Removal of phosphoglycolate in hyperthermophilic archaea.

Many organisms that utilize the Calvin-Benson-Bassham (CBB) cycle for autotrophic growth harbor metabolic pathways to remove and/or salvage 2-phosphoglycolate, the product of the oxygenase activity of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). It has been presumed that the occurrence of 2-phosphoglycolate salvage is linked to the CBB cycle, and in particular, the C2 pathway to the CBB cycle and oxygenic photosynthesis. Here, we examined 2-phosphoglycolate salvage in the hyperthermophilic archaeon Thermococcus kodakarensis, an obligate anaerobe that harbors a Rubisco that functions in the pentose bisphosphate pathway. T. kodakarensis harbors enzymes that have the potential to convert 2-phosphoglycolate to glycine and serine, and their genes were identified by biochemical and/or genetic analyses. 2-phosphoglycolate phosphatase activity increased 1.6-fold when cells were grown under microaerobic conditions compared to anaerobic conditions. Among two candidates, TK1734 encoded a phosphatase specific for 2-phosphoglycolate, and the enzyme was responsible for 80% of the 2-phosphoglycolate phosphatase activity in T. kodakarensis cells. The TK1734 disruption strain displayed growth impairment under microaerobic conditions, which was relieved upon addition of sodium sulfide. In addition, glycolate was detected in the medium when T. kodakarensis was grown under microaerobic conditions. The results suggest that T. kodakarensis removes 2-phosphoglycolate via a phosphatase reaction followed by secretion of glycolate to the medium. As the Rubisco in T. kodakarensis functions in the pentose bisphosphate pathway and not in the CBB cycle, mechanisms to remove 2-phosphoglycolate in this archaeon emerged independent of the CBB cycle.

[Advanced Bladder Cancer with Multiple Pulmonary Metastases Treated with Paclitaxel/Ifosfamide/Nedaplatin Therapy : Two Case Reports].

The standard treatment for advanced urothelial carcinoma includes platinum-based chemotherapy and programmed cell death protein 1 or programmed death ligand 1 inhibitors. However, urothelial carcinomas are often associated with both intrinsic and acquired resistance to these treatments. Paclitaxel, ifosfamide, and nedaplatin (TIN) chemotherapy has been proven to be effective as the second- or third-line treatment for platinum-resistant advanced urothelial cancer. Herein, we report two cases of patients with advanced bladder cancer resistant to platinum-based chemotherapy or pembrolizumab, who were treated with TIN chemotherapy. The first case was in a 66-year-old woman treated with gemcitabine and cisplatin (GC) chemotherapy followed by gemcitabine, paclitaxel, and cisplatin chemotherapy for multiple pulmonary metastases after radical cystectomy. Following reduction in pulmonary metastases after six courses of TIN treatment, metastasectomy and two courses of adjuvant TIN treatment were administered, with no recurrence for eight years. The other case was in a 70-year-old man treated with GC chemotherapy and pembrolizumab for invasive bladder cancer and multiple pulmonary metastases. We treated this patient with salvage pelvic exenteration. Pulmonary metastases significantly decreased after six courses of TIN chemotherapy. After a partial response for seven months; the patient died due to a novel cerebellar metastasis after six courses of TIN chemotherapy. Thus, we conclude that TIN chemotherapy can be considered as a third line treatment for advanced urothelial cancer resistant to platinum-based chemotherapy and pembrolizumab.

Hepatic Stellate Cells in Hepatocellular Carcinoma Promote Tumor Growth Via Growth Differentiation Factor 15 Production.

