[A case of Complete Response(CR)to combination therapy of S-1 and Gemcitabine(GEM)for unresectable pancreatic cancer].

Pancreatic cancer is among the most lethal of all digestive cancers, and it is very difficult to obtain long-term survival of unresectable cases. This case report reveals that combination chemotherapy with S-1/gemcitabine(GEM)was very effective for a patient with unresectable pancreatic body cancer. The patient was a 72-year-old female(Stage IVb). They were administered S-1 80mg/day for 2 weeks and GEM 1, 000mg/m2 on day 8 and 15 followed by a 2-week recovery period. After finishing the 2 courses, there was a notable reduction in tumor size. After finishing 9 courses, the tumor could not be observed and it was judged it to be CR. Currently, at 1 year and 4 months from the initial diagnosis, there is no recurrence of tumor, and the general condition of the patient is very good. Combination chemotherapy with S-1/GEM may be useful to improve the prognosis for unresectable pancreatic cancer.

Role of aldose reductase in the peritoneal changes of patients undergoing peritoneal dialysis.

BACKGROUND/AIMS: The mesothelium of patients undergoing peritoneal dialysis (PD) is exposed to glucose in dialysate. Glucose metabolites 3-deoxyglucosone and advanced glycation endproducts (AGEs) in the PD fluid induce peritoneal damage. Circulating factors also affect the peritoneum in the uremic model and predialysis patients. Aldose reductase (AR) generates precursors of 3-deoxyglucosone. We have reported AR acceleration in uremic patients. Therefore, AR acceleration might affect the peritoneum. The purpose of this study was to evaluate the AR level in PD patients and to determine the factors that change the peritoneum of these patients. METHODS: We measured the PD effluent (eff-) concentration of cancer antigen 125 (CA125) as a marker of mesothelial viability in PD patients. Erythrocyte AR, eff-, and plasma (p-) concentrations of 3-deoxyglucosone, AGEs, and malondialdehyde were also studied in 30 PD patients, 18 patients undergoing hemodialysis, and 8 control subjects. RESULTS: In the PD group, AR, p-3-deoxyglucosone, p-AGEs, and p-malondialdehyde were higher than in the control group. The predictors for eff-CA125 were not only PD duration and eff-3-deoxyglucosone, but also AR. CONCLUSION: AR was upregulated in PD patients. AR acceleration may affect the peritoneum in these patients. Further studies are needed to clarify the role of AR in PD patients.

Endocrine cell and nerve regeneration in autologous in situ tissue-engineered small intestine.

BACKGROUND: The purpose of this study was to regenerate a larger size of small intestinal tissue than that of our previous study and to evaluate the regeneration of the endocrine cells (ECC) and nerve system of autologous tissue-engineered small intestine. The effect of implantation of large numbers of smooth muscle cells (SMC) for the regeneration of small intestine was also investigated. METHODS: Two types of scaffolds with different cell densities were fabricated: low density (LD) of SMC in the scaffold and high density (HD) of SMC in the scaffold. Both scaffolds were implanted into defects of isolated ileum in a canine model. Animals were sacrificed at 8, 12, 18, and 24 weeks. RESULTS: The area of engineered small intestine in the HD group was four times larger than that in the LD group, although that was smaller in size than the original size of the defect. There were no significant changes in the thickness of regenerated smooth muscle layer (SML) in the LD and HD groups. The numbers of endocrine cells gradually increased after implantation. At 18 weeks of regeneration, the number of ECC reached levels comparable to that of normal mucosa. The nerve fibers extended to the center of the graft area and were observed in regenerated SML and regenerated villi at 24 weeks. CONCLUSIONS: The ECC and nerve fibers were regenerated in autologous in situ tissue-engineered small intestine. Seeding a large number of SMC was not sufficient for the regeneration of the small intestine in a tubular configuration.

Down-regulation of RUNX1, RUNX3 and CBFbeta in hepatocellular carcinomas in an early stage of hepatocarcinogenesis.

