Macroscopic portal vein tumor thrombi of liver metastasis from colorectal cancer.
ABSTRACT We present a case of multiple colorectal liver metastases with macroscopic portal vein thrombi. A 55-year-old woman presented to us with rectosigmoid cancer and presented with two liver metastases. The tumor in the posterior sector was associated with invasion of first order branches of the portal vein. We performed low anterior resection, hepatic posterior sectorectomy and partial left anterior sectorectomy. Both the colorectal cancer and liver tumors exhibited histological characteristics of moderately differentiated adenocarcinoma with a substantial amount of mucin production. The liver metastases were associated with prominent tumor thrombi in many branches of the portal vein. Stronger staining for endoglin (CD 105) than for Fas ligand (Fas L) and matrix metalloproteinase (MMP-2) was observed in both the colorectal cancer and metastatic liver tumor cells. Expression of the vascular endothelial growth factor within the tumor cells was seen in both the colorectal cancer as well as the metastatic liver tumor cells. Six months after the operation, she was diagnosed to have multiple, more than about 20 liver metastases, and in 9 months after the operation, the patient died. The colorectal cancer with liver metastases associated with portal vein tumor thrombosis was poor prognosis, found neoplastic microvessel formation.
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ABSTRACT: Matrix metalloproteinases (MMPs) have been reported to play an important role in tumour cell invasion and metastasis. The bioactivity of MMPs in liver metastasis from colorectal cancer was investigated and correlated with clinicopathological variables. Thirty-two patients underwent resection of colorectal cancer liver metastases. Latent and active forms of MMP were measured in tissue extracts, by means of quantitative gelatin zymography and a fluorometric activity assay. Broad-spectrum MMP activity, and levels of both active and latent forms of MMP-2 and MMP-9, were higher in tissues containing metastatic tumour than in normal liver tissue. Median metastatic to normal tissue ratios were 15.0 and 17.6 for active and proMMP-2 respectively, and those for active and proMMP-9 were 6.2 and 2.9. The ratios of active to latent enzyme were higher in metastatic tissue than in normal tissue. Lowered MMP-2 activity was associated with large metastatic lesions and increased proMMP-9 levels with preoperative chemotherapy. Both MMP-2 and MMP-9 activity were linked unfavourably to early recurrent disease. These data suggest a role for MMPs in colorectal cancer liver metastasis, but indicate different roles for individual MMPs.British Journal of Surgery 01/2004; 90(12):1556-64. · 4.84 Impact Factor
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ABSTRACT: Metastatic lesions in the liver derived from colorectal cancer rarely invade the portal vein macroscopically. Little is known about the clinical characteristics and outcome of surgical treatment in patients with tumor thrombus in the portal vein. Medical charts of 142 consecutive patients who underwent hepatic resection for colorectal metastasis were reviewed retrospectively. Of the 142 patients, 4 (2.8%) had macroscopic portal vein invasion. The most prominent characteristic on preoperative imaging was segmental staining in the arterial phase shown by dynamic computed tomography (CT) or by CT arteriography. This finding was positive in all four of the patients. All patients underwent anatomic liver resection and were alive with no evidence of disease for an average of 52.3 months (range 21-102 months). Macroscopic tumor thrombus in the portal vein is rare with colorectal metastasis. It is accurately detected by CT by checking for signs of segmental staining. In this setting, anatomic major resection of the liver is essential for curative treatment.World Journal of Surgery 04/2003; 27(3):299-303. · 2.23 Impact Factor
