Influence of Molecular Status on Recurrence Site in Patients Treated for a Stage III Colon Cancer: a Post Hoc Analysis of the PETACC-8 Trial.

BACKGROUND: Recurrence patterns in stage III colon cancer (CC) patients according to molecular markers remain unclear. The objective of the study was to assess recurrence patterns according to microsatellite instability (MSI), RAS and BRAFV600E status in stage III CC patients. METHODS: All stage III CC patients from the PETACC-8 randomized trial tested for MSI, RAS and BRAFV600E status were included. The site and characteristics of recurrence were analyzed according to molecular status. Survival after recurrence (SAR) was analyzed. RESULTS: A total of 1650 patients were included. Recurrence occurred in 434 patients (26.3%). Microsatellite stable (MSS) patients had a significantly higher recurrence rate (27.2% vs. 18.7%, P = 0.02) with a trend to more pulmonary recurrence (28.8% vs. 12.9%, P = 0.06) when compared to MSI patients. MSI patients experienced more regional lymph nodes compared to MSS (12.9% vs. 4%, P = 0.046). In the MSS population, the recurrence rate was significantly higher in RAS (32.2%) or BRAF (32.3%) patients when compared to double wild-type patients (19.9%) (p < 0.001); no preferential site of recurrence was observed according to RAS and BRAFV600E mutations. Finally, decreased SAR was observed in the case of peritoneal recurrence or more than two recurrence sites. CONCLUSIONS: Microsatellite, RAS and BRAFV600E status influences recurrence rates in stage III CC patients. However, only microsatellite status seems to be associated with specific recurrence patterns. More than two recurrence sites and recurrence in the peritoneum were associated with poorer SAR.

Inter-mesenteric connections between the superior and inferior mesenteric arteries for left colonic vascularization: implications for colorectal surgery.

PURPOSE: There is confusion regarding the names, the number, and the exact location of the colonic arterial arches which provide connections between the superior and inferior (IMA) mesenteric arteries at the level of the left colic angle. The aim of this review was to delineate the "true" colic arches arising in the meso of the left colic angle and to describe their surgical implications. METHODS: A systematic review of the literature was performed using the MEDLINE database. The search included only human studies between 1913 and 2018. All dissection, angiographic, arterial cast and corrosion studies were analyzed. RESULTS: The terms "Riolan arch", "marginal artery of Drummond", "meandering mesenteric artery" and "Villemin's arch" must no longer be used in the scientific literature. Three arterial arches were found at the level of the left colic angle, permitting the communication between the two arterial mesenteric systems: (1) the Marginal Artery (the most peripheral, found in 100% of cases); (2) the "V" termination of the ascending branch of the left colic artery (LCA), existing in more than 2/3 of cases; and (3) the inter-mesenteric trunk, found more centrally located and existing in less than 1/3 of cases. CONCLUSIONS: Three arterial arches exist at the level of the left colic angle: (1) the Marginal Artery, (2) the "V" termination of the ascending branch of the LCA, and (3) the inter-mesenteric trunk. The knowledge of this anatomy is essential for performing colorectal surgeries involving ligation of the IMA.

Technical difficulties of left colic artery preservation during left colectomy for colon cancer.

PURPOSE: Low-tie ligation in colorectal cancer surgery is associated with technical difficulties in left colic artery preservation. We aimed to evaluate and classify the anatomical and technical difficulties of left colic artery (LCA) preservation at its origin and along its route at the inferior border of the pancreas. METHODS: A vascular reconstruction computed tomography prospective series of 113 patients was analyzed. The inferior mesenteric artery (IMA) branching pattern according to Latarjet's classification (Type I, separate LCA origin, Type II, fan-shaped branching pattern) and the distances between the IMA and the LCA origins and between the LCA and the Inferior mesenteric vein (IMV) at the inferior border of the pancreas were measured. RESULTS: The IMA branching pattern was Type I in 80 (71 %) patients and Type II in 33 (29 %) patients. The IMA-LCA distance was 39.8 ± 12.2 mm. The LCA-IMV distance at the inferior border of the pancreas was 20.5 ± 21.7 mm. When classified based on this distance, 75 (66 %) patients were classified into the Near subgroup (<20 mm) (7.7 ± 4.1 mm) and 38 (34 %) into the Far subgroup (≥20 mm) (45.6 ± 20.4 mm, p < 0.001). A Type I subgroup F accounted for 27 % of the patients. CONCLUSIONS: Left colic artery preservation is highly feasible at its origin in more than two-thirds of cases due to the separate origin. The addition of a high IMV ligation increases the risk of damage to the LCA at the inferior border of the pancreas because the distance to the IMV is less than 20 mm in two-thirds of cases.

