Impaired Value of 99m Tc-GSA Scintigraphy as an Independent Risk Factor for Posthepatectomy Liver Failure in Patients with Hepatocellular Carcinoma.

BACKGROUND: Posthepatectomy liver failure (PHLF) was recently defined with the corresponding recommendations as follows: grade A, no change in clinical management; grade B, clinical management with noninvasive treatment; and grade C, clinical management with invasive treatment. In this study, we identified the risk factors for grade B and C PHLF in patients with hepatocellular carcinoma (HCC). METHODS: Of 339 HCC patients who underwent curative hepatic resection, 218 were included for analysis. The LHL15 index (uptake ratio of the liver to that of the liver and heart at 15 min) was measured by 99m Tc-GSA (99m technetium-labelled galactosyl human serum albumin); remnant LHL15 was calculated as LHL15 × [1 - (resected liver weight - tumor volume)/whole liver volume without tumor]. RESULTS: A total of 163 patients were classified as having no PHLF, whereas 17, 37, and 1 patient had PHLF grade A, B, and C, respectively. There were significant differences in indocyanine green R15, serum albumin, prothrombin time, Child-Pugh classification, LHL15 and remnant LHL15 between patients with grades B/C PHLF and patients with grade A or no PHLF. Only remnant LHL15 was identified as an independent risk factor for grades B/C PHLF (p = 0.023), with a cut-off value of 0.755. CONCLUSIONS: Remnant LHL15 was an independent risk factor for grades B/C PHLF. Patients with impaired remnant LHL15 value of <0.755 should be carefully monitored for PHLF.

Short- and long-term outcomes of the Frey procedure for chronic pancreatitis: a single-center experience and summary of outcomes in Japan.

PURPOSE: To evaluate the short- and long-term outcomes of the Frey procedure for chronic pancreatitis (CP). METHODS: The subjects of this study were 12 patients who underwent the Frey procedure for CP between January, 2000 and December, 2016. We assessed pain relief, weight gain, and exocrine/endocrine insufficiency during follow-up. RESULTS: The study population comprised 11 men and 1 woman (91.7% vs. 8.3%; mean age, 50.3 ± 6.8 years; range 39-61 years). Pancreatitis was caused by alcohol in 9 (75%) patients and was idiopathic in 3 (25%) patients. The mean follow-up period was 82.5 ± 46.5 months (range 16.9-152.1 months). There was no operative mortality, but three patients (25%) suffered postoperative morbidity. All patients were pain-free at the time of discharge. There was no case of new-onset diabetes mellitus after surgery, although one patient (8.3%) suffered exocrine insufficiency. The body weight and body mass index of all patients improved during follow-up. Only one patient continued to suffer pain in the long term. CONCLUSION: The findings of this long-term follow-up of patients who underwent the Frey procedure suggest that it offers effective pain relief and is a safe technique for the management of CP.

Primary adenocarcinoma of the minor duodenal papilla with mass-forming chronic pancreatitis: report of a case.

A 70-year-old male was treated for gastric ulcers. Follow-up upper gastrointestinal endoscopy revealed an irregular, elevated tumor in the second portion of the duodenum. Upon pathological inspection of a biopsy specimen, a diagnosis of adenocarcinoma was made, and the patient was admitted to our hospital. Computed tomography showed an irregular mass in the pancreatic head and dilatation of the main pancreatic duct and bile duct. Pancreatic head carcinoma with infiltration of the duodenum was diagnosed, and pylorus-preserving pancreaticoduodenectomy was performed. A histopathological examination of the resected specimen showed moderately differentiated adenocarcinoma in the minor duodenal papilla and chronic pancreatitis in the pancreatic head. Therefore, primary adenocarcinoma of the minor duodenal papilla with mass-forming chronic pancreatitis was diagnosed. Currently, the patient is alive without recurrence 17 months after the surgery. Primary adenocarcinoma of the minor duodenal papilla is extremely rare. We herein report this case, and also provide a review of the literature.

Prediction of Postoperative Hepatic Failure after Liver Resection for Hepatocellular Carcinoma: Significance of the Aspartate Aminotransferase-to-Platelet Ratio Index.