BACKGROUND & AIMS: Although the tumor microenvironment plays an important role in tumor growth, it is not fully understood what role hepatic stellate cells (HSCs) play in the hepatocellular carcinoma (HCC) microenvironment. METHODS: A high-fat diet after streptozotocin was administered to HSC-specific Atg7-deficient (GFAP-Atg7 knockout [KO]) or growth differentiation factor 15 (GDF15)-deficient (GFAP-GDF15KO) mice. LX-2 cells, a human HSC cell line, were cultured with human hepatoma cells. RESULTS: In the steatohepatitis-based tumorigenesis model, GFAP-Atg7KO mice formed fewer and smaller liver tumors than their wild-type littermates. Mixed culture of LX-2 cells and hepatoma cells promoted LX-2 cell autophagy and hepatoma cell proliferation, which were attenuated by Atg7 KO in LX-2 cells. Hepatoma cell xenograft tumors grew rapidly in the presence of LX-2 cells, but Atg7 KO in LX-2 cells abolished this growth. RNA-sequencing revealed that LX-2 cells cultured with HepG2 cells highly expressed GDF15, which was abolished by Atg7 KO in LX-2 cells. GDF15 KO LX-2 cells did not show a growth-promoting effect on hepatoma cells either in vitro or in the xenograft model. GDF15 deficiency in HSCs reduced liver tumor size caused by the steatohepatitis-based tumorigenesis model. GDF15 was highly expressed and GDF15-positive nonparenchymal cells were more abundant in human HCC compared with noncancerous parts. Single-cell RNA sequencing showed that GDF15-positive rates in HSCs were higher in HCC than in background liver. Serum GDF15 levels were high in HCC patients and increased with tumor progression. CONCLUSIONS: In the HCC microenvironment, an increase of HSCs that produces GDF15 in an autophagy-dependent manner may be involved in tumor progression.

Quantification of Regional Cerebral Blood Flow Using Diffusion Imaging With Phase Contrast.

BACKGROUND: The perfusion-related diffusion coefficient obtained from triexponential diffusion analysis is closely correlated with regional cerebral blood flow (rCBF), as assessed by arterial spin labeling (ASL) methods. However, this provides only a semiquantitative measure of rCBF, thereby making absolute rCBF quantification challenging. PURPOSE: To obtain rCBF in a noninvasive manner using a novel diffusion imaging method with phase contrast (DPC), in which the total CBF from phase-contrast (PC) MRI was utilized to convert perfusion-related diffusion coefficients to rCBF values. STUDY TYPE: Prospective. SUBJECTS: Eleven healthy volunteers (nine men and two women; mean age, 23.9 years) participated in this study. FIELD STRENGTH/SEQUENCE: A 3.0 T, single-shot diffusion echo-planar imaging with multiple b-values (0-3000 s/mm2 ), PC-MRI, pulsed continuous ASL, and 3D T1 -weighted fast field echo. ASSESSMENT: rCBF and its correlations in the gray matter (GM) and white matter (WM) were compared between DPC and ASL methods. rCBF in the GM and WM and the GM/WM ratio were compared with the literature values obtained using [15 O]-water positron emission tomography (15 O-H2 O PET). STATISTICAL TESTS: Spearman's correlation coefficient and Wilcoxon signed-rank test were used. Significance was set at P < 0.05. RESULTS: A significant positive correlation between DPC and ASL in terms of rCBF was observed in GM (R = 0.9), whereas the correlation between the two methods was poor in WM (R = 0.09). The rCBF in GM and WM and the GM/WM ratio obtained using DPC were consistent with the literature values assessed using 15 O-H2 O PET. The rCBF value obtained using DPC was significantly higher in the GM and WM than that using ASL. DATA CONCLUSION: DPC enabled noninvasive quantification of rCBF. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Cotreatment with lenvatinib and warfarin potassium caused prothrombin time prolongation.

Lenvatinib is approved as a standard systemic therapy for unresectable hepatocellular carcinoma (HCC) patients; however, experience with lenvatinib in clinical practice is insufficient. We present the case of a patient with advanced HCC whose prothrombin time - international normalized ratio (PT-INR) was elevated after cotreatment with lenvatinib and warfarin potassium. The patient was a 26-year-old man with congenital abnormalities who had to take warfarin potassium because he had a mechanical heart valve. He was diagnosed with unresectable HCC at 24 years old and was treated by transcatheter arterial chemoembolization and transcatheter arterial infusion. After some interventional radiology treatments, lenvatinib was started. After 4 days of treatment with lenvatinib and warfarin potassium, his PT-INR increased to 4.13, and the treatment had to be stopped. No changes were observed in other Child-Pugh score factors. The elevation in the PT-INR after cotreatment with lenvatinib and warfarin potassium was thought to be caused by pharmacological effects of concurrent use or pharmacological sensitivity to warfarin potassium in this patient with liver dysfunction. The PT-INR must be monitored when lenvatinib is given to advanced HCC patients taking warfarin potassium.

Autophagy impairment in pancreatic acinar cells causes zymogen granule accumulation and pancreatitis.

