A comparison of surgical techniques for perineal wound closure following perineal excision: a systematic review and network meta-analysis.

BACKGROUND: To mitigate pelvic wound issues following perineal excision of rectal or anal cancer, a number of techniques have been suggested as an alternative to primary closure. These methods include the use of a biological/dual mesh, omentoplasty, muscle flap, and/or pelvic peritoneum closure. The aim of this network analysis was to compare all the available surgical techniques used in the attempt to mitigate issues associated with an empty pelvis. METHODS: An electronic systematic search using MEDLINE databases (PubMed), EMBASE, and Web of Science was performed (Last date of research was March 15th, 2023). Studies comparing at least two of the aforementioned surgical techniques for perineal wound reconstruction during abdominoperineal resection, pelvic exenteration, or extra levator abdominoperineal excision were included. The incidence of primary healing, complication, and/or reintervention for perineal wound were evaluated. In addition, the overall incidence of perineal hernia was assessed. RESULTS: Forty-five observational studies and five randomized controlled trials were eligible for inclusion reporting on 146,398 patients. All the surgical techniques had a comparable risk ratio (RR) in terms of primary outcomes. The pooled network analysis showed a lower RR for perineal wound infection when comparing primary closure (RR 0.53; Crl 0.33, 0.89) to muscle flap. The perineal wound dehiscence RR was lower when comparing both omentoplasty (RR 0.59; Crl 0.38, 0.95) and primary closure (RR 0.58; Crl 0.46, 0.77) to muscle flap. CONCLUSIONS: Surgical options for perineal wound closure have evolved significantly over the last few decades. There remains no clear consensus on the "best" option, and tailoring to the individual remains a critical factor.

Role of MCD and Mössbauer Spectroscopy in the Explanation of the Properties of a Highly Soluble (µ-Oxo)bis[tetra(tert-butyl)(phthalocyaninato)iron(III)] Complex, Its Pyridine Adduct, and Redox Forms Oxidized under Anaerobic Conditions in Non-Coordinating Solvents.

Solid-state Mössbauer spectra of a highly soluble (µ-oxo)bis[tetra(tert-butyl)(phthalocyaninato)iron(III)] complex 1 ((PctBuFe)2O) consist of two doublets that represent bent geometry in µ-oxo(1) (1a, ΔEQ = 0.43 mm/s, T = 10 K) and linear geometry in µ-oxo(2) (1b, ΔEQ = 1.40 mm/s, T = 10 K) isomers with the ratio between two isomers depending on the purification method. Both isomers were found to be diamagnetic and transform entirely to the 1a isomer in solution. The room- and low-temperature magnetic circular dichroism (MCD) spectra of 1a µ-oxo(1) show one Faraday A- and one B-term between 670 and 720 nm, which correlate with the 690 nm band and 709 nm shoulder observed in the UV-vis spectrum of this compound. UV-vis and MCD spectra of 1a are almost independent of the temperature. Both 1a and 1b are diamagnetic between room temperature and 4 K. Electrochemical experiments show up to three oxidations and up to four reduction processes in 1a. Its oxidation under spectroelectrochemical or chemical (in the absence of oxygen-containing oxidants) conditions in non-coordinating solvents results in the formation of broad NIR bands around 1195 nm (first oxidation) and 1264 nm (second oxidation). The MCD spectra of the redox-active species show a Faraday B-term signal with negative amplitude in this region and are very different from those in the monomeric PctBu(1-)FeIIIX2 complexes 5X (X = Cl- or CF3CO2-). The pyridine adduct of 1a ((PyPctBuFe)2O; 2Py) is paramagnetic (µB = 2.19, g = 2.11, and J = -6.1 cm-1) and has a major peak at 627 nm of its UV-vis spectrum, which is associated with a MCD pseudo A-term. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations, along with the exciton coupling theory, were used to explain the unusually red-shifted intense transitions in 1a as well as the H-aggregate-like spectra of the pyridine adduct 2Py.

Outcomes of endoscopic full thickness resection in the colon rectum at an Italian tertiary center.

