Senescent glia link mitochondrial dysfunction and lipid accumulation.

Senescence is a cellular state linked to ageing and age-onset disease across many mammalian species1,2. Acutely, senescent cells promote wound healing3,4 and prevent tumour formation5; but they are also pro-inflammatory, thus chronically exacerbate tissue decline. Whereas senescent cells are active targets for anti-ageing therapy6-11, why these cells form in vivo, how they affect tissue ageing and the effect of their elimination remain unclear12,13. Here we identify naturally occurring senescent glia in ageing Drosophila brains and decipher their origin and influence. Using Activator protein 1 (AP1) activity to screen for senescence14,15, we determine that senescent glia can appear in response to neuronal mitochondrial dysfunction. In turn, senescent glia promote lipid accumulation in non-senescent glia; similar effects are seen in senescent human fibroblasts in culture. Targeting AP1 activity in senescent glia mitigates senescence biomarkers, extends fly lifespan and health span, and prevents lipid accumulation. However, these benefits come at the cost of increased oxidative damage in the brain, and neuronal mitochondrial function remains poor. Altogether, our results map the trajectory of naturally occurring senescent glia in vivo and indicate that these cells link key ageing phenomena: mitochondrial dysfunction and lipid accumulation.

Aspirin as a thromboprophylaxis agent after revision knee arthroplasty: A retrospective analysis.

Introduction: Total knee arthroplasty is a common and effective procedure. Although complication rates are low, certain complications such as venous thromboembolism are potentially serious. The optimal prophylactic agent and dosage after revision knee arthroplasty remains unclear. The main objective of this work was to study the efficacy and safety of aspirin as a thromboprophylaxis agent following revision knee arthroplasties. Patients and methods: A retrospective review of patients undergoing revision knee arthroplasty between 2013 and 2020at a University Teaching Hospital was undertaken. The primary outcome was the development of a symptomatic thromboembolic event requiring treatment within 90 days post-surgery. The secondary outcomes were adverse events associated with aspirin therapy: surgical site infection rate; incidence of major bleeding; readmission rate and mortality within 90 days post-surgery. Results: 490 patients were included. 374 (76.3%) received prophylactic aspirin (150 mg once daily for 28 days) and 75 (15.3%) patients received dalteparin for 28 days due to contraindication to aspirin use. Those already receiving other thromboprophylaxis agents for pre-existing comorbidities continued these after relevant medical consultation. The overall rates of venous thromboembolism and symptomatic DVT after aspirin prophylaxis were 0.6% (3/490) and 0.8% (3/374), respectively. VTE incidence did not significantly differ between those administered aspirin and other agents. No patient experienced major bleeding within 90 postoperative days. Only 2 of 490 (0.4%) patients had wound infection requiring readmission; neither received prophylactic aspirin. Conclusion: Extended out-of-hospital thromboembolic prophylaxis with aspirin may be at least as effective as other agents in patients undergoing revision knee arthroplasty. Aspirin is safe, effective, and cheap compared with other agents.

Radiological and Long-Term Functional Outcomes of Displaced Distal Clavicle Fractures.

