- Email: [email protected]
Safety and efficacy of hepatic vein reconstruction for colorectal liver metastases
The American Journal of Surgery (2011) 202, 449 – 454
Clinical Science
Safety and efficacy of hepatic vein reconstruction for colorectal liver metastases Akio Saiura, M.D.a,*, Junji Yamamoto, M.D.b, Yoshihiro Sakamoto, M.D.c, Rintaro Koga, M.D.a, Makoto Seki, M.D.a, Yoji Kishi, M.D.a a
Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake Hospital, 3-10-6 Ariake, Koto-ku, Tokyo 135-8500, Japan; bDepartment of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan; cHepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan KEYWORDS: Hepatic vein reconstruction; Liver resection; Colorectal liver metastases
Abstract BACKGROUND: Colorectal liver metastases with hepatic vein (HV) involvement may require combined resection of the liver and HV. However, the short- and long-term outcomes of such a procedure remain unclear. METHODS: We reviewed 16 cases of liver resection with major HV resection and reconstruction. RESULTS: The patients had a median age of 58.5 years (range, 50 –74 y). In total, 18 HVs were reconstructed using a customized great saphenous vein graft (n ⫽ 10), direct anastomosis (n ⫽ 1), external iliac vein (n ⫽ 2), portal vein (n ⫽ 1), umbilical vein patch graft (n ⫽ 3), or ovarian vein patch graft (n ⫽ 1). There was no hospital mortality, and the morbidity rate was 50%. With a median follow-up period of 30 months (range, 4 – 89 mo), 3 patients died of tumor recurrence and 13 were alive with (n ⫽ 6) and without (n ⫽ 7) disease. Cumulative 1-, 3-, and 5-year survival rates were 93%, 76%, and 76%, respectively. CONCLUSIONS: HV resection and reconstruction combined with liver resection can be performed safely with reasonable long-term results. © 2011 Elsevier Inc. All rights reserved.
Liver resection remains the only potentially curative treatment for patients with colorectal liver metastases, despite improvements in local and systemic chemotherapies.1– 4 Hepatic vein (HV) resection is necessary in patients with hepatic tumors involving the HV to secure clear surgical margins. In the past decade, the indication of liver resection in patients with colorectal liver metastases has extended dra* Corresponding author. Tel.: ⫹81-3-3520-0111; fax: ⫹81-3-35700343. E-mail address: [email protected] Manuscript received April 6, 2010; revised manuscript August 11, 2010
0002-9610/$ - see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.amjsurg.2010.08.040
matically, both oncologically as a result of modern chemotherapy and technically as a result of recent improvements in surgical technique. The mortality rates for patients undergoing procedures in high-volume centers have decreased to 0% to 4%.2,3 However, involvement of all 3 major HVs in liver tumors is a remaining contraindication for liver resection in patients with colorectal liver metastases.5 In patients with tumors adjacent to the HV or involving the HV, combined resection of the HV and liver is required to achieve complete resection of the tumor with clear margins. HV resection also is mandatory if functional liver volume is insufficient. The procedure has been performed successfully only in a few reported cases.6 –9 Hemming et al10 reported an increased risk associated with HV reconstruction. Con-
450
The American Journal of Surgery, Vol 202, No 4, October 2011
comitant HV resection can expand the indication for curative resection of colorectal liver metastases; however, the technical feasibility of HV reconstruction remains unknown, as does the possible short- and long-term outcomes of the procedure.6 In contrast to hepatocellular carcinoma, anatomic liver resection is not necessary for colorectal liver metastasis.11,12 Instead, nonanatomic liver resection is recommended to reduce morbidity and mortality without compromising the oncologic outcome.13,14 Here, we report a case series of concomitant liver resection with HV resection and reconstruction in 16 patients with colorectal liver metastases using various autologous vein grafts. The study evaluated the technical and oncologic feasibility of HV reconstruction.
Patients From January 2001 to September 2008, 391 liver resections were performed at our institution. Of these, 16 (4.1%) patients underwent liver resection combined with HV resection and reconstruction, totaling 18 HV reconstructions (single, 14; double, 2), consisting of 14 segmental HV resections and 4 wedge HV resections with patch repair (Table 1). Cases of wedge resection with direct closure were excluded from this study. The study participants comprised 8 women (50%) and 8 men (50%), with a mean age of 60.4 years (range, 50 –74 y; median, 58.5 y). The underlying liver parenchyma was histologically normal in 13 cases, steatohepatitic in 2 cases, and fibrotic in 1 case.
Preoperative management All patients were assessed preoperatively using enhanced computed tomography, with the following selection criteria applied for surgery: (1) no comorbid condition precluded a major hepatic resection; (2) all tumoral liver disease was amenable to resection, while leaving at least 30% of the nontumoral liver with the exception of potentially ischemic or congested areas; and (3) no unresectable extrahepatic tumor. The median preoperative indocyanine green retention rate at 15 minutes was 7.1% (range, 2.1%–32%; normal,
Table 1
Patient and tumor variables (n ⫽ 18)
Variable
Median (range) or no.
Age, y Male sex No. tumors Solitary 2–4 ⬎5 Size of largest tumor, cm Previous liver resection
58.5 (50–74) 8 6 4 6 3.8 (1.5–8) 3
⬍10%). Eight patients (44%) received systemic chemotherapy before surgery (oxaliplatin, 5-fluorouracil and leucovorin [FOLFOX4] regimen, 2; 5-fluorouracil/leukovorin or tegaful, gimeracil, and oteracil (TS)-1, 6). One patient underwent hepatic arterial infusion therapy.
