Kazuki Kato

Distinguishing benign from malignant intraductal papillary mucinous tumors of the pancreas by imaging techniques.

Objectives: It is often difficult to differentiate benign from malignant intraductal papillary mucinous tumors (IPMTs). This study aimed to differentiate them using various imaging techniques. Methods: Receiver operating characteristic curves were used to establish optimal cutoff values to differentiate benign from malignant tumors in 121 patients with histologically confirmed IPMTs. Results: For branch duct type, accuracy for malignancy was highest using endoscopic ultrasonography (EUS) to measure the cyst diameter, and accuracy was 68.2% at a cutoff value of 33.9 mm. For main duct type, accuracy was highest, 71.1% at a cutoff value of 8.4 mm for main duct diameter, with magnetic resonance cholangiopancreatography. For all imaging techniques and findings, accuracy was highest using EUS, 76.4% at a cutoff value of 5.4 mm for height of protrusion. Each imaging technique had a positive predictive value of 80% if the cut off value for the height of the protruding lesion was met. Conclusions: Malignancy can be strongly suspected when the height of protrusion exceeds the respective cutoff values. EUS was most effective to differentiate benign IPMTs from malignant tumors by assessing the height of protrusion.

Chromoendoscopy with indigo carmine dye added to acetic acid in the diagnosis of gastric neoplasia: a prospective comparative study

BACKGROUND Conventional endoscopy and chromoendoscopy with indigo carmine dye are usually performed for recognizing adequate tumor-negative lateral margins for successful endoscopic resection of gastric neoplasia. However, chromoendoscopy with indigo carmine dye added to acetic acid has not been used for this purpose. OBJECTIVE Our purpose was to compare the diagnostic performance of chromoendoscopy with indigo carmine dye added to acetic acid with that of conventional endoscopy and chromoendoscopy with indigo carmine dye or acetic acid alone. DESIGN Prospective study. SETTING Social Insurance Funabashi Central Hospital. PATIENTS Forty-seven consecutive patients (53 lesions) with early gastric cancer and gastric adenomas who underwent endoscopic submucosal dissection (ESD) from April 2006 to July 2007 were studied. INTERVENTIONS All the lesions were examined by the endoscopic modalities before ESD, and the resected specimens were analyzed histopathologically. MAIN OUTCOME MEASUREMENTS Two endoscopists independently evaluated the diagnostic performance of each image in terms of recognition of tumor borders with reference to macroscopic and histopathologic findings of resected specimens. We also conducted a substudy to assess interobserver variability. RESULTS There was good interobserver agreement between the 2 endoscopists in this study (kappa index = 0.764). The diagnostic performance of chromoendoscopy with indigo carmine dye added to acetic acid was significantly greater than that of any of the other modalities (vs each: P < .005). CONCLUSIONS The diagnostic performance of chromoendoscopy with indigo carmine dye added to acetic acid was better compared with conventional endoscopy and chromoendoscopy by using only indigo carmine dye or acetic acid. The applicability of this method for gastric neoplasia merits further investigation.

Immunohistochemical metallothionein expression in hepatocellular carcinoma: relation to tumor progression and chemoresistance to platinum agents.

BackgroundMetallothionein (MT), which is known to detoxify heavy metal ions, is considered to serve as a mechanism of resistance to platinum complex compounds. In the present study, MT expression in hepatocellular carcinoma (HCC) was immunohistologically investigated to clarify its relationship to clinical background factors and responsiveness to anticancer drugs.MethodsSpecimens from 117 patients with HCC were immunohistologically studied, using a monoclonal anti-MT antibody. the percentage of MT-positive HCC (MT ratio) cells was determined, to evaluate the extent of staining with anti-MT antibody. Staining with an MT ratio of more than 50% was categorized as diffusely positive; an MT ratio of 5% to less than 50% was focally positive; and an MT ratio of less than 5% was negative. Twenty-two patients received repeated arterial infusion chemotherapy with carboplatin (CBDCA), a platinum-containing compound, and the MT expression was analyzed in relation to their chemotherapeutic response.ResultsThe ratio of MT-positive cells in HCC decreased with the degree of histological differentiation and also decreased with higher tumor stage. In patients treated with CBDCA, the ratio of MT-positive cells in responders was significantly lower than that in non-responders.ConclusionsMT expression decreases with the degree of histological differentiation and decreases with increasing tumor stage in HCC. In addition, MT expression may lower the antitumor effect of CBDCA.

Assessment of cancer cell differentiation in small hepatocellular carcinoma by computed tomography and magnetic resonance imaging

Aim: To study whether cancer cell differentiation in small hepatocellular carcinoma (HCC) can be assessed by computed tomography (CT) and magnetic resonance (MR) imaging.

Extraction of Quantitative Three-Dimensional Information from Ultrasonic Volumetric Images of Cirrhotic Liver

The cirrhotic liver has many fibrotic tissue structures known as nodule structures. Understanding this characteristic in diseased tissue is important for quantitative diagnosis. In this paper, we present a technique to extract quantitative three-dimensional information from a cirrhotic liver. Consecutive two-dimensional images acquired by fan like scanning were processed using constant false alarm rate (CFAR). The 2D processed images are accumulated to obtain 3D information. The nodular structure is clear in the constructed images.

Measurement of Acoustic Property Distributions of Diseased Heart and Liver Tissues.

Acoustic properties of living tissues are an important parameter for quantitative estimation of the tissue structure. It is very important to determine the relationship between the physical and the chemical change of tissue structure and the change of acoustic properties. In this paper, using a new system with high density measuring points, we present the relationship diagram between the speed of sound and attenuation of human heart and liver tissues at 25 MHz. To compare normal and diseased tissues, we investigate the relationship between the sound speed and the attenuation of tissue. A characteristic relationship of the tissue is found in cirrhotic liver and aortic regurgitation tissue.

