Contribution of mass screening system to resectability of hepatic lesions involving Echinococcus multilocularis

J Gastroenterol 1997; 32:351-354 Journal of Gastroenterology �9 Springer-Verlag 1997

Contribution of mass screening system to resectability of hepatic lesions involving Echinococcus multilocularis

NAOKI SATO, 1 TSUTOMU NAMIENO, 1 KOJI FURUYA, 2 HIROAKI TAKAHASHI, 1 KENICHIRO YAMASHITA, 1 JUNICHI UCHINO, 1

and KIYOSHIGE SUZUKI 3

i First Department of Surgery, Hokkaido University School of Medicine, N-14, W-5, Kita-ku, Sapporo 060, Japan 2 Hokkaido Institute of Public Health, 3 Department of Health and Environment, Hokkaido Prefectural Government, Sapporo 060, Japan

Abstract: The prognosis for patients with alveolar echinococcosis of the liver (AEL) is excellent when the lesion is completely resected. Early detection of the disease and subsequent resection of the lesion are thus indispensable; however, the usefulness of screening sys- tems is now controversial. This study was designed to compare screened and non-screened patients according to stage classification and to re-evaluate the effect of screening. We studied a total of 82 patients (63 screened and 19 non-screened). The stage classification showed a significant intergroup difference (P < 0.002). The largest tumors ranged from 30 to 100mm, and there was a significant intergroup difference (P < 0.0014). Ultrasonography showed even small lesions in the screened patients. The complete resection rate was 74.6% for the screened patients, and 21.1% for the non- screened patients, showing a significant difference (P < 0.0001). The rate of unresectable lesions was higher in the non-screened patients (32%) than in the screened patients (11%), showing a significant difference (P < 0.04). The present screening system contributes to early detection and subsequent resection of AEL, leading to a better outcome.

Key words: alveolar echinococcosis, liver, mass screening, ultrasonography, enzyme-linked immunosorbent assay, resectability

Introduction

Echinococcus multilocularis (EM) is currently endemic in parts of the northern hemisphere. 1 In Hokkaido, Japan, foxes and various rodents are very important in

Offprint requests to." N. Sato (Received July 22, 1996; accepted Nov. 22, 1996)

the life cycle of EM, and foxes infected with EM are regarded as the main source of human infection. 2

Alveolar echinococcosis of the liver (AEL) is con- trolled by complete resection of the lesions. However, resection of the lesions is often impossible in patients with advanced-stage AEL or symptoms such as hepatomegaly, abdominal pain, and jaundice. These patients often die of liver failure, disseminated intravas- cular coagulation, and/or multiple organ failure caused by biliary sepsis.

In Hokkaido, a mass screening system for AEL has been established, in which an enzyme-linked immunosorbent assay (ELISA) and ultrasonography (US) are performed. In this study, screened patients (divided into four sub-groups according to the degree of progression of the lesions) were compared with non- screened patients. This comparison confirmed that our screening system has contributed to an increase in complete resectability of the lesions, suggesting that this system is appropriate for improving the prognosis of AEL patients.

Patients and methods

Patients

In the ten years 1984-1993, an annual number of 48000-96000 individuals, i.e., a total of 779957 residents in Hokkaido, Japan, received first-step screening with an ELISA. The ELISA method used was primarily based on that of Voller et al. 3 in which a crude antigen extracted from whole E. multilocularis larva and pro- toscolex fractions is coated on a solid plastic surface under appropriate conditions? Its sensitivity was 89.5 %, as reported previously2 The annual number of ELISA- positive patients ranged from 410 to 650 (0.51%- 1.27%), and these patients subsequently underwent US as a second step screening, this having been introduced

352 N. Sato et al.: Screening for and resectability of E. multilocularis hepatic lesions

Tab le 1. Staging of a lveo la r echinococcosis of the l iver

Invas ion to Occupied ad jacen t tissue Di s t an t

Stage segments or o rgan a me tas t a ses b

I 1 m - -

II 2 - - I I Ia 3 - - IIIb 1-3 + (Resectable) + (Resectable) IV 4 + (Unresectable) + (Unresectable)

a Hepatic vein, portal vein, vena cava, hepatic artery, extrahepatic bile duct bLung, brain, spleen, lymph nodes, and other organs

in December 1984. Four to twelve asymptomatic subjects (0.6%-6.3% of the seropositive subjects and 0.003%-0.045% of the screened individuals) have been diagnosed with AEL annually since 1984.

