- Email: [email protected]
Health-related quality of life: Return to baseline after major and minor liver resection
Health-related quality of life: Return to baseline after major and minor liver resection Robert C. G. Martin, MD, Sebastian Eid, MD, Charles R. Scoggins, MD, and Kelly M. McMasters, MD, PhD, Louisville, Ky
Background. Assessment of quality of life (QOL) after a major operation has become increasingly pertinent to patient care and may be as important as long-term survival in cancer patients. No current study has evaluated the long-term quality-of-life effects or the time to return to baseline quality of life in oncology patients undergoing hepatic resection for cancer. Thus, the aim of our study was to evaluate that the time to return to baseline QOL after major and minor hepatectomy is similar to other major abdominal operations. Methods. A prospective study of 32 patients with malignant liver tumors completed the FACT-Hep, FACT-FHSI-8, EORTC QLQ-C30, Profile of Mood States, EORTC QLQ-Pan26, and Global Rating Scale at the time of consent, discharge, first postoperative visit, 6 weeks, 3 months, 6 months, and 12 months. Results. Twenty-four patients underwent major (⬎2 segments) and 8 minor hepatectomy. Patients who underwent major hepatectomy demonstrated a significant loss in FACT-physical and functional scores at first postoperative visit and 6 weeks (P ⫽ .04) with return to baseline at 3 months. Similar nadir in all quality-of-life assessment scores were observed for POMS, EORTC QLQ-C30, FHSI-8, and certain global rating scales at 6 weeks, with a return to baseline at 3 months. For minor hepatectomy, the nadir for most quality-of-life scores occurred at the first postoperative visit with a return to baseline at 6 weeks. Conclusion. Patients undergoing major hepatectomy return to their baseline quality of life at 3 months with a progressive and sustained increase in physical, emotional, and global rating scale at 6 months. This study is the first one to demonstrate that major hepatectomy can be performed with short-term adverse QOL effects and long-term improvements in overall QOL. (Surgery 2007;142:676-84.) From the Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Ky
The assessment of a patient’s quality of life (QOL) after operation has become integral to patient care and may be as important as long-term survival in cancer patients. QOL is becoming as important to patients as being disease free and overall survival.1,2 Assessing QOL in surgical oncology patients has been limited primarily from the misleading notion that a surgeon’s judgment is more reliable than QOL data.3 Recent QOL assess-
Accepted for publication April 24, 2007. Reprint requests: Robert C. G. Martin II, MD, Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, 315 East Broadway, Room 313, Louisville, KY 40202. E-mail: [email protected]. 0039-6060/$ - see front matter © 2007 Mosby, Inc. All rights reserved. doi:10.1016/j.surg.2007.04.026
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ments have been performed in patients undergoing resection for esophageal,4 gastric,5 colorectal,6 and pancreatic7 cancers. To date, no study has evaluated the time to return to preoperative QOL after hepatic resection in oncology patients. The only QOL studies to date have evaluated patients with hepatocellular cancer after resection.8 This study did demonstrate a significant QOL benefit after resection when compared with patients who were not resected. Similarly a recent study from our group presented little difference in QOL among major hepatic resection, minor hepatic resection, and hepatic ablation.9 Major hepatectomy demonstrated a worse QOL at 6 weeks when compared with minor and hepatic ablation, with similar QOL effects among all 3 treatment modalities. To date, however, there have been no QOL studies evaluating the time it takes patients who undergo major resection and minor resection to return to their baseline QOL.
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Thus, the objective of this study was to evaluate the time to return to baseline QOL after major and minor hepatectomy. METHODS Patients with primary or metastatic cancer to the liver scheduled for hepatic resection or ablation were recruited for an observational study of QOL before and after surgical treatment. The study protocol was approved by the Institutional Review Board, and all patients were provided written, informed consent. Surgery. Patients were separated into 2 groups by their extent of resection. Extent of hepatectomy was defined as major if 3 or more segments were resected and minor if 2 or fewer segments were resected. The decision to perform these resections was at the surgeon’s discretion. Liver resections were classified as described by Couinaud.10 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. Cholecystectomy at the time of hepatic resection was not considered as an additional organ resection. Intraoperative anesthetic management during hepatectomy has been detailed previously.11 Briefly, all patients were premedicated and underwent general anesthesia. Before hepatic parenchymal transection, fluids were administered to maintain a urine output of 25 mL/h and systolic blood pressure greater than 90 mm Hg, whereas the CVP was reduced to less than 5 mm Hg. Intraoperative blood products were administered when blood loss exceeded 25% of the total blood volume. After the specimen was removed, crystalloid was administered intravenously to achieve euvolemia. Packed red blood cells and autologous blood were given only to maintain a hemoglobin of greater than 10 g/dL in patients with evidence of either coronary or cerebrovascular disease. The liver parenchyma was divided using Kelly clamps to crush liver tissue and to expose bile ducts and blood vessels, which were clipped, tied, or stapled. Inflow control was performed by intermittent vascular occlusion (the Pringle maneuver)12 applied for 5-10-minute intervals, released briefly, and reapplied as necessary. Pringle time was recorded as the total cumulative Pringle time applied during parenchymal transection. Outflow control of the hepatic veins before parenchymal division was nearly always obtained in lobectomy or ex-
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tended resections. Hepatic ablation was performed using intraoperative ultrasound guidance in all ablations to ensure that at least a 1-cm ablation margin was achieved around the tumors. Postoperative complications were defined as any complication that occurred within 30 days postoperatively and were classified according to a 5-point grading system that has been described previously.13,14 A postoperative death was defined as any patient death that occurred within 90 days postoperatively. Study procedures. This study was observational; no study-specific treatment was provided to these patients through this investigation. We used a pre– post test design to assess a patient’s experience of symptoms and concerns before and after hepatic resection or ablation. Patients were assessed at 6 time points, before surgical procedure, at discharge postprocedure, first postoperative visit (defined as with 2-3 weeks from procedure depending on length of hospital stay), 6 weeks postprocedure, 3 months, and 6 months. Upon enrollment, the study coordinator, research assistant, or investigator completed the treatment history and demographics. At this time the patients completed a baseline questionnaire battery consisting of a Functional Assessment in Cancer Therapy core instrument with the hepatobiliary subscale (FACT-HEP), Brief POMS, EORTC QLQ-C30, and EORTC QLQPAN. Upon discharge after hepatectomy, each patient completed the FHSI-8, which differs from the FACT-Hep by including questions that are applicable to the hospitalization. At the 4 remaining time points, each patient completed a questionnaire battery consisting of a FACT-Hep, Brief POMS, EORTC QLQC30, EORTC QLQ-PAN, 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, the follow-up questionnaires were mailed to the patient. For those patients that survived less than 6 months after surgery, QOL assessment was continued until the last follow-up visit by the patient. All questionnaires were completed in English. The quality of the data obtained from each patient was evaluated when the patient completed all questionnaire forms at each visit. The study coordinator, research assistant, or investigator who had enrolled the patient reviewed each form immediately after receiving them to identify any missing data.
