Taylor Patch Research Articles

Abstract 1238: Comprehensive ctDNA monitoring provides early signal of clinical benefit with a novel personalized neoantigen directed immunotherapy for late-stage cancer patients

Abstract Neoantigen directed immunotherapy holds promise to increase the likelihood of patients with solid tumor devoid of immune infiltration benefiting from immune checkpoint immunotherapy (CPI). A heterologous prime-boost vaccination approach consisting of Chimpanzee Adenovirus (ChAd) prime and multiple self-amplifying mRNA (SAM) boosts, delivering 20 neoantigens, has been evaluated in a Phase 1/2 clinical trial in late-stage solid tumor patients in combination with nivolumab and ipilimumab (NCT03639714). Neoantigen dynamics, tumor burden and genomic correlates of response were studied over time in 20 patients (8 GEA, 2 NSCLC, 10 MSS-CRC). Exome sequences from archival (sample used for neoantigen selection), baseline (start of immunization) and on-treatment biopsies were analyzed for 20, 16 and 10 patients respectively. Paired pre- and post-vaccine tumor transcriptomes were analyzed for 6 patients. Personalized capture baits were designed for all non-synonymous mutations detected in archival biopsies (mean 146; range: 67-402) for ctDNA monitoring. Longitudinal ctDNA samples were collected monthly on treatment (mean 7; range: 1-18). ctDNA duplex UMI libraries were captured and sequenced to a target mean raw depth >80,000x and reduced to 3x per strand consensus duplex reads. The majority of vaccine neoantigens were detected in ctDNA (87%; range 45%-100%) and mean neoantigen variant allele frequency (VAF) strongly correlated with all monitored mutations VAF (R2 = 0.90, p < 0.0001) through treatment. The percentage of vaccine neoantigens detected was higher than that for all monitored mutations in the same samples with a median of 80% (21%-98%) in ctDNA and 70% (44%-100%) in biopsies. Five of 9 MSS-CRC patients with measurable baseline ctDNA achieved molecular responses (MR, >50% reduction in ctDNA from baseline) that correlated with OS and PFS, and in some patients, was accompanied by radiologic tumor shrinkage. One MSS-CRC patient with MR for >7 months acquired novel biallelic loss-of-function mutations in TAP1 following 1 year of study treatment. Differential gene expression analysis from paired pre- and post-vaccine biopsies (including 2 MSS-CRC pairs with MR) demonstrated significant upregulation in gene signatures associated with immune-inflamed tumor microenvironments including interferon alpha and gamma responses. We demonstrate that tumor-informed neoantigen selection and vaccine manufacturing while patients receive chemotherapy is feasible, since the majority of neoantigens are retained in the tumor post-chemotherapy. Further, neoantigen-directed immunotherapy appears to drive clinical benefit in patients with advanced MSS-CRC tumors, where CPI alone has provided minimal benefit. Comprehensive ctDNA longitudinal monitoring enables real time assessment of clinical response and acquired resistance. Citation Format: Desiree Schenck, Rita Zhou, Alexis Mantilla, Oliver Spiro, Taylor Patch, Adrienne Johnson, Daniel Navarro Gomez, Brian S. Henick, Chih-Yi Liao, Sameek Roychowdhury, Steve Maron, Benjamin Solomon, Alexander I. Spira, Daniel V. Catenacci, Andrew R. Fergusson, Raphael F. Rousseau, Karin Jooss, Matthew J. Davis. Comprehensive ctDNA monitoring provides early signal of clinical benefit with a novel personalized neoantigen directed immunotherapy for late-stage cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1238.

An accurate local average contact method for nonmatching meshes

The present paper deals with linear and quadratic finite element approximations of the two and three-dimensional unilateral contact problems between two elastic bodies with nonmatching meshes. We propose a simple noninterpenetration condition on the displacements which is local as the well known node-to-segment and node-to-face conditions and accurate like the mortar approach. This condition consists of averaging locally on a few elements the noninterpenetration. We prove optimal convergence rates in 2D and 3D using various linear and quadratic elements. The Taylor patch test and the Hertzian contact test illustrate the theoretical results and show the capabilities of the method.

