Tolerability and safety of a new elimination diet for pediatric eosinophilic gastritis and duodenitis.

BACKGROUND: Non-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs) are chronic inflammatory disorders with massive infiltration of eosinophils into the gastrointestinal tract. Food elimination diets are potentially effective treatments. But the existing dietary therapies have various weak points. We developed a new regimen to compensate for the shortcomings of the elemental diet and 6-food elimination diet. The new regimen consists of an amino-acid-based formula, potatoes, vegetables, fruits and restricted seasonings. We named it the "Rainbow Elimination Diet (ED)." The aims of this study were to evaluate the tolerability and safety of this diet. METHODS: A retrospective medical record examination was conducted at the National Center for Child Health and Development covering the period from January 2010 through December 2018. The medical records of patients (age 2-17 y) with histologically diagnosed non-EoE EGIDs were reviewed. The tolerability, nutritional intake, symptoms, and blood test findings were evaluated. RESULTS: Nineteen patients were offered several kinds of food-elimination diets. Seven patients (eosinophilic gastritis: 5; gastroenteritis: 1; duodenitis: 1) were treated with Rainbow ED. Six patients were compliant with this diet. The median duration of the diet induction phase was 15 days (range 14-30). All 5 patients who had had symptoms just before the induction phase became symptom-free. The body weight decreased in 5 patients (median -0.6 kg), probably because the serum protein increased, resulting in reduced edema. All 5 patients with hypoproteinemia had elevated serum albumin (median 2.9-3.5 g/dL). The ingested nutritional elements were calculated, and most of them were sufficient, except for fat and selenium. CONCLUSIONS: The Rainbow ED was well-tolerated and safe for pediatric non-EoE EGIDs.

[Salvage Surgery Following Chemoradiotherapy for Thymic Basaloid Cell Carcinoma].

We performed salvage surgery after chemoradiotherapy(CRT) in a patient with thymic basaloid cell carcinoma. A 46-year-old man with an abnormal chest shadow on X-ray findings was referred to our hospital. Computed tomography revealed a partially solid tumor along with a multilocular cyst in the anterior mediastinum with mediastinal lymph node swelling infiltrating to the superior vena cava(SVC). Positron emission tomography revealed FDG accumulation (SUVmax 7.94)in the tumor. Pathological findings of a tumor biopsy specimen obtained by thoracoscopy led to a diagnosis of thymic basaloid cell carcinoma. Following CRT (ADOC+RT:60 Gy), a complete resection (R0)with replacement of the SVC was performed. The postoperative course was uneventful, and the patient was alive at 20 months after surgery with metastasis to the cervical lymph nodes and bone.

[Anti-thymocyte Globulin Therapy for Cases of Acute Rejection Following Lung Transplantation].

A 58-year-old male underwent right lung transplantation from a brain-dead donor, after which acute rejection developed that was resistant to steroid pulse therapy. Rabbit-derived anti-thymocyte globulin (rATG) therapy was successful for controlling the rejection. However, following that therapy, the patient was affected by an opportunistic infection and suffered from repeated empyema. It is important to pay attention to immunosuppressive agent levels in blood following treatment, because ATG is a potent immunosuppressive drug and its effects can continue for more than 6 months after administration.

[Spindle Cell Sarcoma Originated in the Anterior Mediastinum;Report of a Case].

An anterior mediastinal sarcoma is a very rare type of mediastinal tumor. A 45-year-old female visited our hospital with swelling in the right anterior chest wall. Radiographically, the tumor was found to originate from the thymus and to infiltrate to the major pectoral muscle through the 1st intercostal space. Positron emission tomography revealed fluorodeoxyglucose accumulation at a standardized uptake maximum value of 16.1. Percutaneous needle biopsy showed the pathological findings of sarcoma. The tumor was resected along with the thymus and chest wall tissues including the right hemi-manubrium of the sternum, clavicle head, 1st and second ribs, and major pectoral muscle. After 4 months, tumor relapse occurred at the site of needle biopsy and additional resection was performed. At 10 months after the 2nd surgery, the patient was free from disease. From histologic and immunohistochemical findings, the tumor was diagnosed as spindle cell sarcoma.

Hangeshashinto-Associated Mesenteric Phlebosclerosis and Highly Atypical Adenoma Requiring Laparoscopic Right Hemicolectomy.