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Because of the paucity of data regarding QOL after hepatectomy, we estimated a 30% difference in QOL at 6 weeks for major versus minor hepatic resections. Assuming an alpha risk of 0.05, a beta risk of 0.8, and a difference of 30% at 6 weeks, the number of patients needed to treat was estimated to be 12 in each group. Assuming a post-planned treatment dropout of 20% because of death or noncompliance, the sample size required for this study was estimated to be at least 32 patients. The quality of data entry is evaluated by the use of range checks on all variables and by double data entry for a small portion (5% to 10%) of the data. This process allowed for the evaluation of the accuracy of the data entered by the primary data entry assistant. QOL instruments. The FACT-Hep is a validated instrument for assessing QOL in patients with hepatobiliary cancers, metastatic colorectal cancers, hepatocellular carcinoma, and pancreatic cancer.15 It is a 45-item self-report instrument that incorporates the 27 FACT-G 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 relating to hepatobiliary cancers.15 The patients circled on a scale of 0 (not at all) to 4 (very much) how true was each statement. After data collection, the scores were adjusted so that lower scores indicated higher QOL on all the items. The possible range of scores is 0-180. The FHSI-8 is a shorter (8 items) symptom index created from the FACT-Hep. It has good internal consistency, test–retest reliability, and provided an acceptable alternative to the lengthy FACT-Hep when the interest is symptom focused.16 The FHSI-8 was completed by the hospitalized patient at discharge because of its reliability, applicability of its items to the hospitalized patient, and brevity. The FHSI-8 also employs a 5-point scale ranging from not at all (0) to very much (4) in evaluating symptoms relevant to patients with hepatobiliary cancers. These scores were adjusted, where 0 indicated highest QOL and scores compromised a range of (0-32). The European Organization for Research and Treatment of Cancer (EORTC) core questionnaire, the EORTC QLQ-C30, is an integrated, modular approach for evaluating the QOL of patients participating in international clinical trials.17 The EORTC QLQ-C30 consists of 30 items incorporating 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health and QOL scale. Several single-item
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symptom measures are also included. The EORTC QLQ-C30 is a reliable and valid measure of the QOL of cancer patients in clinical research settings. Items 1 through 28 used a 4-point scale ranging from not at all (1) to very much (4) in evaluating statements related to cancer. Items 29 and 30 used a 7-point scale ranging from very poor (1) to excellent (7). These scores were adjusted so that 1 indicated highest QOL. The range for the 30-item questionnaire was 30 (excellent QOL) to 126 (poor QOL). The EORTC QLO-PAN consists of 26 items, which 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.18 Each item used a 4-point scale that ranged from (1) not at all to (4) very much, and these scores were adjusted so that (1) not at all indicated greatest QOL. The possible range of scores is 26 (excellent QOL) to 104 (poor QOL). The Brief Profile of Mood States (POMS) is a self-report, 11-item short form of the Profile of Mood States’s 58-item Total Mood Disturbance Score (TMDS). It shows highly satisfactory internal consistency and correlation with the full TMDS and was administered to the patients to measure distress as an adjunct to patient care.19 The brief POMS consist of 11 words that describe feelings (eg, Blue, Discouraged, or on Edge). The patients report on a 5-point scale, with 0 being not at all and 4 being extremely how they have been feeling in the last week. The scores range from 0 (excellent QOL) to 44 (poor QOL). We also used patient-centered global ratings of change to assess patients QOL. Patients were asked to specify the direction and amount of change in 6 domains: 1) physical well-being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, 5) disease-specific well-being, and 6) overall QOL. Patients used a 15-point scale ranging from ⫺7 (a very great deal worse) through 0 (no change) to ⫹7 (a very great deal better). The higher score indicated an 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 its use in prior published studies in hepatic surgery, pancreatic surgery, or upper gastrointestinal surgery. Statistical analysis. Unless otherwise specified, all P-values are based on 1-sided t tests comparing
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Table I. Demographic data for major and minor groups Demographic Age Gender Histology 3 HCC 4 other Comorbid disease Additional organ resection Length of stay
Major (n ⫽ 24)
Minor (n ⫽ 8)
44-82 (median 68 years) 13 F, 11 M 13 MCC 4 CC 5 MCC 1 HCC 2 Other 65% 8%
39-78 (median 64 years) 4 F, 4 M
4-12 days (median 7)
4-25 days (median 7)
60% 40%
CC, Cholangiocarcinoma; F, female; HCC, hepatocellular cancer; M, male; MCC, metastatic colorectal cancer.
major hepatectomy with minor hepatectomy using JMP V4.1 (SAS, Inc., Cary, NC). RESULTS From October 1, 2002 to June 30, 2004, 32 patients were enrolled in this study: This included 15 men and 17 women with a median age of 62 years (range, 39-82). Twenty-four patients underwent major hepatic resections, and 8 underwent minor resections (Table I). The median hospital stay was 7 days, which was similar in both groups. The prevalence of comorbidities, length of stay, and overall operative time were similar in both groups. The minor hepatic resection group had a higher incidence of additional organ resection, but this was not significant among both groups (Table I). All eligible patients completed the questionnaires at the established time points. For the FACT-Physical, in the major hepatectomy group, when compared with the patient’s baseline QOL score (mean 3.0 ⫾ 1.4), there was a significant worse QOL score at the first postoperative visit (6.78 ⫾ 0.9), and the 6 weeks postoperative (9.4 ⫾ 1.8) (P ⫽ .01) with a return to baseline at the 3-month (4.5 ⫾ 1.3) postoperative (Fig 1, A). For the minor hepatectomy group, the baseline QOL score was (4.5 ⫾ 0.98). The QOL FACT-Physical score at 1st postoperative visit was significantly worse (10.1 ⫾ 1.90 (P ⫽ .036) with a return to baseline at 6-weeks postoperative (3.0 ⫾ 0.7) and throughout the follow-up period (Fig 1, A). For the FACT-function QOL scores, in which a higher score denotes a increase in QOL parameters, there were significantly worse QOL scores for the major hepatectomy group when compared with the preoperative visit (19.5 ⫾ 1.3) at both the first postoperative visit (14 ⫾ 1.7) and the 6-week (14 ⫾
Fig 1. A, FACT-Physical QOL scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections. Note: for FACT-physical, a higher score denotes a worse QOL. B, FACT-functional QOL scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections. Note: for FACT functional a higher score denotes an improved QOL.
1.7) (P ⫽ .02) postoperative period, with a return to baseline at the 3-month (22.2 ⫾ 1.0) postoperative period and throughout the follow-up period (Fig 1, B). For the minor hepatectomy group, there was a worse QOL score at the 1st postoperative visit (14 ⫾ 0.8) (P ⫽ .001) and a return to baseline by the 6-week postoperative (21 ⫾ 3.5) period and throughout the follow-up period (Fig 1, B). For both the FACT social (Fig 2, A) and the FACT emotional (Fig 2, B), the QOL scales were not statistically different across all 5 time points for both the major and the minor hepatectomy group. No changes were found in the patient’s social or emotional well-being during the recovery after major or minor hepatectomy. For Brief POMS, we observed a significant difference in the major hepatectomy group at first postoperative visit and at 6 weeks (P ⫽ .0305) with a return to baseline at 3 months. The major resection
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Fig 3. POMS QOL scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections.
Fig 2. A, FACT-Social QOL scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections. B, FACT-Emotional QOL scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections.
group demonstrated a significantly worse mean mood score at 1st postoperative visit (6.1 ⫾ 1.9) and 6 weeks (7.7 ⫾ 1.9) when compared with 3-month (2.2 ⫾ 0.8) and 6-month (2.5 ⫾ 1.2) follow-up. For the minor hepatectomy group, from a baseline score (4.4 ⫾ 1.6), there was a worse mean mood score at initial postoperative visit (7.6 ⫾ 3.4) (P ⫽ .08), which dropped to baseline or better by 6 weeks (1.6 ⫾ 1.36) and then to completion of follow-up (Fig 3). For QLQ-PAN, there is no difference for either the major or the minor resection group at any time points. No variation in QOL scores was found in either group. For the major hepatectomy group, there were significant worse QOL scores observed for EORTC QLQ-C30, at the first postoperative (mean score 63.4 ⫾ 2.4) versus the baseline visit (54 ⫾ 4.2) (P ⫽ .03) and 6-week postoperative (mean 62.0 ⫾ 3.8), with a return to baseline by 3 months (47.3 ⫾ 2.3) and then through the postoperative period (Fig 4). For the minor hepatectomy group, there was a
Fig 4. EORTC scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections.
