Annals of the Royal College of Surgeons of England (1975) vol 56 ASPECTS OF DIAGNOSIS*
Liver
biopsy
Ronald W Raven OBE TD FRCS Consulting Surgeon, Royal Marsden Hospital and Institute of Cancer Research. Consulting Surgeon, Westminster Hospital
Summary An account is given of the findings obtained with open liver biopsy in i i i patients with various diseases, including 78 with cholecystitis and cholelithiasis where unsuspected liver pathology, including biliary cirrhosis, was found in 37 patients. An exact diagnosis of hepatic metastasis by biopsy has therapeutic importance in malignant diseases, and in some patients, particularly those with argentaffinoma, liver involvement is compatible wvith normal life for many years. Introduction Knowledge concerning the structure and function of the liver has been increased by using the electron microscope and more sensitive biochemical tests, but our understanding of the function of the various parts of this compound tubular gland is still imperfect. The liver function tests wAe use today indicate only gross abnormalities, for even with severe liver damage these may give near-normal readings. Valuable additional information is provided by liver biopsy to demonstrate structural changes and unsuspected diseases. This exact biopsy diagnosis can be decisive in the prolongation of life. Liver biopsy is performed by three techniques: by aspiration, by peritoneoscopy, and at laparotomy. The relative advantages of *Fellows interested in submitting papers for this series should first write to the Editor.
TABLE i Liver biopsy in i i i cases No. of Normal Abnormal Disease biopsies histology histology
Cholecystitis and cholelithiasis Ulcerative colitis Carcinoma, various sites Argentaffinoma Laennec's cirrhosis Hepatic infarct Hepatic hydatid cysts Chronic gastric ulcer Total
78
41
6
2
I9 3
37 4
I I I
8 I 3 -I -I I -
2
-
I II
2
44
67
(39.6%)
(60.3 %)
these methods are not discussed, for my purpose is to describe my findings in a series of i i i patients with different diseases (Table I) on whom I performed liver biopsy at laparotomy for definitive treatment or for biopsy alone. A wedge of tissue about I cm long was removed from the anterior edge of the right hepatic lobe, sited where any abnormality was seen. Routine liver function tests were performed to correlate structure with function.
Cholecystitis and cholelithiasis Liver biopsy was performed at the time of cholecystectomy on 77 patients with cholecystitis varving from acute to chronic vari-
considerationi
with a view to publication in
go
Ronald W Raven
eties (29 patients had associated cholelithiasis or cholesterolosis) and on i patient referred wvith a postcholecystectomy fibrous stricture of the common bile duct which I reconstructed. I had not realized before doing this work that the liver is so often implicated, and sometimes seriousW, in gallbladder diseases, for various structtral changes were demonstrated in 37 patients (47.4%); normal liver histology was seen in 4' patients
(5y .6%). Biliary cirrhosis A surprise finding was biliary cirrhosis in 5 patients (6.4%) which might not have been discovered without liver biopsy. Brief clinical details are given about these patients. In one the cirrhosis had progressed to amyloidosis. Case i Female aged 6i; cholecystectomy for an empyema of the gallbladder. Liver biopsy showed fairly severe biliary cirrhosis with dilatation of biliary sinusoids, perilobular fibrosis, lymphocytic infiltration, and proliferation of bile ducts. Liver function tests showed raised serum alkaline phos-
)hatase (I5 King-Armstrong (KA) units). (,ase 2 Female aged 76; cholecystectomy for chronic cholecystitis with cholelithiasis (wall greatly thickened and mucosa ulcerated). Marked atrophy of right hepatic lobe (could be held in palm of hand); left lobe greatly hypertrophied. Biopsy of both lobes showed dilated bile ducts and duct proliferation surrounded by a little dense fibrous tissue, large collection of lymphocytes and plasma cells, and much structureless eosinophilic material taking Congo red stain for amyloid. Occasional distorted liver parenchymal cells were present. Numerous arteries showed endarteritis obliterans and amyloid changes. The condition was amyloidosis probably secondary to biliary cirrhosis. Liver function tests were abnormnal.
