Atsushi Nanashima

Adjuvant photodynamic therapy for bile duct carcinoma after surgery: a preliminary study

BackgroundPhotodynamic therapy (PDT) is a new palliative option in patients with non-resectable bile duct carcinoma (BDC). Here, we assessed the efficacy of adjuvant photodynamic therapy in eight patients with BDC who underwent surgical resection.MethodsFive patients had extrahepatic BDC, two had intrahepatic cholangiocarcinoma, and one had ampullary carcinoma. Cancer cells were microscopically detected in the stump of the hepatic duct in six patients, and biliary stenosis caused by remnant tumor was observed in one patient. One patient had tumor recurrence with occlusion of the bile duct. At 48 h prior to PDT, porfimer sodium was injected intravenously. A pulse laser by an eximer dye laser (50–100 J/cm2) with a wavelength of 630 µm was applied through an endoscope to the hepatic stump or tumor lesion.ResultsMarked destruction of the tumor and ductal epithelium was observed on day 1 after PDT. After PDT, four patients developed mild dermatitis, but no severe morbidity or mortality was noted. In patients who underwent PDT for the stump, one patient showed distant metastasis at 31 months, and four patients did not show tumor recurrence at 17, 12, 12, and 6 months, respectively. However, one of the eight patients died at 2 months, of an unrelated cause. In two patients with occlusion caused by tumor growth, resolution of bile duct stenosis was noted on day 7. These patients showed re-occlusion by tumor at 20 and 8 months.ConclusionsAdjuvant PDT is a safe and useful option for a better survival benefit in patients with BDC undergoing surgical resection.

Prognosis of patients with hepatocellular carcinoma after hepatic resection: Are elderly patients suitable for surgery?

The indication for hepatectomy is still controversial in elderly patients with hepatocellular carcinoma (HCC). We examined the clinicopathological features and survival of 188 HCC patients who underwent hepatectomy.

Relationship Between CT Volumetry and Functional Liver Volume Using Technetium-99m Galactosyl Serum Albumin Scintigraphy in Patients Undergoing Preoperative Portal Vein Embolization Before Major Hepatectomy: A Preliminary Study

To clarify the relationship between morphological measurements of hepatic volume by computed tomography (CT-vol) and functional volume (RI-vol) by technetium-99m galactosyl human serum albumin (99mTc-GSA) scintigraphy, and its clinical significance, we examined 16 patients with a background liver status of either normal liver function (n = 4), chronic hepatitis or cirrhosis (n = 7), or obstructive jaundice (n = 5). In five patients who underwent preoperative portal vein embolization (PVE), volumetric measurement was performed 2 weeks after PVE. The mean values of CT-vol and RI-vol of the right lobe were 692± 147 cm3 (66.1 ± 10.7%) and 668 ± 159 cm3 (67.8 ± 13.2%), respectively, and those of the left lobe were 329 ± 138 cm3 (33.9 ± 10.6%) and 328± 170 cm3 (32.2 ± 13.2%), respectively. There were no significant differences in the volume measurements between the two volumetric techniques. Correlations between CT-vol and RI-vol in the right and left lobes were positive and significant (r = 0.912 and 0.903, respectively; both P′s < 0.001). The mean values of post-PVE CT-vol and RI-vol of the right lobe in five patients were significantly different (628 ± 149 and 456± 211 cm3, respectively; P = 0.033). However, the mean values of post-PVE CT-vol and RI-vol of the left lobe were not different (496 ± 124 and 483± 129 cm3, respectively). We propose that volumetric measurement by 99mTc-GSA scintigraphy is useful for detecting changes in functional volume of individual lobes of the liver and is a more dynamic method compared with detection of morphological changes by CT scan.

Prognostic impact of cathepsin B and matrix metalloproteinase-9 in pulmonary adenocarcinomas by immunohistochemical study.

