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Craniopharyngioma (CP) adherence represents a most baffling problem for the neurosurgeon. The highest priority of current surgical treatment is to maximize tumor removal without compromising the patients' long-term functional outcome. Surgical damage to the hypothalamus may be avoided or at least ameliorated with a precise knowledge regarding the type of adherence for each case. This article presents a comprehensive review of the pathological, surgical, and radiological sources of evidence supporting that CP adherence, despite being heterogenous, is characterized by repeating patterns. The key underlying factors of CP adherence are also discussed. Three components define the type of adherence for each case: (i) the intracranial structures attached to the tumor, (ii) the adherence morphology, and (iii) the adhesion strength. Combination of these three components gives rise to five hierarchical levels of increased risk of hypothalamic injury during tumor removal. Tumor topography has been identified as the major predictor of the type of CP adherence. The most extensive and strongest adhesions to the hypothalamus occur in CPs originated in the suprasellar cistern that secondarily invade the third ventricle (secondary intraventricular CPs) and in those originated within the third ventricle floor itself (not-strictly intraventricular CPs). Three findings observed on preoperative conventional MRI scans have proven to be reliable predictors of adherence severity. A position of the hypothalamus around the middle portion of the tumor, an amputated pituitary stalk, and an elliptical tumor shape points to the severe and critical risk levels, and in those cases, a safer limited removal is strongly recommended.

Objective: Establishing the neurological localization doctrine for the contralateral hemispheric control of motor functions in the second half of the 19th century, researchers faced the challenge of recognizing false localizing signs, in particular paradoxical or ipsilateral hemiparesis (IH). Despite tremendous progress in current methods of neuroradiological and electrophysiological exploration, a complete understanding of this phenomenon has yet to be attained., Methods: The authors researched the well-described cases of hemiparesis/hemiplegia ipsilateral to an intracranial lesion published in the scientific literature in the pre-MRI era (before 1980). A comprehensive review of the physiopathological mechanisms proposed for paradoxical hemiparesis throughout this period, as well as the pathological evidence substantiating them, is provided., Results: A collection of 75 patients with hemiparesis/hemiplegia ipsilateral to the primary intracranial lesion reported between 1858 and 1979 were eligible for analysis. Most cases occurred in adults with supratentorial, slowly developing, extraparenchymatous mass lesions, such as neoplasms (38%) or chronic subdural hematomas (36%). Physiopathological theories proposed by the neurologists who investigated IH can be grouped into 4 major concepts: 1) lack of anatomical decussation of the corticospinal tract; 2) impaired functional activation of the contralateral hemisphere by the lesioned dominant hemisphere through the callosal connections; 3) Kernohan's notch phenomenon, or mechanical injury of the contralateral cerebral peduncle against the free edge of the tentorium; and 4) cerebrovascular dysfunction involving the contralateral hemisphere owing to kinking and mechanical flattening of the carotid artery contralateral to the primary intracranial lesion., Conclusions: IH represents a still underdiagnosed paradoxical neurological phenomenon. With the aid of modern neuroradiological and neurophysiological methods, Kernohan's peduncle notch mechanism has been confirmed to cause IH in many of the cases reported in recent decades. Nevertheless, alternative functional and/or vascular mechanisms must be investigated further for unexplained IH cases, in particular for transitory IH without evidence of peduncle injury. The historical theories reviewed in this paper represent a conceptual framework that may be helpful for this purpose.

