Mass screening for hepatocellular carcinoma: Experience in Hokkaido, Japan

Abstract Mass screening for liver cancer based mainly on abdominal ultrasound was begun in major cities of Hokkaido, Japan, in November 1981, to enable early detection and treatment of hepatocellular carcinoma (HCC). Serum alpha-fetoprotein levels were also measured to minimize false negative studies. Examinees included those who sought liver disease screening as well as high risk individuals: hepatitis B surface antigen carriers and those with a past or current liver disease, history of blood transfusion, family history of liver cancer, and more recently those with positive anti-hepatitis C antibodies. The examination was carried out on each Saturday and Sunday as one round, and by February 1992 48 rounds had been performed. A total of 8090 individuals were investigated, and HCC was detected in 91 with a detection rate of 1.12%. This rate was 1.6% among 5684 individuals who were selected for high risk. Cumulative rates of survival among these patients were 79.0% at 1 year, 43.8% at 3 years, 19.3% at 5 years and 15.4% at 7 years. These survival rates were comparable with those for the patients with HCC diagnosed during follow-up of chronic liver disease and treated at our hospital. The cost for detecting one HCC patient in this programme was ¥ 2 660 000 (∼US$25 000), which was less than those for some other types of cancer in a similar setting. Considering the high detection rate in this programme, we feel that similar programmes should be encouraged and supported.     

Subcutaneous seeding of small hepatocellular carcinoma after fine needle aspiration biopsy

Ultrasonically guided fine needle (21 gauge) aspiration biopsy (FNAB) was performed on a patient with a hepatocellular carcinoma (HCC) measuring 1.5 × 1.5 cm in segment VI of the liver. The tumour was located just beneath the liver surface. Subsegmentectomy of segment VI was performed. Twelve months after the biopsy and 10 months after the operation, levels of alpha-fetoprotein (AFP) and protein induced by Vitamin K absence or antagonist-II (PIVKA-II) increased gradually without any evidence of recurrence of HCC in the liver. Thirteen months after the biopsy, the patient palpated a hard subcutaneous nodule 1.5 cm in diameter in the right lower anterior chest wall at the insertion site of the biopsy needle. A subcutaneous tumour was excised and histological examination revealed moderately differentiated HCC. The levels of AFP and PIVKA-II normalized thereafter. These tumour markers were therefore useful for diagnosing the subcutaneous nodule as a metastatic HCC. The patient is currently doing well without further recurrence of HCC or needle-tract seeding 23 months after subsegmentectomy and 11 months after excision of the subcutaneous tumour.     

Clinical utility of ursodeoxycholic acid in preventing flutamide-induced hepatopathy in patients with prostate cancer: A preliminary study

BACKGROUND: The present study was designed to ascertain retrospectively the validity of ursodeoxycholic acid (UDCA) in the treatment of prostate cancer in terms of prophylactic effects on the occurrence of flutamide-induced hepatopathy in a large number of patients surveyed in a multi-center cooperative study. METHODS: One hundred and eighty-one patients (74.1 +/- 4.9 years) with prostate cancer treated with flutamide with (n = 70) or without (n = 111) UDCA were retrospectively evaluated and the occurrence of hepatopathy was compared between these two patient groups. RESULTS: Between patients treated with UDCA and those without it, no significant differences were noted in age, clinical stage, grade, duration of flutamide administration and serum prostate-specific antigen (PSA) levels before treatment. However, there were significant differences in the presence or absence of previous treatments and treatments used together with flutamide. The incidence of hepatopathy was 11.4% (8/70) in patients with UDCA and 32.4% (36/111) in those without it, showing a statistically significant difference (P < 0.05). The hepatopathy-free rate obtained by the Kaplan-Meier method was also significantly higher in patients with UDCA (88.4% 1 year following flutamide administration) than that in those without it (59.6%) (P < 0.005). CONCLUSION: These results suggest that UDCA has a prophylactic effect against flutamide-induced hepatopathy in patients with prostate cancer.     