OBJECTIVES: To investigate radiological and long-term functional outcomes in modified Neer 2a, 2b, and 5 distal clavicle fractures. DESIGN: Retrospective cohort study. SETTING: A single university teaching hospital. PATIENTS/PARTICIPANTS: One hundred fifteen patients sustaining displaced distal clavicle fractures between January 01, 2010 and December 12, 2017. INTERVENTION: Operative versus nonoperative management. MAIN OUTCOME MEASUREMENTS: Radiographs were reviewed for fracture management and union. A customised questionnaire consisting of QuickDASH (Disabilities of the Arm, Shoulder and Hand), work, sports/performing arts, global satisfaction, and complication modules was used to determine functional outcome. RESULTS: One hundred fifteen patients were included [mean age of 49 (18-89) years]. Thirty-three (29%) underwent early fixation (<6 weeks from injury) and were younger (37 vs. 53 years, P < 0.0001). Radiographs were available for 96 patients. Nonunion rate was 55% (53/96), and majority had undergone initial nonoperative management (49 vs. 4, P < 0.00001). Eleven patients with symptomatic nonunion were deemed appropriate for delayed fixation with all cases uniting. Of the operatively managed patients, 27% (12/44) underwent metalwork removal. There were no differences in functional outcome between operative versus nonoperative and union versus nonunion patient groups at a mean follow-up of 79 months ( P > 0.05). CONCLUSION: Functional outcome and patient satisfaction at long-term follow-up were similar regardless of operative fixation or radiological union. Nonunion in displaced distal clavicle fractures seemed to cause minimal functional deficit in most elderly sedentary individuals, or the outcome measures were not sensitive enough to capture these differences. An individualized approach should be adopted, with less active, comorbid, and elderly patients counseled regarding the minimal functional improvement of surgery and risk of reoperation. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Morphological characteristics and management of greater tuberosity fractures associated with anterior glenohumeral joint dislocation: A single centre 10-year retrospective review.

Introduction: Greater tuberosity (GT) fractures associated with anterior gleno-humeral (GH) dislocations are unstable, with inadequate treatment leading to displacement, malunion, stiffness and functional disability. We explored its morphological characteristics to ultimately optimize their management. Methods: We retrospectively reviewed all shoulder radiographs with GT fractures associated with anterior GH dislocations in a university hospital between December 1, 2009 and December 31, 2019. Special considerations were given to fracture morphology, presence and site of comminution, degree of displacement and need for surgical intervention. Results: 133 patients were identified. Most of the fracture-dislocations were multi-fragmentary (86.5%) and located antero- or postero-superiorly (68.7%). Superiorly comminuted GT fractures were twice as likely to displace compared to other sites of comminution (43% vs. 21%, p = 0.03), and require surgery (p = 0.03). Undisplaced comminuted GT fragments, particularly superior patterns, could undergo secondary migration if conservatively treated (p = 0.01). GT fractures fixed with interfragmentary screw suffered more secondary migration but those treated with double-row suture anchors (DRSA) did not on follow-up x-rays at two months. Conclusion: GT fractures with anterior GH dislocations are frequently comminuted. Those with superiorly situated comminution should have a low threshold for surgical fixation, particularly with DRSA which can prevent secondary fragment migration.

Outcomes and Health Care Utilization After Early Hospital Dismissal in Kidney Transplantation: An Analysis of 1001 Consecutive Cases.

OBJECTIVE: To understand whether reduced lengths of stay after kidney transplantation were associated with excess health care utilization in the first 90 days or long-term graft and patient survival outcomes. BACKGROUND: Reducing length of stay after kidney transplant has an unknown effect on post-transplant health care utilization. We studied this association in a cohort of 1001 consecutive kidney transplants. METHODS: We retrospectively reviewed 2011-2015 data from a prospectively-maintained kidney transplant database from a single center. RESULTS: A total of 1001 patients underwent kidney transplant, and were dismissed from the hospital in 3 groups: Early [≤2 days] (19.8%), Normal [3-7 days] (79.4%) and Late [>7 days] (3.8%). 34.8% of patients had living donor transplants (Early 51%, Normal 31.4%, Late 18.4%, P < 0.001). Early patients had lower delayed graft function rates (Early 19.2%, Normal 32%, Late73.7%, P = 0.001). By the hospital dismissal group, there were no differences in readmissions or emergency room visits at 30 or 90 days. Glomerular filtration rate at 12 months and rates of biopsy-proven acute rejection were also similar between groups. The timing of hospital dismissal was not associated with the risk-adjusted likelihood of readmission. Early and Normal patients had similar graft and patient survival. Late dismissal patients, who had higher rates of cardiovascular complications, had significantly higher late mortality versus Normal dismissal patients in unadjusted and risk-adjusted models. CONCLUSION: Dismissing patients from the hospital 2 days after kidney transplant is safe, feasible, and improves value. It is not associated with excess health care utilization or worse short or long-term transplant outcomes.

