Visceral fat area is a better indicator of surgical outcomes after laparoscopic gastrectomy for cancer than the body mass index: a propensity score-matched analysis.

BACKGROUND: The number of overweight gastric cancer patients who are undergoing laparoscopic gastrectomy (LG) has increased in Japan. However, the relationship between obesity and surgical outcomes of LG remains unclear. Therefore, this study aimed to evaluate the effect of visceral fat area (VFA) on surgical outcomes of LG for gastric cancer compared to the body mass index (BMI). METHODS: This study was a retrospective, cohort study that included 587 patients who underwent LG in our institution between January 2015 and December 2019. The patients were divided into two groups according to VFA (< 100 cm2 and ≥ 100 cm2) and BMI (< 25 kg/m2 and ≥ 25 kg/m2) values, respectively. Surgical outcomes and postoperative complications were compared between the low and high groups for each VFA and BMI value. Propensity score matching was used to minimize potential selection bias. RESULTS: After propensity score matching, 144 pairs of patients in the VFA group and 82 pairs of patients in the BMI group were extracted. Operative time (p = 0.003), intraoperative blood loss (p = 0.0006), and CRP levels on postoperative day 1 (p = 0.002) and on postoperative day 3 (p = 0.004) were significantly higher in the high-VFA group than in the low-VFA group. However, these surgical outcomes were not significantly different between the high-BMI and low-BMI groups. There was no strong correlation between VFA and BMI (R2 = 0.64). There were no significant differences in postoperative complications between the high and low groups for both VFA and BMI values. On multivariate analysis, high VFA was an independent predictor of operative time, but it was not significantly associated with the incidence of postoperative complications. CONCLUSION: VFA is a better indicator of longer operative time than BMI. However, increased VFA did not affect postoperative complications.

Advantages of Laparoscopic Surgery for Gastric Cancer in Elderly Patients Aged Over 80 Years: A Propensity Score Matching Analysis.

BACKGROUND: The short- and long-term efficacy of laparoscopic surgery for elderly patients with gastric cancer has not been evaluated. We aimed to use propensity score matching to clarify the efficacy of laparoscopic gastrectomy (LG) for elderly patients with gastric cancer aged ≥80 years. METHODS: We retrospectively collected data from 159 consecutive patients with gastric cancer aged ≥80 years who underwent gastrectomy with curative intent at our institution between 2004 and 2015. Propensity score matching was applied to compare the open gastrectomy (OG) and LG. Short- and long-term outcomes were evaluated between the propensity-matched groups. RESULTS: Patients' backgrounds and surgical factors were similar in both groups except for blood loss. The median time to first flatus was significantly shorter in the LG group than in the OG group (P = 0.002). The postoperative hospital stay was significantly shorter in the LG group (P = 0.014). The complication rate of Clavien-Dindo grade III or higher was significantly lower in the LG group (3% vs. 23%, P = 0.023). The 5-year overall survival and 5-year disease-specific survival rates were better in the LG group than in the OG group, but the differences were not significant (45% vs. 42% and 67% vs 57%, respectively). CONCLUSION: LG was associated with good short-term outcomes and acceptable oncologic outcomes compared with OG in these propensity-matched patients aged ≥80 years.

Efficacy of Postoperative Chemotherapy After Resection that Leaves No Macroscopically Visible Disease of Gastric Cancer with Positive Peritoneal Lavage Cytology (CY1) or Localized Peritoneum Metastasis (P1a): A Multicenter Retrospective Study.

