[A Case of Double Cancer of Intrahepatic Cholangiocarcinoma and Gastric Carcinoma with Difficult Diagnosis of the Primary Tumor with Peritoneal Metastasis].

Double cancer of intrahepatic cholangiocarcinoma and gastric cancer is rare. A 62-year-old man underwent gastrectomy for gastric cancer. The pathological findings were tub1>tub2, m, ly0, v0, n0, Stage I A. Two years and a month later, a liver tumor(diameter of 3 cm)and a pelvic mass(diameter of 2.5 cm)were observed. Metastasis from gastric cancer was suspected and chemotherapy(SOX)was administered. However, after 5 courses, CT revealed worseningof the liver tumor (diameter of 12 cm)and pelvic mass(diameter of 3 cm). Intrahepatic cholangiocarcinoma and its peritoneal metastasis were also suspected. There was a limit to treatment with chemotherapy, and it was difficult to judge whether to target gastric cancer or intrahepatic cholangiocarcinoma for chemotherapy. In addition, the lesions were localized in the right lobe of the liver and the pelvis. Therefore, we decided to perform resection. As a second-stage operation, pelvic mass extraction and portal vein embolization were performed first. The pathological result of the pelvic mass assessment was mucinous carcinoma. Subsequently, expansive right hepatectomy was performed. The pathological findings were also suggestive of mucinous carcinoma, which was finally diagnosed as intrahepatic cholangiocarcinoma and peritoneal dissemination. Six months after the surgery, several recurrent nodules were observed in the pelvis and GEM plus CDDP was initiated. Currently, 1 year after surgery, there are no restrictions in the activities of daily life of the patient and he is treated on an outpatient basis.

[Resection of Adrenal Metastasis after Chemotherapy and Radiation Therapy for a Patient with Stage IV B Hepatocellular Carcinoma].

In the treatment of hepatocellular carcinoma, atypical, off guideline multidisciplinary approaches are sometimes effective. A 70-year-old man was diagnosed with multiple hepatocellular carcinomas, multiple bone metastases, and a right adrenal metastasis. Sunitinib was started and the primary hepatic lesions and bone metastases disappeared. However, his adrenal metastasis worsened. Sorafenib, radiotherapy, and some investigational agents were administered, but the adrenal metastasis did not respond. There were no other new lesions except the adrenal lesion 4 years after the initial treatment, so we decided to perform a resection. In the left half lateral decubitus position, the adrenal mass was removed with right thoracolaparotomy. After the surgery, his tumor markers quickly returned to normal. Seven years after the initial treatment(2 years and 4 months after the last surgery), he is alive without any recurrence. Multidisciplinary treatment with chemotherapy, radiotherapy, and surgery may result in long term survival even for patients with advanced hepatocellular carcinoma with multiple extra-hepatic lesions.

[Long Term Survival in a Case of Hilar Cholangiocarcinoma Treated with Chemotherapy and Surgery].

A 67-year-old man with elevated hepatobiliary enzymes was referred to our hospital for further examination. Computed tomography indicated hilar cholangiocarcinoma of Bismuth type Ⅳ and revealed invasion of the right hepatic artery and the left portal vein. We diagnosed locally advanced unresectable hilar cholangiocarcinoma, and performed 5 courses of chemotherapy with gemcitabine plus S-1. After chemotherapy, the tumor was significantly reduced in size and vascular invasions were alleviated, so we decided to perform surgical resection. An extended left hepatectomy with caudate lobe and extrahepatic bile duct resection was performed. Although the intraoperative pathological examination was positive for cancer at the hepatic margins, we did not perform further bile duct resection because of the difficulty. After the surgery, we administered adjuvant chemotherapy with gemcitabine for 5 courses. Another 8 courses of gemcitabine plus S-1 therapy were given because of elevation of CA19-9. The tumor marker levels normalized, and the patient is still alive without findings of recurrence 4 years after the first treatment. Multidisciplinary treatment with chemotherapy and surgery may suggest the possibility of increasing long term survival even for patients with locally advanced unresectable cholangiocarcinoma.

Efficacy of sonazoid (perflubutane) for contrast-enhanced ultrasound in the differentiation of focal breast lesions: phase 3 multicenter clinical trial.

