Dragon Lai Hcc Study 1981

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Clin ca Features o f Hepa tocellula r Carcinoma:Review o 211 Patients in H ong Kong

C. L. LAI, MB, MRCP,' K. C. LAM, MB , FRACP,t K. P. WONG, MB, DMRD, FRCR,$P. C. WU, MB, M R C P A T H , ~ND D. TODD, MD, FRCP, FRACP

A retrospective study of 211 patients with proven hepatocellular carcinoma (HCC) was made. Thecommonest symptoms were anorexia and malaise (73%). Five patients (2.5%) had near-normal bio-chemical tests despite the presence of massive tumors. Diagnostic yield from angiography, percutaneousperitoneoscopic biopsy, or scintiscanning was 87-9896. Three percent of the patients had resectabletumors. Median survival for patients with untreated disease was 3.5 weeks. Apart from histology, thetotal serum bilirubin level was the only factor of prognostic value. Only 12 patients had preexistingsymptomatic cirrhosis. When compared with 80 patients with symptomatic postnecrotic cirrhosiswithout malignancy, patients with HCC had higher SGOTSGPT ratio, higher serum albumin levels,and higher platelet counts. There was only minimal overlap of patients with symptomatic postnecroticcirrhosis and those with HCC. The authors conclude that their patients with HCC appeared late fortreatment. A probable difference in the development of symptomatic postnecrotic cirrhosis and ofHCC with asymptomatic postnecrotic cirrhosis is suggested.Cancer 47:2746-2755, 1981.

H E R E H A S B E E N recent interest in the clinicalaspects of hepatocellular carcinoma (HCC).10J1J5-The incidence of HCC among Chinese is high.32

In Hong Kong, it is the second most common malignantt ~ m o r . ~e have examined our recent clinical ex-perience with HCC and have found notable differencesfrom other repqrts. We have also compared the HCCpatients with cirrhotic patients who died withouthaving HCC.

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MaterialsThe study included 21 1 consecutive patients with

histologically proven HCC, 159 by biopsy, and 52 byFrom the University Departments of Medicine and Pathology andthe Institute of Radiology and Oncology, Queen Mary Hospital,Hong Kong.* Lecturer, Universi ty Department of Medicine, Queen Mary

Hospital, Hong Kong.t Reader, University Department of Medicine, Queen MaryHospital, Hong Kong.$ Senior Medical Officer, Institute of Radiology and Oncology,Queen Mary Hospital, Hong Kong.Senior Lecturer, University Department of Pathology, QueenMary Hospital , Hong Kon g.II Professor, University Department of Medicine, Q ueen MaryHospital, Hong Kong.Address for reprints: C. L. Lai, University D epartm ent ofMedicine, Queen Mary Hospital, Hong Kong.The authors thank Drs. K . W . Chan, C. Y heng, K. S. Lai,H. M. Lam, N. W . Lee, and J. L. Taw for the peritoneoscopyexaminations and Drs. S. F. Lok and K . W. Woo for their help inthe preparation of the manuscript.Accepted for publication May 14, 1980.

necropsy ( v ide i n f ra ) , admitted to the UniversityDepartment of Medicine, Queen Mary Hospital, HongKong from January 1970 to June 1977. In addition, 19patients in the biopsy-proven group also had necropsies,making a total of 71 necropsies in the whole series.Other than by histologic diagnosis, the patients in thisstudy were unselected.

For comparison, 80 patients with histologicallyproven postnecrotic cirrhosis of the liver were studied.These were all the postnecrotic cirrhosis patientsadmitted during the same period and shown bynecropsy not to have HCC.

All patients were Chinese; the majority were fromSouthern China.

Sex and Age IncidenceOf the 211 HCC patients, 177 were male and 34female. Their ages ranged from 16 to 78 with a peak in-

cidence of presentation during the sixthdecade (Fig. 1).Clinical Features

With two exceptions, all patients had symptomseither directly related to their tumors or to hepatic de-compensation (99%) (Table 1). One-hundred-ninety-nine patients had no previous history of chronic liverdisease, although most of them had evidence of livercirrhosis on clinical examination, as described bySherlock.26Although close association between HCC

0008-543X/8 /0601/2746 1.05 American Cancer Society2746


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No. 1 1 H E P A T O C E L L U L A RA R C I N O M AN HONGKONG La i e t a l . 2747and liver cirrhosis is well recognized, only 12 patientsin our series (6 ) had previously been diagnosed tohave cirrhosis of the liver. In these, the cirrhosisproduced symptoms 1 .3 to 15 years (median 2.8 years)before the diagnosis of HCC. All 12 patients had newsymptoms (Table 1) that led to the diagnosis of HCC.