Case 3 Female aged 69; cholecystectomy for chronic cholecystitis with cholelithiasis (thickened vall and ulcerated mucosa). Liver biopsy showed multilobular cirrhosis.
Case 4 Male aged 8o; cholecystectomy for chronic cholecystitis and cholelithiasis (oedema and
fibrosis of wall). Liver biopsy showed multilobular cirrhosis. Liver function tests showed raised serum alkaline phosphatase (i6 KA units). Case 5 Female aged 55 referred with recurrent cholangitis and jaundice due to a traumatic fibrous
stricture of the common bile duct which was reconstructed. Liver biopsy showed moderate fibrosis of the portal tracts and little proliferation with bile plugging. Inflammatory reaction (polymorphs, lymphocytes, and plasma cells) in portal tracts especially around the bile ducts. Appearances were those of early secondary biliary cirrhosis with cholangitis. Liver function tests abnormal.
Cholangiohepatitis Liver biopsy showed this abnormality in I male and 2 females. The former had a cholecystectomy for florid cholecystitis with cholelithiasis (pus in gallbladder and ulceration of its mucosa). Liver biopsy showed the portal tracts infiltrated with chronic inflammatory cells and a moderate increase in fibrous tissue, with mild centrilobular fatty change. Liver function tests normal. One female had a cholecystectomy for chronic cholecystitis with cholelithiasis (wall greatly thickened, mucosa ulcerated, and haemorrhagic pus in the cavity). Liver biopsy showed cholangiohepatitis. Liver function tests normal. The other female had a cholecystectomy for cholelithiasis. Liver biopsy showed well-marked small round cell infiltration of the portal tracts, possibly the result of cholangiohepatitis. Liver function tests showed an increase in turbidity tests. Other liver changes In 23 patients there was an inflammatory cell infiltration of the periportal tracts which varied in intensity. The cells were chiefly lymphocytes, but plasma cells and polymorphonuclear leucocytes were also found. These inflammatory changes are part of the biliary tract inflammation and are expected to subside after cholecystectomy. Periportal fibrosis of various degrees, but not so severe as in biliary cirrhotis, was found in i o patients and is evidence of more permanent liver changes. Unless
Liver biopsy this fibrosis progresses to biliary cirrhosis it xvill be likely to cause no trouble. In 3 more patients this periportal fibrosis was associated with proliferation of the intrahepatic bile ducts. Pus cells were present in the hepatic sinusoids in one patient and in another there was some destruction of the liver parenchyma. Subcapsular fibrosis was seen in 3 patients and in another a severe chronic inflammatory reaction was present on the liver surface, with granulation tissue and chronic inflammatory cells. Fatty changes are common in the liver; they were seen in I3 patients-severe in 2, moderate in 7, and mild in 4. In i severe case the liver parenchyma was almost completely relplaced by fat apart from a narrow rim of normal cells at the periphery of the liver lobules and the portal tracts were widened by fibrosis and infiltrated by lymphocytes, but there was no bile retention. In this patient the liver function tests were normal. In the other severe case there was cholesterolosis of the gallbladder and the liver function tests were also normal. In one patient there was dilatation of the intrahepatic radicals of the portal vein associated with mild fatty degeneration and periportal round cell infiltration. In one patient the portal tracts were widened and there was pronounced mononuclear exudate with some centrilobular bile stenosis; these were the appearances of extrahepatic biliary obstruction not yet progressed to biliary cirrhosis. This patient had a cholecystectomy for cholelithiasis (gallbladder full of small stones); the extrahepatic bile ducts were normal but the spleen was enlarged. The liver function tests were abnormal, serum alkaline phosphatase being raised (22 KA units). Three years later the tests were normal and the patient was well. Discussion The results of liver biopsy in this group demonstrate the frequency of in-
91
flammatory and degenerative liver changes in cholecystitis and cholelithiasis. Such changes vary from mild inflammation to biliary cirrhosis and can be present without causing clinical suspicion or abnormal liver function tests. As expected, the latter show abnormalities in biliary cirrhosis-chiefly a mild rise in serum alkaline p4o0sphatase activity. Four patients with biliary cirrhosis had severe cholecystitis with pus formation, mucosal ulceration, and fibrosis of the wall. In one patient amyloidosis was associated with biliary cirrhosis. The fifth patient had recurrent attacks of cholangitis from a fibrous stricture of the common bile duct; the subsequent cirrhosis is understandable. Cholangiohepatitis was demonstrated also in patients with severe cholecystitis and pus in the cavity and is expected to resolve when the inflammatory focus is removed, without progression to biliary cirrhosis. The latter condition may well develop in patients with gallbladder infections of long standing. Periportal fibrosis, less severe than biliary cirrhosis, was seen in I3 patients and might