Surgical procedure The surgical techniques used for liver resection in our institution have been described elsewhere.15 After a laparotomy by inverted L-shaped incision, the whole liver was examined by intraoperative ultrasonography. After mobilizing the liver, transection was performed using a clamp-crushing technique with LigaSure (LigaSureTM vessel sealing system, Covidien, USA). An intermittent Pringle maneuver with periods of 15 minutes of clamping and 5 minutes of unclamping was used routinely. The congestion area was checked before HV resection, as described previously.16 The surgical margins were submitted for frozen sectioning to confirm negative margin status intraoperatively.
Definition of morbidity and mortality Surgical mortality included all in-hospital deaths. Hepatic failure was defined by a serum total bilirubin concentration of greater than 5.0 mg/dL during the postoperative period. Bile leakage was diagnosed when the bilirubin concentration of the drainage fluid was greater than 5.0 mg/dL after 5 or more postoperative days. Grade of complication was defined according to the system of Dindo et al,17 with major complications defined as grade 3 or more. The postoperative course was divided into 3 categories: no morbidity, minor complications only, and major complications.
Results All 16 patients in this series underwent potentially curative resection, as summarized in Table 2. R0 resections were achieved in 14 of the 16 patients. Three patients (18%) had synchronous resection of the primary site: colon cancer (2 cases), and rectal cancer (1 case). Two patients had combined wedge resection of the inferior vena cava, which was directly closed.
Indication of HV reconstruction The indication of HV reconstruction (HVR) includes absolute and relative indications. The absolute indication is a mandatory HVR owing to insufficient future remnant liver volume. There are 2 indications in this group: (1) involving all HV trunks without thick inferior right hepatic vein (IRHV), (2) involving double HV trunks in patients with multiple bilobar metastases and not indicated for portal vein embolization followed by extended hemihepatectomy. The
A. Saiura et al. Table 2
Hepatic vein reconstruction for liver tumors
Procedures of 18 HVRs in 16 hepatectomies n or median (range)
Variable
Hepatic resection Major hepatectomy 5 Minor hepatectomy 11 Associated procedure Hemicolectomy 2 Low anterior resection 1 No. major hepatic veins involved 1 5 2 7 3 4 No. major hepatic veins reconstructed 1 14 2 2 Type of reconstruction and graft (n ⫽ 20) Segmental Customized saphenous graft 10 External iliac graft 2 Direct 1 Portal vein 1 Patch Umbilical vein 3 Ovarian vein 1 Blood loss, mL 1030 (285–2200) Transfusion required 5 Duration of surgery, min 547 (303–935)
relative indication is an optional HVR to avoid major hepatectomy, which spares most of the parenchyma. Patients with HV trunk involvement without involvement of the major portal pedicle are included in this group. According to these criteria, hepatic reconstruction was mandatory in 9 patients (56%). Of these, all HVs were involved in 5 patients, with 1 patient undergoing a second hepatectomy after a previous right hemihepatectomy (cases 2, 4, 10, 11, and
Table 3
451
Figure 1 Intraoperative photograph after reconstruction of the right hepatic vein using a customized saphenous vein graft. CSV ⫽ customized saphenous vein graft; IVC ⫽ inferior vena cava; RHV ⫽ right hepatic vein.
15). In the remaining 4 patients with double HV involvement, mandatory HVR was chosen because portal vein embolization followed by right hemihepatectomy was not indicated because partial resection of the left liver with critical volume was required to remove multiple bilobar metastases (cases 1, 6, 12, and 16).
HV resection with or without autologous vein graft The 18 HVRs used various autografts (Table 3). Ten of the 18 were performed using a customized saphenous vein graft (Fig. 1), as described elsewhere.18 Briefly, the great saphenous vein is excised in a 12-cm length when segmen-
Type of 18 HVRs in 16 patients
Case no.
Involved HV
Type of HV resection
Reconstructed HV (graft)
Indication
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
M, R L, M* M L, M, R R M, R R M M, R L, M, R L, M, R M, R L, M R L, M, R L, R
Segment Segment Segment Segment Wedge Segment Wedge Segment Segment Segment (L) and wedge (R) Segment Segment Segment Wedge Segment (L) and Segment (M) Segment
R (CSV) L (CSV) M (CSV) R (CSV) R (round ligament) M (CSV) R (gonadal vein) M (CSV) R (direct) R (round ligament), L (CSV) R (CSV) M (external iliac vein) M (left portal vein) R (round ligament) R (CSV), M (external iliac vein) R (CSV)
Mandatory Mandatory Not mandatory Mandatory Not mandatory Mandatory Not mandatory Not mandatory Not mandatory Mandatory Mandatory Mandatory Not mandatory Not mandatory Mandatory Mandatory
L ⫽ left hepatic vein; M ⫽ middle hepatic vein; R ⫽ right hepatic vein; CSV ⫽ customized saphenous vein. *The right hepatic vein was resected in the primary hepatectomy.
452 Table 4
The American Journal of Surgery, Vol 202, No 4, October 2011
Postoperative courses
Postoperative data
Variable
Median (range) or n
Postoperative length of stay, d Maximum serum total bilirubin, mg/dL Morbidity Major Minor Mortality
16 (8–44) 1.3 (.7–4.7) 8 (50%) 1 7 0
tal combined HV resection and reconstruction is scheduled after intraoperative ultrasonography. The resected veins were cut longitudinally and divided into 3 pieces, which were stitched together to make a cylindric graft. One HV was reconstructed directly and 1 HV was reconstructed using portal vein excised from the resected liver. In patients undergoing sleeve resection of the HV, we performed patch closure using an umbilical vein (n ⫽ 3) and ovarian vein (n ⫽ 1) as reported previously.19,20 In the 2 cases of unscheduled reconstruction or double reconstruction, the right external iliac vein was excised. No total vascular exclusion was used in this series. All but 1 venous reconstruction was performed using the Pringle maneuver. One patient undergoing a double HV reconstruction required a temporary venous shunt between the middle hepatic vein (MHV) and inferior vena cava using an AnthronR bypass tube (TORAY, Japan).7
Table 5
Case no.
