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Assessment of symptom experience in patients undergoing hepatic resection or ablation
Article first published online: 30 OCT 2006
Copyright © 2006 American Cancer Society
Volume 107, Issue 11, pages 2715–2722, 1 December 2006
How to Cite
Eid, S., Stromberg, A. J., Ames, S., Ellis, S., McMasters, K. M. and Martin, R. C. G. (2006), Assessment of symptom experience in patients undergoing hepatic resection or ablation. Cancer, 107: 2715–2722. doi: 10.1002/cncr.22297
- Issue published online: 17 NOV 2006
- Article first published online: 30 OCT 2006
- Manuscript Accepted: 7 SEP 2006
- Manuscript Revised: 30 AUG 2006
- Manuscript Received: 19 JUN 2006
- hepatic ablation;
- hepatic resection;
- quality of life;
- Functional Assessment of Cancer Therapy
Quality of life (QOL) currently is considered both clinically meaningful and biologically important for patient outcome and is considered as important as disease-free and overall survival. Thus, the objective of the current study was to evaluate the QOL symptoms of patients who underwent major hepatic resection, minor hepatic resection, and ablation for primary or metastatic cancer to the liver.
From October 2002 to June 2004, 40 patients who underwent either hepatic ablation or resection were enrolled. Patients were assessed at 5 time points (the initial visit, the initial postoperative visit, and visits at 6 weeks, 3 months, and 6 months) by questionnaires of the Functional Assessment in Cancer Therapy (FACT) core instrument with the Hepatobiliary subscale (FACT-Hep), the FACT Hepatobiliary Symptom Index (FHSI-8), the Profile of Mood States (POMS), the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire (QLQ) for patients with pancreatic cancer (QLQ-PAN), and the general core EORTC QLQ.
The patients enrolled included 20 men and 20 women with a median age of 62 years (range, 41–77 years), including 24 patients who underwent major hepatectomy, 8 patients who underwent minor hepatectomy, and 8 patients who underwent ablation. An evaluation of the FACT Physical, Social, Emotional, and Functional subscales demonstrated no differences at the initial or first postoperative visits. However, at 6 weeks, both the Physical (P = .0455) and Functional (P = .0372) scores were significantly worse for the major hepatectomy group. At 3 months, all QOL parameters were similar. Similar differences were observed at 6 weeks for the FHSI-8 (P = .02), POMS (P = .007), QLQ-PAN (P = .04), and EORTC (P = .003) with the resolution of this difference at 3 months.
There was little difference in QOL between patients who underwent major hepatic resection, minor hepatic resection, and hepatic ablation. Patients who underwent major hepatectomy demonstrated a worse QOL at 6 weeks compared with patients who underwent minor hepatic resection and hepatic ablation, with the resolution of this difference and significant improvements observed in all 3 groups at 3 months. Cancer 2006. © 2006 American Cancer Society.
During the last decade, there has been growing interest in the assessment of quality of life (QOL) in patients with cancer. QOL currently is considered both clinically meaningful and biologically important in a patient's outcome, and QOL as an outcome is considered as important as disease-free and overall survival.1, 2 QOL assessment has been lacking in the surgical specialties, primarily from the misleading notion that a surgeon's judgment is more reliable than QOL data.3 Recent advances in QOL studies have demonstrated the importance of assessing QOL after major surgical resection in patients with cancer. Successful QOL evaluation has been performed in patients with esophageal,4 gastric,5 colorectal,6 and pancreatic7 cancer after resection. To date, there has been only 1 study that evaluated patients with hepatocellular cancer after they underwent resection.8 That study demonstrated a significant QOL benefit after resection compared with patients who did not undergo resection. To our knowledge, there have been no studies that have evaluated patients' QOL after resection for other hepatic malignancies. There are >1000 hepatic resections and ablations performed each year in the United States for colorectal metastasis, and the overall complication rate is 40%.
There has been significant debate surrounding radiofrequency ablation (RFA) versus hepatic resection with regard to overall survival and recurrence rates. There also is a belief that RFA is a less invasive and less morbid procedure, which translates into an easier recovery compared with the recovery after hepatic resection. Thus, the objectives of the current study were to evaluate patients' QOL after hepatic resection or ablation and to compare the impact on QOL during their recovery after these procedures.
