Koji Okuda

Microvascular Invasion in Patients with Hepatocellular Carcinoma and Its Predictable Clinicopathological Factors

BackgroundMacroscopic vascular invasion is known to be a poor prognostic factor in hepatocellular carcinoma (HCC). The aim of this study was to determine the outcomes and predictive factors after hepatic resection for HCC with microvascular invasion (MVI).MethodsOne hundred ten patients who underwent curative resection for HCC without macroscopic vascular invasion were included in this retrospective study. The risk factors of these patients for recurrence-free and disease-specific survival were investigated, and the clinicopathological factors predicting the presence of MVI were also determined.ResultsOf the 110 resected specimens, 49 (45%) had evidence of MVI. By univariate analysis, MVI was found to be statistically significantly associated with greater tumor size, gross classification, histological grade, and intrahepatic micrometastasis. Gross classification proved to be the only independent predictive factor for MVI by multiple logistic regression analysis. By multivariate analysis, cirrhosis and MVI were identified as independent risk factors for recurrence-free survival. The 5-year recurrence-free survival rates for patients with and without MVI were 20.8% and 52.6%, respectively. By multivariate analysis, the number of tumors, presence of MVI, and intrahepatic micrometastasis were identified as independent predictors of disease-specific survival. The 5-year disease-specific survival rates for patients with and without MVI were 59.3% and 92.0%, respectively.ConclusionsThe presence of MVI was the most important risk factor affecting recurrence and survival in HCC patients after curative resection. Furthermore, this study showed that gross classification of HCC can be very helpful in predicting the presence of MVI.

Evaluation of the mean and entropy of apparent diffusion coefficient values in chronic hepatitis C: Correlation with pathologic fibrosis stage and inflammatory activity grade

PURPOSE To determine whether mean and entropy apparent diffusion coefficient (ADC) values obtained at diffusion-weighted (DW) magnetic resonance (MR) imaging can help detect and stage histopathologic liver fibrosis and grade inflammation activity in patients with chronic hepatitis C. MATERIALS AND METHODS This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. The study included 55 patients with focal hepatic lesions and either chronic hepatitis C (n = 43) or normal hepatic function (control subjects) (n = 12). Mean and entropy of volume histograms were generated in four cubic regions of interest placed in the right hepatic lobe of ADC map images, which were obtained at echo-planar DW MR imaging (gradient factor b values of 0 and 1000 sec/mm(2)). These two parameters (mean and entropy ADC) were compared by using METAVIR histopathologic liver fibrosis and inflammatory activity scores. Statistical analysis was performed with the Kruskal-Wallis test and receiver operating characteristic curves. RESULTS The mean ADC decreased with an increase in the fibrosis stage or inflammatory activity grade, and the entropy ADC increased with an increase in the fibrosis stage or inflammatory activity grade (P < .001 for all comparisons, Kruskal-Wallis test). The area under the receiver operating characteristic curve (A(z)) for the mean ADC was statistically significant in the differentiation of fibrosis stage or inflammatory activity grade (A(z), 0.807-0.926; P < .001 for all comparisons). Entropy of ADC was helpful for classifying normal from abnormal fibrosis stage or inflammatory activity grade (A(z) for both parameters, 0.937; P < .001). CONCLUSION Assessment of a combination of mean ADC and entropy ADC in patients with chronic hepatitis C is more accurate for predicting pathologic hepatic fibrosis stage and inflammatory activity grade and helpful for detecting early fibrotic or inflammatory activity when compared with assessment of mean ADC alone.

Clinicopathologic comparison between resected hepatocellular carcinomas (HCC) and recurrent tumors A special reference to multicentric carcinogenesis of HCC

Abstract Postoperative metachronous multicentric carcinogenesis of hepatocellular carcinoma (HCC) was studied by comparison of the histologic grade of resected and recurrent tumors in 31 cases which underwent ultrasound-guided fine-needle biopsies for the initial recurrent tumors with diameter of less than 20 mm. The criteria that the cases in which recurrent tumors show well-differentiated HCC without regard to the differentiation of resected tumors should be multicentric carcinogenesis, and that the cases in which recurrent tumors show moderate or poorly differentiated HCC with the same or lower degree of differentiation compared with the differentiation of resected tumor was consistent with metastasis, were applied. In 16 (51.6%) out of the 31 cases, multicentric carcinogenesis was thought to occur (multicentric group). In 14 cases, recurrence was thought to be metastasis (metastatic group). The multicentric group tended to have smaller diameters in resected tumors and a high incidence of the association of liver cirrhosis and adenomatous hyperplasia. In gross classification of resected tumors, six cases of all single nodular with perinodular tumor growth type and infiltrative type had metastatic recurrences, and multicentric carcinogenesis was often seen in cases of single nodular type, multinodular type and confluent multinodular type. In the multicentric group, recurrence occurred at every postoperative period as long as 65 months including four cases of early recurrence within 6 months and six cases of late recurrence later than 24 months. On the contrary, in 12 cases in the metastatic group the recurrent interval ranged from 6 to 19 months.

