Triple-drug combination therapy versus six-month proton pump inhibitor monotherapy in non-Helicobacter pylori Helicobacter eradication, and hyperacid environment preference of Helicobacter suis: a clinical study.

BACKGROUND: At present, eradication regimens for non-Helicobacter pylori Helicobacter (NHPH) have not been established yet. We investigated effectiveness of the standard triple-drug combination therapy for Helicobacter pylori eradication and of a proton pump inhibitor (PPI) monotherapy in eradication of NHPH. METHODS: Subjects were the patients who were diagnosed with NHPH-infected gastritis based on microscopic findings, helical-shaped organisms obviously larger than Helicobacter pylori, in the gastric mucosal specimens using Giemsa staining at Kenwakai Hospital between November 2010 and September 2021, whose NHPH species were identified by polymerase chain reaction (PCR) analysis of urease genes in endoscopically-biopsied samples, and who consented to NHPH eradication with either the triple-drug combination therapy for one week or a PPI monotherapy for six months. Six months after the completion of eradication, its result was determined with esophagogastroduodenoscopy, microscopic examination, and PCR analysis. In cases of unsuccessful eradication, a second eradication with the other therapy was suggested to the patient. RESULTS: PCR analysis detected NHPH in 38 patients: 36 as Helicobacter suis and two as Helicobacter heilmannii/Helicobacter ailurogastricus. Fourteen Helicobacter suis-infected and one Helicobacter heilmannii/Helicobacter ailurogastricus-infected patients requested eradication therapy. The triple-drug combination therapy succeeded in four of five patients, while the PPI monotherapy succeeded in five of 10 patients. Three of five patients who had been unsuccessful with the latter therapy requested the triple-drug combination therapy as the second eradication and all three were successful. In total, the triple-drug combination therapy succeeded in seven out of eight (87.5%) attempted cases, while the PPI monotherapy in five out of 10 (50%) attempted cases. CONCLUSIONS: In NHPH eradication, the triple-drug combination therapy was considered to be effective to some extent and to become the first-line therapy. While, although less successful, PPI monotherapy appeared to be a potentially promising option particularly for patients with allergy or resistance to antibiotics. Effectiveness of PPI monotherapy may be attributed to hyperacid environment preference of Helicobacter suis and PPI's acid-suppressive effect. Additionally, male predominance in NHPH-infected gastritis patients may be explained by gender difference in gastric acid secretory capacity. However, further evidence needs to be accumulated. STUDY REGISTRATION: This study was approved by the Research Ethics Committee of Kenwakai Hospital (No. 2,017,024).

Prevalence, clinical features, and esophagogastroduodenoscopy (EGD) findings of non-Helicobacter pylori Helicobacter infection: A study of 50 cases at a single facility in Japan.

BACKGROUND AND AIM: There are only a few reports of non-Helicobacter pylori Helicobacter (NHPH) gastritis in Japanese patients. We aimed to examine its prevalence, clinical features, and esophagogastroduodenoscopy (EGD) findings based on 50 patients encountered in one facility. MATERIALS AND METHODS: Subjects were all patients who had undergone gastric mucosal biopsy endoscopically at Kenwakai Hospital for approximately 10 years. NHPH infection was diagnosed by microscopic findings of Giemsa staining performed on all specimens. PCR analysis of urease genes was performed to detect and identify NHPH, when informed consent was obtained. Helicobacter pylori-diagnostic tests were also performed. NHPH-infected patients were questioned about symptoms and animal contact. RESULTS: NHPH gastritis was found in 50 of 3847 patients (1.30%). The percentage increased to 3.35% (30 of 896 patients) in the latter 2 years and 4 months with increasing recognition of its characteristic endoscopic findings by endoscopists. PCR analysis, performed in 30 patients, detected NHPH in 28 patients: 26 as Helicobacter suis and 2 as Helicobacter heilmanii/Helicobacter ailurogastricus. Helicobacter pylori-diagnostic tests were almost negative. However, anti-H. pylori antibody showed high-negative titer (3.0-9.9 U/ml) in 12. Of 50 patients (consisting of 49 men and 1 woman), almost all were asymptomatic, and 25 were keeping pets. Regarding EGD findings, in all 50 patients, "crack-like mucosa" and/or nodular gastritis was noted in gastric antrum, and regular arrangement of collecting venules (RAC) was noted in gastric corpus. None of the patients infected with NHPH were co-infected with H. pylori. CONCLUSIONS: The prevalence was finally estimated to be approximately 3.35%. Helicobacter suis was the most common NHPH species. "Crack-like mucosa" and/or nodular gastritis in gastric antrum, RAC in gastric corpus, and H. pylori-negativity by H. pylori-diagnostic tests especially containing a high-negative titer of anti-H. pylori antibody may indicate NHPH infection.

