Computational Modeling of the Synergistic Role of GCN2 and HPA Axis in Regulating the Integrated Stress Response in the Central Circadian Timing System.

The circadian timing system and integrated stress response (ISR) systems are fundamental regulatory mechanisms that maintain body homeostasis. The central circadian pacemaker in the suprachiasmatic nucleus (SCN) governs daily rhythms through interactions with peripheral oscillators via the hypothalamus-pituitary-adrenal (HPA) axis. On the other hand, ISR signaling is pivotal for preserving cellular homeostasis in response to physiological changes. Notably, disrupted circadian rhythms are observed in cases of impaired ISR signaling. In this work, we examine the potential interplay between the central circadian system and the ISR, mainly through the SCN and HPA axis. We introduce a semi-mechanistic mathematical model to delineate the suprachiasmatic nucleus (SCN)'s capacity for indirectly perceiving physiological stress through glucocorticoid-mediated feedback from the HPA axis and orchestrating a cellular response via the ISR mechanism. Key components of our investigation include evaluating general control nonderepressible 2 (GCN2) expression in the SCN, the effect of physiological stress stimuli on the HPA axis, and the interconnected feedback between the HPA and SCN. Simulation reveals a critical role for GCN2 in linking ISR with circadian rhythms. Experimental findings have demonstrated that a Gcn2 deletion in mice leads to rapid re-entrainment of the circadian clock following jetlag, as well as to an elongation of the circadian period. These.

GCN2 is required to maintain core body temperature in mice during acute cold.

Nonshivering thermogenesis in rodents requires macronutrients to fuel the generation of heat during hypothermic conditions. In this study, we examined the role of the nutrient sensing kinase, general control nonderepressible 2 (GCN2) in directing adaptive thermogenesis during acute cold exposure in mice. We hypothesized that GCN2 is required for adaptation to acute cold stress via activation of the integrated stress response (ISR) resulting in liver production of FGF21 and increased amino acid transport to support nonshivering thermogenesis. In alignment with our hypothesis, female and male mice lacking GCN2 failed to adequately increase energy expenditure and veered into torpor. Mice administered a small molecule inhibitor of GCN2 were also profoundly intolerant to acute cold stress. Gcn2 deletion also impeded liver-derived FGF21 but in males only. Within the brown adipose tissue (BAT), acute cold exposure increased ISR activation and its transcriptional execution in males and females. RNA sequencing in BAT identified transcripts that encode actomyosin mechanics and transmembrane transport as requiring GCN2 during cold exposure. These transcripts included class II myosin heavy chain and amino acid transporters, critical for maximal thermogenesis during cold stress. Importantly, Gcn2 deletion corresponded with higher circulating amino acids and lower intracellular amino acids in the BAT during cold stress. In conclusion, we identify a sex-independent role for GCN2 activation to support adaptive thermogenesis via uptake of amino acids into brown adipose.NEW & NOTEWORTHY This paper details the discovery that GCN2 activation is required in both male and female mice to maintain core body temperature during acute cold exposure. The results point to a novel role for GCN2 in supporting adaptive thermogenesis via amino acid transport and actomyosin mechanics in brown adipose tissue.

Kinetic proteomics identifies targeted changes in liver metabolism and the ribo-interactome by dietary sulfur amino acid restriction.

Dietary sulfur amino acid restriction (SAAR) protects against diet-induced obesity, extends healthspan, and coincides with an overall reduction in hepatic protein synthesis. To explore the underpinnings of SAAR-induced slowed growth and its impact on liver metabolism and proteostasis, we resolved changes in hepatic mRNA and protein abundances and compared synthesis rates of individual liver proteins. To achieve this, adult male mice were provided deuterium-labeled drinking water while freely consuming either a regular-fat or high-fat diet that was SAA restricted. Livers from these mice and their respective dietary controls were used to conduct transcriptomic, proteomic, and kinetic proteomic analyses. We found that remodeling of the transcriptome by SAAR was largely agnostic to dietary fat content. Shared signatures included activation of the integrated stress response alongside alterations in metabolic processes impacting lipids, fatty acids, and amino acids. Changes to the proteome correlated poorly with the transcriptome, and yet, functional clustering of kinetic proteomic changes in the liver during SAAR revealed that the management of fatty acids and amino acids were altered to support central metabolism and redox balance. Dietary SAAR also strongly influenced the synthesis rates of ribosomal proteins and ribosome-interacting proteins regardless of dietary fat. Taken together, dietary SAAR alters the transcriptome and proteome in the liver to safely manage increased fatty acid flux and energy use and couples this with targeted changes in the ribo-interactome to support proteostasis and slowed growth.

