Long-term outcomes of metabolic surgery in overweight and obese patients with type 2 diabetes in Asia.

AIM: To assess the outcomes of metabolic surgery in overweight and obese patients in Asia with type 2 diabetes (T2D). MATERIALS AND METHODS: The treatment outcomes of 1999 patients from the Asian Diabetes Surgery Summit database were analysed. The changes in treatment effects across time were assessed with respect to the surgical procedures performed by using generalized estimating equations. RESULTS: The most commonly performed procedure was the single-anastomosis gastric bypass (32.6%). Weight (from 106.2 ± 25.1 to 77.9 ± 18.8 kg), body mass index (BMI; from 38.7 ± 7.9 to 28.5 ± 5.9 kg/m2 ), blood sugar (from 9.3 ± 4.1 to 5.7 ± 1.8 mmol/L) and HbA1c (from 8.4% ± 1.8% to 6.0% ± 1.1%) significantly improved from baseline to 1 year (P < .001) and remained stable at 5 years (weight, 86.3 ± 23.3 kg; BMI, 31.7 ± 7.9 kg/m2 ; blood sugar, 5.8 ± 1.8 mmol/L, and HbA1c, 6.4% ± 1.2%; all P < .001 vs. baseline). Blood pressure and most lipid disorders also improved significantly. Of the treatment procedures, single-anastomosis gastric bypass had the most satisfactory outcomes with statistical significance for most disorders, whereas adjustable gastric banding displayed the least satisfactory outcomes. CONCLUSIONS: Metabolic surgery remarkably improved body weight, T2D and other metabolic disorders in Asian patients. However, the efficacy of individual procedures varied substantially.

Glucose-Regulated Protein 94 Mediates the Proliferation and Metastasis through the Regulation of ETV1 and MAPK Pathway in Colorectal Cancer.

Colorectal cancer (CRC) is a worldwide health problem. Glucose-regulated protein 94 (GRP94) is known as an important endoplasmic reticulum-stress response protein that shows correlation with aggressive cancer behavior. However, the role of GRP94 in CRC is still unclear. Our results showed that silencing GRP94 (GRP94-KD) reduced cell proliferation, invasion and migration of CRC cells and suppressed tumorigenesis in the xenograft mouse model. Rescue assay showed that ETV1 overexpression reversed the effect of GRP94 on cell proliferation and migration. In the molecular mechanism, we found that knockdown of GRP94 inhibited the level of MAPK pathway, including ERK/p-ERK, JNK/p-JNK, and p38/p-p38 signals. Cyclooxygenase-2 and epithelial-mesenchymal transformation biomarkers, such as N-cadherin, vimentin, and ß-catenin were suppressed in GRP94 knockdown cells. Treatment of specific inhibitors of MAPK pathway showed that ERK/p-ERK, and p38/p-p38 inhibitors significantly influenced ETV1 expression as compared to JNK/p-JNK inhibitor. Our results indicated that silencing GRP94 repressed the ability of EMT process, cancer cell proliferation, metastasis, and CRC tumorigenesis. Therefore, GRP94 may play an important role in CRC by regulating ETV1 and MAPK pathway.

Predicted Coronary Heart Disease Risk Decreases in Obese Patients After Laparoscopic Sleeve Gastrectomy.

PURPOSE: To assess the reduction of 6 and 12 months postoperatively of Framingham risk score in morbidly obese patients with laparoscopic sleeve gastrectomy (LSG). MATERIAL AND METHODS: In total, 870 morbid obesity patients received LSG in Taipei Medical University Hospital from June 2007 to June 2014 were retrospectively studied preoperatively, 6 and 12 months after surgery. The coronary heart disease risk was calculated using Framingham risk score. RESULTS: The body mass index in men and women decreased from 43.3 ± 6.9, 39.2 ± 6.0 kg/m2 preoperatively to 32.9 ± 6.7, 31.0 ± 5.2 kg/m2 and to 30.4 ± 5.6 , 28.2 ± 4.7 kg/m2, respectively, at 6 and 12 months after surgery (P < 0.0001). At 6 and 12 months after LSG, there was a marked improvement on lipid profile as well as a significant decline in the prevalence of diabetes mellitus, systemic hypertension, and smoking. The Framingham risk score in men and women reduced from 3.2 ± 5.7, 6.1 ± 5.7 preoperatively to 1.4 ± 5.9, 3.3 ± 5.9 and 0.1 ± 6.2, 2.8 ± 6.1, respectively, at 6 and 12 months after surgery (P < 0.0001). CONCLUSIONS: Laparoscopic sleeve gastrectomy is efficient not only in the reduction of obesity and its related comorbidities but also in decreasing the long-term coronary event risk. Early intervention for the high-risk group is strongly recommended.

