Effect of physical activity on fatigue in childhood cancer survivors: a systematic review.

PURPOSE: Many children, adolescents, and young adult survivors of childhood cancer experience fatigue following cancer treatment. Physical activity has been shown to be effective in improving cancer-related fatigue in adult survivors, but there is a lack of evidence on its effect in childhood cancer survivors. In addition, there are no guidelines for treatment of fatigue in childhood cancer survivors. The purpose of this study was to examine the existing literature on the effect of physical activity on fatigue in children, adolescents, and young adult survivors of childhood cancer. METHODS: We conducted a systematic review to examine the effect of physical activity on fatigue in children, adolescents, and young adult survivors of childhood cancer. RESULTS: Nine studies were included. Most of the studies included reported an increase in physical activity and a decline in fatigue in the target patient population. Interpretation of these findings is limited due to small sample sizes, inadequate length of follow-up, and variability among reviewed studies. Quantitative analysis was not conducted due to significant variability in both the type of physical activity implemented and in the measurement of fatigue. CONCLUSIONS: Further research, with a larger sample size and consistency in both physical activity interventions and measurement of fatigue, is needed to add greater precision and confidence in the effect of physical activity on fatigue in childhood cancer survivors. Results of this research will help guide future recommendations on physical activity for the treatment of cancer-related fatigue in children, adolescents, and young adult survivors of childhood cancer.

Surgical and clinical outcomes comparison of mesh usage in laparoscopic hiatal hernia repair.

PURPOSE: Use of absorbable mesh in hiatal hernia (HH) repair has been shown to decrease recurrence rates. Our aim was to compare the efficiency of three meshes in relation to the surgical outcomes of patients undergoing HH repair. METHODS: A single-institution retrospective review was done for adult patients who underwent HH repair with mesh between 2004 and 2016. Demographics, intra-operative, and cost data were collected. Esophageal symptoms and medication use were assessed pre- and postoperatively. Surgical outcomes were evaluated at 6-, 12-months, and long-term follow-up. Three groups were created based on type of mesh: human tissue matrix (HTM), biosynthetic mesh (BIOS), or porcine tissue matrix (PTM). Comparisons were performed between groups using SPSS v.26.0 and PC SAS v9.4, α = 0.05. RESULTS: 292 patients were included (HTM:N = 162, BIOS:N = 83, PTM:N = 47). Majority were male (60.4%), Caucasian (93.2%), median age, and BMI of 59 years [25-90 years] and 29.19 kg/m2 [18.9-58.0 kg/m2], respectively. 69% had a large HH. Median follow-up time was 27 months [1-166 months]. Overall recurrence rate was 39%, being significantly lower in BIOS at long-term (HTM: 31%, BIOS: 17%, PTM: 19%, p = 0.038). All groups had a significant postoperative improvement of esophageal symptoms, all p < 0.001. 65-70% of the cost difference between the groups was incurred by the cost of mesh alone (HTM: $1072, BIOS: $548, PTM: $1295), with the remainder attributable to the surgery itself. CONCLUSION: While outcomes of the three mesh groups were similar in our data, there was a significant difference in mesh cost. Surgeon and hospital preference still play a role in choosing the type of mesh used; however, knowledge of the individual mesh cost will help surgeons make better informed decisions.

How high is too high? Extensive mediastinal dissection in patients with hiatal hernia repair.