Objective: This study provides a systematic review and meta-analysis of psychiatric disorders caused by craniopharyngiomas and the hypothalamic alterations underlying these symptoms., Methods: We investigated a collection of 210 craniopharyngiomas reported from 1823 to 2017 providing detailed clinical and pathologic information about psychiatric disturbances, including 10 of our own series, and compared the hypothalamic damage in this cohort with the present in a control cohort of 105 cases without psychiatric symptoms., Results: Psychiatric disorders occurred predominantly in patients with craniopharyngiomas developing primarily at the infundibulotuberal region (45%) or entirely within the third ventricle (30%), mostly affecting adult patients (61%; P < 0.001). Most tumors without psychic symptoms developed beneath the third ventricle floor (53.5%; P < 0.001), in young patients (57%; P < 0.001). Psychiatric disturbances were classified in 6 major categories: 1) Korsakoff-like memory deficits, 66%; 2) behavior/personality changes, 48.5%; 3) impaired emotional expression/control, 42%; 4) cognitive impairments, 40%; 5) mood alterations, 32%; and 6) psychotic symptoms, 22%. None of these categories was associated with hydrocephalus. Severe memory deficits occurred with damage of the mammillary bodies (P < 0.001). Mood disorders occurred with compression/invasion of the third ventricle floor and/or walls (P < 0.012). Coexistence of other hypothalamic symptoms such as temperature/metabolic dysregulation or sleepiness favored the emergence of psychotic disorders (P < 0.008). Postoperative psychiatric outcome was better in strictly intraventricular craniopharyngiomas than in other topographies (P < 0.001). A multivariate model including the hypothalamic structures involved, age, hydrocephalus, and hypothalamic symptoms predicts the appearance of psychiatric disorders in 81% of patients., Conclusions: Craniopharyngiomas primarily involving the hypothalamus represent a neurobiological model of psychiatric and behavioral disorders., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A heterogeneous group of epithelial cystic tumors developed at the infundibulum and the third ventricle disconcerted pathologists at the dawn of the twentieth century. Very little was known at that time about the physiological role played by the pituitary gland, and there was almost complete ignorance regarding the function of the hypothalamus. Acromegaly, or enlargement of acral body parts, described in 1886 by Pierre Marie, was the only disease linked to primary hypertrophies of the pituitary gland, known as "pituitary strumas". A growing number of young patients manifesting an unexplained combination of physical and mental symptoms, including absent or delayed sexual maturation, progressive obesity, abnormal somnolence, and dementia-like changes in behavior were reported to present large solid-cystic tumors which characteristically expanded within the infundibulum and third ventricle, above an anatomically intact pituitary gland. Between 1899 and 1904, five seminal autopsy studies from different countries thoroughly described the anatomical relationships and histological features of this newly recognized type of infundibular tumors. These cases were instrumental in fostering the systematic investigation of similar lesions by the Austrian pathologist Jakob Erdheim (1874-1937), who in 1904 was able to classify these infundibulo-tuberal cysts under the common category of hypophyseal duct tumors. The pioneering American neurosurgeon Harvey Cushing (1869-1939) unsuccessfully attempted to surgically remove one of these cysts, for the first time in history, in 1902. The term "craniopharyngioma", chosen by Cushing in 1929 to designate these lesions, would eventually prevail over Erdheim's more accurate denomination, which linked their origin to squamous cell remnants derived from the embryological structures that give rise to the pituitary gland. This paper presents a comprehensive, renewed account of the five clinical-pathological reports which laid the groundwork for the proper clinical diagnosis, topographic conceptualization and pathological categorization of craniopharyngiomas.

The field of pituitary surgery was born in the first decade of the twentieth century in Europe, and it evolved rapidly with the development of numerous innovative surgical techniques by some of the founding fathers of neurosurgery. This study investigates the pioneering Italian treatise on pituitary surgery, La Patologia Chirurgica dell'Ipofisi (Surgical Pathology of the Hypophysis), published in 1911 by Giovanni Verga (1879-1923), a surgeon from Pavía and one of Golgi's disciples. This little-known monograph compiles the earliest experience on pituitary surgery through the analysis of the first 50 procedures performed between 1903 and 1911. We conducted a biographical survey of Giovanni Verga and the motivations for his work on pituitary surgery. In addition, a systematic analysis of all original reports and historical documents about these pituitary procedures referenced in Verga's treatise was carried out. Verga's treatise provides a summary of the techniques employed and surgical outcomes for the first 50 attempted procedures of pituitary tumor removal. This monograph is the only scientific source that includes a complete account of the series of 10 pituitary tumors operated on by Sir Victor Horsley in the 1900s. Three major types of surgery were employed: (i) palliative procedures of craniectomy (n = 6); (ii) transcranial approaches to the pituitary gland, either subfrontal or subtemporal (n = 13); and (iii) transphenoidal routes to expose the sella turcica, either using an upper transnasal-transethmoidal approach (n = 19) or a lower sublabial/endonasal-transeptal one (n = 12). An operative mortality rate of 36% (n = 17) was observed in these early series. The pathological nature of the tumors operated on was available in 42 cases. There were 28 adenomas and 15 craniopharyngiomas. Sir Victor Horsley (1857-1916) and the Viennese surgeons Anton von Eiselsberg (1860-1939) and Oskar Hirsch (1877-1965) were the leading European figures in the development of pituitary surgery. Giovanni Verga's treatise La Patologia Chirurgica dell'Ipofisi is a fundamental, pioneering book in the history of pituitary surgery, a work that compiles the foundations of this field in Europe and the only authoritative source providing a complete record of pituitary procedures performed by Sir Victor Horsley.