BACKGROUND: Gastric cancer (GC) patients with positive peritoneal lavage cytology (CY1) and/or localized peritoneum metastasis (P1a) are defined as stage IV in the 15th edition of the Japanese Classification of Gastric Cancer. In Japan, the most common treatment for patients with CY1 and/or P1a is gastrectomy followed by postoperative chemotherapy. PATIENTS AND METHODS: Subjects in this multi-institutional retrospective study were GC patients with CY1 and/or P1a who received surgical resection that leaves no macroscopically visible disease. Patients were selected from 34 institutions in Japan between 2007 and 2012. Selection criteria included adenocarcinoma, no distant metastasis except CY1 and P1a, and no prior treatment for GC before surgery. RESULTS: Among 824 patients registered, 506 were identified as eligible, with a background of P0CY1, P1aCY0, or P1aCY1 (72.5%, 16.0%, and 11.5% of subjects, respectively). Sixty-two patients had not received postoperative chemotherapy (no-Cx), whereas 444 patients had received postoperative chemotherapy: S-1 monotherapy (S-1; n = 267, 52.7%), cisplatin plus S-1 (CS; n = 114, 22.5%), and others (n = 63, 12.6%). Overall survival (OS) was 29.5, 24.7, 25.4 and 9.9 months in the S-1, CS, 'others', and no-Cx groups, respectively [CS vs. S-1: hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.89-1.50; p = 0.275]. In multivariate analysis, OS was similar between the S-1 and CS groups (CS vs. S-1: HR 1.19, 95% CI 0.92-1.55; p = 0.18). CONCLUSIONS: Postoperative chemotherapy after gastrectomy that leaves no macroscopically visible disease may have some survival benefits for GC patients with CY1 and/or P1a. In contrast, S-1 plus cisplatin seems to have no additional benefit over S-1 treatment alone.

Endoscopic Evaluation of Neoadjuvant Chemotherapeutic Efficacy in Gastric Cancer before Gastrectomy Might be as Useful as Histological Assessment after Gastrectomy.

BACKGROUND: Neoadjuvant chemotherapy for advanced gastric cancer is expected to improve prognoses. However, as there is no method to evaluate neoadjuvant chemotherapeutic efficacy before gastrectomy, some patients at high risk for a poor prognosis undergo gastrectomy. The aim of the present study was to investigate whether endoscopy could be useful for assessing the efficacy of neoadjuvant chemotherapy. METHODS: In this retrospective study, we analyzed the data of 41 patients who received neoadjuvant chemotherapy followed by gastrectomy at our institution to investigate whether responsiveness to neoadjuvant chemotherapy, as assessed with endoscopy, can serve as a surrogate marker for histological grades 1b or higher in the Japanese Classification of Gastric Carcinoma (JCGC) scheme. RESULTS: There were 32 (78.0%) responders and 9 (22.0%) nonresponders to neoadjuvant chemotherapy, as observed in endoscopic evaluations. Among the endoscopic responders, 24 (75.0%) had cancer of histological grade 1b or higher, and 15 (46.9%) had cancer of grade 2 or higher. Among the endoscopic nonresponders, 1 (11.1%) patient had histological grade 1b cancer. Compared with endoscopic nonresponders, endoscopic responders were more likely to show a histological response (chi-square test: p = 0.0005 for JCGC grade 1b or higher; p = 0.0099 for JCGC grade 2 or higher). CONCLUSIONS: Most endoscopic responders showed JCGC histological responses. Evaluation of neoadjuvant chemotherapeutic efficacy by endoscopy in gastric cancer may be useful before gastrectomy. As this was a retrospective study, further investigations are required. The protocol was approved by the ethics review committee at Osaka Medical College (No. 2422) and was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000033088).

The usefulness of intraoperative neurological monitoring for esophageal cancer with double aortic arch; a case report.

BACKGROUND: Double aortic arch (DAA) is a congenital anomaly of the aorta. Esophageal cancer with DAA is rare, and consequently, the appropriate surgical approach has not been standardized. Herein, we report the utilization of intraoperative neurological monitoring (IONM) system to preserve the function of the recurrent laryngeal nerve. CASE PRESENTATION: A 79-year-old man with esophageal cancer was diagnosed with DAA incidentally. The descending aorta was located on the right side of the thoracic vertebrae. Safe dissection of the mediastinal lymph nodes was difficult using the right transthoracic approach because of the anatomical abnormalities. During surgery, we used cervical mediastinoscopy combined with the IONM system to preserve the bilateral recurrent laryngeal nerves. Severe complications, including recurrent nerve palsy, were not observed postoperatively. CONCLUSION: IONM may be useful for evaluation of the function of the recurrent laryngeal nerve, and it would be suitable for atypical cases of esophageal cancer.

