A case of early-stage type 3 gastric neuroendocrine tumor in the upper body of the stomach: is endoscopic resection feasible?

Although gastric neuroendocrine tumors (NETs) are uncommon compared with gastric carcinomas, the incidence of NETs has been recently increasing. Gastric NETs are classified into three subgroups, and among these, gastrin-independent sporadic type 3 gastric NETs have a poor prognosis because of frequent lymph node or distant metastasis. We experienced a case of an early-stage type 3 gastric NET associated with lymphovascular and submucosal invasion. In a 54 year-old woman, esophagogastroduodenoscopy performed during a health screening identified an elevated lesion of the upper body of the stomach. The results of immunohistochemical analyses of endoscopic biopsy specimens obtained from the lesion were positive for chromogranin A and synaptophysin, indicating an NET. Because the patient's serum gastrin level was normal and she had no predisposing conditions for NET development, the tumor was diagnosed as a type 3 gastric NET. The patient underwent local resection of the tumor and regional lymph node dissection. The resected specimen indicated a diagnosis of type 3 gastric NET with invasion into the submucosa and lymphatic duct. This is an extremely rare case of an early-stage type 3 gastric NET. Our discussion provides insight into the pathogenesis and development of these tumors and the appropriate therapeutic strategy.

Gastric type III heterotopic pancreas presenting as adenomyoma in the antrum of the stomach: a case report.

Although heterotopic pancreas usually occurs in the stomach and rarely presents as a submucosal tumor, an accurate preoperative diagnosis is often difficult because of the variety of clinical symptoms and findings depending on the size and location of the lesion. We experienced a case of gastric type III heterotopic pancreas presenting as a gastric adenomyoma in the antrum of the stomach. A 62-year-old woman visited a local hospital for epigastric discomfort. An esophagogastroduodenoscopy study indicated a submucosal tumor in the greater curvature of the gastric antrum. The patient underwent surgical resection of the tumor because it was enlarged. The histological sections of the resected specimen showed that the tumor was composed of ductular structures lined by tall columnar epithelia and a prominent smooth muscle stroma with no atypical cells. The tumor was compatible with Heinrich's type III heterotopic pancreas, which presented as an adenomyoma of the stomach. These findings provide useful histological features and some insight into a better understanding of the embryonic origin and development of adenomyoma and heterotopic pancreas in the antrum of the stomach.

Gastric collision tumor composed of early-stage gastric carcinoma and gastrointestinal stromal tumor: a case report.

Collision tumors composed of adenocarcinoma and gastrointestinal stromal tumor (GIST) of the stomach are extremely uncommon, and only a few cases have been reported in the English literature. In the present case, a 67-year-old woman visited a local hospital for vomiting and hematemesis. An esophagogastroduodenoscopy study indicated an elevated lesion with ulceration. Histology of the endoscopic biopsy specimen indicated gastric adenocarcinoma. The patient underwent laparoscopic distal gastrectomy with D2 lymph node dissection. The resected specimen showed that the primary tumor consisted of a GIST and that early-stage gastric carcinoma coexisted in the mucosa surrounding the central ulceration of the GIST. Although close contact of the adenocarcinoma and GIST was observed on the mucosal surface, no intermixing of tumor cells was observed in the primary tumor. This case is an extremely rare case of a collision tumor composed of early-stage gastric adenocarcinoma and GIST occurring in the stomach, which provides some insight into a better understanding of the pathogenesis of collision tumors.

Widespread mesenteric phlebosclerosis presenting as intestinal obstruction due to stenosis of the right-sided colon.

Mesenteric phlebosclerosis is a rare form of intestinal ischemia characterized by thickening of the right-sided colon and calcification of the mesenteric vein. We describe the case of a 58-year-old woman admitted to our hospital because of abdominal pain and distension. An abdominal computed tomography study revealed remarkable dilatation and fluid collection of the small intestine compatible with intestinal obstruction, which was considered to be the result of stenosis of the ascending colon. The thickened wall of the cecum and ascending colon was associated with calcification of the colonic wall and mesenteric veins. Colonoscopy showed dark purple discoloration of the edematous mucosa from the splenic flexure through the hepatic flexure, at which point the colonoscope could not be advanced further because of stenosis of the ascending colon. Over 10 years previously, the patient had taken an herbal medicine containing gardenia fruit, which can cause mesenteric phlebosclerosis. An extensive colonic resection was performed after intestinal decompression. This case highlights extensive mesenteric phlebosclerosis causing intestinal obstruction from the cecum through the proximal portion of the sigmoid colon, which was treated with extensive colonic resection.

A case of gastric ischemia caused by massive gastric dilatation due to superior mesenteric artery syndrome.

Gastric ischemia is extremely rare and its endoscopic findings appear similar to those of malignant tumors, which makes accurate diagnosis difficult. We present the case of a 41-year-old woman who was admitted to our hospital for severe abdominal pain and vomiting. Laboratory data at the time of admission indicated high serum levels of C-reactive protein, fibrin/fibrinogen degradation products and D-dimer. An abdominal computed tomography (CT) scan revealed a massive dilatation of the stomach and descending portion of the duodenum, which abruptly narrowed at the portion between the superior mesenteric artery and the aorta, indicating massive gastric and duodenal dilatation due to superior mesenteric artery syndrome. Decompression of the upper gastrointestinal tract using a nasogastric tube was started immediately. An esophagogastroduodenoscopy revealed a massive, irregular ulcerative lesion with ill-defined boundaries located in the posterior wall along the greater curvature of the stomach. Although this lesion mimicked a malignant lesion, the biopsy findings revealed a benign gastric ulcer, indicating that the lesion was gastric ischemia caused by the increased intragastric pressure resulting from the massive dilatation. The gastric ischemia healing process was successfully observed through repeated endoscopic examinations of the upper gastrointestinal tract. The patient's abdominal symptoms disappeared within 10 days and she was discharged from the hospital 23 days after the abdominal episode. This case highlights gastric ischemia associated with an acute massive gastric dilatation resulting in increased intragastric pressure caused by superior mesenteric artery syndrome.

Response to nutritional support and therapeutic approaches of amino acid and protein metabolism in surgical patients.

The response to critical illness involves alterations in all aspects of metabolic control, favoring catabolism of body protein. In particular, body protein loss occurring as a result of the alteration of protein metabolism has been reported to be inversely correlated with the survival of critically ill patients. Despite the availability of various therapeutic modalities aiming to prevent loss of the body protein pool, such as total parenteral nutrition, enteral nutrition designed to provide excessive calories as a form of energy substrate, and protein itself, the loss of body protein cannot be prevented by any of these. Loss of the boyd protein store occurs as a consequence of the alteration of the intermediate metabolism that works for the production of energy substrate. This alteration of substrate metabolism may be linked to the alteration of protein metabolism. However, no specific factors regulating amino acid and protein metabolism have been identified. Thus, further investigations evaluating amino acid and protein metabolism are required to obtain better understanding of metabolic regulation in the body, which may lead to the development of novel and more effective therapeutic modalities for nutrition in the future.

Laparoscopic repair of hiatal hernia with mesenterioaxial volvulus of the stomach.

Although mesenterioaxial gastric volvulus is an uncommon entity characterized by rotation at the transverse axis of the stomach, laparoscopic repair procedures have still been controversial. We reported a case of mesenterioaxial intrathoracic gastric volvulus, which was successfully treated with laparoscopic repair of the diaphragmatic hiatal defect using a polytetrafluoroethylene mesh associated with Toupet fundoplication. A 70-year-old Japanese woman was admitted to our hospital because of sudden onset of upper abdominal pain. An upper gastrointestinal series revealed an incarcerated intrathoracic mesenterioaxial volvulus of the distal portion of the stomach and the duodenum. The complete laparoscopic approach was used to repair the volvulus. The laparoscopic procedures involved the repair of the hiatal hernia using polytetrafluoroethylene mesh and Toupet fundoplication. This case highlights the feasibility and effectiveness of the laparoscopic procedure, and laparoscopic repair of the hiatal defect using a polytetrafluoroethylene mesh associated with Toupet fundoplication may be useful for preventing postoperative recurrence of hiatal hernia, volvulus, and gastroesophageal reflux.

