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Introduction The empty pelvis syndrome is a significant source of morbidity following pelvic exenteration surgery. It remains poorly defined with research in this field being heterogeneous and of low quality. Furthermore, there has been minimal engagement with patient representatives following pelvic exenteration with respect to the empty pelvic syndrome. ‘PelvEx—Beating the empty pelvis syndrome’ aims to engage both patient representatives and healthcare professionals to achieve an international consensus on a core outcome set, pathophysiology and mitigation of the empty pelvis syndrome.Methods and analysis A modified-Delphi approach will be followed with a three-stage study design. First, statements will be longlisted using a recent systematic review, healthcare professional event, patient and public engagement, and Delphi piloting. Second, statements will be shortlisted using up to three rounds of online modified Delphi. Third, statements will be confirmed and instruments for measurable statements selected using a virtual patient-representative consensus meeting, and finally a face-to-face healthcare professional consensus meeting.Ethics and dissemination The University of Southampton Faculty of Medicine ethics committee has approved this protocol, which is registered as a study with the Core Outcome Measures in Effectiveness Trials Initiative. Publication of this study will increase the potential for comparative research to further understanding and prevent the empty pelvis syndrome.Trial registration number NCT05683795.

Tarlatamab, a DLL3-targeting bispecific T-cell engager, has rapidly assumed the role of a new standard of care in the later-line treatment of extensive-stage SCLC. Little is known about the efficacy of tarlatamab in other histologies such as DLL3-expressing metastatic pulmonary carcinoid tumor, a clinical entity without many approved management options. Here, we report the case of a patient with metastatic atypical carcinoid tumor which had progressed on multiple previous therapies. Her tumor strongly expressed DLL3 protein and had clinical response to tarlatamab therapy. This case indicates that this novel therapy may be an efficacious option in other pulmonary neuroendocrine cancers., Competing Interests: Dr. Cooper reports the following conflicts of interest for the previous 3 years: receiving honoraria from MJH Life Sciences, Ideology Health, Intellisphere LLC, and MedStar Health, and consulting fees from 10.13039/100005564Gilead Sciences, Inc., and Regeneron. She reports receiving research funding to institution from Merck, Monte Rosa, AbbVie, Roche, and Amgen. Dr. Rekhtman reports the following conflicts of interest for the previous 3 years: receiving consulting fees from 10.13039/100004334Merck. Ms. Thomas reports the following conflicts of interest for the previous 3 years: receiving honoraria from MD Outlook. Ms. Lynch reports the following conflicts of interest for the previous 3 years: receiving honoraria from MJH Life Sciences and PrecisionAQ; consulting fees from 10.13039/501100022274Daiichi Sankyo. Dr. Gentzler reports the following conflicts of interest for the previous 3 years: receiving research funding to institution from Pfizer, Tempus, Nalo Therapeutics, Puma, Mirati, Bristol Myers Squibb, Dizal, Chugai, Amgen, AstraZeneca, Janssen, Daiichi Sankyo, Jounce Therapeutics, Takeda, Merck, Alliance Foundation, ECOG/ACRIN, NCI, Big Ten Research Consortium, Hoosier Cancer Research Network, and SWOG; receiving honoraria from Academy for Continued Healthcare Learning, Curio, OncLive, Aptitude Health, MedStar Health, Clinical Care Options, and American Society of Clinical Oncology; receiving travel support to meetings from Dava Oncology, Tempus, American Society of Clinical Oncology (ASCO), and International Association for the Study of Lung Cancer (IASLC); receiving consulting fees from 10.13039/100002429Amgen, 10.13039/100004328Genentech, 10.13039/100004325AstraZeneca, 10.13039/100009857Regeneron, Merus, Takeda, Gilead, Janssen, Mirati, and Daiichi Sankyo; and having leadership roles with Hoosier Cancer Research Network, ASCO, Journal of Clinical Oncology, NCI Investigational Drug Steering Committee, and IASLC Conference Planning Committees. Baine declares no conflicts of interest., (© 2024 The Authors.)

Background and Objectives: Criminal-legal (CL) referrals to addiction treatment have historically had low utilization of medications for opioid use disorder (MOUD). While state differences have been reported, an in-depth longitudinal analysis of state-by-state differences is lacking., Methods: The Substance Abuse and Mental Health Services Administration Treatment Episode Dataset-Admissions 2000-2020 provided data for individuals entering their initial treatment with an opioid as their primary substance. Outcome was planned use of MOUD, assessing odds ratio (OR) of CL referrals relative to non-CL referrals cumulatively over the 21-year period and as incremental change (change in relative disparity) using effect sizes, stratified by each state., Results: 2,187,447 cases met the criteria. Planned MOUD occurred in 37.7% of non-CL clients versus 6.5% of CL clients (OR = 0.11, 95% confidence interval = 0.11-0.12). For all clients, planned MOUD increased from 2000 (33.9%) to 2020 (44.8%). This increase was blunted within CL clients, increasing from 2000 (6.4%) to 2020 (13.3%). Rhode Island saw the greatest improvements in equity., Discussion and Conclusions: While rates of planned MOUD increased over the 21 years, a significant disparity persisted among CL clients in most states. As opioid use disorders and opioid-related overdoses are more prevalent among those involved with the CL system, improving this has high impact., Scientific Significance: Provides the most comprehensive analysis of state-by-state inequities in MOUD access for CL relative to non-CL referrals over a 21-year period through use of a national data set. Positive outliers are used as case examples for others to follow in pursuit of more equitable care., (© 2024 The American Academy of Addiction Psychiatry (AAAP).)

This article describes a post-fellowship preceptorship training program to train sub-specialty colorectal surgeons in gaining proficiency in robotic colorectal surgery using a dual-surgeon model in the Australian private sector. The Australian colorectal surgeon faces challenges in gaining robotic colorectal surgery proficiency with limited exposure and experience in the public setting where the majority of general and colorectal surgery training is currently conducted. This training model uses graded exposure with a range of simulation training, wet lab training, and clinical operative cases to progress through both competency and proficiency in robotic colorectal surgery which is mutually beneficial to surgeons and patients alike. Ongoing audit of practice has shown no adverse impacts., (© 2024. The Author(s).)

The phenomenon of intercellular transfer of cellular material, including membranes, cytoplasm, and even organelles, has been observed for decades. The functional impact and molecular mechanisms of such transfer in the immune system remain largely elusive due to the absence of a robust in vivo model. Here, we introduce a new tumor mouse model, where tumor cells express the soluble ultra-bright fluorescent protein ZsGreen, which allows detection and measurement of intercellular transfer of cytoplasm from tumor cells to infiltrating immune cells. We found that in addition to various types of myeloid lineage cells, a large fraction of T regulatory cells and effector CD8 T cells acquire tumor material. Based on the distribution of tumor-derived ZsGreen, the majority of T cells integrate captured cytoplasm into their own, while most myeloid cells store tumor material in granules. Furthermore, scRNA-seq analysis revealed significant alterations in transcriptomes of T cells that acquired tumor cell cytoplasm, suggesting potential impact on T cell function. We identified that the participation of T cells in intercellular transfer requires cell-cell contact and is strictly dependent on the activation status of T lymphocytes. Finally, we propose to name the described phenomenon of intercellular transfer for tumor infiltrating T cells the "mosquito effect"., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hioki, Ryan, Thesmar, Lynch, Pobezinsky and Pobezinskaya.)

