A Hereditary Enteropathy Caused by Mutations in the SLCO2A1 Gene, Encoding a Prostaglandin Transporter.

Previously, we proposed a rare autosomal recessive inherited enteropathy characterized by persistent blood and protein loss from the small intestine as chronic nonspecific multiple ulcers of the small intestine (CNSU). By whole-exome sequencing in five Japanese patients with CNSU and one unaffected individual, we found four candidate mutations in the SLCO2A1 gene, encoding a prostaglandin transporter. The pathogenicity of the mutations was supported by segregation analysis and genotyping data in controls. By Sanger sequencing of the coding regions, 11 of 12 other CNSU patients and 2 of 603 patients with a diagnosis of Crohn's disease were found to have homozygous or compound heterozygous SLCO2A1 mutations. In total, we identified recessive SLCO2A1 mutations located at seven sites. Using RT-PCR, we demonstrated that the identified splice-site mutations altered the RNA splicing, and introduced a premature stop codon. Tracer prostaglandin E2 uptake analysis showed that the mutant SLCO2A1 protein for each mutation exhibited impaired prostaglandin transport. Immunohistochemistry and immunofluorescence analyses revealed that SLCO2A1 protein was expressed on the cellular membrane of vascular endothelial cells in the small intestinal mucosa in control subjects, but was not detected in affected individuals. These findings indicate that loss-of-function mutations in the SLCO2A1 gene encoding a prostaglandin transporter cause the hereditary enteropathy CNSU. We suggest a more appropriate nomenclature of "chronic enteropathy associated with SLCO2A1 gene" (CEAS).

Measurement of intragastric pressure: an objective method to ascertain whether gastric wall extension is sufficient for assessment of the non-extension sign.

Background and study aims The optimal intragastric pressure (IP) for strong gastric wall extension is unclear. We aimed to develop an accurate method to measure IP using endoscopy and determine the pressure required for strong gastric wall extension. Methods An in vitro experiment using an endoscope with a rubber attached at its tip was conducted. The process of inserting the pressure measurement probe into the forceps channel was skipped, and the tube of the pressure measurement device was directly connected to the forceps channel. In vivo, the pressure in 51 consecutive patients at the time of strong gastric wall extension was measured. Strong extension of the gastric wall was defined as when the folds in the greater curvature were flattened as a result of sufficient extension of the gastric wall by insufflated air during upper gastrointestinal endoscopy. The IP at that time was measured. Results In vitr o , 20 mL of tap water was injected once into the forceps channel and then aspirated for 10 seconds. Pressure measurement after irrigation of the forceps channel as well as the measurement by inserting the probe procedure were accurately performed. In vivo, among the 51 included patients, the mean IP (range) was 14.7 mmHg (10-23). Strong extension of the gastric wall was obtained in 96.1 % of patients when the IP was 20 mmHg. Conclusions We developed an accurate method to measure IP using upper gastrointestinal endoscopy. Strong extension of the gastric wall was obtained in almost all patients when the IP was 20 mmHg.

Crohn's disease-specific mortality: a 30-year cohort study at a tertiary referral center in Japan.

BACKGROUND: In this study, survival and cause of death were investigated in patients with Crohn's disease (CD) at a tertiary referral center. METHODS: A database was created based on the medical records of 1108 CD patients who had a history of visiting our hospital to investigate background characteristics, cumulative survival rates from diagnosis, causes of death, and the standardized mortality ratio (SMR) for each cause of death. A follow-up questionnaire survey of patients followed up inadequately was also conducted. The cumulative survival rate from diagnosis was determined using the life table method and compared with that of a sex- and age-matched population model from the year 2000. RESULTS: The study included 1108 patients whose mean age at diagnosis was 25.6 ± 10.8 years. The mean duration of follow-up was 14.6 ± 9.4 years, and there were 52 deaths. The cumulative survival rate was significantly lower 25 years after the diagnosis of CD (91.7%) than in the standard population model (95.7%). SMRs for both all causes [3.5; 95% confidence interval (CI): 2.7-4.6] and CD-specific causes (36.7; 95% CI 26.1-51.6) were high. Among the CD-specific causes, SMRs were especially high for small intestine and colorectal cancers, gastrointestinal diseases including intestinal failure (IF), perioperative complications, and amyloidosis. CONCLUSION: The SMRs for both all causes and CD-specific causes were high in CD patients. CD-specific causes including intestinal cancer, IF, perioperative complications, and amyloidosis showed especially high SMRs.