Single-port laparoscopic appendicectomy versus conventional three-port approach for acute appendicitis: A systematic review, meta-analysis and trial sequential analysis of randomised controlled trials.

AIMS: The aim of this systematic review and meta-analysis is to compare outcomes of single-port laparoscopic appendicectomy (SPLA) and conventional three-port laparoscopic appendicectomy (CLA) in the management of acute appendicitis. METHODS: A comprehensive systematic review of randomised controlled trials (RCTs) with subsequent meta-analysis and trial sequential analysis of outcomes were conducted. Post-operative pain at 12-h, cosmesis, need for an additional port(s), operative time, port-site hernia, ileus, surgical site infection (SSI), intra-abdominal collection, length of hospital stay (LOS), readmission, and reoperation were the evaluated outcome parameters. RESULTS: Sixteen RCTs with total number of 2017 patients who underwent SPLA (n = 1009) or CLA (n = 1008) were included. SPLA was associated with a significantly higher cosmetic score (MD 1.11, P= 0.03) but significantly longer operative time (MD 7.08, P = 0.00001) compared to CLA. However, the difference was not significant between SPLA and CLA in the post-operative pain score at 12-h (MD -0.13, P = 0.69), need for additional port(s) (RR0.03, P = 0.07), port-site hernia (RD: 0.00, P = 0.68), ileus (RR 0.74, P = 0.51), SSI (RR 1.38, P = 0.28), post-operative intra-abdominal collection (RR 0.00, P = 0.62), LOS (MD -2.41, P = 0.16), readmission to the hospital (RR 0.45, P = 0.22), and return to theatre (RR 0.00, P = 0.49). Trial sequential analysis demonstrated that the meta-analysis is conclusive for most of the outcomes, except LOS and intra-abdominal collection. CONCLUSION: Although SPLA is associated with a slightly longer operative time, its efficacy and safety are comparable to CLA in management of uncomplicated appendicitis. Moreover, it offers improved post-operative cosmesis. The available evidence is conclusive, and further trials may not be required.

Do we need to routinely perform cavity shaving with breast-conserving surgery for breast cancer? A systematic review and meta-analysis.

AIMS: To evaluate comparative outcomes of breast-conserving surgery (BCS) of breast cancer with and without cavity shaving. METHODS: A systematic search of multiple electronic data sources was conducted, and all randomised controlled trials (RCTs) comparing BCS with or without cavity shaving for breast cancer were included. Positive margin rate, second operation rate, operative time, post-operative haematoma, cosmetic appearance and budget cost were the evaluated outcome parameters for the meta-analysis. RESULTS: Six RCTs reporting a total number of 971 patients; 495 of these underwent BCS plus shaving (BCS + S), and 473 underwent BCS alone were included. BCS + S showed significantly lower positive margin rate (Risk Ratio [RR] 0.40, P = 0.00001) and second operation rate (RR 0.38, P = 0.00001). BCS + S demonstrated longer operative time than BCS (79 ± 4 min vs 67 ± 3 min, Mean Difference 12.14, P = 0.002), and there was no significant difference in the risk of post-operative haematoma (RR 0.33, P = 0.20). CONCLUSION: BCS + S is superior to BCS in terms of positive margins rate and second operation rate. Operative time is longer when cavity shaving is performed.

Single-port laparoscopic appendicectomy versus conventional three-port approach for acute appendicitis in children: a systematic review and meta-analysis.

