325 This alarming frequency of side-effects with levamisole forced us to suspend the trial in December, 1977. Before this study was undertaken 53 patients (18 malignant melanoma, 17 hypernephroma, 5 breast cancer, 6 Hodgkin’s disease, 4 malignant teratoma, 1 with lung cancer, 1 gastric cancer, and 1 ovarian cancer) received levamisole in a similar manner for periods ranging from one month to two years. The incidence of side-effects in this group of patients was similar to those reported in other series, and hxmatological disturbances, other than a transient eosinophilia in a patient with hypernephroma, were not observed. We have attributed to levamisole symptom relief in two pa1 tients with advanced Hodgkin’s disease. Like Dr Teerenhovi and others we feel that the frequency of side-effects from levamisole is an important consideration and treatment of neoplastic diseases with this drug should be limited to very carefully selected patients on an individual basis. on our trial was presented to the Breast Trials Review Meeting, held at Heathrow on Feb. 3, 1978, and organised by the Coordinating Committee for Clinical Trials of the Treatment of Human Breast Cancer in Britain and Ireland.

A report

S. RETSAS R. H. PHILLIPS I. W. F. HANHAM K. A. NEWTON

Department of Radiotherapy and Medical Oncology, Westminster Hospital, London SW1P 2AP

CLOFIBRATE AND THE LIVER

.

HISTOPATHOLOGY OF THE LIVER* BEFORE AND AFTER THERAPY WITH CLOFIBRATE 1.5

5 g/day

graded

=(0) no fatty degeneration, (1) mild-to-moderate fatty degeneration, (2) distinct fatty degeneration, (3) severe fatty degeneration and (4) fatty liver. In conclusion, there is some tendency to decreased fatty liver infiltration and no hint of liver damage (by light microscopy) after three months’ clofibrate treatment. Medizinische Klinik II, Klinikum Grosshadern, Universität München, 8000 München 70, West Germany

P. SCHWANDT

Pathologische Institüt, Stadtkrankenhaus, Kassel

O. KLINGE

Institüt für Medizinische Dokumentation, Statistik und Datenverarb., Universität Heidelberg

H. IMMICH

SIR,-A temporary increase of transaminases is a frequent accompaniment of clofibrate treatment for hyperlipoproteinxmia. In

rat

liver ultrastructural

changes2-4

and alterations of

activities,4-’ metabolites and A.D.P.A.T.P. ratio after clofibrate feeding have been reported. Hanefeld et al. reported decreased liver glycogen and manganese content as well as an increase in mitochondria and smooth endoplasmic reticulum in liver-biopsy specimens of clofibric-acid treated patients with hyperlipoproteinaemia. Since this seems to be the only published biopsy evidence for an influence of clofibrate on the .human liver we would like to report a multicentre study on this subject. 40 hyperlipoproteinsemic patients having given their informed consent, had liver biopsies done before and after three months of clofibrate treatment (1-3 g/day in 27,0-55 g/day in 13). Liver tissue was examined by light microscopy by enzyme

of us under "blind" conditions. The results in respect of fatty infiltration are given in the table for the 1.5g/day group. No significant histological changes were seen in the 13 patients on 0.5gclofibrate per day. 17 of 27 patients on 1.5g clofibrate showed distinct fatty degeneration (grade 2) before therapy. 6 of these patients showed histological improvement, 3 deteriorated, and 8 remained unchanged after three months on clofibrate. In respect of other histological criteria there were no differences between patients on 0.5 5 g and 1.5 5 g. Of the 40 patients, 26 showed single-cell necroses; 6 of these remained unchanged at follow-up biopsy, 6 had some more necrosis, but 14 had none after therapy. The same tendency was seen for slight local activity of the mesenchyma, initially present in 32 livers, diminishing in 15 and slightly increasing in 10. Discrete intrahepatic cholestasis was observed 6 times before therapy but only twice at follow-up. Portal fibrosis (12 cases) and siderosis (24) were not influenced by therapy.

