Optimal hepatic surgery: Are we making progress in North America?

BACKGROUND: The aim of this analysis was to determine whether optimal outcomes have increased in recent years. Hepatic surgery is high risk, but regionalization and minimally invasive approaches have evolved. Best practices also have been defined with the goal of improving outcomes. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried. Analyses were performed separately for partial (≤2 segments), major (≥3 segments), and all hepatectomies. Optimal hepatic surgery was defined as the absence of mortality, serious morbidity, need for a postoperative invasive procedure or reoperation, prolonged length of stay (<75th percentile) or readmission. Tests of trend, χ2, and multivariable analyses were performed. RESULTS: From 2014 to 2018, 17,082 hepatectomies, including 11,862 partial hepatectomies and 5,220 major hepatectomies, were analyzed. Minimally invasive approaches increased from 25.6% in 2014 to 29.6% in 2018 (P < .01) and were performed more frequently for partial hepatectomies (34.2%) than major hepatectomies (14.4%) (P < .01). Operative time decreased from 220 minutes in 2014 to 208 minutes in 2018 (P < .05) and was lower in partial hepatectomies (189 vs 258 minutes for major hepatectomies) (P < .01). Mortality (0.7%) and length of stay (4 days) were lower for partial hepatectomies compared with major hepatectomies (1.9%; 6 days), and length of stay decreased for both partial hepatectomies (5 days in 2014 to 4 days in 2018) and major hepatectomies (6 days in 2014 to 6 days in 2018) (all P < .01). Postoperative sepsis (2.9% in 2014 and 2.4% in 2018), bile leaks (6% in 2014 and 4.8% in 2018), and liver failure (3.7% in 2014 and 3.3% in 2018) decreased for all patients (<.05). On multivariable analyses, overall morbidity decreased for major hepatectomies (OR 0.95, 95% CI 0.91-0.99) and all hepatectomies (OR 0.97, 95% CI 0.94-0.99, both P < .01), and optimal hepatic surgery increased over time for partial hepatectomies (OR 1.05, 95% CI 1.02-1.09) and all hepatectomies (OR 1.04, 95% CI 1.02-1.07, both P < .01). CONCLUSION: Over a 5-year period in North America, minimally invasive hepatectomies have increased, while operative time, postoperative sepsis, bile leaks, liver failure, and prolonged length of stay have decreased. Optimal hepatic surgery has increased for partial and all hepatectomies and is achieved more often in partial than in major resections.

Small pancreatic neuroendocrine tumors: Resect or enucleate?

BACKGROUND: The aim of this analysis is to compare the postoperative outcomes of resection and enucleation of small pancreatic neuroendocrine tumors (PNETs). METHODS: The 2014-17 American College of Surgeons-NSQIP dataset was queried. Patients undergoing pancreatoduodenectomy (N = 297) or distal pancreatectomy (N = 712) for nonfunctional, small PNETs (T1/T2) were compared to 127 patients (11%) who were enucleated. RESULTS: Operative time (170 vs 261, p < 0.01) and transfusions were less in the enucleation cohort (1.6% vs 6.7% p < 0.01). There was no difference in postoperative pancreatic fistulas, but morbidity was lower in enucleated patients (36.2% vs 48.7% p < 0.01). Fifteen resected patients died postoperatively (1.5%) while all enucleated patients survived (p = 0.058). Mean postoperative length of stay was shorter after enucleation (5.7 vs 7.2 days p < 0.01). CONCLUSIONS: Enucleation of PNETs is performed in only 11% of patients, but takes less time, requires fewer transfusions, and is associated with reduced morbidity and shorter length of stay than resection.

Surgical Stress Promotes Tumor Progression: A Focus on the Impact of the Immune Response.

Despite advances in systemic therapies, surgery is crucial for the management of solid malignancy. There is increasing evidence suggesting that the body's response to surgical stress resulting from tumor resection has direct effects on tumor cells or can alter the tumor microenvironment. Surgery can lead to the activation of early and key components of the innate and adaptative immune systems. Platelet activation and the subsequent pro-coagulation state can accelerate the growth of micrometastases. Neutrophil extracellular traps (NETs), an extracellular network of DNA released by neutrophils in response to inflammation, promote the adhesion of circulating tumor cells and the growth of existing micrometastatic disease. In addition, the immune response following cancer surgery can modulate the tumor immune microenvironment by promoting an immunosuppressive state leading to impaired recruitment of natural killer (NK) cells and regulatory T cells (Tregs). In this review, we will summarize the current understanding of mechanisms of tumor progression secondary to surgical stress. Furthermore, we will describe emerging and novel peri-operative solutions to decrease pro-tumorigenic effects from surgery.

