Natural history of large regenerative nodules and dysplastic nodules in liver cirrhosis: 28-year follow-up study.

BACKGROUND AND AIMS: Some follow-up studies of large regenerative nodules (LRNs) and dysplastic nodules (DNs) were reported previously. However, the pre-malignant potentiality of LRNs has remained controversial up to now. No LRNs showed malignant transformation in our previous study. We aimed to evaluate the pre-malignant potentiality of LRNs and DNs with a greater number of cases and longer follow-up periods. METHODS: From 1982 to 2005, 1,500 consecutive nodular lesions up to 2 cm in diameter were subjected to US guided thin-needle biopsy in cirrhotic patients at Chiba University Hospital. Of these lesions, 68 LRNs in 60 cases and 20 DNs in 22 cases were followed up for more than 6 months without any anti-cancer therapy. The last US examination was in 2010. The total study period was 28 years. We analyzed the histological findings and the clinical data of all cases retrospectively. The outcome of the lesions was examined. RESULTS: The mean follow-up period was 38.9 (16-119) months in LRNs and 31.9 (6-101 months) in DNs. Rate of nodule enlargement was higher in DNs (8/24 nodules, 33%) than LRNs (11/68 nodules, 16 %), (p = 0.0743, not significant). Rate of malignant transformation was also higher in DNs (10/24 nodules, 42%) than LRNs (9/68 nodules, 13%), (p = 0.0040, significant). The rate of disappearance in images was similar between LRNs and DNs. CONCLUSIONS: We should recognize LRN as low risk pre-malignant lesions whereas DNs as high risk lesions.

[A case of duodenal gangliocytic paraganglioma with lymph node metastasis].

A 28-year-old man complained of tarry stool. A series of examinations showed a submucosal tumor with bleeding at the papilla of Vater and a swollen # 17b lymph node, both of which indicated a hypervascular tumor. The pathological findings of the enucleated tumor specimens revealed gangliocytic paraganglioma with metastasis to the # 17b lymph node. Additional pancreaticoduodenectomy revealed another # 17b lymph node metastasis 7-mm in diameter. Although the majority of gangliocytic paragangliomas are benign, 7% of reported cases have lymph node metastases, as shown in the present case. These findings are important in treating patients with gangliocytic paraganglioma.

Contrast-enhanced US with Levovist for the diagnosis of hepatic hemangioma: time-related changes of enhancement appearance and the hemodynamic background.

BACKGROUNDS/AIMS: To elucidate the diagnostic confidence of contrast-enhanced ultrasound (CEUS) with Levovist for hepatic hemangioma. METHODOLOGY: The subjects were 34 patients with 38 hemangiomas and 12 patients with 15 hypervascular hepatocellular carcinomas. The early-phase (15-60 second) and liver-specific phase (after 5 min) were observed by the first injection. The 2nd injection was done for solo-phase method to observe liver-specific phase images without taking early-phase sonograms. The 3rd injection was done for changing posture method to observe liver-specific sonograms under left lateral ducubitus position. RESULTS: In the early-phase of hemangioma, nodular enhancement (NE) was found transiently in 13 lesions (34%) and continuously in 25 lesions (66%), while hepatocellular carcinoma (HCC, n = 15) did not show this pattern. Intratumoral arterioportal shunt was closely related to the short duration of NE. Two enhancement patterns were observed in the liver-specific phase of hemangioma, diffuse in 12 lesions (31%) and partial in 26 lesions (69%), which were dependent on the early-phase enhancement. Liver-specific findings were also affected by taking early-phase sonograms or changing the posture of the patient. This method provided sensitivity of 79% and specificity of 100% for the diagnosis of hemangioma. CONCLUSIONS: CEUS with Levovist may be promising method for the diagnosis of hepatic hemangioma.

How to characterize non-hypervascular hepatic nodules on contrast-enhanced computed tomography in chronic liver disease: feasibility of contrast-enhanced ultrasound with a microbubble contrast agent.

