Palliative stenting for malignant colorectal stenosis in the elderly.

Objectives: Self-expandable metal stents are widely used for the treatment of malignant colorectal stenosis (MCS). In elderly individuals with MCS, self-expandable metal stents are often used as a palliative treatment, but prophylactic stent placement is not recommended. We investigated the efficacy and safety of self-expandable metal stents for the elderly in a palliative setting, specifically in a prophylactic setting. Methods: Elderly patients with MCS who received a palliative stent (the stent group) or palliative stoma (the stoma group) were retrospectively enrolled between April 2017 and June 2022, and the prognosis and complication rates were assessed. Additionally, patients in the stent group were divided into symptomatic and asymptomatic subgroups, and prognosis, stent patency, and complication rates were evaluated. Results: During the study period, 31 patients with a mean age of 85.4 years and 12 patients with a mean age of 82.0 years were enrolled in the stent and stoma groups, respectively. While overall survival and complication rates were comparable, the length of hospital stay was significantly shorter in the stent group. Of the 31 patients in the stent group, 16 asymptomatic patients received prophylactic stenting, which was not associated with increased complication rates. Conclusions: Palliative stents for MCS appear to be effective and safe even in the elderly, and thus, prophylactic stents can be considered for asymptomatic patients.

Acquired Coagulation Factor V Inhibitor That Was Successfully Treated with Oral Corticosteroid Therapy.

Acquired coagulation factor V (FV) inhibitors are rare disorders in which antibodies against FV develop under various conditions. We herein report the case of a 71-year-old woman with FV inhibitor during radiochemotherapy for pancreatic cancer. Multiple purpuras suddenly appeared on her bilateral upper limbs with prolonged coagulation data (APTT 97.3 seconds). The FV activity was less than 3% and the FV inhibitor was positive (1.7 B.U./mL). Oral prednisolone induced a rapid normalization of the coagulation data and FV activity and a rapid disappearance of FV inhibitor within 7 days. Early diagnosis and treatment may therefore be important in cases of FV inhibitor.

[Dihydropyrimidine dehydrogenase deficiency causes severe adverse effects of capecitabine].

We report the case of a 61-year-old man who experienced severe adverse effects of capecitabine because of dihydropyrimidine dehydrogenase (DPD) deficiency. In 2016, he visited our hospital for adenocarcinoma of the gastroesophageal junction and was prescribed neoadjuvant chemotherapy with capecitabine, cisplatin, and trastuzumab. On day 14 of chemotherapy, he developed severe diarrhea, canker sores, enterocolitis, febrile neutropenia, and thrombocytopenia. He was then urgently hospitalized, and anticancer treatment was stopped. We administered antibiotics and G-CSF, and he gradually recovered. However, he complained of severe bloody stools due to hemorrhagic enteritis;hence, we performed a bowel resection. The level of DPD protein, which metabolizes 5-fluorouracil (FU), was very low (2.83U/mg). Therefore, he was diagnosed with DPD deficiency, based on DPD protein or urinary pyrimidine levels, which caused serious adverse effects of capecitabine. It is a rare condition, and 5-FU administration should be avoided in DPD deficiency cases.

Involvement of IL-10 in exhaustion of myeloid dendritic cells and rescue by CD40 stimulation.

It has recently been shown that immature dendritic cells (DCs) stimulated by a danger signal undergo transient maturation followed by exhaustion. However, the exact mechanism for this has not been elucidated. In this study, we show that interleukin-10 (IL-10) secreted from transiently matured DCs stimulated by danger signals is responsible for this rapid DC exhaustion. Blocking of the autocrine IL-10 enabled transient mature DCs to maintain the mature phenotype for several days. However, these DCs remained phenotypically unstable because the addition of IL-10 altered the transient mature DCs to exhausted DCs. More importantly, stimulation of DCs by CD40 protected transient mature DCs from IL-10-dependent exhaustion, with the result that mature DCs remained stable in the presence of IL-10. Furthermore, in vivo administration of stable mature DCs pulsed with ovalbumin protein induced antigen-specific cytotoxic T lymphocytes (CTLs) effectively, whereas neither exhausted DCs nor transient mature DCs were able to prime a strong antigen-specific CTL response. These results indicate that DC-T cell engagement via CD40-CD154 is required for stable DC maturation leading to effective CTL induction. Otherwise, DCs stimulated solely by a danger signal are temporarily activated, but then rapidly lose their immune-activating capacity under the influence of autocrine IL-10.