Prognosis of Macrophage Density in the Absence of Neutrophils in Differentiated Thyroid Cancer.

BACKGROUND: Despite the advances in treatment of differentiated thyroid cancer (DTC), predicting prognosis remains a challenge. Immune cells in the tumor microenvironment may provide an insight to predicting recurrence. Therefore, the objective of this study was to investigate the association of tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) with recurrence in DTC and to identify serum cytokines that correlate with the presence of these immune cells in the tumor. MATERIALS AND METHODS: Forty-two DTC tissues from our institutional neoplasia repository were stained for immunohistochemistry markers for TAMs and TANs. In addition, cytokine levels were analyzed from these patients from preoperative blood samples. TAM and TAN staining were compared with clinical data and serum cytokine levels. RESULTS: Neither TAM nor TAN scores alone correlated with tumor size, the presence of lymph node metastases, multifocal tumors, lymphovascular or capsular invasion, or the presence of BRAFV600E mutation (all P > 0.05). There was no association with recurrence-free survival (RFS) in TAN density (mean RFS, 169.1 versus 148.1 mo, P = 0.23) or TAM density alone (mean RFS, 121.3 versus 205.2 mo, P = 0.54). However, when scoring from both markers were combined, patients with high TAM density and TAN negative scores had significantly lower RFS (mean RFS, 50.7 versus 187.3 mo, P = 0.04) compared with the remaining cohort. Patients with high TAM/negative TAN tumors had significantly lower serum levels of interleukin 12p70, interleukin 8, tumor necrosis factor alpha, and tumor necrosis factor beta. CONCLUSIONS: In DTCs, high density of TAMs in the absence of TANs is associated with worse outcome. Assessment of multiple immune cell types and serum cytokines may predict outcomes in DTC.

Neutrophil Elastase and Neutrophil Extracellular Traps in the Tumor Microenvironment.

Tumor-associated neutrophils (TANs) play a major role during cancer development and progression in the tumor microenvironment. Neutrophil elastase (NE) is a serine protease normally expressed in neutrophil primary granules. Formation of neutrophil extracellular traps (NETs), a mechanism used by neutrophils, has been traditionally associated with the capture and killing of bacteria. However, there are recent discoveries suggesting that NE secretion and NETs formation are also involved in the tumor microenvironment. Here, we focus on how NE and NETs play a key regulatory function in the tumor microenvironment, such as tumor proliferation, distant metastasis, tumor-associated thrombosis, and antitumor activity. Additionally, the potential use of NETs, NE, or associated molecules as potential disease activity biomarkers or therapeutic targets will be introduced.

Immune Checkpoint Inhibitors in Hepatocellular Cancer: Current Understanding on Mechanisms of Resistance and Biomarkers of Response to Treatment.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy worldwide and a leading cause of death worldwide. Its incidence continues to increase in the US due to hepatitis C infection and nonalcoholic steatohepatitis. Liver transplantation and resection remain the best therapeutic options for cure, but these are limited by the shortage of available organs for transplantation, diagnosis at advanced stage, and underlying chronic liver disease found in most patients with HCC. Immune checkpoint inhibitors (ICIs) have been shown to be an evolving novel treatment option in certain advanced solid tumors and have been recently approved for inoperable, advanced, and metastatic HCC. Unfortunately, a large cohort of patients with HCC fail to respond to immunotherapy. In this review, we discuss the ICIs currently approved for HCC treatment and their various mechanisms of action. We will highlight current understanding of mechanism of resistance and limitations to ICIs. Finally, we will describe emerging biomarkers of response to ICIs and address future direction on overcoming resistance to immune checkpoint therapy.

Identifying subgroups of well-being among patients with cancer: Differences in attitudes and preferences around surveillance after curative-intent surgery.

