Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma.

Nogo-B, located in the endoplasmic reticulum, is an isoform belonging to the reticulon protein family, which is expressed specifically in cholangiocytes and non-parenchymal cells in the liver. Nogo-B expression is down-regulated with the progression of liver fibrosis, but its distinct function in liver malignancies has not been fully clarified. We have hypothesized that Nogo-B expression may be altered in intrahepatic cholangiocarcinoma (ICC), a relatively rare type of primary liver cancer with highly malignant behavior. The present study aimed to investigate the relationship between Nogo-B expression, assessed by immunohistochemical staining, and clinicopathological factors and prognosis in 34 ICC patients. Positive expression was observed in 19 (56%) of 34 ICC specimens: 6 patients (18%) with positivity levels of 1+ (positive cells in 10-50% of cancer cells) and 13 patients (38%) with 2+ (positive cells over 50%). Importantly, the remaining 15 patients (44%) were categorized as negative expression (Nogo-B-positive cells, less than 10%). Conversely, the mass-forming type of ICC tended to express Nogo-B with the degree of 2+ positivity, compared to the periductal infiltration type (p = 0.064), and the mass-forming type showed a better 5-year survival rate (66% vs. 5%) after hepatectomy (p < 0.05). However, the degree of positivity was not associated with tumor relapse rate, disease-free and overall survival, although each of the periductal infiltration type, intrahepatic metastasis, larger tumor size, and lower microvessel counts was associated with lower survival rates. We propose that Nogo-B expression is down-regulated in ICC, the implication of which, however, remains to be investigated.

Usefulness of evaluating hepatic elasticity using artificial acoustic radiation force ultrasonography before hepatectomy.

AIM: To evaluate hepatic fibrosis and tumor diagnosis preoperatively, we investigated the elasticity calculated by the new parameter of ultrasonography, acoustic radiation force impulse (ARFI). METHODS: We examined ARFI of the non-tumorous right and left lateral liver and in the tumor by push pulse of probe in 95 patients with hepatic malignancies undergoing hepatectomy. Measurement of ARFI as hepatic stiffness was indicated as the Vs (m/s). RESULTS: Measuring the Vs in the non-tumor region was achieved in the right liver in 99% and at the left lateral liver in 94%. The Vs in the right liver was significantly lower than in the left lateral liver, and the Vs of the liver tumor was significantly higher than in the non-tumorous liver. The Vs in the right and left lateral liver was correlated with the platelet count, aspartate aminotransferase, fibrotic indices and indocyanine green test. The Vs in the right liver was significantly correlated with the fibrotic marker or index. The Vs of liver cirrhosis and histological stage 4 in the right and left liver was significantly the highest compared to the others. The Vs in the right liver showed a high area under the receiver-operator curve value predicting histological fibrosis. The Vs in the right was significantly correlated with blood loss and postoperative complications, particularly uncontrolled ascites. CONCLUSION: Non-invasive ARFI imaging elastography is useful in evaluating impaired liver function or in the differential diagnosis of liver malignancies, highly hepatic fibrosis and in predicting posthepatectomy morbidity.

Improvement of Surgical Records and Outcomes after Hepatectomy at a Single Academic Institute in Japan.

