Frailty of the elderly in orthopaedic surgery and body composition changes: the musculoskeletal crosstalk through irisin.

In recent years, scientific interest has been developed towards irisin, a novel molecule of the family of myokines, which is directly involved in body mass composition balance, chronic diseases susceptibility and physiologic resilience to stressful events, including surgery. In the context of musculoskeletal disease, the role of this molecule has been associated to the balance of lean and fatty mass, and the production of irisin is subordinated to a healthy lifestyle and exercise. The mechanism of action of irisin on tissues is complex, and several studies described the molecular pathways in animal model and human subjects. In particular, in adipose cells, the key-role of irisin is to stimulate the differentiation of white adipose tissue to brown adipose tissue, through the action on the uncoupling protein 1. Furthermore, in the bony tissue, irisin stimulates osteogenesis through expression of Sost and Opn genes. These features make irisin a suitable molecule to use as a biomarker of the overall musculoskeletal health of the elderly, before undergoing orthopaedic surgery. Further research on this topic should be carried out to highlight the possible clinical role and predictive value of irisin in a multidisciplinary approach to the elderly before musculoskeletal surgery.

Preliminary results of video-assisted anal fistula treatment (VAAFT) in children.

BACKGROUND: Anal fistula is a common acquired anorectal disorder in children. Treatment methods that have been used are associated with inconsistent results and possible serious complications. In 2011 a minimally invasive approach, video-assisted anal fistula treatment (VAAFT) was described for adult patients. The aim of the present study was to assess the first series of pediatric patients treated with VAAFT. METHODS: All patients who underwent VAAFT between August 2013 and May 2015 were included. Demographics, clinical features, preoperative imaging, surgical details, outcome, and medium-term data were prospectively collected for each patient. RESULTS: Thirteen procedures were performed in nine patients. The male to female ratio was 8:1, and the median age was 9.6 years. Five fistulas were idiopathic, three iatrogenic, and one associated with Crohn's disease. Eight complete VAAFT procedures were performed. The remaining five procedures were either fistuloscopy and cutting seton placement or fistuloscopy and electrocoagulation, both without mucosal sleeve. The median length of surgery was 41 min. The median hospital stay was 24 h, and the median length of follow-up was 10 months. Resolution of the fistula was observed in all patients who underwent a complete VAAFT. In four out of five patients who underwent an incomplete procedure (without mucosal sleeve), the fistula recurred. No incontinence or soiling was reported in the medium term. CONCLUSIONS: VAAFT proved to be feasible and safe in children. It also proved to be versatile as it could be applied to fistulas of different etiologies. The key to success seems to be an adequate mucosal sleeve. Older children and adolescents benefit most from VAAFT which is a valid alternative to available surgical procedures.

Shape and size of the medial patellofemoral ligament for the best surgical reconstruction: a human cadaveric study.

PURPOSE: The aim of this study was to investigate the shape and the attachments of the medial patellofemoral ligament (MPFL) in cadaver specimens to determine an anatomical basis for the best MPFL reconstruction. METHODS: Twenty fresh-frozen knees were used. Dissection protocol implied performing dissections from within the knee joint. We investigated the shape and the attachments between the MPFL and the quadriceps tendon, the patellar and femur insertions, and all the other relationships with the medial soft tissues of the knee. RESULTS: The distal fibers of MPFL were interdigitated with the deep layer of the medial retinaculum. All isolated ligament had a sail-like shape with the patellar side bigger than the femoral side. The femoral insertion, distinct both from medial epicondyle and adductor tubercle, was located at 9.5 mm (range 4-22) distal and anterior respect to adductor tubercle and proximal and posterior to epicondyle. The medial third of the thickness of patella was involved in the insertion. The proximal third of the patella is always involved in the MPFL attachment; in 45% of the cases, it was extended to the medial third and in one case, an extension at the distal third was found. Additionally in 35% (7 cases), it extended to the quadriceps tendon and it were inconstantly attached at the vastus medialis obliques (VMO) tendon and at the vastus intermedius (VI) tendon in an aponeurotic structure. CONCLUSIONS: The MPFL is a distinct structure that goes from patella to femur with a sail-like shape; its patellar insertion, that mostly occur via an aponeurosis tissue with VMO and VI, is at the proximal third of the patella but it may extend in some cases to the medial third patella or to the quadriceps tendon, or very rarely to the distal third of the patella. In the femoral side, the MPFL is inserted in its own site, in most cases distinct both from epicondyle and adductor tubercle, located on average at a 9.5 mm distance distally and anteriorly in respect to the adductor tubercle. Its lower margin was difficult to define. Given the importance of this structure, it must be reconstructed as anatomically as possible in its insertion and in its shape. Many attempts have been made to make functional reconstructions with less than excellent results.