BACKGROUND: Approximately 10% of patients receiving anti-reflux procedures present with shortened esophagus. Collis gastroplasty (CG) is the current gold standard for esophageal lengthening, but mediastinal esophageal mobilization without gastroplasty may be an alternative approach. This study assesses preoperative and intraoperative hernia characteristics and mediastinal dissection impact in patients with large hiatal hernia repair (HHR). METHODS: A single-institution, prospectively collected database was reviewed for adults who underwent laparoscopic HHR with mesh and anti-reflux surgery between 2005 and 2016, hernia ≥ 5 cm. Preoperative hernia and follow-up were assessed using upper endoscopy and barium swallow. Intraoperative hernia characteristics were collected from the operative note. Esophageal symptom scores were collected pre- and postoperatively. Analyses were conducted using SPSS v26.0. RESULTS: Among 662 patients who had anti-reflux surgery in this period, a total of 205 patients who underwent HHR with mesh met the inclusion criteria and were included in study. Mean age was 61.7 ± 13.6 years, and majority of patients were female and Caucasian. Mean BMI was 29.9 ± 6.0 kg/m2. Median hernia size was 6.5 cm [5.0-12.0 cm], and intra-thoracic stomach had a prevalence of 21.9%. Analysis of preoperative barium swallow revealed an average of elevated gastroesophageal junction above the diaphragm of 4.10 ± 1.67 cm. Radiographically, average hernia size was 6.34 ± 1.93 cm and 6.38 ± 1.92 cm in the anterior-posterior and obliquus view, respectively. Median follow-up time was 2.7 years [1-9 years]. Esophageal symptoms improved in all patients (p < 0.05). 45% of patients had radiographic recurrence, but only four presented symptomatic or were on PPI. CONCLUSIONS: CG has been the standard for ensuring adequate esophageal length prior to anti-reflux surgery. Our results support that CG is unnecessary in the majority of cases, and extensive mediastinal dissection was successfully used instead of CG with durable, long-term outcomes. Extended mediastinal dissection may mitigate CG risks in patients requiring additional intra-abdominal esophagus.

Formation and characterization of lipid droplets of the bovine corpus luteum.

Establishment and maintenance of pregnancy depends on progesterone synthesized by luteal tissue in the ovary. Our objective was to identify the characteristics of lipid droplets (LDs) in ovarian steroidogenic cells. We hypothesized that LDs are a major feature of steroidogenic luteal cells and store cholesteryl esters. Whole bovine tissues, isolated ovarian steroidogenic cells (granulosa, theca, small luteal, and large luteal), and isolated luteal LDs were assessed for LD content, LD-associated proteins and lipid analyses. Bovine luteal tissue contained abundant lipid droplets, LD-associated perilipins 2/3/5, hormone-sensitive lipase, and 1-acylglycerol-3-phosphate O-acyltransferase ABHD5. Luteal tissue was enriched in triglycerides (TGs) compared to other tissues, except for adipose tissue. Luteal cells were distinguishable from follicular cells by the presence of LDs, LD-associated proteins, and increased TGs. Furthermore, LDs from large luteal cells were numerous and small; whereas, LDs from small luteal cells were large and less numerous. Isolated LDs contained nearly all of the TGs and cholesteryl esters present in luteal tissue. Isolated luteal LDs were composed primarily of TG, with lesser amounts of cholesteryl esters, diglyceride and other phospholipids. Bovine luteal LDs are distinct from LDs in other bovine tissues, including follicular steroidogenic cells.

Trafficking of cholesterol from lipid droplets to mitochondria in bovine luteal cells: Acute control of progesterone synthesis.

The corpus luteum is a transient endocrine gland that synthesizes and secretes the steroid hormone, progesterone, which is vital for establishment and maintenance of pregnancy. Luteinizing hormone (LH) via activation of protein kinase A (PKA) acutely stimulates luteal progesterone synthesis via a complex process, converting cholesterol via a series of enzymatic reactions, into progesterone. Lipid droplets in steroidogenic luteal cells store cholesterol in the form of cholesterol esters, which are postulated to provide substrate for steroidogenesis. Early enzymatic studies showed that hormone sensitive lipase (HSL) hydrolyzes luteal cholesterol esters. In this study, we tested whether HSL is a critical mediator of the acute actions of LH on luteal progesterone production. Using LH-responsive bovine small luteal cells our results reveal that LH, forskolin, and 8-Br cAMP-induced PKA-dependent phosphorylation of HSL at Ser563 and Ser660, events known to promote HSL activity. Small molecule inhibition of HSL activity and siRNA-mediated knock down of HSL abrogated LH-induced progesterone production. Moreover, western blotting and confocal microscopy revealed that LH stimulates phosphorylation and translocation of HSL to lipid droplets. Furthermore, LH increased trafficking of cholesterol from the lipid droplets to the mitochondria, which was dependent on both PKA and HSL activation. Taken together, these findings identify a PKA/HSL signaling pathway in luteal cells in response to LH and demonstrate the dynamic relationship between PKA, HSL, and lipid droplets in luteal progesterone synthesis.

