World J Surg (2008) 32:1067–1074 DOI 10.1007/s00268-007-9393-8
Combined Major Hepatectomy and Pancreaticoduodenectomy for Locally Advanced Biliary Carcinoma: Long-Term Results Toshifumi Wakai Æ Yoshio Shirai Æ Yoshiaki Tsuchiya Æ Tatsuya Nomura Æ Kouhei Akazawa Æ Katsuyoshi Hatakeyama
Published online: 30 January 2008 Ó Socie´te´ Internationale de Chirurgie 2008
Abstract Background This study aimed to define the role of combined major hepatectomy and pancreaticoduodenectomy in the surgical management of biliary carcinoma and to identify potential candidates for this aggressive procedure. Methods A retrospective analysis was conducted on 28 patients who underwent a combined major hepatectomy and pancreaticoduodenectomy for extrahepatic cholangiocarcinoma (n = 17) or gallbladder carcinoma (n = 11). Major hepatectomy was defined as hemihepatectomy or more extensive hepatectomy. Altogether, 11 patients underwent a Whipple procedure, and 17 had a pyloruspreserving pancreaticoduodenectomy. The median followup time was 169 months. Results Morbidity and in-hospital mortality were 82% and 21%, respectively. Overall cumulative survival rates after resection were 32% at 2 years and 11% at 5 years (median survival time 9 months). The median survival time was 6 months with a 2-year survival rate of 0% in 11 patients with residual tumor, whereas the median survival time was 26 months with a 5-year survival rate of 18% in 17 patients with no residual tumor (P = 0.0012). Residual T. Wakai Y. Shirai (&) K. Hatakeyama Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan e-mail:
[email protected] Y. Tsuchiya T. Nomura Department of Surgery, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata 951-8566, Japan K. Akazawa Department of Medical Informatics, Niigata University Medical and Dental Hospital, 1–754 Asahimachi-dori, Chuo-ku, Niigata 951-8520, Japan
tumor status was the only independent prognostic factor of significance (relative risk 4.65; P = 0.003). There were three 5-year survivors (two with diffuse cholangiocarcinoma and one with gallbladder carcinoma with no bile duct involvement) among the patients with no residual tumor. Conclusions Combined major hepatectomy and pancreaticoduodenectomy provides survival benefit for some patients with locally advanced biliary carcinoma only if potentially curative (R0) resection is feasible. Patients with diffuse cholangiocarcinoma and gallbladder carcinoma with no bile duct involvement are potential candidates for this aggressive procedure.
Surgical resection provides the best chance for cure in patients with biliary malignancy [1–5]. In 1980, Takasaki et al. [6] were the first to report the use of combined major hepatectomy and pancreaticoduodenectomy (PD), the socalled hepatopancreatoduodenectomy, in five patients with locally advanced gallbladder carcinoma. Thereafter, some Japanese hepatobiliary surgeons have attempted major hepatectomy (hemihepatectomy or more extensive hepatectomy) combined with PD for locally advanced biliary tumors despite the high morbidity and mortality rates associated with this procedure [7–21]. The role of this procedure and its indications in such patients remain poorly defined [17, 18, 22, 23] despite early reports of its efficacy [17–22]. In 1994, we reported our experience of combined major hepatectomy and PD in seven patients with biliary carcinoma [11]. However, the small number of patients and short follow-up time precluded a definitive conclusion. The current study comprised 28 patients who underwent combined major hepatectomy and PD for biliary carcinoma (seven of whom were included in our previous report [11]).
