[A case of a solitary splenic metastasis from gastric cancer].

A 69-year-old man was brought to our hospital's emergency room with a chief complaint of hematemesis, which had been caused by advanced gastric cancer on the lesser curvature of the stomach's upper body. Subsequently, total gastrectomy with lymph node dissection (D2) was performed. A pathological diagnosis of gastric adenocarcinoma, U, Less, type 2, 100×70mm, tub2, pT3, int, INFb, ly0, v0, pN0 (0/24), pPM0 (30mm), pDM0 (30mm), fStage IIA, was then established. After discharge, the patient was treated with S-1 as adjuvant chemotherapy at a dose of 120mg per day. However, a decrease in the platelet count prompted termination of chemotherapy, which lasted for three courses. Ten months after surgery, serum CEA levels increased to 116.6ng/ml, with enhanced CT showing a solitary splenic tumor with a diameter of 48×52mm suggestive of gastric cancer recurrence. PET/CT revealed no other tumors suggestive of gastric cancer recurrence. Given that only a solitary splenic metastatic tumor was detected, splenectomy was performed eleven months after surgery. Histological findings were the same as the previous gastric cancer, with peritoneal washing cytology being suspicious. Chemotherapy with the SOX regimen (S-1 at a dose of 120mg per day and oxaliplatin at a dose of 100mg/m2) was then started. The patient remained recurrence-free for a half year. Except during the terminal phase, only a few cases of a splenic metastasis from gastric cancer have been reported. We consider splenectomy to be potentially useful for patients with a solitary splenic metastasis from gastric cancer, through which prolonged prognosis could be expected.

Water immersion colonoscopy facilitates straight passage of the colonoscope through the sigmoid colon without loop formation: randomized controlled trial.

BACKGROUND AND AIM: One of the major causes of pain during colonoscopy is looping of the instrument during insertion through the sigmoid colon, which causes discomfort by stretching the mesentery. There are many studies in colonoscope techniques, but they have not been assessed objectively with respect to colonoscope passage through the sigmoid colon without loop formation. The aim of the present study was to determine whether cap-fitted colonoscopy and water immersion increase the success rate of insertion through the sigmoid without loop formation. METHODS: A total of 1005 patients were randomized to standard colonoscopy, cap-fitted colonoscopy or water immersion technique. All examinations were carried out under a magnetic endoscope imaging device. Main outcome was the success rate of insertion without loop formation. RESULTS: Success rate of insertion without loop formation was 37.5%, 40.0%, and 53.8% in the standard, cap, and water groups, respectively (standard vs water P = 0.00014, cap vs water P = 0.00186). There were no significant differences among the groups regarding cecal intubation rate, cecal intubation time and number of polyps ≥5 mm per patient. CONCLUSIONS: Water immersion increases the success rate of insertion through the sigmoid colon without loop formation. This practical technique, requiring only preparation of a cap and water, is useful without compromising cecal intubation rate, cecal intubation time, or polyp detection rate.

Hypoxia-induced up-regulation of angiopoietin-2 in colorectal cancer.

Angiogenesis is a compensatory mechanism that enables malignant tumors to survive in an oxygen-deficient environment. To test our hypothesis that hypoxia stimulates the production of angiopoietin-2 (Ang-2) in colorectal cancer (CRC), we investigated the expression of Ang-2 in three cultured CRC cell lines, and in specimens from 11 CRC metastatic liver tumors. Hypoxia-induced Ang-2 mRNA expression was clearly evident in HCT116 cells that did not express Ang-2 under normoxic conditions. Ang-2 mRNA was detected only after 48 h in hypoxic serum-deprived cultures in a LoVo cell line, and under both normoxic and hypoxic conditions without any noticeable difference in the HT29 cells. There was a stepwise increase in Ang-2 expression from the periphery to the central part of the liver metastatic foci, whereas an inverse result was noted in tumor blood vessels, with a gradual decrease in CD31-positive ECs from the edge to the central region of the metastatic lesion. An expression pattern similar to Ang-2 was found in glucose transporter 1 (Glut-1), a known hypoxia-induced factor. These findings suggest that hypoxia plays an important role in inducing the expression of Ang-2 in CRC.

Methylation and expression of p16INK4 tumor suppressor gene in primary colorectal cancer tissues.

