Is needle biopsy of the liver necessary to diagnose HCC ?

Editor,—Schotman and colleagues (

Gut1999;>45:626–7

[OpenUrl][1][PubMed][2][Web of Science][3]

) reported a patient with subcutaneous seeding of hepatocellular carcinoma (HCC) after percutaneous needle biopsy together with a review of 14 similar cases and correctly outlined the necessity for a critical evaluation of the role of needle biopsy in resectable HCC.1-4 

We agree with their conclusion, namely that: (i) a needle biopsy may be indicated only if it is not possible to diagnose HCC by other means (namely increased α fetoprotein (AFP) concentrations, spiral computed tomography (CT), magnetic resonance imaging); in these cases, a single pass with a large needle (18 gauge) may be preferable to multiple passes with smaller calibre needles; (ii) needle biopsies are not indicated to …

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EDITOR,-Schotman and colleagues (Gut 1999;45:626-7) reported a patient with subcutaneous seeding of hepatocellular carcinoma (HCC) after percutaneous needle biopsy together with a review of 14 similar cases and correctly outlined the necessity for a critical evaluation of the role of needle biopsy in resectable HCC. [1][2][3][4] We agree with their conclusion, namely that: (i) a needle biopsy may be indicated only if it is not possible to diagnose HCC by other means (namely increased fetoprotein (AFP) concentrations, spiral computed tomography (CT), magnetic resonance imaging); in these cases, a single pass with a large needle (18 gauge) may be preferable to multiple passes with smaller calibre needles; (ii) needle biopsies are not indicated to confirm HCC in patients suitable for liver transplantation; and (iii) the entire needle tract should be resected at surgery for the primary tumour. This has been important in other skin recurrences, namely those after laparoscopic cholecystectomy for undiagnosed gall bladder carcinoma. 5 6 However, we have some questions and comments concerning the reported case. Firstly, why did the authors perform tumour biopsy in a 30 year old woman with hepatitis B liver cirrhosis and raised serum AFP, showing a 2 cm diameter subcapsular nodule in segment V and two additional satellite lesions in the same segment? Adequate imaging procedures were already available four years ago. In fact, the patient had percutaneous liver biopsy together with an informative diagnostic procedure such as spiral CT. In addition, subcapsular liver lesions are known to give a high rate of both subcutaneous recurrence and intraperitoneal subdiaphragmatic seeding. 1 Therefore, in contrast with recurrence after laparoscopic surgery which mostly cluster around abdominal port tracts, 5 6 simple removal of the needle tract could not be sufficient to prevent the side eVects of percutaneous liver biopsy. Secondly, why did they perform right hemihepatectomy in a cirrhotic liver rather than segment V segmentectomy? The latter could be a similarly adequate procedure while preserving better residual liver function.
The authors should be congratulated for focusing once again on a very important question (to biopsy or not to biopsy liver nodules in suspected HCC in the present era of highly eVective imaging) and for their collection of 15 cases, which is obviously an underestimation of what occurs in practice and is currently observed in many transplantation centres. However, their message for the reader should be clearer as there is an apparent contradiction between what they state and what they actually did.

Reply
EDITOR,-We read with interest the letter of Cetta et al in which they discussed our case (Gut 1999;45:626-7) of subcutaneous seeding of a hepatocellular carcinoma (HCC) after percutaneous needle biopsy. Firstly, they state that a needle biopsy was not indicated in the case presented. It must be stated that the biopsy was performed elsewhere before the patient was admitted to our hospital. Secondly, they suggest that a smaller partial hepatectomy might have been suYcient to treat the HCC in this 30 year old woman with hepatitis B liver cirrhosis.
In the case presented there was no deterioration in liver function or impaired functional reserve after resection. The postoperative course was uneventful.
In general, we agree with the opinion to limit resection as far as possible and presently we would perform a segmentectomy.

