[Alcohol related problem in the workplace: trial of a screening and brief intervention program for risky drinking in the workplace, via the Internet].

This report describes the effect of a screening and brief intervention via the Internet (6-month Total health Management Program: TMP, a kind of life evolution program), for improvement of alcohol related problem in the workplace. At a certain company, 2,096 employees were screened.using AUDIT-C and CAGE via the Internet (electronic screening). From those screened, 17 risky drinkers were picked up. The classification of "risky drinker" was determined based on employees scoring over six points on AUDIT-C and over two points on_ AGE. These employees were then called to one-day practical seminar program (including the program of food education, music therapy, aro-atherapy, body conditioning etc.). After which, during 6 months, they were followed up via e-mail every month. After the 6-month follow up, their results of AUDIT-C were significantly decreased. Additionally, aside from the frequency of drinking at bedtime, maximum alcohol consumption per day was also significantly decreased. The Visual Analogue Scale for anxiety captured the initial screen and then again after follow-up was reduced significantly. Moreover, quality-of-life index for sleep and dinner were both significantly improved as well..These results suggest that the SBI (screening and brief intervention: TMP) is effective for reducing drinking behavior, can be used to effectively elevate quality of life.

Randomized clinical trial of the effects of perioperative use of immune-enhancing enteral formula on metabolic and immunological status in patients undergoing esophagectomy.

BACKGROUND: Although perioperative immune-enhancing enteral formula (IEEF) is effective to decrease the rate of infectious complications, it is not clear whether perioperative use of IEEF decreases the incidence of postoperative complications and improves clinical outcome in patients who have undergone esophagectomy. A prospective randomized clinical trial was performed to examine the effects of perioperative IEEF on nutritional and immunological status in patients with esophageal carcinoma who have been treated with esophagectomy. METHODS: A total of 30 patients were randomly assigned to two groups, each receiving 3 days of preoperative and postoperative enteral nutrition through jejunostomy started within 24 h after operation, either with immune-enhancing enteral formula (group IEEF, n = 16) or with regular polymeric enteral formula (group C, n = 14). Preoperative and postoperative nutritional and immunological parameters and clinical outcome were examined. RESULTS: A significant increase in the serum concentration of ornithine was noted in group IEEF and it peaked at 5 days after surgery. The equivalent values were significantly lower in group C. There was no difference in serum dochosahexaic acid between the two groups. The n-3/n-6 fatty acid ratio in group IEEF was significantly higher than in group C at 7 days after surgery. Peripheral percent lymphocyte fraction and total lymphocyte count in group IEEF were both significantly higher than those in group C. While T cell fraction of peripheral lymphocytes in group IEEF at 3 days after surgery, B cell fraction in group IEEF at 5 and 7 days after surgery was significantly higher than those in group C, suggesting that perioperative IEEF caused a shift towards B cell proliferation. CONCLUSIONS: Perioperative use of IEEF caused a significant increase in the total lymphocyte count at 3 and 5 days after operation and caused a shift toward B cell proliferation, which may possibly be beneficial to decrease the incidence of postoperative infectious complications.

Incidence of chronic obstructive pulmonary disease, and the relationship between age and smoking in a Japanese population.

BACKGROUND: Accurately evaluating a risk of chronic obstructive pulmonary disease (COPD) requires a large-scale longitudinal study using a standard criterion for diagnosing COPD. There have been only a few such follow-up studies in Europe and no reports in Asia. We estimated the incidence rate and incidence rate ratio (IRR) of age and smoking for COPD in a Japanese population using the diagnosis criterion of the Global Initiative for Chronic Obstructive Lung Disease guidelines. METHODS: Subjects were 17,106 participants aged 25-74 years during health check-ups including spirometry from April 1997 through March 2005 in Japan. Total follow-up of participants were 47,652 person-years in males and 25,224 person-years in females. The IRR of age and smoking was estimated using Cox proportional hazard models with both variables. RESULTS: We identified 466 incidence cases of COPD. The incidence rate per 100 person-years was 0.81 (95% confidence interval [CI], 0.73-0.89) in males and 0.31 (0.24-0.38) in females, and significantly increased with age in both sexes. The incidence rate for current smokers was significantly higher than that for male non-smokers but not significantly for females. Among males, the IRR for current smokers with Brinkman Index < 400, 400-799, and 800+ was 1.2 (0.8-1.9), 2.7 (1.9-3.8), and 4.6 (3.3-6.5), respectively. CONCLUSION: These results indicated that the COPD risk gradually increased with aging, and that there was a dose-response relationship between smoking and COPD risk.

