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Background: Pain after surgery is commonly controlled with opioid pain medications. A multi-modal pain strategy that involves acetaminophen may help minimize the negative consequences of opioids, such as ileus, respiratory depression, and addictive potential. There are limited data on the effectiveness of intravenous (IV) acetaminophen in comparison with other nonopioid pain medications., Materials and Methods: Four databases were queried for the keywords "acetaminophen," "intravenous," and "postoperative". Prospective studies of adult patients receiving at least 24 h of IV acetaminophen after intraabdominal surgery were analyzed for 12- and 24-h pain scores and 24-h narcotic consumption. A random effects model was performed using mean differences and 95% confidence intervals to assess the effect of IV acetaminophen on outcomes. Heterogeneity was assessed using χ 2 and the I 2 statistics., Results: Seventeen articles were identified that complied with inclusion and exclusion criteria. There was no significant difference in 24-h pain scores between IV acetaminophen and any other comparator, or in secondary endpoints of 12-h pain scores and 24-h narcotic consumption. Subgroup analysis demonstrated significant benefit for IV acetaminophen in open surgeries for decreased 24-h narcotic consumption. When analyzing individual medications, non-steroidal anti-inflammatory drugs demonstrated the largest reduction in 24-h narcotic consumption. Data were of moderate quality and demonstrated significant heterogeneity between studies., Conclusions: The lack of significant differences in primary endpoints may be explained by the heterogeneous, moderate-quality data. However, subgroup analyses suggested IV acetaminophen may be advantageous in open surgeries, and non-steroidal anti-inflammatory drugs may lower the 24-h narcotic requirement., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Gallbladder cancer (GBC) is a lethal disease with high incidence among Hispanics. Overall survival (OS) among races/ethnicities has not been described using the most recent National Cancer Database. This study hypothesized that prognosis is worse for Hispanics compared to similar non-Hispanic populations., Methods: Patients with GBC were identified from the National Cancer Database and categorized as White, Black, Hispanic, and Other. Descriptive statistics, OS, and Cox regression were examined., Results: The study identified 12 952 patients. Median age was 71 years and 68.8% were female. The study characterized 69.8% White, 13.9% Black, 11.0% Hispanic, and 5.4% other patients. A 5-year OS curves differed, with survival highest in Hispanic patients (27% vs 23% Other, 18% White, and 17% Black, P < 0.001). Hispanics presented at younger ages (67 vs 72 years, P < 0.001), were more likely to be uninsured (17.3% vs 3.9% P < 0.001), had lower income (P < 0.001), and education levels (P < 0.001) compared to Whites. Following multivariable modeling, treatment at an academic facility (HR 0.90, 95%CI 0.84-0.97) and year of diagnosis (HR 0.90, 95%CI 0.88-0.92) related to survival. Hispanic ethnicity did not show significance (P = 0.207)., Discussion: Hispanic ethnicity exhibits the highest OS for GBC, but after adjusting for covariates, this influence is not significant., (© 2018 Wiley Periodicals, Inc.)

