Search

Summary Background The NIBIT-MESO-1 study demonstrated the efficacy and safety of tremelimumab combined with durvalumab in patient with unresectable mesothelioma followed up for a median of 52 months [IQR 49–53]. Here, we report 4-year survival and outcomes after retreatment, and the role of tumour mutational burden (TMB) in identifying patients who might have a better outcome in response to combined therapy. Methods NIBIT-MESO-1 was an open-label, non-randomised, phase 2 trial of patients with unresectable pleural or peritoneal mesothelioma who received intravenous tremelimumab (1 mg/kg bodyweight) and durvalumab (20 mg/kg bodyweight) every 4 weeks for four doses, followed by maintenance intravenous durvalumab at the same dose and schedule for nine doses. In this follow-up study, patients with disease progression following initial clinical benefit—ie, a partial repsonse or stable disease—were eligible for retreatment and with the same doses and schedules for tremelimumab and durvalumab as used in the NIBIT-MESO-1 trial. The primary endpoint, immune-related objective response rate, was evaluated per immune-related modified Response Evaluation Criteria in Solid Tumors (RECIST) or immune-related RECIST 1.1 criteria for patients with pleural or peritoneal malignant mesothelioma, respectively. Key secondary endpoints were overall survival and safety, and TMB was also evaluated post hoc in patients who had tumour tissue available before treatment. The intention-to-treat population was used for analysis of all efficacy endpoints. This study is registered with ClinicalTrials.gov , number NCT02588131 . Findings 40 patients were enrolled in the NIBIT-MESO-1 study between Oct 30, 2015, and Oct 12, 2016. At data cut-off, April 30, 2020, five (13%) of 40 patients were alive, and 35 (88%) patients had died of progressive disease. At a median follow-up of 52 months (IQR 49–53), median overall survival was 16·5 months (95% CI 13·7–19·2). Survival was 20% (eight of 40 patients) at 36 months and 15% (six of 40 patients) and 48 months. 17 (43%) of 40 patients met the criteria for enrolment in the retreatment study and were retreated with at least one dose of tremelimumab and durvalumab. No immune-related objective responses were observed in the 17 retreated patients. Seven (41%) of 17 patients achieved immune-related stable disease. From the start of retreatment to a median follow-up of 24 months (22·0–25·0), median overall survival was 12·5 months (95% CI 0·0–25·8), and survival at 12 months was 52·9%, at 18 months was 35·3%, and at 24 months was 23·5%. There were no grade 3–4 immune-related adverse events in the retreatment cohort. In a post-hoc analysis of 28 patients for whom tumour tissue before treatment was available, patients with a TMB higher than the median value of 8·3 mutations per Mb had a higher median overall survival compared with patients with TMB below the median value, but this difference was non-significant. Moreover, when patients were additionally stratified for ICI retreatment (n=13), there was a significant difference in survival between those with a TMB higher than the median of 8·3 mutations per Mb and those with TMB lower than the median in the retreated cohort (41·3 months vs 17·4 months; p=0·02). Interpretation Tremelimumab combined with durvalumab was associated with long-term survival in patients with mesothelioma. Retreatment was safe and resulted in clinically meaningful outcomes, thus suggesting its potential application in the clinical practice of mesothalioma patients. Funding NIBIT Foundation, Fondazione AIRC, AstraZeneca.

Purpose of Review Since the past year, the fast spread of coronavirus disease 2019 (COVID-19) has represented a global health threat, especially for cancer patients, that has required an urgent reorganization of clinical activities. Here, we will critically revise the profound impact that the pandemic has generated in lung cancer patients, as well the most significant challenges that oncologists have to face to maintain the highest possible standards in the management of lung cancer patients in the pandemic era. Recent Findings Evidences suggested a higher susceptibility and mortality of lung cancer patients due to COVID-19. The hard management of this patient population has been also due to the potential cross interference of anti-tumor drugs on SARS-Cov-2 infection and to the differential diagnosis between COVID-19 pneumonitis and drug-related pneumonitis. Summary COVID-19 pandemic has generated a profound reshaping of oncological activities and the development of recommendations by the oncology scientific community to prioritize anti-tumor treatments for lung cancer patients.

Several anatomic relationships between the ear and the temporo-mandibular joint have been proposed to account for the presence of tinnitus during temporo-mandibular disorders. Among the otomandibular structures, the discomallear ligament (DML) is interposed between the malleus and the retrodiscal capsular complex. The aim of present paper was to study through dissection the frequency and morphology of DML, to characterize its type of collagen, and to evaluate the DML on routine computed tomography (CT). The study has been conducted on five un-embalmed adult cadavers, and in all cases, the DML was present (100%). It was constituted mainly by fibers of collagen I, with abundant elastic fibers. On CT exams of 40 patients with no reported pathology of the ear, on axial images, a dense structure, going from the upper end of the petrotympanic fissure to the neck of the malleus, was present in all the cases. In 90%, it showed a triangular shape, in 5% a rectangular shape, and in 5% a curved course. The mean length of the antero-medial side was 2 ± 0.6 mm and that of the antero-lateral side was 1.63 ± 0.5, and the mean area was 1.29 ± 0.83 mm2. The DML could represent an anatomical structure that joining the temporo-mandibular joint and the malleus may play a role in the otologic symptoms during temporo-mandibular disorders.

An increasing number of observations have called the general scheme of five renal segments into question: anatomists, radiologists, and surgeons have reported discrepancies between Graves's scheme and morphological observations. The aims of the present study are: (1) to assess the correspondence between a virtual and a real vascular cast of the kidney; (2) to analyze the arterial anatomy with reference to the renal segments. Fifteen kidneys were injected with acrylic resins to obtain vascular casts, which were also analyzed by computed tomography. A mean of 6.3 (range 4-8) avascular fissures was found, indicating a mean of 7.3 segments (range 5-9). In the superior and middle territories there was a single segment in 4 (26.7%) and 8 (53.3%) cases, respectively, and there were two segments in 11 (73.3%) and in 7 (46.7%) cases, respectively. In the inferior territory there was a single segment in two cases (13.3%), two segments in nine (60%), and three segments in four (26.7%). A mean segmental volume of 550.5 mm3 was calculated; the posterior (1,030.1 mm3 , 28.9%) and inferior (450.3 mm3 , 24.2%) segments were the largest. More third order branches were identified in the inferior segments than in the other segments (three branches of the inferior segmental artery in 26.6%). According to these data the inferior segment occupies the inferior pole, extending both anteriorly and posteriorly. In conclusion, the high correspondence between a virtual and a real vascular cast permits more segments to be identified than those described by Graves, and the volume of each segment can be calculated. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc.

