The persistence of interleukin-6 is regulated by a blood buffer system derived from dendritic cells.

The interleukin-6 (IL-6) membrane receptor and its circulating soluble form, sIL-6R, can be targeted by antibody therapy to reduce deleterious immune signaling caused by chronic overexpression of the pro-inflammatory cytokine IL-6. This strategy may also hold promise for treating acute hyperinflammation, such as observed in coronavirus disease 2019 (COVID-19), highlighting a need to define regulators of IL-6 homeostasis. We found that conventional dendritic cells (cDCs), defined in mice via expression of the transcription factor Zbtb46, were a major source of circulating sIL-6R and, thus, systemically regulated IL-6 signaling. This was uncovered through identification of a cDC-dependent but T cell-independent modality that naturally adjuvants plasma cell differentiation and antibody responses to protein antigens. This pathway was then revealed as part of a broader biological buffer system in which cDC-derived sIL-6R set the in-solution persistence of IL-6. This control axis may further inform the development of therapeutic agents to modulate pro-inflammatory immune reactions.

[A case report:the progress of fascioliasis from hepatic phase to biliary phase].

This is a case report of fascioliasis that progressed from the hepatic to the biliary phases over 2 years. A woman in her late 60s ate Zingiber mioga from the field, which was followed by abdominal pain that occurred 1 month later. Although CT and MRI studies revealed an increase in blood eosinophils as well as multiple hepatic nodules, they vanished quickly. After 2 years, an MRCP study revealed multiple flat lesions, which were diagnosed as adult fascioliasis. Definitive diagnosis was provided by enzyme-labeled antibody method using fasciola-specific antigen. Triclabendazole was administered once to complete the treatment.

Benefits of linked color imaging for recognition of early differentiated-type gastric cancer: in comparison with indigo carmine contrast method and blue laser imaging.

BACKGROUND AND AIM: Linked color imaging (LCI) is a novel endoscopy system, which enhances slight differences in mucosal color. However, whether LCI is more useful than other kinds of image-enhanced endoscopy (IEE) in recognizing early gastric cancer remains unclear. This study aimed to evaluate LCI efficacy compared with the indigo carmine contrast method (IC), and blue laser imaging-bright (BLI-brt) in early differentiated-type gastric cancer recognition. METHODS: We retrospectively analyzed early differentiated-type gastric cancer, which were examined by all four imaging techniques (white light imaging, IC, LCI, BLI-brt) at Asahi University Hospital from June 2014 to November 2018. Both subjective evaluation (using ranking score: RS) and objective evaluation (using color difference score: CDS) were adopted to quantify early differentiated-type gastric cancer recognition. RESULTS: During this period, 87 lesions were enrolled in this study. Both RS and CDS of LCI were significantly higher (p < 0.01) than those of IC and BLI-brt. Both RS and CDS of BLI-brt had no significant difference compared with those of IC. Subgroup analysis revealed that LCI was especially useful in post-Helicobacter pylori eradication patients and flat or depressed lesions compared with IC and BLI-brt. CONCLUSIONS: LCI appears to be more beneficial for the recognition of early differentiated-type gastric cancer in endoscopic screenings than IC and BLI-brt from the middle to distant view.

Potential of automatic diagnosis system with linked color imaging for diagnosis of Helicobacter pylori infection.

BACKGROUND AND AIM: It is necessary to establish universal methods for endoscopic diagnosis of Helicobacter pylori (HP) infection, such as computer-aided diagnosis. In the present study, we propose a multistage diagnosis algorithm for HP infection. METHODS: The aims of this study are to: (i) to construct an interpretable automatic diagnostic system using a support vector machine for HP infection; and (ii) to compare the diagnosis capability of our artificial intelligence (AI) system with that of endoscopists. Presence of an HP infection determined through linked color imaging (LCI) was learned through machine learning. Trained classifiers automatically diagnosed HP-positive and -negative patients examined using LCI. We retrospectively analyzed the new images from 105 consecutive patients; 42 were HP positive, 46 were post-eradication, and 17 were uninfected. Five endoscopic images per case taken from different areas were read into the AI system, and used in the HP diagnosis. RESULTS: Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the diagnosis of HP infection using the AI system were 87.6%, 90.4%, 85.7%, 80.9%, and 93.1%, respectively. Accuracy of the AI system was higher than that of an inexperienced doctor, but there was no significant difference between the diagnosis of experienced physicians and the AI system. CONCLUSIONS: The AI system can diagnose an HP infection with significant accuracy. There remains room for improvement, particularly for the diagnosis of post-eradication patients. By learning more images and considering a diagnosis algorithm for post-eradication patients, our new AI system will provide diagnostic support, particularly to inexperienced physicians.