The crossover technique for intracorporeal esophagojejunostomy following laparoscopic total gastrectomy: a simple and safe technique using a linear stapler and two barbed sutures.

BACKGROUND: Totally laparoscopic gastrectomy (LG) is preferred over open gastrectomy because it allows safe anastomosis, a small wound, and early bowel recovery. However, esophagojejunostomy (EJS) following laparoscopic total gastrectomy (LTG) remains technically challenging. To popularize LTG, a secure method of reconstruction must be developed. We present a simple and safe technique for intracorporeal EJS following LTG. METHODS: Our modified technique for intracorporeal EJS as a part of Roux-en-Y reconstruction following LTG incorporates an isoperistaltic stapled EJS with closure of the entry hole using two unidirectional barbed sutures. First, a side-to-side isoperistaltic EJS is created between the dorsal and left side of the esophagus and the jejunal arm. Second, the opening for the stapler is closed with a two-layer continuous suture using two 15-cm 3-0 V-Loc suture devices. The full-thickness inner layer closure commences from the sides of the staple lines and progresses toward the center of the enterotomy. During suturing, the remaining thread is utilized to apply tension and lift the enterotomy. Once the full-thickness layer closure is complete at the center of the enterotomy, suturing of the second seromuscular layer is started in the forward direction toward each corner to give a crossover-shaped suturing line. RESULTS: From February 2012 to October 2017, 27 patients with gastric cancer underwent LTG with intracorporeal stapled EJS as a part of Roux-en-Y reconstruction. All procedures were successfully performed without any intra- or postoperative anastomosis-related complications. No conversion to other procedures was required. The mean suturing time was 19.1 ± 9.5 min. The mean postoperative time to tolerating a liquid diet was 3.3 days, and the mean hospital stay was 12.1 days. CONCLUSIONS: We herein report our procedure for intracorporeal EJS using a linear stapler and barbed sutures. This technique is simple and feasible and has acceptable morbidity.

Analysis of Extracellular Vesicles in Gastric Juice from Gastric Cancer Patients.

Extracellular vesicles (EVs) are secretory membrane vesicles containing lipids, proteins, and nucleic acids; they function in intercellular transport by delivering their components to recipient cells. EVs are observed in various body fluids, i.e., blood, saliva, urine, amniotic fluid, and ascites. EVs secreted from cancer cells play important roles in the formation of their environment, including fibrosis, angiogenesis, evasion of immune surveillance, and even metastasis. However, EVs in gastric juice (GJ-EVs) have been largely unexplored. In this study, we sought to clarify the existence of GJ-EVs derived from gastric cancer patients. GJ-EVs were isolated by the ultracentrifuge method combined with our own preprocessing from gastric cancer (GC) patients. We verified GJ-EVs by morphological experiments, i.e., nanoparticle tracking system analysis and electron microscopy. In addition, protein and microRNA markers of EVs were examined by Western blotting analysis, Bioanalyzer, or quantitative reverse transcription polymerase chain reaction. GJ-EVs were found to promote the proliferation of normal fibroblast cells. Our findings suggest that isolates from the GJ of GC patients contain EVs and imply that GJ-EVs partially affect their microenvironments and that analysis using GJ-EVs from GC patients will help to clarify the pathophysiology of GC.

Nogo-B (Reticulon-4B) functions as a negative regulator of the apoptotic pathway through the interaction with c-FLIP in colorectal cancer cells.

