Preoperative Opioids Associated With Increased Postoperative Opioid Use in Pediatric Appendicitis.

BACKGROUND: In light of current opioid-minimization efforts, we aimed to identify factors that predict postoperative opioid requirement in pediatric appendicitis patients. METHODS: A single-center retrospective cohort study was conducted of children (<18 y) who underwent laparoscopic appendectomy for acute appendicitis between January 1, 2018 and April 30, 2019. Patients who underwent open or interval appendectomies were excluded. The primary outcome was morphine milliequivalents (MMEs) per kilogram administered between 2 and 24 h after surgery. Multivariable analyses were performed to evaluate predictors of postoperative opioid use. Clinically sound covariates were chosen a priori: age, weight, simple versus complicated appendicitis, preoperative opioid administration, and receipt of regional or local anesthesia. RESULTS: Of 546 patients, 153 (28%) received postoperative opioids. Patients who received postoperative opioids had a longer median preadmission symptom duration (48 versus 24 h, P < 0.001) and were more likely to have complicated appendicitis (55% versus 21%, P < 0.001). Patients who received postoperative opioids were more likely to have received preoperative opioids (54% versus 31%, P < 0.001). Regional and local anesthesia use was similar between groups. Nearly all patients (99%) received intraoperative opioids. Each preoperative MME per kilogram that a patient received was associated with receipt of 0.29 additional MMEs per kilogram postoperatively (95% confidence interval, 0.19-0.40). CONCLUSIONS: Preoperative opioid administration was independently associated with increased postoperative opioid use in pediatric appendicitis. These findings suggest that preoperative opioids may potentiate increased postoperative pain. Limiting preoperative opioid exposure, through strategies such as multimodal analgesia, may be an important facet of efforts to reduce postoperative opioid use.

Pancreatic Adenocarcinoma, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology.

Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection.

Outcomes of endoscopic resection for high-grade dysplasia and esophageal cancer.

BACKGROUND: Endoscopic resection (ER) is an important advance in the management of esophageal tumors. It has been used successfully for superficial esophageal cancer and high-grade dysplasia (HGD) arising out of Barrett epithelium. METHODS: From a single institution within the Department of Surgery, patients who underwent ER for esophageal tumors between December 2001 and January 2012 were evaluated. Demographic, clinical, and pathologic variables were collected and reviewed. RESULTS: We identified 81 patients who underwent ER for esophageal lesions. Median patient age was 69 years, and the median follow-up was 3.25 years. In patients with HGD, at the time of last endoscopy, the complete eradication rate of HGD was 84 % and cancer-specific survival was 100 %. During surveillance, one patient developed an invasive carcinoma that required endoscopic therapy. Patients with T1a and negative deep margins on ER had a recurrence-free and cancer-specific survival of 100 %. There were seven patients with T1b and negative margins on ER. Three patients underwent esophagectomy; final pathology revealed no residual malignancy or lymph node metastasis. Two patients had definitive chemoradiation, and two patients were observed. To date, there has been no cancer recurrence. In all patients who underwent ER, there was one episode of bleeding that required endoscopic treatment and admission for observation. CONCLUSIONS: ER can be performed safely and can adequately stage and often treat patients with HGD and superficial cancers. Patients with HGD and T1a disease with negative margins are cured with ER alone. Observation and surveillance may be an option for select patients with low-risk, early submucosal disease (T1b) and negative margins.

Failure of centrosome migration causes a loss of motile cilia in talpid(3) mutants.

BACKGROUND: Loss of function mutations in the centrosomal protein TALPID3 (KIAA0586) cause a failure of primary cilia formation in animal models and are associated with defective Hedgehog signalling. It is unclear, however, if TALPID3 is required only for primary cilia formation or if it is essential for all ciliogenesis, including that of motile cilia in multiciliate cells. RESULTS: FOXJ1, a key regulator of multiciliate cell fate, is expressed in the dorsal neuroectoderm of the chicken forebrain and hindbrain at stage 20HH, in areas that will give rise to choroid plexuses in both wt and talpid(3) embryos. Wt ependymal cells of the prosencephalic choroid plexuses subsequently transition from exhibiting single short cilia to multiple long motile cilia at 29HH (E8). Primary cilia and long motile cilia were only rarely observed on talpid(3) ependymal cells. Electron microscopy determined that talpid(3) ependymal cells do develop multiple centrosomes in accordance with FOXJ1 expression, but these fail to migrate to the apical surface of ependymal cells although axoneme formation was sometimes observed. CONCLUSIONS: TALPID3, which normally localises to the proximal centrosome, is essential for centrosomal migration prior to ciliogenesis but is not directly required for de novo centriologenesis, multiciliated fate, or axoneme formation.

eChickAtlas: an introduction to the database.