The majority of patients had fever during some periodof their observation. In most patients, the cause of thefever could not be conclusively attributed to the tumor,and in none was this a presenting complaint; so feverwas not included in Table 1. Jaundice was usually ofthe mixed conjugated and unconjugated type. In onepatient, it was predominantly of the conjugated type,and necropsy revealed tumor infiltration of the upper 4cm of the common bile duct. The 27 patients witherythrocytosis were diagnosed according to the pro-cedure previously outlined by this Department.18

The two patients who had unrelated features wereadmitted for attempted suicide and cerebral hemor-rhage.

Forty patients (19 ) had no clinically detectableascites. Fifteen patients (7%) had no detectablehepatomegaly. In seven of these patients, this was dueto the tense ascites; in the remaining eight patients,the liver size was within normal limits.obur InvolvementThe predominant lobar involvement of the liver on

presentation was determined by the following methods:clinical examination, scintiscanning, peritoneoscopy,laparotomy, and necropsy in those who died within oneweek of presentation. Thirty-eight percent had pre-

T A B L E. Features on Presentation in 21 1 Patientswith Hepatocellular CarcinomaAs asso-As chief ciatedcomplaint feature Total

N o. No.Abdominal paiddiscomfort 96 46 5 2 48Abdominal distension 69 33 5 2 35Abdominal mass 13 6 2 1 75aundice lo 5Haemetemesishnelena 9 4 27 13 17Anorexia and malaise 9 4 145 69 13Hypoglycemia 5 2 10 5 7Diarrhea 4 2 40 19 21Ankle edema 4 2 - - 23ncephalopathy 3 1 - -Rupture of carcinoma 3 1 24 1 1 12Dyspnoea 2 pleural effusion 2 1 13 6 62nrelated features 2 1Vertebral metastases 1 0.5 - - 0.5Weight loss with no anorexia 40 19 1921 7 7rythrocytosis _ -

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A G E IN YEARSFIG.1. Distribution of the age of presen tation in 21 1 patients withhepatocellular carcinoma.

dominant right lobe involvement, and 10% had pre-dominant left lobe involvement. In 52 , both lobeswere involved to similar extents.

Extrahepat ic Metas tasesExtrahepatic metastases were sought by chest x-ray

(all patients), at laparotomy (39 patients), at necropsy(71 patients), or by other special investigation asjustified by the clinical features. Metastasis was presentin 30 (12 ) of our patients, and the sites involved arelisted in Table 2. This incidence may be an under-estimation, since only 71 patients had necropsy.

Of the 15 patients found to have lung metastasis,only nine (60 ) had detectable lesions on routinechest x-ray.


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ResectabilityThe criteria for resectability of HCC were serum

total bilirubin level of less than 85 pmol/l, localizationof tumor to one anatomic lobe, absence of invasion ofportal vein, and absence of extrahepatic metastases.

Only seven patients (3 ) had surgically resectabletumors. In all of these, resection was attempted.

Alcohol IiitakeA history of excessive alcohol intake was obtained

by direct questioning of the patients. Where possible,cross-checking with patients relatives was tried, butthis was often found to be of little help. Table 3 showsthat significant alcohol intake was uncommon.

TOTAL B IL IRUB IN LEVEL (urnol/l)FIG. . Distribution of the total serum bilirubin levels on pre senta-tion in 205 patients with hepatocellular carcinoma. Mean = 74.5p,moVI; range = 5.1-560.9 pmoV1.

T A B L E . Site and Frequency of Extrahepatic Metastases in 21 1Patients with Hepatocellular CarcinomaNo. of patients Percentage

Lung 15 7Lymph nodes 10 5Brain 3 1Vertebrae 1 0.5Stomach 1 0.5TO TA L 30 14

T A B L E . Consumption of Alcohol in 21 1 Patientswith Hepatocellular CarcinomaNo. of patients Percentage

