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.     

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.     

伴有齿槽嵴裂的单侧唇裂术后继发鼻畸形的修复

目的探讨伴有齿槽嵴裂的单侧唇裂术后继发鼻畸形的修复方法。方法对34例伴有齿槽嵴裂的单侧唇裂术后继发畸形的患者,在行齿槽嵴植骨的同时,行彻底的鼻整形手术。结果术后随访1~3年,植骨区成活良好,鼻畸形较整形前明显改善,接近正常外形,效果满意。结论在行齿槽嵴植骨的同时,行彻底的鼻整形手术,能够取得满意的效果,并且节省了医疗费用,缩短了治疗时间。     

System for inducible expression of cre-recombinase from the Foxa2 locus in endoderm, notochord, and floor plate.

We targeted the reverse tetracycline controlled transactivator (rtTA) to the Foxa2 locus (Foxa2(ITA)) to generate a system for regulating Cre-recombinase activity within Foxa2 expression domains, including the endoderm, notochord, and floor plate of early mouse embryos. The use of an internal ribosomal entry site to obtain rtTA expression preserves Foxa2 function of the targeted allele. Cre activity with this system reflects the level of endogenous Foxa2 activity and is also tightly controlled by doxycycline. The location of Cre activity within the broader Foxa2 expression domain can be restricted by altering the timing of doxycycline administration. Isolated floor plate expression can be obtained in this manner. This system will provide a useful tool for manipulating gene expression in endoderm, notochord, and floor plate, all of which are tissues with important structural and patterning functions during embryogenesis.     

Genetic ablation of FLRT3 reveals a novel morphogenetic function for the anterior visceral endoderm in suppressing mesoderm differentiation

During early mouse development, the anterior visceral endoderm (AVE) secretes inhibitor and activator signals that are essential for establishing the anterior–posterior (AP) axis of the embryo and for restricting mesoderm formation to the posterior epiblast in the primitive streak (PS) region. Here we show that AVE cells have an additional morphogenetic function. These cells express the transmembrane protein FLRT3. Genetic ablation of FLRT3 did not affect the signaling functions of the AVE according to the normal expression pattern of Nodal and Wnt and the establishment of a proper AP patterning in the epiblast. However, FLRT3^−/− embryos showed a highly disorganized basement membrane (BM) in the AVE region. Subsequently, adjacent anterior epiblast cells displayed an epithelial-to-mesenchymal transition (EMT)-like process characterized by the loss of cell polarity, cell ingression, and the up-regulation of the EMT and the mesodermal marker genes Eomes, Brachyury/T, and FGF8. These results suggest that the AVE acts as a morphogenetic boundary to prevent EMT and mesoderm induction in the anterior epiblast by maintaining the integrity of the BM. We propose that this novel function cooperates with the signaling activities of the AVE to restrict EMT and mesoderm induction to the posterior epiblast.     

Laser‐mediated cell ablation during post‐implantation mouse development

BACKGROUND: Laser‐mediated cell ablation is a powerful tool that has been used to understand cell fate in a variety of externally developing organisms but has not been used during mammalian post‐implantation development. RESULTS: We describe a method pairing laser ablation with murine embryo culture and establish parameters that can be used to precisely ablate cells in the selected field with minimal disruption to adjacent cells or the underlying cell matrix. Ablation of a large domain of endoderm, followed by ～1 day of culture results in a phenotypically normal embryo and gut tube, indicating that laser ablation is compatible with normal development. We next focused on one of the three precursor populations that have been shown to produce the liver bud. Ablations of a single progenitor domain result in a unilateral delay in the liver bud while the contralateral side is unaffected. CONCLUSIONS: We demonstrate that laser ablation is a specific and useful technique for studying cell fate in the mouse embryo. This method represents a powerful advance in developmental studies in the mouse and can be used to provide information on the specification of organs, differentiation, cell migration, and vital tissue interactions during development. Developmental Dynamics, 242:1202–1209, 2013. © 2013 Wiley Periodicals, Inc.     

Radiation therapy in cholangiocellular carcinomas

Cholangiocarcinoma can arise in all parts of the biliary tract and this has implications for therapy. Surgery is the mainstay of therapy however local relapse is a major problem. Therefore, adjuvant treatment with chemoradiotherapy was tested in trials. The SWOG-S0809 trial regimen of chemoradiotherapy which was tested in extrahepatic cholangiocarcinoma and in gallbladder cancer can currently be regarded as highest level of evidence for this indication. In contrast to adjuvant therapy where only conventionally fractionated radiotherapy plays a role, stereotactic body radiotherapy (SBRT) today has become a powerful alternative to chemoradiotherapy for definitive treatment due to the ability to administer higher doses of radiotherapy to improve local control. Sequential combinations with chemotherapy are also frequently employed. Nevertheless, in general cholangiocarcinoma is an orphan disease and future clinical trials will have to improve the available level of evidence.     

Lack of definitive presurgical pathological diagnosis is associated with inadequate surgical margins in breast-conserving surgery

PurposeTo determine the impact of definitive presurgical diagnosis on surgical margins in breast-conserving surgery (BCS) for primary carcinomas; clinicopathological features were also analyzed.MethodsThis retrospective study included women who underwent BCS for primary carcinomas in 2016 and 2017. Definitive presurgical diagnosis was defined as having a presurgical core needle biopsy (CNB) and not being upstaged between biopsy and surgery. Biopsy data and imaging findings including breast density were retrieved. Inadequate surgical margins (IM) were defined per latest ASCO and ASTRO guidelines. Univariable and multivariable analyses were performed.Results360 women (median age, 66) met inclusion criteria with 1 having 2 cancers. 82.5% (298/361) were invasive cancers while 17.5% (63/361) were ductal carcinoma in situ (DCIS). Most biopsies were US-guided (284/346, 82.0%), followed by mammographic (60/346, 17.3%), and MRI-guided (2/346, 0.6%). US and mammographic CNB yielded median samples of 2 and 4, respectively, with a 14G needle. 15 patients (4.2%) lacked presurgical CNB. The IM rate was 30.0%. In multivariable analysis, large invasive cancers (>20 mm), dense breasts, and DCIS were associated with IM (p = 0.029, p = 0.010, and p = 0.013, respectively). Most importantly, lack of definitive presurgical diagnosis was a risk factor for IM (OR, 2.35; 95% CI: 1.23–4.51, p = 0.010). In contrast, neither patient age (<50) nor aggressive features (e.g., LVI) were associated with IM.ConclusionLack of a definitive presurgical diagnosis was associated with a two-fold increase of IM in BCS; other risk factors were dense breasts, large invasive cancers, and DCIS.