MATERIALS AND METHODS
From October 1, 2002 through June 30, 2004, we identified 40 patients who were eligible for the clinical study. Patients with primary or metastatic cancer to the liver who were scheduled for hepatic resection or ablation were recruited for an observational study of QOL before and after surgical treatment. Patient eligibility was determined by review of the patient's medical records and by the nursing and medical staff at the University of Louisville. Registration and enrollment of patients was done through the University of Louisville medical staff. The study protocol was approved by the Institutional Review Board, and all patients provided written informed consent.
Patients were separated into 3 groups according to their extent of resection. Extent of hepatectomy was defined as major if ≥3 segments were resected and minor if ≤2 segments were resected.
The decision to undergo segmental resection, larger hepatic resection, or ablation was at the surgeon's discretion. Liver resections were classified as described by Couinaud.9 RFA was performed by using intraoperative ultrasound guidance to ensure that at least a 1-cm ablation margin was achieved around the tumors.
Comorbidities were defined as significant cardiac (past coronary bypass, past coronary stenting, or past myocardial infarction), pulmonary, renal, or hepatic dysfunction. Additional organ resections, excluded cholecystectomy, included colon resection, gastric, or any other solid organ in combination with the hepatic resection.
This was an observational study, and no treatment was provided to patients as part of the investigation. We used a pretest-posttest design to assess each patient's experience of symptoms and concerns before and after hepatic resection or ablation. Patients were assessed at 6 time points: prior to the surgical procedure, at discharge postprocedure, at the first postoperative visit, and at 6 weeks, 3 months, and 6 months. Upon enrollment, the study coordinator, research assistant, or investigator completed the treatment history and demographics. At that time, the patients completed a baseline questionnaire battery, which consisted of the Functional Assessment in Cancer Therapy (FACT) core instrument with the Hepatobiliary subscale (FACT-Hep), the Brief Profile of Mood States (POMS), the European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaire (QLQ-C30), and the EORTC QLQ for patients with pancreatic cancer (QLQ-PAN). Only the FACT Hepatobiliary Symptom Index (FHSI-8) was completed by patients at their discharge from the hospital, because many of the questions on the FACT-Hep were not applicable to hospitalized patient. At the 4 remaining time points, the patients completed a questionnaire battery consisting of the FACT-Hep, Brief POMS, EORTC QLQ-C30, EORTC QLQ-PAN, a Global Rating of Change Scale, and FHSI-8. Clinical events (type of surgery, complications, and repeat hospitalizations) were recorded from medical records and patient interview at these final 4 time points. These visits coincided with the scheduled follow-up appointments and did not burden the patient. If a patient missed an appointment or continued follow-up elsewhere, then the follow-up questionnaires were mailed to the patient. For those patients who survived for less than 6 months after surgery, QOL assessment was continued until the patient's last follow-up visit. All questionnaires were completed in English.
The quality of the data obtained from each patient was evaluated when the patient completed all of the questionnaire forms at each visit. The study coordinator, research assistant, or investigator who enrolled the patient checked all forms immediately after they received them to identify any missing data.
Using observational data from or own clinical experience, because there were no prior publications evaluating QOL in patients who underwent hepatic resection or ablation, we estimated a 30% difference in QOL at 6 weeks for patients who underwent major resection versus patients who underwent minor resection and ablation. Assuming an α risk of .05, a β risk of .8, and a difference of 30% at 6 weeks, we estimated that we would need to treat 12 patients in each group. Assuming a postplanned treatment drop-out rate of 20% because of death or noncompliance, we estimated that the sample size required for this study was at least 32 patients.
The quality of data entry was evaluated by the use of range checks on all variables and by double data entry for a small portion of the data (5–10%). This allowed us to evaluate the accuracy of the data entered by the primary data-entry assistant.
The FACT-Hep is a validated instrument for assessing QOL in patients with hepatobiliary cancers, metastatic colorectal cancers, hepatocellular carcinoma, and pancreatic cancer.10 It is a 45-item self-report instrument that incorporates the 27 FACT General (FACT-G) items and an 18-item hepatobiliary subscale. The 27-item FACT-G measures QOL in 4 life domains: physical (7 items), Social (7 items), Emotional (6 items), and Functional (7 items). The additional 18 items relate to disease-specific issues in patients with hepatobiliary cancers.10, 11 The patients circled numbers on a scale from 0 (not at all) to 4 (very much) to indicate their reaction to each statement. After data collection, the scores were adjusted, so that lower scores indicated higher QOL on all items. The possible scores ranged from 0 to 180.