Amount of alcohol 160 glday 4 2

Hematology and BiochemistryHematologic and biochemical findings on presenta-

tion are listed in Table 4 .Anemia in the patients was usually multifactorial,

and the actual level of hemoglobin was of little signifi-cance in assessing the degree of hypersplenism orhepatocellular dysfunction. The levels of serum totalbilirubin, alkaline phosphatase, glutamic oxaloacetictransaminase (SGOT) and glutamic pyruvic transaminase(SGPT) showed a wide scatter with skewed distribution(Figs. 2, 3, and 4). The SGOT to SGPT ratio wascalculated by linear regression by the least square fitmethod (Fig. 5). The slope of 1.44 confirmed the findingsof OkudaZo nd of Ellis et a1 for hepatic malignancies.The serum total bilirubin levels on presentation werenormal in 56 of patients, and the alkaline phos-phatase was below 200 pmol/minutes 1 i . e . , the rangethat indicates space-occupying lesions in the liver, in38 . Two patients had normal and three patients hadnear-normal biochemical values; yet all five (2.5%) hadgross hepatomegaly caused by tumor infiltration.

Hepatitis B virus surface antigen (HBsAg) wastested for by radioimmunoassay (Austria 11, AbbottLaboratories, IL. ) in the last 20 consecutive patients ofthe series, and it was detected in 19 (95%).Periodic acid Schiff-positive globules in hepatocytesas an indicator of l anti-trypsin deficiency was lookedfor in all liver specimens but was detected in only one.

Diagnostic InvestigationsScintiscanning

Rectilinear anterior liver scanning with colloidalradioactive Indium-113m was performed in 145 patients,the results are presented in Table 5 .


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2750 CANCERu n e 1 1981 Vol. 47Y

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SGPT (umol/min. l )FIG.4. Distribution of serum glutamic oxaloacetic transaminase(SGOT) and serum glutamic pyruvate transaminase (SGPT) levels on

presentation in patients with hepatocellular carcinoma. T o p : mean= 81.1 pmoVmin. I ; range = 11-552. Botrom: mean = 44.3 pmoYrnin. 1; range = 8-260.

TABLE Results of Indium Scintiscanning in 145 Patients with HCCScan diagnosis No. of patients Percentage

Space-occupying lesion w ith orwithout cirrhosis 126 87Suspicious space-occupyinglesion 10 7Cirrhosis of liver without spac e-occupying lesion 8 6Normal 1 1

T A B L E. Frequency of Angiographic Findingsin 41 Patients with HCCN o. of patients Percentage

Neovasculari ty 37 90Tum our staining/poolingof contrast 31 76Space-o ccupy ing lesion with vesseldisplacement 24 59Portal vein infiltration 16 39Arterioven ous shunting 11 27Encasement of vessels 2 5N o evidence of tumor 1 2

appeared to be primary; there was no evidence of gutperforation, of diabetes mellitus, and of known historyof corticosteroid ingestion. N o intraabdominal focus ofcandida infection was found at necropsy.

The patient who died from cerebral hemorrhage hadgeneralized atherosclerosis, and the cerebral hemor-rhage was considered to be unrelated to the HCC.

Prognostic IndicatorsAmong clinical features, survival was found to be

unrelated to age, sex, duration of onset of symptoms topresentation, blood counts, albumin level, globulinlevel, alkaline phosphatase, SGOT, SGPT, and pro-thrombin time. The only biochemical value found to beof prognostic significance was the bilirubin level onpresentation. The correlation between the total serumbilirubin level and survival was calculated by computer(least square fit regression for log y against x) (Fig. 7)and was found to be highly significant P< 0.001).

The only histologic factor found to have prognosticsignificance was the presence of clear cells in the tumor.This finding emerged from a previously published studyof the first 80 of the present series of patients.13Patientswith clear cells in their tumors had significantly bettersurvival than those without clear cells, and those withthe diffuse clear cell pattern ( i . e . ,more than 50% of theirtumor cells being clear cells) survived better than thosewith the focal pattern ( i . e . , less than 30 of their tumorcells being clear cells) P< 0.001 in both cases).13

Comparison with Postnecrotic Cirrhosis withoutSuperimposed Hepatocellular CarcinomaBetween January 1970 and June 1977, 80 patients

with histologically proven postnecrotic cirrhosis wereadmitted into our unit and shown at necropsy not tohave HCC. All had symptoms related to cirrhosis, al-though 11 had unrelated symptoms as their chiefcomplaints.

