Protein kinase B (Akt) is known to be involved in proinflammatory and chemotactic events in response to injury. Akt activation also leads to the induction of heme oxygenase (HO)‐1. Up‐regulation of ...HO‐1 mediates potent, anti‐inflammatory effects and attenuates organ injury. Although studies have shown that 17β‐estradiol (E2) prevents organ damage following trauma‐hemorrhage, it remains unknown whether Akt/HO‐1 plays any role in E2‐mediated attenuation of hepatic injury following trauma‐hemorrhage. To study this, male rats underwent trauma‐hemorrhage (mean blood pressure, ∼40 mmHg for 90 min), followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, E2 (1 mg/kg body weight), E2 plus the PI‐3K inhibitor (Wortmannin), or the estrogen receptor (ER) antagonist (ICI 182,780). At 2 h after sham operation or trauma‐hemorrhage, plasma α‐GST and hepatic tissue myeloperoxidase (MPO) activity, IL‐6, TNF‐α, ICAM‐1, cytokine‐induced neutrophil chemoattractant‐1, and MIP‐2 levels were measured. Hepatic Akt and HO‐1 protein levels were also determined. Trauma‐hemorrhage increased hepatic injury markers (α‐GST and MPO activity), cytokines, ICAM‐1, and chemokine levels. These parameters were markedly improved in the E2‐treated rats following trauma‐hemorrhage. E2 treatment also increased hepatic Akt activation and HO‐1 expression compared with vehicle‐treated, trauma‐hemorrhage rats, which were abolished by coadministration of Wortmannin or ICI 182,780. These results suggest that the salutary effects of E2 on hepatic injury following trauma‐hemorrhage are in part mediated via an ER‐related, Akt‐dependent up‐regulation of HO‐1.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Cytomegalovirus (CMV) esophagitis is the second most common CMV disease of the gastrointestinal tract. This study aims to comprehensively analyze risk factors, clinical characteristics, endoscopic ...features, outcomes, and prognostic factors of CMV esophagitis. We retrospectively collected data of patients who underwent esophageal CMV immunohistochemistry (IHC) staining between January 2003 and April 2021 from the pathology database at the Chang Gung Memorial Hospital. Patients were divided into the CMV and non-CMV groups according to the IHC staining results. We enrolled 148 patients (44 CMV and 104 non-CMV patients). The risk factors for CMV esophagitis were male sex, immunocompromised status, and critical illness. The major clinical presentations of CMV esophagitis included epigastric pain (40.9%), fever (36.4%), odynophagia (31.8%), dysphagia (29.5%), and gastrointestinal bleeding (29.5%). Multiple diffuse variable esophageal ulcers were the most common endoscopic feature. The CMV group had a significantly higher in-hospital mortality rate (18.2% vs. 0%; p < 0.001), higher overall mortality rate (52.3% vs. 14.4%; p < 0.001), and longer admission duration (median, 24 days (interquartile range (IQR), 11−47 days) vs. 14 days (IQR, 7−24 days); p = 0.015) than the non-CMV group. Acute kidney injury (odds ratio (OR), 174.15; 95% confidence interval (CI), 1.27−23,836.21; p = 0.040) and intensive care unit admission (OR, 26.53; 95% CI 1.06−665.08; p = 0.046) were predictors of in-hospital mortality. In conclusion, the mortality rate of patients with CMV esophagitis was high. Physicians should be aware of the clinical and endoscopic characteristics of CMV esophagitis in high-risk patients for early diagnosis and treatment.
Salvage chemotherapy is the mainstay of treatment for metastatic gastric cancer (mGC). This study aimed to clarify the effects of palliative gastrectomy (PG) and identify prognostic factors in mGC ...patients undergoing PG.
This was a retrospective review of 333 mGC patients receiving PG or a non-resection procedure (NR) between 2000 and 2010. Clinicopathological factors affecting the prognosis of these patients were collected prospectively and analyzed.