Objectives: Positive surgical margins (PSM) and lymph node yield (LNY) following radical cystectomy (RC) for urothelial carcinoma of the bladder affect survival. Variations in PSM or LNY at different care facilities are poorly described. We evaluated the relationship between hospital surgical volume and academic hospital status with these surgical outcomes and overall survival (OS)., Methods and Materials: Patients with nonmetastatic urothelial carcinoma of the bladder who underwent RC were identified from the National Cancer Database (2004-2013). Treatment centers were categorized as academic (ACC) and community cancer centers (CCC). Logistic regression was used to identify factors associated with PSM status and LNY, and a multivariate Cox proportional hazards model was used to determine factors associated with OS., Results: In our cohort, 39,274 patients underwent RC. A lower proportion of PSMs (10% vs.12%; P<0.001) and higher median LNY (14 vs. 8, P<0.001) was observed at ACCs compared to CCCs. On logistic regression, there were lower odds of PSM (OR = 0.89, 95% CI: 0.81-0.97) and higher odds of LNY ≥ 10 nodes (OR = 1.84, 95% CI: 1.74-1.96) among patients at ACCs compared to CCCs. Cox proportional hazards analysis demonstrated benefit to OS at high-volume centers (HR = 0.91, 95% CI: 0.87-0.95) but not based on ACC designation. The OS advantage at high-volume centers is attenuated (HR = 0.95, 95% CI: 0.91-0.99) by PSM status and LNY., Conclusions: ACCs demonstrate improved surgical outcomes following RC, and a survival advantage attributable to high surgical volume is identified. Centralization of care may lead to improved outcomes in this lethal malignancy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background and Objectives: Ablation is a common treatment modality for malignant primary liver tumors(PLTs), outcomes following laparoscopic (LA) versus open ablation (OA) are ill-defined. This project compares peri-procedural outcomes of LA versus OA for PLTs., Materials and Methods: Patients with PLTs undergoing radiofrequency ablation were queried from ACS NSQIP Database (2005-2013) using CPT codes. Patients undergoing percutaneous ablation or hepatic resection were excluded. Multivariable logistic regression analyses determined the association of ablation approach with 30-day morbidity and mortality., Results: Of 5747 with PLTs, 655 (11.4%) ablations were identified: 177 (27.0%) underwent OA, 478 (73.0%) underwent LA. Patients undergoing LA had lower mortality (1.9% vs 5.1%, P = 0.026), lower minor morbidity (2.3% vs 5.7%, P = 0.031), and lower major morbidity (4.2% vs 17.0%, P < 0.001). Adjusting for demographics, disease-specific variables (preoperative ascites, total bilirubin, platelet count, albumin, and INR), 30-day mortality (OR 3.85, 95%CI: 1.38-10.80, P = 0.010), minor morbidity (OR 2.98, 95%CI: 1.16-7.67, P = 0.024), and major morbidity (OR 4.59 95%CI: 2.41-8.76, P < 0.001) were statistically lower in LA. OA demonstrated increased length of stay(LOS) (5 vs 2 days, P < 0.001), and longer operative time (152 vs 112 min, P < 0.001)., Conclusion: LA offers decreased peri-procedural morbidity, mortality, and reduced LOS. LA should be the preferred method for hepatic ablation., (© 2018 Wiley Periodicals, Inc.)

