A Gravid Situation: General Surgery Faculty Support for Pregnant Surgical Residents.

INTRODUCTION: The perceptions of teaching faculty toward pregnant general surgery residents have been overlooked despite the daily interactions amongst these groups. METHODS: A 32-question survey designed to measure general surgery teaching faculty perceptions toward pregnant residents was distributed electronically from March 2022 to April 2022 to general surgery teaching faculty in the United States. Descriptive statistics were used to characterize responses and differences in perceptions, and qualitative analysis identified recurring themes from free-text responses. RESULTS: Among 163 respondents included in the final analysis, 58.5% were male and 41.5% were female. Despite 99.4% of surgeons feeling comfortable if a resident told them they were pregnant, 22.4% of surgeons disagreed that their institutions have supportive cultures toward pregnancy. Almost half (45.4%) have witnessed negative comments about pregnant residents and half (50.3%) believe that pregnant surgical residents are discriminated against by their coresidents. Nearly two-thirds of surgeons (64.8%) believe that someone should have a child whenever they wish during training. Given recent reports, 80.2% of surgeons recognized that female surgeons have increased risks of infertility and pregnancy complications. Recurring themes of normalizing pregnancy, improving policies, and creating a culture change were expressed. CONCLUSIONS: In this national survey, although there appears to be positive perceptions of pregnancy in surgical training amongst those surveyed, there is acknowledged necessity of further normalizing pregnancy and improving policies to better support pregnant residents. These data provide further evidence that though perceptions may be improving, changes are still needed to better support pregnancy during training.

Cooperation between PRMT1 and PRMT6 drives lung cancer health disparities among Black/African American men.

Lung cancer is the third most common cancer with Black/AA men showing higher risk and poorer outcomes than NHW men. Lung cancer disparities are multifactorial, driven by tobacco exposure, inequities in care access, upstream health determinants, and molecular determinants including biological and genetic factors. Elevated expressions of protein arginine methyltransferases (PRMTs) correlating with poorer prognosis have been observed in many cancers. Most importantly, our study shows that PRMT6 displays higher expression in lung cancer tissues of Black/AA men compared to NHW men. In this study, we investigated the underlying mechanism of PRMT6 and its cooperation with PRMT1 to form a heteromer as a driver of lung cancer. Disrupting PRMT1/PRMT6 heteromer by a competitive peptide reduced proliferation in non-small cell lung cancer cell lines and patient-derived organoids, therefore, giving rise to a more strategic approach in the treatment of Black/AA men with lung cancer and to eliminate cancer health disparities.

Heterogeneity of weight loss and transcriptomic signatures in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is highly associated with cachexia and weight loss, which is driven by the tumour's effect on the body. Data are lacking on differences in these metrics based on PDAC anatomic location. We hypothesize that the primary tumour's anatomic region influences the prevalence and severity of unintentional weight loss. METHODS: Treatment naïve patients with PDAC who underwent pancreatectomy at a single institution between 2012 and 2020 were identified retrospectively. Patients with pancreatic head or distal tumours were matched by sex, age, N and T stage. Serologic and anthropometric variables were obtained at the time of diagnosis. Skeletal muscle index (SMI), muscle radiation attenuation (MRA) and adiposity were measured. The primary outcome was presence of significant weight loss [>5% body weight (BW) loss in past 6 months]. Signed rank tests, Cochran Mantel Haenszel tests and Kaplan-Meier survival analysis are presented. RNA-seq of tumours was performed to explore enriched pathways related to cachexia and weight loss. RESULTS: Pancreatic head tumours (n = 24) were associated with higher prevalence (70.8% vs. 41.7%, P = 0.081) and degree of weight loss (7.9% vs. 2.5%, P = 0.014) compared to distal tumours (n = 24). BMI (P = 0.642), SMI (P = 0.738) and MRA (P = 0.478) were similar between groups. Combining BW loss, SMI and MRA into a composite score, patients with pancreatic head cancers met more criteria associated with poor prognosis (P = 0.142). Serum albumin (3.9 vs. 4.4 g/dL, P = 0.002) was lower and bilirubin (4.5 vs. 0.4 mg/dL, P < 0.001) were higher with pancreatic head tumours. Survival differed by tumour location (P = 0.014) with numerically higher median overall survival with distal tumours (11.1 vs. 21.8 months; P = 0.066). Transcriptomic analysis revealed inactivation of appetite stimulation, weight regulation and nutrient digestion/metabolism pathways in pancreatic head tumours. CONCLUSIONS: Resectable pancreatic head PDAC is associated with higher prevalence of significant weight loss and more poor prognosis features. Pancreaticobiliary obstruction and hypoalbuminemia in patients with head tumours suggests compounding effects of nutrient malabsorption and systemic inflammation on molecular drivers of cachexia, possibly contributing to shorter survival. Therefore, PDAC-associated cachexia is a heterogenous syndrome, which may be influenced by the primary tumour location. Select patients with resectable pancreatic head tumours may benefit from nutritional rehabilitation to improve outcomes.

