Eureka: objective assessment of the empty pelvis syndrome to measure volumetric changes in pelvic dead space following pelvic exenteration.

BACKGROUND: Large tissue defects following pelvic exenteration (PE) fill with fluid and small bowel, leading to the empty pelvis syndrome (EPS). EPS causes a constellation of complications including pelvic sepsis and reduced quality of life. EPS remains poorly defined and cannot be objectively measured. Pathophysiology of EPS is multifactorial, with increased pelvic dead space potentially important. This study aims to describe methodology to objectively measure volumetric changes relating to EPS. METHODS: The true pelvis is defined by the pelvic inlet and outlet. Within the true pelvis there is physiological pelvic dead space (PDS) between the peritoneal reflection and the inlet. This dead space is increased following PE and is defined as the exenteration pelvic dead space (EPD). EPD may be reduced with pelvic filling and the volume of filling is defined as the pelvic filling volume (PFV). PDS, EPD, and PFV were measured intraoperatively using a bladder syringe, and Archimedes' water displacement principle. RESULTS: A patient undergoing total infralevator PE had a PDS of 50 ml. A rectus flap rendered the pelvic outlet watertight. EPD was then measured as 540 ml. Therefore there was a 10.8-fold increase in true pelvis dead space. An omentoplasty was placed into the EPD, displacing 130 ml; therefore, PFV as a percentage of EPD was 24.1%. CONCLUSIONS: This is the first reported quantitative assessment of pathophysiological volumetric changes of pelvic dead space; these measurements may correlate to severity of EPS. PDS, EPD, and PFV should be amendable to assessment based on perioperative cross-sectional imaging, allowing for potential prediction of EPS-related outcomes.

The complex polyploid genome architecture of sugarcane.

Sugarcane, the world's most harvested crop by tonnage, has shaped global history, trade and geopolitics, and is currently responsible for 80% of sugar production worldwide1. While traditional sugarcane breeding methods have effectively generated cultivars adapted to new environments and pathogens, sugar yield improvements have recently plateaued2. The cessation of yield gains may be due to limited genetic diversity within breeding populations, long breeding cycles and the complexity of its genome, the latter preventing breeders from taking advantage of the recent explosion of whole-genome sequencing that has benefited many other crops. Thus, modern sugarcane hybrids are the last remaining major crop without a reference-quality genome. Here we take a major step towards advancing sugarcane biotechnology by generating a polyploid reference genome for R570, a typical modern cultivar derived from interspecific hybridization between the domesticated species (Saccharum officinarum) and the wild species (Saccharum spontaneum). In contrast to the existing single haplotype ('monoploid') representation of R570, our 8.7 billion base assembly contains a complete representation of unique DNA sequences across the approximately 12 chromosome copies in this polyploid genome. Using this highly contiguous genome assembly, we filled a previously unsized gap within an R570 physical genetic map to describe the likely causal genes underlying the single-copy Bru1 brown rust resistance locus. This polyploid genome assembly with fine-grain descriptions of genome architecture and molecular targets for biotechnology will help accelerate molecular and transgenic breeding and adaptation of sugarcane to future environmental conditions.

Endovascular Ultrasound Renal Denervation to Treat Hypertension: The RADIANCE II Randomized Clinical Trial.

Importance: Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. Objective: To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. Design, Setting, and Participants: Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. Interventions: Ultrasound renal denervation vs a sham procedure. Main Outcomes and Measures: The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. Results: Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, -7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, -1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, -6.3 mm Hg [95% CI, -9.3 to -3.2 mm Hg], P < .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group. Conclusions and Relevance: In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events. Trial Registration: ClinicalTrials.gov Identifier: NCT03614260.

Current intraoperative storage and handling practices of autologous bypass conduit: A survey of the royal australasian college of surgeons.

