Search

General interest in functional gastrointestinal disorders is increasing among Japanese doctors as well as patients. This increase can be attributed to a number of factors, including recent increased interest in quality of life and advances in our understanding of the pathophysiology of gastrointestinal disease. Japan recently became the world's first country to list "functional dyspepsia" as a disease name for national insurance billing purposes. However, recognition and understanding of functional dyspepsia (FD) remain poor, and no standard treatment strategy has yet been established. Accordingly, the Japanese Society of Gastroenterology (JSGE) developed an evidence-based clinical practice guideline for FD, consisting of five sections: concept, definition, and epidemiology; pathophysiology; diagnosis; treatment; and prognosis and complications. This article summarizes the Japanese guideline, with particular focus on the treatment section. Once a patient is diagnosed with FD, the doctor should carefully explain the pathophysiology and benign nature of this condition, establish a good doctor-patient relationship, and then provide advice for daily living (diet and lifestyle modifications, explanations, and reassurance). The proposed pharmacological treatment is divided into two steps: initial treatment including an acid inhibitory drug (H2RA or PPI) or prokinetics, (strong recommendation); second-line treatment including anxiolytics, antidepressants, and Japanese traditional medicine (weak recommendation). H. pylori eradication, strongly recommended with a high evidence level, is positioned separately from other treatment flows. Conditions that do not respond to these treatment regimens are regarded as refractory FD. Patients will be further examined for other organic disorders or will be referred to specialists using other approaches such as psychosomatic treatment.

Background: Lack of a suitable instrument to comprehensively assess symptoms, living status, and quality of life in postgastrectomy patients prompted the authors to develop postgastrectomy syndrome assessment scale (PGSAS)-45., Methods: PGSAS-45 consists of 45 items in total: 8 items from SF-8, 15 items from GSRS, and an additional 22 items selected by 47 gastric surgeons. Using the PGSAS-45, a multi-institutional survey was conducted to determine the prevalence of postgastrectomy syndrome and its impact on everyday life among patients who underwent various types of gastrectomy. Eligible data were obtained from 2,368 patients operated and followed at 52 institutions in Japan. Of these, data from 1,777 patients were used in the current study in which symptom subscales of the PGSAS-45 were determined. We also considered the characteristics of the postgastrectomy syndrome and to what extent these symptoms influence patients' living status and quality of life (QOL)., Results: By factor analysis, 23 symptom-related items of PGSAS-45 were successfully clustered into seven symptom subscales that represent esophageal reflux, abdominal pain, meal-related distress, indigestion, diarrhea, constipation, and dumping. These seven symptom subscales and two other subscales measuring quality of ingestion and dissatisfaction for daily life, respectively, had good internal consistency in terms of Cronbach's α (0.65-0.88)., Conclusion: PGSAS-45 provides a valid and reliable integrated index for evaluation of symptoms, living status, and QOL in gastrectomized patients.

Background: Proximal gastrectomy with esophagogastrostomy (PGEG) has been widely applied as a comparatively simple method. In this study, we used a questionnaire survey to evaluate the influence of various surgical factors on post-operative quality of life (QOL) after PGEG., Methods: In this post-gastrectomy syndrome assessment study, we analyzed QOL in 2,368 cases. Among these, 193 had undergone proximal gastrectomy and 115 had undergone PGEG. The Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-45 is a questionnaire consisting of 45 items, including the SF-8, the Gastrointestinal Symptom Rating Scale (GSRS), and other symptom items seemed to be specific to post-gastrectomy. The 23 symptom items were composed of seven symptom subscales (SS), including esophageal reflux, abdominal pain, and meal-related distress. These seven SS, total symptom score, ingested amount of food per meal, necessity for additional meals, quality of ingestion SS, ability to work, dissatisfaction with symptoms, dissatisfaction with the meal, dissatisfaction with working, dissatisfaction with daily life SS and change in body weight were evaluated as main outcome measures. In PGEG cases, we evaluated the influence on QOL of various surgical factors, such as procedures to prevent gastroesophageal regurgitation and size of the remnant stomach., Results: The scores for esophageal reflux and dissatisfaction with the meal were higher in patients who had not undergone an anti-reflux procedure. In most cases, the preserved remnant stomach was more than two-thirds the size of the pre-operative stomach. When comparing patients with a remnant stomach two-thirds the pre-operative size and those with more than three-quarters, the diarrhea SS and necessity for additional meals scores were lower in the group with more than three-quarters. The indigestion, constipation, and abdominal pain subscales, and the total symptom score, were higher in patients who had not undergone pyloric bougie than in those who had., Conclusion: These results indicated that QOL was better in patients with a large remnant stomach. Procedures to prevent gastroesophageal reflux, and the use of pyloric bougie as a complementary drainage procedure, were considered effective ways to reduce the deterioration of QOL.