Ruptured peroneal aneurysm after infrapopliteal prosthetic bypass with Taylor patch

IntroductionA 45-year-old mailman underwent an implantation of a femoro-peroneal polytetrafluoroethylene (PTFE) bypass with a distal Taylor patch six years prior to admission after two failed autologous reconstructions and extensive fasciotomy. The initial pathology was an acute ischemia due to popliteal entrapment with subsequent popliteal thrombectomy.ReportThe patient was examined because of pain, reduction of walking distance and development of a palpable mass at the medial fasciotomy site. A 6-cm pseudoaneurysm with complete disruption of the suture line of the vein patch was discovered and resected. Arterial continuity with a vein interposition graft was established using non-reversed cephalic vein.ConclusionThe etiology of the aneurysm is not entirely clear. One may argue that the fourth revascularization could have been performed with an arm vein instead of a prosthetic graft with the probability of a better long term patency in a young patient. 15 months after the procedure the bypass is patent and the patient is without any symptoms. This complication of a Taylor patch has not been reported before.

Distal Vein Patch as a Form of Autologus Modification for Infragenicular Prosthetic Bypass

Preferred graft for infragenicular bypass is autologus vein. The problem is when there is not available autologus vein. Literature suggest that in these situations, prosthetic graft with some form of modification of distal anastomosis with autogenic tissue is valuable adjunctive. Frequently used modifications are Miller's cuff, Taylor's patch and St. Mary's boot. Recently, there are reports on "Distal vein patch" as a form of autologus modification which, due to its simplicity and patency rate, attracted attention. The aim of this study was to evaluate benefits of this novel modification by comparing its patencies with other autologus modification of distal anastomosis. Study was performed on 60 patients, diabetics, with critical limb ischemia (CLI). Patients were divided in two groups: Group with distal vein patch modification; and group with some other form modification - control group. Patients were followed at least 22 months. We examined patency of grafts by physical examination or using Color Doppler. For statistical purposes we used KIaplan Meier analysis and curve. Significance was determined by Mann-Whitney, Fisher's exact, Pearsons chi square or Student T test as appropriate. P value less than 0,05 was considered significant. Groups were fairly matched relative to demographics, risk factors, operative intervention and distal anastomosis site. There was not statistical difference in two year primary patency between distal vein patch and control group--50% vs 53% respectivly (X2 = 0,08; p = 0,773). Also, there was not statistically significant difference in extremity survival (77% vs 77%) and patient survival between groups (89% vs 93%; X2 = 2,458; p = 0,117). This study proved equivalent patencies of infragenicular prosthetic bypasses performed using distal vein patch technique as with any other modification of distal anastomosis.

