Quantitative Ultrasound Image Analysis Helps in the Differentiation of Hepatocellular Carcinoma (HCC) From Borderline Lesions and Predicting the Histologic Grade of HCC and Microvascular Invasion.

OBJECTIVES: Quantitative image analysis is one of the methods to overcome the lack of objectivity of ultrasound (US). The aim of this study was to clarify the correlation between the features from a US image analysis and the histologic grade and microvascular invasion (MVI) of hepatocellular carcinoma (HCC) and differentiation of HCC smaller than 2 cm from borderline lesions. METHODS: We retrospectively analyzed grayscale US images with histopathologic evidence of HCC or a precancerous lesion using ImageJ version 1.47 software (National Institutes of Health, Bethesda, MD). RESULTS: A total of 148 nodules were included (borderline lesion, n = 31; early HCC [eHCC], n = 3; well-differentiated HCC [wHCC], n = 16; moderately differentiated HCC [mHCC], n = 79; and poorly differentiated HCC [pHCC], n = 19). A multivariate analysis selected lower minimum gray values (odds ratio [OR], 0.431; P = .003) and a higher standard deviation (OR, 1.880; P = .019) as predictors of HCC smaller than 2 cm. Median (range) minimum gray values of borderline lesions, eHCC, wHCC, mHCC, and pHCC were 29 (0-103), 7 (0-47), 6 (0-60), 10 (0-53), and 2 (0-38), respectively, and gradually decreased from borderline lesions to pHCC (P < 0.001). The multivariate analysis showed a higher aspect ratio (OR, 2.170; P = .001) and lower minimum gray value (OR, 0.475; P = .043) as predictors of MVI. An anechoic area diagnosed by a subjective evaluation was correlated with the minimum gray value (P < .0001). The proportion of the anechoic area gradually increased from eHCC to pHCC (P = .031). CONCLUSIONS: In a US image analysis, HCC smaller than 2 cm had features of greater heterogeneity and a lower minimum gray value than borderline lesions. Moderately differentiated HCC was smoother than borderline lesions, and the anechoic area correlated with histologic grading. Microvascular invasion was correlated with a slender shape and a lower minimum gray value.

Utility of Contrast-Enhanced Ultrasound for Early Therapeutic Evaluation of Hepatocellular Carcinoma After Transcatheter Arterial Chemoembolization.

OBJECTIVES: We aimed to investigate whether contrast-enhanced ultrasound (CEUS) could be useful for early evaluation of the treatment response to transcatheter arterial chemoembolization (TACE) of hepatocellular carcinoma (HCC). METHODS: This study retrospectively selected HCCs in which homogeneous retention of iodized oil was confirmed on non-contrast-enhanced computed tomography performed immediately after TACE. Therapeutic responses of HCCs were evaluated by CEUS 1 to 2 days after TACE and by contrast-enhanced computed tomography (CECT) approximately 4 weeks after TACE. We investigated the noninferiority of CEUS 1 to 2 days after TACE to CECT approximately 4 weeks after TACE in terms of the diagnostic accuracy of the therapeutic response to TACE on HCC. RESULTS: Eighty-nine HCCs were enrolled in this study between April 2014 and June 2016. A complete response was observed in 57 of 89 nodules (64.0%), and an incomplete response was observed in the remaining 32 nodules (36.0%). The accuracy rates for CEUS 1 to 2 days after TACE and CECT approximately 4 weeks after TACE in the therapeutic effect of TACE on HCCs were 83.1% (95% confidence interval, 73.7%-90.2%) and 83.1% (95% confidence interval, 73.7%-90.2%), respectively. The difference in diagnostic accuracy between methods was 0%, which was below the predetermined noninferiority limit of 15%, and CEUS 1 to 2 days after TACE was noninferior to CECT approximately 4 weeks after TACE. CONCLUSIONS: Our results suggest that CEUS is a useful modality for early therapeutic evaluation of TACE for HCC, and we can thus plan the next treatment strategies for HCC within a few days after TACE.

[Use of EUS-FNA in the diagnosis of hilar schwannoma:a case report].

