Suitability of the expanded indication criteria for the treatment of early gastric cancer by endoscopic submucosal dissection: Japanese multicenter large-scale retrospective analysis of short- and long-term outcomes.

OBJECTIVE: The criteria for endoscopic resection for early gastric cancer include absolute and expanded indications. Consensus already exists for the absolute indications. However, the suitability of the expanded indications must be validated by long-term outcome analyses since such lesions have only recently become resectable with the development of endoscopic submucosal dissection. The aim of this study is to clarify the suitability of the expanded indications for the treatment of early gastric cancer with endoscopic submucosal dissection. MATERIALS AND METHODS: The medical records of 1161 patients with early gastric cancers (1332 lesions) treated by endoscopic submucosal dissection and meeting the criteria for absolute or expanded indications without additional treatment with gastrectomy were divided into absolute indication group or expanded indication group. RESULTS: Complete resection rates were 96.4% and 93.4% in absolute and expanded indication groups, respectively, with no significant differences between the groups. Delayed bleeding rates were significantly higher in the expanded indication group, whereas all cases were successfully managed conservatively. The 5-year overall survival and recurrence-free rates were 93.7%/99.77% and 90.49%/98.90% in the absolute and the expanded indication groups, respectively, with no significant differences between the groups for either measure. Multivariate analyses revealed that affected horizontal margin and tumor location were independent predictive factors for recurrence. CONCLUSION: The expanded indication group showed excellent post-endoscopic submucosal dissection short-term and long-term outcomes compared with the absolute indications group, demonstrating that expanded indications are suitable for endoscopic submucosal dissection for early gastric cancer.

Mucosal-incision assisted biopsy for suspected gastric gastrointestinal stromal tumors.

To evaluate the diagnostic yield of the procedure, mucosal-incision assisted biopsy (MIAB), for the histological diagnosis of gastric gastrointestinal stromal tumor (GIST), we performed a retrospective review of the 27 patients with suspected gastric GIST who underwent MIAB in our hospitals. Tissue samples obtained by MIAB were sufficient to make a histological diagnosis (diagnostic MIAB) in 23 out of the 27 patients, where the lesions had intraluminal growth patterns. Alternatively, the samples were insufficient (non-diagnostic MIAB) in remaining 4 patients, three of whom had gastric submucosal tumor with extraluminal growth patterns. Although endoscopic ultrasound and fine needle aspiration is the gold standard for obtaining tissue specimens for histological and cytological analysis of suspected gastric GISTs, MIAB can be used as an alternative method for obtaining biopsy specimens of lesions with an intraluminal growth pattern.

Endoscopic submucosal dissection for superficial esophageal squamous cell neoplasms.

Endoscopic resection is an effective treatment for non-invasive esophageal squamous cell neoplasms (ESCNs). Endoscopic mucosal resection (EMR) has been developed for small localized ESCNs as an alternative to surgical therapy because it shows similar effectiveness and is less invasive than esophagectomy. However, EMR is limited in resection size and therefore piecemeal resection is performed for large lesions, resulting in an imprecise histological evaluation and a high frequency of local recurrence. Endoscopic submucosal dissection (ESD) has been developed in Japan as one of the standard endoscopic resection techniques for ESCNs. ESD enables esophageal lesions, regardless of their size, to be removed en bloc and thus has a lower local recurrence rate than EMR. The development of new devices and the establishment of optimal strategies for esophageal ESD have resulted in fewer complications such as perforation than expected. However, esophageal stricture after ESD may occur when the resected area is larger than three-quarters of the esophageal lumen or particularly when it encompasses the entire circumference; such a stricture requires multiple sessions of endoscopic balloon dilatation. Recently, oral prednisolone has been reported to be useful in preventing post-ESD stricture. In addition, a combination of chemoradiotherapy (CRT) and ESD might be an alternative therapy for submucosal esophageal cancer that has a risk of lymph node metastasis because esophagectomy is extremely invasive; CRT has a higher local recurrence rate than esophagectomy but is less invasive. ESD is likely to play a central role in the treatment of superficial esophageal squamous cell neoplasms in the future.