Basal autophagy degrades many kinds of proteins and organelles to maintain quality and plays important roles in cellular homeostasis. However, the impact of basal autophagy on zymogen granules in pancreatic acinar cells is unknown. In the present study, we examined the influence of autophagy impairment in acinar cells on zymogen granules and homeostasis of the pancreas, using mice with pancreas-specific autophagy impairment (Pdx1-Cre+/-Atg7fl/fl mice). The number of zymogen granules in acinar cells from these mice did not differ from that in acinar cells from their wild-type littermates at 3 weeks of age. However, the number of zymogen granules in acinar cells drastically increased at 4 weeks of age in mice with pancreas-specific autophagy impairment. In addition to the increased number of zymogen granules, serum lipase was elevated, and the pancreas became oedematous at 4 weeks of age, suggesting pancreatitis. After 5 weeks of age, acinar cell death was accelerated, and several histological features of chronic pancreatitis were observed, including glandular atrophy and pseudotubular complexes with fibrotic changes. In conclusion, the impairment of pancreas-specific basal autophagy caused spontaneous zymogen granule accumulation in acinar cells and pancreatitis, which eventually led to chronic pancreatitis.

[An Increase in Cases of Bladder Tamponade Due to Cystitis Among Elderly Women and Clinical Background Factors].

Bladder tamponade is thought to be caused mainly by bladder cancer or radiation cystitis. However, in women, it may often be caused by cystitis in clinical settings. This has not been noted in previous reports of bladder tamponade in Japan. Thus, we retrospectively analyzed the clinical features of 83 male and 41 female patients with bladder tamponade. Seventy-four patients were treated at Nishi-Kobe Medical Center between April 2005 and March 2015, and 50 were treated at Shizuoka City Shizuoka Hospital between November 2008 and March 2015. The patients'median age was 80 years. The cause of bladder tamponade was urological malignancies in 33 of the 83 male patients (40%), benign prostatic hyperplasia in 20 of the 83 male patients (24%), and cystitis in 33 of the 41 female patients (80%). Compared with the men, the women with bladder tamponade were significantly older and the proportion of patients with cerebrovascular disease, diabetes, and dementia was higher. In addition, more women were nursing home residents, with a higher rate of voiding with diapers and antithrombotic use than men. Causative strains of cystitis were diverse, and some were antibiotic resistant. Most of the cases of bladder tamponade in the women occurred in the elderly and were caused by cystitis. In an aging society, increases in the incidences of chronic, complicated cystitis due to impaired independent micturition, dysuria, and systemic diseases such as diabetes, and increased use of antithrombotic drugs may contribute to bladder tamponade in women.

[A Case of ACD-Associated RCC with Lymph Node Metastasis and Contralateral Renal Carcinoma after Nephrectomy].

A 59-year-old man who had undergone hemodialysis for 13 years was diagnosed with left renal cell carcinoma (RCC),cT1aN0M0,in 2010. He had a laparoscopic left nephrectomy,and the pathological diagnosis at that time was clear cell carcinoma,pT1a (multifocal). At 1 year after surgery,he was diagnosed with a left renal hilar lymph node metastasis and a new right RCC,cT1aN0M0. Consequently,he underwent a right nephrectomy and retroperitoneal lymph node dissection in 2012. Pathologic diagnosis by the current classification of the right renal tumor was acquired cystic disease-associated renal cell carcinoma (ACD-associated RCC),and that of the left hilar lymph node was metastatic RCC with sarcomatoid change. According to the revised classification the pathological diagnosis of the left renal tumor was ACD-associated RCC. There has been no evidence of recurrence or metastasis for 3 years after the second operation. The specific classification of dialysis-related renal tumors and their characteristics should be standard knowledge for urologists.

Decreased expression of lysophosphatidylcholine (16:0/OH) in high resolution imaging mass spectrometry independently predicts biochemical recurrence after surgical treatment for prostate cancer.

