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There is concern regarding the competency of today's general surgery graduates as a large proportion defer independent practice in favor of additional fellowship training. Little is known about the graduates who directly enter general surgery practice and if their operative experiences during residency differ from graduates who pursue fellowship.Nineteen Accreditation Council for Graduate Medical Education-accredited general surgery programs from the US Resident OPerative Experience Consortium were included. Demographics, career choice, and case logs from graduates between 2010 to 2020 were analyzed.There were 1,264 general surgery residents who graduated over the 11-year period. A total of 248 (19.6%) went directly into practice and 1,016 (80.4%) pursued fellowship. Graduates directly entering practice were more likely to be a high-volume resident (43.1% vs 30.5%, P.01) and graduate from a high-volume program (49.2% vs 33.0%, P.01). Direct-to-practice graduates performed 53 more cases compared with fellowship-bound graduates (1,203 vs 1,150, P.01). On multivariable analysis, entering directly into practice was positively associated with total surgeon chief case volume (odds ratio = 1.47, 95% confidence interval 1.18-1.84, P.01) and graduating from a US medical school (odds ratio = 2.54, 95% confidence interval 1.45-4.44, P.01) while negatively associated with completing a dedicated research experience (odds ratio = 0.31, 95% confidence interval 0.22-0.45, P.01).This is the first multi-institutional study exploring resident operative experience and career choice. These data suggest residents who desire immediate practice can tailor their experience with less research time and increased operative volume. These data may be helpful for programs when designing their experience for residents with different career goals.

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

Despite the remarkable success of immunotherapy in many types of cancer, pancreatic ductal adenocarcinoma has yet to benefit. Innate immune cells are critical to anti-tumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Here we demonstrate that yeast-derived particulate β-glucan, an inducer of trained immunity, traffics to the pancreas, which causes a CCR2-dependent influx of monocytes/macrophages to the pancreas that display features of trained immunity. These cells can be activated upon exposure to tumor cells and tumor-derived factors, and show enhanced cytotoxicity against pancreatic tumor cells. In orthotopic models of pancreatic ductal adenocarcinoma, β-glucan treated mice show significantly reduced tumor burden and prolonged survival, which is further enhanced when combined with immunotherapy. These findings characterize the dynamic mechanisms and localization of peripheral trained immunity and identify an application of trained immunity to cancer.

Single-center data suggest that general surgery residents perform more cases related to their future fellowship compared with their peers. This study aimed to determine whether this experience was true for residents across multiple programs.Data from graduates of 18 Accreditation Council for Graduate Medical Education (ACGME)-accredited general surgery residency programs in the US Resident OPerative Experience (ROPE) Consortium were analyzed. Residents were categorized as entering 1 of 12 fellowships or entering directly into general surgery practice. Case log operative domains were mapped to each fellowship, and analyses were performed between groups.Of 1,192 graduated general surgery residents, 955 (80%) pursued fellowship training whereas 235 (20%) went directly into general surgery practice. The top 3 fellowships pursued were trauma/surgical critical care (18%), vascular surgery (13%), and minimally invasive surgery (12%). Residents entering minimally invasive surgery performed the most total cases, whereas residents pursuing breast performed the least (1,209 [1,056-1,325] vs 1,091 [1,006-1,171], plt; 0.01). For each fellowship type, graduates completed more total fellowship-specific cases in their future specialty compared with their peers (all plt; 0.05). This association was observed for all 12 fellowships at the surgeon chief level (all plt; 0.05) and for 10 of 12 fellowships at the surgeon junior level (all plt; 0.05).General surgery residents perform more cases related to their future specialty choice compared with their peers. These data suggest that the specialization process begins during residency. This tendency among residents should be considered as general surgery residency undergoes structural redesign in the future.

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.

