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BACKGROUND In hepatocellular carcinoma (HCC), detection and treatment prior to growth beyond 2 cm are important as a larger tumor size is more frequently associated with microvascular invasion and/or satellites. In the surveillance of very small HCC nodules (≤ 2 cm in maximum diameter, Barcelona clinical stage 0), we demonstrated that the tumor markers alpha-fetoprotein and PIVKA-Ⅱ are not so useful. Therefore, we must survey with imaging modalities. The superiority of magnetic resonance imaging (MRI) over ultrasound (US) to detect HCC was confirmed in many studies. Although enhanced MRI is now performed to accurately diagnose HCC, in conventional clinical practice for HCC surveillance in liver diseases, unenhanced MRI is widely performed throughout the world. While, MRI has made marked improvements in recent years. AIM To make a comparison of unenhanced MRI and US in detecting very small HCC that was examined in the last ten years in patients in whom MRI and US examinations were performed nearly simultaneously. METHODS In 394 patients with very small HCC nodules, those who underwent MRI and US at nearly the same time (on the same day whenever possible or at least within 14 days of one another) at the first diagnosis of HCC were selected. The detection rate of HCC with unenhanced MRI was investigated and compared with that of unenhanced US. RESULTS The sensitivity of unenhanced MRI for detecting very small HCC was 95.1% (97/102, 95% confidence interval: 90.9-99.3) and that of unenhanced US was 69.6% (71/102, 95% confidence interval: 60.7-78.5). The sensitivity of unenhanced MRI for detecting very small HCC was significantly higher than that of unenhanced US (P < 0.001). Regarding the location of HCC in the liver in patients in whom detection by US was unsuccessful, S7-8 was identified in 51.7%. CONCLUSION Currently, unenhanced MRI is a very useful tool for the surveillance of very small HCC in conventional clinical follow-up practice.

Oral direct-acting antivirals (DAAs) are the main therapy for hepatitis C virus (HCV)-associated liver disease in Japan. Moreover, many DAAs include an indication for compensated liver cirrhosis. However, patients with decompensated HCV-associated cirrhosis have hitherto not been indicated for therapy with DAAs. Recently, a new DAA, sofosbuvir/velpatasvir (SOF/VEL), was indicated for decompensated HCV-associated cirrhotic patients. Actually, it has been shown to eradicate HCV in many cases. However, it is not clear whether hepatic encephalopathy, ascites, and pleural effusion in patients with decompensated HCV-associated cirrhosis disappear by SOF/VEL treatment. Recently, we encountered a decompensated HCV-associated cirrhosis patient who showed the disappearance of hepatic encephalopathy, ascites, and pleural effusion with marked improvement of serum ammonia level, albumin level, prothrombin time, and platelet count after the eradication of HCV by the administration of SOF/VEL. Her consciousness was cloudy and it took many hours for the preparation of each meal just before SOF/VEL treatment, but after the disappearance of HCV-RNA by the therapy, her consciousness became clear and she could prepare meals in a short time. This case suggests the possibility of improvement from decompensated HCV-associated liver cirrhosis to compensated liver cirrhosis with disappearance of hepatic encephalopathy, ascites, and pleural effusion by SOF/VEL therapy.

BACKGROUND The oral nucleos(t)ide analogue, entecavir (ETV) was demonstrated to reduce the rate of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV)-associated liver cirrhosis. However, the reduction of HCC differs in various regions of the world. AIM To investigate the reduction of HCC development due to ETV therapy by meta-analysis. METHODS We surveyed the differences in HCC development following ETV treatment based on published articles using PubMed (2004-2019). RESULTS The regions with the most marked reduction in HCC development due to ETV therapy were Spain (1.0%/year) and Canada (Southern part, 1.3%/year), and the most ineffective areas were South Korea (3.6%-3.8%/year), China (3.3%/year), Taiwan (2.4%-3.1%/year), and Hong Kong (2.8%/year). Following ETV administration, the incidence of HCC in genotype D regions (1.89% ± 0.28%/year, mean ± SE) was significantly lower than that in genotype C regions (2.91% ± 0.24%/year, P < 0.01). With regard to the initial HBV-DNA level, in genotype C patients (average: 5.61 Log10IU/mL) this was almost the same as that in genotype D patients (average: 5.46 Log10IU/mL). Moreover, there was no association between the prevalence ratio of HBV and the incidence of HCC on ETV treatment. CONCLUSION The effectiveness of ETV in preventing HCC development in HBV-associated liver cirrhosis is genotype-dependent.

BACKGROUND In hepatocellular carcinoma (HCC), detection and treatment prior to growth beyond 2 cm are relevant as a larger tumor size is more frequently associated with microvascular invasion and/or satellites. AIM To examine the impact of the tumor marker alpha-fetoprotein (AFP) or PIVKA-II in detecting very small HCC nodules (≤ 2 cm in maximum diameter, Barcelona stage 0) in the large number of very small HCC. The difference in the behavior of these tumor markers in HCC development was also examined. METHODS A total of 933 patients with single-nodule HCC were examined. They were subdivided into 394 patients with HCC nodules ≤ 2 cm in maximum diameter and 539 patients whose nodules were > 2 cm. The rates of patients whose AFP and PIVKA-II showed normal values were examined. RESULTS The positive ratio of the marker PIVKA-II was significantly different (P < 0.0001) between patients with nodules ≤ 2 cm in diameter and those with nodules > 2 cm, but there was no significant difference in AFP (P = 0.4254). In the patients whose tumor was ≤ 2 cm, 50.5% showed normal levels in AFP and 68.8% showed normal levels in PIVKA-II. In 36.4% of those patients, both AFP and PIVKA-II showed normal levels. The PIVKA-II-positive ratio was markedly increased with an increase in the tumor size. In contrast, the positivity in AFP was increased gradually and slowly. CONCLUSION In the surveillance of very small HCC nodules (≤ 2 cm in diameter, Barcelona clinical stage 0) the tumor markers AFP and PIVKA-II are not so useful.

