Faculty Bibliography

BACKGROUND:Anatomic hepatectomies can be associated with complicated post-operative recoveries, often with discharge to post-acute care facilities. This study identifies preoperative and intraoperative factors associated with increased risk for non-home discharge destination after major hepatectomy. METHODS:Patients undergoing major hepatectomy were identified in the NSQIP Targeted Hepatectomy Dataset (2014-2016). Multivariable logistic regression was performed. Patients from 2014 to 2015 were used for training cohort with nomogram generation and 2016 for validation cohort. RESULTS:Overall, 226 of 3750 patients (6.0%) were discharged to rehab, skilled care, or acute care facilities. Preoperative factors associated with non-home discharge on multivariable analysis were outside patient transfers, older age, presence of ascites, ASA physical status 3 or higher, and low preoperative hematocrit (all p < 0.05). Intraoperative factors significantly predictive were concurrent lysis of adhesions, Pringle maneuver, and biliary reconstruction (all p < 0.05). Predictors from testing cohort were validated in validation cohort. Nomograms based on preoperative variables alone and both preoperative and intraoperative variables were generated. CONCLUSION:We identify several preoperative and intraoperative factors that are associated with increased risk for non-home discharge after major hepatectomy. Preoperative anemia represents a potentially modifiable risk factor. Nomograms for preoperative planning as well as immediately following surgery were generated.

INTRODUCTION:Pancreaticoduodenectomy is a complex surgical procedure. The purpose of this study was to identify factors associated non-home discharge destination and to characterize outcomes after non-home discharge. METHODS:10,719 pancreaticoduodenectomy cases contained in the National Surgical Quality Improvement Program (NSQIP) Targeted Pancreatectomy dataset (years 2014-2016) were examined with univariate and multivariate logistic regression. RESULTS:1336 patients (12.5%) were discharged to rehabilitation, skilled care, or acute care facilities. Preoperative factors significantly associated with non-home discharge on multivariate analysis were female gender, older age, elevated BMI, poor functional status or dyspnea, smoking, low albumin, COPD, and ascites. Intraoperative factors significantly associated with non-home discharge destination on multivariate analysis were longer operative time, open surgery, softer pancreatic texture, drain placement, and jejunostomy tube placement. A nomogram was generated for estimating probability of non-home discharge immediately after surgery. CONCLUSION:Preoperative and intraoperative factors can be used to predict probability of non-home discharge immediately after completion of pancreaticoduodenectomy.

BACKGROUND:Pancreaticoduodenectomy is a complex surgery frequently associated with prolonged hospitalizations. However, there are a subset of patients discharged within 5 days from surgery; the preoperative and intraoperative characteristics of this subset are unknown. METHODS:The NSQIP Targeted Pancreatectomy Dataset was used from 2014 to 2016. Patients who died within 30 days were excluded. A total of 10,741 patients undergoing pancreaticoduodenectomy were identified. Univariable and multivariable logistic regression analyses were performed for preoperative and intraoperative ACS-NSQIP variables to identify predictors of early discharge. Early discharge was defined as discharge 3-5 days after surgery. RESULTS:A total of 1105 patients (10.3%) were discharged within 5 days following pancreaticoduodenectomy. On multivariable analysis, preoperative factors associated with early discharge included younger age (OR 0.988, p < 0.001), non-obesity (OR 0.737, p = 0.001), those receiving neoadjuvant chemotherapy (OR 1.424, p < 0.001), and lack of COPD (OR 0.489, p = 0.005) or hypertension (OR 0.805, p = 0.007). Intraoperative factors associated with early discharge on multivariable analysis were shorter operation duration (OR 0.999, p = 0.002), minimally invasive surgery (OR 3.537, p < 0.001), and hard pancreatic texture (OR 1.480, p < 0.001). Intraoperative factors associated with non-early discharge were epidural placement (OR 0.485, p < 0.001), drain placement (OR 0.308, p < 0.001), and jejunostomy tube placement (OR 0.278, p < 0.001). Patients discharged within 5 days had a 14.7% readmission rate compared to 17.0% for later discharges (p = 0.047). CONCLUSIONS:Multiple preoperative and intraoperative factors, including some that are potentially modifiable, were significantly associated with early discharge after pancreaticoduodenectomy. Patients with these characteristics may benefit from enhanced recovery after surgery programs and expedited disposition planning postoperatively.