Invited commentary

Bosiers et al herein report the first clinical series of infrainguinal bypass with a new, heparin-bonded, expanded polytetrafluoroethylene (ePTFE) prosthesis. This option has now been added to the smorgasbord of options from which vascular surgeons may choose when performing infrainguinal bypass. The menu includes reversed, nonreversed, and in situ great and short saphenous vein; alternate (arm) vein; Dacron; heparin-bonded Dacron; human umbilical vein (HUV); Distaflo (Bard Peripheral Vascular, Inc, Tempe, Ariz) ePTFE; and standard ePTFE, to which one may add adjuncts such as a Miller cuff, St. Mary’s collar, Taylor patch, or distal arteriovenous fistula. Although this report is interesting and provocative, it represents at most a tantalizing tidbit on the smorgasbord of vascular grafts rather than a substantial main course. The study was conducted in a relatively low-risk group of patients and was limited by small sample size, short follow-up, and lack of a control group. Fifty-five of the 99 procedures were above-knee (AK) femoropopliteal (FP) bypasses, and 58 of the procedures were performed for claudication (Rutherford grade I, category 3); only 16 procedures were performed in patients with rest pain (grade II, category 4), and 26 bypasses were performed in individuals with minor tissue loss (category 5). Among 45 infrageniculate bypasses, the insertion site was the below-knee (BK) popliteal artery in 24 patients and a crural vessel in 21. Ten of 86 patients died during the first follow-up year, and 15 of 99 implanted grafts occluded during the first year after surgery, leaving small numbers of patients and grafts available for even short, 1-year follow-up. Reported, 1-year life-table primary patency rates were 84% for AK FP bypasses and 81% for BK FP grafts. The numbers were so small for the crural subgroup that the standard of error was >10% at both 6 and 12 months, making the Kaplan-Meier curve unreliable. Skeptics will note that almost any material performs well for the first 1 to 3 years in claudicants with an AK popliteal insertion site. At least three prospective, randomized trials have demonstrated equivalence between ePTFE and Dacron for AK FP bypass. Although a single study of 209 patients reported early improvement in FP graft patency for heparin-bonded Dacron compared with standard ePTFE at 3 years, by 5 years, results were equivalent. Randomized prospective trials have demonstrated that vein outperforms all prosthetic conduits for all infrainguinal insertion sites; while the demonstration of vein superiority in the AK position requires 3 to 5 years of follow-up, the superiority of vein over prosthetic has been readily demonstrated for BK FP and femorocrural bypasses with only 1 to 2 years of follow-up. A single study of PTFE with a Miller cuff for BK popliteal bypass reported dramatically improved 2-year patency (52% vs 29%) associated with the addition of a distal cuff. If the vascular surgeon of 2005 were to approach the infrainguinal graft smorgasbord and find that vein is unavailable, what conduit should he select? The present study will not help him reach a decision. Available in vitro animal studies suggest that heparin is detectable for up to 4 weeks on polyester Dacron grafts. Heparin activity has been reported to be measurable for up to 12 weeks on heparin-bonded ePTFE grafts. Whether this possibly longer duration of heparin activity confers increased thromboresistance as well as a patency advantage for heparin-bonded ePTFE grafts is uncertain. The clinical utility of this potentially promising off-the-shelf prosthesis will require prospective, randomized trials. Suitable control groups would include standard ePTFE, PTFE with a distal venous adjunct (cuff, collar, or patch), and perhaps ePTFE with a modified distal cuff such as Distaflo. Given the apparent aversion of vascular surgeons to prospective, randomized trials of infrainguinal bypass grafts, we may have to wait for quite a while before we know. Until then, the conduit choice in the absence of suitable vein remains a highly subjective matter of taste.

Numerical manifold method for dynamic nonlinear analysis of saturated porous media

It is well known that the Babuska–Brezzi stability criterion or the Zienkiewicz–Taylor patch test precludes the use of the finite elements with the same low order of interpolation for displacement and pore pressure in the nearly incompressible and undrained cases, unless some stabilization techniques are introduced for dynamic analysis of saturated porous medium where coupling occurs between the displacement of solid skeleton and pore pressure. The numerical manifold method (NMM), where the interpolation of displacement and pressure can be determined independently in an element for the solution of u–p formulation, is derived based on triangular mesh for the requirement of high accurate calculations from practical applications in the dynamic analysis of saturated porous materials. The matrices of equilibrium equations for the second-order displacement and the first-order pressure manifold method are given in detail for program coding. By close comparison with widely used finite element method, the NMM presents good stability for the coupling problems, particularly in the nearly incompressible and undrained cases. Numerical examples are given to illustrate the validity and stability of the manifold element developed. Copyright © 2006 John Wiley & Sons, Ltd.