Objectives: Orthotopic liver transplantation (OLT) is the preferred treatment for hepatocellular carcinoma (HCC) in select patients. Many patients listed for OLT have a history of prior upper abdominal surgery (UAS). Repeat abdominal surgery increases operative complexity and may cause a greater incidence of complication. This study sought to compare outcomes after liver transplantation for patients with and without prior UAS., Methods: Adult HCC patients undergoing OLT were identified using the database from the Organ Procurement and Transplantation Network (1987-2015). Patients were separated by presence of prior UAS into 2 propensity-matched cohorts. Overall survival (OS) and graft survival (GS) were analyzed by log-rank test and graphed using Kaplan-Meier method. Recipient and donor demographic and clinical characteristics were also studied using Cox regression models., Results: A total of 15,043 patients were identified, of whom 6,205 had prior UAS (41.2%). After 1:1 propensity score matching, cohorts (UAS versus no UAS) contained 4,669 patients. UAS patients experienced shorter GS (122 months vs 129 months; P < .001) and shorter OS (130 months vs 141 months; P < .001). Median duration of stay for both cohorts was 8 days. Multivariate Cox regression models revealed that prior UAS was associated with an increased hazard ratio (HR) for GS (HR 1.14; 95% confidence interval (CI) 1.06-1.22; P < .001) and OS (HR 1.14; 95% CI 1.06-1.23; P < .001)., Conclusion: Prior UAS is an independent negative predictor of GS and OS after OLT for HCC. OLT performed in patients with UAS remains a well-tolerated and effective treatment for select HCC patients but may alter expected outcomes and influence follow-up protocols., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Surgical approach may influence morbidity following hepatectomy. This study sought to compare outcomes in minimally invasive surgery (MIS), conversion from MIS to open, and planned open hepatectomy patients and analyze factors leading to conversion., Methods: The 2014 National Surgical Quality Improvement Program dataset was queried for patients undergoing hepatectomy. Patients were divided into three cohorts: MIS, open, or conversion. Propensity matching was performed to compare MIS vs. conversion (3:1) and open vs. conversion (8:1). The logistic regression model was used to identify odds ratios for conversion., Results: Patients undergoing conversion had a higher transfusion rate (26% vs. 9%, p < 0.001), longer length of stay (5 vs. 3 days, p < 0.001), and higher morbidity (38% vs. 18%, p < 0.001) than MIS patients. Patients who underwent conversion had similar short-term outcomes to those who had planned open procedures. Independent predictors of conversion included hypertension (OR 1.91; 95% CI 1.12-3.26) and right lobectomy (OR 20.23; 95% CI 3.74-109.35)., Conclusion: Patients with hypertension and those undergoing right lobectomy had a higher risk of conversion to open procedure. Conversion resulted in higher morbidity and longer length of stay compared to MIS patients, but outcomes were similar to planned open procedures., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Operative resection remains the definitive curative therapy for retroperitoneal sarcoma. Data published recently show a correlation between improved outcomes for complex oncologic operations and treatment at academic centers. For large retroperitoneal sarcomas, operative resection can be complex and require multidisciplinary care. We hypothesized that survival rates vary between type of treating center for patients undergoing resection for retroperitoneal sarcoma., Methods: Patients with stage I to III nonmetastatic retroperitoneal sarcomas who underwent operative resection were identified from the National Cancer Database during the years 2004-2013. Treating centers were categorized as academic cancer centers or community cancer centers. Overall survival was analyzed by log-rank test and graphed using Kaplan-Meier method., Results: A total of 2,762 patients were identified. A majority of patients (59.4%, n = 1,642) underwent resection at an academic cancer centers. Median age at diagnosis was 63 years old. Neoadjuvant radiotherapy was more common at academic cancer centers, while adjuvant radiotherapy was more common at community cancer centers. Improved overall survival was seen at academic cancer centers across all stages compared with community cancer centers (P = .014) but, after multivariable Cox regression analysis, was not a significant independent predictor of survival (hazard ratio = 0.91, 95% confidence interval, 0.79-1.04, P = .171). Academic cancer centers exhibited a greater rate of R0 resection (55.9% vs 47.0%, P < .001) and a lesser odds of positive margins (odds ratio 0.83, 95% confidence interval, 0.69-0.99, P = .044) after multivariable logistic regression., Conclusion: Resection for retroperitoneal sarcoma performed at academic cancer centers was an independent predictor of margin-negative resection but was not a statistically significant factor for survival. This observation suggests that site of care may contribute to some aspect of improved oncologic resection for retroperitoneal sarcoma., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Alpha-fetoprotein (AFP) has a valuable role in postoperative surveillance for hepatocellular carcinoma (HCC) recurrence. The utility of pretreatment or baseline AFP remains controversial. The present study hypothesized that elevated baseline AFP levels are associated with worse overall survival in HCC patients., Methods: Adult HCC patients were identified using the National Cancer Database (2004-2013). Patients were stratified according to baseline AFP measurements into the following groups: Negative (<20), Borderline (20-199), Elevated (200-1999), and Highly Elevated (>2000). The primary outcome was overall survival (OS), which was analyzed by log-rank test and graphed using Kaplan-Meier method. Multivariate regression modeling was used to determine hazard ratios (HR) for OS., Results: Of 41 107 patients identified, 15 809 (33.6%) were Negative. Median overall survival was highest in the Negative group, followed by Borderline, Elevated, and Highly Elevated (28.7 vs 18.9 vs 8.8 vs 3.2 months; P < 0.001). On multivariate analysis, overall survival hazard ratios for the Borderline, Elevated, and Highly Elevated groups were 1.18 (P = 0.267), 1.94 (P < 0.001), and 1.77 (P = 0.007), respectively (reference Negative)., Conclusion: Baseline AFP independently predicted overall survival in HCC patients regardless of treatment plan. A baseline AFP value is a simple and effective method to assist in expected survival for HCC patients., (© 2017 Wiley Periodicals, Inc.)

