Survival outcomes used to validate version 9 of the American Joint Committee on Cancer staging system for appendiceal cancer.

The standard for cancer staging in the United States for all cancer sites, including primary carcinomas of the appendix, is the American Joint Committee on Cancer (AJCC) staging system. AJCC staging criteria undergo periodic revisions, led by a panel of site-specific experts, to maintain contemporary staging definitions through the evaluation of new evidence. Since its last revision, the AJCC has restructured its processes to include prospectively collected data because large data sets have become increasingly robust and available over time. Thus survival analyses using AJCC eighth edition staging criteria were used to inform stage group revisions in the version 9 AJCC staging system, including appendiceal cancer. Although the current AJCC staging definitions were maintained for appendiceal cancer, incorporating survival analysis into the version 9 staging system provided unique insight into the clinical challenges in staging rare malignancies. This article highlights the critical clinical components of the now published version 9 AJCC staging system for appendix cancer, which (1) justified the separation of three different histologies (non-mucinous, mucinous, signet-ring cell) in terms of prognostic variance, (2) demonstrated the clinical implications and challenges in staging heterogeneous and rare tumors, and (3) emphasized the influence of data limitations on survival analysis for low-grade appendiceal mucinous neoplasms.

LMO3 is a suppressor of the basal-like/squamous subtype and reduces disease aggressiveness of pancreatic cancer through glycerol 3-phosphate metabolism.

Pancreatic ductal adenocarcinoma (PDAC) encompasses diverse molecular subtypes, including the classical/progenitor and basal-like/squamous subtypes, each exhibiting distinct characteristics, with the latter known for its aggressiveness. We employed an integrative approach combining transcriptome and metabolome analyses to pinpoint potential genes contributing to the basal-like/squamous subtype differentiation. Applying this approach to our NCI-UMD-German and a validation cohort, we identified LIM Domain Only 3 (LMO3), a transcription co-factor, as a candidate suppressor of the basal-like/squamous subtype. Reduced LMO3 expression was significantly associated with higher pathological grade, advanced disease stage, induction of the basal-like/squamous subtype and decreased survival among PDAC patients. In vitro experiments demonstrated that LMO3 transgene expression inhibited PDAC cell proliferation and migration/invasion, concurrently downregulating the basal-like/squamous gene signature. Metabolome analysis of patient tumors and PDAC cells revealed a metabolic program linked to elevated LMO3 and the classical/progenitor subtype, characterized by enhanced lipogenesis and suppressed amino acid metabolism. Notably, glycerol 3-phosphate (G3P) levels positively correlated with LMO3 expression and associated with improved patient survival. Furthermore, glycerol-3-phosphate dehydrogenase 1 (GPD1), a crucial enzyme in G3P synthesis, showed upregulation in LMO3-high and classical/progenitor PDAC, suggesting its potential role in mitigating disease aggressiveness. Collectively, our findings suggest that heightened LMO3 expression reduces transcriptome and metabolome characteristics indicative of basal-like/squamous tumors with decreased disease aggressiveness in PDAC patients. The observations describe LMO3 as a candidate for diagnostic and therapeutic targeting in PDAC.

ADRA2A promotes the classical/progenitor subtype and reduces disease aggressiveness of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) manifests diverse molecular subtypes, including the classical/progenitor and basal-like/squamous subtypes, with the latter known for its aggressiveness. We employed integrative transcriptome and metabolome analyses to identify potential genes contributing to the molecular subtype differentiation and its metabolic features. Our comprehensive analysis revealed that adrenoceptor alpha 2A (ADRA2A) was downregulated in the basal-like/squamous subtype, suggesting its potential role as a candidate suppressor of this subtype. Reduced ADRA2A expression was significantly associated with a high frequency of lymph node metastasis, higher pathological grade, advanced disease stage, and decreased survival among PDAC patients. In vitro experiments demonstrated that ADRA2A transgene expression and ADRA2A agonist inhibited PDAC cell invasion. Additionally, ADRA2A-high condition downregulated the basal-like/squamous gene expression signature, while upregulating the classical/progenitor gene expression signature in our PDAC patient cohort and PDAC cell lines. Metabolome analysis conducted on the PDAC cohort and cell lines revealed that elevated ADRA2A levels were associated with suppressed amino acid and carnitine/acylcarnitine metabolism, which are characteristic metabolic profiles of the classical/progenitor subtype. Collectively, our findings suggest that heightened ADRA2A expression induces transcriptome and metabolome characteristics indicative of classical/progenitor subtype with decreased disease aggressiveness in PDAC patients. These observations introduce ADRA2A as a candidate for diagnostic and therapeutic targeting in PDAC.