One hundred and ninety-three patients underwent PG and 140 NR. The clinicopathological characteristics were comparable between the two groups except for metastatic pattern. There were no significant differences in postoperative morbidity and mortality between the two groups. The PG group had a significantly longer median overall survival compared with the NR group (7.7 months vs. 4.9 months). In the PG group, age ≤58 years, preoperative albumin level >3 g/dL, ratio of metastatic to examined lymph nodes ≤0.58, and administration of chemotherapy were independent prognostic factors in multivariate analysis.
Patients undergoing PG had better outcomes than those undergoing NR. Among the patients undergoing resection, age ≤58 years, a better preoperative nutritional status, less nodal involvement and postoperative chemotherapy independently affected patient survival.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The survival benefits of conversion surgery in patients with metastatic gastric cancer (mGC) remain unclear. Thus, this study aimed to determine the outcomes of conversion surgery compared to ...in-front surgery plus palliative chemotherapy (PCT) or in-front surgery alone for mGC. We recruited 182 consecutive patients with mGC who underwent gastrectomy, including conversion surgery, in-front surgery plus PCT, and in-front surgery alone at Linkou Chang Gung Memorial Hospital from 2011 to 2019. The tumor was staged according to the 8th edition of the American Joint Committee on Cancer. Patient demographics and clinicopathological factors were assessed. Overall survival (OS) was evaluated using the Kaplan−Meier curve and compared among groups. Conversion surgery showed a significantly longer median OS than in-front surgery plus PCT or in-front surgery alone (23.4 vs. 13.7 vs. 5.6 months; log rank p < 0.0001). The median OS of patients with downstaging (pathological stage I−III) was longer than that of patients without downstaging (stage IV) (30.9 vs. 18.0 months; p = 0.016). Our study shows that conversion surgery is associated with survival benefits compared to in-front surgery plus PCT or in-front surgery alone in patients with mGC. Patients who underwent conversion surgery with downstaging had a better prognosis than those without downstaging.
Determining the survival outcome for gastric cancer patients with metastases to more than 15 regional lymph nodes is difficult. This study aims to develop a lymph node metastatic ratio (LNR)-based ...prognostic model to predict the survival outcome after D2 surgery in such patient groups.
Our study retrospectively enrolled 139 gastric cancer patients with metastases to more than 15 regional lymph nodes who underwent D2 surgery between 2007 and 2014. Clinicopathologic variables to predict overall survival (OS) using multivariate Cox regression were selected to create a prognostic model.
The prognostic model for predicting OS was developed based on five independent factors, namely, T-classification (T2 or T3 vs. T4), LNR (<0.80 vs. ≥0.80), carcinoembryonic antigen level (<5 vs. ≥5 ng/ml), Eastern Cooperative Oncology Group performance scale (scale 0–1 vs. ≥2), and adjuvant chemotherapy (yes vs. no). Using the prognostic score, patients were stratified into good, intermediate, and poor prognostic groups. The median OS in the good, intermediate, and poor prognostic risk groups was 32.0 months (95% confidence interval CI: 22.3–41.7), 12.4 months (95% CI: 8.5–16.3), and 5.4 months (95% CI: 2.1–8.7), respectively. The c-index of the prognostic model was 0.79 (95% CI: 0.71–0.87).
This study developed an accurate LNR-based prognostic model for predicting the survival outcome after D2 surgery in gastric cancer patients with metastasis to more than 15 regional lymph nodes. This model might assist clinicians in prognostic stratification of such patients and convince eligible patients to receive adjuvant chemotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background:
Dexlansoprazole has been shown to be efficacious for the treatment of gastroesophageal reflux disease. However, there is a paucity of data about its efficacy for Helicobacter pylori ...eradication. The aim of this study was to evaluate the efficacy of dexlansoprazole for H. pylori eradication as triple therapy in real-world practice.