Mesenteric phlebosclerosis is a rare ischemic colonic disorder caused by impaired venous drainage. Its prevalence is higher in East Asia, where herbal medicine is widely used. Treatment remains controversial. A 76-year-old woman who had taken Hangeshashinto, an herbal medicine, for 11 years was admitted for endoscopic treatment of high-grade dysplasia in the ascending colon. She had diarrhea and mesenteric phlebosclerosis diagnosed by abdominal computed tomography at age 71. At age 75, small polyps were detected in the ascending colon. A subsequent study revealed an increase in polyp size to 15 mm. Endoscopic mucosal resection failed to remove the lesion. A biopsy showed high-grade dysplasia with possible colon cancer risk. Conservative therapy did not improve mesenteric phlebosclerosis-related diarrhea; therefore, a laparoscopic right hemicolectomy was performed. Intraoperatively, the cecum was adherent to the abdominal wall and the right ovary. The specimen showed high-grade dysplasia in the mucosa and severe submucosal fibrosis. No metastasis was observed. This case shows the link between mesenteric phlebosclerosis and high-grade dysplasia in the ascending colon. Endoscopic mucosal resection was unsuccessful in removing the tumor. Endoscopic submucosal dissection was an alternative, but its safety in mesenteric phlebosclerosis-affected colonic segments remains uncertain. A laparoscopic right hemicolectomy was performed.

Elevated plasma and bile levels of corisin, a microbiota-derived proapoptotic peptide, in patients with severe acute cholangitis.

BACKGROUND: Acute cholangitis is a severe, life-threatening infection of the biliary system that requires early diagnosis and treatment. The Tokyo Guidelines recommend a combination of clinical, laboratory, and imaging findings for diagnosis and severity assessment, but there are still challenges in identifying severe cases that need immediate intervention. The microbiota and its derived products have been implicated in the pathogenesis of acute cholangitis. Corisin is a microbiome-derived peptide that induces cell apoptosis, acute tissue injury, and inflammation. This study aimed to evaluate the potential of plasma and bile corisin as a biomarker of acute cholangitis. METHODS: Forty patients with acute cholangitis associated with choledocholithiasis or malignant disease were enrolled. Nine patients without acute cholangitis were used as controls. Corisin was measured by enzyme immunoassays in plasma and bile samples. Patients were classified into severe and non-severe groups. The associations of plasma and bile corisin with the clinical grade of acute cholangitis and other parameters were analyzed by univariate and multivariate regression analysis. RESULTS: Plasma and bile corisin levels were significantly higher in patients with acute cholangitis than in controls. Patients with severe acute cholangitis had significantly higher plasma and bile corisin levels than those with non-severe form of the disease. Bile corisin level was significantly correlated with markers of inflammation, coagulation, fibrinolysis, and renal function. Univariate analysis revealed a significant association of bile corisin but a weak association of plasma corisin with the clinical grade of acute cholangitis. In contrast, multivariate analysis showed a significant relationship between plasma corisin level and the disease clinical grade. The receiver operating characteristic curve analysis showed low sensitivity but high specificity for plasma and bile corisin to detect the severity of acute cholangitis. The plasma and bile corisin sensitivity was increased when serum C-reactive protein level was included in the receiver operating characteristic curve analysis. CONCLUSIONS: Overall, these findings suggest that plasma and bile corisin levels may be useful biomarkers for diagnosing and monitoring acute cholangitis and that corisin may play a role in the pathophysiology of the disease by modulating inflammatory, coagulation and renal pathways.

Acute necrotizing calculous cholecystitis after treatment with ceftriaxone in an elderly patient: a case report.

BACKGROUND: Ceftriaxone, a third-generation cephalosporin antibiotic with a long plasma half-life, is widely used to treat various infections. The use of ceftriaxone can sometimes induce biliary sludge or stone formation. Although most cases of ceftriaxone-induced pseudolithiasis are asymptomatic or mild and resolve with discontinuation of the drug, we experienced an elderly case of severe acute necrotizing calculous cholecystitis after administration of ceftriaxone. CASE PRESENTATION: A 72-year-old male patient was admitted to our hospital because of acute diverticulitis in ascending colon. Ceftriaxone was administered at a dose of 2 g/day for 6 days. Although he recovered after therapy, he was readmitted about 2 weeks later because of severe pain with rebound tenderness in the right upper quadrant. An abdominal imaging study revealed stones and sludge in the gallbladder that were not observed before starting ceftriaxone therapy. Therefore, antibiotic treatment with flomoxef 2 g/day was indicated. However, on the fifth day of readmission, the peritoneal irritation symptoms in the right upper quadrant worsened, and elevated inflammatory response and liver dysfunction were observed. Cholecystectomy was performed based on these findings. The resected inflamed gallbladder showed acute necrotizing cholecystitis with sand granular gallstones. A comparative analysis of the infrared spectroscopic pattern of the composition of gallstones collected during surgery with that of the ceftriaxone powder revealed that both have very similar infrared spectroscopic patterns. CONCLUSIONS: Ceftriaxone-related pseudolithiasis is generally reversible and mainly observed in children. Here, we report a rare case of ceftriaxone-related acute necrotizing cholecystitis in an elderly patient. We confirmed that the stones in the gallbladder are composed of ceftriaxone. The older age, dehydration, fasting, and long-time bed rest during the administration of high-dose ceftriaxone were the potential risk factors for gallstone formation.

