Completion of the informed consent in radioguided surgery by the General Surgery and Nuclear Medicine services of a radioguided surgery unit.

OBJECTIVE: To identify the frequency of errors in informed consent documents in radioguided surgery in a third level hospital and to detect possible causes or factors associated with a greater risk of error. MATERIAL AND METHODS: Informed consent forms of a total of 369 radioguided surgery interventions, completed by the Nuclear Medicine and General Surgery services, were analyzed, and the degree of completion of the forms and its correlation with the physicians responsible, type of pathology, intervention, and waiting time were compared with the completion of consent by another specialty. RESULTS: Errors were identified in 22 consent forms from Nuclear Medicine and 71 from General Surgery. The most common error was the absence of identification of the physician responsible (17 in Nuclear Medicine, 51 in General Surgery), and the second most common was the absence of a document (2 in Nuclear Medicine, 20 in General Surgery). There were significant differences in the errors made depending on the doctor in charge, with no significant correlation with the other variables. CONCLUSIONS: The physicians responsible were the main factor associated with a greater risk of error in the completion of informed consent forms. Further studies are needed to analyze the causal factors and possible interventions to minimize errors.

2-years retrospective observational case-control study on survival and marginal bone loss of implants in patients with hereditary coagulopathies.

BACKGROUND: Evaluating 2-years implant loss and marginal bone loss in patients with hereditary coagulopathies, comparing with a healthy control group. MATERIAL AND METHODS: 37 implants in 13 patients (17 haemophilia A, 20 Von-Willebrand disease) versus 26 implants in 13 healthy patients. Data measured through Lagervall-Jansson index (after surgery, at prosthetic loading, at 2 years). STATISTICS: Chi-square, Haberman's, ANOVA, Mann-Whitney-U. Significance p<0.05. RESULTS: Haemorrhagic accidents in 2 coagulopathies patients (non-statistical differences). Hereditary coagulopathies patients suffered more hepatitis (p<0.05), HIV (p<0.05) and less previous periodontitis (p<0.01). Non-statistical differences in marginal bone loss among groups. 2 implants were lost in the hereditary coagulopathies and none in the control group (non-statistical differences). Hereditary coagulopathies patients had longer (p<0.001), and narrower implants (p<0.05) placed. 43.2% external prosthetic connection in hereditary coagulopathies patients (p<0.001); change of prosthetic platform more frequent in control group (p<0.05). 2 implants lost: external connection (p<0.05). Survival rate 96.8% (hereditary coagulopathies 94.6%, control group 100%). CONCLUSIONS: Implant and marginal bone loss at 2 years is similar in patients with hereditary coagulopathies and control group. Precautions should be taken on the treatment for hereditary coagulopathies patients, through prior haematological protocol. Implant loss only occurred in in a patient with Von-Willebrand´s disease.

Exposure to Cigarette Smoke Impedes Human Osteoblast Differentiation Independently of Nicotine.

INTRODUCTION: Tobacco smoking has been implicated in an array of adverse health outcomes, including those that affect adult bone. However, little is known about the impact of tobacco products on developing bone tissue as it develops in the embryo. AIMS AND METHODS: Here, human embryonic stem cells were differentiated into osteoblasts in vitro and concomitantly exposed to various concentrations of smoke solutions from two conventional, one additive-free and two harm-reduction brands of cigarettes. Differentiation inhibition was determined by calcium assays that quantified matrix mineralization and compared to the cytotoxicity of the tobacco product. RESULTS: Exposure to mainstream smoke from conventional and additive-free cigarettes caused no inhibition of cell viability or mineralization, while sidestream smoke (SS) concentration-dependently produced cell death. In contrast, mineralization was inhibited only by the highest mainstream concentration of harm-reduction smoke solution. Additionally, sidestream smoke solution from the harm-reduction cigarettes impeded calcification at concentrations lower than those determined to be cytotoxic for conventional products. CONCLUSIONS: Sidestream smoke impaired in vitro osteogenesis at subtoxic concentrations. In addition, though often perceived as safer, smoke from harm-reduction cigarettes was more potent in inhibiting in vitro osteogenesis than smoke from conventional cigarettes. IMPLICATIONS: This study adds to a growing list of adverse outcomes associated with pre-natal tobacco exposure. Specifically, in vitro exposure to tobacco products interfered with osteogenic differentiation of human embryonic stem cells, a well-established surrogate model for human embryonic bone development. Contrasting a diverse array of tobacco products unveiled that sidestream smoke was generally more developmentally osteotoxic than mainstream smoke and that harm-reduction products may not be less harmful than conventional products, adverse effects that were seemingly independent of nicotine.

