Survival outcomes of malignant peripheral nerve sheath tumors (MPNSTs) with and without neurofibromatosis type I (NF1): a meta-analysis.

INTRODUCTION: Malignant peripheral nerve sheath tumors (MPNSTs) are malignancies that demonstrate nerve sheath differentiation in the peripheral nervous system. They can occur sporadically or be associated with neurofibromatosis type 1 (NF1), an autosomal dominant neurocutaneous disorder, with up to 13% of patients developing MPNSTs in their lifetimes. Previous studies have suggested conflicting findings regarding the prognosis of NF1 for patients with MPNSTs. The elucidation of NF1 as an independent prognostic factor on mortality has implications for clinical management. We aim to investigate the role of NF1 status as an independent prognostic factor of overall survival (OS) and disease-specific survival (DSS) in MPNSTs. METHODS: An electronic literature search of PubMed and MEDLINE was performed on studies reporting OS or DSS outcomes of MPNSTs with and without NF1. A grey literature search by reviewing bibliographies of included studies and review articles was performed to find pertinent studies. Data was extracted and assessed in accordance with the PRISMA guidelines. A meta-analysis was performed to calculate hazard ratios (HRs) using a random-effects model. The primary and secondary outcomes were all-cause and disease-specific mortality, respectively, with NF1 as an independent prognostic factor of interest. RESULTS: A total of 59 retrospective studies involving 3602 patients fulfilled the inclusion criteria for OS analysis, and 23 studies involving 704 MPNST patients were included to evaluate DSS outcomes. There was a significant increase in the hazard of all-cause mortality (HR 1.63, 95% CI 1.45 to 1.84) and disease-specific mortality (HR 1.52, 95% CI 1.24 to 1.88) among NF1 as compared to sporadic cases. Subgroup analyses and meta-regression showed that this result was consistent regardless of the quality of the study and year of publication. CONCLUSION: NF1 is associated with a substantially higher risk of all-cause and disease-specific mortality. This finding suggests that closer surveillance is required for NF1 patients at risk of developing MPNSTs.

A New Classification System for Forearm Deformities Caused by Hereditary Multiple Osteochondromas.

PURPOSE: The objective of this study was to evaluate the Masada and Jo classifications for clinical use in patients with forearm deformity caused by hereditary multiple osteochondroma and propose a new classification system that is all-inclusive and can guide clinical management. METHODS: A retrospective review of 275 forearms was performed. A split-sample approach was used, where 138 forearms were analyzed to create a new classification, which was then validated on the remaining 137 forearms. Radiographs were reviewed to determine the number and location of osteochondromas and the presence of radial head dislocation (RHD) and to measure radiographic parameters. Multivariable logistic regression analysis was performed to identify radiological parameters associated with RHD. RESULTS: According to the Masada and Jo classifications, 95 of 275 forearms (34.5%) were unclassifiable. Analyses of the split group (n = 138) revealed 42 forearms with RHD. All these had distal ulna lesions, qualifying as the greatest associated factor for RHD. Further subgroup multivariable logistic regression analysis of forearms with distal ulna lesions identified radiological parameter proportional ulna length as a statistically significant association of RHD, qualifying as "at-risk" criteria. The area under the receiver operating characteristic curve for proportional ulna length was 0.89, with a receiver operating characteristic-derived ideal value of ≤ 0.95 (sensitivity 0.86 and specificity 0.86). CONCLUSIONS: We proposed a new classification system stratified into three groups-high, moderate, and low-risk of RHD-based on the identified factors associated with RHD. Type 1 comprises forearms with distal ulna osteochondromas-subdivided into type 1A (high-risk), where forearms meet the at-risk criteria for RHD and type 1B (moderate-risk), where forearms do not meet the at-risk criteria. Type 2 (low-risk) comprises forearms without distal ulna osteochondromas. CLINICAL RELEVANCE: Our classification system addresses the limitations of existing classifications by risk stratifying forearms into three groups-high, moderate, and low-risk of RHD.

Differential Diagnoses of Pediatric Upper Limb Masses.

