[A Case of Hepatocellular Carcinoma with Haemobilia after Transcatheter Hepatic Arterial Embolization for Tumor Rupture].

A 79-year-old man was scheduled for surgery for hepatocellular carcinoma(HCC)after transcatheter hepatic arterial embolization for rupture. Two weeks before surgery, the patient came to our hospital with a chief complaint of back pain. First, we performed biliary drainage, under the diagnosis of HCC with obstructive jaundice due to haemobilia. Hepatectomy was performed when the patient's condition stabilized. It should be kept in mind that haemobilia may occur after TAE for HCC with bile duct tumor thrombus, and appropriate treatment should be performed when bleeding occurs.

[A Case of Colon Metastasis from Gastric Cancer Treated by Laparoscopic-Assisted Segmental Colectomy].

We report a case of colon metastasis from gastric cancer treated by laparoscopic-assisted segmental colectomy. An 81-year-old man was undergone distal gastrectomy, D2 dissection and Billroth Ⅰ reconstruction for gastric cancer 3 years previously, with a final diagnosis of gastric cancer L, Post, Type 2, sig/por2, pT4a(SE), pN3b(30/56), H0, P0, M0, pStage ⅢC. Three years after gastrectomy, CT scan showed an elevated lesion in the transverse colon, which was suspected to be metastatic colorectal cancer on closer examination. As no metastatic lesions were found other than the tumor of transverse colon, we performed laparoscopic-assisted segmental colon resection. A small incision was placed in the umbilical region, and the transverse colon was extracted from the umbilical region after dissection of the adhesions by single-incision laparoscopic surgery. The transverse colon containing the mass lesion was partially resected extracorporeally and reconstructed with a functional end-to-end anastomosis. The postoperative pathological findings revealed tumor cells predominantly below the submucosal layer and partly showing the signet ring cell carcinoma, and the transvers colon tumor was diagnosed as a metastasis from gastric cancer. The postoperative course was uneventful and the patient was discharged 8 days after surgery, and is alive for 10 months after the segmental colon resection followed by chemotherapy.

[A Case of Recurrent Esophageal Cancer with Long-Term Survival Treated by S-1 Monotherapy].

We report a case of recurrent esophageal cancer with long-term survival treated by S-1 monotherapy. A 66-year-old man underwent subtotal esophagectomy, two-field lymphadenectomy after 2 courses of DCF chemotherapy for esophageal cancer 1 year earlier. The final diagnosis was esophageal cancer, Lt, CT-Type 2, ypT3, ypN0(0/62), M0, ypStage Ⅲ. At 6 months after esophagectomy, CT scan revealed mediastinal lymph node metastasis and pleural dissemination, and paclitaxel monotherapy was performed, but lymph node re-enlargement was observed on CT at 12 months after esophagectomy. Chemotherapy with S-1 monotherapy was performed, and 3 months after initiation of S-1 monotherapy, CT showed reduced lymph node metastases and pleural dissemination remained reduced. Adverse events were CTCAE v5.0 Grade 2 thrombocytopenia and diarrhoea, but no Grade 3 or higher adverse events were observed. Long-term survival was achieved with no disease progression for more than 2.5 years after initiation of S-1 monotherapy.

[Analysis of Short-Term Outcomes and Nutritional Assessment of Elderly Gastric Cancer Surgery Cases].

BACKGROUND: We analyzed the short-term outcomes and nutritional assessment of gastric cancer surgery patients who underwent exercise intervention after gastrectomy. MATERIALS AND METHOD: Gastric cancer patients who underwent gastrectomy at our department from January 2021 were included in the study. Postoperative exercise intervention(lower limb training) was performed in gastric cancer patients aged 75 years or older(group H: 7 patients)and compared retrospectively with gastric cancer patients younger than 75 years(group L: 10 patients)who did not receive exercise intervention. The rate of decrease in each index after 1 week was compared between the 2 groups. RESULTS: Postoperative complications(yes/no) were 3/4(42.8%)in group H and 2/8(20.0%)in group L(p=0.59); postoperative hospital stay was 11.5(10.8-21.3) days in group H and 11.0(9.0-14.0)days in group L(p=0.37). The percentage decrease in each index was as follows: for BMI in groups H/L: 2.9/5.6%(p=0.17), grip strength in groups H/L: 2.4/－7.6%(p=0.07), skeletal muscle mass in groups H/L: －2.3/7.0%(p=1.00), PNI in groups H/L: 26.6/18.1%(p=0.12). CONCLUSION: In this study, no significant differences were noted in postoperative complication rates or postoperative hospital stay between groups H and L.

Inhibition of HDAC and Signal Transduction Pathways Induces Tight Junctions and Promotes Differentiation in p63-Positive Salivary Duct Adenocarcinoma.