PURPOSE: Endoscopic full-thickness resection (EFTR) is an innovative technique for the treatment of colonic lesions not feasible by conventional endoscopic resection. Here, we aimed to evaluate the efficacy and safety of a Full-Thickness Resection Device (FTRD) for colonic lesions in a high-volume tertiary referral center. METHODS: A review of a prospectively collected database on patients that underwent EFTR with FTRD for colonic lesions from June 2016 to January 2021 at our institution was performed. Data regarding the clinical history, previous endoscopic treatments, pathological examination, technical and histological success, and follow-up were evaluated. RESULTS: Thirty-five patients (26 males, median age 69 years) underwent FTRD for colonic lesion. Eighteen lesions were in the left colon, three in the transverse, and 12 in the right colon. The median size of the lesions was 13 (range 10-40) mm. Resection was technically successful in 94% of patients. The mean hospital stay was 3.2 (SD ± 1.2) days. Adverse events were reported in four cases (11.4%). Histological complete resection (R0) was achieved in 93.9% of cases. Endoscopic follow-up was available in 96.8% of patients, at a median duration of 14.6 months (3-46 months). Recurrence was observed in 19.4% of cases at a median time of 3 months (3-7 months). Five patients had multiple FTRD performed, with R0 resection in three cases. In this subset, adverse events were observed in 40% of cases. CONCLUSIONS: FTRD is safe and feasible for standard indication. The non-negligible rate of recurrence observed suggests the need for close endoscopic follow-up in these patients. Multiple EFTR could help achieve complete resection in selected cases; however, in this setting, a higher risk of adverse events was observed.

Efficacy of laparoscopic Toupet fundoplication compared to endoscopic and surgical procedures for GERD treatment: a randomized trials network meta-analysis.

PURPOSE: We aim to review and quantitatively compare laparoscopic Toupet fundoplication (LTF), Nissen fundoplication (LNF), anterior partial fundoplication (APF), magnetic augmentation sphincter (MSA), radiofrequency ablation (RFA), transoral incisionless fundoplication (TIF), proton pump inhibitor (PPI), and placebo for the treatment of GERD. A number of meta-analyses compared the efficacy of surgical and endoscopic procedures for recalcitrant GERD, but considerable debate on the effectiveness of operative strategies remains. METHODS: A systematic review of MEDLINE databases, EMBASE, and Web of Science for randomized controlled trials (RCTs) comparing the aforementioned surgical and endoscopic GERD treatments was performed. Risk ratio and weighted mean difference were used as pooled effect size measures, whereas 95% credible intervals (CrI) were used to assess relative inference. RESULTS: Thirty-three RCTs were included. Surgical and endoscopic treatments have similar RR for heartburn, regurgitation, bloating. LTF has a lower RR of post-operative dysphagia when compared to APF (RR 3.3; Crl 1.4-7.1) and LNF (RR 2.5; Crl 1.3-4.4). The pooled network meta-analysis did not observe any significant improvement regarding LES pressure and pH < from baseline. LTF, APF, LNF, MSA, RFA, and TIF had have a similar post-operative PPI discontinuation rate. CONCLUSION: LTF has a lower rate of post-operative dysphagia when compared to APF and LNF. The pre-post effects, such as GERD-HQRL, LES pressure, and pH <4, should be avoided in meta-analyses because results may be biased. Last, a consensus about the evaluation of GERD treatments' efficacy and their outcomes is needed.

Sex differences in the mouse photothrombotic stroke model investigated with X-ray fluorescence microscopy and Fourier transform infrared spectroscopic imaging.

Stroke is a leading cause of death and disability around the world. To date, the majority of pre-clinical research has been performed using male lab animals and results are commonly generalized to both sexes. In clinical stoke cases females have a higher incidence of ischemic stroke and poorer outcomes, compared to males. Best practices for improving translatability of findings for stroke, encourage the use of both sexes in studies. Since estrogen and progesterone have recognized neuroprotective effects, it is important to compare the size, severity and biochemical composition of the brain tissue following stroke in female and male animal models. In this study a photothrombotic focal stroke was induced in male and female mice. Vaginal secretions were collected twice daily to track the stage of estrous. Mice were euthanized at 24 h post-stroke. Histological staining, Fourier transform infrared imaging and X-ray fluorescence imaging were performed to better define the size and metabolic markers in the infarct core and surrounding penumbra. Our results show while the female mice had a significantly lower body mass than males, the cross-sectional area of the brain and the size of infarct and penumbra were not significantly different between the groups. In addition to the general expected sex-linked differences of altered NADH levels between males and females, estrus females had significantly elevated glycogen in the penumbra compared with males and total phosphorus levels were noted to be higher in the penumbra of estrus females. Elevated glycogen reserves in the tissue bordering the infarct core in females may present alternatives for improved functional recovery in females in the early post-stroke phase.