At the beginning of the twentieth century, the hypothalamus was known merely as an anatomical region of the brain lying beneath the thalamus. An increasing number of clinicopathological reports had shown the association of diabetes insipidus and adiposogenital dystrophy (Babinski-Fröhlich's syndrome), with pituitary tumors involving the infundibulum and tuber cinereum, two structures of the basal hypothalamus. The French physicians Jean Camus (1872-1924) and Gustave Roussy (1874-1948) were the first authors to undertake systematic, controlled observations of the effects of localized injuries to the basal hypothalamus in dogs and cats by pricking the infundibulo-tuberal region (ITR) with a heated needle. Their series of surgical procedures, performed between 1913 and 1922, allowed them to claim that both permanent polyuria and adiposogenital dystrophy were symptoms caused by damage to the ITR. Their results challenged the dominant doctrine of hypopituitarism as cause of diabetes insipidus and adiposogenital dystrophy that derived from the experiments performed by Paulescu and Cushing a decade earlier. With their pioneering research, Camus and Roussy influenced the experimental work on the hypothalamus performed by Percival Bailey and Frederic Bremer at Cushing's laboratory, confirming the hypothalamic origin of these symptoms in 1921. More importantly, they provided the foundations for the physiological paradigm of Neuroendocrinology, the hypothalamus' control over the endocrine secretions of the pituitary gland, as well as over water balance and fat metabolism. This article aims to credit Camus and Roussy for their groundbreaking, decisive contributions to postulate the hypothalamus being the brain region in control of endocrine homeostasis and energy metabolism.

Craniopharyngiomas (CPs) are benign epithelial tumors that develop along the hypothalamus-hypophyseal axis and were first described by Jakob Erdheim in 1904. These tumors have represented a challenge for surgeons since the rise of modern neurosurgery. The study of CPs is linked to the development of this surgical discipline in parallel with neuroendocrinology within the French school of neurology, led by Joseph Babinski. For the present study, all CP cases published in the French scientific literature before the development of modern neuroradiology were gathered, and 65 cases that underwent surgical procedures between 1921 and 1973 were selected. From our analysis of them, useful information has been obtained that can be applied to the management of CPs today. Most tumors were adamantinomatous CPs (62 patients) with an infundibulo-tuberal location (40.6%). The most frequent surgical route employed was subfrontal (69%). Selection of the surgical approach and degree of removal did not appear to have been influenced by the presumed topography of the tumor, and resulted in a poor outcome in 47% of patients. However, the authors were able to recognize the presence of symptoms indicating that the tumor had caused hypothalamic and/or infundibular damage, such as seen in the infundibulo-tuberal syndrome, first described by Claude and Lhermitte in 1917. At present, the optimal surgical approach and degree of removal are still the subject of debate, although the presence of clinical signs pointing to hypothalamic involvement by CPs should always be preoperatively accurately assessed to improve surgical outcomes., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

