Naoki Hirokawa

Solitary cystic tumor of the pancreas: EUS-pathologic correlation

BACKGROUND It is clinically important to distinguish neoplastic from non-neoplastic pancreatic cysts. METHODS Retrospective correlations were made between pathologic and EUS data from 52 pancreatic solitary cystic tumors: mucinous cystadenoma (10), mucinous cystadenocarcinoma (7), serous cystadenoma (5), ductectatic mucinous cystic tumor (10), solid and papillary epithelial neoplasm (5), and non-neoplastic cyst (15). The mean tumor size was 3.5 cm (range, 1.2 cm to 6.0 cm). RESULTS Six classifications of the internal structures of these cysts were developed: thick wall type, tumor protruding type, thick septal type, microcystic type, thin septal type, and simple type. Although all neoplastic cysts belonged to the first four types, all non-neoplastic cysts belonged to the last two types. The accuracy of EUS for differentiating tumors was estimated at 96% and 92%, respectively, by two observers. CONCLUSIONS EUS may become a mandatory modality for differentiating pancreatic solitary cystic tumors and choosing an optimal treatment.

Congenital Arteriovenous Malformation of the Pancreas : Its Diagnostic Features on Images

To analyze diagnostic features on images of congenital arteriovenous malformation (AVM) of the pancreas, we analyzed the diagnostic findings in six patients with the disease, using gray-scale ultrasonography (US), color Doppler US, computed tomography, and angiography and analyzed previously reported cases. AVM characteristic findings on images were multiple, small hypoechoic nodules on US, mosaic appearance of the lesion and pulsatile wave form in the portal vein on color Doppler US, conglomerated small nodular enhancement of the lesion and early appearance of the portal vein on CT, and a racemose network and early appearance of the portal vein on angiography. Five of the six patients underwent surgery, and all resected specimens were histologically found to be AVMs of the pancreas; however, one with developed portal hypertension at surgery died of repeated bleeding from esophageal varices. From analysis of total of 35 cases including our six cases, a mosaic appearance of the lesion was found in 100% and a pulsatile wave form in the portal vein in 77.8% on color Doppler US. Color Doppler US is noninvasive and useful for detecting congenital AVM of the pancreas at an early stage, preventing the portal hypertension causing esophageal varices and their rupture.

Efficacy of SPIO-MR imaging in the diagnosis of liver metastases from colorectal carcinomas.

Aim: To determine whether superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI) could replace intravenous contrast-enhanced spiral CT (iv-CT) and spiral CT during arterial portography (CTAP) combined with spiral CT hepatic angiography (CTHA) in the diagnosis of liver metastases from colorectal carcinomas. Methods: Twenty-six adult patients with liver metastases were studied preoperatively by means of iv-CT, CTAP/CTHA, and SPIO-MRI. Preoperative diagnoses using iv-CT, CTAP/CTHA, and SPIO-MRI were compared with intraoperative and pathological findings in resected specimens. The gold standard for the lesions that were resected was histological examination. Intraoperative findings represented the gold standard for lesions that were not resected. Results: Twenty-six patients were found to have a total number of 43 liver metastases. The sensitivities of iv-CT, CTAP/CTHA, and SPIO-MRI were 74.4, 100, and 90.7%, respectively. SPIO-MRI was significantly superior to iv-CT (p < 0.05). The positive predictive values of iv-CT, CTAP/CTHA, and SPIO-MRI were 97.0, 91.5, and 100%, respectively. CTAP/CTHA yielded four false-positive lesions. In contrast, we detected no false-positive findings using SPIO-MRI. Conclusions: These results suggest that SPIO-MRI might not completely replace CTAP/CTHA, but could replace iv-CT in the diagnosis of liver metastases from colorectal carcinomas. It is thought that SPIO-MRI is a promising imaging modality for diagnosing liver metastases in patients with colorectal carcinoma because of its relatively high sensitivity and extremely high specificity.

