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Debate persists regarding the need for shaking during hyperthermic intraperitoneal chemotherapy. Studies assessing the thermal behaviors of the perfusate throughout the abdomen during hyperthermic intraperitoneal chemotherapy are limited.A closed hyperthermic intraperitoneal chemotherapy technique was performed in an institutional International Animal Care and Use Committee approved porcine model targeting a 41°C outflow temperature. Continuous temperature monitoring was conducted. Abdominal shaking was performed for 60 second intervals and temperatures were allowed to equilibrate without shaking between intervals. Temperature distributions and changes due to shaking were evaluated. These findings were validated against human subjects' data.The experimental procedure was conducted in 2 different animals and with 6 total shaking intervals assessed. Without shaking, temperatures were highly variable ranging between 38.0 to 42.2°C. Shaking the abdomen reduced the mean range of temperatures across all locations observed from 3.9°C to 0.8°C (P.01). The locations of the most divergent temperatures varied based on perfusion cannula position. The point of minimum temperature heterogeneity was achieved in 28.3 (19.1-37.5) seconds. After shaking stopped, heterogeneity equal to the baseline measurements was seen on average within 25.7 (13.3-38.0) seconds. The outflow catheter differed from the system mean temperature by 1.4°C and from the coldest-reading probe by 2.8°C and outperformed the inflow catheter for all time points. With shaking these were significantly reduced to 0.4°C (P.01) and 0.6°C (P.01). The patient data mirrored that of the pig data.Shaking significantly reduces temperature variability within the abdomen during hyperthermic intraperitoneal chemotherapy, and significantly improves the ability of the outflow catheter to estimate internal temperatures.

The aim of this study is to present radiologically designated LAPC found to be resectable upon surgical exploration and evaluate the outcomes of such resections.Sequential LAPC patients between 2013 and 2019 were staged and underwent resection were included in the analysis of both perioperative and long-term outcomes.Twenty-eight patients with radiologically-designated LAPC underwent surgical resection after chemotherapy with a median follow-up of 31.7 m,75% underwent pancreaticoduodenectomy. The margin positivity and local recurrence rates were 21.4% and 35.7%, respectively. When compared to the 30 BRPC controls, the LAPC group had a higher rates of an arterial resection (11vs.1; p = 0.002), but the groups were similar with regard to all other preoperative and intraoperative variables (p 0.05). Perioperative morbidity rates were similar (25.9%vs21.4%; p = 0.53). The LAPC and BRPC groups were also equivalent with respect to median recurrence-free survival (9.0mo; 95%CI 6.3, 11.7vs.8.3mo; 95%CI 5.4, 11.2) and median overall survival (19.9mo; 95%CI 17.0, 22.7 vs. 19.9mo; 95%CI 14.8, 25.1), respectively.Despite a radiologic designation of locally advanced pancreatic cancer, certain subtypes of LAPC warrant surgical exploration provided the operative surgeon is prepared for major arterial and/or venous resection. Pancreatectomy in these patients has acceptable morbidity and oncologic outcomes, similar to patients who are radiologically borderline resectable.

Supplemental Figure Legend from Targeting Acidity in Pancreatic Adenocarcinoma: Multispectral Optoacoustic Tomography Detects pH-Low Insertion Peptide Probes In Vivo

Purpose:Improving our understanding of the immunologic response to cancer cells within the sentinel lymph nodes (SLN) of primary tumors is expected to identify new approaches to stimulate clinically meaningful cancer immunity.Experimental Design:We used mass cytometry by time-of-flight (CyTOF), flow cytometry, and T-cell receptor immunosequencing to conduct simultaneous single-cell analyses of immune cells in the SLNs of patients with melanoma.Results:We found increased effector-memory αβ T cells, TCR clonality, and γδ T cells selectively in the melanoma-bearing SLNs relative to non–melanoma-bearing SLNs, consistent with possible activation of an antitumor immune response. However, we also observed a markedly immunotolerant environment in the melanoma-bearing SLNs indicated by reduced and impaired NK cells and increased levels of CD8+CD57+PD-1+ cells, which are known to display low melanoma killing capabilities. Other changes observed in melanoma-bearing SLNs when compared with non–melanoma-bearing SLNs include (i) reduced CD8+CD69+ T cell/T regulatory cell ratio, (ii) high PD-1 expression on CD4+ and CD8+ T cells, and (iii) high CTLA-4 expression on γδ T cells.Conclusions:Our data suggest that these immunologic changes compromise antimelanoma immunity and contribute to a high relapse rate. We propose the development of clinical trials to test the neo-adjuvant administration of anti–PD-1 antibodies prior to SLN resection in patients with stage III melanoma.See related commentary by Lund, p. 1996

Supplementary Data from Single‐Cell Immune Mapping of Melanoma Sentinel Lymph Nodes Reveals an Actionable Immunotolerant Microenvironment

Supplemental Figure S3: Elliptical 3.5 mm2 ROIs were drawn based upon anatomical location and this size was maintained for relative quantitation of signal accumulation in the pancreas tumor, kidney, and liver. Because the liver and kidney are more easily identified in separate slices, two slices are shown which also contain the pancreas tumor. The location of orthotopic tumors was identified based upon the presence of deoxy-hemoglobin and relative location of the spleen and kidney as indicated by a yellow ellipse (A-B). Due to the location of the pancreas tumor and to prevent errors in organ identification, elliptical 3.5 mm2 ROIs were also drawn in the (A) uninvolved liver (red ellipse) and (B) opposite kidney (white ellipse). The 3.5 mm2 ellipse size was maintained among all ROIs in all mice and for all organs, but ROIs were rotated as needed based upon deoxy-hemoglobin localization to ensure that the probe accumulation within the pancreas tumors as accurate.

