Perioperative Lung Resection Outcomes After Implementation of a Multidisciplinary, Evidence-based Thoracic ERAS Program.

ObjectiveThis prospective study evaluated perioperative lung resection outcomes after implementation of a multidisciplinary, evidence-based Thoracic Enhanced Recovery After Surgery (ERAS) Program in an academic, quaternary-care center.BackgroundERAS programs have the potential to improve outcomes, but have not been widely utilized in thoracic surgery.MethodsIn all, 295 patients underwent elective lung resection for pulmonary malignancy from 2015 to 2019 PRE (n = 169) and POST (n = 126) implementation of an ERAS program containing all major ERAS Society guidelines. Propensity score-matched analysis, based upon patient, tumor, and surgical characteristics, was utilized to evaluate outcomes.ResultsAfter ERAS implementation, there was increased minimally invasive surgery (PRE 39.6%→POST 62.7%), reduced intensive care unit utilization (PRE 70.4%→POST 21.4%), improved chest tube (PRE 24.3%→POST 54.8%) and urinary catheter (PRE 20.1%→POST 65.1%) removal by postoperative day 1, and increased ambulation ≥3× on postoperative day 1 (PRE 46.8%→POST 54.8%). Propensity score-matched analysis that accounted for minimally invasive surgery demonstrated that program implementation reduced length of stay by 1.2 days [95% confidence interval (CI) 0.3-2.0; PRE 4.4→POST 3.2), morbidity by 12.0% (95% CI 1.6%-22.5%; PRE 32.0%→POST 20.0%), opioid use by 19 oral morphine equivalents daily (95% CI 1-36; PRE 101→POST 82), and the direct costs of surgery and hospitalization by $3500 (95$1100-5900; PRE $23,000→POST$19,500). Despite expedited discharge, readmission remained unchanged (PRE 6.3%→POST 6.6%; P = 0.94).ConclusionsThe Thoracic ERAS Program for lung resection reduced length of stay, morbidity, opioid use, and direct costs without change in readmission. This is the first external validation of the ERAS Society thoracic guidelines; adoption by other centers may show similar benefit

Tumor size is a major determinant of prognosis of resected stage I hepatocellular carcinoma

The current American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) includes all solitary tumors without vascular invasion as stage I, regardless of tumor size. The aim of this study is to determine the prognostic significance of tumor size in stage I HCC patients. A total of 230 stage I primary HCCs were selected retrospectively. Based on univariate and multivariate analyses, clinical and pathological factors correlated with 5-year disease-free survival (DFS) and 5-year overall survival (OS) were determined. Univariate and multivariate analyses showed significant correlations of low serum alpha-fetoprotein levels (a parts per thousand currency sign20 ng/ml), small tumor size (a parts per thousand currency sign3 cm), wide resection margin (a parts per thousand yen 1 cm), and absence of cirrhotic liver with better DFS, while smaller tumor size, and wide resection margin with better OS. Of all the parameters, tumor size is the most statistically significant markers for DFS and OS. Interestingly, liver cirrhosis exerted prognostic significance in patients with small-size tumors, while resection margin exerted prognostic significance in patients with large-size tumors. Our results indicated that tumor size is the most important determinant of DFS and OS in resected primary stage I HCC patients. Therefore, we advocate redefining solitary tumors of a parts per thousand currency sign3 cm as T1a disease and tumors > 3 cm as T1b disease. This stratification of stage I HCC patients could aid in the determination of prognosis and the development of superior protocols for patient management. However, further analysis of big registry cohorts is needed to establish a common consensus

Expression of hypoxic marker carbonic anhydrase IX predicts poor prognosis in resectable hepatocellular carcinoma.