Measurement of prostaglandin metabolites is useful in diagnosis of small bowel ulcerations.

BACKGROUND: We recently reported on a hereditary enteropathy associated with a gene encoding a prostaglandin transporter and referred to as chronic enteropathy associated with SLCO2A1 gene (CEAS). Crohn's disease (CD) is a major differential diagnosis of CEAS, because these diseases share some clinical features. Therefore, there is a need to develop a convenient screening test to distinguish CEAS from CD. AIM: To examine whether prostaglandin E major urinary metabolites (PGE-MUM) can serve as a biomarker to distinguish CEAS from CD. METHODS: This was a transactional study of 20 patients with CEAS and 98 patients with CD. CEAS was diagnosed by the confirmation of homozygous or compound heterozygous mutation of SLCO2A1. We measured the concentration of PGE-MUM in spot urine by radioimmunoassay, and the concentration was compared between the two groups of patients. We also determined the optimal cut-off value of PGE-MUM to distinguish CEAS from CD by receiver operating characteristic (ROC) curve analysis. RESULTS: Twenty Japanese patients with CEAS and 98 patients with CD were enrolled. PGE-MUM concentration in patients with CEAS was significantly higher than that in patients with CD (median 102.7 vs 27.9 µg/g × Cre, P < 0.0001). One log unit increase in PGE-MUM contributed to 7.3 increase in the likelihood for the diagnosis of CEAS [95% confidence interval (CI) 3.2-16.7]. A logistic regression analysis revealed that the association was significant even after adjusting confounding factors (adjusted odds ratio 29.6, 95%CI 4.7-185.7). ROC curve analysis revealed the optimal PGE-MUM cut-off value for the distinction of CEAS from CD to be 48.9 µg/g × Cre with 95.0% sensitivity and 79.6% specificity. CONCLUSION: PGE-MUM measurement is a convenient, non-invasive and useful test for the distinction of CEAS from CD.

[Nonsteroidal anti-inflammatory drug-induced enteropathy and chronic nonspecific multiple ulcers of the small intestine].

With the development of double balloon endoscopy and video-capsule endoscopy, it has become inevitable for gastroenterologist to diagnose small intestinal ulcers accurately. Chronic nonspecific multiple ulcers of the small intestine (CNSU) and nonsteroidal antiinflammatory drugs-induced enteropathy (NSAIDs-enteropathy) share common clinicopathologic features characterized by histologically nonspecific ulcers and persistent blood loss. In addition, the two disorders had common enteroscopic findings, namely, circular ulcers and concentric stenoses. However, CNSU is distinctive of NSAIDs-enteropathy with respect to intractable ulcers of various configurations. In consideration of widespread use of NSAIDs, a strategy for the prevention of NSAIDs-enteropathy should be examined. Also, much more cases of CNSU should be analyzed to establish the pathophysiology of the disease.

Clinical features of chronic enteropathy associated with SLCO2A1 gene: a new entity clinically distinct from Crohn's disease.

BACKGROUND: Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a hereditary disease caused by mutations in the SLCO2A1 gene and characterized by multiple small intestinal ulcers of nonspecific histology. SLCO2A1 is also a causal gene of primary hypertrophic osteoarthropathy (PHO). However, little is known about the clinical features of CEAS or PHO. METHODS: Sixty-five Japanese patients recruited by a nationwide survey of CEAS during 2012-2016 were enrolled in this present study. We reviewed the clinical information of the genetically confirmed CEAS patients. RESULTS: We identified recessive SLCO2A1 mutations at 11 sites in 46 patients. Among the 46 patients genetically confirmed as CEAS, 13 were men and 33 were women. The median age at disease onset was 16.5 years, and parental consanguinity was present in 13 patients (28%). Anemia was present in 45 patients (98%), while a single patient experienced gross hematochezia. All patients showed relatively low inflammatory markers in blood tests (median CRP 0.20 mg/dl). The most frequently involved gastrointestinal site was the ileum (98%), although no patient had mucosal injuries in the terminal ileum. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO. CONCLUSIONS: The clinical features of CEAS are distinct from those of Crohn's disease. Genetic analysis of the SLCO2A1 gene is therefore recommended in patients clinically suspected of having CEAS.