Supplementary Figure from Single‐Cell Immune Mapping of Melanoma Sentinel Lymph Nodes Reveals an Actionable Immunotolerant Microenvironment

Supplementary Table from Single‐Cell Immune Mapping of Melanoma Sentinel Lymph Nodes Reveals an Actionable Immunotolerant Microenvironment

Background: pH-low insertion peptides (pHLIP) can serve as a targeting moiety that enables pH-sensitive probes to detect solid tumors. Using these probes in conjunction with multispectral optoacoustic tomography (MSOT) is a promising approach to improve imaging for pancreatic cancer.Methods: A pH-sensitive pHLIP (V7) was conjugated to 750 NIR fluorescent dye and evaluated as a targeted probe for pancreatic adenocarcinoma. The pH-insensitive K7 pHLIP served as an untargeted control. Probe binding was assessed in vitro at pH 7.4, 6.8, and 6.6 using human pancreatic cell lines S2VP10 and S2013. Using MSOT, semiquantitative probe accumulation was then assessed in vivo with a murine orthotopic pancreatic adenocarcinoma model.Results: In vitro, the V7-750 probe demonstrated significantly higher fluorescence at pH 6.6 compared with pH 7.4 (S2VP10, P = 0.0119; S2013, P = 0.0160), whereas no difference was observed with the K7-750 control (S2VP10, P = 0.8783; S2013, P = 0.921). In the in vivo S2VP10 model, V7-750 probe resulted in 782.5 MSOT a.u. signal compared with 5.3 MSOT a.u. in K7-750 control in tumor (P = 0.0001). Similarly, V7-750 probe signal was 578.3 MSOT a.u. in the S2013 model compared with K7-750 signal at 5.1 MSOT a.u. (P = 0.0005). There was minimal off-target accumulation of the V7-750 probe within the liver or kidney, and probe distribution was confirmed with ex vivo imaging.Conclusions: Compared with pH-insensitive controls, V7-750 pH-sensitive probe specifically targets pancreatic adenocarcinoma and has minimal off-target accumulation. The noninvasive detection of pH-targeted probes by means of MSOT represents a promising modality to improve the detection and monitoring of pancreatic cancer. Clin Cancer Res; 21(20); 4576–85. ©2015 AACR.See related commentary by Reshetnyak, p. 4502

BACKGROUND This study aims to compare the LACE + readmission index to a novel hepatopancreatobiliary readmission risk score (HRRS) in predicting post-operative hepatopancreatobiliary (HPB) cancer patient readmissions. METHODS A retrospective review of 104 postoperative HPB cancer patients from January 2017 to July of 2019 was performed. Univariable and multivariable analyses were utilized. RESULTS The LACE + index did not predict 30-day (OR 1.01, 95% CI, 0.97-1.05, p = 0.81, c-statistic = 0.52) or 90-day (OR 1.02, 95% CI, 0.98-1.05, p = 0.43) readmission. Patients readmitted within 30 days had significantly increased HRRS scores compared to those who were not (0 vs 34, p

Purpose: Improving our understanding of the immunologic response to cancer cells within the sentinel lymph nodes (SLN) of primary tumors is expected to identify new approaches to stimulate clinically meaningful cancer immunity. Experimental Design: We used mass cytometry by time-of-flight (CyTOF), flow cytometry, and T-cell receptor immunosequencing to conduct simultaneous single-cell analyses of immune cells in the SLNs of patients with melanoma. Results: We found increased effector-memory αβ T cells, TCR clonality, and γδ T cells selectively in the melanoma-bearing SLNs relative to non–melanoma-bearing SLNs, consistent with possible activation of an antitumor immune response. However, we also observed a markedly immunotolerant environment in the melanoma-bearing SLNs indicated by reduced and impaired NK cells and increased levels of CD8+CD57+PD-1+ cells, which are known to display low melanoma killing capabilities. Other changes observed in melanoma-bearing SLNs when compared with non–melanoma-bearing SLNs include (i) reduced CD8+CD69+ T cell/T regulatory cell ratio, (ii) high PD-1 expression on CD4+ and CD8+ T cells, and (iii) high CTLA-4 expression on γδ T cells. Conclusions: Our data suggest that these immunologic changes compromise antimelanoma immunity and contribute to a high relapse rate. We propose the development of clinical trials to test the neo-adjuvant administration of anti–PD-1 antibodies prior to SLN resection in patients with stage III melanoma. See related commentary by Lund, p. 1996

Early recurrence following liver resection for metastatic colorectal cancer generally portends poor survival. We sought to identify factors associated with early disease recurrence after major hepatectomy for metastatic colorectal cancer in order to improve patient selection and prevent futile hepatectomy. Sequential major (four or more segments) liver resections performed for metastatic colorectal cancer between 1995 and 2019 were selected from our prospectively maintained database. Univariate analyses, multivariable regression modelling, and survival analyses were used to identify predictors of futile resection (recurrence within 6 months of hepatectomy). Of 259 patients included, the median age was 61.3 years (interquartile range [IQR] 15.3) and the median number of liver tumors was 3.0 (IQR 2.0); 78.0% of patients received prehepatectomy chemotherapy. Surgeries were right (56.4%), left (19.3%), and extended hepatectomy (24.3%). Futile resection occurred in 26 (12.6%) patients. Margin positivity was similar in the futile resection group compared with the non-futile resection group (11.5% vs. 11.4%). Extrahepatic disease that disappeared with chemotherapy was present in 23.1% of patients with a futile resection and 7.2% of those without (p = 0.019). After multivariable regression, the factors predictive of futile resection were extrahepatic disease (odds ratio [OR] 5.6; p = 0.004), more than three liver lesions (OR 4.9; p = 0.001), and extended hepatectomy (OR 2.6; p = 0.038). Notably, 70.8% of futile recurrences occurred within the liver remnant and 20.8% were pulmonary metastases. Overall survival was 11.7 months (95% confidence interval [CI] 7.1–16.2) for the futile resection cohort versus 45.6 (95% CI 39.1–52.1) for non-futile hepatectomies (p