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Study results were subjected to univariate and multivariate analyses with longer follow-up times than in our earlier study [11]. We sought to define the role of this procedure in the surgical management of biliary carcinoma and to identify potential candidates for this aggressive procedure.
cholangiocarcinoma (Table 1) and 11 with gallbladder carcinoma (Table 2)—formed the basis of this retrospective study. They comprised 18 women and 10 men with a median age of 63 years (range 35–79 years). Carcinoma arising in the cystic duct (patients 11, 14, 16 in Table 1) was categorized as extrahepatic cholangiocarcinoma according to the TNM staging system [24]. Indications for combined major hepatectomy and PD for extrahepatic cholangiocarcinoma included hepatic involvement and direct invasion of the pancreas or duodenum (n = 9), hepatic involvement and peripancreatic lymph node metastases (n = 2), hepatic involvement and extensive ductal involvement (n = 2), extensive ductal involvement and direct invasion of the pancreas or duodenum (n = 3), and extensive ductal involvement with peripancreatic lymph node metastases (n = 1). Indications for combined major hepatectomy and PD in gallbladder carcinoma included hepatic involvement and direct invasion of the pancreas or duodenum (n = 9) and extensive ductal involvement and peripancreatic lymph node metastases (n = 1). In the remaining patient (patient
Materials and Methods Patient Population From January 1985 through December 2003, a total of 473 consecutive Japanese patients with biliary malignancy (203 with extrahepatic cholangiocarcinoma, 270 with gallbladder carcinoma) underwent a surgical resection with curative intent in Niigata University Medical and Dental Hospital and Niigata Cancer Center Hospital. Of these patients, 29 (6%) underwent a combined major hepatectomy and PD for a locally advanced biliary tumor. One patient with a concomitant hepatocellular carcinoma was excluded. The remaining 28 patients—17 with extrahepatic
Table 1 Clinicopathologic characteristics of 17 patients undergoing combined major hepatectomy and pancreaticoduodenectomy for extrahepatic cholangiocarcinoma Patient no.
Age (years)
Sex
Tumor location
Histologya
TNM classificationa
Type
Grade
pT
pN
pM
Stage
Type of resection
Ra
Outcome (months)
Potentially curative (R0) resection (n = 10 patients) 1
64
M
Diffuse
Adeno
G1
3
1
0
IIB
ERH + PPPD
0
176; NED
2
63
3
67
M
Diffuse
Adeno
G2
4
1
1 (LYM)
IV
Central + PPPD + PV
0
125; NED
F
Upper third
Adeno
G2
3
1
1 (LYM)
IV
ERH + PPPD
0
4
28; DOD
70
M
Upper third
Adeno
G2
3
1
0
IIB
ERH + PD
0
28; DOD
5
50
F
Upper third
Adeno
G2
4
0
0
III
RH + PPPD
0
26; DOD
6
76
M
Middle third
Adeno
G3
4
0
1 (HEP)
IV
ERH + PPPD + PV
0
8; DOD
7
35
F
Upper third
Adeno
G3
3
1
0
IIB
ERH + PPPD + PV
0
8; DOD
8
61
F
Upper third
Adeno
G3
4
1
1 (LYM)
IV
ERH + PPPD + PV
0
4; DODb
9 10
77 72
M M
Upper third Diffuse
As Adeno
G3 G2
3 3
0 1
0 0
IIA IIB
RH + PD ERH + PD
0 0
1; DOOb 1; DOOb
Noncurative (R1 or R2) resection (n = 7 patients) 11
54
F
Diffuse
Adeno
G3
4
1
1 (HEP)
IV
RH + PPPD
2
15; DOD
12
55
M
Upper third
Adeno
G1
4
1
1 (LYM)
IV
LH + PD
2
10; DOD
13
58
F
Upper third
Adeno
G2
4
1
0
III
RH + PD
1
8; DOD
14
64
F
Middle third
Adeno
G2
4
1
0
III
ERH + PPPD
2
6; DOD
15
55
F
Upper third
Adeno
G3
4
0
0
III
ERH + PPPD + PV + Co
2
5; DOD
16
77
M
Middle third
Adeno
G2
4
1
0
III
ERH + PPPD + PV + IVC
2
4; DOOb
17
62
F
Diffuse
Adeno
G3
3
0
0
IIA
ERH + PD
1
2; DOOb
Adeno: adenocarcinoma; As: adenosquamous carcinoma; LYM: lymph nodes; HEP: hepatic; ERH: right hemihepatectomy extended to an inferior part of Couinaud segment IV; Central: central hepatectomy; RH: right hemihepatectomy; LH: left hemihepatectomy; PPPD: pyloruspreserving pancreaticoduodenectomy; PD: Whipple pancreaticoduodenectomy; PV: resection of the portal vein; Co: colectomy; IVC: resection of the inferior vena cava; NED: (alive with) no evidence of disease; DOD: died of disease; DOO: died of other causes a
According to the TNM staging system [24]
b
In-hospital death
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Table 2 Clinicopathologic characteristics of 11 patients undergoing combined major hepatectomy and pancreaticoduodenectomy for gallbladder carcinoma Patient no.
