to resect tumors involving all three hepatic veins.3 Bothauthors use portal vein embolization extensively andhave not described abnormal growth of tumors in thenonembolized liver segments during the waiting time ofliver regeneration.

Liver metastases are supplied mainly by the hepaticartery, whereas normal liver is primarily perfused by theportal vein.4,5 After portal vein embolization, arterialflow in the embolized hemiliver increases significantly,6

resulting in a potential risk for increased tumor progres-sion in the ligated liver segments. Remarkably, becausesmall liver metastases are primarily vascularized by theportal vein,7,8 and left portal flow increases markedlyafter right portal vein ligation or embolization,6 no in-trahepatic recurrences in the left liver are reported in thisseries.1 This may be an indirect sign that surgery in thiscohort was indeed radical, and no microscopic meta-static foci were present in the left lobe.

Some concerns may be raised about pharmacokineticsof oral capecitabine in these patients. This drug passesrapidly and extensively through the intestinal membraneas an intact molecule,9 and it is then activated in tumortissue.10 Ligation of the portal vein of the hemiliver har-boring the residual metastases might impair its clinicalefficacy if administered as adjuvant treatment after theprimary procedure in these patients.

Though promising, this new technique might needfurther studies in animal models to investigate the kinet-ics of liver tumor growth after portal vein ligation andembolization before being routinely applied in humans.

REFERENCES

1. Kianmanesh R, Farges O, Abdalla EK, et al. Right portal veinligation: a new planned two-step all-surgical approach for com-plete resection of primary gastrointestinal tumors with multiplebilateral liver metastases. J Am Coll Surg 2003;197:164–170.

2. Minagawa M, Makuuchi M, Torzilli G, et al. Extension of thefrontiers of surgical indications in the treatment of liver metas-tases from colorectal cancer: long-term results. Ann Surg 2000;231:487–499.

3. Nagino M, Yamada T, Kamiya J, et al. Left hepatic trisegmen-tectomy with right hepatic vein resection after right hepatic veinembolization. Surgery 2003;133:580–582.

4. Breedis C, Young C. The blood supply of neoplasms in the liver.Am J Pathol 1954;30:969.

5. Kemeny N, Fata F. Arterial, portal, or systemic chemotherapyfor patients with hepatic metastasis of colorectal carcinoma.J Hepatobiliary Pancreat Surg 1999;6:39–49.

6. Kito Y, Nagino M, Nimura Y. Doppler sonography of hepaticarterial blood flow velocity after percutaneous transhepatic por-

tal vein embolization. AJR Am J Roentgenol 2001;176:909–912.

7. Ackermann NB. The blood supply of experimental liver metas-tasis. IV. Changes in vascularity with increasing tumor growth.Surgery 1974;2:589–597.

8. Bassermann R. Changes of vascular pattern of tumors and sur-rounding tissue during different phases of metastatic growth.Cancer Res 1986;100:256–264.

9. Schuller J, Cassidy J, Dumont E, et al. Preferential activation ofcapecitabine in tumor following oral administration to colorec-tal cancer patients. Cancer Chemother Pharmacol 2000;45:291–297.

10. Miwa M, Ura M, Nishida M, et al. Design of a novel oralfluoropyrimidine carbamate, capecitabine, which generates5-fluorouracil selectively in tumors by enzyme concentrated inhuman liver and cancer tissue. Eur J Cancer 1998;34:1274–1281.

Reply

Reza Kianmanesh, MD

Jacques Belghiti, MD

Clichy, France

We thank Dr Papadia for his comments concerning ourdescribed two-step all-surgical technique, which is a newstrategy for achievement of “macroscopic cure” in pa-tients with primary intact gross gastrointestinal tumorsand diffuse bilobar liver metastases.

Concerning the definition of “unresectable” liver me-tastases, we consider as “unresectable” in whom all of theliver metastases cannot be removed at one-step surgeryand those who require extensive complex resections, notleaving behind sufficient functional liver parenchymawith adequate inflow and outflow pedicles. As is men-tioned in our article, this is a rare situation, and thestudied population represented less than 10% of thewhole population of liver resection for gastrointestinalmetastases (both from neuroendocrine or colorectal or-igin) in our center.

Dr Papadia is concerned about the eventual growth oftumors in both left and right liver after portal ligation.This concern led us to remove all detected left liver me-tastases (including those in segments 1 and 4). This ispart of the concept of bringing to hypertrophy a“cleared” left liver after right portal vein ligation. Addi-tionally, to avoid right liver tumor growth (and possiblyleft liver micrometastases), we routinely propose sys-temic chemotherapy after the first step, especially if the

332 Letters to the Editor J Am Coll Surg

period before the planned second step (right or extendedright hepatectomy) is estimated to be longer than 6 to 8weeks. As mentioned in the discussion section of ourarticle, more and more patients receive preoperative che-motherapy and might have an injured liver parenchyma.

The risk of major liver resection in these patients justifiesdiffering major complex liver resections and gastrointes-tinal surgery and performing portal vein ligation to in-crease tolerance and safety of the major liver resectionplanned at the second step.

333Vol. 198, No. 2, February 2004 Letters to the Editor