progress to biliary cirrhosis. The important question is whether gallbladder infection is responsible for the biliary cirrhosis; this is likely for we know that liver infection can be present for long periods, as exemplified by the typhoid bacillus. These biopsies show that all degrees of liver infection from necrosis to periportal round cell infiltration coexist with cholecystitis and such infection should be relieved by cholecystectomy. Attention is also called to the importance of fatty degeneration in the liver in patients with gallbladder diseases, for it is a fairly common finding (i6.7%). Such degeneration can be severe and associated with fibrosis, and may ultimately cause cirrhosis. It is of clinical importance to know that fatty degeneration is present for by dietary treatment it may be possible to reverse the process. General obesity and deranged cholesterol meta-
92
Ronald W Raven
bolism are often associated with gallbladder diseases and the liver function tests can be normal even when marked fatty degeneration is present, Ulcerative colitis The hepatic lesions in this disease have been discussed elsewhere1. Six patients underwent total colectomy and liver biopsy. In cases this proved normal. One patient aged 39 was under conservative treatment when it was found that her liver function was deteriorating, the serum alkaline phosphatase having risen to 59 KA units, and because of this condition it was decided to perform a total colectomy with ileorectal anastomosis. Liver biopsy showed multilobular fine cirrhosis. After operation her liver function improved steadily so that 4 years later the alkaline phosphatase level had fallen to 22 KA units. In one patient the liver showed scanty fibrosis and slight periportal round cell infiltration and in another this was associated with mild fatty degeneration of irregular distribution. In one patient moderate fatty degeneration was present. This is probably caused by malnutrition and toxaemia. The liver changes in ulcerative colitis vary from mild to severe, although cirrhosis is not common. It is important to recognize these changes so that the liver is protected from further damage by effective treatment of the ulcerative colitis. For example, marked deterioration in liver function was the decisive factor for total colectomy in one patient here with biliary 2
cirrhosis.
Malignant diseases Approximately one-half of patients who die with malignant diseases have hepatic metastases. In such patients if the serum alkaline phosphatase is above I3 KA units I am always suspicious of hepatic metastases. Hepatic scanograms are also helpful for diagnosis, but in some patients a liver biopsy is required
confirm the presence and variety of the malignancy. For instance, in this series was a man who had orchidectomy for seminoma and 3 years later developed hepatomegaly; the scanogram showed metastatic tumours. It was necessary, however, to know if these were seminomas because radiotherapy would then be beneficial. In fact we know that such hepatic involvement by seminoma is rare, and open liver biopsy revealed adenocarcinoma metastases from a silent primary tumour so that different treatment was instituted. In this series (Table II) 22 patients underwent open liver biopsy with i8 positives-I7 for carcinoma, 2 for an unknown site, and 3 for argentaffinoma. The 3 patients with argentaffinoma showed several interesting features. One patient underwent a partial oesophagogastrectomy and left hepatectomy for an adenocarcinoma also invading the left hepatic lobe. Microscopy confirmed the adenocarcinoma but also revealed an unsuspected argentaffinoma metastasis in the liver. Four weeks later I performed a laparotomy and partial enterectomy for a primary argentaffinoma in the terminal ileum. Another patient underwent a right hemicolectomy for ileal argentaffinoma and hepatic biopsy for a metastasis and survived many years. The
to
TABLE
II
Liver biopsy in malignant diseases
No. Positive Negative Primary tumour 2 2 Carcinoma of breast I I Carcinoma of oesophagus I 2 Carcinoma of stomach 3 Carcinoma of colon 4 4 Carcinoma of rectum 3 3 2 I Carcinoma of pancreas 3 I I Carcinoma of gallbladder 3 3 Argentaffinoma of ileum Seminoma of testis and I unknown primary I* I* I Unknown Total 22 4 I8 *Adenocarcinoma
Liver biopsy third patient underwent a partial enterectomy for ileal argentaffinoma and liver biopsy for metastases; both lobes contained metastases up to i cm in diameter. This patient is alive and well I I4' years later and has given birth to a normal child. The presence and type of hepatic metastases can influence treatment. For example, there may be a solitary metastasis or even several, localized in one lobe, with an operable primary tumour without other demonstrable disease, which can be treated by hepatic lobectomy. Minimal metastatic disease from primary breast carcinoma in patients below 65 years can be effectively treated with oophorectomy and adrenalectomy, but when large metastases are present I have found endocrine surgery gives poor results. Metastatic disease from gastrointestinal carcinoma is responsive to 5-fluorouracil therapy. A number of patients with hepatic metastases live on in comfort sometimes for several years.