Background: Indications for gastric local resection (LR) include gastrointestinal stromal tumors, neuroendocrine tumors, and early gastric cancer. LR is expected to preserve physiological function and ameliorate postgastrectomy syndrome., Methods: Gastric emptying was assessed by the (13)C-acetate breath test in 20 healthy volunteers (HVs) and 60 gastrectomized patients [distal gastrectomy with Billroth I reconstruction (DGBI) in 26 patients, LR in 34 patients]. For the (13)C breath test, 100 mg of (13)C-acetate sodium salt was mixed in a test meal. Breath samples were collected before intake and during the next 3 h. We compared the gastric reservoir capacity using the gastric retention rate at 5 min (RR5) and gastric emptying by the half emptying time (T½). Patients completed a questionnaire survey about their symptoms, dietary intake, body weight, and restriction of activities of daily living [reflecting quality of life (QOL)]., Results: The RR5 values for the HV, LR, and DGBI groups were 93.7, 90.0, and 45.3* %, respectively (*compared to HV and LR, p < 0.0001). The T½ values were 23.3, 20.2, and 5.9* min, respectively. Dietary intake and body weight change were significantly more reduced in the DGBI group than the LR group (p < 0.05). Subgroup analysis indicated that the reservoir capacity in those with LR at the lesser curvature was more disturbed than that in patients with LR at the greater curvature. The questionnaire showed no differences in those patients' QOL., Conclusions: Because the reservoir capacity, the gastric emptying and QOL were maintained, LR is an option for selected patients with early gastric cancer.

Background and Aim: Early gastric cancer (EGC), with wall invasion limited to the submucosa, has approximately 15 to 20% chance of lymph node metastasis. The purpose of this study is to clarify the parameters which affect lymph node metastasis and survey whether lymph node metastasis can be predicted preoperatively., Patients and Methods: We retrospectively analyzed 145 consecutive patients with EGC using multivariate analysis and developed a formula which predicts lymph node metastasis by linear discriminant analysis. In addition, we prospectively validated this formula in another subset of 106 consecutive patients with EGC and compared the predicted with the actual pathological lymph node metastasis., Results: Multivariate analyses revealed that independent factors, which affect lymph node metastasis for EGC, were lymphatic system invasion (p=0.00002, odds ratio 3.11) and venous system invasion (p=0.039, odds ratio 2.44). In addition, we developed the lymph node metastasis-predicting formula using these two factors by linear discriminant analysis. The formula is as follows: Y=0.12 × (venous system invasion: 0, 1, 2 or 3) + 0.19 × (lymphatic system invasion: 0, 1, 2, or 3) - 0.14. If Y>0, we judge that a patient with gastric cancer is susceptible lymph node metastasis. The result of this prospective study showed that the sensitivity and specificity rates were 70% and 61.6%, respectively., Conclusion: We developed a formula which can predict lymph node metastasis using linear discriminant analysis. This formula seems useful in predicting for lymph node metastasis in patients with EGC., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: Billroth-I (BI) and Roux-en-Y (RY) are well-known reconstruction methods that are conducted following distal gastrectomy. However, the relative merits of these 2 methods are not well documented. The newly developed Postgastrectomy Syndrome Assessment Scale (PGSAS)-45 is an integrated questionnaire consisting of 45 items, including 8 items from the 8-Item Short-Form Health Survey (SF-8), 15 items from the Gastrointestinal Symptom Rating Scale, and 22 items selected by gastric surgeons. Postoperative QOL ratings were evaluated for each reconstruction method using PGSAS-45., Methods: The PGSAS-45 questionnaire was distributed to 2,922 patients who underwent gastrectomies at 52 medical institutions. Among the questionnaires distributed, 2520 (86 %) were retrieved and 2368 (81 %) met eligibility requirements. Statistical analyses were conducted to compare 1,384 of the eligible questionnaires, including responses from patients who underwent BI (n = 909) and RY (n = 475) procedures., Results: BI procedures were associated with significantly longer postoperative periods, a significantly greater size of gastric remnants, and a higher frequency of laparoscopic approaches and celiac branch preservation. Postoperative QOL analysis indicated that BI procedures resulted in significantly lower postoperative weight loss and significantly higher esophageal reflux symptoms than RY procedures. There was no significant difference between the two groups on other outcome measures., Conclusions: Although weight loss was significantly lower following BI procedures, esophageal reflux symptoms were significantly higher. Either BI or RY procedures may be recommended based on the individual patient's condition after distal gastrectomy. The newly developed QOL questionnaire, PGSAS-45 and changes in body weight proved useful for evaluation of QOL following gastrectomy.