Musculoskeletal models are commonly used to estimate in vivo spinal loads under various loading conditions. Typically, participant-specific measured kinematics (PSMK) are coupled with participant-specific models, but obtaining PSMK data can be costly and infeasible in large studies or clinical practice. Thus, we evaluated two alternative methods to estimate spinal loads without PSMK: 1) ensemble average kinematics (EAK) based on kinematics from all participants; and 2) using separately measured individual kinematics (SMIK) from multiple other participants as inputs, then averaging the resulting loads. This study compares the dynamic spine loading patterns and peak loads in older adults performing five lifting tasks using PSMK, EAK and SMIK. Median root mean square errors of EAK and SMIK methods versus PSMK ranged from 18 to 72% body weight for compressive loads and from 2 to 25% body weight for shear loads, with median cross-correlations ranging from 0.931 to 0.991. The root mean square errors and cross-correlations between repeated PSMK trials fell within similar ranges. Compressive peak loads evaluated by EAK and SMIK were not different than PSMK in 12 of 15 cases, while by comparison repeated PSMK trials were not different in 13 of 15 cases. Overall, the resulting spine loading magnitudes and profiles using EAK or SMIK were not notably different than using a PSMK approach, and differences were not greater than between two PSMK trials. Thus, these findings indicate that these approaches may be used to make reasonable estimates of dynamic spinal loading without direct measurement of participant kinematics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: People who inject drugs (PWID) have an increased risk of soft tissue infection, drug overdose and death. Females may be particularly vulnerable due to barriers to substance use disorder (SUD) treatment entry, stigma, and telescoping, or the greater severity in substance use-related comorbidity and consequences despite a shorter history of use. We set out to identify sex differences in United States injection drug use (IDU)., Methods: The Treatment Episode Dataset-Admission (2000-2020) provided data to identify PWID undergoing their initial SUD treatment admission. Mann-Whitney U test, chi-square, and Spearman correlations were used for ordinal variables, categorical variables, and to assess similarity of male/female trends over the 21 years, respectively. The probabilistic index (PI) and Cramer's V provided effect sizes for Mann-Whitney U tests and chi-square tests, respectively., Results: A total of 13,612,978 records existed for cases entering their initial treatment. Mapping to a history of IDU left 1,458,695 (561,793 females). Females had a higher prevalence among PWID across all 21 years; IDU trends were essentially identical between males and females ( r  = 0.97). Females endorsed beginning their primary substance later in life (PI = 0.47, p  < 0.0001) and entered treatment after a shorter period of substance use (PI = 0.57, p  < 0.0001)., Conclusions: We saw evidence of telescoping among PWID with a SUD entering their initial episode of treatment. Interventions should be implemented prior to the transition to IDU, and this window of opportunity is shortened in females. Utilizing gender-responsive treatment options may be a way to increase treatment-seeking earlier in the disease course., Competing Interests: No conflict declared., (© 2023 The Authors. Published by Elsevier B.V.)

Objectives: Reentry postcorrectional involvement is a high-risk time for patients with a history of addiction. We investigated whether participation in an addiction medicine clinic with active case management led to improvements in patients' recovery capital and whether there were associated changes in criminal activity and co-occurring methamphetamine or alcohol use., Methods: Participants (n = 136) were patients with an opioid or stimulant use disorder who had Department of Corrections involvement in the preceding year, who completed the Assessment of Recovery Capital (ARC) and reported criminal activity and days of methamphetamine or alcohol use twice over a 6-month study. Three logistic regression models were used to assess changes in total ARC with criminal activity, alcohol use, and methamphetamine use over the previous 30 days., Results: Baseline mean (SD) ARC scores were 34.1 (11.1) and increased to a mean (SD) score of 40.3 (9.4) at study end. A 1-SD shift in ARC was significantly protective across outcomes, with adjusted odds ratios of 0.32, 0.18, and 0.34 for any past 30-day criminal activity, alcohol use, or methamphetamine use. There was no significant difference in baseline ARC, crimes committed, days of alcohol use, or days of methamphetamine use for study completers versus noncompleters; however, unmeasured confounders may have had a differential impact on retention., Conclusions: Recovery capital provides an additional framework to help address patients' substance use and criminal activity in a multifaceted way, which is especially important in the postincarceration community. Recovery capital is dynamic and has multiple areas to target psychosocial interventions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 American Society of Addiction Medicine.)

Purpose: Cravings for drugs and alcohol have been significantly associated with worse treatment outcomes. We investigated if improvements in recovery capital (RC) (eg, a measure of social capital/network, financial resources, education, and cultural factors) over time were associated with decreased reported cravings., Patients and Methods: The original cohort consisted of 133 participants (63 females) with opioid use disorder seeking outpatient treatment, who completed the Assessment of Recovery Capital (ARC) (range 0 to 50) and the Brief Addiction Monitor (BAM) thrice over the 6-month study. Intervention was medication and case management. Analysis included one-way mixed models testing change over time for ARC total scores and single question craving rating (5-point Likert scale). Cross-lagged panel estimates used structural equation models with variables z-scored, allowing for path coefficient evaluation as standard deviations (sd)., Results: Total ARC significantly increased over the study (χ2 = 33.77, df = 2, p < 0.0001), with baseline of 36.6 (n = 114, sd = 11.1) and 6-month of 41.2 (n = 107, sd = 9.5). Craving also changed significantly (χ2 = 8.51, df = 2, p < 0.015), with baseline of 1.1 (n = 101, sd = 1.2) and 6-month of 0.9 (n = 107, sd = 1.1). The cross-lag from baseline RC to 3-month craving was significant (β = -0.28, SE = 0.11, z = -2.53, p < 0.011). The converse was not true; baseline craving did not affect later RC. Results were similarly significant when comparing 3-month to 6-month. The majority of sample was on buprenorphine., Conclusion: As RC improves, the reported cravings at both 3- and 6-month study time points are significantly reduced. When evaluated inversely, there was not a significant association with baseline cravings and follow-up RC. Significant path coefficients provide an estimation of a directional effect from increased RC towards craving reduction., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Bormann et al.)

Purpose: Psychedelics are being explored for their potential therapeutic benefits across a wide range of psychiatric diagnoses and may usher in a new age in psychiatric treatment. There is stigma associated with these currently illegal substances, and use varies by race and age. We hypothesized that minoritized racial and ethnic populations, relative to White respondents, would perceive psychedelic use as riskier., Methods: Using 2019 cross-sectional data from the National Survey of Drug Use and Health, we conducted a secondary analysis of 41,679 respondents. Perceived risk of heroin was used as a surrogate for overall risk of illegal substance use; heroin and lysergic acid diethylamide were the only substances queried this way in the sample., Results: A majority regarded lysergic acid diethylamide (66.7%) and heroin (87.3%) as a great risk if used once or twice. There were clear differences by race, with White respondents and those indicating more than one race having significantly lower perceived risk of lysergic acid diethylamide than respondents from other groups. Perceived risk of use also significantly increased with age., Conclusion: Perceived risk of lysergic acid diethylamide is unevenly distributed across the population. Stigma and racial disparities in drug-related crimes likely contribute to this. As research into potential therapeutic indications for psychedelics continues, perceived risk of use may change., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Musculoskeletal models can uniquely estimate in vivo demands and injury risk. In this study, we aimed to compare muscle activations from subject-specific thoracolumbar spine OpenSim models with recorded muscle activity from electromyography (EMG) during five dynamic tasks. Specifically, 11 older adults (mean = 65 years, SD = 9) lifted a crate weighted to 10% of their body mass in axial rotation, 2-handed sagittal lift, 1-handed sagittal lift, and lateral bending, and simulated a window opening task. EMG measurements of back and abdominal muscles were directly compared to equivalent model-predicted activity for temporal similarity via maximum absolute normalized cross-correlation (MANCC) coefficients and for magnitude differences via root-mean-square errors (RMSE), across all combinations of participants, dynamic tasks, and muscle groups. We found that across most of the tasks the model reasonably predicted temporal behavior of back extensor muscles (median MANCC = 0.92 ± 0.07) but moderate temporal similarity was observed for abdominal muscles (median MANCC = 0.60 ± 0.20). Activation magnitude was comparable to previous modeling studies, and median RMSE was 0.18 ± 0.08 for back extensor muscles. Overall, these results indicate that our thoracolumbar spine model can be used to estimate subject-specific in vivo muscular activations for these dynamic lifting tasks., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

The success of the CD8 T cell-mediated immune response against infections and tumors depends on the formation of a long-lived memory pool, and the protection of effector cells from exhaustion. The advent of checkpoint blockade therapy has significantly improved anti-tumor therapeutic outcomes by reversing CD8 T cell exhaustion, but fails to generate effector cells with memory potential. Here, using in vivo mouse models, we show that let-7 miRNAs determine CD8 T cell fate, where maintenance of let-7 expression during early cell activation results in memory CD8 T cell formation and tumor clearance. Conversely, let-7-deficiency promotes the generation of a terminal effector population that becomes vulnerable to exhaustion and cell death in immunosuppressive environments and fails to reject tumors. Mechanistically, let-7 restrains metabolic changes that occur during T cell activation through the inhibition of the PI3K/AKT/mTOR signaling pathway and production of reactive oxygen species, potent drivers of terminal differentiation and exhaustion. Thus, our results reveal a role for let-7 in the time-sensitive support of memory formation and the protection of effector cells from exhaustion. Overall, our data suggest a strategy in developing next-generation immunotherapies by preserving the multipotency of effector cells rather than enhancing the efficacy of differentiation., (© 2023. Springer Nature Limited.)