Nogo-B is a member of the Nogo/Reticulon-4 family and has been reported to be an inducer of apoptosis in certain types of cancer cells. However, the role of Nogo-B in human cancer remains less understood. Here, we demonstrated the functions of Nogo-B in colorectal cancer cells. In clinical colorectal cancer specimens, Nogo-B was obviously overexpressed, as determined by immunohistochemistry; and Western blot analysis showed its expression level to be significantly up-regulated. Furthermore, knockdown of Nogo-B in two colorectal cancer cell lines, SW480 and DLD-1, by transfection with si-RNA (siR) resulted in significantly reduced cell viability and a dramatic increase in apoptosis with insistent overexpression of cleaved caspase-8 and cleaved PARP. The transfection with Nogo-B plasmid cancelled that apoptosis induced by siRNogoB in SW480 cells. Besides, combinatory treatment with siR-Nogo-B/staurosporine (STS) or siR-Nogo-B/Fas ligand (FasL) synergistically reduced cell viability and increased the expression of apoptotic signaling proteins in colorectal cancer cells. These results strongly support our contention that Nogo-B most likely played an oncogenic role in colorectal cancer cells, mainly by negatively regulating the extrinsic apoptotic pathway in them. Finally, we revealed that suppression of Nogo-B caused down-regulation of c-FLIP, known as a major anti-apoptotic protein, and activation of caspase-8 in the death receptor pathway. Interaction between Nogo-B and c-FLIP was shown by immunoprecipitation and immunofluorescence studies. In conclusion, Nogo-B was shown to play an important negative role in apoptotic signaling through its interaction with c-FLIP in colorectal cancer cells, and may thus become a novel therapeutic target for colorectal cancer.

Preoperative Chemotherapy May Not Influence the Remnant Liver Regenerations and Outcomes After Hepatectomy for Colorectal Liver Metastasis.

BACKGROUND: Various chemotherapy regimens have been shown to improve outcomes when administered before tumor excision surgery. However, there is no consensus on the utility of multidisciplinary treatment with preoperative chemotherapy for treating colorectal liver metastasis (CLM). MATERIALS AND METHODS: Two hundred-fifty patients who underwent hepatectomy were retrospectively analyzed using propensity score matching. Postoperative outcomes were evaluated with a focus on the effect of pre-hepatectomy chemotherapy on regeneration of the remnant liver in patients with CLM. The remnant liver volumes (RLVs) were postoperatively measured with multidetector computed tomography on days 7 and months 1, 2, 5, and 12 after the operation. RESULTS: RLV regeneration and blood test results did not significantly differ between patients who underwent preoperative chemotherapy versus those who did not immediately after surgery or at any time point from postoperative day 7 to postoperative month 12. The 1-, 2-, and 3-year overall survival (OS) rates for all patients were 94.6, 86.2, and 79.9%, respectively; the corresponding disease-free survival (RFS) rates were 49.3, 38.6, and 33.7%, respectively. There were no significant differences in OS and RFS between the two groups after hepatic resection. The recurrence rates, including marginal and intrahepatic recurrences, as well as resection frequency of the remnant liver were not significantly different between the two groups. CONCLUSION: Preoperative chemotherapy may have no appreciable benefit for patients with CLM in terms of perioperative and long-term outcomes.

Protocol for enhanced recovery after surgery improves short-term outcomes for patients with gastric cancer: a randomized clinical trial.

BACKGROUND: The feasibility of the use of the enhanced recovery after surgery (ERAS) protocol in patients with gastric cancer remains unclear. METHODS: This study was a single-center, prospective randomized trial involving patients with gastric cancer undergoing curative gastrectomy. The primary end point was the length of postoperative hospital stay. Secondary end points were the postoperative complication rate, admission costs, weight loss, and amount of physical activity. RESULTS: From July 2013 to June 2015, we randomized 148 patients into an ERAS protocol group (n = 73) and a conventional protocol group (n = 69); six patients withdrew from the study. The hospital stay was significantly shorter in the ERAS protocol group than in the conventional protocol group (9 days vs 10 days; P = 0.037). The ERAS protocol group had a significantly lower rate of postoperative complications of grade III or higher (4.1% vs 15.4%; P = 0.042) and reduced costs of hospitalization (JPY 1,462,766 vs JPY 1,493,930; P = 0.045). The ratio of body weight to preoperative weight at 1 week and 1 month after the operation was higher in the ERAS protocol group (0.962 vs 0.957, P = 0.020, and 0.951 vs 0.937, P = 0.021, respectively). The ERAS protocol group recorded more physical activity in the first week after surgery. CONCLUSIONS: The ERAS protocol is safe and efficient, and seems to improve the postoperative course of patients with gastric cancer.

