Is it the technique or wound protection that is key to reducing wound infections in Roux-en-Y gastric bypass procedures?

INTRODUCTION: An unusually high surgical site infection (SSI) rate after Roux-en-Y gastric bypass (RYGB) was noted on routine outcomes review. Surgeon A, who had a rate of 8.9%, utilized the transoral technique (passage down esophagus into gastric pouch) for anvil insertion for the circular-stapled gastrojejunostomy. By comparison, SSI rate was 0% for Surgeon B, who inserted anvil transabdominally (direct passage into stomach via gastrotomy) and used wound protection (wound protector and plastic drape over stapler). We sought to determine if it was the technique for anvil insertion (transoral or transabdominal) or use of wound protection that could help reduce SSIs. METHODS: In mid-2017, Surgeon A added wound protection (wound protector and plastic drape over stapler) to the transoral technique to minimize oral flora wound contamination. Surgeon B made no changes. In this study, wound-related outcomes are examined, comparing patients who underwent surgery before (Group 1) versus after (Group 2) this intervention. Statistical analysis performed utilizing t tests and Chi square analysis; p < 0.05 considered significant. RESULTS: Three hundred and thirty-three patients underwent RYGB. Group 1 consisted of 182 patients over 17 months; 151 patients over 13 months were in Group 2. Groups were similar in age, BMI, gender, and prevalence of diabetes. There was a decrease in SSIs between Group 1 and Group 2 (5 vs. 0, p = 0.04). 11 wound complications occurred in Group 1 (5 SSIs, 4 seromas and 2 hematomas); whereas 2 wound complications occurred in Group 2 (1 seroma and 1 hematoma); decrease from 6 to 1.3%, p = 0.03. CONCLUSIONS: This study demonstrates that changing technique can lead to best outcomes. There was a dramatic reduction of wound complications and complete elimination of SSIs with a change in operative technique. The higher risk of SSI with the transoral anvil insertion when preforming a circular-stapled anastomosis can be mitigated with use of wound protection.

Roux-en-Y gastric bypass as a salvage procedure in complicated patients with failed fundoplication(s).

BACKGROUND: In symptomatic patients after failed fundoplication, reoperation is considered. In complex or obese patients, Roux-en Y gastric bypass (RYGB) may be the best operation. We sought to characterize the outcomes of patients with failed fundoplication to undergo salvage RYGB, and to compare these outcomes to patients undergoing reoperative fundoplication. METHODS: A prospectively maintained database was queried for procedures performed at a single institution from 2011 to 2017. GERD health-related quality of life (HRQL) surveys were administered at defined intervals. RESULTS: Thirty-six patients underwent salvage RYGB and 84 patients underwent reoperative fundoplication. The RYGB cohort had a higher BMI (35.5 ± 6.8 vs. 28.7 ± 5.3, p < 0.01), more gastroparesis (52.8% vs. 9.5%, p < 0.01), more esophagitis (42.9% vs. 20.2%, p = 0.01), and more prior fundoplications (1.9 vs. 1.2, p < 0.01). The incidence of gastroparesis and esophagitis was directly related to the number of failed fundoplications (p < 0.05). Operative times were longer with RYGB (332.7 ± 131.5 vs. 200.0 ± 67.6 min, p < 0.01) as was length of stay (4.3 ± 3.4 vs. 2.8 ± 1.5 days, p = 0.02), incidence of Clavien-Dindo complications ≥ Grade 3 (19.4% vs. 4.8%, p = 0.01), 30-day reoperation (11.1% vs. 1.2%, p = 0.01), and 30-day readmission (32.4% vs. 11.9%, p < 0.01). In five patients with three or more prior fundoplication attempts, an esophagojejunostomy was necessary. If these patients are excluded, there was no difference for RYGB with gastrojejunostomy compared to reoperative fundoplication for complications, reoperations, or readmissions. GERD-HRQL scores were similar prior to surgery in both cohorts and improved significantly and to a similar degree on long-term follow-up. CONCLUSIONS: In a complex cohort of patients with high rates of obesity and numerous failed previous fundoplication attempts, conversion to RYGB results in good symptomatic outcomes. Patients with three or more previous fundoplication attempts are more likely to require esophagojejunostomy. Complication rates in this subset of patients appear to be quite high.

