Jaundice secondary to isolated porta hepatis metastasis in colorectal cancer: case report and review of the literature.

Abstract: Colorectal cancer occurs mainly after the age of 50. The liver is the most frequent site of metastases, although isolated metastases to the porta hepatis are rarely reported in the literature. From 1924 to 1993, only 16 cases of periportal lymph nodes metastases were reported. We report a case of jaundice secondary to porta hepatis metastases from primary colorectal cancer. The appearance of symptoms was concurrent with the elevation of carcinoembryonic antigen in our case. This emphasizes the importance of polymerase chain reaction to detect the small amount of carcinoembryonic antigen transcript in blood or in peritoneal fluid before the appearance of symptoms. Polymerase chain reaction allows the prediction of high risk of recurrence and the presence of micrometastases. More trials are needed to assess the outcome after treatment by adjuvant chemotherapy for micrometastases.

Key Words: colorectal cancer, micrometastases, porta hepatis

**********

Colorectal cancer is the second most common fatal cancer among men 40 to 79 years old. (1) An estimated 105,500 new cases of colon cancer will be diagnosed in 2003, and 57,100 will die as a result of it in the same year. (1) Colorectal cancer usually occurs after the age of 50. (2) Devesa et al (3) reported that 60 to 85% of colorectal recurrences occur in the first 2 years after the initial operation. The risk of recurrence increases with advanced Dukes stage and the presence of lymphatic or venous invasion. The liver is the most frequent visceral site of metastatic dissemination. (4) Metastases to the porta hepatis without involvement of the liver is rarely reported in the literature. We report a case of jaundice in which the metastasis to the porta hepatis was the only manifestation of recurrence of colon cancer. We discuss the clinical presentation, treatment, and prognosis of this rare manifestation of colorectal cancer.

Case Report

A 64-year-old man presented in September 1999 to our institution for colonoscopy after 2 months of hematochezia and heme-positive stools. He denied any change in bowel habits, melena, and abdominal pain or weight loss.

Physical examination was normal except for positive Hemoccult. A colonoscopy performed on September 15, 1999, showed an obstructive rectosigmoid colon mass 10 cm from the anal margin. The pathology report came back positive for adenocarcinoma. Pertinent laboratory work showed a carcinoembryonic antigen (CEA) level of 91.9 ng/ml (normal, 0-5 ng/ml). A computed tomographic (CT) scan of the abdomen and pelvis showed abnormal asymmetric thickening of the colon in the vicinity of the rectosigmoid junction. No hepatic lesion and no retroperitoneal and/or lymphadenopathy were evident.

Two days later, a low anterior colon resection was performed and the patient was discharged from the hospital 5 days later. Final pathologic findings described infiltrating moderately differentiated adenocarcinoma (3 cm) invading through the muscularis propria and into the serosal fat. Serosa, proximal, and distal surgical margins were free of tumor. Metastatic adenocarcinoma was present in one of six recovered lymph nodes. The tumor was classified Stage III, T3N1M0 Dukes Stage C. He received 5 weeks of continuous infusion of 5-fluorouracil/leucovorin and then six cycles of 5-fluorouracil/leucovorin started 1 month later. He was also treated with concurrent radiotherapy to the pelvis from November 29, 1999, until January 13, 2000. Colonoscopies performed in August 2000 and 2001 were normal.

CEA was repeated in June 2000, at 1 and 3 months, and then sequentially every 3 months. The level was normal until October 2002, when it increased to 293.2, and then up to 660 in January 2003.