Laparoscopic right colectomies with intracorporeal compared to extracorporeal anastomotic techniques are associated with reduced post-operative incisional hernias.

BACKGROUND: Owing to important differences in surgical technique, laparoscopic right colectomy with intracorporeal (ICA) compared to extracorporeal (ECA) anastomotic technique may result in improved patient outcomes. We aimed to compare both techniques according to incisional hernias and other pertinent perioperative characteristics, post-operative complications, and oncologic quality markers. METHODS: All adult patients undergoing laparoscopic right colectomies between 2015 and 2020 at a single institution were included. ICA and ECA techniques were compared based on selected outcomes using univariable and multivariable statistical analyses, as appropriate. Subgroup analyses were restricted to patients with neoplastic indications for surgery and non-urgent operations. RESULTS: A total of 517 patients met inclusion criteria, of which 139 (26.9%) underwent ICA and 378 (73.1%) underwent ECA. ICA and ECA patients had similar baseline characteristics. At two years of follow-up, a lower proportion of ICA patients developed a hernia at the extraction incision (1.5% vs. 7.1%, p = 0.02) and ICA was associated with an 80% reduction in extraction incision hernias (aHR 0.20, p = 0.03). These results were stable through subgroup and sensitivity analyses. Median operative time was longer in the ICA group (186 min vs. 135 min, p < 0.001), but the gap in operative time narrowed during the study period. Median length of stay was one calendar day shorter in the ICA group (3 days vs. 4 days, p = 0.007) and ICA was associated with a 13% decrease in the length of stay (aRR 0.87, p = 0.02). The incidence of superficial wound infections, anastomotic leaks and re-interventions was lower in ICA patients, but this difference was not statistically significant. 90-day unscheduled visits, readmissions, and mortalities were similar across both groups, as were oncologic outcomes. CONCLUSION: Laparoscopic right colectomies with intracorporeal anastomoses are associated with a reduction in incisional hernias and shorter hospital lengths of stay without compromising on patient safety or oncologic principles.

Rates of protein synthesis are maintained in brain but reduced in skeletal muscle during dietary sulfur amino acid restriction.

Dietary interventions such as sulfur amino acid restriction (SAAR) target multiple drivers of aging, and show promise for preventing or delaying the onset of chronic diseases. SAAR promotes metabolic health and longevity in laboratory animals. The effects of SAAR on proteostasis remain relatively unexplored. We previously reported that SAAR promotes mitochondrial proteostatic maintenance, despite suppression of global protein synthesis, in two peripheral tissues, the liver and skeletal muscle. However, the brain, a tissue vulnerable to age-related neurodegenerative diseases due to the loss of proteostasis, has not been thoroughly studied. Therefore, we sought to reveal proteostatic responses in the brains of mice fed SAAR for 35 days. Here, we demonstrate that male C57Bl/6J mice fed two levels of SAAR maintained rates of protein synthesis in all sub-cellular fractions of the pre-frontal cortex. In comparison, rates of skeletal muscle protein synthesis in SAAR fed mice were slower than control-fed mice. To gain mechanistic insight, we examined several key nutrient/energy sensitive signaling proteins: AMP-activated protein kinase (AMPK), eukaryotic initiation factor 2 (eIF2), and ribosomal protein S6 (rpS6). SAAR had minimal to modest effects on the total abundance and phosphorylation of these proteins in both tissues. Our results indicate that the pre-frontal cortex in brain is resistant to perturbations in protein synthesis in mice fed SAAR, unlike skeletal muscle, which had a reduction in global protein synthesis. The results from this study demonstrate that proteostatic control in brain is of higher priority than skeletal muscle during dietary SAAR.

Overprescription of opioid analgesia is common following ambulatory Otolaryngology-Head and Neck surgery procedures: A multicenter study.

