Octogenarians exhibit quality of life improvement but increased morbidity after paraesophageal hernia repair.

BACKGROUND: The benefit of elective laparoscopic paraesophageal hernia repair (eLPEHR) in the elderly is unclear. This study compared quality of life and symptom resolution and morbidity after eLPEHR between octogenarians and younger patients. METHODS: A retrospective review was conducted comparing octogenarians (n = 23) to younger patients (n = 162) undergoing eLPEHR. Primary outcomes were pre and post-operative disease-specific quality of life (GERD-HRQL) and symptom scales (GERSS) and post-operative morbidity and length of stay (LOS). RESULTS: Octogenarians presented with higher ASA and lower preoperative BMI. Compared to controls, octogenarians exhibited higher overall morbidity (34.8% vs 16.1%, p = 0.03), including cardiac events (8.7% vs 0.6%) and mortality (8.7% vs 0%), and longer LOS (3 vs 2 days, p < 0.005). Post-operative reduction in GERD-HRQL/GERSS scores was comparable between groups. CONCLUSION: Octogenarians who undergo eLPEHR exhibit significant improvement in quality of life and symptom burden but may experience increased morbidity, suggesting a role for watchful waiting in this population. SUMMARY: Symptom burden, quality of life, and immediate post-operative morbidity was compared between octogenarians and younger patients undergoing elective laparoscopic paraesophageal hernia repair at a single institution. While exhibiting comparable post-operative improvement in symptom burden and quality of life, octogenarians experience higher post-operative morbidity. This may suggest a role for watchful waiting in the elderly population.

Endoscopic stent placement for treatment of sleeve gastrectomy leak: a single institution experience with fully covered stents.

BACKGROUND: Laparoscopic sleeve gastrectomy (SG) has risen in prevalence as a standalone surgical option for treating obesity over the last 15 years. One of the most worrisome complications is development of a leak at the gastrectomy staple line. OBJECTIVE: The objective of this report is to describe our single-institution experience in managing SG staple-line leaks with fully covered endoscopic stents. SETTING: Academic medical center, United States. METHODS: Data for all patients who underwent endoscopic stent placement for an SG leak between 2010 and 2016 at a single academic institution were retrospectively reviewed. Patient medical history, perioperative information, stent placement details, outcomes, and subsequent interventions were recorded. RESULTS: Twenty-four patients with SG staple-line leaks treated with fully covered endoscopic stents were identified. Leaks were identified at a median of 31.5 days postoperatively (range, 1-1615 d). The majority of patients underwent other treatment(s) for their leak before stent placement at our institution. Stents remained in place for an average of 28.8 ± 16.8 days. Migration occurred in 22% of all stent placements. Three patients were lost to follow-up, and 14 of the remaining 21 patients (66.7%) healed after stent placement. Five patients (23.8%) ultimately required operative revision with partial gastrectomy and Roux-en-Y esophagojejunostomy for management of persistent leaks. CONCLUSION: Endoscopic management using fully covered stents for staple-line leaks after SG is effective in the majority of patients. However, algorithms are needed for the management of chronic staple-line leaks, which are less likely to heal with stent placement.

Surgeon-performed endoscopic retrograde cholangiopancreatography. Outcomes of 2392 procedures at two tertiary care centers.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure that, in the United States, is traditionally performed by gastroenterologists. We hypothesized that when performed by well-trained surgeons, ERCP can be performed safely and effectively. The objectives of the study were to assess the rate of successful cannulation of the duct of interest and to assess the 30-day complication and mortality rates. METHODS: We retrospectively reviewed the charts of 1858 patients who underwent 2392 ERCP procedures performed by five surgeons between August 2003 and June 2016 in two centers. Demographic and historical data, indications, procedure-related data and 30-day complication and mortality data were collected and analyzed. RESULTS: The mean age was 53.4 (range 7-102) years and 1046 (56.3%) were female. 1430 (59.8%) of ERCP procedures involved a surgical endoscopy fellow. The most common indication was suspected or established uncomplicated common bile duct stones (n = 1470, 61.5%), followed by management of an existing biliary or pancreatic stent (n = 370, 15.5%) and acute biliary pancreatitis (n = 173, 7.2%). A therapeutic intervention was performed in 1564 (65.4%), a standard sphincterotomy in 1244 (52.0%), stent placement in 705 (29.5%) and stone removal in 638 (26.7%). When cannulation was attempted, the rate of successful cannulation was 94.1%. When cannulation was attempted during the patient's first ERCP the cannulation rate was 92.4%. 94 complications occurred (5.4%); the most common complication was post-ERCP pancreatitis in 75 (4.2%), significant gastrointestinal bleeding in 7 (0.4%), ascending cholangitis in 11 (0.6%) and perforation in 1 (0.05%). 11 mortalities occurred (0.5%) but none of which were ERCP-related. CONCLUSION: When performed by well-trained surgical endoscopists, ERCP is associated with high success rate and acceptable complication rates consistent with previously published reports and in line with societal guidelines.