AIM: To evaluate comparative outcomes of single-port laparoscopic appendicectomy (SPLA) and conventional three-port laparoscopic appendicectomy (CLA) in the management of acute appendicitis in children. METHODS: A comprehensive systematic review of randomised controlled trials (RCTs) with subsequent meta-analysis of outcomes were conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards. Operative time, surgical site infection, intra-abdominal collection, incisional hernia, length of hospital stay (LOS), additional port/s and conversion to open were the evaluated outcome parameters. RESULTS: Four RCTs reporting a total number of 520 patients who underwent SPLA (n = 260) or CLA (n = 260) were included. There was no difference between SPLA and CLA group in post-operative collection (risk difference (RD) - 0.00, P = 0.94), surgical site infection (RD 0.02, P = 0.25), incisional hernia (RD 0.00 P = 1), LOS (mean difference (MD) 0.73 P = 0.93), need for additional port/s (RD 0.04, P = 0.24) and conversion to open (RD 0.00, P = 1). However, there was a significantly longer operative time in the SPLA group (MD 9.80, P = 0.00001). The certainty of the evidence was judged to be moderate for all outcomes. CONCLUSIONS: SPLA and CLA seem to have comparable efficacy and safety in children with acute appendicitis although the former may be associated with longer procedure time. Future high-quality RCTs with adequate sample sizes are required to provide stronger evidence in favour of an intervention.

Does sites of recurrence impact survival in secondary cytoreduction surgery for recurrent epithelial ovarian cancer?

Outcomes of secondary cytoreduction surgery (SCS) were evaluated for morbidity, progression free survival (PFS) and overall survival (OS) and factors influencing results were explored. Retrospective analysis of all cases of SCS for epithelial ovarian cancer (EOC) was performed from October 2010 to December 2017. 62 patients were prospectively identified as candidates for SCS and 57 underwent SCS. 20(35%) patients required bowel resection/s, 24(42%) had nodal resections and 11(19%) had extensive upper abdominal surgery. 51(89%) achieved complete cytoreduction. After a median follow-up of 30 months (range 9-95 months), median PFS was 32 months (CI 17-76 months) and median OS has not reached. Seventeen patients have died and 32 have progressed. Three patients had Clavien-Dindo grade-3 and two had grade-4 morbidity. Patients who had multi-site recurrence had shorter median PFS (p = 0.04) and patients who required bowel resections had lower median OS (p = 0.009) compared to rest of the cohort.IMPACT STATEMENTWhat is already known on this subject? Retrospective studies have confirmed survival advantage for recurrence in epithelial ovarian cancer and recommend SCS for carefully selected patients. This finding is being evaluated in randomised control trials currently.What do the results of this study add? This study presents excellent results for survival outcomes after SCS and highlights importance of careful selection of patients with a goal to achieve complete cytoreduction. In addition, for the first time in literature, this study also explores various factors that may influence results and finds that there are no differences in survival outcomes whether these patients had early stage or advanced stage disease earlier. Patients who have multisite recurrence tend to have shorter PFS but no difference were noted for overall survival. Patients who have recurrence in bowels necessitating resection/s have a shorter median OS compared to rest of cohorts, however, still achieving a good survival time.What are the implications of these findings for clinical practice and/or further research? These findings will raise awareness for the clinicians and patients while discussing surgical outcomes and would set an achievable standard to improve cancer services. The pattern of recurrence and associated outcomes also point towards difference in biological nature of recurrent disease and could provide an opportunity for scientists to study the biological makeup of these recurrent tumours.

Evaluation of integrin αvß6 cystine knot PET tracers to detect cancer and idiopathic pulmonary fibrosis.

Advances in precision molecular imaging promise to transform our ability to detect, diagnose and treat disease. Here, we describe the engineering and validation of a new cystine knot peptide (knottin) that selectively recognizes human integrin αvß6 with single-digit nanomolar affinity. We solve its 3D structure by NMR and x-ray crystallography and validate leads with 3 different radiolabels in pre-clinical models of cancer. We evaluate the lead tracer's safety, biodistribution and pharmacokinetics in healthy human volunteers, and show its ability to detect multiple cancers (pancreatic, cervical and lung) in patients at two study locations. Additionally, we demonstrate that the knottin PET tracers can also detect fibrotic lung disease in idiopathic pulmonary fibrosis patients. Our results indicate that these cystine knot PET tracers may have potential utility in multiple disease states that are associated with upregulation of integrin αvß6.