Relatively small size linitis plastica of the stomach: multislice CT detection of tissue fibrosis.

BACKGROUND: Linitis plastica (scirrhous gastric carcinoma) has a poor prognosis due to delay in diagnosis. Pathological feature of this tumor is diffuse fibrosis of the gastric wall. Detection of small fibrotic lesion in the gastric wall would contribute to early diagnosis of linitis plastica, since the primary lesion usually lacks remarkable protrusion or ulceration. METHODS: We performed a multislice CT evaluation of 20 patients with gastric carcinoma with 8 data acquisition system (Aquilion, Toshiba Medical Systems Corporation, Japan). RESULTS: Out of 20 primary lesions, 3 were diagnosed as relatively small size (less than 10 cm in maximum diameter) linitis plastica. We have successfully demonstrated an en face virtual endoscopic image of the primary ulcers of linitis plastica by arterial-phase, and reactive fibrosis (a desmoplastic response) of the gastric wall by delayed-phase multiplanar reformation (MPR) images perpendicular to the en face image. This preoperative information was useful to evaluate extent of tumor invasion. CONCLUSIONS: The multislice CT evaluation of linitis plastica using delayed-phase images was potentially useful in the detection of relatively small fibrotic lesion and in determining the optimal mode of resection of the stomach.

Expression of chemoresistance-related proteins in alpha-fetoprotein-producing adenocarcinoma of the digestive organs.

alpha-fetoprotein-producing adenocarcinoma of the digestive organs (APAD) is known to show a poor prognosis. To clarify the characteristics of chemoresistance in APAD, three proteins of fluoropyrimidine chemotherapy association [dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and thymidylate synthase (TS)] and one protein of cisplatin association [metallothionein (MT)] were immunohistochemically evaluated. Tissue samples were taken from 12 AFP-positive gastric cancers and 94 AFP-negative gastric cancers. Four AFP-positive cancer xenografts (one colonic, two pancreatic, and one biliary tract) and 17 AFP-negative cancer xenografts were also examined. In gastric cancers, high expression of TP was observed in 30% of AFP-negative tumors but in none of AFP-positive tumors (p=0.03). High expression of MT was found in 30% of AFP-negative tumors but in only one of the AFP-positive tumors. The TP-low and MT-low phenotype was noted in 92% of AFP-positive tumors and in 46% of AFP-negative tumors (p=0.004). None of the AFP-positive cancer xenografts revealed high TP expression and only one showed high MT expression. In the cellular level, TP and MT were scarcely co-expressed with AFP in either gastric cancer or xenograft series, using double immunostaining and serial sectioning techniques. There were no significant differences in the expression of DPD and TS between AFP-positive group and -negative group. However, DPD was frequently co-expressed with AFP in poorly differentiated medullary areas of the AFP-positive gastric cancers. The data presented herein suggest that APAD should be sensitive to cisplatin, but resistant to capecitabine and 5'-deoxyfluorouridine, fluoropyrimidines which are converted to 5-fluorouracil by TP. S-1, a fluoropyrimidine containing a strong DPD inhibitor, may be effective for AFP-positive gastric cancers with poorly differentiated medullary growth pattern.

[Clinical and prognostic significance of protein and gene expression of orotate phosphoribosyltransferase in gastric carcinoma].