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ABSTRACT: While simultaneous resection has been shown to be safe and effective in patients with synchronous metastasis, neoadjuvant chemotherapy followed by hepatectomy has gradually gained acceptance for both initially nonresectable metastasis and resectable metastasis. The boundary between these treatments is becoming unclear. We hypothesized that factors associated with colorectal cancer may play an important role in the prognosis of patients with synchronous metastasis and may be useful for identifying patients who can be expected to have adequate results following simultaneous resection. Outcome study. Tertiary referral center. From January 1980 to December 2002, 187 patients underwent curative resection for synchronous liver metastasis from colorectal cancer. One hundred forty-two patients received simultaneous resection, 18 underwent staged resection, and 27 underwent delayed hepatic resection. Twenty-one clinicopathological factors were analyzed, and long-term prognosis was assessed. Prognostic factors and patient survival. There was no in-hospital death. In a multivariate analysis, the factors that significantly affected the prognosis of synchronous metastasis were 4 or more lymph node metastases around the primary cancer (P<.001) and multiple liver metastases (P = .003). In patients with 3 or fewer lymph node metastases around the primary cancer, the 5-year survival rates of those with 1, 2 to 3, and 4 or more liver metastases were 63%, 33%, and 40%, respectively, but these rates were 15%, 22%, and 0%, respectively, in patients with 4 or more lymph node metastases around the primary cancer. The results support the application of simultaneous resection in patients with 0 to 3 colorectal lymph node metastases. However, in patients with 4 or more colorectal lymph node metastases, biological selection by neoadjuvant chemotherapy may be more suitable.Archives of Surgery 11/2006; 141(10):1006-12; discussion 1013. · 4.10 Impact Factor
CASE REPORT OF INTEREST
Macroscopic portal vein tumor thrombi of liver metastasis
from colorectal cancer
Takuichi Oikawa Æ Æ Tadatoshi Takayama Æ Æ
Shunji Okada Æ Æ Tomohisa Kamo Æ Æ
Masahiko Sugitani Æ Æ Michiie Sakamoto
Received: 31 August 2007/Accepted: 27 November 2007/Published online: 16 December 2008
? Springer 2008
liver metastases with macroscopic portal vein thrombi.
A 55-year-old woman presented to us with rectosigmoid
the posterior sector was associated with invasion of first
resection, hepatic posterior sectorectomy and partial left
anterior sectorectomy. Both the colorectal cancer and liver
tumors exhibited histological characteristics of moderately
differentiated adenocarcinoma with a substantial amount of
prominent tumor thrombi in many branches of the portal
vein. Stronger staining for endoglin (CD 105) than for Fas
ligand (Fas L) and matrix metalloproteinase (MMP-2) was
observed in both the colorectal cancer and metastatic liver
tumor cells. Expression of the vascular endothelial growth
factor within the tumor cells was seen in both the colorectal
after the operation, she was diagnosed to have multiple,
more than about 20 liver metastases, and in 9 months
after the operation, the patient died. The colorectal cancer
with liver metastases associated with portal vein tumor
We present a case of multiple colorectal
thrombosis was poor prognosis, found neoplastic micro-
Tumor thrombi in the portal vein ? Endoglin ?
Colorectal cancer ? Liver metastasis ?
Portal vein tumor thrombus is a common finding and a
significant negative prognostic indicator in hepatocellular
carcinoma . In patients with colorectal liver metastasis,
macroscopic portal vein thrombus is rare and has been
reported to occur in 2.8% of cases . Microscopic inva-
sion of the portal vein are reportedly present at rates of
22.5% . There are many risk factors for liver metastasis
in colorectal cancer with venous invasion [4–8]. However,
which factor is most important remains controversial.
In this paper, we report a surgical case of liver metas-
tasis from colorectal cancer with prominent portal vein
A 55-year-old woman was referred to us with the com-
plaint of constipation. Her serum CEA level was elevated
1,077 ng/ml (normal range, B2.5 ng/ml) and serum CA
19–9 level to 2,838 U/ml (normal range, B37 ng/ml).
Barium enema and colonoscopic examination revealed an
ulcerative infiltrating type (type 3) of rectosigmoid cancer.
Abdominal computed tomography (CT) showed two liver
metastases, one located in the posterior sector with tumor
thrombi in the portal vein and biliary invasion (Fig. 1), and
T. Oikawa ? T. Takayama (&) ? S. Okada ? T. Kamo
Department of Digestive Surgery,
Nihon University School of Medicine,
30-1 Oyaguchi kami-machi, Itabashi-ku,
Tokyo 173-8610, Japan
Department of Pathology,
Nihon University School of Medicine, Tokyo, Japan
Department of Pathology,
Keio University School of Medicine, Tokyo, Japan
J Hepatobiliary Pancreat Surg (2009) 16:90–93
the other in left lateral sector. Low anterior resection with
D3 lymphadenectomy and posterior sectorectomy and
partial left anterior sectorectomy were performed.