Recent innovations within the field of robotic surgery have particular relevance to colorectal surgery. Although a robotic approach has been associated with satisfactory outcomes, there remains a wide variation in levels of adoption. In particular, this study focuses on patient positioning, docking, and table placement, with the intent of understanding the strength of opinion of colorectal surgeons in the Asia-Pacific region to the practical application of these developments to achieve optimal surgical outcomes. Using a modified Delphi methodology, a steering group of colorectal surgeons with experience in robotic surgery from across the Asia-Pacific region identified 35 consensus statements. An online 4-point Likert scale questionnaire was distributed to surgeons in the Asia-Pacific region using convenience sampling. Respondents were excluded from further analysis if they did not perform colorectal surgery or had no experience in robotic surgery. A total of 140 responses (71.8% response rate) were received between August and October 2021. 22 statements attained a very high degree of agreement (≥ 90%). High agreement (< 90% and ≥ 75%) was achieved in another 12, and one failed to meet the consensus threshold (< 75%). A set of five recommendations were developed based on these results. The high levels of agreement demonstrate recognition amongst colorectal surgeons within the Asia-Pacific region of the potential advantage of recent improvements in robotic surgery technology to further improve surgical outcomes. The recommendations may inform a set of practical principles to help standardise the use of colorectal robotic surgery, which may also be relevant to other surgical fields., (© 2022. The Author(s).)

Static biomechanical simulations are sometimes used to estimate in vivo kinetic demands because they can be solved efficiently, but this ignores any potential inertial effects. To date, comparisons between static and dynamic analyses of spinal demands have been limited to lumbar joint differences in young males performing sagittal lifts. Here we compare static and dynamic vertebral compressive and shear force estimates during axial, lateral, and sagittal lifting tasks across all thoracic and lumbar vertebrae in older men and women. Participant-specific thoracolumbar full-body musculoskeletal models estimated vertebral forces from recorded kinematics both with and without consideration of dynamic effects, at an identified frame of peak vertebral loading. Static analyses under-predicted dynamic compressive and resultant shear forces, by an average of about 16% for all three lifts across the thoracic and lumbar spine but were highly correlated with dynamic forces (average r 2  > .95). The study outcomes have the potential to enable standard clinical and occupational estimates using static analyses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: People with substance use disorders are highly prevalent in the carceral system. Recovery capital (RC) is the resources available to an individual to initiate or maintain substance use cessation. Sex differences have been identified in RC during both active substance use and recovery in the general population, however, less is known about these sex differences in the post-incarceration population., Methods: Participants ( n  = 136) were those with an opioid or stimulant use disorder with past year involvement with the Iowa criminal justice system (USA), who completed the Assessment of Recovery Capital (ARC) twice over a six-month cohort study. Participants were involved in an addiction clinic that utilized active case management. Analysis of covariance evaluated changes in ARC during the study. Separate models compared total ARC and individual ARC domains, with sex as the independent variable of interest. Model means were generated for interpretation based on sex, comparing baseline and study endpoint ARC scores., Results: There were no baseline sex differences in total ARC. ARC increased significantly for the group, however, males showed disproportionate growth. Females ended the study with a mean ARC of 37.8 (SD= 9.3) and males finished at 41.6 (SD= 9.3), which was a significant difference ( p  = 0.044); this significant difference was driven by ARC subdomains of 'Psychological Health' and 'Physical Health.', Conclusions: People post-incarceration are at high risk for return to substance use. Treatment that is informed by sex-based differences may have the potential to decrease the differing rates of growth in RC between sexes.

Background: A robotic approach to total colectomy/proctectomy and ileal pouch reconstruction would seem to be a sensible use of the platform's enhanced reach, visualization, and dexterity., Objective: The study aimed to discuss current published data for robotic ileal pouch surgery., Study Selection: The study selection included a paucity of published data to date, representing early learning curves and case series with small numbers., Conclusions: Current robotic platforms may offer advantages, particularly in the low pelvis beyond what is found with a laparoscopic approach., (Copyright © The ASCRS 2022.)

Background: Pre-clinical studies indicate that dry-cold-carbon-dioxide (DC-CO2) insufflation leads to more peritoneal damage, inflammation and hypothermia compared with humidified-warm-CO 2 (HW-CO2). Peritoneum and core temperature in patients undergoing colorectal cancer (CRC) surgery were compared., Methods: Sixty-six patients were randomized into laparoscopic groups; those insufflated with DC-CO2 or HW-CO2. A separate group of nineteen patients undergoing laparotomy were randomised to conventional surgery or with the insertion of a device delivering HW-CO2. Temperatures were monitored and peritoneal biopsies and bloods were taken at the start of surgery, at 1 and 3 h. Further bloods were taken depending upon hospital length-of-stay (LOS). Peritoneal samples were subjected to scanning electron microscopy to evaluate mesothelial damage., Results: Laparoscopic cases experienced a temperature drop despite Bair-Hugger TM use. HW-CO2 restored normothermia (≥ 36.5 °C) by 3 h, DC-CO2 did not. LOS was shorter for colon compared with rectal cancer cases and if insufflated with HW-CO2 compared with DC-CO2; 5.0 vs 7.2 days, colon and 11.6 vs 15.4 days rectum, respectively. Unexpectedly, one third of patients had pre-existing damage. Damage increased at 1 and 3 h to a greater extent in the DC-CO2 compared with the HW-CO2 laparoscopic cohort. C-reactive protein levels were higher in open than laparoscopic cases and lower in both matched HW-CO2 groups., Conclusions: This prospective RCT is in accord with animal studies while highlighting pre-existing damage in some patients. Peritoneal mesothelium protection, reduced inflammation and restoration of core-body temperature data suggest benefit with the use of HW-CO2 in patients undergoing CRC surgery., (© 2022. The Author(s).)

Background and Aims: The role of laparoscopic rectal cancer resection remains controversial. Thus, we aimed to conduct a one-stage meta-analysis with reconstructed patient-level data using randomized trial data to compare long-term oncologic efficacy of laparoscopic and open surgical resection for rectal cancer., Methods: Medline, EMBASE and Scopus were searched for articles comparing laparoscopic with open surgery for rectal cancer. Primary outcome was disease free survival (DFS) while secondary outcome was overall survival (OS). One-stage meta-analysis was conducted using patient-level survival data reconstructed from Kaplan-Meier curves with Web Plot Digitizer. Shared-frailty and stratified Cox models were fitted to compare survival endpoints., Results: Seven randomized trials involving 1767 laparoscopic and 1293 open resections for rectal cancer were included. There were no significant differences between both groups for DFS and OS with respective hazard ratio estimates of 0.91 (95% CI: 0.78-1.06, p = 0.241) and 0.86 (95% CI:0.73-1.02, p = 0.090). Sensitivity analysis for non-metastatic patients and patients with mid and lower rectal cancer showed no significant differences in OS and DFS between both surgical approaches. In the laparoscopic arm, improved DFS was noted for stage II (HR: 0.73, 95% CI:0.54-0.98, p = 0.036) and stage III rectal cancers (HR: 0.74, 95% CI:0.55-0.99, p = 0.041)., Conclusions: This meta-analysis concludes that laparoscopic rectal cancer resection does not compromise long-term oncologic outcomes compared with open surgery with potential survival benefits for a minimal access approach in patients with stage II and III rectal cancer., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Symptomatic lumbar spinal stenosis is a leading cause of pain and mobility limitation in older adults. It is clinically believed that patients with lumbar spinal stenosis adopt a flexed trunk posture or bend forward and alter their gait pattern to improve tolerance for walking. However, a biomechanical assessment of spine posture and motion during walking is broadly lacking in these patients. The purpose of this study was to evaluate lumbar spine and pelvic sagittal angles and lumbar spine compressive loads in standing and walking and to determine the effect of pain and neurogenic claudication symptoms in patients with symptomatic lumbar spinal stenosis. Seven participants with symptomatic lumbar spinal stenosis, aged 44-82, underwent a 3D opto-electronic motion analysis during standing and walking trials in asymptomatic and symptomatic states. Passive reflective marker clusters (four markers each) were attached to participants at T1, L1, and S2 levels of the spine, with additional reflective markers at other spinal levels, as well as the head, pelvis, and extremities. Whole-body motion data was collected during standing and walking trials in asymptomatic and symptomatic states. The results showed that the spine was slightly flexed during walking, but this was not affected by symptoms. Pelvic tilt was not different when symptoms were present, but suggests a possible effect of more forward tilt in both standing ( p  = 0.052) and walking ( p  = 0.075). Lumbar spine loading during symptomatic walking was increased by an average of 7% over asymptomatic walking ( p  = 0.001). Our results did not show increased spine flexion (adopting a trunk-flexed posture) and only indicate a trend for a small forward shift of the pelvis during both symptomatic walking and standing. This suggests that provocation of symptoms in these patients does not markedly affect their normal gait kinematics. The finding of increased spine loading with provocation of symptoms supports our hypothesis that spine loading plays a role in limiting walking function in patients with lumbar spinal stenosis, but additional work is needed to understand the biomechanical cause of this increase., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Mousavi, Lynch, Allaire, White and Anderson.)

