Comparing Outcomes in Patients Undergoing Colectomy at Veteran Affairs Hospitals and Non-Veteran Affairs Hospitals: A Multiinstitutional Study.

INTRODUCTION: The Veteran Affairs Surgical Quality Improvement Program (VASQIP) and National Surgical Quality Improvement Program (NSQIP) are large databases designed to measure surgical outcomes for their respective populations. We sought to compare surgical outcomes in patients undergoing colectomies at Veterans Affairs (VA) hospitals versus non-VA hospitals. METHODS: After institutional review baord approval, records for 271,523 colectomies from NSQIP and 11,597 from VASQIP between the years 2015 and 2019 were compiled. Demographics, comorbidity, 30-d mortality, and other outcomes were examined using Chi-squared, analysis of variance, Mann Whitney U, and Fisher's Exact Test within SPSS version 26. RESULTS: VASQIP patients were more likely to be male (94.3% versus 48.4%, P < 0.001) and older (median 63, 52-72 versus 67, 60-72 P < 0.001). Veterans were also more likely to have diabetes (25.3% versus 15.8%, P < 0.001), chronic obstructive pulmonary disease (15.4% versus 5.5%, P < 0.001), and congestive heart failure (17.0% versus 1.3%, P < 0.001). Veterans had slightly better 30-d mortality (2.4% versus 2.8%, P = 0.003), less organ space infections (2.8% versus 5.8%, P < 0.001), or postoperative sepsis (3.4% versus 5.3%). Non-VA patients were more likely to be having emergent surgery (13.4% versus 9.6%, P < 0.001) or undergo a laparoscopic approach (57.9% versus 50.2%, P < 0.001). Non-VA patients had shorter postoperative length of stay (5.99 d versus 7.32 d, P < 0.001) and were less likely to return to the operating room (5.3% versus 8.4%, P < 0.001) CONCLUSIONS: Despite increased comorbidity, VA hospitals and hospitals enrolled in NSQIP have managed to achieve markedly similar rates of 30-d mortality following colectomy. Further study is needed to better understand the differences between both the populations and surgical outcomes between VA hospitals and non-VA hospitals.

Robotic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: is there a benefit?

BACKGROUND: Open cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is a therapeutic option for the management of malignancies with peritoneal carcinomatosis and of peritoneal origin. Robotic surgery shows promise as a minimally invasive approach for select patients. We aimed to evaluate the differences in outcomes between robotic versus open CRS/HIPEC and hypothesized less morbidity and faster recovery in the robotic approach group. METHODS: We conducted a retrospective cohort study from our HIPEC database including all tumor origins. We included patients aged 18-89 years who underwent CRS/HIPEC for curative intent at a single institution between January 1, 2017, and December 31, 2023. Patients were stratified by open versus robotic-assisted surgery. Mann-Whitney U and Fisher Exact tests were used to compare differences in patient characteristics and outcomes. RESULTS: A total of 111 patients underwent CRS/HIPEC for curative intent, with 95 (85.6%) cases performed open and 16 (14.4%) robotically. The groups were demographically similar, except patients undergoing robotic CRS/HIPEC had a significantly higher median income ($83,845 vs. $70,519, p < 0.001). Rate of comorbidities and cancer type, including appendiceal, colorectal, and ovarian, were the same. The peritoneal carcinomatosis index and completion of cytoreduction score were similar between groups. Robotic approach was associated with statistically significant lower estimated blood loss (113 vs. 400 mL, p < 0.001) and postoperative transfusions (6.3% vs. 23.2%, p = 0.036). Total complications, readmission rates, and 30-day mortality were similar among groups, but the robotic group had a significantly shorter length of stay (5.5 vs. 9 d., p < 0.001). CONCLUSION: Robotic CRS/HIPEC holds promise to decrease intraoperative blood loss, blood transfusions, and hospital stay while providing similar immediate postoperative outcomes in select patients. These results should be validated in the setting of a prospective trial and effects on long-term oncologic outcomes should be investigated.