CD30 ligand/CD30 interaction is involved in pathogenesis of inflammatory bowel disease.

BACKGROUND AND AIMS: Although CD30 has long been recognized as an important marker in many lymphomas of diverse origin, and as an activation molecule on B and T cells, its primary function has remained obscure. Soluble CD30 (sCD30) is released from CD30 on the cell membrane by enzymatic cleavage. This study investigated the role of CD30 ligand (CD30L)/CD30 signals in intestinal mucosal damage. METHODS: Serum sCD30 in patients with ulcerative colitis (UC) and Crohn's disease (CD) and healthy individuals was assessed. A model of enteritis induced by anti-CD3 monoclonal antibody injection was studied in wild-type mice and in CD30L knockout mice. RESULTS: Increased sCD30 was observed in UC and CD patients, and the level was correlated with disease activity in both conditions. In a murine model of enteritis, histological intestinal damage was significantly reduced in CD30L knockout mice with decreased Th1 and Th17 cytokine levels. Moreover, blocking of CD30L/CD30 signals by CD30-immunoglobulin (CD30-Ig) resulted in reduced inflammation. CONCLUSIONS: Increased sCD30 expression correlating with disease activity suggested that CD30L/CD30 signals play an important role in pathogenesis of UC and CD. CD30L/CD30 pathway acts as an accelerator of enteritis in a murine disease model. Successful blockade of enteritis by CD30-Ig suggests a potential tool for future therapy of inflammatory bowel diseases.

[A case of sigmoid colon cancer with liver and ovarian metastases effectively treated by panitumumab after acquiring resistance to prior chemotherapy regimens].

A 44-year-old female was referred to our hospital with a complaint of abdominal fullness. Computed tomography(CT) showed multiple liver masses and a huge ovarian tumor. Colonoscopy revealed a type 4 advanced cancer in the sigmoid colon. She was diagnosed with unresectable liver and ovarian metastases from advanced sigmoid colon cancer, for which we were obliged to select chemotherapy. As the first line, FOLFOX was applied and performed for 6 cycles, followed by FOLFOX plus bevacizumab(BV)for 5 cycles. While no deterioration of liver and ovarian metastases was observed during the course of those chemotherapy regimens, the patient developed a considerable level of acute sensorimotor neuropathic symptoms associated with oxaliplatin-induced peripheral neurotoxicity, forcing us to replace FOLFOX plus BV with FOLFIRI plus BV. Three cycles of FOLFIRI plus BV, however, turned out to be progressive disease with deterioration of liver and ovarian metastases. Since her oxaliplatin-induced neurotoxicity was improved, a regimen of FOLFOX plus BV was once again applied to her for 3 cycles, which failed to prevent her from having a progressive disease. The sequencing of K-RAS genes from the biopsy specimens of sigmoid colon cancer revealed an expression of a wild-type K-RAS. Thus, an addition of panitumumab to FOLFOX was made. Surprisingly, after 3 cycles of the chemotherapy regimen over 3 months, a significant reduction in the size of liver and ovarian metastases was observed. Her sense of abdominal fullness was apparently reduced and was even lower than what it was at admission. Panitumumab has great potential for effective treatment of patients with unresectable stage IV colorectal cancer, even after having acquired resistance to prior chemotherapy regimens.

Endoscopic submucosal dissection using a grasping-type scissors forceps for early gastric cancers and adenomas.