Green tea component epigallocatechin-3-gallate decreases expression of osteopontin via a decrease in mRNA half-life in cell lines of metastatic hepatocellular carcinoma.

INTRODUCTION: Osteopontin (OPN) mediates metastasis and invasion of hepatocellular carcinoma (HCC). Epigallocatechin-3-gallate (EGCG), found in green tea, suppresses HCC tumor growth in vitro. We sought to investigate the role of EGCG in modulating OPN in cell lines of metastatic HCC. METHODS: Experimental HCC cell lines included HepG2 and MHCC-97H HCC cells, which express high levels of OPN, and the Hep3B cells, which express lesser levels of OPN. Cells were treated with EGCG (0.02-20 µg/mL) before measurement of OPN with enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction. Scratch assay measured cell migration. Binding of the OPN promoter to RNA pol II was evaluated by the use of Chromatin-IP assay after EGCG treatment. Transcriptional regulation of OPN was investigated with luciferase reporter plasmids containing various deletion fragments of the human OPN promoter. Measurement of the half-life of OPN mRNA was conducted using actinomycin D. RESULTS: Treatment of MHCC-97H and HepG2 cells with 2 µg/mL and 20 µg/mL EGCG caused a ∼6-fold and ∼90-fold decrease in secreted protein levels of OPN (All P < .001). OPN mRNA was decreased with EGCG concentrations of 0.2-20 µg/ml (All P < .001). The 3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (ie, MTT) assay revealed that differences in OPN expression were not due to viability of the HCC cell lines. Promoter assay and chromatin immunoprecipitation analysis revealed no effect of EGCG on the transcriptional regulation of OPN. Posttranscriptionally, EGCG decreased the half-life of OPN mRNA from 16.8 hours (95% confidence interval 9.0-125.1) to 2.5 hours (95% confidence interval 2.1-3.2) (P < .001). Migration was decreased in EGCG treated cells at 24 hours (8.0 ± 2.4% vs 21.2 ± 10.8%, P < .01) and at 48 hours (13.2 ± 3.6% vs 53.5 ± 19.8%, P < .001). CONCLUSION: We provide evidence that EGCG decreases OPN mRNA and secreted OPN protein levels by decreasing the half-life of OPN mRNA in MHCC-97H cells. The translatability of EGCG for patients with HCC is promising, because EGCG is an inexpensive, easily accessible chemical with an extensive history of safety.

The "weekend effect" in urgent general operative procedures.

BACKGROUND: There is growing concern that the quality of inpatient care may differ on weekends versus weekdays. We assessed the "weekend effect" in common urgent general operative procedures. METHODS: The Healthcare Cost and Utilization Project Florida State Inpatient Database (2007-2010) was queried to identify inpatient stays with urgent or emergent admissions and surgery on the same day. Included were patients undergoing appendectomy, cholecystectomy for acute cholecystitis, and hernia repair for obstructed/gangrenous hernia. Outcomes included duration of stay, inpatient mortality, hospital-adjusted charges, and postoperative complications. Controlling for hospital and patient characteristics and type of surgery, we used multilevel mixed-effects regression modeling to examine associations between patient outcomes and admissions day (weekend vs weekday). RESULTS: A total of 80,861 same-day surgeries were identified, of which 19,078 (23.6%) occurred during the weekend. Patients operated on during the weekend had greater charges by $185 (P < .05), rates of wound complications (odds ratio [OR] 1.29, 95% confidence interval [95% CI] 1.05-1.58; P < .05), and urinary tract infection (OR 1.39, 95% CI 1.05-1.85; P < .05). Patients undergoing appendectomy had greater rates of transfusion (OR 1.43, 95% CI 1.09-1.87; P = .01), wound complications (OR 1.32, 95% CI 1.04-1.68; P < .05), urinary tract infection (OR 1.76, 95% CI 1.17-2.67; P < .01), and pneumonia (OR 1.41, 95% CI 1.05-1.88; P < .05). Patients undergoing cholecystectomy had a greater duration of stay (P = .001) and greater charges (P = .003). CONCLUSION: Patients undergoing weekend surgery for common, urgent general operations are at risk for increased postoperative complications, duration of stay, and hospital charges. Because the cause of the "weekend effect" is still unknown, future studies should focus on elucidating the characteristics that may overcome this disparity.