The FHSI-8 is a shorter (8-item) symptom index that was created from the FACT-Hep. It has good internal consistency, good test-retest reliability, and provides an acceptable alternative to the lengthy FACT-Hep when the interest is focused on symptoms.11 The FHSI-8 was completed by hospitalized patients at discharge because of its reliability, the applicability of its items to the hospitalized patient, and its brevity. The FHSI-8 also used a 5-point scale ranging from not at all (0) to very much (4) to evaluate symptoms relevant to patients with hepatobiliary cancers. These scores were adjusted, so that 0 indicated highest QOL, and scores ranged from 0 to 32.
The EORTC core questionnaire, the EORTC QLQ-C30, is an integrated, modular approach for evaluating the QOL of patients participating in international clinical trials.12 The EORTC QLQ-C30 consists of 30 items that incorporate 9 multiitem scales: 5 functional scales (Physical, Role, Cognitive, Emotional, and Social); 3 symptom scales (Fatigue, Pain, and Nausea and Emesis); and a Global Health and QOL scale. Several single-item symptom measures also are included.12 The EORTC QLQ-C30 is a reliable and valid measure of QOL for cancer patients in clinical research settings.12 Items 1 through 28 use a 4-point scale ranging from not at all (1) to very much (4) to evaluate statements related to cancer. Items 29 and 30 use a 7-point scale that ranges from very poor (1) to excellent (7). These scores were adjusted, so that 1 indicated the highest QOL. The range for scores on the 30-item questionnaire was 30 (excellent QOL) to 126 (poor QOL).
The EORTC QLQ-PAN consists of 26 items and supplements the EORTC QLQ-C30. It is intended for patients with pancreatic cancer, including those undergoing surgery, chemotherapy, and radiotherapy. Its items relate to the symptoms, body image, sexuality, and emotional and social consequences of pancreatic cancer.13 Each item uses a 4-point scale which range from 1 (not at all) to 4 (very much), and these scores are adjusted so that 1 (not at all indicated) the greatest QOL. The possible range of scores is from 26 (excellent QOL) to 104 (poor QOL).
The Brief POMS is a self-reported, 11-item short form of the Profile of Mood States 58-item Total Mood Disturbance Score (TMDS). It shows highly satisfactory internal consistency and correlation with the full TMDS and was administered to our patients to measure distress as an adjunct to patient care.14 The Brief POMS consists of 11 words that describe feelings (e.g. blue, discourages, on edge, etc.). The patients indicate on a 5-point scale from 0 (not at all) to 4 (extremely) how they have been feeling in the last week. The scores range from 0 (excellent QOL) to 44 (poor QOL).
We also used a patient-centered Global Rating of Change Scale to assess patient QOL. Patients were asked to specify the direction and amount of change in 6 domains: Physical Well Being, Social and Family Well Being, Emotional Well Being, Functional Well Being, Disease-Specific Well Being, and Overall QOL. Patients used a 15-point scale ranging from −7 (a very great deal worse), to 0 (no change), to +7 (a very great deal better). Higher scores indicated improved QOL. This questionnaire was administered at the final 4 time points, and patients were instructed to rate their change in QOL in relation to their prior visit. All QOL instruments were chosen based on their use in prior published studies in patients who underwent hepatic surgery, pancreatic surgery, or upper gastrointestinal surgery.
Unless otherwise specified, all P values were based on 1-sided t tests that compared major hepatectomy to with minor hepatectomy and ablation using JMP software (version 4.1; SAS Inc., Cary, NC).