ObjectiveTo investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS).MethodsIn this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years. Kaplan-Meier and Cox regression analyses investigated early factors influencing the risk of secondary progressive (SP) MS.ResultsFifty-nine patients (27%) converted to SPMS in 6.1 mean years. A larger number of CLs at onset predicted a higher risk of SPMS (hazard ratio [HR] 2.16, 4.79, and 12.3 for 2, 5, and 7 CLs, respectively, p < 0.001) and shorter latency to progression. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset, accrued more CLs, experienced more severe cortical atrophy over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p < 0.001), a larger baseline CL (HR 2.21, p = 0.005) and WM lesion (HR 1.32, p = 0.03) volume, early changes of global Cth (HR 1.36, p = 0.03), and ≥3 ERs (HR 6.08, p < 0.001) independently predicted a higher probability of SP.ConclusionsExtensive cortical damage at onset is associated with florid inflammatory clinical activity and predisposes to a rapid occurrence of the progressive phase. Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy.

The Tauber procedure, i.e., antegrade sclerotherapy for varicocele, can lead to ischemic colitis. The pathogenesis can involve an atypical systemic-portal communication, which could represent an infrequently reported (rare) anatomical variant. The aim of this study is to review clinical cases from the literature to highlight the anatomical bases of such complications. A computer-aided and hand-checked review of the literature was used to identify relevant publications. Also, the computed tomography (CT) examination of a clinical case with medico-legal implications due to severe vascular complication following Tauber's procedure was reviewed. Although specific references to this complication have appeared since the 19th century, reports in the contemporary literature include only a few clinical cases of ischemic colitis following Tauber's procedure. The CT scan images of a filed lawsuit revealed traces suggesting a significant communication between the testicular and left colic veins, forming part of the systemic-portal anastomoses. An anatomical variation consisting of a communication between the testicular and left colic veins has been described from the clinical point of view, corresponding to a significant anatomical finding identified in the past that has been under-reported and its clinical importance subsequently underestimated. For the first time we have demonstrated its pathophysiological significance in a real clinical scenario, linking the anatomical variation to the clinical complication. This demonstrates the importance of raising scientific awareness on this issue to prevent possibly devastating complications in daily clinical practice. Clin. Anat. 31:774-781, 2018. © 2018 Wiley Periodicals, Inc.

The pancreas receives multiple arterial sources that should be considered in patients undergoing pancreatic surgery. The aim of this study is to describe pancreatic vascularization and to explore the anatomical basis of postoperative complications. Ten specimens from unembalmed cadavers, including the retroperitoneal vessels and organs and spleen, were injected with acrylic resins to obtain vascular casts. Thirty computed tomography angiographies (CTA) of subjects with no pancreatic pathology (mean age 70.9 years) were also analyzed. A paucivascular area at the neck of the pancreas was apparent in all vascular casts. At CTA: (1) the transverse pancreatic artery, the only artery running from the cervicocephalic to the somatocaudal segment, was visible in 76.9% of cases; (2) the splenic artery was suprapancreatic in 66.7% and intrapancreatic with a tortuous course in 33.3%; (3) the posterior superior pancreaticoduodenal artery was visible in 100% of cases, the anterior superior pancreatico-duodenal artery in 92.6%, the anterior inferior pancreaticoduodenal artery in 73.1%, the posterior inferior pancreaticoduodenal artery in 86.4%, the dorsal pancreatic artery in 65.4%, the great pancreatic artery in 73.1%, and the pancreatic arteries to the body and caudal pancreatic arteries in 96.2%. Our study demonstrated great individual variability of the pancreatic vasculature, which can be explored by CTA and could be relevant to surgical procedures. Clin. Anat. 30:614-624, 2017. © 2017 Wiley Periodicals, Inc.

Background and objectives A detailed understanding of surgical anatomy is an essential requisite to maximize perioperative and functional outcomes of partial nephrectomy. The objectives of this study were 1) to validate the Graves classification and 2) to verify the real absence of collateral arterial blood-supply between different renal segments. Material and methods The study was performed on 15 normal kidneys sampled from 8 un-embalmed cadavers. Kidneys with the surrounding perirenal fat tissue were removed en bloc with the abdominal segment of the aorta. The renal artery was injected with acrylic and radiopaque resins with the specimen suspended in water. A computed tomography examination of the injected kidneys was performed in order to analyse the branches located deeply. After the imaging acquisition, the specimens were treated with sodium hydroxide for removal of the parenchyma to obtain the vascular casts. Results Ten casts (66.6%) showed the classical subdivision of the main artery in a single posterior and anterior branch. Concerning the distribution of the segmental or second order arteries, only 2 (13%) casts showed a pattern similar to that described by Graves characterized by 4 segmental (second order) branches coming from the anterior renal artery (apical, superior, middle and inferior). In the remaining 13 kidneys (87%) a different arterial vascular network was detected. In 10 (80%) casts a single renal segment resulted vascularised by two or more different branches coming from an artery destined to another segment (multiple vascularisation). In details, multiple vascularisation was observed in 3 (20%) apical segments, in 5 (33%) superior segments, in 6 (40%) middle segments, in 7 (47%) inferior segments, and in 2 (13%) posterior segments. Conclusions This study demonstrates that in the human kidneys the arterial vasculature is frequently different from the classical Graves description. Moreover, in a significant percentage of cases, a single renal segment receives two or more branches coming from an artery destined to another segment. This article is protected by copyright. All rights reserved.

Differential diagnosis between normal/variant anatomy and pathological/traumatic findings represents one of the main matters of investigation of the so-called forensic clinical anatomy. In the literature, many anatomical variations of the laryngeal thyroid cartilage have been reported, with potential implications in forensic pathology. They include triticeal cartilages, foramen thyroideum, asymmetry, segmentation or agenesis of the superior thyroid horns, bone connections with the hyoid bone, absence of cricothyroid facets, hypertrophy of the inferior thyroid tubercle, and asymmetries in the thyroid notch, isthmus, or length of the inferior horn. In this report, we describe a laryngeal anatomical variation never described before, consisting of 2 apophyses symmetrically arising from the posterior margins of the thyroid laminae. Postmortem computed tomography performed on the laryngeal visceral block excluded previous traumatic injuries or natural pathologies of the laryngeal cartilages, confirming the congenital origin of the finding. An "omega epiglottis" and 3 laryngeal cysts in the piriform sinuses also coexisted, suggesting the possibility of underlying common developmental mechanisms.