Locally-advanced pancreatic cancer (LAPC) is traditionally considered stage III unresectable disease. Advances in induction systemic therapy regimens, surgical technique, and perioperative care have led to successful resection of an increasing number of these tumors with reasonable perioperative outcomes and disease-free intervals. Certain anatomic characteristics that meet criteria for locally-advanced disease, however, are more likely to result in a successful surgical outcome. A practical and consistent system is needed to communicate such nuance between surgical and nonsurgical oncologists for optimal treatment planning and to improve recording for cancer registries and research studies. The present study proposes a novel subclassification system for stage III pancreatic cancers based on their pattern of vascular involvement and examines the current evidence for resection in each scenario. Introducing needed detail into the current catch-all stage III categorization will help to direct patient referrals and increase the body of knowledge about the variable presentations of this complex malignancy. This proposed staging revision for LAPC is designed to convey more actionable tumor descriptions for treating oncologists, clinical trial eligibility, and surgical patient selection in the era of effective induction systemic therapy.

INTRODUCTION The 2016 consensus guideline on margins for breast-conserving surgery (BCS) with whole-breast irradiation (WBI) for ductal carcinoma in situ (DCIS) recommended 2 mm margins to decrease local recurrence rates. We examined re-excision rates, cost, and patient satisfaction before and after guideline implementation. METHODS From an Institutional Review Board-approved database, patients with DCIS who underwent BCS with over 1 year of follow-up at one academic institution and one community cancer center were evaluated. Two groups were compared based on when they received treatment, i.e. before (pre-consensus [PRE]) and after November 2016 (post consensus [POST]), with respect to outcome and cost parameters. RESULTS After consensus guideline implementation, re-excision rate (32.1% vs. 20.0%) and mastectomy conversion (8.3% vs. 2.3%) significantly increased, although total resection volume, operative cost per patient, and satisfaction with breast scores did not differ. Not all patients with

Background Although completion lymph node dissection (CLND) is not routinely performed for a positive sentinel lymph node (SLN) anymore, adjuvant therapy depends on the risk factors available from SLN biopsy, including the risk of nonsentinel node metastases (NSNM). A systematic review and meta-analysis was performed in an attempt to identify risk factors that could be used to predict the risk of NSNM. Materials and methods Medline, Web of Science, Embase, and Cochrane were searched for articles discussing predictive factors for NSNM. PRISMA guidelines were followed, and RevMan software was used to calculate pooled odds ratios (OR) using the Mantel-Haenszel test. Results Fifty publications were suitable for additional analysis. The clinical and primary tumor factors that were consistently identified as risk factors for NSNMs were: age >50, T stage 3 or 4, Clark level IV/V, ulceration, microsatellitosis, lymphovascular invasion, nodular histology, and extremity versus trunk primary tumor location. SLN factors that predicted NSNMs were >1 positive SLN, SLN micrometastatic tumor burden, diameter >2 mm, extracapsular extension, nonsubcapsular location (Dewar), and Rotterdam > 1 mm or ≥ 0.1 mm. Conclusions The findings in this study support that many clinical and pathologic risk factors that can be assessed with SLN biopsy alone can be used to predict the risk of NSNMs. The factors identified in this review should be evaluated in clinical prediction models to predict the risk of NSNMS, a prediction that may be used to select patients for adjuvant therapy in high-risk melanoma.

To report an interim analysis of a phase II trial of once weekly, hypofractionated breast irradiation (WH-WBI) following breast conserving surgery (BCS). Patients had stage 0-II breast cancer treated with breast BCS with negative margins. WH-WBI was 28.5 or 30Gy delivered to the whole breast using tangential beams with no elective coverage of lymph nodes. The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were distant disease-free survival (DDFS), recurrence free survival (RFS), overall survival (OS), adverse events and cosmesis. From 2011 to 2015, 158 patients received WH-WBI. Median follow up was 4.4 years (range 0.2-8.1). Stage distribution was DCIS 22%; invasive pN0 68%; invasive pN1 10%. 80 patients received 30 Gy and 78 received 28.5 Gy with median follow up times of 5.6 and 3.7 years, respectively. There were 5 IBTR events, all in the 30 Gy group. The 5- and 7- year risks of IBRT for all patients were 2.2% (95% CI 0.6-5.8) and 6.0% (95% CI 1.1-17.2), respectively. The 7-year rates of DDFS, RFS, and OS were 96.3%, 91.5% and 89.8%, respectively. Improvement in IBTR-free time was seen in DCIS, lobular histology, low grade tumors, Her2 negative tumors and 28.5 Gy dose (all p < 0.0001). Disease-specific outcomes after WH-WBI are favorable and parallel those seen with conventional radiation techniques for stage 0-II breast cancer.