Factors regulating tumor pressure in cases of small hepatocellular carcinoma.

BACKGROUND/AIMS: There is scare information regarding tumor pressure in hepatocellular carcinoma. As the tumor diameter increases, histological manifestations become more diverse. Therefore, studies based on relatively small tumors are needed in order to search for those underlying factors that are directly related to tumor pressure in hepatocellular carcinoma. The purpose of this study was to determine which factors regulate tumor pressure in cases of hepatocellular carcinoma where the diameter of the tumor is 3cm or less. METHODOLOGY: The study included 54 patients with small hepatocellular carcinoma in whom tumor pressure had been determined and in whom the tumor had been confirmed histologically. Tumor pressure was determined percutaneously under ultrasonographic guidance. RESULTS: Hepatic tissue pressure (p = 0.01), tumor size (p < 0.01), number of tumors (p = 0.01), degree of tumor differentiation (p < 0.01), ultrasonographic halo (p < 0.01), angiographic tumor staining (p < 0.01) and angiographic tumor vessel (p = 0.03) all showed significant correlation with tumor pressure. Multivariate analysis revealed that angiographic tumor staining (p = 0.001), hepatic tissue pressure (p = 0.013), and tumor size (p = 0.044) were significant factors associated with tumor pressure. CONCLUSIONS: It was suggested that tumor pressure in small hepatocellular carcinoma was mainly regulated through development of the neovasculature.

[Clinical course of 4 cases of hepatic peribiliary cysts and a summary of the 38 clinical cases reported in Japan].

We encountered 4 cases of hepatic peribiliary cysts (HPBC) in our hospital. Two were asymptomatic, one was complicated by a choledocholithiasis, and one by cholangitis and sepsis. Based on a review of the 38 cases of HPBC clinically diagnosed in Japan, the main problem associated with this disease seemed incorrect preoperative diagnosis leading to an unnecessary hepatectomy. Another problem was concomitant cholangitis, which tended to recur and in some cases needed aggressive treatment using drainage.

Nutritional therapy for Crohn's disease in Japan.

In Japan, nutritional therapy as both a primary and as a secondary treatment is widely used for Crohn's disease (CD). The rationale for its use is based on a variety of reasons. The first is its ability to induce remission and to ameliorate the activity of intestinal lesions in the short term by enteral (EN) or by parenteral nutritional therapy in which overexpressions of chemokine receptors in an active stage are decreased significantly in the remission stage. Second is its ability to maintain remission over the long term through home-based enteral nutrition in which tube feeding during the nighttime is encouraged. Third is its ability to reduce the steroid dosage over the period of a long-term treatment course. However, several disadvantages of this therapy such as unpalatability and sluggish effect have been pointed out. Several studies have attempted to resolve this issue and determine the best components of EN, especially in fat composition. Some data have been suggestive of too much long-chained fatty acid having a hazardous effect on EN's clinical efficacy because it works as a precursor of inflammatory prostaglandins. Our recent data show that medium-chained triglyceride did not have such a hazardous effect on clinical efficacy. Several studies suggested that the patient factors that were resistant to inducing remission in the short term were a long period of suffering CD, a high activity (on Crohn's Disease Activity Index, CDAI), hemorrhagic colitis, and colitis with marked cobblestoning. Japanese guidelines for the treatment of CD recommended nutritional therapy as a first-line therapy and as a maintenance therapy after inducing remission. This treatment policy has led to Japanese CD patients having lower mortality rates than that of patients who do not receive EN. If this therapy could be combined with other drug therapies, including strong immunosuppressants, treatment strategies would be improved over those we have at present.