Laparoscopic Nissen fundoplication controls reflux symptoms and improves disease-specific quality of life in patients with class I and II obesity.

BACKGROUND: Patients with class I obesity and refractory gastroesophageal reflux disease may not qualify for bariatric surgery, and the effectiveness of laparoscopic Nissen fundoplication remains controversial. This study evaluates the early efficacy of laparoscopic Nissen fundoplication in patients with class I and II obesity. METHODS: Data for patients who underwent laparoscopic Nissen fundoplication between 2009 and 2014 were collected prospectively. Cohorts were stratified based on body mass index at the time of surgery: Nonobese (body mass index <30 kg/m2), class I obese (body mass index 30-34.9 kg/m2), and class II obese (body mass index 35-39.9 kg/m2). Primary outcome measures were symptoms assessed using the gastroesophageal reflux symptom scale and the gastroesophageal reflux disease health-related quality of life questionnaires. RESULTS: One hundred seventy-six patients underwent laparoscopic Nissen fundoplication during the study period: 76 nonobese (body mass index 26.2 ± 2.9 kg/m2), 53 class I obese (body mass index 32.4 ± 1.5 kg/m2), and 47 class II obese (body mass index 37.7 ± 2.5 kg/m2). Baseline gastroesophageal reflux symptom scale scores were 35.5 (6-72), 37.0 (5-72), and 45.0 (5-72) in nonobese, class I obese, and class II obese groups, respectively. Six weeks postoperatively, scores decreased to 6.5 (0-72), 4.0 (0-27), and 9.0 (0-64), respectively (P < .001). After 18-months, scores remained improved at 8.0 (0-72), 5 (0-48), and 4 (0-62), respectively (P < .001). A similar trend was seen in gastroesophageal reflux disease-health-related quality of life scores. Overall, 86%, 83%, and 79% remained free of proton-pump inhibitor medications, respectively. CONCLUSION: Laparoscopic Nissen fundoplication provides similar symptom control and quality of life 18-months postoperatively in nonobese and class I and II obese patients. Thus, laparoscopic Nissen fundoplication represents a viable surgical option for patients with class I and II obesity.

The Raf Kinase Inhibitor Sorafenib Inhibits JAK-STAT Signal Transduction in Human Immune Cells.

Sorafenib is an oral multikinase inhibitor that was originally developed as a Raf kinase inhibitor. We hypothesized that sorafenib would also have inhibitory effects on cytokine signaling pathways in immune cells. PBMCs from normal donors were treated with varying concentrations of sorafenib and stimulated with IFN-α or IL-2. Phosphorylation of STAT1 and STAT5 was measured by flow cytometry and confirmed by immunoblot analysis. Changes in IFN-α- and IL-2-stimulated gene expression were measured by quantitative PCR, and changes in cytokine production were evaluated by ELISA. Cryopreserved PBMCs were obtained from cancer patients before and after receiving 400 mg sorafenib twice daily. Patient PBMCs were thawed, stimulated with IL-2 or IFN-α, and evaluated for phosphorylation of STAT1 and STAT5. Pretreatment of PBMCs with 10 µM sorafenib decreased STAT1 and STAT5 phosphorylation after treatment with IFN-α or IL-2. This inhibitory effect was observed in PBMCs from healthy donors over a range of concentrations of sorafenib (5-20 µM), IL-2 (2-24 nM), and IFN-α (10(1)-10(6) U/ml). This effect was observed in immune cell subsets, including T cells, B cells, NK cells, regulatory T cells, and myeloid-derived suppressor cells. Pretreatment with sorafenib also inhibited PBMC expression of IFN-α- and IL-2-regulated genes and inhibited NK cell production of IFN-γ, RANTES, MIP1-α, and MIG in response to IFN-α stimulation. PBMCs from patients receiving sorafenib therapy showed decreased responsiveness to IL-2 and IFN-α treatment. Sorafenib is a Raf kinase inhibitor that could have off-target effects on cytokine-induced signal transduction in immune effector cells.