Dynamic regulation of plasma matrix metalloproteinases in human diabetic ketoacidosis.

BACKGROUND: Diabetic ketoacidosis (DKA) in children is associated with cerebrovascular-related complications. We recently reported that DKA facilitates leukocyte adherence to the brain microvascular endothelium. Adhered leukocytes can release enzymes that instigate vascular dysfunction. Our aims were to measure plasma levels of leukocyte-derived matrix metalloproteinases (MMPs) from DKA patients and to correlate plasma MMP concentrations with DKA severity. METHODS: Plasma was obtained from children with type 1 diabetes, either in DKA (n = 16) or insulin controlled (CON; n = 16). Antibody microarray and gelatin zymography were used to quantify plasma MMPs and their endogenous tissue inhibitors (TIMPs). MMP concentrations were correlated with DKA severity (blood pH). Quantitative PCR of leukocyte mRNA was used to help determine the origin of plasma MMPs. RESULTS: DKA was associated with altered plasma levels of ↓MMP-2 (P < 0.001), ↑MMP-8 (P < 0.001), ↑MMP-9 (P < 0.05), and ↑TIMP-4 (P < 0.001), as compared with CON. Elevated MMP-8 and MMP-9 were both positively correlated with DKA severity (P < 0.05). DKA was associated with increased leukocyte mRNA for MMP-8, MMP-9, and TIMP-4 (P < 0.005). CONCLUSION: MMPs are dynamically regulated during DKA. Plasma MMP-8 and MMP-9 concentrations correlate with DKA severity and are known to degrade brain microvascular endothelial cell tight junctions. Thus, leukocyte-derived MMPs might contribute to DKA-associated cerebrovascular complications.

CXCL1/CXCL8 (GROα/IL-8) in human diabetic ketoacidosis plasma facilitates leukocyte recruitment to cerebrovascular endothelium in vitro.

Diabetic ketoacidosis (DKA) in children is associated with intracranial vascular complications, possibly due to leukocyte-endothelial interactions. Our aim was to determine whether DKA-induced inflammation promoted leukocyte adhesion to activated human cerebrovascular endothelium. Plasma was obtained from children with type 1 diabetes either in acute DKA or in an insulin-controlled state (CON). Plasma concentrations of 21 inflammatory analytes were compared between groups. DKA was associated with altered circulating levels of ↑CXCL1 (GROα), ↑CXCL8 (IL-8), ↑IL-6, ↑IFNα2, and ↓CXCL10 (IP-10) compared with CON. These plasma analyte measurements were then used to create physiologically relevant cytokine mixtures (CM). Human cerebral microvascular endothelial cells (hCMEC/D3) were stimulated with either plasma (DKA-P or CON-P) or CM (DKA-CM or CON-CM) and assessed for polymorphonuclear leukocyte (PMN) adhesion. Stimulation of hCMEC/D3 with DKA-P or DKA-CM increased PMN adhesion to hCMEC/D3 under "flow" conditions. PMN adhesion to hCMEC/D3 was suppressed with neutralizing antibodies to CXCL1/CXCL8 or their hCMEC/D3 receptors CXCR1/CXCR2. DKA-P, but not DKA-CM, initiated oxidative stress in hCMEC/D3. Expression of ICAM-1, VCAM-1, and E-selectin were unaltered on hCMEC/D3 by either DKA-P or DKA-CM. In summary, DKA elicits inflammation in children associated with changes in circulating cytokines/chemokines. Increased CXCL1/CXCL8 instigated PMN adhesion to hCMEC/D3, possibly contributing to DKA-associated intracranial vascular complications.

The impact of non-steroidal anti-inflammatory drugs on the small intestinal epithelium.