AIM: To reduce the risk of complications related to endoscopic submucosal dissection (ESD) using knives, we developed a new grasping-type scissors forceps (GSF) that can grasp and incise the target tissue using electrosurgical current. The aim of the present study was to evaluate the efficacy and safety of ESD using GSF for the removal of early gastric cancers and adenomas. METHODS: ESD using GSF was carried out on 35 consecutive patients with early gastric cancers or adenomas who had preoperative EUS diagnoses of mucosal tumor without lymph node involvement. Therapeutic efficacy and safety were assessed. RESULTS: All lesions were treated easily and safely without unexpected incision. The mean size of epithelial tumors and resected specimens was 15.6mm and 32.7mm, respectively. Curative en-bloc resection rates according to tumor size and location were 96% (26/27) in tumors ≤20mm, 100% (8/8) in tumors >20mm, 100% (18/18) of tumors in the lower portion, 100% (8/8) of tumors in the middle portion, 89% (8/9) of tumors in the upper portion, and 97% (34/35) overall. The mean operating time according to tumor size and location was 93.4min in tumors ≤20mm, 140min in tumors >20mm, 77.6min for tumors in the lower portion, 113.4min for tumors in the middle portion, 148.6min for tumors in the upper portion, and 104.1min overall. No intraoperative complication occurred, and postoperative bleeding was seen in 3% (1/35). CONCLUSIONS: ESD using GSF allows simple and safe en-bloc resection of early gastric cancer or adenoma irrespective of tumor size and location.

Role of EUS and EUS-guided FNA in the diagnosis of rectal implantation cyst at an anastomosis site after a previous low anterior resection for a rectal cancer without evidence of cancer recurrence.

BACKGROUND: Rectal implantation cysts occurring at an anastomosis site after a low anterior resection for rectal cancer need to be distinguished from locally recurrent rectal cancer. OBJECTIVE: Our purpose was to evaluate the role of EUS and EUS-FNA in the diagnosis of rectal implantation cyst. DESIGN: Case series. PATIENTS: A review of medical records identified 3 men and 1 woman who were diagnosed with rectal implantation cyst by EUS and EUS-FNA. RESULTS: All 4 cases had undergone a low anterior resection with the double-stapling technique for a rectal cancer from 12 to 67 months (median 33.8 months) earlier. Follow-up colonoscopy revealed a rectal submucosal tumor at an anastomosis site. EUS revealed cystic lesions with heterogeneous wall thickness from the third layer or the fourth layer to the surroundings. EUS-FNA revealed mucin that contained a few inflammatory cells and no malignant cells in any of the patients. From the findings of EUS and EUS-FNA, all patients were diagnosed with rectal implantation cyst, thus avoiding surgery. LIMITATION: Small number of patients. CONCLUSIONS: EUS and EUS-FNA are useful in the diagnosis of rectal implantation cyst and the avoidance of unnecessary radical surgery.

Duplication cyst of the small intestine found by double-balloon endoscopy: a case report.

A 35-year-old man was admitted due to bloody stool and anemia. The bleeding source could not be detected by esophagogastroduodenoscopy or colonoscopy. Double balloon endoscopy (DBE) revealed a diverticulum-like hole in which coagula stuck in the ileum at 1 meter on the oral side from the ileocecal valve. The adjacent mucosa just to the oral side of the hole was elevated like a submucosal tumor. The lesion was considered the source of bleeding and removed surgically. It was determined to be a cyst with an ileal structure on the mesenteric aspect accompanying gastric mucosa. The diagnosis was a duplication cyst of the ileum, which is a rare entity that can cause gastrointestinal bleeding. In the present case, DBE was used to find the hemorrhagic duplication cyst in the ileum.

Prospective comparative study on the acceptability of unsedated transnasal endoscopy in younger versus older patients.