Acute Calculous Cholecystitis Caused by Streptococcus gallolyticus subspecies pasteurianus: A Case Report.

Acute cholecystitis is an infectious disease of the gallbladder caused mainly by Escherichia coli, Klebsiella, and Enterococcus species. Streptococcus gallolyticus subsp. pasteurianus, previously known as Streptococcus bovis biotype II/2, rarely causes endocarditis, meningitis, and septicemia, mainly in children. Biliary tract infections by Streptococcus gallolyticus subsp. pasteurianus are extremely rare. There have been no reports of cases in Japan. Here, we describe the first case in Japan of acute calculous cholecystitis caused by Streptococcus gallolyticus subsp. pasteurianus infection. A 63-year-old man was admitted to our hospital with epigastric pain and vomiting. He had moderate tenderness and a full sensation in the epigastrium. Abdominal imaging revealed multiple stones in the gallbladder. After admission, he had a high fever that did not improve with antibiotics. Percutaneous transhepatic gallbladder drainage was performed. The patient underwent open cholecystectomy. During surgery, several small stones in the gallbladder and an abscess were observed at the gallbladder base. Streptococcus gallolyticus subsp. pasteurianus was detected by bacterial culture of the bile juice. The gallstones were bilirubin calcium stones. The endoscopic study showed three adenomas in the colon, but the histopathological examination demonstrated no malignant cells. Although infection by this bacterium may not be rare, this is the first reported case in Japan of acute calculous cholecystitis caused by Streptococcus gallolyticus subsp. pasteurianus infection.

Pill-induced esophagitis caused by ingesting excessive caffeine tablets.

A 19-year-old woman with suicidal thoughts consumed 24 anhydrous caffeine tablets and was admitted to our hospital. After being discharged from the hospital, her oral intake remained impaired because of retrosternal pain and she was readmitted. An upper gastrointestinal endoscopy revealed diffuse ulcers throughout the mid-to-lower esophagus; the patient was diagnosed with caffeine-induced esophagitis. She recovered soon after conservative treatment. A follow-up endoscopy performed 1 month after the patient was discharged showed that the ulcers had healed. This case highlights the risk of esophageal injuries after ingesting excessive caffeine tablets, which were sold as dietary supplement without a prescription. Our experience indicates that endoscopic surveillance is advisable to prevent severe complications if a patient presents with esophageal symptoms suggestive of chemical esophagitis.

Conjugative plasmid from Lactobacillus gasseri LA39 that carries genes for production of and immunity to the circular bacteriocin gassericin A.

Gassericin A is a circular bacteriocin produced by Lactobacillus gasseri strain LA39. We found a 33,333-bp plasmid, designated pLgLA39, in this strain. pLgLA39 contained 44 open reading frames, including seven genes related to gassericin A production/immunity (gaa), as well as genes for replication, plasmid maintenance, and conjugative transfer. pLgLA39 was transferred from LA39 to the type strain of L. gasseri (JCM 1131) by filter mating. The transconjugant exhibited >30-fold-higher more resistance to gassericin A and produced antibacterial activity. Lactobacillus reuteri LA6, the producer of reutericin 6, was proved to harbor a plasmid indistinguishable from pLgLA39 and carrying seven genes 100% identical to gaa. This suggests that pLgLA39 might have been transferred naturally between L. gasseri LA39 and L. reuteri LA6. The seven gaa genes of pLgLA39 were cloned into a plasmid vector to construct pGAA. JCM 1131(T) transformed with pGAA expressed antibacterial activity and resistance to gassericin A. pGAA was segregationally more stable than a pGAA derivative plasmid from which gaaA was deleted and even was more stable than the vector. This suggests the occurrence of postsegregational host killing by the gaa genes. pLgLA39 carried a pemIK homolog, and segregational stabilization of a plasmid by the pLgLA39-type pemIK genes was also confirmed. Thus, pLgLA39 was proved to carry the genes for at least two plasmid maintenance mechanisms, i.e., gaa and pemIK. Plasmids containing a repA gene similar to pLgLA39 repA were distributed in several L. gasseri strains.

