Evaluating the Utility of ctDNA in Detecting Residual Cancer and Predicting Recurrence in Patients with Serous Ovarian Cancer.

Ovarian cancer has a high case fatality rate, but patients who have no visible residual disease after surgery have a relatively good prognosis. The presence of any cancer cells left in the peritoneal cavity after treatment may precipitate a cancer recurrence. In many cases, these cells are occult and are not visible to the surgeon. Analysis of circulating tumour DNA in the blood (ctDNA) may offer a sensitive method to predict the presence of occult (non-visible) residual disease after surgery and may help predict disease recurrence. We assessed 48 women diagnosed with serous ovarian cancer (47 high-grade and 1 low-grade) for visible residual disease and for ctDNA. Plasma, formalin-fixed paraffin-embedded (FFPE) tumour tissue and white blood cells were used to extract circulating free DNA (cfDNA), tumour DNA and germline DNA, respectively. We sequenced DNA samples for 59 breast and ovarian cancer driver genes. The plasma sample was collected after surgery and before initiating chemotherapy. We compared survival in women with no residual disease, with and without a positive plasma ctDNA test. We found tumour-specific variants (TSVs) in cancer cells from 47 patients, and these variants were sought in ctDNA in their post-surgery plasma. Fifteen (31.9%) of the 47 patients had visible residual disease; of these, all 15 had detectable ctDNA. Thirty-one patients (65.9%) had no visible residual disease; of these, 24 (77.4%) patients had detectable ctDNA. Of the patients with no visible residual disease, those patients with detectable ctDNA had higher mortality (20 of 27 died) than those without detectable ctDNA (3 of 7 died) (HR 2.32; 95% CI: 0.67-8.05), although this difference was not statistically significant (p = 0.18). ctDNA in post-surgical serum samples may predict the presence of microscopic residual disease and may be a predictor of recurrence among women with ovarian cancer. Larger studies are necessary to validate these findings.

Predictive value of post-void residual volume as an adjunctive tool in the clinical evaluation of cauda equina syndrome.

The early diagnosis of cauda equina syndrome (CES) is crucial for a favourable outcome. Several studies have reported the use of an ultrasound scan of the bladder as an adjunct to assess the minimum post-void residual volume of urine (mPVR). However, variable mPVR values have been proposed as a threshold without consensus on a value for predicting CES among patients with relevant symptoms and signs. The aim of this study was to perform a meta-analysis and systematic review of the published evidence to identify a threshold mPVR value which would provide the highest diagnostic accuracy in patients in whom the diagnosis of CES is suspected. The search strategy used electronic databases (PubMed, Medline, EMBASE, and AMED) for publications between January 1996 and November 2021. All studies that reported mPVR in patients in whom the diagnosis of CES was suspected, followed by MRI, were included. A total of 2,115 studies were retrieved from the search. Seven fulfilled the inclusion criteria. These included 1,083 patients, with data available from 734 being available for meta-analysis. In 125 patients, CES was confirmed by MRI. The threshold value of mPVR reported in each study varied and could be categorized into 100 ml, 200 ml, 300 ml, and 500 ml. From the meta-analysis, 200 ml had the highest diagnostic accuracy, with 82% sensitivity (95% confidence interval (CI) 0.72 to 0.90) and 65% specificity (95% CI 0.70 to 0.90). When compared using summative receiver operating characteristic curves, mPVR of 200 ml was superior to other values in predicting the radiological confirmation of CES. mPVR is a useful tool when assessing patients in whom the diagnosis of CES is suspected. Compared with other values a mPVR of 200 ml had superior sensitivity, specificity, and positive and negative predictive values. In a patient with a suggestive history and clinical findings, a mPVR of > 200 ml should further raise the suspicion of CES. Caution is recommended when considering the mPVR in isolation and using it as an 'exclusion tool', and it should only be used as an adjunct to a full clinical assessment.

Ankle arthrodesis in patients with haemophilia-associated ankle arthropathy - does the technique influence the outcome?

