Interdisciplinary Surgical Approaches in Vaginal and Perineal Reconstruction of Advanced Rectal and Anal Female Cancer Patients

Relapsing or far advanced rectal and anal cancers remain difficult to treat and require interdisciplinary approaches. Due to modern standard protocols all patients receive irradiation and neoadjuvant chemotherapy—and in case of a relapse a second irradiation—rendering the surgical site prone to surgical site infections and oftentimes long lasting sinus and septic complications after exenteration in the pelvis. Despite an improved overall survival rate in these patients the downside of radical tumor surgery in the pelvis is a major loss of quality of life, especially in women when parts of the vagina need to be resected. Derived from our experince with over 300 patients receiving pelvic and perineal reconstruciton with a transpelvic vertical rectus abdominis myocutaneous (tpVRAM) flap we studied the impact of this surgical technique on the outcomes of female patients with or without vaginal reconstruction following pelvic exenteration. We found out that the tpVRAM flap is reliably perfused and helps to reduce long term wound healing desasters in the irradiated perineal/vaginal/gluteal region

Retrospective analysis of free temporoparietal fascial flap for defect reconstruction of the hand and the distal upper extremity

Introduction: Soft tissue reconstruction of the hand and distal upper extremity is challenging to preserve the function of the hand as good as possible. Therefore, a thin flap has been shown to be useful. In this retrospective study, we aimed to show the use of the free temporoparietal fascial flap in soft tissue reconstruction of the hand and distal upper extremity. Methods We analysed the outcome of free temporoparietal fascial flaps that were used between the years 2007and 2016 at our institution. Major and minor complications, defect location and donor site morbidity were the main fields of interest. Results: 14 patients received a free temporoparietal fascial flap for soft tissue reconstruction of the distal upper extremity. Minor complications were noted in three patients and major complications in two patients. Total flap necrosis occurred in one patient. Conclusion The free temporoparietal fascial flap is a useful tool in reconstructive surgery of the hand and the distal upper extremity with a low donor site morbidity and moderate rates of major and minor complications

Does indocyanine green fluorescence angiography impact the intraoperative choice of procedure in free vascularized medial femoral condyle grafting for scaphoid nonunions?

BackgroundFree vascularized medial femoral condyle (MFC) bone grafts can lead to increased vascularity of the proximal pole and restore scaphoid architecture in scaphoid nonunions. The intraoperative perfusion assessment of the bone graft is challenging because the conventional clinical examination is difficult. Indocyanine green (ICG) angiography has previously been shown to provide a real-time intraoperative evaluation of soft tissue perfusion in reconstructive surgery. The present study investigated the utility of ICG angiography in patients treated with a free medial femoral condyle graft for scaphoid nonunions.MethodsWe performed a retrospective analysis of patients with scaphoid nonunions, in which ICG angiography was used intraoperatively for perfusion assessment. The medical records, radiographs, intraoperative imaging, and operative reports of all patients were reviewed. Intraoperative ICG dye was administered intravenously, and laser angiography was performed to assess bone perfusion. The scaphoid union was examined using postoperative CT scans.ResultsTwo patients had documented osteonecrosis of the proximal pole at the time of surgery. Four patients received a nonvascularized prior bone graft procedure, and a prior spongiosa graft procedure was performed in one patient. The mean time from injury to the MFC bone graft surgery was 52.7 months, and the mean time from prior failed surgery was 10.4 months. Perfusion of the vascular pedicle of the MFC and the periosteum could be detected in all patients. In two patients, even perfusion of the cancellous bone could be demonstrated by ICG angiography. Following transplantation of the bone graft, patency of the vascular anastomosis and perfusion of the periost were confirmed by ICG angiography in the assessed cases. No additional surgery regarding a salvage procedure for a scaphoid nonunion advanced collapse was necessary for the further course.ConclusionICG-angiography has shown to be a promising tool in the treatment of scaphoid nonunion with medial femoral condyle bone grafts. It enables intraoperative decision making by assessment of the microvascular blood supply of the periosteum and the vascular pedicle of the MFC bone graft. Further studies need to evaluate the impact on union rates in a long-term follow-up

Engrailed 1 coordinates cytoskeletal reorganization to induce myofibroblast differentiation