DNA sequencing and homologous expression of a small peptide conferring immunity to gassericin A, a circular bacteriocin produced by Lactobacillus gasseri LA39.

Gassericin A, produced by Lactobacillus gasseri LA39, is a hydrophobic circular bacteriocin. The DNA region surrounding the gassericin A structural gene, gaaA, was sequenced, and seven open reading frames (ORFs) of 3.5 kbp (gaaBCADITE) were found with possible functions in gassericin A production, secretion, and immunity. The deduced products of the five consecutive ORFs gaaADITE have homology to those of genes involved in butyrivibriocin AR10 production, although the genetic arrangements are different in the two circular bacteriocin genes. GaaI is a small, positively charged hydrophobic peptide of 53 amino acids containing a putative transmembrane segment. Heterologous expression and homologous expression of GaaI in Lactococcus lactis subsp. cremoris MG1363 and L. gasseri JCM1131(T), respectively, were studied. GaaI-expressing strains exhibited at least sevenfold-higher resistance to gassericin A than corresponding control strains, indicating that gaaI encodes an immunity peptide for gassericin A. Comparison of GaaI to peptides with similar characteristics found in the circular bacteriocin gene loci is discussed.

The effects of Helicobacter pylori eradication on body mass index and dyspeptic symptoms.

BACKGROUND AND AIM: The relationship between Helicobacter pylori infection and body mass index (BMI) and dyspeptic symptoms is controversial. We investigated the changes in BMI and dyspeptic symptoms after H. pylori eradication among stages of atrophic gastritis classified according to the serum pepsinogen (PG) I/II ratio. METHODS: One hundred and sixty-three H. pylori-positive patients underwent eradication therapy for H. pylori. Serum PG I and II concentrations were measured before treatment, and the PG I/II ratio was classified into three groups: PG I/II ratio <2.0, PG I/II ratio >or=2.0 and <4.0, and PG I/II ratio >or=4.0 were considered to be low, middle, and high, respectively. Their BMI and abdominal symptoms were checked before, 1 and 5 years after treatment, and these changes were investigated among the three groups. RESULTS: The mean BMI changes 1 year after treatment in the low PG I/II ratio group were significantly higher than those in other groups. Most abdominal symptoms in the high PG I/II ratio group were most severe before eradication but improved significantly after eradication. CONCLUSIONS: The effects of H. pylori eradication on BMI and dyspeptic symptoms may be different according to the serum PG I/II ratio before eradication.

Phase II study of chemoradiotherapy combined with gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic ductal adenocarcinoma (NUPAT 05 Trial): study protocol for a single arm phase II study.

The efficacy of nab-paclitaxel combined with gemcitabine (GnP) and of chemoradiotherapy (CRT) for unresectable locally advanced pancreatic ductal adenocarcinoma (UR-LA PDAC) is still unclear. We previously conducted a phase I study of CRT using GnP and determined the recommended dose and have now designed a phase II trial to evaluate the efficacy of CRT incorporating GnP for UR-LA PDAC. Eligibility criteria are chemotherapy-naïve patients with UR-LA PDAC as defined by the NCCN guidelines version 2. 2016. Study patients will receive 100 mg/m2 nab-paclitaxel and 800 mg/m2 gemcitabine on Days 1, 8, and 15 per 4-week cycle with concurrent radiation therapy (total dose of 50.4 Gy in 28 fractions of 1.8 Gy per day, 5 days per week). Treatment will be continued until disease progression or surgery, which is to be performed only for patients in whom the disease is well-controlled at 8 months from beginning the protocol treatment. Primary endpoint is 2-year overall survival rate and co-primary endpoint is resection rate. Secondary endpoints are overall survival, progression free survival, time to treatment failure, response rate, disease control rate, early tumor shrinkage, depth of response, reduction of SUV-max on PET-CT, serum tumor markers, relative dose intensity, safety, and Quality of life. This study will show the efficacy and safety of chemoradiotherapy combined with GnP.

Helicobacter pylori evolution: lineage- specific adaptations in homologs of eukaryotic Sel1-like genes.