Immunohistochemical Localization of Type IV Collagen α Chains in the Basement Membrane of the Pancreatic Duct in Human Normal Pancreas and Pancreatic Diseases

The type IV collagen (Col-IV) consists of 3 α chains. Six different α chains [α1(IV), α2(IV), α3(IV), α4(IV), α5(IV), and α6(IV)] have been identified, and their combination is considered to be organ specific. We investigated the immunohistochemical localization of α (IV) chains in the basement membrane (BM) of the pancreatic duct in human normal pancreas (NP) and pancreatic diseases. Fifty specimens [10 NP, 10 chronic pancreatitis (CP), 10 intraductal papillary mucinous tumor (IPMT), and 20 pancreatic adenocarcinoma (PAC)] were examined. α1(IV), α2(IV), α5(IV), and α6(IV) were linearly immunostained in NP, CP, and IPMT. In PAC, α(IV) and α2(IV) were immunostained, but α5(IV) and α6(IV) were not stained in 30% and 40% of the cases, respectively. In conclusion, immunohistochemically, the Col-IV of human normal pancreatic duct consisted of α1(IV), α2(IV), α5(IV), and α6(IV). α5(IV) and α6(IV) were frequently absent in PAC, and their absence might be related to the invasion of cancer cells.

Efficacy of lamivudine or entecavir against virological rebound after achieving HBV DNA negativity in chronic hepatitis B patients.

Nucleos(t)ide analogues (NAs) lead to viral suppression and undetectable hepatitis B virus (HBV) DNA in some individuals infected with HBV, but the rate of virological rebound has been unknown in such patients. We examined the prevalence of virological rebound of HBV DNA among NA-treated patients with undetectable HBV DNA. We retrospectively analyzed 303 consecutive patients [158 entecavir (ETV)- and 145 lamivudine (LAM)-treated] who achieved HBV DNA negativity, defined as HBV DNA < 3.7 log IU/mL for at least 3 months. They were followed up and their features, including their rates of viral breakthrough, were determined. Viral rebound after HBV DNA negativity was not observed in the ETV-group. Viral rebound after HBV DNA negativity occurred in 38.7% of 62 HBe antigen-positive patients in the LAM-group. On multivariate analysis, age was an independent factor for viral breakthrough among these patients (P = 0.035). Viral rebound after HBV DNA negativity occurred in 29.1% of 79 HBe antigen-negative patients in the LAM-group. Differently from LAM, ETV could inhibit HBV replication once HBV DNA negativity was achieved. In contrast, LAM could not inhibit HBV replication even if HBV negativity was achieved in the early phase. Attention should be paid to these features in clinical practice.

Characterization of hyperplastic foci observed in surgical specimens of hepatocellular carcinoma

By reviewing previous surgical specimens of hepatocellular carcinoma, 17 cases with hyperplastic foci (HPF) characterized by discernible increase in nuclear densities, could be histologically selected. Nuclear densities of HPF and control hepatic parenchyma were assessed quantitatively by counting the nuclear number of hepatic cells, and proliferating cell nuclear antigen labeling index was measured. HPF occurred multifocally, confined within a lobular unit, smoothly merging into surrounding hepatic parenchyma. Nuclear densities of HPF were 1.71 times greater than those of control hepatic parenchyma. The hepatocytes of HPF also showed significantly higher proliferative activities than those of control parenchyma. In addition, noticeable structural distortions, such as focal trabecular thickening or microacinar formation of hepatocytes, were sometimes observed in HPF. However, these HPF seemed to be distinguished from minute de novo hepatocellular carcinoma (HCC) or intrahepatic HCC metastasis, because of paucity of distinctive atypical changes, and intimate correlation with neighboring hepatocytes. Several adjacent HPF were aggregated to form a much larger unit of a hyperplastic area with loss of fibrous septa of liver cirrhosis. It was suggested that grossly detectable large regenerative nodules are produced via fusion of several adjacent HPF.

Enhanced detection of lymphovascular invasion in small rectal neuroendocrine tumors using D2‐40 and Elastica van Gieson immunohistochemical analysis

Rectal neuroendocrine tumor (RNET) lymphovascular invasion (LVI) is regarded as an important predictor of nodal metastasis after endoscopic resection (ER). However, little is known about the frequency of immunohistochemical detection of LVI in RNETs. This study was performed to establish the actual detection of LVI rate in RNETs ≤10 mm and to evaluate associated clinical outcomes. We retrospectively reviewed the records for 98 consecutive patients treated by ER with a total of 102 RNETs ≤10 mm. Tissue sections were labeled with hematoxylin–eosin (HE) stain, the D2‐40 monoclonal antibody to evaluate lymphatic invasion, and Elastica van Gieson (EVG) stain to detect venous invasion. LVI detection rate by HE versus immunohistochemical analysis was compared. Follow‐up findings and clinical outcomes were also evaluated for 91 patients who were followed for ≥12 months. Lymphatic and venous invasion were detected using HE staining alone in 6.9% and 3.9% of patients, respectively, whereas they were detected using D2‐40 and EVG staining in 20.6% and 47.1% of the patients, respectively. Thus, the LVI detection frequency using D2‐40 and EVG staining (56.9%) was significantly higher than with HE (8.8%). Two out of seven patients who required additional surgery had regional lymph node metastases. However, among the 84 patients who were followed up without surgery, no distant metastases or recurrences were detected. Compared with HE staining, immunohistochemical analysis significantly increased the frequency of LVI detection in RNETs ≤10 mm. However, the clinical impact of LVIs detected using immunohistochemical analysis remains unclear. Clarification of the actual role of LVI using immunohistochemical analysis requires a patient long‐term follow‐up and outcomes.