Renal Artery Aneurysm: Evaluation with Color Doppler Ultrasonography Before and After Percutaneous Transarterial Embolization

Renal artery aneurysms account for 22% of all visceral aneurysms.1 The prevalence of renal artery aneurysms in the general population is reported to vary between 0.01% and 1.0%2; however, this prevalence has recently increased because of the greater detection of these aneurysms made possible by advances in ultrasonography, CT, and MR imaging. The most serious complication of renal artery aneurysms is their rupture, which is followed by sudden death.3 The likelihood of rupture seems to increase as the diameter of the aneurysm exceeds 1 cm.2,3 Although surgical treatment had been common for these aneurysms (i.e., total renal resection), a percutaneous embolization technique has also recently been performed with success.4 This technique is less invasive than surgical resection for patients with renal artery aneurysms and sometimes preserves renal function. We report a case of a renal artery aneurysm 4 cm in diameter treated with percutaneous transcatheter embolization whose therapeutic effect was better evaluated by color Doppler ultrasonography than CT and MR imaging.

Pancreas: imaging diagnosis with color/power Doppler ultrasonography, endoscopic ultrasonography, and intraductal ultrasonography

Recent advances of ultrasound imaging have made possible to depict various diseases and conditions of the pancreas. Color/power Doppler ultrasonography, endoscopic ultrasonography, and intraductal ultrasonography are feasible to show vascular abnormalities, differentiate the solid and cystic tumors, decide tumor extent, and help to perform interventional treatments of the pancreatic diseases. Those techniques will contribute to the more precise and easier diagnosis and to prompt decision of the treatments of the pancreatic disorders. Radiologists should recognize the diagnostic feasibility and limitations of those techniques in order to avoid unnecessary examinations on the patients, and obtain precise diagnostic images.

Results and DVH analysis of late rectal bleeding in patients treated with 3D-CRT or IMRT for localized prostate cancer

In patients undergoing radiotherapy for localized prostate cancer, dose–volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose–volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9–53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0–1 and Grades 2–3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session.

Delayed Visceral Bleeding from Liver Injury After Cardiopulmonary Resuscitation

BACKGROUND Visceral injury is a life-threatening complication of cardiopulmonary resuscitation (CPR); however, the clinical significance has been masked by the lethal outcome of out-of-hospital cardiac arrest (OHCA). OBJECTIVE The objective is to share our experience of successful treatment of OHCA patients with serious, CPR-related visceral complications. CASE REPORTS We report two cases of cardiac-origin OHCA with liver injury exacerbated by heparinization during mechanical circulatory support. Although both patients presented with delayed massive liver bleeding (intrahepatic or peritoneal) that compromised hemodynamic status, one patient was successfully treated by selective transcatheter arterial embolization and the other by a surgical procedure. CONCLUSION Preventive measures such as careful CPR, as well as interventional or surgical repair after the early diagnosis of visceral injury, are required to improve the outcome in some cases of OHCA.

Does contrast-enhanced ultrasound reveal tumor angiogenesis in pancreatic ductal carcinoma? A prospective study.

The purpose of this study is to evaluate tumor vascularity of pancreatic carcinoma noninvasively by contrast-enhanced ultrasound (US) and clarify the diagnostic value of tumor vascularity in subjects with nonresectable advanced pancreatic carcinoma. The study was approved by our institutional review board and written informed consent was obtained from all subjects. Twenty-seven subjects with advanced pancreatic ductal carcinoma were treated by chemoradiotherapy. Contrast-enhanced US, US guided biopsies and dynamic computed tomography (CT) were performed before and after the therapy. We assigned the intratumoral enhancement pattern of US as an enhanced ultrasound (EU) score, from 1 to 4, according to the degree of enhancement area. Intratumoral microvessel density (IMD) and average vessel diameter (AVD) were calculated by means of CD 34 immunostaining. Vascular endothelial growth factor (VEGF) staining was graded on a scale of 1 to 3. EU scores before chemoradiotherapy were compared with IMD, AVD, VEGF, histological grading and hepatic metastasis. After the therapy, local treatment response was evaluated by dynamic CT calculating the maximum area of the tumor, by comparing it with its size in pre- therapy. Subjects who had at least a 50% or more decrease of tumor size lasting more than 4 wk were estimated as partial response (PR), more than a 50% of increase progressive disease (PD) and if neither PR nor PD criteria were met, they were classified as stabled disease (SD). Next, EU scores were compared with IMD, AVD, VEGF and treatment response. Statistically significant differences were evaluated by Pearsons correlation, post-hoc, Spearmans rank correlation, Wilcoxon rank sum and Students t-test. A p < 0.05 was defined as being statistically significant. Before the therapy, the EU score and IMD were significantly correlated (r = 0.50, p < 0.02), as was VEGF (r = 0.45, p < 0.05). The EU score and AVD were negatively correlated (r = - 0.56, p < 0.02). Significant correlation was found between the EU score and histological grading (p < 0.004). The EU score was higher in subjects who had hepatic metastasis compared with subjects who had no hepatic metastasis (p < 0.05). After chemoradiotherapy, 14 subjects exhibited PR, while 13 showed SD. None of the subjects showed PD. The EU score was smaller in PR than SD (p < 0.05). The EU score significantly decreased after the therapy in PR (p < 0.01) but not in SD. IMD and AVD did not significantly decrease in either PR or SD; however, VEGF decreased significantly in PR (p < 0.01) but not in SD. Contrast-enhanced US could reveal tumor vascularity of pancreatic ductal carcinoma and could be potentially useful to evaluate treatment effect of subjects who receive chemoradiotherapy. Further investigation will be needed to prove the usefulness of contrast-enhanced US.