BACKGROUND: The p53 family p63 is essential for the proliferation and differentiation of various epithelial basal cells. It is overexpressed in several cancers, including salivary gland neoplasia. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors downregulate p63 expression in cancers. METHODS: In the present study, to investigate the roles and regulation of p63 in salivary duct adenocarcinoma (SDC), human SDC cell line A253 was transfected with siRNA-p63 or treated with the HDAC inhibitors trichostatin A (TSA) and quisinostat (JNJ-26481585). RESULTS: In a DNA array, the knockdown of p63 markedly induced mRNAs of the tight junction (TJ) proteins cingulin (CGN) and zonula occuludin-3 (ZO-3). The knockdown of p63 resulted in the recruitment of the TJ proteins, the angulin-1/lipolysis-stimulated lipoprotein receptor (LSR), occludin (OCLN), CGN, and ZO-3 at the membranes, preventing cell proliferation, and leading to increased cell metabolism. Treatment with HDAC inhibitors downregulated the expression of p63, induced TJ structures, recruited the TJ proteins, increased the epithelial barrier function, and prevented cell proliferation and migration. CONCLUSIONS: p63 is not only a diagnostic marker of salivary gland neoplasia, but it also promotes the malignancy. Inhibition of HDAC and signal transduction pathways is, therefore, useful in therapy for p63-positive SDC cells.

[Analysis of Chemotherapy-Induced Nausea and Vomiting during Chemotherapy for Gastric Cancer].

BACKGROUND: Chemotherapy-induced nausea and vomiting(CINV)are typical side effects caused by chemotherapy. We analyzed CINV during first-line chemotherapy for gastric cancer. MATERIALS AND METHOD: Thirty-one patients who received first-line chemotherapy for gastric cancer were retrospectively assessed for CINV. RESULTS: The median age was 70 years, and the gender(male/female)was 23/8 cases. NK1 receptor antagonist, 5-HT3 receptor antagonist, and dexamethasone were used as antiemetic agents in 29 patients(94%). Sixteen patients(52%)had Grade 1 or higher nausea, and 6 patients (19%)had Grade 1 or higher vomiting, and complete control of nausea and vomiting was achieved in 21 patients(68%). Nausea was significantly more frequent in patients with liver metastasis(p=0.0008), but there was no significant difference in vomiting(p=1.0000). There was no significant difference in the occurrence of CINV between chemotherapy regimens or combination of olanzapine. CONCLUSION: During first-line chemotherapy for gastric cancer, 3 antiemetic agents were used in 94% of cases, and the complete control rate of CINV was 67.8%.

[A Case of Early Gastric Cancer with Adachi Type â ¥ Vascular Anomaly Treated by Laparoscopic Distal Gastrectomy].

We report a case of early gastric cancer with Adachi Type Ⅵ vascular anomaly treated by laparoscopic distal gastrectomy. An 81-year-old woman was admitted because of anorexia, and was diagnosed with early gastric cancer. Preoperative MDCT revealed Adachi Type Ⅵ vascular anomaly, where the hepatic artery does not appear at the superior border of the pancreas. The patient was treated successfully with laparoscopic distal gastrectomy with D1+lymph node dissection. At surgery, we identified the portal vein, then, dissection of No. 8a lymph nodes was performed. The postoperative course was uneventful and the patient was discharged 10 days after surgery. The final pathology result showed gastric cancer, M, Less, Type 0-Ⅱc+Ⅲ, 58×50 mm, tub1>pap, pT1a(M), Ly0, V0, pN0(0/40), H0, P0, M0, pStage ⅠA. We understand the arterial running pattern before surgery by using MDCT, and performed laparoscopic surgery safely.

Narrow band imaging accentuates differences in contrast between cartilage and perichondrium in the elevation of the muco-perichondrium flap during septoplasty and open septorhinoplasty.