In studying this group of patients and the 199 patientswith HCC diagnosed on first presentation (66 hadnecropsies), we have chosen for comparison the fac-tors that might indicate the severity of chronic hepato-cellular dysfunction and of portal hypertension, as wellas the morphologic evidence of the degree of advance-ment of cirrhosis (Table 8). The hematologic and bio-chemical values were those obtained on first admission.The comparison of the degree of advancement of cir-rhosis was only carried out in patients with necropsiesbecause accurate morphologic comparisons could onlybe made with large necropsy specimens. The activityand the stage of evolution of the cirrhotic process wereassessed according to the criteria described byAnthony et al. The determination of the activity of the


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N o . I 1 HEPATOCELLULARA R C l N O M A I N HONG KONC L a i e t a l . 275 1cirrhosis was based on following features: the amountof cellular infiltration, the definition of the borders ofthe regeneration nodules, the degree of bile duct proliferd-tion, and the presence or absence of hepatitis. Twelvepercent (8/66) of the HCC patient had no morphologicevidence of cirrhosis. Of the remaining 58 patients, asignificantly higher proportion (38 ) had less activecirrhosis when compared with the 80 patients with post-necrotic cirrhosis without HCC (15 ).

Since there was a difference in the SGOT and SGPTlevels in HCC group (Fig. 5 ) , the SGOT and SGPTlevels in the two groups were also compared. Thedistribution of the SGOT and SGPT values in the 80patients with postnecrotic cirrhosis is shown inFigure 8. The difference in the ratio of SGOT to SGPTvalues in these patients and in the patients with HCC(linear regression by least square fit method) wasstatistically significant (Figs. 5 and 9) ( P < 0.0001).

To examine this problem further, we also analyzedthe hematologic and biochemical data in the 12 patients(five with necropsies) who had HCC after the diagnosisof symptomatic cirrhosis (Table 9). With the develop-ment of HCC, only the SGOT to SGPT ratio changedsignificantly in the direction shown in Figures 5 and 9:the platelet counts and albumin levels did not show anychanges shown in Table 8.

DiscussionR e v i e w of 21 1 Pat ients wi th HeputocellulurCarcinotna

Compared with previous reports, several notabledifferences were found in our present series.

Anorexia and malaise, being present in 73 of pa-tients, were the most common symptoms in our pa-tients but were not emphasized in other reports. Thesesymptoms are known to reflect constitutional disturb-ance in hepatocellular disease.fiA high incidence oftheir occurrence underscores the general disturbanceand hepatocellular dysfunction produced by the tumor.Diarrhea was common (21 ). The 2 frequency ofdiarrhea as a chief complaint is comparable with the3.7 frequency among early symptoms in Okuda'sseries.Iy In addition, 19% of our patients also haddiarrhea as an accompanying feature. The diarrhea wasusually mild and chronic. Stool cultures were almostinvariably negative for pathogenic organisms. Althoughdiarrhea in white persons with cirrhosis had been con-sidered the sine qua n o n of alcoholism,6 alcohol intakewas insignificant in the present series (Table 2) . Thecause of diarrhea requires further study.

The yield of positive results from Indium scinti-scanning (87 ), peritoneoscopic biopsy (96 ), per-cutaneous needle biopsy (97 ), and celiac angiography

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FIG.5 . Correlation between SGOT and SGPT levels on presenta-tion in 174 patients with hepatocellular carcinoma. Y = 16.83+ 1.44 X ; r = 0.647.(98%) was higher than generally reported from HCCpatients in the All of these methodsare more sensitive diagnostically than tests for alpha-fetoprotein in our patients (65 ) reported in a previousstudy.' Such a high yield was at least partly the result

T A B L E . Cause of Death in 104 Patients with Untreated HCCNo. of patients Percentage

Liver failure/cachexiaRupture of carcinomaGastrointestinal bleedingHypoglycemiaPulmonary edemaBronchopneumoniaCerebral metastasisCandida peritonitisCerebral hem orrhage

55181753311I

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F I G .6. Survival curve for 104 patients with un-treated hepatocellular carcinoma. R ange = 1 day-70 weeks.

I 2 3 4 5 6 7 8 9 10 20 30WEEKS

of advanced disease on presentation. However, wemay have underestimated the false negative rates forthese diagnostic methods, since small asymptomaticHCC not detectable by any of these methods wouldbe missed unless necropsy was performed on every pa-tient investigated. The true false negative rates arebeing studied in a continuing prospective study in ourDepartment.

There appears to be general agreement on the valuesof angiography in the detection, localization, andassessment of resectability of HCC.20.24he pitfall withthis technique seemed to be small tumors in the leftlobe of cirrhotic livers. Recent data have shown thatsuch pitfalls may be minimized by noting blockage ordisplacement of branches of the portal vein instead ofarterial changes in the left lobe.31

Late presentation of the patients was likely to be thereason for the low resectability rate of the tumors (3%).