BACKGROUND/AIMS: The serum aspartate aminotransferase-to-platelet ratio index (APRI) is a biomarker for hepatic fibrosis. The relationship between the APRI and postoperative hepatic failure is unclear. METHODOLOGY: The risk factors for postoperative hepatic failure and the APRI were evaluated in 457 patients who underwent liver resection for HCC. RESULTS: Nineteen patients (4.2%) experienced postoperative hepatic failure and five (1.1%) died. An increased APRI (p = 0.039), increased total bilirubin (p = 0.044), longer operation (p = 0.035) and increased intraoperative blood loss (p = 0.028) were independent risk factors in the multivariate analysis. Incidence of postoperative hepatic failure in patients with an APRI ≥ 1.57 (13/127, 10%) was significantly higher than in patients with an APRI < 1.57 (6/330,1.8%, p = 0.0002). Moreover, incidence of hepatic failure in high APRI cases with both an operation ≥ 500 min and intraoperative blood loss ≥ 1L (6/33 (18.1%)) tended to be higher than in those with lower values (7/94 (7.4%), p = 0.051). CONCLUSIONS: Increased APRI (≥ 1.57) may be a preoperative predictor of postoperative hepatic failure. Meticulous surgery with shorter operations and reduced blood loss may reduce the incidence of postoperative hepatic failure, even in patients with a high APRI.

Non-B non-C Hepatocellular Carcinoma: the Risk Factors for Recurrence and the Types of Recurrence Following Hepatic Resection.

BACKGROUND/AIMS: Risk factors for recurrence and types of recurrence following hepatic resection for non-B non-C hepatitis hepatocellular carcinoma (NBC-HCC) have not yet been established. METHODOLOGY: The clinicopathological data of 76 patients with NBC-HCC were retrospectively reviewed. Risk factors for postoperative recurrence were analyzed using univariate and multivariate analyses. In addition, types of intrahepatic recurrence were investigated. RESULTS: Of the 76 patients, 38 (50%) developed recurrence during the follow-up period, with disease-free survival rates at 1/3/5 years of 72%/46%/40%, respectively. Of the 38 patients with recurrence, 36 (95%) were found to have recurrence within three years after surgery. Of the 38 patients, 34 exhibited intrahe patic recurrence. In multivariate analysis, Child-Pugh B (p = 0.009) and microscopic vascular invasion (MVI) (p = 0.002) were independent risk factors for postoperative recurrence. Based on our definitions, of the 34 patients with intrahepatic recurrence, recurrence at the stump was present in one patient, multicentric recurrence in 11 patients and intrahepatic metastasis in 22 patients. CONCLUSIONS: Child-Pugh B and MVI are independent risk factors for the postoperative recurrence. Although most recurrences occurred within three years after hepatic resection, incidence of multicentric recurrence is not negligible. Preventing recurrence according to types of recurrence is therefore considered to be essential.

Safety of hepatic resection for hepatocellular carcinoma in obese patients with cirrhosis.

PURPOSE: This study aimed at investigating the safety of hepatic resection for hepatocellular carcinoma (HCC) in obese patients with cirrhosis in Japan. METHODS: We reviewed the clinical records of 202 patients with liver cirrhosis, who underwent hepatic resection for HCC between January, 2001 and August, 2011. The patients were divided into three groups according to their body mass index (BMI): the normal body weight (BMI < 24.9 kg/m(2)), obese class I (BMI 25.0-29.9 kg/m(2)), and obese class II (BMI ≥ 30 kg/m(2)) groups. We compared the patient backgrounds, intraoperative factors, and postoperative complications among the three groups. RESULTS: The normal body weight, obese class I, and obese class II groups comprised 138 (68.3 %), 55 (27.2 %), and 9 (4.5 %) patients, respectively. The incidence of non-B non-C cirrhosis was higher in the obese class II group (22 %) than in the normal body weight group (14 %, p = 0.034). Intraoperative blood loss tended to be higher in the obese class II patients than in the other two groups. Postoperative complications and mortality did not differ significantly among the three groups. According to multivariate analysis, obesity was not a risk factor for postoperative complications (Clavien-Dindo classification Grade III or higher) or mortality. CONCLUSION: Hepatic resection for HCC can be performed safely in obese patients with cirrhosis.

