Outcomes following two-stage surgical approaches in the treatment of pediatric ulcerative colitis.

INTRODUCTION: Surgery for the treatment of ulcerative colitis (UC) can be performed in one-, two-, or three-stage procedures [1]. The more traditional approach is a total proctocolectomy and creation of an ileo pouch-anal anastomosis and diverting stoma at the initial operation, followed by ileostomy closure several weeks later (TIPPA) [1]. An alternative is an initial subtotal colectomy and end ileostomy [2]. In this alternative approach (NIPAA), a completion proctectomy and definitive ileo pouch-anal anastomosis can be performed without a diverting stoma. We hypothesize that functional outcomes following a NIPAA approach when performed in children, in our experience, are likely similar or improved when compared to those treated by TIPAA. METHODS: After IRB approval, a review of patients who underwent a two-stage Laparoscopic IPAA from 2004 to 2017 occurred. Data included demographics, diagnosis, surgical intervention time to full diet, level of continence, use of antidiarrheals and complications. RESULTS: N = 41 (NIPAA = 14, TIPAA = 27). After establishment of bowel continuity, no significant differences in appetite recovery, continence, or complications were noted. The number of antidiarrheals prescribed were significantly higher in the TIPAA group (p = 0.01). Thirteen patients (31.7%) had pouchitis: 4 NIPAA and 9 TIPAA (p = NS). Of the 41 patients, 11 required subsequent surgery; 2 patients (18.2%) received NIPAA and 9 (81.8%) received TIPAA (p = 0.20). Two TIPAA patients received a diverting ileostomy owing to chronic anal pain and failure to achieve continence. CONCLUSION: This study suggests children with medically refractory UC treated by NIPAA or TIPAA have similar outcomes. Minimal differences in overall outcome were noted following either approach. However, NIPAA may reduce reliance on antidiarrheals to achieve satisfactory defecation outcomes. LEVEL OF EVIDENCE: III Retrospective comparative study.

Inhibition of prolyl hydroxylase domain proteins selectively enhances venous thrombus neovascularisation.

BACKGROUND: Hypoxia within acute venous thrombi is thought to drive resolution through stabilisation of hypoxia inducible factor 1 alpha (HIF1α). Prolyl hydroxylase domain (PHD) isoforms are critical regulators of HIF1α stability. Non-selective inhibition of PHD isoforms with l-mimosine has been shown to increase HIF1α stabilisation and promote thrombus resolution. OBJECTIVE: The aim of this study was to investigate the therapeutic potential of PHD inhibition in venous thrombus resolution. METHODS: Thrombosis was induced in the inferior vena cava of mice using a combination of flow restriction and endothelial activation. Gene and protein expression of PHD isoforms in the resolving thrombus was measured by RT-PCR and immunohistochemistry. Thrombus resolution was quantified in mice treated with pan PHD inhibitors AKB-4924 and JNJ-42041935 or inducible all-cell Phd2 knockouts by micro-computed tomography, 3D high frequency ultrasound or endpoint histology. RESULTS: Resolving venous thrombi demonstrated significant temporal gene expression profiles for PHD2 and PHD3 (P < 0.05), but not for PHD1. PHD isoform protein expression was localised to early and late inflammatory cell infiltrates. Treatment with selective pan PHD inhibitors, AKB-4924 and JNJ-42041935, enhanced thrombus neovascularisation (P < 0.05), but had no significant effect on overall thrombus resolution. Thrombus resolution or its markers, macrophage accumulation and neovascularisation, did not differ significantly in inducible all-cell homozygous Phd2 knockouts compared with littermate controls (P > 0.05). CONCLUSIONS: This data suggests that PHD-mediated thrombus neovascularisation has a limited role in the resolution of venous thrombi. Directly targeting angiogenesis alone may not be a viable therapeutic strategy to enhance venous thrombus resolution.

Systematic review: outcomes and post-operative complications following colectomy for ulcerative colitis.

