Chin J Radiol 2002; 27: 73-77 73

Calcification within the lesion of livermetastases is a well-known phenomenon. Itoccurs in 12-27% of hepatic colorectalmetastases, but its clinical significance and itsinfluence on prognosis are controversial. Thecalcification is either produced by the tumoritself or represents dystrophic calcificationsecondary to necrosis and/or haemorrhagewithin the tumor before or duringchemotherapy. We here present the imagefindings of a case of colon cancer with livermetastases which calcified following 5-fluorouracil chemotherapy.

Key words: calcification, colorectal cancer, 5-fluorouracil, liver metastases

Colorectal carcinoma is one of the most commoncause of cancer-related death in Taiwan. In recentyears, cytotoxic chemotherapy using 5-fluorouracil hasbeen the treatment of choice for metastatic colorectalcancer and the objective response is achieved in 25%of the patients [1]. Liver metastases occur in up to40% of patients with colorectal cancer [2]. Thesemetastases are usually hypovascular and vary in sizefrom large coalescent lesions occupying a major partof an hepatic lobe to small lesions less than 1 cm indiameter. Survival period with liver metastases is 6-15months. Length of survival is known to correlate withthe degree of differentiation of the primary tumor aswell as the volume of tumor presented within the liver[3-5].

Calcification is known to occur in 12-27% of livermetastases and is easily identified on both CT (com-puterized tomography) scan and ultrasound [6-8]. Thesignificance of calcification in hepatic colorectalmetastases is not known, although calcification isthought to be associated with the mucinous variant ofcolorectal cancer [3]. The prognosis of calcified livermetastases is still controversial [9].

CASE REPORT

A 41–year-old female patient was a victim ofchronic hepatitis B virus infection. She had multipleliver and gastric metastases from sigmoid colon cancerdiagnosed in March 1999. Abdominal CT showed mul-tiple metastases with fine calcification in both hepaticlobes (Fig. 1a,b). She was treated with high dose 5-flu-orouracil (5-FU) 2600 mg/m2 chemotherapy weekly.After 26 courses of chemotherapy, the liver metastasesbecame heavily calcified on unenhanced CT images(Fig. 2a,b). There is no tumor found in sigmoidoscopy.

CASE REPORT

Reprint requests to: Dr. Shin-Lin ChangDepartment of Medicine, Taipei Veterans General Hospital.No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan, R.O.C.

Calcification of Liver Metastases in a ColonCancer Patient Following Chemotherapy with5-Fluorouracil : A Case ReportSHIN-LIN CHANG

1 CHUNG-PIN LIN2 RHEW-CHUAN LEE

4 FULL-YOUNG CHANG2 SHOU-DONG LEE

1

SANG-HUE YEM3 YEE CHAO

3

Department of Medicine1, Division of Gastroenterology, Department of Medicine2, Department of Cancer Center3,Department of Radiology4, Taipei Veterans General Hospital, Taipei

Calcification of liver metastases in colon cancer following chemotherapy74

Complete response was impressed and the chemother-apy was stopped in September 1999. However, afollow-up CT scan in December 1999 showed twonew lesions, one about 10 mm at S7 and another about18 mm at S5/6 of right lobe of liver (Fig. 3a,b).Metastatic lesions in progression were considered.

She was then treated with irinotecan (CPT-11) 125mg/m2 in repeated 4-week cycle that consisted of 3consecutive weeks followed by 1-week break. At first,stable disease with regressive change of the calcifiedmasses was noted (Fig. 4a,b). However, after 4 cyclesof treatment, CT scan revealed further progression ofthe disease in May 2000 (Fig. 5a,b) and no furthertreatment was arranged. The patient took herbal medi-cine and was then loss of follow-up. Unfortunately,progressively deteriorated liver function, jaundice andascites developed since August 2000. The patient diedof hepatic failure in November 2000.

DISCUSSION

Colorectal cancer is the third most common causeof cancer-related deaths in both men and women inTaiwan. Despite the introduction of multiagentchemotherapy and improvements in surgical tech-niques, the overall survival rate has not increased sig-nificantly over recent decades and the 5 years survivalrate remains less than 50% [1].

Hepatic metastases are common, occurring at thetime of presentation in 11-25% of patients and in afurther 20-30% of patients after resection of theprimary tumor [l,2].

Calcification within liver metastases is a well-known phenomenon, but little attention has been givento this feature with regards to its significance, if any,in terms of evaluating therapeutic response.Calcification of liver metastases is seen most frequent-ly in primary mucinous adenocarcinomas, common in

Figure 1. a and b CT images revealing fine calcification with liver metastasis at presentation

1a 1b

Figure 2. a and b heavy, eggshell calcification occuping entire metastases developed following three months of 5-FUchemotherapy

2a 2b

Calcification of liver metastases in colon cancer following chemotherapy 75

colorectal cancer, and can be demonstrated in ovariancancer, breast cancer, renal cancer, thyroid cancer andneuroblastoma [9-10]. Calcification in the liver mayalso be seen in primary benign and malignant tumors

[11]. The calcification is either produced by the tumoritself or represents dystrophic calcification secondaryto necrosis and/or haemorrhage within the tumorbefore or during chemotherapy [12].

