Gallbladder hemorrhage associated with segmental arterial mediolysis: a case report.

BACKGROUND: Gallbladder hemorrhage is a rare but fatal condition. The reported causes of gallbladder hemorrhage include iatrogenesis, atherosclerotic changes in the cystic arteries, acute cholecystitis or cholelithiasis, malignancy, trauma, hemophilia, pseudoaneurysm, and the use of oral anticoagulant medications. Recently, segmental arterial mediolysis (SAM) has been reported as a possible etiology of life-threatening abdominal, retroperitoneal, and intracranial hemorrhages. However, no previous reports have described the association between gallbladder hemorrhage and SAM. CASE PRESENTATION: A 59-year-old man was transferred to our hospital complaining of upper abdominal pain and vomiting. Contrast-enhanced computed tomography revealed high-density images of the gallbladder and common bile duct. However, there were no obvious findings of gallstones, cholecystitis, tumors, or aneurysms. He was diagnosed with gallbladder hemorrhage and bile duct obstruction. We performed a laparoscopic cholecystectomy after endoscopic biliary drainage. The gross appearance of the surgically resected specimen showed 12 small (3-12 mm), slightly elevated lesions on the gallbladder mucosa. Histologically, these slightly elevated lesions consisted of dilated muscular arteries of the gallbladder wall with fibrinoid degeneration of the media and focal loss of the internal and external elastic laminae. The histopathological diagnosis was confirmed as SAM. CONCLUSIONS: To the best of our knowledge, this is the first reported case of a gallbladder hemorrhage associated with SAM. Our case report shows that SAM can cause gallbladder hemorrhage, suggesting that SAM should be considered in the differential diagnosis of gallbladder hemorrhage.

A case of multiple hepatocellular carcinoma experiencing complete responses to sorafenib and atezolizumab-bevacizumab and developing severe, refractory venous congestive cutaneous ulcers on either regimen.

A man in his eighties presented with a history of bilateral leg congestive phlebitis, and multiple hepatocellular carcinoma (HCC) treated with sorafenib. When the dose was increased to 400 mg, ulcers appeared under both knees, which worsened, and the drug was discontinued 2 months after administration. However, the ulcers to 30 mm in diameter, requiring debridement and antibiotics. The HCC showed a complete response (CR) based on modified-RECIST criteria; however, after several rounds of locoregional therapy for recurrence, multiple HCCs and metastatic lesions in the Morrison's fossa were detected. Therefore, atezolizumab 1200 mg-bevacizumab 900 mg was started. After the first course, the patient complained of pain below both knees, and when the second course was administered, leg ulcers re-appeared and rapidly worsened. The ulcers were circular and multiple and progressed to deep digging, leading to tendon exposure. Bevacizumab-induced congestive venous ulcer was diagnosed, requiring skin grafts to heal. HCC then showed a CR based on m-RECIST criteria. Initially, the cause of the ulcer was thought to be immune-related adverse effects due to atezolizumab, but experience with sorafenib led us to conclude that the cause was stagnant venous ulcers due to vascular endothelial growth factor receptor inhibitor, which inhibited angiogenesis.

Volume-Outcome Relationship in Cancer Survival Rates: Analysis of a Regional Population-Based Cancer Registry in Japan.

BACKGROUND: There is limited data on the relationship between hospital volumes and outcomes with respect to cancer survival in Japan. The primary objective of this study was to evaluate the effect of hospital volume on cancer survival rate using a population-based cohort database. METHODS: Using the Kanagawa cancer registry, propensity score matching was employed to create a dataset for each cancer type by selecting 1:1 matches for cases from high- and other-volume hospitals. The 5-year survival rate was estimated and the hazard ratio (HR) for hospital volume was calculated using a Cox proportional hazard model. Additional analyses were performed limited to cancer patients who underwent surgical operation, chemotherapy, and other treatments in each tumor stage and at the time of diagnosis. RESULTS: The number of cases with complete data, defined as common cancers (prostate, kidney, bladder, esophagus, stomach, liver, pancreas, colon, breast, and lung), was 181,039. Adjusted HR differed significantly among hospital volume categories for the most common cancers except bladder, and the trends varied according to cancer type. The HR ranged from 0.76 (95%CI, 0.74-0.79) for stomach cancer to 0.85 (0.81-0.90) for colon cancer. CONCLUSIONS: This study revealed that a relationship may exist between hospital volume and cancer survival in Japan.