Summary Background Tremelimumab, an anti-CTLA4 monoclonal antibody, initially showed good activity when used alone in patients with mesothelioma, but did not improve the overall survival of patients who failed on first-line or second-line chemotherapy compared with placebo in the DETERMINE study. We aimed to investigate the efficacy and safety of first-line or second-line tremelimumab combined with durvalumab, an anti-PD-L1 monoclonal antibody, in patients with malignant mesothelioma. Methods In this open-label, non-randomised, phase 2 trial, patients with unresectable pleural or peritoneal mesothelioma received intravenous tremelimumab (1 mg/kg bodyweight) and durvalumab (20 mg/kg bodyweight) every 4 weeks for four doses, followed by maintenance intravenous durvalumab at the same dose and schedule for nine doses. The primary endpoint was the proportion of patients with an immune-related objective response according to the immune-related modified Response Evaluation Criteria in Solid Tumors (RECIST; for pleural mesothelioma) or immune-related RECIST version 1.1 (for peritoneal mesothelioma). The primary analysis was done by intention to treat, whereas the safety analysis included patients who received at least one dose of study drug. This trial is registered with the European Clinical Trials Database, number 2015-001995-23, and ClinicalTrials.gov, number NCT02588131, and is ongoing but no longer recruiting patients. Findings From Oct 30, 2015, to Oct 12, 2016, 40 patients with mesothelioma were enrolled and received at least one dose each of tremelimumab and durvalumab. Patients were followed-up for a median of 19·2 months (IQR 13·8–20·5). 11 (28%) of 40 patients had an immune-related objective response (all partial responses; confirmed in ten patients), with a median response duration of 16·1 months (IQR 11·5–20·5). 26 (65%) patients had immune-related disease control and 25 (63%) had disease control. Median immune-related progression-free survival was 8·0 months (95% CI 6·7–9·3), median progression-free survival was 5·7 months (1·7–9·7), and median overall survival was 16·6 months (13·1–20·1). Baseline tumour PD-L1 expression did not correlate with the proportion of patients who had an immune-related objective response or immune-related disease control, with immune-related progression-free survival, or with overall survival. 30 (75%) patients experienced treatment-related adverse events of any grade, of whom seven (18%) had grade 3–4 treatment-related adverse events. Treatment-related toxicity was generally manageable and reversible with protocol guidelines. Interpretation The combination of tremelimumab and durvalumab appeared active, with a good safety profile in patients with mesothelioma, warranting further exploration. Funding Network Italiano per la Bioterapia dei Tumori Foundation, Associazione Italiana per la Ricerca sul Cancro, AstraZeneca, and Istituto Toscano Tumori.

The Tauber procedure, i.e., antegrade sclerotherapy for varicocele, can lead to ischemic colitis. The pathogenesis can involve an atypical systemic-portal communication, which could represent an infrequently reported (rare) anatomical variant. The aim of this study is to review clinical cases from the literature to highlight the anatomical bases of such complications. A computer-aided and hand-checked review of the literature was used to identify relevant publications. Also, the computed tomography (CT) examination of a clinical case with medico-legal implications due to severe vascular complication following Tauber's procedure was reviewed. Although specific references to this complication have appeared since the 19th century, reports in the contemporary literature include only a few clinical cases of ischemic colitis following Tauber's procedure. The CT scan images of a filed lawsuit revealed traces suggesting a significant communication between the testicular and left colic veins, forming part of the systemic-portal anastomoses. An anatomical variation consisting of a communication between the testicular and left colic veins has been described from the clinical point of view, corresponding to a significant anatomical finding identified in the past that has been under-reported and its clinical importance subsequently underestimated. For the first time we have demonstrated its pathophysiological significance in a real clinical scenario, linking the anatomical variation to the clinical complication. This demonstrates the importance of raising scientific awareness on this issue to prevent possibly devastating complications in daily clinical practice. Clin. Anat. 31:774-781, 2018. © 2018 Wiley Periodicals, Inc.

In forensic clinical anatomy computed tomography (CT) is used in post-mortem radiological investigation as an objective nondestructive documentation of the body surface and of the interior of the body. This technique is applied also in paleopathology, in particular in mummy studies, with the aim of providing a permanent record of the mummy’s features, investigating the embalming procedure employed and analyzing the extent of the preservation in detail. For the Extraordinary Jubilee of Mercy, the mortal remains of Saint Leopold Mandic and Saint Pio da Pietralcina, as examples of Mercy known by everyone, have been brought to Rome in February 2016. During the survey that preceded the preparation for transport to Rome, a whole-body CT was performed on the mummified corpse of Leopold Mandic, Capuchin Saint of Padova, Italy. The CT examination demonstrated the presence of osteoarthritis at the level of the vertebral column, of the left knee and of the left hand. Moreover, CT showed the preservation of skeleton and partial preservation of the some viscera, such as remnants of the brain, heart, oesophagus, urinary bladder, plexuses and spinal nerves, ear ossicles, major arterial vessels (aorta and carotid arteries). It is to emphasize the fact that Saint Leopold was not subjected before the CT to any conservative treatment. Computed tomography demonstrated to be a non-destructive method to investigate Saint Leopold, in order to maintain the integrity of the body and to acquire data on his pathologies and on his preservation. CT allows not only the acquisition of sectional images but also, thanks to dedicated software, the post-processing and reconstruction of three-dimensional models, that can be used also for public displays.

Recent anatomic investigations of the lateral structures of the knee have rediscovered a ligament, called the antero-lateral ligament (ALL). Ten specimens of ALL (6 M, 4 F, mean age 82.3) were sampled from bodies of the Body Donation program of the University of Padova for histological and immuno-histochemical studies. Moreover, a retrospective magnetic resonance (MR) study was carried out in 50 patients (30 M, 20 F, mean age 37.5). MR exams with a normal anatomo-radiological report were selected. From the microscopic point of view the ALL corresponds to a dense connective tissue (mean thickness 893 ± 423 µm), and is composed by collagen I (90 %), collagen III (5 %) and collagen VI (3 %) and scarce elastic fibers (

Treatment of malignant pleural mesothelioma (MPM) represents a highly unmet medical need. Here, we discuss the results and therapeutic potential of first- and second-generation immunomodulatory antibodies targeting distinct immune checkpoints for the treatment of MPM, as well as their prospective therapeutic role in combination strategies. We also discuss the role of appropriate radiological criteria of response for MPM and the potential need of ad hoc criteria of disease evaluation in MPM patients undergoing treatment with immunotherapeutic agents.