BackgroundPancreatic cancer (PC) is a challenging diagnosis that is yet to benefit from the advancements in immuno-oncologic treatments. Irreversible electroporation (IRE), a non-thermal method of tumor ablation, is used in treatment of select patients with locally-advanced unresectable PC and has potentiated the effect of certain immunotherapies. Yeast-derived particulate β-glucan induces trained innate immunity and successfully reduces murine PC tumor burden. This study tests the hypothesis that IRE may augment β-glucan induced trained immunity in the treatment of PC.Methodsβ-Glucan-trained pancreatic myeloid cells were evaluated ex vivo for trained responses and antitumor function after exposure to ablated and unablated tumor-conditioned media. β-Glucan and IRE combination therapy was tested in an orthotopic murine PC model in wild-type and Rag−/−mice. Tumor immune phenotypes were assessed by flow cytometry. Effect of oral β-glucan in the murine pancreas was evaluated and used in combination with IRE to treat PC. The peripheral blood of patients with PC taking oral β-glucan after IRE was evaluated by mass cytometry.ResultsIRE-ablated tumor cells elicited a potent trained response ex vivo and augmented antitumor functionality. In vivo, β-glucan in combination with IRE reduced local and distant tumor burden prolonging survival in a murine orthotopic PC model. This combination augmented immune cell infiltration to the PC tumor microenvironment and potentiated the trained response from tumor-infiltrating myeloid cells. The antitumor effect of this dual therapy occurred independent of the adaptive immune response. Further, orally administered β-glucan was identified as an alternative route to induce trained immunity in the murine pancreas and prolonged PC survival in combination with IRE. β-Glucan in vitro treatment also induced trained immunity in peripheral blood monocytes obtained from patients with treatment-naïve PC. Finally, orally administered β-glucan was found to significantly alter the innate cell landscape within the peripheral blood of five patients with stage III locally-advanced PC who had undergone IRE.ConclusionsThese data highlight a relevant and novel application of trained immunity within the setting of surgical ablation that may stand to benefit patients with PC.

Background: Laparoscopic microwave ablation (MWA) of hepatocellular carcinoma is underutilized and predictors of survival in this setting are not well characterized. Methods: The prognostic value of clinicopathologic variables was evaluated on progression-free survival (PFS) and overall survival (OS) by univariate and multivariate analyses. The aim of this study was to evaluate a preferred laparoscopic MWA approach in HCC patients that are not candidates for percutaneous ablation and further classify clinicopathologic factors that may predict survival outcomes following operative MWA in the setting of primary HCC. Results: 184 patients with HCC (median age 66, (33–86), 70% male) underwent laparoscopic MWA (N = 162, 88% laparoscopic) compared to 12% undergoing open MWA (N = 22). Median PFS was 29.3 months (0.2–170) and OS was 44.2 months (2.8–170). Ablation success was confirmed in 100% of patients. Ablation recurrence occurred in 3% (6/184), and local/hepatic recurrence occurred in 34%, at a median time of 19 months (9–18). Distant progression was noted in 8%. Median follow up was 34.1 months (6.4–170). Procedure-related complications were recorded in six (9%) patients with one 90-day mortality. Further, >1 lesion, AFP levels ≥ 80 ng/mL, and an “invader” on pre-operative radiology were associated with increased risk of progression (>1 lesion HR 2.92, 95% CI 1.06 –7.99, p = 0.04, AFP ≥ 80 ng/mL HR 4.16, 95% CI 1.71–10.15, p = 0.002, Invader HR 3.16, 95% CI 1.91–9.15, p = 0.002 ) and mortality (>1 lesion HR 3.62, 95% CI 1.21–10.81, p = 0.02], AFP ≥ 80 ng/mL HR 2.87, 95% CI 1.12–7.35, p = 0.01, Invader HR 3.32, 95% CI 1.21–9.81, p = 0.02). Conclusions: Preoperative lesion number, AFP ≥ 80 ng/mL, and an aggressive imaging characteristic (Invader) independently predict PFS and OS following laparoscopic operative MWA.

The optimal timing of treatment of liver metastases from low-grade neuroendocrine tumors (LG-NELM) varies significantly due to numerous treatment modalities and the literature supporting various treatment(s). This study sought to create and validate a literature-based treatment algorithm for LG-NELM.A treatment algorithm to maximize overall survival (OS) was designed using peer-reviewed articles evaluating treatment of LG-NELM. This algorithm was retrospectively applied to patients treated for LG-NELM at our institution. Deviation was determined based on whether or not a patient received treatment consistent with that recommended by the algorithm. Patients who did and did not deviate from the algorithm were compared with respect to OS and number of treatments.Applying our algorithm to a 149-patient cohort, 57 (38%) deviated from recommended treatment. Deviation occurred in the form of alternative (28, 49%) versus additional procedures (29, 51%). Algorithm deviators underwent significantly more procedures than non-deviators (median 1 vs. 2, p 0.001). Cox model indicated no difference in OS associated with algorithm deviation (HR 1.19, p = 0.58) when controlling for age and tumor characteristics.This literature-based algorithm helps standardize treatment protocols in patients with LG-NELM and can reduce cost and risk by minimizing unnecessary procedures. Prospective implementation and validation is required.

Age is an important factor for determining the outcome of melanoma patients. Sentinel lymph node (SLN) status is also a strong predictor of survival for melanoma. Paradoxically, older melanoma patients have a lower incidence of SLN metastasis but a higher mortality rate when compared with their younger counterparts. The mechanisms that underlie this phenomenon remain unknown. This study uses three independent datasets of RNA samples from patients with melanoma metastatic to the SLN to identify age-related transcriptome changes in SLNs and their association with outcome. Microarray was applied to the first dataset of 97 melanoma patients. NanoString was performed in the second dataset to identify the specific immune genes and pathways that are associated with recurrence in younger versus older patients. qRT-PCR analysis was used in the third dataset of 36 samples to validate the differentially expressed genes (DEGs) from microarray and NanoString. These analyses show that FOS, NR4A, and ITGB1 genes were significantly higher in older melanoma patients with positive SLNs. IRAK3- and Wnt10b-related genes are the major pathways associated with recurrent melanoma in younger and older patients with tumor-positive SLNs, respectively. This study aims to elucidate age-related differences in SLNs in the presence of nodal metastasis.