worse QOL score at first postoperative visit (64 ⫾ 3.8 vs initial 50 ⫾ 3.1) (P ⫽ .01), with a return to baseline or better by the 6-week visit (mean score 41 ⫾ 6.8) and then through out the postoperative period (Fig 4). For the FHSI-8 self-report scale, the major hepatectomy group demonstrated a significant improvement in scores after the 6-week visit when compared with the discharge scores (mean score 11.8 ⫾ 1.5 vs 6.1 ⫾ 1.3 at 3 months) (P ⫽ .002) (Fig 5). For the minor hepatectomy group, most of the greatest improvement was observed at the 6-week postoperative visit (mean score 3.4 ⫾ 0.5 vs 10.3 ⫾ 2.6 at discharge) (P ⫽ .046), with consistent improvement in scores throughout the remainder of the follow-up (Fig 5). For the overall Global Rating Scale, we observed a significant improvement of QOL at the 3-month postoperative visit (QOL mean score 26.6 ⫾ 2.7)
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Fig 5. FHSI-8 QOL scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections.
when compared with the 1st postoperative visit (mean QOL score 9.5) (P ⫽ .002). This improvement continued throughout the follow-up period. A significant increase in the global QOL score occurred for the minor hepatectomy group from the 1st postoperative visit (mean 14) to the 6-week postoperative visit (mean 27) (P ⫽ .01), with stabilization of scores for the 3-month (mean 25) and 6-month (mean 21) visit. For the physical well-being portion of the Global rating of change scale (GR1), the major hepatectomy group demonstrated an improvement in QOL scores after the 1st postoperative visit (mean score 2.75) to the 3-month post-operative visit (mean score 4.6) and then maintained throughout the postoperative visit. For the minor hepatectomy group, there was an improvement in QOL scores from the 1st postoperative visit (mean score 3) to the 6-week postoperative visit (mean score 5.3), with similar global rating scores at the 3-month (score 5) and the 6-month visits (score 5). For the second part of the global rating scale, which assesses social and family well-being, there was a significant improvement in the QOL scores from 1st postoperative visit (1.6 ⫾ 0.8), when compared with the 3-month visit (score 4.1 ⫾ 0.6). For the minor hepatectomy group as with the FACTsocial scores, there were no significant changes from the 1st postoperative visit (score 3.6) to the 6-week (score 3) to the 3-month (score 3.5) to the 6-month follow-up (score 3.3). For the emotional well-being global rating scale, no differences were observed with either group for major or minor hepatectomy. The global rating scale 4, which assesses the functional well-being of the patients, demonstrated
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a significant improvement in the major resection group QOL scores at 3 months (score 4.3) when compared with 1st postoperative visit (score 0.4) (P ⫽ .002). Similarly for the minor hepatectomy group, there was a significant improvement in this QOL score at 6 weeks (mean score 5.3) when compared with 1st postoperative visit (mean score 0.4) (P ⫽ .001) and then consistent scores at 3 months (score 5.5) and at 6 months (score 4). The global rating scale 5 refers to improvement in symptoms or concerns related to the patient’s specific illness. For the major hepatectomy group, again the greatest improvement occurred at the 3-month postoperative visit (score 4.4) when compared with the 1st postoperative visit (score 1.9), which then was maintained throughout the postoperative follow-up. For the minor hepatectomy group, again we saw a significant improvement at 6 weeks (mean score 6.7) when compared with 1st postoperative visit (mean score 1.8) (P ⫽ .002) and then a decrease in scores at 3 months (mean score 3) and at 6 months (mean score 2.7). The global rating scale 6 refers to the change in overall QOL. For the major hepatectomy group, the 3-month visit (score 4.6) demonstrated the greatest improvement from the 1st postoperative visit (score 1.7) with stabilization throughout the follow-up period. For the minor hepatectomy group, we saw no differences in these scores from 1st postoperative (mean score 3) to 6 weeks postoperative (mean score 3.8) to 3 months (mean score 3) to 6 months (mean score 3.3). Eleven patients experienced 14 complications, including biloma, reoperation for bleeding, pulmonary embolus, deep venous thrombosis, atrial fibrillation, and others, with severity ranging from grade 1 to grade 3. Eight patients experienced 11 complications in the major hepatectomy group, and 3 patients experienced 3 complications in the minor hepatectomy group. In the patients who sustained a grade 3 complication, there was a significant loss in their FACT-physical at 3 months (P ⫽ .003) when compared with baseline and did not return to baseline until 6 months. The severity of the complication was also a predictor of worse FACT-functional at 3 months when compared with baseline (P ⫽ .02). For POMS, there was a significant loss at 3 months (P ⫽ .03) when compared with baseline in patients with complications. Similar loss in all the QOL assessment scores was observed for QLQPAN, EORTC QLQ-C30, FHSI-8, and certain global rating scales at 6 weeks and 3 months for patients who suffered a significant complication.
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Table II. QOL in hepatectomy patients: return to baseline Author
# Pts
Procedure
Verbesey et al
47
Right LRLT
SF-36
Parolin et al27 Walter et al28
19 28
LRLT LRLT
NS WHOQOL-BREF
Basaran et al29
27
Left LRLT
SF-36
NS
Kim-Schluger et al30
30
LRLT
SF-36
Variable postoperative
Pascher31
43
Right LRLT
ACSA
Preoperative, 6 and 12 months postoperative
26
QOL instrument
Time points analyzed
Outcome
Preoperative, and 1 week, 1, 3, 6, and 12 month postoperative Postoperative Preoperative and 6 months postoperative
Returned baseline 3 months Recovery at 9 weeks Better than normal population at both time points No difference than control population Scores higher than general population Improved scores in patients as time lengthen
ACSA, Anamnestic Comparative Self-Assessment Scale; LRLT, living-related liver transplant; NS, not stated; SF-36, Study Short form 36 questionnaire; WHOQOL-BREF, World Health Organization QOL brief form.
