Impact of Locoregional Therapies for Brain Lesions on Survival in Patients With Non-small Cell Lung Cancer With Multiple Extrathoracic Metastases.

BACKGROUND/AIM: The treatment of brain metastases in patients with non-small cell lung cancer (NSCLC) typically involves surgery, irradiation, and chemotherapy (single or combination therapy). However, the impact of these therapies on the survival of patients with NSCLC with multiple extrathoracic metastases has not yet been determined. Therefore, in the present study, we examined the prognostic effect of multimodal treatment for brain metastases in patients with NSCLC with multiple extrathoracic metastases in the absence of driver mutations. PATIENTS AND METHODS: Patients with NSCLC with multiple extrathoracic metastases (including at least one brain metastasis), who visited Saitama Medical Center, Saitama Medical University from January 1, 2010 to December 31, 2016, were enrolled in this study; follow-up was conducted until December 31, 2021. RESULTS: A total of 56 patients were enrolled, including 12 and 44 patients with single and multiple brain metastases, respectively. The median overall survival (OS) for all patients was 4.9 months, and did not differ significantly between patients with single and multiple brain metastases (3.0 vs. 4.9 months, respectively). The selection of locoregional treatment for brain metastases did not depend on Karnofsky performance status (p=0.0862). Among patients with multiple brain metastases, the OS for those who underwent craniotomy followed by whole brain radiation therapy (WBRT), those who received only WBRT, and those treated without locoregional therapy was 47.7, 3.9, and 15.9 months, respectively (p=0.00382). CONCLUSION: Surgical resection followed by radiation therapy is an effective treatment option for brain metastases in patients with multiple metastases. However, WBRT alone did not improve prognosis.

Effects of Sleeve Gastrectomy on Nonalcoholic Fatty Liver Disease in an Obese Rat Model.

BACKGROUND/AIM: Laparoscopic sleeve gastrectomy (SG) is an increasingly used bariatric surgery, which is reported to be effective for nonalcoholic fatty liver disease (NAFLD). Recently, activation of farnesoid X receptor (FXR), which is a nuclear receptor of bile acid (BA), was reported to contribute to the resolution of NAFLD. However, it is unclear whether SG has an effect on expression of FXR in the liver. We aimed to investigate the expression of FXR and its related factors in the liver after SG and to clarify the relationship between changes in FXR expression and NAFLD in an obese rat model. METHODS: Thirty male Zucker fatty rats were divided into three groups: sham-operated (SO) control, pair-fed (PF) control, and SG. Eight weeks after the surgery, metabolic parameters, plasma levels of total BA and liver enzymes, liver triglyceride (TG) content, and mRNA expression of FXR and its related factors, such as small heterodimer partner (SHP) and peroxisome proliferator-activated receptor α (PPARα), were measured. RESULTS: Metabolic parameters in the SG group were significantly improved compared with the SO group. Liver enzymes and TG were significantly lower in the SG group than in the SO group. Plasma levels of BA were significantly higher in the SG group than in the SO and PF groups. mRNA expression of FXR, SHP, and PPARα in the liver was significantly higher in the SG group than in the SO group. CONCLUSIONS: These results suggest that the effects of SG on NAFLD should be associated with the expression of the FXR pathway in the liver in a Zucker fatty rat model.

Effects of sleeve gastrectomy and gastric banding on the hypothalamic feeding center in an obese rat model.

PURPOSE: Laparoscopic sleeve gastrectomy (SG) and gastric banding (GB) are popular bariatric procedures for treating morbid obesity. This study aimed to investigate changes in the hypothalamic feeding center after these surgeries in a diet-induced obese rat model. METHODS: Obesity was induced in 60 Sprague-Dawley rats using a high-energy diet for 6 weeks. These rats were divided into four groups: the sham-operated (SO) control, pair-fed (PF) control, SG and GB groups. Six weeks after the surgery, metabolic parameters, the plasma levels of leptin, ghrelin, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) and the hypothalamic mRNA expressions of neuropeptide Y (NPY) and pro-opiomelanocortin (POMC) were measured. RESULTS: Compared with those observed in the SO group, the body and fat tissue weights were significantly decreased and the metabolic parameters were significantly improved in the PF, SG and GB groups 6 weeks after surgery. The plasma ghrelin levels were significantly lower and the PYY and GLP-1 levels were significantly higher in the SG group than in the PF, GB and SO groups. Compared with that seen in the PF and GB groups, the hypothalamic mRNA expression of NPY was significantly lower and the expression of POMC was significantly higher in the SG group. CONCLUSIONS: SG may affect the neurological pathway associated with appetite in the hypothalamus and thereby control ingestive behavior.

