[A Case of Advanced Esophageal Cancer with Esophago-Bronchial Fistula Closed by Pembrolizumab plus Chemotherapy Therapy].

We report a case of unresectable advanced esophageal cancer with an esophageal fistula that was treated with pembrolizumab plus CDDP plus 5-FU therapy and the fistula was closed. A 73-year-old male was diagnosed with cervical-upper thoracic esophageal cancer and esophago-bronchial fistula on CT and esophagogastroduodenoscopy. He underwent chemotherapy containing pembrolizumab. The fistula was closed after 4 cycles and oral intake became possible. Six months have passed since the first visit and chemotherapy is ongoing. The prognosis of esophago-bronchial fistula is extremely poor, and there is no established treatment, including fistula closure. Chemotherapy containing immune checkpoint inhibitors could considered to be expected not only for local control but also for long-term survival.

Fatty acid potassium improves human dermal fibroblast viability and cytotoxicity, accelerating human epidermal keratinocyte wound healing in vitro and in human chronic wounds.

Effective cleaning of a wound promotes wound healing and favours wound care as it can prevent and control biofilms. The presence of biofilm is associated with prolonged wound healing, increased wound propensity to infection, and delayed wound closure. Anionic potassium salts of fatty acids are tested with commonly used anionic surfactants, such as sodium laureth sulphate (SLES) and sodium lauryl sulphate/sodium dodecyl sulphate (SLS/SDS). The normal human dermal cells demonstrated significantly greater viability in fatty acid potassium, including caprylic acid (C8), capric acid (C10), lauric acid (C12), oleic acid (C18:1), and linoleic acid (C18:2), than in SLES or SLS after a 24-hour incubation. Cytotoxicity by LDH assay in a 5-minute culture in fatty acid potassium was significantly lower than in SLES or SLS. in vitro wound healing of human epidermal keratinocytes during the scratch assay in 24-hour culture was more significantly improved by fatty acid treatment than by SLES or SLS/SDS. In a live/dead assay of human epidermal keratinocytes, C8K and C18:1K demonstrated only green fluorescence, indicating live cells, whereas synthetic surfactants, SLES and SLS, demonstrated red fluorescence on staining with propidium iodide, indicating dead cells after SLES and SLS/SDS treatment. Potassium salts of fatty acids are useful wound cleaning detergents that do not interfere with wound healing, as observed in the scratch assay using human epidermal keratinocytes. As potassium salts of fatty acids are major components of natural soap, which are produced by natural oil and caustic potash using a saponification method, this may be clinically important in wound and peri-wound skin cleaning. In human chronic wounds, natural soap containing fatty acid potassium increased tissue blood flow based on laser speckle flowgraphs after 2 weeks (P < .05), in addition to removing the eschars and debris. Wound cleansing by natural soap of fatty acid potassium is beneficial for wound healing.

Fatty Acid Potassium Had Beneficial Bactericidal Effects and Removed Staphylococcus aureus Biofilms while Exhibiting Reduced Cytotoxicity towards Mouse Fibroblasts and Human Keratinocytes.

Wounds frequently become infected or contaminated with bacteria. Potassium oleate (C18:1K), a type of fatty acid potassium, caused >4 log colony-forming unit (CFU)/mL reductions in the numbers of Staphylococcus aureus and Escherichia coli within 10 min and a >2 log CFU/mL reduction in the number of Clostridium difficile within 1 min. C18:1K (proportion removed: 90.3%) was significantly more effective at removing Staphylococcus aureus biofilms than the synthetic surfactant detergents sodium lauryl ether sulfate (SLES) (74.8%, p < 0.01) and sodium lauryl sulfate (SLS) (78.0%, p < 0.05). In the WST (water-soluble tetrazolium) assay, mouse fibroblasts (BALB/3T3 clone A31) in C18:1K (relative viability vs. control: 102.8%) demonstrated a significantly higher viability than those in SLES (30.1%) or SLS (18.1%, p < 0.05). In a lactate dehydrogenase (LDH) leakage assay, C18:1K (relative leakage vs. control: 108.9%) was found to be associated with a significantly lower LDH leakage from mouse fibroblasts than SLES or SLS (720.6% and 523.4%, respectively; p < 0.05). Potassium oleate demonstrated bactericidal effects against various species including Staphylococcus aureus, Escherichia coli, Bacillus cereus, and Clostridium difficile; removed significantly greater amounts of Staphylococcus aureus biofilm material than SLES and SLS; and maintained fibroblast viability; therefore, it might be useful for wound cleaning and peri-wound skin.

Chirality of camphor derivatives by density functional theory.

Infrared (IR) and vibrational circular dichroism (VCD) spectra of chiral camphor, camphorquinone and camphor-10-sulfonic acid (CSA), known as standard compounds for electronic circular dichroism (ECD) spectroscopy, are measured and their vibrational frequencies, infrared intensities, and rotational strengths are calculated using density functional theory (DFT). The observed IR and VCD spectra of chiral camphor and camphorquinone in carbon tetrachloride solution are reproduced by the DFT calculations, but those of CSA are not. DFT calculations of hydration models, where an anionic CSA specifically binds a few water molecules, are carried out. The average of the simulated VCD spectra in the hydration models is more consistent with the observed spectra. In addition, the wavelengths and dipole and rotational strengths for chiral camphor, camphorquinone, anionic CSA, and the hydration models were calculated by time-dependent DFT. In the region of 280-300 nm, the calculated wavelengths of the ECD bands for chiral camphor and camphorquinone coincide with the observed wavelengths that have been reported, and the calculated wavelengths for the hydration models are closer to the observed wavelengths reported than are those calculated for chiral anionic CSA. Consequently, the analysis combined with VCD and ECD spectroscopy using DFT calculations can elucidate the chirality of optically active molecules, even in an aqueous solution.

Electronic and vibrational circular dichroism of aromatic amino acids by density functional theory.

Structures of model compounds mimicking aromatic amino acid residues in proteins are optimized by density functional theory (DFT), assuming that the main-chain conformation was a random coil. Excitation energies and dipole and rotational strengths for the optimized structures were calculated based on time-dependent DFT (TD-DFT). The electronic circular dichroism (ECD) bands of the models were significantly affected by side-chain conformations. Hydration models of the aromatic residues were also subjected to TD-DFT calculations, and the ECD bands of these models were found to be highly perturbed by the hydration of the main-chain amide groups. In addition to calculating the random-coil conformation, we also performed TD-DFT calculations of the aromatic residue models, assuming that the main-chain conformation was an alpha-helix or beta-strand. As expected, the overall feature of the ECD bands was also perturbed by the main-chain conformations. Moreover, vibrational circular dichroism (VCD) spectra of the hydration models in a random-coil structure were simulated by DFT, which showed that the VCD spectra are more sensitive to the side-chain conformations than the ECD spectra. The present results show that analyses combining ECD and VCD spectroscopy and using DFT calculations can elucidate the main- and side-chain conformations of aromatic residues in proteins.