A prospective study of the prevalence of gastroesophageal reflux disease and confounding factors.

BACKGROUND: The prevalence of gastroesophageal reflux disease (GERD) has reportedly risen in recent years. Difficulties associated with endoscopic diagnosis mean it is not easy to determine its precise prevalence. A prospective study of the prevalence of endoscopy-positive GERD (EP-GERD) was conducted at Higuchi Hospital, a general hospital in Northwestern Kyushu, Japan. The study also correlated factors that might affect prevalence (age, sex, and functions of the gastroesophageal junction). METHODS: From consecutive patients undergoing endoscopic examination at Higuchi Hospital between January 2000 and April 2003, 1234 patients without severe complications were examined for the possible presence of GERD. Patients were stratified by age and sex, and the prevalence in each group ascertained. EP-GERD was defined on the four-level scale of the Los Angeles classification. Endoscopic classification of gastroesophageal flap valve ([GEFV] functional anomalie; using a four-level scale), was done as proposed by Hill et al. in 1996, to assess flap-valve morphology. Six items were evaluated: (1) symptoms and primary diseases; (2) prevalence of development of EP-GERD classified by age and sex; (3) endoscopic morphology of the GEFV as an expression of the functions of the gastroesophageal junction, and its prevalence by age and sex; (4) regression analysis and Spearman's rank correlation of GEFV and EP-GERD grades; (5) prevalence of EP-GERD and GEFV stratified by age and analyzed; and (6) multiple regression analysis of EP-GERD and explanatory variables (age, sex, and GEFV). RESULTS: The overall prevalence of EP-GERD was 5.8% (72/1234) and this patient group was dominated by men. Aging had minimal effect on prevalence in men, but the prevalence rose among women as they aged. The age-stratified prevalence of GEFV functional anomalies was similar to the age-stratified prevalence of EP-GERD in both sexes. The correlation between EP-GERD and GEFV functional anomalies was high regardless of sex. CONCLUSIONS: We postulate that the mechanisms leading to the development of GEFV functional anomalies in men are different from those in women. Future evaluations of EP-GERD should also observe GEFV function.

Deep infiltrative low-grade MALT (mucosal-associated lymphoid tissue) colonic lymphomas that regressed as a result of antibiotic administration: endoscopic ultrasound evaluation.

Since 1997 we have experienced three cases of low-grade colonic mucosal-associated lymphoid tissue (MALT) lymphomas. The depth of tumor invasion was evaluated by endoscopic ultrasonography (EUS) and the mass lesions were all diagnosed as having extended beyond the deep region of the submucosal layer. Although all of these patients tested negative for gastric Helicobacter pylori, their tumor lesions regressed after antibiotic treatment in accordance with H. pylori eradication therapy. In general, consensus has been reached regarding antibiotic therapy for gastric MALT lymphomas. However, as a prerequisite for antibiotic therapy, the therapy has been deemed effective against these gastric tumors if the extent of infiltration, as evaluated by EUS, is limited to the mucosal layer or the superficial region of the submucosal layer. Based on the therapeutic outcomes seen in the three patients studied here, it is suggested that antibiotic therapy might be useful in treating MALT lymphomas of the colon, even in patients with advanced invasive tumors, in contrast to the extent of the lesions in the stomach suitable for antibiotic treatment. The success of the antibiotic treatment also suggests that MALT lymphomas may be caused by unknown luminal microorganisms, other than H. pylori.

Evaluation of the clinical course of acute attacks in patients with ulcerative colitis through the use of an activity index.