Oral direct-acting antivirals (DAAs) are the main therapy for hepatitis C virus (HCV)-associated liver disease in Japan. Daclatasvir/asunaprevir is the first agent and sofosbuvir/ledipasvir is the secondary agent for HCV genotype 1b. More recently, ombitasvir/paritaprevir/ritonavir is also recommended as a potent therapy for HCV genotype 1b. Among the adverse events associated with these oral DAAs, interstitial pneumonia is one of the most severe ones. Regarding treatment with daclatasvir plus asunaprevir or sofosbuvir plus ledipasvir, a few cases have already been reported in a postmarketing surveillance. Recently, we have encountered a HCV-associated genotype 1b cirrhosis patient who developed interstitial pneumonia during treatment with ombitasvir/paritaprevir/ritonavir and who recovered after drug discontinuation without corticosteroid therapy. Interstitial pneumonia was confirmed by chest x-ray and chest computed tomography. The serum KL-6 level was elevated to 1,180 U/mL. The total duration of the drug administration was 7 weeks, and she achieved SVR24. This is the first detailed report in the literature on the development of interstitial pneumonia during treatment with ombitasvir/paritaprevir/ritonavir. When dry cough appeared in the treatment with DAAs, chest computed tomography and the evaluation of serum KL-6 level were recommended.

Background It is well known that the incidence of developing hepatocelluler carcinoma (HCC) is increased in liver cirrhosis of different etiologies. However, comparison of HCC incidence in various liver diseases has not yet been estimated. We surveyed this comparison. Methods The PubMed database was examined (1989‐2017) for studies published in English language regarding the prospective follow‐up results for the development of HCC in various liver diseases. A meta‐analysis was performed for each liver disease. Results The annual incidence (%) of HCC in the non‐cirrhotic stage and cirrhotic stage, and the ratio of HCC incidence in the cirrhotic stage/non‐cirrhotic stage were as follows. (a) hepatitis B virus liver disease: 0.37%→3.23% (8.73‐fold), (b) hepatitis C virus liver diseases: 0.68%→4.81% (7.07‐fold), (c) primary biliary cholangitis (0.26%→1.79%, 6.88‐fold), (d) autoimmune hepatitis (0.19%→0.53%, 2.79‐fold), and (e) NASH (0.03%→1.35%, 45.00‐fold). Regarding primary hemochromatosis and alcoholic liver diseases, only follow‐up studies in the cirrhotic stage were presented, 1.20% and 2.06%, respectively. Conclusions When the liver diseases advance to cirrhosis, the incidence of HCC is markedly increased. The development of HCC must be closely monitored by ultrasonography, magnetic resonance imaging, and computed tomography, irrespective of the different kinds of liver diseases.

OBJECTIVE Right-sided type colonic diverticulosis has been predominant in Japan, in contrast to European counties where the left-sided type is predominant. Considering the recent change in the dietary habits of Japanese people to a more Western diet in urban areas of Japan, the features of colonic diverticulosis may also change to reflect a more Western type. Therefore, we attempted to clarify the current situation. METHODS A total of 435 consecutive outpatients who agreed to a barium enema and complete examination were enrolled in this study. RESULTS 113 patients (26.0%) revealed colon diverticulosis; 50.4% of the patients had more than ten diverticula. The percentage of man with ten or more diverticula (67.4%) was significantly higher than that of women patients (40.0%, p

Objective. To assess retrospectively whether continuously high serum alanine aminotransferase (ALAT) levels (80 IU) in the first three successive years after the diagnosis of liver cirrhosis (LC) are predictive of a subsequent high incidence of hepatocellular carcinoma (HCC) in patients with Child Stage A hepatitis C virus (HCV)-LC. Material and methods. The study comprised 132 HCV-LC (Child Stage A) patients who had not received interferon therapy but had been treated with anti-inflammatory agents. At the end of a 3-year follow-up after the diagnosis of LC, the patients were subdivided into three groups according to their serum ALAT levels and the subsequent incidence of HCC was assessed. Results. The cumulative incidence of HCC starting from 3 years after the diagnosis of LC in the continuously high ALAT group (annual average over 3 years alwaysor =80 IU; n=41; Group A) was markedly higher than that in the continuously low ALAT group (always80 IU; n=48; Group B) (p0.005) during an observation period of 7.9+/-3.7 years. The incidence of HCC in Group A was 11.8%/year. The odds ratios of developing HCC in Group A and Group C (mixed high and low ALAT levels; n=43) were 5.1-fold and 1.5-fold that of Group B, respectively. A multivariate analysis revealed that the ALAT group was independently associated with HCC development. Conclusions. Continuously high ALAT levels for three successive years following the diagnosis of LC can be predictive of a very high incidence of HCC in Child A HCV-LC patients. Prospective trials using therapeutic approaches aimed at decreasing ALAT levels are necessary in order to confirm a positive impact of ALAT reduction on the incidence of HCC in patients with HCV-LC.

Background: The probable role of cyclo-oxygenase-2 (COX-2) in the development of hepatocellular carcinoma (HCC) in patients with chronic liver diseases has been accepted to be relevant. The purpose of the present study was to determine whether overexpressed COX-2 in the background liver affects the clinical course of hepatitis C virus (HCV)-related cirrhosis patients after curative surgery for HCC. Methods: Twenty-nine clinical stage I HCC patients with HCV-related cirrhosis, who underwent curative surgery, were enrolled in the present study (22 men and seven women, age range 53–73 years; follow-up period; range 22–159 months, median 61 months). The COX-2 expression in the cirrhotic liver was examined by immunohistochemistry using the avidin–biotin–peroxidase complex technique on paraffin-embedded formalin-fixed tissue. The COX-2 expression was scored, then correlated with monitored alanine aminotransferase (ALT) levels during the follow-up period after surgery, response to alternative therapy aiming to improve elevated ALT levels, and recurrence/survival after surgery. Results: The COX-2 expression scores were significantly higher in the high-ALT group than in the low-ALT group (Mann–Whitney, P = 0.010), and were significantly higher in non-responders to the alternative therapy than in responders (Mann–Whitney, P = 0.028). The higher COX-2 expression in the cirrhotic liver was the significant independent risk factor for residual liver recurrence (Cox multivariate analysis, P = 0.014), but not for survival. Conclusions: Overexpressed COX-2 in the background liver may play an important role in prolonged acceleration of necroinflammation, resistance to the alternative therapy, and recurrence/new development of HCC in HCV-related cirrhosis patients.