Table 4 summarizes the postoperative courses. The mortality rate was 0% and the morbidity rate was 50%. The median level of postoperative maximum aspartate aminotransferase and alanine aminotransferase were 612 U/L (range, 194 –1,538 U/L) and 781 U/L (range, 177–1,726 U/L), respectively. Minor complications comprised pleural effusion (n ⫽ 2), ileus (n ⫽ 2), wound infection (n ⫽ 2), and edema of extremities (n ⫽ 1). The only major complication occurred in 1 patient who had received preoperative systemic chemotherapy with FOLFOX4; this case developed intractable ascites necessitating a prolonged hospital stay (case 13). Pathologic testing of the background liver tissue showed sinusoidal dilatation and nodular regenerative hyperplasia. There were no cases of postoperative liver failure and no complications relating to the saphenous vein grafting. Adjuvant chemotherapy was administered to 3 patients (tegaful and uracil [UFT]/leukovorin, 2; FOLFOX4, 1).
Survival and recurrence Table 5 details the patient outcomes. The median follow-up period was 30.0 months (range, 4 – 89 mo). Kaplan– Meier curves for overall survival estimated 1-, 3-, and 5-year survival rates of 93%, 76%, and 76%, respectively, with a median follow-up period for survivors of 41 months
Outcome of 16 patients undergoing liver resection combined with HVRs
Disease
Lesions, n
Maximum diameter of lesions, cm
1
CLM
13
6
2 3 4 5 6 7 8 9
CLM CLM CLM CLM CLM CLM CLM CLM
1 2 13 4 2 8 1 1
4.5 2.7 8 1.9 3.5 2.9 1.5 3.8
10 11 12 13
CLM CLM CLM CLM
7 7 18 1
4 6.2 3.5 3.8
14 15
CLM CLM
4 1
2.2 5.5
16
CLM
8
3.5
Procedure
Recurrence
Outcomes
Limited resection, S3 segmentectomy, low anterior resection Limited resection Limited resection Extended left hemihepatectomy Limited resection Limited resection Limited resection Limited resection Limited resection, colectomy, partial resection of IVC Limited resection Extended left hemihepatectomy Extended right hemihepatectomy Extended left hemihepatectomy, partial resection of IVC Limited resection Extended left hemihepatectomy, right hemicolectomy Left lateral sectionectomy, limited resection
Liver (resected) 5 mo
AWD 66 mo
Liver (resected) None Liver (resected) Liver (resected) Lung 5 mo Liver (resected) None None
NED 61 mo NED 89 mo DWD 4 mo NED 42 mo DWD 26 mo NED 82 mo NED 34 mo NED 34 mo
4 mo 1 mo 14 mo 2 mo
Lymph node 2 mo Lung (resected) 7 mo Liver 3 mo Liver (resected) 2 mo
AWD 24 mo NED 41 mo AWD 25 mo DWD 17 mo
Bone 7 mo Liver 3 mo
AWD 14 mo AWD 15 mo
Lung (resected) 3 mo
AWD 19 mo
CLM ⫽ colorectal liver metastases; L ⫽ left hepatic vein; M ⫽ middle hepatic vein; R ⫽ right hepatic vein; IVC ⫽ inferior vena cava; AWD ⫽ alive with disease; NED ⫽ no evidence of disease; DWD ⫽ dead with disease.
A. Saiura et al.
Hepatic vein reconstruction for liver tumors
(range, 14 – 89 mo), respectively. Cumulative 5-year recurrence-free survival was 36% with a median survival of 5 months (95% confidence interval, 1–7 mo). Thirteen patients developed recurrence, with the site of first recurrence being liver (n ⫽ 8), lung (n ⫽ 3), lymph nodes (n ⫽ 1), or bone (n ⫽ 1). Repeat resection was performed in 8 patients (liver, 6; lung, 2). Three patients died of disease. Seven patients were alive with no evidence of disease and 4 were alive with disease.
Graft patency No anticoagulant therapy was administered postoperatively. Patency of the graft was assessed by contrast computed tomography scan every 6 months. Late patency could be assessed in 15 patients (the remaining patient experienced an early death). Patency was confirmed in all patients, but 1 patient with a customized saphenous vein graft developed graft thrombosis at 6 months associated with locoregional recurrence; this had no influence on liver function.