The pancreas receives multiple arterial sources that should be considered in patients undergoing pancreatic surgery. The aim of this study is to describe pancreatic vascularization and to explore the anatomical basis of postoperative complications. Ten specimens from unembalmed cadavers, including the retroperitoneal vessels and organs and spleen, were injected with acrylic resins to obtain vascular casts. Thirty computed tomography angiographies (CTA) of subjects with no pancreatic pathology (mean age 70.9 years) were also analyzed. A paucivascular area at the neck of the pancreas was apparent in all vascular casts. At CTA: (1) the transverse pancreatic artery, the only artery running from the cervicocephalic to the somatocaudal segment, was visible in 76.9% of cases; (2) the splenic artery was suprapancreatic in 66.7% and intrapancreatic with a tortuous course in 33.3%; (3) the posterior superior pancreaticoduodenal artery was visible in 100% of cases, the anterior superior pancreatico-duodenal artery in 92.6%, the anterior inferior pancreaticoduodenal artery in 73.1%, the posterior inferior pancreaticoduodenal artery in 86.4%, the dorsal pancreatic artery in 65.4%, the great pancreatic artery in 73.1%, and the pancreatic arteries to the body and caudal pancreatic arteries in 96.2%. Our study demonstrated great individual variability of the pancreatic vasculature, which can be explored by CTA and could be relevant to surgical procedures. Clin. Anat. 30:614-624, 2017. © 2017 Wiley Periodicals, Inc.

Objectives The frequency of suboccipital injections to treat headaches has increased. The third segment of the vertebral artery is located in the suboccipital triangle and its main muscular branch, the suboccipital artery of Salmon (SAS), supplies blood to the suboccipital muscles. The purpose of this study was to radiographically investigate the morphology and territory of distribution of SAS. Patients and methods Computed tomography angiographs of brains of 50 subjects (25 female, 25 men, mean age 70.2 years) were analyzed. Results SAS was present in 48% of subjects. The vessel was present bilaterally in 37.1%, and had a mean (SD) luminal diameter of 1.71 (0.34) mm and mean (SD) length of 36.42 (17.1) mm. SAS was found to have two morphologic patterns: (1) a single main trunk with collateral branches (52.6%) and (2) a short common trunk that divided into two branches (48.4%). The SAS supplied the obliquus capitis inferior, semispinalis capitis, and splenius capitis muscles. When the SAS was absent, the suboccipital muscles were supplied by a branch of the occipital artery. No anastomoses were found between the SAS and occipital artery. Conclusion The suboccipital muscles are vascularized by the SAS and occipital artery. The detailed course of the SAS is important for clinicians and surgeons who perform procedures in the suboccipital region.

Although the plantar fascia (PF) has been studied quite well from a biomechanical viewpoint, its microscopic properties have been overlooked: nothing is known about its content of elastic fibers, the features of the extracellular matrix or the extent of innervation. From a functional and clinical standpoint, the PF is often correlated with the triceps surae muscle, but the anatomical grounds for this link are not clear. The aim of this work was to focus on the PF macroscopic and microscopic properties and study how Achilles tendon diseases might affect it. Twelve feet from unembalmed human cadavers were dissected to isolate the PF. Specimens from each PF were tested with various histological and immunohistochemical stains. In a second stage, 52 magnetic resonance images (MRI) obtained from patients complaining of aspecific ankle or foot pain were analyzed, dividing the cases into two groups based on the presence or absence of signs of degeneration and/or inflammation of the Achilles tendon. The thickness of PF and paratenon was assessed in the two groups and statistical analyses were conducted. The PF is a tissue firmly joined to plantar muscles and skin. Analyzing its possible connections to the sural structures showed that this fascia is more closely connected to the paratenon of Achilles tendon than to the Achilles tendon, through the periosteum of the heel. The PF extended medially and laterally, continuing into the deep fasciae enveloping the abductor hallucis and abductor digiti minimi muscles, respectively. The PF was rich in hyaluronan, probably produced by fibroblastic-like cells described as ‘fasciacytes’. Nerve endings and Pacini and Ruffini corpuscles were present, particularly in the medial and lateral portions, and on the surface of the muscles, suggesting a role for the PF in the proprioception of foot. In the radiological study, 27 of the 52 MRI showed signs of Achilles tendon inflammation and/or degeneration, and the PF was 3.43 ± 0.48 mm thick (99%CI and SD = 0.95), as opposed to 2.09 ± 0.24 mm (99%CI, SD = 0.47) in the patients in which the MRI revealed no Achilles tendon diseases; this difference in thickness of 1.29 ± 0.57 mm (99%CI) was statistically significant (P < 0.001). In the group of 27/52 patients with tendinopathies, the PF was more than 4.5 mm thick in 5, i.e. they exceeded the threshold for a diagnosis of plantar fasciitis. None of the other 25/52 paitents had a PF more than 4 mm thick. There was a statistically significant correlation between the thicknesses of the PF and the paratenon. These findings suggest that the plantar fascia has a role not only in supporting the longitudinal arch of the foot, but also in its proprioception and peripheral motor coordination. Its relationship with the paratenon of the Achilles tendon is consistent with the idea of triceps surae structures being involved in the PF pathology, so their rehabilitation can be considered appropriate. Finally, the high concentration of hyaluronan in the PF points to the feasibility of using hyaluronan injections in the fascia to treat plantar fasciitis.

Objective Clinical and neuroimaging parameters predictive of the changing clinical course of multiple sclerosis (MS) from relapsing–remitting to secondary progressive have not been clarified yet. We specifically designed a prospective 5-year longitudinal study aimed at assessing demographic, clinical, and magnetic resonance imaging (MRI) parameters that could predict the changing clinical course of MS. Methods At study entry and after 5 years, clinical and MRI (ie, gray matter and white matter lesions, including spinal cord lesions, and global and regional cortical thinning) parameters were assessed in a training set of 334 consecutive relapsing–remitting MS patients and in an independent validation set of 84 relapsing–remitting MS patients. Results Sixty-six (19.7%) relapsing–remitting MS patients changed their clinical course during the study and entered into the secondary progressive phase. Age (p = 0.001, odds ratio [OR] = 1.2), cortical lesion volume (p

Gabriel Falloppius is known for his contributions to anatomy. Indeed, many anatomic structures bear his name, such as the Fallopian tubes, and his descriptions often contradicted those of other notable anatomists, such as Galen and Andreas Vesalius. In his textbook "Observationes Anatomicae," he described for the first time the structures of the ear, eye, and female reproductive organs, and elucidated the development of the teeth. Furthermore, Falloppius described the facial canal. The objectives of this paper are to provide an overview of Falloppius's life and to discuss the clinical relevance of the facial canal as understood from his description of this anatomic structure.

The response to resistance training and protein supplementation in the latissimus dorsi muscle (LDM) has never been investigated. We investigated the effects of resistance training (RT) and protein supplementation on muscle mass, strength, and fiber characteristics of the LDM. Eighteen healthy young subjects were randomly assigned to a progressive eight-week RT program with a normal protein diet (NP) or high protein diet (HP) (NP 0.85 vs. HP 1.8 g of protein·kg−1·day−1). One repetition maximum tests, magnetic resonance imaging for cross-sectional muscle area (CSA), body composition, and single muscle fibers mechanical and phenotype characteristics were measured. RT induced a significant gain in strength (+17%, p < 0.0001), whole muscle CSA (p = 0.024), and single muscle fibers CSA (p < 0.05) of LDM in all subjects. Fiber isometric force increased in proportion to CSA (+22%, p < 0.005) and thus no change in specific tension occurred. A significant transition from 2X to 2A myosin expression was induced by training. The protein supplementation showed no significant effects on all measured outcomes except for a smaller reduction of 2X myosin expression. Our results suggest that in LDM protein supplementation does not further enhance RT-induced muscle fiber hypertrophy nor influence mechanic muscle fiber characteristics but partially counteracts the fast-to-slow fiber shift.