Geographic partitioning is postulated to foster divergence of Helicobacter pylori populations as an adaptive response to local differences in predominant host physiology. H. pylori's ability to establish persistent infection despite host inflammatory responses likely involves active management of host defenses using bacterial proteins that may themselves be targets for adaptive evolution. Sequenced H. pylori genomes encode a family of eight or nine secreted proteins containing repeat motifs that are characteristic of the eukaryotic Sel1 regulatory protein, whereas the related Campylobacter and Wolinella genomes each contain only one or two such "Sel1-like repeat" (SLR) genes ("slr genes"). Signatures of positive selection (ratio of nonsynonymous to synonymous mutations, dN/dS = omega > 1) were evident in the evolutionary history of H. pylori slr gene family expansion. Sequence analysis of six of these slr genes (hp0160, hp0211, hp0235, hp0519, hp0628, and hp1117) from representative East Asian, European, and African H. pylori strains revealed that all but hp0628 had undergone positive selection, with different amino acids often selected in different regions. Most striking was a divergence of Japanese and Korean alleles of hp0519, with Japanese alleles having undergone particularly strong positive selection (omegaJ > 25), whereas alleles of other genes from these populations were intermingled. Homology-based structural modeling localized most residues under positive selection to SLR protein surfaces. Rapid evolution of certain slr genes in specific H. pylori lineages suggests a model of adaptive change driven by selection for fine-tuning of host responses, and facilitated by geographic isolation. Characterization of such local adaptations should help elucidate how H. pylori manages persistent infection, and potentially lead to interventions tailored to diverse human populations.

Keratin and filaggrin expression in keratoacanthoma.

To clarify the histogenesis of keratoacanthoma, we studied keratin (K) expression in keratoacanthoma (KA) using 10 different anti-keratin antibodies against K1, K7, K8, K10, K14, K15, K16, K17, K18 and K19 and anti-filaggrin (filament aggregating protein) antibody. In the centre of KA, K1 and K10 expressions were declined, and K14 and K16 were detected in the tumour cells, suggesting differentiation towards the outer root sheath beneath the orifice of the sebaceous duct. These results suggest that KA differentiates towards the outer root sheath beneath the opening of the sebaceous duct.

Necrobiotic xanthogranuloma with paraproteinemia; an atypical case.

Necrobiotic xanthogranuloma (NXG) is a rare marker for paraproteinemia. An 86-year-old woman had a one year history of large red-yellow to brown annular plaques involving all limbs. Biopsies showed a non-palisading granuloma with numerous multinucleated giant cells showing prominent elastophagocytosis and extensive areas of necrobiosis throughout the entire dermis. Complete loss of elastic fibers was observed in the central atrophic area of an annular plaque. Small vascular thromboses were also present. Laboratory findings revealed paraproteinemia of IgG-lambda type. Immunohistochemical staining detected the presence of roughly equal numbers of IgG-lambda-and IgG-kappa-staining plasma cells in the dermis. We diagnosed NXG with paraproteinemia with monoclonal gammopathy (IgG-lambda type) of unknown significance.

Phase I study of chemoradiotherapy using gemcitabine plus nab-paclitaxel for unresectable locally advanced pancreatic cancer.

PURPOSE: For unresectable locally advanced (UR-LA) pancreatic cancer, chemoradiotherapy has been recommended by the NCCN guidelines. We designed a chemoradiotherapy protocol using nab-paclitaxel combined with gemcitabine (GnP) for patients with UR-LA pancreatic cancer. The purpose of this phase I study was to determine a recommended dose (RD) for this novel regimen. METHODS: Patients with UR-LA pancreatic cancer were eligible. The frequency of dose-limiting toxicities (DLTs) was evaluated, and the RD was determined. Patients were classified according to the designated dose levels of chemoradiotherapy using the GnP regimen. After additional 6 cycles of the GnP regimen were administered, surgery was considered if the patients had stable disease and tumor marker levels had normalized. RESULTS: DLT (grade 4 thrombocytopenia) was observed only in 1 of 12 patients, and the RD was set at level 3. Grade 3-4 leukopenia was observed in 9 (75.0%) patients, and neutropenia in 7 (58.3%). The response rate was 41.7%, and the disease control rate was 100%. Conversion surgery was performed in 6 (50%) patients, and curative resection (R0) was performed in all 6 patients (100%). Stratification according to the Evans classification system demonstrated one patient with grade 1b, one with grade 2, two with grade 3, and two with grade 4 disease. CONCLUSION: The RD for weekly administration was 800 mg/m2 for gemcitabine and 100 mg/m2 for nab-paclitaxel with a 50.4 Gy radiation. The GnP regimen at this dosage was promising with 6 of 12 patients proceeding to conversion surgery, and should be evaluated further in a phase II trial.