BACKGROUND: Because it is not easy to make a clinical decision regarding surgical treatment in patients with acute attacks of ulcerative colitis, an objective, simple, criterion is needed to determine the optimum timing for colectomy. The aim of this study was to retrospectively examine to what extent an activity index (AI) can evaluate the clinical course in such acute attacks. METHODS: One hundred and twenty-seven patients with moderate or severe attacks of ulcerative colitis were examined. AI values and the decline in AI values were compared between surgical and nonsurgical groups after 1 week and 2 weeks of medical therapy. To evaluate the clinical course of acute attacks, cutoff AI values were set at every 10 points between values of 180 and 210. The positive predictive value for surgery was examined. RESULTS: AI values in the surgical group were significantly higher than those in nonsurgical group at pretreatment, and after 1 or 2 weeks of medical therapy. The decline of AI values in the nonsurgical group was significantly higher than that in the surgical group after 1 or 2 weeks of medical therapy. At pretreatment, the prediction of colectomy was less than 50% at any of the cutoff values. After 1 week of therapy, approximately 60% of patients with an AI value greater than any of the cutoff AI values required colectomy. After 2 weeks of therapy, 30 of 43 (70%), 28 of 38 (74%), 24 of 29 (83%), and 17 of 21 (81%) patients with AI values greater than 180, 190, 200, and 210, respectively, required colectomy. Overall accuracy was 86%, 87%, 88%, and 83% for cutoff AI values of 180, 190, 200, and 210, respectively. Because the overall accuracy and positive predictive value for colectomy at AI values of 200 were significantly higher than these parameters at other AI values after 2 weeks of therapy, an AI value of 200 was regarded as the cutoff value most able to predict colectomy. CONCLUSIONS: We concluded that patients with an AI value in excess of 200 after 2 weeks of medical therapy would require surgical treatment.

Abnormal pancreatic imaging in Crohn's disease: prevalence and clinical features.

BACKGROUND: This study aimed to delineate the incidence and the clinical features of abnormal pancreatic imaging in patients suffering from Crohn's disease. METHODS: The subjects of this retrospective study were 255 patients with Crohn's disease who were treated at our unit and who were followed-up for more than 3 years. RESULTS: Sixteen of the 255 Crohn's disease patients (6.3%) had morphological abnormalities of the pancreas. The cumulative incidence of abnormal pancreatic imaging as a complication of Crohn's disease was 5.2% at 5 years and 6.3% at 10 years after the initial diagnosis of Crohn's disease. Four of the patients with Crohn's disease already showed abnormal pancreatic imaging at the initial examination. Morphological examinations of the pancreas showed that none of the sixteen suffered from severe conditions. The abnormal pancreatic imaging was unrelated to the therapeutic regimens employed for Crohn's disease or to its activity. When patients with Crohn's disease with and without abnormal pancreatic imaging were compared, there were no significant differences in any of the background clinical features of Crohn's disease. When we compared pancreatic imaging according to the type of Crohn's disease, in the solely aphthous ulcerations type, the occurrence of abnormal pancreatic imaging was significantly higher (P = 0.02) than that in the other types. In 7 patients who had suffered from Crohn's disease for more than 10 years, the clinical course of abnormal pancreatic imaging was not progressive, regardless of the progression of Crohn's disease. CONCLUSIONS: It is suggested that abnormal pancreatic imaging is not serious a complication of Crohn's disease, and is unrelated to the course of Crohn's disease.

Anti-Saccharomyces cerevisiae antibodies in Japanese patients with inflammatory bowel disease: diagnostic accuracy and clinical value.

BACKGROUND: The diagnostic accuracy of the determination of anti- Saccharomyces cerevisiae antibodies (ASCA) and its clinical significance in Crohn's disease (CD) have been reported in Western countries, but scarcely reported in Japan, where the dietary habits of people differ markedly from those of Western countries. Th present study was undertaken to examine the diagnostic accuracy and clinical significance of ASCA determination in Japanese patients with CD or ulcerative colitis (UC). METHODS: Seventy-five serum samples obtained from 68 patients with CD, 34 serum samples obtained from 30 patients with UC, 35 serum samples from 35 patients with liver cirrhosis, and 31 serum samples from 31 healthy controls were examined. The optical density of each sample was measured by an enzyme-linked immunosorbent assay (ELISA) method to quantify ASCA IgA and IgG. RESULTS: The cutoff level, as determined by discriminant analysis of the data, was 0.1502 for ASCA IgA and 0.156 for ASCA IgG. Of the 68 patients with CD, 31 (45.6%) were ASCA-positive, and of the 30 patients with UC, 4 (13.3%) were ASCA-positive according to these cutoff levels. The sensitivity and specificity of ASCA determination for the differential diagnosis of CD from UC were 45.6% and 86.7%, respectively. When the relationship between ASCA and the clinical features of CD was analyzed, ASCA positivity was found to be correlated with duration of illness. CONCLUSIONS: The specificity of ASCA was high; however, the sensitivity was not. ASCA titers were generally low in the Japanese population examined. It would be desirable to determine cutoff levels for ASCA tailored to the Japanese people for the diagnosis of inflammatory bowel disease.