Management of acute sigmoid volvulus: short- and long-term results.

AIM: The best form of prophylactic management of a decompressed sigmoid volvulus (SV) is controversial especially in the elderly. We have studied our experience with this condition to assess the short- and long-term results of SV management. METHOD: All patients treated for SV in our department between 2003 and 2013 were retrospectively included. Emergency decompression was attempted in all patients in whom there was no sign of peritonitis. Planned surgical resection was the procedure of choice in young patients. Percutaneous endoscopic colopexy (PEC) was used in high surgical risk patients. RESULTS: There were 65 patients (45 males) of median age 71.5 (24-99) years. Non-surgical reduction was performed in 62 with a success rate of 95% (59/62). Recurrence after initial decompression was 67% at a median follow-up of 5 (1-14) years. A prophylactic surgical resection was performed with primary anastomosis in 33 patients. There were no deaths and the major morbidity rate was 6%. At a mean follow-up of 62 months, only 1 (3%) patient had had a recurrence (at 130 months). PEC was performed in six patients of median age 90 (84-99) years and with a median American Society of Anesthesiologists score of 4. Complications included local site infection (n = 2), pain (n = 1) and abdominal wall bleeding (n = 1). After a median follow-up of 2 (1-4) years, three patients died from medical causes and one recurrence occurred 13 months after removal of the PEC tube. CONCLUSION: Prophylactic treatment after initial decompression of SV results in a low rate of recurrence. Planned sigmoid resection is safe and effective. In frail elderly patients, PEC is satisfactory.

[Pronostic value of parenchyma renal invasion of pT3 upper tract urinary carcinoma]. / Impact pronostique de l'envahissement du parenchyme rénal dans la population des tumeurs de la voie excrétrice urinaire supérieure de stade pT3.

INTRODUCTION: Upper tract urinary carcinoma (UTUC) pT3 tumors are a heterogeneous entity including tumors invading the renal parenchyma, tumors with peripelvic fat invasion or peri-ureteral fat invasion. The aim of this study was to evaluate the prognostic significance of these three different groups of pT3 tumors. PATIENTS AND METHODS: Between 1998 and 2012, 205 patients with UTUC were operated in two centers, including 52 patients with pT3 tumor stage. pT3 tumors were divided into three groups: peri-ureteral fat invasion (pT3U, n = 16), peripelvic fat invasion (pT3G, n = 21), and renal parenchyma invasion (pT3P, n = 15). The prognostic significance of the type of tumor infiltration was evaluated on specific and disease-free survival. RESULTS: Median follow-up was 18.9 months [6-133.4]. In univariate analysis, renal parenchyma invasion was associated with a better prognostic in both specific (P = 0.026) and disease-free survival (P = 0.031) compared with peripelvic or peri-ureteral fat invasion. Mutivariate analysis retained the pT3 subgroup as an independant prognostic factor in both specific and disease-free survival (P = 0.02). CONCLUSION: pT3 tumors with renal parenchyma invasion had a better prognosis than those with peripelvic or peri-ureteral fat invasion. The heterogeneity of the pT3 group should be taken into account to improve the care of patients.

Surgeon eye lens dose monitoring in interventional neuroradiology, cardiovascular and radiology procedures.