MIF/NR3C2 axis regulates glucose metabolism reprogramming in pancreatic cancer through MAPK-ERK and AP-1 pathways.

Inflammation and aberrant cellular metabolism are widely recognized as hallmarks of cancer. In pancreatic ductal adenocarcinoma (PDAC), inflammatory signaling and metabolic reprogramming are tightly interwoven, playing pivotal roles in the pathogenesis and progression of the disease. However, the regulatory functions of inflammatory mediators in metabolic reprogramming in pancreatic cancer have not been fully explored. Earlier, we demonstrated that pro-inflammatory mediator macrophage migration inhibitory factor (MIF) enhances disease progression by inhibiting its downstream transcriptional factor nuclear receptor subfamily 3 group C member 2 (NR3C2). Here, we provide evidence that MIF and NR3C2 interactively regulate metabolic reprogramming, resulting in MIF-induced cancer growth and progression in PDAC. MIF positively correlates with the HK1 (hexokinase 1), HK2 (hexokinase 2) and LDHA (lactate dehydrogenase) expression and increased pyruvate and lactate production in PDAC patients. Additionally, MIF augments glucose uptake and lactate efflux by upregulating HK1, HK2 and LDHA expression in pancreatic cancer cells in vitro and in mouse models of PDAC. Conversely, a reduction in HK1, HK2 and LDHA expression is observed in tumors with high NR3C2 expression in PDAC patients. NR3C2 suppresses HK1, HK2 and LDHA expression, thereby inhibiting glucose uptake and lactate efflux in pancreatic cancer. Mechanistically, MIF-mediated regulation of glycolytic metabolism involves the activation of the mitogen-activated protein kinase-ERK signaling pathway, whereas NR3C2 interacts with the activator protein 1 to regulate glycolysis. Our findings reveal an interactive role of the MIF/NR3C2 axis in regulating glucose metabolism supporting tumor growth and progression and may be a potential target for designing novel approaches for improving disease outcome.

ELAPOR1 induces the classical/progenitor subtype and contributes to reduced disease aggressiveness through metabolic reprogramming in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a heterogeneous disease with distinct molecular subtypes described as classical/progenitor and basal-like/squamous PDAC. We hypothesized that integrative transcriptome and metabolome approaches can identify candidate genes whose inactivation contributes to the development of the aggressive basal-like/squamous subtype. Using our integrated approach, we identified endosome-lysosome associated apoptosis and autophagy regulator 1 (ELAPOR1/KIAA1324) as a candidate tumor suppressor in both our NCI-UMD-German cohort and additional validation cohorts. Diminished ELAPOR1 expression was linked to high histological grade, advanced disease stage, the basal-like/squamous subtype, and reduced patient survival in PDAC. In vitro experiments demonstrated that ELAPOR1 transgene expression not only inhibited the migration and invasion of PDAC cells but also induced gene expression characteristics associated with the classical/progenitor subtype. Metabolome analysis of patient tumors and PDAC cells revealed a metabolic program associated with both upregulated ELAPOR1 and the classical/progenitor subtype, encompassing upregulated lipogenesis and downregulated amino acid metabolism. 1-Methylnicotinamide, a known oncometabolite derived from S-adenosylmethionine, was inversely associated with ELAPOR1 expression and promoted migration and invasion of PDAC cells in vitro. Taken together, our data suggest that enhanced ELAPOR1 expression promotes transcriptome and metabolome characteristics that are indicative of the classical/progenitor subtype, whereas its reduction associates with basal-like/squamous tumors with increased disease aggressiveness in PDAC patients. These findings position ELAPOR1 as a promising candidate for diagnostic and therapeutic targeting in PDAC.