OBJECTIVE: In the elevation of the muco-perichondrium flap during septoplasty and septorhinoplasty, it is important to elevate the subperichondrial layer. When performing subperichondrial elevation of the flap, the surgeon uses differences in color tone to distinguish the perichondrium from cartilage; however, it is relatively difficult to understand these differences and to share them with assistants. Furthermore, the perichondrium at the caudal end adheres tightly to the cartilage, making it difficult to detach accurately the subperichondrial layer. Narrow band imaging (NBI) is an optical technology that facilitates detailed observation of microvessels in the mucosal surface layer. In this study, we investigated whether NBI is better than white light (WL) in accentuating differences in contrast between cartilage and perichondrium in the elevation of the muco-perichondrium flap during septoplasty and septorhinoplasty. METHODS: Twenty-six sides of 15 patients (the modified Killian approach was used in two patients, the hemitransfixion approach was used in seven patients, and open septorhinoplasty was used in six patients) with elevated muco-perichondrium flaps were studied under WL endoscopy and NBI. The brightness of the perichondrium and cartilage and the differences between the two tissues were compared between WL and NBI using ImageJ 1.53a. Next, the WL and NBI endoscopic images used for cartilage identification were divided into the three separate primary color channels of red, green, and blue, and the brightness of the perichondrium and cartilage were measured separately for each channel. RESULTS: Under WL, the perichondrium appeared reddish-white and the cartilage appeared white, whereas under NBI the perichondrium appeared greenish-gray, differentiating it from the white cartilage. The difference in brightness between the cartilage and perichondrium was significantly higher on NBI (grayscale difference 80.8 (SD 42.4)) than on WL imaging (grayscale difference 35.6 (SD 31.1)) (p<0.001). In the red channel, the difference in image intensity between cartilage and perichondrium was significantly higher on NBI than on WL imaging (Red WL grayscale difference -1.5 (SD 33.7), Red NBI grayscale difference 90.0 (SD 56.7); p<0.001). CONCLUSIONS: NBI is better than WL at accentuating the difference in contrast between cartilage and the perichondrium during the elevation of the muco-perichondrium flap during septoplasty and septorhinoplasty. The difference in the processing of red light between WL and NBI provides the largest contribution to the differentiation of cartilage from the perichondrium under WL and NBI. We believe that NBI can be usefully applied during septoplasty and septorhinoplasty to distinguish cartilage from the perichondrium with precision.

FOXO3/TGF-ß signal-dependent ciliogenesis and cell functions during differentiation of temperature-sensitive mouse cochlear precursor hair cells.

The transcription factor FOXO3 is necessary to preserve cochlear hair cells. Growth factors, including TGF-ß, closely contribute to cochlear hair cell regeneration. In the present study, to investigate the roles of FOXO3 in the ciliogenesis and cell functions of cochlear hair cells, UB/OC-2 temperature-sensitive mouse cochlear precursor hair cells were treated with TGF-ß receptor type 1 inhibitor EW-7197 or EGF receptor inhibitor AG-1478 after transfection with or without siRNA-FOXO3a. GeneChip analysis revealed that treatment with EW-7197 increased Foxo3 genes and decreased genes of Smads. During cell differentiation, treatment with EW-7197 or AG-1478 induced an increase in length of cilia-like structures that were positive for acetylated tubulin and inhibited cell migration. Treatment with EW-7197 also increased cell metabolism measured as mitochondrial basal respiration (oxygen consumption rate). The effects of EW-7197 were stronger than those of AG-1478. Knockdown of FOXO3 prevented the growth of cilia-like structures induced by EW-7197 or AG-1478 and induced cell migration under treatment with EW-7197. No change of the epithelial cell polarity molecule PAR3 was observed with any treatment. Treatment with the antimicrobial agent amikacin prevented the growth of cilia-like structures induced by EW-7197 and induced apoptosis. Pretreatment with the glucocorticoid dexamethasone inhibited the apoptosis induced by amikacin. This in vitro model of mouse cochlear hair cells suggests that FOXO3/TGF-ß signaling plays a crucial role in ciliogenesis and cell functions during differentiation of cochlear hair cells. This model is useful for analysis of the mechanisms of hearing loss and to find therapeutic agents to prevent it.

[A Case of Stage â £ Gastric Cancer Completely Resected after Successful Second-Line Chemotherapy].

A 60s man was diagnosed with advanced gastric cancer(cT4b[PAN], cN+, cM0, cStage ⅣA). He started first-line chemotherapy consisting of S-1 and cisplatin, but tumor markers remained elevated and CT showed cancer progression. He then started second-line chemotherapy consisting of ramucirumab and paclitaxel. The tumor markers decreased, and CT revealed tumor regression. A distal gastrectomy with D2 lymph node dissection was performed as conversion surgery. The patient had an uncomplicated postoperative course and was discharged early from the hospital. A histological analysis confirmed complete resection of the Grade 1a tumor. The RAM plus PTX regimen was restarted on postoperative day 57. At 15 months postoperative, the patient remained alive and relapse-free.

[A Case of Recurrent Sigmoid Colon Cancer with Peritoneal Metastasis and Liver Metastasis Successfully Treated with Capecitabine plus Bevacizumab].

A 78-year-old man had undergone a laparoscopic sigmoid colon resection; left ureteral resection; and a ureteral reconstruction for sigmoid colon cancer with left ureteral invasion. The patient did not wish to undergo postoperative adjuvant chemotherapy, and he was followed up at fixed intervals. Six months after surgery, CT revealed peritoneal metastasis and liver metastasis(S6). Considering his advanced age and adverse events, the patient was started on capecitabine plus bevacizumab therapy. The patient was able to continue the treatment, even though he had to suspend and reduce the dose due to adverse events of hand-foot syndrome, and achieved CR by CT after 21 courses of treatment. Chemotherapy was discontinued after 24 courses, CR was maintained for 5 years, and the patient is still alive with no evidence of recurrence.