Forty patients were enrolled in the study, including 20 men and 20 women with a median age of 62 years (range, 39–82 tears). Twenty-four patients underwent major hepatic resections, 8 patients underwent minor resections, and 8 patients underwent ablation (Table 1). The median hospital stay was 7 days and was similar in all 3 groups. The prevalence of comorbidities, length of stay, and overall operative time were similar in all groups. The minor hepatic resection group had a higher incidence of additional organ resection, but this was not significant among all 3 groups (Table 1). All eligible patients completed the questionnaires at the established time points.
|Demographic||Major hepatic resection group N = 24||Minor hepatic resection group N = 8||Ablation group N = 8|
|Age range (median), y||44–82 (68)||39–78 (64)||46–71 (54)|
|Sex, no. of patients|
|Histology, no. of patients|
|Comorbid disease, %||65||60||75|
|Additional organ resection, %||8%||40||20|
|Length of stay (median), d||4–12 (7)||4–25 (7)||2–11 (6)|
At each time point, none of the scores on the FACT Physical, Social, Emotional, or Functional QOL scales differed statistically across the 3 groups. Further evaluation was performed among the FACT results by combining the minor resection group and the ablation group for a comparison with the major resection group. There were no differences at the initial visit or the first postoperative visit. At 6 weeks, both the Physical QOL scores (combined minor resection and ablation groups, 4.44444 ± 2.0075; major resection group, 9.40000 ± 1.9045; P = .0455) and the Functional QOL scores (combined minor resection and ablation groups, 8.4444 ± 2.1209; major resection group, 14.0000 ± 2.0121; P = .0372) on the FACT-Hep were worse for the major resection group (higher score = worse QOL) (Fig. 1). At 3 months, there were no differences between the groups. At 6 months, the FACT-Hep Emotional scores for the major resection group (3.00000 ± 1.4351) indicated significantly better QOL (P = .0216) compared with scores in the combined minor resection and ablation groups (8.75000 ± 2.0295).
For the Brief POMS, we observed no differences between the groups at the initial or first postoperative visits. However at 6 weeks, all 3 groups differed (P = .0065), with improved scores in the minor resection and ablation groups compared with scores in the major resection group (P = .0016) (Fig. 2). The ablation group demonstrated a better mood score (0.0000 ± 2.2125) than the minor resection group (1.600000 ± 1.9790) and the major resection group (7.70000 ± 1.3993). The minor resection and ablation groups (0.88889 ± 1.4439) also exhibited better mood scores than the major resection group. There was no difference at 3 months or 6 months, but there was a trend toward improvement in the major resection group (2.87500 ± 1.7089) compared with the minor resection and ablation groups (6.25000 ± 2.4167) at 6 months. (Fig. 3)
For the QLQ-PAN, there was no difference at the initial or first postoperative visits. At 6 weeks, there was no difference between the 3 groups. The QOL scores in the combined minor resection and ablation groups were better compared with scores in the major resection group at 6 weeks (P = .0410), with no differences at the 3-month and 6-month visits.
There were no differences in QOL scores on the EORTC QLQ-C30 at the initial or first postoperative visits. At 6 weeks, the QOL scores for the minor resection group (40.8 ± 6.0329) were better than both the ablation group (46.0 ± 6.7450) and the major resection group (61.90 ± 4.2659; P = .0120). The minor resection and ablation groups (43.1111 ± 4.4072) also reported better QOL at 6 weeks than the major resection group (61.90 ± 4.1810; P = .0033). There was no difference in observed QOL between the groups at 3 months and 6 months (Fig. 4).
For the FHSI-8 self-report scale, no difference in QOL was reported at discharge and the first postoperative visit. At 6 weeks, there also was no difference between the 3 groups. The combined minor resection and ablation groups (3.71429 ± 1.5317) demonstrated significantly better QOL than the major resection group (8.100 ± 1.2815; P = .0221) at 6 weeks. These differences in QOL resolved at 3 months and 6 months (Fig. 5).
For the overall Global Rating of Change Scale, we observed no difference until 3 months, when scores differed for the combined minor resection and ablation groups and the major resection group (P = .0434). The major resection group reported a more significant improvement in QOL (26.5625 ± 2.7316) compared with the minor resection and ablation groups (15.5000 ± 5.4632). There was no difference at 6 months.
For the Physical Well Being portion of the Global Rating of Change Scale, no difference was observed at the first postoperative visit; however, at 6 weeks, all 3 groups differed (P = .0186), and the combined minor resection and ablation groups and the major resection groups also differed significantly (P = .0045). The minor resection group (5.25000 ± 1.1188) and the ablation group (5.25000 ± 1.1188) demonstrated the same improvement in physical well being compared with the major resection group (2.20000 ± 0.7076) at 6 weeks. The combined minor resection and ablation groups (5.25000 ± 0.76598) reported more improvement than the major resection group (2.20000 ± 0.7076) at 6 weeks; however, this trend reversed at 3 months, when the major resection group (4.62500 ± 0.6394) showed greater improvement than the combined segmental resection and ablation group (2.00000 ± 1.2788) (P = .0415). No differences between the 3 groups were observed at 6 months.
