Effect of CT fluoroscopy-guided transpulmonary radiofrequency ablation of liver tumours on the lung.

OBJECTIVE: We retrospectively evaluated the effect of transpulmonary radiofrequency ablation (RFA) of liver tumours on the lung. METHODS: 16 patients (10 males and 6 females; mean age, 65.2 years) with 16 liver tumours (mean diameter 1.5 cm) underwent transpulmonary RFA under CT fluoroscopic guidance. The tumours were either hepatocellular carcinoma (n=14) or liver metastasis (n=12). All 16 liver tumours were undetectable with ultrasonography. The pulmonary function values at 3 months after transpulmonary RFA were compared with baseline (i.e. values before RFA). RESULTS: In 8 of 16 sessions, minor pulmonary complications occurred, including small pneumothorax (n=8) and small pleural effusion (n=1). In two sessions, major pulmonary complications occurred, including pneumothorax requiring a chest tube (n=2). These chest tubes were removed at 4 and 6 days, and these patients were discharged 7 and 10 days after RFA, respectively, without any sequelae. The pulmonary function values we evaluated were forced expiratory volume in 1 s (FEV1.0) and vital capacity (VC). The mean values of FEV1.0 before and 3 months after RFA were 2.55 l and 2.59 l, respectively; the mean values of VC before and 3 months after RFA were 3.20 l and 3.27 l, respectively. These pulmonary values did not show any significant worsening (p=0.393 and 0.255 for FEV1.0 and VC, respectively). CONCLUSION: There was no significant lung injury causing a fatal or intractable complication after transpulmonary RFA of liver tumours.

T cell repertoire in primary biliary cirrhosis: a common T cell clone and repertoire change after treatment.

T cell repertoire was analyzed in three early-stage primary biliary cirrhosis (PBC) patients, using reverse transcription-polymerase chain reaction and single-strand conformation polymorphism. Multiple expanded clones were demonstrated in livers and peripheral blood lymphocytes (PBL) of all three patients. Comparison of the repertoire of different parts of the liver demonstrated the presence of common clones in various Vbeta families. Comparison of the repertoire between the liver and PBL demonstrated that both CD4 and CD8 T cell clones were expanded. Sequence analysis of complementarity determining region 3 of the expanded clones revealed that relatively conserved amino acids were utilized in each patient and that an identical CD4 T cell clone having Vbeta16 was present in all three patients. The number of expanded T cell clones in PBL decreased markedly after the treatment with prednisolone. These results suggest that common T cell clones may play a pathogenic role in PBC.

Laparoscopic findings in primary sclerosing cholangitis.

BACKGROUND AND STUDY AIMS: Primary sclerosing cholangitis (PSC) is a cholestatic disease characterized by segmental narrowing and dilatation of bile ducts. Few studies have been performed on the laparoscopic findings associated with this disease, and the present study was intended to assess the usefulness of laparoscopy for the diagnosis and staging of PSC. PATIENTS AND METHODS: Six patients were examined by laparoscopy with liver biopsy. Repeated laparoscopy was performed in three patients. RESULTS: Laparoscopy revealed coarse surface irregularity and discoloration. Surface irregularity was classified into four grades: smooth, shallowly depressed, undulated, and nodular. The affected area showed whitish yellow discoloration. The discolored area was demonstrated as a poorly stained area by intravenous injection of indocyanine green (ICG). Lobular markings became apparent because of the yellow color change in the portal tract, resulting in a leopardskin-like appearance. Lymph-vessel dilatation was seen in advanced stages. Repeated laparoscopy of a patient without treatment demonstrated a progression from a smooth surface to a shallow depression with leopardskin-like markings. On the other hand, the two patients treated with immunosuppressive agents showed improvement of liver swelling and disappearance of the leopardskin-like markings and lymph-vessel dilatation. CONCLUSIONS: Laparoscopy may provide useful information for the diagnosis and staging of PSC.

Vascular integrin beta 3 and its relation to pulmonary metastasis of colorectal carcinoma.