Discovery of KRB-456, a KRAS G12D Switch-I/II Allosteric Pocket Binder That Inhibits the Growth of Pancreatic Cancer Patient-derived Tumors.

Currently, there are no clinically approved drugs that directly thwart mutant KRAS G12D, a major driver of human cancer. Here, we report on the discovery of a small molecule, KRB-456, that binds KRAS G12D and inhibits the growth of pancreatic cancer patient-derived tumors. Protein nuclear magnetic resonance studies revealed that KRB-456 binds the GDP-bound and GCP-bound conformation of KRAS G12D by forming interactions with a dynamic allosteric binding pocket within the switch-I/II region. Isothermal titration calorimetry demonstrated that KRB-456 binds potently to KRAS G12D with 1.5-, 2-, and 6-fold higher affinity than to KRAS G12V, KRAS wild-type, and KRAS G12C, respectively. KRB-456 potently inhibits the binding of KRAS G12D to the RAS-binding domain (RBD) of RAF1 as demonstrated by GST-RBD pulldown and AlphaScreen assays. Treatment of KRAS G12D-harboring human pancreatic cancer cells with KRB-456 suppresses the cellular levels of KRAS bound to GTP and inhibits the binding of KRAS to RAF1. Importantly, KRB-456 inhibits P-MEK, P-AKT, and P-S6 levels in vivo and inhibits the growth of subcutaneous and orthotopic xenografts derived from patients with pancreatic cancer whose tumors harbor KRAS G12D and KRAS G12V and who relapsed after chemotherapy and radiotherapy. These results warrant further development of KRB-456 for pancreatic cancer. SIGNIFICANCE: There are no clinically approved drugs directly abrogating mutant KRAS G12D. Here, we discovered a small molecule, KRB-456, that binds a dynamic allosteric binding pocket within the switch-I/II region of KRAS G12D. KRB-456 inhibits P-MEK, P-AKT, and P-S6 levels in vivo and inhibits the growth of subcutaneous and orthotopic xenografts derived from patients with pancreatic cancer. This discovery warrants further advanced preclinical and clinical studies in pancreatic cancer.

Cytoplasmic-delivery of polyinosine-polycytidylic acid inhibits pancreatic cancer progression increasing survival by activating Stat1-CCL2-mediated immunity.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer without effective therapies and with poor prognosis, causing 7% of all cancer-related fatalities in the USA. Considering the lack of effective therapies for this aggressive cancer, there is an urgent need to define newer and more effective therapeutic strategies. Polyinosine-polycytidylic acid (pIC) is a synthetic double-stranded RNA (dsRNA) which directly activates dendritic cells and natural killer cells inhibiting tumor growth. When pIC is delivered into the cytoplasm using polyethyleneimine (PEI), pIC-PEI, programmed-cell death is induced in PDAC. Transfection of [pIC]PEI into PDAC cells inhibits growth, promotes toxic autophagy and also induces apoptosis in vitro and in vivo in animal models. METHODS: The KPC transgenic mouse model that recapitulates PDAC development in patients was used to interrogate the role of an intact immune system in vivo in PDAC in response to [pIC]PEI. Antitumor efficacy and survival were monitored endpoints. Comprehensive analysis of the tumor microenvironment (TME) and immune cells, cytokines and chemokines in the spleen, and macrophage polarization were analyzed. RESULTS: Cytosolic delivery of [pIC]PEI induces apoptosis and provokes strong antitumor immunity in vivo in immune competent mice with PDAC. The mechanism underlying the immune stimulatory properties of [pIC]PEI involves Stat1 activation resulting in CCL2 and MMP13 stimulation thereby provoking macrophage polarization. [pIC]PEI induces apoptosis via the AKT-XIAP pathway, as well as macrophage differentiation and T-cell activation via the IFNγ-Stat1-CCL2 signaling pathways in PDAC. In transgenic tumor mouse models, [pIC]PEI promotes robust and profound antitumor activity implying that stimulating the immune system contributes to biological activity. The [pIC]PEI anti-PDAC effects are enhanced when used in combination with a standard of care (SOC) treatment, that is, gemcitabine. CONCLUSIONS: In summary, [pIC]PEI treatment is non-toxic toward normal pancreatic cells while displaying strong cytotoxic and potent immune activating activities in PDAC, making it an attractive therapeutic when used alone or in conjunction with SOC therapeutic agents, potentially providing a safe and effective treatment protocol with translational potential for the effective therapy of PDAC.