40 70

The comparatively high resec ability rate of 20-30%in surgical series16, may be attributable to selectivereferral of patients with potentially resectable tumorsto surgical units and those with advanced tumors tomedical units.

In the literature, serum biochemical measurementsof bilirubin, alkaline phosphatase, SGOT, and SGPTare generally presented as means and standard devia-tions. This would imply normal distribution of thesevalues. However, in the present study, distribution ofsuch values was skewed. Hence, scattergrams, histo-grams, or medians and ranges would appear to be moreappropriate methods of presentation of these values. Ina high percentage of patients, the bikrubin level wasnormal (56 ), and the alkaline phosphatase activity,despite massive tumors, was below the diagnosticrange for space-occupying lesions in the liver (38%).In fact, even normal and near-normal biochemical

TABLE. Comp arison between 199 Patients with HC C (66 with Necropsies) and 80 Patien ts with S ymptom aticPostnecrotic Cirrhosis without HCC on NecropsySymptomaticwithout HCCHC C postnecrotic cirrhosis

All 199 66 Patients*patients with necropsies* 80 PatientsPeak age incidenceDiagnosisDeathIncidence of HBsAg positivity ( )Platelet count x 10y/lAlbumin gllGlobulin g/lMorphology of cirrhosisNo c ir rhos isCirrhosis with little activityEarly stage cirrhosis withincomplete septae

6th decade6th decade95147 2 7728.4 -c 7.440.0 f 8.4

6th decade*6th decade*143 r 84*27.7 5 6.9*42.1 2 7.1*8/66 (12 )*22/58 (38 )*

10158 (17%)*

-5th decade6th decade87.5 N S68 5 77 P < 0.0001 P < O.o00124 t 6.2 P < o.oO01 P < 0.005*42.4 rt 9 .1 N S N S

012/80 ( 15%) P < 0.005*16/80 (20 ) - N S

* Represents those of the 66 HCC patients with necropsies.


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F I G . . Correlation between total serum bilirubin 300level on presentation and survival in 104 patientswith untreated hepatocellular carcinom a. Y = 6.83-X ,3s: r = 0.39; P < 0.001. 252 2002s?-

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findings are encountered in the presence of HCC of con-siderable size.

The prognostic usefulness of the total serum bili-rubin level confirms Bengmark's observation. Fromthe curve (Fig. 7) , the significance of the correlationbetween total serum bilirubin level and patients'survival as a group was high ( P < 0.001). However anr-factor of 0.39 indicates that approximately 85 of thevariation in survival is due to determinants other thanbilirubin.The other clinicobiochemical features, i . e . , age, sex,incidence, and pattern of presentation, did not differmaterially from previous r e p o r t ~ . ' * ~ ~ ~ ' ~ ~ ' 'C o m p a r i so n i t h 8 P a t i en t s w i th P o s tnecro t i cC i rrho si s ~ i t h o i r t u p er im p o sed H ep uto ce ll i tl a rCarcino m u

The processes of liver cirrhogenesis and carcino-genesis may be separate, although a common factorinitiating both processes is p o s ~ i b l e . ~ , ~ ~n the otherhand, liver cirrhosis has been considered a major pre-disposing factor to the development of HCC.' Recently,Kuboet ul. detected 3 1 HCC in patients with an initialclinical diagnosis of cirrhosis or chronic hepatitis. Theyconcluded that HCC occurred when cirrhosis was notadvanced or in a precirrhotic stage of chronic hepatitis.An association incidence of 92 between HCC andpostnecrotic cirrhosis has been reported from thishospital, but failure to find an earlier age incidencefor cirrhosis compared with HCC was considered to beevidence against cirrhosis being an important pre-disposing cause of HCC.In the present study, we found a comparable in-cidence of HBsAg positivity in patients with HCC

SURVIVAL (WEEKS)

(95 ) and in those with symptomatic postnecroticcirrhosis (87.5%) (Table 8).The high incidence in the 20patients with HCC in this series corresponds to theresults of a larger study in progress in our Department

SGOT (umol/min.l)

10

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SGPT (umol/min.l)FIG. . D istribution of SGOT and SGPT levels in 79 patients withsymptomatic postnecrotic cirrhosis. 7 0 p : Mean = 70.7 pmoVmin/lrange = 5-883. Bottom: mean = 75 .6 fimoUmini1: range = 3- 1908.