Background: The rise in the use of prescription opioids for postoperative analgesia within surgery has mirrored an increased trend of opioid-related morbidity within Canada and the United States. This study prospectively studied daily pain levels and medication requirements postoperatively in patients undergoing elective Otolaryngology-Head and Neck surgery procedures. Methods: Patients were asked to prospectively document their pain level and medication use daily for 7 days postoperatively. A final survey was used to quantify unused medication left at home and clarify each patient's disposal plan. We included patients undergoing elective outpatient or short stay surgeries from three tertiary care centers in Toronto, Ontario from September 2016 to September 2017. Previous opioids users or patients suffering from chronic pain were excluded. Results: A final cohort of 56 eligible adult patients were included in the study. The most common procedures were thyroidectomy (n = 19), endoscopic sinus surgery (n = 10), tympanoplasty/ossiculoplasty (n = 7), and cochlear implant (n = 5). Most patients received a prescription for acetaminophen/codeine (n = 29, 51.8%) or acetaminophen/oxycodone (n = 22, 39.3%) and used on average 29% of their initial prescription. Patients most commonly opted to keep their unused narcotics at home (n = 23, 41%). A total of 710 tablets of narcotics were overprescribed in our study population, 351 of which were kept in patients' home for future use. Conclusion: There is a clear tendency to overestimate postoperative pain resulting in significant overprescription of opioids among Otolaryngologists.

Upfront Small Bowel Resection for Small Bowel Neuroendocrine Tumors With Synchronous Metastases: A Propensity-score Matched Comparative Population-based Analysis.

OBJECTIVE: We examined the impact of upfront small bowel resection (USBR) for metastatic small bowel neuroendocrine (SB-NET) compared to nonoperative management (NOM) on long-term healthcare utilization and survival outcomes. SUMMARY OF BACKGROUND DATA: The role of early resection of the primary tumor in metastatic SB-NET remains controversial. Conflicting data exist regarding its clinical and survival benefits. METHODS: This is a population-based retrospective matched comparative cohort study of adults diagnosed with synchronous metastatic SB-NET between 2001 and 2017 in Ontario. USBR was defined as resection within 6 months of diagnosis. Primary outcomes were subsequent unplanned acute care admissions and small bowel-related surgery. Secondary outcome was overall survival. USBR and NOM patients were matched 2:1 using a propensity-score. We used time-to-event analyses with cumulative incidencefunctions and univariate Andersen-Gill regression for primary outcomes. E value methods assessed the potential for residual confounding. RESULTS: Of 1000 patients identified, 785 had USBR. The matched cohort included 348 patients with USBR and 174 with NOM. Patients with USBR had lower 3-year risk of subsequent admissions (72.6% vs 86.4%, P < 0.001) than those with NOM, with hazard ratio 0.72 (95% confidence interval 0.570.91). USBR was associated with lower risk of subsequent small bowel-related surgery (15.4% vs 40.3%, P < 0.001), with hazard ratio 0.44 (95% confidence interval 0.29-0.67). E -values indicated it was unlikely that the observed risk estimates could be explained by an unmeasured confounder. Sensitivity analysis excluding emergent resections to define USBR did not alter the results. CONCLUSIONS: USBR for SB-NETs in the presence of metastatic disease was associated with better patient-oriented outcomes of decreased subsequent admissions and interventions, compared to NOM. USBR should be considered for metastatic SB-NETs.

Textbook Outcome and Survival in Patients With Gastric Cancer: An Analysis of the Population Registry of Esophageal and Stomach Tumours in Ontario (PRESTO).

OBJECTIVE: To examine the association between Textbook Outcome (TO)-a new composite quality measurement-and long-term survival in gastric cancer surgery. BACKGROUND: Single-quality indicators do not sufficiently reflect the complex and multifaceted nature of perioperative care in patients with gastric adenocarcinoma. METHODS: All patients undergoing gastrectomy for nonmetastatic gastric adenocarcinoma registered in the Population Registry of Esophageal and Stomach Tumours of Ontario (PRESTO) between 2004 and 2015 were included. TO was defined according to negative margins; >15 lymph nodes sampled; no severe complications; no re-interventions; no unplanned ICU admission; length of stay ≤21 days; no 30-day readmission; and no 30-day mortality. Three-year survival was estimated using the Kaplan-Meier method. A marginal multivariable Cox proportional-hazards model was used to estimate the association between achieving TO metrics and long-term survival. E-value methodology was used to assess for risk of residual confounding. RESULTS: Of the 1836 patients included in this study, 402 (22%) achieved all TO metrics. TO patients had a higher 3-year survival rate compared to non-TO patients (75% vs 55%, log-rank P < 0.001). After adjustments for covariates and clustering within hospitals, TO was associated with a 41% reduction in mortality (adjusted hazards ratio 0.59, 95% confidence interval 0.48, 0.72, P < 0.001). These results were robust to potential residual confounding. CONCLUSIONS: Achieving TO is strongly associated with improved long-term survival in gastric cancer patients and merits further focus in surgical quality improvement efforts.