Hepatocellular carcinoma (HCC), the most common primary hepatic malignancy worldwide, is the second leading cause of cancer-related death. Underlying liver dysfunction and advanced stage of disease require treatments to be optimally timed and implemented to minimize hepatic parenchymal damage while maximizing disease response and quality of life. Locoregional therapies (LRTs) such as trans-arterial chemo- and radio-embolization remain effective for intermediate liver-only and advanced HCC disease (i.e., Barcelona-Clinic liver cancer stages B and C) not amendable to primary resection or ablation. Additionally, these minimally invasive interventions have been shown to augment the immune system. This and the recent success of immune-oncologic treatments for HCC have generated interest in applying these therapies in combination with such locoregional interventions to improve patient outcomes and response rates. This report reviews the use of trans-arterial LRTs with immunotherapy for stages B and C HCC, potential biomarkers, and imaging methods for assessing the response and safety of such combinations.

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 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.

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.

SARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, a significant number of patients develop severe or critical disease. Patients with severe COVID-19 commonly present with viral pneumonia that may progress to life-threatening acute respiratory distress syndrome (ARDS). Patients with COVID-19 are also predisposed to venous and arterial thromboses that are associated with a poorer prognosis. The present study identified the emergence of a low-density inflammatory neutrophil (LDN) population expressing intermediate levels of CD16 (CD16Int) in patients with COVID-19. These cells demonstrated proinflammatory gene signatures, activated platelets, spontaneously formed neutrophil extracellular traps, and enhanced phagocytic capacity and cytokine production. Strikingly, CD16Int neutrophils were also the major immune cells within the bronchoalveolar lavage fluid, exhibiting increased CXCR3 but loss of CD44 and CD38 expression. The percentage of circulating CD16Int LDNs was associated with D-dimer, ferritin, and systemic IL-6 and TNF-α levels and changed over time with altered disease status. Our data suggest that the CD16Int LDN subset contributes to COVID-19–associated coagulopathy, systemic inflammation, and ARDS. The frequency of that LDN subset in the circulation could serve as an adjunct clinical marker to monitor disease status and progression.

Despite the remarkable success of immunotherapy in many types of cancer, pancreatic ductal adenocarcinoma has yet to benefit. Innate immune cells are critical to anti-tumor immunosurveillance and recent studies have revealed that these populations possess a form of memory, termed trained innate immunity, which occurs through transcriptomic, epigenetic, and metabolic reprograming. Here we demonstrate that yeast-derived particulate β-glucan, an inducer of trained immunity, traffics to the pancreas, which causes a CCR2-dependent influx of monocytes/macrophages to the pancreas that display features of trained immunity. These cells can be activated upon exposure to tumor cells and tumor-derived factors, and show enhanced cytotoxicity against pancreatic tumor cells. In orthotopic models of pancreatic ductal adenocarcinoma, β-glucan treated mice show significantly reduced tumor burden and prolonged survival, which is further enhanced when combined with immunotherapy. These findings characterize the dynamic mechanisms and localization of peripheral trained immunity and identify an application of trained immunity to cancer.

Background For patients with cutaneous melanoma, having >1 positive lymph node (LN) is associated with worse survival. We hypothesized that for stage IIIA patients, N2a disease (2 to 3 positive LN) would be associated with a worse prognosis compared to those with N1a disease (1 positive LN). Study design Stage IIIA melanoma patients in the NCDB Participant User File from 2010 to 2016 were analyzed. Overall survival (OS) between N1a and N2a patients was compared. Subgroup analyses were made between patients undergoing sentinel lymph node (SLN) biopsy alone and those undergoing subsequent completion lymph node dissection (CLND). A separate post hoc analysis of T2a patients undergoing SLN biopsy and CLND from a prospective multicenter randomized clinical trial was performed to validate the findings. Results Records of 2,305 IIIA patients were evaluated. In an adjusted survival model, N2a disease was an independent risk factor for worse OS (hazard ratio [HR] 1.56, p = 0.0052). In the subgroup analysis, there was no difference in OS between N1a and N2a disease for patients who underwent SLN biopsy without CLND (p = 0.59), but there was a significant difference in OS for patients who underwent SLN biopsy plus CLND (p = 0.0009). The separate clinical trial database confirmed that for patients with SLN-only disease, there was no difference in OS between N1a and N2a disease. Conclusions For stage IIIA melanoma patients, the distribution of micrometastatic lymph node disease (SLN or non-SLN), rather than the absolute number of SLNs, should be considered when individualizing adjuvant therapy recommendations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Approximately 20% of infected patients experience a severe manifestation of the disease, causing bilateral pneumonia and acute respiratory distress syndrome. Severe COVID-19 patients also have a pronounced coagulopathy with approximately 30% of patients experiencing thromboembolic complications. However, the etiology driving the coagulopathy remains unknown. Here, we explore whether the prominent neutrophilia seen in severe COVID-19 patients contributes to inflammation-associated coagulation. We found in severe patients the emergence of a CD16IntCD44lowCD11bInt low-density inflammatory band (LDIB) neutrophil population that trends over time with changes in disease status. These cells demonstrated spontaneous neutrophil extracellular trap (NET) formation, phagocytic capacity, enhanced cytokine production, and associated clinically with D-dimer and systemic IL-6 and TNF-α levels, particularly for CD40+ LDIBs. We conclude that the LDIB subset contributes to COVID-19-associated coagulopathy (CAC) and could be used as an adjunct clinical marker to monitor disease status and progression. Identifying patients who are trending towards LDIB crisis and implementing early, appropriate treatment could improve all-cause mortality rates for severe COVID-19 patients. One Sentence Summary In this study, we discover that low-density neutrophils significantly contribute to COVID-19-associated coagulopathy and inflammation