Percutaneous Dilatational Tracheostomy in a Cardiac Surgical Intensive Care Unit: A Single-Center Experience.

Background: A significant proportion of cardiac surgery intensive care unit (CSICU) patients require long-term ventilation, necessitating tracheostomy placement. The goal of this study was to evaluate the long-term postoperative outcomes and complications associated with percutaneous dilatational tracheostomy (PDT) in CSICU patients. Methods: All patients undergoing PDT after cardiac, thoracic, or vascular operations in the CSICU between January 1, 2013 and January 1, 2021 were identified. They were evaluated for mortality, decannulation time, and complications including bleeding, infection, and need for surgical intervention. Multivariable regression models were used to identify predictors of early decannulation and the complication rate. Results: Ninety-three patients were identified for this study (70 [75.3%] male and 23 [24.7%] female). Furthermore, 18.3% of patients had chronic obstructive pulmonary disease (COPD), 21.5% had history of stroke, 7.5% had end-stage renal disease, 33.3% had diabetes, and 59.1% were current smokers. The mean time from PDT to decannulation was 39 days. Roughly one-fifth (20.4%) of patients were on dual antiplatelet therapy and 81.7% had anticoagulation restarted 8 hours post-tracheostomy. Eight complications were noted, including 5 instances of bleeding requiring packing and 1 case of mediastinitis. There were no significant predictors of decannulation prior to discharge. Only COPD was identified as a negative predictor of decannulation at any point in time (hazard ratio, 0.28; 95% confidence interval, 0.08-0.95; p=0.04). Conclusion: Percutaneous tracheostomy is a safe and viable alternative to surgical tracheostomy in cardiac surgery ICU patients. Patients who undergo PDT have a relatively short duration of tracheostomy and do not have major post-procedural complications.

Race and Ethnicity Impacts Overall Survival of Patients with Appendiceal Cancer Who Undergo Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

Appendiceal cancer treatment may include cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We investigated whether patient race/ethnicity influences outcomes and overall survival for patients with appendiceal cancer who undergo CRS/HIPEC. We queried the National Cancer Database for adult patients with appendiceal cancer treated with CRS/HIPEC from 2006 to 2018. Patients were stratified by race/ethnicity: non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic, and Other. Sociodemographics and outcomes were compared using descriptive statistics. Kaplan-Meier survival analysis and Log-rank tests assessed differences in overall survival (OS). Cox Multivariate Regression evaluated factors associated with OS. In total, 2532 patients were identified: 2098 (82.9%) NHW, 186 (7.3%) NHB, 127 (5.0%) Hispanic, and 121 (4.8%) Other patients. The sociodemographics were statistically different across groups. The perioperative and postoperative outcomes were similar. OS was significantly different by race/ethnicity (p = 0.0029). NHB patients compared to Hispanic patients had the shortest median OS (106.7 vs. 145.9 months, p = 0.0093). Race/ethnicity was independently associated with OS: NHB (HR: 2.117 [1.306, 3.431], p = 0.0023) and NHW (HR: 1.549 [1.007, 2.383], p = 0.0463) patients compared to Hispanic patients had worse survival rates. Racial/ethnic disparities exist for patients with appendiceal cancer undergoing CRS/HIPEC. Despite having similar tumor and treatment characteristics, OS is associated with patient race/ethnicity.

