Indian Journal of Surgery Medknow Publications on behalf of Association of Surgeons of India ISSN: 0972-2068 Vol. 65, Num. 4, 2003, pp. 344-346

Indian Journal of Surgery, Vol. 65, No. 4, July-Aug, 2003, pp. 344-346

Review Article

Conservation in hepatic cancer

Parul J. Shukla

Division of GI Surgery, Tata Memorial Hospital, Mumbai 400012.
Address for correspondence Dr. Parul Shukla, Division of GI Surgery, Tata Memorial Hospital, Mumbai 400012.
E-mail: pjshukla@hotmail.com

How to cite this article: Shukla PJ. Conservation in hepatic cancer. Indian J Surg 2003;65:344-6.

Paper Received: January 2002. Paper Accepted: July 2002. Source of Support: Nil

Code Number: is03068

Introduction

The treatment options for primary hepatic cancer are many. Unfortunately, the long-term results and outcomes are far from satisfactory. Indeed, there are some doctors who would consider liver cancer to be a malignancy fit only for either palliative treatment or alternative forms of medicine.

Despite liver surgery being synonymous with higher than the standard surgical morbidity and mortality, one must point out that it is the surgical options that offer any real chance of long-term survival and must always be considered first. Surgery forms the mainstay of the treatment of liver cancer. As the results of hepatic surgery have improved, specialist centres have been emboldened to undertake major and even supra-major resections. Major liver surgery is presently associated with a 0-5 % mortality risk.¹

This article deals with the theme of conservation in hepatic cancer. It is for this reason that the major surgical procedures and their details have not been discussed here.

Surgery

Debulking surgery

Debulking surgery aims at removal or destruction of all macroscopic tumour, but allowing microscopic foci to persist and be dealt with by other forms of therapy. Debulking surgery for good surgical risk patients has been shown to prolong survival and provide excellent symptomatic relief. Resection can be combined with local ablative therapy to induce tumour necrosis.

At the Tata Memorial Hospital, we have experience with debulking resections mainly for metastatic lesions.

This surgery is safe to perform, but the hepatic recurrence rates are higher than for formal resections.² It is now our policy to perform anatomical resections as far as possible.

Laparoscopic surgery

Minimal access surgery has been applied to liver surgery as well. There are reports of major and minor resections being successfully performed either as laparoscopically assisted or completely laparoscopic procedures.³ Obviously, these procedures are restricted to centres where expertise for both liver surgery as well as advanced laparoscopy is available.

Preoperative portal vein embolization

Preoperative portal vein embolization is used for inducing contralateral hepatic hypertrophy. It also helps in decreasing the risk of postoperative liver failure.⁴ There are reports of reduction in intraoperative blood loss as well.

This is also beneficial in cirrhotic patients being considered for resection. The compensatory hypertrophy helps preserve hepatic function, as these patients do not tolerate major resections as well as those patients with normal liver architecture.

Non-surgical techniques

The non-surgical techniques for dealing with hepatocellular carcinoma (HCC) include: chemoembolization, radiofrequency ablation, ethanol injection, intra-arterial radio-embolization and systemic chemotherapy. These are discussed in detail and are important because at best only 10-30 % of all HCCs are amenable for surgical resection.⁵

Local ablative therapy can be applied to patients with small HCC confined to the liver, although the technique is difficult in patients with multiple tumours. It is especially suitable for patients whose tumours cannot be resected because of poor liver function or because of recurrent tumour developing after partial hepatectomy. It is contraindicated in patients with gross ascites, uncorrectable coagulopathy and obstructive jaundice for fear of post-procedural bleeding and biliary peritonitis.

Trans-arterial chemoembolization (TACE)

The liver has a dual blood inflow from the hepatic artery and the portal vein. Occluding the hepatic artery, which is the major blood supply to the tumour, induces ischaemia and necrosis of the tumour, but it does not affect the non-tumorous part of the liver as this part of the liver derives its blood supply mainly from the portal vein.

TACE has the theoretical advantage of achieving a higher concentration of cytotoxic drugs within the tumour because HCC derives its main blood supply from the hepatic artery, thus improving the tumour cell kill and decreasing the side-effects of treatment.

Some trials using single chemotherapeutic agents only suggest a better response rate than that of systemic chemotherapy. TACE using combination drugs appears to achieve a higher tumour response rate than single agents, but at the expense of significantly more toxicity.

A commonly performed TACE is to mix the chemotherapeutic agents in an emulsion with lipiodol. The aim is to slow down the arterial blood flow so as to achieve longer contact time of the drug with tumour cells. In addition, there are the embolization effects to the tumour. The embolization can be temporary by using gelfoam pellets or degradable starch particles, or permanent by using coils or Ivalon particles. TACE can also be done by combining the intraarterial administration of hydrophilic chemotherapeutic agents with lipiodol in an emulsion followed by temporary or permanent embolization of the hepatic artery.