Risk factors for neovascular glaucoma after carbon ion radiotherapy of choroidal melanoma using dose-volume histogram analysis.

PURPOSE: To determine the risk factors for neovascular glaucoma (NVG) after carbon ion radiotherapy (C-ion RT) of choroidal melanoma. METHODS AND MATERIALS: A total of 55 patients with choroidal melanoma were treated between 2001 and 2005 with C-ion RT based on computed tomography treatment planning. All patients had a tumor of large size or one located close to the optic disk. Univariate and multivariate analyses were performed to identify the risk factors of NVG for the following parameters; gender, age, dose-volumes of the iris-ciliary body and the wall of eyeball, and irradiation of the optic disk (ODI). RESULTS: Neovascular glaucoma occurred in 23 patients and the 3-year cumulative NVG rate was 42.6 +/- 6.8% (standard error), but enucleation from NVG was performed in only three eyes. Multivariate analysis revealed that the significant risk factors for NVG were V50IC (volume irradiated > or =50 GyE to iris-ciliary body) (p = 0.002) and ODI (p = 0.036). The 3-year NVG rate for patients with V50IC > or =0.127 mL and those with V50IC <0.127 mL were 71.4 +/- 8.5% and 11.5 +/- 6.3%, respectively. The corresponding rate for the patients with and without ODI were 62.9 +/- 10.4% and 28.4 +/- 8.0%, respectively. CONCLUSION: Dose-volume histogram analysis with computed tomography indicated that V50IC and ODI were independent risk factors for NVG. An irradiation system that can reduce the dose to both the anterior segment and the optic disk might be worth adopting to investigate whether or not incidence of NVG can be decreased with it.

Usefulness of FDG PET for diagnosis and radiotherapy of the patient with malignant lymphoma involving bone marrow.

We experienced a case of relapsed malignant lymphoma with multiple bone marrow or bone lesions. The case was diagnosed as follicular lymphoma by cytological biopsy of the right iliac bone, with (67)Ga scintigraphy showing abnormal, intense uptake in multiple bones. After about 10 months of systemic chemotherapy, a relapse was suspected because of pain in the bilateral legs and a high level of lactate dehydrogenase. Assessment of the lesions in the patient was difficult by computed tomography because the affected sites were localized mainly in the bone marrow. (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was useful for detecting accurately the relapse sites in the bone marrow and enabled us to determine the field for radiotherapy. There are only a few reports of FDG-PET findings for such bone marrow malignant lymphomas. Therefore, we report the findings of FDG-PET for this case and review some of the literature about bone marrow lymphomas.

Associations Between CagA, VacA, and the Clinical Outcomes of Helicobacter Pylori Infections in Okinawa, Japan.

Helicobacter pylori, which is involved in the pathogenesis of gastroduodenal disease, produces CagA and VacA as major virulence factors. CagA is classified into East Asian and Western types based on the number and sequences of its Glu-Pro-Ile-Tyr-Ala motifs. The vacA gene has three polymorphic regions: the signal (s), intermediate (i), and middle (m) regions. The lowest gastric cancer mortality rate is seen in Okinawa. On the Japanese mainland (Honshu), most H. pylori produce s1/m1-VacA, which exhibits strong toxicity, and East Asian-type CagA. However, the H. pylori detected in Okinawa produces s1/m2-VacA, which exhibits weak toxicity, or s2/m2-VacA, which is non-toxic, and Western-type CagA. Studies about the i-region of vacA have been performed around the world, but there have been few such studies in Japan. Therefore, the aim of this study was to assess the relationships between the clinical outcomes of H. pylori infections in Okinawa, vacA (especially the i-region genotype), and cagA. H. pylori strains that were collected from patients with gastric cancer or gastric ulcers in Okinawa only produced the i1-type VacA virulence factor. The vacuolating cytotoxin activity of i1-type VacA was stronger than that of i2-type VacA, suggesting that the i-region genotype of vacA is closely associated with vacuolating cytotoxin activity. These results indicate that the i-region genotype of vacA is a useful marker of both H. pylori virulence and the clinical outcomes of H. pylori infections in Okinawa, Japan.