Comments We report herein 16 cases of liver resection combined with resection and reconstruction of the HV in patients with colorectal liver metastases. Perioperative zero mortality with one major complication indicated the safety of this procedure. This study suggested new resectability criteria for colorectal liver metastases in a modern era of liver surgery. The aims of HV resection in hepatic malignancies are removal of the tumor with adequate clear margins and maintenance of liver function in the drainage area by avoiding congestion. HV resection can achieve these aims reliably and safely, in addition to expanding the indication for curative resection. The defined width of clear surgical margins remains controversial for hepatic malignancies, although not its importance.21 To obtain negative margins, combined resection of the HV adjacent to the tumor should be attempted even if the tumor does not infiltrate the vein pathologically, providing the surgery can be performed safely. In this series, 9 of 16 patients had 4 or more tumors (range 4–18), and 13 patients developed early recurrence (median, 5 mo). This large number of patients with multiple nodules was associated with the short recurrence-free survival. However, we have experienced no local recurrence and 9 patients underwent curative repeat resection. Involvement of all 3 major HVs without the thick IHRV is generally thought to be contraindicative of hepatic resection,5 although several reports cite all 3 HVs being resected successfully. However, the impact of such a procedure on long-term survival is largely unknown.6,10 In our series, 5 of 16 patients underwent resection of the 3 major HVs, with 5-year overall and recurrence-free survival rates of 66% and 23%, respectively. The results indicated that HV resection
453 in patients with tumors involving all 3 major HVs could expand the indication of curative resection and contribute to long-term survival. This series also encompassed minor hepatectomy with combined resection of involved HVs and reconstruction instead of major hepatectomy, with no postoperative liver failure. We reported on 5 cases in which a single HV reconstruction was performed rather than a major hepatectomy. Fortunately, 4 of the patients are alive without disease 33, 34, 82, and 87 months, respectively, after hepatectomy. This is consistent with the previous study showing that patients subjected to minor hepatectomy had an equivalent long-term outcome to patients treated by major hepatectomy for colorectal liver metastases. Major hepatectomy with or without portal vein embolization was a treatment of choice in these patients. Covey et al22 reported the safety and efficacy of combined portal vein embolization and neoadjuvant chemotherapy. However, major hepatectomy is still more hazardous than minor hepatectomy. Gold et all reported that approaches that spare parenchyma were associated with improved mortality rates without changes in oncologic outcome. Although the present study had some limitations because of the small number of patients, we consider that HVR could minimize the surgical risk by maximizing residual liver function. The efficacy of minor hepatectomy to avoid major hepatectomy should be clarified in a prospective randomized study. None of the cases underwent total hepatic vascular exclusion, and only 1 case with double HV resection underwent a temporal bypass between the MHV and inferior vena cava. A single venous anastomosis takes approximately 10 minutes, therefore most HV resections do not require temporal portosystemic bypass. In a recent report, an extended Pringle maneuver of 30 minutes did not ameliorate the outcome.23 HV resection can be performed under an extended Pringle maneuver of 20 to 30 minutes. Therefore, most HV resections also can be performed without total vasucular exclusion. In this series, 1 patient who underwent preoperative systemic chemotherapy with FOLFOX developed major complications of intractable ascites, probably associated with liver impairment because the maximum serum total bilirubin level reached 4.7 mg/dL. In this era of modern chemotherapy, the proportion of patients with preoperative systemic chemotherapy has increased rapidly, and a recent study associated modern systemic chemotherapy with postoperative liver failure.24 –26 Therefore, more functional residual liver volume should be spared in patients with preoperative systemic chemotherapy. HVR with minor hepatectomy is a promising treatment of choice for sparing liver volume and avoiding major hepatectomy. Many reports discuss vein graft selection for the procedures described.10,19,20 In our series, artificial grafts were avoided because of the requirement for concomitant anticoagulant therapy over a long period and the increased possibility of serious postoperative infection.10 Autogenous vein
454 grafts also have some limitations. External iliac vein grafts are most suitable for reconstructing the major HV because of its length and caliber; however, grafting the external iliac vein requires an extensive surgical area and causes edema of the extremities on the same side. Renal vein grafts are easy to use and of adequate caliber, but are limited in length. The customized saphenous vein graft is about 3 cm in length and 8F in caliber, which is sufficient for interposing the major HV. Grafting the great saphenous vein of 12 cm in length takes 20 to 30 minutes. Time could be saved by performing the customized procedure after the grafting on a separate area table, in parallel with the surgery. Customized saphenous vein grafts are therefore the preferred option for segmental HV interposition.
The American Journal of Surgery, Vol 202, No 4, October 2011
7. 8.
9. 10. 11.
12.
13.
Conclusions HV resection can achieve tumor-free margins while maintaining adequate functional liver volume in patients with tumor involving the HV. Consequently, HV resection could be performed safely, confer favorable long-term outcomes, and expand the indications for curative resection of hepatic malignancies. Various autografts, especially customized saphenous vein grafts, are suitable for the vein reconstruction.
14.
15.
16.
17.
Acknowledgments
18.
This study was supported by Grants-in-Aid for basic research from the Ministry of Health and Welfare of Japan (A.S.).
19.
References
21.
1. Belghiti J, Hiramatsu K, Benoist S, et al. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection. J Am Coll Surg 2000;191:38 – 46. 2. Fong Y, Fortner J, Sun RL, et al. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 1999;230:309 –21. 3. Minagawa M, Makuuchi M, Torzilli G, et al. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results. Ann Surg 2000;231:487–99. 4. Aloia TA, Vauthey JN, Loyer EM, et al. Solitary colorectal liver metastasis: resection determines outcome. Arch Surg 2006;141:460 –7. 5. Alberts SR, Horvath WL, Sternfeld WC, et al. Oxaliplatin, fluorouracil, and leucovorin for patients with unresectable liver-only metastases from colorectal cancer: a North Central Cancer Treatment Group phase II study. J Clin Oncol 2005;23:9243–9. 6. Aoki T, Sugawara Y, Imamura H, et al. Hepatic resection with reconstruction of the inferior vena cava or hepatic venous confluence for