Effects of different pressure levels of CO2 pneumoperitoneum on liver regeneration after liver resection in a rat model.

BACKGROUND: A recent study demonstrated that high pressure of carbon dioxide (CO2) pneumoperitoneum before liver resection impairs postoperative liver regeneration. This study was aimed to investigate effects of varying insufflation pressures of CO2 pneumoperitoneum on liver regeneration using a rat model. METHODS: 180 male Wistar rats were randomly divided into three groups: control group (without preoperative pneumoperitoneum), low-pressure group (with preoperative pneumoperitoneum at 5 mmHg), and high-pressure group (with preoperative pneumoperitoneum at 10 mmHg). After pneumoperitoneum, all rats were subjected to 70% partial hepatic resection and then euthanized at 0 min, 12 h, and on postoperative days (PODs) 1, 2, 4, and 7. Following outcome parameters were used: liver regeneration (liver regeneration rate, mitotic count, Ki-67 labeling index), hepatocellular damage (serum aminotransferases), oxidative stress [serum malondialdehyde (MDA)], interleukin-6 (IL-6), and hepatocyte growth factor (HGF) expression in the liver tissue. RESULTS: No significant differences were observed for all parameters between control and low-pressure groups. The liver regeneration rate and mitotic count were significantly decreased in the high-pressure group than in control and low-pressure groups on PODs 2 and 4. Postoperative hepatocellular damage was significantly greater in the high-pressure group on PODs 1, 2, 4, and 7 compared with control and/or low-pressure groups. Serum MDA levels were significantly higher in the high-pressure group on PODs 1 and 2, and serum IL-6 levels were significantly higher in the high-pressure group at 12 h and on POD 1, compared with control and/or low-pressure groups. The HGF tissue expression was significantly lower in the high-pressure group at 12 h and on PODs 1 and 4, compared with that in control and/or low-pressure groups. CONCLUSIONS: High-pressure pneumoperitoneum before 70% liver resection impairs postoperative liver regeneration, but low-pressure pneumoperitoneum has no adverse effects. This study suggests that following laparoscopic liver resection using appropriate pneumoperitoneum pressure, no impairment of liver regeneration occurs.

Effects of the dihydrolipoyl histidinate zinc complex against carbon tetrachloride-induced hepatic fibrosis in rats.

PURPOSE: This study investigated the effects of an antioxidant, dihydrolipoyl histidinate zinc complex (DHLHZn), on the hepatic fibrosis in the carbon tetrachloride (CCl4) rat model. METHODS: The animals were divided into three groups: control, CCl4, and CCl4+DHLHZn. A histological assessment of the liver fibrosis was performed using stained liver samples. The oxidative stress and antioxidant levels were evaluated by measuring the malondialdehyde (MDA) and glutathione (GSH) levels in the liver. In addition, cultured human hepatic stellate cells (LI90) were exposed to antimycin-A (AMA) and divided into four groups: control, DHLHZn, AMA, and AMA+DHLHZn. The effects of DHLHZn on AMA-induced fibrosis were evaluated by measuring the expression of transforming growth factor (TGF)-ß1 and collagen α1 (I). RESULTS: The hepatic fibrosis in the CCl4+DHLHZn group was attenuated compared to that in the CCl4 group. The MDA levels in the CCl4+DHLHZn group were significantly lower than those of the CCl4 group, whereas the GSH levels in the CCl4+DHLHZn group were significantly higher than those of the CCl4 group. Furthermore, the relative mRNA expression of TGF-ß1 and collagen α1 (I) in the AMA+DHLHZn group was significantly lower than that in the AMA group. CONCLUSION: DHLHZn may attenuate the hepatic fibrosis induced by CCl4 by decreasing the degree of oxidative stress.