[Bladder located gastric heterotopy: a case report confronting embryology to histopathology]. / Hétérotopie gastrique de siège vésical: un cas clinique au carrefour de l'embryologie et de l'histopathologie.

We report a case of bladder located gastric heterotopy, which has never been described, to our mind in the scientific literature. We discuss the diagnosis and the physiopathological mechanisms that may have been involved in the genesis of such a lesion.

[Emerging biomarkers for the diagnosis, staging and prognosis of prostate cancer]. / Les biomarqueurs émergents du diagnostic, du staging et du pronostic du cancer de la prostate.

The introduction and widespread adoption of prostate-specific antigen (PSA) has revolutionized the way prostate cancer is diagnosed and treated. However, the use of PSA has also led to overdiagnosis and overtreatment of prostate cancer resulting in controversy about its use for screening. PSA also has limited predictive accuracy for predicting outcomes after treatment and for making clinical decisions about adjuvant and salvage therapies. Hence, there is an urgent need for novel biomarkers to supplement PSA for detection and management of prostate cancer. A plethora of promising blood- and urine-based biomarkers have shown promise in early studies and are at various stages of development (Human kallikrein 2, Early Prostate Cancer Antigen, Transforming Growth Factor-Beta 1 and Interleukin-6, Endoglin, PCA3, AMACR and ETS Gene Fusions). In this article, we review those biomarkers and then discuss the challenges a biomarker has to undergo before it is approved in a clinical use.

[Stenosis of the upper renal pelvis: rare complication of an incomplete ureteral duplicity. Embryological investigation]. / La sténose du pyélon supérieur : complication rare d'une bifidité urétérale. Enquête embryologique.

A stenosis of the upper pole of an incomplete renal duplication is presented. The prenatal diagnosis of a right renal ureteropyelic junction syndrome, isolated, with a normal amniotic liquid was confirmed at birth. Intravenous pyelogram 8 days after birth showed three right dilated calical groups with a dilated renal ureteropyelic junction, but an normal inferior calical group suspected a renal bifidity. Renal MagIII scintigraphy evaluated the anatomical and functional stenosis and indicated surgery. Postoperative followings were simple and results good 3 years after. From this rare case, embryogenesis is discussed.

[Congenital prenatal hemangioma: diagnosis and treatment]. / Hémangiome congénital à révélation anténatale.

An echogenic tumor (22 x 22 mm) isolated from the anterior part of the left leg at 27 WA of pregnancy suggested an angiomatous structure. This mass appeared to be well vascularized on Doppler examination. Three-dimensional imaging showed connections with adjacent tissues. The limbs were mobile. Delivery of a 3990-g-boy occurred normally. On the anterior part of the left leg, there was a plate-shaped mass with a pink hole at the superior part. Excision under general anesthesia was performed at the first month because of the risk of rupture and bleeding. The dissection was easy with the deep plane. Healing was complete 10 days after the surgical procedure and the aesthetic aspect was good 1 year later. Histological findings of the suspect mass emphasize the vascular aspect of the tumor. A hemangioma capillary with venous structures in the dermal hypodermic area was found.

Oncocytic choroid plexus carcinoma: case report.

Herein, we report an unusual choroid plexus carcinoma with extensive oncocytic transformation. A 13-month-old girl presented with acute lethargy which quickly progressed to coma. A CT scan of the head revealed impending herniation due to hemorrhage within an intracranial tumor. An MRI scan showed a large, partly cystic and highly vascular left lateral ventricular mass. A near total resection was achieved. Microsections revealed a WHO Grade III choroid plexus carcinoma with extensive oncocyti c transformation. A minor portion of the moderately to poorly differentiated tumor exhibited classical microscopic features of choroid plexus carcinoma, including marked nuclear atypia, brisk mitotic activity (78/10 HPF), a high MIB-1 labeling index (44%) and zones of necrosis. In contrast, the large, eosinophilic, cytologically malignant but granular-appearing oncocytes comprising the majority of the lesion showed scant (1/10 HPF) mitotic activity and only a low MIB-1 labeling index (5%). A subsequent recurrence at 1 year consisted entirely of non-oncocytic tumor. Choroid plexus carcinoma with oncocytic transformation has not been previously reported. The remarkable extent of this alteration and its clinical significance remains to be determined.