SAGES peritoneal dialysis access guideline update 2023.

BACKGROUND: Minimally invasive surgery has been used for both de novo insertion and salvage of peritoneal dialysis (PD) catheters. Advanced laparoscopic, basic laparoscopic, open, and image-guided techniques have evolved as the most popular techniques. The aim of this guideline was to develop evidence-based guidelines that support surgeons, patients, and other physicians in decisions on minimally invasive peritoneal dialysis access and the salvage of malfunctioning catheters in both adults and children. METHODS: A guidelines committee panel of the Society of American Gastrointestinal and Endoscopic Surgeons reviewed the literature since the prior guideline was published in 2014 and developed seven key questions in adults and four in children. After a systematic review of the literature, by the panel, evidence-based recommendations were formulated using the Grading of Recommendations Assessment, Development and Evaluation approach. Recommendations for future research were also proposed. RESULTS: After systematic review, data extraction, and evidence to decision meetings, the panel agreed on twelve recommendations for the peri-operative performance of laparoscopic peritoneal dialysis access surgery and management of catheter dysfunction. CONCLUSIONS: In the adult population, conditional recommendations were made in favor of: staged hernia repair followed by PD catheter insertion over simultaneous and traditional start over urgent start of PD when medically possible. Furthermore, the panel suggested advanced laparoscopic insertion techniques rather than basic laparoscopic techniques or open insertion. Conditional recommendations were made for either advanced laparoscopic or image-guided percutaneous insertion and for either nonoperative or operative salvage. A recommendation could not be made regarding concomitant clean-contaminated surgery in adults. In the pediatric population, conditional recommendations were made for either traditional or urgent start of PD, concomitant clean or clean-contaminated surgery and PD catheter placement rather than staged, and advanced laparoscopic placement rather than basic or open insertion.

SAGES guidelines for the surgical treatment of hiatal hernias.

BACKGROUND: Hiatal hernia (HH) is a common condition. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians, patients, and others in decisions regarding the treatment of HH. METHODS: Systematic reviews were conducted for four key questions regarding the treatment of HH in adults: surgical treatment of asymptomatic HH versus surveillance; use of mesh versus no mesh; performing a fundoplication versus no fundoplication; and Roux-en-Y gastric bypass (RYGB) versus redo fundoplication for recurrent HH. Evidence-based recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations methodology by subject experts. When the evidence was insufficient to base recommendations on, expert opinion was utilized instead. Recommendations for future research were also proposed. RESULTS: The panel provided one conditional recommendation and two expert opinions for adults with HH. The panel suggested routinely performing a fundoplication in the repair of HH, though this was based on low certainty evidence. There was insufficient evidence to make evidence-based recommendations regarding surgical repair of asymptomatic HH or conversion to RYGB in recurrent HH, and therefore, only expert opinions were offered. The panel suggested that select asymptomatic patients may be offered surgical repair, with criteria outlined. Similarly, it suggested that conversion to RYGB for management of recurrent HH may be appropriate in certain patients and again described criteria. The evidence for the routine use of mesh in HH repair was equivocal and the panel deferred making a recommendation. CONCLUSIONS: These recommendations should provide guidance regarding surgical decision-making in the treatment of HH and highlight the importance of shared decision-making and consideration of patient values to optimize outcomes. Pursuing the identified research needs will improve the evidence base and may allow for stronger recommendations in future evidence-based guidelines for the treatment of HH.

Management of symptomatic, asymptomatic, and recurrent hiatal hernia: a systematic review and meta-analysis.