The purpose of this study was to evaluate the rates of local recurrence and margin positivity in patients with borderline resectable pancreatic cancer after pancreatectomy with or without irreversible electroporation with margin accentuation.Prospective data for preoperative stages IIB (borderline resectable) and III were evaluated, with 75 patients undergoing pancreatectomy with irreversible electroporation with margin accentuation compared to 71 patients who underwent pancreatectomy alone from March 2010 to November 2020.Both irreversible electroporation with margin accentuation and pancreatectomy-alone groups were similar for body mass index, Charleston comorbidity index, and sex. The irreversible electroporation with margin accentuation group had significantly greater preoperative stage III (irreversible electroporation 83% vs pancreatectomy alone 51%; P = .0001), with similar tumor location (head 64% vs 72%) and tumor size (median 2.9 vs 2.8). Neoadjuvant/induction chemotherapy and prior radiation therapy was similar in both groups (irreversible electroporation with margin accentuation 89% vs 72%). Surgical therapy included a greater percentage of pancreaticoduodenectomy in the pancreatectomy-alone group. Despite greater stage and greater percentage of margin positivity (irreversible electroporation with margin accentuation 27% vs 20%; P = not significant), rates of local recurrence were similar. The mean disease-free interval for local recurrence from time of diagnosis was similar (irreversible electroporation with margin accentuation 15.8 vs 16.5 pancreatectomy alone; P = not significant) and time of treatment (irreversible electroporation with margin accentuation 9.4 vs 10.5 months; P = not significant). Overall survival was improved with the irreversible electroporation with margin accentuation group, with a mean of 34.2 months versus 27.9 months in the pancreatectomy-alone group.Irreversible electroporation with margin accentuation is safe and effective in stages IIB and III pancreatic adenocarcinomas that are technically resectable. Despite higher margin positivity rates, the time to local recurrence and the effects of recurrence were the same in the pancreatectomy-alone group.

Hepatic thermal ablation has been found to be effective and equivalent to resection in certain liver histologies. Of the 16,000 annual liver ablations performed in the United States, only 13% (2,080 ablations) are performed laparoscopically. The laparoscopic technique remains underused even with the benefits of improved staging and better access to tumors. The purpose of this study is to compare laparoscopic microwave ablation versus percutaneous microwave ablation in terms of efficacy and recurrence-free survival outcomes in patients with hepatic malignancies.A comparative analysis was performed on 275 patients (289 ablation procedures) who underwent laparoscopic microwave ablation or percutaneous microwave ablation between February 2011 and May 2021. Ablation success was confirmed postprocedure and recurrence was monitored at follow-up via contrast-enhanced computed tomography/magnetic resonance imaging and/or computed tomography/positron emission tomography.The groups were similar for sex, age, body mass index, location of tumor, size of tumor, and number of tumors. Ablation success was 100% in both groups. Local recurrence was significant (5%: laparoscopic microwave ablation vs 22%: percutaneous microwave ablation, P = .002) and same-lobe recurrence (21%: laparoscopic microwave ablation vs 24%: percutaneous microwave ablation) was lower in the laparoscopic microwave ablation group. Median recurrence-free survival was 15.8 months for the laparoscopic microwave ablation group and 5.6 months for the percutaneous microwave ablation group (P = .0002). Overall, 90-day complications were lower in the laparoscopic microwave ablation group (11%) compared with the percutaneous microwave ablation group (21%) (P = .11).Laparoscopic surgical ablation is a critical surgical skill that must be taught in fellowship. Laparoscopic microwave ablation leads to better tumor specific outcomes and oncologic outcomes demonstrating clinical efficacy in the treatment of hepatic malignancies compared with percutaneous microwave ablation.

Few studies have assessed the relationship between serum alpha-fetoprotein (AFP) and yttrium-90 (Y-90) radioembolization response in hepatocellular carcinoma (HCC). The objective of the study was to evaluate whether peri-procedural serum AFP was correlated with Y-90 therapy response in HCC.Patients undergoing Y-90 radioembolization with glass microspheres (TheraSphere™) for HCC between 2006 and 2013 at a single center were evaluated. The relationship between AFP and 6-month radiographic improvement (complete or partial response by modified RECIST criteria), overall (OS), and disease-specific survival (DSS) were analyzed.Seventy-four patients underwent a total of 124 Y-90 infusions. Median age was 65 years, median AFP was 37 ng/mL (range: 2-112,593 ng/mL) and median model for end-stage liver disease score was 6.2 (range:1.8-11.2). Increased AFP was not associated with radiographic improvement (odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.75-1.30, p = 0.92). Median OS was 15.2 months and was increased in patients with low AFP compared to high AFP (30.8 months vs. 7.8 months, p 0.001). On multivariable regression analysis, increased AFP was associated with worse OS (OR = 1.11, 95%CI = 1.01-1.22, p = 0.034) and DSS (OR = 1.13, 95%CI = 1.03-1.25, p = 0.018).Pre-infusion AFP independently predicted survival after Y-90 treatment for HCC, but not radiographic response, and can help guide treatment decisions.