Early vs. standard reversal ileostomy: a systematic review and meta-analysis.

BACKGROUND: Formation of a defunctioning loop ileostomy is common after mid and low rectal resection. Historically, they were reversed between 3 and 6 months after initial resection. Recently, earlier closure (< 14 days) has been suggested by some current randomised controlled trials. The aim of this study was to investigate the effect of early stoma closure on surgical and patient outcomes. METHODS: A systematic review of the current randomised controlled trial literature comparing early and standard ileostomy closure after rectal surgery was performed. Specifically, we examined surgical outcomes including; morbidity, mortality and quality of life. RESULTS: Six studies met the predefined criteria and were included in our analysis. 275 patients underwent early stoma closure compared with 259 patients having standard closure. Overall morbidity was similar between both groups (25.5% vs. 21.6%) (OR, 1.47; 95% CI 0.75-2.87). However, there tended to be more reoperations (8.4 vs. 4.2%) (OR, 2.02, 95% CI 0.99-4.14) and small bowel obstructions/postoperative ileus (9.3% vs. 4.4%) (OR 0.44, 95% CI 0.22-0.90) in the early closure group, but no difference across the other domains. CONCLUSIONS: Early closure appears to be a feasible in highly selective cases after good perioperative counselling and shared decision-making. Further research on quality of life outcomes and long term benefits is necessary to help define which patients are suitable candidates for early closure.

Multimodal imaging of hemorrhagic transformation biomarkers in an ischemic stroke model.

Hemorrhagic transformation of ischemic stroke has devastating consequences, with high mortality and poor functional outcomes. Animal models of ischemic stroke also demonstrate the potential for hemorrhagic transformation, which complicates biochemical characterization, treatment studies, and hinders poststroke functional outcomes in affected subjects. The incidence of hemorrhagic transformation of ischemic stroke in animal model research is not commonly reported. The postmortem brain of such cases presents a complex milieu of biomarkers due to the presence of healthy cells, regions of varying degrees of ischemia, dead and dying cells, dysregulated metabolites, and blood components (especially reactive Fe species released from lysed erythrocytes). To improve the characterization of hemorrhage biomarkers on an ischemic stroke background, we have employed a combination of histology, X-ray fluorescence imaging (XFI), and Fourier transform infrared (FTIR) spectroscopic imaging to assess 122 photothrombotic (ischemic) stroke brains. Rapid freezing preserves brain biomarkers in situ and minimizes metabolic artifacts due to postmortem ischemia. Analysis revealed that 25% of the photothrombotic models had clear signs of hemorrhagic transformation. The XFI and FTIR metabolites provided a quantitative method to differentiate key metabolic regions in these models. Across all hemorrhage cases, it was possible to consistently differentiate otherwise healthy tissue from other metabolically distinct regions, including the ischemic infarct, the ischemic penumbra, blood vessels, sites of hemorrhage, and a region surrounding the hemorrhage core that contained elevated lipid oxidation. Chemical speciation of deposited Fe demonstrates the presence of heme-Fe and accumulation of ferritin.

Prehabilitation in rectal surgery: a narrative review.