Upon abdominal ultrasonography, a woman in her 36 years old was diagnosed with a hypoechoic tumor with a diameter of 60mm surrounding the bile duct in the hepatic portal region. Abdominal computed tomography and magnetic resonance cholangiopancreatography revealed a tumor-like mass in the bile duct. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) confirmed the diagnosis of schwannoma. Considering the lesion location, it appeared to rise from the hepatoduodenal ligament. She was unwilling to undergo tumor resection;however, a year after the diagnosis, no change was observed in the tumor. Here, we report a case of schwannoma in the hepatoduodenal ligament, wherein EUS-FNA was useful for establishing a diagnosis and determining a treatment strategy.

Renal vein dilation predicts poor outcome in patients with refractory cirrhotic ascites.

AIM: Renal venous hypertension is known to be associated with worsening of renal function in patients with decompensated heart failure. Intra-abdominal hypertension including cirrhotic ascites also leads to renal venous hypertension. We aimed to clarify the effect of renal venous hypertension on cirrhotic ascites. METHODS: Two hepatologists measured the left renal vein diameter in 142 consecutive patients with refractory cirrhotic ascites using non-contrast computed tomography. The renal vein diameter was measured at the renal vein main trunk and upstream of the confluence of collateral veins. RESULTS: The inter-observer agreements were high for the measurements of the left renal vein (r = 0.918, P < 0.001). The median overall survival for patients with renal vein diameter ≥11 mm was less than that for patients with renal vein diameter <11 mm (P < 0.001; 2.5 vs. 32.0 months). One-year survival rates were 15.3% versus 66.4%. Multivariate analysis revealed renal vein diameter ≥11 mm (hazard ratio, 2.94; P < 0.001; 95% confidence interval, 1.67-5.20) and a high Model for End-stage Liver Disease score combined with serum sodium level (MELD-Na) (hazard ratio, 3.39; P < 0.001; 95% confidence interval, 2.00-5.74) were significant independent predictors of mortality. CONCLUSIONS: Renal vein dilation is a risk factor of mortality in patients with refractory cirrhotic ascites, independent of the MELD-Na score.

Efficacy of a microballoon catheter in transarterial chemoembolization of hepatocellular carcinoma using miriplatin, a lipophilic anticancer drug: Short-term results.

AIM: The goal of the study was to evaluate the efficacy and safety of balloon-occluded transarterial chemoembolization (B-TACE) of hepatocellular carcinoma (HCC) using miriplatin (a lipophilic anticancer drug) and gelatin particles. METHODS: B-TACE was performed for 62 HCC nodules in 33 patients who could not be treated by surgical resection or radiofrequency ablation. All 33 patients had a history of transarterial chemoembolization (TACE) treatment prior to B-TACE. As a historical comparison, we investigated 40 nodules in 28 patients treated by TACE using a conventional microcatheter (C-TACE), miriplatin and gelatin particles. The therapeutic effect per tumor was compared between the groups based on the Response Evaluation Criteria in Cancer Study Group of Japan (RECICL) and side-effects were compared based on the Common Terminology Criteria for Adverse Events (ver. 4.0). RESULTS: The therapeutic efficacy after 4-12 weeks was evaluated in 59 nodules in the B-TACE group and in 37 nodules in the C-TACE group. Of these nodules, TE4 occurred in 29 (49.2%) in the B-TACE group and in 10 (27%) in the C-TACE group. Local efficacy was significantly higher in nodules treated by B-TACE than by C-TACE. The side-effects on hepatic function were similar in the two groups. CONCLUSION: Our results suggest that B-TACE with miriplatin is a useful treatment for hepatocellular carcinoma.

A case of miriplatin-induced lung injury.

A 69-year-old man with an 8-year history of hepatocellular carcinoma (HCC) was hospitalized for treatment of recurrent tumour. In 2010, the first transcatheter arterial chemoembolization (TACE) using miriplatin with agents (Lipiodol Ultra-Fluid) was performed and did not occur any adverse events. In 2014, since his HCC recurred, the TACE using miriplatin with agents was performed. Following this therapy, pyrexia occurred on day 3, followed by respiratory failure with cough and dyspnea on day 5. Chest radiography revealed scattered infiltration in the right upper lung fields, and chest computed tomography revealed ground grass attenuations, indicating fibrotic non-specific interstitial pneumonia. These findings progressively deteriorated, and a diagnosis of miriplatin-induced lung injury was made. His respiratory failure also progressively deteriorated. Treatment with pulse methylprednisolone therapy resulted in a dramatic improvement in both patient symptoms and radiological abnormalities.

