A Prospective Multicenter Standard of Care Study of Outpatient Laparoscopic Sleeve Gastrectomy.

A global shift is occurring as hospital procedures move to ambulatory surgical settings. Surgeons have performed outpatient sleeve gastrectomy (SG) in bariatric surgery since 2010. However, prospective trials are needed to ensure its safety before widespread adoption. PURPOSE: The study aimed to present a comprehensive report on the prospective data collection of 30-day outcomes of outpatient primary laparoscopic SG (LSG). This trial seeks to assess whether outpatient LSG is non-inferior to hospital-based surgery in selected patients who meet the outpatient surgery criteria set by the American Society for Metabolic and Bariatric Surgery. MATERIALS AND METHODS: This study is funded by the Society of American Gastrointestinal and Endoscopic Surgeons and has been approved by the Advarra Institutional Review Board (Pro00055990). Cognizant of the necessity for a prospective approach, data collection commenced after patients underwent primary LSG procedures, spanning from August 2021 to September 2022, at six medical centers across the USA. Data centralization was facilitated through ArborMetrix. Each center has its own enhanced recovery protocols, and no attempt was made to standardize the protocols. RESULTS: The analysis included 365 patients with a mean preoperative BMI of 43.7 ± 5.7 kg/m2. Rates for 30-day complications, reoperations, readmissions, emergency department visits, and urgent care visits were low: 1.6%, .5%, .2%, .2%, and 0%, respectively. Two patients (0.5%) experienced grade IIIb complications. There were no mortalities or leaks reported. CONCLUSION: The prospective cohort study suggests that same-day discharge following LSG seems safe in highly selected patients at experienced US centers.

Comparative study between laparoscopic adjustable gastric banding and laparoscopic gastric bypass: single-institution, 5-year experience in bariatric surgery.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic adjustable gastric banding (LAGB) are common surgical procedures for morbid obesity. Few single-institution studies have compared LRYGB and LAGB. METHODS: All patients underwent LRYGB or LAGB at Legacy Health System. The data for the study were obtained from a prospectively maintained database. Preoperatively, most patients were allowed to choose between LRYGB and LAGB. Age, gender, body mass index, complications, mortality, and weight loss were examined. RESULTS: From October 2000 to October 2005, 492 patients underwent LRYGB and 406 patients underwent LAGB. The mean age was 44 +/- 10 and 47 +/- 11 years, respectively (P <.001). The mean preoperative body mass index was 49 +/- 8 and 51 +/- 9 kg/m(2) (P <.05). Patients undergoing LRYGB had longer operative times (134 +/- 41 min versus 68 +/- 26 min, P <.001) and longer hospital stays (2.5 +/- 3.5 d versus 1.1 +/- 1.1 d, P <.001). Blood loss was minimal in both groups. The percentage of excess weight loss was significantly better for patients who underwent LRYGB at all points of follow-up, except at 5 years. Total complications occurred in 32% of patients who underwent LRYGB and 24% of patients who underwent LAGB (P = .002). The 90-day mortality rate was .2% in both groups. The reoperation rate was the same (17%) in both groups. CONCLUSIONS: Patients undergoing LAGB had shorter operative times and shorter hospital stays compared with patients undergoing LRYGB. LAGB was associated with a lower complication rate. Early weight loss was significantly greater after LRYGB, but the data comparing long-term weight loss after LRYGB and LAGB have been inconclusive.

Nucleotide-based therapies targeting clusterin chemosensitize human lung adenocarcinoma cells both in vitro and in vivo.