DISCUSSION Although major hepatic resection has been demonstrated to be clearly beneficial in patients with both primary as well as metastatic malignancies, significant risk of morbidity and mortality should be considered. The number of hepatic resections is increasing worldwide and is becoming far more complex. With the ever-increasing demand for multimodality care20-22 as well as the effects these multimodality treatments have on hepatic function,23-25 evaluating QOL effects after therapy has gained greater importance. Simply having the ability to provide aggressive care in the form of multiple lines of different chemotherapy, aggressive surgical resections, and other treatments does not always provide optimal QOL time. It has, thus, become increasingly important to obtain reliable QOL data in patients who chose hepatic resection. We report a prospective, longitudinal QOL study of 32 consecutive hepatic resections at our center. All patients completed this same survey preoperatively and then at 4 postoperative time points allowing for measurement of changes in QOL over time. Demographic data for both the major and the minor hepatic resection groups are similar to other reports in regard to median age, comorbidities, and distribution of histology, with the most common being metastatic colorectal. This report is the 1st one to evaluate a patient’s QOL and to assess the time these patients take in order to return to their baseline QOL after both major and minor hepatic resections. Our study at 6 weeks demonstrated that both the FACT-physical and the FACT-functional QOL scales are worse for the major resection group at 6 weeks with a return
to baseline at 3 months and continue at that range for 6 months and then on. For minor hepatectomy patients, there was a significant difference in the FACT-physical and FACT-functional QOL scores at their 1st postoperative visit with a return to baseline at 6 weeks postoperatively. These changes and return to baseline were similar for both the major resection group and the minor resection group with the Brief-POMS QOL scores, with again a return to baseline at 3 months for the major resection and 6 weeks for the minor hepatectomy. Similar differences were observed in the EORTC QLQ-C30 in both the major resection and the minor resection with a return to baseline at 3 months and 6 weeks, respectively. Similar results were also identified for the FHSI-8 self-report scale with an improvement at 3 months for major resections and 6 weeks for minor resection and then stabilization of their respective scores. The differences in the return to baseline in these groups is in direct relation to the extent of hepatic resection and less related to additional organ resections (Table I). This difference clinically relates to the extent of fatigue that patients undergoing major resection have during their recovery. This fatigue seems to be a major reason for the differences observed in this study. There is a paucity of QOL data for cancer patients treated with hepatic resection; however, a comparison can be made between the current data and those from the transplant literature. Our results compare with the report from Verbesey et al in their review of 47 right living-related liver transplants (Table II).26-31 They used a slightly different QOL instrument with the Study Short Form 36 (SF-36) with time points at preoperatively, 1 week,
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1 month, 3 months, 6 months, and 12 months and demonstrated a return to baseline at the 3-month interval. This report represents probably the purest study in a living-related liver transplant because many other reports have either not assessed QOL preoperatively or had a variable postoperative evaluation (Table II). However, other reports did demonstrate that patients who underwent living-related liver transplant either returned to their baseline QOL or had higher QOL scores when compared with either the control population or the general population.30,31 Similarly, it seems that the QOL continues to improve over time as reported by Pascher et al who found continued improved QOL scores in his right living-related liver transplant patients at the 12-month evaluation. There are limitations to a comparison between the QOL data from living-related transplantations and our current study: Most patients who are eligible for a living-related liver transplant are younger and may have fewer comorbid conditions than patients with liver cancer, especially those with metastatic disease. Similarly, the differences in QOL instruments that were used in the various reports makes comparisons somewhat limited but does demonstrate a relatively reasonable 3 months of recovery time in order to return to baseline. This study used several wide-ranging QOL instrument panels, simply to ensure that we captured any and all physical, functional, and psychologic QOL parameters that are important to the oncology patient. Our study continues to confirm that the FACT Hep QOL scale represents a fairly sensitive and accurate assessment of a patient’s overall QOL. Similarly, the Brief-POM as well as the EORTC questionnaire may also be used to evaluate sensitively a patient’s underlying recovery and QOL assessment after major and minor hepatectomy. With the role of hepatic resection becoming more widely accepted and universally established in the treatment of both patients with primary or metastatic hepatic malignancies, more consistent QOL surgical standards need to be established. Because most of these patients are under multimodality care with the use of either neoadjuvant therapy, adjuvant therapy, or both to maximize their disease-free survival and/or overall survival limiting permanent QOL defects is paramount. In addition, minimizing the time of chemotherapy interruption is becoming more important. This study demonstrates that in patients who are undergoing major hepatic resection that the maximum QOL time to return to baseline is 12 weeks, with most likely a shorter time interval. Because there was such a dramatic improvement in this study from 6 weeks
to 3 months that was not captured with our current time points, it maybe assumed that a return to baseline occurred before the scheduled 3-month office visit. Thus, it is fairly reasonable to accept the concept of “time to resumption of chemotherapy” or “time to the induction of postoperative chemotherapy” should be within an 8-week to 12-week window after major hepatic resection. This concept is important for collaborating as well as for educating other oncology specialties in the benefit as well as the limited QOL effects that major hepatic resection induces. Setting this time goal or, more importantly, this surgical standard in recovery is yet another potential quality measure that hepato-pancreatico-biliary surgeons should consider as we proceed in overall patient outcomes. The limitations of this study are related to the small sample size of patients who underwent minor resections. A possibility exists that a larger number of minor resection patients may create more variance in these results, but because the range of scores was close, this variance would probably be small. Even with these limitations, this study represents a solid foundation in which additional quality standards can be set as well as strived for in all major and minor hepatectomy patients. In conclusion, using various QOL measures, patients undergoing major hepatectomy return to their baseline QOL at 3 months with a progressive and sustained increase in physical, functional, and global rating scale at 6 months. Minor hepatectomies recover more quickly with return at 6 weeks. This study is the first one to demonstrate that major hepatectomy can be performed with short-term adverse QOL effects and long-term improvements in overall QOL parameters. REFERENCES 1. Slevin ML. Quality of life: philosophical question or clinical reality? BMJ 1992;305:466-9. 2. Mayer RJ. Summary of the second international conference on biology, prevention and treatment of gastrointestinal malignancies. Ann Oncol 1995;6:645-9. 3. Fraser SC. Quality-of-life measurement in surgical practice. Br J Surg 1993;80:163-9. 4. Branicki FJ, Law SY, Fok M, Poon RT, Chu KM, Wong J. Quality of life in patients with cancer of the esophagus and gastric cardia: a case for palliative resection. Arch Surg 1998;133:316-22. 5. Thybusch-Bernhardt A, Schmidt C, Kuchler T, Schmid A, Henne-Bruns D, Kremer B. Quality of life following radical surgical treatment of gastric carcinoma. World J Surg 1999;23:503-8. 6. Camilleri-Brennan J, Steele RJ. Quality of life after treatment for rectal cancer. Br J Surg 1998;85:1036-43. 7. McLeod RS. Quality of life, nutritional status and gastrointestinal hormone profile following the Whipple procedure. Ann Oncol 1999;10(Suppl 4):281-4.
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8. Poon RT, Fan ST, Yu WC, Lam BK, Chan FY, Wong J. A prospective longitudinal study of quality of life after resection of hepatocellular carcinoma. Arch Surg 2001;136: 693-9. 9. Eid S, Stromberg AJ, Ames S, Ellis S, McMasters KM, Martin RC. Assessment of symptom experience in patients undergoing hepatic resection or ablation. Cancer 2006;107: 2715-22. 10. Couinaud C. Le foie: Etudes anatomiques et Chirurgicales. Paris: Masson & Cie; 1957. 11. Melendez JA, Arslan V, Fischer ME, Wuest D, Jarnagin WR, Fong Y, et al. Perioperative outcomes of major hepatic resections under low central venous pressure anesthesia: blood loss, blood transfusion, and the risk of postoperative renal dysfunction. J Am Coll Surg 1998;187:620-5. 12. Pringle JH. Notes on the arrest of hepatic hemorrhage due to trauma. Ann Surg 1908;48:541. 13. Martin RC, Jarnagin WR, Fong Y, Biernacki P, Blumgart LH, DeMatteo RP. The use of fresh frozen plasma after major hepatic resection for colorectal metastasis: is there a standard for transfusion? J Am Coll Surg 2003;196:402-9. 14. Martin RC, Edwards MJ, McMasters KM. Morbidity of adjuvant hepatic arterial infusion pump chemotherapy in the management of colorectal cancer metastatic to the liver. Am J Surg 2004;188:714-21. 15. Heffernan N, Cella D, Webster K, Odom L, Martone M, Passik S. Measuring health-related quality of life in patients with hepatobiliary cancers: the functional assessment of cancer therapy-hepatobiliary questionnaire. J Clin Oncol 2002;20:2229-39. 16. Yount S, Cella D, Webster K, Heffernan N, Chang C, Odom L, et al. Assessment of patient-reported clinical outcome in pancreatic and other hepatobiliary cancers: the FACT Hepatobiliary Symptom Index. J Pain Symptom Manage 2002;24:32. 17. Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365-76. 18. Bassi C, Johnson C, Fitzsimmons D, Falconi M, Butturini G, Contro C, et al. [Quality of life assessment in pancreatic carcinoma: results of an European multicentric study]. Chir Ital 1999;51:359-66. 19. Cella DF, Jacobsen PB, Orav EJ, Holland JC, Silberfarb PM, Rafla S. A brief POMS measure of distress for cancer patients. J Chronic Dis 1987;40:939-42.