BACKGROUND: Our previous studies suggested that deficient function of RUNX3 protein is causally related to development and progression of human gastric cancer. RUNX3 is mapped to 1p36, which is frequently deleted in hepatocellular carcinomas (HCC), therefore, these tumors were investigated for expression and copy number changes of RUNX3 and other Runt-related genes, RUNX1, RUNX2, and their co-factor CBFP. Similarly nearby uninvolved liver showing cirrhosis or normal histology was investigated in conjunction with various clinicopathological factors. MATERIALS AND METHODS: Copy number change and expression change of RUNX family genes in 35 hepatocellular carcinoma specimens and adjoining liver with cirrhosis (LC) or normal histology were estimated using quantitative reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization.

Tissue engineering of small intestinal tissue using collagen sponge scaffolds seeded with smooth muscle cells.

In a previously reported attempt to regenerate small intestine with autologous tissues, collagen scaffolds were used without cell seeding or with autologous mesenchymal stem cell seeding. However the regenerated intestine lacked a smooth muscle layer. To accomplish regeneration of a smooth muscle layer, this present study used collagen scaffolds seeded with the smooth muscle cells (SMC) in a canine model. Autologous SMC were isolated from stomach wall and cultured. Two types of scaffolds were fabricated: in SMC (+), cultured SMCs were mixed with collagen solution and poured into a collagen sponge; and in SMC (-), SMCs were omitted. Both scaffolds were implanted into defects of isolated ileum as a patch graft. Animals were euthanized at 4, 8, and 12 weeks; for the last time point, the ileal loop had been reanastomosed at 8 weeks. At 12 weeks, the SMC (-) group showed a luminal surface covered by a regenerated epithelial cell layer with very short villi; however only a thin smooth muscle layer was observed, representing the muscularis mucosae. In the SMC (+) group, the luminal surface was covered completely by a relatively well-developed epithelial layer with numerous villi. Implanted SMCs were seen in the lamina propria and formed a smooth muscle layer. Thus, we concluded that collagen sponge scaffolds seeded with autologous SMCs have a potential for small intestine regeneration.

[Analysis of Reg IV expression in peritoneal dissemination of gastric cancer using real-time RT-PCR].

We had performed a global analysis of the gene expression of gastric cancer cell lines established from malignant ascites to identify the novel markers for the detection of micro-metastasis in peritoneal cavity. One of the up-regulated genes is Reg IV, which is a member of the Reg gene family belonging to calcium dependent lectin (C-type lectin) gene superfamily. But the role of Reg IV in peritoneal dissemination is still unclear. We have examined the potential of Reg IV as a novel marker for the detection of peritoneal micro-metastases of gastric cancer. Reg IV expression was examined by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Mean Reg IV mRNA expression levels in surgically resected specimens (n = 41) were more than 20-times higher than those in normal mucosa from those patients. Furthermore, Reg IV mRNA expression level in the peritoneal wash was strongly higher in peritoneal metastasis compared to those without peritoneal metastasis. These results suggest that Reg IV may be involved in peritoneal dissemination of gastric cancers and Reg IV would be a potential novel marker for peritoneal dissemination of gastric cancers.

[A trial of the new procedure of sentinel node biopsy in the lower rectal cancer by a transsacral approach].

We describe a new method of sentinel node (SN) biopsy in the lower rectal cancer by a transsacral approach. Before the operation, an endoscopic clipping was performed around the tumor. The patient was placed in a jack knife position. A transverse incision was made over the S4-S5 joint. Subsequently, the S4-S5 joint was dissected, and the lower rectum was exposed without destroying the perirectal fatty tissue. CH-40 dye was injected into the submucosal layer of the rectal cancer. The lymph nodes that were blackened within 15 minutes were recognized to be SNs. Few investigations were reported with regard to sentinel node navigation surgery (SNNS) for lower rectal cancer, because the anatomical properties of the lower rectum make it difficult to inject the dye and recognize rectal tumors or lymph nodes. In our method, the lower rectum was exposed without destroying the perirectal fatty tissue, the dye was easily injected, and the SNs were easily found and extirpated. Our method of transsacral approach is considered to be useful.

[Utility of dopa decarboxylase as a novel marker for the detection of peritoneal micro-metastases of gastric cancer with realtime RT-PCR].