The Characterization of 18F-hGTS13 for Molecular Imaging of xC- Transporter Activity with PET.

The aim of this study was development of an improved PET radiotracer for measuring xC- activity with increased tumor uptake and reduced uptake in inflammatory cells compared with (S)-4-(3-18F-fluoropropyl)-l-glutamate (18F-FSPG). Methods: A racemic glutamate derivative, 18F-hGTS13, was evaluated in cell culture and animal tumor models. 18F-hGTS13 was separated into C5 epimers, and the corresponding 18F-hGTS13-isomer1 and 18F-hGTS13-isomer2 were evaluated in H460 tumor-bearing rats. Preliminary studies investigated the cellular uptake of 18F-hGTS13-isomer2 in multiple immune cell populations and states. Results:18F-hGTS13 demonstrated excellent H460 tumor visualization with high tumor-to-background ratios, confirmed by ex vivo biodistribution studies. Tumor-associated radioactivity was significantly higher for 18F-hGTS13 (7.5 ± 0.9 percentage injected dose [%ID]/g, n = 3) than for 18F-FSPG (4.6 ± 0.7 %ID/g, n = 3, P = 0.01). 18F-hGTS13-isomer2 exhibited excellent H460 tumor visualization (6.3 ± 1.1 %ID/g, n = 3) and significantly reduced uptake in multiple immune cell populations relative to 18F-FSPG. 18F-hGTS13-isomer2 exhibited increased liver uptake relative to 18F-FSPG (4.6 ± 0.8 vs. 0.7 ± 0.01 %ID/g), limiting its application in hepatocellular carcinoma. Conclusion:18F-hGTS13-isomer2 is a new PET radiotracer for molecular imaging of xC- activity that may provide information on tumor oxidation states. 18F-hGTS13-isomer2 has potential for clinical translation for imaging cancers of the thorax because of the low background signal in healthy tissue.

Long-term Outcomes Following Kidney Transplantation From Donors With Acute Kidney Injury.

BACKGROUND: Kidneys from deceased donors with acute kidney injury (AKI) are more likely to be discarded because of concerns for poor outcomes after transplantation. The aim of this study was to determine the long-term outcomes of a large cohort of patients transplanted utilizing kidneys from deceased donors with AKI. METHODS: All patients receiving a deceased donor kidney transplant during a recent 10-year period were included. Acute Kidney Injury Network (AKIN) criteria were used to classify the donors. Donor kidneys with >10% cortical necrosis or more than mild chronic changes were discarded. The primary outcome is the combined endpoint of death or graft loss. RESULTS: The cohort included 1313 kidneys from 974 donors, AKIN stage 0 (no AKI) in 319 (24.3%), stage 1 in 370 (28.2%), stage 2 in 177 (13.5), and stage 3 in 447 (34.0%). Estimated 5-year graft survival (95% confidence interval) was 78.5% (72.5-84.5), 77.8% (72.8-82.1), 83.8% (76.8-88.9), and 84.6% (79.5-88.7) for AKIN donor stage 0 to 3, respectively (log-rank P = 0.10). After adjusting for baseline differences, the hazard ratio (95% confidence interval) for the combined endpoint for the AKIN stage 3 group (relative to AKIN 0 group) was 0.70 (0.45-1.10). Delayed graft function occurred in 44.6% and 75.4% of AKIN 2 and 3 groups, as compared to 33.9% and 33.5% in AKIN 0 and 1 (P < 0.001). CONCLUSION: We conclude that transplanting selected kidneys from deceased donors with AKI with preimplantation biopsy showing <10% cortical necrosis and no more than mild chronic changes have excellent long-term graft survival.

Specific Imaging of Bacterial Infection Using 6″-18F-Fluoromaltotriose: A Second-Generation PET Tracer Targeting the Maltodextrin Transporter in Bacteria.