[A case of acute progressive primary inflammatory fibrosarcoma of the retroperitoneum].

A 70-year-old man with liver cirrhosis presented to us with abdominal distention. Computed tomography revealed a giant retroperitoneal tumor. Examination of a biopsy specimen led to a diagnosis of primary inflammatory fibrosarcoma of the retroperitoneum. However, disease progression was rapid, and the patient died 6 weeks after the onset of the disease. Autopsy revealed that the tumor arose from the retroperitoneum and infiltrated the omentum and mesentery. Prognosis of inflammatory fibrosarcoma is poor if resection is incomplete. Establishment of treatment for unresectable cases is necessary.

B-flow imaging of vascular structure for the diagnosis of liver tumor.

PURPOSE: B-flow is a non-Doppler-based technology for visualizing blood flow and has a high spatial resolution. The aim of this study is to evaluate the blood flow information of liver tumors using B-flow in comparison with color Doppler sonography (CDS). METHODS: Seventy-nine patients with 82 hepatic nodules were studied using B-flow and CDS. The study group included 45 HCC nodules, 23 liver metastasis nodules, four intrahepatic cholangiocarcinomas (ICC), and 13 hemangiomas. The visualized vascularity and morphological findings of the hepatic tumor vessel were evaluated. RESULTS: B-flow showed multiple vessels in 48 nodules (58.5 %) and a single vessel in 13 nodules (15.9 %). CDS showed multiple vessels in 44 nodules (53.7 %) and a single vessel in 23 nodules (28.0 %). Multivariate analysis showed basket pattern was significant for HCC (OR 49.263; p = 0.0002), and penetrating vessel was significant for liver metastasis or ICC (OR 14.545; p < 0.0001). CONCLUSION: B-flow detects hepatic tumor blood flow with sensitivity as high as that of CDS. Vascular structure information obtained using B-flow could be potentially used to diagnose liver tumors.

Ultrasonographic grayscale findings related to fibrosis in patients with non-alcoholic fatty liver disease: comparison with transient elastography and Fib-4 index.

PURPOSE: Fibrosis is a predictor of mortality in patients with non-alcoholic fatty liver disease (NAFLD). In our institution, abdominal ultrasonography has been performed based on a unified method consisting of 25 images. We investigated ultrasonographic grayscale findings related to fibrosis in patients with NAFLD. METHODS: This retrospective study comprised 41 cases of pathologically proven fatty liver between January 2015 and September 2020. A total of 26 ultrasonographic findings were subjectively evaluated. These findings, transient elastography (TE) with M probe, and FIB-4 index were compared with fibrosis stage. RESULTS: The frequency of roughness of the dorsal side of the surface (p < 0.001), heterogenicity of the parenchyma (p = 0.003), narrowing of the hepatic vein (p = 0.004), and splenomegaly (p < 0.001) were strongly correlated with the fibrosis stage. Logistic regression analysis for stage ≥ 3 showed narrowing of the hepatic vein (odds ratio [OR] 5.860, p = 0.031) and splenomegaly (OR 6.290, p = 0.028). Logistic regression analysis for stage 4 showed roughness of the ventral side of the surface (OR 42.0, p = 0.019). The AUROC for stage 3 and stage 4 with the number of positive ultrasonographic findings was 0.856, and 0.940, respectively. The AUROC for F3 and F4 with TE was 0.831 and 0.861, respectively. The AUROC for stage 3 and stage 4 with FIB-4 index was 0.815 and 0.806, respectively. CONCLUSIONS: Narrowing of the hepatic vein, roughness of the dorsal side of the surface, heterogenicity of the parenchyma, and splenomegaly and their combination could predict fibrosis in patients with NAFLD.

Treatment Outcome of Nab-paclitaxel Plus Gemcitabine for Leptomeningeal Carcinomatosis from Pancreatic Ductal Adenocarcinoma: An Autopsy Case Report.