Age (years)
Sex
Bile duct involvement
Histologya
TNM classificationa
Type
Grade
pT
pN
pM
Stage
Type of resection
Ra
Outcome (months)
Potentially curative (R0) resection (n = 7) 1
66
F
Absent
Sq
G1
4
0
0
III
ERH + PD + Co
0
99; NED
2 3
61 79
F F
Absent Present
Adeno Adeno
G1 G2
2 4
0 1
0 0
IB III
ERH + PD ERH + PD + IVC
0 0
56; DOO 45; DOD
4
63
F
Present
Adeno
G3
4
1
0
III
ERH + PPPD + PV
0
29; DOD
5
41
F
Present
Adeno
G2
4
1
0
III
ERH + PPPD
0
19; DOD
6
62
M
Absent
Adeno
G2
4
0
1 (LYM)
IV
ERH + PPPD
0
13; DOD
7
44
F
Present
As
G2
4
1
1 (HEP)
IV
ERH + PPPD + Co
0
9; DOD
G2
4
1
0
III
RH + PPPD + PV + IVC
2
9; DOD
Noncurative (R1 or R2) resection (n = 4 patients) 8
77
F
Present
Adeno
9
68
F
Present
Adeno
G2
4
1
1 (LYM)
IV
ERH + PD + Co
2
7; DOD
10
62
F
Absent
As
G3
4
1
0
III
ERH + PPPD
2
5; DODb
11
73
M
Present
As
G1
4
1
0
III
ERH + PD
1
5; DOD
Sq: squamous cell carcinoma a According to the TNM staging system [24] b
In-hospital death
2 in Table 2), the procedure was performed with suspicion of hepatic involvement and peripancreatic nodal disease. Histologic examination of the resected specimen confirmed neither hepatic involvement nor nodal disease.
Surgical Resection Procedures Major hepatectomy was defined as hemihepatectomy (according to the Brisbane 2000 Terminology of Liver Anatomy and Resections [25]) or more extensive hepatectomy. Hepatectomy procedures included right hemihepatectomy extended to an inferior part of Couinaud segment IV in 21 patients, right hemihepatectomy in 5, left hemihepatectomy in 1, and central hepatectomy (removal of Couinaud segments IV, V, VIII) in 1 patient. In the current study, central hepatectomy was included in the category of major hepatectomy. Of the 28 patients, 8 underwent concomitant resection of the caudate lobe. No patient underwent a portal vein embolization before resection. The PD procedures included the Whipple procedure in 11 patients and pylorus-preserving PD in 17 patients. Twelve patients also underwent a combined resection and reconstruction of contiguous tissues comprising the portal vein (n = 8), transverse colon (n = 4), and inferior vena cava (n = 3). All 28 patients underwent en bloc dissection of the regional lymph nodes in the pericholedochal, retroportal, cystic duct, right celiac, anterior/posterior pancreaticoduodenal, and hepatic artery node groups, as well as those in
the right portion of the superior mesenteric node group [5, 24, 26–28]. Twenty-six patients with suspected regional lymph node metastases also underwent dissection of the paraaortic lymph nodes [27, 28]. The median estimated blood loss was 1875 ml (range 500–5066 ml), and the median operating time was 654 minutes (range 335–957 minutes). The median value of the postoperative maximum total bilirubin concentrations in serum was 6.3 mg/dl (range 3.1–28.8 mg/dl).