Background/aim: Ubiquitin-conjugating enzyme H10 (UBCH10) is required in the cell-cycle transition from metaphase to anaphase. Therefore, we investigated whether its expression level in cancerous esophageal lesions affected prognosis of patients with esophageal squamous-cell carcinoma., Materials and Methods: Paraffin-embedded tissue samples from 121 patients with esophageal squamous cell carcinoma were stained with antibody to UBCH10 for immunohistochemical analysis., Results: UBCH10 was expressed in cancerous and dysplastic lesions, but not in normal tissue. Patients were grouped according to expression: High (N=33) or low (N=88), depending on the staining pattern. There were significant differences between the groups in terms of invasion into lymphatic vessels, number of metastatic lymph nodes, TNM classification, and stages, as well as in survival: the 50% survival rate in the high expression group was 2.3 years, whereas it was 9.9 years for the low-expression group (p<0.0001). Even with multivariate adjusting for stage 0 to stage IV using the Cox proportional hazard model, patients belonging to the high-expression group had a poor prognosis (Hazard ratio=2.5; 95% Confidence Interval=1.3-4.5; p=0.004)., Conclusion: High protein expression of UBCH10 is a marker of poor prognosis in esophageal squamous cell carcinoma.

Evaluating hepatic insulin resistance (IR) is the key to making a sensitive an accurate diagnosis of glucose intolerance. However, there is currently no suitable method to perform this procedure. This study was conducted to investigate whether the fasting (13)C-glucose breath test (FGBT) is useful as a convenient and highly sensitive clinical test for evaluating hepatic IR. Healthy nonobese subjects and a disease group consisting of patients with mild glucose intolerance were administered 100 mg (13)C-glucose after an overnight fast. A series of breath samples was collected until 360 minutes after ingestion, and the (13)CO2-to-(12)CO2 ratio was measured using an infrared spectrometer and was plotted as a kinetic curve of (13)C excretion. The area under the curve until 360 minutes (AUC360) of the (13)C excretion kinetic curve of the FGBT reflects the efficiency of energy production in the liver. First, we assessed the correlations between the AUC360 (or the (13)C excretion rate at 120 minutes) and the HOMA-IR and HbA1c levels as standard measurements of IR and diabetes mellitus (DM). There were relatively strong correlation coefficients (r = -0.49 to -0.81, r(2) = 0.24-0.66, P < 0.01; n = 35 males, n = 33 females). Second, we compared the AUC360 of healthy subjects and that of the patients with mild glucose intolerance. The AUC360 of the healthy subjects was consistently higher than that of the patients with mild glucose intolerance. The presence of IR or DM in males and females was diagnosed using cutoff values. The FGBT is a novel glucose metabolism test that can be used conveniently and safely to evaluate the balance of glucose metabolism in the liver. This test has excellent sensitivity for diagnosing alterations in hepatic glucose metabolism, particularly hepatic IR., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Gastrectomy saves the lives of many patients with gastric cancer. However, this surgical treatment is associated with clinical problems called postgastrectomy syndrome (PGS) which affect the quality of life (QOL) of such patients. For surgeons, improving the QOL after gastrectomy is an important goal after performing curative surgery. In the clinical setting, various surgical procedures such as limited resection, function-preserving procedures, and reconstruction using gastric substitutes have been advocated to reduce the severity of PGS. However, the actual conditions and pathophysiology of PGS have not been fully investigated. Various clinical studies and basic research have partially clarified the features and pathophysiology of PGS, although the strategies developed to treat PGS have been limited. The development of standardized, reliable instruments for understanding PGS and performing large-scale collaborative studies are required to improve the diagnosis and treatment of PGS. In Japan, such a project called the PGSAS has recently been completed. The results are being analyzed and will be reported in the near future.

