Kazuya Sugimori

Randomized Phase III Study of Gemcitabine Plus S-1, S-1 Alone, or Gemcitabine Alone in Patients With Locally Advanced and Metastatic Pancreatic Cancer in Japan and Taiwan: GEST Study

PURPOSE The present phase III study was designed to investigate the noninferiority of S-1 alone and superiority of gemcitabine plus S-1 compared with gemcitabine alone with respect to overall survival. PATIENTS AND METHODS The participants were chemotherapy-naive patients with locally advanced or metastatic pancreatic cancer. Patients were randomly assigned to receive only gemcitabine (1,000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle), only S-1 (80, 100, or 120 mg/d according to body-surface area on days 1 through 28 of a 42-day cycle), or gemcitabine plus S-1 (gemcitabine 1,000 mg/m(2) on days 1 and 8 plus S-1 60, 80, or 100 mg/d according to body-surface area on days 1 through 14 of a 21-day cycle). RESULTS In the total of 834 enrolled patients, median overall survival was 8.8 months in the gemcitabine group, 9.7 months in the S-1 group, and 10.1 months in the gemcitabine plus S-1 group. The noninferiority of S-1 to gemcitabine was demonstrated (hazard ratio, 0.96; 97.5% CI, 0.78 to 1.18; P < .001 for noninferiority), whereas the superiority of gemcitabine plus S-1 was not (hazard ratio, 0.88; 97.5% CI, 0.71 to 1.08; P = .15). All treatments were generally well tolerated, although hematologic and GI toxicities were more severe in the gemcitabine plus S-1 group than in the gemcitabine group. CONCLUSION Monotherapy with S-1 demonstrated noninferiority to gemcitabine in overall survival with good tolerability and presents a convenient oral alternative for locally advanced and metastatic pancreatic cancer.

Ablation therapy guided by contrast-enhanced sonography with Sonazoid for hepatocellular carcinoma lesions not detected by conventional sonography.

We evaluated the usefulness of contrast‐enhanced harmonic gray scale sonography with a newly developed sonographic contrast medium as a means of guidance for percutaneous ablation therapy of hepatocellular carcinoma lesions not detected by conventional sonography.

Contrast-enhanced sonography of pancreatic carcinoma: correlations with pathological findings

BackgroundWe examined contrast-enhanced harmonic gray-scale sonographic findings of pancreatic carcinoma in relation to the pathological findings in resected specimens to evaluate correlations between observations made by this modality and the pathological findings.MethodsThe pathological findings of surgical specimens obtained from 16 patients were examined in relation to the contrast-enhanced harmonic gray-scale sonography findings. Lesion vascularity was examined by contrast-enhanced harmonic gray-scale sonography from 20 to 50 s after the injection of Levovist (Schering, Berlin, Germany) (early phase), and lesion enhancement was also monitored at approximately 90 s after injection (delayed phase).ResultsContrast-enhanced harmonic gray-scale sonography showed positive enhancement in 12 of the 16 lesions (peripheral tumor region alone, n = 9; entire tumor, n = 3), while the other 4 lesions showed no contrast enhancement in any region. Twelve enhanced regions (9 peripheral tumor region and 3 entire tumor regions) detected by contrast-enhanced harmonic gray-scale sonography showed: (1) mild fibrosis with inflammation, in 10 regions (83%); (2) the presence of both carcinoma cells and residual acinar cells in 8 (67%); and (3) presence of relatively large arteries in 2 (17%). In contrast, 13 non-enhanced regions (4 entire tumor regions and 9 central regions) showed: (1) severe fibrosis in 10 regions (77%); (2) necrosis in 7 (54%); and (3) mucin in 4 (31%).ConclusionsContrast-enhanced harmonic gray-scale sonographic findings of pancreatic carcinoma are influenced by interstitial histological features associated with tumor growth.

Contrast-Enhanced Sonography of Autoimmune Pancreatitis Comparison With Pathologic Findings