We examined whether sustained alleviation of inflammation as monitored by serum alanine aminotransferase (ALT) levels was associated with longer survival in hepatectomized hepatocellular carcinoma (HCC) patients with hepatitis C virus-associated liver cirrhosis (HCV-LC). Thirty-four hepatectomized patients with HCV-LC and HCC as a single nodule, and for whom more than 5 years had elapsed after the hepatectomy, were studied. They had no histologic evidence of portal or hepatic vein invasion. They were subdivided into two groups according to their serum ALT levels in the 2 years after hepatectomy: the low ALT group comprised 13 patients whose serum ALT levels showed a sustained low level below 80 IU, and the high ALT group comprised 21 patients whose serum ALT levels showed several peaks or plateaus above 80 IU. The patients had been followed-up prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography for recurrence for > 5 years. The survival period, non-recurrence interval and number of recurrences were observed. Recurrences were treated with transcatheter chemoembolization in all cases. The cumulative survival rate in the low ALT group was significantly better than that in the high ALT group (P < 0.05). The 5-year survival in the low ALT group was as high as 92.3% (12 of 13) compared with 33.3% (7 of 21) in the high ALT group (P < 0.05). The cumulative non-recurrence rate in the low ALT group was also significantly better than that in the high ALT group (P < 0.01). The survival period correlated well with the interval until the first recurrence (r = 0.545, P = 0.006). There was a tendency for the number of recurrences in the low ALT group (1.5 +/- 0.4, mean +/- SE) to be fewer than that in the high ALT group (2.2 +/- 0.4), although this was not significant. Sustained alleviation of inflammation, as indicated by low ALT levels, provides a survival advantage mainly due to the longer non-recurrence interval, and possibly because of fewer recurrences, in hepatectomized HCC patients with HCV-LC.

We investigated whether or not a high serum alanine aminotransferase (ALT) level is associated with a more rapid recurrence of hepatocellular carcinoma (HCC) in hepatectomized patients with hepatitis C virus (HCV)-associated liver cirrhosis (LC) (HCV-LC) and HCC. Thirty-three hepatectomized patients with HCV-LC and HCC of a single nodule who had no histologic evidence of portal or hepatic vein invasion and who had been followed up for more than 3 years were included in the study. They were subdivided into two groups according to their serum ALT levels, ALT being a well-known marker of inflammatory necrosis in the liver. Seventeen patients whose serum ALT levels showed several peaks or plateaus above 80 international units (IU) were designated as the high ALT group, and 16 patients whose serum ALT levels showed a sustained low level below 80 IU until the first recurrence were designated as the low ALT group, and the interval between hepatectomy and the first recurrence was observed. In the high ALT group, HCC recurred within 3 years in 70.6% of the patients. In contrast, it recurred in only 18.8% of the low ALT group within the same period (p < 0.05). There was a significant difference (p = 0.0201) between the two groups in the cumulative nonrecurrence rate. The mean interval in recurrent patients between hepatectomy and the first recurrence in the high ALT group (23.6 ± 2.8 months; mean ± SE) was significantly (p < 0.02) shorter than that in the low ALT group (49.3 ± 9.7 months). The expected interval between hepatectomy and recurrence was as short as 2.8 ± 0.5 years (mean ± SE) in the high ALT group, compared with 5.8 ± 0.7 years in the low ALT group (p < 0.05). These results showed that the recurrence of HCC was accelerated in the high ALT group, suggesting that suppression of the rise in ALT level after hepatectomy by treatment with anti-inflammatory drugs may prolong the interval until recurrence by about 2 years in hepatectomized patients with HCC and HCV-LC.

It is accepted that inflammation promotes malignant progression in the development of cancers. Whether, this is true for hepatocellular carcinoma (HCC) remains as an open question. We examined the relationship between the inflammatory histology activity index (HAI) in the background liver cirrhosis (LC) and the histological grading of the HCC in the hepatectomized HCC patients with HCV-associated LC.Out of 264 HCC patients who underwent curative hepatic resection, 197 had HCV-associated LC. Among them, 52 patients with a small solitary HCC nodule (5 cm in diameter) were studied. Inflammation in the background LC was evaluated by modified Knodell's HAI. To evaluate the inflammation, piece meal necrosis, intra lobular cellular degeneration and focal necrosis, portal cellular inflammation (0-4, each) were estimated. The average HAI was calculated. The grade of malignancy of HCC was determined by WHO classification.The average HAI in the 15 patients with moderately differentiated HCC (4.3 ± 0.8, mean ± SD) was significantly larger than that in 11 patients with well differentiated HCC (3.5 ± 0.6, p = 0.036). The HAI in the 24 patients whose HCC nodules contained poorly differentiated HCC (5.2 ± 1.1) was significantly larger than that in patients with moderately differentiated HCC (p = 0.025). Thus, the HAI order was well differentiated groupmoderately differentiated grouppoorly differentiated group.Inflammation in the background non-cancerous cirrhotic portion would evoke malignant progression in HCC development from HCV-associated LC.

The ratio of the number of cases of slightly elevated (flat shaped) nodules to hemispherical nodules on laparoscopical examination was studied in male and female histologically proven cirrhotic patients in Child A stage. The bromodeoxyuridine labeling indices (BrdU Lis) of all of the cirrhotic patients were examined using an in vitro labeling technique. Liver biopsy specimens obtained by a Tru-cut needle were immediately incubated for 45 min. in 0.1% BrdU solution in RPMI 1640 at 37°C under a pressure of 3 atmospheres in a mixture of 95% O2 and 5% CO2. Immunohistochemical detection of BrdU was performed using the ABC method. In the 18 male cirrhotic patients in Child A stage, 12 (67%) were found to have hemispherical nodules, and 6 (33%) were found to have slightly elevated nodules. In the 18 female cirrhotic patients, 5 (28%) had hemispherical nodules, and 13 (72%) had slightly elevated nodules (p< 0.05). The mean BrdU LI in male cirrhotic patients (2.07 ± 0.36%, SE) was greater than that of the female patients (1.21 ± 0.31%). The average BrdU LI of the hemispherical cirrhotic group (2.41 ± 0.39%) was significantly (p< 0.005) greater than that of the slightly elevated cirrhotic group (0.98 ± 0;21%). We found that about 70% of the male cirrhotic patients in Child A stage had a laparoscopically hemispherical nodular liver, as compared to about 30% of the female cirrhotic patients (p

OBJECTIVE Whether severe inflammation in the background liver cirrhosis might correlate with the development of poorly differentiated human hepatocellular carcinoma (HCC) was studied in hepatitis C virus (HCV)-associated liver cirrhosis. METHODS Out of 214 HCC patients who underwent curative hepatic resection, 148 patients were HCV-associated liver cirrhosis (LC) patients. Out of these 148, 31 patients with small solitary HCC nodule (diameter ≤ 3 cm) were included in this study. Inflammation in the background LC was evaluated by modified histology activity index (HAI). To evaluate the inflammation, piece meal necrosis, intra lobular cellular degeneration and focal necrosis, portal cellular inflammation (each 0-4) were estimated. In each case, the average HAI was calculated. The grade of malignancy of HCC was determined by World Health Organization (WHO) classification. RESULTS The average HAI score in the cirrhotic portion in 17 patients with poorly differentiated HCC (5.21 ± 1.15, mean ± standard deviation (SD)) was significantly larger than that in 14 patients without poorly differentiated HCC (4.05 ± 0.83, p