Integrin alpha v-beta 3 is involved in tumor angiogenesis while the clinical significance of beta 3 integrin expression in colorectal cancer and lung metastases. Analysis was performed on 51 colorectal cancer patients (22 with subsequent lung metastasis and 29 without lung metastasis). Fifty-one primary tumors and 22 lung metastases were examined for immunohistochemical detection of integrin beta 3. We found that the antibody VNR 5 to integrin beta 3 prefentially stains the blood vessels of small caliber. Indeed, vascular integrin beta 3 index was significantly higher in tumors of patients with lung metastasis than in those without lung metastasis. In the patients with lung metastases, vascular integrin beta 3 index was significantly lower in lung metastases than in primary tumors. It was immunohistochemically proved that integrin beta 3 is an important vascular endothelial cell market for lung metastasis.

Prognostic significance of expression of thymidine phosphorylase and vascular endothelial growth factor in human gastric carcinoma.

BACKGROUND AND OBJECTIVES: Both thymidine phosphorylase (dThdPase) and vascular endothelial growth factor (VEGF) are well-characterized inducers of angiogenesis. The purpose of this study was to examine the expression of these antigens and their prognostic significance in gastric carcinoma. METHODS: Medical records of 102 patients with stage II tumor were retrospectively reviewed. Primary tumors were studied by immunohistochemical staining for dThdPase and VEGF. RESULTS: Positive dThdPase expression was observed in 52 (51%) tumors and positive VEGF expression in 53 (52%) tumors. There was a significant correlation between the positive expression of VEGF and lymphatic invasion. The patients with dThdPase-positive carcinoma showed a significantly worse prognosis than those with dThdPase-negative carcinoma in stage II. Moreover, the frequency of hepatic recurrence was significantly higher in the patients with dThdPase-positive and VEGF-positive tumors than in those with dThdPase-negative and VEGF-negative tumors. CONCLUSIONS: Combination analysis of dThdPase and VEGF expression in gastric carcinoma appears to be well-characterized inductors of prognosis and metastasis.

Aberrant expression of cytokeratin 7 as a histological marker of progression in primary biliary cirrhosis.

AIM: We evaluated the aberrant expression of cytokeratin 7 (CK-7) in hepatocytes as a marker of cholestasis and progression in primary biliary cirrhosis (PBC). PATIENTS AND METHODS: The expression of CK-7 was studied by immunohistochemistry in 83 cases of PBC. This expression was compared with biochemical data, the deposition of copper-associated protein, and previous histological classifications. RESULTS: In normal liver, CK-7 was expressed exclusively in bile duct epithelial cells (BDE). In PBC, the expression was also observed in hepatocytes. The expression pattern was classified as follows: Grade 0, BDE as in normal; Grade 1, proliferated bile ductules; Grade 2, periportal hepatocytes in addition to proliferated bile ductules; Grade 3, intralobular hepatocytes; Grade 4, the majority of hepatocytes. The grades correlated with serum bilirubin levels but not with serum levels of biliary enzymes. A discrepancy between the CK-7 grading and Ludwig's classification was noted in cases with Stage 1 of the CK-7 grading who were considered Stage 2 or 3 in Ludwig's classification, suggesting that cholestasis and inflammatory activity might be independent events. CONCLUSIONS: These results suggest that the aberrant expression of CK-7 in hepatocytes may be a marker of chronic cholestasis and progression in PBC.

Treatment of patients with gastric cancer and duodenal invasion.

We retrospectively examined clinicopathologic features of gastric cancer with duodenal invasion to clarify the effect of surgical treatment that include pancreaticoduodenectomy (PD). Among 2504 patients with gastric cancer, 69 (2.8%) who had gastric cancer and duodenal invasion resected by surgical treatment were investigated. The mode of the duodenal invasion was grouped into three categories: mucosal type, submucosal type, and nodal type. Mucosal type is invasion of the duodenal mucosal layer, submucosal type is invasion of the submucosal layer or deeper, and nodal type is invasion from nodal metastatic lesions around the pancreatic head. The 5-year survival rates of curative PD and curative gastrectomy were 37.3% and 33.8%, respectively. Despite the incidence of adjacent tissue infiltration and significantly higher duodenal invasion average length in cases with PD than in cases with gastrectomy, there was no significant difference in the survival curves. However, the prognoses of the cases with nodal-type invasion were significantly poorer, and all these patients died within 2 years, regardless of whether curative PD had been performed. Curative PD improves the prognosis of cases with long duodenal invasion or pancreas infiltration except for nodal-type duodenal invasion.

p53 immunoreactivity in Barrett's metaplasia, dysplasia, and adenocarcinoma--a case report.