Transforming growth factor-β (TGFβ) is a key mediator of fibroblast activation in fibrotic diseases, including systemic sclerosis. Here we show that Engrailed 1 (EN1) is reexpressed in multiple fibroblast subpopulations in the skin of SSc patients. We characterize EN1 as a molecular amplifier of TGFβ signaling in myofibroblast differentiation: TGFβ induces EN1 expression in a SMAD3-dependent manner, and in turn, EN1 mediates the profibrotic effects of TGFβ. RNA sequencing demonstrates that EN1 induces a profibrotic gene expression profile functionally related to cytoskeleton organization and ROCK activation. EN1 regulates gene expression by modulating the activity of SP1 and other SP transcription factors, as confirmed by ChIP-seq experiments for EN1 and SP1. Functional experiments confirm the coordinating role of EN1 on ROCK activity and the reorganization of cytoskeleton during myofibroblast differentiation, in both standard fibroblast culture systems and in vitro skin models. Consistently, mice with fibroblast-specific knockout of En1 demonstrate impaired fibroblast-to-myofibroblast transition and are partially protected from experimental skin fibrosis

Neurofilament as a blood marker for diagnosis and monitoring of primary progressive aphasias

Objective: To assess the utility of serum neurofilament for diagnosis and monitoring of primary progressive aphasia (PPA) variants. Methods: We investigated neurofilament light chain (NF-L) levels in blood of 99 patients with PPA (40 with nonfluent variant PPA [nfvPPA], 38 with semantic variant PPA [svPPA], 21 with logopenic variant PPA [lvPPA]) and compared diagnostic performance with that reached by CSF NF-L, phosphorylated neurofilament heavy chain (pNF-H), b-amyloid (Ab(1)-42), tau, and phosphorylated tau. The longitudinal change of blood NF-L levels was measured and analyzed for correlation with functional decline and brain atrophy. Results: Serum NF-L is increased in PPA compared to controls and discriminates between nfvPPA/svPPA and lvPPA with 81% sensitivity and 67% specificity (cutoff 31 pg/mL). CSF NF-L, pNF-H, tau, phosphorylated tau, and Ab1-42 achieved similar performance, and pNF-H was the only marker for discrimination of nfvPPA from svPPA/lvPPA. In most patients with nfvPPA and svPPA, but not lvPPA, serum NF-L increased within follow-up. The increase correlated with functional decline and progression of atrophy of the left frontal lobe of all patients with PPAs and the right middle frontal gyrus of patients with nfvPPA and svPPA. Conclusions: Blood level of NF-L can aid the differential diagnosis of PPA variants, especially in combination with CSF pNF-H. Because serum NF-L correlates with functional decline and atrophy in the disease course, it qualifies as an objective disease status marker. Extended follow-up studies with cases of known neuropathology are imperative

Serum neurofilament light chain in behavioral variant frontotemporal dementia

Objective To determine the association of serum neurofilament light chain (NfL) with functional deterioration and brain atrophy during follow-up of patients with behavioral variant frontotemporal dementia (bvFTD). Methods Blood NfL levels from 74 patients with bvFTD, 26 with Alzheimer disease (AD), 17 with mild cognitive impairment (MCI), and 15 healthy controls (Con) at baseline and follow-up were determined and analyzed for the diagnostic potential in relation to functional assessment (Clinical Dementia Rating Scale Sum of Boxes [CDR-SOB], frontotemporal lobar degeneration-related CDR-SOB, Mini-Mental State Examination [MMSE]) and brain volumetry. Results At baseline, serum NfL level correlated with CSFNfL (bvFTD r = 0.706, p < 0.0001;AD/MCI r = 0.666, p = 0.0003). Highest serum levels were observed in bvFTD (p < 0 0.0001 vs Con and MCI, p = 0.0078 vs AD, respectively). Discrimination of bvFTD from Con/MCI/AD was possible with 91%/74%/74% sensitivity and 79%/74%/58% specificity. At follow-up, serum NfL increased in bvFTD and AD (p = 0.0039 and p = 0.0006, respectively). At baseline and follow-up, NfL correlated with functional scores of patients with bvFTD (e.g., CDR-SOB [baseline] r = 0.4157, p = 0.0006;[follow-up] r = 0.5629, p < 0.0001) and with atrophy in the gray and white matter of many brain regions including frontal and subcortical areas (e.g., frontal lobe: r = -0.5857, p < 0.0001;95% confidence interval -0.7415 to -0.3701). For patients with AD/MCI, NfL correlated with the functional performance as well (e.g., CDR-SOB [baseline] r = 0.6624, p < 0.0001;[follow-up] r = 0.5659, p = 0.0003) but not with regional brain volumes. Conclusions As serum NfL correlates with functional impairment and brain atrophy in bvFTD at different disease stages, we propose it as marker of disease severity, paving the way for its future use as outcome measure for clinical trials. Classification of evidence This study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia