[Successful portal vein stent placement for chronic portal vein stenosis 5 years after pancreatoduodenectomy:a case report].

A 73-year-old man underwent pancreatoduodenectomy 5 years previously, and portal vein stenosis was observed immediately after surgery. A collateral vein with varices around the hepaticojejunostomy gradually developed. The patient experienced repeated episodes of melena that required transfusion. Enteroscopy confirmed varices around the hepaticojejunostomy, caused by portal vein stenosis, which was the source of intestinal bleeding. Varices were treated by placing an expandable metallic stent in the stenotic portal vein through a percutaneous transhepatic route. Although the portal vein stenosis was severe, the guidewire was successfully maneuvered into the superior mesenteric vein and stent placement was successful. Subsequently, the collateral vein disappeared and no further melena was observed.

Cancer-related genetic changes in multistep hepatocarcinogenesis and their correlation with imaging and histological findings.

AIM: The landscape of cancer-related genetic aberrations in hepatocellular carcinoma (HCC) has gradually become clear through recent next-generation sequencing studies. However, it remains unclear how genetic aberrations correlate with imaging and histological findings. METHODS: Using 117 formalin-fixed paraffin-embedded specimens of primary liver tumors, we undertook targeted next-generation sequencing of 50 cancer-related genes and digital polymerase chain reaction of hTERT. After classifying tumors into several imaging groups by hierarchal clustering with the information from gadoxetic acid enhanced magnetic resonance imaging, contrast-enhanced computed tomography, contrast-enhanced ultrasound, and diffusion-weighted imaging magnetic resonance imaging, the correlation between genetic aberrations and imaging and histology were investigated. RESULTS: Most frequent mutations were hTERT (61.5%), followed by TP53 (42.7%), RB1 (24.8%), and CTNNB1 (18.8%). Liver tumors were classified into six imaging groups/grades, and the prevalence of hTERT mutations tended to increase with the advancement of imaging/histological grades (P = 0.026 and 0.13, respectively), whereas no such tendency was evident for TP53 mutation (P = 0.78 and 1.00, respectively). Focusing on the mutations in each tumor, although the variant frequency (VF) of hTERT did not change (P = 0.36 and 0.14, respectively) in association with imaging/histological grades, TP53 VF increased significantly (P = 0.004 and <0.001, respectively). In multivariate analysis, stage III or IV (hazard ratio, 3.64; P = 0.003), TP53 VF ≥ 50% (hazard ratio, 3.79; P = 0.020) was extracted as an independent risk for recurrence in primary HCC patients. CONCLUSIONS: Increased prevalence of hTERT mutation and increased TP53 mutation VF are characteristic features of HCC progression, diagnosed with imaging/histological studies.

Magnetic resonance elastography is as accurate as liver biopsy for liver fibrosis staging.

BACKGROUND: Liver MR elastography (MRE) is available for the noninvasive assessment of liver fibrosis; however, no previous studies have compared the diagnostic ability of MRE with that of liver biopsy. PURPOSE: To compare the diagnostic accuracy of liver fibrosis staging between MRE-based methods and liver biopsy using the resected liver specimens as the reference standard. STUDY TYPE: A retrospective study at a single institution. POPULATION: In all, 200 patients who underwent preoperative MRE and subsequent surgical liver resection were included in this study. Data from 80 patients were used to estimate cutoff and distributions of liver stiffness values measured by MRE for each liver fibrosis stage (F0-F4, METAVIR system). In the remaining 120 patients, liver biopsy specimens were obtained from the resected liver tissues using a standard biopsy needle. FIELD STRENGTH/SEQUENCE: 2D liver MRE with gradient-echo based sequence on a 1.5 or 3T scanner was used. ASSESSMENT: Two radiologists independently measured the liver stiffness value on MRE and two types of MRE-based methods (threshold and Bayesian prediction method) were applied. Two pathologists evaluated all biopsy samples independently to stage liver fibrosis. Surgically resected whole tissue specimens were used as the reference standard. STATISTICAL TESTS: The accuracy for liver fibrosis staging was compared between liver biopsy and MRE-based methods with a modified McNemar's test. RESULTS: Accurate fibrosis staging was achieved in 53.3% (64/120) and 59.1% (71/120) of patients using MRE with threshold and Bayesian methods, respectively, and in 51.6% (62/120) with liver biopsy. Accuracies of MRE-based methods for diagnoses of ≥F2 (90-91% [108-9/120]), ≥F3 (79-81% [95-97/120]), and F4 (82-85% [98-102/120]) were statistically equivalent to those of liver biopsy (≥F2, 79% [95/120], P ≤ 0.01; ≥F3, 88% [105/120], P ≤ 0.006; and F4, 82% [99/120], P ≤ 0.017). DATA CONCLUSION: MRE can be an alternative to liver biopsy for fibrosis staging. LEVEL OF EVIDENCE: 3. Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1268-1275.

