Lichen Sclerosis is Associated With a High Rate of Local Failure After Radio(chemo)therapy for Vulvar Cancer

AimsRadio(chemo)therapy plays an important role in the treatment of vulvar cancer, either as postoperative treatment or as definitive treatment in patients who present with inoperable disease. Only limited data are available regarding outcome after modern state of the art radio(chemo)therapy and more information regarding prognostic factors are warranted. The aim of this study was to evaluate disease outcomes after radio(chemo)therapy in patients with vulvar cancer with special emphasis on the impact of lichen sclerosis on local control.Materials and methodsAll consecutive patients (n = 109) from the western half of Denmark who were treated with definitive (n = 52) or postoperative (n = 57) radio(chemo)therapy between January 2013 and January 2020 were included. Local control, cause-specific survival and overall survival, as well as morbidity, were analysed using Kaplan–Meier statistics. Prognostic factors for local control were analysed in univariate and multivariate analysis.ResultsAt a median follow-up of 35 (4–95) months, 46 (42.0%) patients were diagnosed with recurrence. Eighty per cent of the recurrences were located to the vulva region, leading to a 5-year local control of 58.9% (confidence interval 47.9–69.9). Cause-specific survival was 62.9% (confidence interval 53.1–72.7), whereas overall survival was 58.0% (confidence interval 47.6–68.5). Grade 3–4 morbidity was diagnosed in 10 (9%) patients. Lichen sclerosis (hazard ratio 3.89; confidence interval 1.93–7.79) was an independent risk factors for local recurrence. Patients without lichen sclerosis had a 5-year local control rate of 83.6% (confidence interval 67.2–99.0) and 62.6% (confidence interval 43.2–82.0) after postoperative and definitive radio(chemo)therapy, respectively. In patients with lichen sclerosis, the local control rate was 44.0% (confidence interval 19.3–69.0) and 17.6% (confidence interval 0–30.0) after postoperative and definitive radio(chemo)therapy, respectively.ConclusionRadio(chemo)therapy plays an important role in the treatment of vulvar cancer. However, despite dose escalation, a substantial proportion of patients experienced local relapse. Pre-existing lichen sclerosis seems to have a significant impact on the risk of recurrence. This should influence surveillance programmes for these patients.     

Evaluation of immunogenicity and protection of the Mic1-3 knockout Toxoplasma gondii live attenuated strain in the feline host

Toxoplasmosis is a zoonotic disease caused by the parasite Toxoplasma gondii. Up to a third of the global human population is estimated to carry a T. gondii infection, which can result in severe complications in immunocompromised individuals and pregnant women. Humans and animals can become infected by ingesting either tissue cysts containing T. gondii bradyzoites, from raw or undercooked meat, or sporulated oocysts from environmental sources. T. gondii oocysts are released in the faeces of cats and other felids, which are the parasite's definitive hosts, leading to environmental contamination. Therefore, vaccination of the feline host against T. gondii is an interesting strategy to interrupt the parasitic life cycle and subsequently limit contamination of intermediate hosts. With this goal in mind, we tested in cats, an attenuated live strain of T. gondii deleted for the Mic1 and Mic3 genes (Mic1-3KO) that was previously shown to be an efficient vaccine candidate in mouse and sheep models. Subcutaneous or oral vaccination routes induced a high specific antibody titer in the cat sera, indicating that the Mic1-3KO strain is immunogenic for cats. To assess protection induced by the vaccine candidate strain, we followed oocysts shedding by vaccinated cats, after oral challenge with a T. gondii wild-type strain. Surprisingly, a high antibody titer did not prevent cats from shedding oocysts from the challenge strain, regardless of the vaccination route. Our results show that the Mic1-3KO vaccine candidate is immunogenic in the feline host, is well tolerated and safe, but does not confer protection against oocysts shedding after natural infection with wild type T. gondii. This result highlights the particular relationship between T. gondii and its unique definitive host, which indicates the need for further investigations to improve vaccination strategies to limit environmental and livestock contaminations.     