A comprehensive review of robotic surgery curriculum and training for residents, fellows, and postgraduate surgical education.

BACKGROUND: In 2017, the utilization of robotic-assisted surgery had grown 10-40-fold relative to laparoscopic surgery in common general surgery procedures. The rapid rise in the utilization of robotic-assisted surgery has necessitated a standardized training curriculum. Many curricula are currently being developed and validated. Additionally, advancements in virtual reality simulators have facilitated their integration into robotic-assisted surgery training. This review aims to highlight and discuss the features of existing curricula and robotic-assisted surgery training simulators and to provide updates on their respective validation process. MATERIALS AND METHODS: A literature review was conducted using PubMed from 2000-2019 and commercial websites. Information regarding availability, content, and status of validation was collected for each current robotic-assisted surgery curriculum. This review did not qualify as human subjects research, so institutional review board approval was not required. RESULTS: The daVinci Technology Training Pathway and Fundamentals of Robotic Surgery are purely web-based and self-paced robotic-assisted surgery training. The Society of American Gastrointestinal and Endoscopic Surgeon Robotic Masters Series, Fundamental Skills of Robot-Assisted Surgery training program, and the Robotics Training Network curriculum require trainees to be on site in order to provide expert feedback on surgical techniques and robot maintenance. Currently, there are few virtual reality simulators for robotic-assisted surgical training available on the market. CONCLUSIONS: Didactic courses are available in all of these training programs, but their contents are inconsistent. Furthermore, the availability and nature of hands-on training offered by these curriculums are widely variable.

Updates on Monogenic Obesity in a Multifactorial Disease.

Obesity is a worldwide epidemic with rates nearly doubling over the last 30 years. Despite increasing prevalence, the multifactorial pathogenesis of obesity continues to be widely misunderstood. Investigating genetic drivers in the development of obesity is an important area of focus, as genetics move to the forefront of medicine and personalized treatment evolves. Thus, this narrative review focused on four genes which have genome-wide association study-documented links to obesity and obesity syndromes. We explored their involvement in the predisposition, progression, and prognosis of obesity. Leptin, leptin receptor, pro-opiomelanocortin, and melanocortin 4 receptor are our four genes of interest, and herein we elaborated on the current literature, pathogenesis, and available treatments for patients with these specific genetic mutations.

Review of emerging surgical robotic technology.

BACKGROUND: The use of laparoscopic and robotic procedures has increased in general surgery. Minimally invasive robotic surgery has made tremendous progress in a relatively short period of time, realizing improvements for both the patient and surgeon. This has led to an increase in the use and development of robotic devices and platforms for general surgery. The purpose of this review is to explore current and emerging surgical robotic technologies in a growing and dynamic environment of research and development. METHODS: This review explores medical and surgical robotic endoscopic surgery and peripheral technologies currently available or in development. The devices discussed here are specific to general surgery, including laparoscopy, colonoscopy, esophagogastroduodenoscopy, and thoracoscopy. Benefits and limitations of each technology were identified and applicable future directions were described. RESULTS: A number of FDA-approved devices and platforms for robotic surgery were reviewed, including the da Vinci Surgical System, Sensei X Robotic Catheter System, FreeHand 1.2, invendoscopy E200 system, Flex® Robotic System, Senhance, ARES, the Single-Port Instrument Delivery Extended Research (SPIDER), and the NeoGuide Colonoscope. Additionally, platforms were reviewed which have not yet obtained FDA approval including MiroSurge, ViaCath System, SPORT™ Surgical System, SurgiBot, Versius Robotic System, Master and Slave Transluminal Endoscopic Robot, Verb Surgical, Miniature In Vivo Robot, and the Einstein Surgical Robot. CONCLUSIONS: The use and demand for robotic medical and surgical platforms is increasing and new technologies are continually being developed. New technologies are increasingly implemented to improve on the capabilities of previously established systems. Future studies are needed to further evaluate the strengths and weaknesses of each robotic surgical device and platform in the operating suite.