OBJECTIVE: The objective of our study was to compare the efficacy of contrast-enhanced ultrasound (CEUS) using the ultrasound contrast agent Sonazoid (perflubutane) with unenhanced ultrasound and supplementary contrast-enhanced MRI in the differential diagnosis (benign vs malignant) of focal breast lesions. The safety of Sonazoid was also assessed in this study. SUBJECTS AND METHODS: A total of 127 patients with focal breast lesions were enrolled in this study at five centers in Japan. Three reviewers who were blinded to the patient characteristics independently assessed the ultrasound images and MR images in a randomized sequence. The accuracy, sensitivity, and specificity of CEUS, unenhanced ultrasound, and supplementary contrast-enhanced MRI for the differential diagnosis were compared using generalized estimating equation analyses. Diagnostic confidence was also assessed. RESULTS: The accuracy of CEUS was significantly higher than that of unenhanced ultrasound (87.2% vs 65.5%, respectively; p < 0.001). In addition, CEUS showed significantly higher specificity, although the improvement in sensitivity was not statistically significant. The accuracy and specificity were significantly higher with CEUS than with contrast-enhanced MRI, but the improvement in sensitivity was not statistically significant. The area under the curve in a receiver operating characteristic analysis was significantly greater with CEUS than with unenhanced ultrasound. The incidence of adverse events was 11.4% and the incidence of adverse drug reactions was 3.3%. All adverse drug reactions were mild. CONCLUSION: CEUS using Sonazoid was confirmed to be superior to unenhanced ultrasound for the differential diagnosis (benign vs malignant) of focal breast lesions in terms of diagnostic accuracy with no serious adverse reactions.

Usefulness of contrast-enhanced ultrasonography for intracystic breast tumors: a report of three cases.

Cystic breast lesions are caused by a wide spectrum of breast diseases and can range from simple cysts to malignant tumors. Ultrasonography is a good tool for evaluation of the morphology and vascularity of cystic breast lesions. We report three patients in whom contrast-enhanced ultrasonography (CEUS) was used to evaluate intracystic tumors. One of the three patients was diagnosed with intracystic papilloma. Compared with conventional ultrasonography alone, CEUS more clearly demonstrated that the solid component within the mass was lobulated with a narrow base. The other two patients were diagnosed with intracystic papillary carcinoma, and CEUS clearly revealed the presence of widely elevated solid components within both masses, suggesting malignancy. Therefore, CEUS simplified morphological evaluation by enhancing the solid components within the cystic masses.

A case of reocclusion of the renal artery diagnosed by the color Doppler method with evaluation of blood flow direction in the collateral circulation of the kidney in addition to the non-detectable blood signal in the renal artery.

A 23-year-old woman was referred to our hospital for an interventional procedure for chronic total occlusion of the right renal artery, probably due to fibromuscular dysplasia (FMD), and for control of renal vascular hypertension. Before percutaneous transluminal renal angioplasty (PTRA), aortography revealed collateral circulation to the right kidney from the lower lumbar artery. After PTRA, however, blood flow in the renal side of the collateral circulation flowed outside from the right renal parenchyma. 4 months later, we could not find a blood flow signal in the right renal artery, and there was a contrary flow signal in the right kidney parenchyma continuously from the extrahilar vessel, possibly a collateral artery. These findings indicated reocclusion of the right artery. We confirmed reocclusion of the renal artery and collateral feeding by contrast dynamic computed tomography (CT), and PTRA was performed again without any complications or reocclusion for 5 months. This is the first case report showing that a back-flowing signal in the right renal parenchyma from the extrahilar artery is useful as an indirect finding suggesting reocclusion.

A case of focal nodular hyperplasia with a new characteristic finding on contrast-enhanced ultrasonography using Levovist.

We used contrast-enhanced ultrasound with Levovist, a microbubble contrast agent, to diagnose a case of hepatic focal nodular hyperplasia (FNH). A new characteristic finding of heartbeat-synchronized centrifugal enhancement was discovered. We call this enhancement pattern the "sonographic fireworks sign." It is expected to be useful for diagnosing FNH, especially when the lesions are small and it is difficult to depict a spoke-wheel pattern.

Informatics in radiology: Intuitive user interface for 3D image manipulation using augmented reality and a smartphone as a remote control.

Although widely used as a pointing device on personal computers (PCs), the mouse was originally designed for control of two-dimensional (2D) cursor movement and is not suited to complex three-dimensional (3D) image manipulation. Augmented reality (AR) is a field of computer science that involves combining the physical world and an interactive 3D virtual world; it represents a new 3D user interface (UI) paradigm. A system for 3D and four-dimensional (4D) image manipulation has been developed that uses optical tracking AR integrated with a smartphone remote control. The smartphone is placed in a hard case (jacket) with a 2D printed fiducial marker for AR on the back. It is connected to a conventional PC with an embedded Web camera by means of WiFi. The touch screen UI of the smartphone is then used as a remote control for 3D and 4D image manipulation. Using this system, the radiologist can easily manipulate 3D and 4D images from computed tomography and magnetic resonance imaging in an AR environment with high-quality image resolution. Pilot assessment of this system suggests that radiologists will be able to manipulate 3D and 4D images in the reading room in the near future. Supplemental material available at http://radiographics.rsna.org/lookup/suppl/doi:10.1148/rg.324115086/-/DC1.