The subjects of this study were a total of 63 patients identified through the current mass screening system during the 10 years 1984-1993 and 19 non-screened patients who were transferred from regional hospitals with a confirmed or suspected diagnosis of AEL during the same period; they were suffering from abdominal pain or discomfort, general malaise, and/or jaundice, and they frequently had a space-occupying lesion on US.

Stage classification

We usually employ the stage classification of AEL as previously reported. 6 In brief, each stage is defined according to three criteria: involved hepatic segments, regional spread, and dissemination or distant metastasis. Stages I, II, and IIIa correspond to the number of hepatic segments occupied by EM, without regional or distant spread. Stage IIIb indicates regional and/or distant spread which can be resected. Stage IV indicates unresectable AEL (Table 1).

Statistical analysis

Statistical analysis was performed by the X 2 test, and the analysis was done with a commercial statistical analysis program (Stat-View, Abacus Concepts, Berkeley, CA, USA) with a Macintosh computer. A P value less than 0.05 was defined as significant.

Results

Staging of alveolar echinococcosis o f the liver

Preoperative stage classification of the patients is shown in Table 2. The most common stage in the screened patients was stage II (33.3%), followed by stage I (28.6%); more than 60% of the patients had either stage

I or II disease. Conversely, more than half (52.7%) of the non-screened patients had direct invasion to adja- cent structures and/or distant metastasis; the incidence of stage I or II was only 15.8%. The mass screening system was superior to non-screening in detecting the lesions at an early stage (P < 0.0127 by the )~2 test).

Comparison of largest lesions on US

A single lesion was detected in 39 (61.9%), and multiple lesions in 24 (38.1%) of the 63 screened patients. In contrast, a single lesion was found in 14 (73.1%) of the 19 non-screened patients and multiple lesions in 5 (26.3%). The size of the largest lesions on US was compared in the screened and non-screened patients (Table 3). Although the most frequent sizes in both groups were 30-100mm, there was a significant difference in the size of the largest tumor between the screened and non-screened patients (P < 0.0014 by the ~2 test).

Surgery and reasons for unresectability

All the screened patients underwent surgery; however, only 21.1% of the non-screened patients were suitable for undergoing surgery. Table 4 shows a comparison of resectability in the two groups. The complete resection rate was significantly higher in the screened than in the non-screened patients (P < 0.0001 by the •2 test). The reasons for unresectability are summarized in Table 5; 7 (11%) of the screened patients and 6 (32%) of the non-screened patients were unresectable. The unresectability rate was significantly lower in the screened than in the unscreened patients (P < 0.04 by the )~2 test), the reasons for unresectability being multiple invasions to other structures and/or distant metastases.

Discussion

Since 1936, 166 patients with AEL have been treated in this Department and postoperative complications

Table 2. Preoperative stage classification of screened and non-screened patients with alveolar echinococcosis of the liver

Screened patients (%) Non-screened patients (%) Stage (n = 63) (n = 19)

I 18 (28.6) 2 (10.5) II 21 (33.3) 1 (5.3) I l i a 10 (15.9) 6 (31.6) I I Ib 6 (9.5) 4 (21.1) IV 8 (12.7) 6 (31.6)

For explanation of stages, see Table 1

N. Sato et al.: Screening for and resectability of E. multilocularis

Table 3. Comparison of size of largest tumor in screened and non-screened patients

Screened Non-screened Tumor size (ram) patients (%) patients (%)

Less than 10 17 (27.0) 2 (10.5) 30-100 41 (65.1) 9 (47.4) More than 100 5 (7.9) 8 (42.1)

Table 4. Resectability of lesions in patients with alveolar echinococcosis of liver

Screened Non-screened Resectability patients (%) patients (%)

Complete resection 47 (74.6) Incomplete resection 16 (25.4) No surgery 0 (0)

3 (21.1) 11 (57.8) 4 (21.1)

Total 63 19

Complete resection, no evidence of macroscopically remaining lesions; incomplete resection, remaining lesions suspected

s o m e t i m e s occur red : b l eed ing , bile l eakage , o r hepa t i c fai lure . R e m a i n i n g Ech inococc i o f t en g rew and re- cu r r ed in the res idua l l iver , surgical wound , or i n t r ape r i - t o n e a l cavi ty af ter l iver surgery . Pos tope ra t i ve ly , d i s tan t me tas t a ses to the lung o r b ra in also occu r r ed in pa t i en t s wi th advanced A E L . Since 1984, however , advances in d iagnos t i c moda l i t i e s have led to an inc rease in the ear ly d e t e c t i o n of A E L at a r e s ec t ab l e s tage, and the g r e a t e r ski l l fulness of surgical t echn iques has d e c r e a s e d o p e r a - t ive mor ta l i ty . 7 10 Neve r the l e s s , in this s tudy, app rox i - m a t e l y 38% of our pa t i en t s were f o u n d to be at too