Tumor heterogeneity: An oncogenic driver of PDAC progression and therapy resistance under stress conditions.

Pancreatic ductal adenocarcinoma (PDAC) is a clinically challenging disease usually diagnosed at advanced or metastasized stage. By this year end, there are an expected increase in 62,210 new cases and 49,830 deaths in the United States, with 90% corresponding to PDAC subtype alone. Despite advances in cancer therapy, one of the major challenges combating PDAC remains tumor heterogeneity between PDAC patients and within the primary and metastatic lesions of the same patient. This review describes the PDAC subtypes based on the genomic, transcriptional, epigenetic, and metabolic signatures observed among patients and within individual tumors. Recent studies in tumor biology suggest PDAC heterogeneity as a major driver of disease progression under conditions of stress including hypoxia and nutrient deprivation, leading to metabolic reprogramming. We therefore advance our understanding in identifying the underlying mechanisms that interfere with the crosstalk between the extracellular matrix components and tumor cells that define the mechanics of tumor growth and metastasis. The bilateral interaction between the heterogeneous tumor microenvironment and PDAC cells serves as another important contributor that characterizes the tumor-promoting or tumor-suppressing phenotypes providing an opportunity for an effective treatment regime. Furthermore, we highlight the dynamic reciprocating interplay between the stromal and immune cells that impact immune surveillance or immune evasion response and contribute towards a complex process of tumorigenesis. In summary, the review encapsulates the existing knowledge of the currently applied treatments for PDAC with emphasis on tumor heterogeneity, manifesting at multiple levels, impacting disease progression and therapy resistance under stress.

In vivo models of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high mortality rate. Within the next decade, PDAC is projected to become the second leading cause of cancer-associated death in the United States. Understanding the pathophysiology of PDAC tumorigenesis and metastases is crucial toward developing new therapeutics. One of the challenges in cancer research is generating in vivo models that closely recapitulate the genomic, histological, and clinical characteristics of human tumors. An ideal model for PDAC not only captures the tumor and stromal environment of human disease, but also allows for mutational control and is easy to reproduce in terms of time and cost. In this review, we highlight evolution of in vivo models for PDAC including spontaneous tumors models (i.e., chemical induction, genetic modification, viral delivery), implantation models including patient derived xenografts (PDX), and humanized PDX. We discuss the implementation of each system and evaluate the benefits and shortcomings of these models. Overall, this review provides a broad overview of prior and current techniques of in vivo PDAC modeling and their associated challenges.

Translocation of Oral Microbiota into the Pancreatic Ductal Adenocarcinoma Tumor Microenvironment.

Oral dysbiosis has long been associated with pancreatic ductal adenocarcinoma (PDAC). In this work, we explore the relationship between the oral and tumor microbiomes of patients diagnosed with PDAC. Salivary and tumor microbiomes were analyzed using a variety of sequencing methods, resulting in a high prevalence and relative abundance of oral bacteria, particularly Veillonella and Streptococcus, within tumor tissue. The most prevalent and abundant taxon found within both saliva and tumor tissue samples, Veillonella atypica, was cultured from patient saliva, sequenced and annotated, identifying genes that potentially contribute to tumorigenesis. High sequence similarity was observed between sequences recovered from patient matched saliva and tumor tissue, indicating that the taxa found in PDAC tumors may derive from the mouth. These findings may have clinical implications in the care and treatment of patients diagnosed with PDAC.

General Surgery Faculty Knowledge and Perceptions of Breast Pumping Amongst Postpartum Surgical Residents.