PURPOSE:On computed tomography (CT), intrahepatic cholangiocarcinomas (ICC) are a visibly heterogeneous group of tumors. The purpose of this study was to investigate the associations between CT imaging phenotypes, patient survival, and known genetic markers. METHODS:A retrospective study was performed with 66 patients with surgically resected ICC. Pre-surgical CT images of ICC were assessed by radiologists blinded to tumor genetics and patient clinical data. Associations between qualitative imaging features and overall survival (OS) and disease-free survival (DFS) were performed with Cox proportional hazards regression and visualized with Kaplan-Meier plots. Associations between radiographic features and genetic pathways (IDH1, Chromatin and RAS-MAPK) were assessed with Fisher's Exact test and the Wilcoxon Rank sum test where appropriate and corrected for multiple comparisons within each pathway using the False Discovery Rate correction. RESULTS:Three imaging features were significantly associated with a higher risk of death: necrosis (hazard ratio (HR) 2.95 95% CI 1.44-6.04, p = 0.029), satellite nodules (HR 3.29, 95% CI:1.35-8.02, p = 0.029), and vascular encasement (HR 2.63, 95% CI 1.28-5.41, p = 0.029). Additionally, with each increase in axial size, the risk of death increased (HR 1.14, 95% CI 1.03-1.26, p = 0.029). Similar to findings for OS, satellite nodules (HR 3.81, 95% CI 1.88-7.71, p = 0.002) and vascular encasement (HR 2.25, 95% CI 1.24-4.06, p = 0.019) were associated with increased risk of recurrence/death. No significant associations were found between radiographic features and genes in the IDH1, Chromatin or RAS-MAPK pathways (p = 0.63-84). CONCLUSION:This preliminary analysis of resected ICC suggests associations between CT imaging features and OS and DFS. No association was identified between imaging features and currently known genetic pathways.

Intrahepatic cholangiocarcinomas are histologically heterogenous. Using a cohort of 184 clinically defined, resected intrahepatic cholangiocarcinomas, we retrospectively classified the histology into 4 subtypes: large duct (LD), small duct (SD) (predominantly tubular [SD1] or predominantly anastomosing/cholangiolar, [SD2]), or indeterminate. Then, we tested the 4 subtypes for associations with risk factors, patient outcomes, histology, and immunophenotypic characteristics. SD was the most common (84%; 24% SD1 and 60% SD2) with lower proportions of LD (8%), and indeterminate (8%). Primary sclerosing cholangitis was rare (2%), but correlated with LD (P=0.005). Chronic hepatitis, frequent alcohol use, smoking, and steatosis had no histologic association. LD was associated with mucin production (P<0.001), perineural invasion (P=0.002), CA19-9 staining (P<0.001), CK7, CK19, CD56 immunophenotype (P=0.005), and negative albumin RNA in situ hybridization (P<0.001). SD was histologically nodular (P=0.019), sclerotic (P<0.001), hepatoid (P=0.042), and infiltrative at the interface with hepatocytes (P<0.001). Albumin was positive in 71% of SD and 18% of LD (P=0.0021). Most albumin positive tumors (85%) lacked extracellular mucin (P<0.001). S100P expression did not associate with subtype (P>0.05). There was no difference in disease-specific or recurrence-free survival among the subtypes. Periductal infiltration and American Joint Committee on Cancer eighth edition pT stage predicted survival by multivariable analysis accounting for gross configuration, pT stage, and histologic type. pT2 had worse outcome relative to other pT stages. Significant differences in histology and albumin expression distinguish LD from SD, but there is insufficient evidence to support further subclassification of SD.