BACKGROUND: The surgical management of hiatal hernia remains controversial. We aimed to compare outcomes of mesh versus no mesh and fundoplication versus no fundoplication in symptomatic patients; surgery versus observation in asymptomatic patients; and redo hernia repair versus conversion to Roux-en-Y reconstruction in recurrent hiatal hernia. METHODS: We searched PubMed, Embase, CINAHL, Cochrane Library and the ClinicalTrials.gov databases between 2000 and 2022 for randomized controlled trials (RCTs), observational studies, and case series (asymptomatic and recurrent hernias). Screening was performed by two trained independent reviewers. Pooled analyses were performed on comparative data. Risk of bias was assessed using the Cochrane Risk of Bias tool and Newcastle Ottawa Scale for randomized and non-randomized studies, respectively. RESULTS: We included 45 studies from 5152 retrieved records. Only six RCTs had low risk of bias. Mesh was associated with a lower recurrence risk (RR = 0.50, 95%CI 0.28, 0.88; I2 = 57%) in observational studies but not RCTs (RR = 0.98, 95%CI 0.47, 2.02; I2 = 34%), and higher total early dysphagia based on five observational studies (RR = 1.44, 95%CI 1.10, 1.89; I2 = 40%) but was not statistically significant in RCTs (RR = 3.00, 95%CI 0.64, 14.16). There was no difference in complications, reintervention, heartburn, reflux, or quality of life. There were no appropriate studies comparing surgery to observation in asymptomatic patients. Fundoplication resulted in higher early dysphagia in both observational studies and RCTs ([RR = 2.08, 95%CI 1.16, 3.76] and [RR = 20.58, 95%CI 1.34, 316.69]) but lower reflux in RCTs (RR = 0.31, 95%CI 0.17, 0.56, I2 = 0%). Conversion to Roux-en-Y was associated with a lower reintervention risk after 30 days compared to redo surgery. CONCLUSIONS: The evidence for optimal management of symptomatic and recurrent hiatal hernia remains controversial, underpinned by studies with a high risk of bias. Shared decision making between surgeon and patient is essential for optimal outcomes.

SAGES guideline for the diagnosis and treatment of appendicitis.

BACKGROUND: Appendicitis is an extremely common disease with a variety of medical and surgical treatment approaches. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians and patients in decisions regarding the diagnosis and treatment of appendicitis. METHODS: A systematic review was conducted from 2010 to 2022 to answer 8 key questions relating to the diagnosis of appendicitis, operative or nonoperative management, and specific technical and post-operative issues for appendectomy. The results of this systematic review were then presented to a panel of adult and pediatric surgeons. Evidence-based recommendations were formulated using the GRADE methodology by subject experts. RESULTS: Conditional recommendations were made in favor of uncomplicated and complicated appendicitis being managed operatively, either delayed (>12h) or immediate operation (<12h), either suction and lavage or suction alone, no routine drain placement, treatment with short-term antibiotics postoperatively for complicated appendicitis, and complicated appendicitis previously treated nonoperatively undergoing interval appendectomy. A conditional recommendation signals that the benefits of adhering to a recommendation probably outweigh the harms although it does also indicate uncertainty. CONCLUSIONS: These recommendations should provide guidance with regard to current controversies in appendicitis. The panel also highlighted future research opportunities where the evidence base can be strengthened.

EAES/SAGES evidence-based recommendations and expert consensus on optimization of perioperative care in older adults.

BACKGROUND: As the population ages, more older adults are presenting for surgery. Age-related declines in physiological reserve and functional capacity can result in frailty and poor outcomes after surgery. Hence, optimizing perioperative care in older patients is imperative. Enhanced Recovery After Surgery (ERAS) pathways and Minimally Invasive Surgery (MIS) may influence surgical outcomes, but current use and impact on older adults patients is unknown. The aim of this study was to provide evidence-based recommendations on perioperative care of older adults undergoing major abdominal surgery. METHODS: Expert consensus determined working definitions for key terms and metrics related to perioperative care. A systematic literature review and meta-analysis was performed using the PubMed, Embase, Cochrane Library, and Clinicaltrials.gov databases for 24 pre-defined key questions in the topic areas of prehabilitation, MIS, and ERAS in major abdominal surgery (colorectal, upper gastrointestinal (UGI), Hernia, and hepatopancreatic biliary (HPB)) to generate evidence-based recommendations following the GRADE methodology. RESULT: Older adults were defined as 65 years and older. Over 20,000 articles were initially retrieved from search parameters. Evidence synthesis was performed across the three topic areas from 172 studies, with meta-analyses conducted for MIS and ERAS topics. The use of MIS and ERAS was recommended for older adult patients particularly when undergoing colorectal surgery. Expert opinion recommended prehabilitation, cessation of smoking and alcohol, and correction of anemia in all colorectal, UGI, Hernia, and HPB procedures in older adults. All recommendations were conditional, with low to very low certainty of evidence, with the exception of ERAS program in colorectal surgery. CONCLUSIONS: MIS and ERAS are recommended in older adults undergoing major abdominal surgery, with evidence supporting use in colorectal surgery. Though expert opinion supported prehabilitation, there is insufficient evidence supporting use. This work has identified evidence gaps for further studies to optimize older adults undergoing major abdominal surgery.