A simple, noninvasively determined index predicting hepatic failure following liver resection for hepatocellular carcinoma.

BACKGROUND: A novel index, the serum aspartate aminotransferase activity/platelet count ratio index (APRI), has been identified as a biochemical surrogate for histological fibrogenesis and fibrosis in cirrhosis. We evaluated the ability of preoperative APRI to predict hepatic failure following liver resection for hepatocellular carcinoma. METHODS: Potential preoperative risk factors for postoperative hepatic failure (hepatic coma with hyperbilirubinemia, four patients; intractable pleural effusion or ascites, 30 patients; and variceal bleeding, one patient) as well as APRI were evaluated in 366 patients undergoing liver resection for hepatocellular carcinoma. Prognostic significance was determined by univariate and multivariate analyses. RESULTS: Hepatic failure developed postoperatively in 30 patients, causing death in four. APRI correlated with histological intensity of hepatitis activity and degree of hepatic fibrosis, and was significantly higher in patients who developed postoperative hepatic failure than in others without failure. Risk of postoperative hepatic failure increased as the serum albumin concentration and platelet count decreased and as indocyanine green retention rate at 15 min, aspartate and alanine aminotransferase activities, and APRI increased. Only APRI was an independent preoperative factor on multivariate analysis. Of the four patients who died of postoperative hepatic failure, three had an APRI of at least 10. CONCLUSIONS: Preoperative APRI independently predicted hepatic failure following liver resection for hepatocellular carcinoma. Patients with an APRI of 10 or more have a high risk of postoperative hepatic failure.

Huge liver abscess radiologically mimicking cystadenocarcinoma.

A 72-old-year Japanese man was incidentally found to have out liver dysfunction on serum examination and a cystic tumor in the liver. Dynamic computed tomography revealed a solitary cystic tumor 14 cm in diameter with multiple septa. The cyst wall was occasionally irregular with hyperarterial inflow. After admission, he suffered from fever and right upper abdominal pain. We suspected cystadenocarcinoma with intraluminal infection. Percutaneous transhepatic drainage was performed. However, neither cytologic examination nor culture test was positive. The cystic tumor had been decreasing in size, and hepatic resection performed. Macroscopically, the tumor was a gray-yellow solid tumor with a fine boundary between tumor and liver parenchyma, and the cystic lesion collapsed. Microscopically, the tumor consisted of hepatic infarction, degenerated Glisson's sheath, and chronic inflammation, and chronic liver abscess was diagnosed. Most cases of bacterial liver abscess can be diagnosed because progression is accompanied by typical signs. However, it is difficult to diagnose liver abscess in the chronic phase because chronic liver abscesses exhibit various features on imaging series without typical signs or symptoms. When atypical liver cyst is found, the possibility of liver abscess in chronic phase should be considered.

Overexpression of CYP3A aggravates endotoxin-induced liver injury in hypophysectomized female rats.

AIM: CYP3A2 is a male-specific isoform of cytochrome P450 enzyme which is expressed abundantly in male rats but not in intact female rats. Having previously reported that hepatic CYP3A2 promotes lipopolysaccharide (LPS)-induced liver injury in male rats, we further examined the impact of CYP3A on LPS-induced liver injury by comparing intact and hypophysectomized female rats. In hypophysectomized female rats, phenobarbital (PB), a cytochrome P450 inducer, markedly increased the hepatic content and activity of CYP3A1/2, but did not do so in intact rats. CYP2B1 increased to similar levels in PB-treated hypophysectomized and intact rats. METHODS: Rats were administered 10 mg/kg LPS intravenously and some were given PB for three days before LPS injection. Liver injury was analyzed 8 h after LPS injection. RESULTS: PB-LPS increased plasma alanine aminotransferase significantly more in hypophysectomized female rats than in intact female rats. Ketoconazole, a CYP3A inhibitor, inhibited the increase of liver injury. Hepatic 8-hydroxydeoxyguanosine in nuclei and 4-hydroxy-2-nonenal-modified proteins, measured to evaluate oxidative stress by LPS treatment, increased markedly more in PB-treated, hypophysectomized female rats, than in intact female rats. CONCLUSION: Overexpression of CYP3A aggravated LPS-induced liver injury in rats, apparently through the formation of reactive oxygen species.

