Liver resection and needle liver biopsy cause hematogenous dissemination of liver cells

Abstract

We have investigated whether liver resection and needle liver biopsy cause dissemination of liver cells into peripheral blood circulation, using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay targeted against ␣-fetoprotein (AFP) mRNA. Twelve patients with and 16 without primary liver cancer (PLC) undergoing liver resection were tested before skin incision, after liver mobilization, after hepatic parenchyma transection, after abdominal wall suture, and 4 days after surgery. Two patients with and 20 without PLC were tested before, 20 minutes after, and 24 hours after needle liver biopsy. Six of 14 patients with and 0 of 36 patients without PLC scored positive before intervention (P F .001). Liver cell spreading was induced at different times after surgery and liver biopsy in 14 of 14 patients with but also 23 of 36 without PLC (P F .05). We conclude that liver resection and needle liver biopsy induce release of cells from the liver, which are not necessarily liver tumor cells, into the peripheral blood circulation. This may be, however, an important mechanism of liver cancer cell dissemination deserving further investigations. (HEPATOL-OGY 1999;29:879-882.)Despite several previous reports on the dissemination of tumorous cells during needle liver biopsy, 1-6 the issue of surgical and diagnostic iatrogenic speading of liver cells has never been addressed with appropriated molecular methods and study design.The possibility of detecting circulating tumorous cells in patients with solid tumors, through highly sensitive reversetranscription polymerase chain reaction (RT-PCR)-based assays, has raised major interest and hopes during the last 5 years. 7 We and others 8,9 have used ␣-fetoprotein (AFP)-specific primers to detect spontaneously circulating tumorous cells in patients with primary liver cancer (PLC) and found that a positive test directly correlates with the risk of developing extrahepatic metastases. 10 We have now applied this method, with a carefully defined specificity and sensitivity, to patients with and without PLC. The protocol used consisted in blood sampling before and at different time points during and after liver resection and needle liver biopsy.Our results show that hematogenous dissemination of liver cells is induced very early in surgically treated patients, after liver mobilization, and before hepatic parenchyma transection. It also occurs, albeit less frequently, during needle liver biopsy. These data, therefore, point out a potentially important mechanism of liver cancer spreading that deserves further investigations.

Fate and characterization of circulating tumor cells in a NOD/SCID mouse model of human hepatocellular carcinoma

“…However, tumors recur in 20% of them within 2 years (Bismuth et al, 1993;Majno et al, 1997;Poon et al, 2002). HCC tumor cells can infiltrate the BM and the blood system, as shown by the presence of alpha-fetoprotein (AFP) messenger RNA (mRNA) (Matsumura et al, 1994;Lemoine et al, 1997;Louha et al, 1999;Kienle et al, 2000;Gross-Goupil et al, 2003). The number of circulating tumor cells has been related to tumor size (Matsumura et al, 1994;Lemoine et al, 1997;Minata et al, 2001;Gross-Goupil et al, 2003) and to the risk of recurrence (Minata et al, 2001;Qin and Tang, 2002;Gross-Goupil et al, 2003).…”

“…The number of circulating tumor cells has been related to tumor size (Matsumura et al, 1994;Lemoine et al, 1997;Minata et al, 2001;Gross-Goupil et al, 2003) and to the risk of recurrence (Minata et al, 2001;Qin and Tang, 2002;Gross-Goupil et al, 2003). However, the relevance of AFP mRNA as a marker of circulating tumor cells is controversial because these cells have not been further characterized and because we and others have shown that they may correspond to normal circulating hepatocytes (Lemoine et al, 1997;Louha et al, 1999;Minata et al, 2001). Furthermore, these tumor cells have mostly been sought and detected shortly after liver resection (Matsumura et al, 1994;Lemoine et al, 1997;Louha et al, 1999;Kienle et al, 2000;Minata et al, 2001).…”

Modified hanging manoeuvre facilitates inferior vena cava resection and reconstruction during extended right hepatectomy: A technical case report

“…Ozawa (10) described the anterior transection technique in 1990. This technique was popularized over the next decade (11)(12)(13)(14)(15), driven by the perceived disadvantages of conventional right liver mobilization, namely impaired hepatic blood flow with rotational displacement of the liver (10), potential avulsion of hepatic veins (13), iatrogenic tumour rupture (13,16), and hematogenous dissemination of malignant cells when the hepatic veins remained patent (16)(17)(18)(19).…”

Does surgical resection of hepatocellular carcinoma accelerate cancer dissemination?

“…Louha found unexpectedly that liver cells began spreading at an early stage during surgery, i.e., after liver mobilization and rotation, before liver parenchyma transection. This was probably related to the sponge-like structure of the liver and to the stretching and compression of the organ during liver mobilization [42] . Surgery-related liver cell spreading also occurred more frequently, compared with that induced by needle liver biopsy.…”