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20. Leonard GD, Brenner B, Kemeny NE. Neoadjuvant chemotherapy before liver resection for patients with unresectable liver metastases from colorectal carcinoma. J Clin Oncol 2005;23:2038-48. 21. Folprecht G, Grothey A, Alberts S, Raab HR, Köhne CH. Neoadjuvant treatment of unresectable colorectal liver metastases: correlation between tumour response and resection rates. Ann Oncol 2005;16:1311-9. 22. Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg 2004;240:644-57. 23. Fong Y, Bentrem DJ. CASH (Chemotherapy-Associated Steatohepatitis) costs. Ann Surg 2006;243:8-9. 24. Ellis LM, Curley SA, Grothey A. Surgical resection after downsizing of colorectal liver metastasis in the era of bevacizumab. J Clin Oncol 2005;23:4853-5. 25. Karoui M, Penna C, Amin-Hashem M, Mitry E, Benoist S, Franc B, et al. Influence of preoperative chemotherapy on the risk of major hepatectomy for colorectal liver metastases. Ann Surg 2006;243:1-7. 26. Verbesey JE, Simpson MA, Pomposelli JJ, Richman E, Bracken AM, Garrigan K, et al. Living donor adult liver transplantation: a longitudinal study of the donor’s quality of life. Am J Transplant 2005;5:2770-7. 27. Parolin MB, Lazzaretti CT, Lima JH, Freitas AC, Matias JE, Coelho JC. Donor quality of life after living donor liver transplantation. Transplant Proc 2004;36:912-3. 28. Walter M, Dammann G, Papachristou C, Pascher A, Neuhaus P, Danzer G, et al. Quality of life of living donors before and after living donor liver transplantation. Transplant Proc 2003;35:2961-3. 29. Basaran O, Karakayali H, Emiroglu R, Tezel E, Moray G, Haberal M. Donor safety and quality of life after left hepatic lobe donation in living-donor liver transplantation. Transplant Proc 2003;35:2768-9. 30. Kim-Schluger L, Florman SS, Schiano T, O’Rourke M, Gagliardi R, Drooker M, et al. Quality of life after lobectomy for adult liver transplantation. Transplantation 2002;73: 1593-7. 31. Pascher A, Sauer IM, Walter M, Lopez-Haeninnen E, Theruvath T, Spinelli A, et al. Donor evaluation, donor risks, donor outcome, and donor quality of life in adult-to-adult living donor liver transplantation. Liver Transpl 2002;8: 829-37.
Background. Assessment of quality of life (QOL) after a major operation has become increasingly pertinent to patient care and may be as important as long-term survival in cancer patients. No current study has evaluated the long-term quality-of-life effects or the time to return to baseline quality of life in oncology patients undergoing hepatic resection for cancer. Thus, the aim of our study was to evaluate that the time to return to baseline QOL after major and minor hepatectomy is similar to other major abdominal operations. Methods. A prospective study of 32 patients with malignant liver tumors completed the FACT-Hep, FACT-FHSI-8, EORTC QLQ-C30, Profile of Mood States, EORTC QLQ-Pan26, and Global Rating Scale at the time of consent, discharge, first postoperative visit, 6 weeks, 3 months, 6 months, and 12 months. Results. Twenty-four patients underwent major (⬎2 segments) and 8 minor hepatectomy. Patients who underwent major hepatectomy demonstrated a significant loss in FACT-physical and functional scores at first postoperative visit and 6 weeks (P ⫽ .04) with return to baseline at 3 months. Similar nadir in all quality-of-life assessment scores were observed for POMS, EORTC QLQ-C30, FHSI-8, and certain global rating scales at 6 weeks, with a return to baseline at 3 months. For minor hepatectomy, the nadir for most quality-of-life scores occurred at the first postoperative visit with a return to baseline at 6 weeks. Conclusion. Patients undergoing major hepatectomy return to their baseline quality of life at 3 months with a progressive and sustained increase in physical, emotional, and global rating scale at 6 months. This study is the first one to demonstrate that major hepatectomy can be performed with short-term adverse QOL effects and long-term improvements in overall QOL. (Surgery 2007;142:676-84.) From the Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Ky
The assessment of a patient’s quality of life (QOL) after operation has become integral to patient care and may be as important as long-term survival in cancer patients. QOL is becoming as important to patients as being disease free and overall survival.1,2 Assessing QOL in surgical oncology patients has been limited primarily from the misleading notion that a surgeon’s judgment is more reliable than QOL data.3 Recent QOL assess-
Accepted for publication April 24, 2007. Reprint requests: Robert C. G. Martin II, MD, Division of Surgical Oncology, Department of Surgery and James Graham Brown Cancer Center, University of Louisville School of Medicine, 315 East Broadway, Room 313, Louisville, KY 40202. E-mail: [email protected]. 0039-6060/$ - see front matter © 2007 Mosby, Inc. All rights reserved. doi:10.1016/j.surg.2007.04.026
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ments have been performed in patients undergoing resection for esophageal,4 gastric,5 colorectal,6 and pancreatic7 cancers. To date, no study has evaluated the time to return to preoperative QOL after hepatic resection in oncology patients. The only QOL studies to date have evaluated patients with hepatocellular cancer after resection.8 This study did demonstrate a significant QOL benefit after resection when compared with patients who were not resected. Similarly a recent study from our group presented little difference in QOL among major hepatic resection, minor hepatic resection, and hepatic ablation.9 Major hepatectomy demonstrated a worse QOL at 6 weeks when compared with minor and hepatic ablation, with similar QOL effects among all 3 treatment modalities. To date, however, there have been no QOL studies evaluating the time it takes patients who undergo major resection and minor resection to return to their baseline QOL.
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Thus, the objective of this study was to evaluate the time to return to baseline QOL after major and minor hepatectomy. METHODS Patients with primary or metastatic cancer to the liver scheduled for hepatic resection or ablation were recruited for an observational study of QOL before and after surgical treatment. The study protocol was approved by the Institutional Review Board, and all patients were provided written, informed consent. Surgery. Patients were separated into 2 groups by their extent of resection. Extent of hepatectomy was defined as major if 3 or more segments were resected and minor if 2 or fewer segments were resected. The decision to perform these resections was at the surgeon’s discretion. Liver resections were classified as described by Couinaud.10 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. Cholecystectomy at the time of hepatic resection was not considered as an additional organ resection. Intraoperative anesthetic management during hepatectomy has been detailed previously.11 Briefly, all patients were premedicated and underwent general anesthesia. Before hepatic parenchymal transection, fluids were administered to maintain a urine output of 25 mL/h and systolic blood pressure greater than 90 mm Hg, whereas the CVP was reduced to less than 5 mm Hg. Intraoperative blood products were administered when blood loss exceeded 25% of the total blood volume. After the specimen was removed, crystalloid was administered intravenously to achieve euvolemia. Packed red blood cells and autologous blood were given only to maintain a hemoglobin of greater than 10 g/dL in patients with evidence of either coronary or cerebrovascular disease. The liver parenchyma was divided using Kelly clamps to crush liver tissue and to expose bile ducts and blood vessels, which were clipped, tied, or stapled. Inflow control was performed by intermittent vascular occlusion (the Pringle maneuver)12 applied for 5-10-minute intervals, released briefly, and reapplied as necessary. Pringle time was recorded as the total cumulative Pringle time applied during parenchymal transection. Outflow control of the hepatic veins before parenchymal division was nearly always obtained in lobectomy or ex-
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tended resections. Hepatic ablation was performed using intraoperative ultrasound guidance in all ablations to ensure that at least a 1-cm ablation margin was achieved around the tumors. Postoperative complications were defined as any complication that occurred within 30 days postoperatively and were classified according to a 5-point grading system that has been described previously.13,14 A postoperative death was defined as any patient death that occurred within 90 days postoperatively. Study procedures. This study was observational; no study-specific treatment was provided to these patients through this investigation. We used a pre– post test design to assess a patient’s experience of symptoms and concerns before and after hepatic resection or ablation. Patients were assessed at 6 time points, before surgical procedure, at discharge postprocedure, first postoperative visit (defined as with 2-3 weeks from procedure depending on length of hospital stay), 6 weeks postprocedure, 3 months, and 6 months. Upon enrollment, the study coordinator, research assistant, or investigator completed the treatment history and demographics. At this time the patients completed a baseline questionnaire battery consisting of a Functional Assessment in Cancer Therapy core instrument with the hepatobiliary subscale (FACT-HEP), Brief POMS, EORTC QLQ-C30, and EORTC QLQPAN. Upon discharge after hepatectomy, each patient completed the FHSI-8, which differs from the FACT-Hep by including questions that are applicable to the hospitalization. At the 4 remaining time points, each patient completed a questionnaire battery consisting of a FACT-Hep, Brief POMS, EORTC QLQC30, EORTC QLQ-PAN, 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, the follow-up questionnaires were mailed to the patient. For those patients that survived less than 6 months after surgery, QOL assessment was continued until the last follow-up visit by the patient. All questionnaires were completed in English. The quality of the data obtained from each patient was evaluated when the patient completed all questionnaire forms at each visit. The study coordinator, research assistant, or investigator who had enrolled the patient reviewed each form immediately after receiving them to identify any missing data.