Pathologic Examination Resected specimens were submitted to the Department of Surgical Pathology in each hospital for histologic examination, and findings were described according to the TNM staging system [24]. Two patients with gallbladder carcinoma (patients 6, 11 in Table 2) also had extrahepatic cholangiocarcinoma, in whom the gallbladder tumor represented the case as it had a higher T category than the bile duct tumor. The extent of the primary tumor was determined by examining multiple sections (median 25 sections; range 9–38 sections) of the entire lesion in each resected specimen. Adenocarcinoma was identified as the primary tumor in 23 patients, adenosquamous carcinoma in 4 patients, and squamous cell carcinoma in 1; in the current study, squamous cell carcinoma was included in the category of adenosquamous carcinoma. Histologic grade was determined based on areas of the tumor having the highest grade [24].
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The extrahepatic bile duct was divided into three areas: upper, middle, or lower thirds according to the classification of Tompkins et al. [29]. Diffuse cholangiocarcinoma was defined as tumor affecting all three areas. Among the 17 patients with extrahepatic cholangiocarcinoma, 9 had a tumor arising in the upper third of the bile ducts, and 3 had a tumor arising in the middle third; the remaining 5 patients had a diffuse tumor (Table 1). A total of 831 lymph nodes removed from the 28 patients (median 25/patient) were examined histologically for metastases. A representative 3-lm section was cut from each lymph node and stained with hematoxylin and eosin (H&E). A total of 96 positive lymph nodes (median 5/ patient) were found in 21 patients (75%). Involvement other than that of regional lymph nodes was categorized as pathologic distant metastasis (pM1) according to the TNM staging system [24]. Altogether, 27 patients had involvement of contiguous organs or structures (median of two organs or structures involved; range one to six organs or structures involved). In patients with extrahepatic cholangiocarcinoma, the sites of contiguous involvement were the liver (n = 13), gallbladder (n = 11), pancreas (n = 7), portal vein (n = 7), hepatic artery (n = 7), duodenum (n = 3), transverse colon (n = 1), and inferior vena cava (n = 1). In patients with gallbladder carcinoma, the sites of contiguous involvement were the liver (n = 9), extrahepatic bile ducts (n = 7), pancreas (n = 7), duodenum (n = 4), portal vein (n = 3), hepatic artery (n = 3), transverse colon (n = 3), inferior vena cava (n = 2), and stomach (n = 1). In gallbladder carcinoma, ‘‘bile duct involvement’’ was defined as histologically verified stromal invasion of the extrahepatic bile ducts by the tumor. In the current series, liver metastases were found histologically in the resected specimens of three patients and were classified as pathologic distant metastasis (pM1) [24].
Assessment of Residual Tumor Status Residual tumor status was assessed clinically and histologically according to the TNM staging system [24]. When the surgeon grossly detected residual tumor and the surgical pathologist confirmed it by intraoperative frozen section examination of resection margins or histologic examination of the resected specimen, the residual tumor status was judged R2 (macroscopic residual tumor). When the surgeon detected no residual tumor but the pathologist found microscopic residual tumor on resection margins, the residual tumor status was judged R1 (microscopic residual tumor). When both the surgeon and pathologist detected no residual tumor, the residual tumor status was judged R0 (no residual tumor).
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Patient Follow-up After Resection Adjuvant treatment after resection was administered at the discretion of the individual surgeon. Three patients received oral administration of 5-fluorouracil (5FU). Two patients received intravenous administration of 5FU. Two patients received adjuvant external local radiotherapy with (n = 1) or without (n = 1) intravenous administration of 5FU. Patients were followed regularly in outpatient clinics every 1 to 6 months, with a median follow-up time of 169 months (range 48–268 months). At the time of disease status assessment, 20 patients had died of tumor recurrence. The initial sites of recurrence were remnant liver (n = 8), distant organs (n = 5), hepatic hilum (n = 5), or remnant liver plus distant organs (n = 2). Five patients died of other causes with no evidence of disease: intraabdominal bleeding (n = 2), hepatic failure (n = 1), suppurative cholangitis (n = 1), or hepatic steatonecrosis (n = 1). The remaining three patients were alive with no evidence of disease.