Background and Aim: Functional dyspepsia (FD) is a common condition seen in primary gastroenterology practice. The present study was conducted to compare the clinical effectiveness of mosapride and teprenone in patients with FD., Methods: Prospective clinical comparative study with random allocation of open labeled medications was performed as a multicenter trial in Japan. 1042 patients presenting symptoms of FD, either with gastric stasis (GSS) and/or epigastric pain (EPS), were enrolled. After initial endoscopic evaluation, medication either with mosapride 5 mg tid or teprenone 50 mg tid was started. Severity and frequency of GSS and EPS, health-related quality of life (HR-QOL) by the SF-36 Japanese version, and patients' compliance to medication was evaluated., Results: Organic lesions were found in 90 patients (9%) in the 1027 patients examined by endoscopy. Among those without any specific lesions detected by endoscopy, gastrointestinal symptoms were resolved within one week after the endoscopy in 264 (28%) patients before initiating medication. 618 patients who remained symptomatic were randomized to medication either with mosapride (n = 311) or teprenone (n = 307). Two-week treatment with mosapride significantly improved GSS and EPS, while teprenone tended to improve only GSS. Mosapride also improved HR-QOL. 91% of patients treated with mosapride favored their medication, while only 52% of patients treated with teprenone favored their medication., Conclusions: Endoscopic evaluation at patients' presentation was effective to find active lesions and to improve FD symptoms. Mosapride was more favorably accepted than teprenone by the patients with sufficient safety and efficacy., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background/aims: The gastrointestinal symptoms accompanying dysfunction of the remnant stomach were seen after pylorus-preserving operation. Against such complications, Dai-kenchu-to (DKT) is used, but scientific evidences for efficacy are poor. The effect of DKT on gastrointestinal motility and gastric emptying after pylorus-preserving operation was investigated., Methods: Using beagle dogs, the experimental models mimicking the state after pylorus-preserving pancreaticoduodenectomy were prepared. We sutured strain gauge transducers to the stomach, duodenum and jejunum and inserted indwelling tubes into the stomach. About 4 weeks after operation, DKT 0.1g/kg was administered during the fasting or fed state. At the same time, the gastric emptying was evaluated by the acetoaminophene method., Results: In the fasting state, administration of DKT enhanced the gastrointestinal motility and accelerated gastric emptying. In the postprandial state, no apparent effect on motility was seen., Conclusion: DKT enhances the gastrointestinal motility after pylorus-preserving pancreaticoduodenectomy in the fasting state. The effect of DKT may not be related to the continuity of the intramural nerve.

The purpose of this study was to investigate the effects of the herbal medicine dai-kenchu-to on gastrointestinal motility based on differences in the administration site and timing. We sutured strain-gauge transducers to the stomach (three), duodenum (one), jejunum (one), ileum (one), and colon (two) and inserted indwelling tubes into the stomach, jejunum, and proximal colon of beagles. Dai-kenchu-to was administered to each site during the fasting or fed state. During the fasting state, the prokinetic effects of dai-kenchu-to were evident at all administration sites. The effects were attenuated during the fed state. With intracolonic administration, a contraction similar to the giant migrating contraction-like contraction was induced during the fasting and the fed state, and defecation occurred. Despite the differences in administration site and timing, no contraction complex appeared orad to the administration sites. These results indicate that the prokinetic effects of dai-kenchu-to differ with the site or timing of administration.