Chymase inhibitor prevents the development and progression of non-alcoholic steatohepatitis in rats fed a high-fat and high-cholesterol diet.

The effect of the chymase inhibitor TY-51469 on the development and progression of non-alcoholic steatohepatitis (NASH) was evaluated in rats fed a high-fat and high-cholesterol (HFC) diet. To evaluate the preventive effect of TY-51469 on the development of NASH, stroke-prone spontaneously hypertensive rat 5 (SHRSP5)/Dmcr rats were fed either a normal or HFC diet for 8 weeks, and concurrently administered either placebo or TY-51469 (1 mg/kg per day). To evaluate the effect of TY-51469 on the survival rate, TY-51469 was administered either concurrently with HFC diet (pretreated group) or 8 weeks after HFC diet at which point NASH had developed (posttreated group). Eight weeks after HFC diet, significant increases of steatosis, fibrosis and chymase-positive cells were observed in liver from the placebo-treated rats. Significant increases of myeloperoxidase, transforming growth factor-ß, matrix metalloproteinase-9, and collagen I mRNA levels were also observed. However, all parameters were significantly attenuated in the TY-51469-treated group. A survival rate of the placebo-treated group fed the HFC diet was 0% at 14 weeks. In comparison, the rates of TY-51469-pretreated and TY-51469-posttreated groups were 100% and 50% at 14 weeks, respectively. Chymase inhibitor may be applicable to preventing the development and progression of NASH.

Laparoscopic gastrointestinal anastomoses using knotless barbed absorbable sutures are safe and reproducible: a single-center experience with 242 patients.

OBJECTIVE: Intracorporeal reconstruction of the digestive tract is technically challenging. The V-Loc 180 wound closure device (Covidien) is a self-anchoring unidirectional barbed suture that obviates the need for knot tying. The aim of this prospective cohort study was to investigate the use of the novel suture in gastrointestinal enterotomy closure. METHODS: The subjects comprised patients with malignant disease who were scheduled to undergo laparoscopic gastrectomy with curative intent. The barbed suture was used to close the entry hole for the linear stapler during intracorporeal reconstruction following laparoscopic gastric resection. The primary endpoint was the proportion of patients who developed anastomotic leakage at the site where the barbed suture was applied. RESULTS: Between July 2012 and March 2015, 242 patients were enrolled. Of 362 anastomoses, the enterotomy hole at 256 sites was closed using the barbed suture. These 256 sites consisted of 95 gastroduodenostomies, 25 gastrogastrostomies, 13 gastrojejunostomies, 90 jejunojejunostomies, 17 esophagojejunostomies and 16 primary closures of the stomach following local gastric resection. There were no anastomosis-related complications, conversion to usual sutures, mechanical closure of the entry hole and reoperation due to adhesive obstructions or mortality over a median follow-up period of 17.8 months. CONCLUSIONS: The use of the unidirectional barbed absorbable suture for gastrointestinal closure is safe and effective in laparoscopic gastrectomy.

Reticulon 4 is necessary for endoplasmic reticulum tubulation, STIM1-Orai1 coupling, and store-operated calcium entry.

Despite recent advances in understanding store-operated calcium entry (SOCE) regulation, the fundamental question of how ER morphology affects this process remains unanswered. Here we show that the loss of RTN4, is sufficient to alter ER morphology and severely compromise SOCE. Mechanistically, we show this to be the result of defective STIM1-Orai1 coupling because of loss of ER tubulation and redistribution of STIM1 to ER sheets. As a functional consequence, RTN4-depleted cells fail to sustain elevated cytoplasmic Ca(2+) levels via SOCE and therefor are less susceptible to Ca(2+) overload induced apoptosis. Thus, for the first time, our results show a direct correlation between ER morphology and SOCE and highlight the importance of RTN4 in cellular Ca(2+) homeostasis.