Unusual liver carcinomas with sarcomatous features: analysis of four cases.

Abstract We recently examined the clinicopathological and immunohistochemical features of four cases of primary hepatic carcinoma with sarcomatoid elements. Three of the four patients had associated ordinary hepatocellular carcinoma (HCC) and one had a sarcomatoid carcinoma with no apparent elements of HCC. The presenting symptoms were high fever and hypochondralgia in three patients, and right hypochondralgia without a high fever in one. The preoperative diagnoses were liver abscess in two patients, HCC in one, and cholangioma in one. Preoperative imaging showed necrotic change or abscess formation in the tumors. The sarcomatous elements showed a positive reaction to vimentin in three patients, but the ordinary HCC cells did not. Macroscopically, the tumors appeared as a single nodule with pericapsular growth. The prognoses of these patients were poor due to the early development of intrahepatic or distal metastases. We conclude that symptoms such as a high fever or hypochondralgia are characteristics of these tumors and that they may be histogenetically derived from a dedifferentiation of HCC, although no elements of HCC were found in one of our cases.

Synchronous or metachronous double cancers of the pancreas and other organs: Report on 12 cases

Pancreatic carcinoma carries a poor prognosis, especially invasive ductal carcinoma of the pancreas. This retrospective study describes the results of the treatment and prognosis for double cancers in which cancer of the pancreas was associated with malignancies in other organs in 12 patients who were diagnosed and treated at Kurume University Hospital. The patients included 4 women and 8 men, with an average age of 67 years. Of the 12 tumors, 7 were metachronous pancreatic cancers which occurred after resections of other organ malignancies. Five patients had synchronous double cancers, one of whom was diagnosed to have gastric cancer on admission. Two other patients of this group were diagnosed to have lung cancer, while the remaining 2 patients suffered from colon cancer. By the time pancreatic cancer was diagnosed, gastrectomies had been performed in 7 patients for either gastric cancer or ulcers. In addition, one patient underwent a hysterectomy for uterine carcinoma and another received a low anterior resection for rectal carcinoma. Four of 5 patients in the synchronous group had nonresectable tumors and a palliative bypass operation was performed in 2 of these patients. Six patients who had metachronous double cancers died because of pancreatic cancer recurrence or metastases. We conclude that the prognosis of double cancers, where cancer of the pancreas is associated with other organ malignancies, primarily depends on the prognosis of the pancreatic carcinoma, and the present study suggests the necessity of long-term follow-up examinations for gastrectomy patients in order to make an early diagnosis of pancreatic cancer.

Reliability of hepatic artery configuration in 3D CT angiography compared with conventional angiography – special reference to living-related liver transplant donors

Although an accurate anatomical understanding of the hepatic arteries is the most and essential step in living‐related liver transplantation (LRLT), the need to reduce the burden place on the donor should be considered in imaging diagnosis. The present study examined the reliability of intravenously enhanced three‐dimensional (3D) angiography from multidetector‐row computed tomography (MDCT) in evaluating the anatomical configuration of the hepatic arteries comparing with those from conventional angiography by Seldinger method. A total of 109 patients underwent MDCT and 3D images were reconstructed on arterial phase using the volume rendering (VR) method. In the case of 3D angiography, at an infusion rate of 4 ml/s, the extrahepatic hepatic arteries were visualized successfully in all cases (the right, left and middle hepatic artery). The aberrant hepatic arteries were successfully visualized in 23 of 24 cases. The 3D angiography is a reliable method of visualizing the extrahepatic and aberrant hepatic arteries. This minimally invasive examination procedure is useful in individual operative planning and is help to increase the safety of surgery.

Detection of pannus by multidetector-row computed tomography

Prosthetic valve dysfunction (PVD) due to pannus formation is an infrequent but serious complication. A 72-year-old man who underwent aortic valve replacement was diagnosed with PVD and aneurysm of the Sinus of Valsalva. Multidetector-row computed tomography (MDCT) was used to examine the cause of PVD before reoperation. MDCT demonstrated that tissue regarded as pannus extended from the left ventricular septum into the pivot guard. These findings were confirmed by observations during reoperation. MDCT can be a useful diagnostic technique for the anatomical and functional evaluation of PVD.