Intussusceptive angiogenesis and its counterpart intussusceptive lymphangiogenesis.

Intussusceptive angiogenesis (IA) is currently considered an important alternative and complementary form of sprouting angiogenesis (SA). Conversely, intussusceptive lymphangiogenesis (IL) is in an initial phase of study. We compare their morphofunctional characteristics, since many can be shared by both processes. To that end, the following aspects are considered: A) The concept of IA and IL as the mechanism by which blood and lymphatic vessels split, expand and remodel through transluminal pillar formations (hallmarks of intussusception). B) Terminology and historical background, with particular reference to the group of Burri, including Djonov and Patan, who initiated and developed the vessel intussusceptive concept in blood vessels. C) Incidence in normal (e.g. in the sinuses of developing lymph nodes) and pathologic conditions, above all in vessel diseases, such as dilated veins in hemorrhoidal disease, intravascular papillary endothelial hyperplasia (IPEH), sinusoidal hemangioma, lobular capillary hemangioma, lymphangiomas/lymphatic malformations and vascular transformation of lymph nodes. D) Differences and complementarity between vessel sprouting and intussusception. E) Characteristics of the cover (endothelial cells) and core (connective tissue components) of pillars and requirements for pillar identification. F) Structures involved in pillar formation, including endothelial contacts of opposite vessel walls, interendothelial bridges, merged adjacent capillaries, vessel loops and spilt pillars. G) Structures resulting from pillars with intussusceptive microvascular growth, arborization, remodeling and segmentation (compartmentalization). H) Influence of intussusception in the morphogenesis of vessel tumors/ pseudotumors; and I) Hemodynamic and molecular control of vessel intussusception, including VEGF, PDGF BB, Hypoxia, Notch, Endoglobin and Nitric oxide.

Update on radioguided surgery: from international consensus on sentinel node in head and neck cancer to the advances on gynaecological tumors and localization of non-palpable lesions. / Actualización en cirugía radioguiada: del consenso internacional en ganglio centinela de cabeza y cuello a los avances en tumores ginecológicos y localización de lesiones no palpables.

The aim of this review is to provide an updated perspective on different fields of radioguided surgery. With reference to the sentinel lymph node biopsy in oral squamous cell carcinoma, we present the results of the interactive debate held at the recent Congress of our specialty about the more relevant aspects of the London Consensus. Drainage peculiarities and indications according to the current guidelines on gynaecological tumours, endometrial and cervical cancer, are detailed and new scenarios for nuclear medicine physicians are presented; robotic surgery and hybrid tracers, for instance. Moreover, the notable growth in radioguided surgery indications for non-palpable lesions, widely used in mammary pathology, make it advisable to update two procedures which have shown satisfying results, such as the solitary pulmonary nodule and the osteoid osteoma.

67-Gallium SPECT/CT in febrile syndromes of unknown origin. / SPECT/TC con galio-67 en los síndromes febriles sin foco conocido.

INTRODUCTION AND OBJECTIVE: Febrile syndromes of unknown origin (FSUO) are complex processes in hospital practice. Their management includes an exhaustive medical history and examination, as well as an extensive number of biochemical tests. If these are inconclusive, diagnostic imaging techniques such as SPECT/CT with 67-Gallium Citrate (67Ga-SPECT/CT) could play an important role. We evaluated its role in the management of FSUO in our healthcare area. MATERIAL AND METHODS: We reviewed 57 patients who underwent a 67Ga-SPECT/CT due to a FSUO (32 women and 25 men, age range: 32-83 years old) obtaining scintigraphic findings, previous treatments and final diagnosis. Values of sensitivity, specificity, positive predictive values (VPP) and negative values (NPV) were obtained and compared with the results for PET/CT with 18Fluor-deoxy-glucose (18F-FDG PET/CT) found in the literature. RESULTS: The diagnoses found were: infection in 27/57 (47%), inflammatory disease in 15/57 (26%), neoplasm in 1/57 (1.75%) and patients without final diagnosis in 14/57 (24%). The statistical values of 67Ga-SPECT/CT were: sensitivity, specificity, PPV and NPV of 67%, 93%, 97% y 48%, respectively which were slightly lower than those found for the 18F-FDG PET/CT (86%, 52%, 70% and 92%, respectively). The diagnostic yield was 73% which increased to 80% in the patients who lacked empirical treatment. CONCLUSION: Despite the better results of 18F-FDG PET/CT, 67Ga-SPECT/CT behaved as a useful technique in the management of FSUO. It is advisable to use it if 18F-FDG PET/CT is not available.

