Immunohistochemical evaluation of bone metastases

  Introduction. Metastases are the most common type of malignancy involving the bone, while bone is the third most frequent site for metastases, after the lung and liver. In some patients, previous medical history, physical and laboratory examination are not conclusive to identify the primary tumor site. In such cases a bone biopsy and im­munohistochemical analysis may contribute to the diagnosis, determination of appropriate treatment and evaluation of prognosis. In this study, we tried to evaluate the imunochistochemical expression in bone metastases. Material and methods. We reviewed 125 patients, with a mean age of 63 years, treated for bone metastases in our institution. All patients received palliative orthopaedic surgery for bone metastatic carcinoma. Fifty-eight patients had already an established diagnosis of the primary tumor, while 67 patients presented metastases with an unknown primary tumor origin. Immunohistochemical analysis was performed to intra-operative bone biopsy specimens. The expression of cytokeratine 7, cytokeratin 20 and the expression of a panel of other organ-specific markers were re­corded. In patients with a known primary tumor, we examined the relationship between the origin of metastases, as suggested by the cytokeratin phenotype, compared with the one indicated by the initial histological diagnosis. We also recorded the efficacy of organ-specific markers to identify the primary tumor origin in epithelial bone metastases and we evaluated the prognosis between patients with a immunohistologically determined primary tumor origin, with those with an undetermined one. Results. Associations of cytokeratine 7 and cytokeratine 20 expression confirmed diagnosis in 51 out of the 58 patients (88%) with a known primary tumor (Cohen’s K test 0.79 SE 0.80, P < 0.0005). Immunohistochemical analysis also contributed to establish the diagnosis of patients with an unknown primary tumor, yielding diagnosis in 35 out of the 67 cases (52%). Patients with an immunochistologically undetermined primary tumor site presented a statisti­cally significant poorer prognosis. Conclusions. Cytokeratine 7 and cytokeratine20 are useful immunochistochemical markers in determining a pre­liminary evaluation of bone metastases. Organ-specific immunohistochemical markers have a reliable role in either suggesting or confirming the possible origin of metastases. An indeterminate immunohistochemical phenotype seems to relate to a less differentiated lesion, with a worse prognosis. Introduction. Metastases are the most common type of malignancy involving the bone, while bone is the third most frequent site for metastases, after the lung and liver. In some patients, previous medical history, physical and laboratory examination are not conclusive to identify the primary tumor site. In such cases a bone biopsy and im­munohistochemical analysis may contribute to the diagnosis, determination of appropriate treatment and evaluation of prognosis. In this study, we tried to evaluate the imunochistochemical expression in bone metastases. Material and methods. We reviewed 125 patients, with a mean age of 63 years, treated for bone metastases in our institution. All patients received palliative orthopaedic surgery for bone metastatic carcinoma. Fifty-eight patients had already an established diagnosis of the primary tumor, while 67 patients presented metastases with an unknown primary tumor origin. Immunohistochemical analysis was performed to intra-operative bone biopsy specimens. The expression of cytokeratine 7, cytokeratin 20 and the expression of a panel of other organ-specific markers were re­corded. In patients with a known primary tumor, we examined the relationship between the origin of metastases, as suggested by the cytokeratin phenotype, compared with the one indicated by the initial histological diagnosis. We also recorded the efficacy of organ-specific markers to identify the primary tumor origin in epithelial bone metastases and we evaluated the prognosis between patients with a immunohistologically determined primary tumor origin, with those with an undetermined one. Results. Associations of cytokeratine 7 and cytokeratine 20 expression confirmed diagnosis in 51 out of the 58 patients (88%) with a known primary tumor (Cohen’s K test 0.79 SE 0.80, P < 0.0005). Immunohistochemical analysis also contributed to establish the diagnosis of patients with an unknown primary tumor, yielding diagnosis in 35 out of the 67 cases (52%). Patients with an immunochistologically undetermined primary tumor site presented a statisti­cally significant poorer prognosis. Conclusions. Cytokeratine 7 and cytokeratine20 are useful immunochistochemical markers in determining a pre­liminary evaluation of bone metastases. Organ-specific immunohistochemical markers have a reliable role in either suggesting or confirming the possible origin of metastases. An indeterminate immunohistochemical phenotype seems to relate to a less differentiated lesion, with a worse prognosis