Intraductal neoplasm of the intrahepatic bile duct: Clinicopathological study of 24 cases

AIM To investigate the clinicopathological features of intraductal neoplasm of the intrahepatic bile duct (INihB). METHODS Clinicopathological features of 24 cases of INihB, which were previously diagnosed as biliary papillomatosis or intraductal growth of intrahepatic biliary neoplasm, were reviewed. Mucin immunohistochemistry was performed for mucin (MUC)1, MUC2, MUC5AC and MUC6. Ki-67, P53 and β-catenin immunoreactivity were also examined. We categorized each tumor as adenoma (low grade), borderline (intermediate grade), and malignant (carcinoma in situ, high grade including tumors with microinvasion). RESULTS Among 24 cases of INihB, we identified 24 tumors. Twenty of 24 tumors (83%) were composed of a papillary structure; the same feature observed in intraductal papillary neoplasm of the bile duct (IPNB). In contrast, the remaining four tumors (17%) showed both tubular and papillary structures. In three of the four tumors (75%), macroscopic mucin secretion was limited but microscopic intracellular mucin was evident. Histologically, 16 tumors (67%) were malignant, three (12%) were borderline, and five (21%) were adenoma. Microinvasion was found in four cases (17%). Immunohistochemical analysis revealed that MUC1 was not expressed in the borderline/adenoma group but was expressed only in malignant lesions (P = 0.0095). Ki-67 labeling index (LI) was significantly higher in the malignant group than in the borderline/adenoma group (22.2 ± 15.5 vs 7.5 ± 6.3, P < 0.01). In the 16 malignant cases, expression of MUC5AC showed borderline significant association with high Ki-67 LI (P = 0.0622). Nuclear expression of β-catenin was observed in two (8%) of the 24 tumors, and these two tumors also showed MUC1 expression. P53 was negative in all tumors. CONCLUSION Some cases of INihB have a tubular structure, and are subcategorized as IPNB with tubular structure. MUC1 expression in INihB correlates positively with degree of malignancy.

Maximum Standardized Uptake Value on 18f-fluoro-2-deoxy-glucose Positron Emission Tomography/computed Tomography and Glucose Transporter-1 Expression Correlates With Survival in Invasive Ductal Carcinoma of the Pancreas

Objectives The purpose of this study was to assess the correlations among the maximum standardized uptake value (SUVmax) on 18F-fluoro-2-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT); the expressions of glucose transporter 1 (GLUT-1), glucose transporter 3, and epidermal growth factor receptor (EGFR); as well as prognosis in patients with invasive ductal carcinoma of the pancreas. Methods A total of 41 patients with surgically resected and histologically proven invasive ductal carcinoma of the pancreas who underwent preoperative FDG-PET/CT were assessed. The SUVmax at the primary tumor site was measured by FDG-PET/CT, and immunohistochemical staining of tumor sections was performed for GLUT-1, glucose transporter 3, and EGFR. Results Higher FDG uptake (SUVmax, >3.40) and GLUT-1 expression were significantly associated with shorter overall survival (P < 0.05). The SUVmax was not found to be significantly correlated with clinicopathological characteristics such as TNM classification, lymph node metastasis, and tumor differentiation. The EGFR expression was significantly correlated with the SUVmax (P = 0.024). Conclusions Higher FDG uptake and GLUT-1 expression in invasive ductal carcinoma of the pancreas seems to be an important prognostic factor. In addition, the EGFR expression was significantly correlated with the SUVmax.

A novel tumor necrosis factor-α suppressant, ONO-SM362, prevents liver failure and promotes liver regeneration after extensive hepatectomy

BACKGROUND Tumor necrosis factor (TNF)-alpha is a cytokine that initiates liver regeneration after hepatectomy (HTx), although extensive HTx can cause liver failure with significant rise in serum TNF-alpha levels. To test our hypothesis that modulation of endogenous TNF-alpha attenuates liver failure even after extensive HTx, we used ONO-SM362, a novel TNF-alpha inhibitor, in mice subjected to 85% HTx. METHODS ICR mice were divided into 5 groups: 70% HTx, 85% HTx, 85% HTx plus ONO-SM362, 85% HTx plus monoclonal TNF-alpha antibody (mAb), and 85% HTx plus FR167653, a TNF-alpha inhibitor. We analyzed the survival rate, blood ammonia (NH(3)), serum TNF-alpha levels, TNF-alpha mRNA expression in the liver and spleen by real-time polymerase chain reaction, histologic changes, polymorphonuclear neutrophils (PMNs) infiltration, and proliferating cell nuclear antigen labeling index (PCNA LI) in the 5 groups. RESULTS The survival rate at 7 days after surgery was 100%, 0%, 100%, 50%, and 0%, for the 70% HTx, 85% HTx, 85% HTx + ONO-SM362, 85% HTx + mAb, and 85% HTx + FR167653, respectively. Mice that underwent 85% HTx died from liver failure associated with a significant rise in serum TNF-alpha level. ONO-SM362 and mAb improved animal survival and enhanced PCNA LI. In addition, ONO-SM362 inhibited TNF-alpha mRNA expression in the remnant liver and suppressed PMNs infiltration. CONCLUSIONS Suppression of excessive TNF-alpha production using ONO-SM362 ameliorated liver failure after 85% HTx.