Relevance of liver surface nodularity for preoperative risk assessment in patients with resectable hepatocellular carcinoma.

BACKGROUND: Quantification of liver surface nodularity (LSN) on routine preoperative CT images allows detection of cirrhosis and clinically significant portal hypertension. This study aimed to assess the relevance of LSN in preoperative assessment of operative risks for patients with resectable hepatocellular carcinoma (HCC). METHODS: All patients undergoing hepatectomy for HCC between 2012 and 2017 were analysed retrospectively. LSN was assessed at the liver-fat interface on the left liver lobe on preoperative CT images. The feasibility of LSN quantification was assessed. The association between LSN and outcomes (severe complications and posthepatectomy liver failure (PHLF)) was evaluated by multivariable analysis and after propensity score matching. RESULTS: Among 210 patients, LSN measurement was successful in 187 (89·0 per cent). Among these, the median LSN score was 2·42 (i.q.r. 2·21-2·66) and 52·9 per cent had severe fibrosis, including 33·7 per cent with cirrhosis. LSN score increased with hepatic venous pressure gradient (P = 0·048), severity of steatosis (P = 0·011) and fibrosis grade (P = 0·001). LSN score was independently associated with severe complications (odds ratio (OR) 5·25; P = 0·006) and PHLF (OR 6·78; P = 0·003). After matching with respect to model for end-stage liver disease, aspartate aminotransferase-to-platelet ratio index and fibrosis-4 score, patients with a LSN score of 2·63 or higher retained an increased risk of PHLF (OR 5·81; P = 0·018). In the subgroup of patients without severe fibrosis, LSN was accurate in predicting severe complications (P = 0·005). Patients with (P = 0·039) or without (P = 0·018) severe fibrosis with increased LSN score had a higher comprehensive complication index score. Among patients with cirrhosis who had clinically significant portal hypertension, a LSN value below 2·63 ruled out the risk of PHLF. CONCLUSION: LSN measurement represents a practical tool that may allow improvement in the preoperative evaluation and management of patients with HCC.

ANTECEDENTES: La cuantificación de la nodularidad de la superficie hepática (liver surface nodularity, LSN) en las imágenes de la tomografía computarizada (TC) de rutina preoperatoria permite detectar la cirrosis y la hipertensión portal clínicamente significativa (clinically significant portal hypertension, CSPH). Este estudio tuvo como objetivo evaluar la relevancia de la LSN en la evaluación preoperatoria del riesgo quirúrgico en pacientes con carcinoma hepatocelular resecable (hepatocellular carcinoma, HCC). MÉTODOS: Todos los pacientes sometidos a hepatectomía por HCC entre 2012 y 2017 fueron analizados de forma retrospectiva. La LSN se evaluó en la interfase hígado-grasa en el lóbulo hepático izquierdo en la TC preoperatoria. Se evaluó la viabilidad de la cuantificación de la LSN. La asociación entre la LSN y los resultados (complicaciones graves e insuficiencia hepática poshepatectomía (post-hepatectomy liver failure, PHLF) se analizó en un análisis multivariable y después del método de emparejamiento por puntaje de propensión. RESULTADOS: Del total de 210 pacientes, la medición de la LSN fue exitosa en 187 (89,0%). En estos pacientes, la mediana de LSN fue de 2,42 (rango intercuartílico 2,21-2,66) y el 53,0% tenía fibrosis severa, incluyendo un 33,7% con cirrosis. La LSN aumentó con el gradiente de presión venosa hepática (P = 0,048), la gravedad de la esteatosis (P = 0,011) y el grado de fibrosis (P = 0,001). La LSN se asoció de forma independiente con complicaciones graves (razón de oportunidades, odds ratio, OR = 5,25; P = 0,006) y PHLF (OR = 6,78; P = 0,003). Después de emparejar para el modelo de enfermedad hepática terminal, el índice de relación aspartato amino transferase-plaquetas y el grado de fibrosis-4, los pacientes con LSN ≥ 2,63 mantuvieron un mayor riesgo de PHLF (OR = 5,81; P = 0,018). Dentro del subgrupo de pacientes sin fibrosis severa, la LSN fue precisa en predecir complicaciones graves (P = 0,005). Los pacientes con (P = 0,039) y sin (P = 0,018) fibrosis severa con aumento de la LSN tuvieron un índice de complicación global más alto. De los pacientes cirróticos con CSPH, un valor de LSN de 2,63 descartó el riesgo de PHLF. CONCLUSIÓN: La LSN representa una herramienta práctica, que puede permitir mejorar la evaluación preoperatoria y el manejo de pacientes con HCC.