On Reducing Abnormal Hemodynamics in the Femoral End-to-Side Anastomosis: The Influence of Mechanical Factors

This study was concerned with investigating the influence of mechanical factors on the hemodynamics of the end-to-side anastomosis in an attempt to identify critical factors and establish if it is possible to re-engineer existing, patient-specific, by-pass grafts with a view to increasing their patency. The study chose the femoral artery as the principal subject of interest. Wall shear stresses (WSS) and wall shear stress gradients (WSSG) were taken as the primary quantities of interest. Angle, graft calibre, interposition cuffs, proximal outflow and inlet waveform were studied. The study found that the use of cuffs and patches can significantly reduce abnormal WSS and WSSG by up to 70% when compared to a benchmark 45 degrees conventional anastomosis. The Taylor patch was found to be more robust in reducing peak WSS magnitudes and gradients than the Miller cuff, where design variables proved to be more critical. On the addition of a Taylor patch to a realistic end-to-side femoral anastomosis, the peak WSS and WSSG were found to be reduced by 27% and 57%, respectively. In conclusion, it is possible to use idealised models to identify critical disease influencing factors and to use these findings to reduce the effects of abnormal hemodynamics in realistic, patient-dependant models.

Flow pattern and shear stress distribution of distal end-to-side anastomoses. A comparison of the instantaneous velocity fields obtained by particle image velocimetry

Objective: To describe the local hemodynamics and pressure losses of crural bypass anastomoses using instantaneous velocity fields acquired by particle image velocimetry (PIV). Methods: Silastic models of a Taylor patch, a Miller cuff and a femoro-crural patch prosthesis (FCPP) were attached to a circuit driven by a Berlin Heart, providing a pulsatile flow with an amplitude of 450 to 25 ml/min (mean 200 ml/min). An outflow resistance of 0.5 mmHg/ml/min (peripheral resistance units, PRU) was modeled using small silastic tubes providing a phase shift of −12° between flow and pressure curves. The working fluid consisted of a glycerine/water mixture with a viscosity of 4 mPa s. Hollow glass spheres with a mean size of 9–13 μm were used as tracer particles. Instantaneous velocity fields were obtained by means of PIV and shear rates as well as shear stresses were calculated. Triggered by the flowmeter signal, 10 measurements at 100 ms intervals per cardiac cycle were obtained. The pressures were measured on the inflow and at both distal outflows. The resulting mean pressure losses due to flow separation and distal fluid acceleration were calculated. Results: Inside the Taylor patch anastomosis a large flow separation at the hood containing a clockwise rotating vortex was found. Additionally a smaller flow separation at the heel and a flow stagnation zone on the floor of the recipient artery were observed. Conversely, inside the Miller cuff a counterclockwise rotating vortex was seen inside a large heel flow separation. The FCPP also showed typical separation areas at the hood and heel of the anastomosis, although these were smaller compared to the other anastomoses. Inside the FCPP anastomosis no vortex creation was observed throughout the cardiac cycle. The mainstream velocities at the inlet levels were comparable for the three anastomoses. A significant fluid acceleration was present at the antegrade as well as the retrograde outlets of the Taylor and Miller cuff, while the fluid acceleration at the antegrade outflow of the FCPP was small, which was attributed to the end-to-end configuration of the antegrade FCPP leg. The calculated normalized antegrade and retrograde pressure losses for the Taylor form were 0.90 and 0.88, for the Miller cuff 0.89 and 0.86 and for the FCPP 0.94 and 0.86, respectively. The shear stresses inside the flow separations of the three anastomoses were significantly lower than normal wall shear stresses. High shear stress levels were found inside the transition zones between flow separation and high velocity mainstream. Conclusions: The flow pattern inside cuffed or funnel shaped anastomoses consists of large flow separation zones, which are thought to be associated with intimal hyperplasia development. In addition, fluid accelerations at the distal outlets result in pressure losses, which may contribute to impaired crural perfusion.