Prognostic Factors To elucidate factors influencing long-term survival after resection, 15 conventional variables [24, 30–32] were entered into univariate and multivariate analyses: age (B 65 years vs.[65 years), sex, primary site (extrahepatic bile ducts vs. gallbladder), histologic type (adenocarcinoma vs. adenosquamous carcinoma), histologic grade (G1 vs. G2– G3), lymphatic vessel invasion (absent vs. present), blood vessel invasion (absent vs. present), perineural invasion (absent vs. present), pathologic lymph node metastasis classification (pN0 vs. pN1), pathologic distant metastasis classification (pM0 vs. pM1), number of organs or structures involved (B two vs.[two), residual tumor status (R0 vs. R1– R2), PD procedure (Whipple procedure vs. pylorus-preserving PD), resection of the portal vein (absent vs. present), and adjuvant treatment (absent vs. present).
Statistical Analysis Medical records and survival data were obtained for all 28 patients. The causes of death were determined from the medical records or autopsy records. Survival curves were constructed using the Kaplan-Meier method, and differences in survival were evaluated using the log-rank test. Any death after resection, irrespective of the cause, was treated as an uncensored case with respect to the survival calculations. The Cox proportional hazards regression model identified factors that were independently associated with survival. In this model, a stepwise selection is used for
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variable selection with entry and removal limits of P \ 0.05 and P [ 0.1, respectively. The stability of this model was confirmed using a step-backward and step-forward fitting procedure. The variables identified as having an independent influence on survival were identical with both procedures. All statistical evaluations were performed using the SPSS 11.5J software package (SPSS Japan, Tokyo, Japan). All tests were two-sided and values of P \ 0.05 were considered statistically significant. Results Overall survival rates after resection were 32% at 2 years and 11% at 5 years (median survival time 9 months) (Fig. 1) in all 28 patients with biliary carcinoma. Analysis of survival according to the primary site revealed a comparable rate of survival after resection between patients with extrahepatic cholangiocarcinoma (survival rates 29% at 2 years and 12% at 5 years; median survival time 8 months) and patients with gallbladder carcinoma (survival rates 36% at 2 years and 9% at 5 years; median survival time 13 months; P = 0.4010). In all, 17 patients had no residual tumor (R0), whereas residual tumor (R1 or R2) was found in the remaining 11 patients (Tables 1, 2). Residual tumor was found around the preserved hepatic arteries (four patients), the superior mesenteric artery (two patients), the intrahepatic ductal stump (four patients), and around both the preserved hepatic arteries and the intrahepatic ductal stump (one patient). Morbidity and Mortality After Resection
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pancreatic fistula (n = 7), hepatic insufficiency (n = 6), biliary fistula (n = 4), intraabdominal bleeding (n = 3), cholangitis (n = 2), septicemia (n = 2), pneumonia (n = 2), acute renal failure (n = 1), pseudomembranous enterocolitis (n = 1), and breakdown of the duodenojejunostomy (n = 1). Six patients died during their hospital stay, giving an inhospital mortality rate of 21%; three of these patients were elderly ([70 years of age) (Tables 1, 2). The causes of inhospital mortality were tumor progression (n = 2), intraabdominal bleeding (n = 2), hepatic failure (n = 1), and suppurative cholangitis (n = 1). Thus, two patients in this series (patient 8 in Table 1 and patient 10 in Table 2) died in hospital owing to progression of their original carcinoma (4 and 5 months after resection, respectively). Factors Influencing Long-term Survival After Resection Univariate analysis revealed that residual tumor status (P = 0.0012) and histologic grade (P = 0.0453) were significantly associated with survival after resection. All 15 variables were entered into multivariate analyses, which showed residual tumor status [relative risk 4.65; 95% confidence interval (CI), 1.71–12.61; P = 0.003] to be the only independent significant variable. Long-term Outcomes According to Residual Tumor Status Residual tumor adversely affected survival after resection (Fig. 2). All patients with residual tumor expired within
Complications during the postresection hospital stay occurred in 23 (82%) patients. Intraabdominal sepsis (n = 12) was the most common complication, followed by