Acute gastric mucosal lesions caused by acute infection of non-Helicobacter pylori Helicobacter: a case report.

BACKGROUND: Non-Helicobacter pylori Helicobacter (NHPH) is not widely recognized as a cause of acute gastric mucosal lesions (AGML), as only a few cases of AGML caused by NHPH have been reported. We present here one case and examine the species and eradication of NHPH together with the three previously reported cases. CASE PRESENTATION: A 52-year-old woman presented with a two-day history of severe epigastric pain, nausea, and vomiting. An esophagogastroduodenoscopy showed mucosal edema, multiple erosions, and ulcerations in the antrum. Biopsy specimens taken from the antrum revealed long spiral-shaped organisms, suggesting NHPH. As both serum anti-Helicobacter pylori (H. pylori) antibody and H. pylori stool antigen test were negative, this case was diagnosed as AGML caused by NHPH. After the administration of esomeprazole 20 mg for 14 days and the interval of the following 12 days, AGML was deemed to have been cured endoscopically. In addition, microscopic examination and PCR analysis confirmed the success of NHPH eradication. CONCLUSIONS: NHPH should be considered a probable cause of AGML in cases that are not attributed to the other causes already recognized. Taking probability of spontaneous eradication into consideration, it is appropriate to start eradication therapy after confirming the chronicity of NHPH infection.

[A Case of Adult T-Cell Leukemia/Lymphoma with Severe Hand-Foot Syndrome during Administration of Modified LSG15 Regimen].

The patient was a 56-year-old woman. A modified LSG15(VCAP-AMP-VECP)regimen was initiated as the first-line treatment for acute adult T-cell leukemia/lymphoma. On day 13 from the initiation of the second course of chemotherapy, the onset of hand-foot syndrome(HFS)(hands: Grade 2; feet: Grade 1)occurred. Therefore, the administration of a heparin analog cream and betamethasone butyrate propionate ointment was initiated. On day 20 from the start of the second course of chemotherapy, the foot symptoms improved; however, hand symptoms deteriorated to Grade 3. Frequent use of alcohol-based hand hygiene products is associated with infection prevention during neutropenia, but was likely an exacerbating factor. The symptoms gradually improved after this was taken into consideration, and the usage was discontinued. At the start of the third course, the symptoms had improved to Grade 1, and chemotherapy was continued. On day 11, symptoms worsened(Grade 2). HFS management was performed similar to that in the second course, and symptoms improved again.

[Pneumatosis cystoides intestinalis (PCI) with sigmoid volvulus:a case potentially associated with lymphatic vessels].