BACKGROUND AND AIM: Although hypervascular appearance is characteristic in hepatocellular carcinoma (HCC), hepatic nodules without hypervascular appearance are sometimes found in patients with chronic liver disease (CLD). The aim of the present study was to clarify the efficacy of contrast-enhanced ultrasound (CEUS) with Levovist to characterize small, non-hypervascular hepatic nodules on contrast-enhanced computed tomography (CECT) in patients with CLD. METHODS: The subject was 41 hepatic nodules (<30 mm, 18.5 +/- 5.6 mm) which showed non-hypervascular appearance on CECT in 35 patients with CLD; their histological results were 31 HCC (15 well, 14 moderate, and two poor) and 10 regenerative nodules (RN). CEUS with Levovist was performed under intermittent scanning (1-s interval) using APLIO at the early phase and the liver-specific phase, and the contrast enhancement of the nodule was assessed in comparison to that of the surrounding liver parenchyma. The contrast-enhanced findings with the time-intensity analysis were compared with the histological results. RESULTS: Twelve nodules with weak enhancement in the liver-specific phase were HCC, regardless of their early-phase appearances. The other 29 nodules with equivalent or weak enhancement in the early phase and equivalent enhancement in the liver-specific phase were 19 HCC and 10 RN. Among them, the maximum-intensity ratio of tumor to non-tumor in the early phase was significantly higher in HCC than in RN (P < 0.01, n = 16), and the receiver-operating characteristic analysis showed a sensitivity of 1.0 and a specificity of 0.83 for their characterization. CONCLUSION: CEUS with Levovist may be an alternative to biopsy to characterize small, non-hypervascular hepatic nodules on CECT in patients with CLD.

Contrast-enhanced three-dimensional fusion sonography of small liver metastases with pathologic correlation.

PURPOSE: To demonstrate that liver metastases with a diameter of < or =40 mm show characteristic features on three-dimensional (3D) fusion sonographic images and that these sonographic findings can be correlated with histopathologic features of surgical specimens. METHODS: Liver metastases measuring < or =40 mm were examined via contrast-enhanced 3D fusion sonography. The characteristic sonographic findings of 17 tumor nodules in 11 patients with a histopathologically confirmed diagnosis of liver metastases were investigated, and their correspondence to the pathologic features were examined in 12 resected nodules. RESULTS: On sonograms, central vessels were visualized in all 17 tumor nodules and peripheral vessels were visualized in 12 nodules. On histopathologic examination, the portal triad vessels corresponded to the central vessels and were located at the center of the tumors. A thin layer of peritumoral hepatocytes showing various changes was also observed, and a group of tiny vessels were seen running along this layer of cells. CONCLUSIONS: Liver metastases measuring 40 mm or less in diameter were characterized by the presence of both central and peripheral vessels on contrast-enhanced 3D fusion sonography. There was good correlation between sonographic and histopathologic findings.

Multidetector helical CT plus superparamagnetic iron oxide-enhanced MR imaging for focal hepatic lesions in cirrhotic liver: a comparison with multi-phase CT during hepatic arteriography.

The aim of this study was to evaluate multidetector helical computed tomography (MDCT), superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging, and CT arterial portography (CTAP) and CT during hepatic arteriography (CTHA) for the detection and diagnosis of hepatocellular carcinomas (HCC). This included visual correlations of MDCT and SPIO-MR imaging in the detection of HCC using receiver operating characteristic (ROC) analysis. Twenty-five patients with 57 nodular HCCs were retrospectively analyzed. A total of 200 segments, including 49 segments with 57 HCCs, were reviewed independently by three observers. Each observer read four sets of images (set 1, MDCT; set 2, unenhanced and SPIO-enhanced MR images; set 3, combined MDCT and SPIO-enhanced MR images; set 4, combined CTAP and CTHA). The mean Az values representing the diagnostic accuracy for HCCs of sets 1, 2, 3, and 4 were 0.777, 0.814, 0.849, and 0.911, respectively, and there was no significant difference between sets 3 and 4. The sensitivity of set 4 was significantly higher than those of set 3 for all the lesions and for lesions 10 mm or smaller (p<0.05); however, for lesions larger than 10mm, the sensitivities of the two sets were similar. No significant difference in positive predictive value and specificity was observed between set 3 and set 4. Combined MDCT and SPIO-enhanced MR imaging may obviate the need for more invasive CTAP and CTHA for the pre-therapeutic evaluation of patients with HCC more than 10mm.