GOALS: The aim of this prospective study was to compare the acceptance and tolerance for unsedated transnasal esophagogastroduodenoscopy (EGD) between younger and older patients. BACKGROUND: Little information is available on comparisons of younger and older patients with regard to acceptance and tolerance of transnasal EGD. STUDY: A total of 260 patients were referred for unsedated transnasal EGD and divided into 2 groups according to their age: less than 60 years of age (group A, n=160) and 60 years of age and older (group B, n=100). A questionnaire for tolerance was completed by each patient (a validated 0 to 10 scale where "0" represents no discomfort/well tolerated and "10" represents severe discomfort/poorly tolerated). RESULTS: In 94.4% of group A and 95.0% of group B, insertions were successfully completed (P>0.05). Between groups A and B, discomfort during nasal anesthesia (1.7+/-0.2 vs. 1.6+/-0.2) and overall tolerance during procedure (1.7+/-0.2 vs. 1.5+/-0.2) were similar (P>0.05). However, discomfort during insertion was significantly greater in group A than in group B (2.5+/-0.2 vs. 1.9+/-0.2, P=0.02). Of all, 97.4% of group A and 94.7% of group B were willing to undergo unsedated transnasal EGD in the future (P>0.05). CONCLUSIONS: There was no significant difference in acceptability between younger and older patients for unsedated transnasal EGD. Otherwise, younger patients experienced significantly more discomfort during insertion than did older patients.

[Case of Zollinger-Ellison syndrome diagnosed three years after ulcer perforation in the third portion of the duodenum].

A 61-year-old woman was referred to our hospital for a double balloon endoscopy (DBE) examination of small intestine. She had undergone laparotomy for a perforated ulcer of the 3rd portion in the duodenum 3 years prior to this admission. Esophagogastroduodenoscopy at the previous hospital revealed multiple ulcers in the 2nd and 3rd portions in the duodenum. DBE revealed multiple ulcer scars in the proximal jejunum. Zollinger-Ellison syndrome was suspected from the distribution of the ulcers and scars. Serum gastrin was high and a selective arterial calcium injection test showed a step up of gastrin level only in the gastroduodenal artery area. We diagnosed a gastrinoma located on the ventral side of the 2nd portion of the duodenum from imaging studies. The tumor was extirpated and histologically found to be a neuroendocrine tumor in a lymph node. Serum gastrin level decreased to the normal range a day after surgery.

Endoscopic submucosal dissection by using a grasping-type scissors forceps: a preliminary clinical study (with video).

BACKGROUND: Endoscopic submucosal dissection (ESD) with a knife is a technically demanding procedure associated with a high complication rate. The shortcoming of this method is the difficulty of fixing the knife to the target lesion. It can lead to an unexpected incision and result in major complications, such as perforation and bleeding. To reduce the risk of complications related to ESD, we developed a new grasping-type scissors forceps (GSF), which can grasp and incise the targeted tissue by using electrosurgical current. OBJECTIVE: To evaluate the efficacy and safety of ESD by using GSF for the removal of gastric neoplasms in human beings. DESIGN: Prospective, uncontrolled, single center. SETTING: Department of Gastroenterology, Aso Iizuka Hospital, Iizuka, Japan. PATIENTS: Four patients with early gastric neoplastic lesions. INTERVENTIONS: After marking and injection of a solution into the submucosa, the lesion was separated from the surrounding normal mucosa by complete incision around the lesion by using the GSF. A piece of submucosal tissue was grasped and cut with the GSF by using electrosurgical current to achieve submucosal excision. MAIN OUTCOME MEASUREMENT: Technical success and complications. RESULTS: All lesions were treated easily and safely, without any unexpected incisions. No delayed hemorrhage and perforation occurred. An en bloc resection and a negative resection margin was obtained in all cases. LIMITATIONS: The small number of patients and an uncontrolled study. CONCLUSIONS: ESD with GSF appeared to be an easy, safe, and technically efficient method for resecting GI neoplasms.

A critical role of CD30 ligand/CD30 in controlling inflammatory bowel diseases in mice.