An 80-year-old woman was brought to our hospital in an ambulance because of signs of peritoneal irritation. Computed tomography revealed volvulus, sigmoid colon dilation, and free air and pneumatosis within the colonic and bowel wall. An emergency laparotomy was performed after the diagnosis of colonic perforation associated with volvulus or pneumatosis. Numerous gas-filled cysts, up to 10mm in diameter, were located in the resected bowel wall. The cells at the inner lining of the cysts tested positive for D2-40 immunoreactivity, seemingly originating from the lymphatic vessels. In many cysts, KP-1 positive small mononuclear cells and/or foreign-body-type giant cells adhered to the D2-40 positive cells were observed. Fibrosis and lymphoplasmacytic infiltration was observed around the cysts. Contrary to the influential mechanical cause theory, in the present case, pneumatosis may have preceded volvulus, occurring as an idiopathic disease. Therefore, the lymphatic vessels were hypothesized to be associated with the pathogenesis of PCI.

[Survey of Prophylactic Administration of Naldemedine for Opioid-induced Constipation].

Opioid-induced constipation (OIC), an adverse event that occurs due to opioid analgesics, reportedly causes poor quality of life and adherence to opioid analgesics in patients. Therefore, this issue must be addressed appropriately. Naldemedine (NAL), a peripherally-acting µ-opioid receptor antagonist, is currently recommended for treating OIC when other laxatives are ineffective, but there have been no clinical reports of NAL being used prophylactically for OIC. Therefore, we conducted a retrospective survey of hospitalized patients who received NAL as prophylaxis for OIC with strong opioid analgesics to clarify the reality of this situation and to consider points to be taken into account in its clinical implementation. In this study, 61.7% of the subjects had an Eastern Cooperative Oncology Group performance status score of 3 or higher. The rate of addition of new laxatives and increased laxatives during seven days of NAL prophylaxis was 46.8%, and the rate of diarrhea was 6.1%. This study suggests that patients initiated with strong opioid analgesics during hospitalization often presented with poor performance status, and it is important to pay attention to constipation even under NAL prophylaxis. However, the incidence of diarrhea was low, and the safety of NAL prophylaxis was considered to be good.

Exploring Factors Affecting the Occurrence of Hypersensitivity Reactions Induced by Nonionic Iodine Contrast Media.

Hypersensitivity reactions induced by nonionic iodine contrast media sometimes occur and can be life threatening. However, independent factors affecting their occurrence remain to be fully established. Therefore, the purpose of this study was to clarify independent factors affecting the occurrence of hypersensitivity reactions induced by nonionic iodine contrast media. Patients who received nonionic iodine contrast media at Keiyu Hospital from April 2014 to December 2019 were included. The adjusted odds ratio (OR) and 95% confidence interval (CI) for factors affecting hypersensitivity reactions induced by contrast media were calculated by logistic regression analysis. The multiple imputation method was used to impute missing data. Hypersensitivity reactions occurred in 0.72% (163 cases) of 22,695 cases enrolled in this study. In univariate analysis, 10 variables met the criteria of P < .05 and proportion of missing data <50%. In multivariate analysis, age (OR, 0.98; 95% CI, 0.97-0.99), outpatient status (OR, 2.08; 95% CI, 1.20-3.60), contrast medium iodine content (OR, 1.02; 95% CI, 1.01-1.04), history of drug allergy (OR, 2.41; 95% CI, 1.50-3.88), and asthma (OR, 17.4; 95% CI, 7.53-40.1) were identified as independent factors affecting contrast media-induced hypersensitivity reactions. Among these factors, history of drug allergy and asthma appear to be clinically relevant and reliable due to their high OR and plausible biological mechanisms, but the other three factors require further validation.

Absolute configuration of tetrandrine and isotetrandrine influences their anti-proliferation effects in human T cells via different regulation of NF-κB.