It is known that p16(INK4) tumor suppressor gene expression in colon cancer cells is repressed by methylation at the CpG island of promoter, but in vivo silencing of p16 gene is not fully understood. Some studies showed that primary colorectal cancer (CRC) tissues often overexpress the p16 protein, while others showed the high incidence of p16 methylation. The aim of this study was to clarify p16 gene regulation in vivo. We used real-time methylation-specific PCR (MSP) to examine density of p16 methylation, and immunohistochemistry, Western blot analysis to determine p16 protein expression. Methylation was detected in 5 CRC cell lines tested and 9 of 21 (42.9%) CRCs. Four of 5 CRC cell lines did not express p16 mRNA, but 6 of 9 CRCs did express p16 mRNA even with methylation. Real-time MSP showed that CRC tissues had a wide variety in methylation density (methylation index: 0.28-0.91) and that highly methylated CRC tissues displayed significantly lower p16 mRNA expression than those with no-methylation or low-methylation. Immunohistochemistry showed that the majority of CRCs (53 of 55: 96.4%) overexpressed the p16 protein. Low p16 expression was associated with lymph node metastasis (p=0.003) and large tumor size (p=0.048). Western blot in a subset of non-tumor and tumor samples showed a consistent overexpression of the p16 protein. These results showed that CRC tissues displayed variable methylation density, which may be characteristics of p16 gene methylation in vivo. Our data suggest that a low p16 expression due to methylation may contribute to tumor enlargement and expansion of CRC.

Hepatic expression of ANG2 RNA in metastatic colorectal cancer.

We examined the RNA content of the gene encoding angiopoietin (Ang)-2, a modifier of angiogenesis, in hepatic metastases of colorectal cancer (CRC) to explore the role of this protein in neovascularization of metastatic foci. Metastatic CRC exhibited notable blood flow and tumor vessel formation at tumor frontiers. Reverse-transcription polymerase chain reaction assays indicated that the ANG2 RNA content was greater in metastatic CRC than in primary CRC. Investigation of metastatic foci using laser capture microdissection revealed that the RNA content of ANG2, but not ANG1, increased from the bordering liver region to the periphery of the metastatic disease, and also from the periphery to the intermediate portion of the metastatic lesion; immunohistochemical analysis confirmed that there was a corresponding gradual increase in Ang-2 protein expression. Tie-2, a receptor for angiopoietins, was preferentially expressed in the bordering liver region rather than in metastatic CRC. Vascular endothelial growth factor (VEGF) also exhibited an expression pattern similar to that of Ang-2, and there was a significant correlation between the RNA content of ANG2 and that of VEGF in dissected samples (P =.002). Western blot analysis suggested that expression of Ang-1, Ang-2, Tie-2, and VEGF may be regulated at a transcriptional level. The increase in ANG2 RNA content from the peripheral portion of the tumor to the intermediate portion, coinciding with the decrease in recruitment of periendothelial supporting cells around the vascular endothelial cells, suggests that Ang-2 may play a role in the immaturity of tumor vessels. In conclusion, the current study suggests that Ang-2 and VEGF may cooperate to enhance the formation of new blood vessels in metastases of CRC to the liver.

Overexpression of CDC25A phosphatase is associated with hypergrowth activity and poor prognosis of human hepatocellular carcinomas.

PURPOSE AND EXPERIMENTAL DESIGN: CDC25 genes are cell cycle-activating phosphatases that positively regulate the activity of cyclin-dependent kinase. CDC25A and CDC25B, being oncogenes, are overexpressed in a variety of human malignancies. To investigate the potential roles of CDC25s in hepatocellular carcinoma (HCC), expression of CDC25A and CDC25B was examined in human HCC samples. RESULTS: Reverse transcription-PCR showed that overexpression of CDC25A and CDC25B mRNAs was found in 9 of 13 (69%) and 4 of 13 (31%) HCCs, respectively. Immunohistochemistry of 59 HCCs showed marked increase in CDC25A expression, but not CDC25B, in HCC compared with noncancer tissues, and high expression of CDC25A in 33 of 59 (56%) HCCs. Overexpression of CDC25A in HCC was confirmed by Western blot analysis. High expression of CDC25A was associated with dedifferentiated phenotype and portal vein invasion (P = 0.001 and 0.031, respectively), and expression of CDC25A correlated well with proliferating cell nuclear antigen labeling index (P = 0.005). Univariate analysis indicated that high expression of CDC25A and proliferating cell nuclear antigen were both significant predictive factors for shorter disease-free survival (P = 0.004 and 0.039, respectively). Multivariate analysis indicated that CDC25A was an independent prognostic marker for disease-free survival (risk ratio for cancer relapse, 2.98; P = 0.029), even when analyzed with several clinicopathologic factors. On the other hand, expression of CDC25B did not correlate with any clinicopathological features. CONCLUSION: Our findings suggest that CDC25A, but not CDC25B, could be used as an independent prognostic marker for HCC. Our data would also contribute to forward understanding of tumor biology of HCC that is associated with cell cycle regulation.