Immunohistochemical evaluation of bone metastases

  Introduction. Metastases are the most common type of malignancy involving the bone, while bone is the third most frequent site for metastases, after the lung and liver. In some patients, medical history, physical and laboratory exami­nation are not conclusive to identify the primary tumor site. In such cases a bone biopsy and immunohistochemical analysis may contribute to the diagnosis, determination of appropriate treatment and evaluation of prognosis. In this study, we tried to evaluate the imunochistochemical expression in bone metastases. Material and methods. We reviewed 125 patients, with a mean age of 63 years, treated for bone metastases in our institution. All patients received palliative orthopaedic surgery for bone metastatic carcinoma. Fifty-eight patients had already an established diagnosis of the primary tumor, while 67 patients presented metastases with an unknown primary tumor origin. Immunohistochemical analysis was performed to intra-operative bone biopsy specimens. The expression of cytokeratine 7, cytokeratin 20 and the expression of a panel of other organ-specific markers were re­corded. In patients with a known primary tumor, we examined the relationship between the origin of metastases, as suggested by the cytokeratin phenotype, compared with the one indicated by the initial histological diagnosis. We also recorded the efficacy of organ-specific markers to identify the primary tumor origin in epithelial bone metastases and we evaluated the prognosis between patients with a immunohistologically determined primary tumor origin, with those with an undetermined one. Results. Associations of cytokeratine 7 and cytokeratine 20 expression confirmed diagnosis in 51 out of the 58 patients (88%) with a known primary tumor (Cohen’s K test 0.79 SE 0.80, P < 0.0005). Immunohistochemical analysis also contributed to establish the diagnosis of patients with an unknown primary tumor, yielding diagnosis in 35 out of the 67 cases (52%). Patients with an immunochistologically undetermined primary tumor site presented a statisti­cally significant poorer prognosis. Conclusions. Cytokeratine 7 and cytokeratine20 are useful immunochistochemical markers in determining a pre­liminary evaluation of bone metastases. Organ-specific immunohistochemical markers have a reliable role in either suggesting or confirming the possible origin of metastases. An indeterminate immunohistochemical phenotype seems to relate to a less differentiated lesion, with a worse prognosis

Osteosynthesis-associated infection of the lower limbs by multidrug-resistant and extensively drug-resistant Gram-negative bacteria: a multicentre cohort study

Purpose: The purpose of this study was the clinical and therapeutic assessment of lower-limb osteosynthesis-associated infection (OAI) by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB), which have been poorly studied to date. Methods: A prospective multicentre observational study was conducted on behalf of ESGIAI (the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group on Implant-Associated Infections). Factors associated with remission of the infection were evaluated by multivariate and Cox regression analysis for a 24-month follow-up period. Results: Patients (n=57) had a history of trauma (87.7 %), tumour resection (7 %) and other bone lesions (5.3 %). Pathogens included Escherichia coli (n=16), Pseudomonas aeruginosa (n=14; XDR 50 %), Klebsiella spp. (n=7), Enterobacter spp. (n=9), Acinetobacter spp. (n=5), Proteus mirabilis (n=3), Serratia marcescens (n=2) and Stenotrophomonas maltophilia (n=1). The prevalence of ESBL (extended-spectrum β-lactamase), fluoroquinolone and carbapenem resistance were 71.9 %, 59.6 % and 17.5 % respectively. Most patients (n=37; 64.9 %) were treated with a combination including carbapenems (n=32) and colistin (n=11) for a mean of 63.3 d. Implant retention with debridement occurred in early OAI (66.7 %), whereas the infected device was removed in late OAI (70.4 %) (p=0.008). OAI remission was achieved in 29 cases (50.9 %). The type of surgery, antimicrobial resistance and duration of treatment did not significantly influence the outcome. Independent predictors of the failure to eradicate OAI were age &gt;60 years (hazard ratio, HR, of 3.875; 95 % confidence interval, CI95 %, of 1.540–9.752; p=0.004) and multiple surgeries for OAI (HR of 2.822; CI95 % of 1.144–6.963; p=0.024). Conclusions: Only half of the MDR/XDR GNB OAI cases treated by antimicrobials and surgery had a successful outcome. Advanced age and multiple surgeries hampered the eradication of OAI. Optimal therapeutic options remain a challenge.</p