The small intestine has been called as a dark continent of digestive tract and it had been very difficult to diagnose or treat the disease of small intestine. However recent technological development including video capsule endoscopy or balloon-assisted endoscopy has made us to aware the various diseases of small intestine. By using capsule endoscopy, many researchers reported that more than 70% of patients treated continuously with non-steroidal anti-inflammatory drugs (NSAID) exhibit the mucosal damage of small intestine. In some cases, NSAID not only causes mucosal damage but also results in life threatening bleeding from small intestine, which had not been prevented or cured by gastro-protective drug or anti-gastric acid secretion drug administration. Therefore to investigate and identify the effective drug that protects small intestine from mucosal damage is urgently expected. In spite of extensive investigation in clinical field, only a few drugs such as misoprostol, a synthetic prostaglandin E1 analogue, has been reported as an effective one but is not satisfactory enough to fulfill the requirement of patients who suffer from NSAID-induced mucosal damage of small intestine. And now, extensive study is being performed using several gastro-mucoprotective drugs by many researchers. In this review, we introduce the current clinical situation in small intestinal injury of patients under NSAID treatment, and to summarize the molecular mechanism by which NSAID, including acetyl salicylic acid, cause small intestinal damage. In addition, we present results of clinical trials performed so far, and refer the possible preventive method or treatment in the near future.

Diabetic ketoacidosis elicits systemic inflammation associated with cerebrovascular endothelial cell dysfunction.

OBJECTIVE: To determine if the DKA-induced inflammation in juvenile mice provokes activation and dysfunction of CVECs. METHODS: DKA in juvenile mice was induced with administration of STZ and ALX. Blood from DKA mice was assessed for cytokines and soluble cell adhesion proteins, and either DKA plasma or exogenous compounds were applied to immortalized bEND3. RESULTS: DKA increased circulating levels of IL-6, IL-8(KC), MCP-1, IL-10, sE-selectin, sICAM-1, and sVCAM-1. Stimulation of bEND3 with DKA plasma caused cellular activation (increased ROS and activation of NF-κΒ), upregulation of a proadhesive phenotype (E-selectin, ICAM-1, and VCAM-1), and increased leukocyte-bEND3 interaction (leukocyte rolling/adhesion). TEER, a measure of bEND3 monolayer integrity, was decreased by DKA plasma. Activation and dysfunction of bEND3 with DKA plasma were suppressed by plasma heat treatment (56°C, 1 hour) and replicated with the application of DKA recombinant cytomix (IL-6, IL-8[KC], MCP-1, and IL-10), implicating circulating inflammatory protein(s) as mediators. Treatment of bEND3 with ß-OH-butyrate, the main ketone elevated in DKA, failed to mimic the DKA plasma-induced activation and dysfunction of bEND3. CONCLUSIONS: DKA elicits systemic inflammation associated with CVEC activation and dysfunction, possibly contributing to DKA-associated intracranial microvascular complications.

Protective effect of the Japanese traditional medicine juzentaihoto on myelosuppression induced by the anticancer drug TS-1 and identification of a potential biomarker of this effect.

BACKGROUND: TS-1 is an oral anticancer drug containing a 5-fluorouracil derivative (Tegafur) that is widely used in Japan for the treatment of cancer, especially gastrointestinal tumors. Frequently, however, TS-1 therapy has to be discontinued because of leukopenia. If it were possible to predict the development of bone marrow suppression before the white blood cell (WBC) count had actually decreased, treatment could be improved by strict dosage control and/or the prophylactic administration of hematopoietic drugs. Juzentaihoto (JTT), a traditional Japanese medicine (Kampo), has been reported to activate hematopoiesis and reduce the side effects associated with chemotherapy and radiotherapy. Here, we 1) evaluate the efficacy of JTT in alleviating myelosuppression induced by TS-1 therapy in mice, and 2) explore biomarkers that reflect both induction by TS-1 and alleviation by JTT of bone marrow suppression using a proteomics approach. METHODS: Ten mg/kg of TS-1 was administered to Balb/c mice with or without 1 g/kg of oral JTT for 3, 5 and 7 days. WBC count and ratio of CD34+ bone marrow cells (BMCs) were estimated by flow cytometry. Plasma samples were analyzed using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF-MS). A biomarker candidate from SELDI profiling was identified using a combination of cation exchange spin column purification, SDS-PAGE, enzymatic digestion and LC-MS/MS. RESULTS: After administration of TS-1, a significant decrease in WBC count and CD34+ BMC ratio were observed at days 5 and 3, respectively. JTT treatment improved WBC count on day 7 and CD34+ BMC ratio on days 5 and 7. SELDI analysis highlighted three protein peaks that had increased on day 3 after treatment with TS-1 but remained unchanged in mice co-treated with JTT. One of the three peaks, m/z 4223.1, was further investigated and identified as a specific C-terminal fragment of albumin. CONCLUSION: This study indicates that bone marrow suppression by treatment with TS-1 in mice might be improved by coadministration of JTT. A C-terminal fragment of albumin was identified as a candidate biomarker for predicting TS-1-induced myelosuppression. However, the sensitivity and specificity of the biomarker candidate must be validated in future clinical studies.