Laparoscopic vs open approach for the treatment of gastroesophageal reflux in children.

BACKGROUND: The laparoscopic approach has become increasingly popular for fundoplication over the last few years; however many surgeons are skeptical about its real advantages. METHODS: We conducted a prospective comparative study of children operated on for gastroesophageal reflux (GER). Exclusion criteria included age <1 YEAR AND >14 years, previous surgery on the esophagus or stomach, and neurologic impairment. We compared two groups of patients who met the same inclusion/exclusion criteria. One group was treated via a laparotomic approach between January 1993 and December 1997; the other was treated via a laparoscopic approach between September 1998 and December 2000. A 360 degrees wrap was performed in each group. RESULTS: Group 1 (laparotomic approach) included 17 patients; mean operative time was 100 min and postoperative time was 7 days. Group 2 comprised 49 children operated on via a laparoscopic approach; mean operative time was 78 min and postoperative time was 48 hours. No major complications were encountered in either group. In postoperative period, two patients in group 1 had complications. One had a prolonged bout of gastroplegia, which required nasogastric drainage, and then recovered spontaneously after 20 days; the other had stenosis of the wrap, which required dilation. No relapses occurred during a follow-up of 6 months. Long-term follow-up data are not presented. Comparative analysis of the short-term functional results indicated that there were no differences between the two groups. CONCLUSION: This study confirms that the minimally invasive approach is safe and effective for the treatment of primary gastroesophageal reflux disease in children.

Thromboembolic complications related to indwelling central venous catheters in children with oncological/haematological diseases: a retrospective study of 362 catheters.

Indwelling central venous catheters (CVC) are essential devices in the management of children with oncological/haematological diseases being treated with chemotherapy or undergoing bone marrow transplantation. Our study was aimed at detecting the incidence of important thrombotic events caused by CVC in children, and the coexistence of coagulation disorders in children affected with thromboembolic disease related to CVC. Therefore, we describe some antithrombotic strategies which have been successfully applied to solve functioning problems of correctly inserted CVC. We retrospectively evaluated the clinical records of 308 children (age range 2 months to 14 years) with oncological/haematological diseases undergoing insertion of 362 indwelling CVC from January 1994 to December 1998 at the Gaslini Children's Hospital. We collected data on seven serious asymptomatic thrombotic episodes diagnosed between 1994 and 1998 following catheter malfunctioning and one case of suspected lung embolism with symptoms. Coagulation tests allowed us to identify one case of probable heterozygosis of Protein C deficiency and one case of G20210A prothrombotic prothrombin mutation. This finding suggests the need for further evaluation for thrombophilia in all patients presenting with thrombotic complications of CVC. We therefore emphasise the importance of prophylaxis with low-dose heparin in children with malignancies receiving CVC. A prospective study, which has already been started, should identify the exact role of thromboembolic complications in children with indwelling CVC for oncological/ haematological malignancies.

Pleuropulmonary blastoma.

We report a rare case of pleuropulmonary blastoma arising in a 3-year-old boy and involving the middle and upper lobes of the right lung. Radical resection of the mass was achieved by a bilobectomy. Microscopic examination of the histologic sections showed the typical findings of blastemal and mesenchymal areas with focal zones of rhabdomyoblastic and liposarcomatous differentiation. Monthly cycles of chemotherapy consisting of ifosfamide, vincristine and actinomycin D were given for 10 months after surgical resection. Our patient is presently alive and disease-free two years after diagnosis. As complete tumour ablation is essential to prevent local recurrence and allow any chance of survival, the favourable outcome of our patient is probably due to the radical resection of the neoplasm.

Mechanical complications related to indwelling central venous catheter in pediatric hematology/oncology patients.

Indwelling central venous catheters (CVC) are essential devices in the management of children with oncologic/hematologic diseases or following bone marrow transplantation. The authors report data on the mechanical complications observed in pediatric hematology/oncology patients, collected by a retrospective analysis of clinical records of 482 patients in whom 567 indwelling central venous catheters had been inserted from January 1992 to December 1998 at the G. Gaslini Institute. During the study period, 52 episodes of mechanical complications (9%) were observed: mechanical obstruction (24 episodes), catheter dislocation (13), problems related to catheter material (12), and accidental removal (3). In 25 cases removal and replacement of CVC was necessary for the treatment of complications, while medical treatment (thrombolytic-antithrombotic) was successful and well tolerated in 8. The study shows the importance of mechanical complications in children with indwelling CVC for hematologic or oncologic diseases. Moreover, the experience of administering a systemic low-dosage thrombolytic therapy demonstrates new prospects of reducing CVC replacement by restoring CVC viability.

