Annals of Surgical Oncology, 13(12):1553–1559
DOI: 10.1245/s10434-006-9085-x
Hepatectomy for Peripheral Cholangiocarcinoma in Elderly Patients Chun-Nan Yeh, MD, Yi-Yin Jan, MD, FACS, and Miin-Fu Chen, MD, FACS
Department of Surgery, Chang Gung Memorial Hospital, Chang Gung University, 5 Fu-Hsing Street, Kwei-ShanTaoyuan, Taiwan
Background: Peripheral cholangiocarcinoma (CCC) is less common than hepatocellular carcinoma. Little is known about CCC patients older than 70 years who have undergone hepatectomy. Methods: Between 1977 and 2004, the clinical features of 33 elderly CCC patients (>70 years old) undergoing hepatectomy were reviewed, and 185 CCC patients younger than 70 years (younger CCC) were used for comparison. Results: A total of 218 CCC patients undergoing hepatectomy were investigated with ages ranging from 28 to 93 years (median, 59.0 years). The elderly and younger CCC groups had a similar sex ratio and a similar positive rate of carcinoembryonic antigen (CEA) and CA19-9. A similar rate of hepatolithiasis, mucobilia, papillary pattern, stage distribution, curative hepatectomy, surgical morbidity, and mortality for CCC were also observed between the two groups. During a follow-up duration ranging from 1.1 to 145.0 months (median, 11.7 months), elderly CCC and younger CCC patients had similar prognoses after hepatectomy (P = .827). Elderly CCC patients with a low CEA level, an intraductal papillary growth pattern, curative hepatectomy, and postoperative chemotherapy tended to have favorable survival. However, elderly CCC patients with a low CEA level independently showed favorable survival. Conclusions: Hepatectomy is feasible for selected elderly CCC patients. Elderly CCC patients undergoing hepatectomy had clinicopathologic features and prognoses similar to those of patients younger than 70 years undergoing hepatectomy. Elderly CCC patients with a low CEA level, intraductal papillary growth pattern, curative hepatectomy, and postoperative chemotherapy tended to have favorable survival. However, elderly CCC patients with low CEA level independently showed favorable survival. Key Words: Hepatectomy—Elderly—CCC—Prognosis.
Peripheral cholangiocarcinoma (CCC) is a malignant tumor occurring in the liver or arising from the second or more distal branches of the intrahepatic bile ducts.1 CCC is less common than hepatocellular carcinoma in most parts of the world and accounts for approximately 15% of liver cancer cases.2–4 According to the National Study of Liver Cancer of Japan, histologically proven CCC constitutes 5.4% of all primary liver cancers.1
Thanks to advances in science and civilization, life expectancy is increasing. Nowadays, hepatic surgeons perform hepatic resection on elderly patients with CCC more frequently than they did previously. In 2000, the population in Taiwan older than 70 years constituted 6.42% of the general population. Age is reported as a risk factor for carcinogenesis; however, age could affect cancer behavior in either worsening or improving directions.5 Several investigations have demonstrated that patients younger than 40 years with gastric cancer, colorectal cancer, CCC, or breast cancer have a worse prognosis than those >40 years.6–9 Older patients have associated disease other than the primary disease more often than younger patients do. Therefore, elderly patients are usually
Received May 1, 2006; accepted May 2, 2006; published online September 29 2006 Address correspondence and reprint requests to: Yi-Yin Jan, MD, FACS; E-mail:
[email protected] Published by Springer Science+Business Media, Inc. 2006 The Society of Surgical Oncology, Inc.
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considered a high-risk group for major surgery. Some studies have found a significantly higher morbidity and mortality rate after hepatectomy for hepatocellular carcinoma in the elderly, but comparable outcomes with younger patients have been reported.10,11 The clinicopathologic features and outcomes of patients >70 years with CCC undergoing hepatectomy have never been investigated. Although we have reported that CCC patients younger than 40 years have different characteristics from older patients and an unfavorable prognosis,9 no study has analyzed the influence of old age on CCC patients, particularly with respect to survival, surgical morbidity, and mortality. This study aimed to clarify the effect of old age on CCC patients undergoing hepatectomy.
FIG. 1. Age distribution of the 218 cholangiocarcinoma patients undergoing hepatectomy.