BACKGROUND: There is a lack of data regarding the knowledge and perceptions teaching faculty possess about breast pumping among general surgery residents despite breast pumping becoming more common during training. This study aimed to examine faculty knowledge and perceptions of breast pumping amongst general surgery residents. METHODS: A 29-question survey measuring knowledge and perceptions about breast pumping was administered online to United States teaching faculty from March-April 2022. Descriptive statistics were used to characterize responses, Fisher's exact test was used to report differences in responses by surgeon sex and age, and qualitative analysis identified recurrent themes. RESULTS: 156 responses were analyzed; 58.6% were male and 41.4% were female, and the majority (63.5%) were less than 50 years old. Nearly all (97.7%) women with children breast pumped, while 75.3% of men with children had partners who pumped. Men more often than women indicated "I don't know" when asked about frequency (24.7 vs. 7.9%, p = 0.041) and duration (25.0 vs. 9.5%, p = 0.007) of pumping. Nearly all surgeons are comfortable (97.4%) discussing lactation needs and support (98.1%) breast pumping, yet only two-thirds feel their institutions are supportive. Almost half (41.0%) of surgeons agreed that breast pumping does not impact operating room workflow. Recurring themes included normalizing breast pumping, creating change to better support residents, and communicating needs between all parties. CONCLUSIONS: Teaching faculty may have supportive perceptions about breast pumping, but knowledge gaps may hinder greater levels of support. Opportunities exist for increased faculty education, communication, and policies to better support breast pumping residents.

Call to action: overcoming enrollment disparities in cancer clinical trials with modernized eligibility criteria.

Traditional clinical trial eligibility criteria restrict study populations, perpetuating enrollment disparities. We aimed to assess implementation of modernized eligibility criteria guidelines among pancreatic cancer (PC) clinical trials. Interventional PC trials in the United States since January 1, 2014, were identified via clinicaltrials.gov with December 31, 2017, as the transition for pre- and postguidance eras. Trials were assessed for guideline compliance and compared using Fisher exact test. In total, 198 trials were identified: 86 (43.4%) were pre- and 112 (56.6%) postguidance era. Improvements were seen in allowing patients with history of HIV (8.6% vs 43.8%; P < .0001), prior cancer (57.0% vs 72.3%; P = .034), or concurrent and/or stable cancer (2.1% vs 31.1%; P < .0001) to participate. Most (>95%) trials were compliant with laboratory reference ranges, QT interval corrected for heart rate (QTc) cutoffs, and rationalizing excluding prior therapies both pre- and postguidance eras. However, overall compliance with modernized criteria remains poor. We advocate for stakeholders to update protocols and scrutinize traditionally restrictive eligibility criteria.

Neighbor-specific gene expression revealed from physically interacting cells during mouse embryonic development.

Development of multicellular organisms is orchestrated by persistent cell-cell communication between neighboring partners. Direct interaction between different cell types can induce molecular signals that dictate lineage specification and cell fate decisions. Current single-cell RNA-seq technology cannot adequately analyze cell-cell contact-dependent gene expression, mainly due to the loss of spatial information. To overcome this obstacle and resolve cell-cell contact-specific gene expression during embryogenesis, we performed RNA sequencing of physically interacting cells (PIC-seq) and assessed them alongside similar single-cell transcriptomes derived from developing mouse embryos between embryonic day (E) 7.5 and E9.5. Analysis of the PIC-seq data identified gene expression signatures that were dependent on the presence of specific neighboring cell types. Our computational predictions, validated experimentally, demonstrated that neural progenitor (NP) cells upregulate Lhx5 and Nkx2-1 genes, when exclusively interacting with definitive endoderm (DE) cells. Moreover, there was a reciprocal impact on the transcriptome of DE cells, as they tend to upregulate Rax and Gsc when in contact with NP cells. Using individual cell transcriptome data, we formulated a means of computationally predicting the impact of one cell type on the transcriptome of its neighboring cell types. We have further developed a distinctive spatial-t-distributed stochastic neighboring embedding to display the pseudospatial distribution of cells in a 2-dimensional space. In summary, we describe an innovative approach to study contact-specific gene regulation during embryogenesis.

From Mouth to Muscle: Exploring the Potential Relationship between the Oral Microbiome and Cancer-Related Cachexia.

Cancer cachexia is a multifactorial wasting syndrome associated with skeletal muscle and adipose tissue loss, as well as decreased appetite. It affects approximately half of all cancer patients and leads to a decrease in treatment efficacy, quality of life, and survival. The human microbiota has been implicated in the onset and propagation of cancer cachexia. Dysbiosis, or the imbalance of the microbial communities, may lead to chronic systemic inflammation and contribute to the clinical phenotype of cachexia. Though the relationship between the gut microbiome, inflammation, and cachexia has been previously studied, the oral microbiome remains largely unexplored. As the initial point of digestion, the oral microbiome plays an important role in regulating systemic health. Oral dysbiosis leads to the upregulation of pro-inflammatory cytokines and an imbalance in natural flora, which in turn may contribute to muscle wasting associated with cachexia. Reinstating this equilibrium with the use of prebiotics and probiotics has the potential to improve the quality of life for patients suffering from cancer-related cachexia.