Natural compound tetrandrine was reported to inhibit the proliferation of T cells by inhibiting activation of NF-κB. Chemically, isotetrandrine differs from tetrandrine only in the stereochemistry at the chiral centers. The present study aimed to compare their anti-proliferation effects on human T cells with a focus on NF-κB. The IC50 values of tetrandrine against MOLT-4 cells, MOLT-4/DNR cells, and concanavalin A-activated peripheral blood mononuclear cells of healthy subjects and dialysis patients were 4.43 ± 0.22, 3.62 ± 0.22, 1.91 ± 0.22 and 3.03 ± 0.28 µM, respectively. Whereas, the IC50 values of isotetrandrine against the above immune cells were 2.19 ± 0.27, 2.28 ± 0.33, 1.29 ± 0.14 and 1.55 ± 0.26 µM, respectively. The inhibitory effect of isotetrandrine against the proliferation of T cells was stronger than that of tetrandrine significantly (p < 0.05). Molecular mechanism investigation showed that 10 µM of isotetrandrine largely decreased the expression of p-NF-κB and NF-κB in both MOLT-4 and MOLT-4/DNR T cells (p < 0.05), whereas 10 µM of tetrandrine slightly inhibited the phosphorylation of p-NF-κB with little influence on the expression of NF-κB. Taken together, absolute configurations of tetrandrine and isotetrandrine are suggested to influence on their anti-proliferation effects in human T cells via different regulation of NF-κB.

Clinicopathological analyses of fifty supracricoid laryngectomized specimens: evidence base supporting minimal margins.

OBJECTIVES: Supracricoid laryngectomy (SCL) is a reliable laryngeal preservation surgery. However, close surgical margins are often inevitable. Based on clinicopathological analyses of supracricoid laryngectomized specimens, we evaluated the evidence base supporting minimal margins. METHODS: The distance between tumor edge and resected margin was measured macro- and microscopically at the anterior, posterior, superior and inferior edges, using 50 surgical specimens. The margins were correlated with pathological T staging and the prognoses. RESULTS: The anterior and posterior margins were the shortest, and the superior margin was the longest. The inferior margin was the only edge at which a positive margin was encountered. Cancer extending 10 mm below the glottal free edge significantly decreased the inferior margin. CONCLUSIONS: The surgical potential of SCL with cricohyoidoepiglottopexy was confirmed to be able to cope with tumor extensions showing margins of a few millimeters at the anterior, posterior and superior ends. Accurate assessment and management at the inferior margin is the key to stable local control.

[Clinical review of supracricoid laryngectomy with CHEP and CHP: 50 patients treated in 11 years].

An analysis of clinical data on 50 patients undergoing supracricoid laryngectomy (SCL) between 1997 and 2008 i.e., cricohyoidoepiglottopexy (CHEP) in 47 and cricohyoidopexy (CHP) in 3 cases showed that the number of SCL cases operated on within a year surpassed that of Total Laryngectomy after 2003. Selection criteria included performance status 0-1 and blood gas PO2>80 torr, especially in those patients over 70-years-old. Postoperative wound infection occurred in 16 patients (32%), with four requiring additional surgical intervention (two ruptured pexis and two chondritis induced by C3-C4 osteophytes). A history of radiotherapy and systemic complications, i.e., diabetes and renal failure, added to the risk of wound infection. Introducing a clinical pathway shortened hospitalization. Vocal function was achieved in 96% and swallowing function in 89% of patients. Five-year crude survival in CHEP was 69% and in TL 51%. Laryngeal preservation was 70%, increasing to 89% after the introduction of SCL. SCL-CHEP is thus indicated for unfavorable T2 (ASCO 2006), well-selected T3, T4, and rT1-4 (radiation failures). Effort should emphasize a good balance in prognosis and function in organ preservation for laryngeal cancer.

Ganglioside from eel serum high density lipoprotein (HDL) and its role as a ligand for HDL binding protein.