Although orotate phosphoribosyltransferase (OPRT EC 2.4.2.10) is a key enzyme related to the first-step activation process of 5-fluorouracil, and therefore it has been shown to be an important enzyme that enables to predict sensitivity to 5-fluorouracil, the clinical and prognostic significance of protein and/or gene expression of OPRT has not been well established in gastric carcinoma. We examined the protein level, and mRNA expression of OPRT in gastric carcinoma tissues and relationships with clinicopathologic factors and prognosis were evaluated. A total of 75 surgically-resected gastric carcinoma tissues were subjected to the study. An enzymelinked immunosorbent assay (ELISA) was used to accurately assess intratumoral OPRT, and gene expressions of OPRT were examined using a real-time PCR method. Survival of patients with gastric carcinoma in relation to OPRT protein levels was analyzed using Kaplan-Meier methods along with log-rank test. The mean value of OPRT was 5.4+/-3.6 ng/mg protein, and it was significantly higher in patients with differentiated-type and invasive-type gastric carcinoma. The prognosis of patients in the high OPRT group was better than for those with low OPRT (p<0.05). There was a significant correlation between OPRT levels measured by ELISA and OPRT mRNA expression (p<0.05). Determination of OPRT levels is a useful tool to predict the biological characteristics of gastric carcinoma and possibly predict sensitivity to fluoropyrimidine-based anticancer chemotherapy,particularly dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine, in patients with gastric carcinoma.

Effects of long-term continuous use of immune-enhancing enteral formula on nutritional and immunologic status in non-surgical patients.

OBJECTIVE: Although the perioperative use of immune-enhancing enteral formula (IEEF) effectively reduces the rate of infectious complications, whether chronic use of IEEF is beneficial is unknown. A prospective randomized clinical trial was performed to examine the safety and effectiveness of long-term IEEF on nutritional and immunologic status in non-surgical patients receiving total enteral nutrition through the gastrostomy access route. METHODS: A total of 30 patients were randomly assigned to two groups in which they received total enteral nutrition, an IEEF (n = 15) or a regular polymeric enteral formula (control group; n = 15) for 12 wk. Nutritional and immunologic variables were periodically examined. RESULTS: Serum concentrations of insulin-like growth factor-I increased significantly for the IEEF group throughout the study. Although serum concentrations of dihomo-gamma-linoleic acid decreased significantly in the IEEF group, serum concentrations of eicosapentaenoic acid and docosahexaenoic acid increased significantly, as did concentrations of serum arginine and ornithine. The CD4/CD8 ratio and natural killer cell activity also increased for the IEEF group, but the differences were not significant. The B-cell fraction increased and the T-cell fraction of peripheral lymphocytes decreased for the IEEF group. Neither infectious nor non-infectious complications occurred during the study period in either group, except for a significant increase in serum urea nitrogen and uric acid concentrations for the IEEF group. CONCLUSION: Long-term use of IEEF is safe in non-surgical patients and results in a significant increase in serum insulin-like growth factor-I concentrations in association with increased humoral immunity.

Orotate phosphoribosyltransferase levels measured by a newly established enzyme-linked immunosorbent assay in gastric carcinoma.

A number of enzymes have been shown to be involved in the process of activation and/or degradation of 5-fluorouracil (5-FU), and are potential candidates for predicting chemosensitivity to 5-FU. Among these, orotate phosphoribosyltransferase (OPRT EC 2.4.2.10) is a key enzyme related to the first-step activation process of 5-FU and has been shown to be an important enzyme that helps to predict sensitivity to 5-FU and its related derivatives. We developed a new enzyme-linked immunosorbent assay (ELISA) to accurately assess intratumoral activity of OPRT. A new sandwich ELISA was established using anti-OPRT polyclonal antibodies obtained from the rabbit immunized with the recombinant human peptides of the OPRT molecule. OPRT levels were measured in eight human cancer xenografts and in 75 gastric cancer tissues using both a newly established ELISA and a conventional enzyme assay, using radiolabeled 5-FU as a substrate. There was a significant correlation between OPRT levels measured by this ELISA and OPRT enzyme activity the in eight human cancer xenografts (r2 = 0.782) and gastric carcinoma tissue (r2 = 0.617). The ELISA system for OPRT requires a minimal amount of carcinoma tissue, making it an easy-to-use assay system to predict sensitivity to 5-FU and its derivatives in gastric carcinoma. There was a significant correlation between tumor growth inhibition rates against the oral administration of oral-uracil/tegafur (UFT) and OPRT enzyme activity in the human cancer xenografts (r2 = 0.574). These results suggest that this newly developed sandwich ELISA system for the quantification of OPRT levels is technically simple, feasible and a useful tool to predict sensitivity to fluoropyrimidine-based anticancer chemotherapy in patients with gastric carcinoma and other cancers.