BACKGROUND/AIMS: To clarify improvement of hepatic resection in the recent years, we examined surgical records of 544 patients who underwent hepatectomy in 3 periods between 1994 and 2011 at a single academic institute. METHODOLOGY: Subjects were divided into 3 groups: group 1 (1994-1999, n = 156), group 2 (2000-2006, n = 228) and group 3 (2007-2011, n = 160). Clinical factors, surgical records and post-hepatectomy outcomes during hospitalization were compared between groups. RESULTS: In group 3, patient age was significantly higher and the incidences of alcoholic or fatty liver and obstructive jaundice were significantly higher than in group 1 (p < 0.05). Preoperative liver function was not different between groups, and only prothrombin activity was significantly better in group 1 in comparison with the other groups (p < 0.05). In comparison with group 1, the incidence of resident surgeons as the main operator were significantly higher than in group 3 (p < 0.01). Incidences of laparoscopic hepatectomy and thoraco-abdominal approach were increased in group 3 (p < 0.01). Incidences of combined organ and major vessels resections were significantly higher in group 3 in comparison with group 1 (p < 0.01). Use of omental wrapping and hemostatic devices were significantly more frequent in group 3 than in group 1 (p < 0.01). Surgical records were not different between groups but the red cell transfusion rate in group 3 was significantly lower than in group 1 (p < 0.05). Hospital stay in group 3 was significantly shorter than in group 1. Incidence of hepatectomy-related complication, particularly bile leakage, was significantly lower in group 3 than in group 1 (p < 0.05). CONCLUSIONS: According to this evaluation of different time periods, surgical outcomes have been improved with new surgical procedures and perioperative management.

Intrahepatic cholangiocarcinoma: relationship between tumor imaging enhancement by measuring attenuation and clinicopathologic characteristics.

PURPOSE: Arterial enhancement of intrahepatic cholangiocarcinoma (ICC) has been noted. To precisely identify the characteristics of tumor enhancement patterns, we examined the relationship between CT attenuation in the tumor and clinicopathological parameters or prognosis. METHODS: Subjects were 42 ICC patients who had undergone hepatectomy. microvessel density (MVD) determined by CD34 staining was compared with imaging. Attenuation was calculated in images from multidetector CT of tumor and non-tumorous regions. Enhancement patterns were divided into two groups: arterial enhancement with higher attenuation (>16 HU; Hyper group, n = 12); and arterial enhancement with lower attenuation (Hypo group, n = 30). RESULTS: Univariate analysis identified high tumor marker level, increased size, less-differentiation, incomplete resection, increased bleeding, and lower MVD as significantly associated with poor survival (p < 0.05). Increased attenuation throughout the whole ICC correlated significantly with radiological findings and MVD. Concomitant hepatitis, well-differentiation, and smaller tumor were more significantly frequent in the Hyper group than in the Hypo group (p < 0.05). Postoperative early recurrence was significantly less frequent in the Hyper group, and overall survival was significantly better in the Hyper group (p < 0.05). CONCLUSIONS: Increased CT attenuation correlated with ICC tumor vascularity. Increased tumor enhancement in the arterial phase was associated with chronic hepatitis, lower malignancy, and better survival.

Acute perforating appendicitis caused by metastatic squamous cell carcinoma from the lung: A case report.

INTRODUCTION: Lung cancer is one of the most common cancers. On the other hand, lung cancer metastasis to the appendix is extremely rare, and in many cases it has been diagnosed with the onset of acute perforating appendicitis. PRESENTATION OF CASE: An 85-year-old man with fever and abdominal pain visited our hospital. He had a history of squamous cell carcinoma of the left upper and lower lobes, metastasis to the ipsilateral lung and femur. CT showed that a finding of acute perforating appendicitis, emergency cecal resection was performed. Examination of the resected specimen showed that the appendix was thickened overall, with a white nodular structure at the root and a perforation in the middle. The final diagnosis was acute perforating appendicitis caused by metastatic squamous cell carcinoma from the lung. The patient had no particular problems during the postoperative course. DISCUSSION: A PubMed search was performed, this appears to be the first reported case of appendiceal metastasis of squamous cell carcinoma of the lung. Since squamous cell carcinoma of the lung has a stronger tendency for local extension than other histological types, perforating appendicitis due to distant metastasis to the abdominal organs and metastasis to the appendix was reported as a very valuable case. CONCLUSION: Because the progression of concomitant or secondary appendicitis is rapid, we recommend frequent imaging modalities, prophylactic appendectomy be considered for patients who also have lung cancer and imaging findings show suspected metastasis to the appendix.

Risk factors preventing success of a minilaparotomy approach in the resection of colorectal cancer.