Management of symptomatic osteoarthritis (OA) of the ankle in patients with haemophilia can be challenging. Arthroscopic ankle arthrodesis has been shown in non-haemophiliac patients to provide similar or superior rates of fusion to open ankle fusion. However, the literature regarding ankle arthrodesis in patients with haemophilia is limited. Our aim was to compare the rate of successful fusion between open and arthroscopic assisted ankle arthrodesis in patients with haemophilia. A retrospective study was performed. All patients with haemophilia who underwent ankle arthrodesis at our centre were included. Outcomes including peri- and post-operative complications, and lengths of stay were extracted from patients' records. Radiographs were reviewed for signs of successful arthrodesis. Seventeen arthrodesis procedures were performed in 13 patients between 1980 and 2017. Nine procedures were performed arthroscopically and eight were open. Ten patients were diagnosed with haemophilia A and three with haemophilia B. The success rates of arthroscopic and open tibiotalar arthrodesis were 100% and 87.5% respectively. Four complications occurred. In the open technique group, there was one non-union. The same patient also developed subsequent haematoma after revision surgery. One patient developed a superficial wound infection which resolved with antibiotics. In the arthroscopic group, one patient developed a pseudoarthrosis of the distal tibiofibular joint which required a revision procedure. The results of this study suggest that arthroscopic ankle fusion for haemophilia- associated arthropathy is a viable option, with the rate of successful fusion being comparable to open procedures.

CA125 and Ovarian Cancer: A Comprehensive Review.

Ovarian cancer is the second most lethal gynecological malignancy. The tumour biomarker CA125 has been used as the primary ovarian cancer marker for the past four decades. The focus on diagnosing ovarian cancer in stages I and II using CA125 as a diagnostic biomarker has not improved patients' survival. Therefore, screening average-risk asymptomatic women with CA125 is not recommended by any professional society. The dualistic model of ovarian cancer carcinogenesis suggests that type II tumours are responsible for the majority of ovarian cancer mortality. However, type II tumours are rarely diagnosed in stages I and II. The recent shift of focus to the diagnosis of low volume type II ovarian cancer in its early stages of evolution provides a new and valuable target for screening. Type II ovarian cancers are usually diagnosed in advanced stages and have significantly higher CA125 levels than type I tumours. The detection of low volume type II carcinomas in stage IIIa/b is associated with a higher likelihood for optimal cytoreduction, the most robust prognostic indicator for ovarian cancer patients. The diagnosis of type II ovarian cancer in the early substages of stage III with CA125 may be possible using a higher cutoff point rather than the traditionally used 35 U/mL through the use of point-of-care CA125 assays in primary care facilities. Rapid point-of-care testing also has the potential for effective longitudinal screening and quick monitoring of ovarian cancer patients during and after treatment. This review covers the role of CA125 in the diagnosis and management of ovarian cancer and explores novel and more effective screening strategies with CA125.

Correlation and comparison of syndesmosis dimension on CT and MRI.

INTRODUCTION: Various methods using CT scan have been described to diagnose distal tibiofibular syndesmotic injuries. However, CT scan does not take into account the amount of cartilage within the distal tibiofibular joint and could therefore lead to false positive results. We present the first study correlating the findings of the distal tibiofibular syndesmosis on CT and MRI scans. METHODS: CT and MRI scan of consecutive patients over a period of 18 months, and of a time lapsed less than 12 months between the two imaging modalities, were reviewed. Measurements of the distal tibiofibular syndesmosis were taken according to a previously published study at the level of the distal tibial physeal scar. RESULTS: Twenty-six ankles from 25 patients were included in this study for analysis. Significant difference between CT and MRI assessments in the overall distal tibiofibular dimensions and in the posterior distal tibiofibular distance for those ankles with evidence of osteoarthritis was found. Interclass correlation coefficients suggest that such methodology was reproducible and reliable. CONCLUSION: When the widening found on a CT scan is minor or the diagnosis is equivocal, a contralateral comparative CT or an ipsilateral MRI scan is recommended to prevent misdiagnosis. LEVEL OF EVIDENCE: Level IV.

Functional outcomes of total hip arthroplasty in patients aged 30 years or less: a systematic review and meta-analysis.

