Heritable defects in telomere and mitotic function selectively predispose to sarcomas.

Cancer genetics has to date focused on epithelial malignancies, identifying multiple histotype-specific pathways underlying cancer susceptibility. Sarcomas are rare malignancies predominantly derived from embryonic mesoderm. To identify pathways specific to mesenchymal cancers, we performed whole-genome germline sequencing on 1644 sporadic cases and 3205 matched healthy elderly controls. Using an extreme phenotype design, a combined rare-variant burden and ontologic analysis identified two sarcoma-specific pathways involved in mitotic and telomere functions. Variants in centrosome genes are linked to malignant peripheral nerve sheath and gastrointestinal stromal tumors, whereas heritable defects in the shelterin complex link susceptibility to sarcoma, melanoma, and thyroid cancers. These studies indicate a specific role for heritable defects in mitotic and telomere biology in risk of sarcomas.

Vitamin D, vitamin D-binding protein, free vitamin D and COVID-19 mortality in hospitalized patients.

BACKGROUND: Vitamin D deficiency has been associated with worse coronavirus disease 2019 (COVID-19) outcomes, but circulating 25-hydroxyvitamin D [25(OH)D] is largely bound to vitamin D-binding protein (DBP) or albumin, both of which tend to fall in illness, making the 25(OH)D status hard to interpret. Because of this, measurements of unbound ("free") and albumin-bound ("bioavailable") 25(OH)D have been proposed. OBJECTIVES: We aimed to examine the relationship between vitamin D status and mortality from COVID-19. METHODS: In this observational study conducted in Liverpool, UK, hospitalized COVID-19 patients with surplus sera available for 25(OH)D analysis were studied. Clinical data, including age, ethnicity, and comorbidities, were extracted from case notes. Serum 25(OH)D, DBP, and albumin concentrations were measured. Free and bioavailable 25(OH)D were calculated. Relationships between total, free, and bioavailable 25(OH)D and 28-day mortality were analyzed by logistic regression. RESULTS: There were 472 patients with COVID-19 included, of whom 112 (23.7%) died within 28 days. Nonsurvivors were older (mean age, 73 years; range, 34-98 years) than survivors (mean age, 65 years; range, 19-95 years; P = 0.003) and were more likely to be male (67%; P = 0.02). The frequency of vitamin D deficiency [25(OH)D < 50 nmol/L] was similar between nonsurvivors (71/112; 63.4%) and survivors (204/360; 56.7%; P = 0.15) but, after adjustments for age, sex, and comorbidities, increased odds for mortality were present in those with severe deficiency [25(OH)D < 25 nmol/L: OR, 2.37; 95% CI, 1.17-4.78] or a high 25(OH)D (≥100 nmol/L; OR, 4.65; 95% CI, 1.51-14.34) compared with a 25(OH)D value of 50-74 nmol/L (reference). Serum DBP levels were not associated with mortality after adjustments for 25(OH)D, age, sex, and comorbidities. Neither free nor bioavailable 25(OH)D values were associated with mortality. CONCLUSIONS: Vitamin D deficiency, as commonly defined by serum 25(OH)D levels (<50 nmol/L), is not associated with increased mortality from COVID-19, but extremely low (<25 nmol/L) and high (>100 nmol/L) levels may be associated with mortality risks. Neither free nor bioavailable 25(OH)D values are associated with mortality risk. The study protocol was approved by the London-Surrey Research Ethics Committee (20/HRA/2282).

Diagnosing plantar fibromas - Beware of sarcomas.

Plantar fibromas are a common diagnosis in orthopaedic foot clinic consultation, diagnosis of plantar fibroma is usually from history and examination, and radiological investigation may be needed to confirm diagnosis. Misdiagnosis, however, of plantar fibroma have been known to happen. The management of five cases of plantar soft tissue swellings were reviewed; the clinical presentation and radiological investigation findings of these cases are discussed with the aim of improving knowledge and awareness.

Unusual presentation of metastatic leiomyosarcoma-right forearm swelling.

Leiomyosarcoma (LMS) is a rare smooth muscle connective tissue tumour accounting for around 11% of soft-tissue sarcomas (Ducimetiere F, Lurkin A, Ranchere-Vince D, Decouvelaere AV, Péoc'h M, Istier L et al. Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. PLoS One 2011;6:e20294). LMS are highly unpredictable tumours that can present at any site in the body, most commonly in the uterus, stomach, small intestine and retroperitoneum. There are few published case reports within the literature on the metastatic spread of LMS to skeletal muscle. We present an unusual presentation of metastatic Leiomyosarcoma in the right forearm of a 71-year-old male treated with limb-sparing surgical excision. This case report demonstrates the unusual and unpredictable nature of metastatic LMS presentation, which poses difficulty in diagnosis and management.

Leiomyosarcoma presenting as 'idiopathic' unilateral lower limb lymphoedema.