Biotechnologically assisted peripheral nerve regeneration using adipose-derived stem cells and nerve conduits: experimental study in rats

Introduction: This study assessed the impact of undifferentiated adipose-derived stem cells (ADSCs) in peripheral nerve regeneration. The clinical outcome of undifferentiated ADSCs combined with nerve conduits was compared with the one of nerve autografts and this of simple conduits in the context of peripheral nerve regeneration in an experimental model of sciatic nerve complete transection in rats. Materials & Methods: Forty Wistar rats were equally distributed in four groups. In the SHAM surgery group, the sciatic nerve was dissected but no further intervention was done. In the simple conduit group (SLN), a 10-mm nerve gap was created and subsequently bridged with a fibrin glue conduit that was filled with normal saline. In the autograft group, nerve defect was produce removing 10 mm of the sciatic nerve, which was then used as a reverse autograft. In the ADSC group, the conduit was filled with undifferentiated ADSCs after defect bridging. Nerve regeneration was assessed by means of walking track analysis, electromyography, and neurohistomorphometry. Results: The clinical and microscopical outcome of this study showed that nerve regeneration was achieved in all groups at 12 weeks postoperatively. Walking track analysis confirmed functional recovery in the AUTO and ADSC groups, but there was no difference between them. Recovery in function was also achieved in the SLN group, but with inferior outcome (P<0.05). Electromyography demonstrated superior nerve regeneration in the AUTO and ADSC groups as compared with the SLN group (P<0.05), with no substantial difference between the two former groups. Similarly, histologic examination showed similar superior results in the AUTO and ADSC groups, which both outperformed the SLN group (P<0.001). No complications were observed in any of the study groups. Conclusion: Successful peripheral nerve regeneration can be accomplished after bridging a 10-mm nerve defect with nerve conduits. Superior nerve regeneration is expected when the conduits are loaded with undifferentiated ADSCs. Similar outcomes can be achieved by bridging the defect with nerve autographs.Εισαγωγή: Αυτή η μελέτη αξιολόγησε την επίδραση των αδιαφοροποίητων βλαστοκυττάρων από λιπώδη ιστό (ADSCs) στην περιφερική νευρική αναγέννηση. Συγκρίθηκε το κλινικό αποτέλεσμα που προέκυψε μετά τη χρήση αδιαφοροποίητων ADSCs σε συνδυασμό με νευροαγωγούς με εκείνο των νευρικών αυτομοσχευμάτων και εκείνο των απλών νευροαγωγών, σε πειραματικό μοντέλο πλήρους διατομής του ισχιακού νεύρου σε επίμυες. Υλικό & Μέθοδοι: Σαράντα επίμυες Wistar κατανεμήθηκαν εξίσου σε τέσσερις ομάδες. Στην ομάδα ελέγχου (SHAM) το ισχιακό νεύρο παρασκευάστηκε χωρίς να γίνει άλλη παρέμβαση. Στην ομάδα απλών νευροαγωγών (SLN) δημιουργήθηκε ένα νευρικό έλλειμμα 10 χιλ. το οποίο γεφυρώθηκε με αγωγό γέλης ινικής που περιείχε φυσιολογικό ορό. Στην ομάδα των αυτομοσχευμάτων (AUTO) το έλλειμμα του νεύρου δημιουργήθηκε με την αφαίρεση τμήματος 10 χιλ. του ισχιακού νεύρου το οποίο στη συνέχεια χρησιμοποιήθηκε ως ανάστροφο νευρικό μόσχευμα. Στην ομάδα ADSC, αδιαφοροποίητα βλαστοκύτταρα λιπώδους ιστού τοποθετήθηκαν μέσα στον αυλό του νευροαγωγού μετά τη γεφύρωση του ελλείμματος. Η νευρική αναγέννηση αξιολογήθηκε με ανάλυσης βάδισης, ηλεκτρομυογραφία και νευροϊστομορφομετρία. Αποτελέσματα: Τα κλινικά και μικροσκοπικά ευρήματα της μελέτης έδειξαν ότι νευρική αναγέννηση επιτεύχθηκε σε όλες τις ομάδες 12 εβδομάδες μετεγχειρητικά. Η ανάλυση βάδισης έδειξε καλύτερη λειτουργική αποκατάσταση στις ομάδες AUTO και ADSC, αλλά δεν υπήρχε διαφορά μεταξύ τους. Η ανάκτηση της λειτουργίας του πάσχοντος μέλους επιτεύχθηκε επίσης στην ομάδα SLN αλλά με όχι τόσο ικανοποιητικό αποτέλεσμα (P<0,05). Η ηλεκτρομυογραφία έδειξε ανώτερη αναγέννηση των νεύρων στις ομάδες AUTO και ADSC σε σύγκριση με την ομάδα SLN (P<0,05), χωρίς ουσιαστική διαφορά μεταξύ των δύο πρώτων ομάδων. Ομοίως, η ιστολογική εξέταση έδειξε ανώτερα αποτελέσματα στις ομάδων AUTO και ADSC, χωρίς ουσιαστική διαφορά μεταξύ τους, αλλά πολύ καλύτερη απόδοση από την ομάδα SLN (P<0,001). Δεν παρατηρήθηκαν επιπλοκές σε καμία ομάδα της μελέτης. Συμπέρασμα: Επιτυχής περιφερική νευρική αναγέννηση μπορεί να επιτευχθεί με τη γεφύρωση νευρικού ελλείμματος 10 χιλ με νευροαγωγούς. Ανώτερη νευρική αναγέννηση αναμένεται όταν στους αγωγούς προστεθούν αδιαφοροποίητα βλαστοκύτταρα λιπώδους ιστού. Ομοίως καλά αποτελέσματα μπορούν να επιτευχθούν μετά τη γεφύρωση του ελλείμματος με νευρικά αυτομοσχεύματα