The cost of chemotherapy administration: a systematic review and meta-analysis.

PURPOSE: Cancer treatment is a significant driver of healthcare costs worldwide, however, the economic impact of treating patients with anti-neoplastic agents is poorly elucidated. We conducted a systematic review and meta-analysis to estimate the direct costs associated with administering intravenous chemotherapy in an outpatient setting. METHODS: We systematically searched four databases from 2010 to present and extracted hourly administration costs and the respective components of each estimate. Separate analyses were conducted of Canadian and United States (US) studies, respectively, to address a priori hypotheses regarding heterogeneity amongst estimates. The Drummond checklist was used to assess risk-of-bias. Data were summarized using medians with interquartile ranges and five outliers were identified; costs were presented in 2019 USD. RESULTS: Forty-four studies were analyzed, including sub-analyses of 19 US and seven Canadian studies. 26/44 studies were of moderate-high quality. When components of administration cost were evaluated, physician costs were reported most frequently (24 studies), followed by lab tests (13) and overhead costs (9). The median estimate (excluding outliers) was $142/hour (IQR = $103-166). The median administration cost in the US was $149/hour (IQR = $118-158), and was $128/hour (IQR = $102-137) in Canada. CONCLUSIONS: There is currently a paucity of literature addressing the costs of chemotherapy administration, and existing studies utilize a patchwork of reporting methodologies which renders direct comparison challenging. Our results demonstrate that the cost of administering chemotherapy is approximately $125-150/hour, globally. This value is dependent upon the region of analysis, inclusiveness of cost subcomponents as well as the methodology used to estimate unit prices, as described here.

Physiologic Responses to Dietary Sulfur Amino Acid Restriction in Mice Are Influenced by Atf4 Status and Biological Sex.

BACKGROUND: Dietary sulfur amino acid restriction (SAAR) improves body composition and metabolic health across several model organisms in part through induction of the integrated stress response (ISR). OBJECTIVE: We investigate the hypothesis that activating transcription factor 4 (ATF4) acts as a converging point in the ISR during SAAR. METHODS: Using liver-specific or global gene ablation strategies, in both female and male mice, we address the role of ATF4 during dietary SAAR. RESULTS: We show that ATF4 is dispensable in the chronic induction of the hepatokine fibroblast growth factor 21 while being essential for the sustained production of endogenous hydrogen sulfide. We also affirm that biological sex, independent of ATF4 status, is a determinant of the response to dietary SAAR. CONCLUSIONS: Our results suggest that auxiliary components of the ISR, which are independent of ATF4, are critical for SAAR-mediated improvements in metabolic health in mice.

Population Registry of Esophageal and Stomach Tumours in Ontario (PRESTO): protocol for a multicentre clinical and pathological database including 25 000 patients.

INTRODUCTION: Oesophagogastric cancers carry a high mortality, economic burden and rising incidence. There is a need to monitor and improve care for this disease. Pathologic information is a cornerstone of cancer diagnosis, treatment and prognosis. Few population-based studies combine pathology information and clinical outcomes. The objective of this study is to develop a clinical and pathological database of oesophagogastric cancers to study practice patterns, resource utilisation and clinical outcomes. METHODS AND ANALYSIS: The Population Registry of Esophageal and Stomach Tumours in Ontario (PRESTO) will include all patients with oesophagogastric cancer diagnosed from 2002 onwards within the province of Ontario. We estimate that the sample over the first 14 years of the study will include 26 000 patients. Pathologic information from diagnostic procedures, endomucosal resection specimens and surgical resection specimens is being abstracted into a purpose-built database. Pathology information will be linked to administrative data, which capture baseline demographics, patient-reported symptoms, physician billings, hospital visits, hospital characteristics, geography and vital statistics. The registry will be updated prospectively. ETHICS AND DISSEMINATION: Ethics approval for this study was obtained from the Sunnybrook Health Sciences Centre Research Ethics Board. The PRESTO database will enable the study of oesophagogastric cancer in Ontario under six themes of inquiry: treatment, surgical outcomes, pathology, survival, health system and resource utilisation and cost. This information will be a valuable addition to the global efforts to understand ways to optimise care for these diseases.