A 74-year-old woman presented with an 8-year history of unilateral swelling of her right lower limb, which was thought to be 'idiopathic' lymphoedema until she noticed a painless swelling in her right groin. Physical examination showed a painless, non-pulsatile, deep-seated mass in her right proximal thigh with significant lymphoedema distally. MRI scan showed a large mass at her right inguinal region, involving the common femoral vein. Histological examination on complete excision revealed leiomyosarcoma. It is important to exclude proximal obstructive lesion before making a diagnosis of unilateral idiopathic lower limb lymphoedema.

Giant schwannomas of the sciatic nerve.

We report a very rare case of giant schwannomas of the sciatic nerve in a 39-year-old woman who presented with increasing swelling and discomfort in the posterior aspect of her right thigh. We demonstrate that even with such large tumours, surgical excision could be successfully carried out to resolve all symptoms while causing no permanent nerve damage. It remains paramount that large soft tissue tumours get referred to a sarcoma centre and be managed by a specialist multidisciplinary team.

Partial fasciectomy is a useful treatment option for symptomatic plantar fibromatosis.

Plantar fibromatosis is a rare, benign fibroproliferative disorder of the plantar fascia. It is considered as a low-grade tumour and it can be locally aggressive. It can present as painful swelling with impairment of local function. Upon failure of non-operative management, surgical treatment options include total fasciectomy or partial fasciectomy. Although surgical excision is the mainstay of treatment, recurrence rate can be up to 60%. The aim of this study was to determine the recurrence and complication rates of surgically treated plantar fibromatosis. A retrospective study was conducted involving patients who had a confirmed diagnosis and excision of plantar fibromatosis treated in our institution between 2011 and 2016. Demographic data, follow-up duration, recurrence and complications were reviewed. Eighteen patients underwent 19 operations. Mean age was 41.3 years (20-57). There were 12 male patients. The main presenting features were pain, swelling and impairment of function. They were investigated by ultrasound scan (12 feet, 63%) and/or magnetic resonance imaging (8 feet, 42%). Two patients (11%) had prior surgery at other institutions whilst 3 patients (17%) had multiple nodules at presentation. All patients underwent partial fasciectomy of the plantar fibromatosis. At up to 5 years follow-up, one patient (6%) had a recurrence in our series whilst 3 patients (17%) had scar related problems (2 patients with scar pain and one patient had hypersensitive scar that resolved after 12 months). Symptomatic plantar fibromatosis can be effectively treated with partial plantar fasciectomy.

Delayed diagnosis in primary care-The main cause of sarcoma litigation in the United Kingdom.

BACKGROUND: Poor awareness and knowledge of lumps and bumps can impact on patient outcomes and survival. Late referrals or false reassurance may lead to litigation proceedings. The aim of this study was to identify the litigation cost in sarcoma care and identify areas for improvement. METHOD: Orthopaedic litigation between 1995-2010 in England and Wales was obtained from the National Health Service Litigation Authority. Litigation specifically relating to sarcoma in the extremities was identified. Causation, compensation fee, cost of legal defense, and compensation were analyzed. RESULTS: There were 52 litigation claims. Negligence was proven in 71% (n = 37) of cases. The total cost was £4.4 million (mean of £84,000/case). The mean compensation award was £92,000 (range £650-£978,000) and the mean defense cost was £22,000 (range £0-£102,000). Delayed diagnosis accounted for 89% of cases (n = 48). Negligence following diagnosis was infrequent; inappropriate treatment (n = 2), failure to recognize complications of surgery (n = 2), intra-operative problems (n = 1), failure to refer to a specialist unit after a "whoops procedure" (n = 1). CONCLUSIONS: Once the patient is within the specialist sarcoma unit, there is a very low rate of litigation. Efforts to reduce litigation in sarcoma treatment should focus on early diagnosis and raising awareness of sarcomas. J. Surg. Oncol. 2016;113:361-363. © 2016 Wiley Periodicals, Inc.

The use of a biological graft for the closure of large abdominal wall defects following excision of soft tissue tumours.

Primary soft tissue tumours arising from the abdominal wall are uncommon and surgical excision of such tumours can result in large abdominal wall defects. There are many techniques available for abdominal wall repair following tumour excision, each having its own advantages and disadvantages. The options range from direct closure to the use of tissue flap reconstructions and/or prosthetic meshes. Currently, synthetic material such as polypropylene mesh is a common choice for closure of abdominal wall defects after tumour excision. Biological meshes are an alternative option for repair, and this report outlines two cases of abdominal wall repair using the porcine intestinal submucosa biological graft following excision of abdominal wall tumours. There was no evidence of infection, recurrence, seroma or hernias at 2-year follow-up. Following excision of soft tissue tumours of the abdominal wall, biological reconstructions can be successfully used to bridge the defect with minimal morbidity.

Leiomyosarcoma of the ischiorectal fossa: report of a novel sphincter and sciatic nerve sparing simultaneous trans-abdominal and trans-gluteal resection and review of the literature.