Background and Objectives: Hepatocellular carcinoma (HCC) patients are often not candidates for resection. This study hypothesized that external beam radiation (XRT) could be equally effective compared to ablation therapy (AT) for selected HCC patients., Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify HCC patients (2004-2012) undergoing XRT or AT for solitary HCC lesions. Propensity score modeling was utilized to adjust for baseline characteristics., Results: Propensity matching identified 784 patients: 157 (20%) XRT and 627 (80%) AT. Median OS for XRT and AT was 22, and 32 months (P < 0.001), respectively. AT demonstrated improved OS for tumors 3-5 cm (30 vs 16 m, P < 0.001) and >5 cm (25 vs 9 m, P < 0.001). Similar survival was found in patients with tumor size <3 cm (37 vs 47 m P = 0.508). Following multivariate analyses, XRT was associated with an increased hazard ratio (HR = 1.64, P < 0.001). Elevated AFP at diagnosis (HR = 1.54, P = 0.001) and tumor size >3 were identified as negative predictors of survival., Conclusions: Similar survival for solitary HCC lesions <3 cm exists between XRT and AT. However, AT demonstrates improved survival rates compared to XRT for lesions >3 cm. This 3 cm reference point may serve as a valuable metric to guide treatment decisions and future investigations., (© 2017 Wiley Periodicals, Inc.)

Background: Enhanced recovery pathways have decreased length of stay after colorectal surgery. Loop ileostomy closure remains a challenge, because patients experience high readmission rates, and validation of enhanced recovery pathways has not been demonstrated. This study examined a protocol whereby patients were discharged on the first postoperative day and instructed to advance their diet at home with close telephone follow-up., Objective: The hypothesis was that patients can be safely discharged the day after loop closure, leading to shorter length of stay without increased rates of readmission or complications., Design: Patients undergoing loop ileostomy closure were queried from the American College of Surgeons National Surgical Quality Improvement Project and compared with a single institution (2012-2015). Length of stay, 30-day readmission, and 30-day morbidity data were analyzed., Settings: The study was conducted at a tertiary university department., Patients: The study includes 1602 patients: 1517 from the National Surgical Quality Improvement Project database and 85 from a single institution., Main Outcome Measures: Length of stay and readmission rates were measured., Results: Median length of stay was less at the single institution compared with control (2 vs 4 d; p < 0.001). Thirty-day readmission (15.3% vs 10.4%; p = 0.15) and overall 30-day complications (15.3% vs 16.7%; p = 0.73) were similar between cohorts. Estimated adjusted length of stay was less in the single institution (2.93 vs 5.58 d; p < 0.0001). There was no difference in the odds of readmission (p = 0.22)., Limitations: The main limitations of this study include its retrospective nature and limitations of the National Surgical Quality Improvement Program database., Conclusions: Next-day discharge with protocoled diet advancement and telephone follow-up is acceptable after loop ileostomy closure. Patients can benefit from decreased length of stay without an increase in readmission or complications. This has the potential to change the practice of postoperative management of loop ileostomy closure, as well as to decrease cost. See Video Abstract at http://links.lww.com/DCR/A310.