BACKGROUND: Human prostate cancers are highly heterogeneous, indicating a need for various novel biomarkers to predict their prognosis. Lipid metabolism affects numerous cellular processes, including cell growth, proliferation, differentiation, and motility. Direct profiling of lipids in tissue using high-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS) may provide molecular details that supplement tissue morphology. METHODS: Prostate tissue samples were obtained from 31 patients, with localized prostate cancer who underwent radical prostatectomy. The samples were assessed by HR-MALDI-IMS in positive mode, with the molecules identified by tandem mass spectrometry (MS/MS). The effect of identified molecules on prostate specific antigen recurrence free survival after radical prostatectomy was determined by Cox regression analysis and by the Kaplan-Meier method. RESULTS: Thirteen molecules were found to be highly expressed in prostate tissue, with five being significantly lower in cancer tissue than in benign epithelium. MS/MS showed that these molecules were [lysophosphatidylcholine (LPC)(16:0/OH)+H](+), [LPC(16:0/OH)+Na](+), [LPC(16:0/OH)+K](+), [LPC(16:0/OH)+matrix+H](+), and [sphingomyelin (SM)(d18:1/16:0)+H](+). Reduced expression of LPC(16:0/OH) in cancer tissue was an independent predictor of biochemical recurrence after radical prostatectomy. CONCLUSIONS: HR-MALDI-IMS showed that the expression of LPC(16:0/OH) and SM(d18:1/16:0) was lower in prostate cancer than in benign prostate epithelium. These differences in expression of phospholipids may predict prostate cancer aggressiveness, and provide new insights into lipid metabolism in prostate cancer.

Synthetic lethal interaction of combined CD26 and Bcl-xL inhibition is a powerful anticancer therapy against hepatocellular carcinoma.

AIM: CD26 is a membrane glycoprotein that has multiple functions, including dipeptidyl peptidase IV activity. CD26 expression varies in different tumor types, and its role in tumor growth in hepatocellular carcinoma (HCC) remains unclear. METHODS: CD26 expression levels were examined in resected HCC and surrounding non-cancerous lesions. The effect of CD26 knockdown on the cellular proliferation of HepG2 or Huh7 cells, both of which highly express CD26, was studied in vitro. RESULTS: CD26 mRNA expression levels were significantly increased in HCC compared with their surrounding non-cancerous lesions. We confirmed that various HCC cell lines, especially HepG2 and Huh7 cells, showed high expression levels of CD26. siRNA-mediated knockdown of CD26 suppressed hepatoma cell growth in vitro. CD26 knockdown induced cell cycle arrest through the upregulation of Cip/Kip family proteins, p21 in HepG2 cells and p27 in Huh7 cells. CD26 knockdown did not affect apoptosis, but it increased expressions of the pro-apoptotic proteins Bim and Bak and the anti-apoptotic protein Bcl-xL, suggesting an addiction of CD26 knockdown cells to Bcl-xL for survival. We thus treated CD26 knockdown cells with ABT-737, a Bcl-xL/-2/-w inhibitor, and observed that the synthetic lethal interaction of combined Bcl-xL and CD26 inhibition induced significant apoptosis and impaired cellular viability. CONCLUSION: CD26 mRNA was overexpressed in HCC, and its inhibition suppressed cellular proliferation through cell cycle arrest. The combined use of CD26 knockdown with a Bcl-xL inhibitor further elicited substantial apoptosis and therefore may serve as a powerful anticancer combination therapy against HCC.

Comparative evaluation of three-dimensional Gd-EOB-DTPA-enhanced MR fusion imaging with CT fusion imaging in the assessment of treatment effect of radiofrequency ablation of hepatocellular carcinoma.

PURPOSE: To assess the feasibility of fusion of pre- and post-ablation gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-MRI) to evaluate the effects of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC), compared with similarly fused CT images PATIENTS AND METHODS: This retrospective study included 67 patients with 92 HCCs treated with RFA. Fusion images of pre- and post-RFA dynamic CT, and pre- and post-RFA Gd-EOB-DTPA-MRI were created, using a rigid registration method. The minimal ablative margin measured on fusion imaging was categorized into three groups: (1) tumor protruding outside the ablation zone boundary, (2) ablative margin 0-<5.0 mm beyond the tumor boundary, and (3) ablative margin ≥5.0 mm beyond the tumor boundary. The categorization of minimal ablative margins was compared between CT and MR fusion images. RESULTS: In 57 (62.0%) HCCs, treatment evaluation was possible both on CT and MR fusion images, and the overall agreement between them for the categorization of minimal ablative margin was good (κ coefficient = 0.676, P < 0.01). MR fusion imaging enabled treatment evaluation in a significantly larger number of HCCs than CT fusion imaging (86/92 [93.5%] vs. 62/92 [67.4%], P < 0.05). CONCLUSIONS: Fusion of pre- and post-ablation Gd-EOB-DTPA-MRI is feasible for treatment evaluation after RFA. It may enable accurate treatment evaluation in cases where CT fusion imaging is not helpful.