Macroscopic examination of the resected rectosigmoid
colon cancer revealed a type 3 tumor with severe venous
involvement. Histopathological examination revealed find-
ings consistent with mucinous moderately differentiated
adenocarcinoma, reaching the subserosal layer (a2), with
lymphatic duct involvement (ly2), severe venous involve-
ment (v3), and the presence of lymph node metastasis (n1).
The cut surface of the resected specimen of the liver dem-
onstrated a solid tumor in the posterior sector, which was
whitish in color and measured 10 9 8 cm in size with PV
sector measuring 3 9 2.5 cm in size, also associated with
portal vein tumor thrombi. The extirpated portal vein
thrombi consisted mainly of fibrous tissue, and proliferative
mucinous differentiated adenocarcinoma cells (Fig. 3).
Both the colorectal cancer and liver tumors showed positive
immunostaining for endoglin (CD 105), Fas ligand (Fas L)
and matrix metalloproteinase (MMP-2). Positive staining
for CD 105 was observed in the newly formed tumor
microvessels, with the staining for CD 105 being stronger
and more extensive than that for Fas L or MMP-2 (Fig. 4).
The postoperative course of the patient was uneventful,
and she was discharged from our hospital on day 15 after
the operation. We did not perform adjuvant chemotherapy,
because patient refused it. Six months after the operation,
she was diagnosed to have multiple, more than about 20
liver metastases, and in 9 months after the operation, the
We present a rare case of colorectal cancer with liver
metastases in which gross tumor thrombi were found in the
portal vein, indicative of a poor prognosis. Macroscopic
portal vein involvement is considered to be an indicator of
poor prognosis in patients with hepatic metastasis.
In this case, we thought that the mechanism of portal
tumor thrombus regard to influence angiogenesis, intrava-
sation of tumor cells, transportation by the circulation and
adhesive interaction with endothelial cells or extravasation
In this study, to study the influence of tumor angio-
genesis on the portal vein infiltration in cases of liver
metastasis, we conducted immunostaining for CD 105, Fas
L and MMP-2 in both specimens of the colorectal cancer
Fig. 1 Enhanced CT shows a low density mass located in the
posterior sector and a low-density area along the posterior portal tract.
Arrows indicate liver metastasis involved portal vein in direct
Fig. 2 Liver [S6/7] resected specimen (a). Macroscopic findings of
the resected posterior sectorectomy showing tumor thrombi in the
portal vein (b). Arrow indicates liver metastasis involved portal vein
in direct. The tumors measuring 10 9 8 cm
Fig. 3 Histological examination of the liver metastasis (H&E stain).
Microscopic findings in the resected posterior sector liver metastasis
showing tumor thrombi in many branches of the portal vein. Arrows
indicate liver metastasis involved portal vein in direct. [S6/7
J Hepatobiliary Pancreat Surg (2009) 16:90–9391
and of the liver tumors showing invasion of the portal vein
[4–6]. CD 105 has been shown to be a more useful marker
to identify proliferating endothelium involved in tumor
angiogenesis. CD 105 staining has been shown to have
prognostic significance, showing a positive correlation with
angiolymphatic invasion and metastasis to the lymph nodes
and liver . Both the colorectal cancer and liver tumors
associated with invasion of the portal vein showed strong
staining intensity for CD 105. There was a correlation
between the staining intensity for CD 105 and the presence
of a portal vein tumor thrombus. Liver metastasis from
colorectal cancer may show marked angiogenesis. In
hepatocellular carcinoma, the tumor microvessel density by
CD 105 immunostaining was significantly lower in larger
tumors, more aggressive tumors, as indicated by venous
infiltration, and tumors with advanced TNM stage .