OBJECTIVE Craniopharyngioma (CP) adherence strongly influences the potential for achieving a radical and safe surgical treatment. However, this factor remains poorly addressed in the scientific literature. This study provides a rational, comprehensive description of CP adherence that can be used for the prediction of surgical risks associated with the removal of these challenging lesions. METHODS This study retrospectively analyzes the evidence provided in pathological, neuroradiological, and surgical CP reports concerning 3 components of the CP attachment: 1) the intracranial structures attached to the tumor; 2) the morphology of the adhesion; and 3) the adhesion strength. From a total of 1781 CP reports published between 1857 and 2016, a collection of 500 CPs providing the best information about the type of CP attachment were investigated. This cohort includes autopsy studies (n = 254); surgical studies with a detailed description or pictorial evidence of CP adherence (n = 298); and surgical CP videos (n = 61) showing the technical steps for releasing the attachment. A predictive model of CP adherence in hierarchical severity levels correlated with surgical outcomes was generated by multivariate analysis. RESULTS The anatomical location of the CP attachment occurred predominantly at the third ventricle floor (TVF) (54%, n = 268), third ventricle walls (23%, n = 114), and pituitary stalk (19%, n = 94). The optic chiasm was involved in 56% (n = 281). Six morphological patterns of CP attachment were identified: 1) fibrovascular pedicle (5.4%); 2) sessile or patch-like (21%); 3) cap-like (over the CP top, 14%); 4) bowl-like (around the CP bottom, 13.5%); 5) ring-like (encircling central band, 19%); and 6) circumferential (enveloping the entire CP, 27%). Adhesion strength was classified in 4 grades: 1) loose (easily dissectible, 8%); 2) tight (requires sharp dissection, 32%); 3) fusion (no clear cleavage plane, 40%); and 4) replacement (loss of brain tissue integrity, 20%). The types of CP attachment associated with the worst surgical outcomes are the ring-like, bowl-like, and circumferential ones with fusion to the TVF or replacement of this structure (p < 0.001). The CP topography is the variable that best predicts the type of CP attachment (p < 0.001). Ring-like and circumferential attachments were observed for CPs invading the TVF (secondary intraventricular CPs) and CPs developing within the TVF itself (infundibulo-tuberal CPs). Brain invasion and peritumoral gliosis occurred predominantly in the ring-like and circumferential adherence patterns (p < 0.001). A multivariate model including the variables CP topography, tumor consistency, and the presence of hydrocephalus, infundibulo-tuberal syndrome, and/or hypothalamic dysfunction accurately predicts the severity of CP attachment in 87% of cases. CONCLUSIONS A comprehensive descriptive model of CP adherence in 5 hierarchical levels of increased severity-mild, moderate, serious, severe, and critical-was generated. This model, based on the location, morphology, and strength of the attachment can be used to anticipate the surgical risk of hypothalamic injury and to plan the degree of removal accordingly.

The birth of clinical neuroendocrinology can be dated to the year 1900, when the French neurologist Joseph Babinski (1857-1932) described a particular syndrome of adiposity and sexual infantilism in an adolescent with a craniopharyngioma expanding at the base of the brain. This condition of adipose-genital dystrophy, also known as Babinski-Fröhlich syndrome, represented the first clinical evidence that the brain controlled endocrine functions. Adipose-genital dystrophy forms part of infundibulo-tuberal syndrome, which groups the endocrine, metabolic and behavioral disturbances caused by lesions involving the upper neurohypophysis (median eminence) and the adjacent basal hypothalamus (tuber cinereum). This syndrome was originally described by the French neuropsychiatrists Henri Claude (1869-1946) and Jean Lhermitte (1877-1959) in 1917, also in a patient with a craniopharyngioma. This type of tumor involves specifically the infundibulo-tuberal region of the hypothalamus, providing a clinical model to conceptualize the separation of hypophyseal and hypothalamic functions. The French School of Neurology analyzed and reported the symptoms associated with dysfunction of the basal hypothalamus by craniopharyngiomas and other types of tumors, influencing significantly the development of clinical neuroendocrinology. Experimental lesions performed in the tuber cinereum by the French physiologists Jean Camus (1872-1924) and Gustave Roussy (1874-1948) demonstrated unmistakably the anatomical origin of infundibulo-tuberal syndrome in the basal hypothalamus. This article reviews the original findings on infundibulo-tuberal syndrome reported by the French School of Neurology in the first decades of the twentieth century and the great influence this school had on modern conceptions of hypothalamic control over endocrine functions and behavior.

