Veronica Macchi

Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) Classification of Renal Tumours in Patients who are Candidates for Nephron-Sparing Surgery

BACKGROUND Besides clinical tumour size, other anatomical aspects of the renal tumour are routinely considered when evaluating the feasibility of elective nephron-sparing surgery (NSS). OBJECTIVE To propose an original, standardised classification of renal tumours suitable for NSS based on their anatomical features and size and to evaluate the ability of this classification to predict the risk of overall complications resulting from the surgery. DESIGN, SETTING, AND PARTICIPANTS We enrolled prospectively 164 consecutive patients who underwent NSS for renal tumours at a tertiary academic referral centre from January 2007 to December 2008. INTERVENTION Open partial nephrectomy without vessel clamping. MEASUREMENTS All tumours were classified by integrating size with the following anatomical features: anterior or posterior face, longitudinal, and rim tumour location; tumour relationships with renal sinus or urinary collecting system; and percentage of tumour deepening into the kidney. We generated an algorithm evaluating each anatomical parameter and tumour size (the preoperative aspects and dimensions used for an anatomical [PADUA] score) to predict the risk of complications. RESULTS AND LIMITATIONS Overall rates of complication were significantly correlated to all the evaluated anatomical aspects, excluding clinical size and anterior or posterior location of the tumour. By multivariate analysis, PADUA scores were independent predictors of the occurrence of any grade complications (hazard ratio [HR] for score 8-9 vs 6-7: 14.535; HR for score ≥10 vs 6-7: 30.641). Potential limitations were the limited number of patients with T1b tumours included in the study and the lack of laparoscopically treated patients. Further external validation of the PADUA score is needed. CONCLUSIONS The PADUA score is a simple anatomical system that can be used to predict the risk of surgical and medical perioperative complications in patients undergoing open NSS. The use of an appropriate score can help clinicians stratify patients suitable for NSS into subgroups with different complication risks and can help researchers evaluate the real comparability among patients undergoing NSS with different surgical approaches.

A Literature Review of Renal Surgical Anatomy and Surgical Strategies for Partial Nephrectomy

CONTEXT A detailed understanding of renal surgical anatomy is necessary to optimize preoperative planning and operative technique and provide a basis for improved outcomes. OBJECTIVE To evaluate the literature regarding pertinent surgical anatomy of the kidney and related structures, nephrometry scoring systems, and current surgical strategies for partial nephrectomy (PN). EVIDENCE ACQUISITION A literature review was conducted. EVIDENCE SYNTHESIS Surgical renal anatomy fundamentally impacts PN surgery. The renal artery divides into anterior and posterior divisions, from which approximately five segmental terminal arteries originate. The renal veins are not terminal. Variations in the vascular and lymphatic channels are common; thus, concurrent lymphadenectomy is not routinely indicated during PN for cT1 renal masses in the setting of clinically negative lymph nodes. Renal-protocol contrast-enhanced computed tomography or magnetic resonance imaging is used for standard imaging. Anatomy-based nephrometry scoring systems allow standardized academic reporting of tumor characteristics and predict PN outcomes (complications, remnant function, possibly histology). Anatomy-based novel surgical approaches may reduce ischemic time during PN; these include early unclamping, segmental clamping, tumor-specific clamping (zero ischemia), and unclamped PN. Cancer cure after PN relies on complete resection, which can be achieved by thin margins. Post-PN renal function is impacted by kidney quality, remnant quantity, and ischemia type and duration. CONCLUSIONS Surgical renal anatomy underpins imaging, nephrometry scoring systems, and vascular control techniques that reduce global renal ischemia and may impact post-PN function. A contemporary ideal PN excises the tumor with a thin negative margin, delicately secures the tumor bed to maximize vascularized remnant parenchyma, and minimizes global ischemia to the renal remnant with minimal complications. PATIENT SUMMARY In this report we review renal surgical anatomy. Renal mass imaging allows detailed delineation of the anatomy and vasculature and permits nephrometry scoring, and thus precise, patient-specific surgical planning. Novel off-clamp techniques have been developed that may lead to improved outcomes.

Aggregating Phenotype in Lactobacillus crispatus Determines Intestinal Colonization and TLR2 and TLR4 Modulation in Murine Colonic Mucosa