Diagnosis and treatment of appendicitis: systematic review and meta-analysis.

BACKGROUND: The optimal diagnosis and treatment of appendicitis remains controversial. This systematic review details the evidence and current best practices for the evaluation and management of uncomplicated and complicated appendicitis in adults and children. METHODS: Eight questions regarding the diagnosis and management of appendicitis were formulated. PubMed, Embase, CINAHL, Cochrane and clinicaltrials.gov/NLM were queried for articles published from 2010 to 2022 with key words related to at least one question. Randomized and non-randomized studies were included. Two reviewers screened each publication for eligibility and then extracted data from eligible studies. Random effects meta-analyses were performed on all quantitative data. The quality of randomized and non-randomized studies was assessed using the Cochrane Risk of Bias 2.0 or Newcastle Ottawa Scale, respectively. RESULTS: 2792 studies were screened and 261 were included. Most had a high risk of bias. Computerized tomography scan yielded the highest sensitivity (> 80%) and specificity (> 93%) in the adult population, although high variability existed. In adults with uncomplicated appendicitis, non-operative management resulted in higher odds of readmission (OR 6.10) and need for operation (OR 20.09), but less time to return to work/school (SMD - 1.78). In pediatric patients with uncomplicated appendicitis, non-operative management also resulted in higher odds of need for operation (OR 38.31). In adult patients with complicated appendicitis, there were higher odds of need for operation following antibiotic treatment only (OR 29.00), while pediatric patients had higher odds of abscess formation (OR 2.23). In pediatric patients undergoing appendectomy for complicated appendicitis, higher risk of reoperation at any time point was observed in patients who had drains placed at the time of operation (RR 2.04). CONCLUSIONS: This review demonstrates the diagnosis and treatment of appendicitis remains nuanced. A personalized approach and appropriate patient selection remain key to treatment success. Further research on controversies in treatment would be useful for optimal management.

Dysregulation of HNF1B/Clusterin axis enhances disease progression in a highly aggressive subset of pancreatic cancer patients.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy and is largely refractory to available treatments. Identifying key pathways associated with disease aggressiveness and therapeutic resistance may characterize candidate targets to improve patient outcomes. We used a strategy of examining the tumors from a subset of PDAC patient cohorts with the worst survival to understand the underlying mechanisms of aggressive disease progression and to identify candidate molecular targets with potential therapeutic significance. Non-negative matrix factorization (NMF) clustering, using gene expression profile, revealed three patient subsets. A 142-gene signature specific to the subset with the worst patient survival, predicted prognosis and stratified patients with significantly different survival in the test and validation cohorts. Gene-network and pathway analysis of the 142-gene signature revealed dysregulation of Clusterin (CLU) in the most aggressive patient subset in our patient cohort. Hepatocyte nuclear factor 1 b (HNF1B) positively regulated CLU, and a lower expression of HNF1B and CLU was associated with poor patient survival. Mechanistic and functional analyses revealed that CLU inhibits proliferation, 3D spheroid growth, invasiveness and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cell lines. Mechanistically, CLU enhanced proteasomal degradation of EMT-regulator, ZEB1. In addition, orthotopic transplant of CLU-expressing pancreatic cancer cells reduced tumor growth in mice. Furthermore, CLU enhanced sensitivity of pancreatic cancer cells representing aggressive patient subset, to the chemotherapeutic drug gemcitabine. Taken together, HNF1B/CLU axis negatively regulates pancreatic cancer progression and may potentially be useful in designing novel strategies to attenuate disease progression in PDAC patients.

Incidence, Timing, and Outcomes of Venous Thromboembolism in Patients Undergoing Surgery for Esophagogastric Cancer: A Population-Based Cohort Study.