Recombinant human soluble thrombomodulin improved lipopolysaccharide/d-galactosamine-induced acute liver failure in mice.

The effect of recombinant human soluble thrombomodulin (TM-α) on acute liver failure (ALF) is unclear, and we elucidated the effect of TM-α in lipopolysaccharide (LPS)/d-galactosamine (GalN)-induced ALF in mice. Placebo (saline) or TM-α (100 mg/kg) was administered 1 h after LPS/GalN administration. Survival rates were evaluated for 24 h after LPS/GalN administration. Plasma and liver samples were evaluated 1, 3, and 7 h after LPS/GalN administration. Survival rates were significantly higher in the TM-α-treated group than in the placebo group. A significant augmentation of plasma high-mobility group box 1 protein (HMGB1) was observed 7 h after LPS/GalN administration. In the TM-α-treated mice, plasma HMGB1 was significantly lower than in the placebo group. A significant augmentation of hepatic nuclear factor (NF)-κB p65 was observed in the placebo-treated group, whereas a significant reduction, relative to placebo, was observed in the TM-α-treated group. Hepatic expression of tumor necrosis factor (TNF)-α and myeloperoxidase were significantly increased in the placebo group, and were similarly significantly attenuated in the TM-α-treated group. TM-α treatment also produced a significant attenuation of liver neutrophil accumulation after LPS/GalN administration. Thus, TM-α may become a useful treatment strategy for reducing the symptoms of ALF via the attenuation of LPS/GalN-induced HMGB1 levels.

Absence of Nogo-B (reticulon 4B) facilitates hepatic stellate cell apoptosis and diminishes hepatic fibrosis in mice.

Nogo-B (reticulon 4B) accentuates hepatic fibrosis and cirrhosis, but the mechanism remains unclear. The aim of this study was to identify the role of Nogo-B in hepatic stellate cell (HSC) apoptosis in cirrhotic livers. Cirrhosis was generated by carbon tetrachloride inhalation in wild-type (WT) and Nogo-A/B knockout (Nogo-B KO) mice. HSCs were isolated from WT and Nogo-B KO mice and cultured for activation and transformation to myofibroblasts (MF-HSCs). Human hepatic stellate cells (LX2 cells) were used to assess apoptotic responses of activated HSCs after silencing or overexpressing Nogo-B. Livers from cirrhotic Nogo-B KO mice showed significantly reduced fibrosis (P < 0.05) compared with WT mice. Apoptotic cells were more prominent in fibrotic areas of cirrhotic Nogo-B KO livers. Nogo-B KO MF-HSCs showed significantly increased levels of apoptotic markers, cleaved poly (ADP-ribose) polymerase, and caspase-3 and -8 (P < 0.05) compared with WT MF-HSCs in response to staurosporine. Treatment with tunicamycin, an endoplasmic reticulum stress inducer, increased cleaved caspase-3 and -8 levels in Nogo-B KO MF-HSCs compared with WT MF-HSCs (P < 0.01). In LX2 cells, Nogo-B knockdown enhanced apoptosis in response to staurosporine, whereas Nogo-B overexpression inhibited apoptosis. The absence of Nogo-B enhances apoptosis of HSCs in experimental cirrhosis. Selective blockade of Nogo-B in HSCs may represent a potential therapeutic strategy to mitigate liver fibrosis.

Reticulon 4B (Nogo-B) facilitates hepatocyte proliferation and liver regeneration in mice.