Hepatocellular carcinoma treatment: ablation and arterial embolization. / Tratamiento del hepatocarcinoma: ablación y embolización arterial.

Percutaneous and endovascular techniques take an important role in the therapeutic management of patients with hepatocarcinoma. Different techniques of percutaneous ablation, especially indicated in tumors up to 2cm diameter offer, at least, similar results to surgical resection. Taking advantage of double hepatic vascularization and exclusive tumor nutrition by the artery, several endovascular techniques of treating the tumor have been developed. Intra-arterial administration of embolizing particles, alone or charged with drug (chemoembolization), will produce ischemia and consequent necrosis with excellent results in selected patients. Certain types of particles may exclusively be carriers of a therapeutic agent when they incorporate a radioisotope that facilitates the direct intratumoral selective irradiation (radioembolization). This technique has demonstrated its efficacy in lesions not susceptible to be treated with other methods and should be considered, together with ablation and chemoembolization, in the therapeutic algorithms of hepatocarcinoma.

Morphofunctional basis of the different types of angiogenesis and formation of postnatal angiogenesis-related secondary structures.

We review the morpho-functional basis of the different types of angiogenesis and report our observations, including the formation of angiogenesis-related secondary structures. First of all, we consider the following issues: a) conceptual differences between angiogenesis and vasculogenesis, b) incidence of angiogenesis in pre- and postnatal life, c) regions of vascular tree with angiogenic capacity, d) cells (endothelial cells, pericytes, CD34+ adventitial stromal cells of the microvasculature and inflammatory cells) and extracellular matrix components involved in angiogenesis, e) events associated with angiogenesis, f) different types of angiogenesis, including sprouting and intussusceptive angiogenesis, and other angiogenic or vascularization forms arising from endothelial precursor cells (postnatal vasculogenesis), vasculogenesis mimicry, vessel co-option and piecemeal angiogenesis. Subsequently, we consider the specific morpho-functional characteristics of each type of angiogenesis. In sprouting angiogenesis, we grouped the events in three phases: a) activation phase, which includes vasodilation and increased permeability, EC, pericyte and CD34+ adventitial stromal cell activation, and recruitment and activation of inflammatory cells, b) sprouting phase, encompassing EC migration (concept and characteristics of endothelial tip cells, tip cell selection, lateral inhibition, localized filopodia formation, basal lamina degradation and extracellular changes facilitating EC migration), EC proliferation (concept of endothelial stalk cells), pericyte mobilization, proliferation, recruitment and changes in CD34+ adventitial stromal cells and inflammatory cells, tubulogenesis, formation of a new basal lamina, and vascular anastomosis with capillary loop formation, and c) vascular remodelling and stabilization phase (concept of phalanx cells). Subsequently, the concept, incidence, events and mechanisms are considered in the other forms of angiogenesis. Finally, we contribute the formation of postnatal angiogenesis-related secondary structures: a) intravascular structures through piecemeal angiogenesis, including intravascular papillae in vessel tumours and pseudotumours (intravascular papillary endothelial hyperplasia, vascular transformation of the sinus in lymph nodes, papillary intralymphatic angioendothelioma or Dabska tumour, retiform hemangioendothelioma, hemangiosarcoma and lymphangiosarcoma), vascular septa in hemorrhoidal veins and intravascular projections in some tumours; b) arterial intimal thickening; c) intravascular tumours and pseudotumours (e.g. intravenous pyogenic granulomas and intravascular myopericytoma); d) vascular glomeruloid proliferations; and e) pseudopalisading necrosis in glioblastoma multiform.