Renal impairment during the treatment of telaprevir with peginterferon and ribavirin in patients with chronic hepatitis C.

AIM: Renal damage has been reported as an important complication during combination treatment of peginterferon (PEG IFN), ribavirin (RBV) and telaprevir (TVR) for chronic hepatitis C. However, very little is known about this complication. We investigated the role TVR plays in renal damage during this triple therapy. METHODS: Twenty-five chronic hepatitis C patients with genotype 1 and high viral load received TVR in combination with PEG IFN and RBV for 12 weeks followed by treatment with PEG IFN and RBV. Renal function of these patients was prospectively evaluated for 16 weeks. RESULTS: Creatinine clearance decreased significantly during PEG IFN/RBV/TVR treatment. Consequently, serum creatinine and cystatin C significantly rose during PEG IFN/RBV/TVR treatment. Serum creatinine returned to pretreatment levels after the termination of TVR. The increase of serum creatinine and cystatin C from baseline significantly correlated with serum TVR level at day 7, which was determined by starting dose of TVR per bodyweight . When the patients were classified according to the starting dose of TVR per bodyweight, renal impairment was observed only in the high-dose (TVR ≥33 mg/kg per day) group, not in the low-dose (TVR <33 mg/kg per day) group. CONCLUSION: These results suggest that TVR dose per bodyweight is important for the occurrence of renal impairment in PEG IFN/RBV/TVR treatment.

[Assessing the effect of subcuticular buried sutures with subcutaneous closed suction drain to prevent surgical site infection in patients undergoing total cystectomy with urinary diversion using intestine].

We assessed the effect of subcuticular buried sutures with subcutaneous closed suction drain to prevent surgical site infection (SSI) in patients undergoing total cystectomy with urinary diversion using the intestine. We reviewed the clinical charts of 43 consecutive patients who underwent total cystectomy with urinary diversion using the intestine from February 2006 to March 2011 at Nishi-Kobe Medical Center. All patients received intravenous prophylactic antibiotics before and throughout surgery as well as for three days after surgery. Skin closure was performed with interrupted vertical mattress sutures with 2-0 nylon on the first 22 patients (mattress group), and with interrupted subcuticular buried sutures with 4-0 absorbable monofilament with subcutaneous closed suction drain on the remaining 21 patients (subcuticular buried suture with subcutaneous drain; SBD group). SSI occurred in 7 (31.8%) patients in the mattress group, but did not affect any patient in the SBD group. We compared risk factors for SSI between the groups, and found that the method of skin closure was significant risk factor for SSI (P = 0.005). We concluded that interrupted subcuticular buried sutures with 4-0 absorbable monofilament with subcutaneous suction drain is effective for prevention of SSI in total cystectomy with urinary diversion using the intestine.

[Development of a preoperative criterion to select candidates for nerve-sparing radical prostatectomy at Kyoto University Hospital].

Neurovascular bundle (NVB) preservation is a mandatory procedure to maintain erectile function of localized prostate cancer patients after radical prostatectomy (RP). However, in terms of cancer control, indications to select appropriate patients for nerve-sparing RP are still controversial. In this study, we examined the pathological findings of RP specimens to develop a preoperative criterion for NVB preservation during RP. The study included 76 patients who underwent RP at our institution from 2006 to 2008, and we retrospectively analyzed RP specimens pathologically. The distance between NVB and foci of prostate cancer was measured in 135 prostate sides, and preoperative factors which predict the distance of ≤2 mm was evaluated. Univariate analysis showed that side-specific positive biopsy core rate ≥33.3%, side-specific maximum tumor length in biopsy core ≥5 mm and side-specific tumor involvement rate in biopsy core ≥50% was associated with the risk of the distance of ≤2 mm. Multivariate analysis revealed that side-specific positive biopsy core rate ≥33.3% was the only significant predictor of the ipsilateral NVB-tumor distance ≤2 mm (p = 0.0055, odds ratio 3.49). Based on this study, a nerve-sparing criterion of ＜33.3% side-specific percent positive biopsy core was developed at our institution. Prospective data on patients who were applied this criterion are needed to evaluate its clinical safety and feasibility.

[The safety and efficacy of sunitinib using a modified regimen (2 weeks on/1 week off) for treatment of metastatic renal cell carcinoma].

