Pre- and postoperative prognostic factors for resectable esophageal adenocarcinoma

Background: Prognostication for esophageal cancer has traditionally relied on postoperative tissue specimens. This study aimed to use a histologically homogenous cohort to investigate the relationship between clinical, pathological or radiological variables and overall survival in patients undergoing esophagectomy for adenocarcinoma. Methods: A single-centre study of patients who underwent esophagectomy for adenocarcinoma over 10 years in a tertiary centre was performed. By regression analysis, variables available preoperatively and postoperatively were studied for prognostication. The primary outcome was overall survival. Results: 254 cases were analyzed. Over a median follow-up period of 31.8 months (IQR = 42.5), overall survival was 51.5 months (95% confidence interval: 33.0–69.9). According to hazard ratios (HR) for all-cause death, adverse prognostic factors included: a higher postoperative N-stage (HR ≥ 1.29; p ≤ 0.024), histopathological tumor length ≥25 mm (HR = 2.04; p = 0.03), poorer tumor differentiation (HR ≥ 2.86; p ≤ 0.042), and R1 status (HR = 2.33; p = 0.02). A lymph node yield ≥35 was a favorable prognostic factor (HR = 0.022; p < 0.001). Demographic and radiological variables, preoperative TNM stages, postoperative T-stage, and neoadjuvant/adjuvant treatment were not associated with overall survival. Conclusions: This study identifies several postoperatively factors which are available for the prognostication and identifies factors that should not be used to exclude patients from curative surgery

Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.

Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.Funding for the project was provided by the Wellcome Trust for UK10K (WT091310) and DDD Study. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund [grant number HICF-1009-003] - see www.ddduk.org/access.html for full acknowledgement. This work was supported in part by the Intramural Research Program of the National Human Genome Research Institute and the Common Fund, NIH Office of the Director. This work was supported in part by the German Ministry of Research and Education (grant nos. 01GS08160 and 01GS08167; German Mental Retardation Network) as part of the National Genome Research Network to A.R. and D.W. and by the Deutsche Forschungsgemeinschaft (AB393/2-2) to A.R. Brain expression data was provided by the UK Human Brain Expression Consortium (UKBEC), which comprises John A. Hardy, Mina Ryten, Michael Weale, Daniah Trabzuni, Adaikalavan Ramasamy, Colin Smith and Robert Walker, affiliated with UCL Institute of Neurology (J.H., M.R., D.T.), King’s College London (M.R., M.W., A.R.) and the University of Edinburgh (C.S., R.W.)

Radio-frequency identification (RFID) tag localisation of non-palpable breast lesions a single centre experience

Aim: The purpose of this study is to report the surgical experience and outcomes with pre-operative localisation of non-palpable breast lesions using the RFID tag system. Methods: The cohort for this prospective study included patients over the age of 18 with biopsy proven, non-palpable indeterminate lesions, DCIS or breast cancer requiring pre-operative localisation before surgical excision between September 2020 and July 2022. Results: A total of 312 RFID tags were placed in 299 consecutive patients. Indications for localisation included non-palpable invasive cancer in 255 (85.3%) patients, in situ disease in 38 (12.7%) and indeterminate lesions requiring surgical excision in 6 (2.0%). Both in situ and invasive lesions had a median size of 13 mm (range 4–100 mm) on pre-operative imaging. The RFID tags were in situ for a median time of 21 days before surgery (range 0–233 days). Of the 213 tags, 292 (93.6%) were introduced using ultrasound (USS) guidance and stereotactically in 20 (6.4%). In 3 (1.0%) cases the RFID tag was either not satisfactorily deployed at the intended target or retrieved intra-operatively. Following discussion of post-operative histology by the multi-disciplinary team, further surgery for close or involved margins was for 26 (8.7%) patients. Conclusion: The Hologic RFID tag system can be used for accurate pre-operative localisation of non-palpable masses as well as diffuse abnormalities such as mammographic distortions and calcifications. It has advantages of flexibility for scheduling image-guided insertion independently of scheduled operating lists and can be placed to localise lesions prior to initiating neoadjuvant systemic treatment

The Extended Chest Wall Perforator Flap: Expanding the Indication for Partial Breast Reconstruction

Background:. The intercostal artery perforator flap has traditionally been used to reconstruct small or moderate-sized single defects in the lateral or lower medial breast during breast-conserving surgery. We report a modification of the intercostal artery perforator flap that allows for reconstruction of larger breast tumors than previously described flap designs. Methods:. A retrospective study of breast cancer patients undergoing breast-conserving surgery and immediate partial breast reconstruction with an extended chest wall perforator flap. Primary outcomes were successful tumor excision, adequate radial margins, postoperative complications, and delays to adjuvant radiotherapy. Results:. Thirty patients were included. Mean radiological tumor size was 27 mm (11–56 mm) and excision volume, 123 cm3 (18–255 cm3). All tumors had satisfactory excision margins, and no patient required further surgery for re-excision. In the early postoperative period, one patient required radiological drainage of seroma, and one returned to theater for debridement of fat necrosis affecting the flap. Ten other patients were managed on an outpatient basis for minor wound complications. All patients were followed up annually for 5 years. No patients had a delay to adjuvant treatment or required revisional procedures for cosmesis. Conclusions:. The modified chest wall perforator flap allows for breast conservation for larger tumors from all quadrants of the breast, including centrally located tumors and reconstruction of the axillary defect following lymph node clearance. The length of the flap allows for the use of multiple perforators in the pedicle area and freedom of the flap to reach the defects. This can be performed with low morbidity and no delay to adjuvant radiotherapy