We have examined the utility of DDC as a novel marker for the detection of peritoneal micrometastases of gastric cancer. DDC mRNA in the peritoneal wash from 114 gastric cancer patients was quantified for a comparison of carcinoembryonic antigen (CEA) mRNA by means of real-time RT-PCR with a fluorescently labeled probe to predict peritoneal recurrence. The cut-off value was set at the upper limit of the quantitative value for non-cancer patients, and those above this cut-off value constituted the micrometastasis (MM+) group. Thirteen of 15 cases with peritoneal dissemination were MM+DDC (87% sensitivity), and one of 48 t1 cases was MM+ (98% specificity). DDC levels in peritoneal washes from patients with synchronous peritoneal metastases were more than 50 times higher than in those from patients without metastasis (p<0.01). For 15 cases of peritoneal dissemination (seven cases were cytologically positive), DDC was positive in 13 cases (87% sensitivity), but CEA failed to detect micrometastases in four cases (73% sensitivity), indicating that DDC is in some cases superior to CEA for the detection of peritoneal micrometastases of gastric cancer in terms of sensitivity as well as specificity, especially for poorly differentiated adenocarcinomas. Combination of CEA and DDC improved the accuracy of diagnosis up to 93%. These results suggest that DDC is potentially a novel marker for peritoneal dissemination of gastric cancer and that quantitative RT-PCR of DDC is reliable and efficient for the selection of patients for adjuvant intraperitoneal chemotherapy to prevent peritoneal recurrence.

[Over expression of Reg IV in peritoneal dissemination of gastric cancer].

We previously performed a global analysis of the gene expression of gastric cancer cell lines established from peritoneal dissemination (SNU-5, SNU-16, SNU-719, KATO-III and GT3TKB) with the cDNA microarray method to identify the novel markers for the detection of micro-metastasis in peritoneal cavity. One of the up-regulated genes is Reg IV, which is a member of the Reg gene family belonging to calcium dependent lectin (C-type lectin) gene superfamily. We have examined Reg IV potential as a novel marker for the detection of peritoneal micro-metastases of gastric cancer. Reg IV expression was examined in five gastric cancer cell lines established from peritoneal dissemination and compared with myeloid leukemia cell (HL60), methothelial cell lines Met5A and the other gastric cell line established from primary tumor (SNU-1) by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Reg IV was highly overexpressed in 4 gastric cancer cell lines established from peritoneal dissemination, but weakly expressed in other cell lines. According to Reg IV mRNA expression levels in surgically resected specimens, the quantity of Reg IV correlated with wall penetration. Furthermore, Reg IV mRNA expression level in the peritoneal wash from 35 gastric cancer patients was also prone to correlation with wall penetration. These results suggest that Reg IV may be involved in peritoneal dissemination of gastric cancers and Reg IV may be a potential novel marker for peritoneal dissemination of gastric cancers.

Combination of L-3-phosphoserine phosphatase and CEA using real-time RT-PCR improves accuracy in detection of peritoneal micrometastasis of gastric cancer.

Peritoneal metastasis is the most frequent form of recurrence for advanced gastric cancer. We previously performed a global analysis of the gene expression of gastric cancer cell lines established from peritoneal metastasis with cDNA microarray. One of the up-regulated genes is L-3-phosphoserine phosphatase (L3-PP). We have examined its potential as a novel marker for the detection of peritoneal micrometastasis of gastric cancer. L3-PP mRNA in peritoneal wash from 88 gastric cancer patients was quantified for comparison of carcinoembryonic antigen (CEA) mRNA by means of real-time RT-PCR with a fluorescently-labeled probe to predict peritoneal recurrence. The quantity of L3-PP and CEA correlated with wall penetration. The cut-off value was set at the upper limit of the quantitative value of T1 cases (tumor invades within submucosa) and those above the cut-off value constituted the micrometastasis (MM+) group; eight out of 14 cases with peritoneal dissemination were MM+ L3-PP (57.1% sensitivity) and two out of 57 T1 and T2 cases were MM+ (93% specificity). For two out of 14 cases of peritoneal dissemination only L3-PP could detect micrometastasis of gastric cancer, indicating that L3-PP is superior to CEA especially in poorly-differentiated adenocarcinoma. The combination of CEA and L3-PP improved the accuracy of diagnosis up to 85.7%. Consequently, free cancer cells that cannot be detected by CEA mRNA could be detected using L3-PP mRNA. CEA alone was not sufficient, but L3-PP and CEA in combination can attain a higher accuracy of detection.