The objective of this study was to report post-operative complications and outcomes in canines undergoing elbow arthrodesis (EA) with fixation techniques including bone plate fixation with a non-locking dynamic compression plate (DCP), bone plate fixation with a locking plate (LCP), and external skeletal fixator (ESF). Medical records of twenty-two cases that underwent EA between January 2009-December 2019 from 8 referral hospitals including both private practice and academic institutions were reviewed. Post-operative complications were classified as either minor or major, surgical evaluations were performed 8 weeks post operatively, and a follow-up questionnaire was sent to owners. Of the total 22 cases that met inclusion criteria, a total of 19/22 cases had complications, 12 major and 7 minor. Complications reported in 8/9, 7/9, and 4/4, for the DCP, LCP, and ESF fixation groups, respectively. Mild to moderate mechanical lameness was identified at surgical evaluation in 16/22 cases. Complete radiographic bone healing was achieved after 9 weeks in 19/22 cases. Long term owner follow up was available in 14/22 cases. Owners reported a good to normal quality of life in 13/14 cases and poor in one case. The majority of owners (11/14) reported good to excellent satisfaction with the outcome irrespective of persistent lameness. This study demonstrates that successful EA can be achieved using a variety of fixation methods, but persistent lameness is expected and complication rate is high., Competing Interests: The authors have declared that no competing interests exist.

Motion analysis is increasingly applied to spine musculoskeletal models using kinematic constraints to estimate individual intervertebral joint movements, which cannot be directly measured from the skin surface markers. Traditionally, kinematic constraints have allowed a single spinal degree of freedom (DOF) in each direction, and there has been little examination of how different kinematic constraints affect evaluations of spine motion. Thus, the objective of this study was to evaluate the performance of different kinematic constraints for inverse kinematics analysis. We collected motion analysis marker data in seven healthy participants (4F, 3M, aged 27-67) during flexion-extension, lateral bending, and axial rotation tasks. Inverse kinematics analyses were performed on subject-specific models with 17 thoracolumbar joints allowing 51 rotational DOF (51DOF) and corresponding models including seven sets of kinematic constraints that limited spine motion from 3 to 9DOF. Outcomes included: (1) root mean square (RMS) error of spine markers (measured vs. model); (2) lag-one autocorrelation coefficients to assess smoothness of angular motions; (3) maximum range of motion (ROM) of intervertebral joints in three directions of motion (FE, LB, AR) to assess whether they are physiologically reasonable; and (4) segmental spine angles in static ROM trials. We found that RMS error of spine markers was higher with constraints than without ( p < 0.0001) but did not notably improve kinematic constraints above 6DOF. Compared to segmental angles calculated directly from spine markers, models with kinematic constraints had moderate to good intraclass correlation coefficients (ICCs) for flexion-extension and lateral bending, though weak to moderate ICCs for axial rotation. Adding more DOF to kinematic constraints did not improve performance in matching segmental angles. Kinematic constraints with 4-6DOF produced similar levels of smoothness across all tasks and generally improved smoothness compared to 9DOF or unconstrained (51DOF) models. Our results also revealed that the maximum joint ROMs predicted using 4-6DOF constraints were largely within physiologically acceptable ranges throughout the spine and in all directions of motions. We conclude that a kinematic constraint with 5DOF can produce smooth spine motions with physiologically reasonable joint ROMs and relatively low marker error., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Alemi, Burkhart, Lynch, Allaire, Mousavi, Zhang, Bouxsein and Anderson.)

Background: The management of patients presenting with malignant small bowel obstruction is a challenging paradigm. The aim of this systematic review was to examine different management strategies in these complex patients. The primary outcomes evaluated were the type of intervention, 30-day morbidity and mortality and overall survival rates., Methods: A systematic literature review of EMBase, Medline, PubMed and the Cochrane Library was performed using Preferred Reporting Items for Systematic reviews and Meta-Analyses for studies reporting on conservative and operative management of malignant small bowel obstruction., Results: Fifteen studies (n = 882 patients) reporting on outcomes for malignant small bowel obstruction were analysed. Outcomes measured were primarily survival and relief of obstructive symptoms. The median age ranged from 52 to 66 years. The most common cause of malignant small bowel obstruction was gynaecological in nature (56%), followed by colorectal (19%). Four hundred and eighty-six patients underwent primary surgical management and the remaining 396 patients were assigned to non-surgical intervention. Median overall survival in the operative studies ranged from 2.5 to 7.4 months compared with 0.9 to 1.9 months (P < 0.05). The 30-day mortality ranged from 13% to 28% in those who underwent surgical interventions versus 2% to 61% in the non-surgical group (P = 0.09). No significant difference in median survival in gastrointestinal (GI) and gynaecological malignancies was observed (4.3 versus 5.0 months, P = 0.12). Morbidity ranged from 21% to 85% in the surgical group and 12% to 29% in the percutaneous groups (P < 0.05)., Conclusion: Surgical intervention in malignant small bowel obstruction is associated with significant morbidity, although it may improve survival in selected patients with gynaecological and colorectal malignancy. It is imperative that realistic goals and expectations are discussed with patients preoperatively., (© 2020 Royal Australasian College of Surgeons.)

Background: Opioid use disorder (OUD), a chronic disease, is a major public health problem. Despite availability of effective treatment, too few people receive it and treatment retention is low. Understanding barriers and facilitators of treatment access and retention is needed to improve outcomes for people with OUD., Objectives: To assess 3-month outcomes pilot data from a patient-centered OUD treatment program in Iowa, USA, that utilized flexible treatment requirements and prioritized engagement over compliance., Methods: Forty patients (62.5% female: mean age was 35.7 years, SD 9.5) receiving medication, either buprenorphine or naltrexone, to treat OUD were enrolled in an observational study. Patients could select or decline case management, counseling, and peer recovery groups. Substance use, risk and protective factors, and recovery capital were measured at intake and 3 months., Results: Most participants reported increased recovery capital. The median Assessment of Recovery Capital (ARC) score went from 37 at enrollment to 43 (p < 0.01). Illegal drug use decreased, with the median days using illegal drugs in the past month dropping from 10 to 0 (p < 0.001). Cravings improved: 29.2% reported no cravings at intake and 58.3% reported no cravings at 3 months (p < 0.001). Retention rate was 92.5% at 3 months. Retention rate for participants who were not on probation/parole was higher (96.9%) than for those on probation/parole (62.5%, p = 0.021)., Conclusion: This study shows preliminary evidence that a care model based on easy and flexible access and strategies to improve treatment retention improves recovery capital, reduces illegal drug use and cravings, and retains people in treatment.