Diagnostic value of MRCP and indications for ERCP.

BACKGROUND/AIMS: To assess the diagnostic value of magnetic resonance cholangiopancreatography (MRCP) and examine the indications for endoscopic retrograde cholangiopancreatography (ERCP). METHODOLOGY: MRCP was performed in 185 patients with hepatobiliary disease in whom abdominal ultrasonography (US) had not been of diagnostic value. These patients were selected for MRCP in view of their abdominal symptoms, high levels of hepatobiliary enzymes, and pancreatic/bile duct dilatation found by abdominal US. Based on MRCP findings, 75 patients were selected for ERCP. RESULTS: ERCP provided new findings in 14 (18.%) patients. In 110 patients subjected to only MRCP and follow-up as well as in 75 patients with MRCP followed by ERCP, MRCP-based diagnosis corresponded with the final diagnosis. In our study, patients who would have conventionally required ERCP, such as those with natural passed choledocholithiasis and postoperative bile duct dilatation, could be followed up without ERCP. These results the importance of considering indications for ERCP. CONCLUSIONS: MRCP can be an alternative to ERCP at least for diagnosis.

Microbubble disappearance-time is the appropriate timing for liver-specific imaging after injection of Levovist.

Contrast enhancement in the portal vein was repeatedly observed at 1 min intervals with wide-band Doppler ultrasonography in 152 consecutive patients (132 with liver cirrhosis and HCC, 20 controls), 5 min after the injection of Levovist. The duration time of contrast enhancement in the portal vein (microbubble disappearance-time; MD-T) was measured in all patients and contrast-enhanced appearances were compared between the 5 min phase and MD-T phase in 68 HCC nodules. MD-T in patients with liver cirrhosis (572.4 +/- 117.9 s) was significantly longer than in controls (481.6 +/- 89.3 s, p < 0.05). MD-T was prolonged in patients with Child B and C compared with Child A (p < 0.05). The contrast-enhanced appearances between the two phases were different in 30 of 68 HCC nodules (44.1%), showing positive enhancement in the 5 min phase and negative enhancement in the MD-T phase. The proposed MD-T may become an essential factor for the evaluation of liver-specific sonograms.

Recent applications of ultrasound: diagnosis and treatment of hepatocellular carcinoma.

Ultrasound (US) has the advantages of real-time observation, simple technique, and a noninvasive procedure compared to other imaging modalities. The recent development of digital technologies has enabled the observation of sonograms with improved signal-to-noise ratio, penetration, and spatial and contrast resolutions. Furthermore, microbubble contrast agents have increased the diagnostic ability of US examination, and the use of three-dimensional sonograms is now not unusual. These advances have furthered the usefulness of US for liver tumors in clinical practice. This article reviews the recent applications of US in the diagnosis and treatment of hepatocellular carcinoma.

Ring-shaped appearance in liver-specific image with Levovist: a characteristic enhancement pattern for hypervascular benign nodule in the liver of heavy drinkers.