During bypass surgery for peripheral arterial occlusive disease and ischaemic heart disease, autologous graft conduit including great saphenous veins and radial arteries are frequently stored in solution. Endothelial damage adversely affects the performance and patency of autologous bypass grafts, and intraoperative graft storage solutions have been shown to influence this process. The distribution of storage solutions currently used amongst Cardiothoracic and Vascular Surgeons from Australia and New Zealand is not well defined in the literature. The aim of this study was to determine current practices regarding autologous graft storage and handling amongst this cohort of surgeons, and discuss their potential relevance in the context of early graft failure. From this survey, the most frequently used storage solutions were heparinized saline for great saphenous veins, and pH-buffered solutions for radial arteries. Duration of storage was 30-45 min for almost half of respondents, although responses to this question were limited. Further research is required to investigate whether ischaemic endothelial injury generates a prothrombotic state, whether different storage media can alter this state, and whether this is directly associated with clinical outcomes of interest such as early graft failure.

The 70-gene signature test as a prognostic and predictive biomarker in patients with invasive lobular breast cancer.

PURPOSE: Genomic expression assays provide prognostic information and guide adjuvant chemotherapy decisions for patients with estrogen receptor (ER)-positive breast cancer. Few studies have evaluated the utility of such assays for invasive lobular carcinoma (ILC). The objective of this study is to evaluate the 70-gene signature test (ST) as a prognostic and predictive tool for ILC using a national cancer database. METHODS: We identified patients diagnosed with stage I-III ER-positive ILC from 2004 to 2016 using the National Cancer Database. All patients underwent 70-gene ST testing. We used the Kaplan-Meier method and Cox proportional hazard analyses to determine overall survival based on genomic risk classification. We also determined the benefit of adjuvant chemotherapy for patients with high-genomic risk ILC based on 70-gene ST testing. RESULTS: We identified 2610 patients with ILC who underwent 70-gene ST testing; 280 (11%) were classified as high genomic risk. Five-year overall survival rates were significantly worse for patients classified as high risk (83%) as compared with those classified as low risk (94%, p < 0.05). In Cox models, high genomic risk was independently associated with a significantly increased hazard of death. In our Cox models of patients who were high genomic risk, adjuvant chemotherapy was not significantly associated with improved overall survival. CONCLUSION: In this large database study, we found that the genomic risk category determined by the 70-gene ST was significantly associated with survival outcomes for patients with ILC. However, the 70-gene ST failed to predict the benefit of adjuvant chemotherapy for patients with high genomic risk.

Preoperative assessment and optimisation for pelvic exenteration in locally advanced and recurrent rectal cancer: A review.

The pre-operative phase in planning a pelvic exenteration or extended resections is critical to optimising patient outcomes. This review summarises the key components of preoperative assessment and planning in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LLRC) being considered for potential curative resection. The preoperative period can be considered in 5 key phases: 1) Multidisciplinary meeting (MDT) review and recommendation for neoadjuvant therapy and surgery, 2) Anaesthetic preoperative assessment of fitness for surgery and quantification of risk, 3) Shared decision making with the patient and the process of informed consent, 4) Prehabilitation and physiological optimisation 5) Technical aspects of surgical planning. This review will focus on patients who have been recommended for surgery by the MDT and have completed neoadjuvant therapy. Other important considerations beyond the scope of this review are the various neoadjuvant strategies employed which in this patient group include Total Neo-adjuvant Therapy and reirradiation. Critical to improving perioperative outcomes is the dual aim of achieving a negative resection margin in a patient fit enough for extended surgery. Advanced, realistic communication is required pre-operatively and should be maintained throughout recovery. Optimising patient's physiological and psychological reserve with a preoperative prehabilitation programme is important, with physiotherapy, psychological and nutritional input. From a surgical perspective, image based technical preoperative planning is important to identify risk points and ensure correct surgical strategy. Careful attention to the entire patient journey through these 5 preoperative phases can optimise outcomes with the accumulation of marginal gains at multiple timepoints.

Comparison of peak wall stress and peak wall rupture index in ruptured and asymptomatic intact abdominal aortic aneurysms.