BACKGROUND & AIMS: A CD30-ligand (CD30L) is a 40-kilodalton, type II membrane-associated glycoprotein belonging to the tumor necrosis factor family. Serum levels of soluble CD30 increased in inflammatory bowel diseases (IBD), suggesting that CD30L/CD30 signaling is involved in the pathogenesis of IBD. In this study, we investigated the role of CD30L in oxazolone (OXA)- and trinitrobenzene sulfonic acid (TNBS)-induced colitis in CD30L knockout (KO) mice. METHODS: Colitis was induced by OXA or TNBS in CD30LKO mice with BALB/c or C57BL/6 background, respectively, and diverse clinical signs of the disease were evaluated. Cytokine production from lamina propria T cells of the colon was assessed by enzyme-linked immunosorbent assay. Anti-interleukin (IL)-4 monoclonal antibody (mAb) or agonistic anti-CD30 mAb was inoculated in mice with colitis induced by OXA or TNBS. RESULTS: CD30LKO mice were susceptible to OXA-induced colitis but resistant to TNBS-induced acute colitis. The levels of T helper cell 2 type cytokines such as IL-4 and IL-13 in the LP T cells were significantly higher, but the levels of interferon gamma were lower in OXA- or TNBS-treated CD30LKO mice than in wild-type mice. In vivo administration of agonistic anti-CD30 mAb ameliorated OXA-induced colitis but aggravated TNBS-induced colitis in CD30LKO mice. CONCLUSIONS: These results suggest that CD30L/CD30 signaling is involved in development of both OXA- and TNBS-induced colitis. Modulation of CD30L/CD30 signaling by mAb could be a novel biologic therapy for IBD.

Eosinophilic gastroenteritis observed by double balloon enteroscopy and endoscopic ultrasonography in the whole gastrointestinal tract.

Eosinophilic gastroenteritis is a chronic inflammatory disorder of the gastrointestinal tract characterized by the infiltration of eosinophils. It is a rare disease. There are no reports in the history of eosinophilic gastroenteritis being consecutively observed in the whole gastrointestinal tract by esophagogastroduodenoscopy (EGD), double-balloon enteroscopy (DBE), and endoscopic ultrasonography (EUS). A 66-year-old woman was admitted to our hospital because of abdominal pain and diarrhea. Laboratory findings included peripheral eosinophilia and a high serum immunoglobulin E level. We observed the whole gastrointestinal tract by EGD, DBE (antegrade and retrograde approaches), and EUS. DBE showed slightly edematous and reddish mucosa in the jejunum, ileum, and ascending colon, respectively. EUS in all portion of the gastrointestinal tract demonstrated almost normal five-layered structure without ascites. Histologic examination of the biopsy specimens from the stomach, duodenum, jejunum, ileum, colon and rectum revealed eosinophilic infiltration. No evidence of parasites, granulomas, malignancy, vasculitis or embolism was founded in any of the biopsy specimens. The patient was diagnosed with eosinophilic gastroenteritis with predominant mucosal layer form. She was treated with oral corticosteroid, and her symptoms subsided. To the best of our knowledge, this is the first case of eosinophilic gastroenteritis in which the whole gastrointestinal tract was consecutively observed by EGD, DBE, and EUS.

Gastric emptying in diabetic patients by the (13)C-octanoic acid breath test: role of insulin in gastric motility.

BACKGROUND: Impairment of gastric emptying is well recognized in patients with diabetes mellitus (DM), especially long-standing insulin-dependent diabetes mellitus (IDDM). The aim of this study was to evaluate the cause of delayed gastric emptying in DM patients. METHODS: In 16 controls, 16 non-insulin-dependent diabetes mellitus (NIDDM) patients and 23 IDDM patients, gastric emptying was studied using the (13)C octanoic acid breath test. Breath samples were taken before a test meal labeled with 100 mg of (13)C octanoic acid, and at 15-min intervals over a 300-min period postprandially. RESULTS: In all DM patients, the gastric emptying coefficient was lower than that in the controls (P < 0.05), and lag time and half-emptying time were significantly longer (P < 0.05). Both NIDDM and IDDM patients showed delayed (13)CO(2) excretion compared with the controls, but IDDM patients showed more delayed gastric emptying than NIDDM patients (P < 0.05). There were no significant differences in sex, HbA1c level, or the rate of neuropathy between the two groups. CONCLUSIONS: IDDM patients showed delayed gastric emptying compared with NIDDM patients, and the (13)C octanoic acid breath test is useful for evaluating DM patients with delayed gastric emptying.