SERUM-AMYLASE ISOENZYME PATTERN AFTER PANCREATECTOMY

SIR,-A raised serum-amylase after

surgery isusually indicating postoperative pancreatitis,’-3 even when the patient has no signs or symptoms of pancreatitis. Studies of amylase isoenzyme patterns suggest that increased

accepted

as

one

1. Phillips, R. H., Retsas, S., Newton, K. A. Br. med. J. 1977, i, 1447. 2. Best, M., Duncan, C. J. Lab. clin. Med. 1964, 64, 634. 3. Svoboda, D., Azarnoff, D. J. Cell Biol. 1966, 40, 442. 4. Gear, A., Albert, A., Bednarek, J. J. biol. Chem. 1974, 249, 6495. 5. Hess, R., Staäubli, W., Riess, W. Nature, 1965, 208, 856. 6. Cederbaum, A., Madhayan, T., Rubin, E., Biochem. Pharmac. 1976, 25, 1825.

7. Wilkening, J., Schwandt, P. Horm. Metab. Res. 1977, 8. Hanefeld, M. Dt. Gesundh Wesen 1977, 32, 2267.

9, 132.

Fig. 1-Serum-amylase-activity

after total pancreatectomy.

amylase activity after an operation, even upper-abdominal surgery, may not always derive from the pancreas. However, the mechanism remains unknown. We have monitored changes in serum-amylase isoenzyme patterns after total pancreatectomy, Perryman, R. G., Hoerr, S. O. Am. J.Surg. 1954, 88, 417. Ponka, J. L., Lamdrum, S. E., Chaikof, L. Archs Surg. 1961, 83, 475. 3. White, T. T. Morgan, A., Hopton, D.Am. J.Surg. 1970, 120, 132. 4. Maeda, M. Jap. J. Gastrœnterol. (inthepress). 1. 2.

326 PANCREATIC POLYPEPTIDE: A MARKER FOR ZOLLINGER-ELLISON SYNDROME?

SIR,-Polak et al.’ have suggested that raised circulating concentration of pancreatic polypeptide (P.P.) is a marker for the Zollinger-Ellison syndrome. Like Taylor et al.2 we have measured serum-PP in Zollinger-Ellison syndrome. 4 of 24 patients had serum-PP values over 300 pmol/1 (335, 380, 550, and 1215). In contrast, none of 72 healthy controls (mean age 42, range 13-84) and none of 12 normogastrinaemic patients with hyperparathyroidism from families with multiple endocrine adenomatosis type I had serum-PP levels of more than

Fig. 2-Changes of amylase isoenzyme pattern after

total pan-

createctomy.

The preoperative sample was diluted.

and our results provide a basis for explaining postoperative hyperamylasaemia of non-pancreatic type. A 45-year-old man who had been a habitual drinker for than 20 years underwent total pancreatectomy for chronic relapsing pancreatitis with pancreatic pseudocyst. The serum-amylase activity before operation was above 1000 Somogyi units/dl, rapidly falling to 116 units/dl 24 h after the operation and continuing to fall thereafter; however, on the 4th postoperative day it began to increase (fig. 1). The changes of amylase isoenzyme pattern are shown in fig. 2. Pancreatic-type isoamylases (amylase 1 and 2) due to the pancreatic pseudocyst were found before surgery; at 24 h after the operation, salivary-type isoamylase (amylase 3) was identified for the first time, while the pancreatic-type isoamylase decreased. Both the pancreatic and salivary type isoamylases decreased in parallel with the depression of the total serumamylase activity. However, the increase in amylase activity that began on the 4th postoperative day was due to the salivary type. In 292 cases undergoing various operations we found 19.2% postoperative hyperamylassemia—10-7% pancreatic-type and 89.3% salivary.4 Salivary-type hyperamylasamlia was found after all types of operation, while pancreatic-type hyperamylasxmia was limited to -surgery of the pancreas itself or adjacent organs. In salivary-type hyperamylassemia the patients had no clinical evidence of pancreatitis and the raised amylase levels did not last long. In the patient studied in detail the salivary-type isoamylase that first appeared 24 h after the operation might have been different from that found on the 4th postoperative day. The former might be the same as the isoenzyme found in the other cases of postoperative salivary-type hyperamylassemia, since it decreased in parallel with the reduction of the total serumamylase activity. The latter might not be the salivary-type isoamylase, but salivary amylase originating from the parotid gland to compensate for pancreatic amylase. Although the mechanism for postoperative hyperamylassemia is not completely clear, isoenzyme studies in this case did suggest that the amylase responsible was salivary, not pancreatic in type, even though the operation was on the pancreas, and that salivary amylase might compensate the serum-amylase activity after total pancreatectomy. more