Convenience of a tape-guiding technique in different types of hepatectomy.

BACKGROUND/AIMS: The liver hanging maneuver is widely used in right lobectomy to resect huge tumors and harvest living donors. The convenience of tape assistance in other types of hepatectomy is not well known. METHODOLOGY: Tape-guiding technique (TGT) was applied in 30 hepatectomies of different type between April 2003 and April 2006. The indications were liver carcinoma in 22 and living-donor in 8. Hepatectomies included right lobectomy, 14; left lobectomy with caudate lobectomy, 8; left lobectomy without caudate lobectomy, 2; lateral segmentectomy, 3; central bisegmentectomy, posterior segmentectomy, and superior dorsal partial resection, 1 each. A tape was placed in front of the inferior vena cava for right hepatectomy and left hepatectomy with caudate lobectomy. In other hepatectomies, the tape was positioned to be the target of parenchymal dissection. RESULTS: TGT was successfully performed in all 30 cases. Tape facilitated dissection by helping the surgeon maintain orientation, and traction on the tape flattened the parenchyma, making it easier to identify and manage vessels and ducts. With an assistant holding the tape, the surgeon's left hand was free, and ligation and suturing was easier and more secure. CONCLUSIONS: The TGT is a convenient technique that is applicable to different types of liver resection.

Is Noncurative Hepatic Resection Justified for Advanced Hepatocellular Carcinoma?

It has been obscure whether or not noncurative hepatic resection (Hx) has a favorable impact on the clinical course in patients with advanced hepatocellular carcinoma (HCC). The aim of this study is to clarify the significance of noncurative Hx for advanced HCC. Among 666 consecutive patients undergoing Hx for HCC in our department, 79 patients underwent noncurative Hx. These patients were classified as Group A (presence of macrovascular invasion [MVI]; n = 29), Group B (residual tumors in the remnant liver; n = 37), Group C (residual tumors in the remnant liver with MVI; n = 7), or Group D (residual tumors in the remnant liver with distant metastasis [with or without MVI]; n = 6). The three-year survival rates were 49.6 per cent in Group A, 30.3 per cent in Group B, 14.3 per cent in Group C, and 0.0 per cent in Group D, respectively (Groups A and B vs Group D, P < 0.05). Moreover, the survival rate was significantly higher in patients with ≤3 tumors than in those with ≥4 tumors (P < 0.05), when Group B was divided into subgroups according to the number of residual tumors in the remnant liver. In conclusion, noncurative Hx might be acceptable for advanced HCC with MVI or ≤3 residual tumors in the remnant liver.

Difficulty Achieving a Preoperative Diagnosis of IgG4-Related Sclerosing Cholangitis.

A 75-year-old male was admitted to our hospital because of bile duct stenosis. He had no medical history of autoimmune disease. The level of tumor markers, serum IgG, and IgG4 were within normal ranges. Computed tomography showed perihilar and distal bile duct stenosis and wall thickening without swelling or abnormal enhancement of the pancreas. Endoscopic retrograde cholangiopancreatography showed perihilar and distal bile duct stenosis. A biopsy and cytology from the distal bile duct stenosis suggested adenocarcinoma, and cytology from the perihilar bile duct also suggested adenocarcinoma. A preoperative diagnosis of perihilar and distal bile duct cancer was made, and the patient underwent left hepatectomy and pancreaticoduodenectomy. Resected specimens showed wall thickening in the perihilar and distal bile duct; however, tumors were unclear. A histopathological examination revealed lymphoplasmacytic infiltration, storiform fibrosis, and obliterative phlebitis in the perihilar and distal bile ducts. Immunohistochemistry revealed diffuse infiltration of IgG4-positive plasma cells in the perihilar and distal bile ducts. Lymphoplasmacytic infiltration, inflammatory change, storiform fibrosis, and obliterative phlebitis were shown in the pancreas. A final diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC) with autoimmune pancreatitis was made. We herein report a case in which a preoperative diagnosis of IgG4-SC was difficult due to normal serum IgG4 levels and no obvious pancreatic lesion.