First, we attempted to isolate glycosphingolipids from eel serum HDL. A single ganglioside containing N-acetylneuraminic acid (NeuAc), which is positive with resorcinol and orcinol reactions, was purified. The mobilities of the purified ganglioside and its lyso-form on high performance TLC were similar as those of authentic GM4 and its lyso-form, respectively. The mass of the purified ganglioside was determined by TOF mass spectrometer, and the mass of its oligosaccharide was the same as that of authentic GM4 from human brain consisting of disaccharide of NeuAc and galactose. The ganglioside from eel HDL was not hydrolyzed by recombinant endoglycoceramidase II, which cannot hydrolyze between galactose and ceramide of gangliosides, but hydrolyzes between glucose and ceramide. We concluded from these results that the ganglioside purified from eel serum HDL is GM4. Second, we investigated the effects of the ganglioside on binding of HDL labeled with fluorescein isothiocyanate (FITC-HDL) to cultured eel hepatocytes and on FITC-HDL ligand blotting by using plasma membrane proteins of the hepatocytes. Stimulatory effect of GM4 on FITC-HDL binding to the hepatocytes and FITC-HDL ligand blotting suggests strongly that GM4 is a ligand for HDL binding protein of eel hepatocytes.

Ubiquitous distribution of fluorescent protein in muscles of four species and two subspecies of eel (genus Anguilla).

In this study, the localization of fluorescent protein (FP) was characterized in the muscles of four species and two subspecies of eels Anguilla anguilla, A. australis, A. bicolor bicolor (b.), A. bicolor pacifica (p.) and A. mossambica in addition to the previously reported A. japonica. The open reading frame of each eel FP was 417 bp encoding 139 amino acid residues. The deduced amino acid sequences among the four species and two subspecies exhibited 91.4-100% identity, and belonged to the fatty-acid-binding protein (FABP) family. The gene structure of eel FPs in A. japonica, A. anguilla, A. australis, A. bicolor b., A. bicolor p. and A. mossambica have four exons and three introns, and were common to that of FABP family. The apo eel FPs expressed by Escherichia coli with recombinant eel FP genes were analysed for the fluorescent properties in the presence of bilirubin. The excitation and emission spectra of holo eel FPs had the maximum wavelengths of 490-496 and 527-530 nm, respectively. The holo eel FPs indicated that the fluorescent intensities were stronger in A. japonica and A. bicolor than in A. mossambica, A. australis and A. anguilla. The comparison of amino acid sequences revealed two common substitutions in A. mossambica, A. australis and A. anguilla with weak fluorescent intensity.

[A case of the extrahepatic bile duct carcinoid tumor].

A 76-year-old man presented with back discomfort and jaundice. CT and MRI of the abdomen revealed a mass in the common bile duct. Cytology of the bile juice obtained by percutaneous transhepatic cholangio-drainage revealed class V. The patient underwent laparotomy and pancreatoduodenectomy. Pathology showed a carcinoid tumor of the biliary tract, 14 x 10 mm in size. Grimelius staining demonstrated the presence of argyrophilic granules. On immunochemistry, the tumor stained positive for chromogranin A and synaptophysin. He had two liver metastases 8 months postoperatively.

Eel green fluorescent protein is associated with resistance to oxidative stress.

Green fluorescent protein (GFP) from eel (Anguilla japonica) muscle (eelGFP) is unique in the vertebrates and requires bilirubin as a ligand to emit fluorescence. This study was performed to clarify the physiological function of the unique GFP. Investigation of susceptibility to oxidative stress was carried out using three types of cell lines including jellyfish (Aequorea coerulescens) GFP (jfGFP)-, or eel GFP (eelGFP)-expressing HEK293 cells, and control vector-transfected HEK293 cells. Binding of eelGFP to bilirubin was confirmed by the observation of green fluorescence in HEK293-eelGFP cells. The growth rate was compared with the three types of cells in the presence or absence of phenol red which possessed antioxidant activity. The growth rates of HEK293-CV and HEK293-jfGFP under phenol red-free conditions were reduced to 52 and 31% of those under phenol red. Under the phenol red-free condition, HEK293-eelGFP had a growth rate of approximately 70% of the phenol red-containing condition. The eelGFP-expressing cells were approximately 2-fold resistant to oxidative stress such as H2O2 exposure. The fluorescence intensity partially decreased or disappeared after exposure to H2O2, and heterogeneous intensity of fluorescence was also observed in isolated eel skeletal muscle cells. These results suggested eelGFP, but not jfGFP, coupled with bilirubin provided the antioxidant activity to the cells as compared to non-bound free bilirubin.

