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Biomedical subjects

K Hirohashi

Publications and source records attributed to K Hirohashi.

At least 37 records · Page 2Linked to original sources

Reactivation of viral replication after liver resection in patients infected with hepatitis B virus.

OBJECTIVE: To investigate the mechanisms and risk factors underlying postoperative reactivation of hepatitis after liver resection for hepatitis B virus-related hepatocellular carcinoma. SUMMARY BACKGROUND DATA: Although risk factors for acute hepatic failure after liver resection have been reported in patients with chronic liver disease, the issue of reactivation of hepatitis B virus replication after liver resection is unresolved. METHODS: Fifty-five patients with hepatocellular carcinoma and hepatitis B surface antigen underwent liver resection. In 25 of these 55 patients, serum levels of hepatitis B virus DNA and the type of hepatitis B virus were determined before and after surgery. RESULTS: Postoperative hepatitis occurred in 13 of the 55 patients (24%). Reactivation of viral replication occurred after liver resection in 7 of the 25 patients tested, and alanine aminotransferase activity increased in 6 of these 7 patients. High preoperative alanine aminotransferase activity, high levels of hepatitis B virus DNA, presence of wild-type DNA, and detection of hepatitis B core antigen in hepatocytes, all features of the immune clearance phase in the natural course of hepatitis B virus infection with no surgery, were more likely to be found in patients with reactivation than in patients without reactivation. CONCLUSIONS: During the immune clearance phase of hepatitis B virus infection, especially the period of acute exacerbation, changes in serum hepatitis B virus DNA level should be monitored for early warnings of reactivation of viral replication, likely to cause severe postoperative hepatitis and acute hepatic failure.

Adult↗

Influence of previous interferon therapy on recurrence after resection of hepatitis c virus-related hepatocellular carcinoma.

Interferon (IFN) therapy decreases the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV). One hundred and fifty-nine consecutive patients who underwent liver resection for HCV-related HCC were studied. In 17 (group 1) of the 159 patients, HCC was detected during or after IFN therapy. The incidences of recurrence after surgery in the group 1 patients and the other 142 patients (group 2) were compared. Eight patients had a complete response to IFN, 4 had a partial response, and 5 had no response. The proportion of patients without HCV viremia was significantly higher in the group 1 patients (P < 0.0001). The tumor-free survival rate was significantly higher in the group 1 patients (P = 0.0010). By multivariate analysis of various risk factors for recurrence, no previous IFN was a significant independent risk factor for recurrence (risk ratio = 6.336; 95%CI, 1.512 - 26.50). The patients with HCC who underwent IFN therapy previously are good candidates for liver resection because recurrence after the operation was rarely observed.

Aged↗

Relationship of the microvascular type to the tumor size, arterialization and dedifferentiation of human hepatocellular carcinoma.

Unlike normal liver with the sinusoids, hepatocellular carcinomas (HCCs) possess capillaries. Whether these capillaries derive from the sinusoids remains unclear in human HCCs. This study aimed to examine sinusoidal capillarization in human HCCs and its relationship to the tumor size, arterialization and dedifferentiation. Thirty-eight HCCs with a diameter of 10 - 140 mm were pathologically and angiographically examined. By electron microscopy, the microvasculature of tumors was classified into sinusoidal, intermediate and capillary types, which were all negative, partially positive and all positive, respectively, for four parameters, i.e., endothelial defenestration, continuous basement membrane, lack of Kupffer cells, and lack of lipid-containing hepatic stellate cells. Well-, moderately and poorly differentiated HCCs displayed sinusoidal / intermediate / capillary types, intermediate / capillary types and only capillary type, respectively, suggesting the transition from the sinusoids to capillaries in well-differentiated (and probably moderately differentiated) HCCs. Furthermore, well-differentiated HCCs with a diameter of less than 30 mm often received preferential portal venous blood, while moderately and poorly differentiated ones were all supplied with arterial blood, indicating a relationship between dedifferentiation and arterialization. In contrast, the microvascular type displayed no significant relationship with tumor size or arterialization in well-differentiated HCCs. The present study has demonstrated that sinusoidal capillarization occurs in human well-differentiated HCCs and seems to be related to dedifferentiation of parenchymal tumor cells, but not to tumor size or arterialization.