We prospectively investigated the safety and efficacy of sunitinib using a modified regimen (2 weeks on/1 week off) in 24 patients (22 males, 2 females ; age range 39-86 years, median 64 years) with metastatic renal cell carcinoma (RCC). During the observation period (3-62 weeks, median 21 weeks), thrombocytopenia was seen in 13 (54.2%), leukopenia in 11 (45.8%), hand-foot syndrome in 5 (20.8%), hypertension in 4 (16.7%), and hypothyroidism in 3 (12.5%) patients, while grade 3 or higher adverse events were found in 4 (16.7%), 1 (4.2%), 1 (4.2%), 2 (8.3%), and 0 patients, respectively. Of the 21 patients evaluable for response, 5 (23. 8%) showed partial response, 8 (38.1%) stable disease, and 8 (38.1%) progressive disease. This new modified regimen may lead to a reduction in adverse events for treatment of patients with metastatic RCC as a substitute for the standard dosing regimen of sunitinib.

Oncogenic GNAS drives a gastric pylorus program in intraductal papillary mucinous neoplasms of the pancreas.

OBJECTIVE: Intraductal Papillary Mucinous Neoplasms (IPMNs) are cystic lesions and bona fide precursors for pancreatic ductal adenocarcinoma (PDAC). Recently, we showed that acinar to ductal metaplasia, an injury repair program, is characterized by a transcriptomic program similar to gastric spasmolytic polypeptide expressing metaplasia (SPEM), suggesting common mechanisms of reprogramming between the stomach and pancreas. The aims of this study were to assay IPMN for pyloric markers and to identify molecular drivers of this program. DESIGN: We analyzed RNA-seq studies of IPMN for pyloric markers, which were validated by immunostaining in patient samples. Cell lines expressing Kras G12D +/- GNAS R201C were manipulated to identify distinct and overlapping transcriptomic programs driven by each oncogene. A PyScenic-based regulon analysis was performed to identify molecular drivers in the pancreas. Expression of candidate drivers was evaluated by RNA-seq and immunostaining. RESULTS: Pyloric markers were identified in human IPMN. GNAS R201C drove expression of these markers in cell lines and siRNA targeting of GNAS R201C or Kras G12D demonstrates that GNAS R201C amplifies a mucinous, pyloric phenotype. Regulon analysis identified a role for transcription factors SPDEF, CREB3L1, and CREB3L4, which are expressed in patient samples. siRNA-targeting of Spdef inhibited mucin production. CONCLUSION: De novo expression of a SPEM phenotype has been identified in pancreatitis and a pyloric phenotype in Kras G12D -driven PanIN and Kras G12D ;GNAS R201C -driven IPMN, suggesting common mechanisms of reprogramming between these lesions and the stomach. A transition from a SPEM to pyloric phenotype may reflect disease progression and/or oncogenic mutation. IPMN-specific GNAS R201C amplifies a mucinous phenotype, in part, through SPDEF.

Ultrasonography fusion imaging system increases the chance of radiofrequency ablation for hepatocellular carcinoma with poor conspicuity on conventional ultrasonography.

OBJECTIVES: To investigate the usefulness of the ultrasonography (US) fusion imaging system for radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: Since the US fusion imaging system became available in 2010, we have conducted RFA with this system in all cases. The characteristics of 75 patients with 120 HCCs and 89 patients with 123 HCCs who underwent RFA before the introduction of this system (period A) and after it (period B), respectively, were retrospectively compared. RESULTS: Significant difference in the characteristics of the patients and HCCs between the two periods was found only in the proportion of HCCs with poor conspicuity on grayscale US treated with RFA (1.7%, 2/120 for period A vs. 15.4%, 19/123 for period B, p < 0.01). Among the 19 HCCs with poor conspicuity on grayscale US for period B, 5 and 9 HCCs were identified on grayscale US and contrast-enhanced US, respectively, by the use of the US fusion imaging system, whereas the 5 remaining undetectable HCCs were treated by using the system in conjunction with reference images displayed side-by-side with grayscale US. CONCLUSION: Since the introduction of the US fusion imaging system, it has become possible to perform RFA for HCCs with poor conspicuity on grayscale US.

Usefulness of the extracted-overlay function in CT/MR-ultrasonography fusion imaging for radiofrequency ablation of hepatocellular carcinoma.