A systematic review of combined pelvic and acetabular injuries

PurposeInjuries of both pelvic ring and acetabulum as rare very few articles are available in literature. There are no set protocols in defining the injury let alone defining early and definitive management strategies. This article is an attempt to encompass all available data to give us guidelines in managing these injuries.MethodsAn extensive literature review was carried out on PubMed/Medline, google scholar and Embase databases was done with the eligibility criteria of 1) Case series with a minimum of 20 cases. 2) The patient’s outcome reported. 3) Full article available. 4) Article in English. 5) Minimum Jadad score of 3. As per PRISMA guidelines the search was done and gradually filtered down to relevant articles which were 8 in number.ResultsThe incidence of these injuries range from 5 to 16%. The transverse acetabular fracture pattern is the commonest followed by associated both column fractures. There is equal propensity of Anteroposterior compression and lateral compression injuries. The injury mechanism appears to transmitted lateral force from the greater trochanter inwards with an implosion injury causing acetabular and pelvic injury as a continuum. The initial management is similar to managing pelvic ring injuries with focus on patient resuscitation, hemodynamic stabilization and temporary stabilization. The injury severity score and the mortality rates are comparable to isolated unstable pelvic ring injuries. Definitive management focuses on fixing the posterior pelvic ring first followed by the acetabular fracture and then the anterior pelvic ring. The displacement rates and outcome is worse than isolated acetabular injuries or pelvic injuries.ConclusionCombined Pelvic and acetabular injuries are complex injuries which need to be managed initially as we manage pelvic injury and later as we fix as an acetabular fracture meticulously.     

A meta-analysis on salvage surgery as a potentially curative procedure in patients with isolated local recurrent or persistent esophageal cancer after chemoradiotherapy

BackgroundIsolated local recurrent or persistent esophageal cancer (EC) after curative intended definitive (dCRT) or neoadjuvant chemoradiotherapy (nCRT) with initially omitted surgery, is a potential indication for salvage surgery. We aimed to evaluate safety and efficacy of salvage surgery in these patients.Material and methodsA systematic literature search following PRISMA guidelines was performed using databases of PubMed/Medline. All included studies were performed in patients with persistent or recurrent EC after initial treatment with dCRT or nCRT, between 2007 and 2017. Survival analysis was performed with an inverse-variance weighting method.ResultsOf the 278 identified studies, 28 were eligible, including a total of 1076 patients. Postoperative complications after salvage esophagectomy were significantly more common among patients with isolated persistent than in those with locoregional recurrent EC, including respiratory (36.6% versus 22.7%; difference in proportion 10.9 with 95% confidence interval (CI) [3.1; 18.7]) and cardiovascular complications (10.4% versus 4.5%; difference in proportion 5.9 with 95% CI [1.5; 10.2]). The pooled estimated 30- and 90-day mortality was 2.6% [1.6; 3.6] and 8.0% [6.3; 9.8], respectively. The pooled estimated 3-year and 5-year overall survival (OS) were 39.0% (95% CI: [35.8; 42.2]) and 19.4% [95% CI:16.5; 22.4], respectively. Patients with isolated persistent or recurrent EC after initial CRT had similar 5-year OS (14.0% versus 19.7%, difference in proportion −5.7, 95% CI [-13.7; 2.3]).ConclusionsSalvage surgery is a potentially curative procedure in patients with locally recurrent or persistent esophageal cancer and can be performed safely after definitive or neoadjuvant chemoradiotherapy when surgery was initially omitted.     

Final Results of NRG Oncology RTOG 0246: An Organ-Preserving Selective Resection Strategy in Esophageal Cancer Patients Treated with Definitive Chemoradiation

IntroductionThe impact of selective surgical resection for patients with esophageal cancer treated with definitive chemoradiation has not been clearly evaluated long-term.MethodsNRG (National Surgical Adjuvant Breast and Bowel Project, Radiation Therapy Oncology Group, Gynecologic Oncology Group) Oncology Radiation Therapy Oncology Group 0246 was a multi-institutional, single-arm, open-label, nonrandomized phase II study that enrolled 43 patients from September 2003 to March 2008 with clinical stage T1–4N0–1M0 squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction from 19 sites. Patients received induction chemotherapy with fluorouracil (650 mg/m²/d), cisplatin (15 mg/m²/d), and paclitaxel (200 mg/m²/d) for two cycles followed by concurrent chemoradiation consisting of 50.4 Gy of radiation (1.8 Gy per fraction) and daily fluorouracil (300 mg/m²/d) with cisplatin (15 mg/m²/d) over the first 5 days. After definitive chemoradiation, patients were evaluated for residual disease. Selective esophagectomy was considered only for patients with residual disease after chemoradiation (clinical incomplete response) or recurrent disease on surveillance.ResultsThis report looks at the long-term outcome of this selective surgical strategy. With a median follow-up of 8.1 years (minimum to maximum for 12 alive patients 7.2–9.8 years), the estimated 5- and 7-year survival rates are 36.6% (95% confidence interval [CI]: 22.3–51.0) and 31.7% (95% CI: 18.3–46.0). Clinical complete response was achieved in 15 patients (37%), with 5- and 7-yearr survival rates of 53.3% (95% CI: 26.3–74.4) and 46.7% (95% CI: 21.2–68.7). Esophageal resection was not required in 20 of 41 patients (49%) on this trial.ConclusionsThe long-term results of NRG Oncology Radiation Therapy Oncology Group 0246 demonstrate promising efficacy of a selective surgical resection strategy and suggest the need for larger randomized studies to further evaluate this organ-preserving approach.