Lumbar hernias are protrusions of intra-abdominal contents classically through the superior (Grynfeltt) and inferior (Petit) lumbar triangles. The anatomy of the triangles is variable and quantitative data are few. No radiological data on the anatomy of the triangles are available. Fifty computed tomography angiography of the upper abdomen (M25, F25, mean age 72.5-year-old) were analyzed. The dimensions and the contents of the lumbar triangles were analyzed. The characteristics of the space between the two triangles were also documented. The superior lumbar triangle showed a mean surface area of 5.10 ± 2.6 cm2. In the area of the triangle, the 12th intercostal pedicle and the 1st lumbar branches of the iliolumbar vessels were found in 42 and 46 %, respectively. The inferior lumbar triangle had a mean surface of area 18.7 ± 8.4 cm2. In this area, the 2nd, 3rd, and 4th lumbar branches were found in 9, 67, and 8 %, respectively. On oblique coronal images, a direct tunnel between the superior and the inferior lumbar triangles was found, showing an oblique course, with a postero-anterior direction (mean length 36.5 ± 5.8 mm, mean caliber 7.4 ± 3.1 mm). Among the anatomical factors of weakening of the abdominal wall, the course of branches of the lumbar vessels was documented not only in the superior but also in the inferior lumbar triangle. A real musculoaponeurotic tunnel between the superior and the inferior lumbar triangles located in the oblique coronal plane was found, that could play a role in the development of incarceration or strangulation of lumbar hernias.

When the anomalous origin of coronary arteries (AOCA) is suspected in children (especially athletes), due to signs and symptoms of myocardial ischemia or on the basis of echocardiographic assessment, three-dimensional coronary magnetic resonance angiography (3D-CMRA) can be proposed for the fine morphological evaluation of coronary branches anatomy and course. We tested the diagnostic potential of CMRA angiography in a prospective study on AOCA in young patients. Between July 2005 and June 2008, 15 patients aged 6–29 years (mean age, 13.5 years±5.6 S.D.; median, 14) with clinical and echocardiographic suspicion of AOCA underwent CMRA (1.5 T), 3D whole-heart, free-breathing technique, without the use of contrast medium and β-blockers, with a mean examination time of 30 min. We acquired a second scan of all patients to ameliorate the quality of the acquisition and to improve our experience. AOCA was confirmed by 3D-CMRA in 8 out of 15 cases (53%) and three different anatomical variants were demonstrated, that is, ectopic origin of the left circumflex artery arising from the right coronary artery with retro-aortic course in four cases, single coronary artery arising from the right sinus of Valsalva with interarterial course in one case, ectopic right coronary artery arising from the left sinus of Valsalva with interarterial course in one case; in two patients without anomalies of origin of the coronary arteries, elongated LMCA with angulation of the proximal segment of the left circumflex artery was present. When AOCA is suspected particularly in children (especially athletes), CMRA without the use of contrast medium is an effective diagnostic technique, which is useful to clarify the spatial position of the anomalous course of the main coronary branches in order to suggest the most convenient management of the disease. CMRA does not need contrast medium, needles, and β-blockers; is repeatable in the same examination without the exposure to X-rays; allows a parent to stay near the child; and needs low collaboration in low-stress conditions.

Background Poor wound-healing and skin necrosis are potentially devastating complications after total knee arthroplasty. Primary soft-tissue coverage with a medial or lateral gastrocnemius transposition flap is typically the first choice for reconstruction. The aim of this study was to evaluate the use of a distally based secondary-pedicle flap of the gracilis muscle for reconstruction of a soft-tissue defect. Methods The characteristics of the distally based (secondary) pedicles of the gracilis muscle were studied with use of dissection (ten cadavers) and computed tomographic angiograms (fifty patients). On the basis of the anatomical features, an extended reversed gracilis flap based on the secondary pedicles was used in three patients with severe soft-tissue complications of total knee arthroplasty. Results The mean number of secondary pedicles was 1.8 (range, one to four). The pedicles originated from the superficial femoral or popliteal artery. The most proximal pedicle was often the largest (mean caliber, 2.0 mm), and its point of entry into the gracilis muscle was an average (and standard deviation) of 21 +/- 3.6 cm (range, 16 to 28 cm) from the ischiopubic branch. A significant positive association (p = 0.001; r(2) = 0.49) was found between the caliber of the proximal secondary pedicle and the number of other secondary pedicles. In all three patients, the adequate caliber of the secondary pedicles (as shown on preoperative computed tomographic angiograms) and good muscle vascularization confirmed the utility of the gracilis as a distally based pedicle flap. Conclusions For the treatment of large soft-tissue defects of the patella or the proximal part of the knee, or for soft-tissue reconstruction over an exposed total knee prosthesis, the reversed gracilis pedicle flap may be an alternative to, or may be integrated with, a lateral or medial gastrocnemius flap.

This report presents a case of a 16-year-old hypertensive boy who presented to our clinic. Laboratory findings showed severe hypokalemia and markedly increased plasma renin activity. Abdominal ultrasonography and contrast-enhanced computed tomography of the abdomen revealed a well-circumscribed, solid, hypoenhancing cortical lesion (2 cm) in the lower pole of the left kidney. The patient under- went nephron-sparing surgery. Histopathologic examination gave a diagnosis of juxtaglomerular cell tumor. Reninoma is an uncommon cause of hypertension in a young adult and should be included in the differential diagnosis as a potential life-threatening and curable condition. The conservative surgical management is the gold standard for small, circumscribed lesions.

Fibromuscular dysplasia (FMD) is one of the most common causes of renovascular hypertension in children and women. It is characterized by short multiple stenoses alternated to focal expansions that usually involve the lateral third of the renal artery. Digital subtraction angiography is considered the most accurate method in the diagnosis of renal artery FMD. An indirect sign of FMD-the notches on the ureter secondary to the hypertrophy of the branches of ureteric arteries "climbing" along the ureters-can be visualised during urography. We report the case of a 38-years-old woman with hypertension and no history of familiar predisposition, in which the multidetector computed tomography angiography was able to show both direct and indirect radiological signs of renal artery FMD. 2D and 3D visualisations are useful to suggest the diagnosis of FMD and in the follow-up in patients who underwent to percutaneous transluminal angioplasty.