Clinical outcome and clinicopathological characteristics of recurrence after laparoscopic gastrectomy for advanced gastric cancer.

BACKGROUND: Although laparoscopic gastrectomy has been recognized as a treatment of early gastric cancer, the indication for laparoscopic gastrectomy with D2 lymph node dissection has remained controversial. D2 lymph node dissection is considered to be feasible for advanced gastric cancer in some high-volume institutions specifically trained for the laparoscopic procedure. This study was undertaken to determine the clinical outcome and clinicopathological characteristics of patients who showed recurrence following laparoscopic gastrectomy for advanced gastric cancer. METHODS: From August 1999 through February 2009, among 805 patients who underwent laparoscopic gastrectomy associated with regional lymph node dissection, a total of 209 patients undergoing gastrectomy associated with lymph node dissection who consequently obtained complete resection for advanced gastric cancer were subjected to the retrospective analysis to evaluate clinical outcome. RESULTS: The mean period of postoperative observation was 1,068 days. The final stages of the 209 cases were as follows: 83 in IB, 56 in II, 46 in IIIA, and 24 in IIIB. The 5-year survival rate was 89.1% in stage IB, 93.1% in stage II, 52.5% in stage IIIA, and 46.5% in stage IIIB, respectively. A total of 27 patients (12.9%) had recurrence. Postoperative recurrence of gastric carcinoma occurred in peritoneal dissemination in 13 patients, liver in 7, distant lymph nodes in 6, ovary in 3, lung in 2, skin in 1, and meninges in 1 patient. There were neither port-site metastases nor locoregional recurrence. CONCLUSION: The characteristics and the rate of postoperative recurrence after laparoscopic gastrectomy for advanced gastric cancer were not greatly different from those of the open conventional procedure. Although further observation is required to finally conclude long-term survival, laparoscopic radical gastrectomy may possibly be indicated for patients with advanced gastric cancer.

Laparoscopic excision of subdiaphragmatic bronchogenic cyst occurring in the retroperitoneum: report of a case.

Although bronchogenic cysts (BCs) are benign congenital malformations usually occur in thoracic cavity, retroperitoneal location is extremely uncommon. We reported a case of BC occurred in the retroperitoneum, which was excised laparoscopically. A 64-year-old Japanese woman was admitted to the hospital because of submucosal tumor in the upper part of the stomach. An upper gastrointestinal endoscopy revealed a submucosal tumor located just distal to the esophagogastric junction. The abdominal computed tomography scan revealed a cystic mass located in contact with lesser curvature of the stomach and the dorsal surface of the liver. As the cystic mass was well-circumscribed and showed no positive findings suggestive of malignancy, the laparoscopic excision of the cystic mass was performed. The cystic tumor was completely excised with a laparoscopic procedure. The histologic findings indicated that the cyst was surfaced by the ciliated pseudostratified epithelium without the presence of the cartilage, which was compatible with the BC of the retroperitoneum. This case highlights the safety and the feasibility of complete laparoscopic excision of retroperitoneal BC. Laparoscopic excision of retroperitoneal BC definitely provides all advantages of minimally invasive procedure, which improves postoperative patient discomfort and pain and shortens hospital stay. Laparoscopic procedure may definitely be a standard approach for the excision of retroperitoneal BC.

[Clinical characteristics of cases showing complete regression of the primary tumor after S-1 combined with cisplatin administered as neoadjuvant chemotherapy in advanced gastric carcinoma].

