Abstract
Purpose
To determine the utility of abdominal imaging to further evaluate abnormal pre-operative liver function tests (LFTs) in patients with head and neck squamous cell carcinoma (HNSCC).
Methods
Records of patients evaluated by the head and neck surgery service from January 2004 through December 2009 were reviewed. For patients with abnormal alkaline phosphatase, alanine transaminase, or aspartate transaminase, subsequent abdominal imaging was assessed.
Results
Of the 862 patients with HNSCC who had documented LFTs, 109 (12.6%) had one or more abnormal values. In the same time period, LFTs were also obtained on 361 patients with benign head and neck tumors; of these, 40 (11.1%) had abnormalities. Of the 109 patients with HNSCC and abnormal LFTs, 78 (71.6%) underwent abdominal imaging (ultrasound, CT, MRI, or PET/CT). Overall, liver metastasis was demonstrated in only 1 of 109 patients with abnormal LFTs (0.92%) and in only 1 of 862 patients with HNSCC (0.12%).
Conclusions
While HNSCC patients rarely present with liver metastasis, they often have abnormal LFTs. Although the presence of liver metastasis can dramatically change patient management, the yield of follow-up liver imaging for all patients with elevated LFTs is exceedingly low. Thus, the use of risk-stratified abdominal imaging may be prudent and cost effective in a select group of patients in whom distant metastasis is more likely. However, characteristics of this group are difficult to define given the rarity of liver metastasis in HNSCC.
1
Introduction
The presence of distant metastasis can dramatically alter the treatment plan for patients with head and neck squamous cell carcinoma (HNSCC); thus, standard practice has been to perform a metastatic work-up when a primary HNSCC is detected. Historically, the metastatic work-up included a chest X-ray, alkaline phosphatase, and liver function tests (LFTs) to evaluate for lung, bone, and liver metastases, respectively. More currently, in many cancer centers, imaging is the preferred method of evaluating for the presence of distant metastasis, particularly in patients with advanced locoregional disease. However, LFTs are often still obtained in patients with HNSCC prior to surgery, radiotherapy, and/or chemotherapy, and the optimal management of abnormal LFTs is unclear, particularly in patients who have not undergone imaging beyond the head and neck.
LFTs include lactate dehydrogenase (LDH), alanine transaminase (ALT), and aspartate transaminase (AST). In general, elevation of serum transaminases indicates hepatocellular injury, but the degree of elevation does not correlate well with the extent of liver cell damage. Liver metastases, heavy alcohol use and other liver pathologies such as hepatitis can all raise LFTs, and the degree of elevation does not indicate a specific cause.
Liver metastases are rare in HNSCC, especially at the time of presentation . HNSCC tends to spread via lymphatics rather than hematogenously; as a result, disease is generally detected when the primary tumor or regional lymph nodes expand, which usually precedes distant spread occurs. When metastasis occurs, it often starts with pulmonary and mediastinal nodal disease, followed by hepatic and/or bone metastasis . It is rare that these latter sites develop disease without first affecting the lungs, and Merino et al. found only 0.7% of 5019 patients to have liver metastasis as the initial metastatic site .
Given the rarity of hepatic metastasis in patients with HNSCC at the time of presentation, LFTs are a poor screening test , but they are often of utility in other aspects of patient assessment. In the present study, we evaluate the frequency of abnormal LFTs in a large series of patients with HNSCC and the cost and utility of subsequent abdominal imaging prior to definitive therapy.
2
Methods
The University of Virginia Institutional Review Board for Health Sciences Research approved this retrospective review (IRB-HSR #15181). The Head and Neck Tumor Research Database was searched for patients who were initially evaluated in our Head and Neck Surgery Clinic between January 1, 2004 and December 31, 2009 and who had LFTs performed as part of their work-up. Patients were excluded if they already carried a diagnosis of liver metastasis at the time of presentation or if their primary pathology was never diagnosed. Management changes based on elevated LFTs were gleaned from the medical record. Most patients with an abnormal value in alkaline phosphatase, alanine transaminase, or aspartate transaminase, underwent subsequent abdominal imaging or further workup including liver ultrasound, CT scan of the chest or abdomen, MRI of the abdomen, whole body PET/CT scan, and/or liver biopsy. The results of these additional studies were reviewed and the related costs were determined. Statistical analysis was conducted using a standard chi-square test.
2
Methods
The University of Virginia Institutional Review Board for Health Sciences Research approved this retrospective review (IRB-HSR #15181). The Head and Neck Tumor Research Database was searched for patients who were initially evaluated in our Head and Neck Surgery Clinic between January 1, 2004 and December 31, 2009 and who had LFTs performed as part of their work-up. Patients were excluded if they already carried a diagnosis of liver metastasis at the time of presentation or if their primary pathology was never diagnosed. Management changes based on elevated LFTs were gleaned from the medical record. Most patients with an abnormal value in alkaline phosphatase, alanine transaminase, or aspartate transaminase, underwent subsequent abdominal imaging or further workup including liver ultrasound, CT scan of the chest or abdomen, MRI of the abdomen, whole body PET/CT scan, and/or liver biopsy. The results of these additional studies were reviewed and the related costs were determined. Statistical analysis was conducted using a standard chi-square test.
3
Results
3.1
Patients
1808 patients with head and neck tumors had documented LFTs. 1223 of these patients were included in this study, 862 of whom had HNSCC and 361 of whom had benign lesions and were used as a control group. 585 patients were excluded because they had other types of head and neck malignancies.
3.2
Liver Function Test Results
As summarized in Table 1 , 109 patients (12.6%) with HNSCC had abnormalities of one or more of the LFTs and 71.6% of these (78 patients) had follow-up imaging. Seven patients underwent secondary imaging when the initial imaging modality was inconclusive. One patient with HNSCC had imaging consistent with hepatic metastasis; this represents 0.92% of patients with HNSCC and elevated LFTs and 0.12% of all patients with HNSCC. None of the 31 patients with abnormal LFTs who did not undergo additional workup had subsequent documented evidence of liver metastasis during their follow-up. Of note, 11.1% of patients without malignancy (40 patients) had abnormalities of one or more of the LFTs and 30.0% of these (12 patients) had subsequent imaging demonstrating no liver pathology. The rate of abnormal LFTs in the benign and malignant groups was not statistically different (p = 0.45), but the difference between those groups in the rate of abdominal imaging was significant (p = < 0.001). This likely reflects the low index of suspicion for significant hepatic pathology in patients with benign head and neck tumors.
| Patients | Benign | HNSCC | |
|---|---|---|---|
| All LFTs (% of all) | 1223 (100%) | 361 (100%) | 862 (100%) |
| Abnormal LFTs (% of all) | 149 (12.2%) | 40 (11.1%) | 109 (12.6%) |
| Abdominal Imaging (% of all) {% of abnormal} | 90 (7.4%) {60.4%} | 12 (3.3%) {30.0%} | 78 (9.0%) {71.6%} |
| Liver Metastasis (% of all) {% of abnormal} | 1 (0.08%) {0.7%} | 0 (0.0%) {0.0%} | 1 (0.12%) {0.92%} |
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