BACKGROUND: Previous studies have suggested that finite element analysis (FEA) can estimate the rupture risk of an abdominal aortic aneurysm (AAA); however, the value of biomechanical estimates over measurement of AAA diameter alone remains unclear. This study aimed to compare peak wall stress (PWS) and peak wall rupture index (PWRI) in participants with ruptured and asymptomatic intact AAAs. METHODS: The reproducibility of semiautomated methods for estimating aortic PWS and PWRI from CT images was assessed. PWS and PWRI were estimated in people with ruptured AAAs and those with asymptomatic intact AAAs matched by orthogonal diameter on a 1 : 2 basis. Spearman's correlation coefficient was used to assess the association between PWS or PWRI and AAA diameter. Independent associations between PWS or PWRI and AAA rupture were identified by means of logistic regression analyses. RESULTS: Twenty individuals were included in the analysis of reproducibility. The main analysis included 50 patients with an intact AAA and 25 with a ruptured AAA. Median orthogonal diameter was similar in ruptured and intact AAAs (82·3 (i.q.r. 73·5-92·0) versus 81·0 (73·2-92·4) mm respectively; P = 0·906). Median PWS values were 286·8 (220·2-329·6) and 245·8 (215·2-302·3) kPa respectively (P = 0·192). There was no significant difference in PWRI between the two groups (P = 0·982). PWS and PWRI correlated positively with orthogonal diameter (both P < 0·001). Participants with high PWS, but not PWRI, were more likely to have a ruptured AAA after adjusting for potential confounders (odds ratio 5·84, 95 per cent c.i. 1·22 to 27·95; P = 0·027). This association was not maintained in all sensitivity analyses. CONCLUSION: High aortic PWS had an inconsistent association with greater odds of aneurysm rupture in patients with a large AAA.

Body Composition and Dose-limiting Toxicity in Colorectal Cancer Chemotherapy Treatment; a Systematic Review of the Literature. Could Muscle Mass be the New Body Surface Area in Chemotherapy Dosing?

Chemotherapy dosing is traditionally based on body surface area calculations; however, these calculations ignore separate tissue compartments, such as the lean body mass (LBM), which is considered a big pool of drug distribution. In our era, colorectal cancer patients undergo a plethora of computed tomography scans as part of their diagnosis, staging and monitoring, which could easily be used for body composition analysis and LBM calculation, allowing for personalised chemotherapy dosing. This systematic review aims to evaluate the effect of muscle mass on dose-limiting toxicity (DLT), among different chemotherapy regimens used in colorectal cancer patients. This review was carried out according to the PRISMA guidelines. MEDLINE and EMBASE databases were searched from 1946 to August 2019. The primary search terms were 'sarcopenia', 'myopenia', 'chemotherapy toxicity', 'chemotherapy dosing', 'dose limiting toxicity', 'colorectal cancer', 'primary colorectal cancer' and 'metastatic colorectal cancer'. Outcomes of interest were - DLT and chemotoxicity related to body composition, and chemotherapy dosing on LBM. In total, 363 studies were identified, with 10 studies fulfilling the selection criteria. Seven studies were retrospective and three were prospective. Most studies used the same body composition analysis software but the chemotherapy regimens used varied. Due to marked study heterogeneity, quantitative data synthesis was not possible. Two studies described a toxicity cut-off value for 5-fluorouracil and one for oxaliplatin based on LBM. The rest of the studies showed an association between different body composition metrics and DLTs. Prospective studies are required with a larger colorectal cancer cohort, longitudinal monitoring of body composition changes during treatment, similar body composition analysis techniques, agreed cut-off values and standardised chemotherapy regimens. Incorporation of body composition analysis in the clinical setting will allow early identification of sarcopenic patients, personalised dosing based on their LBM and early optimisation of these patients undergoing chemotherapy.

Residual lymph node tumour burden following removal of a single axillary sentinel lymph with macrometastatic disease in women with screen-detected invasive breast cancer.