Preoperative diagnosis of gastrointestinal stromal tumor by endoscopic ultrasound-guided fine needle aspiration.

AIM: To evaluate the role of endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) in the preoperative diagnosis of gastrointestinal stromal tumor (GIST). METHODS: From September 2002 to June 2006, Fifty-three consecutive EUS-FNAs of GI tract subepithelial hypoechoic tumors with continuity to proper muscle layer suspected as GIST by standard EUS were evaluated prospectively. The reference standards for the final diagnosis were surgery (n = 31), or clinical follow-up (n=22). Additionally, immunophenotyping of specimens obtained by EUS-FNA and surgical resection specimens were compared. RESULTS: In 2 cases puncture was not performed because of anatomical problems. The collection rate of adequate specimens from the GI tract subepithelial hypoechoic tumor with continuity to proper muscle layer was 82% (42/51). The diagnostic rate for the tumor less than 2 cm, 2 to 4 cm, and 4 cm or more were 71% (15/21), 86% (18/21), and 100% (9/9), respectively. In 29 surgically resected cases, the sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of EUS-FNA using immunohistochemical analysis of GIST were 100% (24/24), 80% (4/5), 96% (24/25), 100% (4/4), and 97% (28/29), respectively. No major complications were encountered. CONCLUSION: EUS-FNA with immunohistochemical analysis is a safe and accurate method in the pretherapeutic diagnosis of GIST. It should be taken into consideration in decision making, especially in early diagnosis following minimal invasive surgery for GIST.

Newly developed all in one EUS system: one cart system, forward-viewing optics type 360 degrees electronic radial array echoendoscope and oblique-viewing type convex array echoendoscope.

Most endosonographers use radial scanning instruments for diagnostic imaging, and use longitudinal scanning instruments primarily for endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). The use of two separate instruments for radial and longitudinal scanning means 2 different echoendoscopes are required, each with its own dedicated US processing unit. Currently available electronic radial echoendoscopes and linear instruments made by the same company require the same other brand US unit. Furthermore, no forward-viewing optics type 360 degrees electronic radial echoendoscope currently exists. We have developed an all-in-one one cart EUS system that saves space and is available for both the forward-viewing type 360 degrees radial electronic echoendoscope and the oblique-viewing type convex echoendoscope. These scopes have a transducer with variable frequency (5.0, 7.5, 10.0, 12.0 MHz) and color and power Doppler flow mapping capabilities. We performed a clinical development test for thirteen patients with sixteen lesions (Radial EUS on 8 lesions and EUS-FNA on 8 lesions) using this new EUS system. These new instruments provided satisfactory US and endoscopic images. The forward-viewing optics of the prototype enhanced intubation and instrument advancement. The radial scanning prototype provided an adequate diagnosis in 8 (100%) out of 8 lesions for EUS. The convex type achieved successful puncture in 8 (100%) out of 8 lesions and collection of adequate specimen for diagnosis of EUS-FNA in 4 (50%) out of 8 lesions. There were no complications in this series. This new system appears to be an attractive alternative for efficient EUS.

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of peripancreatic tuberculous lymphadenitis.

The percentage of patients with atypical extrapulmonary forms of tuberculosis has been increasing. Among extrapulmonary tuberculosis cases, tuberculosis of the pancreas and peripancreatic lymph nodes is a rare clinical entity. Here, we present a case of peripancreatic tuberculous lymphadenitis diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) both cytologically and microbiologically. A 23-year-old man had a 1-week history of epigastralgia and low-grade fever. Subsequently, he was found to have an abnormality on abdominal ultrasound. A computed tomography scan of the abdomen showed a solitary mass consisting of multiple cystic components with rim enhancement in the peripancreatic portion contiguous to the gall bladder. Endoscopic ultrasound-guided fine-needle aspiration was performed to confirm the diagnosis. The cytological examination revealed epithelioid cells with caseous necrosis, indicating tuberculosis. The aspirated fluid was positive by polymerase chain reaction (PCR) analysis and culture for Mycobacterium tuberculosis. Antituberculosis therapy with isoniazid, rifampicin, ethambutol, and pyrazinamide was started based on the PCR and cytology results, and a good response to the treatment was noted. Endoscopic ultrasound-guided fine-needle aspiration cytology with PCR analysis is very useful for the diagnosis of peripancreatic tuberculosis.