BACKGROUND: Colectomy for ulcerative colitis is associated with short- and long-term complications. Estimates of the frequency of such complications are variable and may have changed since the introduction of biological therapy. Understanding the true burden of surgical complications is important to clinicians in assessing risks and benefits of colectomy vs. continued medical therapy. AIM: To ascertain the outcomes of colectomy and ileal pouch surgery in patients with ulcerative colitis in the biologics era. METHODS: Embase, MEDLINE and The Cochrane Library were searched for studies (2002-2015) reporting the outcomes of colorectal procedures (total and subtotal colectomy, IPAA with J-, S-, W-pouch) in adults with ulcerative colitis. Conferences proceedings (2011-2015) were hand-searched. RESULTS: We identified 28 studies (20,801 patients) reporting outcomes from procedures conducted from 2002-2015. Early complications (≤30 days post-operatively), reported in 10 studies, occurred in 9-65% of patients with ulcerative colitis; late complications (>30 days post-operatively) occurred in 17-55% of patients. Most frequent short-term complications: infectious complications and ileus (mean incidence 20% and 18%). Most frequent long-term complications: pouchitis, faecal incontinence and small bowel obstruction (mean incidence 29%, 21% and 17%). Rates of early infection and late pouch failure decreased from 22% and 13% in 2002-2009 to 11% and 2% in 2010-2015. The mean incidence of post-operative mortality was 1.0% across 11 studies. CONCLUSIONS: Early and late complications arise in about one-third of patients undergoing surgery for ulcerative colitis. While colorectal surgical procedures are recommended for a specific group of patients, the post-operative complications associated with these procedures should not be underestimated.

Editor's choice--Angulation of the C-arm during complex endovascular aortic procedures increases radiation exposure to the head.

OBJECTIVES/BACKGROUND: The increased complexity of endovascular aortic repair necessitates longer procedural time and higher radiation exposure to the operator, particularly to exposed body parts. The aims were to measure directly exposure to radiation of the bodies and heads of the operating team during endovascular repair of thoracoabdominal aortic aneurysms (TAAA), and to identify factors that may increase exposure. METHODS: This was a single-centre prospective study. Between October 2013 and July 2014, consecutive elective branched and fenestrated TAAA repairs performed in a hybrid operating room were studied. Electronic dosimeters were used to measure directly radiation exposure to the primary (PO) and assistant (AO) operator in three different areas (under-lead, over-lead, and head). Fluoroscopy and digital subtraction angiography (DSA) acquisition times, C-arm angulation, and PO/AO height were recorded. RESULTS: Seventeen cases were analysed (Crawford II-IV), with a median operating time of 280 minutes (interquartile range 200-330 minutes). Median age was 76 years (range 71-81 years); median body mass index was 28 kg/m(2) (25-32 kg/m(2)). Stent-grafts incorporated branches only, fenestrations only, or a mixture of branches and fenestrations. A total of 21 branches and 38 fenestrations were cannulated and stented. Head dose was significantly higher in the PO compared with the AO (median 54 µSv [range 24-130 µSv] vs. 15 µSv [range 7-43 µSv], respectively; p = .022), as was over-lead body dose (median 80 µSv [range 37-163 µSv] vs. 32 µSv [range 6-48 µSv], respectively; p = .003). Corresponding under-lead doses were similar between operators (median 4 µSv [range 1-17 µSv] vs. 1 µSv [range 1-3 µSv], respectively; p = .222). Primary operator height, DSA acquisition time in left anterior oblique (LAO) position, and degrees of LAO angulation were independent predictors of PO head dose (p < .05). CONCLUSIONS: The head is an unprotected area receiving a significant radiation dose during complex endovascular aortic repair. The deleterious effects of exposure to this area are not fully understood. Vascular interventionalists should be cognisant of head exposure increasing with C-arm angulation, and limit this manoeuvre.

Angiogenic cell therapy for critical limb ischemia: an update on concepts and trials.

Therapeutic neovascularization is a novel approach used to salvage critically ischemic limbs that are not amenable to conventional treatments. Initial efforts were based on single injections of angiogenic factors but there is now a realization that delivering angiogenic cells is more likely to achieve effective revascularization. Clinical studies to date have mostly used mixtures of mononuclear cells harvested from the bone marrow or peripheral blood. The modest results achieved with these cells, only a proportion of which are angiogenic, has stimulated a search for more potent cell types. Preclinical studies have identified several candidates, including adipose derived, embryonic and induced pluripotent stem cells. This review provides an update on the current status of angiogenic cell therapy for the ischemic limb and outlines efforts aimed at enhancing the clinical efficacy of treatments.

Pathology specific early outcome after thoracic endovascular aortic repair.