Oxidative stress-induced apoptotic insults to rat osteoblasts are attenuated by nitric oxide pretreatment via GATA-5-involved regulation of Bcl-X L gene expression and protein translocation.

Nitric oxide (NO) has biphasic effects on regulating osteoblast survival and death. This study was aimed to evaluate the effects of NO pretreatment on hydrogen peroxide (HP)-induced insults of rat osteoblasts and the possible mechanisms. Exposure of osteoblasts prepared from rat calvarias to HP significantly increased intracellular reactive oxygen species levels, decreased alkaline phosphatase activity and cell survival, and ultimately induced cell apoptosis. However, NO pretreatment lowered HP-induced oxidative stress and apoptotic insults. In parallel, HP increased Bax levels and its translocation from the cytoplasm to mitochondria. NO pretreatment caused significant attenuations in HP-induced modulations in Bax synthesis and translocation. In contrast, pretreatment with NO enhanced levels and translocation of antiapoptotic Bcl-XL protein in rat osteoblasts. RNA analyses further revealed that HP inhibited Bcl-XL mRNA expression without affecting Bax mRNA levels. In comparison, NO induced Bcl-XL mRNA production and alleviated HP-caused inhibition of this mRNA expression. As to the mechanism, HP suppressed RNA and protein levels of transcription factor GATA-5 in rat osteoblasts. Pretreatment with NO induced GATA-5 mRNA and protein expressions and simultaneously attenuated HP-induced inhibition of this gene's expression. Consequently, GATA-5 knockdown using RNA interference inhibited Bcl-XL mRNA expression and concurrently lowered NO's protection against HP-induced apoptotic insults. Therefore, this study showed that NO can protect rat osteoblasts from HP-induced apoptotic insults. The protective mechanisms are mediated by GATA-5-mediated transcriptional induction of Bcl-X L gene, and translocational modulation of Bcl-XL and Bax proteins.

E1A-mediated inhibition of HSPA5 suppresses cell migration and invasion in triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is defined by reduced expression of the estrogen receptor, progesterone receptor, and HER2. TNBC is an especially aggressive group of breast cancers with poor prognosis. There are currently no validated molecular targets to effectively treat this disease. Thus, it is necessary to identify effective molecular targets and therapeutic strategies for TNBC patients. METHODS: The expression of HSPA5 in patients with breast cancer was examined by immunohistochemistry. The association of HSPA5 expression with tumor grade and metastatic events in TNBC patients was analyzed using the Oncomine database. The knockdown and overexpression of HSPA5 protein were performed to investigate the effects on E1A-suppressed cell migration/invasion of TNBC using in vitro transwell assays and tumor growth/experimental metastasis studies in animal models. RESULTS: The expression of HSPA5 was positively correlated with high-grade tumors, metastatic events, and poor overall survival in breast cancer patients with TNBC. E1A-inhibited HSPA5 expression suppressed cell migration/invasive ability of TNBC cell lines. Moreover, E1A significantly abolished lung metastases from breast cancer cells by inhibiting HSPA5 expression in a xenograft tumor model. CONCLUSIONS: The overexpression of HSPA5 is critical for high-risk metastasis of breast cancer and TNBC. The results of our study suggest that HSPA5 may be a crucial mediator of E1A-suppressed metastatic ability of breast cancer cells. Thus, E1A may be a potential target for diagnosis and individualized treatment in clinical practice.

Thrombomodulin mediates the migratory ability of hormone-independent prostate cancer cells through the regulation of epithelial-to-mesenchymal transition biomarkers.