Cell Competition in Carcinogenesis.

The majority of human cancers evolve over time through the stepwise accumulation of somatic mutations followed by clonal selection akin to Darwinian evolution. However, the in-depth mechanisms that govern clonal dynamics and selection remain elusive, particularly during the earliest stages of tissue transformation. Cell competition (CC), often referred to as 'survival of the fittest' at the cellular level, results in the elimination of less fit cells by their more fit neighbors supporting optimal organism health and function. Alternatively, CC may allow an uncontrolled expansion of super-fit cancer cells to outcompete their less fit neighbors thereby fueling tumorigenesis. Recent research discussed herein highlights the various non-cell-autonomous principles, including interclonal competition and cancer microenvironment competition supporting the ability of a tumor to progress from the initial stages to tissue colonization. In addition, we extend current insights from CC-mediated clonal interactions and selection in normal tissues to better comprehend those factors that contribute to cancer development.

Patient-Derived Pancreatic Cancer Cells Induce C2C12 Myotube Atrophy by Releasing Hsp70 and Hsp90.

Pancreatic cancer (PC) patients are highly prone to cachexia, a lethal wasting syndrome featuring muscle wasting with an undefined etiology. Recent data indicate that certain murine cancer cells induce muscle wasting by releasing Hsp70 and Hsp90 through extracellular vesicles (EVs) to activate p38ß MAPK-mediated catabolic pathways primarily through Toll-like receptor 4 (TLR4). However, whether human PC induces cachexia through releasing Hsp70 and Hsp90 is undetermined. Here, we investigated whether patient-derived PC cells induce muscle cell atrophy directly through this mechanism. We compared cancer cells isolated from patient-derived xenografts (PDX) from three PC patients who had cachexia (PCC) with those of three early-stage lung cancer patients without cachexia (LCC) and two renal cancer patients who were not prone to cachexia (RCC). We observed small increases of Hsp70 and Hsp90 released by LCC and RCC in comparison to non-cancer control cells (NCC). However, PCC released markedly higher levels of Hsp70 and Hsp90 (~ 6-fold on average) than LCC and RCC. In addition, PCC released similarly increased levels of Hsp70/90-containing EVs. In contrast to RCC and LCC, PCC-conditioned media induced a potent catabolic response in C2C12 myotubes including the activation of p38 MAPK and transcription factor C/EBPß, upregulation of E3 ligases UBR2 and MAFbx, and increase of autophagy marker LC3-II, resulting in the loss of the myosin heavy chain (MHC ~50%) and myotube diameter (~60%). Importantly, the catabolic response was attenuated by Hsp70- and Hsp90-neutralizing antibodies in a dose-dependent manner. These data suggest that human PC cells release high levels of Hsp70 and Hsp90 that induce muscle atrophy through a direct action on muscle cells.

Racial Disparities in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Does Aggressive Surgical Treatment Overcome Cancer Health Inequities?