A 57-year-old woman with a sudden-onset seizure was hospitalized. Brain magnetic resonance imaging findings led to a suspicion of leptomeningeal carcinomatosis (LMC) without a brain parenchymal tumor, and abdominal computed tomography showed a tumor in the pancreatic tail. Endoscopic ultrasonography-guided fine needle aspiration of the pancreatic mass revealed adenocarcinoma. Therefore, LMC from pancreatic ductal adenocarcinoma was strongly suspected. She received three courses of nab-paclitaxel plus gemcitabine and whole-brain radiation. Shortly thereafter, she developed a severe consciousness impediment and died. A pathological autopsy showed adenocarcinoma in a wide area of the leptomeninges.

Renal vein measurement using ultrasonography in patients with cirrhotic ascites and congestive heart failure.

PURPOSE: Ascites can cause compression of the inferior vena cava (IVC), leading to increased renal venous pressure and renal congestion. Previously, the left renal vein diameter in liver cirrhosis patients with ascites was measured using computed tomography, showing that enlargement of the left renal vein diameter affects the prognosis. Herein, the diameter and flow velocity of the renal veins were measured using ultrasonography. METHODS: Abdominal ultrasonography was performed on 186 patients. The patients were divided into four groups: normal liver (n = 102), liver cirrhosis (LC) without ascites (n = 37), LC with ascites (n = 30), and congestive liver (n = 17). Ultrasonographic measurements for diameter and flow velocity of the IVC, left renal vein main trunk, and segmental renal vein were performed. RESULTS: The left renal vein diameter increased in the following order: normal liver, LC, LC with ascites, and congestive liver groups (P < 0.001). IVC flow velocity was lower and left renal vein diameter was larger in the congestive liver and LC with ascites groups. These results suggest that the two groups have different pathological conditions, but the mechanism of renal congestion is similar. In patients with LC, IVC compression due to ascites might cause blood stagnation and renal congestion. CONCLUSION: The left renal vein and IVC can be measured using ultrasonography. It might help in furthering our understanding of the pathophysiology of renal congestion in these patients.

Comparison of local recurrence in transcatheter arterial chemoembolization of hepatocellular carcinoma with or without accumulation of iodized oil beyond corona enhancement area: Short-term results.

BACKGROUND: Local tumor recurrence of hepatocellular carcinoma (HCC) often occurs in blood drainage areas. Corona enhancement is determined by computed tomography during hepatic arteriography (CTHA) and is considered to represent the blood drainage area. This study aimed to investigate the relationship between embolization of corona enhancement area and local tumor recurrence of patients with HCC who underwent transcatheter arterial chemoembolization (TACE). PATIENTS AND METHODS: The study retrospectively selected 53 patients with 60 HCC nodules that showed corona enhancement area on late-phase CTHA and showed homogenous accumulation of iodized oil throughout the nodule on non-contrast-enhanced CT performed immediately after TACE. We divided the nodules into two groups, according to whether the accumulation of iodized oil covered the entire corona enhancement area (group A) or not (group B). Local tumor recurrence was compared between the two groups. RESULTS: The cumulative local tumor recurrence rates for group A (n = 36) were 2.8%, 2.8%, 8.3% at 3, 6, and 12 months, respectively, whereas the recurrence rates for group B (n = 24) were 20.8%, 45.8%, 75% at 3, 6, and 12 months, respectively. The cumulative local tumor recurrence rates for group A were significantly lower than those for group B (hazard ratio, 0.079; 95% confidence interval, 0.026-0.24; p < 0.001). CONCLUSIONS: The results of the study suggest that the corona enhancement area may be an accurate safety margin in TACE which should be performed until the embolic area covers the entire corona enhancement area.

The influence of esophagogastroduodenoscopy using carbon dioxide insufflation on abdominal ultrasonographic imaging efficiency.

PURPOSE: The ability to perform abdominal ultrasonography after esophagogastroduodenoscopy (EGD) is hypothesized to improve examination efficiency. Therefore, we performed abdominal ultrasonography before and after EGD to verify the effects of EGD on abdominal ultrasonographic imaging efficiency. METHODS: We performed abdominal ultrasonography before, immediately after, 30 min after, and 60 min after EGD with carbon dioxide (CO2) insufflation in 23 consecutive patients who visited our center between July 2015 and December 2016. We examined the visualization status of the head, body, and tail of the pancreas; extrahepatic bile duct; and inferior pole of the right kidney. RESULTS: The visualization status of the pancreas decreased immediately after EGD in approximately 50% of patients; however, at 30 min and after, the status was almost the same as for imaging performed before endoscopy. Visualization of the extrahepatic bile duct decreased slightly immediately after the procedure; however, 30 min and later, it was almost the same as before endoscopy. The inferior pole of the right kidney was observable from the dorsal side and could be visualized at all examination points in all patients. CONCLUSION: There was no difficulty in performing abdominal ultrasonography at 30 min or later following EGD with CO2 insufflation. Additionally, visualization of the head, body, and tail of the pancreas as well as the extrahepatic bile duct was improved in some patients.