Fig. 1 Kaplan-Meier survival estimates in all 28 patients who underwent combined major hepatectomy and pancreaticoduodenectomy for biliary carcinoma
Fig. 2 Kaplan-Meier survival estimates according to residual tumor status. Survival after resection was significantly worse in patients with residual tumor (median survival time 6 months; cumulative 2-year survival rate 0%) than in patients with no residual tumor (median survival time 26 months; cumulative 5-year survival rate 18%; P = 0.0012)
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15 months after resection. In contrast, three patients with no residual tumor survived more than 5 years after resection, including two with diffuse cholangiocarcinoma and one with gallbladder carcinoma but no bile duct involvement (Tables 1, 2). The three long-term survivors with biliary carcinoma underwent combined major hepatectomy and PD for histologically verified adjacent organ (or structure) involvement, comprising extensive intrahepatic ductal involvement with direct invasion of the pancreas (patient 1 in Table1), hepatic involvement with direct invasion of the pancreas (patient 2 in Table 1), and extensive hepatic involvement with direct invasion of the pancreas and duodenum (patient 1 in Table 2).
Discussion Although some patients with locally advanced biliary malignancy may benefit from combined major hepatectomy and PD [7–22], factors influencing long-term survival after this aggressive procedure have not been established [15–18, 22, 23]. This prompted us to conduct the current study, which demonstrated that residual tumor status was the only independent prognostic factor; a prerequisite for long-term survival was the absence of residual tumor. This observation indicates that combined major hepatectomy and PD provides survival benefit for some patients with locally advanced biliary carcinoma only if potentially curative (R0) resection is feasible. Combined major hepatectomy and PD is usually associated with high mortality rates [6–9, 11, 16–18, 22]. Our findings supported this, with an in-hospital mortality rate (21%) in the current study being twice the 5-year survival rate (11%). We previously showed that nonanatomic resection of the gallbladder bed (minor hepatectomy) combined with PD can be performed safely for gallbladder carcinoma [15]. Doty and colleagues [33] also found this procedure to be safe, and Sasaki et al. [34] reported no mortalities among 12 patients who underwent minor hepatectomy plus PD compared with one in-hospital death among four patients who underwent major hepatectomy plus PD. Finally, a recent study at Memorial Sloan-Kettering [22] revealed no mortalities following minor hepatectomy plus PD, but a 50% mortality rate following major hepatectomy plus PD [22]. The above observations clearly indicate that the extent of hepatectomy (minor vs. major) influences mortality rates after hepatectomy combined with PD. Because an operation with a mortality rate that is higher than long-term survival rates is not justified [23], careful patient selection is mandatory when planning a combined major hepatectomy and PD. The deaths of three elderly patients ([70 years of age) from a total of six in-hospital deaths suggested that
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such patients are not good candidates for combined major hepatectomy and PD. Peritoneal seeding, liver metastasis, or involvement of the major vessels to be preserved precludes combined major hepatectomy and PD for biliary carcinoma. Highresolution computed tomography (CT) [35] and staging laparoscopy [36] have been used to detect unresectability due to such adverse findings before definitive procedures. However, the main site of residual tumor in the current series was soft tissue around the major vessels to be preserved, and preoperative imaging including three-phase dynamic CT, magnetic resonance imaging (MRI), and angiography failed to reveal stromal invasion of these sites. We therefore propose that predicting potential candidates for R0 resection depends largely on intraoperative assessment of resectability by meticulous inspection, palpation, and frozen section examination (if necessary). The issue of whether extrahepatic cholangiocarcinoma or gallbladder carcinoma is more suitable for combined major hepatectomy and PD remains uncertain [7, 11, 37]. Primary site (extrahepatic bile ducts vs. gallbladder) did not affect long-term survival after resection in the current series. Among