UNLABELLED: Nogo-B, also known as reticulon 4B, promotes liver fibrosis and cirrhosis by facilitating the transforming growth factor ß (TGF-ß) signaling pathway in activated hepatic stellate cells. The aim of this study was to determine the role of Nogo-B in hepatocyte proliferation and liver regeneration. Partial hepatectomy (PHx, 70% resection) was performed in male wild-type (WT) and Nogo-A/B knockout mice (referred to as Nogo-B KO mice). Remnant livers were isolated 2 hours, 5 hours, and 1, 2, 3, 7, and 14 days after PHx. Hepatocyte proliferation was assessed by Ki67 labeling index. Quantitative real-time polymerase chain reaction was performed for genes known to be involved in liver regeneration. Hepatocytes isolated from WT and Nogo-B KO mice were used to examine the role of Nogo-B in interleukin-6 (IL-6), hepatocyte growth factor (HGF), epidermal growth factor (EGF), and TGF-ß signaling. Nogo-B protein levels increased in the regenerating livers in a time-dependent manner after PHx. Specifically, Nogo-B expression in hepatocytes gradually spread from the periportal toward the central areas by 7 days after PHx, but receded notably by 14 days. Nogo-B facilitated IL-6/signal transducer and activator of transcription 3 signaling, increased HGF-induced but not EGF-induced hepatocyte proliferation, and tended to reduce TGF-ß1-induced suppression of hepatocyte proliferation in cultured hepatocytes. Lack of Nogo-B significantly induced TGF-ß1 and inhibitor of DNA binding expression 1 day after PHx and IL-6 and EGF expression 2 days after PHx. Lack of Nogo-B delayed hepatocyte proliferation but did not affect the liver-to-body ratio in the regenerative process. CONCLUSION: Nogo-B expression in hepatocytes facilitates hepatocyte proliferation and liver regeneration.

Chymase inhibition attenuates lipopolysaccharide/ d-galactosamine-induced acute liver failure in hamsters.

BACKGROUND/AIMS: Chymase inhibition has been shown to attenuate matrix metalloproteinase (MMP)-9 and tumor necrosis factor (TNF)-α, both of which are associated with the pathogenesis of acute liver failure (ALF). This study investigated the effects of the chymase inhibitor TY-51469 on lipopolysaccharide (LPS)/D-galactosamine (GalN)-induced ALF in hamsters. METHODS: TY-51469 (10 or 30 mg/kg) or placebo was administered 1 h before the LPS (160 µg/kg)/GalN (400 mg/kg) injection. RESULTS: Hepatic chymase activity was significantly increased after the LPS/GalN injection, but the significant increase was dose-dependently and significantly attenuated by treatment with TY-51469. Significant increases in hepatic MMP-9 activity and TNF-α concentration were observed after the LPS/GalN injection, but these increases were also attenuated by treatment with TY-51469. Plasma aspartate aminotransferase and alanine aminotransferase activities were significantly increased after LPS/GalN injection in the placebo-treated group, but the increases were significantly attenuated in the TY-51469-treated group. The area of hepatic necrotic after LPS/GalN injection was significantly reduced by treatment with TY-51469. Treatment with TY-51469 resulted in significant reductions in the hepatic malondialdehyde concentration, mast cell numbers, and gene expressions of interleukin-1ß and myeloperoxidase. DISCUSSION: Chymase inhibition could be a useful strategy to attenuate LPS/GalN-induced ALF in hamsters.

Chymase inhibitor ameliorates hepatic steatosis and fibrosis on established non-alcoholic steatohepatitis in hamsters fed a methionine- and choline-deficient diet.