PURPOSE: Upper limb masses are one of the most common presentations in the outpatient setting. However, there is a paucity of information in the literature regarding the epidemiology of upper-extremity masses in the pediatric population. The aim of this study was to determine the differential diagnoses and clinical characteristics in children aged ≤18 years presenting with upper limb masses. METHODS: A retrospective review of patients aged ≤18 years managed at our institution over a 5-year period was performed. We obtained information on patient demographics, clinical features, radiological investigations, intraoperative features, and histology. We also evaluated the correlation between the clinical and histopathological diagnoses in patients who underwent surgery. RESULTS: There were 141 upper limb masses in our series. The mean age at presentation was 12 years (SD, 5 years). The most common presenting complaints were asymptomatic swelling, pain, and paresthesia. The majority (128; 91%) of tumors were benign; there were 5 locally aggressive tumors and 6 malignant tumors. The dominant hand was involved in 60 patients. Of 140 patients, 43 (31%) patients had surgery. The procedures included incisional biopsy, excisional biopsy, wide resection, and reconstruction. One patient required a below elbow amputation for an osteosarcoma. CONCLUSIONS: Ten percent of cases represented malignant or locally aggressive disease. We have used our observations to develop a clinical algorithm that can assist clinicians in evaluating and managing children and adolescents presenting with upper-extremity masses. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

Emergency Hand and Reconstructive Microsurgery in the COVID-19-Positive Patient.

The case spectrum in hand surgery is one of extremes-purely elective day surgery cases under local anesthesia to mangling limb injuries that require immediate, and frequently, lengthy, surgery. Despite the cancellation of most elective orthopedic and plastic surgical procedures, hand surgeons around the world continue to see a steady stream of limb-threatening cases such as severe trauma and infections that require emergent surgical care. With the increase in community-spread, an increasing number of COVID-19-infected patients may be asymptomatic or have mild, nonspecific or atypical symptoms. Some of them may already have an ongoing, severe infection. The time-sensitive nature of some of these cases means that hand surgeons may need to operate urgently on patients who may be suspected of COVID-19 infections, often before confirmatory test results are available. General guidelines for perioperative care of the COVID-19-positive patient have been published. However, our practices differ from those of general orthopedic and plastic surgery, primarily because of the focus on trauma. This article discusses the perioperative and technical considerations that are essential to manage the COVID-19 patient requiring emergency care, without compromising clinical outcomes and while ensuring the safety of the attending staff.

The Role of Negative-Pressure Wound Therapy in Lower-Limb Reconstruction.

Negative-pressure wound therapy (NPWT) has gained increasing popularity among clinicians since its introduction in 1997 as a potential aid to wound healing. Multiple benefits of NPWT have since been proven in studies, including increase in granulation tissue formation, decrease in bacterial load, and the improved survival of flaps. With our increasing use and greater understanding of the tissue and cellular changes that occur in a wound treated with NPWT, our lower-limb reconstructive practice has also evolved. Although controversial, the definite timing for lower-limb reconstruction has stretched from 72 hours to longer than 2 weeks as NPWT contains the wound within a sterile, closed system. It has also shown to decrease the rate of infection in open tibia fractures. Previously, a large number of critical defects of the lower limb would require free tissue transfer for definitive reconstruction. NPWT has reduced this rate by more than 50% and has allowed for less complicated resurfacing procedures to be performed instead.

Reconstruction of Extensive Soft-Tissue Defects with Concomitant Bone Defects in the Lower Extremity with the Latissimus Dorsi-Serratus Anterior-Rib Free Flap.

BACKGROUND: The combined latissimus dorsi-serratus anterior-rib (LD-SA-rib) free flap provides a large soft-tissue flap with a vascularized bone flap through a solitary vascular pedicle in a one-stage reconstruction. METHODS: Seven LD-SA-rib free flaps were performed in seven patients to reconstruct concomitant bone and extensive soft-tissue defects in the lower extremity (tibia, five; femur, one; foot, one). The patients were all male, with an average age of 34 years (range, 20-48 years). These defects were secondary to trauma in five patients and posttraumatic osteomyelitis in two patients. RESULTS: All flaps survived and achieved bony union. The average time to bony union was 9.4 months. Bone hypertrophy of at least 20% occurred in all flaps. All patients achieved full weight-bearing ambulation without aid at an average duration of 23.7 months. Two patients developed stress fractures of the rib flap. There was no significant donor site morbidity, except for two patients who had pleural tears during harvesting of the flap. CONCLUSION: The LD-SA-rib flap provides a large soft-tissue component and a vascularized bone flap for reconstruction of composite large soft-tissue defects with concomitant bone defects of the lower extremity in a one-stage procedure.

Tumors of the Brachial Plexus: A Critical Analysis Review.