Although the results of studies with TACE have been promising, meta-analysis⁶ on the published randomized studies have failed to substantiate the benefit of TACE in any form.

HCC has been shown to shrink with TACE and unresectable HCC has become resectable.

Contraindications to TACE include main portal vein thrombosis, marked arteriovenous shunting to portal or hepatic vein, and poor liver function. Side-effects are quite common and include fever, abdominal pain, nausea and vomiting. The chemotherapeutic and embolizing agents may cause cholecystitis, pancreatitis, gastric erosions or ulcer if they are inadvertently injected into these organs.

Radiofrequency ablation (RFA)

RFA directs treatment specifically to the tumour location, thereby allowing for greater preservation of uninvolved hepatic parenchyma. This feature is particularly beneficial in patients with HCC in the background of cirrhosis, where hepatic reserve is often limited. RFA has been developed partially in response to limitations of other ablative approaches, such as cryotherapy. Overall, reported complications have been rare with RFA.⁷

Lencioni et al⁸ have reported that they consider RFA as the treatment of choice for nodular-type HCC lesions smaller than 3-4 cm. In the presence of multiple HCC nodules, RFA is an effective therapy when the patient has up to 3 lesions, preferably smaller than 3 cm each. RFA can be used as a percutaneous procedure done under imaging guidance, or as an open surgical or laparoscopically guided procedure.

At the Tata Memorial Hospital, we have performed RFA for 2 patients with HCC. Both the procedures were performed under ultrasonography guidance in the radiology room. The procedures were performed under local anaesthesia, and both patients tolerated the procedure well without any side effects.

Percutaneous ethanol injection (PEI)

Percutaneous ethanol injection (PEI) is commonly used. Although non-randomized studies showed PEI to give reasonably good results in terms of survival, post-treatment recurrence within the liver is high and occurs in almost 50% by 2 years.⁹ Side-effects occur in less than a third of the patients and include pain and fever. Complications are rare and result from the passage of ethanol into the bile ducts (resulting in cholangitis) or the portal radicles (resulting in thrombosis). The presence of ascites is a relative contraindication because it prevents adhesions between the liver and the abdominal wall and increases the likelihood of intraperitoneal bleeding.

Intra-arterial radioembolization

Conventional external radiotherapy has a limited role in the treatment of HCC because of the adverse effects of irradiation on the surrounding non-tumorous liver tissue leading to radiation hepatitis. Selective internal radiation therapy is based on the principle that if radioactive isotopes are concentrated in the tumour, a therapeutic dose of irradiation can be delivered to the tumour while the rest of the liver and the patient's body receive minimal irradiation, thus minimizing the side-effects.¹⁰

Studies have shown lipiodol I₁₃₁ and yttrium 90 microspheres to be effective in treating HCC.¹⁰ The radiation hazards to medical personnel administering a large dose of radioactive iodine to treat big tumours are significant as I₁₃₁ gives off gamma and beta irradiation.

Systemic chemotherapy

HCC is relatively resistant to most chemotherapeutic agents. Published randomized studies have failed to show any survival benefit of systemic chemotherapy for HCC patients. Systemic chemotherapy is not recommended as standard therapy outside a clinical trial protocol.

A combination of cisplatin, doxorubicin, 5-fluorouracil and interferon alpha has resulted in a partial response rate of 26%, down-staged unresectable tumours to resectable ones and induced complete pathological remission in some of the resected specimens.^11,12 The treatment, although quite toxic, shows promising results.

Conclusion

Improvements have been made in the treatment of primary liver cancers. Surgery still remains the mainstay of therapy for resectable tumours, and it offers the potential of a cure. Conservation in liver cancer includes preservation of hepatic function with adequate clearance and control of the cancer as far as possible. It is very important to offer the appropriate treatment to patients, taking into consideration their general condition and the stage of the disease.

References

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9. Shiina S, Tagawa K, Unuma T, Fujino H, Uta Y, Niwa Y, et al. Percutaneous ethanol injection therapy of hepatocellular carcinoma. Am J Roentgenol 1990;155:1221-6.

10. Lau WY. Radiotheapy with emphasis on radioembolisation for liver tumours. In: Blumgart LH, Fong Y, editors, Diseases of the Liver and Biliary Tract. 3^rd edn. London: WB Saunders Co Ltd; 2000. pp. 1545-64.

11. Lau WY, Leung TW, Lai BS, Liew CT, Ho SK, Yu SC, Tang AM. Preoperative systemic chemoimmunotherapy and sequential resection for unresectable hepatocellular carcinoma. Ann Surg 2001;233:236-41.

12. Leung TW, Patt YZ, Lau WY, Ho SK, Yu SC, Chan AT, et al. Complete pathological remission is possible with systemic combination chemotherapy for inoperable hepatocellular carcinoma. Clin Cancer Research 1999;5:1676-81.

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