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 90 or ≥ 90 days after mastectomy or completion of their reconstruction. Clinicopathologic and operative parameters as well as preoperative and postoperative opioid usage were compared.Patients with opioid use ≥ 90 days after last procedure (POU) had a history of preoperative opioid use (29.3% vs 8.2%, p = 0.002), were more likely to have concomitant psychiatric illness (70% vs 35.6%, p 0.001), and had received adjuvant chemotherapy (43.1% vs 24.7%, p = 0.03). Patients with POU also had greater daily opioid doses prescribed upon discharge (59.6 mg vs 44.6 mg, p 0.001). On multivariable analysis, preoperative opioid use (OR 3.61, 95% CI 1.16-11.22, p = 0.03), daily oral morphine equivalents prescribed at discharge (OME-D) (OR 1.02, 95% CI 1.01-1.05, p = 0.003), and psychiatric illness (OR 4.48, 95% CI 1.85-10.89, p 0.001) were independently associated with POU. Among opioid-naïve patients, 37% were found to have POU. Among these patients, OME at discharge (OR 1.02, 95% CI 1.003-1.04, p = 0.02) and psychiatric illness (OR 3.23, 95% CI 1.25-8.31, p = 0.02) independently predicted POU.Preoperative opioid use, psychiatric illness, and daily OME at discharge independently predict POU after mastectomy.

Introduction The production of excessive amounts of nitric oxide (NO) through inducible nitric oxide synthase (iNOS) contributes to organ injury, inflammation, and mortality after shock. Resveratrol (RSV) is a natural polyphenol that decreases shock-induced hepatic injury and inflammation. We hypothesized that RSV would mediate these effects by decreasing hepatocyte iNOS production. Methods Rat hepatocytes were isolated, cultured with varying concentrations of RSV, and then stimulated to induce iNOS with interleukin-1 and interferon. Induction of iNOS protein was measured by Western blot, iNOS mRNA by polymerase chain reaction, and NO production was measured by culture supernatant nitrite. Activation of intracellular signaling pathways involving Akt, c-Jun N-terminal kinase (JNK), and nuclear factor κB (NF-κB) were measured by Western blot using isoform-specific antibodies. Results RSV decreased the expression of iNOS mRNA, protein, and supernatant nitrite in a dose-dependent manner. Our previous work demonstrated that Akt and JNK both inhibit hepatic iNOS production, whereas NF-κB increases iNOS expression. Analysis of signaling pathways in this study demonstrated that RSV increased JNK phosphorylation but decreased Akt phosphorylation and increased NF-κB activation. Conclusion RSV decreases cytokine-induced hepatocyte iNOS expression, possibly through up-regulation of the JNK signaling pathway. RSV merits further investigation to determine its mechanism as a compound that can decrease inflammation after shock.