Noninvasive hepatic fibrosis staging using mr elastography: The usefulness of the bayesian prediction method.

PURPOSE: To evaluate the usefulness of the Bayesian method for hepatic fibrosis staging with magnetic resonance elastography (MRE). MATERIALS AND METHODS: The sample of this retrospective study comprised patients with chronic liver disease (n = 309), in whom histopathological fibrosis staging and MRE using either a 1.5T (n = 214) or a 3T magnetic resonance imaging (MRI) system (n = 95) had been performed. The optimal cutoff stiffness value was determined and used to calculate the discrimination ability of fibrosis staging by the cutoff method. The Bayesian method calculated post-MRE probability of each fibrosis stage, yielding MRE-based fibrosis staging without a cutoff value as well as the confidence of staging. We compared the discrimination ability in all patients and in a subgroup of patients with high (≥90%) posterior probability. RESULTS: The discrimination ability for hepatic fibrosis staging was comparable between the Bayesian method and the cutoff method in all patients because the accuracy of staging with the Bayesian method and the cutoff method in all patients was not different (P = 1.0000). However, in patients with high posterior probability by the Bayesian method, the accuracy of staging with the Bayesian method was significantly improved compared with that of the cutoff method in all patients; for discriminating stage ≥F2 from F0-F1 (98.9% vs. 94.8%, P = 0.0069); for ≥F3 (99.6% vs. 92.6%, P < 0.0001); and for F4 (100% vs. 94.2%, P = 0.0002). CONCLUSION: The Bayesian method has a highly accurate discrimination ability for noninvasive hepatic fibrosis staging using MRE, if the posterior probability is high. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:375-382.

Outcome of hypovascular hepatic nodules with positive uptake of gadoxetic acid in patients with cirrhosis.

OBJECTIVES: To evaluate the longitudinal risk to patients with cirrhosis of hypervascular hepatocellular carcinoma (HCC) developing from hypovascular hepatic nodules that show positive uptake of gadoxetic acid (hyperintensity) on hepatocyte phase images. METHODS: In 69 patients, we evaluated findings from serial follow-up examinations of 633 hepatic nodules that appeared hypovascular and hyperintense on initial gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) until the nodules demonstrated hypervascularity and were diagnosed as hypervascular HCC. Cox analyses were performed to identify risk factors for the development of hypervascular HCCs from the nodules. RESULTS: The median follow-up was 663 days (range, 110 to 1215 days). Hypervascular HCCs developed in six of the 633 nodules (0.9 %) in five of the 69 patients. The only independent risk factor, the nodule's initial maximum diameter of 10 mm or larger, demonstrated a hazard ratio of 1.25. The one-year risk of hypervascular HCC developing from a nodule was 0.44 %. The risk was significantly higher for nodules of larger diameter (1.31 %) than those smaller than 10 mm (0.10 %, p < 0.01). CONCLUSIONS: Hypervascular HCC rarely develops from hypovascular, hyperintense hepatic nodules. We observed low risk even for nodules of 10 mm and larger diameter at initial examination. KEY POINTS: • Hypervascularization was rare on follow-up examination of hypovascular, hyperintense nodules • The risk of hypervascularization in a nodule increased with large size • Hypovascular, hyperintense nodules require neither treatment nor more intense follow-up.