BACKGROUND: A minilaparotomy approach is technically feasible for the resection of colorectal cancer in select patients. The aim of this study was to clarify the risk factors preventing the success of a minilaparotomy in the resection of colorectal cancer. METHODS: Between April 2005 and August 2008, 141 consecutive patients were enrolled in this prospective study and scheduled to undergo resection of colorectal cancer using a minimal skin incision. The minilaparotomy involved a colorectal resection performed through a skin incision <7 cm in length. Neither a hand-port nor a laparoscope was used. RESULTS: A minilaparotomy was successful in 74 (52.5%) of 141 patients. Multivariate logistic regression analysis revealed that the failure of the minilaparotomy in the remaining 67 (47.5%) was independently related to gender (male), BMI (> or =25.5), tumor location (splenic flexure and rectum), tumor adhesion/invasion on/into adjacent organs and the maximum tumor diameter (> or =7.0 cm). CONCLUSION: Gender (male), BMI (> or =25.5), tumor location (splenic flexure and rectum) and tumor aggressiveness [tumor adhesion/invasion on/into adjacent organs and maximum tumor diameter (> or =7.0 cm)] were independent risk factors preventing the success of the minilaparotomy approach in the resection of colorectal cancer.

Photodynamic Therapy Using Novel Glucose-conjugated Chlorin Increases Apoptosis of Cholangiocellular Carcinoma in Comparison with Talaporfin Sodium.

BACKGROUND/AIM: Photodynamic therapy (PDT) is an effective laser treatment for locally treating advanced bile duct carcinoma (BDC). The study's objective was to evaluate the increased cytocidal effect by apoptotic PDT using a novel photosensitizer, glucose-conjugated chlorin, by irradiation of light-emitting diode laser (G-PDT) in comparison with conventional PDT using talaporfin sodium (T-PDT). MATERIALS AND METHODS: The cytocidal effect of G-PDT was compared to that of T-PDT as a control. Tumor viability was determined by an in vitro MTS assay. The percentage of apoptosis-positive cells was examined by triple stain flow cytometry (annexin V, ethidium homodimer III and Hoechst 33342) in the BDC cell line (NOZ cell) in vitro. The change in transplanted tumor volume in vivo (4-week-old male BALB/c mice) was examined 7 days after PDT. RESULTS: Cell death was induced in a light dose-dependent manner by PDT. The laser power was set at 5 Jules/cm(2) to obtain half maximal inhibitory concentration (IC50) in T-PDT and G-PDT and the concentration of photosensitivity for G-PDT (2.02 µg/ml) was lower than that for T-PDT (4.14 µg/ml). Both T-PDT and G-PDT showed increased induction rates in comparison to the light only or G-chlorin only. Furthermore, the rate of apoptosis in the G-PDT (92.6%) was increased in comparison to that in the T-PDT (38.9%). The increased rates of tumor volume during the 7 days in both the G-PDT and T-PDT groups were significantly lower than that in the non-PDT group (p<0.01). At day 7, the increased rates of tumor volume in the G-PDT group were significantly lower than that in the T-PDT group (p<0.05). CONCLUSION: The new G-PDT treatment showed a high prevalence of apoptosis and inhibition of tumor growth in treatment of BDC cells.

Clinical significances of cancer stem cells markers in patients with intrahepatic cholangiocarcinoma who underwent hepatectomy.