Spontaneous Development of Acute Obstructive Suppurative Pancreatic Ductitis Associated with Pancreatic Carcinoma: A First Case Report.

A 68-year-old man with a history of diabetes mellitus was admitted to our hospital with a diagnosis of acute pancreatitis. Abdominal computed tomography revealed a suspicious tumor in the body of the pancreas, along with a dilated main pancreatic duct and edema of the pancreatic tail. Endoscopic retrograde pancreatography was performed after treating the patient's pancreatitis. When a cannula tip was advanced beyond the stenosis, deep into the distal pancreatic duct, thick white pus was evacuated. A bacteriological examination of the aspirated pancreatic juice revealed Enterobacter cloacae, and a cytological examination revealed adenocarcinoma. The diagnosis was acute obstructive suppurative pancreatic ductitis associated with pancreatic carcinoma.

Evaluation of malignancy of hepatocellular carcinoma using the ultrasonic B-mode method: clinical significance of extracapsular invasion of hepatocellular carcinoma using ultrasonography.

PURPOSE: To determine the influence of capsule formation or presence of capsular invasion on the prognosis of hepatocellular carcinoma (HCC) patients. METHODS: The patient group consisted of 70 patients with 74 HCC lesions who had been examined by US and undergone surgical tumor resection at our institution. For these patients, we conducted the following comparative studies: (a) comparison between halo findings on US and microscopic capsular results; (b) comparison between halo findings on US and tumor diameter, tumor histological differentiation, and serum value of each tumor marker; and (c) comparison between halo findings on US and tumor recurrence. RESULTS: (a) The corresponding value between sonographic halo and histological capsule was 90.1%, and that between presence of extracapsular invasion on US and that seen by histology was 88.0%. (b) There was no relation between US images and histological differentiation of tumors. (c) Presence of extracapsular invasion on US was a predisposing factor for the development of tumor recurrence. CONCLUSION: (1) Globally speaking, sonographic halo corresponded to the histological tumor capsule. (2) In patients with extracapsular invasion, tumor recurrence after treatment increased. Thus, a better understanding of sonographic halo findings helps determine diagnostic and therapeutic strategies in HCC patients.

Clinical efficacy of contrast-enhanced ultrasonography (CEUS) in the diagnosis of ruptured hepatocellular carcinoma (HCC).

PURPOSE: To evaluate the role of contrast-enhanced ultrasonography (CEUS) in the diagnosis of ruptured hepatocellular carcinoma (HCC). METHODS: CEUS and angiography were performed in ten cases of ruptured HCC. We evaluated whether this technique allowed us to determine the bleeding point by observing an extravasation of contrast media into the ascites. RESULTS: In four of the ten cases, CEUS demonstrated an extravasation of Levovist into ascites. Angiography showed an extravasation of contrast medium in three of these four cases. In three of the remaining six cases, in which CEUS did not show the presence of contrast medium in ascites, angiography demonstrated an extravasation. In eight cases, it yielded cessation of bleeding. In two cases, embolization was not successful. The bleeding point was not determined by CEUS or angiography in one case. CONCLUSION: CEUS allows us to differentiate active bleeding (presence of contrast medium in the ascites) from nonactive bleeding.

Severe Hypertriglyceridemia Possibly Masked Acute Pancreatitis and Led to a Difficult Diagnosis in an Obese Patient with Ketoacidosis-onset Type 2 Diabetes.

A young obese man with ketoacidosis-onset type 2 diabetes mellitus, associated with severe hypertriglyceridemia, was admitted to a local hospital complaining of abdominal pain. Although the abdominal pain worsened, his serum amylase level remained normal with persistent severe hypertriglyceridemia until the second day of hospitalization. The next day, computed tomography showed severe acute pancreatitis (AP) with serum amylase elevation, while the patient's triglyceride level decreased to 558 mg/dL. He was transferred to our hospital and recovered after intensive care. AP accompanied by diabetic ketoacidosis is not rare but an early diagnosis can be difficult to make due to normal amylase levels in the presence of severe hypertriglyceridemia.