MiR-21 enhances melanoma invasiveness via inhibition of tissue inhibitor of metalloproteinases 3 expression: in vivo effects of MiR-21 inhibitor.

Metastatic melanoma is the most aggressive form of this cancer. It is important to understand factors that increase or decrease metastatic activity in order to more effectively research and implement treatments for melanoma. Increased cell invasion through the extracellular matrix is required for metastasis and is enhanced by matrix metalloproteinases (MMPs). Tissue inhibitor of metalloproteinases 3 (TIMP3) inhibits MMP activity. It was previously shown by our group that miR-21, a potential regulator of TIMP3, is over-expressed in cutaneous melanoma. It was therefore hypothesized that increased levels of miR-21 expression would lead to decreased expression of TIMP3 and thereby enhance the invasiveness of melanoma cells. miR-21 over-expression in the melanoma cell lines WM1552c, WM793b, A375 and MEL 39 was accomplished via transfection with pre-miR-21. Immunoblot analysis of miR-21-overexpressing cell lines revealed reduced expression of TIMP3 as compared to controls. This in turn led to a significant increase in the invasiveness of the radial growth phase cell line WM1552c and the vertical growth phase cell line WM793b (p < 0.05), but not in the metastatic cell lines A375 or MEL 39. The proliferation and migration of miR-21 over-expressing cell lines was not affected. Reduced expression of TIMP3 was achieved by siRNA knockdown and significantly enhanced invasion of melanoma cell lines, mimicking the effects of miR-21 over-expression. Treatment of tumor cells with a linked nucleic acid antagomir to miR-21 inhibited tumor growth and increased tumor expression of TIMP3 in vivo in 01B74 Athymic NCr-nu/nu mice. Intra-tumoral injections of anti-miR-21 produced similar effects. This data shows that increased expression of miR-21 enhanced the invasive potential of melanoma cell lines through TIMP3 inhibition. Therefore, inhibition of miR-21 in melanoma may reduce melanoma invasiveness.

Metastatic melanoma: lactate dehydrogenase levels and CT imaging findings of tumor devascularization allow accurate prediction of survival in patients treated with bevacizumab.

PURPOSE: To predict survival in patients with metastatic melanoma by evaluating a combination of serum lactate dehydrogenase (LDH) level and initial computed tomographic (CT) findings of tumor devascularization after antiangiogenic therapy. MATERIALS AND METHODS: Consent was waived for this institutional review board-approved, retrospective, secondary analysis. Forty-four patients with metastatic melanoma received bevacizumab therapy in a randomized prospective phase II trial. Target lesions on the initial posttherapy CT images were evaluated by using Response Evaluation Criteria in Solid Tumors, the Choi criteria, and Morphology, Attenuation, Size, and Structure (MASS) criteria. Cox proportional hazards models were used to assess the association of baseline clinical variables including serum LDH and imaging findings with progression-free and overall survival. The receiver operating characteristic curve with area under the curve (AUC) was used to evaluate accuracy. RESULTS: In multivariate analysis, a high baseline serum LDH level was associated with decreased progression-free survival (hazard ratio = 1.29 for each increase of 100 IU/L; P = .002) and overall survival (hazard ratio = 1.44 for each increase of 100 IU/L; P = .001). Evaluation with MASS criteria of the first CT examination after therapy strongly predicted progression-free (P < .001) and overall (P < .001) survival. Baseline serum LDH level was moderately accurate for predicting progression-free survival at 9 months (AUC = 0.793) and overall survival at 18 months (AUC = 0.689). The combination of baseline serum LDH levels and evaluation with MASS criteria at the first CT examination after therapy had significantly higher accuracy for predicting progression-free survival at 9 months (AUC = 0.969) and overall survival at 18 months (AUC = 0.813) than did baseline serum LDH levels alone for prediction of progression-free survival (P = .020). CONCLUSION: A combination of baseline serum LDH levels and evaluation with MASS criteria at the first CT examination after bevacizumab therapy had the highest accuracy for predicting survival in patients with metastatic melanoma.