Background: Pelvic exenteration remains a viable and effective treatment option for the management of locally advanced or recurrent pelvic malignancy. The aim of this study was to present an early experience of robotic multivisceral resection of pelvic malignancy, and to compare this experience with similar series through a systematic review of the literature., Methods: A retrospective study was performed on patients who had robotic-assisted multi-visceral resection for pelvic malignancy at a single Colorectal Surgical unit based between two tertiary academic hospitals. Primary outcomes observed included operation type, operation time, perioperative complications, and hospital length of stay. Secondary outcomes included R0 resection status, lymph node harvest, and rate of recurrence at clinical follow-up., Results: Eight cases of robotic multivisceral resection were performed for primary locally advanced pelvic malignancy involving a rectal resection as part of their operative management. The median age of patients undergoing resection was 56 years (range 29-83 years). The male:female ratio was 6:2. The mean total operating time was 8.3 h (range 6-10 h). Perioperative blood transfusion requirements were minimal. Mean hospital length of stay was 15 days (range 7-26 days). No patients experienced any serious postoperative morbidity or mortality. All patients had clear margins on histological assessment and no patients have recurrence at 12-month follow-up., Conclusions: Robotic multivisceral resection for malignant disease of the pelvis is a safe and feasible minimally invasive approach in highly selected cases.

Aim: The decision to perform an abdominoperineal excision (APR) rather than restorative bowel resection relies on a number of clinical factors. There remains great variability in APR rates internationally. The aim of this study was to demonstrate trends of APR surgery in low rectal cancer (< 6 cm from the anal verge) in Australasia and identify predictors of nonrestoration., Method: This study reviewed a prospectively maintained colorectal registry - the Binational Colorectal Cancer Audit (BCCA) - from general/colorectal surgical units across Australia and New Zealand. Data were analysed to determine factors predictive of nonrestorative resection. Patients were analysed based on the presence (control) or absence (comparison) of a primary anastomosis., Results: Of 3628 patients with rectal cancer, 2096 were diagnosed with low rectal cancer between 2007 and 2017. The incidence of APR remained constant over the study period, with 58% of all resections of low rectal cancer being APR. The majority of resections were performed by consultants in urban hospitals (86% vs 14%). Tumours ≤ 3 cm from the anal verge, T4, M1 disease and neoadjuvant therapy were the greatest predictors of APR (P < 0.001). A significantly increased rate of restorative surgery was observed in public hospital settings (59% vs 41%, P < 0.05). The rate of positive circumferential resection margin (CRM) was 7.95%, with significantly increased rates in patients undergoing APR (12.2% vs 6.2%, P < 0.001). CRM positivity was increased in open approaches, T4, N2 and M1 staged disease and in an emergency/urgent setting (P < 0.001 and P < 0.045, respectively). Significantly increased wound and pulmonary complications were observed in the APR cohort (P < 0.01)., Conclusion: The rates of APR in Australia and New Zealand remain high but are comparable to international figures, with one-third of rectal cancers being treated by APR. The main determinants of APR are tumour height, T stage and neoadjuvant therapy requirement. CRM positivity was higher in APR patients., (Colorectal Disease © 2020 The Association of Coloproctology of Great Britain and Ireland.)

Background: Insufflation with CO 2 can employ continuous flow, recirculated gas and/or additional warming and humidification. The ability to compare these modes of delivery depends upon the assays employed and opportunities to minimize subject variation. The use of pigs to train colorectal surgeons provided an opportunity to compare three modes of CO 2 delivery under controlled circumstances., Methods: Sixteen pigs were subjected to rectal resection, insufflated with dry-cold CO 2 (DC-CO 2 ) (n = 5), recirculated CO 2 by an AirSeal device (n = 5) and humidification and warming (HW-CO2) by a HumiGard device (n = 6). Peritoneal biopsies were harvested from the same region of the peritoneum for fixation for immunohistochemistry for hypoxia-inducible factor 1 alpha (HIF-1α) and scanning electron microscopy (SEM) to evaluate hypoxia induction or tissue/cellular damage, respectively., Results: DC-CO 2 insufflation by both modes leads to significant damage to mesothelial cells as measured by cellular bulging and retraction as well as microvillus shortening compared with HW-CO 2 at 1 to 1.5 h. DC-CO 2 also leads to a rapid and significant induction of HIF-1α compared with HW-CO 2 ., Conclusions: DC-CO 2 insufflation induces substantive cellular damage and hypoxia responses within the first hour of application. The use of HW-CO 2 insufflation ameliorates these processes for the first one to one and half hours in a large mammal used to replicate surgery in humans.

Background: Pelvic exenteration has increasingly been shown to improve disease-free and overall survival for patients with locally advanced pelvic malignancies. Squamous cell carcinoma (SCC) is the second most common pelvic malignancy requiring exenteration., Objective: The aim of this study was to report the clinical and oncological outcomes from patients treated with pelvic exenteration for anal and urogenital SCC from a single, high-volume unit., Methods: A review of a prospectively maintained database from 1991 to 2018 at a high-volume specialised institution was performed. Primary endpoints included R0 resection rates, local recurrence and overall survival (OS) rates., Results: From January 1999 to July 2018, 361 patients underwent pelvic exenteration of which 31 patients were identified with SCC (15 anal SCC, 16 urogenital SCC). The majority of patients were females (n = 24, 77.4%). Median age was 59 (range 35-81). Twenty-seven patients underwent resection with curative intent with an R0 resection rate of 81.5%. Four patients underwent a palliative procedure [R1 = 3 (8%), R2 = 1 (3.3%)]. Mean hospital length of stay was 32 days (range 8-122 days). Disease-free survival was significantly increased in anal SCC with no significant difference in OS compared to urogenital SCC (p = 0.03, p = 0.447 respectively). Advanced pathological T stage was associated with decreased OS (p = 0.023). In the curative intent group the disease-free survival and OS rate was 59.3% and 70% at 24 months, respectively., Conclusion: Complete R0 resection is achievable in a high proportion of patients. Urogenital SCC is associated with significantly worse disease-free survival, and advanced T-stage was a significant prognostic factor for OS.

Aim: Patients who undergo radical pelvic surgery often have problems with perineal wound healing and pelvic collections. While there is recognition of the perineal morbidity, there also remains uncertainty around the benefit of vertical rectus abdominus myocutaneous (VRAM) flaps due to the balance between primary healing and the complications associated with this form of reconstruction. This study aimed to evaluate factors associated with significant flap and donor site related complications following VRAM flap reconstruction for radical pelvic surgery., Method: A retrospective analysis of VRAM flap related complications was undertaken from prospectively maintained databases for all patients undergoing radical pelvic surgery (2001- 2017) in two cancer centres., Results: In all, 154 patients were identified [median age 62 years (range 26-89 years), 80 (52%) men]. Thirty-three (21%) patients experienced significant donor or flap related complications. Major complications (Clavien-Dindo ≥ 3) related to the abdominal donor site occurred in nine (6%) patients, while those related to the flap or perineal site occurred in 28 (18%) patients. Only smoking (P = 0.003) and neoadjuvant radiotherapy (P = 0.047) were associated with the development of significant flap related complications on univariate analysis. Flap related complications resulted in a significantly longer hospital stay (P < 0.001)., Conclusion: Careful patient selection is required to balance the risks vs the benefits of VRAM flap reconstruction. Immediate VRAM reconstruction in patients undergoing radical pelvic surgery can achieve early healing and stable perineal closure; it has a low but significant morbidity. Major flap related complications are significantly associated with smoking status and neoadjuvant radiotherapy and result in a prolonged length of hospital stay., (Colorectal Disease © 2019 The Association of Coloproctology of Great Britain and Ireland.)

Background: Familial cases of appendiceal mucinous tumours (AMTs) are extremely rare and the underlying genetic aetiology uncertain. We identified potential predisposing germline genetic variants in a father and daughter with AMTs presenting with pseudomyxoma peritonei (PMP) and correlated these with regions of loss of heterozygosity (LOH) in the tumours., Methods: Through germline whole exome sequencing, we identified novel heterozygous loss-of-function (LoF) (i.e. nonsense, frameshift and essential splice site mutations) and missense variants shared between father and daughter, and validated all LoF variants, and missense variants with a Combined Annotation Dependent Depletion (CADD) scaled score of ≥10. Genome-wide copy number analysis was performed on tumour tissue from both individuals to identify regions of LOH., Results: Fifteen novel variants in 15 genes were shared by the father and daughter, including a nonsense mutation in REEP5. None of these germline variants were located in tumour regions of LOH shared by the father and daughter. Four genes (EXOG, RANBP2, RANBP6 and TNFRSF1B) harboured missense variants that fell in a region of LOH in the tumour from the father only, but none showed somatic loss of the wild type allele in the tumour. The REEP5 gene was sequenced in 23 individuals with presumed sporadic AMTs or PMP; no LoF or rare missense germline variants were identified., Conclusion: Germline exome sequencing of a father and daughter with AMTs identified novel candidate predisposing genes. Further studies are required to clarify the role of these genes in familial AMTs.