Second Department of Internal Medicine, Kobe University School of Medicine, Kusunoki-cho, Ikuta-ku, Kobe, Japan 650

MITSUO MAEDA MAKOTO OTSUKI SHIGEAKI BABA

Second Department of Surgery, Hyogo Medical College

TAKEHEI YAMAMURA NOBUYOSHI ITO

300 pmol/l. No correlation between serum-PP and serumgastrin was found in the Zollinger-Ellison patients (r=0.040). Multiple endocrine adenomatosis type I was present in 3 of 4 patients with Zollinger-Ellison syndrome and serum-PP levels over 300 pmol/l, in 7 of 9 such patients with serum-PP levels between 100 and 300 pmol/l, and in only 3 of 11 (27%) Zollinger-Ellison syndrome patients with serum-PP levels below 100 pmol/1 (=mean+ 2 S.D. for 72 healthy controls). Although the correlation between raised serum-PP and multiple endocrine adenopathy did not reach statistical significance, these data give some support to the suggestion of Bloom et al. that raised serum-PP levels may be more frequent in patients with Zollinger-Ellison syndrome as a component of multiple endocrine adenomatosis. In the study of Taylor et al. all 4 Zollinger-Ellison patients with raised PP levels had undergone surgery, and 3 had proven or presumed liver metastases. 3 of our 4 patients with Zollinger-Ellison syndrome and high serum PP levels had no previous gastric or pancreatic surgery, while the remaining patient was studied after total gastrectomy. Liver metastases were found in only 1 of these patients, whereas the other 3 had pancreatic tumours without metastases at sub-

sequent surgery. Our study confirms that very high serum-PP levels may be an indication of a gastrinoma. In most patients with ZollingerEllison Syndrome, however, circulating PP levels are normal or

only slightly raised. Further, Zollinger-Ellison syndrome readily be diagnosed by radioimmunoassay of serum-gas-

can

trin, and there is in

equivocal diagnosis.

cases

no

is

evidence that measurement of serum-PP helpful in establishing or excluding this

Division of Gastroenterology, St Radboud Hospital,

University of Nijmegen, Nijmegen, Netherlands. *Present address: C.U.R.E., V. A. Wadsworth California 90073, U.S.A.

C. B. H. LAMERS* J. M. DIEMEL W. ROEFFEN Hospital Center,

Los

Angeles,

ATROPINE SUPPRESSION TEST FOR PANCREATIC POLYPEPTIDE A SERIOUS error by our printer obliges us to reprint, with apologies to Dr Thue W. Schwartz, the last paragraph of his letter published in our issue of July 1 (p. 44).-ED.L. "In duodenal-ulcer patients with high preoperative concentrations PP values return to normal after truncal vagotomy.4 Accordingly we found that PP concentrations and the fluctuations of these in both duodenal patients and elderly controls

depressed by atropine (15 .g/kg body-weight)5 (see figure). The suppression was most striking in subjects with raised PP levels. Thus, cholinergic blockade (atropine-suppression test) may be useful in eliminating the disturbing vagal in-

were

1. 2. 3. 4. 5.

Polak, J. M., Bloom, S. R., Adrian, T. E., Heitz, P. H., Bryant, M. G., Pearse, A. G. E. Lancet, 1976, i, 328. Taylor, I. L., Walsh, J. H., Rotter, J., Passaro, E. ibid. 1978, i, 845. Bloom, S. R., Adrian, T. E., Bryant, M. G., Polak, J. M. ibid. 1978, i, 1155. Schwartz, T. W., Rehfeld, J. F., Stadil, F., Larsson, L.-I., Chance, R. E., Moon, N. Lancet, 1976, i, 1102. Schwartz, T. W., Stenquist, B., Olbe, L., Stadil, F. Gastroenterology (in the

press).