Contribution of chemotherapy to improved prognosis in stage 4 gastric cancer: trend analysis of a regional population-based cancer registry in Japan.

OBJECTIVES: Little is known about time trends in the prognosis of gastric cancer (GC), since the introduction of new chemotherapeutic agents. This study aimed to analyze how the increased number of available chemotherapeutic options affected the prognosis of GC and which patient types benefited within in a large population. METHODS: From a population-based cancer registry in Japan, 35,751 cases of GC were identified. Of these, 8214 cases were stage 4. The time trend for 3-year survival in stage 4 GC according to patient characteristics (age and tumor location) was estimated in relation to the introduction of new anticancer drugs. Multiple imputation was performed for sensitivity analysis to strengthen the missing data. In addition, we estimated the 5-year survival rate for distal-GC (DGC) and proximal-GC (PGC), and the hazard ratio (HR) was estimated by Cox proportional hazard model. RESULTS: Improvement of overall survival was accelerated in stage 4 cases over time. The prognosis was improved from 11.4% to 13.2%, subsequent to the approval of several oncologic drugs since 2009. Younger patients were more likely to have improved survival rates in response to the increase in chemotherapy options (< 60-year-old, 5.4%: 60-70, 2.2%; 70-80, 0.3%) from 2007 to 2015. The HR for DGC vs. PGC was 1.11 (95% CI 1.08-1.15), and PGC showed a higher rate of improved outcomes (2.4% vs. 0.6%). CONCLUSIONS: This analysis showed that improvement in the GC survival rate was accelerated by the introduction of new chemotherapeutic strategies and it was most evident among younger patients and in patients with PGC.

A case of primary hepatic mixed neuroendocrine-non-neuroendocrine tumor (MiNEN) associated with gallbladder carcinosarcoma.

A woman in her seventies visited our hospital because of abdominal pain. Multiple hepatic tumors were detected and a liver biopsy revealed mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN), which was composed of cholangiocellular carcinoma and neuroendocrine tumor (NET). Diagnostic imaging ruled out primary malignancies other than the liver and identified that the tumor originated from the liver. Because a predominant and aggressive part of the tumor was considered to be cholangiocellular carcinoma, gemcitabine and S-1 were used as first-line treatment. After the treatment, octreotide acetate was administered for the NET component, followed by transcatheter arterial embolization. Subsequently, her gallbladder (GB) rapidly swelled with biliary tract obstruction, and cholecystectomy revealed carcinosarcoma of the GB. She is still undergoing treatment at 44 months after diagnosis. Herein we report this case of primary hepatic MiNEN consisting of cholangiocarcinoma and NET, followed by GB carcinosarcoma. This is the first case illustrating that a multidisciplinary treatment approach for MiNEN accompanied with carcinosarcoma, involving assessment and treatment targeting the most aggressive component, can result in a long survival time.

The Prognosis of Hepatocellular Carcinoma Treated with Sorafenib in Combination with TACE.

OBJECTIVE: Sorafenib have been shown to be effective in the treatment of advanced HCC and has been standard therapy since its release in Japan in 2009 (Llovet et al., 2008; Cheng et al., 2009). However, due to a low response rate, more aggressive combination treatment has been utilized as a multimodal strategy. The present study aimed to determine the efficacy of sorafenib alone and in combination with transarterial chemoembolization (TACE) for the treatment of advanced HCC. METHODS: All patients with unresectable advanced HCC who were prescribed sorafenib at Kanto Rosai Hospital were included in the study. Five-year overall survival (OS) rates were estimated for patients treated with sorafenib alone or in combination with TACE. Multivariate and univariate regression analyses were performed to identify factors affecting OS. Analysis using propensity score matching and inverse-probability weights were also performed. RESULTS: A total of 46 patients were treated with sorafenib up to June 2018. The total sorafenib dose administered was higher in the TACE combination group (70900 mg vs. 24000 mg vs. with sorafenib alone), although the relative dose intensity was lower (11.7% vs. 17.6%, respectively). The 5-year survival prognosis estimated using the Kaplan-Meier method was longer in patients treated with sorafenib in combination with TACE versus sorafenib alone (36.3% vs. 7.7%). Combination with TACE was the only factor associated with improved OS in both univariate and multivariate analysis. Among cases matched by propensity scores the hazard rate for combination with TACE was 0.067 (95% CI 0.091-1.128). CONCLUSION: With an array of therapeutic options currently available, it is important to determine the efficacy of different multimodal strategies, such as sorafenib combined TACE, for patients with unresectable HCC.