93
chronic gastric ulcer. In one the liver showed fibrosis, inflammatory cell infiltration, and proliferation of bile canaliculi. In the other there was lymphocytic infiltration of the portal tracts and patchy fatty degeneration. In a patient with multiple hepatic hydatid cysts the liver showed fibrosis of the portal tracts, which were infiltrated by lymphocytes and eosinophils. A few eosinophils were scattered throughout the liver parenchyma. The liver function tests were normal. In a patient with liver infarction patchy fatty degeneration only was seen. One patient with hepatomegaly was proved to have Lacnnec's cirrhosis; the liver function tests were normal. In this work I have had valuable co-operation for many years from the staffs of the pathology departments of Westminster Hospital and the Royal Marsden Hospital, and this I gratefully acknowledge.
Reference Other conditions Raven, R W (1957) Proceedings of the Royal Society Biopsy was performed on 2 patients with a of Medicine, 50, 775.
Liver
biopsy
Ronald W Raven OBE TD FRCS Consulting Surgeon, Royal Marsden Hospital and Institute of Cancer Research. Consulting Surgeon, Westminster Hospital
Summary An account is given of the findings obtained with open liver biopsy in i i i patients with various diseases, including 78 with cholecystitis and cholelithiasis where unsuspected liver pathology, including biliary cirrhosis, was found in 37 patients. An exact diagnosis of hepatic metastasis by biopsy has therapeutic importance in malignant diseases, and in some patients, particularly those with argentaffinoma, liver involvement is compatible wvith normal life for many years. Introduction Knowledge concerning the structure and function of the liver has been increased by using the electron microscope and more sensitive biochemical tests, but our understanding of the function of the various parts of this compound tubular gland is still imperfect. The liver function tests wAe use today indicate only gross abnormalities, for even with severe liver damage these may give near-normal readings. Valuable additional information is provided by liver biopsy to demonstrate structural changes and unsuspected diseases. This exact biopsy diagnosis can be decisive in the prolongation of life. Liver biopsy is performed by three techniques: by aspiration, by peritoneoscopy, and at laparotomy. The relative advantages of *Fellows interested in submitting papers for this series should first write to the Editor.
TABLE i Liver biopsy in i i i cases No. of Normal Abnormal Disease biopsies histology histology
Cholecystitis and cholelithiasis Ulcerative colitis Carcinoma, various sites Argentaffinoma Laennec's cirrhosis Hepatic infarct Hepatic hydatid cysts Chronic gastric ulcer Total
78
41
6
2
I9 3
37 4
I I I
8 I 3 -I -I I -
2
-
I II
2
44
67
(39.6%)
(60.3 %)
these methods are not discussed, for my purpose is to describe my findings in a series of i i i patients with different diseases (Table I) on whom I performed liver biopsy at laparotomy for definitive treatment or for biopsy alone. A wedge of tissue about I cm long was removed from the anterior edge of the right hepatic lobe, sited where any abnormality was seen. Routine liver function tests were performed to correlate structure with function.