Adult↗

Virologic and biochemical changes and prognosis after liver resection for hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND/AIMS: During the natural course of hepatitis B virus (HBV) infection, clearance of HB e antigen (HBeAg) and HB surface antigen (HBsAg) occurs with remission of liver disease. We investigated the effects of postoperative changes in virologic and biochemical parameters on the prognosis after liver resection for HBV-related hepatocellular carcinoma (HCC). METHODS: We investigated the relationship between postoperative changes in virologic and biochemical parameters and the incidence of intrahepatic recurrence and the outcome during a 3-year period following surgery in 30 HCC patients with HBsAg. RESULTS: The incidence of intrahepatic recurrence of HCC was significantly higher in patients with acute postoperative exacerbation of hepatitis (p = 0.0084), a sustained high serum concentration of HBV DNA (> or = 5.0 mEq/ml, p = 0.001), and sustained expression of HBsAg after surgery (p = 0.0421). A high serum concentration of HBV DNA was significantly associated with a shorter survival time (p = 0.0447) and the cause of death was recurrence of HCC. CONCLUSION: Patients with acute postoperative exacerbation of hepatitis, sustained HBsAg expression, and sustained high serum concentrations of HBV DNA after surgery may require more intensive postoperative monitoring for HCC recurrence.

Adult↗

Successful treatment of dissemination of hepatocellular carcinoma to the pleura and diaphragm after percutaneous liver biopsy.

BACKGROUND/AIM: Treatment for dissemination of hepatocellular carcinoma to the pleura and diaphragm following percutaneous needle biopsy has not been established. METHODS: The case of a 57-year-old man who underwent percutaneous needle biopsy for liver tumor is presented. RESULTS: Ten months after resection of the tumor (moderately differentiated hepatocellular carcinoma), masses in the right pleural cavity and on the diaphragm were detected by computed tomography. Resections of the masses with surrounding tissue and the diaphragm and wedge resection of the right lung were performed. A wide range of the pleura and the diaphragm was coagulated with an argon beam coagulator. The patient is in good health without recurrence 4 years after the operation. CONCLUSION: Aggressive surgical treatment should be considered for patients with dissemination of hepatocellular carcinoma by needle biopsy when the lesions are limited.

Biopsy, Needle↗

Treatment of adrenal metastases after hepatic resection of a hepatocellular carcinoma.

BACKGROUND: The adrenal gland is a common site of extrahepatic metastases from a hepatocellular carcinoma (HCC). However, treatment of adrenal metastases has not been well characterized. METHODS: Of 562 patients who underwent hepatic resection for a HCC, 91 developed extrahepatic metastases. We reviewed the medical records of 10 patients with adrenal metastases (9 males and 1 female; mean age 63 years at the time of hepatic resection). RESULTS: The mean diameter of the primary tumors was 5 cm, and all were located in the right lobe of the liver. The mean interval from hepatic resection to recurrence was 18 months. Seven patients underwent treatment of intrahepatic recurrence. To treat the adrenal metastases, surgical resection was performed in 4 patients, and transcatheter arterial embolization was performed in 1 patient. The patients treated had no other extrahepatic metastases. The mean diameter of the resected adrenal tumors was 6 cm. There was no hospital mortality. With surgical resection, 1 patient has been alive 63 months after recurrence. CONCLUSIONS: Adrenal metastases from a HCC were often large at the time of diagnosis. Since surgical resection was a safe procedure, and some patients could be alive for a long time, it should be performed whenever possible.

Adrenal Gland Neoplasms↗

Resectable pleomorphic giant cell carcinoma of the pancreas.

We present a 72-yr-old woman who underwent surgical resection of a large pancreatic tumor. On preoperative imaging, an intratumoral cavity containing necrotic tissue was noted, mimicking the appearance of a cystic tumor. There was no invasion of adjacent organs nor distant metastasis, and histopathologic examination revealed the tumor to be a giant cell carcinoma. Postoperatively, the patient has been followed for 1.5 yr without evidence of recurrence. Giant cell carcinoma generally is associated with a poor prognosis, and patients usually die within months despite intensive multimodality therapy. Some patients with giant cell carcinomas, however, achieve long-term survival when invasion of adjacent organs and distant metastases are absent. Surgical resection is the appropriate treatment for tumors with these favorable characteristics.