The present and future for peripheral nerve regeneration

Peripheral nerve injury can have a potentially devastating impact on a patient&apos;s quality of life, resulting in severe disability with substantial social and personal cost. Refined microsurgical techniques, advances in peripheral nerve topography, and a better understanding of the pathophysiology and molecular basis of nerve injury have all led to a decisive leap forward in the field of translational neurophysiology. Nerve repair, nerve grafting, and nerve transfers have improved significantly with consistently better functional outcomes. Direct nerve repair with epineural microsutures is still the surgical treatment of choice when a tension-free coaptation in a well-vascularized bed can be achieved. In the presence of a significant gap (&gt;2-3 cm) between the proximal and distal nerve stumps, primary end-to-end nerve repair often is not possible; in these cases, nerve grafting is the treatment of choice. Indications for nerve transfer include brachial plexus injuries, especially avulsion type, with long distance from target motor end plates, delayed presentation, segmental loss of nerve function, and broad zone of injury with dense scarring. Current experimental research in peripheral nerve regeneration aims to accelerate the process of regeneration using pharmacologic agents, bioengineering of sophisticated nerve conduits, pluripotent stem cells, and gene therapy. Several small molecules, peptides, hormones, neurotoxins, and growth factors have been studied to improve and accelerate nerve repair and regeneration by reducing neuronal death and promoting axonal outgrowth. Targeting specific steps in molecular pathways also allows for purposeful pharmacologic intervention, potentially leading to a better functional recovery after nerve injury. This article summarizes the principles of nerve repair and the current concepts of peripheral nerve regeneration research, as well as future perspectives. © 2016 SLACK Incorporated