PURPOSE: This study investigated the radiation dose to surgeon eye lens for single procedure and normalised to exposure parameters for eight selected neuroradiology, cardiovascular and radiology interventional procedures. METHODS: The procedures investigated were diagnostic study, Arteriovenous Malformations treatment (AVM) and aneurysm embolization for neuroradiology procedures, Coronary Angiography and Percutaneous Transluminal Coronary Angioplasty (CA-PTCA), Pacemaker and Implantable Cardioverter-Defibrillator implantation (PM-ICD), Endovascular Aortic Repair (EVAR) and Fenestrated Endovascular Aortic Repair (FEVAR) for cardiovascular and electrophysiology procedures. CT-guided lung biopsy was also monitored. All procedures were performed with table-mounted and ceiling-suspended shields (0.5 mm lead equivalent thickness), except for FEVAR and PM-ICD where only a table mounted shield was present, and CT-guided lung biopsy where no shield was used. Dose assessment was performed using a dosemeter positioned close to the most exposed eye of the surgeon, outside the protective eyewear. RESULTS: The surgeon most exposed eye lens median Hp(3) equivalent dose for a single procedure, without protective eyewear contribution, was 18 µSv for neuroradiology diagnostic study, 62 µSv for AVM, 38 µSv for aneurysm embolization, 33 µSv for CA-PTCA, 39 µSv for PM-ICD, 49 µSv for EVAR, 2500 µSv for FEVAR, 153 µSv for CT-guided lung biopsy. CONCLUSIONS: In interventional procedures, the 20 mSv/year dose limit for surgeon eye lens exposure might be exceeded if shields or protective eyewear are not used. Surgeon eye lens doses, normalised to single procedures and to exposure parameters, are a valuable tool for determining appropriate radiation protection measures and dedicated eye lens dosemeter assignment.

Operating room hygiene: Clinical practice recommendations.

INTRODUCTION: The French Society of Gastro-Intestinal Surgery (SociétéFrançaisedeChirurgieDigestive) and the Association of hepato-bilio-pancreatic and transplantation surgery (AssociationdeChirurgieHépato-Bilio-PancréatiqueetTransplantation) requested that clinical practice recommendations be established with regard to operating room hygiene. METHODS: The literature was analyzed according to the High Authority of Health (HauteAutoritédesanté [HAS]) methodology and after consultation of the Cochrane and Medline databases. Pertinent references were selected, and supplementary references were hand-picked from the reference lists. Only English or French language papers were retained. The recommendations of learned societies and the World Health Organization were also considered. RESULTS: Recommendations were proposed with regard to pre-operative patient preparation, skin preparation, draping, wound edge protectors, surgeon hygiene, wound closure, and operating room environment. CONCLUSION: These clinical practice recommendations should guide and improve the daily practice of gastro-intestinal surgeons.

Measurement of the microstructural fracture toughness of cortical bone using indentation fracture.

The purpose of this work is to investigate the use of indentation fracture as a method of measuring toughness at the microscale in cortical bone. Indentation fracture employs sharp indenters to initiate cracks, whose length can be used to calculate the toughness of the material. Only a cube corner indenter tip is found to initiate cracks at a suitable size scale for microstructural measurement. Cracks from 7 to 56 microm in length are produced using loads from 0.05 to 3N. Preliminary data predicts rising toughness with increasing crack length (rising R-curve behaviour) at the microscale. This technique provides a new insight into fracture in cortical bone since it allows the investigator to observe mechanisms and measure toughness at a size scale at which in vivo damage is known to exist.

Finite element comparison of performance related characteristics of balloon expandable stents.

Cardiovascular stents are commonly made from 316L stainless steel and are deployed within stenosed arterial lesions using balloon expansion. Deployment involves inflating the balloon and plastically deforming the stent until the required diameter is obtained. This plastic deformation induces static stresses in the stent, which will remain for the lifetime of the device. In order to determine these stresses, finite element models of the unit cells of geometrically different, commercially available balloon expandable stents have been created, and deployment and elastic recoil have been simulated. In this work the residual stresses associated with deployment and recoil are compared for the various stent geometries, with a view to establishing appropriate initial stress states for fatigue loading for the stents. The maximum, minimum, and mean stresses induced in the stent due to systolic/diastolic pressure are evaluated, as are performance measures such as radial and longitudinal recoil.