To examine whether the marked increase in DNA synthesis of hepatocytes in cirrhotic liver might elicit multicentric hepatocarcinogenesis, we examined the relationship between new development of hepatocellular carcinoma (HCC) and the bromodeoxyuridine (BrdU) labeling index (LI) of hepatocytes in the residual liver of hepatectomized patients with liver cirrhosis (LC) and HCC. Eighteen hepatectomized patients with LC and HCC, whose resected liver revealed neither portal nor hepatic vein invasion by histologic examination, were studied (to exclude cases with intrahepatic metastasis). DNA synthesis activity of hepatocytes from the residual cirrhotic liver was measured by a BrdU/anti-BrdU in vitro method. The incidence of HCC recurrence was studied during a 3-year follow-up period. Among 18 patients, 9 patients had recurrence and 9 did not. The average BrdU LI in the recurrent patients was 2.6 +/- 1.3% and was significantly higher than that in patients without recurrence (1.4 +/- 0.5%, P < 0.05). All five patients who had a BrdU LI of 2.4% or above showed recurrence within 3 years, as compared with 4 of 13 (30.8%) patients with BrdU LI of less than 2.4% (P < 0.05). Our data indicate that abnormally high DNA synthesis in hepatocytes in the background cirrhosis might lead to the development of multicentric carcinogenesis in human cirrhotic liver, and in the residual cirrhotic liver of hepatectomized patients with HCC and LC, it may be a predictor of new development of HCC.

Nowadays, patients with chronic hepatitis C in all countries are generally treated with interferon (IFN), and more than 50% of patients become HCV-RNA negative following PEG-IFN plus ribavirin therapy, but unfortunately, the IFN therapy is not effective in about 70% of patients with HCV-associated LC. In Japan, HCC actually develops in about 7% of those patients every year. A strategy for preventing HCC development other than IFN therapy is, therefore, urgently needed for those patients. We reported that the recurrence rate and the development of HCC was more rapid in the high serum ALT level (>80 IU) patients with HCV-associated LC. Sho-saiko-to, Juzen-taiho-to, and stronger-neo minophagen C are herbal medicines used in Japan to treat chronic viral liver diseases, and they work by reducing inflammatory processes and controlling ALT levels. Aggressive reduction therapy for ALT levels in HCV-LC patients could significantly prevent HCC development.

Background. The relationship between the DNA synthetic activity of hepatocytes from cirrhotic liver tissue and the incidence of hepatocellular carcinoma (HCC) during a 3-year follow-up period was studied in male and female patients with posthepatitic cirrhosis. Methods. The bromodeoxyuridine labeling index (BrdU LI) of hepatocytes was estimated in 38 cirrhotic patients (Child A stage, 23 men and 15 women) using a BrdU/anti-BrdU in vitro method. The incidence of HCC was compared between male and female cirrhotic patients during a 3-year follow-up period. Results. Sixteen of 23 (69.6%) male patients belonged to the high-DNA synthesis group (BrdU LI ⩽ 1.5%), and only 7 (30.4%) were in the low-DNA synthesis group (BrdU LI < 1.5%). Among female patients, only 5 of 15 (33.3%) were in the high-DNA synthesis group, and 10 of 15 (66.7%) were in the low-DNA synthesis group (P < 0.05). Eleven of 23 (47.8%) male patients and 3 of 15 (20.0%) female patients had HCC develop. In the high-DNA synthesis group, 10 of 16 (62.5%) of the men and 3 of 5 (60.0%) of the women had HCC develop during the follow-up period. In contrast, only one of seven (14.3%) male patients and none of ten (0%) female patients in the low-DNA synthesis group had HCC develop. Conclusions. It was concluded that HCC developed frequently (about 60% of the time within 3 years) in patients of both sexes who were in a high-DNA synthesis group. Thus, the larger proportion of men in the high-DNA synthesis group compared with the number of women in the group (69.6% versus 33.3%) might be one possible reason for the male predominance in the development of HCC in cirrhotic patients.

BACKGROUND There is a concept that a cancer often maintains some of the traits of the background tissue cells. Thus, the possibility exists that the DNA synthetic activity of the hepatocytes in cirrhotic tissue affects that of hepatocellular carcinoma (HCC) cells. METHODS DNA synthesis activity of hepatocytes from background cirrhotic tissue and HCC cells from cancerous tissue was studied in 30 patients with liver cirrhosis (LC) and HCC who had undergone hepatectomy; the study was done using the bromodeoxyuridine (BrdU)-anti-BrdU in vitro method. The correlation between the BrdU labeling index (LI) of hepatocytes from noncancerous cirrhotic tissue and that of HCC cells was studied. The relationship between both BrdU LI values and the survival after hepatectomy also was studied. RESULTS A significant correlation (r = 0.572; P < 0.001) was identified between the BrdU LI for HCC and that for noncancerous cirrhotic tissue. A significant correlation (r = -0.572; P < 0.05) was found between the BrdU LI of HCC cells and the survival after hepatectomy. A significant correlation (r = -0.678; P < 0.01) was observed between the BrdU LI of the noncancerous cirrhotic tissue and the survival. CONCLUSIONS It was concluded that a significant correlation existed between DNA synthesis of hepatocytes from the background cirrhotic tissue and that of HCC cells and that DNA synthesis activity of hepatocytes from noncancerous cirrhotic tissue and that of HCC cells from cancerous tissue could predict the survival of patients with HCC who had undergone hepatectomy.

Colonic diverticulosis is now a common global disease, but the treatment has conventionally been directed towards its associated complications, such as infection and bleeding, and the treatment of diverticulosis itself has rarely been discussed. This is a case of complete resolution (disappearance) of multiple diverticula in the ascending colon of a Japanese 58-year-old male patient who undertook a frequent, long distance running program for a period of about 8 months. The disappearance was confirmed by barium enema. The patient continued the running program thereafter, and the third barium enema, which was performed 1 year and 3 months after the second, again revealed no diverticula in the ascending colon. He consumed more vegetables after the first barium enema examination (1.52-fold increase). The stools were solid and compact, and effort was needed to void before the running program, but after the running program began, they were loose and easy to void. This case suggests that frequent, vigorous physical exercise, such as long distance running, in conjunction with the consumption of more vegetables can resolve or reduce right-sided colonic diverticula. The decreased intracolonic luminal pressure after running was presumed to be effective.