Purpose: Infundibulo-tuberal syndrome groups endocrine, metabolic and behavioral disturbances caused by lesions involving the upper neurohypophysis (median eminence) and adjacent basal hypothalamus (tuber cinereum). It was originally described by Henri Claude and Jean Lhermitte in 1917, in a patient with a craniopharyngioma. This study investigates the clinical, pathological and surgical evidence verifying the infundibulo-tuberal syndrome caused by craniopharyngiomas (CPs)., Methods: A systematic retrospective review of craniopharyngiomas reported in French literature between 1705 and 1973 was conducted. A total of 128 well described reports providing a comprehensive clinical and pathological description of the tumors were selected. This series represents the historical French cohort of CPs reported in the pre-CT/MRI era., Results: Three major syndromes caused by CPs were categorized: pituitary syndrome (35%), infundibulo-tuberal syndrome (52%) and hypothalamic syndrome (49%). CP topography was significantly related to the type of syndrome described (p < 0.001). Infundibulo-tuberal syndrome occurred in CPs which replaced or invaded the third ventricle floor. In contrast, the majority of sellar/suprasellar CPs growing below the third ventricle showed a pituitary syndrome (82%). Cases with hypothalamic syndrome were characterized by anatomical integrity of the pituitary gland and stalk (p = 0.033) and occurred predominantly in adults older than 41 years old (p < 0.005). Among infundibulo-tuberal symptoms, abnormal somnolence was not related with the presence of hydrocephalus. All squamous-papillary CPs presented psychiatric disturbances (p < 0.001)., Conclusion: This historical CP cohort evidences a clinical-topographical correlation between the patient's type of syndrome and the anatomical structures involved by the tumor along the hypophysial-hypothalamic axis.

Introduction and Objectives: This study evaluates the pathological and magnetic resonance imaging evidence to define the precise topographical relationships of craniopharyngiomas and to classify these lesions according to the risks of hypothalamic injury associated with their removal., Material and Methods: An extensive, systematic analysis of the topographical classification models used in the surgical series of craniopharyngiomas reported in the literature (n=145 series, 4,588 craniopharyngiomas) was performed. Topographical relationships of well-described operated craniopharyngiomas (n=224 cases) and of non-operated cases reported in autopsies (n=201 cases) were also analysed. Finally, preoperative and postoperative magnetic resonance imaging studies displayed in craniopharyngiomas reports (n=130) were compared to develop a triple-axis model for the topographical classification of these lesions with qualitative information regarding the associated risk of hypothalamic injury., Results: The 2 major variables with prognostic value to define the topography of a craniopharyngioma are its position relative to the sellar diaphragm and its degree of invasion of the third ventricle floor. A multivariate diagnostic model including 5 variables -patient age, presence of hydrocephalus and/or psychiatric symptoms, the relative position of the hypothalamus and the mammillary body angle- makes it possible to differentiate suprasellar craniopharyngiomas displacing the third ventricle upwards (pseudointraventricular craniopharyngiomas) from either strictly intraventricular craniopharyngiomas or lesions developing primarily within the third ventricle floor (infundibulo-tuberal or not strictly intraventricular craniopharyngiomas)., Conclusions: A triple-axis topographical model for craniopharyngiomas that includes the degree of hypothalamus invasion is useful in planning the surgical approach and degree of resection. Infundibulo-tuberal craniopharyngiomas represent 42% of all cases. These lesions typically show tight, circumferential adhesion to the third ventricle floor, with their removal being associated with a 50% risk of hypothalamic injury. The endoscopically-assisted extended transsphenoidal approach provides a proper view to assess the degree and extension of craniopharyngioma adherence to the hypothalamus., (Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.)

