Takeyuki Nakajima

Should gastric cancer patients more than 80 years of age undergo surgery? Comparison with patients not treated surgically concerning prognosis and quality of life

This study investigated the performance status, mental status, and prognosis of 24 patients older than 80 years whose gastric cancer had been managed surgically during the past 6 years, and 21 patients who were observed conservatively. The advantages and disadvantages of surgery for elderly patients with gastric cancer is discussed. The 3-year survival rate for patients with advanced gastric cancer was 31% for those surgically treated and 0% for those observed conservatively. The difference is statistically significant. The survival rate for patients with early gastric cancer was 62.5% in the surgical treatment group and 33.3% in the conservative observation group, a difference that is not significant. Decline in performance status and deterioration of mental status after open surgery were slight, and the survival rate for patients treated surgically was significantly higher than for conservatively observed patients, regardless of performance status and whether mental status had deteriorated. On univariate and multivariate analyses, the presence or absence of open surgery and macroscopic classification were the only significant prognostic factors, whereas performance status and the presence or absence of mental deterioration were not significant prognostic factors. These results suggest that surgical treatment should not be discouraged even for patients older than 80 years.

Improvement of proteinuria in a case of hepatitis B-associated glomerulonephritis after treatment with interferon

Disappearance of proteinuria was observed in a patient with hepatitis B-associated chronic glomerulonephritis after treatment with leukocyte interferon. The decrease of proteinuria was preceded by the disappearance of both deoxyribonucleic acid polymerase activity and hepatitis B e antigen from the patients sera.

Muscle cramps in chronic liver diseases and treatment with antispastic agent (eperisone hydrochloride)

To The Editor: Muscle cramps, which can be defined as involuntary and painful contractions of skeletal muscles, frequently occur in a variety of pathologic conditions related to neuromuscular, endocrine, or metabolic disease (1, 2), although muscle cramps sometimes occur in healthy persons. Among patients with liver disease, muscle cramps are most frequently seen in individuals with cirrhosis. Konikoff and Theodor reported that 88% of cirrhotic patients had experienced muscle cramps (3). We have prospectively determined the incidence of muscle cramps in patients with chronic liver diseases and in healthy individuals and have evaluated the effectiveness of treatment with eperisone hydrochloride, an antispastic agent (4), on muscle cramps in cirrhotic patients. One hundred seventy-six consecutive patients with chronic liver disease (103 males, 73 females, median age 54 years) visiting the liver clinic of Hamamatsu University Hospital and 142 healthy subjects (63 males, 79 females, median age 54 years) were examined. The group with chronic liver disease consisted of 80 patients with cirrhosis (44 males, 36 females, median age 59 years) and 96 patients with chronic hepatitis without cirrhosis (59 males, 37 females, median age 50 years). Patients with alcoholic liver injury were excluded because of the possibility that muscle cramps in alcoholics could be associated with alcoholic myopathy and/or neuropathy. No patients had drug-induced liver injury or any malignant neoplasm. Each subject was questioned about the frequency and localization of muscle cramps using a standardized questionnaire. Serum electrolytes (Na, K, CI, Ca) were measured in all of the cirrhotic patients, since a substantial number of these patients were taking diuretics flurosemide and/or spironolactone) for ascites and peripheral edema. An oral glucose tolerance test (75 g load) was also performed in all cirrhotic patients except for those who were known to be diabetic. The incidence of muscle cramps in patients with chronic liver diseases and healthy subjects is shown in Table 1. Twenty-five of 80 cirrhotics (31%) cornplained of frequent muscle cramps (more than once a week), while only 10 of 142 healthy subjects (7%) reported such a high frequency. The incidence of muscle cramps in the patients with chronic hepatitis without cirrhosis was 5%, which was not statistically different from healthy subjects. Most of muscle cramps (63% in the cirrhotics, 72% in patients with chronic hepatitis without cirrhosis, and 81% in healthy subjects) occurred in the calves. The incidence of muscle cramps in the toes, fingers, and thighs were 23%, 25%, and 19% for the cirrhotics, compared to 32%, I I%, and 5% for healthy subjects. The cirrhotic patients had a higher incidence of muscle cramps in the fingers or thighs than the patients with chronic hepatitis without cirrhosis or healthy subjects (P < 0.01). Serum electrolyte (Na, K, CI, Ca) concentrations as well as the administration of diuretics did not correlate with the frequency of muscle cramps in the patients with liver cirrhosis. There was no significant difference in the incidence of muscle cramps between cirrhotic patients with or without diabetes (27% versus 23%, respectively). To determine the efficacy of eperisone hydrochloride in the treatment of muscle cramps, doses of 150-300 mg per day were given orally to 21 of the 25 cirrhotic patients reporting frequent muscle cramps (more than once a week). This research was carried out in accordance with the Helsinki Declaration. Three of the remaining patients refused treatment, and one patient was not given the drug due to renal dysfunction. The frequency of muscle cramps was evaluated before and after eight weeks of treatment. Of 18 patients who continued the treatment for eight weeks, muscle cramps completely disappeared in 11 patients (61%), decreased in frequency in six (33%), and were unaltered in only one patient. Side effects were observed in four patients: fatigue occurred in one, epigastric discomfort in two, and dizziness in one patient. In three of these patients, the treatment was discontinued. No change in liver function tests was detected. The results of our study confirm the previous report that patients with liver cirrhosis experience a higher frequency of muscle cramps than healthy subjects (3). Although the pathophysiology of muscle cramps in liver cirrhosis still remains obscure, a suitable treatment for these distressing symptoms is