BACKGROUND: Women with screen-detected invasive breast cancer who have macrometastatic disease on axillary sentinel lymph node biopsy (SLNB) are usually offered either surgical axillary node clearance (ANC) or axillary radiotherapy. These treatments can lead to significant complications for patients. The aim of this study was to identify a group of patients who may not require completion ANC. METHODS: Data from the NHS Breast Screening Programme between 1 April 2012 and 31 March 2017 were interrogated to identify women with invasive breast carcinoma and a single sentinel lymph node (SLN) with macrometastatic disease who subsequently proceeded to completion ANC. Univariable and multivariable analyses were performed to identify patients with a single positive SLN who had no further lymph node metastasis on ANC. RESULTS: Of the 2401 women included in the cohort, the presence of non-sentinel node disease was significantly affected by: the number of nodes obtained at SLNB (odds ratio (OR) 0.49 for retrieval of more than 1 node), invasive size of tumour (OR 1.63 for size greater than 20 mm), surgical treatment (OR 1.34 for mastectomy), human epidermal growth factor receptor (HER) 2 status (OR 0.71 for HER2 positivity), and patient age (OR 1.10 for age less than 50 years; OR 1.46 for age greater than 70 years). Patients aged less than 70 years, with tumour size smaller than 2 cm, more than one node retrieved on SLNB, and who had breast-conserving surgery had a lower chance of positive non-sentinel nodes on completion ANC compared with other patients. CONCLUSION: This study, of a purely screen-detected breast cancer cohort, identified a subset of patients who may be spared completion ANC in the event of a single axillary SLN with macrometastasis.

Implementation of a clinical pathway for the surgical treatment of colorectal cancer during the COVID-19 pandemic.

AIM: This report summarizes the early experience of implementing elective colorectal cancer surgery during the COVID-19 pandemic. METHODS: A pathway to minimize the risk of including COVID-19-positive patients for elective surgery was established. Prioritization and additional safety measures were introduced into clinical practice. Minimal invasive surgery was used where appropriate. RESULTS: Thirty-eight patients were prioritized, and 23 patients underwent surgery (eight colon, 14 rectal and one anal cancer). The minimal invasive surgery rate was 78%. There were no major postoperative complications or patients diagnosed with COVID-19. Histopathological outcomes were similar to normal practice. CONCLUSION: A safe pathway to offer standard high-quality surgery to colorectal cancer patients during the COVID-19 pandemic is feasible.

An assessment of the potential impact of the introduction of male mammographers into the National Health Service breast screening programme.

INTRODUCTION: The NHS breast screening programme only employs female mammographers to carry out breast screening. The screening service is experiencing a shortage of staff and introducing male mammographers into the service is a potential solution. This research aimed to determine if the introduction of male mammographers would impact acceptance rates of the offer of screening, how women feel about the potential change and what the impact would be at a programme level. METHODS: The research was conducted in 3 stages. Initially 24 face-to-face interviews were conducted with women aged 45-70 and 19 interviews over the telephone with stakeholders; these interviews explored what women's reaction would be to the introduction of male mammographers. These interviews informed the content of a questionnaire that was completed online by 1000 women aged 50-71. It explored what women would do if offered a test with a male mammographer and how they felt about the potential change. RESULTS: Over half, 53.4% stated they would attend a routine mammogram if the mammographer was male, 15.3% said they would attend if a female chaperone was present, and 31.3% stated they would refuse to attend. The face-to-face interviews suggested women view routine breast screening differently to other healthcare interactions because it is an optional service and not a treatment. As a result, participants had higher expectations both in terms of expecting a choice over the gender of the mammographer and a need to feel comfortable. CONCLUSION AND IMPLICATIONS FOR PRACTICE: The findings indicate that the percentage of eligible women attending breast screening may decrease if male mammographers were introduced. This impact of introducing male mammographers would need to be carefully weighed up against the potential gains in workforce numbers in opening up mammography to male practitioners.

The emerging role of sarcopenia as a prognostic indicator in patients undergoing abdominal wall hernia repairs: a systematic review of the literature.