Morphophenotypic changes in human multistep hepatocarcinogenesis with translational implications.

BACKGROUND & AIMS: Human hepatocarcinogenesis in cirrhosis is thought to be multistep and characterized by a spectrum of nodular lesions, ranging from low to high grade dysplastic nodules (LGDN and HGDN) to early and progressed hepatocellular carcinoma (eHCC and pHCC). The aim of this study was to investigate the morphophenotypical changes of this sequence and their potential translational significance. METHODS: We scored the vascular profile, ductular reaction/stromal invasion and overexpression of five biomarkers (GPC3, HSP70, GS, CHC, and EZH2), in a series of 100 resected nodules (13 LGDN, 16 HGDN, 42 eHCC and 29 small pHCC). RESULTS: The score separated the four groups of nodules as individual entities (p<0.01). In the sequence, biomarker's overexpression progressively increased with parallel decrease of ductular reaction; the vascular remodeling started very early (LGDN) but did not further develop in a proportion of HCC. eHCC was the most heterogeneous entity, with marginal overlap with HGDN and pHCC. Liver environment (fibrosis, etiology) did not impact on the phenotype of the different nodules. A subclass of eHCC (16/42) without evidence of stromal invasion was identified, suggesting a "preinvasive stage" (p<0.05). For diagnosis, the application of four and five biomarkers (rather than the usual three) improved the sensitivity of the assay for the detection of eHCC (76% and 93% vs. 52%); biomarkers in alternative combinations, and also increased the sensitivity of the assay (GS+CHC+EZH2: 76%; GS+CHC+EZH2+HSP70: 90%). CONCLUSIONS: This study supports the multistep nature of human hepatocarcinogenesis, and suggests that eHCC is more heterogeneous than previously thought. This provides further information of the potential translational significance into clinical practice.

[Acute Hyperuricemia and Kidney Injury after Three Cycles of Dose-Dense Chemotherapy for Retroperitoneal Choriocarcinoma -- A Case Report].

CASE: A 32 year-old man was diagnosed with retroperitoneal choriocarcinoma with metastasis to the lungs and liver. One cycle of modified BEP regimen did not sufficiently decrease the hCG. Therefore, we chose the GETUG 13 protocol of dose dense chemotherapy. After 6 days of cisplatin administration(3 cycles), he was diagnosed with acute hyperuricemia and kidney injury. He was treated with intravenous hydration and rasburicase. The hyperuricemia improved after a few days.

MRI-based staging of hepatic fibrosis: Comparison of intravoxel incoherent motion diffusion-weighted imaging with magnetic resonance elastography.

PURPOSE: To evaluate the use of intravoxel incoherent motion (IVIM) imaging for staging hepatic fibrosis, and compare its staging ability with that of magnetic resonance elastography (MRE). MATERIALS AND METHODS: This study included 129 patients with pathologically staged liver fibrosis, and 53 patients with healthy livers. All patients underwent both MRE and IVIM imaging. Four diffusivity indices were calculated with 11 b-values; slow diffusion coefficient related to molecular diffusion (D), fast diffusion coefficient related to perfusion in micro-vessels (D*), perfusion-related diffusion fraction (f), and apparent diffusion coefficient (ADC). Receiver operating characteristic curve analysis was performed to determine the accuracy of IVIM imaging and MRE for staging hepatic fibrosis. RESULTS: D*, f, and ADC values decreased significantly with fibrosis stage (P < 0.0124), and liver stiffness increased (P < 0.0001). The Az value of MRE was significantly higher than that of D* for all fibrosis stages (D* vs. MRE for ≥ F1, 0.851 vs. 0.992 [P < 0.0001]; ≥ F2, 0.898 vs. 0.998 [P = 0.0003]; ≥ F3, 0.904 vs. 0.995 [P = 0.0004]; F4, 0.885 vs. 0.996 [P < 0.0001]). CONCLUSION: IVIM imaging is a useful technique for evaluating hepatic fibrosis, but MRE is better able to discriminate fibrosis stages than IVIM imaging.