¼ Tumors of the brachial plexus are uncommon and can present as a mass, with or without neurological symptoms. At times, asymptomatic tumors are also picked up incidentally when imaging is performed for other reasons.¼ Magnetic resonance imaging is the main imaging modality used to evaluate tumors of the brachial plexus. Other imaging modalities can be used as required.¼ Benign tumors that are asymptomatic should be observed. Excision can be considered for those that are found to be growing over time.¼ Biopsies of tumors of the brachial plexus are associated with the risk of nerve injury. Despite this, they should be performed for tumors that are suspected to be malignant before starting definitive treatment.¼ For malignant tumors, treatment decisions should be discussed at multidisciplinary tumor boards, and include both the oncology and peripheral nerve surgical team, musculoskeletal radiology, neuroradiology, and general radiology.

Comparison of proximal and distal involvement of upper extremity metastatic lesions: an analysis of 55 cases.

We analysed the differences in clinical presentation between proximal (above elbow) and distal (below elbow) upper limb metastases in a retrospective review of patients presenting to our centre from 2011 to 2019. There were 55 cases, 64% involving the humerus and 62% occurring in men. The median age at the time of diagnosis was 64 years. Thirty-one per cent of the cases were proximal lesions. Distal upper limb metastases were more likely to be soft tissue lesions (71%) compared with proximal lesions (8%). The median age of patients with distal lesions was significantly lower at 58 years compared with 65 years for proximal lesions. Overall, non-small cell lung carcinoma was the most common primary malignancy (25%), however haematological cancers were most common in the distal group (29%). Distal upper limb metastases have distinct features that distinguish them from proximal lesions.Level of evidence: IV.

Rice bodies, millet seeds, and melon seeds in tuberculous tenosynovitis of the hand and wrist.

Tuberculosis (TB) is still endemic in many developed countries. Involvement of the hand and wrist at presentation is extremely rare, and the diagnosis is often missed. Operative findings of "rice bodies, millet seeds, or melon seeds" are highly suggestive of tuberculous tenosynovitis. Six patients with TB of the hand and wrist at various stages of disease with characteristic operative findings are reviewed. Four patients had underlying immunosuppression. One patient had previous pulmonary TB, whereas 3 patients had radiographic evidence of previously undiagnosed pulmonary TB. The interval to presentation ranged from 1 week to 2 years. Two patients had median nerve irritation, 3 patients had osteomyelitis, and 1 patient had flexor tendon rupture. Mycobacterial cultures were positive in 4 patients; acid-fast bacilli stain, and polymerase chain reaction were positive in remaining 1 patient; and both stain and culture were negative in the last patient who had history of pulmonary TB. All 6 patients were managed with combination therapy comprising antituberculous chemotherapy and at least 1 debulking tenosynovectomy. Two patients had 2 debridements. Of these 2 patients, 1 underwent wrist arthrodesis during the second procedure. Mean follow-up was 4 years. There were no recurrences after the most recent debridement. The diagnosis of TB of the hand and wrist is often missed. The surgeon has to be aware of the significance of loose bodies when performing routine excision of innocuous looking wrist ganglia. Combination therapy comprising thorough excisional debridement and antituberculous chemotherapy will minimize recurrence of this difficult-to-treat disease.

MNK1 and MNK2 enforce expression of E2F1, FOXM1, and WEE1 to drive soft tissue sarcoma.

Soft tissue sarcoma (STS) is a heterogeneous disease that arises from connective tissues. Clinical outcome of patients with advanced tumors especially de-differentiated liposarcoma and uterine leiomyosarcoma remains unsatisfactory, despite intensive treatment regimens including maximal surgical resection, radiation, and chemotherapy. MAP kinase-interacting serine/threonine-protein kinase 1 and 2 (MNK1/2) have been shown to contribute to oncogenic translation via phosphorylation of eukaryotic translation initiation factor 4E (eIF4E). However, little is known about the role of MNK1/2 and their downstream targets in STS. In this study, we show that depletion of either MNK1 or MNK2 suppresses cell viability, anchorage-independent growth, and tumorigenicity of STS cells. We also identify a compelling antiproliferative efficacy of a novel, selective MNK inhibitor ETC-168. Cellular responsiveness of STS cells to ETC-168 correlates positively with that of phosphorylated ribosomal protein S6 (RPS6). Mirroring MNK1/2 silencing, ETC-168 treatment strongly blocks eIF4E phosphorylation and represses expression of sarcoma-driving onco-proteins including E2F1, FOXM1, and WEE1. Moreover, combination of ETC-168 and MCL1 inhibitor S63845 exerts a synergistic antiproliferative activity against STS cells. In summary, our study reveals crucial roles of MNK1/2 and their downstream targets in STS tumorigenesis. Our data encourage further clinical translation of MNK inhibitors for STS treatment.