BACKGROUND: There is strong evidence suggesting that excessive fat distribution, for example, in the bowel mesentery or a reduction in lean body mass (sarcopenia) can influence short-, mid-, and long-term outcomes from patients undergoing various types of surgery. Body composition (BC) analysis aims to measure and quantify this into a parameter that can be used to assess patients being treated for abdominal wall hernia (AWH). This study aims to review the evidence linking quantification of BC with short- and long-term abdominal wall hernia repair outcomes. METHODS: A systematic review was performed according to the PRISMA guidelines. The literature search was performed on all studies that included BC analysis in patients undergoing treatment for AWH using Medline, Google Scholar and Cochrane databases by two independent reviewers. Outcomes of interest included short-term recovery, recurrence outcomes, and long-term data. RESULTS: 201 studies were identified, of which 4 met the inclusion criteria. None of the studies were randomized controlled trials and all were cohort studies. There was considerable variability in the landmark axial levels and skeletal muscle(s) chosen for analysis, alongside the methods of measuring the cross-sectional area and the parameters used to define sarcopenia. Only two studies identified an increased risk of postoperative complications associated with the presence of sarcopenia. This included an increased risk of hernia recurrence, postoperative ileus and prolonged hospitalisation. CONCLUSION: There is some evidence to suggest that BC techniques could be used to help predict surgical outcomes and allow early optimisation in AWH patients. However, the lack of consistency in chosen methodology, combined with the outdated definitions of sarcopenia, makes drawing any conclusions difficult. Whether body composition modification can be used to improve outcomes remains to be determined.

Single incision laparoscopic assisted double balloon enteroscopy: a novel technique to manage small bowel pathology.

BACKGROUND AND AIMS: Double balloon enteroscopy (DBE) has revolutionised the diagnosis and treatment of small bowel (SB) conditions. However, deep SB insertion can be challenging in patients with a history of abdominal surgery and a two-step procedure is required when findings are not amenable to endoscopic therapy. This case series reports the development of laparoscopically assisted DBE (LA-DBE) using single incision laparoscopic surgery (SILS). METHODS: Retrospective review of LA-DBE procedures performed in a single tertiary centre over 6 years. RESULTS: Seventeen patients (median age: 40 years, male 41%) underwent 17 LA-DBE procedures. The approach was oral in 13 and rectal in 4. Laparoscopic approach was standard (multi-port) in the first four cases, SILS was then used in all subsequent patients (13/17). Indications for LA-DBE were previously failed standard DBE (n = 16) and need for a combined procedure (n = 1). Indications for DBE were Peutz-Jeghers syndrome (PJS) (n = 10), suspected submucosal/polypoid lesion at small bowel imaging (n = 5) and obscure gastrointestinal bleeding (OGIB) with vascular abnormalities seen at capsule endoscopy (n = 2). In 1/17 the suggested pathology on imaging was not identified. Therapy was applied in 15/17 (88%) cases. Diagnoses were PJS polyps (n = 8), neuroendocrine tumour (NET) (n = 2), PJS and NET (n = 1), transmural arteriovenous malformation (n = 1), angioectesia (n = 1), inflammatory polyp (n = 1), leiomyoma (n = 1) and Meckel's diverticulum (n = 1). The median (range) procedure time was 147 (84-210) mins. Median (range) length of stay post-procedure was 2 (1-19) days. Three patients developed complications. The 30-day mortality rate was 0%. CONCLUSIONS: LA-DBE is a safe, effective and minimally invasive procedure that can be applied for the management of selected patients with small bowel pathology. A SILS approach allows all therapeutic modalities to be available, including conversion to intraoperative enteroscopy (IOE), laparoscopic small bowel resection and laparotomy.

Safety and efficacy of laparoscopic near-total colectomy and ileo-distal sigmoid anastomosis as a modification of total colectomy and ileorectal anastomosis for prophylactic surgery in patients with adenomatous polyposis syndromes: a comparative study.

AIM: Colectomy in patients with adenomatous polyposis (AP) syndromes demands good oncological and surgical outcome. Total colectomy with ileorectal anastomosis (TC-IRA) is one surgical option for these patients. Anastomotic leakage rates of 11% have been reported following TC-IRA. Ileo-distal sigmoid anastomosis (IDSA) is a recent modification of our practice. Our aim was to compare postoperative outcome in patients with AP following near-total colectomy with IDSA (NT-IDSA) and TC-IRA at a single institution. METHOD: A prospectively maintained database was reviewed to identify patients with AP who underwent laparoscopic NT-IDSA and TC-IRA. Patient demographics, early morbidity and mortality and outcome of endoscopic surveillance were evaluated. RESULTS: A total of 191 patients with AP underwent laparoscopic colectomy between 2006 and 2017, of whom 139 (72.8%) underwent TC-IRA and 52 (27.2%) NT-IDSA. The median age at surgery in the TC-IRA and NT-IDSA groups was 20 years (IQR 17-45) and 27 years (IQR 19-50), respectively. Grade II complications were comparable between the two groups. There were no anastomotic leakages in the NT-IDSA group compared with 15 (10.8%) in the TC-IRA group (P = 0.0125) and no reoperation in the NT-IDSA group compared with 17 (12.2%) in the TC-IRA group (P = 0.008). The frequency of polypectomies per flexible sigmoidoscopy was comparable between the two groups. CONCLUSION: This study demonstrates that laparoscopic NT-IDSA for polyposis is associated with a significant improvement in anastomotic leakage rates and surgical outcome. It is too soon to tell whether NT-IDSA alters the need for further intervention, either endoscopic polypectomy or further surgery.