AIM: Neoadjuvant chemotherapy (NACRT) can make decompensated patients more vulnerable prior to rectal surgery. Prehabilitation is an intervention which enhances functional capacity to withstand the stress of surgery. The aim of this review was to evaluate the impact of prehabilitation for patients undergoing rectal surgery on physical fitness and clinical outcomes and to establish feasibility of prehabilitation. METHODS: An analysis of the literature was conducted of PubMed, the Cochrane Library, MEDLINE, EMBASE and ScienceDirect. Articles were initially included based on their title and abstracts reviewed. Full-text copies of those selected were obtained for confirmation of inclusion. RESULTS: Eight studies were included. Heterogenicity was observed in the structure of exercise programmes. Improvements in physical fitness were observed in six studies. One study demonstrated a statistically significant improvement in quality of life. The prehabilitation programmes were shown to be feasible, with high completion rates. No adverse events were reported. There was limited data regarding the impact of prehabilitation on postoperative outcomes. CONCLUSION: Current evidence on prehabilitation in rectal surgery has considerable heterogenicity in both structure of programmes and outcome measures. Standardisation is required for future evaluation of the impact on outcomes. A trimodal approach of exercise, nutritional and psychological interventions has been employed in similar programmes, and should be used in rectal surgery. The intervention should be tailored to the patient and environment. This review highlights the benefits, safety and feasibility of prehabilitation and provides a platform for consensus-building for international trials.

Oncological outcomes of laparoscopic versus open rectal cancer resections: meta-analysis of randomized clinical trials.

BACKGROUND: The role of laparoscopic rectal cancer surgery has been questioned owing to conflicting reports on pathological outcomes from recent RCTs. However, it is unclear whether these pathological markers and the surgical approach have an impact on oncological outcomes. This study assessed oncological outcomes of laparoscopic and open rectal cancer resections. METHODS: A meta-analysis of RCTs was performed. Primary endpoints included oncological outcomes (disease-free survival (DFS), overall survival (OS), local recurrence). Secondary endpoints included surrogate markers for the quality of surgical resection. RESULTS: Twelve RCTs including 3744 patients (2133 laparoscopic, 1611 open) were included. There was no significant difference in OS (hazard ratio (HR) 0.87, 95 per cent c.i. 0.73 to 1.04; P = 0.12; I2 = 0 per cent) and DFS (HR 0.95, 0.81 to 1.11; P = 0.52; I2 = 0 per cent) between laparoscopic and open rectal resections. There was no significant difference in locoregional (odds ratio (OR) 1.03, 95 per cent c.i. 0.72 to 1.48; P = 0.86; I2 = 0 per cent) or distant (OR 0.87, 0.70 to 1.08; P = 0.20; I2 = 7 per cent) recurrence between the groups. Achieving a successful composite score (intact mesorectal excision, clear circumferential resection margin and distal margin) was significantly associated with improved DFS (OR 0.55, 0.33 to 0.74; P < 0.001; I2 = 0 per cent). An intact or acceptable mesorectal excision (intact mesorectal excision with or without superficial defects) had no impact on DFS. Finally, a positive CRM was associated with worse DFS. CONCLUSION: Well performed surgery (laparoscopic or open) achieves excellent oncological outcomes with very little difference between the two modalities. The advantage and benefit of minimally invasive surgery should be assessed on an individual basis.

Lateral pelvic lymphadenectomy for low rectal cancer: a META-analysis of recurrence rates.

BACKGROUND: Locoregional recurrence (LR) remains a problem for patients with lower rectal cancer despite standardized surgery and improved neoadjuvant treatment regimens. Lateral pelvic lymph node dissection (LPLND) has been routine practice for some time in the Orient/East, but other regions have concerns about morbidity. As perioperative care and surgical approaches are refined, this has been revisited for selected patients. The question as to whether LPLND improves oncological outcomes was explored here. METHODS: A systematic review of patients who underwent TME with or without LPLND from 2000 to 2020 was performed. The primary endpoint was the rate of LR between the two groups. RESULTS: Seven papers met the predefined search criteria in which 2000 patients underwent TME alone, while 1563 patients had TME and LPLND. The rate of LR was marginally higher with TME alone when compared with TME plus LPLND, but this result was not statistically significant (9.8 vs 9.4%, odds ratio 0.75, 95% CI 0.41-1.38, *p = 0.35). In addition, four studies reported on distant recurrence rates, with TME and LPLND showing a slight reduction in overall rates (27.3 vs 29.9%, respectively, OR 0.65, 95% CI 0.45-0.92, *p = 0.02). CONCLUSION: The addition of LPLND to TME is not associated with a significantly lower risk of LR in patients who undergo surgery for lower rectal cancer.