Single ray amputation for tumors of the hand.

UNLABELLED: Single ray amputation after hand trauma or infection can result in good aesthetic and functional outcomes. The role of this procedure in the management of aggressive benign or malignant hand tumors has been described only in case reports and small case series. We retrospectively reviewed the records of all 25 patients who underwent single ray amputations at our center during a 10-year period; there were seven index, five middle, six ring, and seven small ray amputations performed. The minimum followup was 2 months (mean, 36 months; range, 2-120 months), with four patients having a followup of 1 year or less. No patients had local recurrences, although two patients had positive resection margins. One underwent repeat resection followed by radiotherapy. The other was treated with radiotherapy alone, as local tumor control would have required a hand amputation. Functional assessment based on the Musculoskeletal Tumor Society staging system showed an average of 27.5 (range, 21-30). Patients who underwent perioperative radiotherapy experienced a decrease in functional ability. Grip strength was an average of 66% (range, 38%-100%) of the contralateral side. Our study suggests single ray amputation for hand tumors has a low local recurrence rate and high functional scores. However, function can be compromised by radiotherapy and a decrease in grip strength by a mean of 34% is to be expected. LEVEL OF EVIDENCE: Level IV, case series. See Guidelines for Authors for a complete description of levels of evidence.

MnSOD is implicated in accelerated wound healing upon Negative Pressure Wound Therapy (NPWT): A case in point for MnSOD mimetics as adjuvants for wound management.

Negative Pressure Wound Therapy (NPWT), a widely used modality in the management of surgical and trauma wounds, offers clear benefits over conventional wound healing strategies. Despite the wide-ranging effects ascribed to NPWT, the precise molecular mechanisms underlying the accelerated healing supported by NPWT remains poorly understood. Notably, cellular redox status-a product of the balance between cellular reactive oxygen species (ROS) production and anti-oxidant defense systems-plays an important role in wound healing and dysregulation of redox homeostasis has a profound effect on wound healing. Here we investigated potential links between the use of NPWT and the regulation of antioxidant mechanisms. Using patient samples and a rodent model of acute injury, we observed a significant accumulation of MnSOD protein as well as higher enzymatic activity in tissues upon NPWT. As a proof of concept and to outline the important role of SOD activity in wound healing, we replaced NPWT by the topical application of a MnSOD mimetic, Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP5+, MnE, BMX-010, AEOl10113) in the rodent model. We observed that MnE is a potent wound healing enhancer as it appears to facilitate the formation of new tissue within the wound bed and consequently advances wound closure by two days, compared to the non-treated animals. Taken together, these results show for the first time a link between NPWT and regulation of antioxidant mechanism through the maintenance of MnSOD activity. Additionally this discovery outlined the potential role of MnSOD mimetics as topical agents enhancing wound healing.

Bromodomain and extraterminal proteins foster the core transcriptional regulatory programs and confer vulnerability in liposarcoma.

Liposarcomas (LPSs) are a group of malignant mesenchymal tumors showing adipocytic differentiation. Here, to gain insight into the enhancer dysregulation and transcriptional addiction in this disease, we chart super-enhancer structures in both LPS tissues and cell lines. We identify a bromodomain and extraterminal (BET) protein-cooperated FUS-DDIT3 function in myxoid LPS and a BET protein-dependent core transcriptional regulatory circuitry consisting of FOSL2, MYC, and RUNX1 in de-differentiated LPS. Additionally, SNAI2 is identified as a crucial downstream target that enforces both proliferative and metastatic potentials to de-differentiated LPS cells. Genetic depletion of BET genes, core transcriptional factors, or SNAI2 mitigates consistently LPS malignancy. We also reveal a compelling susceptibility of LPS cells to BET protein degrader ARV-825. BET protein depletion confers additional advantages to circumvent acquired resistance to Trabectedin, a chemotherapy drug for LPS. Moreover, this study provides a framework for discovering and targeting of core oncogenic transcriptional programs in human cancers.

Angiomyofibroblastoma of the Foot: a Rare Soft Tissue Tumor at Unusual Site.

Angiomyofibroblastoma is a rare benign soft tissue tumor that arises predominantly in the female genital tract. It occurs less commonly in the scrotum, spermatic cord, and the retroperitoneum. Its diagnosis is based on specific histological and immunopathological features. However, the condition has never been previously described in the extremities. We present the first case report of angiomyofibroblastoma presenting as a slow-growing tumor in the foot of a 48-year-old lady.