6″-18F-fluoromaltotriose is a PET tracer that can potentially be used to image and localize most bacterial infections, much like 18F-FDG has been used to image and localize most cancers. However, unlike 18F-FDG, 6″-18F-fluoromaltotriose is not taken up by inflammatory lesions and appears to be specific to bacterial infections by targeting the maltodextrin transporter that is expressed in gram-positive and gram-negative strains of bacteria. Methods: 6″-18F-fluoromaltotriose was synthesized with high radiochemical purity and evaluated in several clinically relevant bacterial strains in cultures and in living mice. Results: 6″-18F-fluoromaltotriose was taken up in both gram-positive and gram-negative bacterial strains. 6″-18F-fluoromaltotriose was also able to detect Pseudomonas aeruginosa in a clinically relevant mouse model of wound infection. The utility of 6″-18F-fluoromaltotriose to help monitor antibiotic therapies was also evaluated in rats. Conclusion: 6″-18F-fluoromaltotriose is a promising new tracer that has significant diagnostic utility, with the potential to change the clinical management of patients with infectious diseases of bacterial origin.

Development of [18F]DASA-23 for Imaging Tumor Glycolysis Through Noninvasive Measurement of Pyruvate Kinase M2.

PURPOSE: A hallmark of cancer is metabolic reprogramming, which is exploited by cancer cells to ensure rapid growth and survival. Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key step in tumor metabolism and growth. Recently, we reported the radiosynthesis of the first positron emission tomography tracer for visualizing PKM2 in vivo-i.e., [11C]DASA-23. Due to the highly promising imaging results obtained with [11C]DASA-23 in rodent model glioblastoma, we set out to generate an F-18-labeled version of this tracer, with the end goal of clinical translation in mind. Herein, we report the radiosynthesis of 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) and our initial investigation of its binding properties in cancer cells. PROCEDURE: We synthesized [18F]DASA-23 via fluorination of 1-((2-fluoro-6-nitrophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine (10) with K[18F]F/K2.2.2 in N,N-dimethylformamide at 110 °C for 20 min. Subsequently, we evaluated uptake of [18F]DASA-23 in HeLa cervical adenocarcinoma cells and in vitro stability in human and mouse serum. RESULTS: We successfully prepared [18F]DASA-23 in 2.61 ± 1.54 % radiochemical yield (n = 10, non-decay corrected at end of synthesis) with a specific activity of 2.59 ± 0.44 Ci/µmol. Preliminary cell uptake experiments revealed high uptake in HeLa cells, which was effectively blocked by pretreating cells with the structurally distinct PKM2 activator, TEPP-46. [18F]DASA-23 remained intact in human and mouse serum up to 120 min. CONCLUSION: Herein, we have identified a F-18-labeled PKM2 specific radiotracer which shows potential for in vivo imaging. The promising cell uptake results reported herein warrant the further evaluation of [18F]DASA-23 for its ability to detect and monitor cancer noninvasively.

Development and Validation of an Immuno-PET Tracer as a Companion Diagnostic Agent for Antibody-Drug Conjugate Therapy to Target the CA6 Epitope.

PURPOSE: To develop and compare three copper 64 ((64)Cu)-labeled antibody fragments derived from a CA6-targeting antibody (huDS6) as immuno-positron emission tomography (immuno-PET)-based companion diagnostic agents for an antibody-drug conjugate by using huDS6. MATERIALS AND METHODS: Three antibody fragments derived from huDS6 were produced, purified, conjugated to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), and evaluated in the following ways: (a) the affinity of the fragments and the DOTA conjugates was measured via flow cytometry, (b) the stability of the labeled fragments was determined ex vivo in human serum over 24 hours, and (c) comparison of the in vivo imaging potential of the fragments was evaluated in mice bearing subcutaneous CA6-positive and CA6-negative xenografts by using serial PET imaging and biodistribution. Isotype controls with antilysozyme and anti-DM4 B-Fabs and blocking experiments with an excess of either B-Fab or huDS6 were used to determine the extent of the antibody fragment (64)Cu-DOTA-B-Fab binding specificity. Immunoreactivity and tracer kinetics were evaluated by using cellular uptake and 48-hour imaging experiments, respectively. Statistical analyses were performed by using t tests, one-way analysis of variance, and Wilcoxon and Mann-Whitney tests. RESULTS: The antibody fragment (64)Cu-DOTA-B-Fab was more than 95% stable after 24 hours in human serum, had an immunoreactivity of more than 70%, and allowed differentiation between CA6-positive and CA6-negative tumors in vivo as early as 6 hours after injection, with a 1.7-fold uptake ratio between tumors. Isotype and blocking studies experiments showed tracer-specific uptake in antigen-positive tumors, despite some nonspecific uptake in both tumor models. CONCLUSION: Three antibody fragments were produced and examined as potential companion diagnostic agents. (64)Cu-DOTA-B-Fab is a stable and effective immuno-PET tracer for CA6 imaging in vivo.