Figure 3. a one new lesion about 10 mm at S7 of right lobe of liver. b another new lesion about 18 mm at S5/6 of rightlobe of liver

3a 3b

Figure 4. a and b One year later, regression of the metastatic lesion in S7 and S4/5 were noted in the initial period ofchemotherapy with CPT-11

4a 4b

Figure 5. a and b several variable sized calcified masses with recurrent tumor were noted

5a 5b

REFERENCE

1. NIH Consensus Conference. Adjuvant therapy forpatients with colon and rectal cancer. JAMA 1990; 264:1444-1450

2. Lise M, Dabian PP, Nitti D, et al. Colorectal metastasesto the liver. Present status of management. Dis ColonRectum 1990; 35: 688-694

3. Daly JD, Kemeny N. Therapy of Colorectal HepaticMetastases.In: DeVita VT Jr, Hellman S, Rosenberg SA(eds): “Important Advances in Oncology.” Philadelphia:Lippincott, 1986, 251-267

4. Jaffe BM, Donegan WL, et al. Factors influencing sur-vival in patients with untreated hepatic metastases. SurgGynecol Obstet 1968; 127: 1-11

5. Bengtsson B, Carlsson G, Hafstrom L, Johsson PE.Natural history of patients with untreated liver metas-tases from colorectal cancer. Am J Surg 1981; 141: 586-589

6. Scatarige JC, Fishman FK, Saksouk FA, Siegelman SS.Computed tomography of calcified liver masses. JComput Assist Tomogr 1983; 7: 83-89

7. Bernardino ME: Computed tomography of calcifiedliver metastases. J Comput Assist Tomogr 1979; 3: 32-35

8. Katragadda CS, Goldstein HM, Green R. Gray scaleultrasonography of calcified liver metastases. Am JRoentgenol 1997; 129: 591-593

9. Hale HL, Husband JE, Gossios K. CT of calcified livermetastases in colorectal carcinoma. Clin Radiol 1998;53: 735-741

10. Federle MP, Jeffrey RB Jr, Minagi II. Calcified livermetastases from renal cell carcinoma. J Comput AssistTomogr 1981; 5: 771-772

11. Frick MP, knight LC, Feinberg SB, et al. Computertomography, radionuclide imaging and ultrasonographyin hepatic mass lesion. J Comput Assist Tomogr 1979;3: 49-55

12. Bernardino ME, Chuang VP, Wallace S et al.Therapeutically infarcted tumors: CT finding. Am JRoentgenol 1981; 136: 527-530

13. Easson AM, Barron PT, Cripps C et al. Calcification incolorectal hepatic metastases correlates with longer sur-vival. J Surg Oncol 1996; 63: 221-225

Calcification of liver metastases in colon cancer following chemotherapy76

Hale et al. [9] studied a group of 265 patients withlocally advanced or metastatic cancer. Twenty-nine(11%) patients had calcified liver metastases at presen-tation and 10 (4%) developed calcification duringchemotherapy. Analysis of the lesions showed that themost frequent (22 of the 29 patient with calcified livermetastases) characteristic was fine calcification (< 1mm in size or linear ) with a variable distribution. Themost frequent change on treatment was alteration inthe extent of calcification. Calcification developedduring treatment was usually central within the lesion(8 of the 10 patient with calcification developedduring chemotherapy). Liver metastatic calcificationmay not carry any prognostic significance in colorec-tal cancer.

In another study, Easson et al. [13] looked at agroup of 112 patients with hepatic colorectal metas-tases. In their study, nine patients had calcification ofhepatic metastases at presentation, and 22 developedcalcification during chemotherapy, giving an overallincidence of 28%. They found that the presence of cal-cification was independent of degree of tumor differ-entiation, the presence of mucinous adenocarcinoma,or hepatic tumor burden. They also found that thepresence of calcification was a highly significant prog-nostic factor indicating improvement in survival,which is in contrast to the result of the previous reportwhich showed that the presence of calcification had norelationship to patients’ survival.

In summary, we have presented the imaging findingof a colon cancer with calcified liver metastasis fol-lowing 5-FU chemotherapy which is rarely encoun-tered in clinical practice. Calcification in liver metas-tases from colorectal cancer develops in over 12-27%of patients and has a varied appearance and variablecourse on therapy. The prognosis of calcified livermetastases is still under debating.

Calcification of liver metastases in colon cancer following chemotherapy 77