A new stabilized enhanced strain element with equal order of interpolation for soil consolidation problems

In order to accurately model the behaviour of geostructures it is usually not possible to neglect the interaction between the soil skeleton and the pore fluid. Classical finite element models taking into account this interaction are formulated in terms of the displacement and pore pressure fields and are based on the assumption that the fluid acceleration relative to the soil skeleton is negligible. This type of mixed problems is similar to others found in solid and fluid mechanics and might give rise to numerical instabilities unless certain requirements are met. There are two classical approaches to this problem. The first is usually known as the Zienkiewicz–Taylor patch test for mixed formulations. As a consequence of this test the interpolation degree of the displacement field is required to be higher than the corresponding one of the pressure field. Mathematically speaking this is a necessary condition for stability. The second approach, mathematically more involved, is usually known as the Babŭska–Brezzi inf–sup condition and constitutes a sufficient condition for stability. However it is possible to obtain stable formulations circumventing the interpolation degree requirement through the so-called stabilization techniques. These techniques were initially applied in the context of fluid mechanics and later extended to solid mechanics. This article presents a new formulation in which stabilization is achieved through an approach based on the Simo–Rifai enhanced strain element.

A fractional step algorithm allowing equal order of interpolation for coupled analysis of saturated soil problems

The accurate prediction of the behaviour of geostructures is based on the strong coupling between the pore fluid and the solid skeleton. If the relative acceleration of the fluid phase relative to the skeleton is neglected, the equations describing the problem can be written in terms of skeleton displacements (or velocities) and pore pressures. This mixed problem is similar to others found in solid and fluid dynamics. In the limit case of zero permeability and incompressibility of the fluid phase, the restrictions on the shape functions used to approximate displacements and pressures imposed by Babuska–Brezzi conditions or the Zienkiewicz–Taylor patch test hold. As a consequence, it is not possible to use directly elements with the same order of interpolation for the field variables. This paper proposes a generalization of the fractional-step method introduced by Chorin for fluid dynamics problems, which allows to circumvent BB restrictions in the incompressibility limit, thus making it possible to use elements with the same order of interpolation. Copyright © 2000 John Wiley & Sons, Ltd.

Vein patching reduces neointimal thickening associated with prosthetic graft implantation

Purpose: Modified anastomotic techniques utilizing autogenous vein-cuffs or patches have been devised with the hope of improving prosthetic graft patency. The mechanisms of the presumed improvement in patched anastomoses have never been elucidated and remain speculative. We characterized the healing response of the Taylor vein patch in prosthetic arteriovenous fistulae in a canine model of intimal hyperplasia. Methods: Six adult dogs underwent placement of bilateral (6 patched, 6 control) 4-mm diameter expanded polytetrafluoroethylene loop femoral artery-vein fistulae. Serial duplex ultrasound examinations confirmed graft patency until explant at 6 weeks. Differential light microscopy with computerized image analysis was performed on serial 5-μm sections. Intimal thickness through the venous anastomosis and outflow veins of Taylor patch and control (nonpatched) grafts were compared. Cell type-specific immunocytochemical antibody stains for smooth muscle cells (α SMC actin) and endothelial cells (von Willebrand factor) were performed. Results: Eleven of 12 grafts remained patent for 6 weeks, 1 control graft thrombosed. Mean duplex-derived peak systolic velocities of patched (96 cm/sec) and control (108 cm/sec) grafts were similar. Microscopy revealed more intimal pannus anastomotic suture line ingrowth in controls (mean thickness = 178 μm) than Taylor patched grafts (mean 147 μm, p = 0.0002). Significantly less intimal thickening was present in the outflow vein of patched (mean thickness = 90 μm) versus control grafts (mean 195 μm, P <0.0001). The intima maintained a single cell layer of vWF + endothelial cells, while the majority of the cells comprising the lesion expressed α SMC actin. Conclusion: Perianastomotic pannus is primarily composed of intimal smooth muscle cells. Neointimal thickening is significantly reduced in prosthetic arteriovenous fistulae created with the Taylor vein patch in a canine model. Reduction in perianastomotic intimal thickening may explain the reported clinical improvement in prosthetic bypass graft patency when modified with vein patch techniques.

26.18 Long term follow up of infrageniculate PTFE bypass coupled with an autogenous remote distal arteriovenous fistula

Although the quality of the distal run-off has been considered as an important factor affecting the success of bypass grafting, reasonable results have nevertheless been reported for bypass grafts to a popliteal artery with no direct communication with the tibial or peroneal vessels (isolated popliteal segment, IPS). The use of autogenous vein has produced the best results in this situation with most authors finding polytetrafluoroethylene (PTFE) less satisfactory. Improved results have nevertheless been shown for femoro-popliteal and femorotibial PTFE grafts by the incorporation of vein patches into the anastomoses. In this paper, the influence of this technique on the patency of PTFE grafts to IPS is evaluated. Thirty-three PTFE grafts to an IPS and 67 to the below knee (BK) popliteal artery with one or more run-off vessels were studied. All IPS grafts were carried out for limb salvage and in the BK popliteal group, 46 (69%) were for limb salvage and 21 (31%) were for severe claudication. Groups were matched in terms of age, smoking history and prevalence of diabetes mellitus. Cumulative patency rates of 84% at 1 year and 76% at 3 years were achieved in the IPS group compared to 90 and 81% for the BK popliteal group with one or more run-off vessels. Using the Taylor patch technique, comparable 3 year patency rates can be expected for PTFE grafts to IPSs and to BK popliteal arteries with patent tibial or peroneal run-off.

Hemodynamic simulations and computer-aided designs of graft-artery junctions.

Severe occlusion of graft-artery junctions due to restenosis, e.g., excessive tissue overgrowth and renewed plaque formation, may occur within a few months or years after bypass surgery. Our hypothesis is that nonuniform hemodynamics, represented by large sustained wall shear stress gradients, trigger abnormal biological processes leading to rapid restenosis and hence early graft failure. In turn, this problem may be significantly mitigated by designing graft-artery bypass configurations for which the wall shear stress gradient (WSSG) is approximately zero and hence nearly uniform hemodynamics are achieved. Focusing on the distal end of several femoral artery bypass junctions, a validated finite volume code has been used to compute the transient three-dimensional velocity vector fields and its first and second surface derivatives in order to test the idea. Specifically, it is shown that the Taylor patch, which generates higher patency rates than standard end-to-side anastomoses, exhibits lower WSSG levels than standard configurations, and that further geometric design improvements reduce the WSSG in magnitude and local extent even more.

Computational design of a bypass graft that minimizes wall shear stress gradients in the region of the distal anastomosis.

Recent experimental and theoretic studies show that large wall shear stress gradients characterize disturbed flow patterns associated with the location of myointimal hyperplasia, atheroma, or both. Graft-to-artery anastomoses that minimize wall shear stress gradients may reduce the degree of myointimal development and the propensity for thrombosis. This study analyzes the distribution of distal anastomotic wall shear stress gradients for conventional geometries and for the optimized geometry assuming idealized merging of the graft with the artery. A validated computational fluid dynamics program was used to solve the transient three-dimensional partial differential equations and auxiliary equations that describe laminar incompressible blood flow. Time-averaged wall shear stresses and wall shear stress gradients were calculated for three distal graft-artery anastomoses: a standard end-to-side, a Taylor patch, and an optimized geometry. The latter was obtained iteratively by minimizing the local wall shear stress gradients and was analyzed under resting and exercise inflow waveforms. Both the standard and Taylor patch anastomoses have relatively high wall shear stress gradients in the regions of the toe and heel. For all flow inputs studied nonuniform hemodynamics in the optimized graft design are largely eliminated, and the time-averaged wall shear stress gradients are greatly reduced throughout the anastomotic zone. At resting flow the Taylor patch produces slightly lower wall shear stress gradients in the anastomotic region than the standard end-to-side anastomosis. The optimized design reduces wall shear stress gradients to almost one half of that of the standard and Taylor patch geometries. At exercise flow wall shear stress gradients almost triple in the standard anastomosis and increase approximately 30% in the Taylor patch. In contrast, the geometrically optimized design is basically independent of the type of flow input waveform in terms of time-averaged wall shear stress gradients and disturbed flow patterns. This study demonstrates that it is possible to design a terminal graft geometry for an end-to-side anastomosis that significantly reduces wall shear stress gradients. If the wall shear stress gradient is confirmed to be a major hemodynamic determinant of intimal hyperplasia and restenosis, these results may point to the design of optimal bypass graft geometries.