Readmission and risk factors for readmission following esophagectomy for esophageal cancer.

INTRODUCTION: Readmission after esophagectomy for esophageal cancer has not been systematically evaluated. STUDY OBJECTIVE: The objectives of this study were to determine national 30-day readmission rates after esophagectomy for esophageal cancer and evaluate risk factors associated with readmission. METHODS: Retrospective review of the 2011-2012 National Surgical Quality Improvement Program dataset was performed to identify patients who underwent elective esophagectomy for esophageal cancer. RESULTS: One thousand sixty-eight patients satisfied study criteria. One hundred and thirty-five patients were admitted within 30 days resulting in a readmission rate of 12.6%. Patients with a history of pulmonary disease were 3.9 times more likely to be readmitted. Patients who developed postoperative wound-related complications were 9 times more likely to be readmitted than patients who did not develop wound-related complications. Increasing length of hospital stay was associated with a marginal but significant decrease in risk of readmission. CONCLUSIONS: National 30-day readmission rate after esophagectomy for esophageal cancer is around 12.6%. Risk factors associated with 30-day readmission include history of pulmonary disease, postoperative wound-related complications, and length of hospital stay.

Dosimetry and first clinical evaluation of the new 18F-radiolabeled bombesin analogue BAY 864367 in patients with prostate cancer.

UNLABELLED: The aim of this first-in-man study was to demonstrate the feasibility, safety, and tolerability, as well as provide dosimetric data and evaluate the imaging properties, of the bombesin analogue BAY 864367 for PET/CT in a small group of patients with primary and recurrent prostate cancer (PCa). METHODS: Ten patients with biopsy-proven PCa (5 with primary PCa and 5 with prostate-specific antigen recurrence after radical prostatectomy) were prospectively selected for this exploratory clinical trial with BAY 864367, a new (18)F-labeled bombesin analogue. PET scans were assessed at 6 time points, up to 110 min after intravenous administration of 302 ± 11 MBq of BAY 864367. Imaging results were compared with (18)F-fluorocholine PET/CT scans. Dosimetry was calculated using the OLINDA/EXM software. RESULTS: Three of 5 patients with primary disease showed positive tumor delineation in the prostate, and 2 of 5 patients with biochemical relapse showed a lesion suggestive of recurrence on the BAY 864367 scan. Tumor-to-background ratio averaged 12.9 ± 7.0. The ratio of malignant prostate tissue to normal prostate tissue was 4.4 ± 0.6 in 3 patients with tracer uptake in the primary PCa. Mean effective dose was 4.3 ± 0.3 mSv/patient (range, 3.7-4.9 mSv). CONCLUSION: BAY 864367, a novel (18)F-labeled bombesin tracer, was successfully investigated in a first-in-man clinical trial of PCa and showed favorable dosimetric values. Additionally, the application was safe and well tolerated. The tracer delineated tumors in a subset of patients, demonstrating the potential of gastrin-releasing-peptide receptor imaging.

High-resolution manometry patterns of lower esophageal sphincter complex in symptomatic post-fundoplication patients.