Validating biologic age in selecting elderly patients with pancreatic cancer for surgical resection.

BACKGROUND AND OBJECTIVES: Selecting frail elderly patients with pancreatic cancer (PC) for pancreas resection using biologic age has not been elucidated. This study determined the feasibility of the deficit accumulation frailty index (DAFI) in identifying such patients and its association with surgical outcomes. METHODS: The DAFI, which assesses frailty based on biologic age, was used to identify frail patients using clinical and health-related quality-of-life data. The characteristics of frail and nonfrail patients were compared. RESULTS: Of 242 patients (median age, 75.5 years), 61.2% were frail and 32.6% had undergone pancreas resection (surgery group). Median overall survival (mOS) decreased in frail patients (7.13 months, 95% confidence interval [CI]: 5.65-10.1) compared with nonfrail patients (16.1 months, 95% CI: 11.47-34.40, p = 0.001). In the surgery group, mOS improved in the nonfrail patients (49.4%; 49.2 months, 95% CI: 29.3-79.9) compared with frail patients (50.6%, 22.1 months, 95% CI: 18.3-52.4, p = 0.10). In the no-surgery group, mOS was better in nonfrail patients (54%; 10.81 months, CI 7.85-16.03) compared with frail patients (66%; 5.45 months, 95% CI: 4.34-7.03, p = 0.02). CONCLUSIONS: The DAFI identified elderly patients with PC at risk of poor outcomes and can identify patients who can tolerate more aggressive treatments.

Age-related next-generation sequencing mutational analysis in 1196 melanomas.

BACKGROUND AND OBJECTIVES: Melanoma mutational burden is high and approximately 50% have oncogenic mutations in BRAF. We sought to evaluate age-related mutational differences in melanoma. METHODS: We analyzed melanoma samples in the Genomics Evidence Neoplasia Information Exchange database. Targetable mutations were identified using the Precision Oncology Knowledge Base (OncoKB). RESULTS: We found 1194 patients with a common set of 30 genes. The top mutated genes in patients <40 years old (y/o) (n = 98) were BRAF (59%), TP53 (31%), NRAS (17%), and PTEN (14%); in 40-59 y/o (n = 354) were BRAF (51%), NRAS (30%), TP53 (26%), and APC (13%); and in ≥60 y/o (n = 742) were BRAF (38%), NRAS (33%), TP53 (26%), and KDR (19%). BRAF mutations were almost mutually exclusive from NRAS mutations in <40 y/o (58/59). Mutational burden increased with age, with means of 2.39, 2.92, and 3.67 mutations per sample in patients <40, 40-59, and ≥60 y/o, respectively (p < 0.0001). There were 10 targetable mutations meeting OncoKB criteria for melanoma: BRAF (level 1), RET (level 1), KIT (level 2), NRAS (level 3A), TP53 (level 3A), and FGFR2, MET, PTEN, PIK3CA, and KRAS (level 4). CONCLUSIONS: Mutations in melanoma have age-related differences and demonstrates potential targetable mutations for personalized therapies.

Establishing Novel Molecular Subtypes of Appendiceal Cancer.

PURPOSE: Appendiceal cancer is a rare disease process with complex treatment strategies. The objective of this study was to identify mutation-based genetic subtypes that may differ from the current histological classification, compare the genetic make-up of primaries and metastases, and find novel targetable alterations. METHODS: The analyses involved the curation and normalization of gene mutation panels from appendiceal adenocarcinoma and mucinous adenocarcinoma (n = 196) stored in the AACR GENIE Database v6.0. Genes mutated in less than one patient and tumors profiled with incomplete mutation panels were excluded from the study. The optimal number of AC subtypes was established using the Nonnegative Matrix Factorization algorithm. Statistical comparisons of mutation frequencies were performed using Pearson's χ2 test. RESULTS: AC patients were stratified into five mutation subtypes, based on a final set of 41 cancer-related genes. AC0 had no mutations. The most frequently mutated genes varied between the subtypes were: AC1: KRAS (91.9%) and GNAS (77.4%); AC2: KRAS (52.5%), APC (32.5%), and GNAS (30%); AC3: KMT2D (38.7%), TP53 (38.7%), KRAS (35.5%), EP300 (22.6%); and AC4: TP53 (97.2%), KRAS (77.8%), and SMAD4 (36.1%). Additionally, AC3 was less likely to be mucinous (22.6% vs. 50.0-74.2%, p < 0.001) and had a higher mutation frequency (3.6 vs. 0-3.1, p < 0.001). There were no significant differences between primary tumors and metastases in the 41 assessed genes (p = 0.35). CONCLUSIONS: The characterization of these subtypes suggests a need for molecular approaches to complement anatomical and histopathological staging for AC. A prospective comparison of subtype prognosis and response to surgery and adjuvant treatment is needed to identify the clinical applications of the novel molecular subtypes.