BACKGROUND/AIMS: The aim was to clarify the features of contrast-enhanced ultrasound (CEUS) with Levovist for diagnosis of hypervascular benign nodules in the liver of heavy drinkers. PATIENTS AND METHODS: Seven heavy drinkers with hypervascular nodules in the liver were studied. Findings of CEUS with Levovist (wide-band Doppler, 7/7), contrast-enhanced computed tomography (CECT, 7/7) and magnetic resonance imaging (MRI, 5/7) were compared for one nodule in each patient. RESULTS: Diagnosis of all seven nodules on CECT was HCC, whereas pathological results were HCC for four nodules and benign lesion for three nodules. The former four showed compatible findings for HCC on CEUS (4/4) and MRI (2/4). However, the latter three showed characteristic liver-specific sonograms with a ring-shaped appearance--peripheral enhancement with a central non-enhanced area. Two of the three nodules showed decreased signal-intensity in the periphery on SPIO-enhanced MRI. CONCLUSIONS: The ring-shaped appearance on liver-specific sonograms with Levovist may be a useful sign for the differential diagnosis of hypervascular benign nodule from HCC in heavy drinkers.

An improved diagnostic method for chronic hepatic disorder: analyses of metallothionein isoforms and trace metals in the liver of patients with hepatocellular carcinoma as determined by capillary zone electrophoresis and inductively coupled plasma-mass spectrometry.

It is desirable to diagnose hepatocellular carcinoma (HCC) in the early stages during its development since its treatment is usually difficult. We previously proposed a new diagnostic method that made use of the total metallothionein (MT), zinc (Zn), and copper (Cu) concentrations in the liver of the HCC patients. We recently found that MT-1 is involved in the metabolism or detoxification of toxic metals, such as cadmium; on the other hand, MT-2 is responsible for the homeostasis of essential metals such as copper, in experimental models such as Long Evans Cinnamon (LEC) rats. In order to device a better diagnostic method than the one we proposed previously, in this study, we newly propose an improved method that includes the discriminative determination data regarding the MT isomers, namely, MT-1 and MT-2, in the liver of patients with or without HCC as compared with the total MT level. The total MT and Zn concentrations in the HCC patients were confirmed to be significantly lower than those in patients without hepatic disorders (Ctrl). In contrast, Cu concentrations of the HCC patients were higher than those of the Ctrl patients. In addition, in the juxta-tumor portion with HCC, MT-1 concentrations were significantly higher than those of MT-2. In contrast, the MT-1 concentrations in the tumor portion were significantly lower than that in the juxta-tumor portion. In addition, MT-1/MT-2 ratio in the tumor portion was significantly lower than that of the juxta-tumor portion. By using parameters such as concentrations of Cu, Zn, total MT, and MT isomers, we performed the multivariate discriminative analysis (MDA). The results suggest that the concentrations of MT isomers change depending on the progress of the tumor, and information on MT isomers and trace elements is very useful in determining the stage of the chronic hepatic disorder.

Relationship between therapeutic efficacy of arterial infusion chemotherapy and expression of P-glycoprotein and p53 protein in advanced hepatocellular carcinoma.

AIM: To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein (PGP) and p53 protein in advanced hepatocellular carcinoma (HCC). METHODS: The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the forty-one patients were treated with an anthracycline drug (epirubicin hydrochloride; anthracycline group), and the remaining 21 were treated with a non-anthracycline drug (mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group). The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups. RESULTS: Before the start of the treatment, PGP-positive rate was 90.2% (strongly-positive, 36.6%) and p53 protein-positive rate was 34.1% (strongly-positive, 19.5%). In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression (P=0.005), and their prognoses were poor (P=0.001). In the non-anthracycline group, the response rate was 42.9%, and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53 protein expression. When only the data from the 11 patients treated with anthraquinone drug, mitoxantrone, were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients (P=0.012), irrespective of the survival outcome. CONCLUSION: The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP expression. Similarly, immunostaining to evaluate p53 protein may be useful to predict the response in patients treated with an anthraquinone drug.

A pilot approach for quantitative assessment of liver fibrosis using ultrasound: preliminary results in 79 cases.