Alcohol inhibits osteopontin-dependent transforming growth factor-ß1 expression in human mesenchymal stem cells.

Alcohol (EtOH) intoxication is a risk factor for increased morbidity and mortality with traumatic injuries, in part through inhibition of bone fracture healing. Animal models have shown that EtOH decreases fracture callus volume, diameter, and biomechanical strength. Transforming growth factor ß1 (TGF-ß1) and osteopontin (OPN) play important roles in bone remodeling and fracture healing. Mesenchymal stem cells (MSC) reside in bone and are recruited to fracture sites for the healing process. Resident MSC are critical for fracture healing and function as a source of TGF-ß1 induced by local OPN, which acts through the transcription factor myeloid zinc finger 1 (MZF1). The molecular mechanisms responsible for the effect of EtOH on fracture healing are still incompletely understood, and this study investigated the role of EtOH in affecting OPN-dependent TGF-ß1 expression in MSC. We have demonstrated that EtOH inhibits OPN-induced TGF-ß1 protein expression, decreases MZF1-dependent TGF-ß1 transcription and MZF1 transcription, and blocks OPN-induced MZF1 phosphorylation. We also found that PKA signaling enhances OPN-induced TGF-ß1 expression. Last, we showed that EtOH exposure reduces the TGF-ß1 protein levels in mouse fracture callus. We conclude that EtOH acts in a novel mechanism by interfering directly with the OPN-MZF1-TGF-ß1 signaling pathway in MSC.

Clinical and pathologic features influencing survival in patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma.

OBJECTIVE: The aim of the study was to determine the clinicopathological features that influence survival in patients with resected pancreatic ductal adenocarcinoma (PDA). METHODS: The study used a single institution retrospective review of patients undergoing pancreaticoduodenectomy (PD) for PDA from 1993 to 2010. RESULTS: Two hundred forty-six consecutive cases of resected PDA were identified: 128 males (52 %), median age 68 years. Median hospital length of stay was 8 days and 30-day mortality rate was 2.4 %. There were 101 (41.1 %) postoperative complications, 77 % of which were Dindo-Clavien Grade 3 or less. Overall survival was 85, 63, 25, and 15 % at 6 months, 1 year, 3 years, and 5 years, respectively, with a median survival of 17 months. Multivariate Cox proportional hazard modeling demonstrated lymph node ratio was negatively correlated with survival at all time points. Preoperative hypertension was a poor prognostic factor at 6 months, 3 years, and 5 years. The absence of postoperative complications was protective at 6 months whereas pancreatic leaks were associated with worse survival at 6 months. Abdominal pain on presentation, operative time, and estimated blood loss were also associated with decreased survival at various time points. CONCLUSION: The strongest prognostic variable for short- and long-term survival after PD for PDA is lymph node ratio. Short-term survival is influenced by the postoperative course.

An MAPK-dependent pathway induces epithelial-mesenchymal transition via Twist activation in human breast cancer cell lines.