Differential diagnosis and laparoscopic resection of an adrenal pseudocyst: A case report.

BACKGROUND: Adrenal pseudocysts are infrequent entities and definite preoperative diagnosis is difficult. We present a case of left adrenal pseudocyst, which was intraoperatively identified as having an adrenal origin and was resected using a laparoscopic approach. PRESENTATION OF CASE: A 41-year-old female was referred to our hospital for examination and treatment of a cystic lesion in the pancreatic tail. Preoperative diagnostic imaging studies showed a cystic lesion with intramural nodular structure, measuring 39 mm in the largest diameter and located between the pancreatic tail and the left adrenal gland. However, the origin of the cystic lesion remained unclear, and a definite preoperative diagnosis was not established. The cystic lesion was intraoperatively identified as having an adrenal origin after the division of the loose connective tissue layer around the lesion under the laparoscopic magnified view. Laparoscopic left adrenalectomy was performed as radical treatment and the histopathological diagnosis confirmed the presence of an adrenal pseudocyst. DISCUSSION: We could not ascertain the origin of the cystic lesion from the left adrenal gland and establish a definite diagnosis based on the findings of the preoperative diagnostic imaging modalities. Laparoscopic surgery could be more advantageous than the conventional open approach as not only a minimally invasive treatment option but also as an intraoperative diagnostic tool for cystic lesions in the pancreatic tail. CONCLUSION: This case report suggests that laparoscopic surgery could be clinically useful as not only a minimally invasive treatment but also an intraoperative diagnostic tool for cystic lesions in the pancreatic tail region.

Effect of Hepatic Inflammation in Chronic Hepatitis C Infection on Fibrosis Assessment by Arrival Time Parametric Imaging.

Arrival time parametric imaging (At-PI) in contrast-enhanced ultrasonography is useful for assessing liver fibrosis in chronic hepatitis C (CHC) infection. The study aimed to elucidate the effect of hepatic inflammation on At-PI efficiency. Subjects were 159 CHC patients who underwent contrast-enhanced ultrasonography immediately before liver biopsy. Ultrasound contrast agent was injected, and contrast dynamics of the S5 to S6 region of the liver and right kidney were recorded for 40 seconds. The At-PI of liver parenchyma blood flow was generated using saved video clips. Hepatic blood flow during the first 5 seconds after starting contrast injection was displayed in red and that after another 5 seconds was displayed in yellow. The ratio of red (ROR) in At-PI images of the entire liver was measured with ImageJ. Ratio of red values of livers with different activity grades (0-3) were compared for each fibrosis (F) stage as determined by biopsy. Correlations of ROR with alanine aminotransferase (ALT) levels were analyzed using a linear regression line from the distribution map. Comparison of ROR for different activity grades in each F stage revealed no significant differences. Correlation coefficient R (P value) for ALT and ROR was R = -0.0094 (P = 0.43) at F0 to F1, R = -0.186 (P = 0.21) at F2, R = -0.233 (P = 0.27) at F3, and R = 0.041 (P = 0.89) at F4, with no significant correlation between ALT and ROR in any F stage. Hepatic inflammation in CHC infection does not affect At-PI diagnostic accuracy.

Efficacy of intra-arterial contrast-enhanced ultrasonography during transarterial chemoembolization with drug-eluting beads for hepatocellular carcinoma.

AIM: To assess the usefulness of intra-arterial contrast-enhanced ultrasonography (IAUS) during transarterial chemoembolization (TACE) with drug-eluting beads (DEB) for hepatocellular carcinoma (HCC). METHODS: Thirty two patients with 39 HCC underwent DEB-TACE guided with IAUS, and examined by contrast-enhanced ultrasonography (CEUS) or dynamic CT after DEB-TACE were enrolled in this study. CEUS findings before DEB-TACE and IAUS findings were compared. Treatments judged to be complete and incomplete for lesions were appropriate and insufficient, respectively. Findings on CEUS and/or dynamic CT performed 1, 3 and 6 mo after DEB-TACE were evaluated using mRECIST (CR/PR/SD/PD). RESULTS: The treatments were complete and incomplete in 26 and 13 lesions, respectively. On imaging evaluation using CEUS and/or dynamic CT one month after treatment, 25 and 1 lesions were judged to be CR and PR, respectively, and at 6 mo after treatment, the results were CR, PR, SD and PD for 24, 1, 0 and 1 of these lesions, respectively, in the 26 completely treated lesions. Of the 13 lesions in which treatment was incomplete, the results on imaging at one month after treatment were CR, PR, SD and PD for 0, 6, 4 and 3 lesions, respectively. The overall CR rate at 6 mo after treatment was 61.5% (24/39). CONCLUSION: A combination of DEB-TACE with IAUS can improve the therapeutic effects in patients with HCC.