OBJECTIVES: We developed a novel technique of the extracted-overlay function in CT/MR-ultrasonography (US) fusion imaging for radiofrequency ablation (RFA), in which only a tumor extracted from CT/MR images with a virtual ablative margin of arbitrary thickness is overlaid on US. The usefulness of this function is investigated in this preliminary report. METHODS: The volume data of the extracted tumor with a virtual ablative margin were created on an image-processing workstation, and transported into a US unit equipped with a CT/MR-US fusion imaging system. After the positional registration of US and transported images, the extracted tumor with an ablative margin could be overlaid on US. In RFA, using this function, an electrode was inserted targeting the overlaid tumor with an ablative safety margin of 5 mm on US, and the treatment effect was evaluated by dynamic CT. Treatment results of 23 consecutive hepatocellular carcinomas (HCCs) that underwent RFA using this function were retrospectively analyzed. RESULTS: Complete tumor ablation was achieved in 22 (95.7%) and 1 (4.3%) HCCs in 1 and 2 treatment sessions, respectively. CONCLUSIONS: Due to the visualization of an extracted tumor with an ablative safety margin on a US image, even during and after ablation, this function is useful for treatment planning and guidance of RFA.

Utility of computed tomography fusion imaging for the evaluation of the ablative margin of radiofrequency ablation for hepatocellular carcinoma and the correlation to local tumor progression.

AIM: To demonstrate the usefulness of the computed tomography (CT) fusion imaging for the evaluation of treatment effect of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: Eighty-five patients with 94 HCC with complete ablation judged on conventional side-by-side interpretation of pre-RFA and post-RFA CT at the time of RFA were included in this retrospective study. CT data was retrospectively used to create fusion images of pre-RFA and post-RFA CT using automatic rigid registration and manual correction referring to intrahepatic structures and hepatic contours around a tumor. Clinical factors including a minimal ablative margin (MAM) measured on fusion images were examined to prove risk factors for local tumor progression (LTP). RESULTS: LTP was observed in 13 (13.8%) tumors with a median follow up of 21.0 months (range, 2-75). The mean MAM on the fusion image was 1.4 ± 3.1 mm and 23 tumors (24.5%) were judged to be protruding from the ablation zone. Multivariate analysis revealed that protruding from the ablation zone was the only significant factor for LTP (hazard ratio, 7.09; 95% confidential interval, 2.26-22.3; P < 0.001). CONCLUSION: Some HCC were assessed as incomplete ablation on the CT fusion images, although considered completely ablated on side-by-side images at the time of treatment, and incomplete ablation was revealed to be the only independent risk factor for LTP. The CT fusion imaging enables quantitative and accurate evaluation of treatment effect of RFA.

Diffusion-weighted Imaging of the Abdomen during a Single Breath-hold Using Simultaneous-multislice Echo-planar Imaging.

PURPOSE: This multi-scanner study aimed to investigate the validity of single breath-hold (BH) diffusion-weighted imaging (DWI) using simultaneous-multislice (SMS) echo-planar imaging in multiple abdominal organs to enable faster acquisition and reliable quantification of apparent diffusion coefficient (ADC). METHODS: SNR, geometric distortion (GD), and ADC in a phantom; the ADC in the liver, renal cortex, paraspinal muscle, spleen, and pancreas; and the signal intensity ratio of the portal vein-to-muscle (SIRPV-M) in healthy volunteers were compared between BH- and respiratory-triggered (RT) DWI with b-values of 0 and 800 s/mm2 in two different MRI scanners. RESULTS: The phantom study showed that the SNR of BH-DWI was significantly lower than that of the RT-DWI (P < 0.05 for both scanners), whereas the GD and ADC of BH-DWI did not differ significantly from those of the RT-DWI (P = 0.09-0.60). In the volunteer study, the scan times were 23 seconds for BH-DWI and 184±33 seconds for RT-DWI, respectively. The ADC of the liver in BH-DWI was significantly lower than that in RT-DWI (P < 0.05 for both scanners), whereas there were no significant differences in the ADCs of the renal cortex, paraspinal muscle, spleen, or pancreas between BH-DWI and RT-DWI (P = 0.07-0.86). The SIRPV-M in BH-DWI was significantly smaller than in RT-DWI (P < 0.05 for both scanners). CONCLUSION: The proposed method enables the acquisition of abdominal diffusion-weighted images in a single BH.