The relationship between DNA synthesis activity in hepatocytes from cirrhotic tissue and development of hepatocellular carcinoma was studied in 33 posthepatitic patients with Child's grade A cirrhosis. DNA synthesis activity was measured by a bromodeoxyuridine (a thymidine analogue) labeling index, using the bromodeoxyuridine-antibromodeoxyuridine in vitro method, and the patients were followed up prospectively with frequent liver ultrasonography for 2 years. During the 2-year follow-up, 11 of the 33 cirrhotic patients developed hepatocellular carcinoma; they included 8 of the 15 patients (53%) in the high labeling index (greater than 1.5%) group compared with only 3 of the 18 patients (17%) in the low labeling index (less than 1.5) group (P less than 0.05). Five of the latter 18 subsequently had increased synthesis activity. Of these 20 patients who showed high synthesis activities either initially or subsequently, 10 (50%) developed hepatocellular carcinoma, in contrast to 1 of 13 (8%) with persistently low activities (P less than 0.05). Thus, hepatocellular carcinoma seems to develop or may become detectable when DNA synthesis in the background cirrhosis is increasing or remains high.

The deoxyribonucleic acid (DNA) synthetic potency of hepatocytes in liver biopsy specimens was investgated in: 6 patients with primary biliary cirrhosis (PBC) with a laparoscopical finding of a “reddish patch”, 5 patients with PBC without a “reddish patch”, 10 patients with chronic aggressive hepatitis with a typical “patchy liver” as seen on laparoscopy, 14 patients with cirrhosis of a viral origin with a laparoscopic “nodular liver”, and in 6 patients with gastric cancer without liver involvement (control subjects). The bromodeoxyuridine (BrdU, a thymidine analogue) -anti-BrdU method was used. The mean BrdU L. I. (±SE) of the PBC patients with a “reddish patch”, PBC patients without a “reddish patch”, patients with a “patchy liver”, patients with a “nodular liver” and of the control subjects was 3.5±0.6%, 0.5±0.1%, 1.3±0.3%, 1.1±0.3%, and 0.2±0.1% respectively. The BrdU L.I. of the PBC patients with a “reddish patch” was significantly greater than that of the PBC patients without a “reddish patch” (p>0.001) and greater than that of patients with a “patchy liver” or a “nodular liver” (p>0.001, respectively). It was the greatest in all of the benign liver diseases examined. Thus, the so-called laparoscopical finding of a “reddish patch” in PBC may represent a marked regeneration of hepatocytes.

Vancomycin hydrochloride (2 g daily) was administered to 12 patients with cirrhosis and lactulose resistant portal systemic encephalopathy in a double blind crossover trial. All 12 patients showed a remarkable clinical improvement after vancomycin treatment. The mean (SE) electroencephalographic (EEG) frequency changed from 6.3 (0.2) to 8.5 (0.2) cps (p less than 0.001) and the mean arterial ammonia concentration from 152 (4) micrograms/ml to 97 (8) micrograms/ml (p less than 0.001). Their clinical condition deteriorated when treatment was switched to lactulose, returning to the previous slower EEG frequency and high arterial ammonia concentrations. Vancomycin seems to be effective in chronic portal systemic encephalopathy in patients who are not helped by lactulose alone.

Bromodeoxyuridine (BrdU) labeling indices (LI) of liver biopsied specimens from 27 control liver cirrhosis patients (control LC) without hepatocellular carcinoma (HCC), 26 cirrhotic patients with HCC, and from 6 control subjects were examined using an in vitro BrdU labeling technique. The mean BrdU LI +/- S.E. of HCC cancerous portion, HCC non-cancerous cirrhotic portion, control LC, and control subjects were 6.6 +/- 0.8%, 2.7 +/- 0.3%, 1.7 +/- 0.3% and 0.25 +/- 0.09%, respectively. Interestingly, there was a significant difference (p less than 0.025) between the non-cancerous LC portion and control LC. While 25 of 26 non-cancerous LC portion of HCC patients were in the high LI group (greater than or equal to 1.4%), 15 of 27 in the control LC were in the low LI group (less than 1.4%) (p less than 0.001). Of the 12 control LC with high LI, 6 developed HCC within 2 years, whereas only one of the 15 control LC with low LI developed HCC (p less than 0.05). In conclusion, HCC may develop in cirrhotic patients with high DNA synthetic potency.

無黄疸の原発性胆汁性肝硬変症の各病期における肝容積と肝細胞DNA合成能を検討した.全例女性でPBC 13例(I期4例,II期6例,III期3例),健常肝6例,慢性活動性肝炎(CAH) 19例,代償性肝硬変症(LC) 14例について肝容積をCT scanで測定し,さらに肝生検組織のBromodeoxyuridine (BrdU)の摂取率(Labeling Index)を抗BrdU抗体を用いてin vitro法によって検索した.結果:肝容積は,健常肝835±42 (SE) cm3, CAH 1,029±101cm3, LC 1,090±95cm3, PBC I期1,210±29cm3, II期1,236±69cm3,II1期1,170±73cm3, PBC全例1,207±36cm3であり,PBC全例は健常肝の約1.5倍と有意に大きく,II期が最大であった.一方,BrdU L.I.は健常肝0.2±0.1%, CAH 0.9±0.2%, LC 1.0±0.3%, PBC I期2.3±0.3%, II期4.1±0.4%,III期0.4±0.04%, PBC全例2.7±0.5%であり,PBC全例は,健常肝,CAH, LCに対し,それぞれ有意に高率であった.早期PBCでは肝容積が有意に増大しており,肝細胞のDNA合成亢進によると思われた.

肝硬変(LC)の肝細胞のDNA合成能に男女差が存在するか否かを,Bromodeoxyuridine (BrdU)によるLabeling Index(L.I.)から検討した.腹腔鏡下肝生検にて採取した組織を,0.1%BrdU RPMI1640溶液中で45分間振盪培養し,免疫染色にてBrdUのL.I.を算出した.男性LCのL.I.は2.2±0.3%と高値であったのに対し,女性LCのL.I.は1.1±0.3%と低く,2%の危険率をもって男性が有意の高値を示した.血液肝機能検査で,男女間に有意差は無かった.慢性活動性肝炎(CAH)についても同様に検討し,男性CAHのL.I.が1.2±0.2%であったのに対し,女性CAHのL.I.は0.9±0.2%であり,両群間に有意差は無かった.肝硬変症例のうち,2年以上の経過観察を行った男性14例から6例のHCC発生を認めたが,女性7例からはHCCの発生は無かった.HCCの発生率における男女差に,LC組織におけるDNA合成能の男女差が関与しているものと推察された.