Hepatitis activity should be considered a confounder of liver stiffness measured with MR elastography.

PURPOSE: To evaluate the effect of hepatitis activity on liver stiffness measurements and the role of serum alanine aminotransferase (ALT) in liver fibrosis staging by MR elastography (MRE). MATERIALS AND METHODS: We measured liver stiffness (kPa) in 135 patients by MRE and histologically assessed fibrosis and hepatitis activity within 2 months. Stepwise multiple linear regression was performed to determine the maximum adjusted R(2) against liver stiffness, after adjusting for nothing (model 1), ALT/upper limit of normal categories (model 2), and hepatitis activity (A grade) by METAVIR (model 3). Logistic regression was used to identify independent factors associated with pathologically proven cirrhosis. RESULTS: Platelet count and METAVIR F score were strongly associated with liver stiffness. The adjusted R(2) value of model 3 (0.7026) was higher than those of models 1 (0.6472) and 2 (0.6564), showing that hepatitis activity affected liver stiffness measurement. High ALT levels (odds ratio, 0.0066; P = 0.0003) as well as MRE (odds ratio, 9.91; P < 0.0001) were independently associated with cirrhosis. CONCLUSION: Hepatitis activity may be a confounder of liver stiffness measurement during liver fibrosis staging using MRE. MRE can potentially make an overdiagnosis of liver cirrhosis if the patient has high ALT levels.

Hepatic resection for hepatocellular carcinoma in a patient with situs ambiguous with polysplenia: report of a case.

We report a case of successful resection of hepatocellular carcinoma (HCC) in a patient with situs ambiguous with polysplenia (PS), a rare congenital anomaly. A 62-year-old Japanese man was admitted to our hospital for investigation and treatment of a hepatic tumor. Imaging studies revealed two HCCs, 2.5 and 0.7 cm in diameter, in the anterior section and segment 3 of the reversed liver, respectively. He also had multiple spleens in the right side of the abdomen, right side of the stomach, and duodenum, as well as azygous continuation of the inferior vena cava (IVC) with absence of the retro-hepatic IVC, a truncated pancreas, rare variation of the hepatic artery, and dextrocardia. We performed anterior sectionectomy of the liver and partial resection of segment 3. We found only two previous reports of HCC in patients with situs ambiguous with PS, but our patient is the first to have undergone anatomical hepatic resection of the reversed liver. Accurate anatomical assessment is essential during surgery on such patients.

Presence of a hypovascular hepatic nodule showing hypointensity on hepatocyte-phase image is a risk factor for hypervascular hepatocellular carcinoma.

PURPOSE: To determine whether the presence of a hypovascular nodule in the liver showing hypointensity on hepatocyte-phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) is a risk factor for hypervascular hepatocellular carcinoma (HCC) in patients with chronic liver disease. MATERIALS AND METHODS: Forty-one patients with pathologically confirmed hypervascular HCC and 41 age- and gender-matched controls were retrospectively selected. These patients had undergone EOB-MRI at least twice: the latest EOB-MRI and EOB-MRI performed more than 6 months earlier. History of hypervascular HCC, presence of a hypointense hypovascular nodule in previous hepatocyte-phase MR images, percent prothrombin time, platelet count, serum levels of albumin, total bilirubin, aspartate aminotransferase, alanine aminotransferase, α-fetoprotein, and protein induced by vitamin K absence-II (PIVKA-II) were variables evaluated by multivariate logistic regression analysis. RESULTS: Multivariate analysis revealed that serum albumin level (odds ratio [95% confidence interval], 0.19 [0.06-0.57]; P = 0.0024), history of hypervascular HCC (8.62 [2.71-32.8]; P = 0.0001), and presence of a hypointense hypovascular nodule (4.18 [1.18-17.2]; P = 0.0256) were significant risk factors for hypervascular HCC. CONCLUSION: Patients with chronic liver disease showing a hypointense hypovascular nodule in the liver on hepatocyte-phase EOB-MRI have a high risk of HCC development.