When the patient presented in October 2002, he had lost 22 lb over the previous couple of months, with decreased appetite, abdominal pain with bloating, acholic stool, and dark urine for the previous 2 weeks. He denied bone pain. The pertinent finding on physical examination was icteric sclerae without lymphadenopathy, and the abdomen was tender in the right upper quadrant without hepatomegaly or splenomegaly. The pertinent laboratory work included the following: total bilirubin, 3 mg/dl (normal: 0.2-1 mg/dl); alkaline phosphatase, 353 U/L (normal, 38-126 U/L); alanine aminotransferase, 284 U/L (normal, 7-56 U/L); aspartate aminotransferase, 182 U/L (normal, 15-46 U/L); hemoglobin, 13.8 g/dl (normal, 13.6-17.3 g/dl); and CA 19-9, 3,273 U/L (normal, 0-37 U/L).

CT scan of the abdomen and pelvis obtained on November 1, 2002, revealed an ill-defined low-density mass in the porta hepatis with intrahepatic biliary dilation (Fig. 1). Magnetic resonance imaging of the abdomen performed on November 26, 2002, showed prominence of the intrahepatic biliary ducts. Endoscopic retrograde cholangiopancreatography (ERCP) was performed on December 13, 2002. The brushing was negative for malignancy; two attempts to place the stent through ERCP were unsuccessful, and the stent was finally placed percutaneously. The abdominal pain decreased after stent placement along with normal color of urine and stool and decreased bilirubin from 6.9 to 1.2 mg/dl (normal, 0.2-1 mg/dl). CT scanguided fine-needle aspiration performed on January 24, 2003, was positive for adenocarcinoma. The patient was started on irinotecan/5-fluorouracil/leucovorin.

Discussion

Colorectal cancer is frequent. Jaundice is almost an ultimate manifestation of advanced colon cancer. (5) The most common mechanism of jaundice in colon cancer is extensive liver metastases. Isolated porta hepatis metastasis without liver involvement or colon recurrence is extremely rare. (6) From 1924 to 1993, only 16 cases of periportal lymph node metastases were reported. (6)

The primary site of metastases to the porta hepatis is usually within the gastrointestinal tract. (7) Carcinoma of the breast, lung, stomach, kidney, malignant melanoma, and lymphoid neoplasm can also cause extrahepatic biliary tree compression by lymphatic metastasis. (8-10) Nonmalignant causes of lymphadenopathy of the porta hepatis include tuberculous (11,12) and cryptococcal lymphadenitis. (13)

Metastatic colorectal cancer can cause obstructive jaundice by lymph node metastases along the common bile duct or in the porta hepatis, (6,9) bile duct metastases, (6,14) or floating tumor inside the bile duct. (15,16) These patients usually present with jaundice, abdominal pain, nausea, anorexia, dark urine, acholia, and pruritus. (5,10,17,18)

CEA is a glycoprotein that helps metastatic colorectal cancer cells in aggregation and implantation in distant organs, (19) and is the marker of first choice for detecting recurrence of colon cancer. (20,21) In the series studied by Zheng et al, (22) preoperative serum levels of CEA did not predict the occurrence of recurrence. Another marker, called CA 19-9, however, is a good predictor of prognosis. Positive pre- and postoperative level of CA 19-9 is associated with poor outcome. (22) This emphasizes the importance of measuring CA 19-9 along with CEA for early detection of recurrence.

The porta hepatis metastases can be visualized by performing abdominal ultrasonography, which shows a hypoechoic area at the hepatic hilum with enlargement of the intrahepatic tree. (5,17) CT scan of the abdomen can also reveal low-density masses in the porta hepatis.

Harned et al, (23) however, concluded after following 32 patients that current high-resolution cross-sectional imaging is unable to detect microscopic tumor deposits. These micrometastatic cells are probably not numerous enough to increase the CEA level. Therefore, neither the routine measurement of CEA nor standard imaging is able to detect micrometastases. In our patient, the CEA level remained low until the appearance of symptoms. The detection of micrometastases became possible after the introduction of polymerase chain reaction (PCR) and immunohistochemistry.

Micrometastases detected by PCR can predict outcome. (24) PCR has also been applied to detect CEA transcripts in the peritoneal fluid or blood. According to Guller et al, (25) 71% of patients with positive transcripts will have recurrence. The final diagnosis needs to be confirmed by biopsy, given the various causes of lymphadenopathy in this area.