[A Case of Advanced Gastric Cancer Successfully Treated with mFOLFOX6 Therapy].

We report a case of advanced gastric cancer that was successfully treated with mFOLFOX6 therapy. A 78-year-old man presented to our hospital with a chief complaint of weight loss. Esophagogastroduodenoscopy(EGD)and computed tomography( CT)revealed the presence of type 3 advanced gastric cancer with distant lymph node metastasis and peritoneal dissemination. Biopsy specimen examination revealed moderately differentiated adenocarcinoma with a HER2 score of 1. Chemotherapy comprising 5-fluorouracil, Leucovorin, and oxaliplatin(mFOLFOX6)was administered because of renal failure. Subsequently, the gastric lesion, distant lymph node metastasis, and peritoneal dissemination were seen to be reduced on EGD and CT. After 7 courses, the regimen was changed to 5-fluorouracil and Leucovorin(5-FU/l -LV)chemotherapy because of thrombocytopenia. For more than 10 months, he has continued to receive chemotherapy without the recurrence of metastasis.

Effects of HMGB1 on Tricellular Tight Junctions via TGF-ß Signaling in Human Nasal Epithelial Cells.

The airway epithelium of the human nasal mucosa acts as a physical barrier that protects against inhaled substances and pathogens via bicellular and tricellular tight junctions (bTJs and tTJs) including claudins, angulin-1/LSR and tricellulin. High mobility group box-1 (HMGB1) increased by TGF-ß1 is involved in the induction of nasal inflammation and injury in patients with allergic rhinitis, chronic rhinosinusitis, and eosinophilic chronic rhinosinusitis. However, the detailed mechanisms by which this occurs remain unknown. In the present study, to investigate how HMGB1 affects the barrier of normal human nasal epithelial cells, 2D and 2.5D Matrigel culture of primary cultured human nasal epithelial cells were pretreated with TGF-ß type I receptor kinase inhibitor EW-7197 before treatment with HMGB1. Knockdown of angulin-1/LSR downregulated the epithelial barrier. Treatment with EW-7197 decreased angulin-1/LSR and concentrated the expression at tTJs from bTJs and increased the epithelial barrier. Treatment with a binder to angulin-1/LSR angubindin-1 decreased angulin-1/LSR and the epithelial barrier. Treatment with HMGB1 decreased angulin-1/LSR and the epithelial barrier. In 2.5D Matrigel culture, treatment with HMGB1 induced permeability of FITC-dextran (FD-4) into the lumen. Pretreatment with EW-7197 prevented the effects of HMGB1. HMGB1 disrupted the angulin-1/LSR-dependent epithelial permeability barriers of HNECs via TGF-ß signaling in HNECs.

Syntheses of Tetrasubstituted [10]Cycloparaphenylenes by a Pd-catalyzed Coupling Reaction. Remarkable Effect of Strain on the Oxidative Addition and Reductive Elimination.

A small library of tetrasubstituted [10]cycloparaphenylene ([10]CPP) derivatives bearing alkyl, alkenyl, alkynyl and aryl substituents was constructed by a Pd-catalyzed cross-coupling reaction starting from tetratriflate [10]CPP 5 e, which was readily available in high yields on a >2 g scale. The CPP skeleton increases the reactivity of aryl triflate for oxidative addition to the Pd species, and 5 e is 10 times more reactive than its linear paraphenylene analogue, as determined by competition experiments. Theoretical calculations suggest that the accumulation of the small strain relief from each paraphenylene unit not involved in the reaction is responsible for the observed enhanced reactivity.

Palladium-catalyzed perarylation of 3-thiophene- and 3-furancarboxylic acids accompanied by C-H bond cleavage and decarboxylation.

3-thiophene- and 3-furancarboxylic acids efficiently undergo perarylation accompanied by cleavage of the three C-H bonds and decarboxylation upon treatment with excess aryl bromides in the presence of a palladium catalyst to give the corresponding tetraarylated products in good yields.

Palladium-catalyzed selective 2,3-diarylation of alpha,alpha-disubstituted 3-thiophenemethanols via cleavage of C-H and C-C bonds.

Alpha,alpha-disubstituted 3-thiophenemethanols undergo selective diarylation accompanied by cleavage of the C-H and C-C bonds of the 2- and 3-positions, respectively, upon treatment with aryl bromides in the presence of a palladium catalyst to give the corresponding 2,3-diarylthiophenes in good yields.