Although neoadjuvant chemotherapy has been recognized as an important option to improve the clinical outcome of patients with advanced gastric carcinoma, the precise histological effects of neoadjuvant chemotherapy on the primary and metastatic foci have not well been documented. The aim of the present study was thus to evaluate histological effects of S-1-based neoadjuvant chemotherapy on the resected specimens of gastric carcinoma and regional lymph nodes, and primarily to focus on the histology of the cases showing complete regression of the primary cancer cells. A total of 164 patients received neoadjuvant chemotherapy with the combination of S-1 (80 to 120 mg/body/day for 3 weeks) and cisplatin (35 to 60 mg/m2 on day 8). One course of the regimen was completed in 5 weeks and the next course was started after 2 weeks. A total of 9 patients who showed complete regression of the primary gastric cancer were subjects of the study. A total of 77 cases (46.9%) responded to the neoadjuvant chemotherapy and 9 cases (5.5%) showed a complete regression of the primary gastric carcinoma. Three out of 9 cases had remnant cancer cells in the metastatic foci; 1 in the liver and 2 in the regional lymph nodes. Five of 9 cases were solid-type poorly-differentiated adenocarcinoma (por1), and the incidence of responders was the highest in patients with por1. A total of 8 cases were alive and the mean postoperative survival was 612±192 days. One patient died 518 days after gastrectomy associated with hepatic resection. S-1-based neoadjuvant chemotherapy has significant histological effects on gastric carcinoma and metastatic foci, which may further improve long-term clinical outcome in patients with advanced gastric carcinoma.

[Recent changes in perioperative nutritional support in patients undergoing thoracoscopic esophagectomy].

The advent of thoracoscopic esophagectomy (TSE) has enabled early patient recovery in association with changes in perioperative nutritional support. This article reviews recent changes in the perioperative nutritional support for patients undergoing TSE. TSE associated with a laparoscopic procedure facilitates the recovery of gastrointestinal motility and function while decreasing the incidence of vocal cord paralysis and/or difficulties in swallowing due to accurate mediastinal lymph node dissection. Thus, recent trends in perioperative nutritional support have been early oral feeding and perioperative enteral feeding using a disease-specific polymeric immunoenhancing or immunomodulating enteral formula. Although TSE is associated with less surgical invasiveness, nutritional support still plays an important role in perioperative care to prevent postoperative complications and contribute to the early recovery of nutritional status. Moreover, since TSE is now performed to treat advanced esophageal cancer, patients are frequently malnourished preoperatively and therefore in the group at high risk for postoperative complications. The early start of oral feeding after the evaluation of swallowing function, selecting the appropriate route for enteral nutrition, and sufficient calorie intake during the perioperative period are essential to prevent postoperative pulmonary and/or infectious complications and consequently to improve patient quality of life.

Laparoscopic excision of the cystic lymphangioma occurred in the lesser omentum: report of a case and review of literature.

Intraperitoneal cyst occurring in the lesser omentum is extremely rare entity. Because of the absence of abdominal symptoms, omental cyst is occasionally found accidentally in imaging examination performed during health screening. We experienced a case of cystic lymphangioma that occurred in the lesser omentum, which was successfully resected under complete laparoscopic procedure. A 50-year-old Japanese woman was admitted to our hospital because a cystic mass was found in the abdomen. Abdominal computed tomography scan was performed because she had a traffic accident, despite complaining no abdominal symptoms. The abdominal computed tomography scan and magnetic resonance imaging revealed a large cystic mass in the lesser omentum adjacent to the lesser curvature of the stomach, which was resected with a complete laparoscopic procedure. As the cystic wall was closely attached to the lesser curvature of the gastric wall, an ultrasonic coagulating shear was quite helpful to entirely mobilize the cyst from the surrounding structure such as lesser curvature of the stomach. After placing clips to the feeding vessels to the cyst branched from the accessory hepatic vessels, the entire cyst was mobilized without leakage of cystic content. The postoperative course was uneventful with slight delayed gastric emptying due to partial denervation of the lesser curvature of the stomach. The patient was discharged on eighth day after surgery without any postoperative complications. This is the first case of cyst of lesser omentum resected under complete laparoscopic procedure and certainly highlights advantage and feasibility of laparoscopic approach for cases with abdominal cystic lesions. Laparoscopic excision of cystic lymphangioma in the lesser omentum provides all the advantage of minimally invasive procedure.

Delayed vascular injury and severe respiratory distress as a rare complication of a central venous catheter and total parenteral nutrition.