Elevation of serum thioredoxin levels in patients with type 2 diabetes.

To evaluate the clinical significance of thioredoxin in diabetic patients, serum thioredoxin levels measured with a recently established sandwich enzyme-linked immunosorbent assay kit were compared with clinical laboratory data and complications in 174 patients with Type 2 diabetes. Thioredoxin levels were significantly higher in diabetic patients (mean value, 38 ng/ml) than in healthy controls (21 ng/ml) (p < 0.05). Fasting blood sugar and hemoglobin A1c did not correlate with thioredoxin. Plasma non-esterified fatty acids levels were significantly higher in patients with higher thioredoxin levels (>or= 40 ng/ml) than in those with lower thioredoxin levels (< 40 ng/ml) (p < 0.001). There was a significant correlation both between thioredoxin and non-esterified fatty acids in patients with diet/exercise therapy (p < 0.01) and between thioredoxin and fasting immunoreactive insulin in those treated with diet/exercise or oral hypoglycemic agents (p < 0.05). Thioredoxin did not correlate with diabetic complications. In conclusion, serum thioredoxin levels may reflect the status of insulin resistance in Type 2 diabetic patients.

Serum thioredoxin elucidates the significance of serum ferritin as a marker of oxidative stress in chronic liver diseases.

BACKGROUND/AIMS: Serum thioredoxin (TRX) levels have recently been established as an indicator of oxidative stress in various diseases. The aim of the present study was to clarify the clinical significance of serum ferritin in chronic liver diseases. METHODS: Levels of ferritin, transferrin saturation (TS), aspartate aminotransferase (AST), and TRX were measured in the sera of patients with chronic hepatitis C (CH-C, n=92), chronic hepatitis B (CH-B, n=28), nonalcoholic fatty liver (FL, n=31), or alcoholic liver diseases (ALD, n=17). Serum TRX levels were evaluated with a recently established sandwich enzyme-linked immunosorbent assay kit. RESULTS: Serum TRX levels were significantly higher in CH-C, FL, and ALD than in healthy volunteers. A larger proportion of patients with CH-C, FL, and ALD had elevated levels of serum ferritin than CH-B. Serum ferritin levels were positively correlated with levels of TS, AST, and TRX in CH-C, but were merely correlated with TS values in CH-B. Ferritin levels were also well correlated with AST and TRX, but not with TS in FL and ALD. CONCLUSION: Oxidative stress, which was evaluated by measuring serum TRX, in addition to storage iron and hepatocyte damage is a cause of increasing serum ferritin levels in chronic liver diseases. An elevated serum ferritin level, which was correlated with TS, indicates that iron-induced oxidative stress contributes to CH-C. Elevated ferritin levels in FL and ALD may be mostly due to iron-unrelated stresses.

Differences in the efficacy of ursodeoxycholic acid and bile acid metabolism between viral liver diseases and primary biliary cirrhosis.

AIM AND METHODS: The effects of ursodeoxycholic acid (UDCA, 600 mg/day) on liver function test values, and serum and urinary bile acids levels in hepatitis C virus-related chronic hepatitis (CH, n = 39) and liver cirrhosis (LC, n = 25), and in primary biliary cirrhosis (PBC, n = 25) were compared. RESULTS: The percentages of improvement in alanine transaminase (ALT) and gamma-glutamyl transpeptidase (gamma-GTP) in CH were almost the same in LC. The rates of improvement in ALT in PBC were negatively correlated with histological stages in the liver. Total serum bile acid levels in LC rose to the same extent as in CH, but the increases in PBC were significantly smaller at stages 3-4 than stages 1-2. The urinary levels of hydroxylated metabolites of UDCA only slightly increased in LC, but they increased significantly at PBC stages 3-4. CONCLUSIONS: The efficacy of UDCA was preserved in LC, but diminished at PBC stages 3-4. The poor enrichment of UDCA in the bile acid pool and extensive biotransformation of UDCA may cause the limited efficacy of UDCA in the cirrhotic stage of PBC.

Serum thioredoxin levels as an indicator of oxidative stress in patients with hepatitis C virus infection.