Epilepsy is three to six times more frequent in MS than in the general population. Previous studies based on conventional magnetic resonance (MR) imaging have suggested a possible correlation between cortical inflammatory pathology and epileptic seizures. However, pure intracortical lesions (ICLs) are unlikely to be demonstrated with conventional MR. We applied the double inversion recovery (DIR) sequence in relapsing remitting MS (RRMS) patients with or without epileptic seizures in order to clarify the relationship between ICLs and epilepsy in MS in vivo.Twenty RRMS patients who had epileptic seizures (RRMS/E) during the course of the disease were studied for the presence of ICLs. A group of 80 RRMS patients with no history of seizures and matched for gender, age, disease duration, Expanded Disability Status Scale (EDSS) grading, and T2 lesion volume (T2-WMLV) was selected as reference population. ICLs were detected by applying the DIR sequence.ICLs were observed in 18/20 (90%) RRMS/E and in 39/80 (48%) RRMS (p = 0.001). RRMS/E showed five times more ICLs (7.2 +/- 8.4) than RRMS (1.5 +/- 2.4; p = 0.015). The total ICLs volume was 6 times larger in RRMS/E than in RRMS (1.2 +/- 1.7 cm3 versus 0.2 +/- 0.2 cm3, p = 0.016). No significant difference was observed between RRMS and RRMS/E with regard to the number and volume of juxtacortical lesions and T2-WMLV.Our findings indicate that RRMS/E have more extensive cortical inflammation than RRMS patients with no history of epilepsy. Inflammatory ICLs may be responsible for epilepsy in MS.

Pulmonary sequestration is a pulmonary malformation in which a portion of nonfunctioning bronchopulmonary tissue is separated from the rest of the lung parenchyma. We report the case of a 48-year-old woman with history of chronic pneumonia, studied with computed tomography and in whom we obtained three dimensional evaluation of the pathological structures.

Increasing evidence suggests relevant cortical gray matter pathology in patients with Multiple Sclerosis (MS), but how early this pathology begins; its impact on clinical disability and which cortical areas are primarily affected needs to be further elucidated.115 consecutive patients (10 Clinically Isolated Syndrome (CIS), 32 possible MS (p-MS), 42 Relapsing Remitting MS (RR-MS), 31 Secondary Progressive MS (SP-MS)), and 40 age/gender-matched healthy volunteers (HV) underwent a neurological examination and a 1.5 T MRI. Global and regional Cortical Thickness (CTh) measurements, brain parenchyma fraction and T2 lesion load were analyzed.We found a significant global cortical thinning in p-MS (2.22 +/- 0.09 mm), RR-MS (2.16 +/- 0.10 mm) and SP-MS (1.98 +/- 0.11 mm) compared to CIS (2.51 +/- 0.11 mm) and HV (2.48 +/- 0.08 mm). The correlations between mean CTh and white matter (WM) lesion load was only moderate in MS (r = -0.393, p = 0.03) and absent in p-MS (r = -0.147, p = 0.422). Analysis of regional CTh revealed that the majority of cortical areas were involved not only in MS, but also in p-MS. The type of clinical picture at onset (in particular, pyramidal signs/symptoms and optic neuritis) correlated with atrophy in the corresponding cortical areas.Cortical thinning is a diffuse and early phenomenon in MS already detectable at clinical onset. It correlates with clinical disability and is partially independent from WM inflammatory pathology.

In addition to the optic canal and the superior orbital fissure, orbits are connected with the cranial cavity via inconstant canals including the orbitomeningeal foramen. This study has been carried out in order to define many anatomical and radiological details of the orbitomeningeal foramen that are relevant in the clinical practice. Almost 1000 skulls and 50 computerized tomographies were examined to determine incidence, number, length, and caliber of the orbitomeningeal foramen as well as the topography of their orbital and cranial openings. A retrospective study of angiographies carried out on more than 100 children was performed to look for arteries candidate to run through the orbitomeningeal foramen. Orbitomeningeal foramina were detected in 59.46 % of skulls and in 54 % of individuals by computerized tomography. Orbits with two to five foramina were found. Canals were classified as M-subtype or A-subtype depending on their cranial opening. Large foramina, with the caliber ranging between 1 and 3 mm, were found in 12.17 % of orbitomeningeal foramen-bearing orbits. By computed tomography the average caliber measured 1.2 ± 0.3 and 1.5 ± 0.5 mm (p

Myostatin (MSTN) is a negative regulator of muscle growth even if some studies have shown a counterintuitive positive correlation between MSTN and muscle mass (MM). Our aim was to investigate the influence of 2 months of resistance training (RT) and diets with different protein contents on plasma MSTN, interleukin 1 beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and insulin-like growth factor 1 (IGF-1). Eighteen healthy volunteers were randomly divided in two groups: high protein (HP) and normal protein (NP) groups. Different protein diet contents were 1.8 and 0.85 g of protein·kg bw(-1)·day(-1) for HP and NP, respectively. Subjects underwent 8 weeks of standardized progressive RT. MSTN, IGF-1, IL-1β, IL-6, and TNF-α were analyzed before and after the first and the last training sessions. Lean body mass, MM, upper-limb muscle area, and strength were measured. Plasma MSTN showed a significant increase (P

Branching variations of the left portal vein can be managed but they may require technical adaptation. The aim of the present study was to investigate the pattern of ramification of the left portal vein in vascular casts and in radiological images. 50 vascular casts and 200 computed tomography (CT) angiographies of the upper abdomen were analyzed. Analyses of the vascular casts and of the radiological images were conducted to evaluate the morphology of the left liver, the modality of division of the portal vein, and the number of branches destined for segments 2, 3, 4. In the vascular casts the portal vein presented bifurcation in 75 %, trifurcation in 20 %, and quadrifurcation in 5 %, whereas in the radiological study the portal vein presented bifurcation in 90 % and trifurcation in 10 % of the cases. For segment 2 in the vascular casts, in their CT and in the radiologic in vivo study a number from 1 to 3 branches was found, coming from the medial or posterior aspects of the left portal vein. For segment 3 in the vascular casts, in their CT and in the radiologic in vivo study a number from 1 to 6 branches was found, coming from the posterior and medial aspects of the left portal vein and its the cul-de-sac. For segment 4 in the vascular casts, in their CT a number from 5 to 9 branches was found (in the radiologic in vivo study from 4 to 9), coming from the posterior and ventral aspects of the left portal vein and from its cul-de-sac. No branches were found to come from the lateral aspect of the left portal vein. Moreover, the modality of branching of the left portal vein correlated with the morphology of left liver. Knowledge of the pattern of branching of the left portal vein is important for surgical purpose. CT angiography is a valuable preoperative examination to visualize the branching pattern of adult patients.