Aim: Minimally invasive surgical approaches for cancer of the right colon have been well described with significant patient and equivalent oncological benefits. Robotic surgery has advanced in its ability to provide multi-quadrant abdominal access, leading the surgical community to widen its application outside of the pelvis to other abdominal compartments. Globally it is being realized that a patient's surgical episode of care is becoming the epicentre of cancer treatment. In order to establish the role of robotic surgery in a patient's episode of care, 'successful patient-oriented surgical' parameters in right hemicolectomy for malignancy were measured. The objective was to examine the rates of successful patient-oriented surgical outcomes in robotic right hemicolectomy (RRH) compared to laparoscopic right hemicolectomy (LRH) for cancer., Methods: A systematic search of MEDLINE (Ovid: 1946-present), PubMed (NCBI), Embase (Ovid: 1966-present) and Cochrane Library was conducted using PRISMA for parameters of successful patient-oriented surgical outcomes in RRH and LRH for malignancy alone. The parameters measured included postoperative ileus, anastomotic complication, surgical wound infection, length of stay (LOS), incisional hernia rate, conversion to open, margin status, lymph node harvest and overall morbidity and mortality., Results: There were 15 studies which included 831 RRH patients and 3241 LRH patients, with a median age of 62-74 years. No study analysed the concept of successful patient-oriented surgical outcomes. There was no significant difference in the incidence of postoperative ileus, with less time to first flatus in RRH (2.0-2.7 days, compared with 2.5-4.0 days, P < 0.05). Anastomotic leak rate in one study reported a significant increase in LRH compared to RRH (P < 0.05, 0% vs 8.3%). Significantly decreased LOS following RRH was outlined in six studies. One study reported a significantly higher rate of incisional hernias following LRH with extracorporeal anastomoses compared to RRH with intracorporeal anastomoses. Overall rates of conversion to open surgery were less with RRH (0%-3.9% vs 0%-18%, P < 0.001, 0.05). One study outlined significantly higher rates of incomplete resection with an open right hemicolectomy compared with minimally invasive laparoscopic and robotic resections, with positive margin rates of 2.3%, 0.9% and 0% respectively (P < 0.001). Two studies reported significantly higher lymph node harvest in RRH (P < 0.05). Overall morbidity and 30-day mortality were comparable in both approaches., Conclusion: Thirty-day morbidity and mortality were comparable between the two approaches, with patients undergoing RRH having lower anastomotic complications, increased lymph node harvest, and reduced LOS, conversion to open and incisional hernia rates in a number of studies. There are limited data on surgical approach and impact on quality of life and what patients deem successful surgical outcomes. There is a further need for a randomized controlled trial examining successful patient-oriented outcomes in right hemicolectomy for malignancy., (Colorectal Disease © 2019 The Association of Coloproctology of Great Britain and Ireland.)

Background: Pseudomyxoma peritonei (PMP) is a rare clinical presentation, with considerable morbidity and mortality if left untreated. In recent decades, there is growing acceptance for the use of cytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC). The aim of this study was to report on our 10-year single-center experience on outcomes following CRS and HIPEC for PMP of appendiceal origin., Methods: A retrospective analysis of a prospectively maintained database of all patients undergoing CRS and HIPEC for PMP of appendiceal origin over a 10-year period at a statewide referral center was conducted., Results: One hundred and seventy-five cytoreductive procedures were undertaken in 140 patients. The mean patient age was 57.4 years, with a female preponderance (56%). The median PCI was 16, with 73.1% of cases having a complete cytoreduction. Grade III/IV complications occurred in 36 (20.6%) cases, with no mortalities. The median overall and disease-free survival was 100 months and 40 months, respectively, with a 71% 5-year survival. High-grade histology was the main factor identified as an independent predictor of worse overall survival., Conclusion: CRS and HIPEC are safe with acceptable rates of morbidity. It can provide very favorable survival in patients with PMP. High-grade histology is a key prognostic factor associated with a worse overall survival.

Objective: To examine the changes in exenterative surgery over three decades analysing oncological outcomes and whether changes in surgical approach have led to improved patient outcomes., Background: Advances in surgical technology, perioperative care and pattern of disease recurrence have coincided with an evolutionary change in exenterative surgery., Methods: A review of a prospectively maintained databases of pelvic exenteration surgery from 1988 to 2018  at two high volume specialised institutions. The total cohort was divided into three major time points (1988-2004, 2005-2010 and 2011 to 2018) to allow comparative analysis. Primary endpoints were overall survival in primary and recurrent disease at each time point. Secondary endpoints included anastomotic leak, blood transfusion, ileus, wound infection rates and evolution of case complexity. Data were analysed using R with a p < 0.05 considered significant., Results: Six hundred and seventy patients underwent exenterative surgery. In 2011-2018 there was an increase in resection of recurrent malignancy with a continuous increase in GI malignancies resected over each time period(p < 0.001,<0.01) and a reduction in gynaecological malignancy(p < 0.001). A significant increase in sacrectomy, pelvic sidewall resection and ileal conduit reconstruction was observed (p < 0.01,<0.001).In 2005-2010 patients had increased rates of ileus and anastomotic leak(p < 0.05). Patients undergoing resection for primary disease had improved overall survival at time points 1988-2004 and 2011-2018 compared to those with recurrent disease(p = 0.007,<0.001). Overall survival was significantly improved in patients with primary versus recurrent disease(p = 0.022)., Conclusion: There has been a significant improvement in survival in patients undergoing pelvic exenteration surgery from primary disease. Case complexity has increased without significant morbidity., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: The exposure of the peritoneum to desiccation during surgery generates lasting damage to the mesothelial lining which impacts inflammation and tissue repair. We have previously explored open abdominal surgery in mice subjected to passive airflow however, operating theatres employ active airflow. Therefore, we sought an engineering solution to recapitulate the active airflow in mice. Similarly, to the passive airflow studies we investigated the influence of humidified-warm carbon dioxide (CO 2 ) on this damage in the context of active airflow. Additionally, we addressed the controversial role of surgery in exacerbating desmoidogenesis in a mouse model of familial adenomatous polyposis., Methods: An active airflow mouse-operating module manufactured to produce the equivalent downdraft airflow to that of a modern operating theatre was employed. We quantified mesothelial cell integrity by scanning electron microscopy (SEM) sampled from the peritoneal wall that was subjected to mechanical damage or not, with and without the delivery of humidified-warm CO 2 . To explore the role of open and laparoscopic surgery in the process of desmoidogenesis we crossed Apc min/ + C57Bl/6 mice with p53 +/- mice to generate animals that developed desmoid tumors with 100% penetrance., Results: One hour of active airflow generates substantial damage to peritoneal mesothelial cells and their microvilli as measured at 24 h post intervention, which is significantly greater than that generated by passive airflow. Use of humidified-warm CO 2 mostly protects the mesothelium that had not experienced additional mechanical (surgical) damage at 24 h. Maximal damage was evident in all treatment groups regardless of flow or use of gas. At day 10 mechanically-damaged peritoneum remains in mice but is essentially repaired in the gas-treated groups. Regarding desmoidogenesis, operating procedures did not increase the frequency of desmoid tumors but their frequency correlated with time following surgery but not age of mice., Conclusions: Active airflow generates more peritoneal damage than passive airflow and is reduced significantly by the use of humidified-warm CO 2 . Introduced peritoneal damage is largely repaired in mice by day 10 with gas. Desmoid tumor incidence is not increased substantially by surgery itself but rises over time following surgery compared to non-surgery mice., Competing Interests: Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication., (© 2019 Chittleborough et al., published by De Gruyter.)