Vascular surgery

Vascular surgery Robert B. Rutherford, Philadelphia, 1995, WB Saunders, 2240 pages, $260. A correspondent apologized for writing a long letter with the excuse that he had no time to write a short one. The 14 editors of this enormous and successful book, struggling to martial an army of 181 experts into 2000 pages of text by a common deadline, will know just what he meant. The casual reader will be tempted to admire this book on grounds of labor and size alone, and the diligent will identify significant improvements since the previous edition of 1989 when there were only 159 contributors. Many chapters give authoritative help with clarity and economy. A few, including some by editors who should know better, are gridlocked with an abundance of unprocessed data posing as useful information. A textbook should try to represent all aspects of vascular surgery from its academic peaks to its idiosyncratic troughs, but we must judge it by the standards of analytical rigor and efficient access. Many chapters include historical vignettes that range from the intriguing (Jobst in the swimming pool), through the regurgitated (Hunter's observations on the antler), to the traditional but incomplete (sympathectomy). Worthy ancestors are sometimes neglected, as in the description of Homan's operation, whereas ghosts of the past, like renal ptosis, are given more respect than they deserve. Some contributors include techniques that really should be history, such as the Unna boot and the use of isotopes to determine amputation level. Occasionally we have a glimpse of history in the making as when attractive but discredited ideas are recycled without evidence. The quality of a chapter is often well illustrated by its tables. Many are exemplary ("Intermittent laudication"), but a few are marred by significant omissions, and the European literature is frequently neglected. Because tabulated errors are more influential than bias concealed in prose, the editors need comprehensive knowledge and vigilance to avoid them. The rules for life-table analysis are given in the text, but editors have nonetheless allowed them to be broken (endarterectomy) and have also allowed statements that are blatantly clumsy ("long in length"), unhelpful because unqualified ("acute renal dysfunction varies from 0% to 92%"), or simply wrong (amputation [is] inevitable in critical ischemia). Hazards should be fully acknowledged. This is particularly important when a difficult operation with uncertain indications has been popularized by easier endoscopic access. Compensatory hyperhidrosis after sympathectomy can be serious. Radiologic changes in the bones with severe sympathetic dystrophy deserve a showing. Not unnaturally, enthusiasts are well represented in this text, but some of their recommendations, for example redissecting the distal anastomosis of a failed bypass graft rather than looking elsewhere, are hard for ordinary folk to understand. Many chapters incorporate useful summaries. Rutherford's own on extracranial fibromuscular dysplasia is an excellent example, but not all authors conform to this style, and greater uniformity would make access easier. References are numerous and should be more selective. They should certainly be disciplined into alphabetical or text order and not both at once. In one chapter, 50% of the references are by the author himself and, in another, an author cites an unpublished previous communication written by himself. The index is as comprehensive as a computer-generated list can be but also gives rise to some interesting concepts ("occupation – see also disability") and omits personal references that might be useful, such as the Taylor patch, although that is referred to in the text. Illustrations are copious. Some should be cropped, and clinical illustrations deserve color. It is surprising to find the few color plates printed remote from the relevant text. Some illustrations are redundant, and one might be calculated to deceive because it is a mirror image of another printed four pages previously. Twelve diagrams of stump bandaging are 12 too many. With such a vast undertaking, lapses in editorial control over the volunteer army are inevitable, but the quality of the best chapters is outstanding, such as those on hemodynamics and visceral ischemia. Now is the time for the supreme commander to martial his generals, retire a few, and discipline the others so that they achieve the high standards set by the best. This fourth edition is bigger and better than the third. The real challenge, as every correspondent knows, is to make the fifth edition smaller and better.