BACKGROUND Studies have shown that angiogenesis is one of the factors that influences the prognosis of patients with solid tumors, including pancreatic carcinomas. However, none have assessed noninvasively the relation between angiogenesis and prognosis in patients with pancreatic carcinoma. Contrast-enhanced ultrasonography (US) not only is a convenient, harmless, and noninvasive imaging modality, but it also provides detailed information on tumor vascularity. The objectives of this study were to assess the vascularity of pancreatic carcinoma noninvasively by contrast-enhanced US and to clarify the prognostic value of tumor vascularity in patients with nonresectable pancreatic carcinoma. METHODS Thirty-five consecutive patients with pathologically confirmed, nonresectable pancreatic carcinoma were examined with contrast-enhanced US before systemic chemotherapy. The correlations among tumor vascularity, clinicopathologic factors, and clinical outcomes then were analyzed statistically to investigate prognostic indicators. RESULTS The median time to progression (TTP) was longer in patients who had avascular tumors compared with patients who had vascular tumors (110 days vs. 28 days, respectively; P = 0.0072; log-rank test). The median survival also was longer in patients who had avascular tumors (267 days vs. 115 days, respectively; P = 0.0034; log-rank test). A multivariate analysis using a Cox proportional hazards model revealed that tumor vascularity was a significant, independent factor that influenced TTP (P < 0.001) and survival (P = 0.022) along with primary tumor size and serum lactate dehydrogenase (LDH) level, which are well known as prognostic factors in patients with pancreatic carcinoma. CONCLUSIONS The current results indicated that contrast-enhanced US may be useful in assessing the prognosis of patients with nonresectable pancreatic carcinoma who receive systemic chemotherapy. Cancer 2005. © 2005 American Cancer Society.

In a previous study of patients with hepatitis C virus (HCV)–associated liver cirrhosis (HCV-LC), we showed that increased liver inflammation, as assessed by higher serum alanine aminotransferase (ALT), was associated with increased risk for the development of hepatocellular carcinoma (HCC). This suggested that suppression of inflammation might inhibit HCC development in HCV-LC. Several agents have been suggested to possess chemopreventive potential against the development of HCC in chronic HCV-associated liver disease, including herbal medicines, such as Stronger-Neo-Minophagen C (glycyrrhizin) and Sho-saiko-to (TJ-9). Ursodiol [ursodeoxycholic acid (UDCA)], a bile acid widely used to treat cholestatic liver diseases, also possesses anti-inflammatory properties in liver disease. We hypothesized that suppression of liver inflammation, as assessed by decreases in serum ALT, might inhibit HCC occurrence in patients with HCV-LC. In this study, the preventive effect of UDCA on HCC was examined in patients with early-stage HCV-LC. One hundred two patients with HCV-LC (Child stage A) were treated with anti-inflammatory drugs, Stronger-Neo-Minophagen C,Sho-saiko-to, or UDCA, with the goal of lowering the average serum ALT level to 5 years and were retrospectively subdivided into two groups: 56 UDCA users (group A) and 46 UDCA nonusers (group B). The mean ± SD dosage of UDCA administered in group A was 473.7 ± 183.0 mg/d. The average duration of UDCA administration in group A was 37.3 ± 15.9 months over the 5-year study period. The cumulative incidence of HCC was recorded. The 5-year incidence of HCC in group A was 17.9% (10 of 56) and was significantly lower than that in group B (39.1%, 18 of 46; P = 0.025). The risk for HCC incidence, calculated by a logistic regression model, showed that the administration of UDCA significantly decreased hepatocarcinogenesis (P = 0.036). The herbal medicines used were comparable in dosage and treatment duration in the UDCA and non-UDCA groups. In conclusion, UDCA might prevent HCC development in HCV-LC. Interestingly, because the serum ALT trends over time were nearly the same in both groups, the chemopreventive effectiveness of UDCA was not accompanied by greater reductions in ALT compared with the UDCA nonusers.

A 46-year-old woman with a 3-month history of upper abdominal pain was referred to our hospital because of the presence of a pancreatic mass and multiple hepatic nodules on abdominal ultrasonography (US) and computed tomography (CT). We concluded that the patient had pancreatic cancer with multiple hepatic metastases on the findings of endoscopic retrograde cholangiopancreatography (ERCP) and fine needle aspiration biopsy of the hepatic nodule. The patient received gemcitabine treatment. Gemcitabine 1,000 mg/m2 was administered once a week for 3 weeks followed by a week of rest, this constituting 1 cycle of treatment. Partial responses (PR) of both pancreatic and hepatic lesions were observed after the first cycle of the gemcitabine treatment, and serum concentrations of CEA and CA19-9 remarkably decreased. We considered that clinical benefit was obtained because Karnofsky performance status improved and analgesic consumption decreased. Such effectiveness of the gemcitabine treatment lasted for the following 4 cycles. In general, chemotherapy has few effects on an advanced pancreatic cancer. We report a case of advanced pancreatic cancer that could obtain remarkable antineoplastic effect and clinical benefit with gemcitabine treatment.

An analysis was performed of the patients with hepatitis C virus-associated liver cirrhosis (HCV-LC) who never developed hepatocellular carcinoma (HCC) for 10 years after the histological diagnosis of LC. Seventy-four consecutive HCV-LC patients of Child stage A were observed for >10 years prospectively for the development of HCC with frequent ultrasonography and magnetic resonance imaging or computed tomography. Of the 63 patients who fulfilled the study, 48 patients were treated and 15 were nontreated because of their stable state. They were subdivided into three groups according to their serum alanine aminotransferase (ALT) levels: the high ALT group comprised of 23 patients whose annual average serum ALT level was persistently high (≧80 IU); the low ALT group comprised of 28 patients whose annual average serum ALT level was persistently low (

Percutaneous microwave coagulation therapy (PMCT) and radio frequency ablation therapy (RFA) as treatments for metastatic liver cancer were examined. PMCT or RFA was administered for 18 metastatic liver cancer lesions (primary lesion: 11 colon rectal cancer, one esophagus cancer, one thyroid cancer, one pancreatic cancer, one pheochromocytoma) in 16 patients from July 1999 to March 2002. RFA was performed 1 time for 12 minutes in principle, using a Cool-tip RF system from Radionics. Patients had a mean age of 58.8 years and the mean diameter of the neoplasms was about 22 mm. Critical complications were not seen. The rate of partial recurrence was 35.3% as of March, 2002, in an average observation period of 7.3 months. On the other hand, with the medical treatment for the hepatocellular carcinoma provided during this period, the rate of partial recurrence was 14.8%. The treatment of metastatic liver cancer by PMCT and RFA is associated with a high rate of a recurrence as compared with hepatocellular carcinoma, and needs to be examined to discover ways of adaptation and improvement of the technology.