Background The preoperative and intraoperative factors that could predict a higher risk of anastomotic/staple line leak for gastric cancer patients has not been accurately defined. Methods Patients who underwent surgery with curative intent for gastric malignancies between 2002 and 2018 were evaluated from a single prospective database. Results A total of 195 patients were evaluated with an overall complication rate of 40%. Anastomotic/staple line leak occurred in 13%, with 4% undergoing reoperation during the same hospitalization. Significant risk factors affecting postoperative complications (POC) were identified in the patients including number of comorbidities (≥2) (HR, 5.30; 95% CI, 1.1–15.3; P = 0.037) and operation type (Total vs Distal) (HR, 2.5; CI 1.08–8.5; p = 0.048). Subset analysis of gastric adenocarcinoma patients demonstrates a five-year overall survival (OS) for patients without perioperative complications was 68%, compared with 41% for patients with POCs (p 0.001). Conclusions In a large single-institutional study, POCs were associated with decreased survival in patients undergoing surgery for gastric adenocarcinoma. Optimizing these patients post-operatively with limited anastomotic stress and enteral feeding tube may allow for a less complicated course.

BACKGROUND Primitive neuroectodermal tumors (PNETs) comprise less than 1% of all sarcomas. The rarity of this disease has resulted in a paucity of information about disease process and management. This study sought to evaluate the incidence, treatment patterns, and outcomes among patients with PNET. METHODS The National Cancer Database was queried for diagnoses of PNET between 2004 and 2014. Patients were dichotomized based on tumor type (central [cPNET] vs peripheral [pPNET]). Demographic, tumor, treatment, and outcome variables were analyzed for the entire patient cohort and by type of PNET. RESULTS White (86.4%) males (56.6%) represented the majority of patients. The incidence of PNET remained stable over the study period (r2 = 0.0821). A total of 70.7% underwent surgical resection of the primary site, 50.3% received radiation, and 74.7% received systemic chemotherapy. Compared to those with pPNET, patients with cPNET more often received radiation treatment (P

Background The COVID-19 pandemic has posed extraordinary demands from patients, providers, and health care systems. Despite this, surgical oncologists must maintain focus on providing high-quality, empathetic care for the almost 2 million patients nationally who will be diagnosed with operable cancer this year. The focus of hospitals is transitioning from initial COVID-19 preparedness activities to a more sustained approach to cancer care. Methods Editorial Board members provided observations of the implications of the pandemic on providing care to surgical oncology patients. Results Strategies are presented that have allowed institutions to successfully prepare for cancer care during COVID-19, as well as other strategies that will help hospitals and surgical oncologists manage anticipated challenges in the near term. Perspectives are provided on: (1) maintaining a safe environment for surgical oncology care; (2) redirecting the multidisciplinary model to guide surgical decisions; (3) harnessing telemedicine to accommodate requisite physical distancing; (4) understanding interactions between SARS CoV-2 and cancer therapy; (5) considering the ethical impact of professional guidelines for surgery prioritization; and (6) advocating for our patients who require oncologic surgery in the midst of the COVID-19 pandemic. Conclusions Until an effective vaccine becomes available for widespread use, it is imperative that surgical oncologists remain focused on providing optimal care for our cancer patients while managing the demands that the COVID-19 pandemic will continue to impose on all of us.

Background The global pandemic of respiratory disease cause by the novel human coronavirus (SARS-CoV-2) has caused untold suffering, loss of life and upheaval in society. The pandemic has lead to massive redirection of health care resources to treat the surge of COVID-19 patients, and enforcement of social distancing to reduce the rate of transmission. Methods Editorial Board members provided observations of the implications of the pandemic on academic surgical oncology. Results Delivery of health care to other populations including cancer patients has been significantly disrupted. The implications both short term and long term threaten preservation of the academic mission in medicine at large, and certainly in the field of surgical oncology. Conclusions The effects on surgical oncology training, research and clinical trials are major.

Introduction In women with T1-2 breast cancer and one to two positive axillary lymph nodes (LN) at low risk for recurrence, postmastectomy radiation therapy (PMRT) may provide insufficient benefit to justify its toxicity. This study evaluated the interaction of factors associated with overall survival (OS) after PMRT in these patients. Methods The National Cancer Database was queried for women with T1-2 breast cancer undergoing mastectomy with one to two positive LN identified on lymphadenectomy. Patients were grouped according to number of positive LN and then stratified by PMRT use. Differences in OS were evaluated. Results Multivariable modeling demonstrated an interaction effect of age on the efficacy of PMRT. In patients more than or equal to 60 years old, PMRT was associated with improved survival when adjusting for age and tumor grade in patients with 1 to 2 positive LN (risk ratio = 0.62, 95% confidence interval = 0.40-0.93, P = .018). In patients less than 60 years old, tumor size and grade, but not PMRT, were associated with improved OS. Conclusion For women with T1-2 breast cancer and one to two positive LN, PMRT's association with OS is influenced by age, tumor grade, and number of positive LN. PMRT appears to be associated with improvements in OS in older patients, but not younger patients, regardless of tumor size or nodal status.

Background Peritoneal carcinomatosis of colorectal adenocarcinoma (CRC) origin is common and is the second-most frequent cause of death in colorectal cancer. There is survival benefit to surgical resection plus hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with metastatic CRC. However, there remains controversy between oxaliplatin (Oxali) and mitomycin C (MMC), as the agent of choice. Methods A review of our 285 patients prospective HIPEC database from July 2007 to May 2018 identified 48 patients who underwent cytoreductive surgery plus HIPEC with MMC or Oxali. Patients were stratified based on preoperative and postoperative peritoneal cancer indices (PCI). The primary outcomes of survival and progression-free survival were compared. Results Type of HIPEC chemotherapy was not found to be predictive of overall survival. Preoperative PCI (P = .04), preoperative response to chemotherapy (P = .0001), and postoperative PCI (P = .05) were predictive for overall survival. Conclusions MMC or Oxali based HIPEC chemotherapy are both safe and effective for the management of peritoneal only metastatic CRC. Both perfusion therapies should be considered with all patients receiving modern induction chemotherapy.