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F I G .9 . Correlation between SGOT and SGPTlevels on presentation in 7 9 patients with sympto-matic postnecrotic cirrhosis. Y = 16.84 0.74 Xr = 0.889.

SGPT urnol/rnin.)

(Lam and Lai, unpublished data) and is also similar tothat reported in Chinese patients in TaiwanzsThe highassociation rate of hepatitis B virus with both HCC andsymptomatic postnecrotic cirrhosis suggests that hepa-titis B virus infection may be one of the possibleinitiating factors for both disease processes.

However, several other factors, including plateletcounts, serum albumin levels, and SGOT to SGPT ratioas well as the activity of the cirrhosis were significantlydifferent in patients with HCC and in those withsymptomatic postnecrotic cirrhosis (Table 8). The riseof the SGOT to SGPT ratio could be attributed to pro-gkession of the tumor, as may be concluded from the 12patients who were observed to have detectable HCCfrom preexisting cirrhosis (Table 9). To explain thehigher albumin levels and platelet counts in the HCCgroup when compared with the symptomatic postne-crotic cirrhosis group (Table 81, we considered threepossibilities. First, the 12 of HCC patients withoutcirrhosis could have contributed to the higher values ofalbumin concentration and platelet count. However,T A B L E . Comparison of Hematologic and Biochemical Findingsin 12 Patients with Symptomatic Cirrhosis Before and AfterDiagnosis of Hepatocellular Carcinoma

Onpresentation On firstwith diagnosiscirrhosis of HCCPlatelet coun t x 10Yl 84.2 38 83.5 -c 4 6 N SAlbumin g/l 29.6 6.8 24.2 ? 8 . 6 N SGlobulin g/l 31 . 1 ? 13.0 44.8 ? 8.0 N SSlope of SG 0 T:SG lTratio 0.549 2.152 P < O.OOO1

recalculation of the mean albumin levels and plateletcounts after exclusion of the highest 12 of values inthe HCC group still revealed significantly higher valuesin those with HCC. Second, paraneoplastic manifesta-tions of HCC may be associated with abnormally highalbumin levels or platelet This was notencountered in any individual patient in this series, butthis mechanism cannot be excluded. Last , those highervalues may simply be the result of less severe livercirrhosis. This corroborates with the rarity of preexist-ing symptomatic cirrhosis in our patients with HCC(6 ). Further evidence for this is the morphologicfinding of significantly less active cirrhosis in the HCCpatients when compared with the patients havingsymptomatic cirrhosis without HCC (Table 8).

Possibly, the sequence of events runs as follows.Some common factor, possibly hepatitis B virus in-fection (v ide s u p r a ) , initiates the development of bothcirrhosis and HCC. Additional factors, perhaps thestatus of nutrition or immunologic response, may pro-mote severe hepatocellular destruction, so that cirrhosissubsequently becomes symptomatic. On the otherhand, differences in the status of the same additionalfactors may have promoted carcinogenesis with thecirrhosis progressing more slowly and remainingasymptomatic. Thus overlap between the two groups isminimal, as was found in this study. With less severechronic hepatocellular dysfunction and less activecirrhosis, the albumin levels were higher, and a lesserdegree of portal hypertension with milder hyper-splenism could explain the higher platelet counts.

In Figure 10, we have introduced a modification intothe last two steps in the scheme of Larouzeer a1.I4 o in-clude our current findings. Cirrhogenesis following


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N o. 11 HEPATOCELLULARA R C I N O M AN H O N GK O N G Lai et a l . 2755

CIRRHOGENESIS

CHRONICARRIERF HBV- HEPATITIS >I G . 10. Proposed sequelae of chronic hepatitisB virus (HBV) infection. CARCINOGENESIS

CIRRHOSIS POOL - YMPTOMATICI...: SET a CIRRHOSIS S t l.....- ON-COMPL AINANTchronic hepatitis will lead to a pool of cirrhosis patients(continuous circle), some of whom become sympto-matic (hatched square). Carcinogenesis occurring inparallel to cirrhogenesis will lead to a set of patientswith HCC (rectangle) largely within the pool ofcirrhotic patients. This HCC set overlaps the sympto-matic cirrhosis set minimally. A small group of patientsaffected by carcinogenesis is uninvolved by cirrho-genesis and lies outside the continuous circle. To com-plete the picture, a fourth group of patients with cir-rhosis who do not complain may be accidentally foundto have cirrhosis or HCC (dotted circle); these patientsmay later become symptomatic.

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Dragon Lai Hcc Study 1981