Usefulness of endoscopic ultrasound-guided fine-needle aspiration biopsy for the diagnosis of pancreatic cancer.

BACKGROUND: Endoscopic ultrasonography-guided fine-needle aspiration biopsy (EUS-FNAB) has come into widespread use, mainly in Western countries, as an efficient and safe method for the cytologic or histologic diagnosis of pancreatic cancer. However, it still has received relatively little attention in Japan. To evaluate the clinical status of EUS-FNAB in Japan, we retrospectively analyzed the results with regard to the ability of EUS-FNAB to diagnose pancreatic cancer, as well as its safety. METHODS: A total of 52 patients (37 male, 15 female; mean age, 62.5 years; range, 33-85 years) with focal pancreatic lesions underwent EUS-FNAB at our group of hospitals in one region of Japan. Final diagnosis was confirmed by histologic examination of surgical specimens or clinical follow-up. RESULTS: The final diagnoses were malignant tumors in 32 patients and benign ones in 20. Insertion of the needle into the lesion was successful in 50 of the 52 patients (96.2%). Adequate specimens were obtained by EUS-FNAB from 47 of the 50 pancreatic lesions (94.0%). With five false-negative and no false-positive results, the accuracy, sensitivity, specificity, and positive and negative predictive values were 89.4%, 82.1%, 100%, 100%, and 79.2%, respectively. No complications occurred. CONCLUSIONS: EUS-FNAB is an efficient and safe method for the histologic diagnosis of pancreatic cancer. It should be considered as one of the indispensable modalities for the histological diagnosis of pancreatic cancer in Japan, as it is in Western countries.

Comparative genomic hybridization analysis for pancreatic cancer specimens obtained by endoscopic ultrasonography-guided fine-needle aspiration.

BACKGROUND: Comparative genomic hybridization (CGH) analysis of pancreatic cancer has been done exclusively for surgical and autopsy specimens, because of the difficulty of tissue sampling without surgery. To overcome this difficulty, we applied CGH technology to cells obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). METHODS: In the present study, we performed EUS-FNA for 17 patients with pancreatic cancer before surgery. Tumor cells were selected by microdissection. DNA was extracted from the cells and amplified by degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR). Then CGH was carried out. RESULTS: In the 15 patients with tubular adenocarcinoma, the most common loci of gains (including amplification) were 5p, 8q, and 20q (60% of the patients); and 1q, 7p, and 12p (27%). The most frequent losses were 17p (73%); 9p, 18q, and 19p (47%); and 8p (33%). These findings were similar to our previously reported data. Both of the patients with acinar cell carcinoma showed gains of 2q and 5p, and losses of 1p, 9p, 9q, 11p, 11q, 14q, 17p, 17q, and 18q. CONCLUSIONS: The results of this study suggest that comprehensive genetic analysis is possible for EUS-FNA biopsy specimens, with a combination of microdissection and DOP-PCR. This analytical strategy will enable us to evaluate the biological characteristics of pancreatic cancer before treatment.

Increased expression of matrix metalloproteinase-7 in invasive early gastric cancer.

BACKGROUND: Matrix metalloproteinase-7 (MMP-7), a proteolytic enzyme, is suspected to play an important role in the progression of various cancers. To clarify the clinical importance of MMP-7, we retrospectively analyzed MMP-7 expression in gastric epithelial tumors. METHODS: We tested 201 lesions (from 172 patients) of surgically or endoscopically resected gastric epithelial tumors (gastric cancer, 158 lesions; gastric adenoma, 32 lesions; hyperplastic polyp, 11 lesions). MMP-7 expression was immunohistochemically examined. Sections with immunostaining signals in more than 30% of tumor cells were judged to show positive expression. RESULTS: MMP-7 was expressed in 33.3% (67/201) of all lesions. MMP-7-positive tumors were significantly more frequent in diffuse-type adenocarcinomas (62.2%; 28/45) compared with intestinal-type lesions (31.9%; 36/113; P < 0.001). Cancers invading the submucosa or deeper (60.5%; 46/76) were showed positivity significantly more frequently than mucosal cancers (22.0%; 18/82; P < 0.001). MMP-7-positive lesions increased with the progression of gastric epithelial tumors, including adenomas, mucosal cancers, and cancers invading the submucosal layer or deeper (P < 0.001). MMP-7 expression occurred significantly more often in lymphatic invasion-positive cancers (65.1%; 41/63) than in lymphatic invasion-negative cancers (24.2%; 23/95; P < 0.001). CONCLUSIONS: The MMP-7-positive rate increased with the progression of gastric epithelial tumors, such as adenoma, mucosal cancer, and cancer invading the submucosal layer or deeper. MMP-7 was significantly associated with aggressive pathological phenotypes of cancer. The detection of the MMP-7 protein may be useful in pretherapeutic diagnosis.

Vascular endothelial growth factor-C expression in human gallbladder cancer and its relationship to lymph node metastasis.

Lymph node metastasis is a major prognostic factor in human cancer. Vascular endothelial growth factor C (VEGF-C) is a lymphangiogenic polypeptide that has been implicated in several human solid tumors. However, the clinical significance of VEGF-C has remained unknown in gallbladder carcinoma. Paraffin-embedded tumor specimens of 52 surgically resected gallbladder cancers were immunohistochemically stained for VEGF-C, VEGF, and CD34. The correlations among VEGF-C expression, VEGF expression, microvessel density (MVD), clinicopathologic features, and clinical outcomes were statistically analyzed. Thirty-three (63%) of the 52 gallbladder cancers were highly positive for VEGF-C protein by immunohistochemistry. VEGF-C expression was significantly correlated with lymphatic vessel involvement, lymph node metastasis, and worse outcomes after operation (p<0.001, p<0.001, p<0.001, respectively), but not with MVD. By the Cox regression model, lymphatic vessel involvement emerged as an independent prognostic parameter. These results suggest that VEGF-C may play a role in tumor progression via lymphangiogenesis and lymph node metastasis in human gallbladder cancer.

[Low dose exposure to cadmium and its health effects (1). Genotoxicity and carcinogenicity].

We reviewed studies on genotoxicity and carcinogenicity of cadmium (Cd). Salmonella typhimurium and Escherichia coli exposed to Cd did not show mutagenicity, whereas cultured mammalian cells exposed to Cd showed mutation, DNA strand breaks, and chromosomal aberrations. Carcinogenicity tests showed that exposure to Cd increased the occurrence of tumors in testis, lung, prostate, hematopoietic tissues, and injection sites. On the other hand, recent epidemiologic studies are not supportive of earlier observations on the association between Cd and prostate cancer. The US NIOSH data on a possible association between Cd and lung cancer may need reevaluation. No studies which show a positive relationship between oral Cd exposure and carcinogenesis have been reported. All available data suggest that Cd should be reassigned to IARC Group 2A (probably carcinogenic to humans) from the current Group 1.