Thrombomodulin (TM) is highly expressed in endothelial cells and plays the key role in maintaining physical homeostasis. In addition, many pieces of evidence also show that TM contains the diagnostic value for malignant diseases. TM has been found to correlate with metastatic status in multiple cancers, but its role in prostate cancer progression remains unclear. TM expression was determined in prostate cancer cells (DU-145 and PC-3 cells) using real-time PCR and Western blotting. TM expression was manipulated in prostate cancer cells using TM-specific shRNA and an overexpression system. The proliferation, adhesion, and migratory ability of prostate cancer cells expressing various TM levels were determined using the x'Celligence biosensor system and a transwell migration assay. Higher levels of TM transcription and translation were found in DU-145 cells and were negatively correlated with the low migratory ability of DU-145 cells. After silencing TM expression in DU-145 cells, cell growth decreased, but cell adhesion and migration dramatically increased. TM overexpression in PC-3 cells reduced their metastatic ability. We investigated the possible mechanisms of this phenomenon and determined that the enhanced cell migration was mediated through the expression of E-cadherin and vimentin. TM may be a modulator of hormone-independent prostate cancer (HIPC) metastasis. The downregulation of TM expression enhanced the migratory ability of these cells via an increase in vimentin expression and a decrease in E-cadherin expression.

Single-incision versus conventional laparoscopic appendectomy in 688 patients: a retrospective comparative analysis.

BACKGROUND: Laparoscopic surgery has become the standard for treating appendicitis. The cosmetic benefits of using single-incision laparoscopy are well known, but its duration, complications and time to recovery have not been well documented. We compared 2 laparoscopic approaches for treating appendicitis and evaluated postoperative pain, complications and time to full recovery. METHODS: We retrospectively reviewed the cases of consecutive patients with appendicitis and compared those who underwent conventional laparoscopic appendectomy (CLA) performed using 3 incisions and those who underwent single-incision laparoscopic appendectomy (SILA). During SILA, the single port was prepared to increase visibility of the operative site. RESULTS: Our analysis included 688 consecutive patients: 618 who underwent CLA and 70 who underwent SILA. Postsurgical complications occurred more frequently in the CLA than the SILA group (18.1% v. 7.1%, p = 0.018). Patients who underwent SILA returned to oral feeding sooner than those who underwent CLA (median 12 h v. 22 h, p < 0.001). These between-group differences remained significant after controlling for other factors. Direct comparison of only nonperforated cases, which was determined by pathological examination, revealed that SILA was significantly longer than CLA (60 min v. 50 min, p < 0.001). Patients who underwent SILA had longer in-hospital stays than those who underwent CLA (72 v. 55 h, p < 0.001); however, they had significantly fewer complications (3.0% v. 14.4%, p = 0.006). CONCLUSION: In addition to its cosmetic advantages, SILA led to rapid recovery and no increase in postsurgical pain or complications.

CONTEXTE: La chirurgie laparoscopique est devenue la norme pour le traitement de l'appendicite. Les avantages de la laparoscopie à simple incision au plan esthétique sont bien connus, mais la durée de l'intervention, ses complications et le temps de récupération n'ont pas été adéquatement documentés. Nous avons comparé 2 approches laparoscopiques pour le traitement de l'appendicite et évalué la douleur et les complications postopératoires, de même que le temps de récupération complète. MÉTHODES: Nous avons passé en revue de manière rétrospective les dossiers de patients consécutifs atteints d'appendicite et comparé ceux qui ont subi une appendicectomie laparoscopique classique (ALC) à 3 incisions à ceux qui ont subi une appendicectomie laparoscopique à simple incision (ALSI). Durant l'ALSI, l'incision était préparée de manière à améliorer la visibilité du champ opératoire. RÉSULTATS: Notre analyse a inclus 688 patients consécutifs : 618 qui ont subi une ALC et 70, une ALSI. Les complications postopératoires ont été plus nombreuses dans le groupe soumis à l'ALC qu'à l'ALSI (18,1 % c. 7,1 %, p = 0,018). Les patients soumis à l'ALSI ont repris l'alimentation orale plus rapidement que ceux qui avaient subi une ALC (temps médian 12 h c. 22 h, p < 0,001). Ces différences entre les groupes sont demeurées significatives après incorporation d'autres facteurs. La comparaison directe des cas non perforés seulement, révélés par l'examen anatomopathologique, a révélé que l'ALSI a demandé significativement plus de temps que l'ALC (60 min c. 50 min, p < 0,001). Les patients soumis à l'ALSI ont séjourné plus longtemps à l'hôpital que les patients soumis à l'ALC (72 h c. 55 h, p < 0,001); toutefois, ils ont présenté significativement moins de complications (3,0 % c. 14,4 %, p = 0,006). CONCLUSION: En plus de ses avantages au plan esthétique, l'ALSI a permis une récupération rapide, sans accroissement de la douleur ou des complications postopératoires.