Tracking elemental changes in an ischemic stroke model with X-ray fluorescence imaging.

Stroke is a leading cause of long-term disability in adults and a leading cause of death in developed nations. The cascade of cellular events and signalling that occur after cerebral ischemia are complex, however, analyzing global element markers of metabolic state affords the means to monitor stroke severity, status of injury, and recovery. These markers provide a multi-parameter method for assessing changes through the post-stroke time course. We employ synchrotron-based elemental mapping to follow elemental changes in the brain at 1 h, 1-, 2-, and 3-days, and at 1-, 2-, 3-, and 4-weeks post-stroke in a photothrombotic stroke model in mice. Our analysis reveals a highly consistent metabolic penumbra that can be readily identified based on the level of dysregulated potassium and other key elements. Maps of elemental distributions are also useful to demarcate events in the cellular response to the inflammatory cascade, including ion dysregulation, recruitment of cells to the lesion, and glial scar formation.

Management options for chronic anal fissure: a systematic review of randomised controlled trials.

INTRODUCTION: Anal fissure is the most common cause of severe anorectal pain in adults, contributing significantly to coloproctology workloads. There are a wide variety of management options available, including topical nitrites, calcium channel blockers, botulinum toxin injection and sphincterotomy. The aim of this study was to review current options for the treatment of chronic anal fissure. METHODS: A comprehensive search identifying randomized controlled trials comparing treatment options for anal fissure published between January 2000 and February 2020 was performed. The primary outcome assessed was healing at 8 weeks post commencing treatment. Secondary outcomes included recurrence, intolerance of treatment and complications. RESULTS: A total of 2822 studies were identified. After removal of duplicates and non-relevant studies, we identified nine randomized controlled trials which met pre-defined criteria. There was a total of 775 patients. At 8 weeks, healing rates were 95.13% in those treated with sphincterotomy, 66.7% in the botulinum toxin group, 63.8% in the nitrate group, 52.3% for topical diltiazem and 50% for topical minoxidil. Recurrence was highest amongst those treated with botulinum toxin injection (41.7%) and lowest for sphincterotomy (6.9%). Although the absolute number is low, there was a risk of permanent incontinence with sphincterotomy. CONCLUSION: This review of the randomized control data demonstrates that healing was significantly higher amongst those treated with sphincterotomy versus more conservative modalities. Topical nitrites had similar outcomes to botulinum toxin injection but were poorly tolerated in comparison to other treatments. The benefit of sphincterotomy was at a cost of increased complications, notably permanent incontinence.

Management of anal intraepithelial neoplasia and anal squamous cell carcinoma at a tertiary referral centre with a dedicated infectious diseases unit: an 18-year review.

INTRODUCTION: Anal squamous cell carcinoma (ASCC) is a rare malignancy with rising incidence rates. Risk factors include human immunodeficiency virus (HIV) infection, high-risk sexual activity and HPV-related genitourinary dysplasia/neoplasia. There is an overlap between high-risk patients and those attending HIV Medicine/Sexual Health (HMSH) services. We hypothesised that HMSH involvement may facilitate earlier referral to colorectal surgeons, with better outcomes. METHODS: Retrospective review of all ASCC and anal intraepithelial neoplasia (AIN) treated at a tertiary-referral hospital with a dedicated HMSH clinic between 2000 and 2018. Comparative analysis was performed of demographics, management and outcomes between HMSH and non-HMSH patients. RESULTS: One hundred and nine patients had anal pathology, eighty-five with ASCC (78%) and twenty-four with AIN (22%). Seventy (64%) were male. Median (range) age at ASCC diagnosis was 51 years (26-88). Thirty-six percent of all patients attended HMSH services, 28% were HIV positive, and 41% of males were men-who-have-sex-with-men (MSM). Eighty-one ASCC patients (97.5%) were treated with curative intent. Sixty-seven (80%) had primary chemoradiation therapy. Fifteen (17.5%) had primary surgical excision. Twelve (14%) developed recurrent disease. Ultimately, seven required salvage APR. Overall 3-year survival (3YS) was 76%. HMSH patients were significantly younger at ASCC diagnosis (p < 0.001), with a higher prevalence of HIV, HPV and MSM. HMSH attenders also tended to be diagnosed at earlier stages, were less likely to develop recurrence and achieved better overall outcomes, with a superior overall 3YS than non-HMSH patients (92% vs 72%, p = 0.037). CONCLUSION: ASCC incidence is increasing worldwide. The HMSH cohort has emerged as a distinct subpopulation of younger, high-risk, male patients. Collaboration between HMSH and colorectal surgeons offers an opportunity for risk reduction strategies and earlier intervention.

