Sprouty2 inhibition promotes proliferation and migration of periodontal ligament cells.

OBJECTIVES: We previously demonstrated that a dominant-negative Sprouty2 (Spry2) mutation promotes osteoblast proliferation and differentiation after basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) stimulation, whereas it diminishes proliferation of gingival epithelial cells, thereby inducing favourable conditions for periodontal tissue regeneration. In this study, we investigated how Spry2 inhibition affects the cellular physiology of periodontal ligament (PDL) cells. METHODS: A total of 1-17 PDL cells (multipotent clonal human PDL cell line) were stimulated with bFGF and EGF after transfection of Spry2 siRNA. Cell proliferation, migration, ALP staining, real-time PCR, Western blot and immunofluorescence assays were performed. RESULTS: ERK1/2 activation and proliferation of 1-17 PDL cells were significantly upregulated by the addition of Spry2 siRNA in the presence of bFGF and EGF. In addition, Spry2 siRNA reduced transcription of osteogenesis-related genes and ALP staining relative to control cells. Furthermore, it increased AKT/phosphatidylinositol 3-kinase (PI3K) phosphorylation; consequently, Rac1 but not Cdc42 was activated, thereby promoting lamellipodia formation, cell proliferation and migration after stimulation by bFGF and EGF. CONCLUSION: Spry2 combined with bFGF and EGF stimulation reduced PDL cell migration and proliferation with inducing osteoblastic differentiation. These in vitro findings may provide a molecular basis for novel therapeutic approaches for establishing periodontal tissue regeneration.

Histopathological grading does not affect survival after R0 surgery for gastric cancer.

AIM: It is unclear whether Histopathological Grading (UICC, TNM Classification) affects survival after resection for gastric cancer. METHODS: To investigate the prognostic significance of Histopathological Grading after gastrectomy, 1455 patients who underwent gastric resection for gastric adenocarcinoma were reviewed. RESULTS: The R0 (UICC, R Classification) resection rate was inversely correlated with the grade (86.5% for Grade 1, 79.7% for Grade 2 and 69.2% for Grade 3) and the R1 and R2 resection rates increased with the grade. The Histopathological Grading did not influence survival in the 1119 patients who underwent R0 resection (71.0% for Grade 1, 65.7% for Grade 2 and 66.7% for Grade 3). When multivariate analysis was performed for the 1119 cases undergoing R0 resection, the Histopathological Grading was not a determinant prognostic factor. CONCLUSION: We conclude that the UICC Histopathological Grading affects R0 resection rates, but does not affect survival independently.

Length of the antral segment in pylorus-preserving gastrectomy.

BACKGROUND: Pylorus-preserving gastrectomy (PPG) has the advantages of preventing dumping syndrome and duodenogastric reflux. However, time was required to reduce symptoms of gastric fullness or to improve food intake after surgery. The aim of this study was to investigate whether the length of the retained antral segment influenced the postoperative symptoms in patients who underwent PPG. METHODS: Thirty patients with early gastric cancer who underwent PPG were divided into two groups according to the length of the retained antrum. In group 1 (n = 20) the transection was 1.5 cm and in group 2 (n = 10) it was 2.5 cm proximal to the oral edge of the pyloric ring. The subjects were interviewed and examined periodically to assess symptoms, food intake, body-weight and serum nutritional variables. Endoscopy and a radioisotope gastric emptying test were performed 1 year after the operation. RESULTS: In group 1 gastric fullness after meals was common, resulting in poor food intake and poor recovery of body-weight. A high incidence of food residue in the remnant stomach was found in group 1. With regard to gastric emptying, seven of 20 patients in group 1 and one of ten in group 2 had a delayed emptying curve 1 year after operation. CONCLUSION: Group 2 was superior to group 1 in terms of postprandial symptoms, food intake, recovery of body-weight and gastric emptying. The length of the retained antrum may play an important role in the motility of the pyloric ring following PPG.

A randomized clinical trial of pouch reconstruction after total gastrectomy for cancer: which is the better technique, Roux-en-Y or interposition?

BACKGROUND/AIMS: To determine the optimum pouch reconstruction after total gastrectomy, we conducted a randomized trial to compare the usefulness between PR and PI in terms of quality of life. METHODOLOGY: Thirty patients younger than 70 years of age were selected and randomly classified into the following 2 groups: pouch and Roux-en-Y (PR; n = 15) and pouch and interposition (PI; n = 15). In each subject, the postoperative symptoms, food intake in a single meal, body weight, serum nutritional parameters, endoscopy, emptying time of the gastric substitute, and gallstone formation were evaluated. RESULTS: There were no significant differences in terms of the postprandial symptoms, food intake, body weight, and serum nutritional parameters until 2 years postoperative. Endoscopy showed a tendency of food stasis in the PR group, although this was not significant. The gastric emptying test in the PR group indicated that the retention capacity was slightly superior to that in the PI group. CONCLUSIONS: The impact of the duodenal passage on symptoms and nutrition could not be ascertained.

Billroth I gastrectomy using a circular stapler to treat gastric cancer.