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metastatic liver tumor from colorectal cancer. J Am Coll Surg 2004;198:366 –72. Takayama T, Nakatsuka T, Yamamoto J, et al. Re-reconstruction of a single remnant hepatic vein. Br J Surg 1996;83:762–3. Sakamoto Y, Yamamoto J, Kosuge T, et al. Extended left hepatectomy by severing all major hepatic veins with reconstruction of the right hepatic vein. Surg Today 2004;34:482– 4. Nakamura S, Sakaguchi S, Hachiya T, et al. Significance of hepatic vein reconstruction in hepatectomy. Surgery 1993;114:59 – 64. Hemming AW, Reed AI, Langham MR, et al. Hepatic vein reconstruction for resection of hepatic tumors. Ann Surg 2002;235:850 – 8. Yamamoto J, Sugihara K, Kosuge T, et al. Pathologic support for limited hepatectomy in the treatment of liver metastases from colorectal cancer. Ann Surg 1995;221:74 – 8. Kokudo N, Tada K, Seki M, et al. Anatomical major resection versus nonanatomical limited resection for liver metastases from colorectal carcinoma. Am J Surg 2001;181:153–9. Finch RJ, Malik HZ, Hamady ZZ, et al. Effect of type of resection on outcome of hepatic resection for colorectal metastases. Br J Surg 2007;94:1242– 8. Gold JS, Are C, Kornprat P, et al. Increased use of parenchymalsparing surgery for bilateral liver metastases from colorectal cancer is associated with improved mortality without change in oncologic outcome: trends in treatment over time in 440 patients. Ann Surg 2008; 247:109 –17. Saiura A, Yamamoto J, Koga R, et al. Usefulness of LigaSure for liver resection: analysis by randomized clinical trial. Am J Surg 2006;192: 41–5. Sano K, Makuuchi M, Miki K, et al. Evaluation of hepatic venous congestion: proposed indication criteria for hepatic vein reconstruction. Ann Surg 2002;236:241–7. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg 2004;240:205–13. Sakamoto Y, Yamamoto J, Saiura A, et al. Reconstruction of hepatic or portal veins by use of newly customized great saphenous vein grafts. Langenbecks Arch Surg 2004;389:110 –3. Kubota K, Makuuchi M, Sugawara Y, et al. Reconstruction of the hepatic and portal veins using a patch graft from the right ovarian vein. Am J Surg 1998;176:295–7. Miyazaki M, Ito H, Kimura F, et al. Hepatic vein reconstruction using autologous vein graft for resection of advanced hepatobiliary malignancy. Hepatogastroenterology 2004;51:1581–5. Pawlik TM, Scoggins CR, Zorzi D, et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg 2005;241:715–22, discussion: 722– 4. Covey AM, Brown KT, Jarnagin WR, et al. Combined portal vein embolization and neoadjuvant chemotherapy as a treatment strategy for resectable hepatic colorectal metastases. Ann Surg 2008;247: 451–5. Esaki M, Sano T, Shimada K, et al. Randomized clinical trial of hepatectomy using intermittent pedicle occlusion with ischaemic intervals of 15 versus 30 minutes. Br J Surg 2006;93:944 –51. Zorzi D, Laurent A, Pawlik TM, et al. Chemotherapy-associated hepatotoxicity and surgery for colorectal liver metastases. Br J Surg 2007;94:274 – 86. Rubbia-Brandt L, Audard V, Sartoretti P, et al. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol 2004;15:460 – 6. Vauthey JN, Pawlik TM, Ribero D, et al. Chemotherapy regimen predicts steatohepatitis and an increase in 90-day mortality after surgery for hepatic colorectal metastases. J Clin Oncol 2006;24:2065–72.
Clinical Science
Safety and efficacy of hepatic vein reconstruction for colorectal liver metastases Akio Saiura, M.D.a,*, Junji Yamamoto, M.D.b, Yoshihiro Sakamoto, M.D.c, Rintaro Koga, M.D.a, Makoto Seki, M.D.a, Yoji Kishi, M.D.a a
Department of Gastroenterological Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Ariake Hospital, 3-10-6 Ariake, Koto-ku, Tokyo 135-8500, Japan; bDepartment of Surgery, National Defense Medical College, Tokorozawa, Saitama, Japan; cHepatobiliary and Pancreatic Surgery Division, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan KEYWORDS: Hepatic vein reconstruction; Liver resection; Colorectal liver metastases
Abstract BACKGROUND: Colorectal liver metastases with hepatic vein (HV) involvement may require combined resection of the liver and HV. However, the short- and long-term outcomes of such a procedure remain unclear. METHODS: We reviewed 16 cases of liver resection with major HV resection and reconstruction. RESULTS: The patients had a median age of 58.5 years (range, 50 –74 y). In total, 18 HVs were reconstructed using a customized great saphenous vein graft (n ⫽ 10), direct anastomosis (n ⫽ 1), external iliac vein (n ⫽ 2), portal vein (n ⫽ 1), umbilical vein patch graft (n ⫽ 3), or ovarian vein patch graft (n ⫽ 1). There was no hospital mortality, and the morbidity rate was 50%. With a median follow-up period of 30 months (range, 4 – 89 mo), 3 patients died of tumor recurrence and 13 were alive with (n ⫽ 6) and without (n ⫽ 7) disease. Cumulative 1-, 3-, and 5-year survival rates were 93%, 76%, and 76%, respectively. CONCLUSIONS: HV resection and reconstruction combined with liver resection can be performed safely with reasonable long-term results. © 2011 Elsevier Inc. All rights reserved.
Liver resection remains the only potentially curative treatment for patients with colorectal liver metastases, despite improvements in local and systemic chemotherapies.1– 4 Hepatic vein (HV) resection is necessary in patients with hepatic tumors involving the HV to secure clear surgical margins. In the past decade, the indication of liver resection in patients with colorectal liver metastases has extended dra* Corresponding author. Tel.: ⫹81-3-3520-0111; fax: ⫹81-3-35700343. E-mail address: [email protected] Manuscript received April 6, 2010; revised manuscript August 11, 2010
0002-9610/$ - see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.amjsurg.2010.08.040
matically, both oncologically as a result of modern chemotherapy and technically as a result of recent improvements in surgical technique. The mortality rates for patients undergoing procedures in high-volume centers have decreased to 0% to 4%.2,3 However, involvement of all 3 major HVs in liver tumors is a remaining contraindication for liver resection in patients with colorectal liver metastases.5 In patients with tumors adjacent to the HV or involving the HV, combined resection of the HV and liver is required to achieve complete resection of the tumor with clear margins. HV resection also is mandatory if functional liver volume is insufficient. The procedure has been performed successfully only in a few reported cases.6 –9 Hemming et al10 reported an increased risk associated with HV reconstruction. Con-
450
The American Journal of Surgery, Vol 202, No 4, October 2011
comitant HV resection can expand the indication for curative resection of colorectal liver metastases; however, the technical feasibility of HV reconstruction remains unknown, as does the possible short- and long-term outcomes of the procedure.6 In contrast to hepatocellular carcinoma, anatomic liver resection is not necessary for colorectal liver metastasis.11,12 Instead, nonanatomic liver resection is recommended to reduce morbidity and mortality without compromising the oncologic outcome.13,14 Here, we report a case series of concomitant liver resection with HV resection and reconstruction in 16 patients with colorectal liver metastases using various autologous vein grafts. The study evaluated the technical and oncologic feasibility of HV reconstruction.