Introduction and Objectives: This study reviews the historical evolution of pathological, neuroradiological and surgical evidence that influenced the topographical concepts and classification schemes of craniopharyngiomas., Material and Methods: An extensive, systematic analysis of the surgical series of craniopharyngiomas reported in the literature was performed (n=145 series, 4,588 tumours) to describe the fundamental anatomical findings guiding the topographical classification schemes used for this tumour throughout history. These findings were compared with topographical relationships reported for well-described operated craniopharyngiomas (n=224 cases) as well as for non-operated cases studied in autopsies (n=201 cases)., Results: Two major variables define the topography of a craniopharyngioma: its position relative to the sellar diaphragm and its degree of invasion of the third ventricle floor. Suprasellar lesions displacing the third ventricle floor upwards (pseudointraventricular craniopharyngiomas) are amenable to safe, radical resection and must be differentiated from lesions developing primarily within the third ventricle floor (infundibulo-tuberal or not strictly intraventricular craniopharyngiomas). The latter group typically shows tight, circumferential adhesion to the third ventricle floor and represents approximately 40% of all cases., Conclusions: A triple-axis topographical model for craniopharyngiomas that includes the degree of hypothalamus invasion is useful in planning surgical approach and degree of resection. The group of infundibulo-tuberal craniopharyngiomas associates the highest risk of hypothalamic injury (50%). The endoscopically-assisted extended transsphenoidal approach provides a proper view to assess the topography of the craniopharyngioma and its degree of adherence to the hypothalamus., (Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.)

Aim: The aim of this study was to measure the capacity of glucose- and weight-related parameters to predict pregnancy-induced hypertensive disorders in women with gestational diabetes., Methods: An observational study was conducted involving 2037 women with gestational diabetes. The associations of glycaemic and weight-related parameters with pregnancy-induced hypertensive disorders were obtained by univariate and adjusted multivariate analyses. Also, model predictability and attributable predictor risk percentages were calculated, and collinearity and factor interactions examined., Results: Multivariate analyses revealed that hypertensive disorders were mainly predicted by average third-trimester glycated haemoglobin (HbA(1c)) levels ≥ 5.9%, by being overweight or obese before pregnancy and by excess gestational weight gain after adjusting for age, tobacco use, chronic hypertension, parity, urinary tract infections and gestational age at delivery. Prepregnancy body weight (overweight and obesity) had the strongest impact on pregnancy-related hypertensive disorders (attributable risk percentages were 51.5% and 88.8%, respectively). The effect of being overweight or obese on hypertensive disorders was enhanced by HbA(1c) levels and gestational weight gain, with elevated HbA(1c) levels multiplying the effect of being overweight before pregnancy., Conclusion: The average third-trimester HbA1c level is a novel risk factor for pregnancy-induced hypertensive disorders in women with gestational diabetes. HbA(1c) levels ≥ 5.9%, prepregnancy overweight or obesity and excess gestational weight gain are all independent risk factors of pregnancy-related hypertensive disorders in such women. In treated gestational diabetes patients, the strongest influence on hypertensive disorders is prepregnancy obesity., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Object: The development of surgical procedures for the removal of craniopharyngiomas (CPs) was greatly influenced by the enormous topographical and morphological heterogeneity displayed by these lesions. In this study the authors reviewed the intracranial approaches designed to treat CPs during the early historical period (1891-1938) with the aim of finding the CP topographical and pathological features that influence patient outcomes., Methods: The authors conducted a systematic retrospective review of well-described cases of surgically treated CPs in publications from the period 1891-1938. Valuable information regarding the diagnosis of the lesion, type of craniotomy performed, CP topography, and outcome was selected from 418 reports included in medical publications from this period. The type of surgical procedure used, degree of tumor removal, CP position and histological variety, and clinical evidence of postoperative hypothalamic injury were the variables analyzed with the aim of defining their influence on the final patient outcome., Results: A collection of 160 cases was eligible for analysis. Craniopharyngioma topography was significantly related to the existence of postoperative hypothalamic damage and the degree of tumor removal achieved (p < 0.001). The infundibulo-tuberal, or not strictly intraventricular, topography was associated with the highest rate of hypothalamic injury (84%) and impossibility of tumor removal (51%). This topography also showed the worst prognosis (p = 0.001). Additional variables correlated with patient outcome were the presence of hypothalamic damage, type of surgical approach used, and degree of tumor removal. Patients having a poor outcome, suffering from permanent coma, or dying after surgery presented with symptoms of hypothalamic injury in 40% of cases (p < 0.001). The surgical approach associated with the best outcome was the transsphenoidal (58%), followed by the subfrontal (45%) and the transcallosal (45%). Subtotal resection of the lesion yielded the best postoperative results, with only 17% of patients dying or suffering from a poor outcome, in contrast to the 39% reported for gross-total removal of the lesion (p = 0.001)., Conclusions: Two major variables influenced the results of early surgical experience with CPs for the period from 1891 to 1938: 1) the inaccuracy in defining CP topography with the diagnostic methods available at that time; and 2) the ignorance about the risks associated with the dissection of lesions showing tenacious adherence to the hypothalamus. The degree of functional and morphological disturbance of the hypothalamus caused by a CP remains a fundamental variable helping the surgeon to predict the risks associated with the radical excision of the tumor and patient outcome.