Preoperative enzymo-histochemical diagnosis of dysganglionoses associated with anorectal malformations (ARM) with recto-vestibular and recto-perineal fistula.

The posterior sagittal anorectoplasty (PSARP) is widely recognized as the best technique available today for the surgical treatment of anorectal malformations (ARM). However, different retrospective studies on the functional results of PSARP in the treatment of ARM have shown different postoperative degrees of constipation. In particular, even in patients with normal sacrum, about 70% of operated ARM with vestibular fistula and about 50% with perineal fistula can be complicated by fecal constipation and pseudoincontinence. In order to identify preoperatively whether ARM patients present abnormal innervation patterns of rectal pouch and fistula (as reported by Holschneider et al [7]), we decided to study suction rectal biopsies performed by introducing SBT-100 rectal suction biopsy tool into the fistula at 6, 4, 3 and 2 cm from the meatus. To date, this approach has been adopted in 22 ARM cases (15 females and 7 males, age range 7 days-4 years), 6 of them with recto-vestibular fistula and 13 with recto-perineal fistula. Biopsies were frozen in isopentane at liquid nitrogen temperature and cryostatic sections were studied by acetylcholinesterase (AChE), succinic-dehydrogenase (SDH) and alpha-naphthyl-esterase (ANE) enzymo-histochemical techniques. The results concerning the innervation-type of fistula and proximal rectal pouch were confirmed by the biopsies obtained during PSARP. Our overall incidence of rectal innervation intrinsic disorders was 81.82%. In particular, all our cases of vestibular fistula presented associated dysganglionoses. The incidence of associated Hirschsprung's disease was high, corresponding to 18% of cases. Our results suggest that the high frequency of constipation in low forms of ARMS depends on primary intestinal neuronal malformations and it cannot be ascribed to a denervation secondary to rectal dissection and to PSARP procedure. We propose the introduction of this type of preoperative enzymo-histochemical diagnosis in ARM cases because it can select those patients with severe associated dysganglionoses. In our opinion, if this diagnosis is available preoperatively, PSARP can be performed without using abnormally innervated structures and reducing postoperative functional complications.

Anorectal malformations associated with enteric dysganglionosis in Danforth's short tail (Sd) mice.

BACKGROUND: The spontaneous mutant Danforth's short tail (Sd) mouse has been studied over the last 60 years from the morphological, embryological, and genetic point of view. The Sd mutation affects a gene essential to notochordal development, and the Sd mouse phenotype represents an analogue of human caudal regression syndrome. The Sd/Sd mouse presents different types of anorectal malformations (ARM) and was suggested as a simple and cheap model of investigation of ARM morphology and embryology. In the current study, the Sd mouse enteric nervous system (ENS) was thoroughly investigated with specific immunohistochemical markers. METHODS: Macroscopic analysis, normal histology, and immunohistochemical techniques for detecting neurofilaments (NF) and NOS1 were used to study ENS of 138 Sd mice and 25 controls. RESULTS: The surprising results of this study showed that Sd mutation is associated with different degrees of hypoganglionosis and aganglionosis. In 41% of Sd/SD-affected mice, the rectal pouch was aganglionic and in the remaining 58% was severely hypoganglionic. In addition, 4.1% of heterozygous mice presented a distal aganglionosis and 8.3% hypoganglionosis. CONCLUSIONS: These results suggest that Sd mutation independently affects distinct cell lines during early organogenesis, as notochord cells, ventral hingut endoderm, and neuroblasts migrating from neural crest cells. Comparing the Sd murine model with human pathology, this study confirms that the association between ARM and intestinal dysganglionosis is not rare and underlines the importance of detecting in every ARM patient the innervation abnormalities of rectal pouch and fistulas.

GDNF deficit in Hirschsprung's disease.