[Clinicopathological significance of orotate phosphoribosyltransferase in gastric carcinoma].

Orotate phosphoribosyltransferase (OPRT EC 2.4.2.10) is a key enzyme related to the first-step phosphorylation process of 5-fluorouracil. We have recently developed an ELISA system to measure OPRT levels in cancerous tissues. We examined OPRT levels in 75 gastric carcinoma tissues using this ELISA, and the relationships with clinicopathologic factors were evaluated. A total of 75 surgically-resected gastric carcinoma tissues were subjected to the present study. The intratumoral OPRT level was determined by a newly-developed enzyme-linked immunosorbent assay (ELISA). Enzyme activities of OPRT were also determined using a conventional enzyme assay using radiolabeled 5-fluorouracil as a substrate. OPRT levels in gastric carcinoma tissues measured by ELISA were 5.4+/-3.6 ng/mg protein, ranging from 0.2 to 15.7 ng/mg protein. There was a significant correlation between the OPRT level measured by the ELISA and OPRT enzyme activity (y=0.545x - 0.017, r(2)=0.617, p<0.0001). OPRT levels were significantly higher in patients with differentiated type and invasive type of gastric carcinoma, whereas OPRT levels were not associated with the pathological stage of gastric carcinoma. These results suggest that OPRT levels were related to the histopathological characteristics of gastric carcinoma, and may be related to the response to fluoropyrimidine-based anticancer chemotherapy.

Laparoscopy-assisted uncut Roux-en-Y operation after distal gastrectomy for gastric cancer.

In order to prevent the Roux stasis syndrome that sometimes follows Roux-en-Y gastrojejunostomy after distal gastrectomy, a new type of reconstruction, called the uncut Roux-en-Y technique, has been reported. We successfully performed 42 laparoscopy-assisted uncut Roux-en-Y gastrojejunostomies. Here we describe our technique and the initial outcome.

Immunohistochemical demonstration of fluoropyrimidine-metabolizing enzymes in various types of cancer.

Fluoropyrimidines [5-Fluorouracil (5-FU) and its prodrugs] have been widely used in the treatment of solid cancers. The anticancer effects primarily depend on intratumoral levels of enzymes metabolizing the drugs, such as dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS). In order to know the tumor types susceptible to respective fluoropyrimidines, we investigated the expression of DPD, OPRT, TP and TS in various types of cancer with the immunoperoxidase method. These four enzymes existed in all of the cancer types studied, such as pulmonary, gastric, colorectal, hepatic, cholecystic, pancreatic, renal, urocystic, and mammary cancers. Respective types of cancers presented characteristic immunohistochemical features as follows: pulmonary adenocarcinoma, DPD- and TP-high; pulmonary squamous cell carcinoma, TS- and TP-high; intestinal-type gastric adenocarcinoma, TP-high; diffuse-type gastric adenocarcinoma, DPD-low and TS-high; colorectal adenocarcinoma, DPD- and TP-low, hepatocellular carcinoma, DPD-high, and TS- and OPRT-low; cholecystic adenocarcinoma, DPD- and TS-high; renal cell carcinoma, DPD-low, and OPRT- and TP-high; urocystic transitional cell carcinoma, DPD-high and OPRT-low; and mammary ductal carcinoma, OPRT-low, and TS- and TP-high. The enzyme expression pattern in cancer tissue was generally similar to that of their normal counterparts. However, TP immunoreactivity in adenocarcinomas of the lung, stomach and gallbladder, and urothelial carcinoma of the urinary bladder was stronger, and DPD immunoreactivity in adenocarcinoma of the breast was weaker, when compared with normal epithelial cells. Non-epithelial cells were also positive for these enzymes. These results indicated that the key enzymes influencing the effects of fluoropyrimidines differ from cancer to cancer. Fluoropyrimidine treatment may be selected, based on the simultaneous immunohistochemical evaluation of the fluoropyrimidine metabolic enzymes.