Patients From January 2001 to September 2008, 391 liver resections were performed at our institution. Of these, 16 (4.1%) patients underwent liver resection combined with HV resection and reconstruction, totaling 18 HV reconstructions (single, 14; double, 2), consisting of 14 segmental HV resections and 4 wedge HV resections with patch repair (Table 1). Cases of wedge resection with direct closure were excluded from this study. The study participants comprised 8 women (50%) and 8 men (50%), with a mean age of 60.4 years (range, 50 –74 y; median, 58.5 y). The underlying liver parenchyma was histologically normal in 13 cases, steatohepatitic in 2 cases, and fibrotic in 1 case.
Preoperative management All patients were assessed preoperatively using enhanced computed tomography, with the following selection criteria applied for surgery: (1) no comorbid condition precluded a major hepatic resection; (2) all tumoral liver disease was amenable to resection, while leaving at least 30% of the nontumoral liver with the exception of potentially ischemic or congested areas; and (3) no unresectable extrahepatic tumor. The median preoperative indocyanine green retention rate at 15 minutes was 7.1% (range, 2.1%–32%; normal,
Table 1
Patient and tumor variables (n ⫽ 18)
Variable
Median (range) or no.
Age, y Male sex No. tumors Solitary 2–4 ⬎5 Size of largest tumor, cm Previous liver resection
58.5 (50–74) 8 6 4 6 3.8 (1.5–8) 3
⬍10%). Eight patients (44%) received systemic chemotherapy before surgery (oxaliplatin, 5-fluorouracil and leucovorin [FOLFOX4] regimen, 2; 5-fluorouracil/leukovorin or tegaful, gimeracil, and oteracil (TS)-1, 6). One patient underwent hepatic arterial infusion therapy.
Surgical procedure The surgical techniques used for liver resection in our institution have been described elsewhere.15 After a laparotomy by inverted L-shaped incision, the whole liver was examined by intraoperative ultrasonography. After mobilizing the liver, transection was performed using a clamp-crushing technique with LigaSure (LigaSureTM vessel sealing system, Covidien, USA). An intermittent Pringle maneuver with periods of 15 minutes of clamping and 5 minutes of unclamping was used routinely. The congestion area was checked before HV resection, as described previously.16 The surgical margins were submitted for frozen sectioning to confirm negative margin status intraoperatively.
Definition of morbidity and mortality Surgical mortality included all in-hospital deaths. Hepatic failure was defined by a serum total bilirubin concentration of greater than 5.0 mg/dL during the postoperative period. Bile leakage was diagnosed when the bilirubin concentration of the drainage fluid was greater than 5.0 mg/dL after 5 or more postoperative days. Grade of complication was defined according to the system of Dindo et al,17 with major complications defined as grade 3 or more. The postoperative course was divided into 3 categories: no morbidity, minor complications only, and major complications.
Results All 16 patients in this series underwent potentially curative resection, as summarized in Table 2. R0 resections were achieved in 14 of the 16 patients. Three patients (18%) had synchronous resection of the primary site: colon cancer (2 cases), and rectal cancer (1 case). Two patients had combined wedge resection of the inferior vena cava, which was directly closed.
Indication of HV reconstruction The indication of HV reconstruction (HVR) includes absolute and relative indications. The absolute indication is a mandatory HVR owing to insufficient future remnant liver volume. There are 2 indications in this group: (1) involving all HV trunks without thick inferior right hepatic vein (IRHV), (2) involving double HV trunks in patients with multiple bilobar metastases and not indicated for portal vein embolization followed by extended hemihepatectomy. The
A. Saiura et al. Table 2
Hepatic vein reconstruction for liver tumors
Procedures of 18 HVRs in 16 hepatectomies n or median (range)
Variable
Hepatic resection Major hepatectomy 5 Minor hepatectomy 11 Associated procedure Hemicolectomy 2 Low anterior resection 1 No. major hepatic veins involved 1 5 2 7 3 4 No. major hepatic veins reconstructed 1 14 2 2 Type of reconstruction and graft (n ⫽ 20) Segmental Customized saphenous graft 10 External iliac graft 2 Direct 1 Portal vein 1 Patch Umbilical vein 3 Ovarian vein 1 Blood loss, mL 1030 (285–2200) Transfusion required 5 Duration of surgery, min 547 (303–935)
relative indication is an optional HVR to avoid major hepatectomy, which spares most of the parenchyma. Patients with HV trunk involvement without involvement of the major portal pedicle are included in this group. According to these criteria, hepatic reconstruction was mandatory in 9 patients (56%). Of these, all HVs were involved in 5 patients, with 1 patient undergoing a second hepatectomy after a previous right hemihepatectomy (cases 2, 4, 10, 11, and
Table 3
451
Figure 1 Intraoperative photograph after reconstruction of the right hepatic vein using a customized saphenous vein graft. CSV ⫽ customized saphenous vein graft; IVC ⫽ inferior vena cava; RHV ⫽ right hepatic vein.
15). In the remaining 4 patients with double HV involvement, mandatory HVR was chosen because portal vein embolization followed by right hemihepatectomy was not indicated because partial resection of the left liver with critical volume was required to remove multiple bilobar metastases (cases 1, 6, 12, and 16).
HV resection with or without autologous vein graft The 18 HVRs used various autografts (Table 3). Ten of the 18 were performed using a customized saphenous vein graft (Fig. 1), as described elsewhere.18 Briefly, the great saphenous vein is excised in a 12-cm length when segmen-
Type of 18 HVRs in 16 patients
Case no.