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Because of the paucity of data regarding QOL after hepatectomy, we estimated a 30% difference in QOL at 6 weeks for major versus minor hepatic resections. Assuming an alpha risk of 0.05, a beta risk of 0.8, and a difference of 30% at 6 weeks, the number of patients needed to treat was estimated to be 12 in each group. Assuming a post-planned treatment dropout of 20% because of death or noncompliance, the sample size required for this study was estimated to be at least 32 patients. The quality of data entry is evaluated by the use of range checks on all variables and by double data entry for a small portion (5% to 10%) of the data. This process allowed for the evaluation of the accuracy of the data entered by the primary data entry assistant. QOL instruments. The FACT-Hep is a validated instrument for assessing QOL in patients with hepatobiliary cancers, metastatic colorectal cancers, hepatocellular carcinoma, and pancreatic cancer.15 It is a 45-item self-report instrument that incorporates the 27 FACT-G 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 relating to hepatobiliary cancers.15 The patients circled on a scale of 0 (not at all) to 4 (very much) how true was each statement. After data collection, the scores were adjusted so that lower scores indicated higher QOL on all the items. The possible range of scores is 0-180. The FHSI-8 is a shorter (8 items) symptom index created from the FACT-Hep. It has good internal consistency, test–retest reliability, and provided an acceptable alternative to the lengthy FACT-Hep when the interest is symptom focused.16 The FHSI-8 was completed by the hospitalized patient at discharge because of its reliability, applicability of its items to the hospitalized patient, and brevity. The FHSI-8 also employs a 5-point scale ranging from not at all (0) to very much (4) in evaluating symptoms relevant to patients with hepatobiliary cancers. These scores were adjusted, where 0 indicated highest QOL and scores compromised a range of (0-32). The European Organization for Research and Treatment of Cancer (EORTC) core questionnaire, the EORTC QLQ-C30, is an integrated, modular approach for evaluating the QOL of patients participating in international clinical trials.17 The EORTC QLQ-C30 consists of 30 items incorporating 9 multi-item scales: 5 functional scales (physical, role, cognitive, emotional, and social); 3 symptom scales (fatigue, pain, and nausea and vomiting); and a global health and QOL scale. Several single-item
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symptom measures are also included. The EORTC QLQ-C30 is a reliable and valid measure of the QOL of cancer patients in clinical research settings. Items 1 through 28 used a 4-point scale ranging from not at all (1) to very much (4) in evaluating statements related to cancer. Items 29 and 30 used a 7-point scale ranging from very poor (1) to excellent (7). These scores were adjusted so that 1 indicated highest QOL. The range for the 30-item questionnaire was 30 (excellent QOL) to 126 (poor QOL). The EORTC QLO-PAN consists of 26 items, which 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.18 Each item used a 4-point scale that ranged from (1) not at all to (4) very much, and these scores were adjusted so that (1) not at all indicated greatest QOL. The possible range of scores is 26 (excellent QOL) to 104 (poor QOL). The Brief Profile of Mood States (POMS) is a self-report, 11-item short form of the Profile of Mood States’s 58-item Total Mood Disturbance Score (TMDS). It shows highly satisfactory internal consistency and correlation with the full TMDS and was administered to the patients to measure distress as an adjunct to patient care.19 The brief POMS consist of 11 words that describe feelings (eg, Blue, Discouraged, or on Edge). The patients report on a 5-point scale, with 0 being not at all and 4 being extremely how they have been feeling in the last week. The scores range from 0 (excellent QOL) to 44 (poor QOL). We also used patient-centered global ratings of change to assess patients QOL. Patients were asked to specify the direction and amount of change in 6 domains: 1) physical well-being, 2) social/family well-being, 3) emotional well-being, 4) functional well-being, 5) disease-specific well-being, and 6) overall QOL. Patients used a 15-point scale ranging from ⫺7 (a very great deal worse) through 0 (no change) to ⫹7 (a very great deal better). The higher score indicated an 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 its use in prior published studies in hepatic surgery, pancreatic surgery, or upper gastrointestinal surgery. Statistical analysis. Unless otherwise specified, all P-values are based on 1-sided t tests comparing
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Table I. Demographic data for major and minor groups Demographic Age Gender Histology 3 HCC 4 other Comorbid disease Additional organ resection Length of stay
Major (n ⫽ 24)
Minor (n ⫽ 8)
44-82 (median 68 years) 13 F, 11 M 13 MCC 4 CC 5 MCC 1 HCC 2 Other 65% 8%
39-78 (median 64 years) 4 F, 4 M
4-12 days (median 7)
4-25 days (median 7)
60% 40%
CC, Cholangiocarcinoma; F, female; HCC, hepatocellular cancer; M, male; MCC, metastatic colorectal cancer.
major hepatectomy with minor hepatectomy using JMP V4.1 (SAS, Inc., Cary, NC). RESULTS From October 1, 2002 to June 30, 2004, 32 patients were enrolled in this study: This included 15 men and 17 women with a median age of 62 years (range, 39-82). Twenty-four patients underwent major hepatic resections, and 8 underwent minor resections (Table I). The median hospital stay was 7 days, which was similar in both groups. The prevalence of comorbidities, length of stay, and overall operative time were similar in both groups. The minor hepatic resection group had a higher incidence of additional organ resection, but this was not significant among both groups (Table I). All eligible patients completed the questionnaires at the established time points. For the FACT-Physical, in the major hepatectomy group, when compared with the patient’s baseline QOL score (mean 3.0 ⫾ 1.4), there was a significant worse QOL score at the first postoperative visit (6.78 ⫾ 0.9), and the 6 weeks postoperative (9.4 ⫾ 1.8) (P ⫽ .01) with a return to baseline at the 3-month (4.5 ⫾ 1.3) postoperative (Fig 1, A). For the minor hepatectomy group, the baseline QOL score was (4.5 ⫾ 0.98). The QOL FACT-Physical score at 1st postoperative visit was significantly worse (10.1 ⫾ 1.90 (P ⫽ .036) with a return to baseline at 6-weeks postoperative (3.0 ⫾ 0.7) and throughout the follow-up period (Fig 1, A). For the FACT-function QOL scores, in which a higher score denotes a increase in QOL parameters, there were significantly worse QOL scores for the major hepatectomy group when compared with the preoperative visit (19.5 ⫾ 1.3) at both the first postoperative visit (14 ⫾ 1.7) and the 6-week (14 ⫾
Fig 1. A, FACT-Physical QOL scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections. Note: for FACT-physical, a higher score denotes a worse QOL. B, FACT-functional QOL scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections. Note: for FACT functional a higher score denotes an improved QOL.