OBJECTIVES: Endovascular intervention is established for treatment of thoracic aortic dissection and aneurysm. The aim of this study was to compare the incidence of all-cause and aortic-related in-hospital mortality, stroke, spinal cord ischaemia, and major adverse event rate for patients undergoing thoracic aortic endovascular intervention to see if there is a pathology-specific effect. METHODS: Data were collected prospectively and analysed retrospectively for a cohort of 309 consecutive patients with either thoracic aortic dissection or aneurysm over a 14-year period. RESULTS: There were 209 men and 100 women with a median age of 72 years (interquartile range [IQR] 63-78 years). Aneurysm affected 62% (193/309) of patients and 37% (116/309) had complicated type B aortic dissection, of whom 43% (50/116) had acute and 57% (66/116) chronic presentations. In patients with aortic dissection compared to aneurysm, there was no significant difference in all-cause in-hospital mortality (6.9% vs. 8.3% respectively, p = 0.827, relative risk [RR] 0.83, 95% confidence interval [CI] 0.37-1.88), stroke (6.0% vs 6.2%, p = 1.00, RR 0.971, CI 0.39-2.39), spinal cord ischaemia (6.0% vs 6.2%, p = 1.00, RR 1.030, CI 0.42-2.54), or major adverse event rate (16.4% vs. 16.6%, p = 1.00, RR 0.988, CI 0.59-1.66). The rate of aortic related death was four times greater in the dissection than in the aneurysm group (4/8 = 50% vs 2/16 = 12.5%, p = 0.06, RR 6.99, CI 0.92-52.5) although this did not reach statistical significance. CONCLUSIONS: There was no difference in the incidence of in-hospital mortality, stroke, and spinal cord ischaemia between aneurysm and dissection. The higher rate of aortic related death in the dissection group may indicate the need to refine the clinical management of these patients, including procedural planning, endograft design, and operative technique.

A 14-year experience with aortic endograft infection: management and results.

OBJECTIVES: The management of thoracic and abdominal aortic endograft infection is complex and associated with high mortality. Cases are rare: a recent systematic review identified 117 reported cases; the largest reported series comprises 12 infected endografts. METHODS: We report 22 consecutive patients with infected abdominal or thoracic aortic endovascular devices implanted from 1998 to 2012. Management included extension with new devices, aneurysm sac drainage of pus/irrigation with antibiotics, endograft explantation, and axillo-(bi)femoral reconstruction. RESULTS: Twenty-two patients (16 men) were identified. Median age was 71 years (range, 43-88 years). Index devices were infra-renal endovascular repair (n = 13), and thoracic endovascular repair (n = 9) all for aneurysmal or pseudoaneurysmal disease. Seven (32%) had prior aortic surgery. Follow-up was complete in all cases; in survivors follow-up was a median of 29 (range, 12-45) months. The mortality from explantation of ten infra-renal devices was 1/10 (10%) on-table and a further 2/10 (20%) within 30 days. Device retention led to disease progression and death in all patients with infected endografts. Sac drainage/irrigation provided only temporary control of sepsis. Device extension can treat rupture, but additional devices became infected. CONCLUSION: Abdominal endograft explantation is high risk but may be curative. Appropriate selection of patients for infected endograft explantation remains a major challenge.

Risk of radiation exposure during endovascular aortic repair.

OBJECTIVE: Exposure to radiation doses above 2 Gray (Gy) can cause skin burns. There is also a lifetime cancer risk of ≈5.5% for every Sievert (Sv) of radiation. We assessed the radiation burden associated with endovascular treatment of the aorta. METHOD: Thoracic (TEVAR), Infra-renal (IEVAR) and branched/fenestrated (BEVAR/FEVAR) endovascular aortic repairs were studied. The prospectively recorded dosimetric parameters included: fluoroscopy time and dose area product (DAP). Exposure films, placed underneath 10 patients intra-operatively, recorded skin dose and were used to calculate skin (Gy) and tissue (Sv) doses. RESULTS: The TEVAR cohort (n = 232) were younger (p < 0.0001) than BEVAR/FEVAR (n = 53) and IEVAR (n = 630). The median DAP was higher (p = 0.004) in the BEVAR/FEVAR group compared with IEVAR and TEVAR: 32,060 cGy cm(2) (17,207-213,322) vs 17,300 cGy cm(2) (10,940-33,4340) vs 19,440 cGy cm2 (11,284-35,101), respectively. The equivalent skin doses were BEVAR/FEVAR: 1.3 Gy (0.71-8.75); IEVR: 0.71 Gy (0.44-13.7); TEVAR: 0.8 Gy (0.46-1.44). The whole body effective doses were BEVAR/FEVAR: 0.096 Sv (0.052-0.64); IEVR: 0.053 Sv (0.033-1.00); TEVAR: 0.058 Sv (0.034-0.11). CONCLUSIONS: The radiation exposure during endovascular aortic surgery is relatively low for the majority but some patients are exposed to very high doses. Efforts to minimise intra-operative exposure and graft surveillance methods that do not use radiation may reduce the cumulative lifetime malignancy risk.