Demarcation Line Determination for Diagnosis of Gastric Cancer Disease Range Using Unsupervised Machine Learning in Magnifying Narrow-Band Imaging.

BACKGROUND AND AIMS: It is important to determine an accurate demarcation line (DL) between the cancerous lesions and background mucosa in magnifying narrow-band imaging (M-NBI)-based diagnosis. However, it is difficult for novice endoscopists. We aimed to automatically determine the accurate DL using a machine learning method. METHODS: We used an unsupervised machine learning approach to determine the DLs. Our method consists of the following four steps: (1) an M-NBI image is segmented into superpixels using simple linear iterative clustering; (2) the image features are extracted for each superpixel; (3) the superpixels are grouped into several clusters using the k-means method; and (4) the boundaries of the clusters are extracted as DL candidates. The 23 M-NBI images of 11 cases were used for performance evaluation. The evaluation investigated the similarity of the DLs identified by endoscopists and our method, and the Euclidean distance between the two DLs was calculated. For the single case of 11 cases, the histopathological examination was also conducted to evaluate the proposed system. RESULTS: The average Euclidean distances for the 11 cases were 10.65, 11.97, 7.82, 8.46, 8.59, 9.72, 12.20, 9.06, 22.86, 8.45, and 25.36. The results indicated that the proposed method could identify similar DLs to those identified by experienced doctors. Additionally, it was confirmed that the proposed system could generate pathologically valid DLs by increasing the number of clusters. CONCLUSIONS: Our proposed system can support the training of inexperienced doctors as well as enrich the knowledge of experienced doctors in endoscopy.

Endogenous hydrogen sulfide is an anti-inflammatory molecule in dextran sodium sulfate-induced colitis in mice.

BACKGROUND: Endogenous hydrogen sulfide (H(2)S) is increasingly being recognized as an important gaseous physiological mediator. Accumulating evidence shows the functions of H(2)S in various models of disease, but rarely in colitis. In this study, we investigated the role of endogenous H(2)S in a dextran sodium sulfate (DSS)-induced colitis model. METHODS: Acute colitis was induced using 8% DSS in male BALB/c mice. The mRNA expression of cystathionine γ-lyase (CSE), the primary synthetase of H(2)S in the gastrointestinal tract, and cystathionine-ß-synthetase (CBS) was measured by real-time RT-PCR. The amount of H(2)S in the colonic mucosa was measured by gas chromatography. Colitis severity was evaluated clinically, histologically, and biochemically under the condition of co-treatment with DL-propargylglycine (PAG), an irreversible CSE inhibitor, and sodium sulfide (Na(2)S), an H(2)S donor. RESULTS: The mRNA expression levels of CSE and CBS, and the H(2)S content in the colonic mucosa were increased with time after DSS administration. The disease activity index, which was determined by weight loss, stool consistency, and intestinal bleeding, increased after DSS administration. PAG significantly enhanced the increase in the disease activity index scores. PAG also significantly increased tissue-associated myeloperoxidase activity and thiobarbituric acid-reactive substances in the inflamed mucosa. Moreover, Na(2)S counteracted these effects of PAG. CONCLUSIONS: Taken together, the results indicated that the inhibition of endogenous H(2)S generation caused the deterioration of DSS-induced colitis. We conclude that physiological H(2)S might act as an anti-inflammatory molecule in colitis.

Daikenchuto, a Kampo medicine, regulates intestinal fibrosis associated with decreasing expression of heat shock protein 47 and collagen content in a rat colitis model.

Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time-course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200 g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor ß1 (TGF-ß1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14 d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with α-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-ß1, HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine.

Carbon monoxide enhance colonic epithelial restitution via FGF15 derived from colonic myofibroblasts.