INTRODUCTION: Lung cancer is highly lethal and resistant to most anticancer interventions. Treatment resistance is mediated, in part, by enhanced expression of cell survival proteins that help facilitate tumor progression. Clusterin is a stress-associated cytoprotective protein up-regulated by various apoptotic triggers in many cancers and confers treatment resistance when overexpressed. The objectives in this study were to evaluate clusterin expression levels in human lung cancer tissue, and to test effects of clusterin silencing using antisense oligonucleotides (ASOs) and short interfering double-stranded RNAs (siRNAs) on chemosensitivity in human lung cancer A549 cells. METHODS: Clusterin immunostaining was evaluated in a tissue microarray of 149 spotted human lung cancers. The effects of clusterin ASO or siRNA treatment on clusterin expression and chemosensitivity to paclitaxel was examined in A549 cells in vitro while the ability of clusterin ASO to chemosensitize in vivo was evaluated in immunocompromised mice bearing A549 tumors. RESULTS: More than 80% of human non-small cell lung cancers are immunoreactive for clusterin. Clusterin ASO or siRNA decreased clusterin mRNA expression in A549 cells >75% in a dose-dependent, sequence-specific manner, and significantly enhanced chemosensitivity to paclitaxel in vitro. Characteristic apoptotic DNA laddering was observed after combined treatment with ASO plus paclitaxel, but not with either agent alone. In vivo administration of clusterin ASO, compared to mismatch control oligonucleotide, synergistically enhanced the effects of paclitaxel or gemcitibine to significantly delay A549 tumor growth. CONCLUSION: These findings identify clusterin as a valid therapeutic target in strategies employing novel multimodality therapy for advanced lung cancer.

Targeting anti-apoptotic genes upregulated by androgen withdrawal using antisense oligonucleotides to enhance androgen- and chemo-sensitivity in prostate cancer.

The main obstacle to improved survival of advanced prostate cancer is our failure to prevent its progression to its lethal and untreatable stage of androgen independence. New therapeutic strategies designed to prevent androgen-independent (AI) progression must be developed before significant impact on survival can be achieved. Characterization of changes in gene expression profiles after androgen ablation and during progression to androgen-independence suggest that the various therapies used to kill neoplastic cells may precipitate changes in gene expression that lead to the resistant phenotype. Castration-induced increases in antiapoptosis genes, Bcl-2 and clusterin, help create a resistant phenotype, while antisense oligonucleotides can inhibit these adaptive cell survival mechanisms and enhance both hormone and chemotherapy. Ongoing efforts are necessary to identify additional molecular pathways mediating AI progression and chemoresistance, since complexities of tumor heterogeneity and adaptability dictate that optimal control over tumor progression will require multi-target systemic therapies.

Clusterin expression is significantly enhanced in prostate cancer cells following androgen withdrawal therapy.

INTRODUCTION AND OBJECTIVES: Progression of prostate cancer to androgen independence (AI) results in part from the upregulation of anti-apoptotic genes following androgen withdrawal, and androgen-independent disease remains the primary obstacle to improved survival. Testosterone-repressed prostate message-2 (TRPM-2) encodes the anti-apoptotic protein clusterin, which is upregulated in response to cellular compromise as observed in normal and malignant tissues undergoing apoptosis. Systemic administration of antisense clusterin oligonucleotides in prostate cancer xenograft models delays progression to AI and enhances chemosensitivity. The objective of this study was to define changes in clusterin expression following neoadjuvant hormone therapy (NHT) in prostate cancer patients. MATERIALS AND METHODS: Archival radical prostatectomy (RP) specimens were obtained for 128 patients who received either no NHT or treatment for 2-8 weeks, 3 months, or 8 months. Paired needle biopsy specimens were acquired for 30 patients and all tissues were subjected to clusterin immunohistochemistry. Western blot analysis was performed on frozen tissue from 5 untreated and 5 treated patients. RESULTS: Clusterin expression in malignant prostatic tissue was significantly greater in patients who underwent preoperative NHT (P < 0.001). Needle biopsies obtained prior to NHT consistently demonstrated lower staining intensity than corresponding RP specimens (P < 0.001). Western blot analysis confirmed clusterin levels increased 17-fold beginning within 4 weeks after androgen withdrawal. CONCLUSIONS: Upregulation of clusterin levels following androgen ablation therapy may represent an adaptive cell survival response following apoptotic signals like androgen withdrawal. These findings support clusterin as a valid therapeutic target in strategies employing novel multimodality therapy for advanced prostate cancer.