Delay in surgery is associated with axillary upstaging of clinically node negative breast cancer patients.

BACKGROUND AND OBJECTIVES: Most breast cancer (BC) patients present with early disease and clinically negative lymph nodes (cN0). Timing of surgery has not been standardized. We hypothesized that surgical delay results in an increased likelihood of nodal metastasis. METHODS: Patients diagnosed with cN0 BC undergoing surgery with sentinel lymph node biopsy as initial therapy between 2006 and 2014 were identified in the NCDB and divided into four groups based on time intervals between diagnosis and surgery (<4 weeks, 4-8 weeks, 8-12 weeks, and >12 weeks). Regression analysis evaluated the independent impact of surgical timing on axillary upstaging and survival. RESULTS: Of 355,443 patients with cN0 BC, 39.6% had surgery within 4 weeks and 5.4% more than 12 weeks from diagnosis. After controlling for relevant factors, a month delay in surgery was associated with an increased likelihood of nodal positivity (odds ratio: 1.04; 95% confidence interval [CI]: 1.04-1.05; p < .001) and decreased overall survival (hazard ratio: 1.03; 95% CI: 1.02-1.04; p < .001). When compared to patients who underwent surgery less than 4 weeks from diagnosis, the absolute increase in nodal positivity and relative risks were 5.3% (95% CI: 0.047-0.059) and 1.34 (95% CI: 1.30-1.38), respectively, in the more than 12 weeks group. CONCLUSIONS: Delay in BC surgery in cN0 patients was associated with an increased likelihood of axillary upstaging and decreased survival.

Inaccurate pretreatment staging can impact survival in early stage esophageal adenocarcinoma.

BACKGROUND: Given the survival advantage of neoadjuvant treatment for locally advanced esophageal cancer, accurate clinical staging is necessary. The aim of this study was to assess the clinical (c) and pathologic (p) staging concordance rates for presumably early stage esophageal adenocarcinoma patients that had upfront esophagectomy (UFE) and evaluate if survival (OS) was negatively affected by inaccurate preoperative staging and subsequent treatment selection. METHODS: An NCDB retrospective review of nonmetastatic esophageal adenocarcinoma patients that had UFE. The rates of concordance between c and p staging system and OS were calculated. RESULTS: Of 2775 patients, most patients presented with cN0 (82.8%) and cT1 tumors (53.6%). The overall concordance between c and p staging was 78.8% for T-classification (moderate agreement; weighted κ = 0.729; P < .001) and 78.8% for N-classification (weak agreement; weighted κ = 0.448; P < .001). Patients that were upstaged due to a lack of concordance between T-classification had decreased 5- and 10-year OS (30% and 16%, P < .001) and those upstaged due to discordant N-classification had decreased 5- and 10-year OS (28% and 23%, P < .001)." CONCLUSIONS: Preoperative staging of esophageal adenocarcinoma has moderate reliability and accuracy for predicting pT and pN classification. Up to 25% of patients have discordant clinical and pathological staging, which impacts OS.

Changing Trends in Industry Funding for Surgical Oncologists.