hepatic lesions 353

a d v a n c e d a s tage to u n d e r g o c o m p l e t e resect ion; 78.9% of the n o n - s c r e e n e d pa t i en t s cou ld no t r ece ive c o m p l e t e resec t ion , w he re a s this su rge ry was p e r f o r m e d on 74.6% of the s c r eened pa t ien ts . A l t h o u g h op in ions a b o u t mass sc reen ing sys tems vary , n-13 the p resen t s tudy conf i rms tha t the screening is useful . Since 1984, w h e n the cu r r en t mass sc reening sys t em was ins t i tu ted , we have r a r e ly e n c o u n t e r e d p o s t o p e r a t i v e compl ica t ions . This is a t t r i b u t a b l e to the ea r l i e r de t ec t i on of les ions and to i m p r o v e m e n t s in o p e r a t i v e techniques . US , in pa r t i cu la r , is capab le of r evea l ing smal l lesions.

V a r ious sc reen ing sys tems for ech inococcos is have b e e n r e p o r t e d f rom France , Swi tze r land , I ta ly , and o t h e r count r ies , n-13 These r e p o r t s have d o c u m e n t e d

tha t E L I S A is the bes t se ro log ica l test , whi le US shows the na tu r e and loca t ion of the les ions morpho log i ca l l y , pe rmi t t i ng p lann ing of t h e r a p e u t i c p rog rams . To d e t e c t A E L in a s y m p t o m a t i c pa t ien t s , we have a d o p t e d the c o m b i n e d sc reen ing sys tem, wi th E L I S A and US, and if necessary , we test pa t i en t ' s s e r u m by W e s t e r n b lo t - ting. 14.15 This sys tem a ppe a r s to be b e t t e r than e i the r

E L I S A or US, used a lone , wi th the high ear ly d e t e c t i o n ra te of A E L lead ing to an inc rease in the c o m p l e t e r e sec t ion ra te .

The i s land of H o k k a i d o has an a r ea of nea r ly 83 520 square k i l ome te r s , and a p o p u l a t i o n of 5 800000. Thus , the sc reen ing p r o g r a m mus t be m o r e ex tens ive t han tha t in o t h e r e nde mic regions , which are gene ra l ly smal le r in ex t en t and popu la t i on . Fa l se nega t ive resul ts have no t b e e n e nc oun t e r e d , thus far, wi th the cu r r en t mass sc reen ing system. Ce r t a in n o n - s c r e e n e d pa t i en t s in w h o m A E L was d e t e c t e d at r eg iona l hospi ta l s re- qu i r ed e x t e n d e d hepa t i c r e sec t ion o r were not su i t ab le

Table 5. Causes of unresectability

Extensive hepatic Sex Age involvement Hepatic hilum

Direct invasion to

Diaphragm/ Distant Vena cava Retroperi toneum metastases

Screened patients F 39 + - + - - M 52 - - - + + M 65 - - - + + F 47 + + - + + M 55 - + + + + F 23 - + + - - M 61 - - - + +

Non-screened patients M 57 - + + + + M 65 - + + + - M 59 - - - + - M 62 - - + - - M 45 - + - - - F 68 - + + +

One of the eight screened, stage IV patients was finally resected M, Male; F, female; +, positive; - , negative

354 N. Sato et al.: Screening for and resectability of E. multilocularis hepatic lesions

for liver surgery, while, conversely, in the screened patients, the lesions were small enough for them to receive non-extended liver surgery such as subsegmentectomy or partial resection of the liver.

AEL is not limited to the residents of Hokkaido, although to date, in Japan it has been designated as endemic only in this prefecture. 16 Infection with EM in foxes is actually quite frequent throughout Hokkaido, and most patients are within the designated areas; however, the prevalence of AEL has recently begun to increase in other regions. Thus, the current mass screening system will become even more necessary and its application should be extended. The percentage of individuals who undergo the mass screening remains low; aigproximately 60% undergo primary screening and 50%-60%, secondary screening. It is, therefore, necessary not only to provide education on hygiene, but also to promote the efficacy of the mass screening system in the detection of AEL, as well as the advantages of early diagnosis, which leads to a complete cure.

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Contribution of mass screening system to resectability of hepatic lesions involving Echinococcus multilocularis