BACKGROUND: Twist is an epithelial-mesenchymal transition (EMT) transcription factor that instigates cell invasion. Our research has shown that osteopontin (OPN) regulates the EMT factor Twist. The underlying signaling pathway is unknown. We hypothesized that OPN activates Twist to induce EMT in human breast cancer. METHODS: Potential kinases for Twist were identified using NetPhosK. Inhibitors of MEK1/2, JNK, p38 MAPK, and PI3K were applied to human breast cancer cells MDA-MB231 (OPN high). After 24 h, Twist was immunoprecipitated and incubated with phosphoserine. Expression of the Twist target protein, Bmi-1, was determined following 24-h osteopontin aptamer (APT) treatment; mutant aptamer (MuAPT) was used as the control. Scratch-wound assay was imaged 12, 24, and 48 h after APT and MuAPT treatment. RESULTS: MEK1/2 inhibition caused ≈ twofold decrease in Twist serine phosphorylation (P < .05). APT blockade of OPN in MB231 decreased Bmi1 protein twofold (P < .05). Aptamer-treated cells were significantly decreased in cell migration and wound closure in the scratch wound-assay (P < .001). CONCLUSION: We demonstrate that OPN extracellular binding to MB231 activates an autocrine MAPK intracellular signaling pathway resulting in Twist activation and promoting Bmi1 expression to further EMT initiation and cellular migration. Our results elucidate a previously undescribed role for OPN as a prime regulator of EMT in human breast cancer cells.

Obesity and trends in malpractice claims for physicians and surgeons.

BACKGROUND: The increasing prevalence of obesity has altered the practice of medicine and surgery, with the emergence of new operations and medications. We hypothesized that the landscape of medical malpractice claims has also changed. METHODS: We queried the Physician Insurers Association of American database for 1990 through 1999 and 2000 through 2009 for cases corresponding to International Classification of Diseases, 9th edition, codes for obesity. We extracted adjudicatory outcome, closed and paid claims data, indemnity payments, primary alleged error codes, National Association of Insurance Commissioners severity of injury class, procedural codes, and medical specialty data. RESULTS: A total of 411 obesity claims were filed from 1990 to 1999 and 1,591 obesity claims were filed from 2000 to 2009. General surgery was the specialty with the greatest number of obesity claims from 1990 to 1999 and was second to family practice for 2000 to 2009. Although the percentage of paid general surgery obesity claims has decreased significantly from 69% in 1990-1999 to 36% in 2000-2009, the mean indemnity payments have increased substantially ($94,000 to $368,000). CONCLUSION: Recently, the percentage of paid general surgery obesity claims has significantly decreased; however, individual and total indemnity payments have increased. Obesity continues to impact general surgery malpractice substantially. Efforts to manage this component of physician and hospital practices must continue.

Osteopontin up-regulates critical epithelial-mesenchymal transition transcription factors to induce an aggressive breast cancer phenotype.

BACKGROUND: Tumor cells undergoing epithelial-mesenchymal transition (EMT) develop cellular properties leading to stroma invasion and intravasation. We have previously shown in a xenograft breast cancer model that blocking osteopontin (OPN), a secreted phosphoprotein, decreases EMT. This study examines OPN's role in EMT initiation through its regulation of EMT transcription factors (TFs) Snail, Slug, and Twist. OPN's role in Twist activation is examined through immunoprecipitation and Western blot. STUDY DESIGN: MDA-MB-231 breast cancer cells secreting high levels of OPN were treated with OPN aptamer (APT) or mutant APT. Osteopontin APT binds to and inhibits extracellular OPN. Low-OPN-secreting breast cancer cells, MCF-7, were treated with OPN, OPN+APT, or OPN+mutant APT. Twist was isolated in MDA-MB-231 with immunoprecipitation. Phospho-serine antibody detected activated Twist in Western blot. Activation of Twist was confirmed by chromatin immunoprecipitation. RESULTS: Analysis through quantitative polymerase chain reaction demonstrated APT inhibition of OPN in MDA-MB-231 cells caused a decrease in EMT-TF expression (MDA-MB-231 vs MDA-MB-231+APT: *Twist ΔΔCT: 1.0 vs 0.07; *Snail ΔΔCT: 1.0 vs 0.11; *Slug ΔΔCT: 1.0 vs 0.11; *p < 0.001). Mutant APT did not change EMT-TF expression (NS). Treatment of MCF-7 cells with OPN caused an increase in EMT-TF expression (MCF-7 vs MCF-7+OPN: Twist ΔΔCT: 1.0 vs 9.1; *Snail ΔΔCT: 1.0 vs 11.2; *Slug ΔΔCT: 1.0 vs 10.9; *p < 0.001). The EMT-TF expression in MCF-7 treated with OPN+APT did not differ significantly from MCF-7 alone. Phosphorylated Twist protein was reduced 2-fold with APT in MDA-MB-231 compared with MDA-MB-231 and MDA-MB-231+mutant APT. Twist phorphorylation induced binding to the promoter regions of Twist-regulated gene, B lymphoma Mo-MLV insertion region 1 homolog, a critical protein for EMT progression. CONCLUSIONS: This study shows that OPN is critical in EMT initiation through activation of Twist via serine phosphorylation. These unique observations indicate that OPN APT can serve a clinical role as a novel therapeutic agent by diminishing breast cancer oncogenesis.