Background and Objective: To evaluate the influence of peripheral neuropathy, autonomic neuropathy and arterial wall calcification on the concordance of ankle-brachial index (ABI) and toe-brachial index (TBI) in diabetic patients., Patients and Method: We evaluated in 221 diabetic patients (73.8% type 2; 66.6% male) the presence of: peripheral arterial disease, peripheral neuropathy, autonomic neuropathy and arterial wall calcification., Results: The mean (standard deviation) difference between ABI and TBI in our population was 0.33 (0.25). Patients with arterial wall calcification had a higher mean difference between ABI and TBI than patients without arterial wall calcification -0.87 (0.39) vs 0.30 (0.21) (p < 0.005)-. Mean difference between ABI and TBI was similar for patients with and without autonomic neuropathy -0.36 (0.26) vs 0.30 (0.24) (p = 0.057)- and for patients with and without peripheral neuropathy -0.34 (0.28) vs 0.31 (0.21) (p = 0.423)-. Among all patients there was a significant linear association (r = 0.506; p < 0.001) between ABI and TBI. For patients with arterial wall calcification there was no correlation between both indices (r = -0.070; p = 0,857)., Conclusions: Our findings indicate that in diabetic patients, TBI is the method of choice to evaluate lower limb perfusion in the presence of overt arterial wall calcification.

Objective: To identify clinic and metabolic risk factors for diabetic neuropathy and peripheral arterial disease in patients evaluated in a diabetic foot unit care., Method: From 2000 to 2005 we evaluated the presence of diabetic neuropathy (monofilament, tuning fork and Boulton's clinic scale) and peripheral arterial disease (ankle-brachial index and toe-brachial index) in 304 diabetic patients. We classified patients in four groups: patients without pathology (normal group), with neuropathy (neuropathic group), with peripheral arterial disease (vascular group) and with both pathologies (mixed group) and we compared the characteristics of each group. We analysed other poblational characteristics: age, gender, type of diabetes, duration, microvascular and macrovascular complications, hypertension, smoking habit, antiagregation and mean HbA1c in the last year., Results: Age, frequency of hypertension and coronary disease were significantly higher (p < 0.005) in vascular and mixed group than in normal group (63 +/- 13 and 65 +/- 10 vs. 55 +/- 14; 69.2 and 70.3 vs. 45.5%; 46,2% and 39.2% vs 23.8%, respectively). Frequency of retinopathy, nephropathy and HbA1c were significantly higher (p < 0.05) in neuropathic and mix group than in normal group (62.5 and 66.2 vs. 32.7%; 45.3 and 47.3 vs. 24.8%; 8.1 +/- 1.6 and 8.0 +/- 1.3 vs 7.4 +/- 1.2 respectively)., Conclusion: This study indicates that the development of diabetic neuropathy is related with worse metabolic control and the presence of other microvascular complications; while age, hypertension and coronary disease are risk factors for peripheral arterial disease.