Increased glycine-amidated hyocholic acid correlates to improved early weight loss after sleeve gastrectomy.

BACKGROUND: Bile acids (BAs) are post-prandial hormones that play an important role in glucose and lipid homeostasis as well as energy expenditure. Total and glycine-amidated BAs increase after sleeve gastrectomy (SG) and correlate to improved metabolic disease. No specific bile acid subtype has been shown conclusively to mediate the weight loss effect. Therefore, the objective of this study was to prospectively evaluate the comprehensive changes in meal-stimulated BAs after SG and determine if a specific change in the BA profile correlates to the early weight loss response. METHODS: Patients were prospectively enrolled at the University of Nebraska Medical Center who were undergoing a SG for treatment of morbid obesity. Primary and secondary plasma bile acids and their amidated (glycine, G-, or taurine, T-) subtypes were measured at fasting, 30 and 60 min after a liquid meal performed pre-op, and at 6 and 12 weeks post-op. Area under the curve (AUC) was calculated for the hour meal test for each bile acid subtype. BAs that were significantly increased post-op were correlated to body mass index (BMI) loss. RESULTS: Total BA AUC was significantly increased at 6 (p < 0.01) and 12 weeks post-op (p < 0.01) compared to pre-operative values. The increase in total BA AUC was due to a statistically significant increase in G-BAs. Nine different BA AUC subtypes were significantly increased at both 6 and 12 weeks post-op. Increased total and G-chenodeoxycholic acid AUC was significantly correlated to the 6 week BMI loss (p = 0.03). Increased G-hyocholic acid was significantly correlated to increased weight loss at both 6 (p = 0.05) and 12 weeks (p = 0.006). CONCLUSIONS: SG induced an early and persistent post-prandial surge in multiple bile acid subtypes. Increased G-hyocholic consistently correlated with greater early BMI loss. This study provides evidence for a role of BAs in the surgical weight loss response after SG.

Emergent cholecystectomy is superior to percutaneous cholecystostomy tube placement in critically ill patients with emergent calculous cholecystitis.

BACKGROUND: The role of percutaneous cholecystostomy (PC) is undefined in patients with multiple comorbidities presenting with emergent calculous cholecystitis (CC). This study compared outcomes between PC, laparoscopic (LC), and open cholecystectomy (OC). METHODS: The Vizient UHC database was queried for high-risk patients with CC who underwent PC, LC, OC, or laparoscopic converted to open cholecystectomy (CONV). Demographics, outcomes, mortality, length of stay (LOS), and direct cost were compared between the groups. RESULTS: LC was the most common approach with the lowest risk of death, complications, LOS, and cost. Complication risk was highest in OC. Nearly 20% of patients underwent PC. Complication rate, LOS, infection, aspiration pneumonia, and mortality were higher in PC. Direct cost was lowest in LC, followed by CONV, PC, and OC. CONCLUSIONS: Emergent cholecystectomy for CC in high-risk patients is safer and more cost effective than PC and this study supports the use of cholecystectomy as the primary treatment approach in these patients.

Long-Term Effectiveness of Strattice in the Laparoscopic Closure of Paraesophageal Hernias.