The expression of Cathepsin B (CB) and matrix metalloproteinase-9 (MMP-9) in extirpated tissues of adenocarcinomas in non-small cell lung cancer from 90 cases was investigated immunohistologically, and the correlations between the extent of the expression and the clinicopathological features were assessed for investigating the process of tumor metastasis. It is important to reveal the mechanisms of destruction of the basal membrane and infiltration of tumor cells at the primary lesion. Sections were obtained from 10%-formalin-fixed and paraffin-embedded tissues. They were reacted with an anti-human CB polyclonal antibody or an anti-human MMP-9 polyclonal antibody. Of 90 patients, 58 (64.4%) and 39 (48.3) cases were found to be positive for CB and MMP-9 expression, respectively. A significantly higher extent of the CB expression was observed in the tissues of patients who showed postoperative recurrence of the tumor (P = 0.013). Especially, a similar observation was obtained among early cases of T1N0 (P = 0.023). In contrast, no such tendency was demonstrated in the expression profile of MMP-9. Furthermore, the enzyme expressions were compared among different types of metastases. Patients with higher extents of CB expression tended to show significantly higher rates of hematogenous and intrapulmonary metastases (P = 0.023 and P = 0.010, respectively). However, there was no significant correlation between MMP-9 expression and the prognostic factor of the patients. Therefore, we suggested that evaluation of CB expression in the tumor tissue might be useful as a postoperative prognostic factor of pulmonary adenocarcinoma. Especially, early cancer of T1N0 cases showing higher expression of CB may need postoperative adjuvant chemotherapy.

Significance of Angiogenic Factors in Liver Metastatic Tumors Originating from Colorectal Cancers

We examined the expression of vascularendothelial growth factor (VEGF) and microvessel countsexpressed by CD34 staining in 39 patients with primaryand 44 patients with metastatic liver tumors ofmetastatic colorectal carcinoma, and 29 patients withnonmetastatic colorectal carcinoma as control in orderto determine their value in the evaluation of prognosisand recurrence after hepatectomy. Microvessel counts in primary colorectal carcinomas of themetastatic group were significantly higher than those incontrol (P < 0.05). Neither factor correlated withany clinicopathological feature of primary or metastatic liver carcinomas. Higher microvessel counts inmetastatic liver tumors tended to be associated with ashorter disease-free interval to second recurrence inthe remaining liver (P = 0.069) and were significantly associated with poor prognosis afterhepatectomy (P < 0.05). We conclude that microvesselcount is an important marker of liver metastatasis andprognosis in patients with colorectal carcinoma treated with hepatectomy.

Relationship between pattern of tumor enhancement and clinicopathologic characteristics in intrahepatic cholangiocarcinoma

Common enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on computed tomography (CT) is that of hypovascular enhancement; however, in some cases, tumor shows identical enhancement in the arterial phase to that in hepatocellular carcinoma. To identify the specific characteristics of different enhancement patterns, we examined the relationship between CT enhancement pattern and clinicopathological features or postoperative prognosis.

Modified Japan Integrated Staging is currently the best available staging system for hepatocellular carcinoma patients who have undergone hepatectomy

BackgroundWe previously reported the effectiveness of the modified Cancer of the Liver Italian Program (CLIP) score in hepatocellular carcinoma (HCC) staging. To determine the best predictive staging system for HCC patients, we conducted a comparative analysis of prognosis using multivariate analysis in 230 Japanese HCC patients following hepatic resection.MethodsWe compared overall survival as predicted by different staging systems: the tumor node metastasis (TNM) system by the Liver Cancer Study Group of Japan, the Japan Integrated Staging (JIS) score (Japanese TNM and Child-Pugh classification), the modified JIS score using liver damage grade, the CLIP score, and our modified CLIP score using protein induced by vitamin K absence or the antagonist II (PIVKA-II).ResultsBy a univariate analysis the PIVKA-II level (cut-off level, 400 mAU/ml) was significantly associated with patient survival (P = 0.031); however, alpha-fetoprotein level was not related to survival. Liver damage grade was significantly associated with patient survival (P = 0.039), although Child-Pugh classification was not related to survival. Univariate analysis showed that prediction of survival, according to disease stage, was better with the modified JIS score than with the TNM system, CLIP, modified CLIP, or JIS score. Multivariate analysis showed the modified JIS score showed the best ability to predict overall survival according to disease stage (Hazard ratio, 1.77; P = 0.002), and its Akaike information criteria statistic was the lowest (634.3).ConclusionsThe modified JIS score, a staging system that combines tumor factors and hepatic function, is a better predictor of prognosis than other systems in HCC patients who have undergone hepatic resection.

Surgical Treatment and Subsequent Outcome of Patients with Carcinoma of the Splenic Flexure

Abstract Extended resection, comprising extended right hemicolectomy, splenectomy, and distal pancreatectomy, has been advocated for carcinoma of the splenic flexure because the lymphatic drainage at this site is variable. The present study addresses the problems associated with selecting the most appropriate operative procedure to achieve cure of splenic flexure cancers. We conducted a retrospective review of 27 patients with splenic flexure cancer who under-went curative resection. Left partial colectomy was performed in 20 patients and partial resection of the transverse/descending colon was performed in 7 patients. The combined resection of adjacent organs due to tumor adherence was performed in three patients. The spleen and distal pancreas were the organs most frequently resected among a collective total of six adjacent organs. The median duration of follow-up was 60.9 months after resection for splenic flexure cancer. No patient developed local recurrence. There was no significant difference in 5-year survival between patients with splenic flexure cancers and those with colon cancers at other sites. In conclusion, splenic flexure cancer resected by left partial colectomy or partial resection of the transverse/descending colon without routine extended resection was not associated with a worse prognosis than colon cancers at other sites.