Background Both gray-matter (GM) atrophy and lesions occur from the earliest stages of Multiple Sclerosis (MS) and are one of the major determinants of long-term clinical outcomes. Nevertheless, the relationship between focal and diffuse GM damage has not been clarified yet. Here we investigate the regional distribution and temporal evolution of cortical thinning and how it is influenced by the local appearance of new GM lesions at different stages of the disease in different populations of MS patients. Methods We studied twenty MS patients with clinically isolated syndrome (CIS), 27 with early relapsing-remitting MS (RRMS, disease duration

Summary Background CTLA4 blockade by tremelimumab 15 mg/kg every 90 days provided preliminary evidence of activity in patients with pretreated malignant mesothelioma; however, retrospective exposure–response analysis of data from patients with melanoma suggested that this schedule could result in underexposure to tremelimumab. We therefore investigated the efficacy and safety of an intensified schedule of tremelimumab in patients with advanced malignant mesothelioma. Methods In this open-label, single-arm, phase 2 study, participants aged 18 years or older with unresectable, advanced malignant mesothelioma (measurable in accordance with the Response Evaluation Criteria in Solid Tumors [RECIST]), a life expectancy of 3 months or more, an Eastern Cooperative Oncology Group performance status of 2 or less, and who had failed a first-line platinum-based regimen were enrolled at the University Hospital of Siena, Siena, Italy. Participants received tremelimumab 10 mg/kg once every 4 weeks for six doses, then every 12 weeks until disease progression, unacceptable toxic effects, or refusal to continue treatment. The primary endpoint was the proportion of patients achieving an immune-related objective response (complete or partial), assessed in all patients who received at least one dose of the study drug. This study is registered with the European Union Clinical Trials Register, number 2012-002762-12, and ClinicalTrials.gov, number NCT01655888. Findings Between July 30, 2012, and July 15, 2013, we enrolled 29 patients with a median age of 65 years (range 42–78), stage III (n=11) or IV (n=18) disease, and an Eastern Cooperative Oncology Group performance status of 0–1 (n=23) or 2 (n=6). Malignant mesothelioma histology was epithelioid (n=21, including one peritoneal), biphasic (n=6), sarcomatoid (n=1), or undefined (n=1). Patients received a median of six doses of tremelimumab (range 1–13). After a median follow-up of 21·3 months (IQR 18·7–25·9), four immune-related-partial responses were recorded, one at the first tumour assessment (after about 12 weeks) and three at the second tumour assessment (about 24 weeks), with two responses occurring after initial progressive disease and one response after initial stable disease. 15 (52%) of patients achieved disease control, with a median duration of 10·9 months (95% CI 8·2–13·6). According to modified RECIST, one patient (3%) achieved a partial response and 11 (38%) patients achieved disease control rate. Grade 1–2 treatment-related adverse events occurred in 26 (90%) patients and grade 3–4 adverse events in two (7%) patients. The most common treatment-related adverse events were gastrointestinal, dermatological, and fever. Interpretation Our results suggest that the intensified schedule of tremelimumab investigated seems to have clinical and immunological activity in patients with advanced malignant mesothelioma, and a good safety profile. The same intensified schedule is now being investigated in an ongoing randomised, double-blind, placebo-controlled, phase 2b study. Funding Associazione Italiana per la Ricerca sul Cancro, Istituto Toscano Tumori, and MedImmune.

8558 Background: The anti-CTLA-4 tremelimumab at two different dose-schedules of administration showed promising activity in second-line malignant mesothelioma (MM) patients (Calabrò et al., Lancet Oncol, 2013; Calabrò et al., Lancet Respir Med, 2015). These initial results and the efficacy of targeting the PD-1/PD-L1 axis in different tumor types, prompted the NIBIT-MESO-1 study aimed at investigating the efficacy and safety of tremelimumab combined with the anti-PD-L1 durvalumab in mm patients. We report the safety analysis from the fully-enrolled NIBIT-MESO-1 study. Methods: The NIBIT-MESO-1 is a phase II, open-label, single Center study. Forty mm patients received tremelimumab at 1 mg/Kg i.v. every 4 weeks (Q4W) for 4 doses, and durvalumab at 20 mg/Kg i.v. Q4W for 13 doses. Primary objective is immune-related (ir)-objective response rate; secondary are safey, ir-disease control rate, ir-progression free survival, and overall survival. Tumor assessment per ir-modified RECIST or ir-RECIST 1.1 for pleural or peritoneal MM, respectively, was performed at baseline and q12 weeks. Adverse events (AEs) were recorded according to CTC v4.0. (ClinicalTrials.gov Id: NCT02588131). Results: From October 2015 to October 2016, 40 mm patients (38 pleural and 2 peritoneal), median age 64 years (range 41-80), ECOG performance status 0 (n = 19) or 1 (n = 21) were enrolled in the study. mm histology was epithelioid (n = 32), biphasic (n = 5), sarcomatoid (n = 2) or undefined (n = 1). As of January 2017, 12 first or 28 second-line mm patients received a median of 5.5 doses of therapy (range = 1-13). Twenty-four patients (60%) experienced any grade irAEs: 5 patients (12.5%) had grade 3-4 AEs, the most frequent being hepatotoxicity (7.5%). AEs were generally manageable and reversible per protocol guidelines. Three patients (7.5%) were discontinued due to treatment-related AEs (1 trombocytopenia, 1 limbic encephalitis, 1 liver toxicity). Conclusions: The combination of tremelimumab and durvalumab is safe and manageable in mm patients. Clinical trial information: NCT02588131.

The aim of this paper was to examine the macroscopic and microscopic characteristics of the paratendineous tissues (paratenon, epitenon and endotenon) of the calcaneal tendon to better understand their role in the pathogenesis of “tendinopathy”. Ten non-embalmed legs from cadavers were used. Histological and immunohistochemical studies were done at the middle third of the tendon. Magnetic resonance images of the hind foot were made in 60 living subjects to analyze the morphological alterations of tendon and paratenon. The paratenon is a thick fibrous layer with few elastic fibers, continuous with the crural fascia, well vascularized and innervated. It forms a sheath around the tendon similar to a synovial layer, but less organized. Indeed, it has no complete epithelium, but only some cells producing hyaluronan, called fasciacytes. Crural fascia and paratenon can be clearly observed by MRI, appearing as homogeneous, low signal intensity bands, sharply defined in the context of subcutaneous tissue in T1-weighted sequences. The mean thickness of the crural fascia was 1.11 mm in healthy subjects and 1.30 mm in patients (p < 0.005). The mean value of paratenon thickness in patients was 1.34 mm, 0.85 in healthy (p < 0.0001). The paratenon is more highly vascularized and innervated than the tendon, supporting the hypothesis that it is the origin of pain in tendinopathy. The imaging study suggests that, an increase in the thickness of the paratenon more than 1.35 mm is predictive of paratendinopathy, even before tendon damage.