PTFE bypass grafting to isolated popliteal segments in critical limb ischaemia

Although the quality of the distal run-off has been considered as an important factor affecting the success of bypass grafting, reasonable results have nevertheless been reported for bypass grafts to a popliteal artery with no direct communication with the tibial or peroneal vessels (isolated popliteal segment, IPS). The use of autogenous vein has produced the best results in this situation with most authors finding polytetrafluoroethylene (PTFE) less satisfactory. Improved results have nevertheless been shown for femoropopliteal and femorotibial PTFE grafts by the incorporation of vein patches into the anastomoses. In this paper, the influence of this technique on the patency of PTFE grafts to IPS is evaluated. Thirty-three PTFE grafts to an IPS and 67 to the below knee (BK) popliteal artery with one or more run-off vessels were studied. All IPS grafts were carried out for limb salvage and in the BK popliteal group, 46 (69%) were for limb salvage and 21 (31%) were for severe claudication. Groups were matched in terms of age, smoking history and prevalence of diabetes mellitus. Cumulative patency rates of 84% at 1 year and 76% at 3 years were achieved in the IPS group compared to 90 and 81% for the BK popliteal group with one or more run-off vessels. Using the Taylor patch technique, comparable 3 year patency rates can be expected for PTFE grafts to IPSs and to BK popliteal arteries with patient tibial or peroneal run-off.

PTFE, collars, and patches.

The results of PTFE grafts to crural vessels have been sufficiently poor for some surgeons to consider primary amputation for critical ischemia in the absence of suitable lengths of autologous vein from arm or leg. However, the results of two anastomotic techniques using a short segment of interposed vein, are encouraging. We have attained 1-year patency rates of 74% (n = 72) using PTFE with the Taylor patch technique (personal communication) and 47% (n = 27) using PTFE with Miller collar anastomoses to distal crural vessels. To investigate the hemodynamic benefit of these techniques, they have been tested (using a pulsatile flow model incorporating standard pressure, viscosity, graft and vessel length, and anastomotic angle) against a standard end-to-side PTFE anastomosis to cadaver internal mammary artery. There was no significant difference in flow between the anastomotic methods. Downstream resistance was dictated by the diameter of the recipient vessel providing a vein interposition technique was used (r greater than .80), but this relationship was lost if a direct PTFE-arterial anastomosis was performed (r = .06), suggesting additional anastomotic resistance in the latter. This constitutes experimental evidence to suggest that direct PTFE-arterial anastomosis risks hemodynamically important technical errors, which are avoidable by the use of either the Miller collar or Taylor patch.

Experimental evidence to support the use of interposition vein collars/patches in distal PTFE anastomoses

We have conducted three in vitro experiments (using cadaver internal mammary artery as a model for crural artery), which establish the advantage of the Miller collar and Taylor patch over direct PTFE-artery anastomoses: (1) A new method of simultaneously measuring longitudinal and circumferential elasticity in human saphenous vein (n = 16) has demonstrated the latter to be anisotropic (i.e.: greater longitudinal than transverse compliance, P less than 0.002). This suggests that benefit may be gained by aligning the saphenous vein's longitudinal axis with that of the arteriotomy--a feature of both vein interposition anastomoses. (2) We have compared maximal pulsatile and constant flow across each type of anastomosis (n = 10 of each) using a flow model incorporating standard pressure, viscosity, graft and outflow vessel length, and anastomotic angle. This experiment has demonstrated loss of anastomotic reliability only in direct PTFE-artery anastomoses (i.e. no correlation between flow and vessel diameter, r = 0.04). (3) Casts of the internal anatomy of the anastomoses (n = 10 of each) have demonstrated a greater degree of oval distortion of the toe of the outflow vessel of direct PTFE-artery anastomoses than either of the other techniques (P less than 0.01). This experimental evidence suggests that both of these vein interposition techniques optimise the mechanical properties of saphenous vein and protect small arteries from anastomotic distortion. These benefits do not occur with direct PTFE-artery anastomoses.