Changes in extent and zonal distribution of prostatic adenocarcinoma in patients preoperatively treated with neoadjuvant endocrine therapy: Analysis on whole-mounted prostatectomy specimens

BACKGROUND: An increasing number of pharmacologic agents that induce reversible androgen deprivation are available for neoadjuvant endocrine therapy (NET) for prostatic adenocarcinoma (PCA). If information about the regression pattern of PCA after NET is recognized, more effective decision-making for subsequent therapies such as prostatectomy and radiotherapy, will be possible. METHODS: The extent and zonal distribution of PCA with or without NET were examined in totally embedded radical prostatectomy specimens obtained from 103 patients with PCA. Seventy-nine of the 103 patients received androgen deprivation therapy (castrated). The zonal location of PCA lesions (non-transition vs transition zone), was identified in three slices from the inferior, middle and superior parts of the prostate. The area of the PCA lesions in these zones was measured. RESULTS: Prostatic adenocarcinoma was identified in 94 of 103 cases: 24 of 24 cases (100%) and 70 of 79 cases (87%) in the non-castrated and castrated groups, respectively. The NET induced a mean of 21% reduction of the prostate volume and lowered the serum PSA level by one eighth. The frequency of capsular penetration in the castrated cases (57%) was lower than in the non-castrated cases (83%) and confinement of the PCA lesion was found in 32% of the castrated and 17% of the non-castrated cases. The reduction rate of the extent of the PCA lesions in the non-transition and transition zone was 33% and 28%, respectively. The extent of the PCA lesions were smaller in the anterior parts, especially at the superior portion of the prostate. CONCLUSION: Neoadjuvant endocrine therapy induced involutional changes of the PCA evenly across both the non-transition and transition zones. The density of the PCA lesions was low in the anterior part of the prostate. This information is useful for decision-making in post-NET.     

Comparison of 25 and 75 mg/day naftopidil for lower urinary tract symptoms associated with benign prostatic hyperplasia: A prospective, randomized controlled study

BACKGROUND: The present study investigated the efficacy, safety, and utility of starting an alpha(1d)-selective antagonist, naftopidil, at 75 or 25 mg/day in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). METHODS: In this prospective comparative study, the subjects comprised 153 patients with LUTS associated with BPH. Patients were randomized to receive either 25 mg/day (Group LD) or 75 mg/day (Group HD) of naftopidil for 4 weeks. The lower urinary tract disease symptom score (LUTDSS), the International Prostate Symptom Score (IPSS), the Quality of life assessment index, the maximum flow rate (Q(max)), and the residual urine volume were compared between the groups. RESULTS: In both groups, the LUTDSS and the IPSS were significantly improved at the endpoint and no significant intergroup differences were identified. However, the improvement in the Q(max) was significantly better for Group HD than for Group LD. The overall efficacy did not differ significantly between the groups. The degree of improvement in voiding symptoms and LUTDSS among patients with moderate symptoms was significantly greater for Group HD than for Group LD. The frequency of adverse reactions did not differ significantly between the groups. CONCLUSIONS: Starting administration at 75 mg/day rather than 25mg/day is helpful for LUTS associated with BPH for patients with moderate symptoms, particularly in improving voiding symptoms. The 75 mg/day administration was considered to be a recommendable therapeutic dose in some patients.     

Characteristics of patients with staghorn calculi in our experience

PURPOSE: To elucidate the factors contributing to staghorn stone formation in patients. MATERIALS AND METHODS: The records of 82 patients (44 men and 38 women) with complete staghorn calculi were reviewed retrospectively for clinical presentation, metabolic disturbances and anatomical abnormalities. RESULTS: There were 79 unilateral and three bilateral cases. The patient performance of the activities of daily life was assessed with the modified Rankin scale (MRS) and it was found that 69 patients were functionally independent (84.1%, MRS 0-1) and 10 patients had a severe disability (12.2%, MRS 4-5). Seven patients had chronic indwelling catheters (8.5%). A positive urine culture was found in 24.4% of patients. Analysis of stone composition revealed magnesium ammonium phosphate and mixed calcium oxalate-phosphate were the most frequently identified types of stone (32.1% and 22.2%, respectively). Urinary pH was low in patients with uric acid stones (mean 5.4). Hyperuricemia, cystinuria and hypercalciuria were found in 14.6%, 2.4% and 37.8%, respectively. Hypercalciuria was found more frequently in calcium-stone cases. Eleven patients (13.4%) showed structural abnormalities of the kidney. CONCLUSIONS: Our data show that the patients with severe disability, urinary tract infection and hypercalciuria could be recognized more frequently in staghorn calculi compared with common urolithiasis. However, in Western countries, the frequency of both urinary tract infection and struvite stones is much higher than in our data. Other Japanese authors have also reported the low frequency of struvite stones in staghorn calculi, suggesting that various factors other than urinary tract infection possibly contribute to the formation of staghorn calculi in Japan.     