Aged↗

Tumor-suppressor effect of interferon regulatory factor-1 in human hepatocellular carcinoma.

IFN regulatory factor-1 (IRF-1) regulates the IFN system, inhibits cell growth, and has tumor-suppressor activities. p21 is a universal cyclin-dependent kinase inhibitor, the induction of which depends on both p53 and IRF-1 in mouse embryonic fibroblasts. The expression of p21 in hepatocellular carcinomas (HCCs) is regulated by wild-type p53. We examined the expressions of IRF-1 and p21 in 32 HCCs by quantitative reverse transcription-PCR and the mutation p53 gene in 32 HCCs by single-strand conformation polymorphism and direct sequencing. The expression of IRF-1 mRNA in 15 of 32 HCCs was lower than that in adjacent noncancerous tissue. IRF-1 mRNA expression was reduced in 0 of 3 specimens of well-differentiated HCC, 9 of 21 (42%) specimens of moderately differentiated HCC, and 6 of 8 (75%) specimens of poorly differentiated HCC. IRF-1 mRNA expression was significantly lower in tumors with portal thrombus than in those without portal thrombus (P = 0.003). p53 mutations were detected in 7 of 32 HCCS: p21 expression was reduced in 6 of the 7 (86%) HCCs with p53 mutations. In contrast, p21 expression was reduced in 13 of 25 (52%) HCCs with wild-type p53. IRF-1 expression was reduced in 7 of 13 (53%) HCCs with both wild-type p53 and reduced expression of p21. These results suggest that IRF-1 may be a tumor-suppressor gene for HCC and that IRF-1 is related to p21 expression in HCC with wild-type p53.

Aged↗

[Clinical significance of interferon therapy in treatments for hepatitis C virus-related hepatocellular carcinoma].

The results of liver resection for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) are affected by persistent active hepatitis and/or hepatic fibrosis including cirrhosis. In patients infected with HCV, interferon therapy prevents the development of HCC by eradication of HCV and/or the remission of active hepatitis. Although HCCs are found even in some patients treated with interferon, the results of liver resection for such HCCs were satisfactory, especially in patients successfully treated with interferon. Postoperative interferon-alpha therapy decreased recurrence after resection of HCV-related HCC in a randomized controlled trial. Strategies for viral infection as well as the carcinoma can improve the outcome after treatment of HCV-related HCC. Interferon therapy is useful to improve the outcome after treatments for HCV-related HCC.

Antineoplastic Agents↗

Large focal nodular hyperplasia of the liver: possible to evade surgical resection.

PURPOSE: Although recent advances in diagnostic imaging have allowed a number of patients with focal nodular hyperplasia (FNH) to avoid surgical treatment, the natural course of large FNH is still unknown. CASE REPORT: A 25-year-old man was admitted because of a large hepatic mass detected on routine examination in June 1998. The only laboratory abnormality was an elevated gamma-GTP. Computed tomography, angiography, positron emission tomography using F-18 fluorodeoxyglucose (FDG-PET), and scintigraphy using technetium-99m-galactosylneoglycoalbumin(99mTc-NGA) demonstrated a spoke-wheel appearance of vessels, normal hepatocytes, and no malignancy. Histologic findings on needle biopsy were consistent with FNH. After informed consent, the patient agreed to observation. Two years after the initial diagnosis, he has no symptoms, and there are no changes in the size or character of the lesion on computed tomography. DISCUSSION: Careful observation of patients with FNH is required because its natural course is unknown and these lesions can bleed or rupture.

