13%, respectively; p < 0.001). These results remained similar in the elderly population. CONCLUSIONS: Our study highlights that FT is greater among patients with ASCVD compared with those with cancer, with the highest burden among those with both conditions.

Perioperative Outcomes Following Combined Versus Isolated Colorectal and Liver Resections: Insights From a Contemporary, National, Propensity Score-Based Analysis.

Our objective was to compare outcomes following combined versus isolated resections for metastatic colorectal cancer and/or liver metastases using a large, contemporary national database. Background: Controversy persists regarding optimal timing of resections in patients with synchronous colorectal liver metastases. Methods: We analyzed 11,814 patients with disseminated colorectal cancer and/or liver metastases who underwent isolated colon, rectal, or liver resections (CRs, RRs, or LRs) or combined colon/liver or rectal/liver resections (CCLRs or CRLRs) in the National Surgical Quality Improvement Program Participant Use File (2011-2015). We examined associations between resection type and outcomes using univariate/multivariate analyses and used propensity adjustment to account for nonrandom receipt of isolated versus combined resections. Results: Two thousand four hundred thirty-seven (20.6%); 2108 (17.8%); and 6243 (52.8%) patients underwent isolated CR, RR, or LR; 557 (4.7%) and 469 (4.0%) underwent CCLR or CRLR. Three thousand three hundred ninety-five patients (28.7%) had serious complications (SCs). One hundred forty patients (1.2%) died, of which 113 (80.7%) were failure to rescue (FTR). One thousand three hundred eighty-six (11.7%) patients experienced unplanned readmission. After propensity adjustment and controlling for procedural complexity, wound class, and operation year, CCLR/CRLR was independently associated with increased risk of SC, as well as readmission (compared with LR). CCLR was also independently associated with increased risk of FTR and death (compared with LR). Conclusions: Combined resection uniformly confers increased risk of SC and increased risk of mortality after CCLR; addition of colorectal to LR increases risk of readmission. Combined resections are less safe, and potentially more costly, than isolated resections. Effective strategies to prevent SC after combined resections are warranted.

Acetyl-CoA Synthetase 2: A Critical Linkage in Obesity-Induced Tumorigenesis in Myeloma.

Obesity is often linked to malignancies including multiple myeloma, and the underlying mechanisms remain elusive. Here we showed that acetyl-CoA synthetase 2 (ACSS2) may be an important linker in obesity-related myeloma. ACSS2 is overexpressed in myeloma cells derived from obese patients and contributes to myeloma progression. We identified adipocyte-secreted angiotensin II as a direct cause of adiposity in increased ACSS2 expression. ACSS2 interacts with oncoprotein interferon regulatory factor 4 (IRF4), and enhances IRF4 stability and IRF4-mediated gene transcription through activation of acetylation. The importance of ACSS2 overexpression in myeloma is confirmed by the finding that an inhibitor of ACSS2 reduces myeloma growth both in vitro and in a diet-induced obese mouse model. Our findings demonstrate a key impact for obesity-induced ACSS2 on the progression of myeloma. Given the central role of ACSS2 in many tumors, this mechanism could be important to other obesity-related malignancies.

Normothermia to prevent surgical site infections after gastrointestinal surgery: holy grail or false idol?

OBJECTIVE: To analyze the association between perioperative normothermia (temperature ≥36°C) and surgical site infections (SSIs) after gastrointestinal (GI) surgery. SUMMARY OF BACKGROUND DATA: Although active warming during colorectal surgery reduces SSIs, there is limited evidence that perioperative normothermia is associated with lower rates of SSI. Nonetheless, hospitals participating in the Surgical Care Improvement Project must report normothermia rates during major surgery. METHODS: We conducted a nested, matched, case-control study; cases consisted of GI surgery patients enrolled in our National Surgical Quality Improvement Program database between March 2006 and March 2009 who developed SSIs. Patient/surgery risk factors for SSI were obtained from the National Surgical Quality Improvement Program database. Perioperative temperature/antibiotic/glucose data were obtained from medical records. Cases/controls were compared using univariate/random effects/logistic regression models. Independent risk factors for SSIs were identified using multivariate/random effects/logistic regression models. RESULTS: A total of 146 cases and 323 matched controls were identified; 82% of patients underwent noncolorectal surgery. Cases were more likely to have final intraoperative normothermia compared with controls (87.6% vs. 77.8%, P = 0.015); rates of immediate postoperative normothermia were similar (70.6% vs. 65.3%, respectively, P = 0.19). Emergent surgery/higher wound class were associated with higher rates of intraoperative normothermia. Independent risk factors for SSI were diabetes, surgical complexity, small bowel surgery, and nonlaparoscopic surgery. There was no independent association between perioperative normothermia and SSI (adjusted odds ratio, 1.05; 95% confidence interval, 0.48-2.33; P = 0.90). CONCLUSIONS: Pay-for-reporting measures focusing on perioperative normothermia may be of limited value in preventing SSI after GI surgery. Studies to define the benefit of active warming after noncolorectal GI surgery are warranted.

Mathematical prediction of clinical outcomes in advanced cancer patients treated with checkpoint inhibitor immunotherapy.

We present a mechanistic mathematical model of immune checkpoint inhibitor therapy to address the oncological need for early, broadly applicable readouts (biomarkers) of patient response to immunotherapy. The model is built upon the complex biological and physical interactions between the immune system and cancer, and is informed using only standard-of-care CT. We have retrospectively applied the model to 245 patients from multiple clinical trials treated with anti-CTLA-4 or anti-PD-1/PD-L1 antibodies. We found that model parameters distinctly identified patients with common (n = 18) and rare (n = 10) malignancy types who benefited and did not benefit from these monotherapies with accuracy as high as 88% at first restaging (median 53 days). Further, the parameters successfully differentiated pseudo-progression from true progression, providing previously unidentified insights into the unique biophysical characteristics of pseudo-progression. Our mathematical model offers a clinically relevant tool for personalized oncology and for engineering immunotherapy regimens.

BMI, physical activity, and breast cancer subtype in white, black, and Sea Island breast cancer survivors.

Higher BMI, lower rates of physical activity (PA), and hormone receptor-negative breast cancer (BC) subtype are associated with poorer BC treatment outcomes. We evaluated the prevalence of high BMI, low PA level, and BC subtype among survivors with white/European American (EA) and African American (AA) ancestry, as well as a distinct subset of AAs with Sea Island/Gullah ancestry (SI). We used the South Carolina Central Cancer Registry to identify 137 (42 EAs, 66 AAs, and 29 SIs) women diagnosed with BC and who were within 6-21 months of diagnosis. We employed linear and logistic regression to investigate associations between BMI, PA, and age at diagnosis by racial/ethnic group. Most participants (82%) were overweight/obese (P=0.46). BMI was highest in younger AAs (P=0.02). CDC PA guidelines (≥150min/week) were met by only 28% of participants. The frequency of estrogen receptor (ER)-negative BC subtype was lower in EAs and SIs than in AAs (P<0.05). This is the first study to identify differences in obesity and PA rates, and BC subtype in EAs, AAs, and SIs. BMI was higher, PA rates were lower, and frequency of ER-negative BC was higher in AAs as compared to EAs and SIs. This study highlights the need to promote lifestyle interventions among BC survivors, with the goal of reducing the likelihood of a BC recurrence. Integrating dietary and PA interventions into ongoing survivorship care is essential. Future research could evaluate potential differential immune responses linked to the frequency of triple negative BC in AAs.