Carbonic anhydrase IX (CA-IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA-IX in hepatocellular carcinomas (HCCs) remains largely unknown. We examined the expression of 277 unifocal, resectable, primary HCC tumors using immunohistochemistry. The CA-IX protein was expressed in 110 of the 227 (48.5%) HCC tumors. The expression of CA-IX correlated with younger age (P = 0.0446), female sex (P = 0.0049), high serum α-fetoprotein levels (P<1x10-6), larger tumor size (P = 0.0031), high tumor grade P<1x10-6) and high tumor stage (P = 1.5x10-6). Patients with HCC tumors that expressed CA-IX were more likely to have lower 5-year disease-free survival (DFS; P = 0.0001) and 5-year overall survival (OS; P<1x10-6). The multivariate analysis indicated that CA-IX expression was an independent predictor for high tumor stage (P = 0.0047) and DFS (P = 0.0456), and a borderline predictor for OS (P = 0.0762). Furthermore, CA-IX expression predicted poor DFS and OS in patients with high tumor stage (P = 0.0004 and P<1x10-6, respectively). Interestingly, CA-IX expression might contribute to the worse prognosis of female patients with advanced HCCs. Our study indicates the expression of the CA-IX protein is a crucial predictor of poor prognosis in resectable HCC, and it is also an unfavorable prognostic predictor in HCC patients with high tumor stage

Univariate analysis of CA-IX protein expression with various clinical and pathological features in 227 patients with surgically resectable primary hepatocellular carcinoma.

<p>Univariate analysis of CA-IX protein expression with various clinical and pathological features in 227 patients with surgically resectable primary hepatocellular carcinoma.</p

Expression of CA-IX protein in non-cancerous liver parenchyma and HCC.

<p>(A and C) Immunohistochemical staining showed heterogeneous and diffuse membranous/cytoplasmic expression of CA-IX in HCC. (E) In the region of tumor necrosis, the viable tumor cells surrounding the necrotic area (<i>N</i>) exhibited strong CA-IX expression. (B, D, F) B, D, and F were the nontumorous counterpart of A, C, and E, respectively. They exhibited strong staining in the bile duct epithelial cells in the portal area but not in the hepatocytes or the mesenchymal cells. A-F x200 (original magnification).</p

Analysis of CA-IX protein expression in 227 patients with surgically resectable primary hepatocellular carcinoma stratified by gender and tumor stage

<p>Abbreviations: H, high tumor stage; L, low tumor stage.</p><p>a, b, and c designate comparison between the indicated two groups.</p><p><i>P</i> values:</p><p>^a0.0275;</p><p>^b0.0385;</p><p>^c< 1x10^-6</p><p>Analysis of CA-IX protein expression in 227 patients with surgically resectable primary hepatocellular carcinoma stratified by gender and tumor stage</p

Kaplan–Meier analyses of 5-year disease free survival (DFS) and 5-year overall survival (OS) in 227 patients with HCC.

<p>(A and B) The HCCs with CA-IX protein expression correlated with significantly lower DFS and OS than the HCCs without CA-IX protein expression (<i>P</i> = 0.0001 and <i>P</i><1x10^-6, respectively). (C and D) The combinatorial analyses revealed that CA-IX-positive high-stage HCCs had the lowest DFS (<i>P</i><1 x10^-6) and OF (<i>P</i><1x10^-6), which were lower than CA-IX negative high-stage HCCs (<i>P</i> = 0.0004 and <i>P</i><1x10^-6, respectively). However, there were no differences concerning both DFS and OS in low-stage HCCs regardless presence or absence of CA-IX expression. (E and F) The female patients presenting with high-stage HCCs exhibited the lowest DFS (<i>P</i><1 x 10^-6) and OS (<i>P</i><1x10^-6), which were lower than male patients presenting with high-stage HCCs (<i>P</i> = 0.0214 and <i>P</i> = 0.0188, respectively). However, there were no differences concerning DFS and OS in male and female patients with low-stage HCCs. (+): The presence of CA-IX protein expression. (-): The absence of CA-IX expression.</p

Multivariate analyses of the risk factors associated with high stage tumor, disease-free survival and overall survival of patients with surgically resectable primary hepatocellular carcinoma.

<p>Abbreviations: S.E., Standard error; O.R., Odds ratio; H.R., Hazard ratio; C.I., Confidence interval; AFP, α-fetoprotein; L, Low or Large; H, High; S, Small; P, presence; N, absences.</p><p>^† Logistic regression model</p><p>^‡ Cox’s proportional hazards model</p><p>Multivariate analyses of the risk factors associated with high stage tumor, disease-free survival and overall survival of patients with surgically resectable primary hepatocellular carcinoma.</p