Prosthetic reinforcement reduces the recurrence rate of large paraesophageal hernias (PEH), but the use of synthetic or biosynthetic mesh in the repair remains controversial. PEH repair has reported recurrence rates of 12% to 42%, and primary repair of PEH by suture closure under tension is at high risk of disruption. Synthetic mesh use in large PEH repair has shown to reduce recurrence but can lead to problems including mesh erosion, ulceration, stricture, and dysphagia. The objective of this study was to examine the long-term safety and efficacy of Strattice biologic mesh, a porcine acellular dermal matrix, in crural reinforcement of laparoscopic large PEH repair. Thirty-five patients with symptomatic PEH (>5 cm) were consented to receive Strattice for PEH repair. Patients were seen in clinic preoperatively, at surgery, and 2 weeks, 6 months, and 12 months postoperatively. Patients were given a standard subjective reflux test at each visit and a 12-month barium swallow X-ray to test for recurrence. Hernia recurrence was documented in 14.3% of cases by the end of the 1-year follow-up. Symptoms improved in 75% to 100% of patients by 6 months, and 33% to 100% of patients were still reporting symptom improvement at 12 months. Strattice mesh in PEH repair results in similar outcomes to other absorbable meshes, and the recurrence rate is within the 12% to 42% range of recurrences reported in studies outside of our institution. The use of Strattice mesh in large PEH repair had results similar to other biomaterial meshes and successfully decreased patients' symptom scores through surgical intervention.

Sleeve gastrectomy and anti-reflux procedures.

BACKGROUND: Obesity is an epidemic in the USA that continues to grow, becoming a leading cause of premature avoidable death. Bariatric surgery has become an effective solution for obesity and its comorbidities, and one of the most commonly utilized procedures, the sleeve gastrectomy, can lead to an increase in gastroesophageal reflux following the operation. While these data are controversial, sometimes operative intervention can be necessary to provide durable relief for this problem. METHODS: We performed an extensive literature review examining the different methods of anti-reflux procedures that are available both before and after a sleeve gastrectomy. RESULTS: We reviewed several different types of anti-reflux procedures, including those that supplement the lower esophageal sphincter anatomy, such as magnetic sphincter augmentation and radiofrequency ablation procedures. Re-operation was also discussed as a possible treatment of reflux in sleeve gastrectomy, especially if the original sleeve becomes dilated or if a conversion to a Roux-en-Y gastric bypass or biliopancreatic diversion is deemed necessary. Sleeve gastrectomy with concomitant anti-reflux procedure was also reviewed, including the anti-reflux gastroplasty, hiatal hernia repair, and limited fundoplication. CONCLUSION: A number of techniques can be used to mitigate the severity of reflux, either by maintaining the normal anatomic structures that limit reflux or by supplementing these structures with a plication or gastroplasty. Individuals with existing severe reflux should not be considered for a sleeve gastrectomy. New techniques that incorporate plication at the time of the index sleeve gastrectomy show some improvement, but these are in small series that will need to be further evaluated. The only proven method of treating intractable reflux after sleeve gastrectomy is conversion to a Roux-en-Y gastric bypass.

Paraesophageal hernia repair in the emergency setting: is laparoscopy with the addition of a fundoplication the new gold standard?

BACKGROUND: Laparoscopic repair of paraesophageal hernia (PEH) with fundoplication is currently the preferred elective strategy, but emergent cases are often done open without an anti-reflux (AR) procedure. This study examined PEH repair in elective and urgent/emergent settings and investigated patient characteristic influence on the use of adjunctive techniques, such as AR procedures or gastrostomy tube (GT) placement. METHODS: Utilizing the University HealthSystem Consortium Clinical Database Resource Manager, selected discharge data were retrieved using International Classification of Disease 9 diagnosis codes for PEH and procedure specific codes. Chi-squared and paired t tests were applied (α = 0.05). RESULTS: Discharge data from October 2010 through June 2014 indicated 7950 patients (≥18 years) underwent PEH surgery, 84.7 % were performed laparoscopically and 15.3 % open. 24.6 % of cases were classified urgent/emergent upon admission, and almost 70 % of these were completed laparoscopically. Open paraesophageal hernia repairs (OHR) represented a higher proportion of urgent/emergent cases but were only 30 % of this total. Laparoscopic paraesophageal hernia repair (LHR) patients were more likely to receive an AR procedure in all situations (54.9 % LHR vs. 26.3 % OHR). Almost 90 % of elective PEH repairs in this cohort were laparoscopic. Elective cases were more commonly associated with AR procedures than emergent cases which frequently incorporated GT placement. CONCLUSION: We demonstrate that laparoscopic PEH repair has become accepted in emergent cases. Open PEH repair is often reserved for emergent surgeries and less commonly includes an AR procedure. Laparoscopy with an AR procedure is clearly the standard of care in elective surgery. The decision to perform an open or laparoscopic surgery, with or without adjunctive techniques, may be based more on the physician's comfort with laparoscopic surgery and surgical practices than the patient's condition. Long-term follow-up studies are needed to determine the functional outcomes of these strategies.