We describe herein our technique of performing gastrectomy followed by side-to-end gastroduodenostomy. Because the clamp is removed at the resection line of the greater curvature, there is no need to perform an additional gastrotomy for insertion of the instrument. This feature differentiates our technique from previous methods of anastomosis using the circular stapler. We believe that our technique is superior in simplicity and security to the traditional hand-sewn anastomosis. Moreover, it allows for a shorter operative time. This technique is recommended for practical surgery over conventional techniques.

Negative effect of transforming growth factor-beta-1 on intestinal anastomotic tissue regeneration.

To examine the involvement of transforming growth factor-beta(1 )(TGF-beta(1)) in intestinal anastomotic repair, we administered a TGF-beta(1)-neutralizing antibody to rats after operation, and then examined its influence on the healing process and interaction with other peptide growth factors. Thirty male Sprague-Dawley rats were subjected to primary anastomosis after transection of the small intestine (n = 30) and treated by intraperitoneal administration of IgG (n = 15) or the TGF-beta(1) neutralizing antibody (n = 15). Treatment with the antibody against TGF-beta(1) resulted in more definite mucosal growth and increased vascularity on day 5 after surgery. Augmented mRNA expression of epidermal growth factor and vascular endothelial growth factor, and an increased number of cells that expressed these peptides in granulation tissue were demonstrated by RT-PCR and immunohistochemical staining. Taken together it was indicated that TGF-beta(1) has negative effects on regeneration of the bowel wall mucosa and angiogenesis in the course of intestinal anastomotic wound healing.

Postoperative evaluation of pylorus-preserving gastrectomy for early gastric cancer.

BACKGROUND/AIMS: There have been many reports proposing some advantages of pylorus-preserving gastrectomy for gastric ulcer compared to the conventional distal gastrectomy. However, it is not clear whether similar results will be obtained from the patients with early gastric cancer. METHODOLOGY: Of 50 patients with early gastric cancer, 25 underwent pylorus-preserving gastrectomy under strict criteria and the other 25 underwent distal gastrectomy with Billroth I anastomosis by the same surgeon. The subjects were then interviewed and examined periodically to assess symptoms, food intake, body weight and serum nutritional parameters. Endoscopy and a radioisotope gastric emptying test was performed 1 year after the operation. RESULTS: Many of the patients with pylorus-preserving gastrectomy complained of gastric fullness after meals, resulting in poor food intake; a significant between-group difference was found up to 1 year after the operation. A low incidence of reflux gastritis and slow gastric emptying were confirmed in the patients after pylorus-preserving gastrectomy. CONCLUSIONS: Pylorus-preserving gastrectomy has advantages over distal gastrectomy in terms of the avoidance of dumping syndrome and protection against duodeno-gastric reflux. However, more time was necessary for improved gastric fullness or food intake. Pylorus-preserving gastrectomy should be applied in younger patients with early gastric cancer expecting long survival.

Inhibitory effect of retinoid on esophageal carcinogenesis in rats induced by N-nitroso-N-methylbutylamine in relation to cellular retinoic acid-binding protein.

The inhibitory effect of a synthetic retinoid, ethyl alltrans-9-(4-methoxy-2, 3, 6-trimethyl-phenyl)-3, 7-dimethyl-2, 4, 6, 8-nonatetraenoate (Tigason), on esophageal carcinogenesis in F344 rats induced by N-nitroso-N-methylbutylamine (NMBA) was evaluated. The animals were given NMBA daily in their drinking water for 21 weeks at a concentration of 15 mg per liter ad libitum starting at 8 weeks of age. One week before the beginning of NMBA treatment, the rats were divided randomly into Tigason-fed and -unfed groups. Thirty-five rats were fed a diet supplemented with Tigason at a concentration of 30 mg per kg of diet, and 80 rats were given a basal diet alone. In NMBA-treated rats, multiple papillomas were seen 11 weeks after NMBA treatment and squamous cell carcinoma developed 12 weeks after NMBA; the tumors increased in number thereafter, and the numbers of papillomas and carcinomas were the same at 17 and 21 weeks after NMBA. At 21 weeks after NMBA treatment, the number of papillomas was similar, regardless of the dietary Tigason supplement, however, the number of esophageal squamous cell carcinomas was significantly lower in the Tigason-fed rats than in -unfed animals (p < 0.025). In normal esophageal tissues, a small amount of cellular retinoic acid-binding protein (cRABP) was detected throughout the experimental period, while during carcinogenesis, the levels of cRABP increased continuously until 16 weeks after NMBA; the cRABP level was higher in papillomas than in squamous cell carcinomas. As Tigason specificially blocked the progression of papillomas to carcinomas, it may be a promising candidate chemopreventive agent in esophageal carcinogenesis.

Increased expression of CD44v6 mRNA significantly correlates with distant metastasis and poor prognosis in gastric cancer.