INTRODUCTION: Young adult hip surgery is a growing subspecialty. Increasingly total hip arthroplasty (THA) is offered to patients aged 30 or less suffering from end-stage hip arthropathy from a variety of congenital, developmental and acquired conditions. There is a paucity of evidence to advise such patients and surgeons alike on the functional outcomes of THA in this age group, as individual studies tend to include small cohorts. METHODS: A systematic review and meta-analysis was performed to assess whether THA in patients aged 30 years or less provides significant functional improvement. The primary outcome measure was change in Harris Hip Score. Secondary outcome measures were implant survivorship and the effect of fixation type and bearing surface. RESULTS: The results of 743 primary THA procedures were included. Weighted mean patient age was 22.7 years. Harris Hip Score improved by a weighted mean difference of 42.17 points out of 100 (95% confidence interval, 36.48-47.86 points, p<0.001) after THA at a weighted mean follow-up of 8.4 years. Pooled revision rate was 5.0% for the same time period. CONCLUSIONS: This is the largest review to date of THA in patients aged 30 or less. The results show significant functional improvement measured by Harris Hip Score. The revision rate of 5% at 8.4 years is comparable to the general THA population. This contrasts high revision rates reported in older reviews of the literature, suggesting adoption of improved techniques and implants in the more recent literature.

A case of femoral fracture in klippel trenaunay syndrome.

We present a case of Klippel Trenaunay syndrome (KTS) who presented with severe bilateral knee osteoarthritis (OA). Preoperative planning was commenced for a total knee replacement (TKR). Whilst on the waiting list the patient suffered a fall and sustained a complete femoral diaphysis fracture. Conservative management in the form of skin traction was initially chosen as significant extra- and intramedullary vascular malformations posed an increased risk of perioperative bleeding. This failed to progress to union, and so open reduction and internal fixation was performed. This subsequently resulted in on-going delayed union, which was subsequently managed with low intensity pulsed ultrasound (LIPUS, otherwise known as Exogen (Bioventus. exogen. Secondary exogen, 2012)). There are only two previous documented cases of femoral fracture in KTS. This is the first report of a patient with this rare syndrome receiving this treatment. We discuss the management of fracture in this challenging group of patients.

Long-term result and patient reported outcome of wrist splint treatment for carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) is the commonest peripheral neuropathy presenting to specialist hand and wrist clinics. This study investigated the long-term outcome of carpal tunnel syndrome treated with isolated night wrist splint and the factors determining the likelihood of success of this intervention. Seventy-five patients referred to a specialist hand clinic with CTS were given night wrist splint treatment for 3 months as per a previous study protocol. Fifty-two patients from this cohort did not wish to have surgery after wrist splint treatment and were followed for a further 33-month period. Baseline pain and numbness levels were recorded on a Visual Analogue Scale (VAS) using a questionnaire upon first presentation. A further questionnaire at 36 months reassessed pain and numbness levels, patients' satisfaction with the treatment, and whether they had subsequent surgical decompression. Of the patients who completed the follow-up questionnaire 33 months after their period of conservative management, 43% were successfully treated with splint treatment alone. There was no difference in the VAS for pain or numbness at the baseline and at 36 months between successful and failed treatment groups. Patients successfully treated with wrist splinting alone reported a higher level of satisfaction with their treatment compared to patients who failed wrist splint treatment or had surgical decompression. The results reinforce the previous recommendation on wrist splinting as a first-line treatment in the Primary Care setting. Referral to specialist hand and wrist clinics should be reserved for patients with symptoms refractory to this initial measure.

The use of the ligament augmentation and reconstruction system (LARS) for posterior cruciate reconstruction.

PURPOSE: To systematically review and assess the use of the Ligament Advanced Reinforcement System (LARS; Surgical Implants and Devices, Arc-sur-Tille, France) for posterior cruciate ligament (PCL) reconstruction. METHODS: A search of multiple databases was conducted using the following terms: (LARS[All Fields] AND posterior[All Fields]) OR (LARS[All Fields] AND PCL[All Fields]). The methodologic quality of each article was assessed by use of abridged Downs and Black criteria. RESULTS: Fifty-four studies were found from the database search, of which 5 were included in the final review (4 case series and 1 case-control study). One hundred twenty-nine PCL reconstructions with LARS were performed. The mean patient age was 32.2 years, with 89 male and 40 female patients included. The mean follow-up time ranged from 10.5 to 44 months. Lysholm scores improved from a mean of 64.8 preoperatively to 89.8 postoperatively. No patients had International Knee Documentation Committee grade 1 or 2 preoperatively, with 93.0% achieving this postoperatively. Only 1 case of synovitis and 1 case of graft rupture were reported. CONCLUSIONS: There is little evidence on the effectiveness of PCL reconstructions using LARS ligaments. What data there are show great promise, with short- and medium-term outcome data appearing favorable to autograft reconstruction. Complication rates are encouragingly low. CLINICAL RELEVANCE: LARS has great potential for PCL reconstruction. Further studies are needed regarding the use of LARS ligaments during PCL reconstruction, including longer follow-up periods and investigation into the optimal timing for reconstruction. This may be best achieved by way of a multicenter study.