Modified enhanced recovery after surgery protocol in octogenarians undergoing minimally invasive colorectal cancer surgery.

BACKGROUND: Colorectal cancer (CRC) is a major health issue worldwide. As the population ages, more older patients including octogenarians will require CRC treatment. However, this vulnerable group has decreased functional reserves and increased surgical risks. Enhanced recovery after surgery (ERAS) pathways aim to reduce surgical stress and complications, but concerns remain about applying ERAS protocols to older patients. We assessed whether a modified ERAS (mERAS) protocol combined would improve outcomes in octogenarian CRC patients undergoing minimally invasive surgery. METHODS: In this retrospective cohort study, we compared 360 non-octogenarians aged 50-64 years and 114 octogenarians aged 80-89 years before and after mERAS protocol implementation. Outcomes including postoperative functionary recovery, length of stay, complications, emergency department visits, and readmissions were analyzed. RESULTS: Despite comparable tumor characteristics, octogenarians had poorer nutrition, American Society of Anesthesiologists status, and more comorbidities. After mERAS, octogenarians had reduced complications, faster return of bowel function, and shorter postoperative length of stay, similar to non-octogenarians. mERAS implementation improved recovery in both groups without increasing emergency department visits or readmissions. CONCLUSION: Although less remarkable than in non-octogenarians, mERAS protocols mitigated higher complication rates and improved recovery in octogenarians after minimally invasive surgery for CRC, confirming protocol feasibility and safety in this vulnerable population.

Machine Learning Models for Predicting Significant Liver Fibrosis in Patients with Severe Obesity and Nonalcoholic Fatty Liver Disease.

PURPOSE: Although noninvasive tests can be used to predict liver fibrosis, their accuracy is limited for patients with severe obesity and nonalcoholic fatty liver disease (NAFLD). We developed machine learning (ML) models to predict significant liver fibrosis in patients with severe obesity through noninvasive tests. MATERIALS AND METHODS: This prospective study included 194 patients with severe obesity who underwent wedge liver biopsy and metabolic bariatric surgery at Taipei Medical University Hospital between September 2016 and December 2020. Significant liver fibrosis was defined as a fibrosis score ≥ 2. Patients were randomly divided into a training group (70%) and a validation group (30%). ML models, including support vector machine, random forest, k-nearest neighbor, XGBoost, and logistic regression, were trained to predict significant liver fibrosis, using DM status, AST, ALT, ultrasonographic fibrosis scores, and liver stiffness measurements (LSM). An ensemble model including these ML models was also used for prediction. RESULTS: Among the ML models, the XGBoost model exhibited the highest AUROC of 0.77, with a sensitivity, specificity, and accuracy of 61.5%, 75.8%, and 69.5%, in validation set, while LSM, AST, ALT showed strongest effects on the model. The ensemble model outperformed all ML models in terms of sensitivity, specificity, and accuracy of 73.1%, 90.9%, and 83.1%. CONCLUSION: For patients with severe obesity and NAFLD, the XGBoost model and the ensemble model exhibit high predictive performance for significant liver fibrosis. These models may be used to screen for significant liver fibrosis in this patient group and monitor treatment response after metabolic bariatric surgery.

Essential trace element and phosphatidylcholine remodeling: Implications for body composition and insulin resistance.