Phase II clinical study of DD-723 (perflubutane): dose-response study in patients with breast tumors.

PURPOSE: We compared the contrast effect of three doses of DD-723 in subjects with breast tumors to determine the recommended dose. We then evaluated differential diagnosis results using plain ultrasonography, contrast-enhanced ultrasonography (plain + enhanced), and contrast-enhanced magnetic resonance imaging (MRI) compared to the pathological diagnosis. METHODS: To evaluate the contrast effect, contrast-enhanced ultrasonic images were independently evaluated in a randomized sequence by three blinded reviewers trained in the evaluation method beforehand. Multiple evaluation results from the three reviewers were used to assess the overall contrast effect. The differential diagnosis was evaluated independently by three blinded reviewers using contrast-enhanced ultrasonic images and contrast-enhanced magnetic resonance images in a randomized sequence; reviewers were also blinded to subject characteristics. Multiple evaluation results from the three reviewers were used to assess the overall differential diagnosis. RESULTS: The recommended dose of DD-723 is an intermediate dose of 0.12 µL MB/kg. Accuracy, sensitivity, and specificity were improved more in the differential diagnosis by contrast-enhanced ultrasonography than in plain ultrasonography. Accuracy and specificity were better and sensitivity similar compared to contrast-enhanced MRI. CONCLUSIONS: An intermediate dose showed the highest efficacy in terms of overall contrast effect. Contrast-enhanced ultrasonography is safe and useful when used in differential diagnosis.

Clinical significance of serum levels of vascular endothelial growth factor, angiopoietin-1, and angiopoietin-2 in patients with rheumatoid arthritis.

OBJECTIVE: To evaluate the clinical significance of serum levels of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), and angiopoietin-2 (Ang-2) in patients with rheumatoid arthritis (RA). METHODS: The subjects were 70 patients with RA. Serum VEGF, Ang-1, and Ang-2 levels were determined by ELISA. As indices of disease activity, serum levels of C-reactive protein (CRP) and matrix metalloprotease (MMP)-3 were examined, and the 28-joint count Disease Activity Score (DAS28)-CRP was calculated. Power Doppler ultrasonography was performed in the bilateral wrists, elbows, shoulders, knees and ankles. The synovial blood flow signals were scored using a 3-grade scale (0-2), and the total of the scores in the 10 joints was regarded as the total signal score (TSS). RESULTS: Serum VEGF level showed significant correlations with serum CRP and MMP-3 levels, DAS28-CRP, and TSS. Serum Ang-1 level showed significant correlations with serum MMP-3 level and DAS28-CRP. Serum Ang-2 level showed significant correlations with serum CRP level and TSS. CONCLUSION: The serum VEGF level is important as an index of the activity of RA based on angiogenesis and a prognostic factor regarding joint destruction. Serum Ang-1 level may be useful as an index of sustained arthritis based on the maintenance of newly formed vessels. Serum Ang-2 level may reflect a state of marked angiogenesis.

Sonographic hemodynamic evaluation of spleno-renal shunt using the Valsalva maneuver.

PURPOSE: The purpose of this study was to assess the characteristic features of hemodynamic changes in portal venous hypertension with spleno-renal shunt on conventional B-mode and color Doppler imaging before and after the Valsalva maneuver. MATERIALS AND METHODS: A total of 11 patients with portal venous hypertension underwent conventional B-mode and color Doppler ultrasound during follow-up examinations. Sonographic imaging of the splenic vein and the left renal vein was performed before and after the Valsalva maneuver. RESULTS: In the six patients with spleno-renal shunt formation, dilated left renal veins were depicted after the Valsalva maneuver. In the five patients without spleno-renal shunt, there was no apparent dilatation of the left renal vein either before or after the Valsalva maneuver. In all six patients with spleno-renal shunt, color flow mapping of the left renal veins was emphasized during the Valsalva maneuver. In the five patients without spleno-renal shunt formation, there were no apparent changes on color flow mapping of the left renal vein before or after the Valsalva maneuver. CONCLUSION: The sonographic findings of the splenic vein and the left renal vein on conventional B-mode and color Doppler imaging before and after the Valsalva maneuver are useful for diagnosis of spleno-renal shunt and for grading the hemodynamic changes caused by spleno-renal shunt.