Pancreatic accessory spleen. False positive with 99mTc-Octreotide.

The case is presented on a patient with abdominal pain and suspicion of neuroendocrine tumor in the tail of the pancreas shown in the abdominal CT and MRI. Whole-body scintigraphy and abdominal SPECT/CT with 99mTc-octreotide were performed that showed a nodular lesion partially on the posterior side of the pancreas tail. This nodule showed faint tracer uptake, and was reported as probable neuroendocrine tumor. Partial pancreatectomy and splenectomy were performed, and the histological study identified the lesion as an ectopic spleen. There are similar cases in the literature that match these findings, but this lesion is still frequently diagnosed after performing unnecessary surgery. When an asymptomatic intrapancreatic mass is detected, an accessory spleen should be considered and specific diagnostic techniques should be performed, such as labeled and denatured red blood cell SPECT/CT.

Telocyte Behaviour During Inflammation, Repair and Tumour Stroma Formation.

In this chapter, we outline the role of human CD34+ stromal cells/telocytes (CD34+ SC/TCs) as progenitor cells during repair. The in vivo activation phenomena of CD34+ SC/TCs in this process include increased size; separation from the neighbouring structures (mainly of the vascular walls); association with inflammatory cells, predominantly macrophages; development of the organelles of synthesis (rough endoplasmic reticulum and Golgi apparatus); cell proliferation with presence of mitosis and high proliferative index (transit-amplifying cells); and fibroblastic and myofibroblastic differentiation. A procedure to study these tissue-resident cells, comparison of their behaviour in vivo and in vitro and different behaviour depending on location, time, type of injury (including tumour stroma) and greater or lesser proximity to the injury are also considered.

Cellular changes in the hamster testicular interstitium with ageing and after exposure to short photoperiod.

The aim of this study was to evaluate the cellular changes that occur in the hamster testicular interstitium in two very different physiological situations involving testicular involution: ageing and exposure to a short photoperiod. The animals were divided into an 'age group' with three subgroups - young, adult and old animals - and a 'regressed group' with animals subjected to a short photoperiod. The testicular interstitium was characterised by light and electron microscopy. Interstitial cells were studied histochemically with regard to their proliferation, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP in situ nick end labelling (TUNEL+) and testosterone synthetic activity. We identified two types of Leydig cell: Type A cells showed a normal morphology, while Type B cells appeared necrotic. With ageing, pericyte proliferation decreased but there was no variation in the index of TUNEL-positive Leydig cells. In the regressed group, pericyte proliferation was greater and TUNEL-positive cells were not observed in the interstitium. The testicular interstitium suffered few ultrastructural changes during ageing and necrotic Leydig cells were observed. In contrast, an ultrastructural involution of Leydig cells with no necrosis was observed in the regressed group. In conclusion, the testicular interstitium of Mesocricetus auratus showed different cellular changes in the two groups (age and regressed), probably due to the irreversible nature of ageing and the reversible character of changes induced by short photoperiod.

Role of SPECT-CT in breast cancer sentinel node biopsy when internal mammary chain drainage is observed.

INTRODUCTION: SPECT-CT in the detection of the sentinel lymph node (SLN) of breast cancer offers known advantages over conventional planar lymphoscintigraphy. Sometimes, it shows atypical findings like mediastinal lymphatic drainage. We have evaluated these atypical findings showed by SPECT-CT performed in patients with migration to the internal mammary chain (IMC) and their roles in the management of the patients. MATERIALS AND METHODS: We reviewed the 56 lymphoscintigraphies (planar and SPECT-CT) of 56 women (average age: 55 years) diagnosed with breast cancer with IMC migration observed in the planar images. We compared the two techniques, obtaining the number of depicted nodes, atypical locations, their exact anatomical location and their role in the management of the patient. RESULTS: Planar images showed a total number of 81 IMC nodes. SPECT-CT showed 74 nodes in the IMC territory and 14 mediastinal lymphatic nodes in 6 patients. Out of the 81 IMC nodes reported by planar images, seven corresponded to mediastinal nodes. Planar and hybrid images showed 110 and 130 axillary nodes, respectively. SPECT-CT showed additional findings in five patients: three infraclavicular and two supraclavicular nodes that were exactly located. One intramammary node was discarded by the SPECT-CT as a focal skin contamination. CONCLUSION: Mediastinal nodes are unexpected, but not uncommon findings that are important in the planning of SLN biopsy. SPECT-CT found more nodes than planar images, being able to separate mediastinal and IMC nodes, helping to exactly depict the SLN and its relations with anatomical structures.