Cholecystitis and cholelithiasis Liver biopsy was performed at the time of cholecystectomy on 77 patients with cholecystitis varving from acute to chronic vari-
considerationi
with a view to publication in
go
Ronald W Raven
eties (29 patients had associated cholelithiasis or cholesterolosis) and on i patient referred wvith a postcholecystectomy fibrous stricture of the common bile duct which I reconstructed. I had not realized before doing this work that the liver is so often implicated, and sometimes seriousW, in gallbladder diseases, for various structtral changes were demonstrated in 37 patients (47.4%); normal liver histology was seen in 4' patients
(5y .6%). Biliary cirrhosis A surprise finding was biliary cirrhosis in 5 patients (6.4%) which might not have been discovered without liver biopsy. Brief clinical details are given about these patients. In one the cirrhosis had progressed to amyloidosis. Case i Female aged 6i; cholecystectomy for an empyema of the gallbladder. Liver biopsy showed fairly severe biliary cirrhosis with dilatation of biliary sinusoids, perilobular fibrosis, lymphocytic infiltration, and proliferation of bile ducts. Liver function tests showed raised serum alkaline phos-
)hatase (I5 King-Armstrong (KA) units). (,ase 2 Female aged 76; cholecystectomy for chronic cholecystitis with cholelithiasis (wall greatly thickened and mucosa ulcerated). Marked atrophy of right hepatic lobe (could be held in palm of hand); left lobe greatly hypertrophied. Biopsy of both lobes showed dilated bile ducts and duct proliferation surrounded by a little dense fibrous tissue, large collection of lymphocytes and plasma cells, and much structureless eosinophilic material taking Congo red stain for amyloid. Occasional distorted liver parenchymal cells were present. Numerous arteries showed endarteritis obliterans and amyloid changes. The condition was amyloidosis probably secondary to biliary cirrhosis. Liver function tests were abnormnal.
Case 3 Female aged 69; cholecystectomy for chronic cholecystitis with cholelithiasis (thickened vall and ulcerated mucosa). Liver biopsy showed multilobular cirrhosis.
Case 4 Male aged 8o; cholecystectomy for chronic cholecystitis and cholelithiasis (oedema and
fibrosis of wall). Liver biopsy showed multilobular cirrhosis. Liver function tests showed raised serum alkaline phosphatase (i6 KA units). Case 5 Female aged 55 referred with recurrent cholangitis and jaundice due to a traumatic fibrous
stricture of the common bile duct which was reconstructed. Liver biopsy showed moderate fibrosis of the portal tracts and little proliferation with bile plugging. Inflammatory reaction (polymorphs, lymphocytes, and plasma cells) in portal tracts especially around the bile ducts. Appearances were those of early secondary biliary cirrhosis with cholangitis. Liver function tests abnormal.