Relation between Ku80 and microRNA-99a expression and late rectal bleeding after radiotherapy for prostate cancer

BACKGROUND AND PURPOSE Late rectal bleeding is one of the severe adverse events after radiotherapy for prostate cancer. New biomarkers are needed to allow a personalized treatment. MATERIALS AND METHODS Four patients each with grade 0-1 or grade 2-3 rectal bleeding were randomly selected for miRNA array to examine miRNA expression in peripheral blood lymphocytes (PBLs). Based on results of miRNA array, 1 of 348 miRNAs was selected for microRNA assays. Then, expression of DNA-dependent protein kinase mRNA and miR-99a was analyzed in the PBLs of 97 patients. PBLs were exposed to 4Gy of X-ray ex-vivo. RESULTS In the discovery cohort, grade 2-3 rectal bleeding was significantly higher in the Ku80 <1.09 expression group compared with ⩾1.09 group (P=0.011). In radiation-induced expression of miR-99a, grade 2-3 rectal bleeding was significantly higher in the miR-99a IR(+)/IR(-) >0.93 group compared with ⩽0.93 group (P=0.013). Most patients with grade 2-3 rectal bleeding were in the group with low Ku80 and high miR-99a expression. In the validation cohort, similar results were obtained. CONCLUSION A combination of low Ku80 expression and highly-induced miR-99a expression could be a promising marker for predicting rectal bleeding after radiotherapy.

Concurrent Radiotherapy and Gemcitabine for Unresectable Pancreatic Adenocarcinoma: Impact of Adjuvant Chemotherapy on Survival

PURPOSE To retrospectively analyze results of concurrent chemoradiotherapy (CCRT) using gemcitabine (GEM) for unresectable pancreatic adenocarcinoma. METHODS AND MATERIALS Records of 108 patients treated with concurrent external beam radiotherapy (EBRT) and GEM were reviewed. The median dose of EBRT in all 108 patients was 50.4 Gy (range, 3.6-60.8 Gy), usually administered in conventional fractionations (1.8-2 Gy/day). During radiotherapy, most patients received GEM at a dosage of 250 to 350 mg/m(2) intravenously weekly for approximately 6 weeks. After CCRT, 59 patients (54.6%) were treated with adjuvant chemotherapy (AC), mainly with GEM. The median follow-up for all 108 patients was 11.0 months (range, 0.4-37.9 months). RESULTS Initial responses after CCRT for 85 patients were partial response: 26 patients, no change: 51 patients and progressive disease: 8 patients. Local progression was observed in 35 patients (32.4%), and the 2-year local control (LC) rate in all patients was 41.9%. Patients treated with total doses of 50 Gy or more had significantly more favorable LC rates (2-year LC rate, 42.9%) than patients treated with total doses of less than 50 Gy (2-year LC rate, 29.6%). Regional lymph node recurrence was found in only 1 patient, and none of the 57 patients with clinical N0 disease had regional lymph node recurrence. The 2-year overall survival (OS) rate and the median survival time in all patients were 23.5% and 11.6 months, respectively. Patients treated with AC had significantly more favorable OS rates (2-year OS, 31.8%) than those treated without AC (2-year OS, 12.4%; p < 0.0001). On multivariate analysis, AC use and clinical T stage were significant prognostic factors for OS. CONCLUSIONS CCRT using GEM yields a relatively favorable LC rate for unresectable pancreatic adenocarcinoma, and CCRT with AC conferred a survival benefit compared to CCRT without AC.