BACKGROUND AND OBJECTIVES: A previous analysis of breast cancer care after the 2014 Medicaid expansion in Kentucky demonstrated delays in treatment despite a 12% increase in insurance coverage. This study sought to identify factors associated with treatment delays to better focus efforts for improved breast cancer care. METHODS: The Kentucky Cancer Registry was queried for adult women diagnosed with invasive breast cancer between 2010 and 2016 who underwent up-front surgery. Demographic, tumor, and treatment characteristics were assessed to identify factors independently associated with treatment delays. RESULTS: Among 6225 patients, treatment after Medicaid expansion (odds ratio [OR] = 2.18, 95% confidence interval [CI] = 1.874–2.535, P < .001), urban residence (OR = 1.362, 95% CI = 1.163–1.594, P < .001), treatment at an academic center (OR = 1.988, 95% CI = 1.610–2.455, P < .001), and breast reconstruction (OR = 3.748, 95% CI = 2.780–5.053, P < .001) were associated with delay from diagnosis to surgery. Delay in postoperative chemotherapy was associated with older age (OR = 1.155,95% CI = 1.002–1.332, P = .0469), low education level (OR = 1.324, 95% CI = 1.164–1.506, P < .001), hormone receptor positivity (OR = 1.375, 95% CI = 1.187–1.593, P < .001), and mastectomy (OR = 1.312, 95% CI = 1.138–1.513, P < .001). Delay in postoperative radiation was associated with younger age (OR = 1.376, 95% CI = 1.370–1.382, P < .001), urban residence (OR = 1.741, 95% CI = 1.732–1.751, P < .001), treatment after Medicaid expansion (OR = 2.007, 95% CI = 1.994–2.021, P < .001), early stage disease (OR = 5.661, 95% CI = 5.640–5.682, P < .001), and mastectomy (OR = 1.884, 95% CI = 1.870–1.898, P < .001). CONCLUSIONS: Patient, tumor, and socioeconomic factors influence the timing of breast cancer treatment. Improving timeliness of treatment will likely require improvements in outreach, education, and healthcare infrastructure.

Women who undergo mastectomy for breast cancer may be prone to prolonged opioid use (POU). However, risk factors for long-term opioid use after mastectomy remain unclear. This study seeks to identify risk factors for POU after mastectomy. A single-institution database was queried for women who underwent mastectomy for breast cancer between January 2016 and December 2017. Patients were stratified based on opioid use

Metastasis is the leading cause of cancer-related deaths and myeloid cells are critical in the metastatic microenvironment. Here, we explore the implications of reprogramming pre-metastatic niche myeloid cells by inducing trained immunity with whole beta-glucan particle (WGP). WGP-trained macrophages had increased responsiveness not only to lipopolysaccharide but also to tumor-derived factors. WGP in vivo treatment led to a trained immunity phenotype in lung interstitial macrophages, resulting in inhibition of tumor metastasis and survival prolongation in multiple mouse models of metastasis. WGP-induced trained immunity is mediated by the metabolite sphingosine-1-phosphate. Adoptive transfer of WGP-trained bone marrow-derived macrophages reduced tumor lung metastasis. Blockade of sphingosine-1-phosphate synthesis and mitochondrial fission abrogated WGP-induced trained immunity and its inhibition of lung metastases. WGP also induced trained immunity in human monocytes, resulting in antitumor activity. Our study identifies the metabolic sphingolipid-mitochondrial fission pathway for WGP-induced trained immunity and control over metastasis.

This study aimed to evaluate the impact of expert breast pathology consultation on operative management and predictive factors of discordant diagnosis.A retrospective review of patients referred with breast biopsies and subsequent expert pathology consultation from 2014 to 2019. Discordance in diagnosis and documented changes in therapy were recorded. Univariate and multivariable analyses were performed.Ninety-one (91/263, 35%) patients had discordant findings after expert pathology consultation. No benign or in situ diagnoses were upgraded to invasive cancer. Tumor subtype changed in 10% while change in invasive cancer grade was most common (45%). Clinical management was altered in 3/263 (1%) with one change in surgical plan. Benign lesions without atypia (7.5% vs. 1.1%, p = 0.03) and excisional biopsies (8.7% vs. 2.2%, p = 0.04) were more often associated with non-discordant pathology. No independent predictors of discordance were observed.Discordant diagnoses after expert pathology consultation are common despite few changes in operative management. Excisional biopsy and benign lesions without atypia may be associated with less pathologic discordance after expert review.

Description, Macrophages use mitochondrial lactate metabolism for ACLY-dependent histone acetylation, immune suppression, and tumor progression., Lactate accumulation is a hallmark of solid cancers and is linked to the immune suppressive phenotypes of tumor-infiltrating immune cells. We report herein that interleukin-4 (IL-4)–induced M0 → M2 macrophage polarization is accompanied by interchangeable glucose- or lactate-dependent tricarboxylic acid (TCA) cycle metabolism that directly drives histone acetylation, M2 gene transcription, and functional immune suppression. Lactate-dependent M0 → M2 polarization requires both mitochondrial pyruvate uptake and adenosine triphosphate–citrate lyase (ACLY) enzymatic activity. Notably, exogenous acetate rescues defective M2 polarization and histone acetylation following mitochondrial pyruvate carrier 1 (MPC1) inhibition or ACLY deficiency. Lastly, M2 macrophage–dependent tumor progression is impaired by conditional macrophage ACLY deficiency, further supporting a dominant role for glucose/lactate mitochondrial metabolism and histone acetylation in driving immune evasion. This work adds to our understanding of how mitochondrial metabolism affects macrophage functional phenotypes and identifies a unique tumor microenvironment (TME)–driven metabolic-epigenetic link in M2 macrophages.