Characteristics of hepatic insulin-sensitive nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) plays a crucial role in type 2 diabetes and hepatocellular carcinoma. The major underlying pathogenesis is hepatic insulin resistance. The aim of the present study was to characterize patients with NAFLD with paradoxically normal hepatic insulin sensitivity relative to patients with NAFLD with hepatic insulin resistance. We recruited 26 patients with NAFLD and divided them into three groups ranked by the level of hepatic insulin sensitivity (HIS; high-HIS, mid-HIS, low-HIS), as assessed by the hyperinsulinemic-euglycemic clamp studies using stable isotope. Hepatic insulin sensitivity of the high-HIS group was identical to that of the non-NAFLD lean control (clamped percent suppression of endogenous glucose production, 91.1% ± 5.2% versus 91.0% ± 8.5%, respectively) and was significantly higher than that of the low-HIS group (66.6% ± 7.5%; P < 0.01). Adiposity (subcutaneous, visceral, intrahepatic, and muscular lipid content), hepatic histopathology, and expression levels of various genes by using liver biopsies, muscle, and adipose tissue insulin sensitivity, plasma metabolites by metabolomics analysis, putative biomarkers, and lifestyles were assessed and compared between the high-HIS and low-HIS groups. Among these, adipose tissue insulin sensitivity assessed by clamped percent suppression of free fatty acid, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites, such as citric acid and cis-aconitic acid, were significantly higher in the high-HIS group compared to the low-HIS group. In contrast, there were no differences in adiposity, including intrahepatic lipid content assessed by proton magnetic resonance spectroscopy (28.3% ± 16.1% versus 20.4% ± 9.9%, respectively), hepatic histopathology, other putative biomarkers, and lifestyles. Conclusion: High levels of adipose tissue insulin sensitivity, serum high molecular weight adiponectin, and plasma tricarboxylic acid cycle metabolites are unique characteristics that define patients with hepatic insulin-sensitive NAFLD regardless of intrahepatic lipid content. (Hepatology Communications 2017;1:634-647).

Evaluation of sorafenib for advanced hepatocellular carcinoma with low α-fetoprotein in arrival time parametric imaging using contrast-enhanced ultrasonography.

PURPOSE: To determine the usefulness of arrival time parametric imaging (AtPI) using contrast-enhanced ultrasonography (CEUS) with Sonazoid in evaluating early response to sorafenib for hepatocellular carcinoma (HCC). METHODS: Twenty-one advanced HCC patients with low α-fetoprotein (AFP) levels (≤35 ng/ml) who received sorafenib for at least 4 weeks were enrolled in this study. CEUS was performed before and 2 weeks after treatment, and the images of the target lesion in the arterial phase were analyzed by AtPI. In the color mapping images obtained by AtPI, the mean arrival time of the contrast agent in the target lesion from the reference point (mean time: MT) was calculated. In each patient, differences between MT before and MT 2 weeks after treatment were compared. MT (+) and MT (-) groups were defined as difference of 0 s or greater and less than 0 s, respectively. Overall survival was evaluated between the two groups. RESULTS: In the MT (+) (11 patients) and MT (-) (10 patients) groups, the median survival time was 792 and 403 days, respectively, which was statistically significant. CONCLUSIONS: The results suggested that AtPI was useful for evaluating early response to sorafenib for advanced HCC with low AFP level.

Comparison of contrast-enhanced ultrasonograpy with Gd-EOB-DTPA-enhanced MRI in the diagnosis of liver metastasis from colorectal cancer.