Anterior cruciate ligament injury and radiologic progression of knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis after anterior cruciate ligament (ACL) injury has previously been reported. However, there has been no meta-analysis reporting the development and progression of osteoarthritis. PURPOSE: We present the first meta-analysis reporting on the development and progression of osteoarthritis after ACL injury at a minimum mean follow-up of 10 years, using a single and widely accepted radiologic classification, the Kellgren & Lawrence classification. STUDY DESIGN: Meta-analysis. METHOD: Articles were included for systematic review if they reported radiologic findings of ACL-injured knees and controls using the Kellgren & Lawrence classification at a minimum mean follow-up period of 10 years. Appropriate studies were then included for meta-analysis. RESULTS: Nine studies were included for systematic review, of which 6 studies were further included for meta-analysis. One hundred twenty-one of 596 (20.3%) ACL-injured knees had moderate or severe radiologic changes (Kellgren & Lawrence grade III or IV) compared with 23 of 465 (4.9%) uninjured ACL-intact contralateral knees. After ACL injury, irrespective of whether the patients were treated operatively or nonoperatively, the relative risk (RR) of developing even minimal osteoarthritis was 3.89 (P < .00001), while the RR of developing moderate to severe osteoarthritis (grade III and IV) was 3.84 (P < .0004). Nonoperatively treated ACL-injured knees had significantly higher RR (RR, 4.98; P < .00001) of developing any grade of osteoarthritis compared with those treated with reconstructive surgery (RR, 3.62; P < .00001). Investigation of progression to moderate or severe osteoarthritis (grade III or IV only) after 10 years showed that ACL-reconstructed knees had a significantly higher RR (RR, 4.71; P < .00001) compared with nonoperative management (RR, 2.41; P = .54). It was not possible to stratify for return to sports among the patients undergoing ACL reconstruction. CONCLUSION: Results support the proposition that ACL injury predisposes knees to osteoarthritis, while ACL reconstruction surgery has a role in reducing the risk of developing degenerative changes at 10 years. However, returning to sports activities after ligament reconstruction may exacerbate the development of arthritis.

Epidural collection following a late infected total knee replacement--a case report.

Prosthetic joint infection is a well-described complication following primary joint replacement. The association between an epidural abscess and joint replacement surgery following the use of epidural anaesthetics has been previously documented. There is however, no report in the literature of an epidural abscess forming as a result of haematogenous spread from an infected prosthetic joint. This case report presents such a scenario and highlights the importance of early diagnosis and treatment of infected prosthetic joints to avoid further systemic complications.

Publication trends in knee surgery: a review of the last 16 years.

The trends in the publication of articles regarding knee arthroplasty and soft tissue surgery were analysed with regard to geographical authorship, institutional funding and number of authors. Over 7500 articles from relevant journals with the highest impact factors according to the Thomson Reuters Journal Citation Report (2010) were evaluated from 1995 to 2010. The rate of publication increased by 16.9 per year for arthroplasty articles and by 13.9 per year for soft tissue surgery articles. The relative supremacy of the USA has declined over the 16 years, its share dropping from 72.2% to 39.2% for arthroplasty articles and from 61.7% to 36.6% for soft tissue surgery articles. The UK, Japan, South Korea and smaller countries in Asia and South America have become increasingly prolific.

Balloon kyphoplasty treatment for a spontaneous vertebral fracture in renal osteodystrophy.

Renal osteodystrophy is a spectrum of musculoskeletal abnormalities. Bony fractures can occur spontaneously or with minor trauma in this condition. The authors report the first case of balloon kyphoplasty treatment for painful renal osteodystrophy vertebral body collapse secondary to end-stage renal failure on dialysis. The authors have demonstrated that kyphoplasty is a safe procedure for pain management in severe dystrophic patients. In addition, pain treatment with kyphoplasty can be achieved without anatomical restoration of vertebral body height.