The precise control of gene expression is critical in embryonic development. Quantitative assays, such as microarrays and RNA sequencing, provide gene expression levels for a large number of genes, but do not contain spatial information. In contrast, in situ methods, such as in situ hybridization and immunohistochemistry, provide spatial resolution, but poor quantification and can only reveal the expression of one, or very few genes at a time. Furthermore, the usual methods of documenting the results, by photographing whole mounts or sections, makes it very difficult to assess the three-dimensional (3D) relationships between expressing and nonexpressing cells. Optical projection tomography (OPT) can capture the full 3D expression pattern in a whole embryo at a reasonable level of resolution and at moderately high throughput. A large database containing spatio-temporal patterns of expression for the mouse (e-Mouse Atlas Project, EMAP, www.emouseatlas.org) has been created, incorporating 3D information. Like the mouse, the chick is an important model in developmental biology and translational studies. To facilitate comparisons between these important model organisms, we have created a 3D anatomical atlas, accompanied by an anatomical ontology of the chick embryo and a database of gene expression patterns during chick development. This database is publicly available (www.echickatlas.org).

Rapid development of squamous cell carcinoma at a split-thickness skin graft donor site.

The development of a Marjolin ulcer at the site of a split-thickness skin graft donor site is exceptionally rare. Here we describe the rapid development of squamous cell carcinoma at a split-thickness skin graft donor site in the setting of severe burn. We present a case of a 52-year-old male with no past medical history who presented with a 24% total body surface area burn caused by a flash flame. Four months after his initial excision and grafting, he presented for revision of a burn scar with an additional complaint of a rapidly developing skin lesion at his donor site, which arose over 2 weeks. The lesion was excised en bloc and found to be invasive squamous cell carcinoma. There are 5 previous cases of squamous cell carcinoma development at the site of split-thickness skin harvest in the setting of severe burn. While the typical Marjolin ulcer has a latency period of up to 30 years, lesions that arise in split-thickness skin graft donor sites appear to have a rapid onset of weeks to months. Squamous cell carcinoma at the site of split-thickness skin grafting is an uncommon but important sequelae of burn care.

Healthcare Utilization Among Infants Discharged From the Neonatal Intensive Care Unit: A Descriptive Cost Analysis.

The cost of readmissions of neonatal intensive care unit (NICU) graduates within 6 months and a year of their life is well-studied. However, the cost of readmissions within 90 days of NICU discharge is unknown. This study's objective was to estimate the overall and mean cost of healthcare use for unplanned hospital visits of NICU graduates within 90 days of discharge A retrospective review of all infants discharged between 1/1/2017 and 03/31/2017 from a large hospital system NICUs was conducted. All unplanned hospital visits (readmissions or stand-alone emergency department (ED) visits) occurring within 90 days post NICU discharge were included. The total and mean cost of unplanned hospital visits were computed and adjusted to 2021 US dollars. The total cost was estimated to be $785 804 with a mean of $1898 per patient. Hospital readmissions accounted for 98% ($768 718) of the total costs and ED visits for 2% ($17 086). The mean cost per readmission and stand-alone ED visit were $25 624 and $475 respectively. The highest mean total cost of unplanned hospital readmission was noted in extremely low birth weight infants ($25 295). Interventions targeted to reduce hospital readmissions after NICU discharge have the potential to significantly reduce healthcare costs for this patient population.

Quality of colonoscopy withdrawal technique and variability in adenoma detection rates (with videos).