Adult↗

Effect of viral status on recurrence after liver resection for patients with hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: Risk factors for recurrence after resection of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) require more precise definition. METHODS: Forty patients who underwent liver resection for HBV-related HCC were studied. Their clinical findings, laboratory data (including viral status), pathologic findings, and operative methods were evaluated for recurrence risk in univariate and multivariate analyses. RESULTS: The HB envelope (HBe) antigen, wild-type HBV, intrahepatic metastases, elevated serum activities of aspartate aminotransferase and alanine aminotransferase, and moderately or severely active hepatitis were more likely to be found in patients with a high viral load than in patients with a low viral load. Precore mutant-type HBV was more likely to be found in patients with a low viral load than in patients with a high viral load. The platelet count was significantly lower in the patients with a high viral load. A high viral load, the presence of wild-type HBV, the absence of anti-HBe, the absence of precore mutant-type HBV, Child score B, a low platelet count, and a positive surgical margin were risk factors for recurrence in univariate analysis. A nonanatomic resection tended to be a risk factor. A high viral load and positive surgical margin were independent risk factors for recurrence. CONCLUSIONS: The measurement of viral load and detection of anti-HBe, wild-type HBV, and precore mutant-type HBV are useful for estimating a patient's prognosis after resection of HBV-related HCC.

Adult↗

A case of recurrent cholangitis after bile duct injury during laparoscopic cholecystectomy: value of scintigraphy with Tc-99m GSA and hepatobiliary scintigraphy for indication of lobectomy.

A 39-year-old woman with acute cholecystitis and gallstones underwent laparoscopic cholecystectomy. She suffered from recurrent episodes of cholangitis due to injury of the major bile ducts during laparoscopic cholecystectomy. Hepatobiliary scintigraphy with Tc-99m Sn-N-pyridoxyl-5-methyltryptophan was performed. Although normal bile excretion was found from the left hepatic duct to the percutaneous transhepatic biliary drainage (PTBD) tube, excretion from the right hepatic lobe was prolonged. Scintigraphy with Tc-99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin demonstrated atrophy of the right hepatic lobe and enlargement of the left hepatic lobe. Cholangiography via the PTBD tube revealed complete obstruction of the left hepatico-jejunal anastomosis and could not enhance the right intrahepatic bile duct. A right hepatic lobectomy was performed because of the atrophy, glissonitis and the absence of an appropriate bile duct for reconstruction. Postoperatively she was active and exhibited no evidence of recurrent cholangitis.

Adult↗

Spontaneous regression of a large hepatocellular carcinoma with portal vein tumor thrombi: report of a case.

A 65-year-old man with chronic hepatitis C showed a markedly elevated serum alpha-fetoprotein concentration. Computed tomography revealed a huge tumor occupying the entire right hepatic lobe. Three months later, the tumor regressed spontaneously from 12 cm to 7 cm in diameter without any medical treatment. A right hepatic lobectomy was performed 4 months after the initial diagnosis. The main tumor, located in the posterior inferior segment, was completely necrotic, and had a thick fibrous capsule. Many inflammatory cells had also infiltrated into the tumor. Only a small portion of a tumor thrombus in the portal vein and one of three intrahepatic metastases contained viable cancer cells. The tumor was found to be poorly differentiated hepatocellular carcinoma. Tumor regression may have been caused by a disturbance in hepatic circulation associated with the portal vein thrombus.

Aged↗

Risk factors for recurrence after resection of hepatitis C virus-related hepatocellular carcinoma.

Although there have been many studies of the risk factors for recurrence after resection of hepatocellular carcinoma (HCC), the subjects were patients with various viral status in the previous studies, and hepatitis C viremia has not been evaluated. We investigated risk factors, including hepatic C viremia and histologic findings of noncancerous hepatic tissue, for recurrence after resection of hepatitis C virus (HCV)-related HCC. A total of 223 patients who underwent liver resection for HCV-related HCC were studied. HCV viremia, laboratory data, degree of HCC malignancy, histologic findings in noncancerous hepatic tissue, preoperative interferon therapy, and operative methods were evaluated for recurrence risk by univariate and multivariate analyses. Serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin, and the proportion of patients with a high histologic activity score (mild to severe active hepatitis) were significantly higher in patients with HCV viremia than in those without viremia. Serum albumin was significantly lower in patients with HCV viremia. By univariate analysis, older age (> 65 years old), HCV viremia, elevated AST (> 40 IU/L) and ALT (> 45 IU/L), large tumors (> 40 mm), multiple HCCs, moderately or poorly differentiated HCC, portal invasion, mild to severe active hepatitis, and lack of preoperative interferon therapy were risk factors for recurrence. Multivariate analysis showed that older age, HCV viremia, high AST, multiple HCCs, and portal invasion were independent risk factors. For HCV-related HCCs, not only the degree of malignancy of the HCC but also HCV viremia and active hepatitis are risk factors for recurrence.