Carbon monoxide (CO) has been reported to ameliorate colonic inflammation and improve experimental colitis. It is well known that mucosal restitution is important to improve colitis as well as reduction of mucosal inflammation. However, it has not been clear whether CO effects to colonic mucosal restitution or not. In general, colonic myofibroblast (MF) has been reported to play an important role of colonic epithelial cell restitution via constitutive secretion of TGF-beta. In this study, we showed CO (supplied by CO-releasing molecule; CORM) treated MF conditioned medium enhanced colonic epithelial cell (YAMC) restitution and we determined gene expression in colonic MF treated with CO using microRNA. The microRNA array suggested that miR-710 was significantly reduced in MF by CO treatment and the target gene of miR-710 is determined to fibroblast growth factor (FGF)15. The CO treated MF conditioned medium which FGF15 expression was silenced extinguished the enhancement effect of epithelial cell restitution. Our findings demonstrate that CO treatment to MF increased FGF15 expression via inhibition of miR-710 and FGF15 enhanced colonic epithelial cell restitution.

Identification of inflammation-related proteins in a murine colitis model by 2D fluorescence difference gel electrophoresis and mass spectrometry.

BACKGROUND AND AIMS: The aim of this study was to identify new intestinal proteins potentially associated with acute inflammation using proteomic profiling of an in vivo mice model of ulcerative colitis. METHODS: 2D fluorescence difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight spectrometer (MALDI-TOF) peptide mass fingerprinting were used to determine differentially expressed proteins between normal and inflamed intestinal mucosa. Acute colitis was induced by 8.0% dextran sodium sulfate (DSS) given p.o. for 7 days. RESULTS: Among a total of seven protein spots showing differential expression, we identified five different proteins, of which two were upregulated and three downregulated in colitis in comparison to normal mucosa, using the MASCOT search engine. 3-Hydroxy-3-methylglutaryl-coenzyme A synthase 2 and serpin b1a were upregulated proteins, and protein disulfide-isomerase A3, peroxiredoxin-6 and vimentin were identified as downregulated proteins. CONCLUSION: These identified proteins may be responsible for the development of the intestinal inflammation. 2D-DIGE and MALDI-TOF mass spectrometry are useful in the search for the differentially expressed proteins.

Inhalation of carbon monoxide ameliorates TNBS-induced colitis in mice through the inhibition of TNF-α expression.

BACKGROUND: Carbon monoxide (CO), long considered a toxic gas, has recently been shown to mediate anti-inflammatory effects in various animal models. The aim of this study was to investigate whether the inhalation of CO ameliorated 2,4,6-trinitrobenzine sulfonic acid (TNBS)-induced colitis in mice. METHODS: The CO treatment group was exposed to CO gas at a concentration of 200 ppm in a closed cage starting on the day when TNBS was administered and throughout the remaining study period. The distal colon was removed, and ulcerative lesions were subsequently evaluated with macroscopic damage scores. Furthermore, thiobarbituric acid (TBA)-reactive substances and tissue-associated myeloperoxidase (MPO) activity in colonic mucosa were measured as indices of lipid peroxidation and neutrophil infiltration. The expressions of TNF-α in colonic mucosa were also measured by enzyme-linked immunosorbent assay. In additional experiments in vitro, CD4(+) T cells isolated from the spleen were stimulated with anti-CD3/CD28 Ab, and the cells and supernatants were collected and evaluated for TNF-α expression. RESULTS: The increased colonic damage after TNBS administration was significantly inhibited by the treatment with CO. Furthermore, CO significantly inhibited the increases in TBA-reactive substances, MPO activity and TNF-α production in colonic mucosa after the induction of TNBS colitis. In CD4(+) T cells isolated from mice treated with CO inhalation, the production of TNF-α was significantly inhibited. CONCLUSIONS: The inhalation of CO protected mice from developing intestinal inflammation. Based on these data, the beneficial effects of CO in a murine colitis model may be attributed to its anti-inflammatory properties.

Hemostatic radiotherapy for inoperable gastric cancer: a pilot study.