Objective. We evaluated the vascularity of autoimmune pancreatitis lesions on contrast‐enhanced harmonic gray scale sonographic images in comparison with the pathologic findings. Methods. Six patients with autoimmune pancreatitis were examined. All patients held their breath from 20 to 50 seconds after the injection of a contrast agent while the vascularity of the lesion was examined by contrast‐enhanced harmonic gray scale sonography (early phase), and lesion enhancement was monitored at about 90 seconds after the injection while the patients held their breath for a few seconds (delayed phase). We then compared the vascularity on the contrast‐enhanced harmonic gray scale sonographic images with the pathologic findings (fibrosis and inflammation) in all lesions. The vascularity of 3 of the 6 lesions was also evaluated by contrast‐enhanced harmonic gray scale sonography before and after treatment with corticosteroids. Results. The autoimmune pancreatitis lesions exhibited mild (n = 1), moderate (n = 3), or marked (n = 2) enhancement throughout almost the entire lesions in both the early and delayed phases. The grade of lesion vascularity on the contrast‐enhanced harmonic gray scale sonographic images correlated with the pathologic grade of inflammation and inversely correlated with the grade of fibrosis associated with autoimmune pancreatitis. The vascularity of all 3 lesions had decreased on the contrast‐enhanced harmonic gray scale sonographic images after steroid therapy. Conclusions. Contrast‐enhanced harmonic gray scale sonography may be useful for evaluating the vascularity of autoimmune pancreatitis lesions and the therapeutic efficacy of steroid therapy.

Differential diagnosis of gallbladder diseases with contrast-enhanced harmonic gray scale ultrasonography

We evaluated the usefulness of contrast‐enhanced harmonic gray scale ultrasonographic findings for differential diagnosis of gallbladder diseases.

Extension of radiofrequency ablation of the liver by transcatheter arterial embolization with iodized oil and gelatin sponge: results in a pig model.

PURPOSE To determine whether transcatheter arterial embolization (TAE) with iodized oil and gelatin sponge particles can be used to expand radiofrequency (RF)-induced coagulation necrosis, the morphology and histologic characteristics of ablation lesions were evaluated in the normal pig liver after three different TAE procedures. MATERIALS AND METHODS Ten consecutive animals with 33 ablation lesions produced with an RF ablation system were randomly assigned to one of three treatment groups and a control group: a group treated with TAE with iodized oil, a group treated with TAE with gelatin sponge, a group treated with TAE with iodized oil and gelatin sponge, and a control group in which TAE was not performed. After the completion of ablation, the lesions were excised for gross and histologic examination. RESULTS The longest and shortest diameters of ablation lesions were greatest in the group treated with TAE with iodized oil and gelatin sponge, followed by the groups treated with TAE with gelatin sponge and TAE with iodized oil (P < .05 vs controls, respectively). The hemorrhagic rim was also widest in the group treated with TAE with iodized oil and gelatin sponge (P < .05 vs controls), and it spread toward the liver periphery like a segmental hemorrhagic area adjacent to the ablation lesion. Histochemical staining for lactate dehydrogenase, maleate dehydrogenase, and nicotinamide adenine dinucleotide diaphorase showed what appeared to be 100% cellular destruction in all the ablation lesions and their hemorrhagic rims. CONCLUSION RF ablation combined with TAE with iodized oil and gelatin sponge induces the greatest area of coagulation necrosis accompanied by peripherally spreading segmental necrosis in normal pig liver tissue.

Three-Dimensional Contrast-Enhanced Sonography of Vascular Patterns of Focal Liver Tumors: Pilot Study of Visualization Methods

OBJECTIVE We investigated visualization methods of 3D sonography with a perflubutane-based contrast agent in the imaging evaluation of vascular patterns of focal liver tumors. MATERIALS AND METHODS Eighty-four patients with focal liver tumors underwent automatic scanning with 3D sonography 20-60 seconds after administration of a perflubutane contrast agent. The confirmed final diagnoses were 50 hepatocellular carcinomas, 20 metastatic lesions, nine hemangiomas, and five cases of focal nodular hyperplasia. Tomographic sonographic images reconstructed in 3D parallel slices and rendered sonographic images resembling angiograms were reviewed by two readers. RESULTS Sonographic angiograms rendered by maximum intensity of gray values in surface smooth mode showed tumor vessels and early tumor enhancement. The average intensity of gray values with surface texture mode showed unenhanced areas within tumors. Interobserver agreement for classifying enhancement patterns with both tomographic sonography and sonographic angiography was excellent (kappa=0.84). The main pattern, intratumoral vessels with early homogeneous or heterogeneous tumor enhancement, had a sensitivity of 97% (average of both readers), specificity of 94%, and positive predictive value (PPV) of 96% for hepatocellular carcinomas. The presence of tumor vessels with early peripheral ringlike tumor enhancement had a sensitivity of 90%, specificity of 95%, and PPV of 86% for metastatic lesions. Peripheral nodular enhancement had a sensitivity of 84%, specificity of 99%, and PPV of 89% for hemangioma. The presence of spoke-wheel arteries with early tumor enhancement had a sensitivity of 80%, specificity of 100%, and PPV of 100% for focal nodular hyperplasia. CONCLUSION Three-dimensional sonography with a perflubutane-based contrast agent is useful in the evaluation of vascular patterns of focal liver tumors.