PURPOSE: To compare contrast-enhanced ultrasonography (CEUS) using Sonazoid with Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in the diagnosis of liver metastases in patients with colorectal cancer. METHODS: A total of 69 patients diagnosed with or suspected of having liver metastasis were enrolled. These hepatic lesions were diagnosed by histopathological examination after surgical resection or based on follow-up using various imaging modalities. The diagnostic accuracies of CEUS and EOB-MRI were compared. RESULTS: One hundred thirty-three lesions were detected. Of these lesions, 109 were diagnosed as liver metastases. Of the 133 lesions, 90.2% were detected on CEUS, and 98.5% on EOB-MRI. One hundred nine lesions were diagnosed as liver metastasis. The areas under the receiver operating characteristic curve for diagnosis were 0.906 and 0.851 on CEUS and EOB-MRI, respectively (p = 0.41). Sensitivity, specificity, positive predictive value (PPV), negative predictive value, and overall accuracy were 90.8%, 84.5%, 97.1%, 67.1%, and 90.2%, respectively, for CEUS, and 95.4%, 70.8%, 93.7%, 77.3%, and 91%, respectively, for EOB-MRI. CONCLUSIONS: CEUS has a higher specificity and PPV for the diagnosis of liver metastasis than EOB-MRI. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:138-144, 2017.

[Plasma Biomarkers as Predictive Factors for Advanced Hepatocellular Carcinoma with Sorafenib].

We examined plasma biomarkers as predictive factors for advanced hepatocellular carcinoma(ad-HCC)patients treated with sorafenib. We analyzed a-fetoprotein(AFP), AFP-L3, des-g-carboxy prothrombin(DCP), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and vascular endothelial growth factor(VEGF)before sorafenib therapy, and changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy in 16 patients. High AFP-L3(hazard ratio: 1.058, 95%CI: 1.019-1.098, p=0.003)and high NLR(hazard ratio: 1.475, 95%CI: 1.045-2.082, p=0.027)were significantly associated with poor prognosis in ad-HCC patients treated with sorafenib. There were no significant differences in changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy. We suggest that AFP-L3 and NLR levels before sorafenib therapy in patients with ad-HCC are an important predictive factor for the therapeutic effect of sorafenib and patient survival.

Therapeutic evaluation of sorafenib for hepatocellular carcinoma using contrast-enhanced ultrasonography: Preliminary result.

The present study aimed to determine the usefulness of contrast-enhanced ultrasonography (CEUS) with Sonazoid in evaluating the therapeutic response to sorafenib for hepatocellular carcinoma (HCC). In total, 26 patients with advanced HCC who received sorafenib and were followed up by CEUS were enrolled in the present study. CEUS was performed prior to and within 2-4 weeks of treatment, and the images of the target lesion in the post-vascular phase with a re-injection method were analyzed. The presence (+) or absence (-) of intratumoral necrosis and the intratumoral vascular architecture on micro-flow imaging (MFI) were compared prior to and subsequent to treatment. Target lesions that exhibited non-enhancement after re-injection were considered to indicate intratumoral necrosis. The intratumoral vascular architecture was classified into three groups, as follows: Vd, the intratumoral vessels visually narrowed or decreased; Vnc, the vessels remained unchanged; and Vi, the vessels were thickened or increased. Survival curves were estimated using the Kaplan-Meier method and compared using the log rank test between the intratumoral necrosis (+) and (-) groups, and among the Vd, Vnc and Vi groups. P<0.05 was considered to indicate a statistically significant difference. The number of patients in the intratumoral necrosis (+) and (-) groups was 8 and 18 patients, respectively, and the median survival time (MST) was 7.2 months [95% confidence interval (CI), 2.2-12.2] and 9.5 months (95% CI, 5.1-13.8), respectively (P=0.44). The MFI findings were observed in 11 patients in the Vd group, 10 patients in the Vnc group and 5 patients in the Vi group. The MSTs in the Vd, Vnc and Vi groups were 15.6 months (95% CI, 5.0-23.3), 11.0 months (95% CI, 3.5-17.6) and 3.6 months (95% CI: 1.2-6.0), respectively. The P-value for the differences between the Vd and Vnc groups, Vd and Vi groups, and Vnc and Vi groups were 0.78, 0.016 and 0.047, respectively, which indicated that the survival time decreased significantly in the Vi group. Evaluation of intratumoral vascular architecture using MFI demonstrates promise for assessing the therapeutic response to sorafenib in patients with HCC.

[Evaluation of Sorafenib for Hepatocellular Carcinoma with Low α-Fetoprotein by Arrival Time Parametric Imaging Using Contrast-Enhanced Ultrasonography with Sonazoid].