Cataract surgery after retinal surgery.

Many patients require surgery for cataract after retinal surgery. When evaluating patients preoperatively, the surgeon should pay careful attention to the assessment of visual function and potential acuity, and to the slit lamp examination of the lens, posterior capsule, anterior cortical vitreous, and zonules. The surgeon's technique must account for increased nuclear sclerosis, intraoperative miosis, a characteristically longer axial length, and fluctuations in anterior chamber depth from movement of the iris-lens diaphragm. Posterior capsule plaques are not unusual. Posterior capsule opacification is the most frequent late complication. Visual outcomes are usually good except when limited by pre-existing macular pathology. Vision-threatening complications of cataract surgery are unusual.

Cytogenetics and cancer.

Techniques based on fluorescence in situ hybridization (FISH) have bridged the gap between molecular genetics and conventional cytogenetics. Since its introduction in the late 1980s, advanced FISH-based methods have greatly enhanced the cytogenetic analysis of hematopoietic and solid tumors and are rapidly gaining ground in clinical cytogenetic diagnostics. As interest in FISH technologies has grown, it has inspired an era of new FISH-based technologies such as multiplex FISH, spectral karyotyping, and comparative genomic hybridization. In this review, the focus is on the impact of these technologies in the field of cancer genetics.

Evaluation of an unused 1952 Ridley intraocular lens.

PURPOSE: To evaluate an unused 1952 historic Ridley intraocular lens (IOL) brought to Bombay, India, in 1952 from an Oxford Ophthalmologic Conference in England and given to 1 of the authors during his residency. SETTING: Alcon Laboratories, Fort Worth, Texas, USA. METHODS: The Ridley IOL was evaluated at Alcon Laboratories, Inc., using the established procedures of its Intraocular R&D Laboratories. Various optical and physical aspects of the Ridley lens were evaluated including (1) dimensions, (2) weight, (3) power, (4) resolution efficiency and modulation transfer function (MTF), (5) surface sphericity by interferometry, (6) ultraviolet (UV)-visible transmission characteristic, (7) attenuated total reflectance (ATR)-Fourier transform infrared reflectance spectrum, and (8) cosmetics by visual inspection using light microscopy. RESULTS: This 8.5 mm diameter, 2.4 mm thick, 23 diopter biconvex IOL weighed 108 mg. The ATR spectrum, UV-visible transmission, and refractive index confirmed its poly-(methyl methacrylate) material. The 0.56 MTF value at 100 line pairs/mm, per the International Standards Organization--IOL Optics Standard, and 93% resolution efficiency in water, per the American National Standard Institute IOL Optics Standard, revealed the IOL's excellent optics. This was confirmed by 0.278 wave root mean square surface figure as measured by Zygo interferometer using a 633 nm wavelength. Visual inspection revealed rough edges with sharp corners and some surface scratches. Early clinical experience with Ridley IOLs in Bombay, India, is briefly given. CONCLUSION: The Ridley IOL had excellent optical quality, meeting the requirements of current IOL optics standards. The selection of its dimensions was guided by the human crystalline lens, and the Ridley IOL was half as bulky. Although its clinical results were mixed, successful cases inspired subsequent improvements, leading to modern, highly satisfactory IOLs. This IOL represented a revolutionary innovation in ophthalmology.

Overexpression of EMS1/cortactin in NIH3T3 fibroblasts causes increased cell motility and invasion in vitro.

Cortactin, a p80/85 protein first identified as a src kinase substrate, is thought to be involved in the signaling pathway of mitogenic receptors and adhesion molecules mediating cytoskeletal reorganization. The cortactin gene, EMS1, maps to chromosome 11q13, a region amplified in head and neck squamous cell carcinomas (HNSCC) and breast cancer, which display lymph node metastasis and an unfavorable clinical outcome. To further address the role of cortactin in the malignant phenotype of cells, we stably overexpressed cortactin in NIH3T3 fibroblasts and evaluated the effects of elevated cortactin on cellular proliferation, motility and invasiveness. Cortactin overexpressing cells did not display any striking morphological changes, nor any significant differences in cell proliferation or saturation density as compared to control NIH3T3 cells. Furthermore, the cortactin overexpressing cells were anchorage dependent for growth. Interestingly, cortactin overexpressing cells were more motile and invasive in modified Boyden chamber assays. These results suggest that overexpression of cortactin may play a role in tumor progression by influencing tumor cell migration and invasion.