BACKGROUND/AIM: It has recently been suggested that oxidative stress may be associated with hepatitis C virus (HCV) infection. Thioredoxin (TRX) is a stress-inducible thiol-containing protein. The aim of this study was to evaluate the clinical significance of serum TRX levels in patients with HCV-related chronic liver diseases. METHODS: Serum TRX levels were determined with a sandwich enzyme-linked immunosorbent assay kit in 174 serum HCV-RNA positive patients, including 6 asymptomatic carriers, 124 chronic hepatitis, 20 liver cirrhosis, and 24 hepatocellular carcinoma, and in 15 healthy volunteers. RESULTS: The serum TRX levels (medians and [ranges], ng/ml) were significantly elevated in the HCV-infected patients; 30.9 [20.7-37.7] in asymptomatic carriers, 34.5 [8.6-135.6]* in chronic hepatitis, 42.5 [21.4-97.2]* in liver cirrhosis, and 43.9 [11.7-180.3]** in hepatocellular carcinoma (*p<0.05, **p<0.001, vs. 24.9 [1.3-50.7] in healthy controls). Serum TRX levels were significantly correlated with the serum levels of ferritin and fibrogenesis markers, and with the histological stage of hepatic fibrosis. The serum TRX levels before interferon treatment of patients whose serum HCV-RNA was still positive on day 14 following interferon treatment (42.6 [20.1-90.0]) were significantly higher than those of patients whose serum HCV-RNA was negative on day 14 following interferon treatment (25.8 [7.4-59.8], p<0.05). CONCLUSIONS: The serum TRX levels of patients with HCV infection increased with their serum ferritin levels and the progression of liver fibrosis. Patients with higher serum TRX levels exhibited resistance to interferon therapy. Oxidative stress may therefore be responsible for the pathological mechanism of HCV-related liver diseases and be one of the impediments to eradication of HCV during interferon treatment.

Thioredoxin levels in the sera of untreated viral hepatitis patients and those treated with glycyrrhizin or ursodeoxycholic acid.

Thioredoxin (TRX), a thiol-containing protein, is induced by various oxidative stresses. Serum TRX levels were measured with a sandwich enzyme-linked immunosorbent assay kit in 210 hepatitis C virus (HCV)-infected patients, 39 hepatitis B virus (HBV)-infected patients, and 17 healthy volunteers. The effects of hepatoprotective drugs on TRX levels were also examined. The median TRX levels were significantly higher in HCV-infected patients than in controls (34.2 vs. 23.5 ng/ml, respectively; p < 0.005), but were not elevated in HBV-infected patients (26.7 ng/ml). The TRX levels were significantly correlated with serum lipid peroxide levels and indocyanine green exclusion test values, and were markedly decreased following treatment with Stronger Neo-Minophagen C or ursodeoxycholic acid. In conclusion serum TRX levels, a marker of oxidative stress, were higher in patients with HCV infection than those with HBV infection and healthy controls. The therapeutic efficacy of hepatoprotective drugs may be connected with the decrease in oxidative stress in hepatitis patients.

Ursodeoxycholic acid protects hepatocytes against oxidative injury via induction of antioxidants.

The therapeutic efficacy of ursodeoxycholic acid (UDCA) has been widely demonstrated in various liver diseases, suggesting that UDCA might protect hepatocytes against common mechanisms of liver damage. A candidate for such protection is oxidative injury induced by reactive oxygen species. This study was designed to assess the effects of UDCA on oxidative injury and antioxidative systems in cultured rat hepatocytes. The viability of the hepatocytes dose-dependently decreased after hydrogen peroxide or cadmium administration. Pretreatment with UDCA significantly prevented this decrease in viability. The amounts of glutathione (GSH) and protein thiol increased significantly, but the activities of antioxidative enzymes such as superoxide dismutase, glutathione peroxidase and catalase were unchanged in UDCA-treated hepatocytes. The mRNA levels of gamma-glutamylcysteine synthetase and metallothionein (MT) were significantly higher in UDCA-treated hepatocytes than in controls. In conclusion, UDCA increased hepatocyte levels of GSH and thiol-containing proteins such as MT, thereby protecting hepatocytes against oxidative injury. Our results provide a new perspective on the hepatoprotective effect of UDCA.

Transfer of nitric oxide from the liver to erythrocytes--an ESR study using nitroglycerin-treated mice.

Nitric oxide (NO) formation in the liver and blood of the mouse following intraperitoneal treatment with nitroglycerin (glycerol trinitrate, GTN) was determined using electron spin resonance (ESR) spectroscopy. ESR signals of heme-NO complexes were detected at maximum levels within 5 min in the liver, but increased to a maximum level about 15-30 min later in the blood. GTN is not metabolized to release NO in vitro in the blood of the mouse. The hepatic microsomes which showed the heme-NO complexes ESR signals were incubated with mouse erythrocytes, with the result that a hemoglobin-NO signal was obtained from the erythrocytes. The activities of microsomal cytochrome P-450, the hepatic level of glutathione, and the reduction rate of nitroxide radicals in the in vivo liver, measured using L-band ESR spectroscopy, were temporarily decreased following GTN administration. In conclusion, NO in the liver could be scavenged by circulating erythrocytes, which might minimize NO-induced liver damage.