BACKGROUND: Studies suggest that endoscopist-related factors such as colonoscopy withdrawal time are important in determining the adenoma detection rate (ADR). OBJECTIVE: To determine the importance of withdrawal technique in differentiating among endoscopists with varying ADRs. DESIGN: Prospective, multicenter study. SETTING: Five academic tertiary-care medical centers. PARTICIPANTS: This study involved 11 gastroenterology faculty endoscopists. INTERVENTION: A retrospective review of screening colonoscopies was performed to categorize endoscopists into low, moderate, and high ADR groups. Video recordings were randomly obtained for each endoscopist on 20 (10 real, 10 sham) withdrawals during colonoscopies performed for average-risk colorectal cancer screening. Three blinded reviewers assigned withdrawal technique scores (total of 75 points) on 110 video recordings. A separate reviewer recorded withdrawal times. MAIN OUTCOME MEASUREMENTS: Withdrawal technique scores and withdrawal times. RESULTS: Mean (± standard deviation [SD]) withdrawal technique scores were higher in the moderate (62 ± 2.5) and high (59.5 ± 3) ADR groups compared with the low (40.8±3) ADR group (P = .002). Mean (± SD) withdrawal times were 6.3 ± 1.8 minutes (low ADR), 10.2 ± 1.5 minutes (moderate ADR), and 8.2 ± 1.8 minutes (high ADR) (P = .29). A comparison of the withdrawal times and technique scores of the two individual endoscopists with the lowest and highest ADRs did not find a significant difference in withdrawal times (6.6 ± 1.7 vs 7.4 ± 1.7 minutes) (P = .36) but did find a nearly 2-fold difference in technique scores (36.2 ± 9 vs 62.8 ± 9.9) (P = .0001). LIMITATIONS: Not adequately powered to detect small differences in withdrawal times. CONCLUSION: Withdrawal technique is an important indicator that differentiates between endoscopists with varying ADRs. It is possible that withdrawal technique is equal to, if not more important than, withdrawal time in determining ADRs.

Pancreatic rest resection using band ligation snare polypectomy.

BACKGROUND: Although pancreatic rests have characteristic endoscopic features, confirming a histological diagnosis may be desirable to exclude other significant pathology. AIMS: The aim of this study was to assess the efficacy and safety of endoscopic band ligation snare polypectomy (EBLSP) for removal of suspected pancreatic rests and to compare the diagnostic yield to other endoscopic tissue sampling methods. METHODS: An electronic endoscopic report database was searched for patients referred for evaluation of incidentally found gastric antral subepithelial lesions. Tissue sampling technique, pathology, and complications were recorded. RESULTS: Removal of suspected pancreatic rests with EBLSP was successful in all 21 cases without complications. Nineteen of 21 (90%) who underwent EBLSP had a histological diagnosis of heterotopic pancreas compared with 5 of 14 (36%) who underwent tissue sampling with biopsy and/or snare (P = 0.001). The endoscopic characteristics of the histology proven pancreatic rests were an antral subepithelial mass with central umbilication measuring 6-10 mm in diameter and located 2-6 cm from the pylorus in the 3-7 o'clock position. CONCLUSIONS: Endoscopic band ligation snare polypectomy resection of gastric antral lesions suspected to be pancreatic rests had a diagnostic yield superior to standard biopsy forceps and snare polypectomy techniques. However, because all pathologically confirmed pancreatic rests had typical endoscopic appearances of pancreatic rests, it may not be necessary to obtain histologic diagnosis for every suspected gastric antral heterotopic pancreas.

Clinical and Lifestyle-Related Prognostic Indicators among Esophageal Adenocarcinoma Patients Receiving Treatment at a Comprehensive Cancer Center.