Complications related to central venous catheters (CVCs) in the postoperative period can be fatal. We recently had a case of bilateral pleural effusion and respiratory distress caused by delayed vascular injury. A 79-y-old Japanese woman was admitted to our hospital because of advanced gastric carcinoma. A multiple-lumen CVC was placed through the left subclavian vein 1 d before surgery for postoperative nutritional management. The patient suddenly complained of dyspnea, and the chest X-ray film revealed right massive pleural effusion. Although the patient's symptoms soon disappeared after the thoracentesis, she again developed severe respiratory distress, and an endotracheal intubation was performed and her respiration was managed by mechanical ventilation. Computed tomographic scan of the chest revealed a displacement of the tip of the CVC out of the wall of the superior vena cava, mediastinitis, and leakage of intravenous fluid, which may have been caused by delayed vascular injury due to the CVC. The CVC was removed immediately after the diagnosis of delayed vascular injury at 10 d after surgery. The patient soon recovered with conservative treatment and was discharged from the hospital 43 d after surgery. This case highlights an extremely rare presenting complication of CVC placement and total parenteral nutrition.

Percutaneous endoscopic gastrostomy for gastric decompression after repeated intestinal obstruction after open abdominal surgery.

In patients with repeated intestinal obstructions after open abdominal surgery, aerophagia associated with disturbances in gastrointestinal passage causes the accumulation of large amounts of air, resulting in chronic symptoms including abdominal pain and distention and consequently malnutrition. We successfully used percutaneous endoscopic gastrostomy (PEG) for long-term gastric decompression in 2 cases with aerophagia. The first case was a 69-year-old Japanese man admitted for repeated intestinal obstruction after an appendectomy. After the last surgery for intestinal obstruction, the patient experienced repeated abdominal distention and anorexia, resulting in weight loss and malnutrition. The second case was a 79-year-old man complaining of abdominal pain and distention. He had a history of resection of the lower pharynx and larynx owing to total laryngectomy and had received a permanent tracheostomy. He then underwent surgery for intestinal obstruction. Because the patients' abdominal symptoms were unresponsive to administration of a peristalsis stimulant and a laxative, we performed PEG to deflate the gastrointestinal tract. An abdominal x-ray taken after the PEG placement showed the elimination of the gas and a remarkable improvement in the gastric dilatation, and the abdominal symptoms soon disappeared. These cases highlight the clinical importance and usefulness of PEG for gastric decompression in patients with aerophagia associated with repeated intestinal obstruction.

Pneumatosis cystoides intestinalis associated with massive free air mimicking perforated diffuse peritonitis.

While pneumatosis cystoides intestinalis (PCI) is a rare disease entity associated with a wide variety of gastrointestinal and non-gastrointestinal disorders, PCI associated with massive intra- and retroperitoneal free air is extremely uncommon, and is difficult to diagnose differentially from perforated peritonitis. We present two cases of PCI associated with massive peritoneal free air and/or retroperitoneal air that mimicked perforated peritonitis. These cases highlight the clinical importance of PCI that mimics perforated peritonitis, which requires emergency surgery. Preoperative imaging modalities and diagnostic laparoscopy are useful to make an accurate diagnosis.

[Predictive value of orotate phosphoribosyltransferase in chemoresistant patients with gastric carcinoma who underwent S-1-based neoadjuvant/adjuvant chemotherapy].