BACKGROUND:Racial disparities in colorectal cancer (CRC) screening are frequently attributed to variations in insurance status. The objective of this study was to ascertain whether universal insurance would lead to more equitable utilization of CRC screening for black patients in comparison with white patients. METHODS:Claims data from TRICARE (insurance coverage for active, reserve, and retired members of the US Armed Services and their dependents) for 2007-2010 were queried for adults aged 50 years in 2007, and they were followed forward in time for 4 years (ages, 50-53 years) to identify their first lower endoscopy and/or fecal occult blood test (FOBT). Variations in CRC screening were compared with descriptive statistics and multivariate logistic regression. RESULTS:Among the 24,944 patients studied, 69.2% were white, 20.3% were black, 4.9% were Asian, and 5.6% were other. Overall, 54.0% received any screening: 83.7% received endoscopy, and 16.3% received FOBT alone. Compared with whites, black patients had higher screening rates (56.5%) and had 20% higher risk-adjusted odds of being screened (95% confidence interval [CI], 1.11-1.29). Asian patients had a likelihood of screening similar to that of white patients (odds ratio [OR], 1.06; 95% CI, 0.92-1.23). Females (OR, 1.20; 95% CI, 1.10-1.33), active-duty personnel (OR, 1.15; 95% CI, 1.06-1.25), and officers (OR, 1.28; 95% CI, 1.18-1.37) were also more likely to be screened. CONCLUSION:Within an equal-access, universal health care system, black patients had higher rates of CRC screening in comparison with prior reports and even in comparison with white patients within the population. These findings highlight the need to understand and develop meaningful approaches for promoting more equitable access to preventative care. Moreover, equal-access, universal health insurance for both the military and civilian populations can be presumed to improve access for underserved minorities.

PURPOSE:Clinician gestalt may hold unexplored information that can be capitalized upon to improve existing nomograms. The study objective was to evaluate physician ability to predict 2-year overall survival (OS) in resected pancreatic ductal adenocarcinoma (PDAC) patients based on pre-operative clinical characteristics and routine CT imaging. METHODS:Ten surgeons and two radiologists were provided with a clinical vignette (including age, gender, presenting symptoms, and pre-operative CA19-9 when available) and pre-operative CT scan for 20 resected PDAC patients and asked to predict the probability of each patient reaching 2-year OS. Receiver operating characteristic curves were used to assess agreement and to compare performance with an established institutional nomogram. RESULTS:Ten surgeons and 2 radiologists participated in this study. The area under the curve (AUC) for all physicians was 0.707 (95% CI 0.642-0.772). Attending physicians with > 5 years experience performed better than physicians with < 5 years of clinical experience since completion of post-graduate training (AUC = 0.710, 95% CI [0.536-0.884] compared to AUC = 0.662, 95% CI [0.398-0.927]). Radiologists performed better than surgeons (AUC = 0.875, 95% CI [0.765-0.985] compared to AUC = 0.656, 95% CI [0.580-0.732]). All but one physician outperformed the clinical nomogram (AUC = 0.604). CONCLUSIONS:This pilot study demonstrated significant promise in the quantification of physician gestalt. While PDAC remains a difficult disease to prognosticate, physicians, particularly those with more clinical experience and radiologic expertise, are able to perform with higher accuracy than existing nomograms in predicting 2-year survival.

BACKGROUND:Post-hepatectomy liver insufficiency (PHLI) is a significant cause of morbidity and mortality after liver resection. Quantitative imaging analysis using CT scans measures variations in pixel intensity related to perfusion. A preliminary study demonstrated a correlation between quantitative imaging features of the future liver remnant (FLR) parenchyma from preoperative CT scans and PHLI. The objective of this study was to explore the potential application of quantitative imaging analysis in PHLI in an expanded, multi-institutional cohort. STUDY DESIGN:We retrospectively identified patients from 5 high-volume academic centers who developed PHLI after major hepatectomy, and matched them to control patients without PHLI (by extent of resection, preoperative chemotherapy treatment, age [±5 years], and sex). Quantitative imaging features were extracted from the FLR in the preoperative CT scan, and the most discriminatory features were identified using conditional logistic regression. Percent remnant liver volume (RLV) was defined as follows: (FLR volume)/(total liver volume) × 100. Significant clinical and imaging features were combined in a multivariate analysis using conditional logistic regression. RESULTS:From 2000 to 2015, 74 patients with PHLI and 74 matched controls were identified. The most common indications for surgery were colorectal liver metastases (53%), hepatocellular carcinoma (37%), and cholangiocarcinoma (9%). Two CT imaging features (FD1_4: image complexity; ACM1_10: spatial distribution of pixel intensity) were strongly associated with PHLI and remained associated with PHLI on multivariate analysis (p = 0.018 and p = 0.023, respectively), independent of clinical variables, including preoperative bilirubin and %RLV. CONCLUSIONS:Quantitative imaging features are independently associated with PHLI and are a promising preoperative risk stratification tool.