BACKGROUND: With reductions in public funding, alternate research funding is essential to surgical oncologists (SOs). We aimed to examine current trends in industry funding of SOs. METHODS: Society of Surgical Oncology surgeons were identified and matched with board certification and years in practice. Departmental and hospital data were evaluated, and industry payments from 2013 to 2017 were matched with the Open Payment Data. RESULTS: Of the 1670 SOs identified, 922 (55%) had academic positions: 588 (64%) males and 334 (36%) females. Between 2013 and 2017, research payments totaling $46,596,706 were made to 162 SOs (17.5%): $40,774,716 (87%) for research related to drugs and clinical trials, compared with $5,194,199 (11%) for surgical devices (p = 0.018). Funding correlated with academic leadership and years in practice (p = 0.0001 and p = 0.0037). Massachusetts ($9,060,976), Texas ($7,656,228), and New York ($4,210,864) received the most funding, whereas Utah ($1,533,166/SO), Massachusetts ($1,294,425/SO), and Oregon ($1,241,702/SO) received the highest average payments per SO. The majority of funding was from Novartis ($16,045,608), Amgen ($6,810,832), and Merck ($3,758,299), for an oncolytic vaccine (talimogene laherparepvec, $5,939,007), a BRAF inhibitor (dabrafenib, $5,727,309), and a KIT inhibitor (imatinib, $4,323,586). Male SOs received funding more frequently than females (120/588 [20%] vs. 42/334 [12.6%]; p = 0.0027). Males also received more general payments (travel/lodging, food/beverage, consulting/speaker fees): $48,830 vs. $11,867 per male and female, respectively (p = 0.0001). CONCLUSIONS: The majority of industry research payments to SOs are related to novel pharmaceuticals, which highlights the expanding influence SOs play in systemic therapies. Industry payments are influenced by location, gender, and academic leadership.

Venous thromboembolism in patients with cancer undergoing surgical exploration.

Malignancy and surgery are both independent risk factors for venous thromboembolism (VTE) events. The current NCCN guidelines recommend VTE prophylaxis for up to 28 days after major abdominal or pelvic surgery for malignancy. We set out to evaluate the rate and timing of VTEs among patients with gastric, pancreatic, colorectal, and gynecologic malignancies who underwent surgery. We performed a retrospective review of the NSQIP database (2005-2013) focusing on patients with gastric, colorectal, pancreatic, and gynecologic malignancies. Our primary endpoint was a diagnosis of VTE within 30 days of surgery. We analyzed 128,864 patients in this study. On multivariable analysis, patients with pre-operative sepsis (OR 2.36, CI 2.04-2.76, p < 0.001), disseminated cancer (OR 1.73, CI 1.55-1.92, p < 0.001), congestive heart failure (OR 1.69, CI 1.25-2.28, p = 0.001), gastric cancer (OR 1.3, CI 1.09-1.56, p = 0.004), and pancreatic cancer (OR 1.2, CI 1.03-1.30, p = 0.021) were more likely to have a VTE. Of patients who had a VTE event, 34% occurred after discharge from surgery (gastric: 25%, colorectal 34%, pancreatic 31%, gynecologic malignancy 42%). Our study demonstrates that patients who undergo an operation for malignancy with pre-operative sepsis, disseminated cancer, congestive heart failure, gastric cancer, or pancreatic cancer are more likely to develop a VTE within 30 days of their operation. Of those patients who developed a VTE, approximately one-third occurred after discharge during a 30 day post-operative period. This data supports that further studies are needed to determine the appropriate length of post-operative VTE chemoprophylaxis in patients with cancer.

SRT1720, a sirtuin 1 activator, attenuates organ injury and inflammation in sepsis.