BACKGROUND: Recent studies indicated that bioactive lipids of phosphatidylcholines (PCs) and lysophosphatidylcholines (LysoPCs) predict unhealthy metabolic phenotypes, but results remain inconsistent. To fill this knowledge gap, we investigated whether essential trace elements affect PC-Lyso PC remodeling pathways and the risk of insulin resistance (IR). METHODS: Anthropometric and blood biochemical data (glucose, insulin, and lipoprotein-associated phospholipase A2 (Lp-PLA2)) were obtained from 99 adults. Blood essential/probably essential trace elements and lipid metabolites were respectively measured by inductively coupled plasma mass spectrometry (ICP-MS), and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). RESULT AND CONCLUSION: Except for LysoPC (O-18:0/0:0), an inverse V shape was observed between body weight and PC and LysoPC species. A Pearson correlation analysis showed that essential/probably-essential metals (Se, Cu, and Ni: r=-0.4∼-0.7) were negatively correlated with PC metabolites but positively correlated with LysoPC (O-18:0/0:0) (Se, Cu, and Ni: r=0.85-0.64). Quantile-g computation showed that one quantile increase in essential metals was associated with a 2.16-fold increase in serum Lp-PLA2 (ß=2.16 (95 % confidence interval (CI): 0.34, 3.98), p=0.023), which are key enzymes involved in PC/Lyso PC metabolism. An interactive analysis showed that compared to those with the lowest levels (reference), individuals with the highest levels of serum PCs (pooled, M2) and the lowest essential/probably essential metals (M1) were associated with a healthier body composition and had a 76 % decreased risk of IR (odds ratio (OR)=0.24 (95 % CI: 0.06, 0.90), p<0.05). In contrast, increased exposure to LysoPC(O-18:0/0:0) (M2) and essential metals (M2) exhibited an 8.22-times highest risk of IR (OR= 8.22 (2.07, 32.57), p<0.05) as well as an altered body composition. In conclusion, overexposure to essential/probably essential trace elements may promote an unhealthy body weight and IR through modulating PC/LysoPC remodeling pathways.

Mid- and long-term renal outcomes after metabolic surgery in a multi-center, multi-ethnic Asian cohort with T2DM.

Background: Metabolic surgery is recognized for its effectiveness in weight loss and improving outcomes for individuals with type 2 diabetes mellitus (T2DM). However, its impact on renal function, especially in multi-ethnic Asian populations, remains underexplored. This study investigates mid- and long-term renal outcomes following metabolic surgery in Asian patients with T2DM. Methods: This retrospective cohort study utilized data from the Asian Diabetes Surgery Study (ADSS), involving T2DM patients aged 20-79 who underwent metabolic surgery from 2008 to 2015. The primary outcome was the change in estimated glomerular filtration rate (eGFR) at 1, 3, and 5 years post-surgery, with adjustments for confounders. Secondary outcomes included changes in chronic kidney disease (CKD) stages and the relationship between weight loss and eGFR changes. Data were analyzed using univariate and multivariable regression analyses, along with the McNemar test. Results: The study included 1513 patients with a mean age of 42.7 years. The results revealed that a significant improvement in eGFR was observed at 1-year post-surgery (112.4 ± 32.0 ml/min/1.73 m², P < .001), with a shift toward less severe CKD stages. However, this improvement was not sustained at 3 and 5 years. No significant correlation was found between weight loss and eGFR changes at 1-year follow-up. Conclusion: Metabolic surgery significantly improves renal function at 1 year postoperatively in Asian individuals with T2DM, highlighting its potential benefits beyond glycemic control and weight loss. The long-term effects on renal function require further investigation.

MicroRNA-200a/b influenced the therapeutic effects of curcumin in hepatocellular carcinoma (HCC) cells.

MicroRNAs (miRNAs) play an essential role in regulating gene expression in normal and malignant cells. Expression of the microRNA-200 (miR-200) family has been correlated with malignancy in cancers. However, whether miR-200a/b plays a role in curcumin-mediated treatment of hepatocellular carcinoma (HCC) is unknown. We performed miRNA array analyses in two different HCC cell lines (HepG2 and HepJ5). The expression patterns of miR-200 family members were assessed with real-time PCR. We overexpressed miR-200 family members using a lentiviral system and selected stably transduced clones with antibiotics. The anticancer effects of curcumin on J5-200a, J5-200b, and J5-control cells were assessed by MTT assay, flow cytometry cell cycle analysis, and TUNEL assay. We found that HepG2 cells, which were more resistant to curcumin treatment than HepJ5 cells, expressed higher levels of miR-200a/b. The MTT assay revealed that the overexpression of miR-200a/b in HepJ5 cells conferred enhanced resistance to curcumin treatment compared with the control cells. By cell cycle analysis and TUNEL assay, we found that apoptosis was increased dramatically in J5-control cells compared with J5-200a and J5-200b cells after curcumin treatment. Finally, we evaluated the levels of Bcl-2, Bax, and Bad, and found a decrease of Bcl-2 levels and increase of Bad levels in the J5-control cells treated with curcumin. The expression levels of miR-200a/b might determine the therapeutic efficacy of curcumin on HCC cells.