Background: Transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) remains controversial. This systematic review sought to examine the role of TACE in the treatment of HCC with PVT in either the main portal vein (MPV) or portal vein branches (PVB)., Methods: PubMed was searched for "hepatocellular carcinoma" and "transarterial chemoembolization" from January 1, 2006 to August 31, 2016. Cohorts treated with TACE for HCC with PVT were included. Meta-analysis of overall survival (OS), mRECIST response, and complication incidence was performed. MPV and PVB subgroups were compared., Results: Of 136 search results, 13 studies with 1933 TACE patients were included. Median OS (95% CI) was eight (5-15) months. Survival rates after one, three, and five years were 29% (20%-40%), 4% (1%-11%), and 1% (0%-5%), respectively. Only 1% experienced liver failure and 18% had post-treatment complications. Patients with MPV thrombosis had worse survival than PVB patients (p < 0.001), but similar mRECIST response rates (14% vs. 16%, p = 0.238)., Conclusion: TACE is a safe treatment for a highly selected population of HCC patients with PVT. Despite worse survival rates compared to PVB thrombosis, PVT in the MPV should not be considered an absolute contraindication to TACE., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The role of radiotherapy (RT) for surgically resected intrahepatic cholangiocarcinoma (ICC) remains poorly defined. Radiotherapy is often considered when positive resection margins exist. The present study sought to examine the impact of radiotherapy following ICC resection., Methods: Patients with early-stage disease, who underwent surgical resection, were identified from the National Cancer Database (1998-2013). Patients were stratified by the receipt of RT. Survival outcomes were examined following propensity score matching (PS), and a Cox regression for survival analysis was used to examine predictors of survival., Results: A total of 2897 patients were identified. R0 status was achieved in 1951 patients (67.3 %). RT was delivered to 525 patients (R0 = 255, R1/R2 = 230, unknown = 43). Following PS matching, the overall survival for R0 versus R1/R2 resection was 31.2 versus 19.5 months (p < .001), respectively. RT was associated with a trend toward improved survival for R1/R2 lymph node negative patients (39.5 vs. 21.1 months; p = .052). In a multivariate model accounting for different patient and disease characteristics, RT was not associated with survival. In contrast, age, comorbidities, tumor grade, resection margins, lymph nodes status, and tumor's T stage were identified as negative predictors of survival., Conclusions: Patients with negative resection margins demonstrated improved survival outcome among ICC patients. In patients with positive resection margins and node negative disease, radiotherapy did not provide a survival benefit. Further studies are warranted to confirm and further define these results.

Postoperative Ileus (POI), which occurs after surgical manipulation of the bowel during abdominal operations, is associated with prolonged hospital stay, increasing medical costs, and delayed advancement of enteral diet, which contributes to a significant economic burden on the healthcare system. The use of accelerated care pathways has shown to positively impact gut function, but inevitable postoperative opioid use contributes to POI. Alvimopan is a peripherally acting μ-opioid receptor antagonist designed to mitigate antimotility effects of opioids. In our review, we examined ten trials on alvimopan's use after abdominal operations. Several of the earlier studies on patients undergoing bowel resection showed correlations between the study group and GI recovery as defined by passage of flatus, first bowel movement, and time to readiness for discharge. Data in patients undergoing total abdominal hysterectomy showed similarly decreased GI recovery time. Additionally, data within the past few years shows alvimopan is associated with more rapid GI recovery time in patients undergoing radical cystectomy. Based on our review, use of alvimopan remains a safe and potentially cost-effective means of reducing POI in patients following open GI surgery, radical cystectomy, and total abdominal hysterectomy, and should be employed following these abdominal operations.

Background: Fatty liver disease (FLD) is commonly associated with insulin resistance and obesity, but interestingly it is also observed at low insulin states, such as prolonged fasting. Thus, we asked whether insulin is an independent modulator of hepatic lipid accumulation., Methods/principal Findings: In mice we induced, hypo- and hyperinsulinemia associated FLD by diet induced obesity and streptozotocin treatment, respectively. The mechanism of free fatty acid induced steatosis was studied in cell culture with mouse liver cells under different insulin concentrations, pharmacological phosphoinositol-3-kinase (PI3K) inhibition and siRNA targeted gene knock-down. We found with in vivo and in vitro models that lipid storage is increased, as expected, in both hypo- and hyperinsulinemic states, and that it is mediated by signaling through either insulin receptor substrate (IRS) 1 or 2. As previously reported, IRS-1 was up-regulated at high insulin concentrations, while IRS-2 was increased at low levels of insulin concentration. Relative increase in either of these insulin substrates, was associated with an increase in liver-specific fatty acid transport proteins (FATP) 2&5, and increased lipid storage. Furthermore, utilizing pharmacological PI3K inhibition we found that the IRS-PI3K pathway was necessary for lipogenesis, while FATP responses were mediated via IRS signaling. Data from additional siRNA experiments showed that knock-down of IRSs impacted FATP levels., Conclusions/significance: States of perturbed insulin signaling (low-insulin or high-insulin) both lead to increased hepatic lipid storage via FATP and IRS signaling. These novel findings offer a common mechanism of FLD pathogenesis in states of both inadequate (prolonged fasting) and ineffective (obesity) insulin signaling.