Background: Despite advances in the rates of total mesorectal excision (TME) for rectal cancer surgery, decreased local recurrence rates and increased 5-year survival, there still exists large variation in the quality of treatment received. Up to 30 per cent of rectal cancers are locally advanced at presentation and approximately 5-10 per cent still breach the mesorectal plane and invade adjacent structures despite neoadjuvant therapy. With the evolution of extended resections for rectal cancers beyond the TME plane, proponents advocate that these resections should be performed only in specialist centres. The aim was to assess the prognostic factors and patterns of failure after beyond TME surgery for T4 rectal cancers., Methods: Data were collected from prospective databases at three high-volume institutions specializing in beyond TME surgery for T4 rectal cancers between 1990 and 2013. The primary outcome measures were overall survival, local recurrence and patterns of first failure., Results: Three hundred and sixty patients were identified. The negative resection margin (R0) rate was 82·8 per cent (298 patients) and the local recurrence rate was 12·5 per cent (45 patients). The type of surgical procedure (Hartmann's: hazard ratio (HR) 4·49, 95 per cent c.i. 1·99 to 10·14; P = 0·002) and lymphovascular invasion (HR 2·02, 1·08 to 3·77; P = 0·032) were independent predictors of local recurrence. The 5-year overall survival rate for all patients was 61 (95 per cent c.i. 55 to 67) per cent. The 5-year cumulative incidence of first failure was 8 per cent for local recurrence, 6 per cent for local and distant disease, and 18 per cent for distant disease., Conclusion: This study has demonstrated that a coordinated approach in specialist centres for beyond TME surgery can offer good oncological and long-term survival in patients with T4 rectal cancers., (© 2019 BJS Society Ltd Published by John Wiley & Sons Ltd.)

Objective : Nocturnal fears are associated with trauma-related sleep disturbance in adults, yet research is limited addressing this relationship in adolescents. This study evaluated the validity of the Fear of Sleep Inventory (FoSI) as a measure of nocturnal fears broadly and in relation to trauma exposure in adolescents. Participants : Students ages 14-18 from two urban school-based health centers were the participants. Methods : De-identified clinical data were utilized from a mental health screening battery. Two exploratory factor analyses (EFA) were conducted using the full 23-item FoSI and the 13-item short form. Cronbach's α and Pearson correlation coefficients were employed to examine the convergent and divergent validity of the total scores and the factors derived from the EFA with Insomnia Severity, probable PTSD, and parental monitoring respectively. Results : The 23-item FoSI showed high internal consistency (α = .84); however, EFA yielded an unclear factor structure. Further analysis indicated that an 11-item FoSI yielded a clear 2-factor structure with subscales conceptualized as (a) Fear of Sleep and (b) Vigilant Behavior. Conclusions : The FoSI-11 demonstrates promise as a measure of nocturnal fears in adolescents and can help reveal distinctions between trauma-related nocturnal fears and nocturnal fears associated with psychological or environmental factors. It can be utilized as a screener to highlight adolescent nocturnal fears in large group settings, while also identifying individuals in need of further assessment of trauma exposure. Future studies should include the FoSI-11 to provide a more thorough examination of the role of adolescent nocturnal fears in the relationship between trauma and sleep disturbance.

Background: Colorectal cancer is the second leading cause of cancer-related mortality worldwide. Peritoneal metastases carry the worst prognosis among all sites of colorectal cancer metastases. In recent years, the advent and acceptance of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have greatly improved survival for selected patients with low-volume peritoneal metastases., Objective: Here, we report the evolution of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases at a statewide tertiary referral center over an 8-year period., Design: This is a retrospective study from 2009 to 2017., Setting: The study was conducted at a single center over 8 years., Patients: Patients with colorectal peritoneal metastases undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy were included., Main Outcomes: Main outcomes included evaluation of grade III/IV morbidity rate, mortality rate, overall and relapse-free survival, and prognostic factors influencing survival on a Cox multivariate analysis model., Results: One hundred one cytoreductive surgeries were undertaken on 96 patients during this time for colorectal peritoneal metastases. The median patient age was 60 years with 55.2% being female. The median Peritoneal Carcinomatosis Index was 9, with complete cytoreduction achieved in 76 (75.2%) cases. Grade III or IV complications occurred in 26 cases (25.7%) with 2 (2%) perioperative mortalities. Median overall survival for the entire cohort was 32 months, with a 3-year survival of 38%. For patients who achieved a complete cytoreduction, median overall survival was 37 months, with a relapse-free survival of 13 months and a 3-year survival of 54%. Complete cytoreduction and nonmucinous histology were key factors independently associated with improved overall survival., Limitations: The main limitation this study is its retrospective nature., Conclusion: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for isolated low-volume colorectal peritoneal metastases is safe and effective, with low morbidity. It offers selected patients a highly favorable overall and relapse-free survival. See Video Abstract at http://links.lww.com/DCR/B2. EVOLUCIÓN DE LA CIRUGÍA CITORREDUCTIVA Y QUIMIOTERAPIA INTRAPERITONEAL HIPERTÉRMICA (HIPEC) PARA METÁSTASIS PERITONEALES COLORRECTALES: EXPERIENCIA INSTITUCIONAL DE 8 AÑOS: El cáncer colorrectal es la segunda causa de mortalidad relacionada con el cáncer en todo el mundo. Las metástasis peritoneales tienen el peor pronóstico entre todos los sitios de metástasis del cáncer colorrectal. En los últimos años, el advenimiento y la aceptación de la cirugía citorreductiva y la quimioterapia intraperitoneal hipertérmica ha mejorado enormemente la supervivencia de pacientes seleccionados con metástasis peritoneales de bajo volumen., Objetivo: Aquí, informamos sobre la evolución de la cirugía citorreductiva y la quimioterapia intraperitoneal hipertérmica para las metástasis peritoneales colorrectales en un centro de referencia terciario para todo el estado durante un período de ocho años. DISEÑO:: Estudio retrospectivo del 2009 a 2017. CONFIGURACIÓN:: Centro único a lo largo de ocho años., Pacientes: Pacientes con metástasis peritoneales colorrectales sometidos a cirugía citorreductiva y quimioterapia intraperitoneal hipertérmica., Resultados Principales: Los resultados principales incluyeron la evaluación de la tasa de morbilidad de grado III / IV, la tasa de mortalidad, la supervivencia general y libre de recaída y los factores pronósticos que influyen en la supervivencia en el modelo de análisis multivariado Cox., Resultados: Se realizaron el ciento uno cirugías citorreductivas en noventa y seis pacientes durante este tiempo por metástasis peritoneales colorrectales. La edad media de los pacientes fue de 60 años, con un 55.2% de mujeres. El Índice de Carcinomatosis Peritoneal mediano fue de 9, con una citorreducción completa lograda en 76 (75.2%) casos. Las complicaciones de grado III o IV ocurrieron en 26 casos (25.7%) con dos (2%) de mortalidad perioperatoria. La supervivencia mediana general para toda la cohorte fue de 32 meses, con una supervivencia de 3 años del 38%. Para los pacientes que lograron una citorreducción completa, la supervivencia global media fue de 37 meses, con una supervivencia sin recaída de 13 meses y una supervivencia de 3 años del 54%. La citorreducción completa y la histología no mucinosa fueron factores clave asociados de forma independiente con una mejor supervivencia general., Limitaciones: La principal limitación es la naturaleza retrospectiva del estudio. CONCLUSIÓN:: La cirugía citorreductiva y la quimioterapia intraperitoneal hipertérmica para las metástasis peritoneales colorrectales aisladas de bajo volumen son seguras y eficaces, con baja morbilidad. Ofrece a los pacientes seleccionados una supervivencia global altamente favorable y libre de recaída. Vea el Resumen del video en http://links.lww.com/DCR/B2.

Methotrexate is a dihydrofolate reductase inhibitor that interferes with DNA synthesis, DNA repair, and cellular replication. We present the first adult case of a patient who received intravenous contrast prior to administration of high-dose methotrexate, who subsequently experienced delayed methotrexate clearance and renal impairment necessitating the use of glucarpidase. This case displays a possible correlation between intravenous radiographic contrast administration and resulting toxicity due to delayed methotrexate clearance.