PURPOSE: The incidence of esophageal adenocarcinoma (EAC) has risen substantially in recent decades, while the average 5-year survival remains only ~20%. Disease stage and treatment are the strongest prognostic factors. The role of lifestyle factors in relation to survival remains uncertain, with a handful of studies to date investigating associations with obesity, smoking, physical activity, diet, or medications. METHODS: This study included patients diagnosed with primary adenocarcinoma of the esophagus, gastroesophageal junction, or cardia (N = 371) at Roswell Park Comprehensive Cancer Center between 2003 and 2019. Leveraging extensive data abstracted from electronic medical records, epidemiologic questionnaires, and a tumor registry, we analyzed clinical, behavioral, and environmental exposures and evaluated stage-specific associations with survival. Survival distributions were visualized using Kaplan-Meier curves. Cox proportional hazards regression models adjusted for age, sex, stage, treatment, and comorbidities were used to estimate the association between each exposure and all-cause or cancer-specific mortality. RESULTS: Among patients presenting with localized/regional tumors (stages I-III), current smoking was associated with increased overall mortality risk (HR = 2.5 [1.42-4.53], p = 0.002), while current physical activity was linked to reduced risk (HR = 0.58 [0.35-0.96], p = 0.035). Among patients with stage IV disease, individuals reporting pre-diagnostic use of statins (HR = 0.62 [0.42-0.92], p = 0.018) or NSAIDs (HR = 0.61 [0.42-0.91], p = 0.016) had improved overall survival. Exploratory analyses suggested that high pre-diagnostic dietary consumption of broccoli, carrots, and fiber correlated with prolonged overall survival in patients with localized/regional disease. CONCLUSION: Our data suggest that lifestyle exposures may be differentially associated with EAC survival based on disease stage. Future investigation of larger, diverse patient cohorts is essential to validate these findings. Our results may help inform the development of lifestyle-based interventions to improve EAC prognosis and quality of life.

Use of Fecal Microbial Transplantation for Immune Checkpoint Inhibitor Colitis.

Immune checkpoint inhibitors (ICIs) can result in immune-related adverse events which require rapid identification and treatment. Gastrointestinal immune-related adverse events are among the most frequent and severe of these events. ICI colitis can be refractory to current therapies such as corticosteroids and biologic therapy. Fecal microbiota transplantation (FMT) is currently used in cases of recurrent Clostridioides difficile colitis. Many investigations are underway to test the utility of FMT for additional indications, including inflammatory bowel disease (IBD). We present a 71-year-old man with ICI colitis that was nonresponsive to currently defined management options and treated with benefit from FMT.

Integrating technologies for comparing 3D gene expression domains in the developing chick limb.

Chick embryos are good models for vertebrate development due to their accessibility and manipulability. Recent large increases in available genomic data from both whole genome sequencing and EST projects provide opportunities for identifying many new developmentally important chicken genes. Traditional methods of documenting when and where specific genes are expressed in embryos using whole amount and section in-situ hybridisation do not readily allow appreciation of 3-dimensional (3D) patterns of expression, but this can be accomplished by the recently developed microscopy technique, Optical Projection Tomography (OPT). Here we show that OPT data on the developing chick wing from different labs can be reliably integrated into a common database, that OPT is efficient in capturing 3D gene expression domains and that such domains can be meaningfully compared. Novel protocols are used to compare 3D expression domains of 7 genes known to be involved in chick wing development. This reveals previously unappreciated relationships and demonstrates the potential, using modern genomic resources, for building a large scale 3D atlas of gene expression. Such an atlas could be extended to include other types of data, such as fate maps, and the approach is also more generally applicable to embryos, organs and tissues.

Role of fluoroquinolones in the primary prophylaxis of spontaneous bacterial peritonitis: meta-analysis.

BACKGROUND & AIMS: The use of antibiotics in the primary prophylaxis for spontaneous bacterial peritonitis (SBP) in patients with cirrhosis is controversial. Our purpose was to determine the beneficial effect of fluoroquinolones as compared with placebo in primary prophylaxis of SBP in high-risk patients with cirrhosis by using meta-analysis. METHODS: Medline, Embase, Cochrane, and Web of Science databases were searched in all languages until August 2008 for randomized placebo-controlled studies evaluating the role of fluoroquinolones in primary prevention of SBP in patients with low protein ascites (total ascitic protein, <1.5 g/dL) and without history of SBP. Two investigators independently performed literature search and data extraction, and then another investigator independently reviewed whether the studies met prespecified criteria and rechecked data extraction. Odds ratios (Peto method) for the risk reduction with fluoroquinolones were calculated for each study and combined by using a random-effects model. RESULTS: Four randomized controlled studies met predefined criteria. The odds ratios for developing first episode of SBP, serious infections, and mortality with fluoroquinolone prophylaxis (n = 194) versus placebo (n = 190) were 0.18 (95% confidence interval [CI], 0.09-0.35), 0.18 (95% CI, 0.10-0.32), and 0.60 (95% CI, 0.37-0.97), respectively. All studies were unidirectional in showing the beneficial effect of fluoroquinolone prophylaxis. We were limited by finding few studies with relatively small sample sizes. CONCLUSIONS: Daily oral fluoroquinolone prophylaxis reduces the risk of development of first episode of SBP and mortality in cirrhotic patients with low total protein in the ascitic fluid. Fluoroquinolones might be advisable for the primary prophylaxis of SBP in selected high-risk patients with cirrhosis.