MATERIALS AND METHODS From 1977 to 2004, 218 consecutive patients with peripheral CCC underwent hepatectomy at the Department of Surgery, Chang-Gung Memorial Hospital, Taipei, Taiwan. CCC was defined as carcinoma arising from second-order or more distal branches of the intrahepatic ducts. Ten patients died within 1 month after the operation (mortality rate, 4.6%) and were excluded from survival analysis. Curative resection was defined as a negative resection margin observed on histopathologic examination. The 218 patients were further classified into younger CCC (age 36 (n = 9) ALP (IU/L) £94 (n = 14) >94 (n = 16) Bilirubin (total) (mg/dL) £1.3 (n = 25) >1.3 (n = 5) Albumin (g/dL) £3.5 (n = 13) >3.5 (n = 17) Serum CEA (ng/dL) >5 (n = 14) £5 (n = 9) Serum CA19-9 (ng/dL) >37 (n = 18) £37 (n = 12)
TABLE 6. Univariate analysis of factors influencing the overall survival of the 30 cholangiocarcinoma patients
Survival rate (%)
Median Mean 1 y
2y
Survival rate (%)
Median Mean 1 y 2 y P value
Factor Associated with biliary stones With biliary stones (n = 20) Without biliary stones (n = 10) Hepatectomy Curative (n = 19) Noncurative (n = 11) Mucobilia Positive (n = 5) Negative (n = 25) Tumor spreading type Papillary (n = 9) Nonpapillary (n = 21) Postoperative chemotherapy Positive (n = 12) Negative (n = 18) Postoperative radiotherapy Positive (n = 4) Negative (n = 26) Tumor staging Early stage (I and II) (n = 10) Advanced stage (III and IV) (n = 20)
15.81
15.92
54.5 32.7
23.90
20.02
70.0 28.0
.343
23.90 4.14
21.30 9.41
73.7 48.4 34.1 11.4
.015
3.68 17.23
14.75 17.77
40.0 40.0 63.5 32.5
.929
30.38 16.54
21.74 15.16
66.7 53.3 56.3 25.3
.049
23.90 4.14
22.59 82.5 41.3 1.345 44.4 31.7
.0358
17.23 11.70
17.97 15.58
61.5 36.5 50.0 25.0
.641
26.14
21.88
66.7 53.3
15.81
15.10
55.0 24.8
.272
P value
23.90 9.34
21.78 14.63
83.3 39.1 43.8 31.3
.264
20.45 16.54
16.57 20.96
55.3 33.5 100.0 50.0
.374
18.02 16.59
17.82 15.81
60.0 37.5 66.7 31.3
.725
17.23 16.54
17.98 14.33
61.1 38.2 53.8 23.9
.532
20.45 4.37
20.38 13.91
71.3 45.4 42.9 21.4
.434
20.45 4.37
19.43 16.42
76.9 32.1 42.9 42.9
.920
17.82 17.23
17.65 15.23
59.4 35.3 60.0 30.0
.819
9.34 23.90
13.50 20.61
40.0 26.7 76.5 42.5
.224
4.08 30.38
9.28 25.50
37.5 12.5 75.2 64.5
.002
30.38 17.82
23.38 19.67
77.8 58.3 57.1 42.9
.786
The types of hepatectomy for the 33 elderly CCC patients are listed in Table 4. We used univariate and multivariate analysis to calculate overall survival rates for 30 elderly CCC patients undergoing hepatectomy in terms of 17 clinicopathologic factors. Elderly CCC patients undergoing hepatectomy with a low CEA level, intraductal papillary growth pattern, curative hepatectomy, and postoperative chemotherapy seemed to have a better overall survival rate (Tables 5 and 6; Fig. 3). However, elderly CCC patients with low CEA level independently showed favorable survival (Table 7).
DISCUSSION
CCC, cholangiocarcinoma; AST, aspartate aminotransferase; ALT, alanine aminotransferase; ALP, alkaline phosphatase; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9.
Ann. Surg. Oncol. Vol. 13, No. 12, 2006
Survival time (mo)
The average age at CCC clinical detection in Japan and the United States is 60 to 65 years; the hilar type is normally detected a little earlier than the peripheral type. In the United Kingdom, the average age at clinical CCC detection is 48 ± 11 years for the peripheral type and 52 ± 12.5 years for the hilar type.14 Similar to United Kingdom’s report, this study demonstrated that the age distribution of Taiwanese peripheral CCC peaked for those older than 50 years. CCC commonly affects elderly people, and 15.1% of
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FIG. 3. Overall survival of 30 elderly cholangiocarcinoma patients undergoing hepatectomy in terms of (A) carcinoembryonic antigen (CEA), (B) tumor spreading type, (C) type of operation, and (D) postoperative chemotherapy.
CCC patients are older than 70 years. This study is the largest and the first series dealing with the effect of old age on CCC prognosis after hepatectomy. Similar associations with manifestations and underlying diseases were observed between the elderly and younger CCC groups. Laboratory data and tumor markers were similar in both groups. Increased blood urea nitrogen levels were, however, observed in the elderly CCC group, possibly as a result of increased age, and the average value is still within the reference range. Younger CCC patients had a hepatolithiasis association similar to that of elderly CCC patients. To our knowledge, CCC pathogenesis is still unknown. CCC occurring in association with hepatolithiasis is probably the cumulative result of several possible etiological agents, including nutritional, genetic, environmental, and immunological factors.15–18 Less mucobilia, fewer CCC papillary patterns, and a less advanced stage of tumor were observed in the younger CCC patients, although this was not statistically significant. This study also used univariate and multivariate analysis to calculate overall survival rates for 30 elderly CCC patients undergoing hepatectomy in terms of 17 clinicopathologic factors. Diagnostic adjuncts for CCC, such as a serum marker, are useful for the clinical management of this disease. Several investi-
TABLE 7. Cox proportional hazards analysis
Factor
Relative risk (95% confidence interval) P value
CEA (>5/