In our study, we evaluated the feasibility of a new sampling method for splenic stiffness (SS) measurement by Quantitative Acoustic Radiation Force Impulse Elastography (Virtual Touch Tissue Quantification (VTTQ)).We measured SS in 54 patients with HCV-related cirrhosis of whom 28 with esophageal varices (EV), 27 with Chronic Hepatitis C (CHC) F1–F3, and 63 healthy controls. VTTQ-SS was significantly higher among cirrhotic patients with EV (3.37 m/s) in comparison with controls (2.19 m/s,P<0.001), CHC patients (2.37 m/s,P<0.001), and cirrhotic patients without EV (2.7 m/s,P<0.001). Moreover, VTTQ-SS was significantly higher among cirrhotic patients without EV in comparison with both controls (P<0.001) and CHC patients (P<0.01). The optimal VTTQ-SS cut-off value for predicting EV was 3.1 m/s (AUROC = 0.96, sensitivity 96.4%, specificity 88.5%, positive predictive value 90%, negative predictive value 96%, positive likelihood ratio 8.36, and negative likelihood ratio 0.04). In conclusion, VTTQ-SS is a promising noninvasive and reliable diagnostic tool to screen cirrhotic patients for EV and reduce the need for upper gastrointestinal endoscopy. By using our cut-off value of 3.1 m/s, we would avoid endoscopy in around 45% of cirrhotic subjects, with significant time and cost savings.

Atrial electrode position was determined by radiographic analysis in 160 patients paced in single-lead VDD for second- or third-degree A-V block, implanted > 1 year with Phymos single pass leads and Phymos 3D pacemakers. The packing lead features an atrial dipole with a 30-mm electrode interspace. In 44% of patients, the upper atrial electrode was positioned within a band of 20 mm centered at the level of the superior vena caval insertion (junctional area) and was in the inferior vena cava or in the atrium in 35% and 21% of cases, respectively. In spite of these different dipole locations, all patients had stable atrium-driven pacing at routine follow-up visits. With the electrode in the junctional area, unipolar stimulation of up to 5 V for 1 ms resulted in stable atrial capture in 63% and 59% of the patients in supine and upright positions, respectively. With the electrode in the atrium, corresponding success rates were 45% and 54%. In the atrium, however, the prevalence of diaphragmatic stimulation was significantly lower than at the junction (10% vs 42% in supine position; 21% vs 47% upright). Though atrial sensing function proved adequate in a wide range of positions, these results suggest that the Phymos lead atrial dipole should be positioned within the atrium, as close as possible to the atrial wall, to maximize the number of VDD patients who might benefit from single-lead DDD pacing.

Obesity is associated with structural alterations in subcutaneous small resistance arteries. The aim of the present work is to study modifications of perforators vessels of abdominal wall and subcutaneous tissue characteristics in obese patients after massive weight loss. An anatomo-radiologic study was carried out on 15 patients (5M, 10F, mean age 54.9 y), who underwent abdominoplasty after massive weight loss. Their pre-operative Computed Tomographic (CT) results of the anterior abdominal wall were compared with CT of 15 normal weighted controls. Anatomo-microscopic and morphometric examinations were conducted on full-thickness specimens of panniculectomy samples. 10 right panniculectomy were sampled from donor cadavers. All the measurements were taken on transverse sections. In patients, at CT the mean luminal diameter (LD) and standard deviation of perforator branches of the deep inferior epigastric artery (DIEA) was 3.7 ± 0.4 mm (control 2.2 ± 0.1 mm; p < 0.05). At microscopic examination, the wall thickness of perforator arteries was 212.7 μ ± 83.9 versus 143.9 ± 32.8 (p < 0.05) deep to the superficial fascia and 120.4 μ ± 74.8 versus 72.3 ± 23.5 (p < 0.05) superficial to it. A thickening of the muscular layer was observable and the tunica media represented 71.4% ± 5.6 of the whole area of the wall (controls 37.1% ± 3.5, p < 0.0001). Our data demonstrate that the major LD of the perforators in patients matches with hypertrophy of the tunica media and we think that the major thickness of perforator walls can facilitate the microsurgical technique in free microsurgical flap reconstruction.

TPS8575Background: Malignant mesothelioma (MM) has a very dismal prognosis and treatment of MM patients remains largely unsatisfactory; thus, new therapeutic approaches are eagerly awaited. In the ...

Gabriel Falloppius is known for his contributions to anatomy. Indeed, many anatomic structures bear his name, such as the Fallopian tubes, and his descriptions often contradicted those of other notable anatomists, such as Galen and Andreas Vesalius. In his textbook "Observationes Anatomicae," he described for the first time the structures of the ear, eye, and female reproductive organs, and elucidated the development of the teeth. Furthermore, Falloppius described the facial canal. The objectives of this paper are to provide an overview of Falloppius's life and to discuss the clinical relevance of the facial canal as understood from his description of this anatomic structure.

Background: Although a more favorable course of multiple sclerosis is associated with a low degree of cortical pathology, only longitudinal studies could definitely confirm this association. Materials and Methods: We followed 95 early relapsing–remitting MS (RRMS; median Expanded Disability Status Scale (EDSS) = 1.5, mean disease duration = 3.1 ± 1.3 years) and 45 benign MS patients (EDSS ≤ 3.0, disease duration ≥ 15 years, normal cognition) for 6 years, with EDSS evaluations every 6 months and brain magnetic resonance imaging (MRI) at baseline and then yearly. Results: At baseline, we detected 406 cortical lesions (CLs) in 67/95 (70.5%) early RRMS and in 24/45 (53.3%) benign MS patients ( p = 0.046). After 6 years, the appearance of new CLs was observed in 80/95 (84.2%; 518 CLs) of our early RRMS and in 25/45 (55.5%; 63 CLs; p < 0.001) benign MS patients. At baseline, after corrections for age and disease duration, we observed a cortical thinning of several frontal and temporal regions in our RRMS study patients, compared to the benign MS patients ( p ranging between 0.001–0.05). After 6 years, the cortical thinning had increased significantly in several cortices of RRMS patients, but only in the occipital-temporal ( p = 0.036) and superior parietal gyrus ( p = 0.035) of those with benign MS. Stepwise regression analysis revealed the CL volume ( p = 0.006) and the cortical thickness of the temporal middle ( p < 0.001), insular long ( p < 0.001), superior frontal ( p < 0.001) and middle frontal gyri ( p < 0.001) as the most sensitive independent predictors of a favorable disease course. Conclusions: Our data confirmed that a significantly milder cortical pathology characterizes the most favorable clinical course of MS. Measures of focal and diffuse grey matter should be combined to increase the accuracy in the identification of a benign MS course.