The interferon-α2b gene in Japanese patients with chronic viral hepatitis who developed antibodies after treatment with recombinant interferon-α2a

DNA was extracted from leucocytes of 23 Japanese patients with chronic viral hepatitis who received treatment with recombinant interferon-alpha 2a (IFN-alpha 2a) and nine healthy controls, as well as eight human cell lines of Caucasian or African origin. A part of the gene encoding IFN-alpha 2 was amplified by polymerase chain reaction and the sequence of nucleotides 1-231 was determined. Interferon-alpha 2a, -alpha 2b and -alpha 2c genes were tested for in five clones each from a patient or control, or a cell line, based on adenine or guanine at nucleotide positions 68 and 101. The IFN-alpha 2b gene was detected in all 160 clones from 23 Japanese patients and nine controls, but the IFN-alpha 2a or -alpha 2c gene was not found in any. Of five cell lines derived from Caucasians, four exhibited only the IFN-alpha 2b gene, while the remaining one exhibited both IFN-alpha 2a and -alpha 2b genes. Of three cell lines derived from Africans, one each showed only the IFN-alpha 2b or -alpha 2c gene, and the remaining one both IFN-alpha 2b and -alpha 2c genes. The 23 patients with the IFN-alpha 2b gene and chronic viral hepatitis included 10 who developed antibodies against IFN after treatment with recombinant IFN-alpha 2a. These results indicated a distinct geographical distribution of the three IFN-alpha 2 genes, and suggested the use of a recombinant IFN-alpha 2 preparation in agreement with the IFN-alpha 2 gene possessed by the recipient to avoid antibody responses.     

Flow cytometric analysis of cell proliferation kinetics during duodenal ulcer healing

Cell proliferation in the gastroduodenal mucosa of patients with duodenal ulcers was evaluated using flow cytometry. Forty patients with duodenal ulcers and 12 normal subjects were investigated. Biopsy samples were obtained during endoscopic examination and subjected to DNA analysis by flow cytometry. Thirty patients with duodenal ulcers were healed within 3 months with H₂ blockers (tractable or responsive ulcers), whereas 10 patients did not respond to treatment (intractable ulcers). The percentage of cells at the DNA-synthetic phase, an index of cell proliferation, was constant in the adjacent duodenal mucosa 2cm from ulcer margin and antral mucosa during duodenal ulcer healing. The index at the margin of tractable ulcers was elevated during the active stage (12.9 ± 1.3), peaked during the healing stage (15.4 ± 2.8) and returned to the same level at the scarring stage (10.9 ± 2.0) as normal controls (10.3 ± 1.7). However, the index was not elevated in intractable ulcers (10.3 ± 1.7 in the healing stage) and was smaller than in tractable ulcers. These data indicate that augmented mucosal cell proliferation at the ulcer margin plays an important role in duodenal ulcer healing and intractable ulcers are characterized by an abnormal failure to accelerate DNA synthesis to achieve ulcer repair.     

Marked atrophy of the right lobe seen in idiopathic portal hypertension confirmed by laparoscopy

A 70‐year‐old‐male was hospitalized for the treatment of esophageal varices and close examination of the liver. Blood chemistry tests revealed mild liver dysfunction. Abdominal ultrasound and computed tomography scan revealed marked atrophy of the right and quadrate lobes of the liver without abnormalities of the biliary system. Abdominal angiography revealed marked atrophy of the right lobe of the liver, without obliteration in the portal venous system, but it could not be determined whether the atrophy was congenital or secondary. Subsequently performed laparoscopy revealed marked atrophy of the anterior segment of the right lobe and quadrate lobe with the whitish scarred edge demarcating the border between the edge and neighboring liver parenchyma. The liver surface appeared to be undulant, but non‐cirrhotic. These findings suggest secondary lobar atrophy of the liver, without cirrhosis. Liver biopsy of the left lobe showed the findings to be compatible with idiopathic portal hypertension (IPH), and we diagnosed IPH based on these findings and hepatic lobar atrophy was attributable to IPH. There have been few reports of cases with hepatic lobar atrophy associated with IPH, and the mechanism of atrophy is unclear. We report a case of IPH with marked liver atrophy in which laparoscopy is a decisive means whether liver atrophy is congenital or secondary.