Despite the recent advances in chemotherapy and other
treatment modalities, surgical resection is still gold stan-
dard for the treatment of liver metastases from colorectal
cancer [11, 12]. Tada et al., observed that precise diagnosis
of the tumor thrombus followed by anatomic major hepatic
resection is the key to curative treatment . Macroscopic
portal vein thrombus is not a contraindication for surgical
treatment if removed completely. Patients with synchro-
nous liver metastases from colorectal cancer should
undergo radical resection of the primary lesion and
simultaneous hepatectomy with an adequate tumor-free
margin as a standard surgical course. However, in patients
with four or more colorectal lymph node metastases, bio-
logical selection by neoadjuvant chemotherapy may be
more suitable .
In conclusion, although the principle of surgical resec-
tion for colorectal liver metastases is complete removal of
the tumor, indications for surgical resection remain con-
troversial. This case was poor prognosis with positive
correlation with proliferating neoplastic microvessels in
colorectal cancer and liver metastases.
1. Izumi R, Shimizu K, Li T, Yagi M, Matsui O, Nonomura A, et al.
Prognostic factors of hepatocellular carcinoma in patients
undergoing hepatic resection. Gastroenterology. 1994;106:720–7.
2. Tada K, Kokudo N, Seki M, Ueno M, Azekura K, Ohata H, et al.
Hepatic resection for colorectal metastasis with macroscopic
tumor thrombus in the portal vein. World J Surg. 2003;27:299–
3. Yamamoto J, Sugihara K, Kosuge T, Takayama T, Shimada K,
Yamasaki S, et al. Pathologic support for limited hepatectomy in
the treatment of liver metastasis from colorectal cancer. Ann
4. Saad RS, Liu YL, Nathan G, Silverman JF. Endoglin (CD 105)
and vascular endothelial growth factor as prognostic markers in
colorectal cancer. Mod Pathol. 2004;17:197–203.
5. Yokomizo H, Yoshimatsu K, Ishibashi K, Hashimoto M, Ogawa
K. Fas ligand expression is a risk factor for liver metastasis in
colorectal cancer with venous invasion. Anticancer Res. 2003;
6. Waas ET, Wobbes T, Lomme RM, et al. Matrix metallopro-
teinase 2 and 9 activity in patients with colorectal cancer liver
metastasis. Br J Surg. 2003;90:1556–64.
7. Nagashima I, Takada T, Matsuda K, Adachi M, Nagawa H,
Okinaga K, et al. A new scoring system to classify patients with
colorectal liver metastases: proposal of criteria to select candi-
dates for hepatic resection. J Hepatobiliary Pancreat Surg. 2004;
8. Nakamura S, Suzuki S, Konno H. Resection of hepatic metastases
of colorectal carcinoma: 20 years’ experience. J Hepatobiliary
Pancreat Surg. 1999;6:16–22.
9. Tanaka A, Takeda R, Mukaihara S, Hayakawa K, Takasu K,
Terajima H, et al. Tumor thrombi in the portal vein system
originating from gastrointestinal tract cancer. J Gastroenterol.
10. Yongzhong Y, Yiming P, Jun C, Xitai S, Yudong Q, Yitao D.
Endoglin (CD 105) expression in angiogenesis of primary hepa-
tocellular carcinoma: analysis using tissue microarrays and
comparisons with CD 34 and VEGF. Ann Clin Lab Sci. 2007;
Fig. 4 Endoglin staining is strongest in intensity, with staining of
most of the microvessels in both the colorectal cancer (a) and the liver
tumors (b) (magnification 9100)
92 J Hepatobiliary Pancreat Surg (2009) 16:90–93
11. Kemeny N, Fata F. Arterial, portal or systemic chemotherapy for
patients with hepatic metastasis of colorectal carcinoma. J He-
patobiliary Pancreat Surg. 1999;6:39–49.
12. Kokudo N, Imanura H, Sugawara Y, Sakamoto Y, Yamamoto J,
Makuuchi M, et al. Surgery for multiple hepatic colorectal
metastases. J Hepatobiliary Pancreat Surg. 2004;11:84–91.
13. Minagawa M, Yamamoto J, Miwa S, Sakamoto Y, Kokudo N,
Makuuchi M, et al. Selection criteria for simultaneous resection
in patients with synchronous liver metastasis. Arch Surg. 2006;
J Hepatobiliary Pancreat Surg (2009) 16:90–9393