Radiofrequency ablation in a pig liver model: effect of transcatheter arterial embolization on coagulation diameter and histologic characteristics.

To determine whether transcatheter arterial embolization (TAE) can alter radiofrequency (RF)-induced coagulation necrosis, we evaluated the morphology and histologic characteristics of RF ablation lesions combined with TAE in normal pig liver. Using a RF ablation system, consisting of a RF generator and 2-cm expandable LeVeen needle electrodes, nine lesions were generated by RF ablation combined with TAE and 11 lesions by RF ablation alone in five animals. On completion of treatment, the lesions were excised for gross and histologic examination. Gross examination demonstrated a core of ablated tissue surrounded by a narrow rim of hemorrhagic necrosis. The final shape of the lesion in the RF ablation group was frequently altered by patent intrahepatic vessels at the periphery of the lesion, whereas the lesions in the RF ablation and TAE group were spherical (P<0.05, chi(2)-test). The coagulation diameter was significantly larger in the RF ablation and TAE group than in the RF ablation group (28.7+/-4.2 vs. 24.1+/-3.2 mm, P<0.05). Histochemical (lactate-dehydrogenase, maleate-dehydrogenase and NADPH-diaphorase) stainings showed what appeared to be 100% cellular destruction in the ablated lesion and its hemorrhagic rim in both groups. We conclude that RF ablation combined with TAE induces greater and more spherical areas of coagulation necrosis in normal pig liver tissue than RF ablation alone.

Sonazoid-Enhanced Ultrasonography for Evaluation of the Enhancement Patterns of Focal Liver Tumors in the Late Phase by Intermittent Imaging With a High Mechanical Index

Objective. The purpose of this study was to evaluate the enhancement patterns of focal liver tumors in the late phase of Sonazoid‐enhanced ultrasonography by intermittent imaging with a high mechanical index (MI). Methods. A total of 142 patients with 208 lesions, including 109 hepatocellular carcinomas (HCCs), 61 metastases, 30 hemangiomas, and 8 focal nodular hyperplasias (FNHs), were enrolled in this prospective study. Contrast‐enhanced ultrasonography with intermittent scanning at 2 frames per second (MI, 0.7–1.2) was conducted in the late phase (>5 minutes after bolus intravenous injection of the perflubutane‐based contrast agent Sonazoid; Daiichi Sankyo, Tokyo, Japan). Two blinded readers classified the enhancement patterns of the lesions. The sensitivity, specificity, and positive predictive value (PPV) of the dominant enhancement patterns and inter‐reader agreement were assessed. Results. A combination of diffuse enhancement with intratumoral vessels and intratumoral vessels alone yielded sensitivity of 85% (average of both readers), specificity of 88%, and a PPV of 88% for HCC. For metastasis, a combination of peripheral ringlike enhancement with peritumoral vessels and peripheral ringlike enhancement with intratumoral vessels yielded sensitivity of 79%, specificity of 95%, and a PPV of 85%. For hemangiomas, a combination of peripheral nodular enhancement with peritumoral vessels and peripheral nodular enhancement without peritumoral vessels yielded sensitivity of 75%, specificity of 99%, and a PPV of 92%. Diffuse enhancement with spoked wheel arteries yielded sensitivity of 82%, specificity of 100%, and a PPV of 87% for FNHs. Good inter‐reader agreement was achieved. Conclusions. Sonazoid‐enhanced ultrasonography using intermittent imaging with a high MI can potentially be used for evaluating the enhancement patterns of focal liver tumors in the late phase.

Retrograde Transvenous Obliteration of Gastric Varices Associated with Large Collateral Veins or a Large Gastrorenal Shunt

Balloon-occluded retrograde transvenous obliteration of gastric varices by a microcatheter insertion method was performed in eight patients with large collateral veins or a large gastrorenal shunt. A 3-F microcatheter was selectively inserted into the gastric varices through a 6-F balloon catheter wedged in the left adrenal vein. Selective venography of the gastric varices and injection of the sclerosing agent, a mixture of 10% ethanolamine oleate and iopamidol, through the microcatheter system without occluding the collateral veins was accomplished in one treatment session in all patients. There have been no complications or recurrences of gastric varices in any of the patients during the follow-up period.