The clinical characteristics and outcome of intraabdominal abscess in Crohn's disease.

BACKGROUND: We aimed to elucidate the incidence and natural course of abdominal abscess complicating Crohn's disease (CD). METHODS: Of 352 patients with CD who were observed at our hospital between 1985 and October 2001, we studied 35 patients (9.9%) with abscesses in the mid-abdominal region (the abdominal wall, peritoneal cavity, retroperitoneum, and subphrenic region). RESULTS: The cumulative incidence of complication with an abscess was 9% and 25%, respectively, 10 and 20 years after CD onset. Of the 35 CD patients with abscess, 60% had had surgery by the time of the present study. The age when the abscess developed was 30.1 +/- 8.1 years, and the duration of illness from the onset of CD until development of an abscess was 10.8 +/- 6.3 years (range, 0-29 years). The location of involvement was: abdominal wall, n = 14 (40%); peritoneal cavity, n = 10 (29%); retroperitoneum or iliopsoas, n = 9 (26%); and subphrenic region, n = 2 (6%). In terms of location of abscess, it occurred most often on the right side (65.7%). Almost all abscesses occurred near the site of an anastomosis. Diseased segments of the bowel responsible for abscess formation were categorized radiographically as showing mild stenosis (6.5%), intermediate stenosis and/or simple fistula (41.9%), and severe stenosis and/or multiple fistulas (51.6%). Conservative treatment (including drainage of abscess) alone was effective in 7 patients (20%) and surgery was needed in 28 patients (80%). During the 5.3-year follow-up after treatment for the abdominal abscess, 9 of the 35 patients (26%) had recurrence of an abscess, mostly within 3 years. CONCLUSIONS: Abscess formation was noted in about 10% of patients with CD, with 46% of abscesses occurring in a diseased bowel segment near an anastomotic site. Of the diseased bowel segments responsible for abscess formation, half had neither severe stenosis nor multiple fistulas. Almost all patients underwent surgery for the abscess, and, in more than a quarter of the patients, there was recurrence within a few years after surgery.

Clinical features and pattern of indeterminate colitis: Crohn's disease with ulcerative colitis-like clinical presentation.

BACKGROUND: Although an accurate diagnosis of inflammatory bowel disease (IBD) and differentiation between ulcerative colitis (UC) and Crohn's disease (CD) can be made in most patients, it is sometimes impossible to distinguish UC from CD even after thorough pathological study. Recently, clinicians have used the term indeterminate colitis (IC) for patients with features of both diseases that overlap temporarily or persistently. The frequency, reasons, and outcome of patients with a clinical diagnosis of IC based on radiological, endoscopic, and histopathological findings were investigated retrospectively. METHODS: Based on records of 735 patients with IBD, IC was defined as having features of both UC and CD, with differentiation from each other impossible at least once during the observation period (average 6.8 years) based on diagnostic criteria using endoscopic, radiological, and histological findings. RESULTS: Twenty-three patients were identified as having IC. They were classified into three patterns according to the clinical course and the final diagnosis: (1) UC changing to CD (n = 8); (2) CD changing to UC (n = 5); and (3) UC or CD (n = 10). The frequency of IC was 24.5%-43.4% of colitis-type CD (n = 53), 2.3%-6.5% of all CD (n = 352), and 3.1% of IBD (n = 735). The reasons for the indetermination were temporary (56.5%) or persistent (43.5%) overlapping of UC-like and CD-like presentations. Treatment of IC was inappropriate in only two patients, and the prognoses of all patients except one were fairly good. CONCLUSIONS: Overlapping of UC-like presentations (persistent bloody stool and diffuse colitis) was frequently observed with Crohn's colitis but less so in CD patients during their clinical course. The basis of differentiation and treatment of IC needs more attention.