OBJECTIVE: Standard treatment for progressive gastric cancer with bleeding includes hemostatic radiotherapy (RT); however, the only prospective study using a fixed dose with fractions during hemostatic RT did not introduce re-irradiation. Therefore, we determined the utility of RT including re-irradiation for gastric cancer. METHODS: In this study, 31 patients with gastric cancer and bleeding were treated with an initial dose of 20 Gy/5 fractions for the whole stomach and a salvage dose of 15 Gy/5 fractions for the partial stomach. Patients achieving hemostasis, defined as a stable hemoglobin level within 30 days following irradiation, were considered responders, whereas those with no cessation of bleeding and those with re-bleeding within 30 days of irradiation were considered non-responders. We evaluated response rate, disease-free survival, overall survival (OS), re-irradiation, and adverse events (AEs). RESULTS: The response rate of initial RT was 80% (25/31). 6 of the 25 patients underwent re-irradiation, and all 6 were responders (100%). The median OS was significantly different among the entire cohort and one-time irradiation and re-irradiation groups (91, 76, and 112 days, respectively). No AEs of grade ≥3 were observed. Initial low-dose RT followed by reirradiation was effective in reducing AEs and did not cause any further AEs. CONCLUSION: Hemostatic RT was an effective approach with low toxicity, and re-irradiation was effective and tolerable, with no patients developing severe AEs. Further, randomized controlled studies are warranted to determine the ideal dose and number of fractions for initial RT in patients with gastric cancer and bleeding. ADVANCES IN KNOWLEDGE: In this prospective study on hemostatic radiotherapy for gastric cancer, the response rate was 80% using a fixed dose of 20 Gy/5 fractions and the salvage dose of 15 Gy for re-bleeding was effective. Future comparative studies should include other doses with 20 Gy as a control.

Successful treatment of unresectable advanced rectal cancer with liver metastases by hemostasis re-irradiation of the rectal cancer and palliative low-dose whole-liver radiation therapy: a case report.

A 72-year-old man was admitted to the hospital with fatigue. Colonoscopy revealed a 50 × 50 mm rectal tumor with bleeding. Based on close inspection, he was diagnosed with unresectable advanced rectal cancer with multiple liver metastases. Chemotherapy was administered as 10 cycles of bevacizumab + mFOLFOX6 and 7 cycles of bevacizumab + FOLFIRI. Nine months later, he presented with hematochezia and progression of anemia. It was difficult to stop the bleeding via endoscopy. He underwent radiation therapy (39 Gy in 13 fractions), and hemostasis was confirmed. Then, further chemotherapy was performed with 3 cycles of bevacizumab + FOLFIRI and 2 cycles of TAS102. However 14 months after the initial visit, he presented with right hypochondralgia and abdominal fullness due to the progression of multiple liver metastases. Palliative low-dose whole-liver radiation therapy (WLRT) (30 Gy in 10 fractions) was performed. He developed Grade 2 nausea, but his right hypochondralgia reduced, liver dysfunction improved, and he successfully completed radiotherapy. At approximately the same time his anemia progressed, and colonoscopy revealed recurrent bleeding from the tumor. Re-irradiation (15 Gy in 5 fractions) of the rectal tumor was carried out and a blood transfusion was performed for the bleeding. He was discharged after confirmation the anemia had not progressed. Few reports have been published on the use of both palliative re-irradiation to stop bleeding from rectal cancer and palliative low-dose WLRT. Based on our experience with this case, we believe that palliative radiotherapy can be useful in treating patients with a poor prognosis.

A case of phlegmonous gastritis with hepatic portal venous gas caused by Aeromonas hydrophila successfully treated with medication.

A 74-year-old woman was admitted to the hospital with epigastric pain, severe nausea and vomiting, and diarrhea that had started 3 days previously. She had eaten raw Ayu fish 4 days before admission. An abdominal contrast-enhanced computed tomography scan revealed the presence of gas in the portal vein and remarkable thickening of the gastric wall. In many cases, the gas in the portal vein indicates the existence of intestinal necrosis. Esophagogastroduodenoscopy showed a submucosal tumor-like elevation in the gastric corpus. She was diagnosed with sepsis and phlegmonous gastritis (PG) with hepatic portal venous gas (HPVG) caused by Aeromonas hydrophila, which was detected in her stool. The patient was treated with antibiotics and discharged from the hospital 23 days after admission in a stable condition. When caused by PG, HPVG is not necessarily considered a poor prognostic factor and is expected to be treatable with medication. However, patients should be closely monitored for signs of a life-threatening pathology such as intestinal necrosis.