Yvonne H. Sada

Hepatocellular Carcinoma in the Absence of Cirrhosis in United States Veterans is Associated With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS Hepatocellular carcinoma (HCC) can develop in individuals without cirrhosis. We investigated risk factors for development of HCC in the absence of cirrhosis in a U.S. METHODS We identified a national cohort of 1500 patients with verified HCC during 2005 to 2010 in the U.S. Veterans Administration (VA) and reviewed their full VA medical records for evidence of cirrhosis and risk factors for HCC. Patients without cirrhosis were assigned to categories of level 1 evidence for no cirrhosis (very high probability) or level 2 evidence for no cirrhosis (high probability), which were based on findings from histologic analyses, laboratory test results, markers of fibrosis from noninvasive tests, and imaging features. RESULTS A total of 43 of the 1500 patients with HCC (2.9%) had level 1 evidence for no cirrhosis, and 151 (10.1%) had level 2 evidence for no cirrhosis; the remaining 1203 patients (80.1%) had confirmed cirrhosis. Compared with patients with HCC in presence of cirrhosis, greater proportions of patients with HCC without evidence of cirrhosis had metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), or no identifiable risk factors. Patients with HCC without evidence of cirrhosis were less likely to have abused alcohol or have hepatitis C virus infection than patients with cirrhosis. Patients with HCC and NAFLD (unadjusted odds ratio, 5.4; 95% confidence interval, 3.4-8.5) or metabolic syndrome (unadjusted odds ratio, 5.0; 95% confidence interval, 3.1-7.8) had more than 5-fold risk of having HCC in the absence of cirrhosis, compared with patients with HCV-related HCC. CONCLUSIONS Approximately 13% of patients with HCC in the VA system do not appear to have cirrhosis. NAFLD and metabolic syndrome are the main risk factors for HCC in the absence of cirrhosis.

Referral and receipt of treatment for hepatocellular carcinoma in United States veterans: effect of patient and nonpatient factors.

The delivery of treatment for hepatocellular carcinoma (HCC) could be influenced by the place of HCC diagnosis (hospitalization versus outpatient), subspecialty referral following diagnosis, as well as physician and facility factors. We conducted a study to examine the effect of patient and nonpatient factors on the place of HCC diagnosis, referral, and treatment in Veterans Administration (VA) hospitals in the United States. Using the VA Hepatitis C Clinical Case Registry, we identified hepatitis C virus (HCV)‐infected patients who developed HCC during 1998‐2006. All cases were verified and staged according to Barcelona Clinic Liver Cancer (BCLC) criteria. The main outcomes were place of HCC diagnosis, being seen by a surgeon or oncologist, and treatment. We examined factors related to these outcomes using hierarchical logistic regression. These factors included HCC stage, HCC surveillance, physician specialty, and facility factors, in addition to risk factors, comorbidity, and liver disease indicators. Approximately 37.2% of the 1,296 patients with HCC were diagnosed during hospitalization, 31.0% were seen by a surgeon or oncologist, and 34.3% received treatment. Being seen by a surgeon or oncologist was associated with surveillance (adjusted odds ratio [aOR] = 1.47; 95% CI: 1.20‐1.80) and varied by geography (1.74;1.09‐2.77). Seeing a surgeon or oncologist was predictive of treatment (aOR = 1.43; 95% CI: 1.24‐1.66). There was a significant increase in treatment among patients who received surveillance (aOR = 1.37; 95% CI: 1.02‐1.71), were seen by gastroenterology (1.65;1.21‐2.24), or were diagnosed at a transplant facility (1.48;1.15‐1.90). Conclusion: Approximately 40% of patients were diagnosed during hospitalization. Most patients were not seen by a surgeon or oncologist for treatment evaluation and only 34% received treatment. Only receipt of HCC surveillance was associated with increased likelihood of outpatient diagnosis, being seen by a surgeon or oncologist, and treatment. (HEPATOLOGY 2013;)

Cirrhosis is under-recognised in patients subsequently diagnosed with hepatocellular cancer.

Most clinical practice guidelines recommend screening for HCC in patients with cirrhosis. However, patients with compensated cirrhosis are often asymptomatic and may remain unrecognised for years.

Validation of Case Finding Algorithms for Hepatocellular Cancer From Administrative Data and Electronic Health Records Using Natural Language Processing.