Comparing 20 years of national general surgery malpractice claims data: obesity versus morbid obesity.

BACKGROUND: We hypothesized that the increasing body mass index of the population has affected general surgery malpractice claims. METHODS: We queried the Physician Insurers Association of America database from 1990 to 1999 (ie, period 1) and 2000 to 2009 (ie, period 2) for claims associated with obesity and morbid obesity. We analyzed the error involved, injury severity, procedure, and outcome. RESULTS: Five hundred seventy-five claims were identified. The percentage of paid claims did not differ by body mass index. Improper performance was the most common alleged error, gastric bypass was the most common procedure, and death was the most common injury. For obesity claims, the case was more likely to be settled in period 1 and withdrawn/dismissed in period 2 (P < .001). The number of morbid obesity claims rose from 9 in period 1 to 249 in period 2. CONCLUSIONS: The significant rise in morbid obesity claims between periods is likely caused by the substantial increase in the number of bariatric procedures performed.

Impact of business infrastructure on financial metrics in departments of surgery.

BACKGROUND: In the current environment, pressure is ever increasing to maximize financial performance in surgery departments. Factors such as physician extenders, billing and collection, payor mix, contracting, incentives from the Centers for Medicare and Medicaid Services, and administrative incentives may greatly influence financial performance. However, despite a plethora of information from the University HealthSystem Consortium and the Association of American Medical Colleges, best-practice information for business infrastructure is lacking. To obtain a sampling of current practices, we conducted a survey of departments of surgery. METHODS: An anonymous 30-question survey addressing demographics, productivity, revenue and expense profile, payor mix, physician extender and staff personnel, billing and collections methodology, and financial performance was distributed among members of the Society of Surgical Chairs via SurveyMonkey. This was approved by the Loyola Institutional Research Board. Multivariate linear regression analyses and t tests/rank-sum tests were performed, as appropriate. Data are presented as mean ± SEM. RESULTS: A total of 25 (19%) departments responded; 14 were integrated with the hospital/health system, and 11 were integrated with the medical school. In 60% (n = 15), the main hospital had 500 to 1,000 beds; 48% (n = 12) had >4 hospitals in their system. For FY10, MD clinical full-time equivalents (FTEs) were 49 ± 10; total work relative value units (wRVUs) were 320 ± 8 k; and total billed cases were 43 ± 16 k. A total of 23 of 25 used physician-extenders with an average of 18 ± 5 per department and in 22 of 23, the physician extenders billed. On average, there were 18 ± 6 clinical-support staff, 25 ± 11 front-office staff, and 13 ± 3 back-office support staff FTEs. Among these FTEs, there were 16 ± 5 devoted to business operations (billing, coding, denial/claims management, financial oversight). Collections/wRVUs were $60 ± 3 (range, 39-80). Regression modeling demonstrated that total wRVUs were determined by the number of MD FTEs (P = .01), number of physician extenders (P = .01), number of front-office staff (P = .01), number of back-office staff (P = .02), and number of total business staff (P = .01). Collections/wRVUs were predicted by number of hospitals (P = .04), number of MD FTEs (P = .03), number of physician extenders (P = .01), and number of cases/total business staff (P = .02). Interestingly, wRVUs/MD was predicted by number of MD FTEs (P = .01) but were not greatly impacted by numbers of clinical or business support staff. In 4 of 25, the billing and coding staff were incentivized and had a Collections/wRVU = 64 ± 5 whereas nonincentivized staff had collections/wRVU = 59 ± 3. (P = NS) Also, %Accounts receivable >90 days (15% vs 25%) were not substantially different. Only 48% (12/25) have departments have recouped Centers for Medicare and Medicaid dollars for Physician Quality Reporting Initiative, Meaningful Use, Patient-Centered Medical Homes, or other Accountable Care-like programs. One-half (13) of the departments had both an inpatient and outpatient electronic medical record. Finally, on a scale of 1-10 (10 = highest), the average level of satisfaction with billing and collections processes was 6. CONCLUSION: Our results indicate that the physician extender, clinical support staff, and business staff environment can impact surgeon productivity, and there is opportunity for improvement. Determining best practices for ratios of support staff/MD and optimizing the role of electronic medical record in workflow and billing/collections are critical in the current environment. Our pilot study requires extension across more institutions for validation.