AIM: Chymase plays a role in the augmentation of angiotensin II formation, which is involved in liver fibrosis. The therapeutic effects of a chymase inhibitor, TY-51469, on established hepatic steatosis and fibrosis were investigated in a model of developed non-alcoholic steatohepatitis. METHODS: Hamsters were fed a normal diet or methionine- and choline-deficient (MCD) diet for 12 weeks. Then, treatment with TY-51469 (1 mg/kg per day) or placebo was initiated, and the treatment was continued concurrently with the MCD diet for an additional 12 weeks. RESULTS: At 12 weeks after initiating the MCD diet, marked hepatic steatosis and fibrosis were observed in MCD diet-fed hamsters. Malondialdehyde and gene expression levels of collagen I, collagen III, α-smooth muscle actin (α-SMA) and Rac-1 in liver extracts were also increased in the MCD-diet-fed hamsters at 12 weeks. At 24 weeks, hepatic steatosis and fibrosis were more prominent in the placebo-treated hamsters that were fed the MCD-diet for 24 weeks versus 12 weeks. Hamsters treated with TY-51469 for 12 weeks after being on a 12-week MCD diet had significant ameliorations in both hepatic steatosis and fibrosis, and there were no significant differences compared to normal diet-fed hamsters. There were significant augmentations in angiotensin II and malondialdehyde, and gene expressions of collagen I, collagen III, α-SMA and Rac-1 in the placebo-treated hamsters at 24 weeks; however, these levels were reduced to normal levels in the TY-51469-treated hamsters. CONCLUSION: TY-51469 not only prevented the progression of hepatic steatosis and fibrosis, but also ameliorated hepatic steatosis and fibrosis.

Esophago-bronchial fistula treated by the Over-The-Scope-Clipping (OTSC) system with argon beam electrocoagulation: A case report.

RATIONALE: An esophago-bronchial fistula is one of the rare postoperative complications of esophageal cancer. There are various medical treatments, including suturing, endoscopic clip, and fibrin glue. However, these treatments often lead to unsatisfactory results, causing physicians to opt for surgical alternatives. The Over-The-Scope-Clipping (OTSC) system offers an alternative method for fistula closure. It can capture a large amount of tissue and is able to compress the lesion until it has fully healed. However, data indicating the efficacy of OTSC for esophago-bronchial fistula are limited. PATIENT CONCERNS: A 64-year-old man presented with an esophago-bronchial fistula after surgery for esophageal cancer. We chose to use a stent as the first line of treatment, but the fistula did not close. DIAGNOSES: Intractable esophago-bronchial fistula associated with esophageal surgery. INTERVENTIONS AND OUTCOMES: On the 94th postoperative day, fistula closure with OTSC was performed, and no leakage of the contrast agent was observed during fluoroscopy. We also attempted to close the fistula by combining OTSC and argon plasma coagulation (APC) to burn off the scar tissue from around the fistula. The fistula gradually shrank after a total of 4 rounds of OTSC, and closure of the fistula was achieved on the 185th postoperative day. There were no adverse events during the treatment of this case. LESSONS: We demonstrate that OTSC is useful in the management of esophago-bronchial fistulas, and may become a standard procedure for the endoscopic treatment of esophago-bronchial fistulas, replacing the use of stents, clips, or glue.

Combined Intraoperative Identification and Monitoring of Recurrent Laryngeal Nerve Paresis during Minimally Invasive Esophagectomy: Surgical Technique Using Nerve Integrity Monitoring for Esophageal Carcinoma.

Recurrent laryngeal palsy occurs after No. 106 rec RL lymphadenectomy procedure, which is assumed to cause postoperative respiratory complications. A 71-year-old Japanese man with T1b N0 M0 stage 1 esophageal cancer was scheduled for thoracoscopic esophagectomy with two-field lymph node dissection using nerve integrity monitoring (NIM). The patient demonstrated an uneventful postoperative course with 56 days remission. Under general anesthesia conditions, a single-lumen intubation tube was inserted for NIM. The automatic periodic stimulation electrode was placed on the bilateral vagus nerves on the left and right, respectively. The NIM had set and enabled the identification of the nerve accurately and continuous intraoperative nerve monitoring using impulses from the stimulation probe. The postoperative outcomes and comparison of the potential amplitudes of electromyography were observed while no postoperative vocal cord paresis was present. Combined intraoperative identification and monitoring of recurrent laryngeal nerve significantly changes the quality of the lymphadenectomy procedure and is a promising optical imaging technique. It has gained recognition for being able to reduce or prevent recurrent laryngeal nerve paralysis. It was considered a reasonable method, but it has been superseded by NIM, which is a novel technology.