Barrett's esophagus is a condition in which the stratified squamous epithelium of the esophagus is replaced by a columnar epithelium with malignant potential. Mutations of the tumor-suppressor gene p53 have been implicated in the evolution of esophageal carcinomas. The aim of this study was to determine whether p53 immunoreactivity in Barrett's esophagus is a marker of neoplasia and, if so, when it occurs in the metaplasia-dysplasia-carcinoma sequence. We treated a patient with esophageal carcinoma arising from the Barrett's esophagus. Consecutive evidence existed for a metaplasia-dysplasia-carcinoma in the same specimen. Immunohistochemical staining with the monoclonal antibody was used to detect the intranuclear protein product of mutated p53. No p53 immunoreactivity was seen in specimen of Barrett's mucosa. p53 immunoreactivity was found only in specimen of dysplasia and carcinoma. Immunoreactivity occurs late in the metaplasia-dysplasia-carcinoma sequence, during the transition to high-grade dysplasia.

Long-term postoperative functional evaluation of pylorus preservation in Imanaga pancreatoduodenectomy.

Our purpose was to determine whether pylorus-preservation in the Imanaga (PpPDI) method minimizes postoperative impairment of gastrointestinal function. Nine patients who had undergone PpPDI (postoperative years: 5.7 +/- 2.6) and nine patients who had undergone conventional Imanaga pancreatoduodenectomy (PDI) (postoperative years: 6.8 +/- 2.0) were evaluated for symptoms, nutritional parameters, and physiologic function of the biliary tract and residual stomach using gastric emptying and hepatobiliary scintigraphy. The body weight recovered to 99.3% +/- 3.8% of pre-illness body weight in PpPDI, showing a significantly better recovery than in patients after the PDI procedure (91.0% +/- 6.4%, P < 0.05). The mean gastric emptying half-time (GET1/2) in the upright position after PDI was significantly shorter (42.3 min) than after PpPDI (80.8 min, P < 0.05). Mixture of food with bile was conserved better in the PpPDI group than in the PDI group. In the long term, the pylorus-preserving Imanaga-type procedure minimizes disruption of gastric function and asynchrony between ingested food and bile.

Expression of perforin and Fas ligand mRNA in the liver of viral hepatitis.

Cytotoxic T lymphocytes (CTLs) play an important role in the pathogenesis of viral hepatitis. We studied the expression of mRNAs of perforin and Fas ligand (Fas-L) in biopsy specimens from chronic hepatitis B (CHB) (15 cases) and hepatitis C (CHC) patients (13 cases). Both perforin and Fas-L mRNAs were detected in all cases of both CHB and CHC. No messages were detected in the control livers from two cases of fatty liver, a case of Gilbert's syndrome, and a case of Dubin-Johnson syndrome. Semiquantitative analysis revealed a positive correlation between the intensity of perforin and Fas-L mRNAs in both CHB and CHC. In CHB, the intensity of both perforin and Fas-L mRNAs showed a positive correlation with the histological activity and serum alanine aminotransferase level, while the correlation was not apparent in CHC. These results suggest that both perforin and Fas/Fas-L systems are involved in the pathogenesis of liver cell injury of CHB and CHC.

Apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas induced by preoperative administration of 5-fluorouracil.