Management of gastric fundal varices associated with a gastrorenal shunt
EDITOR,-We read with great interest the article by Jalan and colleagues (Gut 2000;46:578-81) on the clinical position of transjugular intrahepatic portosystemic stent-shunt (TIPSS). This procedure is a useful method of reducing portal pressure by creating a portosystemic shunt in the liver. They suggested that TIPSS can be a successful treatment for bleeding gastric fundal varices (FV) unresponsive to pharmacological and endoscopic therapy. However, Sanyal et al reported that TIPSS was ineVective for FV associated with a large gastrorenal shunt, even when the hepatic venous pressure gradient falls below the critical bleeding threshold of 12 mm Hg. 1 The behaviour of varices at diVerent sites seems to diVer. 2 Therefore, FV should be treated on the basis of their haemodynamics.
FV arise from the dilation of short or posterior gastric veins and are frequently associated with a large gastrorenal shunt that decompresses the portal system. 3 Balloon occluded retrograde transvenous obliteration (B-RTO) is a novel radiological treatment for FV that was developed by Kanagawa and colleagues. 4 This procedure involves insertion of a balloon catheter into a gastrorenal shunt via the femoral or internal jugular vein. It is similar to TIPSS but less invasive. The therapeutic eVect of B-RTO is excellent without major complications, even for patients with poor liver function. 4 5 However, there have been few controlled trials of this technique. 6 Patients with bleeding from FV have a high risk of dying from an episode of variceal bleeding or from liver failure, even when TIPSS is successful in stopping acute bleeding. 7 Hence patients with high risk FV should preferably undergo prophylactic treatment. Although the risk factors for the first episode of bleeding from FV are still not clear, Kim et al determined the one year probability of bleeding as a function of all possible combinations of two endoscopic variables (variceal size and the presence of red spots) for patients in Child's class A, B, or C. 8 According to their classification, FV with a one year probability of bleeding (16%) can be considered as high risk varices.
As TIPSS seems to be ineVective for FV associated with a gastrorenal shunt, blockers or nitrates (which are widely used to treat high risk oesophageal varices) may also be ineVective for primary prophylaxis of bleeding from FV. Accordingly, prophylactic B-RTO may be justifiable due to its simplicity and safety.
Because the gastrorenal shunt tends to be occluded after B-RTO, 4 5 however, the long term eVect of this procedure on portal haemodynamics needs to be evaluated.
Although a prospective randomised study comparing B-RTO with TIPSS for the prevention of bleeding or rebleeding from FV is still needed, we hope that B-RTO will become a firstline treatment for high risk FV associated with a gastrorenal shunt in the near future. Matsumoto et al also suggest that there is likely to be a place for B-RTO in the primary prophylaxis of bleeding from fundal varices and that pharmacological agents have no place in their management. Again, the data for their suggestion do not exist in the literature. We think that it is extremely diYcult to suggest failure of pharmacological therapy for primary prophylaxis of fundal varices based on the assumption that portal pressure changes are unlikely to be important in the management of fundal varices. With research and clinical evidence pointing to a prevalence of HCV infection far in excess of human immunodeficiency virus (HIV), 1 the issue has now become urgent. Patients and clinicians alike will await the forthcoming NICE appraisal in the hope it recommends in favour of allocating suYcient resources to cover treatment costs for those most in need and best able to benefit. However, while a positive response will be welcome it will also uncover issues that have still to be fully addressed. These centre on who will/should be selected for treatment and the eVects of the treatment itself.
Regarding the first issue there remains a debate around who will benefit most from treatment. The tendency is to assess outcome in terms of genotyping, age, duration of viraemia, extent of liver damage, and other complicating factors, such as continued drug and alcohol abuse. While there may be some validity to such categorisations, they are not at all absolute and can demoralise patients. Nevertheless, and leaving such considerations aside, if HCV infection is as widespread as some clinicians anticipate, it would be unrealistic to assume that funding will be available to treat everyone. This means that some form of treatment selection will need to be adopted. Should this occur, the question remains as to how clinicians will make choices and what criteria they will use. Furthermore, will protocols be in place to govern these criteria to ensure they are standardised nationwide?
Although Dusheiko et al cite the potential priority given by the NHS to combination treatment as the salient issue, this needs to be addressed in conjunction with the equally important matter of who should receive this treatment. Whether patients are oVered standard combination therapy, combination therapy with pegylated interferon (PEG IFN), or PEG IFN alone is in some ways secondary to the issue of who is actually going to be given treatment. Will it be based on disease progression or expected response to treatment, or both?
Before considering this further, a factor that needs to be implicated in discussions around HCV, but which clinicians tend to underestimate, is patient tolerance and possible lingering eVects of therapy. Although there seems to be a fairly clear cut case in favour of the greater eYcacy of combination treatment, it is harder for patients to tolerate than monotherapy with IFN, particularly when taken over 48 weeks. Dusheiko et al state that the 20% (approximately) of patients who discontinue therapy before 48 weeks usually do so because of "insomnia, depression, irritability, or anaemia". This would seem to be a minimising of the extent and intensity of side eVects from combination therapy, which can be equally as debilitating for some patients as those of chemotherapy. In addition, the sequelae of treatment can sometimes linger for months following its cessation.
Given the potential severity of side eVects, many patients with mild HCV have resisted conventional treatment methods and opted instead to try to minimise disease progression by recourse to alternative therapies. A recent nationwide trial oVered to patients with mild HCV failed to recruit anywhere near its target numbers. This would seem to imply that those with less risk of progressive disease, and therefore less motivation to seek a cure, are more resistant to therapeutic intervention.
Notwithstanding the obvious factor of the greater and more urgent need of treatment for patients with progressive disease following HCV infection, perhaps this trend in mild HCV suVerers might oVer some insight as to how patients sometimes choose for themselves, suggesting to those involved with the healthcare of HCV patients an indicator of how best to prioritise treatment should such selection prove necessary.

Reply
EDITOR,-Our preliminary study set out to examine the clinical usefulness of screening a targeted population for genetic haemochromatosis. The costing given in our paper was as stated, based solely on laboratory costs, a summary of which is given below. Costs of the clinician, nursing, and clerical time were not included in the paper, and are detailed below. Laboratory costs: + Screening for blood samples with elevated ALT incurred no additional costs as these samples were processed routinely as part of the normal hospital and GP biochemistry requests. + The marginal costs for the measurement of 1490 serum irons and transferrins, £1085; 33 serum ferritins, £51; and genetic testing: £264 (total £1400). + Although serum ferritins were performed on all 1490 specimens as part of the study, at a cost of £1788, we felt that they did not help in the screening process. Thus we advocated "In those patients found to have a raised ALT, the cost of screening with iron saturation and follow up when appropriate with ferritin and gene testing would be £1400".
Other costs: We were awarded a research grant of £5000 from the Health Authority, and the rest of the money was used for employing a medical laboratory assistant, (8 h/week) who picked out the relevant specimens and batched them for future testing. Information on haemochromatosis, plus oVering genetic screening to the 56 patients found to have a transferrin saturation >60 % and recontacting the non-responders was done by means of a standard letter to the clinicians who had requested the original liver fuction tests. Consent for genetic testing was obtained by these clinicians. Management of the 12 patients (homozygotes and compound heterozygotes) was undertaken (with no extra funding) by one of the authors (MB) as part of the routine Clinical Haematology service.
Since then, the Health Authority has awarded us continuing revenue for this targeted screening, and included in these monies are the clinical, clerical, and nursing costs incurred in providing this service as a routine for patients in our District.