Thrombomodulin mediates the progression of epithelial ovarian cancer cells.

Thrombomodulin (TM), a natural anticoagulation factor, maintains circulation homeostasis in endothelial cells. TM has additional roles in modulating inflammation, thrombosis, and carcinogenesis. However, there is little information on the role of TM in the progression and metastasis of ovarian cancer. RNA silencing and cDNA expression vectors were used to manipulate target gene expression in ovarian cancer cells. Cell growth and migration were evaluated by an MTT assay, a wound-healing migration assay, a transwell migration assay, and a biosensor system. In this study, we found that TM silencing may enhance the growth rate of cells. The migratory ability of ovarian cancer cells was enhanced dramatically after TM silencing. TM overexpression in ovarian cells suppressed the proliferation and migration capability. Furthermore, we found that skov-3 cells treated with TM shRNA expressed high levels of fibronectin and vimentin and that the expression of these markers correlated positively with their migratory ability. Our results demonstrate that TM expression may regulate cell growth and migration in ovarian cancer cells. This finding suggests that TM may be a novel prognostic and therapeutic target for ovarian cancer.

Intersphincteric resection for very low rectal cancer: clinical outcomes of open versus laparoscopic approach and multidimensional analysis of the learning curve for laparoscopic surgery.

BACKGROUND: Laparoscopic rectal cancer surgery is regarded as more complex because of its technical difficulties in pelvic exposure, dissection, and sphincter preservation. This study therefore aimed to investigate the feasibility of laparoscopic resection for low rectal cancer using intersphincteric resection (ISR) and to assess its short-term oncological outcomes. Further, we intended to analyze the learning curve for laparoscopic surgery and identify the factors influencing the learning curve. METHODS: Patients with low rectal cancer who received open or laparoscopic ISR were retrospectively chart reviewed. The surgical and oncological outcomes were evaluated. Comparisons of operating time, estimated blood loss, surgical outcomes, and histopathologic status were analyzed. Also, operating time was used as a technical indicator for learning curve analysis. RESULTS: The mean estimated blood loss was 265 mL (range, 100-800 mL) in the open group and 104 mL (range, 30-250 mL) in the laparoscopic group. There was a significant difference between these two groups (P < 0.001). Operative experience analysis showed that the mean operating time was 402.1 min (range, 210-570 min) in the first stage and 331.4 min (range, 210-450 min) in the second stage, and on pathologic examination the mean number of lymph nodes harvested was 11.1 (range, 5-21) in the first stage and 18.3 (range, 11-31) in the second stage, with statistical differences between these two stages (P = 0.034 and P = 0.004, respectively). Multifactorial analysis showed that operating time was associated with surgeons' experience (<18 or ≥18 cases) (odds ratio = 2.918, 95% CI 1.078-7.902). Protective stoma creation was also associated with surgeons' experience (odds ratio = 3.999, 95% CI 1.153-13.86). CONCLUSIONS: Our data show that laparoscopic ISR for low rectal cancer is feasible and safe. Surgeons' experience improved operating time and postoperative complications.

Comparison of robotic reduced-port and laparoscopic approaches for left-sided colorectal cancer surgery.

BACKGROUND/OBJECTIVE: The reduced-port approach can overcome the limitations of single-incision laparoscopic surgery while maintaining its advantages. Here, we compared the effects of robotic reduced-port surgery and conventional laparoscopic approaches for left-sided colorectal cancer. METHODS: Between January 2015 and December 2016, the clinicopathological characteristics and treatment outcomes of 17 patients undergoing robotic reduced-port surgery and 49 patients undergoing laparoscopic surgery for left-sided colorectal cancer were compared. RESULTS: The two groups were comparable in almost all outcome measures except for the distal resection margin, which was significantly longer in the laparoscopic group (P < 0.001). The between-group differences in reoperation, incisional hernia development, and overall and progression-free survival were nonsignificant; however, the total hospital cost was significantly higher in the robotic group than in the laparoscopic group (US$13779.6 ± US$3114.8 vs. US$8556.3 ± US$2056.7, P < 0.001). CONCLUSION: Robotic reduced-port surgery for left-sided colorectal cancer is safe and effective but more expensive with no additional benefit compared with the conventional laparoscopic approach. This observation warrants further evaluation.