BACKGROUND: Sepsis affects 800,000 patients in the United States annually with a mortality rate of up to 30%. Recent studies suggest that sepsis-associated metabolic derangements due to hypoxic tissue injury, impaired oxygen utilization, and mitochondrial dysfunction contribute to mortality. Sirtuin 1 (Sirt1) is a crucial modulator of energy metabolism during starvation states and has anti-inflammatory effects. Here, we hypothesized that SRT1720, a Sirt1 activator, could attenuate the severity of sepsis. MATERIALS AND METHODS: Male C57BL/6 mice (20-25 g) were subjected to cecal ligation and puncture (CLP) to induce sepsis. SRT1720 (5 or 20 mg/kg BW) or 10% dimethyl sulfoxide (vehicle) in 0.2-mL saline was injected intravenously at 5 h after CLP. Control animals were not subjected to any surgery. Blood and liver samples were harvested at 20 h after CLP for analysis. RESULTS: Administration of SRT1720 markedly reduced the serum levels of tissue injury markers (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase) and renal injury markers (blood urea nitrogen and creatinine) in a dose-dependent manner after CLP. Furthermore, the levels of proinflammatory cytokines interleukin (IL)-1ß and IL-6 in the serum and liver were significantly inhibited by SRT1720 treatment after CLP. SRT1720 treatment resulted in a significantly decreased mRNA expression of inflammasome components (nucleotide oligomerization domain-like receptor protein 3, adapter apoptosis-associated speck-like protein containing caspase-recruitment domain, IL-1ß, and IL-18) in the liver, compared with the vehicle group. CONCLUSIONS: SRT1720 treatment attenuates multiorgan injury in septic mice. SRT1720 treatment also decreases the production of proinflammatory cytokines and reduces inflammasome activation. Thus, pharmacologic stimulation of Sirt1 may present a promising therapeutic strategy for sepsis.

Sirtuin 1 Stimulation Attenuates Ischemic Liver Injury and Enhances Mitochondrial Recovery and Autophagy.

OBJECTIVES: Hepatic ischemia-reperfusion is a major clinical problem with limited treatment options. The pathophysiology of hepatic ischemia-reperfusion is characterized by mitochondrial dysfunction and cellular energy deficits. Sirtuin 1 is an energy-sensing enzyme known to modulate mitochondrial biogenesis. We hypothesized that pharmacologic activation of sirtuin 1 is protective after hepatic ischemia-reperfusion injury. DESIGN: Animal study. SETTING: University-based experimental laboratory. SUBJECTS: Wild-type C57BL/6 mice. INTERVENTIONS: C57BL/6 mice were subjected to 60-minute partial hepatic ischemia-reperfusion and posttreated with sirtuin 1 activator, SRT1720 (20 mg/kg), or vehicle. Blood and liver were collected at 24 hours after ischemia-reperfusion for analyses of hepatic injury, adenosine triphosphate levels, mitochondrial mass, autophagy, inflammation, and oxidative stress. H4IIE hepatoma cells and rat primary hepatocytes were incubated with oxyrase to induce hypoxia followed by reoxygenation in the presence or absence of SRT1720 for assessment of mitochondrial mass, mitochondrial membrane potential, and autophagy. MEASUREMENTS AND MAIN RESULTS: SRT1720 restored the reduction in mitochondrial mass, enhanced autophagy, and preserved adenosine triphosphate levels in the liver after ischemia-reperfusion, which was associated with a decrease in ischemia-reperfusion-induced hepatic injury, apoptosis, and necrosis. Ischemia-reperfusion-induced inflammation was also significantly reduced by SRT1720 as measured by systemic and hepatic cytokine and chemokine levels, as well as a decrease in neutrophil infiltration to the liver. Furthermore, oxidative stress was markedly attenuated in the SRT1720-treated mice compared with the vehicle. SRT1720 treatment increased adenosine triphosphate levels and survival of cultured hepatocytes after hypoxia-reoxygenation. SRT1720 not only increased the mitochondrial mass but also increased mitochondrial membrane potential per cell in cultured hepatocytes after hypoxia-reoxygenation. Moreover, SRT1720 prevented the hypoxia-reoxygenation-induced mitochondrial depolarization and resulted in an enhancement of autophagy in cultured hepatocytes after hypoxia-reoxygenation. CONCLUSIONS: Pharmacologic stimulation of sirtuin 1 attenuates liver injury after hepatic ischemia-reperfusion by restoring mitochondrial mass and membrane potential, which is associated with the enhancement of autophagy.