Effects of sleeve gastrectomy on lipid metabolism in an obese diabetic rat model.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is a popular bariatric procedure for treating morbid obesity. This study aimed to investigate the relation between SG and lipid metabolism in an obese diabetic rat model. METHODS: Forty-five male Zucker diabetic fatty (ZDF) rats were divided into three groups: sham-operated (SO) control, gastric banding (GB), and SG. Six weeks after surgery, metabolic parameters, including plasma adiponectin level, small bowel transit, mRNA expression of peroxisome proliferator-activated receptor (PPAR)-α and PPARγ in the liver, skeletal muscle and white adipose tissue, and that of adiponectin in white adipose tissue, and triglyceride (TG) contents in the liver and skeletal muscle were measured. RESULTS: Metabolic parameters in the GB and SG groups were significantly improved compared with those in the SO group. However, plasma total cholesterol (TC) and free fatty acid (FFA) concentrations were significantly lower while the plasma adiponectin level was significantly higher in the SG group than in the GB and SO groups. In addition, small bowel transit time was significantly shorter in the SG group than in the other two groups. Furthermore, in the SG group, mRNA expression of PPARα in the liver and skeletal muscle and that of adiponection and PPARγ in white adipose tissue were significantly higher, while TG in the liver and skeletal muscle were significantly lower, compared with those in the other two groups. CONCLUSIONS: These results suggest that SG improves lipid metabolism compared with GB, although there were no significant differences in the effect on weight loss between the two procedures.

Increased oxidative stress may lead to impaired adaptive cytoprotection in the gastric mucosa of portal hypertensive rat.

BACKGROUND AND AIMS: In the gastric mucosa of portal hypertensive rats, adaptive cytoprotection against ethanol-induced damage is impaired. The aim of this study was to determine relation between impaired adaptive cytoprotection and oxidative stress. METHODS: Portal hypertension was produced in male Sprague-Dawley rats by inducing staged portal vein occlusion. Oxidative stress levels were evaluated by measuring malondialdehyde and nitrotyrosine levels in the rat gastric mucosa with or without 10% ethanol pretreatment. Inhibition of oxidative stress by an anti-oxidant agent was estimated, and glutathione levels were also measured. Adaptive cytoprotection to 70% ethanol treatment was evaluated by measuring the gastric mucosal injury index in the presence or absence of the anti-oxidant. RESULTS: The portal hypertensive gastric mucosa pretreated with 10% ethanol had significantly higher oxidative stress levels than the mucosa not pretreated with 10% ethanol. However, the sham-operated gastric mucosa pretreated with 10% ethanol had significantly lower oxidative stress levels than the mucosa not pretreated with 10% ethanol. Pretreatment with 10% ethanol increased glutathione levels in the sham-operated but not in the portal hypertensive gastric mucosa. Administration of the anti-oxidant agent prior to 10% ethanol pretreatment significantly reduced oxidative stress levels, increased glutathione levels, and decreased the injury index in response to 70% ethanol in the portal hypertensive gastric mucosa. CONCLUSION: Increased oxidative stress may lead to impaired adaptive cytoprotection in the gastric mucosa of portal hypertensive rats, probably through damage to the system of endogenous anti-oxidant production.

Initial Japanese experience with the LAP-BAND system.

INTRODUCTION: Laparoscopic bariatric surgery has gradually spread in Japan since it was introduced in 2000. In 2005, we introduced laparoscopic adjustable gastric banding (LAGB) with the LAP-BAND system into Japan. Here, we evaluate our intermediate-term results with the LAP-BAND system. METHODS: Between August 2005 and June 2010, 27 Japanese patients with morbid obesity (BMI ≥ 35 kg/m(2) ) underwent LAGB with the LAP-BAND system in our institution. Our patients' average weight was 111 kg and BMI was 41 kg/m(2) . All LAGB procedures were performed through the pars flaccida pathway with band fixation using gastric-to-gastric sutures. The average follow-up period was 48 months. RESULTS: All procedures were completed laparoscopically. One early complication (sudden cardiac arrest due to postoperative bleeding) and three late complications (port trouble, megaesophagus, and band slippage) were experienced, and reoperations were performed in three of the patients. Weight loss and percentage of excess weight loss on average were 26 kg and 53% after 3 years and 22 kg and 53% after 6 years, respectively. In line with this good weight loss, comorbidities, especially those of type 2 diabetes and metabolic syndrome were frequently resolved or improved. CONCLUSION: LAGB with the LAP-BAND system appears to be beneficial in obese Japanese patients.

Measurement of skin permeation/penetration of nanoparticles for their safety evaluation.