Background:Accurate identification of hepatocellular cancer (HCC) cases from automated data is needed for efficient and valid quality improvement initiatives and research. We validated HCC International Classification of Diseases, 9th Revision (ICD-9) codes, and evaluated whether natural language processing by the Automated Retrieval Console (ARC) for document classification improves HCC identification. Methods:We identified a cohort of patients with ICD-9 codes for HCC during 2005–2010 from Veterans Affairs administrative data. Pathology and radiology reports were reviewed to confirm HCC. The positive predictive value (PPV), sensitivity, and specificity of ICD-9 codes were calculated. A split validation study of pathology and radiology reports was performed to develop and validate ARC algorithms. Reports were manually classified as diagnostic of HCC or not. ARC generated document classification algorithms using the Clinical Text Analysis and Knowledge Extraction System. ARC performance was compared with manual classification. PPV, sensitivity, and specificity of ARC were calculated. Results:A total of 1138 patients with HCC were identified by ICD-9 codes. On the basis of manual review, 773 had HCC. The HCC ICD-9 code algorithm had a PPV of 0.67, sensitivity of 0.95, and specificity of 0.93. For a random subset of 619 patients, we identified 471 pathology reports for 323 patients and 943 radiology reports for 557 patients. The pathology ARC algorithm had PPV of 0.96, sensitivity of 0.96, and specificity of 0.97. The radiology ARC algorithm had PPV of 0.75, sensitivity of 0.94, and specificity of 0.68. Conclusions:A combined approach of ICD-9 codes and natural language processing of pathology and radiology reports improves HCC case identification in automated data.

“What Bothers You the Most?” Initial Responses From Patients Receiving Palliative Care Consultation

The purpose of this investigation is to describe how hospitalized palliative care patients respond to the question “What bothers you the most?” at the time of initial consultation. A retrospective descriptive content analysis of first person responses routinely recorded during initial interview (n = 286) was carried out. Responses were grouped in 7 major categories: physical distress (44%); emotional, spiritual, existential, or nonspecific distress (16%); relationships (15%); concerns about the dying process and death (15%); loss of function and normalcy (12%); distress about location (11%); and distress with medical providers or treatment (9%). Fifteen percent of responses were unable to be reliably categorized. Although many of our patients were not able to answer open-ended questions because of illness, those who did shared a wide range of concerns that provided a starting point for clinical prioritization. Further research into the use of such simple questions at time of initial consultation is warranted.

The effect of age and comorbidity on patient-centered health outcomes in patients receiving adjuvant chemotherapy for colon cancer

OBJECTIVES While the impact of age, comorbidity and receipt of adjuvant chemotherapy on survival are known, less is known about their effect on patient-centered outcomes including living situation and unplanned health care services. The current study describes the impact of age and comorbidity on patient-centered outcomes in patients with colon cancer. MATERIALS AND METHODS Patients with resected stage III colon cancer and high risk stage II colon cancer were identified from a colorectal cancer center database. Using data collected from chart abstraction, we describe unplanned health care utilization and trajectories of living situation (use of home health, skilled nursing facility, etc.) among high-risk stage II and III colon cancer patients with regard to age categories and receipt of adjuvant chemotherapy. RESULTS Among 126 eligible patients, 66% received adjuvant chemotherapy and 34% did not. Older patients receiving chemotherapy were more likely to be living independently (81%) compared to those older patients who did not receive chemotherapy (63%). Older patients receiving chemotherapy were less likely to be started on an oxaliplatin-containing regimen compared to younger patients (54% vs. 81%, p=0.02). On multivariate analysis, both diabetes mellitus (OR 3.70 [95% CI 1.3-10.2]) and chronic obstructive pulmonary disease (OR 4.26 [95% CI 1.1-16.0]) were significantly associated with unplanned health care service use. CONCLUSION Medical oncologists appear to factor clinical and sociodemographic variables when making recommendations for adjuvant chemotherapy. Older patients deemed eligible for chemotherapy did not experience significant changes in living situation. Among patients with colon cancer receiving adjuvant chemotherapy, diabetes mellitus and COPD are associated with emergency visits and hospital admissions.

Utility of Adjuvant Chemotherapy After Neoadjuvant Chemoradiation and Esophagectomy for Esophageal Cancer.