BACKGROUND/PURPOSE: In 1996, the glial cell line-derived neurotrophic factor (GDNF) was identified as one of the ligands of the RET transmembrane receptor. In the same year, GDNF mutations were found in association with RET protooncogene mutations in Hirschsprung patients. Mutations in GDNF per se are thought neither necessary nor sufficient to cause Hirschsprung's disease (HD). To date, our study group has identified GDNF mutations only in 2 of 98 cases of intestinal dysganglionosis. The aim of our study was to investigate a possible expression deficit of GDNF in the enteric nervous system of Hirschsprung patients not mutated for the GDNF gene. METHODS: We used rabbit polyclonal antibodies raised against a peptide corresponding to amino acids 186-205 mapping within the carboxy-terminal domain of human GDNF. GDNF expression was studied immunohistochemically in surgical specimens from 30 HD cases (27 classic forms and 3 ultralong forms) and from 10 age-matched controls. Serial sections from the same full-thickness specimens were investigated with the following histochemical and immunohistochemical techniques: acetylcholinesterase, lactate dehydrogenase, succinic dehydrogenase, alpha-naphthyl-esterase, glial fibrillary acid protein, S-100 protein, and neuron-specific enolase. RESULTS: A high level of GDNF expression was found in normal intestine and in Hirschsprung ganglionic segment. Satellite elements of myenteric ganglia presented a strong immunoreactivity to GDNF. Conversely, the aganglionic segment showed cholinergic hyperinnervation and hypertrophic trunks of nerve fibers in the muscular interstitium with complete absence of GDNF expression. The small ganglia of the hypoganglionic segment showed a reduced GDNF immunoreactivity. CONCLUSIONS: GDNF, a distantly related member of the transforming growth factor-beta superfamily, is a potent neurotrophic and survival factor for neurons and enteric ganglion cells. Mutations of the GDNF gene or GDNF expression deficit interrupt the faithful GDNF signaling via Ret, contributing to HD pathogenesis.

[Congenital deformities of the chest wall. Surgical treatment]. / Le malformazioni congenite della parete toracica. Trattamento chirurgico.

BACKGROUND AND AIMS: Malformations of the front chest wall are congenital defects that have been reported since the seventeenth century and which include the clinical syndromes of funnel chest, pigeon chest and Poland's syndrome. Although they have been reported for such a long time, their pathogenesis is in many ways still unknown and the theories proposed up until now reveal uncertain and unsatisfactory findings. Attempts to gather precise information regarding their real incidence are equally ineffective given that frequently those cases which are not particularly severe are not referred for specialist care. These malformations usually involve severe psychological problems caused by the deformity and, in more severe cases, may lead to alterations in normal cardiac and respiratory function which are above all evident during intense physical effort. METHODS: The authors critically review the cases of chest malformation corrected by the Department of Pediatric Surgery at the G. Gaslini Institute during the period from 1986 to date. They describe the surgical techniques used, justifying their choice and discussing any postoperative complications. RESULTS: This experience shows that there is a clear preference for less invasive surgery for the correction of funnel chest compared to the technique proposed by Ravitch in which the sternum was totally mobilised following its extensive detachment from the other bone and muscular structures of the thoracic cage, with a high risk of damaging the internal mammary artery. The operation that was felt to be most suitable for correcting this defect was that described by Wesselhoett and De Luca in 1982. It is easier to perform and less invasive: it eliminates the detachment phase by inserting a support in titanium alloy through the sternal frame. Autologous grafts taken from the bottom contralateral ribs to the defect were used to treat Poland's syndrome in line with the technique suggested by Ravitch, thus achieving good stability of the whole chest; in view of the young age of the patients undergoing correction, it was not thought appropriate to proceed with the cosmetic reconstruction of the pectoral muscles using a peduncled flap of latissimus dorsi. A total of 70 patients were operated in this way; the cosmetic results were very satisfactory, whereas complications were limited to 5 cases of intraoperative pneumothorax, 5 cases of serohematic subcutaneous collection which were treated conservatively, and 1 case of hypertrophic scarring.

A prospective evaluation of a test for lateral meniscus tears.

A test for diagnosing lesions to the lateral meniscus is described. Due to our inability to find its description in the literature we called it 'dynamic test'. The accuracy of this test was assessed in 421 knees. The test was compared against arthroscopic findings in all cases. Inter-rater reliability was also estimated among three observers, who were shown to have a K coefficient ranging from 0.61 to 0.85. In a series of healthy subjects, the test was positive in eight normal knees (9.4%), but none of these false-positives was unanimously identified by more than one rater. This manipulative test was very accurate: sensitivity 85%, specificity 90.3%, positive predictive value 73.2%, negative predictive value 95% prevalence 23.7% and accuracy 89%. Thus, the test seems to be a tool that can improve the diagnostic accuracy of meniscal lesions. An important feature of this test is that it can be performed in patients with acute injuries.