Effects of a novel hydrogen sulfide prodrug in a porcine model of acute limb ischemia.

OBJECTIVE: Previous studies have shown that hydrogen sulfide (H2S) exerts potent proangiogenic properties under in vitro conditions and in rodent models. We sought to determine whether a novel H2S prodrug promotes peripheral revascularization in a swine model of acute limb ischemia (ALI). METHODS: ALI was induced in 17 female miniswine via intravascular occlusion of the external iliac. At day 7 after ALI induction, miniswine (n = 17) were randomized to received placebo or the H2S prodrug, SG-1002 (800 mg per os twice a day), for 35 days. At day 35 SG-1002 increased circulating levels of H2S (5.0 ± 1.2 µmol/L vs 1.8 ± 0.50 µmol/L; P < .05), sulfane sulfur (10.6 ± 2.3 µmol/L vs 2.6 ± 0.8 µmol/L; P < .05), and nitrite (0.5 ± 0.05 µmol/L vs 0.3 ± 0.03 µmol/L; P < .005) compared with placebo. SG-1002 therapy increased angiographic scoring in ischemic limb vessel number (27.6 ± 1.6 vs 22.2 ± 1.8; P < .05) compared with placebo. Treatment with SG-1002 preserved existing capillaries in ischemic limbs (128.3 ± 18.7 capillaries/mm2 vs 79.0 ± 9.8 capillaries/mm2; P < .05) compared with placebo. Interestingly, treatment with SG-1002 also improved coronary vasorelaxation responses to bradykinin and substance P in miniswine with ALI. CONCLUSIONS: Our results suggest that daily administration of the H2S prodrug, SG-1002, leads to an increase in circulating H2S and nitric oxide signaling and preserves vessel number and density in ischemic limbs. Furthermore, SG-1002 therapy improved endothelial-dependent coronary artery vasorelaxation in the setting of ALI. Our data demonstrate that SG-1002 preserves the vascular architecture in ischemic limbs and exerts vascular protective effects in the coronary vasculature in a model of peripheral vascular disease.

An analysis of 11.3 million screening tests examining the association between needle biopsy rates and cancer detection rates in the English NHS Breast Cancer Screening Programme.

AIM: To examine the association between recall, needle biopsy, and cancer detection rates to inform the setting of target ranges to optimise the benefit to harm ratio of breast screening programmes. MATERIALS AND METHODS: Annual screening programme information from 2009/10 to 2015/16 for the 80 screening units of the English National Health Service Breast Screening Programme (totalling 11.3 million screening tests) was obtained from annual (KC62) returns. Linear regression models were used to examine the association between needle biopsy rates and recall rates and non-linear regression models to examine the association between cancer detection rates and needle biopsy rates. RESULTS: The models show and quantify the diminishing returns for prevalent screens with increasing biopsy rates. A biopsy rate increase from 10 to 20 per 1,000 increases the cancer detection rate by 2.13 per 1,000 with four extra biopsies per extra cancer detected. Increasing the biopsy rate from 40 to 50 per 1,000, increases the cancer detection rate by only 0.25 per 1,000, with 40 extra biopsies per extra cancer detected. Although diminishing returns are also seen at incident screens, screening is generally more efficient. CONCLUSIONS: Increasing needle biopsy rates leads to rapidly diminishing returns in cancer detection and a marked increase in non-malignant/benign needle biopsies. Much of the harms associated with screening in terms of false-positive recall rates and non-cancer biopsies occur at prevalent screens with much lower rates at incident screens. Needle biopsy rate targets should be considered together with recall rate targets to maximise benefit and minimise harm.