For the Social and Family Well Being portion of the Global Rating of Change Scale, the only significant difference was at the first postoperative visit. At that time point, the combined minor resection and ablation groups (3.55556 ± 0.78371) displayed greater improvement in Social and Family Well Being compared with the major resection group (1.55556 ± 0.78371; P = .0450). No difference was observed between the 3 groups at the remaining time points.
The Emotional Well Being portion of the Global Rating of Change Scale assesses emotional well being. There were no differences observed in scores between the 3 groups.
For the Functional Well Being portion of the Global Rating of Change Scale, at 6 weeks, the minor resection group (5.25000 ± 1.0607) demonstrated the greatest improvement, followed by the ablation group (4.25000 ± 1.0677), and the major resection group (2.00000 ± 0.6708; P = .0208). The combined minor resection and ablation groups (4.75000 ± 0.73686) reported greater improvement than the major resection group (2.00000 ± 0.65907; P = .0066) at 6 weeks.
For the Disease-Specific Well Being portion of the Global Rating of Change Scale, which assesses improvements in symptoms or concerns related to the patient's specific illness, the only significant difference observed occurred at 6 weeks, when the combined minor resection and ablation groups (5.28571 ± 0.81316) had greater improvement compared with the major resection group (3.00000 ± 0.68034; P = .0237).
The Overall QOL portion of the Global Rating of Change Scale assesses the change in overall QOL. At 3 months, the major resection group (4.56250 ± 0.48836) reported greater improvement compared with the combined minor resection and ablation groups (2.25000 ± 0.97673; P = .0242), with no other differences observed for any of the remaining time points.
Hepatic malignancies are among the most common neoplasms worldwide. Because recurrence is the natural course of disease and palliative treatment is 1 of the only options for patients with hepatic malignancies, symptom experience becomes a very important parameter for these patients. During the last decade, there has been growing interest in assessing the QOL of patients with cancer. The patient's QOL currently is considered both clinically meaningful and biologically important in terms of patient outcome, and QOL as an outcome is considered to be as important as disease-free and overall survival.1, 2 Nevertheless, successful QOL evaluation has been performed in patients with esophageal,4 gastric,5 colorectal,6 and pancreatic,7 cancer after resection. To date, there has been only 1 study evaluating patients with hepatocellular cancer after resection.8 That study demonstrated a significant QOL benefit after patients underwent resection compared with patients who did not undergo resection.
To date, the current report represents the first evaluation to our knowledge of patients' QOL after resection for other hepatic malignancies. In this study, significant differences were demonstrated in QOL scores on the FACT Physical and Functional subscales, the Brief POMS, the EORTC QLQ-C30, and the Global Rating of Change Scale at 6 weeks after recovery for the major resection group compared with the RFA group. All of those differences resolved at 3 months, with improved FACT Emotional scores in the major resection group. Overall, the major resection group had significantly lower QOL scores compared with the minor resection group at 6 weeks, and there was a similar improvement at the last 2 time points (3 months and 6 months).
With >1000 hepatic resections/ablations performed each year in the United States for colorectal metastases, various surgical options are available in treating patients with hepatic malignancies. There have been no prospective studies evaluating QOL differences after hepatic resection or ablation, or how the extent of resection delays a return to QOL, or the differences between treatment options.
The role of surgical resection for metastatic hepatic malignancies has become more widely accepted, even without prospective randomized trials, because of the improved survival outcomes reported in other types of studies. We attempted to compare the QOL of patients who underwent various forms of hepatic resection at set time points. There was overall deterioration of QOL after surgery, which was expected; however, all groups quickly returned to baseline. It is noteworthy that we observed very little difference between the reported QOL of the various groups at each time point. Therefore, it is important to ask, “does the treatment modality for hepatic malignancies influence the patient's QOL, or are other factors responsible?”