Correlation between synovial blood flow signals and serum vascular endothelial growth factor levels in patients with refractory rheumatoid arthritis.

The objective of the study is to examine the relationship between synovial blood flow signals and vascular endothelial growth factor (VEGF) involved in angiogenesis by Doppler ultrasound. Twenty-one patients meeting the diagnostic criteria of the American College of Rheumatology (ACR) were enrolled in this study. Doppler ultrasound signals of blood flow in the wrist synovial membrane were measured and classified into three grades: grade 1 = no flow; grade 2 = mild flow; grade 3 = intense flow. A significant correlation was observed between blood flow signals in the wrist synovial membrane and serum VEGF levels (r = 0.5681, P = 0.0072). These results suggest that the measurement of Doppler ultrasound signals of blood flow in the wrist synovial membrane is useful in the evaluation of angiogenesis.

[Clinical usefulness of B-flow imaging in the diagnosis of superficial soft tissue tumors].

B-flow imaging is a recently developed ultrasound technique that extends the B-mode imaging quality of blood flow, including high-frame-rate and high-spatial-resolution imaging. The purpose of the present study was to clarify the usefulness of B-flow for evaluation of the hemodynamics of superficial soft tissue tumors. All 33 cases of superficial soft tissue tumors were examined by both B-flow and Color/Power Doppler methods on the same plane. The B-flow images that were obtained were evaluated by comparison with corresponding Color/Power Doppler images. The following four items were compared and evaluated: (1) sensitivity to the detection of tumor vessels; (2) quality of background B-mode imaging; (3) frame rate; and (4) spatial resolution of tumor vessels. B-flow was somewhat inferior to Color/Power Doppler imaging in sensitivity to the detection of tumor vessels. B-flow was clearly inferior in the quality of background B-mode imaging. B-flow provided high-frame-rate imaging. The diameter of tumor vessels on B-flow imaging was clearly thinner than that on Color/Power Doppler images and appeared to indicate the true diameter of tumor vessels. By providing high-frame-rate imaging and high spatial resolution, B-flow makes it possible to clarify the precise vascular structure.

Distinct diagnostic criteria for ultrasonographic examination of papillary thyroid carcinoma: a multicenter study.

Recent advances permitting high-resolution ultrasonography have made ultrasonographic examination of nodular thyroid diseases an accessible examination for routine practice. However, diagnostic criteria for ultrasonographic examination of thyroid nodules are not surely established. To identify the optimal strategy for well standardized differential diagnosis of papillary thyroid carcinoma and benign nodules, we evaluated the significance of individual ultrasonographic characteristics of thyroid nodules in a multicenter study. Ten characteristics in ultrasonograms from 53 patients scored by 17 investigators from 15 centers were analyzed by t tests and logistic regression analyses. Between benign and papillary thyroid cancer groups, all characteristics but not size or multiplicity of strong echoes, which suggest calcifications, were significant parameters. Logistic regression analyses showed that border character, shape, and internal echo level are highly significant parameters (p < 0.0005). A multiple logistic regression showed to be the most important predictors of pathologic diagnosis. The diagnostic criterion with border character and internal echo level yielded 93% sensitivity and 92% specificity. In conclusion, univariate and multivariate analyses identified border character, shape, internal echo level, but not strong echoes (calcifications), as important characteristics in differentiating papillary thyroid carcinoma from benign nodules. These results will contribute to standardization of accurate ultrasonographic diagnosis of papillary thyroid carcinoma.

[A clinical scoring system may identify good candidates for hepatic arterial infusion chemotherapy after hepatic resection for colorectal cancer].

The significance of hepatic arterial infusion chemotherapy (HAI) for the prognosis of metastatic colorectal cancer is controversial. We applied a clinical scoring system to find good candidates for HAI after hepatic resection. Ninety-four consecutive cases of hepatic metastases resected at a single institute were analyzed retrospectively. The cases were divided into 4 subgroups: those with a low risk score (0-2 points) with and without HAI and those with a high risk score (3-5 points) with and without HAI. The number of cases and the cumulative 5 year survival rate of each case were as follows: low risk score with HAI (n = 17) 64.1%, low risk score without HAI (n = 25) 27.4%, high risk score with HAI (n = 28) 16.9%, and high risk score without HAI (n = 24) 14.7%, respectively. These results suggest that hepatic resection with HAI seemed to contribute to the outcome for selected cases. The clinical scoring system may identify good candidates for HAI as well as predict recurrence after hepatic resection for metastatic colorectal cancer.