Model for end-stage liver disease score versus Child score in predicting the outcome of surgical procedures in patients with cirrhosis.

AIM: To determine factors affecting the outcome of patients with cirrhosis undergoing surgery and to compare the capacities of the Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) score to predict that outcome. METHODS: We reviewed the charts of 195 patients with cirrhosis who underwent surgery at two teaching hospitals over a five-year period. The combined endpoint of death or hepatic decompensation was considered to be the primary endpoint. RESULTS: Patients who reached the endpoint had a higher MELD score, a higher CTP score and were more likely to have undergone an urgent procedure. Among patients undergoing elective surgical procedures, no statistically significant difference was noted in the mean MELD (12.8 +/- 3.9 vs 12.6 +/- 4.7, P = 0.9) or in the mean CTP (7.6 +/- 1.2 vs 7.7 +/- 1.7, P = 0.8) between patients who reached the endpoint and those who did not. Both mean scores were higher in the patients reaching the endpoint in the case of urgent procedures (MELD: 22.4 +/- 8.7 vs 15.2 +/- 6.4, P = 0.0007; CTP: 9.9 +/- 1.8 vs 8.5 +/- 1.8, P = 0.008). The performances of the MELD and CTP scores in predicting the outcome of urgent surgery were only fair, without a significant difference between them (AUC = 0.755 +/- 0.066 for MELD vs AUC = 0.696 +/- 0.070 for CTP, P = 0.3). CONCLUSION: The CTP and MELD scores performed equally, but only fairly in predicting the outcome of urgent surgical procedures. Larger studies are needed to better define the factors capable of predicting the outcome of elective surgical procedures in patients with cirrhosis.

Lef-1 and Tcf-3 transcription factors mediate tissue-specific Wnt signaling during Xenopus development.

Wnt signaling functions repeatedly during embryonic development to induce different but specific responses. What molecular mechanisms ensure that Wnt signaling triggers the correct tissue-specific response in different tissues? Early Xenopus development is an ideal model for addressing this fundamental question, since there is a dramatic change in the response to Wnt signaling at the onset of zygotic gene transcription: Wnt signaling components encoded by maternal mRNA establish the dorsal embryonic axis; zygotically expressed Xwnt-8 causes almost the opposite, by promoting ventral and lateral and restricting dorsal mesodermal development. Although Wnt signaling can function through different signal transduction cascades, the same beta-catenin-dependent, canonical Wnt signal transduction pathway mediates Wnt signaling at both stages of Xenopus development. Here we show that, while the function of the transcription factor XTcf-3 is required for early Wnt signaling to establish the dorsal embryonic axis, closely related XLef-1 is required for Wnt signaling to pattern the mesoderm after the onset of zygotic transcription. Our results show for the first time that different transcription factors of the Lef/Tcf family function in different tissues to bring about tissue-specific responses downstream of canonical Wnt signaling.

Laparoscopic Intragastric Surgery With Endoscopic Assistance: A 2 Gastrostomy Approach With Multiple Applications.

PURPOSE: Laparoscopic intragastric resection is a surgical modality with acceptable oncologic outcomes for gastrointestinal stromal tumors and leiomyomas, particularly for masses located near the gastroesophageal junction (GEJ). We describe our technique of 2 gastrostomy laparoscopic, intragastric resection with endoscopic assistance. METHODS: We detail our technique and report a unique application of this versatile approach. RESULTS: Between December 2015 and July 2016, 4 patients underwent our combined technique of intragastric surgery. Complete resection was performed in the 2 patients who had gastrointestinal stromal tumors and 1 patient with a leiomyoma without complications. One patient had the unique diagnosis of gastritis cystica profunda. This mass could not be resected, but an effective Tru-cut core needle biopsy was obtained, and the mass was able to be diagnosed and decompressed. CONCLUSIONS: Our technique of 2 gastrostomy laparoscopic intragastric surgery is feasible and offers an effective oncologic approach for resection of tumors near the GEJ.