Therapeutic Effect of Human Adipocyte-derived Stem Cell-derived Exosomes on a Transgenic Mouse Model of Parkinson's Disease.

BACKGROUND/AIM: Stem cell therapy and regenerative medicine are promising for treating Parkinson's disease (PD) not only for the potential for cell replacement but also for the paracrine effect of stem cell secretion, especially proteins and nucleotide-enriched exosomes. This study investigated the neuroprotective effect of exosomes secreted from human adipocyte-derived stem cells (hADSCs) on PD. MATERIALS AND METHODS: hADSCs were isolated from the visceral fat tissue of individuals without PD who underwent bariatric surgery and were validated using surface markers and differentiation ability. Exosomes were isolated from the culture medium of hADSCs through serial ultracentrifugation and validated. Condensed exosomes were administered intravenously to 12-week-old MitoPark mice, transgenic parkinsonism mouse model with conditional knockout of mitochondrial transcription factor A in dopaminergic neurons, monthly for 3 months. Motor function, gait, and memory were assessed monthly, and immunohistochemical analysis of neuronal and inflammatory markers was performed at the end of the experiments. RESULTS: The hADSC-derived exosome-treated mice exhibited better motor function in beam walking and gait analyses than did the untreated mice. In the novel object recognition tests, the exosome-treated mice retained better memory function. Immunohistochemical analysis revealed that although exosome treatment did not prevent the loss of dopaminergic neurons in the substantia nigra of mice, it down-regulated microglial activation and neuroinflammation in the midbrain. CONCLUSION: hADSC-derived exosomes were neuroprotective in this in vivo mouse model of PD, likely because of their anti-inflammatory effect. Use of hADSC-derived exosomes may offer several beneficial effects in stem cell therapy. Since they can also be produced at an industrial level, they are a promising treatment option for PD and other neurodegenerative diseases.

Bariatric surgery trends and progress in Taiwan: 2010-2021.

INTRODUCTION: Taiwan is a leading country regarding bariatric surgery in Asia-Pacific. Since 2010, the Taiwan Society for Metabolic and Bariatric Surgery (TSMBS) has been accountable for the national evolution of bariatric surgery and inaugurated a national database accordingly. This study aimed to analyze the bariatric surgery trends and progress in Taiwan from 2010 to 2021. MATERIALS AND METHODS: The TSMBS database was collected on the basis of structured inquiries filled out by bariatric surgeons in Taiwan. All patients involving bariatric surgery were included. The data were stratified with the following objectives, including the types of bariatric procedures, demographic characteristics, and perioperative variables. A nationwide database was comprehensively analyzed and evaluated to determine the trends in the applications of the procedure. RESULTS: Data of 30,026 patients were enrolled. A 2.5-fold increase was observed in bariatric procedures, from 1218 in 2010 to 3005 in 2021. Within 12 years, female accounts for 61.8 %. The revisional rate was 3.40 % during the exploration stage (2010-2013), 2.77 % during the maturity stage (2013-2018), and 5.10 % during the expansion stage (2019-2021). The top five of primary bariatric surgery is sleeve gastrectomy (SG, 63.05 %), gastric clipping surgery (GC, 11.17 %), Roux-en-Y gastric bypass (RYGB, 9.34 %), one anastomosis gastric bypass (OAGB, 8.80 %), and sleeve plus surgery (SG plus, 4.43 %). CONCLUSION: The trends and progress of Taiwan's bariatric surgery within recent decades are presented in this article. Taiwan's bariatric surgery case number has increased steadily from 2010 to 2021. Amongst all, SG has become the most dominant procedure since 2011 while OAGB takes up second place in 2020.

Prediction of 5-Year Weight Loss and Weight Regain According to Early Weight Loss after Sleeve Gastrectomy.