Methods:
Adult patients with endoscopically proven H. pylori related peptic ulcer diseases or gastritis were recruited for this study. The eradication status was assessed based on the results of the 13C-urea breath test performed 4 weeks after treatment. According to the different treatment regimens, the patients were allocated to group A: Esomeprazole 40 mg b.i.d. + amoxicillin 1 g b.i.d. + clarithromycin 500 mg b.i.d. for 7 days; group B: Esomeprazole 40 mg q.d. + amoxicillin 1 g b.i.d. + clarithromycin 500 mg b.i.d. for 7 days, or group C: Dexlansoprazole 60 mg q.d. + amoxicillin 1 g b.i.d. + clarithromycin 500 mg b.i.d. for 7 days.
Results:
A total of 215 patients (49% males) were enrolled in this study, with a mean age of 55 years. The eradication rates in group A, B, and C were 94.7% (71/75), 89.6% (69/77), and 93.7% (59/63) (p = 0.457), respectively. The adverse events were similar between the three groups (p = 0.068).
Conclusions:
This study suggests that dexlansoprazole-based triple therapy has an acceptable eradication rate for H. pylori infection.
Radical gastrectomy and extended lymph node (D2) dissection followed by adjuvant chemotherapy is the optimal treatment for patients with stage III gastric cancer in Asian population. The clinical ...factors associated with patient propensity to receive adjuvant chemotherapy and outcomes were analyzed.
In total, 509 patients with stage III gastric cancer who had undergone D2 surgery between 2007 and 2017 at a single medical center in Taiwan were analyzed. The patients' preoperative clinical characteristics relevant to adjuvant chemotherapy adherence were analyzed using multivariate regression. Significant variables were analyzed using recursive partitioning analysis (RPA) for identifying specific patient groups with the lowest and highest probabilities of adjuvant chemotherapy adherence.
After surgery, 361 (70.9%) patients in the cohort had received adjuvant chemotherapy. All patients were categorized into five probability groups with adherence to adjuvant chemotherapy according to age, Eastern Cooperative Oncology Group (ECOG) performance status grade, and American Society of Anesthesiologists (ASA) class, which were discovered to be independent factors in the RPA-based probability prediction. In general, adjuvant chemotherapy improved survival across broad categories of stage III gastric cancer patients (overall survival hazard ratio: 0.53–0.75 and disease-free survival hazard ratio: 0.47–0.76).
Our study identified that age, ECOG grade, and ASA class were independent clinical factors associated with patient propensity to receive adjuvant chemotherapy in stage III gastric cancer. Knowledge of the clinical factors of patients may help clinicians identify and encourage specific patients to receive the adjuvant chemotherapy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Gastrointestinal stromal tumors (GISTs), leiomyomas, and schwannomas are the most common gastric subepithelial tumors (GSETs) with similar endoscopic findings. Preoperative prediction of GSETs is ...difficult. This study analyzed and predicted GSET diagnosis through a retrospective review of 395 patients who underwent surgical resection of GISTs, leiomyomas, and schwannomas measuring 2-10 cm. GSETs were divided by size (group 2-5, >2 and ≤5 cm; group 5-10, >5 and ≤10 cm) for analysis. Demographics, clinical symptoms, and images were analyzed. A recursive partitioning analysis (RPA) was used to identify optimal classifications for specific GSET diagnoses. GIST patients were relatively older than other patients. Both groups had higher proportions of UGI bleeding, lower hemoglobin (Hb) levels, and a higher ratio of necrosis on their computed tomography (CT) scans. The RPA tree showed that (a) age ≤ 55, Hb ≥ 10.7, and CT necrosis; (b) age ≤ 55 and Hb < 10.7; (c) age >55 and Hb < 12.9; and (d) age >55 and CT hetero-/homogeneity can predict high GIST risk in group 2-5. Positive or negative CT necrosis, with age >55, can predict high GIST risk in group 5-10. GIST patients were older and presented with low Hb levels and tumor necrosis. In RPA, the accuracy reached 85% and 89% in groups 2-5 and 5-10, respectively.