In our results for the FACT QOL, scale we observed that QOL in the large resection group was lower at 6 weeks. However, that difference no longer was evident at the later time points, except for the Emotional subscale, in which the major resection group had better QOL. The POMS scale demonstrated similar results, in that the major resection group had a better mood at the end of the study. This emotional difference seems to relate to the return of functional and physical QOL these patients. There are many other factors that may contribute to this finding. This difference may be caused by the expectations of various patients. Although patients with large cancers may not expect to return to a certain QOL, they appreciate small advances in their lives more than patients who undergo small resections or ablations. This increased QOL also may be a result of the patients' acceptance of the disease and/or increased knowledge of the disease process. Because we followed our patients for 6 months, which is well past the expected recovery time of most surgical procedures, the difference at 6 months probably is related more to the disease than the surgical therapy used.
The EORTC QLQ-C30 and QLQ-PAN were similar, in that there were no differences in scores between the 3 groups, except that the major resection group reported lower QOL at 6 weeks. At long-term follow-up (6 months), there was no difference in patients' assessments of symptom experience. This reflects the fact that, regardless of tumor size or extent of resection, patients do not necessarily fair worse with major surgery as a form of treatment for hepatic malignancies. The difference easily may be accounted for by the longer time required to return to baseline after a major surgery.
Most of the recently validated measures of cancer-specific QOL incorporate an assessment of certain prevalent symptoms, such as pain and fatigue, within the multidimensional assessment.12, 15, 16 More broad-based, cancer-specific QOL questionnaires, such as the FACT-G15 and the EORTC QLQ-C30,12 assess a few common cancer symptoms, such as pain, fatigue, and nausea, adding more detailed, site-specific symptom assessment to the “core” general questionnaire. The FACT-G uses this modular approach, resulting in 4 domains of Well Being (Physical, Social/Family, Emotional, and Functional), to assess general QOL concerns and adding Disease-Specific module as a fifth domain. The recently validated FACT-Hep consists of 18 hepatobiliary disease-specific questions, resulting in a 43 item assessment tool. In the sentinel validation article, the FACT-Hep10 was validated for sensitivity and reproducibility. It differentiated patients according to Eastern Cooperative Oncology Group performance and treatment status. Although it is relatively brief, an instrument of this length may not be suitable for situations in which the patient is too ill to complete it. A common request, therefore, is for a more symptom-focused approach to QOL assessment tools to assure that the disease symptoms measured by these multidimensional QOL questionnaires are aggregated in such a way that they are clinically relevant and psychometrically acceptable. The FHSI-8, a much shortened, 8-item symptom index, recently was been created from this longer, more detailed, 45-item questionnaire. The FSHI-8 may be used in settings like clinical trials or longitudinal cohort studies, in which only grouped data on symptoms may be of interest.
Potential biases from this study may be perceived from the patients based on their perceptions of “cure” versus “palliation.” However, because this report concerns primarily patients with metastatic colorectal cancer, hepatocellular carcinoma, and cholangiocarcinoma, who have a significant risk of recurrence, the perception or even the discussion of a “cure” is not presented. Thus, similarly, the type of resection offered to the patient would not change the preoperative discussion with regard to disease control; thus, this perceived bias should not be a factor in the current study.
The limitations of the current study are related to the small sample size of patients who underwent RFA and minor resection. Larger studies evaluating patients who undergo surgical ablation may be needed to solidify our results. Even with these limitations, this study represents a solid foundation from which to expand QOL studies that identify which patients are the optimal candidates for surgical therapy and which patients who should receive other treatment modalities.
QOL is becoming very important in the evaluation of outcomes after cancer treatment and is becoming an influential tool in making treatment decisions. We have attempted to asses the QOL of patients by using various treatment modalities for hepatic malignancy and observed little difference between these treatments according to the patients themselves. We recognize that there are many treatment options other than surgical resection that need to be assessed, including certain chemotherapeutic options and liver transplantation. Survival outcome and tumor recurrence will be important considerations when comparing various options in future studies.
In conclusion, using various QOL measures, there was little difference between patients who underwent major and minor resection for hepatic malignancies over a 6-month period. The current results demonstrated a return to baseline QOL after hepatic resection, with a minimum of 6 weeks required to recover to baseline QOL. This finding supports the use of surgery as an effective treatment for hepatic malignancies. Final validation of these results in will be needed from future studies that assess additional treatment options in larger study groups and that incorporate survival outcome. When making treatment decisions, QOL must be considered as important as survival in assessing treatments for patients with cancer.
- 9Le foie: etudes anatomiques et chirurgicales. Paris: Masson & Cie, 1957..