Methods of biliary decompression have included surgical bypass procedures and radiotherapy. (14) These high obstructions are difficult to bypass surgically, however. (7) In addition, drainage by surgery is associated with higher perioperative complications and longer hospitalization. (26,27) The postoperative death rate can be as high as 20 to 28.6%. (28,29)

[FIGURE 1 OMITTED]

Endoprostheses inserted endoscopically or percutaneously have been used successfully (30) as an alternative to surgical bypass. Self-expandable stainless-steel endoprostheses have replaced the plastic endoprostheses, because of the lower risk of migration and occlusion with the former. (30) The goal of these procedures is not only improvement of the quality of life (31) but also increased survival. The mean survival in untreated patients with extrahepatic biliary obstruction by metastatic colorectal carcinoma is 0.6 month, (6) whereas the survival after biliary decompression can be as long as 42 months. (15) This can be explained by the fact that obstructive liver failure rather than disseminated cancer is the cause of death of these patients. (32)

The choice of the means of insertion of endoprostheses for high biliary obstruction is still controversial. Besser (31) recommended ERCP as the first choice because of the lower complication rate compared with percutaneous transhepatic biliary drainage (PTBD). PTBD remains an alternative in case of failure of ERCP. Ducreux et al (33) recommended PTBD as an initial procedure for high obstruction because of the high failure rate of ERCP to access this high level. The mortality rate secondary to cholangitis after incomplete drainage by ERCP may be as high as 40%. Nelsen et al (18) also recommended PTBD because of the lower risk of contaminating the bile ducts by enteric flora in PTBD compared with ERCP.

Complications of PTBD include sepsis, cholangitis, bile peritonitis, and bleeding. (34,35) The endoscopic procedure is associated more with occlusion and migration. (30) PTBD is contraindicated by the presence of ascites, because the fluid of ascites will overflow from the incision through the catheter insertion. (17)

Thus, the optimal procedure varies from one series to another. This could be related to the experience of the center and the level of obstruction. We can conclude that if the level of obstruction is proximal to the distal third of the common bile duct and the radiologist expertise is high in PTBD, PTBD remains the first choice. However, in cases of lower obstruction and higher expertise in ERCP, ERCP should be the initial procedure. Survival after biliary decompression of extrahepatic obstructive jaundice due to colorectal cancer ranges from 60 days (36) to 42 months. (15) Biliary decompression is recommended even in the presence of liver metastasis, (6, 14) given the long survival and better quality of life associated with prostheses.

Conclusions

The appearance of jaundice in a patient with colorectal cancer is an ominous prognostic sign. It usually indicates extensive liver metastasis. (14) We should keep in mind the possibility of porta hepatis involvement with resultant obstructive jaundice because the treatment is different from liver metastases. Endoprostheses is the treatment of choice for biliary decompression, but the means of insertion remains controversial. Our case emphasizes also the importance of CEA as a marker for colon cancer recurrence. Thus, elevation of CEA permits early detection of recurrence, when treatment seems to be more efficacious. CEA alone is not sufficient, however, because it did not increase in the presence of micrometastases and it increases in only 70% of patients with recurrence. (37) More trials should be conducted on the application of PCR in the routine detection of micrometastases. Other studies should assess the beneficial outcome of adjuvant chemotherapy in the presence of micrometastases.

Accepted March 6, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9703-0287

References

1. Jemal A, Murray T. Samuels A, et al. Cancer statistics, 2003. CA Cancer J Clin 2003;53:5-26.

2. Makela J, Kiviniemi H, Laitinen S. Prognostic factors after surgery in patients younger than 50 years old with colorectal adenocarcinoma. Hepatogastroenterology 2002;49:971-975.