PURPOSE/OBJECTIVE:To evaluate the prevalence of major and ancillary imaging features from liver imaging reporting and data systems (LI-RADS) version 2014 and their interreader agreement when comparing hepatocellular carcinoma (HCC) to intrahepatic cholangiocarcinoma (ICC) and combined tumor (cHCC-CC). METHODS:The Institutional Review Board approved this HIPAA-compliant retrospective study and waived the requirement for patients' informed consent. Patients with resected HCC (n = 51), ICC (n = 40), and cHCC-CC (n = 11) and available pre-operative contrast-enhanced MRI were included from 2000 to 2015. Imaging features and final LI-RADS category were evaluated by four radiologists. Imaging features were compared by Fisher's exact test and interreader agreements were assessed by κ statistics. RESULTS:None of the features were unique to either HCC or non-HCC. Imaging features that were significantly more common among HCC compared to ICC and cHCC-CC included washout (76%-78% vs. 10%-35%, p < 0.001), capsule (55%-71% vs. 16%-49%, p < 0.05), and intralesional fat (27%-52% vs. 2%-12%, p < 0.002). Features that were more common among ICC and cHCC-CC included peripheral arterial phase hyperenhancement (40%-64% vs. 10%-14%, p < 0.001) and progressive central enhancement (65%-82% vs. 14%-25%, p < 0.001). The interreader agreement was moderate for each of these imaging features (κ = 0.41-0.55). Moderate agreement was also achieved in the assignment of LR-M (κ = 0.53), with an overall sensitivity and specificity for non-HCC malignancy of 86.3% and 78.4%, respectively. CONCLUSION/CONCLUSIONS:HCC and non-HCC show significant differences in the prevalence of imaging features defined by LI-RADS, and are identified by radiologists with moderate interreader agreement. Using LI-RADS, radiologists also achieved moderate interreader agreement in the assignment of the LR-M category.

BACKGROUND:Microvascular invasion (MVI) is a significant risk factor for early recurrence after resection or transplantation for hepatocellular carcinoma (HCC). Knowledge of MVI status would help guide treatment recommendations, but is generally identified after operation. This study aims to predict MVI preoperatively using quantitative image analysis. STUDY DESIGN/METHODS:One hundred and twenty patients from 2 institutions underwent resection of HCC from 2003 to 2015 were included. The largest tumor from preoperative CT was subjected to quantitative image analysis, which uses an automated computer algorithm to capture regional variation in CT enhancement patterns. Quantitative imaging features by automatic analysis, qualitative radiographic descriptors by 2 radiologists, and preoperative clinical variables were included in multivariate analysis to predict histologic MVI. RESULTS:Histologic MVI was identified in 19 (37%) patients with tumors ≤5 cm and 34 (49%) patients with tumors >5 cm. Among patients with tumors ≤5 cm, none of the clinical findings or radiographic descriptors were associated with MVI; however, quantitative features based on angle co-occurrence matrix predicted MVI with an area under curve of 0.80, positive predictive value of 63%, and negative predictive value of 85%. In patients with tumors >5 cm, higher α-fetoprotein level, larger tumor size, and viral hepatitis history were associated with MVI, and radiographic descriptors were not. However, a multivariate model combining α-fetoprotein, tumor size, hepatitis status, and quantitative feature based on local binary pattern predicted MVI with area under curve of 0.88, positive predictive value of 72%, and negative predictive value of 96%. CONCLUSIONS:This study reveals the potential importance of quantitative image analysis as a predictor of MVI.