Background: Advanced cancer states perpetuate health-related disparities. Peritoneal-based cancers are clinically advanced cancers that present a significant clinical dilemma. Peritoneal cancers are managed aggressively with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). While racial and ethnic disparities are prevalent in cancer, there are no studies investigating if racial disparities exist in patients with peritoneal carcinomatosis managed with CRS and HIPEC. We hypothesized that this advanced disease state further delineates racial disparities. Methods: A retrospective chart review was conducted on patients with peritoneal carcinomatosis receiving CRS and HIPEC at a single institution from January 1, 2017-October 4, 2021. Descriptive statistics were used to compare racial groups. The Cox Proportional Hazards Model and Log Rank Test were used for multivariate and overall survival analysis. Results: In total, 67 patients underwent CRS and HIPEC, of which 41 (61.2%) were White, 20 (29.8%) were Black, 3 (4.5%) were Asian, and 3 (4.5%) were Other race. When compared to White patients, Black patients had lower income (p=0.0011), higher incidence of hypertension (p=0.0231), and lower performance status (p=0.0441). Cancer type, including colorectal, appendiceal, ovarian, etc., was similar between groups (p=0.8703). Despite these differences in sociodemographic and morbidity factors, when comparing Black patients to White patients, there were no differences in peritoneal cancer index score (13.2 vs. 12.3, p=0.6932), estimated blood loss (748 vs. 655 mL, p=0.6332), minor/major complication rates (1.1 vs. 1.2, p=0.7281; 0.4 vs. 0.7, p=0.3470, respectively), 30-day readmission rates (25.0% vs. 17.1%, p=0.6210), disease recurrence (40.0% vs. 51.2%, p=0.3667), or 30-day mortality (0.0% vs. 2.4%, p=1.0000). Overall survival was similar for Black and White patients (p=0.2693). The occurrence of a major complication was the only factor associated with overall survival (HR 2.188 [1.502, 3.188], p< 0.0001). Conclusions: Despite differences in patient socioeconomic factors and comorbid conditions, outcomes were similar between Black and White patients receiving CRS and HIPEC at our institution. While larger studies with more diverse patient populations are needed to confirm these findings, our data provide evidence that aggressive surgical management across diverse patient populations allows for equitable outcomes.

A Review of the Clinical Implications of Cachexia, Sarcopenia, and BMI in Patients with Peritoneal Carcinomatosis Receiving Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Peritoneal carcinomatosis (PC) is the dissemination of cancer throughout the peritoneal cavity. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is the surgical treatment of choice in highly selected patients. The aim of this narrative review was to assess the impact of cachexia, sarcopenia, and body mass index (BMI) on patient outcomes for patients undergoing CRS and HIPEC for peritoneal carcinomatosis. A narrative review was performed and articles pertaining to cachexia, sarcopenia, BMI, peritoneal carcinomatosis, and CRS/HIPEC were reviewed and selected. In total, 3041 articles were screened and seven original studies met the inclusion criteria. In summary, obesity was found to not be a contraindication to surgery, but the impact of BMI was variable across the spectrum. Decreased skeletal muscle mass was found to be associated with poorer postoperative outcomes in three studies and with worse overall survival in two. With limited data, evaluating the impact of BMI, sarcopenia, and cachexia on patients with PC undergoing CRS and HIPEC was difficult as most studies included heterogeneous cancer patient populations; thus, postoperative outcomes and survival were inconsistent across studies. More research is needed to better understand its impact and to better generalize the results for each cancer subset treated with CRS and HIPEC across diverse patient populations.

Utilization of Supplemental Regional Anesthesia in Lobectomy for Lung Cancer in the United States: A Retrospective Study.

Background: Pulmonary lobectomy is the standard of care for the treatment of early-stage non-small cell lung cancer. This study investigated the rate of utilization of supplemental anesthesia in patients undergoing video-assisted thoracoscopic surgery (VATS) or open lobectomy using a national database and assessed the effect of regional block (RB) on postoperative outcomes. Methods: Patients who underwent lobectomy for lung cancer between 2014-2019 were identified in the American College of Surgeons National Surgical Quality Improvement Program. The patients' primary mode of anesthesia and supplemental anesthesia were recorded. Preoperative characteristics and postoperative outcomes were compared between 2 surgical groups: those who underwent general anesthesia (GA) alone versus GA with RB. Multivariable regression analyses were performed on the outcomes of interest. Results: In total, 13,578 patients met the study criteria, with 87% undergoing GA and the remaining 13% receiving GA and RB. The use of neuraxial anesthesia decreased over the years, while RB use increased up to 20% in 2019. Age, body mass index, and preoperative comorbidities were comparable between groups. Patients who underwent VATS were more likely to receive RB than those who underwent thoracotomy. RB was most often utilized by thoracic surgeons. An adjusted analysis showed that RB use was associated with shorter hospital stays and a reduced likelihood of prolonged length of stay, but a higher rate of surgical site infections (SSIs). Conclusion: In a large surgical database, there was underutilization of supplemental anesthesia in patients undergoing lobectomy for lung cancer. RB utilization was associated with a shorter length of hospital stay and an increase in SSI incidence.