1.7) (P ⫽ .02) postoperative period, with a return to baseline at the 3-month (22.2 ⫾ 1.0) postoperative period and throughout the follow-up period (Fig 1, B). For the minor hepatectomy group, there was a worse QOL score at the 1st postoperative visit (14 ⫾ 0.8) (P ⫽ .001) and a return to baseline by the 6-week postoperative (21 ⫾ 3.5) period and throughout the follow-up period (Fig 1, B). For both the FACT social (Fig 2, A) and the FACT emotional (Fig 2, B), the QOL scales were not statistically different across all 5 time points for both the major and the minor hepatectomy group. No changes were found in the patient’s social or emotional well-being during the recovery after major or minor hepatectomy. For Brief POMS, we observed a significant difference in the major hepatectomy group at first postoperative visit and at 6 weeks (P ⫽ .0305) with a return to baseline at 3 months. The major resection
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Fig 3. POMS QOL scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections.
Fig 2. A, FACT-Social QOL scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections. B, FACT-Emotional QOL scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections.
group demonstrated a significantly worse mean mood score at 1st postoperative visit (6.1 ⫾ 1.9) and 6 weeks (7.7 ⫾ 1.9) when compared with 3-month (2.2 ⫾ 0.8) and 6-month (2.5 ⫾ 1.2) follow-up. For the minor hepatectomy group, from a baseline score (4.4 ⫾ 1.6), there was a worse mean mood score at initial postoperative visit (7.6 ⫾ 3.4) (P ⫽ .08), which dropped to baseline or better by 6 weeks (1.6 ⫾ 1.36) and then to completion of follow-up (Fig 3). For QLQ-PAN, there is no difference for either the major or the minor resection group at any time points. No variation in QOL scores was found in either group. For the major hepatectomy group, there were significant worse QOL scores observed for EORTC QLQ-C30, at the first postoperative (mean score 63.4 ⫾ 2.4) versus the baseline visit (54 ⫾ 4.2) (P ⫽ .03) and 6-week postoperative (mean 62.0 ⫾ 3.8), with a return to baseline by 3 months (47.3 ⫾ 2.3) and then through the postoperative period (Fig 4). For the minor hepatectomy group, there was a
Fig 4. EORTC scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections.
worse QOL score at first postoperative visit (64 ⫾ 3.8 vs initial 50 ⫾ 3.1) (P ⫽ .01), with a return to baseline or better by the 6-week visit (mean score 41 ⫾ 6.8) and then through out the postoperative period (Fig 4). For the FHSI-8 self-report scale, the major hepatectomy group demonstrated a significant improvement in scores after the 6-week visit when compared with the discharge scores (mean score 11.8 ⫾ 1.5 vs 6.1 ⫾ 1.3 at 3 months) (P ⫽ .002) (Fig 5). For the minor hepatectomy group, most of the greatest improvement was observed at the 6-week postoperative visit (mean score 3.4 ⫾ 0.5 vs 10.3 ⫾ 2.6 at discharge) (P ⫽ .046), with consistent improvement in scores throughout the remainder of the follow-up (Fig 5). For the overall Global Rating Scale, we observed a significant improvement of QOL at the 3-month postoperative visit (QOL mean score 26.6 ⫾ 2.7)
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Fig 5. FHSI-8 QOL scores at 5 time points with patients who underwent major hepatic resections and minor hepatic resections.
when compared with the 1st postoperative visit (mean QOL score 9.5) (P ⫽ .002). This improvement continued throughout the follow-up period. A significant increase in the global QOL score occurred for the minor hepatectomy group from the 1st postoperative visit (mean 14) to the 6-week postoperative visit (mean 27) (P ⫽ .01), with stabilization of scores for the 3-month (mean 25) and 6-month (mean 21) visit. For the physical well-being portion of the Global rating of change scale (GR1), the major hepatectomy group demonstrated an improvement in QOL scores after the 1st postoperative visit (mean score 2.75) to the 3-month post-operative visit (mean score 4.6) and then maintained throughout the postoperative visit. For the minor hepatectomy group, there was an improvement in QOL scores from the 1st postoperative visit (mean score 3) to the 6-week postoperative visit (mean score 5.3), with similar global rating scores at the 3-month (score 5) and the 6-month visits (score 5). For the second part of the global rating scale, which assesses social and family well-being, there was a significant improvement in the QOL scores from 1st postoperative visit (1.6 ⫾ 0.8), when compared with the 3-month visit (score 4.1 ⫾ 0.6). For the minor hepatectomy group as with the FACTsocial scores, there were no significant changes from the 1st postoperative visit (score 3.6) to the 6-week (score 3) to the 3-month (score 3.5) to the 6-month follow-up (score 3.3). For the emotional well-being global rating scale, no differences were observed with either group for major or minor hepatectomy. The global rating scale 4, which assesses the functional well-being of the patients, demonstrated
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a significant improvement in the major resection group QOL scores at 3 months (score 4.3) when compared with 1st postoperative visit (score 0.4) (P ⫽ .002). Similarly for the minor hepatectomy group, there was a significant improvement in this QOL score at 6 weeks (mean score 5.3) when compared with 1st postoperative visit (mean score 0.4) (P ⫽ .001) and then consistent scores at 3 months (score 5.5) and at 6 months (score 4). The global rating scale 5 refers to improvement in symptoms or concerns related to the patient’s specific illness. For the major hepatectomy group, again the greatest improvement occurred at the 3-month postoperative visit (score 4.4) when compared with the 1st postoperative visit (score 1.9), which then was maintained throughout the postoperative follow-up. For the minor hepatectomy group, again we saw a significant improvement at 6 weeks (mean score 6.7) when compared with 1st postoperative visit (mean score 1.8) (P ⫽ .002) and then a decrease in scores at 3 months (mean score 3) and at 6 months (mean score 2.7). The global rating scale 6 refers to the change in overall QOL. For the major hepatectomy group, the 3-month visit (score 4.6) demonstrated the greatest improvement from the 1st postoperative visit (score 1.7) with stabilization throughout the follow-up period. For the minor hepatectomy group, we saw no differences in these scores from 1st postoperative (mean score 3) to 6 weeks postoperative (mean score 3.8) to 3 months (mean score 3) to 6 months (mean score 3.3). Eleven patients experienced 14 complications, including biloma, reoperation for bleeding, pulmonary embolus, deep venous thrombosis, atrial fibrillation, and others, with severity ranging from grade 1 to grade 3. Eight patients experienced 11 complications in the major hepatectomy group, and 3 patients experienced 3 complications in the minor hepatectomy group. In the patients who sustained a grade 3 complication, there was a significant loss in their FACT-physical at 3 months (P ⫽ .003) when compared with baseline and did not return to baseline until 6 months. The severity of the complication was also a predictor of worse FACT-functional at 3 months when compared with baseline (P ⫽ .02). For POMS, there was a significant loss at 3 months (P ⫽ .03) when compared with baseline in patients with complications. Similar loss in all the QOL assessment scores was observed for QLQPAN, EORTC QLQ-C30, FHSI-8, and certain global rating scales at 6 weeks and 3 months for patients who suffered a significant complication.