Background: Totally laparoscopic surgery for early gastric cancer and subepithelial tumors has been popularized worldwide, yet localization of early or small-sized tumors is a persistent challenge ...due to difficulty being identified with the lack of manual tactile sensation. Thus, accurate localization with tattooing before the surgery would help improve efficiency during surgery. There are multiple methods to localize tumors before laparoscopy, each with varying advantages and disadvantages. The use of endoscopic tattooing with dye has been carried out for several decades due to its safety, lower cost, and convenience. However, there is a lack of studies on endoscopic tattooing before totally laparoscopic resection. Aims: To evaluate the effect of endoscopic tattooing with dye for gastric subepithelial tumors localization before laparoscopic resection and to evaluate the tattooing effect on different locations of tumors in stomach. Method: We retrospectively collected data of patients with gastric subepithelial tumors who underwent endoscopic tattooing before totally laparoscopic resection from 2017 to 2020 in a university affiliated medical center. All patients were analyzed for preoperative characteristics and then categorized into two groups based on tumor locations concerning the difficulty of laparoscopic surgery. The independent t test and Chi-square test were performed to compare perioperative outcome and complications between these two groups. Result: A total of 19 patients were included retrospectively at our center. The individuals were 5 male and 14 female patients with a mean age of 58.2 years old. Most patients had no symptoms, and the tumors were found incidentally in 12 patients (63%). All tumors were identified clearly during laparoscopic resection. The mean tumor size was 2.3 cm. The surgeries took an average of 111 min and a mean of 7 mL blood loss was found. All tumors had negative resection margins with no recurrence during follow-up. Gastrointestinal stromal tumor was the major pathologic diagnosis, found in 12 patients (63%), followed by the leiomyoma in 5 patients (26%). Only three patients had mild adverse effects after surgery and the symptoms were self-limited. Our analysis found no significant difference in preoperative patient characteristics and perioperative outcomes between patients with differing tumor locations. Conclusion: This study is the first and largest report on endoscopic tattooing with dye before laparoscopic resection of gastric subepithelial tumor resection. Our results emphasize that endoscopic tattooing with dye is a safe and reliable method for localizing subepithelial tumors in the stomach prior to totally laparoscopic resection, with no correlation to where the tumor is located.
OBJECTIVES:Because administration of 17β-estradiol following trauma-hemorrhage improves cardiovascular responses, we investigated whether the salutary effects of 17β-estradiol on cardiac function are ...mediated via Akt-dependent heme oxygenase-1 up-regulation under those conditions.
DESIGN:Experimental animal study.
SETTING:University laboratory.
SUBJECTS:Male Sprague-Dawley rats.
INTERVENTIONS:Rats underwent trauma-hemorrhage (mean blood pressure ∼40 mm Hg for 90 mins) followed by fluid resuscitation. Before resuscitation, rats received either vehicle, 17β-estradiol (1 mg/kg), or 17β-estradiol plus the phosphoinositide 3-kinase inhibitor wortmannin (1 mg/kg). At 2 hrs after trauma-hemorrhage or sham operation, the rats were killed.
MEASUREMENTS AND MAIN RESULTS:Cardiac function, heart tissue myeloperoxidase activity, cardiac and circulatory cytokine levels, cardiac intercellular adhesion molecule-1, and chemokine levels were measured. Cardiac Akt and heme oxygenase-1 were also determined. We found that 17β-estradiol prevented the trauma-hemorrhage-induced impairment in cardiac function and increase in cardiac myeloperoxidase activity. Cardiac and systemic interleukin-6 and tumor necrosis factor-α levels as well as cardiac intercellular adhesion molecule-1, cytokine-induced neutrophil chemoattractant-1, and macrophage inflammatory protein-2 contents were increased following trauma-hemorrhage, which were normalized by 17β-estradiol. Administration of 17β-estradiol following trauma-hemorrhage restored cardiac Akt phosphorylation and further increased heme oxygenase-1 expression. Coadministration of wortmannin following trauma-hemorrhage abolished the previous effects by 17β-estradiol.
CONCLUSIONS:These results suggest that the 17β-estradiol-meditated improvement in cardiac function following trauma-hemorrhage occurs via Akt-dependent heme oxygenase-1 up-regulation.
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