BACKGROUND/AIMS: Ultrasound is noninvasive and useful to evaluate liver disease despite its operator dependency. This pilot study was conducted to quantitatively assess liver fibrosis using ultrasound. METHODS: Fibrosis extraction ratios (FER) (fiber volume/total volume) of ultrasound and histological images of 8 autopsy specimens were compared. We also compared FER of ultrasound images from clinical patients (n=79) with histological fibrosis stages. RESULTS: In the autopsy study, FER correlation coefficient between histological images and ultrasound images was 0.992. Regarding clinical patients, there was sufficient evidence to indicate differences in the distributions of FER for each fibrosis stage (Kruskal-Wallis test P<0.0001). With FER cut-off to distinguish > or =F2 from F0 and F1 defined as mean plus standard deviation of F0 and F1, sensitivity, specificity, positive predictive value, negative predictive value, and likelihood ratio were 62, 75, 78, 57%, and 2.47, respectively. Regarding HCV cohort (n=44), they were 55, 87, 89, 50%, and 4.14, respectively. Areas under receiver operating characteristic curves were 0.78, 0.79, 0.83 and 0.83 for > or =F1, > or =F2, > or =F3 and =F4, respectively. Regarding HCV cohort, they were 0.74, 0.71, 0.79 for > or =F2, > or =3 and =4, respectively. CONCLUSIONS: The FER method has great potential for diagnosing liver fibrosis using ultrasound.

Large regenerative nodule perfused by the portal vein.

In a 42-year-old Japanese woman with esophageal varices, abdominal ultrasound (US) demonstrated a hyperechoic lesion 3 cm in diameter in segment 4 (S4). This nodular lesion had high intensity on T1-weighted magnetic resonance imaging (MRI), low intensity on T2, and very high intensity on superparamagnetic iron oxide (SPIO) enhanced MRI. Angiography showed sparse distribution of arterial branches and dense distribution of portal branches in S4. Meandering, thin arteries were seen in the peripheral area of the right lobe. The second branches of the portal vein were hardly visualized anywhere in the liver. Computed tomography arterioportography (CTAP) revealed portal blood flow dominance in this nodular lesion. There was no evidence of ischemic liver damage, such as thromboembolic episodes, laboratory data of liver damage, coagulation abnormalities etc. Therefore this abnormality was more likely to be caused by anomalous changes than thrombotic changes. Needle biopsy revealed no atypical cells. Two years later, the nodule size was reduced to 1.9 cm, showing its benign nature. Based on these findings, this lesion was classified as a new type of large regenerative nodule (LRN) associated with anomalies in the portal veins and arteries. This is the first report of an LRN of this size in which portal vein perfusion was dominant. Moreover, this lesion was difficult to differentiate from hepatocellular carcinoma (HCC) by imaging. Analysis of the images and pathological features of this case would contribute to a better understanding of the pathogenesis of nodular lesions of the liver.

Evaluation of distribution patterns for copper and zinc in metallothionein and superoxide dismutase in chronic liver diseases and hepatocellular carcinoma using high-performance liquid chromatography (HPLC).

It has been reported that the copper (Cu) content of hepatocytes increases in chronic liver diseases and small hepatocellular carcinoma (HCC). In cells, Cu exists mainly as Cu-metallothionein (MT) or Cu, zinc (Zn)-superoxide dismutase (SOD). In this study, we investigated the biochemical state of Cu in the hepatocytes of patients with HCC using high-performance liquid chromatography (HPLC). The subjects of present study were 23 patients with HCC who underwent liver resection. The cancerous tissue and non-cancerous hepatic parenchyma with chronic disease were analyzed. In addition, as a normal control, hepatic tissue was collected at autopsy from 13 patients with no liver disease. Each sample was diluted with buffer, chilled, homogenized, and centrifuged. The supernatant was fractionated using HPLC. The metal contents of each fraction were measured using a desktop-type inductively coupled plasma (ICP) emission spectrochemical analyzer. HPLC analysis showed that MT existed mainly as Zn-MT in the normal hepatic tissue. The case of Cu,Zn-MT was significantly greater than Zn-MT in the non-cancerous, but diseased hepatic parenchyma than in the normal hepatic tissue (p<0.01). In comparison with non-cancerous hepatic parenchyma, the Cu-MT in the cancerous section was significantly greater than the Cu,Zn-MT (p<0.01). The Cu content for MT was significantly higher in small HCC (<40 mm) (p<0.01), and the absence of Cu or Zn in the MT fraction was significantly more frequent in the large HCC (>or=40 mm) (p<0.01). The Cu and Zn content for SOD in the samples showed no significant difference. Increase in the Cu content in the cancerous hepatic tissue were, thought to be reflecting changes in the distribution of Cu in the MT fraction of hepatic tissues.