Objective: To determine whether adjuvant chemotherapy (AC) after neoadjuvant chemoradiation and esophagectomy is associated with improved overall survival for patients with locally advanced esophageal cancer, and to evaluate how pathologic disease response to neoadjuvant treatment impacts this effect. Background: Neoadjuvant chemoradiation is currently the preferred management approach for locoregional esophageal cancer. Although there is interest in the use of AC, the benefit of systemic therapy after neoadjuvant chemoradiation and esophagectomy is unclear. Methods: Retrospective cohort study of patients with esophageal cancer treated with neoadjuvant chemoradiation and esophagectomy in the National Cancer Data Base (2006–2012). Results: Among 3592 patients with esophageal cancer (84.7% adenocarcinoma, 15.2% squamous cell carcinoma), 335 (9.3%) were treated with AC. AC was not associated with a significantly lower risk of death among patients with no residual disease (ypT0N0) or residual non-nodal disease (ypT+N0). Among patients with residual nodal disease (ypTanyN+), AC was associated with a 30% lower risk of death in the overall cohort [hazard ratio (HR) 0.70, (0.57–0.85)] and among those with adenocarcinoma [HR 0.69 (0.57–0.85)]. Using a 90-day postoperative landmark, findings were similar. Among patients with postoperative length of stay ⩽10 days and no unplanned readmission, AC was associated with approximately 40% lower risk of death among patients with residual nodal disease [overall cohort, HR 0.63 (0.48–0.84); adenocarcinoma, HR 0.66 (0.49–0.88)]. Conclusions: AC after neoadjuvant chemoradiation and esophagectomy is associated with improved survival in patients with residual nodal disease. Our findings suggest AC may provide additional benefit for esophageal cancer patients, and merits further investigation.

Transarterial bland versus chemoembolization for hepatocellular carcinoma: rethinking a gold standard

BACKGROUND Transarterial chemoembolization (TACE) is the most common procedure for the treatment of hepatocellular carcinoma (HCC). However, HCC is generally considered chemoresistant and data demonstrating the superiority of TACE over bland embolization (TAE) are lacking. MATERIALS AND METHODS A nationwide, retrospective cohort study of HCC patients treated with first-line TACE or TAE within the Veterans Affairs health care system (2005-2012) was performed. The primary outcome was overall survival. Risk of death by treatment type (TACE or TAE) was evaluated using multivariate (adjusted for age, presence of cirrhosis, Barcelona Clinic Liver Cancer stage, and Charlson comorbidity score) and propensity score-adjusted Cox regression. RESULTS The cohort included 405 patients treated with first-line transarterial embolization. Among these patients, 32 (7.9%) underwent TAE. Most of the patients (76.8%) had intermediate or advanced stage at presentation. Similar proportions of patients (TACE 53.3% versus TAE 43.7%; P = 0.30) received more than one embolization procedure. There was no difference in median survival (20.1 versus 23.1 mo, respectively; log-rank P = 0.84). Compared to TACE, there was no difference in risk of death associated with TAE after multivariate (hazard ratio [HR] 0.92; 95% CI, 0.61-1.37) and propensity score adjustment (HR = 0.86; 95% CI = 0.58-1.29). CONCLUSIONS There is no clear benefit associated with chemotherapy infusion over bland embolization for HCC treatment. Given the rising incidence of HCC in the United States and considering the added costs associated with TACE compared to TAE, future work comparing these competing management strategies is needed.

The role of surgery and adjuvant therapy in lymph node‐positive cancers of the gallbladder and intrahepatic bile ducts

Lymph node metastasis is a poor prognostic factor for biliary tract cancers (BTCs). The optimal management of patients who have BTC with positive regional lymph nodes, including the impact of surgery and adjuvant therapy (AT), is unclear.

Vandetanib for the treatment of lung cancer

Introduction: VEGF and EGFR are validated pathways for targeted therapy in non-small cell lung cancer (NSCLC). Once considered to be separate targets, VEGF and EGFR are now shown to have interconnected downstream pathways, potentiating the effectiveness of their dual signaling inhibition in cancer therapy. Molecules such as vandetanib that inhibit VEGFR and EGFR have also been reported to inhibit other receptors, including RET and additional kinases, and may be beneficial in treating patients with solid tumors. Areas covered: This review covers the significance of targeting VEGF and EGFR in the treatment of NSCLC and the rationale behind their dual inhibition. Clinical trials that evaluate the use of vandetanib in the setting of refractory NSCLC are also explored. Expert opinion: Vandetanib is currently not approved in the setting of NSCLC. However, its approval for medullary thyroid cancer makes it promising for identifying markers and potentially a NSCLC patient population who will benefit from the treatment.