Secondary aneurysmal bone cyst in McCune-albright syndrome

Polyostotic fibrous dysplasia in combination with caféau- lait macules and hyperfunctioning endocrinopathies consists of a rare clinical condition termed as McCune- Albright syndrome. Aneurysmal bone cysts are tumorlike cystic lesions, composed of blood-filled compartments. They may occur as primary lesions or secondary to other pathologies; most commonly giant cell tumors of bone. However, secondary aneurysmal bone cysts in McCune-Albright syndrome are exceptional. We present a 28-year-old female with McCune-Albright syndrome. She experienced precocious puberty at age 3 months. In childhood, she experienced multiple long bone fractures, facial deformity and progressive visual and hearing impairment. One year ago, she experienced a painful, gradually enlarging bone lesion involving the right ilium, pubic and ischial bone with groundglass appearance, septa, marginal sclerosis, endosteal scalloping and blow-out expansion resulting in localized thinning of the cortex. CT-guided needle biopsy of the pelvic lesion showed aneurysmal bone cyst. Selective arterial embolization was recommended, however, the patient and her relatives did not consent to proceed to treatment, and she remained in close surveillance thereafter

Ultrasonography in trauma: Physics, practice, and training

» Ultrasonography has gained a unique role in assisting emergency medicine physicians in the trauma setting. Its major advantages include safety, bedside availability, repeatability, and portability. In addition, it does not have to interrupt resuscitation, it does not require sedation, it takes images in real time using multiplanar and nonstandard imaging, and it provides interventional guidance.» Advances in technology have enabled portable ultrasonography devices to offer excellent imaging quality and a quick-start function. In trauma, it can be used in the pre-hospital setting, in disaster situations, during patient retrieval, and in the hospital setting from the emergency department to the operating room, intensive care units, and the wards. It can be used by pre-hospital medical staff, emergency physicians, trauma surgeons, anesthesiologists, radiologists, and sonographers after adequate training.» The limitations of ultrasonography in trauma include the skill of the operators, the need for training and experience, and image artifacts and display. COPYRIGHT © 2018 BY THE JOURNAL OF BONE AND JOINT SURGERY, INCORPORATE

Ultrasound-guided versus palpation-guided corticosteroid injections for tendinosis of the long head of the biceps: A randomized comparative study

Purpose: To compare accuracy, patient discomfort, and clinical outcome of ultrasound-guided versus palpation-guided corticosteroid injections to the bicipital groove in patients with long head of biceps (LHB) tendinosis. Materials and methods: Forty-four patients with primary LHB tendinosis were randomized into two groups (group A, n = 22; group B, n = 22). All patients underwent treatment with a single corticosteroid injection to the bicipital groove. Injections in group A were performed under ultrasound-guidance, while in group B using a palpation-guided technique. The duration of each procedure was recorded. To assess accuracy, ultrasound examination was performed in both groups after injection. Patient discomfort was evaluated with visual analogue scale (VAS) for pain. The clinical outcome was assessed comparing the VAS, the Single Assessment Numeric Evaluation (SANE) score and the QuickDASH score before treatment and after 4 weeks and 6 months. Results: The mean duration of the procedure was 64 ± 6.87 s in group A and 81.91 ± 8.42 s in group B (p &lt; 0.001). Injection accuracy in group A was 100% and in group B 68.18%. Discomfort was lower in group A, as compared to group B (22.10 vs. 35.50; p &lt; 0.001). Symptoms, as measured by VAS, SANE and QuickDASH scores, improved in both groups at 4 weeks and 6 months (p &lt; 0.05). Superior clinical improvement was recorded in group A in both time points (p &lt; 0.05). Conclusions: Corticosteroid injections are an effective treatment for primary LHB tendinosis. Under ultrasound guidance, injections to the bicipital groove are faster and produce lower discomfort. Superior accuracy and clinical outcomes can be achieved using the ultrasound-guided technique. Level of evidence: Level II; Prospective Randomized Comparative Study. © 2019, ISS