Percutaneous ethanol injection for small hepatocellular carcinoma: therapeutic efficacy based on 20-year observation.

BACKGROUND/AIMS: To evaluate the therapeutic efficacy of percutaneous ethanol injection (PEI) for patients with < or = 3 lesions of small (< or = 3 cm diameter) hepatocellular carcinoma (HCC). METHODS: PEI was applied to 270 patients with small HCC as the first-line treatment option during a 20-year period. RESULTS: (1) There was no treatment-related deaths, and only 2.2% of severe complications; (2) PEI induced a complete response of all HCCs according to CT evaluation performed within one month after the procedure, and the local recurrence rate at 3 years was 10%; (3) the overall 3- and 5-year survival rates after treatment were 81.6 and 60.3%, respectively, but the rates were higher, 87.3 and 78.3%, in Child A patients with a solitary tumor < or = 2 cm in diameter; (4) factors significantly influencing survival were liver function (P = 0.0033) and serum alpha-fetoprotein level (P = 0.0014), and (5) the recurrence rate at remote sites in the liver was lower in patients with HCC < or = 2 cm (P = 0.0395) and in those with a solitary HCC (P < 0.0001) according to Cox's proportional hazard model. (6) Radiofrequency ablation would not have been performed in approximately 25% of these patients. CONCLUSIONS: PEI is considered a reliable treatment for small HCC in terms of safety and efficacy.

A role for c-fos/activator protein 1 in B lymphocyte terminal differentiation.

Expression of B lymphocyte-induced maturation protein 1 (Blimp-1) transcription factor is essential for promoting B cell differentiation into plasma cells. However, a critical transcription factor for Blimp-1 expression in activated B cells is unclear. When splenic B cells were stimulated with CD40 ligand (CD40L) and IL-4, terminal differentiation was induced in the B cells from c-fos transgenic (H2-c-fos) mice but barely in those from control littermates and from c-fos-deficient mice. AP-1 family and Blimp-1 mRNAs were transiently induced in the control B cells, and overexpression of c-Fos induced a sufficient amount of Blimp-1 for terminal differentiation in the H2-c-fos B cells. When normal and c-fos-deficient B cells were stimulated with LPS, a sufficient amount of Blimp-1 for terminal differentiation was induced in those B cells. However, expression of c-fos/AP-1 family mRNAs in LPS-stimulated normal B cells was similar to that of normal B cells stimulated with CD40L and IL-4. EMSA and chromatin immunoprecipitation assays using the AP-1-binding DNA sequence in the murine Blimp-1 promoter region demonstrated that AP-1-binding activity in nuclear protein of LPS-stimulated normal B cells was prolonged more than that in normal B cells stimulated with CD40L and IL-4. Furthermore, the percentage of CD138(+) B cells within germinal center B cells in the spleen and the number of Ab-forming cells in the bone marrow of H2-c-fos mice was larger than that of control mice 12 days after immunization. Thus, although c-Fos is not essential for Blimp-1 expression, c-Fos/AP-1 positively regulates Blimp-1 expression and terminal differentiation of activated B cells.

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

BACKGROUND: Metallothionein (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. METHODS: Specimens 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. RESULTS: The 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. CONCLUSIONS: MT 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.

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.