Involved HV
Type of HV resection
Reconstructed HV (graft)
Indication
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
M, R L, M* M L, M, R R M, R R M M, R L, M, R L, M, R M, R L, M R L, M, R L, R
Segment Segment Segment Segment Wedge Segment Wedge Segment Segment Segment (L) and wedge (R) Segment Segment Segment Wedge Segment (L) and Segment (M) Segment
R (CSV) L (CSV) M (CSV) R (CSV) R (round ligament) M (CSV) R (gonadal vein) M (CSV) R (direct) R (round ligament), L (CSV) R (CSV) M (external iliac vein) M (left portal vein) R (round ligament) R (CSV), M (external iliac vein) R (CSV)
Mandatory Mandatory Not mandatory Mandatory Not mandatory Mandatory Not mandatory Not mandatory Not mandatory Mandatory Mandatory Mandatory Not mandatory Not mandatory Mandatory Mandatory
L ⫽ left hepatic vein; M ⫽ middle hepatic vein; R ⫽ right hepatic vein; CSV ⫽ customized saphenous vein. *The right hepatic vein was resected in the primary hepatectomy.
452 Table 4
The American Journal of Surgery, Vol 202, No 4, October 2011
Postoperative courses
Postoperative data
Variable
Median (range) or n
Postoperative length of stay, d Maximum serum total bilirubin, mg/dL Morbidity Major Minor Mortality
16 (8–44) 1.3 (.7–4.7) 8 (50%) 1 7 0
tal combined HV resection and reconstruction is scheduled after intraoperative ultrasonography. The resected veins were cut longitudinally and divided into 3 pieces, which were stitched together to make a cylindric graft. One HV was reconstructed directly and 1 HV was reconstructed using portal vein excised from the resected liver. In patients undergoing sleeve resection of the HV, we performed patch closure using an umbilical vein (n ⫽ 3) and ovarian vein (n ⫽ 1) as reported previously.19,20 In the 2 cases of unscheduled reconstruction or double reconstruction, the right external iliac vein was excised. No total vascular exclusion was used in this series. All but 1 venous reconstruction was performed using the Pringle maneuver. One patient undergoing a double HV reconstruction required a temporary venous shunt between the middle hepatic vein (MHV) and inferior vena cava using an AnthronR bypass tube (TORAY, Japan).7
Table 5
Case no.
Table 4 summarizes the postoperative courses. The mortality rate was 0% and the morbidity rate was 50%. The median level of postoperative maximum aspartate aminotransferase and alanine aminotransferase were 612 U/L (range, 194 –1,538 U/L) and 781 U/L (range, 177–1,726 U/L), respectively. Minor complications comprised pleural effusion (n ⫽ 2), ileus (n ⫽ 2), wound infection (n ⫽ 2), and edema of extremities (n ⫽ 1). The only major complication occurred in 1 patient who had received preoperative systemic chemotherapy with FOLFOX4; this case developed intractable ascites necessitating a prolonged hospital stay (case 13). Pathologic testing of the background liver tissue showed sinusoidal dilatation and nodular regenerative hyperplasia. There were no cases of postoperative liver failure and no complications relating to the saphenous vein grafting. Adjuvant chemotherapy was administered to 3 patients (tegaful and uracil [UFT]/leukovorin, 2; FOLFOX4, 1).
Survival and recurrence Table 5 details the patient outcomes. The median follow-up period was 30.0 months (range, 4 – 89 mo). Kaplan– Meier curves for overall survival estimated 1-, 3-, and 5-year survival rates of 93%, 76%, and 76%, respectively, with a median follow-up period for survivors of 41 months
Outcome of 16 patients undergoing liver resection combined with HVRs
Disease
Lesions, n
Maximum diameter of lesions, cm
1
CLM
13
6
2 3 4 5 6 7 8 9
CLM CLM CLM CLM CLM CLM CLM CLM
1 2 13 4 2 8 1 1
4.5 2.7 8 1.9 3.5 2.9 1.5 3.8
10 11 12 13
CLM CLM CLM CLM
7 7 18 1
4 6.2 3.5 3.8
14 15
CLM CLM
4 1
2.2 5.5
16
CLM
8
3.5
Procedure
Recurrence
Outcomes
Limited resection, S3 segmentectomy, low anterior resection Limited resection Limited resection Extended left hemihepatectomy Limited resection Limited resection Limited resection Limited resection Limited resection, colectomy, partial resection of IVC Limited resection Extended left hemihepatectomy Extended right hemihepatectomy Extended left hemihepatectomy, partial resection of IVC Limited resection Extended left hemihepatectomy, right hemicolectomy Left lateral sectionectomy, limited resection
Liver (resected) 5 mo
AWD 66 mo
Liver (resected) None Liver (resected) Liver (resected) Lung 5 mo Liver (resected) None None
NED 61 mo NED 89 mo DWD 4 mo NED 42 mo DWD 26 mo NED 82 mo NED 34 mo NED 34 mo
4 mo 1 mo 14 mo 2 mo
Lymph node 2 mo Lung (resected) 7 mo Liver 3 mo Liver (resected) 2 mo
AWD 24 mo NED 41 mo AWD 25 mo DWD 17 mo
Bone 7 mo Liver 3 mo
AWD 14 mo AWD 15 mo
Lung (resected) 3 mo
AWD 19 mo
CLM ⫽ colorectal liver metastases; L ⫽ left hepatic vein; M ⫽ middle hepatic vein; R ⫽ right hepatic vein; IVC ⫽ inferior vena cava; AWD ⫽ alive with disease; NED ⫽ no evidence of disease; DWD ⫽ dead with disease.