The present study aimed to elucidate the relationship between cancer stem cells markers (CSCs), according to cell adhesion molecule (CD44) and glioma-associated oncogene homolog-1 (GLI1) expression, and clinicopathological factors and prognosis in 38 patients with intrahepatic cholangiocarcinoma (ICC) who underwent hepatectomy. CD44 and GLI1 expression was examined by immunohistochemical staining methods. The relationship with tumor angiogenesis or proliferation activity was also analyzed. Positivity of CD44 was 18% and that of GLI1 was 39%, but there was no significant correlation between the expressions of both. On macroscopic findings, CD44 expression in the periductal infiltration-type of ICC was significantly higher than in other types (p<0.01), and this type showed significantly worse survival after hepatectomy. Positive expression of GLI1 was significantly associated with older age. Although expression of neither CD44 nor GLI1 was significantly associated with disease-free survival, positive expression of both CD44 and GLI1 led to a significantly lower 3-year disease-free survival rate (0%; p<0.05). With respect to 5-year overall survival after hepatectomy, expression of both CD44 and GLI1 was not significantly associated with survival rate. CSCs might be useful markers for tumor-free survival in patients with ICC after hepatectomy and further investigation in larger series is warranted.

Correlation between morphological and functional liver volume in each sector using integrated SPECT/CT imaging by computed tomography and technetium-99m galactosyl serum albumin scintigraphy in patients with various diseases who had undergone hepatectomy.

OBJECTIVES: The aim of the study was to accurately examine the functional volume (RI-vol) of the hepatic segments on single photon emission computed tomography/computed tomography (CT) fusion imaging by technetium-99m galactosyl human serum albumin scintigraphy and compare it with the RI-vol and morphological volume obtained on computed tomography (CT-vol). METHODS: In 60 patients with various liver background statuses who had undergone hepatectomy, the RI-vol and CT-vol were examined in each sector using imaging analysis. The values from a control group (n=91) were used as reference data. RESULTS: The mean RI-vol and CT-vol of the right liver were 64 ± 10 and 63 ± 6%, respectively, whereas the values for the left liver were 36 ± 10 and 37 ± 6%, respectively. Compared with the control group, the ratios in each hemiliver were similar. The mean RI-vol and CT-vol for each sector were also similar, and significant positive correlations were identified between the two volumes (P<0.01). In four patients with hepatic tumors involving the main hepatic vessels or the bile duct and in 10 patients who had undergone portal vein embolization, the actual RI-vol in the injured sector was significantly decreased compared with CT-vol (P<0.05). There were marked changes in functional volume in segment 6+7 and segment 2+3 after portal vein embolization (P<0.05). CONCLUSION: Volumetric measurement using single photon emission computed tomography/CT imaging with technetium-99m galactosyl human serum albumin scintigraphy is useful for evaluating the functional volume in separated livers and offers a good reflection of the background liver status.

Usefulness of examining hepatic functional volume using technetium-99m galactosyl serum albumin scintigraphy in hepatocellular carcinoma.

OBJECTIVES: The aim of the study was to clarify the clinical significance of single-photon emission computed tomography/computed tomography (SPECT/CT) imaging in terms of technetium-99m galactosyl human serum albumin (99mTc-GSA) scintigraphy. To this end, we examined the relationship using data from surgical records of 67 patients with hepatocellular carcinoma who underwent hepatectomy. MATERIALS AND METHODS: Liver functional parameters or functional volume was estimated by 99mTc-GSA scintigraphy and computed tomography volumetry was used to estimate morphological volume. RESULTS: Liver uptake ratio at 15 min (LHL15) was correlated with the indocyanine green retention rate at 15 min (ICGR15; R=-0.608, P<0.01); however, five patients (7.5%) had values outside this correlation. In these patients, LHL15 reflected clinical status and patient outcomes more. Although morphological and functional volumes were well correlated (P<0.01), functional volume was decreased in the diseased liver with portal vein tumor thrombus or portal vein embolization. By applying 99mTc-GSA volumetry, portal pressure and alkaline phosphatase level were correlated with decreased volume of the embolized liver, and platelet count and cholesterol level were correlated with increased volume of the nonembolized liver (P<0.05). By measuring functional volume, four patients who were functionally borderline on the basis of the ICGR15 test safely underwent scheduled major hepatectomy. CONCLUSION: Under the ICGR15 test as the standard for preoperative hepatic function, auxiliary application of LHL15 and functional volumetry provides useful information on hepatocellular carcinoma patients undergoing hepatectomy.