Systematic review and meta-analysis comparing primary resection and anastomosis versus Hartmann's procedure for the management of acute perforated diverticulitis with generalised peritonitis.

BACKGROUND: Surgical strategies for acute perforated diverticulitis with generalised peritonitis remain controversial. This study aimed to meta-analyse trials comparing primary resection and anastomosis (PRA) to Hartmann's procedure (HP) for Hinchey III/IV diverticulitis. METHODS: A systematic literature search was conducted to identify observational studies and randomised control trials (RCTs) of patients with Hinchey III/IV diverticulitis undergoing sigmoidectomy that compared PRA to HP. The methodological quality of the included studies was assessed systematically (Newcastle-Ottawa, Jadad and Cochrane risk of bias scores) and a meta-analysis was performed. RESULTS: After removal of duplicates, 12 studies including 4 RCTs were identified. The analysis included 918 patients, of whom 367 (39.98%) underwent PRA. Both the initial stoma rate (risk ratio [RR] persistent stoma 0.43, 95% confidence interval [CI] 0.26, 0.71, p = 0.001; I2 = 99%, p < 0.0001) and the rate of permanent stoma after combining the first (emergency surgery) and second (stoma reversal) procedures were lower in the PRA group. There was no difference in in 30-day mortality; however, PRA resulted in a reduction in overall mortality as well as major complications after the initial operation (RR 0.67, 95% CI 0.46, 0.97, p = 0.03; I2 = 22%, p = 0.26), stoma reversal (RR 0.48, 95% CI 0.26, 0.92, p = 0.03; I2 = 0%, p = 0.58) and when combining both procedures (RR 0.67, 95% CI 0.51, 0.88, p = 0.005; I2 = 0%, heterogeneity p = 0.58). A subgroup analysis of stoma reversal rates using data from only RCTs were consistent (RR permanent stoma, 0.33, 95% CI 0.13, 0.85, p = 0.02; I2 = 77%, p = 0.004) with the findings of the overall analysis. CONCLUSIONS: This meta-analysis demonstrates that PRA used in the management of haemodynamically stable patients with Hinchey grade III/IV diverticulitis leads to a lower overall persistent stoma rate, with reduced morbidity compared with the traditional management.

Sample preparation with sucrose cryoprotection dramatically alters Zn distribution in the rodent hippocampus, as revealed by elemental mapping.

Transition metal ions (Fe, Mn, Cu, Zn) are essential for healthy brain function, but altered concentration, distribution, or chemical form of the metal ions has been implicated in numerous brain pathologies. Currently, it is not possible to image the cellular or sub-cellular distribution of metal ions in vivo and therefore, studying brain-metal homeostasis largely relies on ex vivo in situ elemental mapping. Sample preparation methods that accurately preserve the in vivo elemental distribution are essential if one wishes to translate the knowledge of elemental distributions measured ex vivo toward increased understanding of chemical and physiological pathways of brain disease. The choice of sample preparation is particularly important for metal ions that exist in a labile or mobile form, for which the in vivo distribution could be easily distorted by inappropriate sample preparation. One of the most widely studied brain structures, the hippocampus, contains a large pool of labile and mobile Zn. Herein, we describe how sucrose cryoprotection, the gold standard method of preparing tissues for immuno-histochemistry or immuno-fluorescence, which is also often used as a sample preparation method for elemental mapping studies, drastically alters hippocampal Zn distribution. Based on the results of this study, in combination with a comparison against the strong body of published literature that has used either rapid plunge freezing of brain tissue, or sucrose cryo-protection, we strongly urge investigators in the future to cease using sucrose cryoprotection as a method of sample preparation for elemental mapping, especially if Zn is an analyte of interest.