ABSTRACT The colonic microbiota is a major modulator of the mucosal immune system; therefore, its manipulation through supplementation with probiotics may significantly affect the hosts immune responses. Since different probiotics seem to exert various effects in vivo, we tested the relevance of the autoaggregation phenotype on the intestinal persistence of lactobacilli and their ability to modulate the hosts innate immune responses. After 14 days of diet supplementation, the aggregating strain Lactobacillus crispatus M247 but not aggregation-deficient isogenic mutant MU5 was recovered from the feces and colonic mucosa of mice. This observation was confirmed by strain-specific PCR amplification and by Lactobacillus-specific denaturing gradient gel electrophoresis analysis. Indeed, L. crispatus M247 increased Toll-like receptor 2 (TLR2) mRNA levels, while it reduced TLR4 mRNA and protein levels in the colonic mucosa, whereas MU5 was ineffective. In colonic epithelial cells (CMT-93 cells) L. crispatus M247 but not MU5 induced time-dependent extracellular signal-regulated kinase-1 (ERK1) tyrosine phosphorylation and TLR modulation, which were abolished in the presence of PD98059 (an ERK1 inhibitor). To assess the functional relevance of probiotic-induced TLR modulation, we determined the consequences of L. crispatus preexposure on TLR4 (lipopolysaccharide [LPS]) and TLR2 [Pam3Cys-Ser-(Lys)4] ligand-mediated effects in intestinal epithelial cells. Preexposure to L. crispatus M247 blunted LPS-induced interleukin-6 (IL-6) release and inhibition of CMT-93 migration over a wound edge, whereas it enhanced TLR2-mediated IL-10 up-regulation. In summary, the aggregation phenotype is required for L. crispatus persistence in the colon and for modulation of TLR2/TLR4 expression through an ERK-dependent pathway. We speculate that the aggregation phenotype in L. crispatus M247 is required to temper epithelial cell responsiveness to bacterial endotoxins, which thus affects the evolution of intestinal inflammatory processes.

Histological study of the deep fasciae of the limbs

The aim of this study is to analyse the deep fasciae of limbs in order to evaluate the collagen and elastic fibre arrangement and the types of innervation. Histological and immunohistochemical stains were performed in 72 specimens. The deep fascia of the limbs is a sheath presenting a mean thickness of 1mm, formed by two to three layers of parallel collagen fibre bundles. In the adjacent layers, they show different orientations. Each layer is separated from the adjacent one by loose connective tissue, permitting the sliding of the collagen layers. Nerve fibres were found in all specimens, while muscular fibres were evidenced only in one specimen. The described structure permits the fasciae of the limbs to have a strong resistance to traction, even when exercised in different directions. The capacity of the different collagen layers to glide one on the other could be altered in cases of overuse syndrome, trauma, or surgery.

Lactobacillus crispatus M247-Derived H2O2 Acts as a Signal Transducing Molecule Activating Peroxisome Proliferator Activated Receptor-γ in the Intestinal Mucosa

BACKGROUND & AIMS Accumulating evidence indicates that the peroxisome proliferator activated receptor (PPAR)-gamma is a major player in maintaining intestinal mucosa homeostasis, but whether PPAR-gamma is directly involved in probiotic-mediated effects and the molecular events involved in its activation are not known. METHODS We investigated the role of PPAR-gamma in the immunomodulatory effects of Lactobacillus crispatus M247 on intestinal epithelial cells (IEC) and the role of probiotic-derived H(2)O(2) on PPAR-gamma activity. RESULTS L crispatus M247 supplementation in mice significantly increased PPAR-gamma levels and transcriptional activity in the colonic mucosa. L crispatus M247 induced PPAR-gamma nuclear translocation and enhanced transcriptional activity in epithelial (CMT-93) cells, as demonstrated by the increased luciferase activity of a PPAR-gamma-responsive element, PPAR-gamma-responsive gene up-regulation, and reduced activity of an nuclear factor-kappaB-responsive element. Pharmacologic PPAR-gamma inhibition or silencing by small interfering RNA cancelled the L crispatus M247-mediated effects in CMT-93 cells. Because Lactobacillus strains producing little H(2)O(2) failed to activate PPAR-gamma, we investigated the role of L crispatus M247-derived H(2)O(2) in PPAR-gamma activation. L crispatus M247 induced a transient rise in intracellular H(2)O(2) and PPAR-gamma transcriptional activity was cancelled by antioxidant or H(2)O(2) scavenger. Toll-like receptor (TLR)-2 was not required for PPAR-gamma up-regulation mediated by L crispatus M247 in mice, although the protective effects of L crispatus M247 on dextran sodium sulfate-induced colitis were less pronounced in TLR-2(-/-) mice. CONCLUSIONS L crispatus M247 uses H(2)O(2) as a signal transducing molecule to induce PPAR-gamma activation in IEC, directly modulating epithelial cell responsiveness to inflammatory stimuli.

Plantar fascia anatomy and its relationship with Achilles tendon and paratenon

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.

The human area postrema and other nuclei related to the emetic reflex express cAMP phosphodiesterases 4B and 4D

Phosphodiesterase 4 (PDE4) inhibitors, i.e. rolipram, are being extensively investigated as therapeutic agents in several diseases. Emesis is one of the most common side effects of PDE4 inhibitors. Given the fact that the area postrema is considered the chemoreceptor trigger zone for vomiting, the present study investigates the regional distribution and cellular localization of the four gene transcripts of the PDE4 subfamily (PDE4A, PDE4B, PDE4C and PDE4D) in human brainstem. In situ hybridization histochemistry was used to locate the mRNA distribution of the four PDE4 subfamilies in the area postrema and related nuclei of human postmortem brainstem. We have found that in the brainstem PDE4B and PDE4D mRNA expression is abundant and distributed not only in neuronal cells, but also in glial cells, and on blood vessels. The hybridization signals for PDE4B and PDE4D mRNAs in the area postrema were stronger than those in any other nuclei in the brainstem. They were also found in vomiting-related nuclei such as the nucleus of the solitary tract and the dorsal vagal motor nucleus. These findings suggest that cAMP signaling modification in the area postrema could mediate the emetic effects of PDE4 inhibitors in human brainstem.