patients with extrahepatic cholangiocarcinoma, only two with a diffuse tumor in whom a potentially curative (R0) resection was feasible survived more than 10 years (Table 1). Long-term survivors with diffuse tumor have also been treated with major hepatectomy with PD [19–21]. Diffuse cholangiocarcinoma often spreads superficially along the bile ducts without deep transmural invasion [19, 38–40]. This may explain in part why some patients with diffuse tumor survived long term after a potentially curative (R0) resection. Thus, patients with diffuse tumors are potential candidates for this aggressive procedure only if negative ductal resection margins are achievable. Bile duct involvement (stromal invasion of the extrahepatic bile ducts), which is sometimes accompanied by diffuse involvement of the hepatoduodenal ligament, is a prominent predictor of worse survival in patients with gallbladder carcinoma, probably because it frequently results in residual tumor within the hepatoduodenal ligament [15, 41]. Miyazaki et al. [14] reviewed 44 surgically treated patients with gallbladder carcinoma. None with bile duct involvement survived more than 3 years after resection. Other Japanese authors [17, 41, 42] have argued that the survival benefit of major hepatectomy with PD is limited for patients with gallbladder tumor and bile duct involvement. The Memorial Sloan-Kettering study [43] revealed that six patients with gallbladder carcinoma presenting with jaundice (due to bile duct involvement) died of recurrence within 6 months despite aggressive resections. Also in our series, three of the four patients who underwent noncurative (R1 or R2) resection for gallbladder
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carcinoma had bile duct involvement, whereas only one 5year survivor had no bile duct involvement (Table 2). The above observations indicate that gallbladder carcinoma cases with bile duct involvement are not suitable for major hepatectomy with PD. Nodal status is an established prognostic factor in patients with biliary carcinoma [24]. Even among patients who underwent combined major hepatectomy and PD for biliary tumors, those with lymph node metastases generally had a dismal outcome [17, 18, 41, 44]. However, recent studies by some Japanese institutions revealed that selected patients with lymph node metastases survived for more than 5 years after this aggressive procedure [37, 41, 44, 45]. None of the node-positive patients who survived 5 years after major hepatectomy and PD had residual tumor. In the current series, two of the three 5-year survivors had nodal disease with no residual tumor. Therefore, we believe that lymph node metastasis is not a contraindication for combined major hepatectomy and PD in patients with biliary carcinoma when a potentially curative (R0) resection is achievable. Involvement of the hepatic arteries to be preserved and/ or that of the superior mesenteric artery preclude a potentially curative (R0) resection when performing combined major hepatectomy and PD for biliary carcinoma. In the current series, the main site of residual tumor was the soft tissue around the preserved hepatic arteries or around the superior mesenteric artery. Thus, the involvement of such vital arteries must be assessed meticulously during the operation before starting a resection [36, 46]. Any involvement of the hepatic arteries to be preserved and/or the superior mesenteric artery should exclude the choice of combined major hepatectomy and PD because reconstruction of such vital arteries provides little survival benefit for patients with histologically verified invasion of these vessels [8, 37]. The main limitation of the current study is that it is a retrospective analysis of a small number of patients. To our knowledge, however, this is one of the largest series dealing with combined major hepatectomy and PD for biliary carcinoma, and it analyzed the survival data using multivariate analysis. We believe that the limitation did not significantly influence the outcome of the study as the differences between groups were too marked to have resulted from these biases.
Conclusions Combined major hepatectomy and PD provides survival benefit for some patients with locally advanced biliary carcinoma only if potentially curative (R0) resection is feasible. Patients with diffuse tumor and gallbladder
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carcinoma with no bile duct involvement are potential candidates for this aggressive procedure.
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