BACKGROUND: Abdominal surgery and chemotherapy are well-established risk factors for venous thromboembolism (VTE) in patients with cancer, but their specific contribution in patients with esophageal and gastric cancer is unclear. We aim to quantify the risk of VTE, identify risk factors associated with VTE, and determine the association between VTE and survival in patients undergoing surgery for esophageal or gastric cancer. METHODS: A retrospective, population-based cohort study was conducted using linked administrative healthcare databases. We used the Ontario Cancer Registry to identify patients with esophageal or gastric cancer between January 1, 2007 and December 31, 2016 who underwent surgical resection. Incidence of first VTE event was identified using International Classification of Diseases 9 and 10 codes. VTE incidence was calculated at clinically relevant time points 180 days before and after surgery. Logistic regression was used to identify factors associated with VTE with odds ratios (OR) and 95% confidence intervals (CI) reported. Cox proportional hazards regression models were used to estimate associations between covariates and survival. Kaplan-Meier method was used to compare overall (OS) and cancer-specific survival (CSS) by VTE status. RESULTS: A total of 4894 patients had esophagectomy or gastrectomy, of which 8% (n = 383/4894) had VTE. VTE risk was 2.5% (n = 123/4894) 180 days before surgery, 2.8% (n = 138/4894) within 30 days of surgery, and 2.5% (n = 122/4894) from 31 to ≤ 180 days after surgery. Of the patients with VTE within 30 days of surgery, 34% (n = 47/138) were diagnosed after discharge from hospital. Receipt of preoperative chemotherapy was associated with VTE 180 days before surgery (odds ratio [OR] 3.84, 95% confidence interval [CI] 2.41, 6.11). Increased hospital length of stay (LOS) was associated with VTE 30 days after surgery (OR 1.08, 95% CI 1.02, 1.14, per week). Patients with VTE had inferior median OS and CSS (2.2 vs. 3.7 years; 2.3 vs. 4.4 years, respectively). In adjusted models VTE was associated with inferior OS (HR 1.36, 95% CI 1.13, 1.63) and CSS (HR 1.42, 95% CI 1.16, 1.75). CONCLUSIONS: The highest risk of VTE is within 30 days of surgery with one third of patients diagnosed after discharge from hospital. Longer hospital LOS and receipt of preoperative chemotherapy are associated with increased risk of VTE. VTE is an independent risk factor for inferior survival in patients with esophageal or gastric cancer.

SAGES 2022 guidelines regarding the use of laparoscopy in the era of COVID-19.

BACKGROUND: SARS-CoV-2 has changed global healthcare since the pandemic began in 2020. The safety of minimally invasive surgery (MIS) utilizing insufflation from the standpoint of safety to the operating room personnel is currently being explored. The aims of this guideline are to examine the existing evidence to provide guidance regarding MIS for the patient with, or suspecting of having, the SARS-CoV-2 as well as the healthcare team involved. METHODS: Systematic literature reviews were conducted for 2 key questions (KQ) regarding the safety of MIS in the setting of COVID-19 pandemic. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis criteria. Evidence-based recommendations were formulated using a narrative synthesis of the literature by subject experts. Recommendations for future research were also proposed. RESULTS: In KQ1, a total of 1361 articles were reviewed, with 2 articles meeting inclusion. In KQ2, a total of 977 articles were reviewed, with 4 articles met inclusions criteria, of which 2 studies reported on the SARS-CoV2 virus specifically. Despite many publications in the field, very little well-controlled and unbiased data exist to inform the recommendations. Of that which is available, it shows that both laparoscopic and open operations in Covid-positive patients had similar rates of OR staff positivity rates; however, patients who underwent laparoscopic procedures had a lower perioperative mortality than open procedures. Also, SARS-CoV-2 particles have been detected in the surgical plume at laparoscopy. CONCLUSION: With demonstrated equivalence of operating room staff exposure, and noninferiority of laparoscopic access with respect to mortality, either laparoscopic or open approaches to abdominal operations may be used in patients with SARS-CoV-2. Measures should be employed for all laparoscopic or open cases to prevent exposure of operating room staff to the surgical plume, as virus can be present in this plume.