Medium and long-term outcomes after pneumatic dilation or laparoscopic Heller myotomy for achalasia: a meta-analysis.

Recent randomized studies comparing outcomes after pneumatic dilation (PD) and laparoscopic Heller myotomy (LHM) for the treatment of achalasia are conflicting and limited to short-term follow-up. Our meta-analysis compared the long-term durability of these approaches, with the hypothesis that LHM offers superior long-term remission compared with PD. We identified 36 studies published between 2001 and 2011 with at least 5 years of follow-up. Those studies describing PD included 3211 patients (mean age, 49.8 y). For PD, the mean 5-year remission rate was 61.9% and the mean 10-year remission rate was 47.9%. Overall, 1526 patients (mean age, 46.3 y) were treated with LHM; 83% received a fundoplication. In contrast, the mean 5- and 10-year remission rates after LHM were 76.1% and 79.6%, respectively. Finally, the perforation rate for LHM was twice that of PD (4.8% vs. 2.4%; P<0.05). We conclude that despite a higher frequency of perforation, LHM affords greater long-term durability.

Epithelial-mesenchymal transition, TGF-ß, and osteopontin in wound healing and tissue remodeling after injury.

Epithelial-mesenchymal transition (EMT) is a process essential to wound healing and tissue remodeling after a thermal burn or other injury. EMT is characterized by phenotypic changes in epithelial cells that render them apolar, with decreased cell-cell adhesions, increased motility, and changes in cytoskeletal architecture similar to mesenchymal stem cells. With regard to healing a thermal burn wound, many facets of wound healing necessitate cells to undergo these phenotypic changes; two will be described in the following review. The first is the differentiation of epithelial cells into myofibroblasts that rebuild the extracellular matrix and facilitate wound contraction. The second is reepithelialization by keratinocytes. The primary cytokine signal identified in the literature that triggers EMT is transforming growth factor (TGF)-ß. In addition to its vital role in the induction of EMT, TGF-ß has many other roles in the wound healing process. The following review will provide evidence that EMT is a central event in wound healing. It will also show the importance of a regulated amount of TGF-ß for proper wound healing. Finally, osteopontin will be briefly discussed with its relation to wound healing and its connections to EMT and TGF-ß.

The tumor microenvironment.

The concept of the tumor microenvironment, developed from Paget's "seed and soil" theory is made up of the cancer cells, the stromal tissue, and the extracellular matrix. In this mini-review, each of the components of this dynamic network will be examined. We will show that there are a multitude of complex interactions and a host of molecules involved in tumorogenesis and metastasis. We will further illustrate this notion with examples from the tumor microenvironment of breast cancer. Lastly, we conclude with thoughts about how this will influence the surgical field with examples of therapeutic agents already in use that target aspects of this microenvironment.