S-1, a most effective DPD-inhibitory fluoropyrimidine, used as neoadjuvant/adjuvant chemotherapy has recently been shown to improve clinical outcome in patients with stage II and III advanced stage gastric carcinoma. Orotate phosphoribosyltransferase(OPRTEC 2.4.2.10)is a primary enzyme involved in the first-step phosphorylation process of 5-fluorouracil and is an important enzyme that possibly enables to predict sensitivity to S-1 irrespective of tissue DPD levels. To test the hypothesis that a low OPRT level in gastric carcinoma tissue is an indicator of chemoresistance to S-1-based chemotherapy, the predictive value of OPRT levels in chemoresistance was evaluated in patients with gastric carcinoma undergoing S-1-based-neoadjuvant/adjuvant chemotherapy using survival analyses. A total of 67 patients with advanced-stage gastric carcinoma who underwent S-1-based neoadjuvant/adjuvant chemotherapy were subjected to the study. The OPRT level was determined by an enzyme-linked immunosorbent assay(ELISA)that has recently been developed. Postoperative cumulative survival rates were determined by the Kaplan-Meier method. The patients who underwent S-1-based adjuvant/neoadjuvant chemotherapy(n=67)were divided into 2 groups using various cut-off values to determine the prognostic significance of the OPRT level. The prognostic significance of OPRT levels was analyzed using Cox's proportional hazard model. The P value of the survival rate between the groups of low and high OPRT levels was the lowest(p=0.0018), when 2.0 ng/mg protein was used as a cut-off value for the OPRT level. The 3-year survival rate of Group L and Group H was 0% and 60%, respectively. In particular, there was a significant difference in the survival rates between Group L and Group H in stage III patients(p<0.05 by logrank test). T he survival rate of Group L(OPRT<2.0 ng/mg protein)was significantly lower than that of group H(OPRT> or =2.0 ng/mg protein)(p<0.05 by logrank test). The multivariate analysis using Cox' proportional hazard model indicated that venous invasion of carcinoma(>v2), lymph node metastasis(>5), and low OPRT level (OPRT<2.0 ng/mg protein) were significant prognostic factors in patients who were underwent S-1-based neoadjuvant/adjuvant chemotherapy. These results suggest that patients with a low OPRT level(OPRT<2.0 ng/mg protein)are non-responders to S-1- based adjuvant/neoadjuvant chemotherapy. The determination of OPRT levels in gastric carcinoma tissue enables to predict the response to S-1-based neoadjuvant/adjuvant chemotherapy.

Changes of gene expression of thymidine phosphorylase, thymidylate synthase, dihydropyrimidine dehydrogenase after the administration of 5'-deoxy-5-fluorouridine, paclitaxel and its combination in human gastric cancer xenografts.

BACKGROUND: Although a variety of combination chemotherapies has been tested in gastric carcinoma, the most effective chemotherapeutic regimen and the precise mechanisms underlying anticancer agent combination have not yet been sufficiently elucidated. MATERIALS AND METHODS: Experimental chemotherapy was performed using human gastric carcinoma xenografts, MKN-45 and TMK-1, to examine the anticancer effects and gene expressions of the enzymes involved in 5-fluorouracil metabolism, thymidine phosphorylase (dThdPase), thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD). Nude mice were treated with 5'-deoxy-5-fluorouridine (5'-dFUrd), or paclitaxel alone or in combination. The in vivo antitumor effects on gene expressions of the enzymes were examined using the quantitative real-time RT-PCR method. RESULTS: The combined use of 5'-dFUrd and paclitaxel showed additive to synergistic antitumor effects on both gastric cancer xenografts. There were significant differences of the gene expressions of dThdPase, TS, and DPD between the xenografts. The expression of dThdPase mRNA was consistently up-regulated by the administration of paclitaxel, while no constant direction of TS mRNA and DPD mRNA change was found in the xenografts. CONCLUSION: A synergistic antitumor effect of the combined administration of 5'-dFUrd and paclitaxel was found in gastric cancer xenografts and up-regulation of dThdPase mRNA may be an important underlying mechanism especially in tumors with high gene expression of this enzyme.

Effects of combined administration of DPD-inhibitory oral fluoropyrimidine, S-1, plus paclitaxel on gene expressions of fluoropyrimidine metabolism-related enzymes in human gastric xenografts.