Adsorptive granulocyte and monocyte apheresis for refractory Crohn's disease: an open multicenter prospective study.

BACKGROUND: Active Crohn's disease (CD) is often associated with elevated levels of platelets, granulocytes, and monocytes that are activated and resistant to apoptosis. The level of neutrophils in the intestinal mucosa has been quantitatively related to the severity of intestinal inflammation in CD. We postulated that patients with CD that is refractory to conventional medications might respond to a reduction of granulocytes and monocytes by adsorptive apheresis. METHODS: Twenty-one patients with a CD activity index (CDAI) of 200-399 and unresponsive to standard medication, which included nutritional intervention, received granulocyte and monocyte adsorptive apheresis (GCAP) as an adjunct to their ongoing medication. GCAP was performed with an Adacolumn, which adsorbs granulocytes, monocytes, and a small fraction of lymphocytes (FcgammaR and complement receptor-bearing leucocytes). Patients received one GCAP session/week for 5 consecutive weeks. CDAI, International Organization for the Study of Inflammatory Bowel Disease (IOIBD), and IBD questionnaire (IBDQ) scores were evaluated. RESULTS: During the initial conventional/nutritional therapy, no significant improvement was seen in any patient. However, at week 7 of GCAP therapy, significant improvements in CDAI, IOIBD, and IBDQ scores were observed. The CDAI, IOIBD, and IBDQ scores before GCAP were 275.6+/-54.2, 3.4+/-1.4, and 152+/-22, respectively. The corresponding values after GCAP were 214.8+/-89.2 (P=0.0005), 2.54+/-1.5 (P=0.0224), and 165+/-29 (P=0.0327), respectively. CONCLUSIONS: GCAP could be effective for inducing remission and improving quality of life in patients with active CD that is refractory to conventional therapy.

Short-term efficacy of enteral nutrition in the treatment of active Crohn's disease: a randomized, controlled trial comparing nutrient formulas.

BACKGROUND: The optimal dietary fat content to induce clinical remission in active Crohn's disease has been the subject of controversy. We therefore performed a prospective, randomized, controlled study to compare the effects of nutrient formulas differing in the amount of medium-chain triglycerides (MCT). METHODS: Thirty-six patients with active Crohn's disease whose Crohn's disease activity index (CDAI) was > or =150 were included in the study. A formula with 3.4 g of fat per 2000-kcal dose was used as the nutrient formula with a low-fat content (ED group), and a formula with 55.6 g of fat per 2000-kcal dose was used as the nutrient formula with a high amount of MCT (TL group). RESULTS: The rate of short-term remission induction at 6 weeks was 67% in the ED group and 72% in the TL group (p = NS). Therapy markedly reduced the high CDAI and van Hees activity index in both groups, with no significant difference in the pattern of the time-course changes. C-reactive protein levels, erythrocyte sedimentation rate, and low serum albumin and plasma prealbumin levels normalized over the course of therapy, with no significant difference between the 2 groups. The assessment of fatty acid fractions revealed that the triene/tetraene ratio began to increase at 2 weeks in the ED group. The serum levels of linoleic acid, an omega-6 fatty acid, almost always varied within the normal range during the treatment period in the TL group, but in the ED group, levels began to decrease significantly at 2 weeks. The levels of linolenic acid, an omega-3 fatty acid, decreased in both groups. CONCLUSIONS: Both nutrient formulas induced clinical remission in about two-thirds of patients. The results of the present study suggest that it is not necessary to restrict the amount of MCT when given in liquid form to patients with active Crohn's disease.