Novel resveratrol analogues attenuate renal ischemic injury in rats.

BACKGROUND: Renal ischemia-reperfusion (I/R) is a severe clinical complication with no specific treatment. Resveratrol has been shown as a promising experimental agent in renal I/R due to its effect on cellular energy metabolism, oxidative stress, and inflammation. Recently, we identified two biologically active resveratrol analogues (RSVAs), RSVA405 and RSVA314. We hypothesized that both RSAVs would attenuate I/R-induced renal injury. METHODS: Adult male rats were subjected to renal I/R through bilateral renal pedicle clamping for 60 min, followed by reperfusion. RSVA405 (3 mg/kg Body Weight), RSVA314 (3 mg/kg Body Weight), or vehicle (10% dimethyl sulfoxide and 33% Solutol in phosphate buffered saline) were administered by intraperitoneal injection 1 h before ischemia. Blood and renal tissues were collected 24 h after I/R for evaluation. RESULTS: Administration of RSVA405 and RSVA314 significantly reduced the serum levels of renal dysfunction and injury markers, including creatinine, blood urea nitrogen, aspartate aminotransferase, and lactate dehydrogenase, compared with vehicle. The protective effect of RSVA405 and RSVA314 was also reflected on histologic evaluation. Both RSVAs reduced the number of apoptotic cells by more than 60% as determined by transferase dUTP nick end labeling assay, compared with vehicle. The renal adenosine triphosphate levels of the vehicle group was decreased to 52.4% of control, whereas those of the RSVA405 and RSVA314 groups were restored to 72.3% and 79.6% of control, respectively. Both RSVAs significantly reduced the protein expression of inducible nitric oxide synthase and nitrotyrosine and the messenger RNA levels of tumor necrosis factor-α, interleukin-6, and interleukin-1ß. CONCLUSIONS: RSVA405 and RSVA314 attenuate I/R-induced renal injury through the modulation of energy metabolism, oxidative stress, and inflammation.

Neutralization of osteopontin attenuates neutrophil migration in sepsis-induced acute lung injury.

INTRODUCTION: Sepsis refers to severe systemic inflammation leading to acute lung injury (ALI) and death. Introducing novel therapies can reduce the mortality in ALI. Osteopontin (OPN), a secretory glycoprotein produced by immune reactive cells, plays a deleterious role in various inflammatory diseases. However, its role in ALI caused by sepsis remains unexplored. We hypothesize that treatment with an OPN-neutralizing antibody (anti-OPN Ab) protects mice against ALI during sepsis. METHODS: Sepsis was induced in 8-week-old male C57BL/6 mice by cecal ligation and puncture (CLP). Anti-OPN Ab or non-immunized IgG as control, at a dose of 50 µg/mouse, was intravenously injected at the time of CLP. After 20 hours, the expression of OPN and proinflammatory cytokines in tissues and plasma was examined by real-time PCR, Western blot, and ELISA. Plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) and the lung myeloperoxidase (MPO) levels were determined by colorimetric assays. Lung damage and neutrophil infiltrations were determined by histological H&E and Gr-1 staining, respectively. The effect of recombinant mouse OPN (rmOPN) on human neutrophil-like cell (HL-60) migration was performed by Boyden chamber assays and the involvement of intracellular signaling molecules in HL-60 cells was revealed by Western blot. RESULTS: After 20 hours of sepsis, mRNA and protein levels of OPN were significantly induced in lungs, spleen, and plasma. Treatment with an anti-OPN Ab in septic mice significantly reduced the plasma levels of ALT, AST, and LDH, and the proinflammatory cytokines IL-6, IL-1ß and the chemokine MIP-2, compared with the vehicle group. Similarly, the lung mRNA and protein expressions of proinflammatory cytokines and chemokine were greatly reduced in anti-OPN Ab-treated animals. The lung histological architecture, MPO and neutrophil infiltration were significantly improved in anti-OPN Ab-treated mice compared with the vehicle animals. Treatment of rmOPN in HL-60 cells significantly increased their migration, in vitro. The neutrophils treated with rmOPN remarkably increased the levels of phospho focal adhesion kinase (pFAK), phospho extracellular signal-regulated kinase (pERK) and phospho p38. CONCLUSIONS: Our findings clearly demonstrate the beneficial outcomes of anti-OPN Ab treatment in protecting against ALI, implicating a novel therapeutic strategy in sepsis.