A. Saiura et al.
Hepatic vein reconstruction for liver tumors
(range, 14 – 89 mo), respectively. Cumulative 5-year recurrence-free survival was 36% with a median survival of 5 months (95% confidence interval, 1–7 mo). Thirteen patients developed recurrence, with the site of first recurrence being liver (n ⫽ 8), lung (n ⫽ 3), lymph nodes (n ⫽ 1), or bone (n ⫽ 1). Repeat resection was performed in 8 patients (liver, 6; lung, 2). Three patients died of disease. Seven patients were alive with no evidence of disease and 4 were alive with disease.
Graft patency No anticoagulant therapy was administered postoperatively. Patency of the graft was assessed by contrast computed tomography scan every 6 months. Late patency could be assessed in 15 patients (the remaining patient experienced an early death). Patency was confirmed in all patients, but 1 patient with a customized saphenous vein graft developed graft thrombosis at 6 months associated with locoregional recurrence; this had no influence on liver function.
Comments We report herein 16 cases of liver resection combined with resection and reconstruction of the HV in patients with colorectal liver metastases. Perioperative zero mortality with one major complication indicated the safety of this procedure. This study suggested new resectability criteria for colorectal liver metastases in a modern era of liver surgery. The aims of HV resection in hepatic malignancies are removal of the tumor with adequate clear margins and maintenance of liver function in the drainage area by avoiding congestion. HV resection can achieve these aims reliably and safely, in addition to expanding the indication for curative resection. The defined width of clear surgical margins remains controversial for hepatic malignancies, although not its importance.21 To obtain negative margins, combined resection of the HV adjacent to the tumor should be attempted even if the tumor does not infiltrate the vein pathologically, providing the surgery can be performed safely. In this series, 9 of 16 patients had 4 or more tumors (range 4–18), and 13 patients developed early recurrence (median, 5 mo). This large number of patients with multiple nodules was associated with the short recurrence-free survival. However, we have experienced no local recurrence and 9 patients underwent curative repeat resection. Involvement of all 3 major HVs without the thick IHRV is generally thought to be contraindicative of hepatic resection,5 although several reports cite all 3 HVs being resected successfully. However, the impact of such a procedure on long-term survival is largely unknown.6,10 In our series, 5 of 16 patients underwent resection of the 3 major HVs, with 5-year overall and recurrence-free survival rates of 66% and 23%, respectively. The results indicated that HV resection
453 in patients with tumors involving all 3 major HVs could expand the indication of curative resection and contribute to long-term survival. This series also encompassed minor hepatectomy with combined resection of involved HVs and reconstruction instead of major hepatectomy, with no postoperative liver failure. We reported on 5 cases in which a single HV reconstruction was performed rather than a major hepatectomy. Fortunately, 4 of the patients are alive without disease 33, 34, 82, and 87 months, respectively, after hepatectomy. This is consistent with the previous study showing that patients subjected to minor hepatectomy had an equivalent long-term outcome to patients treated by major hepatectomy for colorectal liver metastases. Major hepatectomy with or without portal vein embolization was a treatment of choice in these patients. Covey et al22 reported the safety and efficacy of combined portal vein embolization and neoadjuvant chemotherapy. However, major hepatectomy is still more hazardous than minor hepatectomy. Gold et all reported that approaches that spare parenchyma were associated with improved mortality rates without changes in oncologic outcome. Although the present study had some limitations because of the small number of patients, we consider that HVR could minimize the surgical risk by maximizing residual liver function. The efficacy of minor hepatectomy to avoid major hepatectomy should be clarified in a prospective randomized study. None of the cases underwent total hepatic vascular exclusion, and only 1 case with double HV resection underwent a temporal bypass between the MHV and inferior vena cava. A single venous anastomosis takes approximately 10 minutes, therefore most HV resections do not require temporal portosystemic bypass. In a recent report, an extended Pringle maneuver of 30 minutes did not ameliorate the outcome.23 HV resection can be performed under an extended Pringle maneuver of 20 to 30 minutes. Therefore, most HV resections also can be performed without total vasucular exclusion. In this series, 1 patient who underwent preoperative systemic chemotherapy with FOLFOX developed major complications of intractable ascites, probably associated with liver impairment because the maximum serum total bilirubin level reached 4.7 mg/dL. In this era of modern chemotherapy, the proportion of patients with preoperative systemic chemotherapy has increased rapidly, and a recent study associated modern systemic chemotherapy with postoperative liver failure.24 –26 Therefore, more functional residual liver volume should be spared in patients with preoperative systemic chemotherapy. HVR with minor hepatectomy is a promising treatment of choice for sparing liver volume and avoiding major hepatectomy. Many reports discuss vein graft selection for the procedures described.10,19,20 In our series, artificial grafts were avoided because of the requirement for concomitant anticoagulant therapy over a long period and the increased possibility of serious postoperative infection.10 Autogenous vein
454 grafts also have some limitations. External iliac vein grafts are most suitable for reconstructing the major HV because of its length and caliber; however, grafting the external iliac vein requires an extensive surgical area and causes edema of the extremities on the same side. Renal vein grafts are easy to use and of adequate caliber, but are limited in length. The customized saphenous vein graft is about 3 cm in length and 8F in caliber, which is sufficient for interposing the major HV. Grafting the great saphenous vein of 12 cm in length takes 20 to 30 minutes. Time could be saved by performing the customized procedure after the grafting on a separate area table, in parallel with the surgery. Customized saphenous vein grafts are therefore the preferred option for segmental HV interposition.
The American Journal of Surgery, Vol 202, No 4, October 2011
7. 8.
9. 10. 11.
12.
13.
Conclusions HV resection can achieve tumor-free margins while maintaining adequate functional liver volume in patients with tumor involving the HV. Consequently, HV resection could be performed safely, confer favorable long-term outcomes, and expand the indications for curative resection of hepatic malignancies. Various autografts, especially customized saphenous vein grafts, are suitable for the vein reconstruction.
14.
15.
16.
17.
Acknowledgments
18.
This study was supported by Grants-in-Aid for basic research from the Ministry of Health and Welfare of Japan (A.S.).
19.
References
21.
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