Human resident CD34+ stromal cells/telocytes have progenitor capacity and are a source of αSMA+ cells during repair.

We studied the progenitor capacity of human resident CD34+ stromal cells/telocytes (SC/TCs) in the enteric wall affected by inflammatory/repair processes (appendicitis, diverticulitis of large bowel and Crohn's disease of the terminal ileum) at different stages of evolution (inflammatory, proliferative and remodelling). In these conditions, CD34+ SC/TCs are activated, showing changes, which include the following overlapping events: 1) separation from adjacent structures (e.g., from vascular walls) and location in oedematous spaces, 2) morphological modifications (in cell shape and size) with presence of transitional cell forms between quiescent and activated CD34+ SC/TCs, 3) rapid proliferation and 4) loss of CD34 expression and gain of αSMA expression. These events mainly occur in the inflammatory and proliferative stages. During the loss of CD34 expression, the following findings are observed: a) irregular cell labelling intensity for anti-CD34, b) co-localization of CD34 and actin, c) concurrent irregular labelling intensity for αSMA and d) αSMA expression in all stromal cells, with total loss of CD34 expression. While CD34 expression was conserved, a high proliferative capacity (Ki-67 expression) was observed and vice versa. In the segments of the ileum affected by Crohn's disease, the stromal cells around fissures were αSMA+ and, in the transitional zones with normal enteric wall, activated CD34+ SC/TCs were observed. In conclusion, human resident CD34+ SC/TCs in the enteric wall have progenitor capacity and are activated with or without differentiation into αSMA+ stromal cells during inflammatory/repair processes.

CD34+ stromal cells/fibroblasts/fibrocytes/telocytes as a tissue reserve and a principal source of mesenchymal cells. Location, morphology, function and role in pathology.

We review the morphofunctional characteristics of CD34+ stromal fibroblastic/fibrocytic cells (CD34+ SFCs) and report our observations. We consider the following aspects of CD34+ SFCs: A) The confusing terms applied to this cell type, often combining the prefix CD34 with numerous names, including fibroblasts, fibrocytes, dendrocytes, keratocytes, telocytes and stromal, dendritic, adventitial, supraadventitial, perivascular, paravascular and delimiting cells; B) Changes in their immunophenotype, e.g., loss of CD34 expression and gain of other markers, such as those defining mesenchymal and derivate cells (myofibroblasts, osteoblasts, chondroblasts, adipocytes); C) Morphology (elongated or triangular cell body and thin, moniliform, bipolar or multipolar cytoplasmic processes), immunohistochemistry (co-expression of and changes in molecular expression) and structure (characteristics of nucleus and cytoplasmic organelles, and points of contact and junctions in quiescent and activated stages by light and electron microscopy); D) Location and distribution in the vessels (adventitia or external layer), in the tissues (connective, adipose, blood, muscle and nervous) and in the organs and systems (skin, oral cavity and oropharynx, respiratory, digestive, urinary, male, female, endocrine and lymphoid systems, serosal and synovial membranes, heart, eye and meninges); E) Origin from the mesoderm and cranial neural crest in the embryo, and from stem cells (themselves or other cells) and/or peripheral blood pluripotent stem cells (circulating progenitor cells) in post-natal life; F) Functions, such as synthesis of different molecules, progenitor of mesenchymal cells, immunomodulation, parenchymal regulation (growth, maturation and differentiation of adjacent cells), induction of angiogenesis, scaffolding support of other cells and phagocytic properties. Since CD34+ SFCs are the main reservoir of tissue mesenchymal cells (great mesenchymal potential, probably higher than that proposed for pericytes and other stromal cells), we dedicate a broad section to explain their in vivo behaviour during proliferation and differentiation in different physiologic and pathologic conditions, in addition to their characteristics in the human tissues of origin (adult stem cell niches); G) Involvement in pathological processes, e.g., repair (regeneration and repair through granulation tissue), fibrosis, tumour stroma formation and possible CD34+ SFC-derived tumours (e.g., solitary fibrous tumour, dermatofibrosarcoma protuberans, giant cell fibroblastoma, nuchal-type fibroma, mammary and extramammary myofibroblastoma, spindle and pleomorphic cell lipoma, and elastofibroma) and H) Clinical and therapeutic implications.