Cloning of serum RNA associated with hepatitis C infection suggesting heterogeneity of the agent(s) responsible for the infection

SummaryFifty-six lambda gt11-random-primed-cDNA recombinants of which translation products react with antibodies in the serum drawn from patients with hepatitis C (blood-borne non-A, non-B hepatitis) were cloned from serum pooled from donors presumably infected with hepatitis C. The specificity of these clones for hepaitits C infection was determined using 3 test panels. Of these 29 clones were determined to be specific for Japanese hepatitis C infection. However one of the 29 clones was positive for 1 out of 5 normals in an American test panel while 12 clones were positive for the American panel as well. The remaining 28 clones reacted well with serum from transfusion associated chronic hepatitis C comparing to the sporadic cases in the Japanese panel. When they were tested with normal donors, another clone reacted with a distinct donor group with which the other clones did not react. These results may suggest the presence of heterogeneity in Japanese hepatitis C.

Surface markers of NK cells in peripheral blood of patients with cirrhosis and hepatocellular carcinoma.

The surface markers and NK activity of blood lymphocytes in 38 normal controls, 57 cirrhotic patients and 22 cirrhotics with hepatocellular carcinoma were studied by the flow cytofluorometry using monoclonal antibodies. A reduction of OKM1+ cells was remarkable in cirrhotics, and a further decrease in HNK-1+ cells as well as OKM1+ cells was observed in cirrhotics with hepatocellular carcinoma, accompanied by depression of NK activity. We postulate that the decreased NK activity in these patients may result from the disturbed maturation of NK cells.

Effects of branched chain amino acid infusion on glucose metabolism in cirrhotic patients with encephalopathy

SummaryAn amino acid solution enriched in branched chain amino acids (BCAA) was administered to cirrhotic patients with encephalopathy and serial determinations of serum glucose,IRI and IRG were performed. Slight decrease of serum glucose was observed when only BCAA was given. On the other hand, when BCAA was infused with glucose, the serum glucose level decreased significantly after infusion (-77.5 ±26.2 mg/dl, p<0.01) and two cases of hypoglycemic shock were observed. Although both serum insulin and glucagon increased in these cases, the IRI/IRG molar ratio which was 8.9 at the start of infusion increased to 20.6 at the end of infusion. It was suggested that administration of BCAA with glucose caused hypoglycemia in cirrhotics with encephalopathy, possibly by synergistic action of BCAA and glucose on serum insulin level.