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Table II. QOL in hepatectomy patients: return to baseline Author
# Pts
Procedure
Verbesey et al
47
Right LRLT
SF-36
Parolin et al27 Walter et al28
19 28
LRLT LRLT
NS WHOQOL-BREF
Basaran et al29
27
Left LRLT
SF-36
NS
Kim-Schluger et al30
30
LRLT
SF-36
Variable postoperative
Pascher31
43
Right LRLT
ACSA
Preoperative, 6 and 12 months postoperative
26
QOL instrument
Time points analyzed
Outcome
Preoperative, and 1 week, 1, 3, 6, and 12 month postoperative Postoperative Preoperative and 6 months postoperative
Returned baseline 3 months Recovery at 9 weeks Better than normal population at both time points No difference than control population Scores higher than general population Improved scores in patients as time lengthen
ACSA, Anamnestic Comparative Self-Assessment Scale; LRLT, living-related liver transplant; NS, not stated; SF-36, Study Short form 36 questionnaire; WHOQOL-BREF, World Health Organization QOL brief form.
DISCUSSION Although major hepatic resection has been demonstrated to be clearly beneficial in patients with both primary as well as metastatic malignancies, significant risk of morbidity and mortality should be considered. The number of hepatic resections is increasing worldwide and is becoming far more complex. With the ever-increasing demand for multimodality care20-22 as well as the effects these multimodality treatments have on hepatic function,23-25 evaluating QOL effects after therapy has gained greater importance. Simply having the ability to provide aggressive care in the form of multiple lines of different chemotherapy, aggressive surgical resections, and other treatments does not always provide optimal QOL time. It has, thus, become increasingly important to obtain reliable QOL data in patients who chose hepatic resection. We report a prospective, longitudinal QOL study of 32 consecutive hepatic resections at our center. All patients completed this same survey preoperatively and then at 4 postoperative time points allowing for measurement of changes in QOL over time. Demographic data for both the major and the minor hepatic resection groups are similar to other reports in regard to median age, comorbidities, and distribution of histology, with the most common being metastatic colorectal. This report is the 1st one to evaluate a patient’s QOL and to assess the time these patients take in order to return to their baseline QOL after both major and minor hepatic resections. Our study at 6 weeks demonstrated that both the FACT-physical and the FACT-functional QOL scales are worse for the major resection group at 6 weeks with a return
to baseline at 3 months and continue at that range for 6 months and then on. For minor hepatectomy patients, there was a significant difference in the FACT-physical and FACT-functional QOL scores at their 1st postoperative visit with a return to baseline at 6 weeks postoperatively. These changes and return to baseline were similar for both the major resection group and the minor resection group with the Brief-POMS QOL scores, with again a return to baseline at 3 months for the major resection and 6 weeks for the minor hepatectomy. Similar differences were observed in the EORTC QLQ-C30 in both the major resection and the minor resection with a return to baseline at 3 months and 6 weeks, respectively. Similar results were also identified for the FHSI-8 self-report scale with an improvement at 3 months for major resections and 6 weeks for minor resection and then stabilization of their respective scores. The differences in the return to baseline in these groups is in direct relation to the extent of hepatic resection and less related to additional organ resections (Table I). This difference clinically relates to the extent of fatigue that patients undergoing major resection have during their recovery. This fatigue seems to be a major reason for the differences observed in this study. There is a paucity of QOL data for cancer patients treated with hepatic resection; however, a comparison can be made between the current data and those from the transplant literature. Our results compare with the report from Verbesey et al in their review of 47 right living-related liver transplants (Table II).26-31 They used a slightly different QOL instrument with the Study Short Form 36 (SF-36) with time points at preoperatively, 1 week,
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1 month, 3 months, 6 months, and 12 months and demonstrated a return to baseline at the 3-month interval. This report represents probably the purest study in a living-related liver transplant because many other reports have either not assessed QOL preoperatively or had a variable postoperative evaluation (Table II). However, other reports did demonstrate that patients who underwent living-related liver transplant either returned to their baseline QOL or had higher QOL scores when compared with either the control population or the general population.30,31 Similarly, it seems that the QOL continues to improve over time as reported by Pascher et al who found continued improved QOL scores in his right living-related liver transplant patients at the 12-month evaluation. There are limitations to a comparison between the QOL data from living-related transplantations and our current study: Most patients who are eligible for a living-related liver transplant are younger and may have fewer comorbid conditions than patients with liver cancer, especially those with metastatic disease. Similarly, the differences in QOL instruments that were used in the various reports makes comparisons somewhat limited but does demonstrate a relatively reasonable 3 months of recovery time in order to return to baseline. This study used several wide-ranging QOL instrument panels, simply to ensure that we captured any and all physical, functional, and psychologic QOL parameters that are important to the oncology patient. Our study continues to confirm that the FACT Hep QOL scale represents a fairly sensitive and accurate assessment of a patient’s overall QOL. Similarly, the Brief-POM as well as the EORTC questionnaire may also be used to evaluate sensitively a patient’s underlying recovery and QOL assessment after major and minor hepatectomy. With the role of hepatic resection becoming more widely accepted and universally established in the treatment of both patients with primary or metastatic hepatic malignancies, more consistent QOL surgical standards need to be established. Because most of these patients are under multimodality care with the use of either neoadjuvant therapy, adjuvant therapy, or both to maximize their disease-free survival and/or overall survival limiting permanent QOL defects is paramount. In addition, minimizing the time of chemotherapy interruption is becoming more important. This study demonstrates that in patients who are undergoing major hepatic resection that the maximum QOL time to return to baseline is 12 weeks, with most likely a shorter time interval. Because there was such a dramatic improvement in this study from 6 weeks
to 3 months that was not captured with our current time points, it maybe assumed that a return to baseline occurred before the scheduled 3-month office visit. Thus, it is fairly reasonable to accept the concept of “time to resumption of chemotherapy” or “time to the induction of postoperative chemotherapy” should be within an 8-week to 12-week window after major hepatic resection. This concept is important for collaborating as well as for educating other oncology specialties in the benefit as well as the limited QOL effects that major hepatic resection induces. Setting this time goal or, more importantly, this surgical standard in recovery is yet another potential quality measure that hepato-pancreatico-biliary surgeons should consider as we proceed in overall patient outcomes. The limitations of this study are related to the small sample size of patients who underwent minor resections. A possibility exists that a larger number of minor resection patients may create more variance in these results, but because the range of scores was close, this variance would probably be small. Even with these limitations, this study represents a solid foundation in which additional quality standards can be set as well as strived for in all major and minor hepatectomy patients. In conclusion, using various QOL measures, patients undergoing major hepatectomy return to their baseline QOL at 3 months with a progressive and sustained increase in physical, functional, and global rating scale at 6 months. Minor hepatectomies recover more quickly with return at 6 weeks. This study is the first one to demonstrate that major hepatectomy can be performed with short-term adverse QOL effects and long-term improvements in overall QOL parameters. REFERENCES 1. Slevin ML. Quality of life: philosophical question or clinical reality? BMJ 1992;305:466-9. 2. Mayer RJ. Summary of the second international conference on biology, prevention and treatment of gastrointestinal malignancies. Ann Oncol 1995;6:645-9. 3. Fraser SC. Quality-of-life measurement in surgical practice. Br J Surg 1993;80:163-9. 4. Branicki FJ, Law SY, Fok M, Poon RT, Chu KM, Wong J. Quality of life in patients with cancer of the esophagus and gastric cardia: a case for palliative resection. Arch Surg 1998;133:316-22. 5. Thybusch-Bernhardt A, Schmidt C, Kuchler T, Schmid A, Henne-Bruns D, Kremer B. Quality of life following radical surgical treatment of gastric carcinoma. World J Surg 1999;23:503-8. 6. Camilleri-Brennan J, Steele RJ. Quality of life after treatment for rectal cancer. Br J Surg 1998;85:1036-43. 7. McLeod RS. Quality of life, nutritional status and gastrointestinal hormone profile following the Whipple procedure. Ann Oncol 1999;10(Suppl 4):281-4.
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