BACKGROUND: S-1 is the most effective oral fluoropyrimidine derivative widely used for patients with gastric carcinoma in Japan. Although S-1 plus taxane has been a promising candidate as an effective chemotherapeutic regimen, the mechanisms of its additive or synergistic anticancer effects and changes in gene expression after the administration of these agents have not yet been fully elucidated. METHODS: Experimental chemotherapy was performed using human gastric carcinoma xenografts, MKN-45 and TMK-1, to examine anticancer effects and gene expressions of fluoropyrimidine metabolism-related enzymes including thymidine phosphorylase (TP), thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), and uridine phosphorylase (UP). Nude mice were treated with S-1, paclitaxel, and their combination. After treatment, in vivo antitumor effects of S-1, paclitaxel alone, and their combination and the effects on gene expressions of enzymes involved in 5-fluorouracil metabolism were examined using the RT-PCR method. RESULTS: The combined use of S-1 and paclitaxel showed additive to synergistic antitumor effects on both gastric cancer xenografts. While consistent upregulation of dThPase and DPD gene expression was exhibited after administration of S-1, no further increase of dThPase gene expression after combined use of S-1 with paclitaxel was observed. There was no increase in TS gene expression after the administration of either S-1 alone or paclitaxel alone. CONCLUSION: These results provide some insight into the mechanism and/or rationale underlying the additive to synergistic effect of combined administration of S-1 and paclitaxel in gastric carcinoma.

Levels and expressions of orotate phosphoribosyltransferase in gastric carcinoma and normal gastric mucosa tissues.

BACKGROUND: Orotate phosphoribosyltransferase (OPRT; EC 2.4.2.10), a key enzyme that catalyzes one of the primary steps in the phosphorylation of fluoropyrimidine, was recently recognized as an important enzyme that determines the anticancer effects of the dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine, S-1. METHODS: Levels of OPRT were examined in 97 gastric carcinoma tissues and 65 normal gastric mucosa tissues obtained from patients with gastric carcinoma. The relation between OPRT levels and clinicopathological variables was evaluated, and correlations of OPRT with thymidylate synthase and dihydropyrimidine dehydrogenase levels in gastric carcinoma tissues were evaluated. RESULTS: Although OPRT levels were high in well-differentiated and localized carcinomas, they were not correlated with other clinicopathological variables or with the pathological stage of gastric carcinoma. Levels of OPRT were significantly higher in gastric carcinoma tissue than in normal gastric mucosa. OPRT levels were not correlated with levels of either thymidylate synthase or dihydropyrimidine dehydrogenase. In samples of gastric carcinoma tissues and normal gastric mucosa tissues obtained simultaneously from 24 patients, no correlation was found between OPRT levels in gastric carcinoma and levels in normal gastric mucosa. CONCLUSION: These results suggest that the OPRT level is significantly higher in gastric carcinoma tissue than in normal gastric mucosa and that the OPRT level in gastric carcinoma is a novel variable that is independent of the levels of other previously known enzymes related to 5-fluorouracil (FU) metabolism.

[Orotate phosphoribosyltransferase levels in gastric carcinoma and normal gastric mucosa - correlation with thymidylate synthase and dihydropyrimidine dehydrogenase levels and the changes after neoadjuvant chemotherapy].

Orotate phosphoribosyltransferase (OPRT, EC 2.4.2.10), a key enzyme that catalyzes one of the primary first-step phosphorylation processes of fluoropyrimidine, has recently been recognized as an important factor that primarily determines the anticancer effects of S-1. The OPRT levels were examined in 97 gastric carcinoma tissues and 65 normal gastric mucosa tissues obtained from patients with gastric carcinoma using a newly-developed enzyme-linked immunosorbent assay. Correlations with thymidylate synthase and dihydropyrimidine dehydrogenase levels and the effects of neoadjuvant chemotherapy were evaluated. The OPRT level in gastric carcinoma tissue was significantly higher than that in normal gastric mucosa. There was no correlation of OPRT level with either TS or DPD levels. There was no correlation of OPRT level between those in gastric carcinoma and those in normal gastric mucosa simultaneously obtained from identical patients. The OPRT levels in patients who underwent neoadjuvant chemotherapy were not different from those without neoadjuvant chemotherapy. These results suggest that activation of fluoropyrimidine mainly occurs in carcinoma tissues and the OPRT levels in carcinoma tissues were not influenced by neoadjuvant chemotherapy with fluoropyrimidine.