Fulminant hepatic failure associated with aplastic anaemia after treatment with danazol. Case report

A 29-year-old woman was admitted to Hamamatsu University Hospital on 21 September 1983, because of jaundice and a skin eruption. She had no history of liver disease. She had been suffering from dysmenorrhoea due to endometriosis for several years and had received hormone therapy including androgens and progestogens. Baldy-Websters operation was performed in 1982. Dysmenorrhoea recurred in 1983 and treatment with danazol (SterlingWinthrop Research Institute, New York), 400 mg/day, was started on 8 September 1983. On 17 September she began to complain of fatigue, anorexia and nausea and she had a skin rash on her trunk and extremities. On 19 September she visited a local doctor because of the rash and jaundice. Investigation revealed hepatic dysfunction with total bilirubin 6.4 mg/dl(lO9 pmoll I), glutamate-oxaloacetate transaminase (GOT) 2118 units (normal values <30), glutamatepyruvate transaminase (GPT) 2094 units (normal <20). Danazol was stopped and she was referred to Hamamatsu University Hospital on 21 September. On admission, she was a well-

Cloning of hepatitis C virus genomes and their properties

SummaryA random primed lambda gt11-cDNA library was constructed from donors plasma presumably infected by blood-borne non-A, non-B hepatitis (hepatitis C:HC) agent and immunoscreened with serum pooled from patients with acute or chronic HC. Twelve lambda gtll-cDNA clones were isolated that was shown to encode antigens associated specifically with HC infection in Japan as well as in USA. Of these two, as well as another clone which is specific only to Japanese HC infection, have unique nucleotide sequences and were extensively studied. They are not derived from host DNA and have no homology to the sequences of known human viruses including hepatitis A, B and D viruses, Ebstein-Barr virus, coxsackievirus, immunodeficiency virus type 1 or Japanese encephalitis virus. These results suggest that they are derived from the genome of HC agent(s). In addition, of these, one clone seems to encode epitopes derived from both the core and the surface polypeptides of the agent.

Treatment of chronic hepatitis B with recombinant leukocyte interferon and cyanidanol

SummaryTwelve male patients with chronic hepatitis B were treated by the combination of recombinant human α-interferon and cyanidanol. They received 3 million units of interferon twice a week and 2,250 mg of cyanidanol daily for 24 weeks. Four patients had sustained clinical improvement in which hepatitis B e antigen and DNA polymerase disappeared from sera and aminotransferase activities fell to normal levels. Elevated pretreatment aminotransferases were associated with the response to therapy. Also, decreased number of OKT4-positive cells prior to treatment were observed among responders. Side effects were minimal and all patients tolerated treatment on an outpatient basis.Twice weekly administration of recombinant leukocyte interferon with cyanidanol may be effective in treating chronic hepatitis when patients are appropriately selected.

CASE REPORT: Clinical and virological analyses of a patient positive for hepatitis C virus‐RNA by branched DNA assay but negative for anti‐hepatitis C virus antibodies

Infection with hepatitis C virus (HCV) is usually diagnosed by the presence of antibodies against fusion proteins or peptides derived from different regions of the HCV genome. However, a subgroup of patients with HCV viraemia are seronegative for antibody against hepatitis C virus (anti‐HCV) by conventional antibody assays. We analysed serum samples from a patient with liver cirrhosis who tested negative for anti‐HCV by a second‐generation assay, but positive for HCV‐RNA by reverse transcription‐polymerase chain reaction (RT‐PCR) and branched DNA signal amplification. To identify possible mutations that could explain the failure of detection of anti‐HCV by second‐generation assay, PCR‐amplified DNA fragments of the core region derived from the serum were cloned and sequenced. Nucleotide (nt) and amino acid (aa) sequence analyses (nt 1–486, aa 1–162) showed no mutations revealing stop codons, frame‐shifts, deletions or insertions, but the presence of two amino acid substitutions (aa 75 and 91) when compared with HCV‐J, a prototype strain of genotype 1b isolated from a Japanese patient. One of these two mutations (aa 75) was situated in the second hydrophilic domain of the core peptide, but analysis of the hydropathy profile showed only a little change. The two mutations were identical to those identified in other Japanese HCV isolates. The serum immunoglobulin level and T and B cell counts were normal in our patient. Our data suggest that the absence of anti‐HCV in this patient was not due to mutations of major epitopes of HCV. Low‐dose prednisolone administration just after transfusion may have induced immunological tolerance against HCV in this patient.