Distribution and functional significance of angiotensin-II AT1-AND AT2-Receptor subtypes in the rat adrenal gland

The distribution and the functional significance of angiotensin-II (ANG-II) receptor subtypes, AT1 and AT2, in the rat adrenal gland has been investigated in vitro. Autoradiographic assessment of the selective displacement of [125I]ANG-II binding by selective ligands of the two receptor subtypes indicated that zona glomerulosa (ZG) was provided with both AT1 and AT2, and adrenal medulla (AM) almost exclusively with AT2 receptors. ANG-II (10(-9) M) evoked a marked rise in the secretion of aldosterone by dispersed ZG cells and catecholamines by AM fragments. The selective AT1-receptor antagonist DuP753 blocked aldosterone response to ANG-II, while the selective AT2-receptor antagonist PD123319 was ineffective. Catecholamine response to ANG-II was inhibited by PD123319 and only moderately affected by high concentrations of DuP753. The selective AT2-receptor agonist CGP42112 did not change basal aldosterone release of ZG cells, but concentration-dependently enhanced basal catecholamine release by AM fragments. In light of these findings the conclusion is drawn that in the rat the aldosterone secretagogue effect of ANG-II is exclusively mediated by the AT1 receptors present in the ZG, while the catecholamine secretagogue action preminently involves the activation of AT2 receptor located on medullary chromaffin cells.

Surgical anatomy of the pectoral nerves and the pectoral musculature

The pectoral nerves (PNs) may be selectively injured through various traumatic mechanisms such as direct trauma, hypertrophic muscle compression, and iatrogenic injuries (breast surgery and axillary node dissection, pectoralis major muscle transfers). The PN may be surgically recovered through nerve transfers. They may also be used as donors to the musculocutaneous, axillary, long thoracic, and spinal accessory nerves and for reinnervation of myocutaneous free flaps. Thus, in this article, we reviewed the surgical anatomy of PN. A meta‐analysis of the available literature showed that the lateral pectoral nerve (LPN) arises most frequently with two branches from the anterior divisions of the upper and middle trunks (33.8%) or as a single root from the lateral cord (23.4%). The medial pectoral nerve (MPN) usually arises from the medial cord (49.3%), anterior division of the lower trunk (43.8%), or lower trunk (4.7%). The two PN are usually connected immediately distal to the thoracoacromial artery by the so‐called ansa pectoralis. The MPN may also show communications with the intercostobrachial nerve. In 50%–100% of cases, it may pass, at least with some branches, through the pectoralis minor muscle. The LPN supplies the upper portions of the pectoralis major muscle; the MPN innervates the lower parts of the pectoralis major and the pectoralis minor muscle. Among the accessory muscles of the pectoral girdle, the LPN may also innervate the tensor semivaginae articulationis humero‐scapularis, pectoralis minimus, sternoclavicularis, axillary arch, sternalis, and infraclavicularis muscles; the MPN may innervate the pectoralis quartus, chondrofascialis, axillary arch, chondroepitrochlearis, and sternalis muscles. Clin. Anat. 25:559–575, 2012.

Histotopographic study of the fibroadipose connective cheek system.

The purpose of this study was to investigate the morphology of the superficial musculoaponeurotic system (SMAS). Eight embalmed cadavers were analyzed: one side of the face was macroscopically dissected; on the other side, full-thickness samples of the parotid, zygomatic, nasolabial fold and buccal regions were taken. In all specimens, a laminar connective tissue layer (SMAS) bounding two different fibroadipose connective layers was identified. The superficial fibroadipose layer presented vertically oriented fibrous septa, connecting the dermis with the superficial aspect of the SMAS. In the deep fibroadipose connective layer, the fibrous septa were obliquely oriented, connecting the deep aspect of the SMAS to the parotid-masseteric fascia. This basic arrangement shows progressive thinning of the SMAS from the preauricular district to the nasolabial fold (p < 0.05). In the parotid region, the mean thicknesses of the superficial and deep fibroadipose connective tissues were 1.63 and 0.8 mm, respectively, whereas in the region of the nasolabial fold the superficial layer is not recognizable and the mean thickness of the deep fibroadipose connective layer was 2.9 mm. The connective subcutaneous tissue of the face forms a three-dimensional network connecting the SMAS to the dermis and deep muscles. These connective laminae connect adipose lobules of various sizes within the superficial and deep fibroadipose tissues, creating a three-dimensional network which modulates transmission of muscle contractions to the skin. Changes in the quantitative and qualitative characteristics of the fibroadipose connective system, reducing its viscoelastic properties, may contribute to ptosis of facial soft tissues during aging.