Gastrectomy case volume and textbook outcome: an analysis of the Population Registry of Esophageal and Stomach Tumours of Ontario (PRESTO).

OBJECTIVE: To determine the association between gastric cancer surgery case-volume and Textbook Outcome, a new composite quality measurement. BACKGROUND: Textbook Outcome included (a) negative resection margin, (b) greater than 15 lymph nodes sampled, (c) no severe complication, (d) no re-intervention, (e) no unplanned ICU admission, (f) length of stay of 21 days or less, (g) no 30-day readmission and (h) no 30-day mortality following surgery. METHODS: All patients undergoing gastrectomy for non-metastatic gastric adenocarcinoma registered in the Population Registry of Esophageal and Stomach Tumours of Ontario between 2004 and 2015 were included. We used multivariable generalized estimating equation (GEE) logistic regression modelling to estimate the association between gastrectomy volume (surgeon and hospital annual volumes) and Textbook Outcome. Volumes were considered as continuous variables and quintiles. RESULTS: Textbook Outcome was achieved in 378 of 1660 patients (22.8%). The quality metrics least often achieved were inadequate lymph node sampling and presence of severe complications, which occurred in 46.1% and 31.7% of patients, respectively. Accounting for covariates and clustering, neither surgeon volume nor hospital volume were significantly associated with Textbook Outcome. However, hospital volume was associated with adequate lymphadenectomy and fewer unplanned ICU admissions. CONCLUSIONS: Higher case volume can impact certain measures of quality of care but may not address all care structures necessary for ideal Textbook recovery. Future quality improvement strategies should consider using case-mix adjusted Textbook Outcome rates as a surgical quality metric.

Intra-arterial therapies for unresectable and chemorefractory colorectal cancer liver metastases: a systematic review and meta-analysis.

BACKGROUND: A large proportion of patients with colorectal cancer liver metastases (CRCLM) not amenable to curative liver resection will progress on systemic therapy. Intra-arterial therapies (IAT) including conventional transarterial chemoembolization (cTACE), drug eluting beads (DEB-TACE) and yttrium-90 radioembolization (Y-90) are indicated to prolong survival and palliate symptoms. The purpose of this systematic review and meta-analysis is to compare the survival benefit and radiologic response of three intra-arterial therapies in patients with chemorefractory and unresectable CRCLM. METHODS: A systematic search for eligible references in the Cochrane Library and the EMBASE, MEDLINE and TRIP databases from January 2000 to November 2016 was performed in accordance with PRISMA guidelines. Methodological quality of included studies was assessed using the MINORS scale. One-year overall survival rates and RECIST responder rates were pooled using inverse-variance weighted random-effects models. Overall survival outcomes were collected according to transformed pooled median survivals from first IAT with a subgroup analysis of patients with extrahepatic disease. RESULTS: Twenty-three prospective studies were included and analyzed: 5 cTACE (n = 746), 5 DEB-TACE (n = 222) and 13 Y-90 (n = 615). All but five were clinical trials. Eleven of 13 Y-90 studies were industry funded. Pooled RECIST response rates with 95% confidence intervals (CI) were: cTACE 23% (9.7, 36), DEB-TACE 36% (0, 73) and Y-90 23% (11, 34). The pooled 1-year survival rates with CI were: cTACE, 70% (49, 87), DEB-TACE, 80% (74, 86) and Y-90, 41% (28, 54). Transformed pooled median survivals from first IAT and ranges for cTACE, DEB-TACE and Y-90 were 16 months (9.0-23), 16 months (7.3-25) and 12 months (7.0-15), respectively. Significant heterogeneity in inclusion criteria and reporting of confounders, including previous therapy, tumor burden and post-IAT therapy, precluded statistical comparisons between the three therapies. CONCLUSION: Methodological and statistical heterogeneity precluded consensus on the optimal treatment strategy. Given the common use and significant cost of radioembolization in this setting, a more robust prospective comparative trial is warranted.

Liver Transplantation Without Venovenous Bypass: Does Surgical Approach Matter?