We aimed to determine the usefulness of arrival time parametric imaging (AtPI) using contrast-enhanced ultrasonography (CEUS)with Sonazoid in the evaluation of early response to sorafenib for hepatocellular carcinoma (HCC). Thirteen ad- vanced HCC patients with low a / -fetoprotein (AFP) level (≤35 ng/mL) who received sorafenib for at least 4 weeks were enrolled in this study. CEUS was performed before and after treatment (2 weeks), and the images of the target lesion in the arterial phase were analyzed by AtPI. In the color mapping images obtained by AtPI, the mean arrival time of the contrast agent in the target lesion from the starting point (mean time: MT) was calculated. In each patient, differences between MT before and MT 2 weeks after treatment were compared. MT (+) and MT(-) groups were designated as such if the difference was 0 or greater(blood flow velocity of the lesion was reduced)and less than 0 sec(blood flow velocity of the lesion was increased), respectively. The overall survival was evaluated between the 2 groups. In the MT (+) group (7 patients) and MT (-) group (6 patients), the median survival times were 307 and 208 days, respectively, which was statistically significant. We suggest AtPI is useful for evaluating early response to sorafenib in advanced HCC patients with low AFP level.

Evaluation of contrast-enhanced ultrasonography for hepatocellular carcinoma prior to and following stereotactic body radiation therapy using the CyberKnife® system: A preliminary report.

The CyberKnife® is expected to be a novel local treatment for hepatocellular carcinoma (HCC), however, a long-term follow-up using dynamic computed tomography and magnetic resonance imaging is required to determine the effect of treatment in a number of the affected patients. Therefore, there is a requirement to evaluate procedures for early determination of the effect of CyberKnife treatment. The present study aimed to evaluate the changes in the hemodynamics of the tumors and the hepatic parenchyma surrounding the tumor prior to and following CyberKnife treatment for HCC. A total of 4 HCC patients were enrolled in this study. These patients underwent CyberKnife treatment and were evaluated by image analysis prior to and following treatment using contrast-enhanced ultrasonography (CEUS) with Sonazoid. CEUS was performed prior to treatment, at 2 and 4 weeks post-treatment, and every 4 weeks thereafter for as long as possible. The dynamics of the enhancement of the tumor and the hepatic parenchyma surrounding the tumor in the vascular phase, and the presence or absence of a hypoechoic area in the hepatic parenchyma surrounding the tumor in the post-vascular phase were assessed. Results showed that: i) In the patient with earlier changes, hemodynamic changes were evident in the tumor at 4 weeks and in the hepatic parenchyma surrounding the tumor at 2 weeks post-treatment, respectively; ii) the tumor showed hypoenhancement in all patients; and iii) with regard to findings in the hepatic parenchyma surrounding the tumor, strong hyperenhancement appeared in the vascular phase initially, followed by a hypoechoic area in the post-vascular phase. Evaluation of the hemodynamics of tumors and hepatic parenchyma surrounding the tumor using CEUS with Sonazoid may be therapeutically applicable, as it is less invasive than dynamic computed tomography (CT) and provides an early evaluation of the effectiveness of CyberKnife treatment.

[Efficacy of Sorafenib versus Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma Refractory to Transcatheter Arterial Chemoembolization].

We compared the benefits of sorafenib with that of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (ad-HCC) refractory to transcatheter arterial chemoembolization (TACE). We evaluated the patient characteristics, the median survival time (MST), and the prognostic factors in 17 patients in the sorafenib group and in 26 patients in the HAIC group. No significant difference was observed in the patient characteristics between the groups. The MST in the sorafenib group and HAIC group was 483 days and 284 days, respectively. A significantly longer survival time was noted in the sorafenib group (p=0.033). The prognostic factors were sorafenib therapy in all 43 patients(hazard ratio: 3.32 [95% CI: 1.36-8.10], p=0.008) and the longer treatment period of sorafenib in the sorafenib group(hazard ratio: 0.99 [95% CI: 0.984- 0.999], p=0.009). When compared with HAIC, sorafenib showed favorable treatment results in patients with ad-HCC refractory to TACE.

A case of contiguous primary hepatic marginal zone B-cell lymphoma and hemangioma ultimately diagnosed using contrast-enhanced ultrasonography.