Objective: To determine if a history of infertility is associated with alcohol abuse risk factors, depression, and other psychiatric disorders., Methods: Pregnant women awaiting their first prenatal visit completed a questionnaire and subsequently participated in an interview consisting of the Structured Clinical Interview for DSM-IIIR and the Family Alcohol and Drug Survey. The data obtained from women with a history of infertility were compared with the data from women without prior infertility., Results: Eighty-nine pregnant women participated in the study, 27 with prior infertility and 62 without. Subjects were demographically similar, except that women with a history of infertility were slightly older than controls (34.7 vs. 31.1 years, p < 0.001). Pregnant women with a history of infertility reported needing significantly more drinks to get high, (3.3 vs. 2.7, p = 0.04) and were more likely to have clinically elevated tolerance, annoyance, cut-down, and eye-opener (T-ACE) alcohol tolerance scores (83.3% vs. 52.3%, p < 0.01) than women without such history. Major depression (lifetime) was diagnosed in 69.2% of infertility subjects compared with 30% of controls (p < 0.05). Lifetime simple phobia (23.1% vs. 10%, p < 0.01), generalized anxiety disorder (23.1% vs. 3%, p < 0.01), panic disorder (15.4% vs. 0%, p < 0.05), and bulimia (7.7% vs. 0%, p < 0.05) were also more common in women with a history of infertility compared with controls., Conclusions: Pregnant women with a history of infertility are at increased risk for alcohol abuse and are more likely to suffer from other psychiatric disorders than women without such history. Special attention to these issues is warranted when caring for pregnant women who were previously infertile.

Objective: The World Health Organization laboratory manual, last revised in 1992, states that the normal pH of semen ranges from 7.2 to 8.0. Our experience has been that values in our patient population are consistently higher than this range. To confirm this we reviewed >1100 semen records., Study Design: All patient records from January 1994 to December 1998 that had semen pH measurements and sperm concentration and motility measurements recorded were included in this study. We also determined the semen pH in a subgroup of patients who underwent sperm preparations for intrauterine inseminations that resulted in documented pregnancies. Histograms were used to describe the populations and the Mann-Whitney test was used for group comparisons., Results: For all patients (N = 1199) mean (+/-SD) semen pH was 8.2 +/- 0.3. The range was 7.3 to 9.5, with pH <8.0 in 32% of the samples. The semen pH among the patients with normal sperm concentration and motility values (n = 602) was not different from that among those with abnormal parameters (n = 597). Mean semen pH value was 8.2 for both groups. In a small group of patients (n = 19) whose sperm preparations had been documented to result in a clinical pregnancy after intrauterine insemination the semen pH was 8.3 +/- 0.3, with a range of 7.9 to 8.7., Conclusion: Our study questions the reference range defined by the World Health Organization for semen pH of 7.2 to 8.0. The mean values that we observed in our population, including those of samples from patients with normal sperm parameters, consistently lay outside that range.

A 37-year-old woman with a history consistent with polycystic ovarian disease became pregnant and developed exceedingly high levels of serum testosterone. The female fetus showed no evidence of virilization. A clinical diagnosis of bilateral theca lutein cysts was made. Modes of fetal protection from maternal androgenemia as well as suggestions for future investigations are discussed.

The optimal treatment for depressive disorders in pregnancy remains controversial. Clinicians are often hesitant to prescribe pharmacologic agents during pregnancy, especially in the first trimester, and the effects of electroconvulsive therapy in pregnancy have not been prospectively evaluated. The present case reports on the apparent safety and efficacy of electroconvulsive therapy for the treatment of depression in pregnancy when used in carefully selected and carefully monitored patients. Fetal heart rate monitoring and real-time ultrasonography were performed, and the results suggest that maternal electroconvulsive therapy has little effect on fetal status.