We report two patients with suture line recurrence in the jejunal pouch after curative proximal gastrectomy for gastric cancer. The first patient was a 60-year-old asymptomatic woman with gastric cancer (T2N0M0) after curative proximal gastrectomy with jejunal pouch interposition. She had to undergo a second resection for suture line recurrence in the jejunal pouch 12 months later. On examination of the resected specimen, histological examination revealed a moderately differentiated adenocarcinoma, which was similar to that of the primary tumor. The second patient was a 74-year-old man who was also diagnosed as having locoregional recurrences in the jejunal pouch after a curative proximal gastrectomy with an S-shaped pouch for gastric cancer (T2N0M0). Histological examination of the resected specimen revealed moderately differentiated adenocarcinoma, which had a similar histopathology to that of the primary tumor. During the first procedure, the jejunal pouch was formed using several disposable devices and the end-to-side esophagojejunostomy was performed with another circular stapler to avoid contamination through surgical instruments. Exfoliated cancer cells that may have detached from the primary tumor during the surgical procedures could have contributed to local recurrence along the longitudinal suture line of the pouch.

Background/aims: We have performed ileocolon interposition for reconstruction (IR) after total gastrectomy in order to reduce postoperative symptoms such as heartburn, reflux esophagitis and nutritional disturbance. After IR, however, the frequency of diarrhea increased in the postoperative period. We therefore investigated whether post-IR diarrhea could be prevented by preserving the vagus nerve., Methodology: The vagus nerve was not preserved in 46 (non-PV group) stage I and II gastric cancer patients treated with the IR method, and preserved in 28 for stage IA (PV group). By means of a mailed and interviewed questionnaire, we surveyed the patients at six months postoperatively to examine how diarrhea had occurred in either group., Results: The frequency of diarrhea of the PV group was as low as 26% (7/27) which was significantly lower than 76% (35/46) of the non-PV group., Conclusions: Preservation of the vagus nerve during reconstruction using ileocolon interposition after total gastrectomy for stage IA is a superior approach for the prevention of postoperative diarrhea.

Morphine is known to delay gastric emptying and intestinal transit, although epidural morphine is believed to decrease postoperative complications. However, these findings are still controversial and based only on clinical observations. We investigated the effects of epidural morphine administration on gut motility by measuring interdigestive migrating complex after open surgery in dogs. Twenty-eight beagles were divided into four groups (n = 7 each) to receive epidural saline (control group), epidural morphine, epidural ropivacaine, or low-dose continuous intravenous morphine. Strain gauge force transducers were sutured under open operation to the serosal surface of the stomach, duodenum, jejunum, and ileum to monitor gut motility. Time of appearance of first interdigestive migrating complex from the stomach propagated to the distal intestine was significantly shorter in the group that received epidural morphine compared with the other three groups. These results suggest that epidural administration of morphine may facilitate recovery from paralytic ileus after open abdominal surgery, perhaps through its effects on the central nervous system.

Esophageal squamous cell carcinoma has heterogeneous clinical outcomes that cannot be predicted well using any existing clinical or molecular prognostic factors. Gene expression profiling may enable more precise prediction of the clinical outcome of these patients. We developed a new approach using gene expression ratios of paired cancerous and normal tissue specimens from the same patient to reduce the effects of variation among individuals. Using oligonucleotide microarrays, we analyzed total RNA expression levels corresponding to 12,600 transcript sequences in 24 paired cancerous and normal tissue operative specimens from 12 patients with esophageal squamous cell carcinoma. Hierarchical clustering analysis using gene expression ratios (cancer:normal) divided the 12 patients into two groups; all 7 patients in the first cluster survived without relapse (median follow-up, 483 days), whereas all 5 patients in the second cluster relapsed (median relapse-free survival time, 280 days; log-rank test, P = 0.006). In contrast, clustering either with cancerous tissue alone or with normal tissue alone did not show significant differences in the outcomes. The expressions of a variety of genes related with cell cycle, gene-repair, apoptosis and chemoradiotherpay resistance were up-regulated in the poor prognostic cluster. These results suggest that ratios of paired gene expression profiles may more efficiently predict relapse-free survival of esophageal squamous cell carcinoma than existing prognostic factors or than gene expression profiling with cancerous tissue alone.