Determining the imaging quality of intraocular lenses.

PURPOSE: To validate the proposed optical requirements of a draft international standard for intraocular lenses (IOLs). SETTING: Eight optical testing laboratories in the United States, Germany, Japan, and The Netherlands. METHODS: The testing laboratories performed modulation transfer function (MTF) tests on various IOLs using a model eye and visual resolution tests in air. Each laboratory performed duplicate measurements on a set of 43 lenses that was circulated among the testing laboratories. RESULTS: The interlaboratory tests showed that the MTF measurements using a model eye had better repeatability and reproducibility than the more common industry practice of resolution testing in air with parallel light and the United States Air Force three-bar target. However, the two methods correlated well. The commonly applied criterion that an IOL resolve in air at least 60% of the Rayleigh cutoff spatial frequency corresponded to a minimum requirement of 0.43 MTF units at 100 mm-1 in a model eye. CONCLUSIONS: Either criterion may be applied in accordance with a proposed international standard for IOLs. The model eye method can be applied over a broader range of dioptric powers and is relevant for materials that interact with aqueous. Both tests appear to have a greater ability to detect unwanted surface aberrations than resolution testing of IOLs in a water cell using parallel light, a method described in the current American National Standards Institute standard.

In vitro adherence of Pseudomonas aeruginosa to four intraocular lenses.

PURPOSE: To compare the relative degrees of adherence of a clinical strain of Pseudomonas aeruginosa to the optic material of four intraocular lenses (IOLs). SETTING: Center for Applied and Environmental Microbiology, Georgia State University, Atlanta, Georgia, USA. METHODS: Intraocular lens optics made of poly(methyl methacrylate) (PMMA), AcrySof-acrylic, and silicone were included in this study. The IOLs were incubated in a minimal medium with cells of P. aeruginosa for 2 hours and 18 hours. Cells in the 2 hour experiment were prelabeled with 3H-leucine; those in the 18 hour experiments were postlabeled. After rinsing the IOLs to remove loosely adherent cells, we determined the number of cells adhered to coded lenses from calibration curves of disintegrations per minute versus cells per square millimeter. Additional lenses were incubated with P. aeruginosa and examined with scanning electron microscopy. RESULTS: The adherence of P. aeruginosa in order of increasing magnitude was AcrySof-acrylic < PMMA < silicone 1 < silicone 2. The differences between all groups were statistically significant. The scanning electron microscopy observations were in general agreement with the radiolabel studies. CONCLUSIONS: The AcrySof-acrylic IOL was less susceptible to primary adherence and 18 hour biofilm formation by P. aeruginosa than the PMMA and silicone IOLs, indicating that this material reduced pseudomonad adherence and the risk of endophthalmitis following cataract surgery.

Accuracy in determining intraocular lens dioptric power assessed by interlaboratory tests.

PURPOSE: To describe a testing program conducted by a standards group as a guide for setting international tolerances for intraocular lens (IOL) dioptric power. SETTING: Multicenter study. METHODS: Seven biconvex, poly(methyl methacrylate) IOLs ranging in power from 10.00 through 30.00 diopter (D) were circulated among nine participating laboratories experienced in IOL optical measurements. Each laboratory performed repeated optical tests to determine dioptric power. These results were analyzed for repeatability and reproducibility in accordance with methods specified by the International Organization for Standardization. RESULTS: Intralaboratory repeatability was less than 0.5% of the dioptric power, and interlaboratory reproducibility, when following a normalized procedure for correction and conversion, was less than 1.0% of the dioptric power. CONCLUSION: Tolerance limits of +/0 0.30 D in the range 0 to 15.00 D, +/- 0.40 D for 15.50 to 25.00 D, and +/- 0.50 D for 25.50 to 30.00 D have been proposed as an international standard for IOLs. The contribution of IOL power error within the limits of the standard are estimated to contribute less than 1.0% to the total error in postoperative refractive prediction.

Construction of an ultrasound biopsy phantom.

The technique for construction of an agar-based ultrasound biopsy phantom is described. Features include tissue equivalent reflectivity, long life and non-shadowing targets. The phantom is useful for learning the necessary co-ordination between needle and probe for ultrasound needle guidance. This skill should initially be practised in vitro, on a device such as this.