[Conservative treatment of postoperative chylothorax in a patient with chronic traumatic aneurysm of thoracic aorta].

A 66-year-old male was admitted to our hospital because of a chronic traumatic aneurysm of the thoracic aorta caused by a traffic accident 5 years earlier. Although he had been treated successfully by patch closure under extracorporeal circulation, chylothorax gradually manifested 9 days after the operation. The fact that our conservative treatment resulted in complete recovery from chylothorax, strongly suggested that progress of nutriology was a contributing factor.

[A case of old pulmonary tuberculosis with repeated hemoptysis which presented therapeutic difficulties].

A 74-year-old male who had been infected with pulmonary tuberculosis since 1938 underwent thoracoplasty in 1955. After the operation, no symptoms manifested until 1988 when he developed hemosputum and hemoptysis in association with a cold with fever. Although he was admitted to a hospital, the symptoms could not be controlled, so he was referred to our department. The lesion causing the hemorrhage was considered to be in the upper lobe of the left lung. However, it would have been difficult to preserve respiratory function in the case of left upper lobectomy, because he had already undergone thoracoplasty on the right side. Therefore, bronchial artery embolization (BAE) using Spongel was performed. Second embolization was performed because hemoptysis referred after one month. However, the hemoptysis recurred again, so that two branches of the left subclavian artery and the left internal thoracic artery were ligated. No hemoptysis and hemosputum occurred for a while, but 2 years and 9 months after the operation, the patient was admitted due to hemoptysis with fever and coughing. Since the bronchial artery was embolized twice with spongel and twice with platinum coil, the patient's course has been good for 5 months.

[A case of pulmonary solitary metastasis of renal cell carcinoma nine years after radical nephrectomy].

A 65-year-old woman was admitted to our department when a routine screening chest X-ray film demonstrated pulmonary solitary nodule. Nine years before, left nephrectomy had been performed with a diagnosis of renal cell carcinoma, and postoperative course was uneventful. Chest X-ray and CT confirmed the presence of well-circumscribed mass in the right lower lobe of lung. With a presumptive diagnosis of pulmonary metastasis of renal cell carcinoma, right lower lobectomy and resection of mediastinal lymph nodes was performed. The pathological diagnosis was metastasis of renal cell carcinoma, granular cell subtype. Pulmonary solitary metastasis of renal cell carcinoma, especially nine years after radical nephrectomy is rare case.

[A rare case of mediastinal neuroblastoma with pectus excavatum in a 4-month-old boy--a surgical report].

Screening of neuroblastoma is commonly performed on 6-month-old infants; therefore, its discovery in children younger than that age is extremely rare. However, a 4-month-old boy with pectus excavatum was found to also have mediastinal neuroblastoma after close examination. This 7 kg child had no apparent symptoms, yet revealed an egg-sized shadow along the right atrium in the chest X-ray film, and along the right side of the vertebrae on CT. Due to the increase in the size of the tumor after two months of observation, we suspected malignant neurogenic tumor and performed a thoracotomy. With a right posterolateral thoracotomy we removed the dark-brown, elastic tumor measuring 6 x 4 x 3 cm and located along the right side of the vertebrae from III through VIII ribs. The origin was the thoracic sympathicus and the pathological diagnosis of the tumor was neuroblastoma with rosset formation. After conducting a post-operative chemotherapy (Jame's protocol), no evidence of recurrence was observed at 33 months after surgical treatment. We summarized the previously reported seven surgically treated cases of Stage I mediastinal neuroblastoma at less than 12 months of age. Among the 2500 pectus excavatum surgeries that have been held at our department, non has been found to have mediastinal neuroblastoma.

Necrosis of the small intestine after resection of an abdominal aortic aneurysm.

Small bowel infarction following abdominal aortic reconstruction is extremely rare, and the prognosis remains poor. This report describes a 65-year-old man with small bowel infarction after resection of an abdominal aortic aneurysm. He was successfully treated with resection of the ischemic segment from the distal duodenum to the mid-small bowel and construction of a duodenoileostomy. The postoperative course was uneventful.

[Surgical management in synchronous bilateral renal cell carcinoma].