Cholangiohepatitis Liver biopsy showed this abnormality in I male and 2 females. The former had a cholecystectomy for florid cholecystitis with cholelithiasis (pus in gallbladder and ulceration of its mucosa). Liver biopsy showed the portal tracts infiltrated with chronic inflammatory cells and a moderate increase in fibrous tissue, with mild centrilobular fatty change. Liver function tests normal. One female had a cholecystectomy for chronic cholecystitis with cholelithiasis (wall greatly thickened, mucosa ulcerated, and haemorrhagic pus in the cavity). Liver biopsy showed cholangiohepatitis. Liver function tests normal. The other female had a cholecystectomy for cholelithiasis. Liver biopsy showed well-marked small round cell infiltration of the portal tracts, possibly the result of cholangiohepatitis. Liver function tests showed an increase in turbidity tests. Other liver changes In 23 patients there was an inflammatory cell infiltration of the periportal tracts which varied in intensity. The cells were chiefly lymphocytes, but plasma cells and polymorphonuclear leucocytes were also found. These inflammatory changes are part of the biliary tract inflammation and are expected to subside after cholecystectomy. Periportal fibrosis of various degrees, but not so severe as in biliary cirrhotis, was found in i o patients and is evidence of more permanent liver changes. Unless
Liver biopsy this fibrosis progresses to biliary cirrhosis it xvill be likely to cause no trouble. In 3 more patients this periportal fibrosis was associated with proliferation of the intrahepatic bile ducts. Pus cells were present in the hepatic sinusoids in one patient and in another there was some destruction of the liver parenchyma. Subcapsular fibrosis was seen in 3 patients and in another a severe chronic inflammatory reaction was present on the liver surface, with granulation tissue and chronic inflammatory cells. Fatty changes are common in the liver; they were seen in I3 patients-severe in 2, moderate in 7, and mild in 4. In i severe case the liver parenchyma was almost completely relplaced by fat apart from a narrow rim of normal cells at the periphery of the liver lobules and the portal tracts were widened by fibrosis and infiltrated by lymphocytes, but there was no bile retention. In this patient the liver function tests were normal. In the other severe case there was cholesterolosis of the gallbladder and the liver function tests were also normal. In one patient there was dilatation of the intrahepatic radicals of the portal vein associated with mild fatty degeneration and periportal round cell infiltration. In one patient the portal tracts were widened and there was pronounced mononuclear exudate with some centrilobular bile stenosis; these were the appearances of extrahepatic biliary obstruction not yet progressed to biliary cirrhosis. This patient had a cholecystectomy for cholelithiasis (gallbladder full of small stones); the extrahepatic bile ducts were normal but the spleen was enlarged. The liver function tests were abnormal, serum alkaline phosphatase being raised (22 KA units). Three years later the tests were normal and the patient was well. Discussion The results of liver biopsy in this group demonstrate the frequency of in-
91
flammatory and degenerative liver changes in cholecystitis and cholelithiasis. Such changes vary from mild inflammation to biliary cirrhosis and can be present without causing clinical suspicion or abnormal liver function tests. As expected, the latter show abnormalities in biliary cirrhosis-chiefly a mild rise in serum alkaline p4o0sphatase activity. Four patients with biliary cirrhosis had severe cholecystitis with pus formation, mucosal ulceration, and fibrosis of the wall. In one patient amyloidosis was associated with biliary cirrhosis. The fifth patient had recurrent attacks of cholangitis from a fibrous stricture of the common bile duct; the subsequent cirrhosis is understandable. Cholangiohepatitis was demonstrated also in patients with severe cholecystitis and pus in the cavity and is expected to resolve when the inflammatory focus is removed, without progression to biliary cirrhosis. The latter condition may well develop in patients with gallbladder infections of long standing. Periportal fibrosis, less severe than biliary cirrhosis, was seen in I3 patients and might progress to biliary cirrhosis. The important question is whether gallbladder infection is responsible for the biliary cirrhosis; this is likely for we know that liver infection can be present for long periods, as exemplified by the typhoid bacillus. These biopsies show that all degrees of liver infection from necrosis to periportal round cell infiltration coexist with cholecystitis and such infection should be relieved by cholecystectomy. Attention is also called to the importance of fatty degeneration in the liver in patients with gallbladder diseases, for it is a fairly common finding (i6.7%). Such degeneration can be severe and associated with fibrosis, and may ultimately cause cirrhosis. It is of clinical importance to know that fatty degeneration is present for by dietary treatment it may be possible to reverse the process. General obesity and deranged cholesterol meta-
92
Ronald W Raven
bolism are often associated with gallbladder diseases and the liver function tests can be normal even when marked fatty degeneration is present, Ulcerative colitis The hepatic lesions in this disease have been discussed elsewhere1. Six patients underwent total colectomy and liver biopsy. In cases this proved normal. One patient aged 39 was under conservative treatment when it was found that her liver function was deteriorating, the serum alkaline phosphatase having risen to 59 KA units, and because of this condition it was decided to perform a total colectomy with ileorectal anastomosis. Liver biopsy showed multilobular fine cirrhosis. After operation her liver function improved steadily so that 4 years later the alkaline phosphatase level had fallen to 22 KA units. In one patient the liver showed scanty fibrosis and slight periportal round cell infiltration and in another this was associated with mild fatty degeneration of irregular distribution. In one patient moderate fatty degeneration was present. This is probably caused by malnutrition and toxaemia. The liver changes in ulcerative colitis vary from mild to severe, although cirrhosis is not common. It is important to recognize these changes so that the liver is protected from further damage by effective treatment of the ulcerative colitis. For example, marked deterioration in liver function was the decisive factor for total colectomy in one patient here with biliary 2
cirrhosis.