Multicentric development of hepatocellular carcinoma (HCC) is a characteristic feature of hepatitis C virus (HCV)-associated cirrhosis (HCV-LC). In this study, the objective was to determine whether the persistent elevation of the serum alanine aminotransferase (ALT) level, which represents the inflammatory necrosis of hepatocytes, is correlated with the multicentric development of hepatocellular carcinoma (HCC) in patients with early-stage HCV-LC.Ninety-three consecutive patients with biopsy proven HCV-LC (Child Stage A) who had been followed for5 years for the development of HCC were studied. They were subdivided into three groups according to their serum ALT level: Group A included 33 patients with annual average serum ALT levels that were persistently high (or = 80 IU; high ALT group), Group B included 41 patients with annual average serum ALT levels that were persistently low (80 IU; low ALT group), and Group C included 19 unclassified patients. The patients had been studied prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography (CT) scans for5 years. When the development of HCC was suspected, angiography, infusion of lipiodol into the hepatic artery, and lipiodol-CT scans were performed in all patients to determine the number of HCC nodules.In Group A, 27 patients (81.8%) developed HCC. Seventeen of 27 patients (63.0%) had multiple nodules. In contrast, in Group B, only 12 patients (29.3%) developed HCC, and only 1 of these 12 patients (8.3%) had multiple nodules. There was a significant difference between Groups A and B in the incidence of developing HCC (P0.001) and developing multiple nodules (P = 0.006). In addition, among the male patients, the incidence of developing multiple HCC nodules in Group A (12 of 19 patients; 63.2%) was significantly higher (P0.05) compared with the incidence in Group B (0 of 6 patients; 0%). The same tendency was observed among the female patients.These results showed a close correlation between multicentric hepatocarcinogenesis and sustained necroinflammation of the liver in patients with HCV-LC.

Many studies have demonstrated in animal experiments that persistent inflammation may accelerate the development of carcinoma. In this article, the question of whether the persistent elevation of serum alanine aminotransferase (ALT) levels (which represents the inflammatory necrosis of hepatocytes) correlates with the development of hepatocellular carcinoma (HCC) was studied in patients with early stage hepatitis C virus (HCV)-associated cirrhosis.Sixty-nine consecutive patients with biopsy proven HCV-associated cirrhosis (mostly Child's Stage A) who had been followed for5 years for the development of HCC were studied. They were subdivided into 3 groups according to their serum ALT levels: Group A was comprised of 28 patients whose annual average serum ALT level was persistently high (/= 80 IU) (high ALT group), Group B was comprised of 28 patients whose annual average serum ALT level was persistently low (80 IU) (low ALT group), and Group C was comprised of 13 unclassified patients. The patients had been studied prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography for5 years.In the high ALT group HCC developed in 71.4% of patients compared with 25.0% in the low ALT group over the observation period (P0.005). The 5-year rate of incidence of HCC in the high ALT group was as high as 53.6% compared with only 7.1% in the low ALT group (P0.001). The expected interval between the diagnosis of cirrhosis and the development of HCC was 6.0 +/- 0.7 years (mean +/- standard error) in the high ALT group and 12.7 +/- 1.2 years in the low ALT group (P0.001).The results of the current study demonstrated that the development of HCC was more rapid in the high ALT group with HCV-associated cirrhosis.

The relationship between the recurrence of hepatocellular carcinoma (HCC) and the serum alanine aminotransferase (ALT) level was studied in hepatectomized patients with hepatitis C virus (HCV)-associated cirrhosis and HCC.Twenty-six hepatectomized patients with HCV-associated cirrhosis and HCC whose resected specimens showed neither portal vein nor hepatic vein invasion by HCC histologically were divided into 2 groups: 15 patients who had no recurrence 3 years after surgery (Group A) and 11 patients whose disease recurred 1-3 years after surgery (Group B). The patients' serum ALT levels during this period were examined.In Group A, serum ALT generally showed sustained low levels80 international units (INU) in 12 patients (80%). In contrast, ALT levels in Group B showed several peaks or plateaus80 INU in all patients except 2. The recurrence rate of HCC in the hepatectomized patients with sustained low levels of ALT was 14.3% (2 of 14 patients) at 3 years, and was significantly lower (P0.01) than that in those patients whose ALT levels showed several peaks or plateaus80 INU (9 of 12 patients; 75.0%). The average level of mode of ALT in Group A (48.8 +/- 26.0 INU) was significantly smaller than that in Group B (101.1 +/- 47.3 INU) (P0.005).The importance of hepatocytic necrosis in the recurrence of HCC in hepatectomized patients with cirrhosis and HCC of HCV origin was demonstrated and the significance of subsiding hepatic necroinflammatory process in the prevention of HCC recurrence suggested.

Background. The relationships between echosonographic patterns of patients with cirrhosis who are antihepatitis C virus (HCV)-positive, the DNA synthesis of hepatocytes, and the risk for HCC were studied. Methods. Thirty-eight patients with anti-C-100 antibody-positive and Child's grade A posthepatitic cirrhosis were studied. DNA synthesis activity was measured by a bromodeoxyuridine (BrdU, a thymidine analogue)-labeling index (LI), using the BrdU-anti-BrdU in vitro method, and the patients were followed prospectively by frequent liver ultrasonography for 3 years. The ultrasound patterns were classified into fine, coarse, and coarse-nodular (CN) patterns, and the reproducibility of the classification in practical use also was confirmed. Results. Of the 21 patients with high DNA synthesizing cirrhosis (BrdU LI ⩾ 1.5%), 10 (48%) showed coarse-nodular, 5 (24%) coarse, and 6 (29%) fine pattern in ultrasonography. Conversely, of the 17 patients with low DNA synthesizing LC (BrdU LI < 1.5%), only 1 (6%) showed coarse-nodular, 2 (12%) coarse, and 14 (82%) fine pattern.A significant relationship was found between the two groups of BrdU LI and ultrasound imaging patterns [P < 0.05). The incidence of CN pattern was significantly higher (P < 0.01) in the high DNA synthesizing group than in low DNA synthesizing group. Of the 11 patients with CN pattern by ultrasound imaging, 10 (91%) were in the high DNA synthesizing group, and 9 (82%) developed HCC during the follow-up period, compared with 3 of 7 (43%) with coarse, and only one of 20 (5%) with fine pattern developed HCC. The incidence of HCC was significantly higher (P < 0.01) in patients with a CN cirrhosis pattern than in those with a fine pattern. Conclusions. In patients with cirrhosis who are anti-HCV-positive, the CN pattern by ultrasound imaging indicates increased DNA synthesis of hepatocytes and a high risk for developing HCC. Cancer 1995;75:1255-62.