Circulating sialyl Lewis(x), sialyl Lewis(a), and sialyl Tn antigens in colorectal cancer patients: multivariate analysis of predictive factors for serum antigen levels.

Abstract: Preoperative serum levels of sialyl Lewisa (CA 19-9), sialyl Lewisx (SLX), and sialyl Tn (STN) antigens in colorectal cancer patients were examined to establish predictive factors for serum levels of these antigens compared with carcinoembryonic antigen (CEA). A total of 308 patients who underwent resection for a colorectal cancer were divided into low and high antigen groups (higher or lower than a selected diagnostic-based cutoff value). The cutoff values were 37 U/ml for CA19-9, 38 U/ml for SLX, 45 U/ml for STN, and 2.5 ng/ml for CEA. The American Joint Committee on Cancer Classification and Stage grouping was used to classify the tumors. Statistical tests were conducted using univariate and multivariate logistic regression analyses. For CA19-9, 81 patients (26.3%) were assigned to the high antigen group; for SLX, 39 (12.7%); for STN, 33 (10.7%); and for CEA, 133 (43.2%). Multivariate logistic regression analysis revealed that predictive factors associated with high antigen levels were female sex (odds ratio [OR], 1.78 vs male sex), T4 (OR, 3.26 vs T1/T2), and M1 (OR, 3.35 vs M0) for CA19-9; M1 (OR, 6.40 vs M0) for SLX; mucinous carcinoma (OR, 8.45 vs well differentiated adenocarcinoma) and M1 (OR, 8.24 vs M0) for STN; and mucinous carcinoma (OR, 7.21 vs well differentiated adenocarcinoma), T3/T4 (OR, 3.84/4.18, respectively, vs T1/T2), and M1 (OR, 6.39 vs M0) for CEA. In conclusion, high serum levels of CA19-9, SLX, and STN are strongly associated with distant metastasis. In addition, high serum levels of CA19-9 may be an independent predictor for female gender and T4, and high serum levels of STN may be an independent predictor for mucinous carcinoma.

Expression of Lewis(a), sialyl Lewis(a), Lewis(x) and sialyl Lewis(x) antigens as prognostic factors in patients with colorectal cancer.

BACKGROUND Altered expression of blood group-related carbohydrate antigens such as sialyl Lewis (Le)(x) antigen in tumours is associated with tumour progression behaviour and subsequent prognosis. However, the prognostic value of the expression of Le-related antigens in colorectal tumours remains unclear. PURPOSE To clarify the prognostic value of Le(a), sialyl Le(a), Le(x) and sialyl Le(x) expression in colorectal carcinomas as prognostic factors after surgery. PATIENTS AND METHODS Colorectal carcinoma samples from 101 patients with primary colorectal carcinoma who underwent surgical resection were subject to immunohistochemical analyses for Lea, sialyl Lea, Lex and sialyl Le(x) expression with the respective monoclonal antibodies. RESULTS Le(a), sialyl Le(a), Le(x) and sialyl Le(x) were expressed in 69 (68.3%), 73 (72.3%), 66 (65.4%) and 76 (75.3%) carcinomas, respectively. The patients with sialyl Lex-expressing tumours had more advanced cancer than those with nonsialyl Lex-expressing tumours (P=0.0029). The survival time after surgery of patients with Le(x)- or sialyl Le(x)-expressing tumours was significantly shorter than the survival time of those with non-Le(x)- or nonsialyl Le(x)-expressing tumours, respectively (P=0.023 and P=0. 0001, respectively). Coxs regression analysis revealed that Le(x) and sialyl Le(x) expression, separate from stage and histological type, were prognostic variables for patient survival (hazard ratio [HR] for sialyl Le(x)-positive expression to sialyl L(x)-negative expression 2.90; HR for Le(x)-positive expression to Le(x)-negative expression 12.76 in stage I/IV, 0.63 in stage II and 1.69 in stage III). CONCLUSIONS Le(x) expression and sialyl Le(x) expression in colorectal carcinomas are each associated with poor prognosis. These variables should be considered in the design of future trials.