3. Devesa JM, Morales V, Enriquez JM, et al. Colorectal cancer: The bases for a comprehensive follow-up. Dis Colon Rectum 1988;31:636-652.

4. Berlin JW, Gore RM, Yaghmai V, et al. Staging of colorectal cancer. Semin Roentgenol 2000;35:370-384.

5. Olm M, Pera M, Fuster J, et al. Acute severe jaundice in a young patient. Arq Gastroenterol 1990;27:204 (letter).

6. Lo CY. Lai EC. Palliation for extrahepatic biliary obstruction by metastatic colorectal carcinoma. Am J Gastroenterol 1994;89:1852-1855.

7. Contractor FM, Sharma P. Dash N, et al. Extension of hepatic metastatic tumor along a biliary drainage catheter tract: Case report. Cardiovasc Intervent Radiol 1987;10:303-304.

8. Takasan H, Kitamura O, Ozawa K, et al. Metastatic cancer of the liver resulting in obstruction of the extrahepatic bile duct. Am J Surg 1973; 125:782-785.

9. Warshaw AL, Welch JP. Extrahepatic biliary obstruction by metastatic colon carcinoma. Ann Surg 1978;188:593-597.

10. Maroy B, Moullot P, Daloubeix H, et al. Intraductal biliary metastasis of a colonic cancer [in French]. Ann Radiol (Paris) 1988;31:309-311.

11. Stanley JH, Yantis PL, Marsh WH. Periportal tuberculous adenitis: A rare cause of obstructive jaundice. Gastrointest Radiol 1984;9:227-229.

12. Caroli-Bosc FX, Conio M, Maes B, et al. Abdominal tuberculosis involving hepatic hilar lymph nodes: A cause of portal vein thrombosis and portal hypertension. J Clin Gastroenterol 1997;25:541-543.

13. Markowitz SM, Kerkering TM, Gervin AS. Biliary obstruction and cholestasis in AIDS: Case report. Va Med 1990;117:114-116.

14. Sung MW, Bruckner HW, Szabo S, et al. Extrahepatic obstructive jaundice due to colorectal cancer. Am J Gastroenterol 1988;83:267-270.

15. Levine AW, Donegan WL, Irwin M. Adenocarcinoma of the colon with hepatic metastases: Fifteen-year survival. JAMA 1982;247:2809-2810.

16. Roslyn JJ, Kuchenbecker S, Longmire WP, et al. Floating tumor debris: A cause of intermittent biliary obstruction. Arch Surg 1984;119:1312-1315.

17. Iwasaki M, Furuse J, Yoshino M, et al. Percutaneous transhepatic biliary drainage for the treatment of obstructive jaundice caused by metastases from nonbiliary and nonpancreatic cancers. Jpn J Clin Oncol 1996;26:465-468.

18. Nelsen KM, Kastan DJ, Shetty PC, et al. Utilization pattern and efficacy of nonsurgical techniques to establish drainage for high biliary obstruction. J Vasc Interv Radiol 1996;7:751-756.

19. Benchimol S, Fuks A, Jothy S, et al. Carcinoembryonic antigen, a human tumor marker, functions as an intercellular adhesion molecule. Cell 1989; 57:327-334.

20. Northover J. The use of prognostic markers in surgery for colorectal cancer. Eur J Cancer 1995;31A:1207-1209.

21. Gervaz P, Blanchard A, Pampallona S, et al. Prognostic value of postoperative carcinoembryonic antigen concentration and extent of invasion of resection margins after hepatic resection for colorectal metastases. Eur J Surg 2000;166:557-561.

22. Zheng CX, Zhan WH, Zhao JZ, et al. The prognostic value of preoperative serum levels of CEA, CA19-9 and CA72-4 in patients with colorectal cancer. World J Gastroenterol 2001;7:431-434.

23. Harned RK II, Chezmar JL, Nelson RC. Recurrent tumor after resection of hepatic metastases from colorectal carcinoma: Location and time of discovery as determined by CT. AJR Am J Roentgenol 1994;163:93-97.