Typical fibrolamellar hepatocellular carcinoma in a Japanese boy: report of a case.

We report a case of typical fibrolamellar hepatocellular carcinoma (FL-HCC) in a 16-year-old Japanese boy. This is very rare malignancy in Japan. The patient was referred for investigation of a large hepatic tumor and the results of tests for hepatitis B virus surface antigen and hepatitis C virus antibody were negative. Liver function test results and serum alpha-fetoprotein (AFP) levels were normal; however, the prothrombin induced by vitamin K absence/antagonist II was elevated. Computed tomography (CT) showed a large lobulated heterogeneously enhanced tumor in the posterior section of the liver. We diagnosed FL-HCC and performed posterior sectionectomy of the liver. The resected specimen contained a light brown and green tumor with a central fibrous scar, 10.0 cm in diameter. Microscopic and electron microscopic examinations revealed the typical features of FL-HCC. Immunohistochemically, the tumor cells were positive for cytokeratin (CK) 7, but negative for CK19 and AFP. The patient was alive without recurrence 48 months after surgery. Following this case report, we summarize the clinical features of the Japanese cases documented in the literature.

[Virtual enteroscopy for the evaluation of stenosis in a case of chronic multiple ulcers of the small intestine].

A 39-year-old female presented to our hospital with diarrhea, vomiting, anemia, and hypoalbuminemia. Virtual enteroscopy was performed to evaluate the small bowel; we found annular stenoses at 89, 100, 116, 147, and 154 cm from the ligament of Treitz. Small bowel resection was performed, and annular ulcers were confirmed at 58, 71, 90, 130, 138, 218, and 225 cm from the ligament of Treitz. Clinical records and pathological examination failed to determine the cause of these ulcers, and we diagnosed chronic multiple ulcers of the small intestine. Thus, we believe that virtual enteroscopy can be beneficial in preoperatively diagnosing multiple ulcers and stenoses in the small bowel.

Prospective study on planned biliary stent placement to treat small common bile duct stones.

Aims: Small common bile duct stones are known to occasionally clear spontaneously. This study aimed to prospectively assess the role of biliary stent placement in promoting the spontaneous clearance of small common bile duct stones. Methods and Results: We analyzed patients presenting with common bile duct stones of ≤5 mm diameter between June 2020 and May 2022. The exclusion criteria included asymptomatic patients, biliary pancreatitis, altered gastrointestinal anatomy, bile duct strictures (malignant or benign), and a history of EST. The biliary stents were inserted without stone removal. Stone clearance was assessed using endoscopic ultrasonography or endoscopic retrograde cholangiopancreatography after 3 months. Our primary endpoint was the clearance rate of common bile duct stones over 6 months, targeting a lower limit for the 95% confidence interval (CI) exceeding 25%. Of the 32 enrolled patients, 18 (56.3%; 95% CI: 37.7-73.6%) exhibited stone clearance. Early complications occurred in 11 patients (34.4%), totaling 12 incidents: acute cholecystitis in four, acute pancreatitis in three, biliary pain in three, and cholangitis in two patients. No severe complications occurred. Six (18.8%) patients experienced asymptomatic stent migration. Following stone clearance, four (12.5%) patients experienced stone recurrence, with an average duration of 256 ± 164 days. Conclusion: Biliary stenting appeared to effectively promote the clearance of small common bile duct stones in approximately half of the patients. However, the potential complications and risks of stone recurrence warrant close monitoring.This trial was registered in the Japan Registry of Clinical Trials (jRCT1042200020).

Liver stiffness measured by magnetic resonance elastography as a risk factor for hepatocellular carcinoma: a preliminary case-control study.