Circadian phase assessment by ambulatory monitoring in humans: correlation with dim light melatonin onset.

The increased prevalence of circadian disruptions due to abnormal coupling between internal and external time makes the detection of circadian phase in humans by ambulatory recordings a compelling need. Here, we propose an accurate practical procedure to estimate circadian phase with the least possible burden for the subject, that is, without the restraints of a constant routine protocol or laboratory techniques such as melatonin quantification, both of which are standard procedures. In this validation study, subjects (N = 13) wore ambulatory monitoring devices, kept daily sleep diaries and went about their daily routine for 10 days. The devices measured skin temperature at wrist level (WT), motor activity and body position on the arm, and light exposure by means of a sensor placed on the chest. Dim light melatonin onset (DLMO) was used to compare and evaluate the accuracy of the ambulatory variables in assessing circadian phase. An evening increase in WT: WTOnset (WTOn) and "WT increase onset" (WTiO) was found to anticipate the evening increase in melatonin, while decreases in motor activity (Activity Offset or AcOff), body position (Position Offset (POff)), integrative TAP (a combination of WT, activity and body position) (TAPOffset or TAPOff) and an increase in declared sleep propensity were phase delayed with respect to DLMO. The phase markers obtained from subjective sleep (R = 0.811), WT (R = 0.756) and the composite variable TAP (R = 0.720) were highly and significantly correlated with DLMO. The findings strongly support a new method to calculate circadian phase based on WT (WTiO) that accurately predicts and shows a temporal association with DLMO. WTiO is especially recommended due to its simplicity and applicability to clinical use under conditions where knowing endogenous circadian phase is important, such as in cancer chronotherapy and light therapy.

Effect of aluminum sulfate on litter composition and ammonia emission in a single flock of broilers up to 42 days of age.

New alternatives are necessary if the environmental impact linked to intensive poultry production is to be reduced, and different litter handling methods should be explored. Among these, acidifying amendments added to poultry litters has been suggested as a management practice to help reduce the potential environmental effect involved in multiple flock cycles. There have been several studies on the use of aluminum sulfate (alum) and its benefits, but almost no data are available under farm conditions in Europe. An experiment with Ross 308 broilers from 1 to 42 days of age was conducted to evaluate the effect of alum on litter composition, the solubility of some mineral elements and NH3 emission during a single flock-rearing period in commercial houses located in southeast Spain. Broilers were placed on clean wood shavings in four commercial houses, containing 20 000 broilers each. Before filling, alum was applied at a rate of 0.25 kg/m2 to the wood shavings of two poultry houses, whereas the remaining two were used as control. Litter from each poultry house was sampled every 3 to 5 days. Ammonia emissions from the poultry houses were monitored from 37 to 42 days of age. In comparison with the control group, alum treatment significantly reduced the pH level of the litter (P < 0.001) with an average difference of 1.32 ± 0.24 units. Alum-treated litter showed, on average, a higher electrical conductivity than the control litter (5.52 v. 3.63 dS/m). The dry matter (DM) and total N and P contents did not show differences between the treatments (P > 0.05). Regarding the NH4 +-N content, alum-treated litter showed a higher value than the untreated litter, with an average difference of 0.16 ± 0.07% (on a DM basis). On average, alum-treated litter had lower water-soluble P, Zn and Cu contents than the untreated litter. Alum noticeably reduced the in-house ammonia concentration (P < 0.001), with an average of 4.8 ppm at 42 days of age (62.9% lower than the control), and ammonia emissions from 37 to 42 days of age were significantly reduced by the alum treatment (P < 0.001), representing a reduction of 73.3%. The lower pH values might have reduced ammonia volatilization from the litter, with a corresponding positive effect on the building environment and poultry health. For these reasons, litter amendment with alum could be recommended as a way of reducing the pollution potential of European broiler facilities during a single flock cycle.