Novel strategies for the treatment of inflammatory bowel disease: Selective inhibition of cytokines and adhesion molecules.

The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which non-specifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Such recent advances in the understanding of the pathogenesis of IBD created a recent trend of novel biological therapies which specifically inhibit the molecules involved in the inflammatory cascade. Major targets for such treatment are inflammatory cytokines and their receptors, and adhesion molecules. A chimeric anti-TNF-alpha monoclonal antibody, infliximab, has become a standard therapy for CD and it is also likely to be beneficial for UC. Several anti-TNF reagents have been developed but most of them seem to not be as efficacious as infliximab. A humanized anti-TNF monoclonal antibody, adalimumab may be useful for the treatment of patients who lost responsiveness or developed intolerance to infliximab. Antibodies against IL-12 p40 and IL-6 receptor could be alternative new anti-cytokine therapies for IBD. Anti-interferon-gamma and anti-CD25 therapies were developed, but the benefit of these agents has not yet been established. The selective blocking of migration of leukocytes into intestine seems to be a nice approach. Antibodies against alpha4 integrin and alpha4beta7 integrin showed benefit for IBD. Antisense oligonucleotide of intercellular adhesion molecule 1 (ICAM-1) may be efficacious for IBD. Clinical trials of such compounds have been either recently reported or are currently underway. In this article, we review the efficacy and safety of such novel biological therapies for IBD.

An inverse correlation of human peripheral blood regulatory T cell frequency with the disease activity of ulcerative colitis.

Evidence suggests that CD4+CD25+ regulatory T cells play a crucial role in the suppression of intestinal inflammation. However, their role in the suppression of inflammatory bowel disease has not yet been addressed. We examined the proportion of regulatory T cells in inflammatory bowel disease. First, we isolated CD4+CD45RO+CD25+ T cells from the peripheral blood of healthy persons and showed that these cells suppressed T cell proliferation profoundly and expressed FoxP3 abundantly, revealing that they are regulatory cells. Then the proportion of CD45RO+CD25+ in peripheral blood CD4+ T cells was analyzed in patients and healthy controls by flow cytometry. CD4+CD45RO+CD25+ T cell frequency was significantly lower in active ulcerative colitis than in the control and inactive ulcerative colitis. CD4+CD45RO+CD25+ T cell frequency was inversely correlated with the clinical and endoscopic severity of ulcerative colitis. These results suggest that a deficiency of regulatory T cells is associated with the progression of ulcerative colitis.

Acute pancreatitis associated with peroral double-balloon enteroscopy: a case report.

A 58-year-old Japanese man had tarry stool and severe anemia. Neither upper nor lower gastrointestinal (GI) endoscopy showed any localized lesions. Thus, the source of his GI bleeding was suspected to be in the small intestine, and he underwent peroral double-balloon enteroscopy (DBE) using EN-450T5 (Fujinon-Toshiba ES System Co., Tokyo, Japan). There were no lesions considered to be the source of GI bleeding. After the procedure, the patient began to experience abdominal pain. Laboratory tests revealed hyperamylasemia and abdominal computed tomography revealed an inflammation of the pancreas and the peripancreas. He was thus diagnosed to have acute pancreatitis. Conservative treatments resulted in both clinical and laboratory amelioration. He had no history of alcohol ingestion, gallstone disease or pancreatitis. Magnetic resonance cholangiopancreatography demonstrated no structural alterations and no stones in the pancreatobiliary ductal system. As his abdominal pain started after the procedure, his acute pancreatitis was thus thought to have been related to the peroral DBE. This is the first reported case of acute pancreatitis probably associated with peroral DBE.