OBJECTIVE: To examine if liver stiffness measured by magnetic resonance elastography (MRE) is a risk factor for hepatocellular carcinoma (HCC) in patients with chronic liver disease. METHODS: By reviewing the records of magnetic resonance (MR) examinations performed at our institution, we selected 301 patients with chronic liver disease who did not have a previous medical history of HCC. All patients underwent MRE and gadoxetic acid-enhanced MR imaging. HCC was identified on MR images in 66 of the 301 patients, who were matched to controls from the remaining patients without HCC according to age. MRE images were obtained by visualising elastic waves generated in the liver by pneumatic vibration transferred via a cylindrical passive driver. Risk factors of HCC development were determined by the odds ratio with logistic regression analysis; gender and liver stiffness by MRE and serum levels of aspartate transferase, alanine transferase, alpha-fetoprotein, and protein induced by vitamin K absence-II. RESULTS: Multivariate analysis revealed that only liver stiffness by MRE was a significant risk factor for HCC with an odds ratio (95 % confidence interval) of 1.38 (1.05-1.84). CONCLUSION: Liver stiffness measured by MRE is an independent risk factor for HCC in patients with chronic liver disease.

Early hepatocellular carcinomas showing isointensity or hyperintensity in gadoxetic acid-enhanced, hepatocyte-phase magnetic resonance images.

Hypointensity in the hepatocyte phase is believed to be a key feature of hypovascular early hepatocellular carcinoma, which indicates malignancy. The 3 cases we present suggest that the converse is not true. Three small hepatocellular lesions showed isointensity/hyperintensity on gadoxetic acid-enhanced, hepatocyte-phase magnetic resonance images and were pathologically confirmed as early hepatocellular carcinomas. We conclude that isointensity or hyperintensity in the hepatocyte phase does not always represent benignity of hepatocellular lesions in the cirrhotic liver.

[Locally advanced squamous cell carcinoma of the buttocks, which had complete remission induced by chemoradiotherapy with carboplatin].

The patient was a 72-year-old male who had locally advanced squamous cell carcinoma(10×7 cm)in his buttocks that developed 18 months prior to admission. The lesion was unresectable because of the size and its invasion to the sacrum. We performed concomitant chemoradiotherapy with curative intent. External beam radiotherapy(68 Gy)was given with weekly carboplatin(AUC 2)and paclitaxel(30mg/m2). Because he developed cellulites in the irradiated skin, the concurrent chemotherapy was stopped during treatment(at 10 Gy). After improvement of the cellulites, paclitaxel was switched to S-1(80 mg/body/day)and concurrent chemoradiotherapy was completed without further toxicities. Progression of the tumor outside the irradiated field was seen 4 months after the treatment. Four courses of carboplatin (AUC 5)+infusional 5-FU(1, 000mg/m2 day 1-4)was administered as the tumor regressed. He died of sepsis 36 months post-treatment but the tumor remained stable without progression. Chemoradiotherapy may be an option for locally advanced non-melanoma skin cancer.

Factors contributing to the overall survival in patients with hepatocellular carcinoma treated by sorafenib.

BACKGROUND/AIMS: In both SHARP and Asia-Pacific Study, sorafenib was proved to improve the overall survival of the patients with hepatocellular carcinoma. However, factors contributing to the improvement of overall survival of the patients treated by sorafenib have not been fully evaluated. In this study, patient-derived, background liver disease-derived and tumor-derived factors before treatment were evaluated whether they have contributed to the improvement of the overall survival. METHODOLOGY: Forty-seven cases with HCC treated by sorafenib between Sept 2009 and Feb 2011 were included in this analysis. The survival of these cases was analyzed by Kaplan-Meier Method. Factors used for univariate analysis were two patient-derived parameters, two background liver disease-derived, five tumor-derived. Factors related to the over-all survival were analyzed by multivariate analysis using Cox regression model. RESULTS: In the multivariate analysis, only background liver disease-derived parameter Child-Pugh class A vs. B, (p=0.007, HR=0.21 (0.07-0.65)) was significant. No other parameters including tumor-derived factors were statistically significant by multivariate analysis. CONCLUSIONS: We undertook the statistical analysis on the three categories. Surprisingly, no tumor derived parameter contributed to the overall survival. Background liver disease-derived parameter rather than tumor-derived parameter was found to define the prognosis of patients with advanced HCC treated by sorafenib.