The aim of the present study was to quantitatively evaluate the skin permeation/penetration of nanomaterials and to consider their penetration pathway through skin. Firstly, penetration/permeation of a model fluorescent nanoparticle, Fluoresbrite®, was determined through intact rat skin and several damaged skins. Fluoresbrite® permeated through only needle-punctured skin. The permeation profiles of soluble high molecular compounds, fluorescein isothiocyanate-dextrans (FITC-dextrans, FDs), with different molecular weights were also measured for comparison. The effects of molecular sizes and different skin pretreatments on the skin barrier were determined on the skin penetration/permeation of Fluoresbrite® and FDs. Fluoresbrite® was not permeated the intact skin, but FDs were permeated the skin. The skin distribution of titanium dioxide and zinc oxide nanoparticles was also observed after topical application of commercial cosmetics. Nanoparticles in sunscreen cosmetics were easily distributed into the groove and hair follicles after their topical application, but seldom migrated from the groove or follicles to viable epidermis and dermis. The obtained results suggested that nanoparticles did not permeate intact skin, but permeated pore-created skin. No or little permeation was observed for these nanomaterials through the stratum corneum.

A comparative study of gastric banding and sleeve gastrectomy in an obese diabetic rat model.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is now a typical restrictive bariatric procedure. The aim of this study was to evaluate the efficacy of SG in comparison with gastric banding (GB) in an obese diabetic rat model. METHODS: Forty-five male Zucker diabetic fatty rats were divided into three groups: sham-operated (SO) control, GB, and SG. The rats were followed for 6 weeks after surgery, and their body weight change, cumulative food intake, metabolic parameters, plasma levels of ghrelin, glucagon-like peptide-1 and adiponectin, oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and gastric emptying rate were measured. RESULTS: The GB and SG groups showed significant decreases in weight, cumulative intake, and metabolic parameters and significant improvement of OGTT and ITT results compared with the SO group. There were no significant differences in weight and cumulative food intake between the groups. However, the SG group showed significantly higher gastric emptying rate and plasma level of adiponectin and lower plasma levels of free fatty acid, total cholesterol, and ghrelin compared with the GB group. Furthermore, the SG group showed improvement of OGTT and ITT results in comparison with the GB group. CONCLUSIONS: In obese diabetic rats, SG may improve glucose and lipid metabolism compared with GB, although there was no significant difference in the effect on body weight loss between the two procedures. The hormonal and digestive changes induced by SG may have relevance to the effects on metabolism.

Multiple Tracheal Diverticula Detected by Multidetector-row Computed Tomography.

Multiple tracheal diverticula are rare. We report a case of a 62-year-old man who had multiple tracheal diverticula that were detected using multidetector-row computed tomography. Axial computed tomography images showed multiple air collections contiguous to the trachea. The multiple air collections were visible as outpouchings of the parts of the trachea between the cartilages, being located almost symmetrically on both lateral sides of the tracheal wall as seen on coronal multiplanar reconstruction images. Virtual bronchoscopy confirmed the presence of multiple openings in the tracheal wall of the diverticular necks. The alteration of the airway was better seen using volume-rendered reconstruction. Thin-slice multidetector-row computed tomography and advanced imaging techniques may increase the frequency of identification of multiple tracheal diverticula.

Short- and long-term outcomes after hepatic resection for hepatocellular carcinoma with concomitant esophageal varices in patients with cirrhosis.

BACKGROUND: Hepatic resection for hepatocellular carcinoma (HCC) in cirrhotic patients with esophageal varices (EV) is often avoided because of poor liver function reserve. Outcomes of resection in such cases have not been fully investigated. METHODS: We conducted a retrospective study of 134 cirrhotic patients (Child-Pugh class A or B) who underwent hepatic resection for HCC, comparing short- and long-term outcomes in patients with EV (n = 31) to those in patients without EV (n = 103). RESULTS: Patients with EV had higher tumor differentiation, fewer instances of portal invasion, lower liver function reserve, and more limited resections than did patients without EV. Of 31 patients with EV, four died of postoperative complication, and nine of liver failure, seven of HCC, two of ruptured EV, and two of other causes. Median survival time for patients who died of liver failure was 59 months. Mortality and morbidity rates after hepatic resection did not differ between patients with and without EV. The 5-year overall survival rate was significantly higher in patients with EV (70.1%) than in those without EV (47.5%, P = 0.045) but did not differ between patients without portal invasion with and without EV (P = 0.55). Presence of EV was not an independent predictor for survival. CONCLUSIONS: Short- and long-term outcomes of hepatic resection in HCC patients with and without EV are similar. Limited hepatic resection for early-stage tumor is an option for Child-Pugh class A or B patients with EV.