[Advancce in laparoscopic treatment for gastric cancer].

Many laparoscopic surgeries for gastric cancer are presented, including D 2 lymphadenectomy, gastrectomy with preservation of vagus nerve and intracorporeal anastomosis after some gastrectomies. The great advances in laparoscopic treatments in gastric cancer are described.

[Establishment of enzyme-linked immunosorbent assay for quantification of orotate phosphoribosyltransferase in gastric carcinoma].

A number of enzymes have been shown to be involved in the process of activation and/or degradation of 5-fluorouracil, and they are potential candidates for predicting factors of chemosensitivity to 5-fluorouracil. Among them, orotate phosphoribosyltransferase (OPRT EC 2.4.2.10) is a key enzyme related to the first-step activation process of 5-fluorouracil and therefore it has been shown to be an important enzyme for the prediction of sensitivity to 5-fluorouracil and its related derivatives. We developed a new enzyme-linked immunosorbent assay (ELISA) system to accurately assess intratumoral activity of orotate phosphoribosyltransferase. A new sandwich ELISA system was established using anti-OPRT polyclonal antibodies obtained from the rabbit immunized with the recombinant human peptides of the OPRT molecule. OPRT levels were measured in 8 human cancer xenografts transplanted in nude mice and 58 gastric cancer tissues using both a newly established ELISA and a conventional enzyme assay using radiolabeled 5-fluorouracil as a substrate. OPRT levels in 8 human cancer xenografts measured by this ELISA were significantly correlated with the OPRT enzyme activities (r2=0.782). Furthermore, OPRT activities measured in 58 gastric cancer tissues by enzyme assay were significantly correlated with those measured by the newly-established ELISA (r2=0.664). The ELISA system developed for the measurement of OPRT required a minimal amount of carcinoma tissue samples, which could be an easy-of-use assay system to predict sensitivity to 5-fluorouracil in gastric carcinoma. These results suggest that this newly-developed sandwich ELISA system for the quantification of OPRT is technically simple, feasible, and may be a useful tool to predict sensitivity to fluoropyrimidine-based anticancer chemotherapy in patients with gastric carcinoma and other cancers.

Abdominal wall abscess associated with perforated jejunal diverticulitis: report of a case.

We report a case of abdominal wall abscess caused by diverticulitis of the jejunum penetrating through the abdominal wall. A 53-year-old Japanese woman visited a local hospital complaining of abdominal pain and a mass in the left lower abdomen. An abdominal computed tomography scan showed a tumor with isodensity in the left lower abdominal wall. Magnetic resonance imaging showed a mass in the abdominal wall with isointensity in the T1-intensified image and high intensity in the T2-intensified images. The mass was heterogeneous inside and protruded partially toward the intraperitoneal cavity. Ultrasound examination showed a heteroechoic mass extending into the intraperitoneal cavity. Laparotomy revealed a tumor in the abdominal wall with a fistulous tract extending to the jejunum. We resected the abdominal wall tumor with partial resection of the small intestine. The resected specimen contained a tumor with a fistulous tract passing through the abdominal wall. Histological examination revealed remarkable infiltration of neutrophils and a bacterial mass in the abdominal wall tumor, with a fistulous tract connected to the area adjacent to the mesenteric border of the jejunum. These findings suggested that diverticulitis of the jejunum had penetrated through the abdominal wall, leading to the formation of an abscess. We report this case to highlight the need for complete gastrointestinal evaluation with gastrointestinal barium studies and imaging analysis to examine extension of intra-abdominal lesions in patients with an unexplained abdominal wall abscess.

Successful downstaging by S-1-based chemotherapy followed by surgical resections for gastric carcinoma with extensive distant lymph node metastasis - report of two cases and a review of cases with surgical resection after downstaging by S-1-based chemotherapy.

