ERCC1, defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

BACKGROUND: Excision repair cross-complementation group 1 (ERCC1) expression status has been identified as a candidate marker for predicting efficacy of oxaliplatin (OX) treatment for metastatic colorectal cancer (CRC) in several trials. Also, an association between expression of mismatch repair (MMR) genes and favourable postoperative survival in stage II CRC receiving 5-FU chemotherapy has been identified. It is unknown if the expression of ERCC1 protein and MMR status are associated with survival of stage III colon cancer receiving OX-based chemotherapy. METHODS: Immunohistochemistry (IHC) analysis of the expression of MMR and ERCC1 was performed on tumour tissue of 255 patients with stage III colon cancer. In all, 95 patients received fluoropyrimidine-based chemotherapy and 160 patients received OX-based chemotherapy. A predictive model for 5-year disease-free survival (DFS) and overall survival (OS) was constructed using Kaplan-Meier analysis, logistic and Cox regression. RESULTS: Patients who were treated with OX-based therapy with positive ERCC1 tumours had lower 5-year DFS (54%) and OS (60%) than those with negative ERCC1 tumours (72% and 78%, respectively; DFS HR: 1.98, 95% confidence interval (CI): 1.19-3.31, P=0.009; OS HR: 2.44, 95% CI: 1.37-4.34, P=0.02). Excision repair cross-complementation group 1 status did not impact DFS or OS in fluorouracil group (DFS HR: 1.16, 95% CI: 0.63-2.14, P=0.62; OS HR: 1.16, 95% CI: 0.63-2.14, P=0.63), whereas MMR status had no impact on DFS or OS in either group. CONCLUSION: Excision repair cross-complementation group 1 status is highly predictive of which patients will benefit from the addition of OX to 5-FU for stage III colon cancer. Mismatch repair status had no predictive value in this setting.

The role of hepatic veins in liver operations.

In this report we review the role of the hepatic veins in resective operations of the liver. Emphasis is placed on the distribution of the hepatic veins, their relationship to hepatic arterial and portal venous inflow tracts, and the drainage patterns of hepatic lobules. An extensive review of the older literature has emphasized the necessity to preserve hepatic venous drainage for the various hepatic segments to prevent postoperative liver congestion and injury. Recent experimental and clinical reports have identified the mechanisms through which hepatic vein obstruction can be well tolerated. These mechanisms include interlobar and interlobular collateral development, reversal of blood flow in the portal vein with conversion of the portal vein to an outflow tract, development of extrahepatic collaterals, drainage through the caudate lobe, and increased lymphatic draining to relieve hepatic congestion.

Hepatic vein ligation and preservation of liver segments in major resections.

To preserve as much normal liver tissue as possible in patients having segmental and major anatomical liver resections for primary and metastatic cancer, one of us (Q.-J.O.) performed segmental hepatic vein ligation with preservation of the involved liver segments in eight patients undergoing hepatic resections. No early complications were found related to necrosis of the involved segments. Needle biopsy of the segments in five patients revealed normal survival of the hepatic tissue. The results in these patients indicate that hepatic vein ligation is a safe procedure that permits preservation of segments of the liver in patients having hepatic resection and can be used as an alternative to routine hepatic lobectomy for the treatment of liver tumors in selected patients.

Effects of hepatocyte growth-promoting factor and panax notoginseng saponins on intrasplenic hepatocellular autotransplantation.

AIM: To increase the weight of liver tissue mass present in spleen and to shorten the regeneration period of transplanted hepatocytes by stimulating DNA synthesis and protection against ischemic-reperfusion injury. METHODS: Hepatocyte growth-promoting factor (PHGF) and panax notoginseng saponins (PNGS) were used after intrasplenic hepatocellular autologous transplantation (IHAT) with 70 % partial hepatectomy. Histological examinations were carried out under both light and electron microscopy and content of ALT in hepatized spleen homogenate was investigated 2 weeks after transplantation. Furthermore, 99mTc diethyl-iminodiacetic acid (99mTc-HIDA) splenic scintiphotography was carried out and proliferation index of transplanted hepatocytes was detected by flow cytometry at the 12th week after operation. RESULTS: (1) Hepatocellular degeneration was slightly less in group B [intrasplenic hepatocyte autologous transplantation (IHAT) + PNGS 25 mg/kg, im, qd] vs the control group (group C, IHAT without drugs) at the 2nd week after transplantation, and the ALT content of group B (928 U/g +/- 268 U/g) was higher than that of group C (639 U/g +/- 138 U/g, P < 0.01). (2) At the 12th week, hepatocellular regeneration in group A (IHAT + PHGF 5 mg/kg, im, qd) was obviously better than that in group C, and the ALT content (2325 U/g +/- 401 U/g ), the radioactivity accumulation of 99mTc-HIDA (58 Bq +/- 18 Bq), and proliferation index (3.8 % +/- 0.4 %) of group A were all higher than those of control (P < 0.05). CONCLUSION: PHGF has effects in increasing the weight of liver tissue grown in spleen and shortening the regeneration period of the transplanted hepatocytes, while PNGS has certain effects on protecting the hepatocytes against ischemic reperfusion injury in the early stage of transplantation.