BACKGROUND: Patient perceptions and preferences related to postoperative surveillance are not yet well defined. METHODS: A cross-sectional analysis of the surveillance practice preferences and attitudes was undertaken based on subgroups derived from clustering participants for measures of well-being, including financial toxicity, emotional, family/social, and functional well-being. RESULTS: Among 212 participants, the average age was 58.1 years and most patients were female (57.1%) and white (90.2%). Common malignancies included melanoma/sarcoma (26.4%), thyroid (25.5%), breast (18.9%), gastrointestinal (18.4%), and lung (7.5%) cancer. Respondents within the highest well-being subgroup rated their perception of communication as being the highest more consistently compared with the other well-being subgroups (P = .005). Participants with the highest level of well-being felt more reassured by follow-up appointments (Subgroup 1, Med = 4.00, interquartile range (IQR) = 0.25 vs subgroup 4, Med = 3.75, IQR = 0.73, P = .023). In contrast, patients with the lowest sense of well-being had the highest level of nervousness related to surveillance (subgroup 1, Med = 1.60, IQR = 1.00 vs subgroup 4, Med = 2.20, IQR = 1.15, P < .001). There were no differences in surveillance frequency preferences among different well-being subgroups. CONCLUSION: Attitudes towards postoperative surveillance varied with regard to perception of provider communication, nervous anticipation, and assuredness depending on overall patient well-being. Providers should attempt to assess patient well-being as part of a tailored approach to postcancer surgery surveillance.

Long-Term Efficacy of Lymph Node Reoperation for Persistent Papillary Thyroid Cancer: 13-Year Follow-Up.

BACKGROUND: Current recommendations for persistent or recurrent locoregional papillary thyroid cancer (PTC) include consideration of surgical resection versus active surveillance. The purpose of this study is to determine long-term outcomes after surgical resection of recurrent or persistent metastatic PTC in cervical lymph nodes after failure of initial surgery and radioactive iodine therapy using newer validated clinical outcomes measures. METHODS: Outcomes of 70 patients who underwent cervical lymphadenectomy (n = 110) from 1999 to 2013 for recurrent or persistent locoregional PTC metastases were reviewed. Measures included biochemical remission (BCR) based on Tg levels, American Thyroid Association classifications for response to treatment [biochemical incomplete response (BIR), structural incomplete response (SIR), indeterminate response (IR), and excellent response (ER)], need for reoperation, surgical complications, disease progression, and death. RESULTS: The median follow-up was 13.1 years, with only two additional reoperations since 2010, one of which had no metastasis on pathology with the other developing anaplastic thyroid cancer in background PTC. ER was achieved in 31 (44%) patients, all of whom remained in ER at time of last follow-up (median 14.1 years). There were no structural recurrences in patients with persistent BIR or IR after reoperation. Patients with SIR had stable disease, except for one who died due to anaplastic thyroid cancer. CONCLUSIONS: Patients who achieved ER after reoperation had no need for further treatment. Patients with persistent detectable Tg levels after reoperation rarely developed structural recurrence. ATA outcomes can be safely used to guide treatment decisions over a decade after reoperation for PTC.

Patient preferences on the use of technology in cancer surveillance after curative surgery: A cross-sectional analysis.

BACKGROUND: Advances in communication technology have enabled new methods of delivering test results to cancer survivors. We sought to determine patient preferences regarding the use of newer technology in delivering test results during cancer surveillance. METHODS: A single institutional, cross-sectional analysis of the preferences of adult cancer survivors regarding the means (secure digital communication versus phone call or office visit) to receive surveillance test results was undertaken. RESULTS: Among 257 respondents, the average age was 59.1 years (SD 13.5) and 61.8% were female. Common malignancies included melanoma/sarcoma (29.5%), thyroid (25.7%), breast (22.8%), and gastrointestinal (22.0%) cancer. Although patients expressed a relative preference to receive normal surveillance results via MyChart or secure e-mail, the majority preferred abnormal imaging (87.2%) or blood results (85.9%) to be communicated by in-office appointments or phone calls irrespective of age or cancer type. Patients with a college degree or higher were more likely to prefer electronic means of communication of abnormal blood results compared with a telephone call or in-person visit (odds ratio 2.18, 95% confidence interval: 1.01-4.73, P < .05). In contrast, patients >65 years were more likely to express a preference for telephone or in-person communication of normal imaging results (odds ratio: 2.03, 95% CI: 1.16-3.56, P < .05) versus patients ≤65 years. Preference also varied according to malignancy type. CONCLUSION: Although many cancer patients preferred to receive "normal" surveillance results electronically, the majority preferred receiving abnormal results via direct conversation with their provider. Shifting routine communication of normal surveillance results to technology-based applications may improve patient satisfaction and decrease health care system costs.