INTRODUCTION: There has been an increase in the number of patients seeking treatment after an anti-reflux surgical procedure. The objective of this study is to describe high-resolution manometry (HRM) topography as it relates to the post-fundoplication anatomy. METHODS: Retrospective review of a prospectively maintained database was conducted to identify patients who underwent esophagogastroduodenoscopy and HRM at Creighton University Medical Center (CUMC) between November 2008 and October 2010, for symptoms after a previous fundoplication. Patients were categorized as having intact, intrathoracic, disruptured, twisted, or slipped fundoplication based on endoscopic findings. RESULTS: Sixty-one patients {intact, 17(28%), disrupted, 2(3%), twisted, 3(5%), intra-thoracic, 18(30%), slipped, 21(34%)} are included in this study. A double high-pressure zone (HPZ) configuration was identified in both intra-thoracic and slipped fundoplication. This was not noted in appropriately positioned fundoplications. In intra-thoracic fundoplications, the HPZ below the fundoplication was lower pressure and showed respiratory variations. In slipped fundoplication, the higher HPZ had lower pressure and no respiratory variations. In appropriately positioned fundoplication, the lower esophageal sphincter (LES) pressure and extent of relaxation in the single HPZ correlated with intact (normal pressure and good relaxation), disrupted (low pressure and good relaxation), and twisted (high pressure with incomplete relaxation) fundoplication. Patients with only a recurrent para-esophageal hernia had characteristics of an appropriately positioned fundoplication. CONCLUSION: LES complex HRM findings correlate well with anatomical status of the fundoplication.

The relationship between dysphagia, pump function, and lower esophageal sphincter pressures on high-resolution manometry.

INTRODUCTION: Study objective was to compare high-resolution impedance manometry (HRIM) findings between patients with and without dysphagia. METHODS: After Institutional Review Board approval, a prospectively maintained database was reviewed to identify patients who underwent HRIM. Patients without upper endoscopy within 7 days of manometry, patients with achalasia, history of previous foregut surgery, esophageal strictures, or a large hiatus hernia were excluded. A new parameter called lower esophageal sphincter pressure integral (LESPI) was compared between patients with and without dysphagia. For subanalysis, subjects were categorized: (a) group A: no dysphagia and <60% hypocontractile or absent waves, (b) group B: dysphagia and <60% hypocontractile or absent waves, and (c) group C: ≥ 60% hypocontractile or absent waves. RESULTS: One hundred thirteen patients satisfied study criteria. Patients with dysphagia had a significantly higher LESPI and distal contractile integral (DCI). On multivariate regression analysis, the following were associated with dysphagia: (a) ≥ 60% hypocontractile or absent waves, (b) LESPI >400 mmHg s cm, and (c) DCI >3,000 mmHg s cm. However, 32% of patients with <60% hypocontractile or absent waves (group B) had dysphagia. These patients had a significantly higher DCI and LESPI than group A. Group C had a significantly lower DCI than all other patients. CONCLUSIONS: Dysphagia in patients with ≥ 60% hypocontractile or absent waves is indicative of an intrinsic pump failure as they have low DCI, while dysphagia in patients with <60% hypocontractile or absent waves is more indicative of significant outflow obstruction as they have high LESPI and integrated relaxation pressure.

GLUT 5 is not over-expressed in breast cancer cells and patient breast cancer tissues.

F18 2-Fluoro 2-deoxyglucose (FDG) has been the gold standard in positron emission tomography (PET) oncologic imaging since its introduction into the clinics several years ago. Seeking to complement FDG in the diagnosis of breast cancer using radio labeled fructose based analogs, we investigated the expression of the chief fructose transporter-GLUT 5 in breast cancer cells and human tissues. Our results indicate that GLUT 5 is not over-expressed in breast cancer tissues as assessed by an extensive immunohistochemistry study. RT-PCR studies showed that the GLUT 5 mRNA was present at minimal amounts in breast cancer cell lines. Further knocking down the expression of GLUT 5 in breast cancer cells using RNA interference did not affect the fructose uptake in these cell lines. Taken together these results are consistent with GLUT 5 not being essential for fructose uptake in breast cancer cells and tissues.