BACKGROUND: The use of venovenous bypass in liver transplantation has declined over time. Few studies have examined the impact of surgical approach in cases performed exclusively without venovenous bypass. We hypothesized that advances in liver transplant anesthesia and perioperative care have minimized the importance of surgical approach in the modern era. METHODS: Deceased donor liver transplants at the University of Toronto from 2000 to 2015 were reviewed, all performed without venovenous bypass. First, an unadjusted analysis was performed comparing perioperative outcomes and graft/patient survival for 3 different liver transplant techniques (caval interposition, piggyback, side-to-side cavo-cavostomy). Second, a propensity-matched analysis was performed comparing caval interposition to caval-preserving techniques. RESULTS: One thousand two hundred thirty-three liver transplants were included in the study. On unadjusted analysis, blood loss, transfusion requirement, postoperative complications, and graft/patient survival were equivalent for the 3 different techniques. To account for possible confounding patient variables, propensity matching was performed. Analysis of the propensity-matched cohorts also demonstrated similar outcomes for caval interposition versus caval-preserving approaches. CONCLUSIONS: In the modern era at centers with a multidisciplinary team, the importance of specific liver transplant technique is minimized. Full or partial cross-clamping of the inferior vena cava is feasible without the use of venovenous bypass.

Ameliorative response to detoxification, psychotherapy, and medical management in patients maintained on opioids for pain.

BACKGROUND AND OBJECTIVES: The prevalence of opioid-induced hyperalgesia (OIH) among patients maintained on opioids for chronic non-malignant pain has not been estimated. As a contribution toward establishing its prevalence, we report a case series of opioid maintained patients whose pain tolerance was measured by the cold pressor test at baseline. METHODS: A case series of 117 patients who had undergone detoxification was reviewed retrospectively. Most patients (n = 108) and selected non-addicted support persons who accompanied them (controls; n = 37) had cold pressor time (CPT) assessments at baseline. Twenty patients had a repeat CPT after 1 month. RESULTS: When 61 patients completed one month abstinent reported pain was improved (51%), unchanged (46%), or worse (3%). Baseline CPT was 48 sec for patients and 102 sec for controls, suggesting that opioid maintained patients were more pain sensitive than opioid naïve controls. CPT increased for 90% of 1-month completers, suggesting improved pain tolerance. Ameliorative response to detoxification, psychotherapy, and medical management, as defined as the absence of worsening pain with removal of opioids, was 97% in this population. CONCLUSION: The difference in CPT between opioid maintained patients and controls, and the response to detoxification, psychotherapy and medical management suggest the possibility that the prevalence of OIH may be high. SCIENTIFIC SIGNIFICANCE: This study adds to the growing evidence that chronic opioid treatment contributes little to the management of chronic pain and in fact appears to frequently make it worse. (Am J Addict 2017;26:738-743).

Diagnostic Laparoscopy with Ultrasound Still Has a Role in the Staging of Pancreatic Cancer: A Systematic Review of the Literature.

Background. The reported incidence of noncurative laparotomies for pancreatic cancer using standard imaging (SI) techniques for staging remains high. The objectives of this study are to determine the diagnostic accuracy of diagnostic laparoscopy with ultrasound (DLUS) in assessing resectability of pancreatic tumors. Study Design. We systematically searched the literature for prospective studies investigating the accuracy of DLUS in determining resectability of pancreatic tumors. Results. 104 studies were initially identified and 19 prospective studies (1,573 patients) were included. DLUS correctly predicted resectability in 79% compared to 55% for SI. DLUS prevented noncurative laparotomies in 33%. Of those, the most frequent DLUS findings precluding resection were liver metastases, vascular involvement, and peritoneal metastases. DLUS had a morbidity rate of 0.8% with no mortalities. DLUS remained superior to SI when analyzing studies published only in the last five years (100% versus 81%), enrolling patients after the year 2000 (74% versus 58%), or comparing DLUS to modern multidimensional CT (100% versus 78%). Conclusion. DLUS seems to still have a role in the preoperative staging of pancreatic cancer. With its ability to detect liver metastases, vascular involvement, and peritoneal metastases, the use of DLUS leads to less noncurative laparotomies.

An approach to pneumatosis intestinalis: Factors affecting your management.

Pneumatosis Intestinalis (PI) is defined as the presence of extra-luminal gas confined to the bowel wall. PI is an ominous condition often requiring emergent surgery. The management can be challenging in some circumstances, as the choice of surgery versus medical treatment can be difficult. In this study, we first report the case of a seventy-seven year old woman presenting to the emergency department with the presence of PI on computed tomography of the abdomen. Secondly, we review the existing literature regarding the management of PI and we suggest a treatment algorithm based on clinical, laboratory and radiological findings.