BACKGROUND: Patients with morbid obesity exhibit sustained weight loss after sleeve gastrectomy (SG), but some individuals exhibit subsequent weight regain in the following years. Early weight loss was proven as a predictor of short- and mid-term weight loss and regain. However, the long-term effects of early weight loss have yet to be fully investigated. This study investigated the predictive effects of early weight loss on long-term weight loss and regain after SG. METHODS: Data of patients who underwent SG from November 2011 to July 2016 and followed through July 2021 were collected retrospectively. Weight regain was defined by weight increase more than 25% of their lost weight at the first postoperative year. Linear regression analysis and Cox proportional hazards analysis were performed to evaluate the correlations among early weight loss, weight loss, and weight regain. RESULTS: Data of 408 patients were included. The percentages of total weight loss (%TWL) at postoperative months 1, 3, 12, and 60 were 10.6%, 18.1%, 29.3%, and 26.6%, respectively. The %TWL at months 1 and 3 were significantly correlated with %TWL after 5 years (P < .01). The weight regain rate was 29.8% at 5 years. The %TWL at months 1 and 3 significantly influenced weight regain (hazard ratio: 0.87 and 0.89, P = .017 and .008). CONCLUSION: Early weight loss may be used to predict weight loss and regain 5 years after SG. Patients with poor early weight loss are recommended to receive early interventions to achieve long-term weight loss and prevent weight regain.

Potential Hepatic Lipid Markers Associated with Nonalcoholic Steatohepatitis and Fibrosis in Morbid Obesity Patients.

This study investigated differences in lipidomic profile features in nonalcoholic steatohepatitis (NASH) between mild and significant liver fibrosis cases among patients with morbid obesity. Wedge liver biopsy was performed during sleeve gastrectomy and significant liver fibrosis was defined as a fibrosis score ≥ 2. We selected patients with NASH with non/mild fibrosis (stage F0-F1; n = 30) and NASH with significant fibrosis (stage F2-F4; n = 30). The results of the liver tissue lipidomic analysis revealed that the fold changes of triglyceride (TG) (52:6); cholesterol ester (CE) (20:1); phosphatidylcholine (PC) (38:0) and (50:8); phosphatidic acid (PA) (40:4); phosphatidylinositol (PI) (49:4); phosphatidylglycerol (PG) (40:2); and sphingomyelin (SM) (35:0) and (37:0) were significantly lower in patients with NASH with F2-F4 than those with NASH with F0-F1 (p < 0.05). However, the fold changes of PC (42:4) were relatively higher in patients with NASH with stage 2-4 fibrosis (p < 0.05). Moreover, predictive models incorporating serum markers levels, ultrasonographic studies, and levels of specific lipid components [PC (42:4) and PG (40:2)] yielded the highest area under receiver operating curve (0.941), suggesting a potential correlation between NASH fibrosis stages and liver lipid accumulation among specific lipid species subclasses. This study demonstrated that the concentrations of particular lipid species in the liver correlate with NASH fibrosis stages and may indicate hepatic steatosis regression or progression in patients with morbid obesity.

NNK enhances cell migration through α7-nicotinic acetylcholine receptor accompanied by increased of fibronectin expression in gastric cancer.

BACKGROUND: In this study, we intended to dissect the mechanism of 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-enhanced migration of gastric cancer. Smoking has been defined as a risk factor for gastric cancer. Tobacco-specific carcinogen, NNK, was reported to enhance cancer progression in gastric cancer. Currently, metastasis is the major issue for clinical cancer therapy, but the influence of NNK on the migration of gastric cancer remains to be determined. METHODS: The expression of nicotinic receptor in gastric cancer cells was identified by real-time polymerase chain reaction and Western blotting. The influence of NNK on migration of gastric cancer cells was evaluated by the transwell migration assay system. Receptor-mediated migration was studied by both inhibitor and small interfering RNA. RESULTS: Alpha7 nicotinic acetylcholine receptor, alpha7-nicotinic acetylcholine receptor (nAChR), was identified higher than alpha9-nAChR in gastric cancer cell lines, AGS cells. NNK enhanced significantly gastric cancer cell migration in transwell assay. We used inhibitor and siRNA to demonstrate that alpha7-nAChR mediated NNK-enhanced gastric cancer cell migration and upregulation of fibronectin were involved in NNK-enhanced migration of gastric cancer cells. Finally, we found that silenced fibronectin expression level inhibited the migratory ability in AGS cells. CONCLUSIONS: NNK enhanced gastric cancer metastasis through alpha7-nAChR and fibronectin-one of the hallmarks of epithelial mesenchymal transition.