Malignant diseases Approximately one-half of patients who die with malignant diseases have hepatic metastases. In such patients if the serum alkaline phosphatase is above I3 KA units I am always suspicious of hepatic metastases. Hepatic scanograms are also helpful for diagnosis, but in some patients a liver biopsy is required
confirm the presence and variety of the malignancy. For instance, in this series was a man who had orchidectomy for seminoma and 3 years later developed hepatomegaly; the scanogram showed metastatic tumours. It was necessary, however, to know if these were seminomas because radiotherapy would then be beneficial. In fact we know that such hepatic involvement by seminoma is rare, and open liver biopsy revealed adenocarcinoma metastases from a silent primary tumour so that different treatment was instituted. In this series (Table II) 22 patients underwent open liver biopsy with i8 positives-I7 for carcinoma, 2 for an unknown site, and 3 for argentaffinoma. The 3 patients with argentaffinoma showed several interesting features. One patient underwent a partial oesophagogastrectomy and left hepatectomy for an adenocarcinoma also invading the left hepatic lobe. Microscopy confirmed the adenocarcinoma but also revealed an unsuspected argentaffinoma metastasis in the liver. Four weeks later I performed a laparotomy and partial enterectomy for a primary argentaffinoma in the terminal ileum. Another patient underwent a right hemicolectomy for ileal argentaffinoma and hepatic biopsy for a metastasis and survived many years. The
to
TABLE
II
Liver biopsy in malignant diseases
No. Positive Negative Primary tumour 2 2 Carcinoma of breast I I Carcinoma of oesophagus I 2 Carcinoma of stomach 3 Carcinoma of colon 4 4 Carcinoma of rectum 3 3 2 I Carcinoma of pancreas 3 I I Carcinoma of gallbladder 3 3 Argentaffinoma of ileum Seminoma of testis and I unknown primary I* I* I Unknown Total 22 4 I8 *Adenocarcinoma
Liver biopsy third patient underwent a partial enterectomy for ileal argentaffinoma and liver biopsy for metastases; both lobes contained metastases up to i cm in diameter. This patient is alive and well I I4' years later and has given birth to a normal child. The presence and type of hepatic metastases can influence treatment. For example, there may be a solitary metastasis or even several, localized in one lobe, with an operable primary tumour without other demonstrable disease, which can be treated by hepatic lobectomy. Minimal metastatic disease from primary breast carcinoma in patients below 65 years can be effectively treated with oophorectomy and adrenalectomy, but when large metastases are present I have found endocrine surgery gives poor results. Metastatic disease from gastrointestinal carcinoma is responsive to 5-fluorouracil therapy. A number of patients with hepatic metastases live on in comfort sometimes for several years.
93
chronic gastric ulcer. In one the liver showed fibrosis, inflammatory cell infiltration, and proliferation of bile canaliculi. In the other there was lymphocytic infiltration of the portal tracts and patchy fatty degeneration. In a patient with multiple hepatic hydatid cysts the liver showed fibrosis of the portal tracts, which were infiltrated by lymphocytes and eosinophils. A few eosinophils were scattered throughout the liver parenchyma. The liver function tests were normal. In a patient with liver infarction patchy fatty degeneration only was seen. One patient with hepatomegaly was proved to have Lacnnec's cirrhosis; the liver function tests were normal. In this work I have had valuable co-operation for many years from the staffs of the pathology departments of Westminster Hospital and the Royal Marsden Hospital, and this I gratefully acknowledge.
Reference Other conditions Raven, R W (1957) Proceedings of the Royal Society Biopsy was performed on 2 patients with a of Medicine, 50, 775.