Participation of high-density lipoprotein in vitellogenesis in Japanese eel hepatocytes.

To investigate effect of estradiol-17beta (E(2)) treatment in vivo on binding of eel hepatocytes to HDL, we developed hepatocytes binding assay. When hepatocytes were incubated with 200 times excess of eel HDL, the binding of hepatocytes to HDL precoated on wells was inhibited competitively. This indicates that eel hepatocytes bound specifically to HDL. E(2) treatment in vivo induced vitellogenin (VTG) synthesis. Hepatocytes prepared from the same E(2) treatment eel showed 3-fold higher ability of binding to HDL compared to hepatocytes prepared from ells without E(2) treatment. We also examined effects of E(2) and HDL on VTG induction in cultured hepatocytes. VTG, determined by enzyme-linked immunosorbent assay (ELISA), induction was about two-times higher in the presence of both 10(-5) M of E(2) and 400 microg of HDL than in the presence of 10(-5) M E(2) alone. At concentrations below 10(-6) M E(2), VTG was not induced in the presence or absence of HDL. By SDS-PAGE and immunoblotting, VTG was detected only in the presence of both 10(-5) M of E(2) and HDL. Our findings strongly support the idea that HDL correlates with vitellogenesis in eel liver.

Cell proliferation and expression of Cbfa-1 in a peripheral osteo-chondroma arising from the mandibular oral mucosa of an edentulous alveolar ridge.

This report describes the proliferation and the expression of Cbfa-1 in a rare case of peripheral osteo-chondroma arising from the mandibular oral mucosa of an edentulous alveolar ridge. Histologically, the lesion consisted of mesenchymal cells with either bone or cartilage tissue in the center. Almost all the tumor cells were reactive for PCNA, however, only the cells around the bone and cartilage tissues were reactive for Cbfa-1. These results suggest that both the bone and the cartilage tissues in this case were produced by mesenchymal cells that originated from the peripheral periosteum of the alveolar ridge. Furthermore, we have shown that immunohistochemical staining for PCNA and Cbfa-1 can be used to investigate lesions with bone or cartilage formation and to distinguish between those produced by osteogenic cells from those that are just reactive and produced by dystrophic calcification.

Inverted epiglottis: a postoperative complication of supracricoid laryngectomy with cricohyoidoepiglottopexy.

OBJECTIVES: Among the 50 laryngeal cancer patients who received SCL-CHEP between 1997 and 2008, we experienced three patients with complete epiglottis prolapse, which obstructed the neoglottis. By defining this complication as "Inverted epiglottis" and presenting the clinical features, we intend to elucidate the mechanism, risk factors, and management of this complication. METHODS: Details of the clinical features are presented. We conducted the following analyses: (1) distance from anterior commissure to the upper resected end of the surgical specimen was grossly measured. (2) Based on the analysis of sagittal cut CT images, the level of vallecula was identified and compared with the level of hyoid bone. (3) Distance between hyoid bone and cricoid arch (cricohyoid gap) after SCL-CHEP was measured using sagittal cut CT images. RESULTS: Prolonged edema of the neoglottis and delayed stomal closure were the main symptoms. In patients with the vallecula lower than the hyoid bone, excessive resection of the epiglottic petiole (anterior commissure-upper edge>25 mm) might be a risk factor. CONCLUSIONS: We reported a post-SCL-CHEP complication "Inverted epiglottis". Extensive excision of the epiglottic petiole, patients with a low vallecula profile, and incorrect suturing of epiglottic petiole during pexis are the three factors most related. Inverted epiglottis was treatable and most of the laryngeal function could be retrieved.