S-allyl cysteine prevents CCl(4)-induced acute liver injury in rats.

Aged garlic extract (AGE) possesses multiple biological activities. We evaluated the protective effect of S-allyl cysteine (SAC), one of the organosulfur compounds of AGE, against carbon tetrachloride (CCl(4))-induced acute liver injury in rats. SAC was administrated intraperitoneally (50-200 mg/kg). SAC significantly suppressed the increases of plasma ALT and LDH levels. SAC also attenuated histological liver damage. CCl(4) administration induced lipid peroxidation accompanied by increases in the plasma malondialdehyde and hepatic 4-hydroxy-2-nonenal levels, and SAC dose-dependently attenuated these increases. The hepatic total level of hydroxyoctadecadienoic acid (HODE), a new oxidative stress biomarker, was closely correlated with the amount of liver damage. These results suggest that SAC decreased CCl(4)-induced liver injury by attenuation of oxidative stress, and may be a better therapeutic tool for chronic liver disease.

Effects of lamivudine on outcome after liver resection for hepatocellular carcinoma in patients with active replication of hepatitis B virus.

AIM: Patients with high serum hepatitis B virus (HBV) DNA concentrations are at high risk of tumor recurrence after liver resection for HBV-related hepatocellular carcinoma (HCC). METHODS: Among 24 patients with high serum HBV DNA concentrations who underwent liver resection for HBV-related HCC, postoperative lamivudine therapy was chosen by 14 (lamivudine group). The other 10 patients were controls. RESULTS: Clinicopathologic findings did not differ between the groups. Tumor-free survival rate after surgery was significantly higher in the lamivudine than the control group (P = 0.0086). By univariate analysis, multiple tumors were also a risk factor for a short tumor-free survival. By multivariate analysis, lack of lamivudine therapy and multiple tumors were independent risk factors for a short tumor-free survival. In four patients YMDD mutant viruses were detected after beginning lamivudine administration; in two of them, adefovir dipivoxil was administered because of sustained serum alanine aminotransferase elevations. CONCLUSION: Lamivudine therapy improved tumor-free survival rate after curative resection of HBV-related HCC in patients with high serum concentrations of HBV DNA, although careful follow up proved necessary for the detection of YMDD mutant viruses.

A histopathological study on combined hepatocellular and cholangiocarcinoma: cholangiocarcinoma component is originated from hepatocellular carcinoma.

BACKGROUND/AIMS: Combined hepatocellular and cholangiocarcinoma of the liver is relatively infrequent, and its pathogenesis remains obscure. The aim of this study is to investigate its clinical and pathological features and proliferative activity. METHODOLOGY: In this study, we investigated the histopathological features, Ki-67 labeling index, and p53 immunohistochemistry of 18 surgically resected cases of combined hepatocellular and cholangiocarcinoma among 1102 consecutive cases of surgically resected primary liver cancers. All tumors were compatible with the WHO definition of this tumor. Microscopically, we classified the cases into the following three categories according to the arrangement of the hepatocellular carcinoma and cholangiocarcinoma components; (1) Type I in which hepatocellular carcinoma and cholangiocarcinoma formed nodules that could easily be distinguished from each other, (2) Type II in which the both components were finely mixed, so that the two components were almost indistinguishable, and (3) Type III in which the tumors had lobular structures with hepatocellular carcinomas existing centrally and cholangiocarcinomas existing peripherally. RESULTS: Microscopically, the tumors were classified into type I 7 tumors, type II 5 tumors, and type III 6 tumors. In one case of type I, well differentiated hepatocellular carcinoma demonstrated cholangiocarcinoma in "nodules-in-nodules" fashion. The average of Ki-67 labeling index of hepatocellular carcinoma component of combined hepatocellular and cholangiocarcinoma was 4.4 +/- 3.4% and the index of cholangiocarcinoma component was 11.0 +/- 8.5%, which is significantly higher than that of the hepatocellular carcinoma component. On p53 immunohistochemistry, 5 of 18 cases (29.4%) were positive. In one case, the cholangiocarcinoma component was positive for p53, but the hepatocellular carcinoma component was negative. In the other 4 cases, both the hepatocellular carcinoma and cholangiocarcinoma components were positive. CONCLUSIONS: Microscopically, type III seems to be a feature of metaplasia or proliferation of bipotential progenitor cells. Metaplasia of hepatocellular carcinoma to intrahepatic cholangiocarcinoma is assumed to be one of the pathogenic pathways of combined hepatocellular and cholangiocarcinoma.