24. Noura S, Yamamoto H, Ohnishi T, et al. Comparative detection of lymph node micrometastases of Stage II colorectal cancer by reverse transcriptase polymerase chain reaction and immunohistochemistry. J Clin Oncol 2002;20:4232-4241.

25. Guller U, Zajac P, Schnider A, et al. Disseminated single tumor cells as detected by real-time quantitative polymerase chain reaction represent a prognostic factor in patients undergoing surgery for colorectal cancer. Ann Surg 2002;236:768-776.

26. McPherson SJ, Gibson RN, Collier NA, et al. Percutaneous transjejunal biliary intervention: 10-year experience with access via Roux-en-Y loops. Radiology 1998;206:665-672.

27. An ZY, Reed WD. Placement of stent for bile drainage by using combined percutaneous and endoscopic technique [in Chinese]. Zhonghua Nei Ke Za Zhi 1994;33:379-381.

28. Dixon JM, Armstrong CP, Duffy SW, et al. Factors affecting morbidity and mortality after surgery for obstructive jaundice: A review of 373 patients. Gut 1983;24:845-852.

29. Blamey SL, Fearon KC, Gilmour WH, et al. Prediction of risk in biliary surgery. Br J Surg 1983;70:535-538.

30. Men S, Hekimoglu B, Kaderoglu H, et al. Palliation of malignant obstructive jaundice: Use of self-expandable metal stents. Acta Radiol 1996;37:259-266.

31. Besser P. Percutaneous treatment of malignant bile duct strictures in patients treated unsuccessfully with ERCP. Med Sci Monit 2001;7(Suppl 1):120-122.

32. Koven IH, Steinhardt MI, Reichstein B. Percutaneous antegrade biliary drainage: A nonoperative approach to biliary obstruction. Can J Surg 1981;24:591-593.

33. Ducreux M, Liguory C, Lefebvre JF, et al. Management of malignant hilar biliary obstruction by endoscopy: Results and prognostic factors. Dig Dis Sci 1992;37:778-783.

34. Molnar W, Stockum AE. Relief of obstructive jaundice through percutaneous transhepatic catheter: A new therapeutic method. Am J Roentgenol Radium Ther Nucl Med 1974;122:356-367.

35. Joseph PK, Bizer LS, Sprayregen SS, et al. Percutaneous transhepatic biliary drainage: Results and complications in 81 patients. JAMA 1986; 255:2763-2767.

36. Thomas JH, Pierce GE, Karlin C, et al. Extrahepatic biliary obstruction secondary to metastatic cancer. Am J Surg 1981;142:770-773.

37. Minton JP, Hoehn JL, Gerber DM, et al. Results of a 400-patient carcinoembryonic antigen second-look colorectal cancer study. Cancer 1985;55:1284-1290.

RELATED ARTICLE: Key Points

* Colorectal cancer is very common after the age of 50.

* Isolated metastases to the porta hepatis from colorectal cancer are rarely reported in the literature.

* Polymerase chain reaction is able to detect the small amount of carcinoembryonic antigen transcript present even before the elevation of carcinoembryonic antigen in blood.

* Prostheses is the treatment of choice for biliary decompression, but the means of insertion remains controversial.

* More studies are needed to assess the beneficial outcome of adjuvant chemotherapy for the treatment of micrometastases.

Souad S. Youssef, MD, and Pullatikurthi Pradeep Kumar, MD

From the Division of Radiation Oncology, James H. Quillen College of Medicine, East Tennessee State University, James H. Quillen Veterans Affairs Medical Center, Johnson City, TN.

Reprint requests to Pullatikurthi Pradeep Kumar, MD, Radiation Oncology Service, James H. Quillen Veterans Affairs Medical Center, Mountain Home, TN 37684. Email: [e-mail]