Solitary Variceal Rupture in the Small Intestine.

A 70-year-old man was referred to our hospital to undergo treatment for hepatocellular carcinoma. In hospital, he complained of hematochezia and a laboratory analysis revealed a decreased level of hemoglobin. Abdominal computed tomography revealed a tumor in the small intestine, with slow enhancement of the dorsal region. Double-balloon enteroscopy revealed a submucosal tumor with a depression in the jejunum. Partial enterectomy was performed and a pathological examination demonstrated the presence of a solitary varix. Solitary varix in the small intestine has not been reported previously. We herein report an extremely rare case of solitary varix in the jejunum.

Contrast-enhanced ultrasonographic findings of serum amyloid A-positive hepatocellular neoplasm: Does hepatocellular adenoma arise in cirrhotic liver?

Hepatocellular adenoma (HCA) was recently classified into four pathological subtypes. There have been few studies describing the findings of contrast-enhanced ultrasonography (CEUS) of each type. Our case concerns a 78-year-old man who had undergone routine medical check-ups for hepatitis C for 11 years. Abdominal ultrasonography showed a 28 mm, hypo-echoic mass in the segment 4 of the liver. His integrating amount of drinking was 670 kg convert into ethanol. CEUS with Sonazoid demonstrated mild uniform hypo-enhancement with inflow of microbubbles from the periphery of the tumor in the arterial phase, and heterogeneously hypo-enhancement in the post vascular phase. Because the mass increased in size within 3 mo, a well differentiated hepatocellular carcinoma was suspected, and hepatic resection was performed. Microscopic findings showed homogeneous cell proliferation with low grade atypia, infiltration of inflammatory cells, ductular reactions, fatty deposit in part, and sinusoidal dilation. Immunohistochemistry revealed geographic positive for serum amyloid A (SAA), focal positive for glutamine synthetase, diffuse and strong positive for C-reactive protein, and positive for liver-type fatty acid binding protein. These pathological features corresponded to that of an inflammatory HCA. However, we could not make a clear diagnosis, because HCAs were defined as not to arise in cirrhotic liver. Finally, this tumor was diagnosed as a SAA positive hepatocellular neoplasm.

Quantitative sonographic image analysis for hepatic nodules: a pilot study.

PURPOSE: The aim of this study was to investigate the feasibility of quantitative image analysis to differentiate hepatic nodules on gray-scale sonographic images. METHODS: We retrospectively evaluated 35 nodules from 31 patients with hepatocellular carcinoma (HCC), 60 nodules from 58 patients with liver hemangioma, and 22 nodules from 22 patients with liver metastasis. Gray-scale sonographic images were evaluated with subjective judgment and image analysis using ImageJ software. Reviewers classified the shape of nodules as irregular or round, and the surface of nodules as rough or smooth. RESULTS: Circularity values were lower in the irregular group than in the round group (median 0.823, 0.892; range 0.641-0.915, 0.784-0.932, respectively; P = 3.21 × 10(-10)). Solidity values were lower in the rough group than in the smooth group (median 0.957, 0.968; range 0.894-0.986, 0.933-0.988, respectively; P = 1.53 × 10(-4)). The HCC group had higher circularity and solidity values than the hemangioma group. The HCC and liver metastasis groups had lower median, mean, modal, and minimum gray values than the hemangioma group. Multivariate analysis showed circularity [standardized odds ratio (OR), 2.077; 95 % confidential interval (CI) = 1.295-3.331; P = 0.002] and minimum gray value (OR 0.482; 95 % CI = 0.956-0.990; P = 0.001) as factors predictive of malignancy. The combination of subjective judgment and image analysis provided 58.3 % sensitivity and 89.5 % specificity with AUC = 0.739, representing an improvement over subjective judgment alone (68.4 % sensitivity, 75.0 % specificity, AUC = 0.701) (P = 0.008). CONCLUSION: Quantitative image analysis for ultrasonic images of hepatic nodules may correlate with subjective judgment in predicting malignancy.