Aim: We recently demonstrated that severe inflammation in the background cirrhotic tissue correlate with the development of histologically more malignant hepatocellular carcinoma (Edmondson III HCC) in HCV-associated liver cirrhosis (LC), and that histology activity index (HAI) was the only one significant contributor to the development of Edmondson III (Ed III) HCC in small nodular HCC. There is a possibility, in the contrary of this phenomenon, that subsided inflammation correlates with the development of histologically less malignant HCC (Ed I type HCC) and that long-term subsided inflammation correlates with the development of large Ed I HCC. We examined the possibility. Methods: Curative hepatic resection for HCC with LC was performed in 264 patients during the past 10 years in Kanagawa Cancer Center hospital. Of 264 patients 197 patients were anti-HCV-positive or HCV-RNA positive. Out of the 197 patients, 32 patients whose HCC revealed only one small HCC nodule (≤ 3 cm) were selected for this study. Furthermore, the cases whose HCC nodules were large (> 3 cm), but consisted of predominantly Ed I component, were also examined. For the evaluation of inflammation in the background LC, modified Knodell's histology activity index (HAI) was used. (for the evaluation of pure inflammation, items of fibrosis was omitted); piece meal necrosis (1-4), intra lobular cellular degeneration and focal necrosis (1-4), portal cellular inflammation (1-4), were estimated by two well experienced pathologist. In each case, the HAI score was estimated in five field and average HAI score was calculated. All the sections of resected HCC tissue was examined pathologically in all patients for determining the grade of malignancy according to Edmondson Steiner's classification; Ed I (well differentiated), Ed II (moderately diff.), Ed III (poorly diff.). Results: The average HAI score in 7 Ed I HCC patients was as low as 3.61 ± 0.70 (mean ± SD), and was significantly lower than that in 17 Ed III HCC patients (5.21 ± 1.15, P Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 394. doi:1538-7445.AM2012-394

Aim: Hamada et al. succeeded in converting ER-1, a weakly tumorigenic cloned cell line of a rat mammary carcinoma, into a highly tumorigenic and metastatic cell line by interaction with host cell reactive to a foreign body (plastic plates). They attributed these phenomenon to the cytokines such as LL-6 derived from host reactive inflammatory cells crowded around the foreign body. It is possible that the same mechanism is involved in the development of human HCC, and that inflammation in the background cirrhotic tissue might accelerate the process of promotion. Methods: Curative hepatic resection for HCC with LC was performed in 223 patients during the past 8 years in Kanagawa Cancer Center hospital. Of 223 patients 182 patients were anti-HCV-positive or HCV-RNA positive without habitual alcohol intake. Out of 182 patients, 32 patents whose HCC revealed only one small HCC nodule of less than 3 centimeter in diameter were selected for this study. For the evaluation of inflammation in the background LC, modified Knodell's histology activity index (HAI) was used. (for the evaluation of pure inflammation, items of fibrosis was omitted); piece meal necrosis (1-4), intra lobular cellular degeneration and focal necrosis (1-4), portal cellular inflammation (1-4), were estimated by two well experienced pathologist. In each case, the HAI score was estimated in five field and average HAI score was calculated. All the sections of resected HCC tissue was examined pathologically in all patients for determining the grade of malignancy according to Edmondson Steiner's classification; Ed I (well differentiated), Ed II (moderately diff.), Ed III (poorly diff.) Results: The average HAI score in the non-cancerous cirrhotic portion in HCC patients with Ed III was 5.50 ± 0.98 (mean ± SD), and was significantly larger than that in HCC patients without Ed III (4.18 ± 0.70, p < 0.001). Furthermore, the occurence rate of HCC containing Ed III component in the HCC patients whose HAI score was more than 5.0 was as high as 88.9% (16 out of 18), and was highly significant as compared with those in HCC patients whose HAI score was less than 5.0% (3 out of 14, 21.4%, p < 0.005).Conclusions: It is suggested that inflammation in the surrounding non-cancerous cirrhotic tissue would accelerate the process of promotion in the HCC development. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2712. doi:10.1158/1538-7445.AM2011-2712

To clarify sex differences in DNA synthesis in hepatocellular carcinoma (HCC), bromodeoxyuridine labeling indices (BrdU LI) of HCC cells included in tumor biopsy specimens from 12 consecutive male patients and from 5 consecutive female patients all with liver cirrhosis and HCC were examined using an in vitro labeling technique. The mean BrdU LI +/- SE of HCC from male patients (7.7 +/- 0.8%) was significantly (P less than 0.05) higher than that from female patients (4.4 +/- 1.0%). While 7 of the 12 male HCC patients belonged to the high DNA synthesis group (BrdU LI greater than or equal to 7.0%), none of the 5 female HCC patients showed high DNA synthesis (P less than 0.05). We conclude that DNA synthesis in HCC was higher in males than in females.

The relationship between DNA synthesis activities of hepatocytes in biopsied specimens and liver volume was studied in various stages of primary biliary cirrhosis using an in vitro bromodeoxyuridine (a thymidine analogue)-anti-bromodeoxyuridine reaction and computed tomography. The mean bromodeoxyuridine (+/- SE) labeling index for 10 patients in an early histological stage (stage I, 4, and stage II, 6, 3.4% +/- 0.4%) of primary biliary cirrhosis was 17 times that for 6 control subjects (0.2% +/- 0.1%, P less than 0.001), and was significantly higher than that for 19 female patients with chronic aggressive hepatitis (0.9% +/- 0.2%, P less than 0.001), 14 compensated cirrhotic patients of viral origin (all female, 1.1% +/- 0.3%, P less than 0.01), and 5 patients with stage III primary biliary cirrhosis (0.5% +/- 0.1%, P less than 0.001). The mean (+/- SE) liver volume in the early stage of primary biliary cirrhosis (1225 +/- 40 cm3) was about 1.5 times that in control subjects (835 +/- 42 cm3, P less than 0.001). These results suggest that liver volume has already become large in the early stage of primary biliary cirrhosis perhaps because of markedly increased DNA synthesis in hepatocytes.