Risk factors for massive blood loss during liver resection for hepatocellular carcinoma in patients with cirrhosis.

BACKGROUND/AIMS: Liver resection for hepatocellular carcinoma in patients with cirrhosis carries risk of major hemorrhage and sometimes requires blood transfusion. We investigated risk factors for massive blood loss during liver resection and indications for storing blood for autologous intraoperative transfusion. METHODOLOGY: We analyzed clinical records of 100 patients with cirrhosis who underwent liver resection for hepatocellular carcinoma. Autologous blood was stored preoperatively for 19 patients. RESULTS: Intraoperative blood loss ranged from 5 to 3000 mL (mean, 640). Liver resection was performed without transfusion in 67 patients and with autologous blood storage in 17 patients not receiving homologous blood. In the other 16 patients, homologous blood was transfused. Univariate analysis identified youth, large tumors (> 4cm), major hepatectomy, portal tumor involvement, hepatic vein involvement, and prolonged operation time as risk factors for massive blood loss; multivariate analysis identified portal involvement and hepatic vein involvement as independent risk factors. Blood loss exceeded 1000 mL in the 4 transfused group B patients and 3 of the 4 patients had hepatic vein involvement. CONCLUSIONS: Portal involvement and hepatic vein involvement were risk factors for massive blood loss during liver resection for hepatocellular carcinoma in patients with cirrhosis. Autologous blood storage is indicated in patients with such risk factors.

Multifocal Mass Lesions in Autoimmune Pancreatitis.

A 59-year-old male patient with jaundice was referred to our hospital because of mass lesions in the pancreatic head and tail. An immunological examination revealed an elevated serum IgG4 level. Computed tomography showed two clear boundary mass lesions in the pancreatic head and tail. Magnetic resonance imaging showed that the mass lesions exhibited low intensity on T1-weighted images and iso-intensity on T2-weighted images. Magnetic resonance cholangiopancreatography showed an obstruction of the main pancreatic duct in the pancreatic head and tail. The possibility of malignant tumors could not be ruled out; therefore, we performed total pancreatectomy. A histopathological examination of the nodular lesions revealed severe lymphoplasmacytic infiltration and inflammatory change around the pancreatic ducts. Immunohistochemistry revealed diffuse infiltration of IgG4-positive plasma cells in the nodules. According to these pathological findings, we diagnosed the patient with IgG4-related multifocal mass lesions of autoimmune pancreatitis (AIP). It is difficult to distinguish between focal type AIP and pancreatic cancer. We herein report a rare case of multifocal mass lesions in AIP and include bibliographical comments.

Hepatectomy for Hilar Cholangiocarcinoma with Right-Sided Ligamentum Teres Using a Hepatectomy Simulation System.

Right-sided ligamentum teres (RSLT) is a rare congenital anomaly often accompanied by variation of the hepatic vasculature. We herein report a surgical case of a hilar cholangiocarcinoma with RSLT in whom preoperative hepatectomy simulation proved useful for understanding the anatomical structure of the liver. A 78-year-old male with obstructive jaundice was referred to our department for further examination. The patient was suspected of having a hilar cholangiocarcinoma originating from the left hepatic bile duct by contrast-enhanced computed tomography (CT), and CT also showed right umbilical portion (RUP). Three-dimensional images of the hepatic vasculature and biliary system reconstructed using a hepatectomy simulation system suggested that all portal branches ramified from RUP were right paramedian branches, and three leftward portal branches from these ran parallel to the peripheral bile ducts confluent with the left hepatic bile duct, where the tumor was present. Hepatic resection of part of the ventral area of the right paramedian sector and left hemiliver was performed along the demarcation line drawn after clamping the portal branches; the ratio of estimated liver resection volume was 28.9%. After the operation, bile leakage occurred. However, the leakage was treated with percutaneous drainage alone, and the patient was discharged 77 days after the operation. The patient is doing well without any signs of recurrence 21 months after the operation. The vascular and biliary anatomy in patients with RSLT is complicated and should be evaluated in detail preoperatively using a hepatectomy simulation system.