Aged↗

Additional hepatocellular carcinomas undetectable before surgery.

The presence of small additional hepatocellular carcinomas (HCCs) undetectable before hepatic resection is a crucial topic for hepatic surgeons. We assessed the incidence of pathologically diagnosed multiple HCCs in 267 patients who underwent hepatic resection for HCC. Ninety-five additional HCC nodules were detected in 72 of the patients (27%). The survival rate of these 72 patients was significant worse than for the 195 with single nodular HCC (p = 0.0013). Twenty-one (22%) were detected before surgery, 29 (31%) during surgery, and 45 (47%) on pathologic examination after surgery. The mean nodule diameters for each group were 2.1, 1.0, and 0.9 cm, respectively (p < 0.0001). None of the 21 nodules detected before surgery was well differentiated, whereas 30 of the 74 nodules in the other two groups were well-differentiated. Although the mean nodule diameter of the well-differentiated HCC group was the smallest, there was no significant difference among the three groups assigned according to tumor differentiation (p = 0.2355). Altogether, 9 of 16 patients with additional nodules detected before surgery (56%) and 49 of 59 with additional nodules detected during or after surgery (88%) had cirrhosis of the liver. The odds ratio for detecting a new HCC nodule during or after surgery in the presence of cirrhosis was 5.444 (p = 0.0087). Improvement in the detection of small additional HCC nodules before and during surgery and meticulous follow-up after surgery are necessary for patients with cirrhosis. For patients without cirrhosis, surgical treatment may be performed according to the results of preoperative imaging studies.

Analysis of Variance↗

Post-ischemic intraportal adenosine administration protects against reperfusion injury of canine liver.

Although adenosine has been postulated to inhibit ischemia-reperfusion injury in various tissues, its in vivo cytoprotective mechanism is not fully known. The aim of this study was to determine the effect of intraportally infused adenosine on reperfusion injury in the canine liver. Two h ischemia and reperfusion of the liver were induced in beagle dogs by clamping the portal triad. Either adenosine or saline was infused in the portal vein after reperfusion for 60 min. Levels of serum aspartate aminotransferase and alanine aminotransferase and the survival of animals were examined. Hepatic levels of protein carbonyls and glutathione were also measured, as markers of oxidative stress. One h after reperfusion, the liver was perfused with nitroblue tetrazolium and the formation of formazan was observed to evaluate superoxide formation. Twenty-four h after reperfusion, 100% of animals in the adenosine group and 33% of animals in the control group survived. Adenosine significantly decreased the reperfusion-induced increase in serum levels of aspartate aminotransferase and alanine aminotransferase. Adenosine also suppressed the formation of protein carbonyls and the decrease in glutathione levels. Histologically, neutrophil infiltration, superoxide formation, and apoptosis were decreased by adenosine. These results suggest that intraportally infused adenosine attenuates reperfusion injury of the liver, presumably by suppressing the activation of neutrophils and oxidative stress.

Adenosine↗

The clinical significance of lymph node metastases in patients undergoing surgery for hepatocellular carcinoma.

The frequency of lymph node (LN) metastasis in patients undergoing surgery for hepatocellular carcinoma (HCC) has rarely been studied. We evaluated the clinicopathologic characteristics and outcomes of six patients with nodal metastases from HCC among a total of 504 patients who underwent hepatic resection for HCC in our department over a 16-year period. The nodal metastases were diagnosed preoperatively in two patients. The average diameter of the resected tumors was 7.8 cm and all were confirmed as poorly differentiated HCC. All of the six patients had intrahepatic metastatic nodules and five also had portal vein invasion. One patient underwent limited resection, and the other five underwent bisegmentectomy. All of the regional LNs were removed in one patient, while only enlarged LNs were removed in the other five. One patient died of postoperative liver failure and the others all died later of intrahepatic or nodal recurrence. Our findings suggest that the prognosis of patients with nodal metastasis from HCC is generally poor, even if hepatic resection with regional LN dissection is performed.

Aged↗