Long-term outcome of laparoscopic rectopexy for full-thickness rectal prolapse.

BACKGROUND: The aim of this study was to assess the long-term outcomes of laparoscopic rectopexy for full-thickness rectal prolapse (FTRP). METHODS: Data of a prospectively maintained database were analysed. A structured telephone interview was conducted to assess a consecutive series of long-term outcomes of an unselected population who had laparoscopic rectopexy at a single centre between April 2006 and April 2014. The primary outcome was recurrence of FTRP. Secondary outcomes were functional outcomes and morbidity associated with the procedure. RESULTS: A total of 80 patients (74 female, median age of 66 years, range 23-96 years) underwent a laparoscopic rectopexy, of whom 35 (44%) were for recurrent prolapse. Seventy-two patients (90%) had a posterior suture rectopexy, six (8%) had a ventral mesh rectopexy, one (1%) had a combination of both procedures, and one (1%) had a posterior suture rectopexy with a sacrocolpopexy. There was no conversion to open surgery. Three patients (4%) needed reoperation within 30 days after surgery: two due to small bowel obstruction and one for a suspected port site hernia. Seventy-four patients (93%) were available for either clinical follow-up (FU) or telephone interview and there were 17 (23%) recurrences of FTRP at the median FU of 57 months (range 1-121 months). The median time to recurrence was 12 months (range 1-103 months). Recurrence of FTRP was seen in nine patients (12%) within 1 year following surgery. A history of multiple previous prolapse repairs increased the risk of prolapse recurrence (odds ratio 8.33, 95% confidence interval 1.38-50.47, p = 0.020). Based on clinical follow-up of 71 patients up to 1 year, there were 41 patients (58%) who had faecal incontinence prior to rectopexy of whom two patients (5%) had complete resolution of symptoms and 14 (34%) had improvement. CONCLUSIONS: Laparoscopic rectopexy is a safe operation for full-thickness rectal prolapse. The durability of the repair diminished over time, particularly for patients operated on for recurrent prolapse.

Physiological changes after colorectal surgery suggest that anastomotic leakage is an early event: a retrospective cohort study.

AIM: Anastomotic leakage (AL) is often identified 7-10 days after colorectal surgery. However, in retrospect, abnormalities may be evident much earlier. This study aims to identify the clinical time point when AL occurs. METHOD: This is a retrospective case-matched cohort comparison study, assessing patients undergoing left-sided colorectal resection between 2006 and 2015 at a specialist colorectal unit. Patients who developed AL (LEAK) were case-matched to two CONTROL patients by procedure, gender, laparoscopic modality and diverting stoma. Case note review allowed the collection of basic observation data and blood tests (leukocyte count, C-reactive protein, bilirubin, alanine transaminase, creatinine) up to postoperative day (POD) 4. The cohorts were compared, with the main outcome measure being changes in basic observation data. RESULTS: Of 554 patients, 49 developed AL. These were matched to 98 CONTROL patients. Notes were available for 105 patients (32 LEAK/73 CONTROL). Groups were similar in demographics, tumour or nodal status, preoperative radiotherapy, intra-operative air-leak integrity and drain usage. AL was detected clinically at a median of 7.5 days postoperatively. There was a significantly increased heart rate by the evening on POD 1 in LEAK patients (82.8 ± 14.2/min vs 75.1 ± 12.7/min, P = 0.0081) which persisted for the rest of the study. By POD 3, there was a significant increase in respiratory rate (18.0 ± 4.2/min vs 16.5 ± 1.3/min, P = 0.0069) and temperature (37.0 ± 0.4C vs 36.7 ± 0.3C, P = 0.0006) in LEAK patients. C-reactive protein was significantly higher in LEAK patients from POD 2 (165 ± 95 mg/l vs 121 ± 75 mg/l, P = 0.023). CONCLUSIONS: Physiological and biochemical changes associated with AL happen very early postoperatively, suggesting that AL may occur within 36 h after surgery, despite much later clinical detection.