Primary hepatic marginal zone B-cell malignant lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is extremely rare. We present a case in which a lesion was diagnosed as 2 contiguous tumors (MALT lymphoma and hemangioma) using contrast-enhanced ultrasonography (US) with sonazoid. There has been no previous case of contiguous hepatic MALT lymphoma and hemangioma. The present case was a female with no medical history. We detected a snowman-like appearance, which was a tumor of 15 mm in diameter with hypo- and hyper-echogenicities in the lateral and medial parts, respectively, in the Couinaud's segment (S6) of the liver on US. The tumor appeared as a single lesion with a low-density area in the unenhanced phase and prolonged enhancement in the equilibrium phases on dynamic CT. On MRI, the whole lesion showed a low-intensity signal on T1-weighted imaging, but isointensity in the lateral part and high intensity in the medial part were seen on T2-weighted imaging. On contrast-enhanced US, the lateral hypoechoic region was homogenously hyperenhanced in the early vascular phase, and the contrast medium was washed out after about 30 s; in contrast, the medial hyperechoic region was gradually stained from the margin toward the central region. The tumor showed a defect in both hypo- and hyperechoic regions in the postvascular phase. Hemangioma was suspected for the medial part based on the typical image findings, but the lateral part was not given a diagnosis. Thus, surgical resection was performed. The medial part was a hemangioma, and the lateral part was a MALT lymphoma by histopathological findings.

Comparison of percutaneous radiofrequency ablation and CyberKnife(®) for initial solitary hepatocellular carcinoma: A pilot study.

AIM: To compare therapeutic outcomes and adverse events in initial solitary hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) and CyberKnife(®). METHODS: Seventy three consecutive patients with initial solitary HCC treated with RFA (38 patients; RFA group) and CyberKnife(®) (35 patients; CK group) were enrolled in this study. Background factors were compared between the two groups. Local and intrahepatic distant recurrence control, and cumulative survival rates were compared between the two groups. These were determined using the Kaplan-Meier method, and the significance of differences was analyzed by log-rank test. The presence of more grade 3 on CTCAE ver. 4.0 early and late adverse events was investigated. RESULTS: In background factors, age was significantly higher (P = 0.005) and the tumor diameter was significantly larger (P = 0.001) in the CK group. The 1-year local recurrence control rates were 97.4% and 97.1% in the RFA and CK groups, respectively (P = 0.71); the 1-year intrahepatic distant recurrence control rates were 85.6% and 86.1%, respectively (P = 0.91); and the 1-year cumulative survival rates were 100% and 95.2%, respectively (P = 0.075), showing no significant difference in any rate between the two groups. There were no late adverse event in the RFA group, but 11.4% in the CK group had late adverse events. In the CK group, the Child-Pugh score at 12 mo after treatment was significantly higher than that in the RFA group (P = 0.003) and significantly higher than the score before treatment (P = 0.034). CONCLUSION: The occurrence of adverse events is a concern, but CyberKnife(®) treatment is likely to become an important option for local treatment of early HCC.

Delayed intratumoral hemorrhage after drug-eluting bead transarterial chemoembolization for hepatocellular carcinoma.

Transarterial chemoembolization (TACE) using a drug-eluting bead (DEB-TACE) for hepatocellular carcinoma (HCC) is a new treatment method. We report on a case of delayed intratumoral hemorrhage after DEB-TACE. An 81-year-old male with hepatitis C virus-related cirrhosis was diagnosed with a HCC of 35 mm in diameter in S5 detected by dynamic computed tomography (CT) and contrast-enhanced ultrasonography (CEUS). DEB-TACE with DC Bead (®) and epirubicin hydrochloride was performed because the patient declined to undergo surgical resection. The treatment was completed, and the course after DEB-TACE was favorable. However, right hypochondriac pain suddenly developed about 1 month after DEB-TACE. Unenhanced CT showed an increase of the tumor diameter and intratumoral high-intensity area, which was not enhanced in the arterial phase. CEUS performed at the time of right hypochondriac pain (5 weeks after DEB-TACE) showed nonenhancement of almost the entire tumor in the vascular phase. The cause of the symptom may have been DEB-TACE-associated intratumoral hemorrhage. Tumor hemorrhage has been reported after DEB-TACE with tumors >5 cm in diameter, and the tumor locations were subcapsular in all previous reports. There has been no case of a tumor with a diameter <5 cm distinct from the subcapsular, as was observed in our patient. Incomplete embolization might be the cause of the intratumoral hemorrhage experienced by this case presenting a few risks. To obtain the therapeutic effect of DEB-TACE while preventing the adverse events, it may be important to understand the characteristics of the beads and to apply the appropriate embolization to each individual case.