The purpose of this study was to examine the correlations among enhancement of apoptosis, cell proliferation and expression of oncogenes in gastric carcinomas induced by preoperative oral administration of 5-fluorouracil (5-FU). The occurrence of spontaneous apoptotic cell death in 42 patients with gastric carcinoma was analyzed in the biopsy specimens preoperatively. p53 status was examined by polymerase chain reaction-single strand confirmation polymorphism and sequencing. Fourteen patients received oral administration of 5-FU at 300 mg/body/day for 7 days preoperatively. For detection of apoptotic cells, apoptotic incidences (AIs) were examined by the terminal deoxynucleotidyl transferase-mediated deoxy-uridine triphosphate biotin nick end labeling method, on gastric carcinoma lesions based on the endoscopic findings before administration in the biopsy and resected tissues. Expressions of p53, Bcl-2, Bax gene and proliferating cell nuclear antigen (PCNA) were also examined by immunohistochemical staining. On preoperative biopsy, p53 point mutation was observed in 14 of the 42 tumors. The immunohistochemical staining status and point mutation of p53 gene (positive or negative) were identical in 32 of the 42 tumors (76.2%). The average AIs of the biopsy specimens were 1.58+/-1.26% on p53-negative staining (n=19) and 1.14+/-1.02% on p53-positive staining (n=23), a significant association was not recognized between p53 expression and AI. In the preoperative administration group, the PCNA labeling index was significantly higher in the biopsy specimens than in the resected tissues (43. 6+/-12.8% vs. 35.3+/-8.8%, p<0.01). In addition, postoperatively, the rate of AI was significantly more accelerated in p53-negative staining (n=6) than in p53-positive staining (n=8) (0.89+/-0. 65%right curved arrow 4.18+/-3.26%, p<0.05 vs. 1.20+/-0.60%right curved arrow 2.60+/-2.60%, NS). There was no significant correlation between AI and Bcl-2 or Bax staining. Immunohistochemical analysis of p53 and PCNA stainings in biopsy specimens appears to be a well-characterized indicator of sensitivity of chemotherapy in gastric carcinomas.

Evaluation of PCNA, p53, K-ras and LOH in endocrine pancreas tumors.

BACKGROUND/AIMS: The object of this study was to evaluate the characters of the endocrine pancreas tumors including proliferative activity, p53 mutation, K-ras mutation and microsatellite instability. METHODOLOGY: The 13 endocrine tumors of the pancreas were enrolled in this study. There were 8 hypervascular tumors and 4 normo- or hypovascular tumors. All cases were immunohistochemically characterized in paraffin sections for the presence of proliferating cell nuclear antigen and p53 protein. Mutation in K-ras at codon 12 was detected by the Mutant-allele-specific amplification system. Microsatellite instability was examined by using frozen tissues in the 2 cases. RESULTS: Proliferating cell nuclear antigen labeling index range was 0.00-0.62 (0.26 +/- 0.23). p53 was positive in 4/13 tumors. K-ras codon 12 mutation was not detected in any tumors. PCNA LI was significantly lower in hypervascular tumors (0.16 +/- 0.20) than normo- or hypovascular tumors (0.44 +/- 0.17) (P < 0.05). PCNA LI was significantly lower in the p53-positive tumors (0.48 +/- 0.17) than the p53-negative tumors (0.17 +/- 0.18) (P < 0.05). K-ras codon 12 mutation was not detected in any tumors. Loss of heterozygosity in 3p was detected in 1 tumor. CONCLUSIONS: Hypervascular endocrine pancreas tumors have low proliferative activity. p53 mutation influences proliferation as the late event of tumor progression.

Strategy for pancreatic endocrine tumors.

BACKGROUND/AIMS: The endocrine tumors of the pancreas are rare diseases and there is no established standard therapy for the liver metastasis of pancreatic endocrine tumors. In this study, the therapy for the pancreatic endocrine tumors was evaluated. METHODOLOGY: The endocrine pancreas tumors of 13 patients had been surgically treated. All primary tumors were completely resected. The liver metastasis was recognized in 4 patients. Partial resection of the liver was performed in 2 patients. Lipiodol-transcatheter arterial embolization was performed for synchronous unresectable liver metastases in the other 2 patients. RESULTS: The patients with no liver metastases survived without recurrence (max: 18.8 yr; mean follow-up: 9.2 yr). The patient with resected synchronous solitary liver metastasis died of recurrent multiple liver metastases 5 months after surgery. The other patient with the metachronous liver metastasis completely resected survived 13.9 years. In the 2 patients with unresectable numerous liver metastases, after lipiodol-transcatheter arterial embolization, tumor necrosis rate was more than 90% in both cases and serum gastrin level was normalized. CONCLUSIONS: Complete resection of liver metastasis is favorable, whereas lipiodol-transcatheter arterial embolization is effective for unresectable liver metastases from pancreatic endocrine tumors as palliation. Complete resection of the primary site is recommended even in the cases with unresectable numerous liver metastases.