Background: There is increasing literature emerging on the significance of tumor-infiltrating lymphocytes in colorectal cancer. However, there have been inconsistent findings, secondary to small patient numbers and varied methods for identifying these lymphocytes., Objective: The aim of this study was to determine the prognostic and predictive power of tumor-infiltrating lymphocytes in colon, rectal (in neoadjuvant setting), and metastatic colorectal cancer., Data Sources: A comprehensive search of PubMed and Embase was undertaken from January 2006 to December 2016., Study Selection: The inclusion criteria included a description of the tumor-infiltrating lymphocyte subset(s) assessed with reporting of associated short- and long-term outcomes., Main Outcome Measures: The main outcome measures, were disease-free and overall survival., Results: A total of 25 studies were included, 15 for primary colorectal cancer (4719 patients), 7 for locally advanced rectal cancer (727 patients), and 3 studies for metastatic colorectal cancer (418 patients). High CD3, CD8, FoxP3, and CD45RO densities were associated with improved overall survival for primary colorectal cancer, with pooled estimated HRs of 0.88, 0.81, 0.70, and 0.63 (all p < 0.001) respectively. Furthermore, in locally advanced rectal cancer, the levels of CD8 cells were a significant predictor of good tumor regression grade after chemoradiotherapy., Limitations: The retrospective nature of included studies and the significant interstudy heterogeneity were limitations., Conclusions: There is increasing evidence that tumor-infiltrating lymphocytes play an important role in predicting prognosis in colorectal cancer and tumor regression after neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Clinical researchers are now in a unique position to build on this work to identify robust predictive markers to stratify patients not only to currently available therapies but also to immunotherapy, which has demonstrated success in improving patient outcomes.

Objective:  The main aim of this study was to evaluate a percutaneous method of bone alignment using a diaphyseal tibial fracture model., Materials and Methods:  Mid-shaft diaphyseal fractures were created in 12 large-breed canine tibiae. Interaction pins were inserted into the proximal and distal bone segments. Computed tomography scans of the fractured tibiae and pins were imported into three-dimensional (3D) modelling software and the fractures were virtually reduced. A multi-component 3D printed alignment jig was created that encompassed the pins in their aligned configuration. Orthogonal radiographs were taken after alignment jig application. Intact and post-alignment tibial lengths and joint angles were compared. Rotational alignment was subjectively evaluated., Results:  Post-alignment tibial lengths differed on the mediolateral and craniocaudal radiographs by an average of 1.55 and 1.43% respectively. Post-alignment mechanical medial proximal tibial angle, mechanical medial distal tibial angle and mechanical caudal proximal tibial angle had an average difference of 1.67°, 1.92° and 2.17° respectively. Differences in tibial length and joint angles were not significant ( p  > 0.05)., Clinical Significance:  While in vivo evaluation is necessary, this technique to align diaphyseal fractures percutaneously using computer modelling and 3D printing is technically feasible and may facilitate the clinical use of minimally invasive osteosynthesis techniques., Competing Interests: Albert C. Lynch and John A. Davies have a patent US Patent Application # 15/937,842 pending to 3D Osteo., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: The presence of tumor-infiltrating lymphocytes (TILs) in tumors is superior to conventional pathologic staging in predicting patient outcome. However, their presence does not define TIL functionality. Here we developed an assay that tests TIL cytotoxicity in patients with locally advanced rectal cancer before definitive treatment, identifying those who will obtain a pathologic complete response (pCR). We also used the assay to demonstrate the rescue of TIL function after checkpoint inhibition blockade (CIB)., Patients and Methods: Thirty-four consecutive patients were identified initially, with successful completion of the assay before surgery in those 17 patients who underwent full treatment. An in vitro cytotoxic assay of rectal cancer tumoroids cocultured with patient-matched TILs was established and validated. Newly diagnosed patients were recruited with pretreatment biopsy specimens processed within 1 month. Evaluation of TIL-mediated tumoroid lysis was performed by measuring the mean fluorescence intensity of cell death marker, propidium iodide. CIB (anti-programmed cell death protein 1 [anti-PD-1] antibody) response was also assessed in a subset of patient specimens., Results: Six of the 17 patients achieved an objective pCR on final evaluation of the resected specimen after neoadjuvant chemoradiotherapy. Cytotoxic killing identified the pCR group with a higher mean fluorescence intensity (27,982 [95% CI, 25,340 to 30,625]) compared with the non-pCR cohort (12,428 [95% CI, 9,434 to 15,423]; p < .001). Assessment of the effectiveness of CIB revealed partial restoration of cytotoxicity in TILs with increased PD-1 expression with anti-PD-1 antibody exposure., Conclusion: Evaluating TIL function can be undertaken within weeks of the diagnostic biopsy, affording the potential to alter patient management decisions and refine selection for a watch-and-wait protocol. This cytotoxic assay also has the potential to serve as a platform to assist in the additional development of CIB.

Aim: The current standard of care for locally advanced rectal cancer involves neoadjuvant chemoradiotherapy (CRT) followed by total mesorectal excision. There is a spectrum of response to neoadjuvant therapy; however, the prognostic value of tumour regression grade (TRG) in predicting disease-free survival (DFS) or overall survival (OS) is inconsistent in the literature., Method: This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search was undertaken using Ovid MEDLINE, Embase and Google Scholar. Inclusion criteria were Stage II and III locally advanced rectal cancer treated with long-course CRT followed by radical surgery. The aim of the meta-analysis was to assess the prognostic implication of each TRG for rectal cancer following neoadjuvant CRT. Long-term prognosis was assessed. The main outcome measures were DFS and OS. A random effects model was performed to pool the hazard ratio (HR) from all included studies., Results: There were 4875 patients from 17 studies, with 775 (15.9%) attaining a pathological complete response (pCR) and 719 (29.9%) with no response. A significant association with OS was identified from a pooled-estimated HR for pCR (HR = 0.47, P = 0.002) and nonresponding tumours (HR = 2.97; P < 0.001). Previously known tumour characteristics, such as ypN, lymphovascular invasion and perineural invasion, were also significantly associated with DFS and OS, with estimated pooled HRs of 2.2, 1.4 and 2.3, respectively., Conclusion: In conclusion, the degree of TRG was of prognostic value in predicting long-term outcomes. The current challenge is the development of a high-validity tests to predict pCR., (Colorectal Disease © 2018 The Association of Coloproctology of Great Britain and Ireland.)

Background: The aim of this study was to monitor the effect of humidified-warm carbon dioxide (HWCO 2 ) delivered into the open abdomen of mice, simulating laparotomy., Methods: Mice were anaesthetized, ventilated and subjected to an abdominal incision followed by wound retraction. In the experimental group, a diffuser device was used to deliver HWCO 2 ; the control group was exposed to passive air flow. In each group of mice, surgical damage was produced on one side of the peritoneal wall. Vital signs and core temperature were monitored throughout the 1-h procedure. The peritoneum was closed and mice were allowed to recover for 24 h or 10 days. Tumour cells were delivered into half of the mice in each cohort. Tissue was then examined using scanning electron microscopy and immunohistochemistry., Results: Passive air flow generated ultrastructural damage including mesothelial cell bulging/retraction and loss of microvilli, as assessed at 24 h. Evidence of surgical damage was still measurable on day 10. HWCO 2 maintained normothermia, whereas open surgery alone led to hypothermia. The degree of tissue damage was significantly reduced by HWCO 2 compared with that in controls. Peritoneal expression of hypoxia inducible factor 1α and vascular endothelial growth factor A was lowered by HWCO 2 . These effects were also evident at the surgical damage sites, where protection from tissue trauma extended to 10 days. HWCO 2 did not reduce tumorigenesis in surgically damaged sites compared with passive air flow., Conclusion: HWCO 2 diffusion into the abdomen in the context of open surgery afforded tissue protection and accelerated tissue repair in mice, while preserving normothermia. Surgical relevance Damage to the peritoneum always occurs during open abdominal surgery, by exposure to desiccating air and by mechanical trauma/damage owing to the surgical intervention. Previous experimental studies showed that humidified-warm carbon dioxide (HWCO 2 ) reduced peritoneal damage during laparoscopic insufflation. Additionally, this intervention decreased experimental peritoneal carcinomatosis compared with the use of conventional dry-cold carbon dioxide. In the present experimental study, the simple delivery of HWCO 2 into the open abdomen reduced the amount of cellular damage and inflammation, and accelerated tissue repair. Sites of surgical intervention serve as ideal locations for cancer cell adhesion and subsequent tumour formation, but this was not changed measurably by the delivery of HWCO 2 ., (© 2017 The Authors. BJS published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)