Laparoscopic Resection of an Epithelial Cyst in an Intrapancreatic Accessory Spleen.

An epithelial cyst in an intrapancreatic accessory spleen (ECIAS) is rare. We herein report a case of a patient with ECIAS who underwent laparoscopic surgery. A 57-year-old woman was referred to our hospital because of a pancreatic tail tumor. She was asymptomatic, and a physical examination revealed no remarkable abnormalities. The levels of the tumor marker carbohydrate antigen 19-9 (CA19-9) and s-pancreas-1 antigen (SPan-1) were elevated. Ultrasonography showed a well-defined homogeneous cystic tumor. Computed tomography showed a well-demarcated cystic tumor in the pancreatic tail. Magnetic resonance imaging showed that the cystic tumor exhibited low intensity on T1-weighted images and high intensity on T2-weighted images. The cystic tumor was diagnosed as mucinous cystic neoplasm preoperatively. The patient underwent laparoscopic spleen-preserving distal pancreatectomy. A histopathological examination revealed the cyst wall to be lined by stratified squamous epithelium within splenic parenchyma, and the ultimate diagnosis was ECIAS. The postoperative course was uneventful, and the patient was discharged on postoperative day 12. ECIAS is very difficult to diagnose preoperatively. Laparoscopic surgery is a safe and minimally invasive procedure for patients with difficult-to-diagnose pancreatic tail tumor suspected of having low-grade malignancy.

Vitamin E deficiency accelerates nitrate tolerance via a decrease in cardiac P450 expression and increased oxidative stress.

Organic nitrates, such as nitroglycerin (NTG), have been used to relieve the symptoms of angina pectoris. However, their biochemical mechanisms of action, particularly in relation to the development of tolerance, are incompletely defined. It has been reported that supplemental antioxidants such as vitamin E attenuate the development of nitrate tolerance. Therefore, we examined the role of vitamin E in the regulation of nitrate tolerance. Continuous NTG infusion induced nitrate tolerance in rats after 48 h, and vitamin E concentrations decreased in a time-dependent manner in tissues and plasma. Vitamin E supplementation (0.5 g/kg diet) maintained higher concentrations of vitamin E during NTG infusion. The onset and extent of the tolerance, estimated by the decrease in blood pressure following NTG bolus injection during the infusion of NTG, were accentuated in the vitamin E-deficient group. Vitamin E supplementation inhibited nitrate tolerance 48 h after NTG infusion. Cardiac P450 expression (CYP1A2) assessed by immunoblotting, markedly decreased 48 h after NTG administration in control rats. The supplementation of vitamin E significantly attenuated the decrease in P450. Treatment of NTG enhanced vascular superoxide production (L-012 chemiluminescence, DHE fluorescence). The peak of lipid peroxidation and free radical generation in the heart was reached before tolerance developed. In contrast, vitamin E-deficient hearts had lower P450 expression and higher free radical generation than control hearts. To evaluate other vitamin E-inhibitable mechanisms of nitrate tolerance, we studied the NO-cGMP pathway. NTG markedly reduced the vasodilator-stimulated phosphoprotein (VASP) serine 239 phosphorylation (specific substrate of cGMP-activated protein kinase I; cGK-I) in tolerant hearts. Vitamin E inhibited the depletion of pVASP. In conclusion, because continuous NTG infusion causes vitamin E depletion as well as nitrate tolerance, vitamin E deficiency may further accelerate nitrate tolerance via an increase in oxidative stress, the reduced bioconversion because of decreased P450 expression, and impairment of the NO/cGMP pathway in tolerant heart tissues.