Micromechanical modelling of cortical bone.

Cortical bone is a heterogeneous material with a complex hierarchical microstructure. In this work, unit cell finite element models were developed to investigate the effect of microstructural morphology on the macroscopic properties of cortical bone. The effect of lacunar and vascular porosities, percentage of osteonal bone and orientation of the Haversian system on the macroscopic elastic moduli and Poisson's ratios was investigated. The results presented provide relationships for applying more locally accurate material properties to larger scale and whole bone models of varying porosity. Analysis of the effect of the orientation of the Haversian system showed that its effects should not be neglected in larger scale models. This study also provides insight into how microstructural features effect local distributions and cause a strain magnification effect. Limitations in applying the unit cell methodology approach to bone are also discussed.

Improvements in CVD diamond properties for radiotherapy dosimetry.

The goal of this work was to compare the behaviour of a chemical vapour deposited (CVD) diamond sample, grown at the University of Florence using a local procedure, with that of a commercial CVD diamond. The comparison was performed exposing both systems to 25 MV photons and measuring the current response during irradiation. Properties of dosimetric interest such as stability of response, dose rate dependence and rise time were investigated. After a preliminary study, which evidenced better performances of the commercial device with respect to the local CVD diamond, the latter was irradiated with a high fluence of fast neutrons. As a result of the neutron treatment, the quality of the CVD home-made diamond has been improved to match with that of the commercial dosemeter.

The effect of crystallographic texture on stress-induced martensitic transformation in NiTi: A computational analysis.

NiTi׳s superelasticity is exploited in a number of biomedical devices, in particular self-expanding endovascular stents. These stents are often laser-cut from textured micro-tubing; texture is the distribution of crystallographic grain orientations in a polycrystalline material which has been experimentally shown to have a marked influence on mechanical properties. This study offers a computational examination into the effect of texture on the stress-induced martensite transformation (SIMT) in a micro-dogbone NiTi specimen subject to tensile loading. Finite Element Analysis (FEA) is employed to simulate the transformational behaviour of the specimen on a micro-scale level. To represent a realistic grain structure in the FEA model, grains present in a 200µm×290µm test site located at the centre edge of the specimen were identified using Scanning Electron Microscopy (SEM). Grains are assumed to have homogenous behaviour with properties varying according to their crystallographic orientation to the loading direction. Required material properties were extracted from uniaxial stress-strain curves of single crystals for each crystallographic orientation for input into the in-built UMAT/Nitinol. The orientation of each grain in the test site was identified using Electron Back-Scatter Diffraction (EBSD) techniques. In this way, a quantitative explanation is offered to the effect of crystallographic texture on SIMT. Finally, the evolution of grains in the specimen, during the transformation process, was experimentally investigated by means of an in-situ SEM tensile test.

Evaluation of cover effects on bare stent mechanical response.

Covered tracheobronchial stents are used to prevent tumour growth from reoccluding the airways. In the present work a combination of experimental and computational methods are used to present the mechanical effects that adhered covers can have on stent performance. A prototype tracheobronchial stent is characterised in bare and covered configurations using radial force, flat plate and a novel non-uniform radial force test, while computational modelling is performed in parallel to extensively inform the physical testing. Results of the study show that cover configuration can have a significant structural effect on stent performance, and that stent response (bare or covered) is especially loading specific, highlighting that the loading configuration that a stent is about to be subjected to should be considered before stent implantation.

[Considerations concerning respiratory physiopathology in a case of total arhinia]. / Considerazioni di fisiopatologia respiratoria a proposito di un caso di arina.