Expression of CD44 and its variants is associated with clinically aggressive behavior of some human cancers. The present study was undertaken to determine the expression level of these CD44 mRNAs in relation to the clinicopathologic features and prognosis of gastric cancer. Using reverse transcription polymerase chain reaction followed by Southern blotting, we examined the expression of the standard and variant (v6 and v9) forms of CD44 mRNA in 73 cases of gastric cancer. We determined the ratio of mRNA expression in cancer tissue to normal tissue (T/N ratio) and evaluated the correlations of the ratio with clinico-pathologic features, tumor progression and prognosis. The expression level of the standard form of CD44 (CD44s) mRNA correlated with peritoneal dissemination only, and that of CD44v9 mRNA did not significantly correlate with any clinicopathologic factor. The expression level of CD44v6 mRNA was significantly higher in patients with lymph node metastasis and liver metastasis. In 48 curatively resected patients, the expression level of CD44v6 mRNA correlated with the site of recurrence. Furthermore, there was a significant survival advantage in patients with low expression of CD44v6 mRNA compared with those with high expression. The level of CD44v6 mRNA expression may be a potential prognostic indicator and may be useful as a predictor for distant metastasis and recurrence in patients with gastric cancer.

[Jejunal pouch and interposition reconstruction after a total gastrectomy for cancer].

The authors modified the operative procedures used in pouch and interposition (PI) reconstruction in an attempt to improve the surgical results after a total gastrectomy, because a randomized controlled trial had revealed that the clinical assessment of PI was quite poor, even though it is a physiological route. In most of the treated patients, the gastric emptying test revealed delayed emptying, and an X-ray video film showed folding and twisting of the jejunal conduit between the pouch and duodenum, which disturbed the transmission of the nutrition. Modified PI (m-PI) was performed by decreasing the length of the jejunal conduit and widening the jejunal pedicle to preserve the blood and nerve supply. The m-PI group showed a lower incidence of symptoms, a greater food intake, and a greater weight recovery than the PI group. The gastric emptying test also revealed an acceptable degree of emptying. We conclude that the m-PI reconstruction is more useful for improving the postoperative quality of life than the previously used method of PI reconstruction.

Absence of colorectal cancer metastasis to the cirrhotic liver.

Hepatic metastasis of colorectal cancer was found in 40 (16%) of 250 patients with colorectal cancer treated in our department during the past 5 years. Liver cirrhosis was not found among the 40 patients with metastases (16%) but was present in 46 (21.9%) of the 210 nonmetastatic patients, with a significant difference between the two groups (p less than 0.001). The rate of patients who were positive for hepatitis B surface antibody was 10% in the metastatic group and 34.3% in the nonmetastatic group, with a significant difference (p less than 0.01). These findings suggest that colorectal cancer does not metastasize to the injured liver, especially the cirrhotic liver.

[Clinical evaluation of the measurement of hepatosplenic volume ratio by computed tomography].

The liver and spleen volume ratio (S/L ratio) was estimated with X-ray computed tomography. Clinical usefulness of S/L ratio was evaluated by comparison with other liver functions (retention rate of ICG, total bilirubin, serum albumin and cholinesterase activity) in 42 hepatocellular carcinoma patients with liver cirrhosis. The correlation between S/L ratio and retention rate of ICG, total bilirubin, serum albumin or cholinesterase activity was good (r = 0.870, r = 0.719, r = -0.691, or r = -0.606, respectively p less than 0.001). Positive correlation was observed between S/L ratio and retention rate of ICG or total bilirubin. Negative correlation was observed between S/L ratio and serum albumin or cholinesterase activity. In conclusion, the measurement of S/L ratio on computed tomography was considered to be useful as an evaluation for the degree of severity in liver cirrhosis by considering both effective hepatic blood flow and portal hypertension.

[A double cancer of the gallbladder and common bile duct associated with an anomalous arrangement of the choledocho-pancreatic ductal junction--a case report and a review of the literature].

Reported is the case of a 65-year-old woman who complained of general fatigue and itching. The cancer of the gallbladder and the common bile duct associated with anomalous arrangement of choledocho-pancreatic ductal junction was diagnosed after examination by ERCP, PTCS, US, and CT. The cancer of the common bile duct had metastasized to the pancreas, the portal vein, and the regional lymph nodes and was unresectable. It is well known that an anomalous arrangement of the choledocho-pancreatic ductal junction is highly associated with a cancer of the common bile duct or the gallbladder. But a case that is associated with double cancers is rare and only 6 cases have been reported in the Japanese literature. In addition to a discussion of this case, the literature is reviewed.

[Primary liver cancer coincident with schistosomiasis japonica].

The etiologic relationship of a parasitic liver disease to primary liver cancer has long been debated, and reported is a case that has been encountered of a primary liver cancer coincident with Schistosomiasis japonica. A fifty-nine year-old-man was diagnosed as having a primary liver cancer complicated with liver cirrhosis. A posterior segmentectomy was performed and a microscopic examination revealed a primary liver cancer with multiple ovae of Schistosoma japonicum in the fibrous stroma of the portal spaces. Discussed is the etiologic relationship of Schistosomiasis japonica to the primary liver cancer.