Six patients with synchronous bilateral renal cell carcinoma were treated surgically over a 7-year period in our department. They were all males and the mean age was 60.3 years. They comprised 7.1% of all patients with renal cell carcinoma encountered during the same period. In four out of the six cases, radical nephrectomy for the larger tumor plus partial nephrectomy for contralateral kidney was performed simultaneously. In the remaining two cases, bilateral partial nephrectomy was performed simultaneously or as separate procedures. Two patients required chronic hemodialysis and died of cardio-pulmonary insufficiency on the 70th and 75th day. One patient, who underwent bilateral partial nephrectomy with incomplete tumor removal, subsequently died of metastatic disease at 27 months. Although one of them required transient hemodialysis, the remaining three patients were alive and disease-free 84, 42, and 17 months after operation, without evidence of tumor. This series suggests that partial nephrectomy is an appropriate option in the management of selected cases of bilateral renal cell carcinoma.

[A case of idiopathic esophageal perforation (Boerhaave's syndrome)].

76 year-old man was transferred to emergency room because of severe epigastralgia and dyspnea. He was well until 5 hours before admission, when he suddenly felt severe epigastralgia followed by vomiting. He was found to be in warm shock state. Chest X-ray film showed dilation of mediastinum, pneumo mediastinum, left pleural effusion and subcutaneous emphysema, which were consistent with esophageal perforation. Esophageal contrast study was diagnostic. Emergency operation was performed in which rupture of the lowest esophagus causing remarkable mediastinitis and pleuritis was observed. Esophageal tear was primarily closed and chest drains were placed. Despite severe post-operative complications, he was discharged with recovery 5 months later.

[A case of giant phyllodes tumor with special reference to its process of enlargement].

A phyllodes tumor of the breast can grow into an extremely large oncoides occasionally and be a cause of poor prognosis without adequate treatment in some cases. A case of giant phyllodes tumor which is thought to be one of the largest and heaviest among reported cases in Japan was treated in our clinic. The process of enlargement of the tumor and the treatment of this patient are reported.

[A case of secretory carcinoma of the breast in an adult].

This report describes a case of secretory carcinoma of the breast in the adult. The patient, a 56-year-old female, had a tumor, 1 cm in size, in the upper outer quadrant of her left breast, and Patey's modified radical mastectomy was performed. No nodal metastases were found. Although secretory carcinoma of the breast has been called "juvenile carcinoma", 27 adult cases have been reported previously in the English and Japanese literature. It is reported to have a good prognosis but surgical therapy with an axillary node dissection is recommended, since axillary metastases have been found in approximately 30% of the recorded cases.

[Juxtapapillary duodenal diverticula and cholelithiasis].

One hundred and thirteen cases of juxtapapillary duodenal diverticula were found in 5573 cases which were examined by upper gastrointestinal barium meal X-ray examination. Seventy-nine percent of those 113 cases had complications, while 21% of the cases were suffered from juxtapapillary duodenal diverticula alone. Among the complications, cholelithiasis showed the highest incidence. (33 cases out of 113 cases, 29.2%). Twenty-four cases of juxtapapillary duodenal diverticula of which serum amylase and serum bilirubin values were found to be over the normal range, were subjected to the ERCP and hepatocholedocal RI scintigraphy using 99mTcPI. Fourteen cases out of the 24 cases had complication of cholelithiasis. In 4 cases (28.6%) in this group, delaying of bile-flow was observed. While in 3 cases (30%) out of 10 cases without cholelithiasis, bile-flow disturbance was found. According to above mentioned observations, the following steps were recommended for the treatment of juxtapapillary duodenal diverticula: When juxtapapillary duodenal diverticula is revealed, examinations should be carefully done in order to find out other complications. Treatment for juxtapapillary duodenal diverticula may be done simultaneously with operation of the complications. Surgical indication of the juxtapapillary duodenal diverticula alone should be decided by the result of bile-flow examination.

Renal cell carcinoma with intracaval tumor thrombus extending to the diaphragm: ultrasonography and surgical management.

We describe the successful management of a patient with intracaval extension of renal cell carcinoma to the level of the diaphragm. Ultrasonography delineated clearly the upper extent of the tumor thrombus and revealed no invasion of the vena caval wall at or above the entrance of the main hepatic veins. To prevent severe hypotension caused by intrapericardial control of the inferior vena cava, the aorta was clamped temporarily just above the celiac axis. The tumor was removed completely en bloc with the thrombus. Blood loss was minimal and the patient recovered promptly.