The Authors describe their personal experience in a rare case of total arhinia in a young boy, now seven years old, whose psycho-physical development is normal and who is healthy except for recurrent conjunctivitis due to the absence of nasolacrimal ducts. The Authors consider the possibility that in the case of total absence of the nasal function, as in total arhinia, the oropharyngeal and laryngotracheobronchial mucosa may acquire those functional and defensive properties typically belonging to nasal mucosa. In the subject in question, in fact, functional respiratory and immunosecretory parameters are normal. On the other hand, being well known how problematic acquired severely compromised nasal functions are one would think that only in the case of congenital absence of the nose can the lower aerodigestive structures compensate successfully. In the Authors' opinion this clinic observation contradicts the widely held belief that nasal respiration is absolutely necessary from the moment of birth on.

Nitinol stent design - understanding axial buckling.

Nitinol׳s superelastic properties permit self-expanding stents to be crimped without plastic deformation, but its nonlinear properties can contribute towards stent buckling. This study investigates the axial buckling of a prototype tracheobronchial nitinol stent design during crimping, with the objective of eliminating buckling from the design. To capture the stent buckling mechanism a computational model of a radial force test is simulated, where small geometric defects are introduced to remove symmetry and allow buckling to occur. With the buckling mechanism ascertained, a sensitivity study is carried out to examine the effect that the transitional plateau region of the nitinol loading curve has on stent stability. Results of this analysis are then used to redesign the stent and remove buckling. It is found that the transitional plateau region can have a significant effect on the stability of a stent during crimping, and by reducing the amount of transitional material within the stent hinges during loading the stability of a nitinol stent can be increased.

BioInnovate Ireland--fostering entrepreneurial activity through medical device innovation training.

In the midst of a rich environment for medical device development and manufacturing, universities can play a critical role by developing relevant training programs to produce entrepreneurs who can be efficient and successful in creating early stage companies by understanding deeply the issues involved in creating a useful device, how to raise money, designing early clinical studies and locating manufacturing partners.

Differences in the crack resistance of interstitial, osteonal and trabecular bone tissue.

The purpose of this work was to investigate differences which may exist in the crack resistance of the microstructural bone tissues, i.e., osteonal, interstitial and trabecular bone. Indentations, using varying loads were used to initiate cracks of the same size scale as those which exist habitually in bone. The crack lengths and corresponding toughness values are presented for each of the tissues. Specimens were prepared using standard nanoindentation preparation techniques. Young's modulus and hardness were measured using a Berkovich tip, while cracks were produced using a cube-corner tip. Crack lengths were subsequently measured using scanning electron microscopy. Cracks produced at the same loads were significantly longer in trabecular bone than in interstitial and osteonal cortical bone. Similarly, within individual subjects, cracks produced in interstitial bone were longer than those produced in osteonal bone. These results provide significant experimental evidence that bone microstructural tissues exhibit differing resistance to crack growth and may help explain the incidence of more microcracks in interstitial than osteonal bone. The ability of the technique to distinguish differences between individual bone tissues is promising in an area where the focus has switched to the microscale, and in particular, to measures bone quality.

Calibration of a constitutive model for the post-yield behaviour of cortical bone.

In this work, the post-yield behaviour of cortical bone is investigated using finite element modelling, nanoindentation and atomic force microscopy. Based on recent investigations, it is proposed that, since pressure dependent deformation mechanisms may contribute to yielding in bone, constitutive models attempting to capture its post-yield behaviour should also incorporate pressure dependence. Nanoindentation testing is performed using a spheroconical indenter tip, and subsequent atomic force microscopy at the indented site shows that bone does not exhibit surface pile-up. By simulating the nanoindentation test, it is found that a Mises based constitutive law cannot simultaneously capture the deformations and load-displacement curve produced during nanoindentation. However, an extended Drucker-Prager model can capture the post-yield behaviour of bone accurately, since it accounts for pressure dependent yield. This suggests that frictional mechanisms are central to the post-yield behaviour of bone. In this work, the extended Drucker-Prager model is calibrated and validated using further simulations.