We report two cases of gastric carcinoma with successful downstaging using S-1-based chemotherapy followed by surgical resection, which enabled us to confirm the histological effect of chemotherapy. These patients were associated with extensive distant lymph node metastases for which curative resections were unlikely to be performed. We performed anticancer chemotherapy using S-1 with or without concomitant administration of cisplatin in a neoadjuvant setting. After the successful downstaging of these metastatic gastric carcinomas evaluated by imaging analyses, the patients underwent surgical resections. Effect of the chemotherapy was confirmed by the histological analyses. These cases provide further evidence, suggesting that S-1-based chemotherapy enabled downstaging of stage IV gastric carcinoma associated with distant extensive lymph node metastasis and consequently the following possible curative resections. The review of 16 cases of S-1-based chemotherapy followed by surgical resections indicated that, although downstaging may not be expected when N3 lymph node metastases are evident, the S-1-based chemotherapeutic regimens were effective in short cycles for patients in whom potential curative resection is expected. Survival benefit of downstaging followed by surgical resection, however, remains to be further elucidated.

Complete obstruction of the lower common bile duct caused by autoimmune pancreatitis: is biliary reconstruction really necessary?

Recent observations suggest that an immune response is involved in the development of chronic pancreatitis. We report a case of autoimmune pancreatitis in a patient who showed complete obstruction of the lower common bile duct. A 63-year-old man was admitted to a local hospital, complaining of appetite loss and back pain. The patient had obstructive jaundice, and percutaneous transhepatic gallbladder drainage was performed. Fluorography through the biliary drainage catheter showed complete obstruction of the lower common bile duct. The patient had no history of alcohol consumption and no family history of pancreatic disease. Physical examination revealed an elastic hard mass palpable in the upper abdomen. Abdominal ultrasound and abdominal computed tomography (CT) scans showed enlargement of the pancreas head. While autoimmune pancreatitis was highly likely, due to the patient's high serum immunoglobulin level, the possibility of carcinoma of the pancreas and/or lower common bile duct could not be ruled out. Laparotomy was performed, and wedge biopsy samples from the pancreas head and body revealed severe chronic pancreatitis with infiltration of reactive lymphocytes, a finding which was compatible with autoimmune pancreatitis. Cholecystectomy and biliary reconstruction, using choledochojejunostomy, were performed, because the complete bile duct obstruction was considered to be irreversible, due to severe fibrosis. After the operation, prednisolone (30 mg/day) was given orally for 1 month, and the entire pancreas regressed to a normal size. Complete obstruction of the common bile duct caused by autoimmune pancreatitis has not been reported previously; this phenomenon provides an insight into autoimmune pancreatitis and provokes a controversy regarding whether biliary reconstruction is needed for the treatment of complete biliary obstruction caused by autoimmune pancreatitis.

Intraductal papillary-mucinous tumor of the pancreas head with complete absence of the ventral pancreatic duct of Wirsung.

A case of intraductal papillary mucinous tumor of the pancreas with complete absence of the ventral pancreatic duct of Wirsung is presented. A 74-year-old Japanese man was admitted to our hospital because of elevated serum amylase concentration. Abdominal computed tomography (CT) scanning revealed diffuse dilatation of the main pancreatic duct and a diffuse and uncircumscribed area with heterogeneous density in the pancreas head. Endoscopic retrograde cholangiopancreatography revealed that the main pancreatic duct was connected with an accessory papilla and was diffusely dilated, without any irregularity of the duct wall being observed in the entire length of the duct. The common bile duct was detected only by cannulation through Vater's papilla, and no pancreatic duct or its communicating branch was found. Some branches, directed to the dorsal portion of the pancreas head, were found arising from the accessory pancreatic duct. Intraductal ultrasound examination performed through the accessory papilla and the common bile duct revealed a small tumor with a heterogeneous echo level in the pancreas head. From these findings, intraductal papillary-mucinous tumor (IPMT) occurring in the pancreas head was diagnosed, and pylorus-preserving pancreaticoduodenectomy was performed. The resected specimen revealed IPMT in the pancreas head. A roentgenographic study of the resected specimen revealed a defect caused by the tumor located in the pancreatic duct connected with the accessory papilla and showed that there was complete absence of the pancreatic duct connected with Vater's papilla. Surgical resection enabled us to completely analyze the duct system of pancreas divisum. Although it is not known whether there is a relationship between the pathogenesis of IPMT and embryological anomaly of the pancreatic duct system, this case may provide an insight into the pathogenesis of IPMT.