Incidence and Risk Factors of Venous Thromboembolism Following Hepatectomy for Colorectal Metastases: A Population-Based Retrospective Cohort Study.

BACKGROUND: Incidence of venous thromboembolism (VTE) following hepatectomy for colorectal cancer (CRC) metastases is unclear. These patients may represent a vulnerable population due to increased tumour burden. We aim to identify the risk of VTE development in routine clinical practice among patients with resected CRC liver metastases, the associated risk factors, and its impact on survival. METHODS: We conducted a population-based retrospective cohort study of Ontario patients undergoing hepatectomy for CRC metastases between 2002 and 2009 using linked universal healthcare databases. Multivariable logistic regression was used to estimate the association between patient characteristics and VTE risk at 30 and 90-days after surgery. Cox proportional-hazards regression was used to estimate the association between VTE and adjusted cancer specific (CSS) and overall survival (OS). RESULTS: 1310 patients were included with a mean age of 63 ± 11. 62% were male. 51% had one metastatic deposit. Major hepatectomy occurred in 64%. VTE occurred in 4% within 90 days of liver resection. Only longer length of stay was associated with VTE development (OR 6.88 (2.57-18.43), p <0.001 for 15-21 days versus 0-7 days). 38% of VTEs were diagnosed after discharge, comprising 1.52% of the total cohort. VTE was not associated with inferior CSS or OS. CONCLUSIONS: Risk of VTE development in this population is similar to those undergoing hepatectomy for other indications, and to the risk following other cancer site resections where post-operative extended VTE prophylaxis is currently recommended. The number of VTEs occurring after discharge suggests there may be a role for extended VTE prophylaxis.

Thoracic duct embolization via chest tube for a patient with postoperative traumatic chylothorax.

We present the case of a 53-year-old man who experienced a postoperative chyle leak after minimally invasive esophagectomy with mass ligation of the thoracic duct; conservative management failed. Interventional radiology was unsuccessful initially in accessing the cisterna chyli with conventional methods, yet ethiodized oil was noted at the tip of his right chest tube. The chest tube and its tract were used as an avenue to access the thoracic duct and successfully facilitate its embolization.

NO• /RUNX3/kynurenine metabolic signaling enhances disease aggressiveness in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy and is refractory to available treatments. Delineating the regulatory mechanisms of metabolic reprogramming, a key event in pancreatic cancer progression, may identify candidate targets with potential therapeutic significance. We hypothesized that inflammatory signaling pathways regulate metabolic adaptations in pancreatic cancer. Metabolic profiling of tumors from PDAC patients with a high- (>median, n = 31) and low-NOS2 (inducible nitric oxide synthase;

Validation of a smartphone-based event recorder for arrhythmia detection.

INTRODUCTION: Ambulatory cardiac monitoring devices such as external loop recorders (ELRs) are often used in the outpatient clinic to evaluate palpitations. However, ELRs can be bulky and uncomfortable to use, especially in public, at work, or in social situations. An alternative approach is a smartphone-based electrocardiographic (ECG) recorder/event recorder (Kardia Mobile [KM]), but the comparative diagnostic yield of each approach has not been studied. METHODS: Thirty-three patients with palpitations wore an ELR and carried a KM for a period of 14-30 days. They were instructed to transmit ECGs via KM and also to activate the ELR whenever they had symptoms. The tracings obtained from both devices were independently analyzed by two cardiologists, and the overall arrhythmia yield, as well as patient preference and compliance, were evaluated. The paired binomial data obtained from both devices were compared using an unconditional test of noninferiority. RESULTS: Of the 38 patients enrolled in the study, more patients had a potential diagnosis for their symptoms (i.e., at least one symptomatic recording during the entire monitoring period) with KM than with the ELR (KM = 34 [89.5%] vs ELR = 26 [68.4%]; χ2  = 5.1, P = 0.024). In the per protocol analysis, all 33 patients (100%) had a potential diagnosis using the KM device, which was significantly higher compared to 24 patients (72.2%) using the ELR (χ2  = 10.4, P = 0.001). CONCLUSIONS: KM is noninferior to an ELR for detecting arrhythmias in the outpatient setting. The ease of use and portability of this device make it an attractive option for the detection of symptomatic arrhythmias.