B1-B cells are the main antigen presenting cells in CpG-ODN-stimulated peritoneal exudate cells.

Peritoneal exudate cells (PEC) have long been used as antigen presenting cells (APC), because they have been considered to contain mainly macrophages. However, it is still unclear specifically which cells of the peritoneal exudate function as APC. Herein, we focused on macrophages and B1-B cells of the PEC and examined their APC function and cytokine production. B1-B cells purified from PEC functioned effectively as APC after CpG-stimulation and mainly produced IL-10. In contrast, macrophages purified from PEC were not able to present incorporated antigens to T cells, despite the production of IL-12 and expression of co-stimulatory molecules after CpG stimulation. These results suggest that previously held ideas regarding the functions of the mixture of cells in the PEC need to re-evaluated. In summary, the antigen presenting function of PEC was mainly attributed to B1-B cells and immunoenhancing cytokine production was dominantly derived from peritoneal macrophages.

Phenotypic stability of mature dendritic cells tuned by TLR or CD40 to control the efficiency of cytotoxic T cell priming.

It is generally accepted that after stimulation immature DCs turn into mature DCs, which present exogenous antigens together with their MHC class I molecules and then activate the antigen-specific CTLs. Although both TLR and CD40 stimulation appeared to provide the same effects on DC maturation, CD40-dependent CTL activation is much more potent than CTL activation through LPS stimulation. Despite their different outcomes, the factors that lead mature DCs to different functions remain largely undefined. In this study, we defined the transient maturation and subsequent deactivation of DCs by TLR stimuli, including those by LPS and CpG-ODN. In contrast, CD40 stimulation induced stable mature DCs that elicited sufficient CTL proliferation. The deactivated DCs, which we defined as "expired DCs," were phenotypically similar to immature DCs, except for their phenotype stability, MHC class I expression level and IL-10 production. Moreover, the functions of expired DCs were comparable to those of immature DCs in terms of CTL induction and tolerogenicity. These results may provide an explanation for the role of CD40 stimulation in antigen-specific CTL induction.

The cytotoxicity of hydrophobic bile acids is ameliorated by more hydrophilic bile acids in intestinal cell lines IEC-6 and Caco-2.

Bile acids, especially those with hydrophobic properties, are known to possess cytotoxicity. However, the mechanisms responsible for the cytotoxicity of bile acids are still under investigation. On the other hand, the hydrophilic bile acid, ursodeoxycholic acid has been reported to exhibit therapeutic effects against cytotoxic hydrophobic bile acids. The aim of the present study was to investigate the cytotoxicity of individual bile acids and combinations of bile acids using the intestinal cell lines IEC-6 and Caco-2 cells. The cytotoxicities of individual bile acids and the effects of various bile acid combinations were evaluated using the MTS [3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. The bile acids induced cytotoxic effects depending on their hydrophobicity except for hyodeoxycholic acid. In the study for the effects of combined bile acids, not only ursodeoxycholic acid but other hydrophilic bile salts such as cholic acid and hyocholic acid exhibited cytoprotection against deoxycholic acid-induced cytotoxicity. Moreover, even some hydrophobic bile acids, such as chenodeoxycholic acid also exhibited cytoprotection. It is possible that the cytotoxicity of hydrophobic bile acids is ameliorated by more hydrophilic bile acids under certain conditions. The understanding of the precise mechanism of this phenomenon remains to be determined.

Analysis of alpha-amylase-derived pyridylamino-dextran sulfate oligomers by the combination of size-exclusion and reversed-phase high-performance liquid chromatography.

In a previous study, we reported a novel method for the separation and quantification of a strong negatively charged material, dextran sulfate sodium (DSS), using fluorometric labeling with 2-aminopyridine and size-exclusion high-performance liquid chromatography. In the present study, we developed a method for the separation of pyridylamino-DSS (PA-DSS) using reversed-phase high-performance liquid chromatography (RPLC). In vitro enzymatic degradation of the PA-DSS was carried out using alpha-amylase. In RPLC, depolymerized PA-DSS was eluted on the basis of molecular mass (in the order pentamer, trimer, dimer, and monomer of PA-DSS) and separations were more sharply than in size-exclusion chromatography. The combination of RPLC and size-exclusion chromatography also separated depolymerized PA-DSS as effectively as RPLC alone.