Just the gastrointestinal stromal tumor: A case report of medical modeling of a rectal gastrointestinal stromal tumor.

A 54-year-old African-American male presented to the colorectal surgery clinic with the chief complaint of a painful anal swelling that had been ongoing for several weeks. An adequate rectal examination was not possible due to severe pain. Therefore, he was taken to the operating room for an exam under anesthesia where a presacral mass was identified. A transgluteal core needle biopsy was performed which was consistent with gastrointestinal stromal tumor. Computed tomography imaging identified a 16 cm ×10 cm ×9 cmrectal gastrointestinal stromal tumor. Given the size and location, the patient began treatment with neoadjuvant Imatinib. His progress was followed with serial computed tomography scans and clinic visits. A 3D model was created the tumor and surrounding structures to aide in pre- and intraoperative planning. The model was utilized during patient education and found to valuable in describing the potential for levator invasion and framing potential post-operative outcomes. The patient was able to undergo rectal preservation via a robotic low anterior resection with a transanal total mesorectal excision, coloanal anastomosis, and diverting ileostomy.

Exploring the Genomic Landscape of Hepatobiliary Cancers to Establish a Novel Molecular Classification System.

Taxonomy of hepatobiliary cancer (HBC) categorizes tumors by location or histopathology (tissue of origin, TO). Tumors originating from different TOs can also be grouped by overlapping genomic alterations (GA) into molecular subtypes (MS). The aim of this study was to create novel HBC MSs. Next-generation sequencing (NGS) data from the AACR-GENIE database were used to examine the genomic landscape of HBCs. Machine learning and gene enrichment analysis identified MSs and their oncogenomic pathways. Descriptive statistics were used to compare subtypes and their associations with clinical and molecular variables. Integrative analyses generated three MSs with different oncogenomic pathways independent of TO (n = 324; p < 0.05). HC-1 "hyper-mutated-proliferative state" MS had rapidly dividing cells susceptible to chemotherapy; HC-2 "adaptive stem cell-cellular senescence" MS had epigenomic alterations to evade immune system and treatment-resistant mechanisms; HC-3 "metabolic-stress pathway" MS had metabolic alterations. The discovery of HBC MSs is the initial step in cancer taxonomy evolution and the incorporation of genomic profiling into the TNM system. The goal is the development of a precision oncology machine learning algorithm to guide treatment planning and improve HBC outcomes. Future studies should validate findings of this study, incorporate clinical outcomes, and compare the MS classification to the AJCC 8th staging system.

Trends in Resident Supervision and Patient Outcomes of Laparoscopic Cholecystectomies Within the Veterans Affairs Healthcare System.

OBJECTIVE: We sought to use the Veterans Affairs Surgical Quality Improvement Program (VASQIP) database to determine if there is an increase in morbidity or mortality when resident physicians independently perform laparoscopic cholecystectomy compared to when an attending surgeon is scrubbed. DESIGN: We performed a retrospective review of 54,144 cases of laparoscopic cholecystectomy performed within the Veterans Affairs (VA) Healthcare system from 2000 to 2020. Cases were divided into groups based on if the attending was scrubbed or not scrubbed. We then performed 1:1 case matching without replacement based on sex, race, and major comorbidities. PARTICIPANTS: Veterans over age 18 undergoing laparoscopic cholecystectomy within the VA healthcare system between 2000 and 2020. Cases were excluded if a resident was not involved in the surgery or if the level of autonomy was not defined. RESULTS: Significantly more operative cases were performed without the attending scrubbed before 2003 than after (14.6% vs 1.60%, p < 0.01). After matching, in 1464 (48.6%) cases the attending physician was scrubbed, and in 1549 (51.4%) the attending physician was not scrubbed. Patients were statistically similar in all measured comorbidities between the groups. Operative time was noted to be slightly longer when the attending was scrubbed (1.86 hours ± 0.79 vs 1.72 ± 0.67, p < 0.01) as well as increased complication rates (9.0% vs 6.1%, p < 0.01). No differences existed for 30-day mortality (0.8% vs 0.5%, p = 0.416), postoperative length of stay (2.7 days vs 2.96 days, p = 0.43), or superficial infection (1.9% vs 1.7%, p = 0.73). CONCLUSIONS: Our analysis of the VASQIP database indicates that decreased resident supervision during laparoscopic cholecystectomy has minimal impact on patient outcomes. Rates of resident independent operating have declined 10-fold since the early 2000's. Further research is required to better define the changes in resident surgical education and their impact on patient outcomes.