A new examination for both biliary and gastrointestinal function after pancreatobiliary surgery--single-isotope two-day method.

BACKGROUND/AIMS: There are no established tests for both biliary and gastrointestinal function after pancreatobiliary surgery. In this study, mixing of ingested food with bile after long-term postoperative period was evaluated. METHODOLOGY: Sixteen patients having undergone Imanaga pancreatoduodenectomy (postoperative years = 6.2 +/- 2.0) were evaluated concerning physiologic function of biliary tract and residual stomach using gastric emptying and hepatobiliary scintigraphy. RESULTS: At least 24 months after Imanaga pancreatoduodenectomy, postoperative patients had reached 95.8 +/- 4.9% of the pre-illness bodyweight. Gastric emptying half-time (GET1/2) ranged from 9-147 min (mean: 60.6 +/- 35.0). The time of bile excretion from liver to jejunum ranged from 5-45 min (mean: 11.3 +/- 7.8). Asynchrony time ranged from -5-40 min (mean: 11.3 +/- 7.8). There was no significant correlation between GET1/2 and recovery of bodyweight (r = -0.042, P = 0.8809). Similarly, there was no significant correlation between the time of bile excretion and recovery of bodyweight (r = 0.042, P = 0.8791). On the other hand, asynchrony time had a significant inverse correlation with recovery of bodyweight (r = -0.590, P = 0.0146). CONCLUSIONS: Single-isotope two-day method is an original and useful technique to evaluate biliary and gastrointestinal physiologic function after long-term postoperative period.

Fcgamma receptor expression on hepatic macrophages and histological activity of chronic hepatitis.

AIMS/BACKGROUND: Activated liver macrophages in chronic hepatitis express a high affinity receptor for IgG named FcgammaRI. This study was performed to find the difference in FcgammaRI expression between chronic hepatitis B (CHB) and C (CHC) with reference to histological activity. METHODS: Consecutive patients with CHB (20 cases) and CHC (25 cases) were enrolled in the study. Inflammatory activity was evaluated using the modified histological activity index (HAI). FcgammaRI-positive macrophages were quantitatively measured by computer assisted morphometry. RESULTS: Total HAI score was significantly higher in CHB than in CHC. Confluent necrosis was observed in significantly higher frequency in CHB at Stages 3 5 than in CHC. The percentage area of FcgammaRI-positive macrophages was significantly higher in CHB than in CHC. In CHB, the percentage area of FcgammaRI-positive macrophages correlated with total HAI (<0.01) as well as the degree of confluent necrosis (<0.01), interface hepatitis (<0.05) and portal inflammation (<0.05). FcgammaRI-positive macrophages accumulated mainly at the site of confluent necrosis. In CHC, no correlation was observed between activated macrophages and any histological categories. CONCLUSION: These results suggest that FcgammaRI-positive macrophages are associated with confluent necrosis in CHB, which is more common in CHB patients than in CHC.

Esophageal sarcomas: report of three cases.

BACKGROUND/AIMS: Sarcomas of the esophagus, including carcinosarcoma, are rare neoplasms. METHODS: The clinical and pathologic characteristics of 3 patients with esophageal sarcomas are presented, including the only recorded esophageal carcinosarcoma and 2 patients with leiomyosarcoma. RESULTS: All 3 patients were males who presented with dysphagia or an abnormal shadow of the mediastinum on a plain chest X-ray. Two tumors were in the middle esophagus, and the remaining one was in the distal esophagus. On endoscopic examination, all three tumors were noted to be polypoid. These patients underwent surgical excision. One patient died 7 days following the operation, and the remaining 2 patients died of liver metastasis 10 and 22 months following the treatment. CONCLUSION: Esophagectomy or esophagogastrectomy is a surgical choice. Even if metastases are present, a palliative resection can still be performed.