Acute acalculous cholecystitis in the critically ill: risk factors and surgical strategies.

PURPOSE: Acute acalculous cholecystitis (AAC) is characterized by severe gallbladder inflammation without cystic duct obstruction. Critical illness and neurological deficits are often associated with AAC, and early radiologic imaging is necessary for the detection and timely treatment of AAC. In critically ill patients, effective surgical management is difficult. This review examines the three common surgical treatments for AAC (open cholecystectomy (OC), laparoscopic cholecystectomy (LC), or percutaneous cholecystostomy (PC)), their prevalence in current literature, and the perioperative outcomes of these different approaches using a large retrospective database. MATERIALS AND METHODS: This review examined literature gathered from PubMed and Google Scholar to select more than 50 sources with data pertinent to AAC; of which 20 are described in a summary table. Outcomes from our previous research and several updated results were obtained from the University HealthSystem Consortium (UHC) database. RESULTS: LC has proven effective in treating AAC when the risks of general anesthesia and the chance for conversion to OC are low. In critically ill patients with multiple comorbidities, PC or OC may be the only available options. Data in the literature and an examination of outcomes within a national database indicate that for severely ill patients, PC may be safer and met with better outcomes than OC for the healthier set of AAC patients. CONCLUSIONS: We suggest a three-pronged approach to surgical resolution of AAC. Patients that are healthy enough to tolerate LC should undergo LC early in the course of the disease. In critically ill patients, patients with multiple comorbidities, a high conversion risk, or who are poor surgical candidates, PC may be the safest and most successful intervention.

Population dynamics of Hawaiian seabird colonies vulnerable to sea-level rise.

Globally, seabirds are vulnerable to anthropogenic threats both at sea and on land. Seabirds typically nest colonially and show strong fidelity to natal colonies, and such colonies on low-lying islands may be threatened by sea-level rise. We used French Frigate Shoals, the largest atoll in the Hawaiian Archipelago, as a case study to explore the population dynamics of seabird colonies and the potential effects sea-level rise may have on these rookeries. We compiled historic observations, a 30-year time series of seabird population abundance, lidar-derived elevations, and aerial imagery of all the islands of French Frigate Shoals. To estimate the population dynamics of 8 species of breeding seabirds on Tern Island from 1980 to 2009, we used a Gompertz model with a Bayesian approach to infer population growth rates, density dependence, process variation, and observation error. All species increased in abundance, in a pattern that provided evidence of density dependence. Great Frigatebirds (Fregata minor), Masked Boobies (Sula dactylatra), Red-tailed Tropicbirds (Phaethon rubricauda), Spectacled Terns (Onychoprion lunatus), and White Terns (Gygis alba) are likely at carrying capacity. Density dependence may exacerbate the effects of sea-level rise on seabirds because populations near carrying capacity on an island will be more negatively affected than populations with room for growth. We projected 12% of French Frigate Shoals will be inundated if sea level rises 1 m and 28% if sea level rises 2 m. Spectacled Terns and shrub-nesting species are especially vulnerable to sea-level rise, but seawalls and habitat restoration may mitigate the effects of sea-level rise. Losses of seabird nesting habitat may be substantial in the Hawaiian Islands by 2100 if sea levels rise 2 m. Restoration of higher-elevation seabird colonies represent a more enduring conservation solution for Pacific seabirds.