Disparities in the impact of the AJCC 8th edition staging system on differentiated thyroid cancer outcomes.

BACKGROUND: The impact of AJCC8 among self-reported racial/ethnic groups on differentiated thyroid cancer (DTC) outcomes is unknown. METHODS: Multivariate-regression evaluated the association between AJCC7 to AJCC8 stage change and race/ethnicity in patients with DTC in the NCDB. Cox-proportional-regression evaluated whether AJCC7 to AJCC8 stage change affects overall survival (OS) differently based on reported race/ethnicity. RESULTS: After adjusting for confounders, Hispanics and Asian-Pacific-Islanders (APIs) were 27% and 12% less likely to be down-staged compared to white-non-Hispanics (WNHs) (p < 0.001); black-non-Hispanics (BNHs) had no significant down-staging difference. Down-staged patients had an increased risk of death compared to patients with unchanged staging, regardless of race/ethnicity. However, based on two-way interaction, the magnitude of this negative change on survival from down-staging was only different between WNHs (HR = 2.64) and BNHs (HR = 1.77), (p = 0.04). CONCLUSIONS: Outcome disparities persist among self-reported racial/ethnic groups with AJCC8. Down-staged patients across all racial/ethnic groups had decreased survival compared to those with unchanged stage, with the least impact in BNHs.

Prognostic Impact and Utility of Immunoprofiling in the Selection of Patients with Colorectal Peritoneal Carcinomatosis for Cytoreductive Surgery (CRS) and Heated Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND: Recent studies have shown an association in non-metastatic colorectal cancer between patient survival and immunoprofiling (expression of CD3, CD4, CD8, CD45, and FOXP3 T cells at the invasive margin (IM) and the tumor center (TC)) regardless of stage. Patients with peritoneal carcinomatosis have a dismal prognosis, but survival can be significantly improved in selected patients who undergo cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). However, current patient selection for CRS/HIPEC is suboptimal. The purpose of this study is to evaluate immune profiles of patients with peritoneal carcinomatosis and their correlation with overall survival (OS). METHODS: The study cohort included patients from a prospectively maintained database of adults with colorectal peritoneal carcinomatosis who underwent CRS/HIPEC. Immunohistochemistry (IHC) using antibodies to CD3, CD4, CD8, CD45RO, and FOXP3 T cells was performed. IHC image density was calculated using ImageJ software, and an immunoscore was determined. RESULTS: Eighty tumors were evaluated from 66 patients. These included 14 primary sites and 66 metastatic sites. R0/R1 resection was achieved in 44 (66.7%) patients. Known prognostic factors including resection status (HR 1.99, p = 0.004) and lymph node status (HR 3.49, p = 0.002) were associated with overall survival. On multivariate analysis, increased CD3/CD4 IM (HR 0.54, p = 0.03) ratio positively was associated with improved OS. DISCUSSION: This is the first study to assess the utility of subtypes of T cells as prognostic markers in patients with colorectal peritoneal carcinomatosis, which may play a role in patients with low-volume disease. Further studies into immune mechanisms may improve patient selection for cytoreductive surgery and HIPEC as well as provide novel pathways for effective immunotherapy.