Leiomyosarcomas are rare tumours of smooth muscle origin, and there have been no reported cases of such tumours arising within the ischiorectal fossa. Surgical resection with clear margins remains the gold standard treatment; however, there is limited literature on surgical approaches to the ischiorectal fossa for such tumours. We report a case of a high-grade leiomyosarcoma in a 59-year-old lady, occurring within the ischiorectal fossa that was managed using a novel simultaneous sphincter and sciatic nerve preserving trans-abdominal and trans-gluteal technique. This novel approach could be utilized not only for sarcomas but also for other tumours of the ischiorectal fossa extending into the gluteal region.

Use of a superficial femoral artery autograft as a femoral vein replacement during en bloc sarcoma resection.

INTRODUCTION: Soft tissue malignancy encasing axial vessels presents a surgical challenge when the goal is limb-preserving radical excision. REPORT: We describe a case where limb-preserving resection of a myxoid liposarcoma involving the femoral vessels was successfully performed in the absence of autologous superficial vein for vascular reconstruction. The proximal ipsilateral superficial femoral artery was harvested as an autograft for venous reconstruction, with the arterial defect bridged using a polytetrafluoroethylene interposition graft. DISCUSSION: This technique may be selectively extended to other indications where limb viability is dependent upon availability of a high-quality graft, and conventional conduits are either unavailable or unreliable.

Patient-oriented functional results of total femoral endoprosthetic reconstruction following oncologic resection.

BACKGROUND AND OBJECTIVES: Functional outcomes following oncologic total femoral endoprosthetic reconstruction (TFR) are lacking. We compared patient-oriented functional results of TFRs to proximal femur and distal femur reconstructions (PFR and DFR). We also compared function and complications with regard to knee and hip componentry. METHODS: Fifty-four TFR patients were identified from three institutional prospective databases. Forty-one had fixed- and 13 had rotating-hinge knees, 37 hemiarthroplasty and 17 total hip arthroplasty componentry. Toronto Extremity Salvage Scores (TESS) for n = 27 were compared between groups and to cohorts of PFR (n = 31) and DFR (n = 85) patients using the Mann-Whitney U-test. RESULTS: Follow-up averaged 4 years. Mechanical complications included five hip dislocations and one femoral malrotation. Four dislocations were in fixed-hinge implants, all in those lacking abductor reattachment. TESS averaged 69.3 ± 17.8, statistically decreased from DFR (P = 0.002) and PFR patients (P = 0.036). No significant differences were detected between patients in the fixed-hinge (n = 18) and rotating-hinge (n = 9) groups (P = 0.944), or total hip (n = 8) and hemiarthroplasty (n = 19) groups (P = 0.633). CONCLUSIONS: TFR is reserved for extreme cases of limb salvage, portending a poor prognosis overall. Function reflects additive impairments from PFR and DFR. TFR outcomes differ little with rotating- or fixed-hinge, total hip or hemiarthroplasty implants.

Revision hip replacement for recurrent Hydatid disease of the pelvis: a case report and review of the literature.

A case of a large recurrent hydatid cyst involving the right ilium and right hip treated with excision of the cyst, Total hip replacement and revision of the acetabular component with a Tripolar articulation for cyst recurrence and acetabular component loosening is presented along with a review of the relevant literature. To our knowledge there is no reported case of Total Hip replacement and revision for hydatid disease involving the bony pelvis.

Modular endoprosthetic replacement for metastatic tumours of the proximal femur.

BACKGROUND AND AIMS: Endoprosthetic replacements of the proximal femur are commonly required to treat destructive metastases with either impending or actual pathological fractures at this site. Modular prostheses provide an off the shelf availability and can be adapted to most reconstructive situations for proximal femoral replacements. The aim of this study was to assess the clinical and functional outcomes following modular tumour prosthesis reconstruction of the proximal femur in 100 consecutive patients with metastatic tumours and to compare them with the published results of patients with modular and custom made endoprosthetic replacements. METHODS: 100 consecutive patients who underwent modular tumour prosthetic reconstruction of the proximal femur for metastases using the METS system from 2001 to 2007 were studied. The patient, tumour and treatment factors in relation to overall survival, local control, implant survival and complications were analysed. Functional scores were obtained from surviving patients. RESULTS AND CONCLUSION: There were 45 male and 55 female patients. The mean age was 60.2 years. The indications were metastases. Seventy five patients presented with pathological fracture or with failed fixation and 25 patients were at a high risk of developing a fracture. The mean follow up was 15.9 months [range 0-77]. Three patients died within 2 weeks following surgery. 69 patients have died and 31 are alive. Of the 69 patients who were dead 68 did not need revision surgery indicating that the implant provided single definitive treatment which outlived the patient. There were three dislocations (2/5 with THR and 1/95 with unipolar femoral heads). 6 patients had deep infections. The estimated five year implant survival (Kaplan-Meier analysis) was 83.1% with revision as end point. The mean TESS score was 64% (54%-82%). We conclude that METS modular tumour prosthesis for proximal femur provides versatility; low implant related complications and acceptable function lasting the lifetime of the patients with metastatic tumours of the proximal femur.