Post Traumatic Avascular Necrosis of the Proximal Carpal Row--A Case Report.

We report a case of avascular necrosis of the scaphoid, lunate and triquetrum in a young 21-year-old patient, after a purely ligamentous peri-lunate dislocation of the wrist. He presented with a Mayfield III peri-lunate dislocation after a road traffic accident and underwent an open reduction and internal fixation. Post-operatively, the scapho-lunate gap widened after removal of the temporary K-wires, and he gradually developed avascular necrosis of the scaphoid, lunate and triquetrum, and osteoarthritis of his wrist. We present this unusual case of simultaneous avascular necrosis of multiple carpal bones and discuss the possible risk factors and subsequent management plans for this complex injury. Our patient has no identifiable contributing factors to developing avascular necrosis. We suspect that the violence of the injury and surgery may have compromised the circulation, and advise caution when treating and counseling these patients pre-operatively.

Characteristics of Fingertip Injuries in Children in Singapore.

Fingertip injuries are common in children, with varying degrees of severity. However, there is limited epidemiological information in the literature. An understanding of the characteristics of these injuries can be used as a basis to prevent such injuries. Epidemiological data was gathered through a retrospective review of all fingertip injuries affecting children, that presented to our department. There were 202 children with 234 injured fingertips in a period of 36 months. Most children were boys and most children injured their left hand. The mode age affected was 2 years. Accidental crush injuries in doors was the most common cause of fingertip injuries in children. An unexpectedly high number of children have fingertip injuries, with many requiring surgical treatment. Safety awareness and prevention of door crush injuries could reduce a large number of fingertip injuries in young children.

Intramuscular schwannoma: clinical and magnetic resonance imaging features.

INTRODUCTION: Schwannomas that arise within the muscle plane are called intramuscular schwannomas. The low incidence of these tumours and the lack of specific clinical features make preoperative diagnosis difficult. Herein, we report our experience with intramuscular schwannomas. We present details of the clinical presentation, radiological diagnosis and management of these tumours. METHODS: Between January 2011 and December 2013, 29 patients were diagnosed and treated for histologically proven schwannoma at the National University Hospital, Singapore. Among these 29 patients, eight (five male, three female) had intramuscular schwannomas. RESULTS: The mean age of the eight patients was 40 (range 27-57) years. The most common presenting feature was a palpable mass. The mean interval between surgical treatment and the onset of clinical symptoms was 17.1 (range 4-72) months. Six of the eight tumours (75.0%) were located in the lower limb, while 2 (25.0%) were located in the upper limb. None of the patients had any preoperative neurological deficits. Tinel's sign was present in one patient. Magnetic resonance (MR) imaging showed that the findings of split-fat sign, low signal margin and fascicular sign were present in all patients. The entry and exit sign was observed in 4 (50.0%) patients, a hyperintense rim was observed in 7 (87.5%) patients and the target sign was observed in 5 (62.5%) patients. All patients underwent microsurgical excision of the tumour and none developed any postoperative neurological deficits. CONCLUSION: Intramuscular schwannomas demonstrate the findings of split-fat sign, low signal margin and fascicular sign on MR imaging. These findings are useful for the radiological diagnosis of intramuscular schwannoma.

MRI and PET-CT in the diagnosis and follow-up of a lymphoma case with multifocal peripheral nerve involvement.

Lymphoma of the peripheral nerve, particularly of the T-cell variety, is an extremely rare subtype of extra nodal lymphoma that has a variable response to current therapeutic regimens. Here, we present a patient with natural killer (NK)/T-cell lymphoma in remission who presented with a two-month history of right forearm swelling and paresthesia in the ulnar nerve distribution. Magnetic resonance imaging (MRI) showed an ulnar nerve mass identified as a nerve sheath tumor. Frozen section and postresection biopsies showed an Epstein-Barr virus-positive NK/T-cell lymphoma, nasal type. Consequently, the patient received chemotherapy following resection. Four months later, the patient developed a proximal leg mass, which was diagnosed as tibial nerve lymphoma. The patient was then treated with chemotherapy and follow-up was done by positron emission tomography-computed tomography (PET-CT). In conclusion, lymphoma should be considered in the differential diagnosis of a peripheral nerve mass. MRI is a useful imaging tool together with PET-CT, which plays a beneficial role in the follow-up of these patients on therapy as well as diagnosis of new lesions.