Early recurrence following liver resection for metastatic colorectal cancer generally portends poor survival. We sought to identify factors associated with early disease recurrence after major hepatectomy for metastatic colorectal cancer in order to improve patient selection and prevent futile hepatectomy.Sequential major (four or more segments) liver resections performed for metastatic colorectal cancer between 1995 and 2019 were selected from our prospectively maintained database. Univariate analyses, multivariable regression modelling, and survival analyses were used to identify predictors of futile resection (recurrence within 6 months of hepatectomy).Of 259 patients included, the median age was 61.3 years (interquartile range [IQR] 15.3) and the median number of liver tumors was 3.0 (IQR 2.0); 78.0% of patients received prehepatectomy chemotherapy. Surgeries were right (56.4%), left (19.3%), and extended hepatectomy (24.3%). Futile resection occurred in 26 (12.6%) patients. Margin positivity was similar in the futile resection group compared with the non-futile resection group (11.5% vs. 11.4%). Extrahepatic disease that disappeared with chemotherapy was present in 23.1% of patients with a futile resection and 7.2% of those without (p = 0.019). After multivariable regression, the factors predictive of futile resection were extrahepatic disease (odds ratio [OR] 5.6; p = 0.004), more than three liver lesions (OR 4.9; p = 0.001), and extended hepatectomy (OR 2.6; p = 0.038). Notably, 70.8% of futile recurrences occurred within the liver remnant and 20.8% were pulmonary metastases. Overall survival was 11.7 months (95% confidence interval [CI] 7.1-16.2) for the futile resection cohort versus 45.6 (95% CI 39.1-52.1) for non-futile hepatectomies (p 0.001).Futile hepatic resection can be predicted based on preoperative factors and carries a poor prognosis. Improved risk stratification for futility will aid in patient selection and treatment discussions.

Broad patterns of use of the gene signature panel Oncotype DX DCIS and its large-scale impact on postoperative administration of radiation therapy in women with ductal carcinoma in situ of the breast remain unclear. This study sought to evaluate the patterns of use of this gene signature panel in women with ductal carcinoma in situ and the impact of these tools on postoperative radiation therapy administration.The National Cancer Database was queried for women with ductal carcinoma in situ treated with breast-conserving therapy who had information regarding whether a gene signature panel was performed between 2010 and 2015. Demographic characteristics, the characteristics of their ductal carcinoma in situ, and whether they received postoperative radiation therapy were compared among patients who did have a gene signature panel performed and those who did not. Patterns of radiation therapy administration were also evaluated based on the recurrence risk score by the gene signature panel.Gene signature panel use increased over time, with a sharp increase in utilization occurring in 2015 (8.0% in 2015 vs 4.4% in 2014, P.001). Patients with estrogen receptor-positive ductal carcinoma in situ were somewhat more likely to have a gene signature panel ordered (3.9% estrogen receptor positive vs 1.7% estrogen receptor negative, P.001), as were patients with lower-grade ductal carcinoma in situ (4.5% grade I/II vs 3.1% grade III, P.001). Gene signature panel utilization was associated with a decrease in the administration of postoperative radiation therapy (48.6% gene signature panel vs 83.4% no gene signature panel, P.001). Among patients in whom a gene signature panel was performed, postoperative radiation therapy was administered in 81.9%, 72.0%, and 35.9% of patients with high-, intermediate-, and low-recurrence scores, respectively.Gene signature panel use in patients with ductal carcinoma in situ has increased over time and is more commonly used in women with lower-risk, clinicopathologic features to determine the magnitude of benefit afforded by radiation therapy. Gene signature panel use is associated with decreased rates of postoperative radiation therapy administration, particularly among patients with scores suggesting a low rate of recurrence.

The Sunbelt Melanoma Trial, a multicenter, prospective randomized clinical study, evaluated the role of high-dose interferon alfa-2b (HDI) therapy for patients with a single positive sentinel lymph node (SLN) metastasis treated with a completion lymph node dissection (CLND). A second protocol in the trial evaluated the prognostic significance of using molecular markers to identify submicroscopic metastases in sentinel lymph nodes that were negative by routine pathologic analysis. The role of CLND with or without adjuvant HDI was evaluated in this group of patients. The results of the study demonstrated that adjuvant HDI offered no survival benefit for patients with a single positive SLN in terms of disease-free or overall survival. Molecular staging using polymerase chain reaction (PCR) for melanoma markers did not identify a high-risk group of patients at increased risk of melanoma recurrence. Additional treatment of these patients who were PCR-positive with either CLND alone or CLND plus HDI did not improve their survival. Additional studies from the Sunbelt Melanoma Trial helped to validate the operational standards of the SLN biopsy procedure and defined the complication rates for both SLN biopsy and CLND. A prognostic risk calculator has been developed from trial data, and the importance of different micrometastatic tumor burden measurements was reported. Although the Sunbelt Melanoma Trial did not demonstrate an improvement in survival with HDI, it is an important trial that highlights the significance of surgeon-initiated randomized clinical trials that incorporate surgical techniques, molecular biomarkers, and adjuvant therapy.