Citations

Vascularized lymph node (VLN) transfer has been of high interest in the past decade for the treatment of lymphedema, since it has been shown to be effective in reducing limb volumes, decreasing infectious episodes and improving quality of life. Multiple donor sites have been described in the quest for the optimal one. Herein, we describe a novel lymph node flap option based on the ileocolic artery and vein. The ileocecal vascularized lymph node (IC‐VLN) flap was used in the management of a 33‐year‐old male patient with lower extremity lymphedema secondary to left inguinal trauma. The patient had previously underwent a pedicled omentum flap transposition with minimal improvement in limb size and persistent episodes of infection. At 15 month follow‐up, the IC‐VLN flap improved the lymphatic drainage in the affected limb with a mean limb circumference reduction rate of 26.3%. No donor site complications or further episodes of infection were noted. According to our findings, the IC‐VLN flap may be another option for VLN transfer in very selected cases. Nevertheless, larger series with a longer follow‐up are required to analyze the efficacy and long‐term results of this flap.

ObjectiveDegeneration of oligodendroglial distal processes has been identified as an early event in multiple sclerosis (MS) lesion development. Our objective was to further define the development of the “dying‐back” oligodendrocyte lesion in situ and to model the development and potential reversibility of such responses using dissociated cultures of adult human brain‐derived oligodendrocytes.MethodsIn situ analyses were performed on glutaraldehyde‐fixed thin sections of clinically acute and pathologically active cases of MS. In vitro studies were conducted using adult human brain‐derived oligodendrocytes challenged by metabolic stress conditions (low nutrient/glucose).ResultsIn situ analyses indicated a spectrum of myelin changes in the presence of morphologically intact oligodendrocytes; these included degeneration of the inner cytoplasmic tongue with increasing sizes of intramyelinic bleb formation that could result in radial fractures of the myelin sheath. Macrophages with ingested myelin fragments were identified only once the fragmentation was established. In vitro studies indicated that oligodendrocyte process retraction, which was linked to reduced glycolytic respiratory activity, is reversible until a critical time point. Subsequent cell death was not linked to caspase‐3–dependent programs. Gene expression studies conducted at the latest reversible time point revealed reduced expression of pathways associated with cell process outgrowth and myelination, as well as with metabolic activity.InterpretationOur findings reveal the potential to protect and possibly restore myelin elaborated by existent oligodendrocytes in early and evolving MS lesions, and suggest the necessity of ongoing studies of the mechanisms underlying subsequent adult human oligodendrocyte cell death. Ann Neurol 2017;81:811–824

AbstractBackgroundVascularized lymph node (VLN) transfer for lymphedema treatment has shown promising results. Optimal donor and recipient sites remain a matter of debate. We describe the technique and outcomes of a laparoscopically harvested extended gastroepiploic VLN flap with two levels of inset.Patients and MethodsBetween 2014 and 2015, four‐patients with upper limb breast cancer‐related lymphedema and three‐patients with lower limb pelvic cancer‐related lymphedema who underwent VLN transfers were included. After harvest, the gastroepiploic VLN flap was divided into two halves that were separately inset at the level of elbow and wrist (upper limb) or knee and ankle (lower limb). The mean patient age was 53.1 years (range, 42–65 years).ResultsThe average flap size after division was 6.3 cm in length (range, 5–7 cm) and 3.4 cm in width (range, 3–4 cm). The mean pedicle length was 3.2 cm (range, 2.5–4 cm). All flaps survived completely. No donor or recepient site complication was noted. At a mean follow‐up of 9.7 months (range, 8–11 months), the mean circumference reduction rate was 43.7 ± 2.5% along the entire limb (P < 0.05). No episode of infection was noted postoperatively.ConclusionsDouble gastroepiploic VLN transfers to middle and distal limb are a safe approach with very promising results. This technique may be used to improve clinical outcomes by enhancing the lymphatic drainage of the entire affected limb in a uniform fashion. In addition, the laparoscopic harvest can provide decreased donor site morbidity with a faster recovery.

NAD + can influence DNA repair by modulating protein interactions.

AbstractVascularized lymph node transfer has demonstrated promising results for the treatment of extremity lymphedema. In an attempt to find the ideal donor site, several vascularized lymph nodes have been described. Each has a common goal of decreasing morbidity and avoiding iatrogenic lymphedema while obtaining good clinical results. Herein, we present the preliminary clinical outcomes of an intra‐abdominal lymph node flap option based on the appendicular artery and vein used for the treatment of extremity lymphedema. A 62 year‐old woman with moderate lower extremity lymphedema, on chronic antibiotics because of recurrent infections and unsatisfactory outcomes after conservative treatment underwent a vascularized appendicular lymph node (VALN) transfer. At a follow‐up of 6 months, the reduction rate of the limb circumference was 17.4%, 15.1%, 12.0% and 9% above the knee, below the knee, above the ankle and foot respectively. In addition, no further episodes of infection or other complications were reported after VALN transfer. Postoperative lymphoscintigraphy demonstrated that the VALN flap was able to improve the lymphatic drainage of the affected limb. According to our findings, the use of VALN transfer minimizes donor‐site morbidity, avoids iatrogenic lymphedema and may provide a strong clearance of infection because of the strong immunologic properties of the appendiceal lymphatic tissue in selected patients. Despite these promising results, further research with larger number of patients and longer follow‐ up is needed.

SummaryThe randomized, double‐blind, double‐dummy, phase 3b RELIEF trial evaluated polycythaemia vera (PV)‐related symptoms in patients who were well controlled with a stable dose of hydroxycarbamide (also termed hydroxyurea) but reported PV‐related symptoms. Patients were randomized 1:1 to ruxolitinib 10 mg BID (n = 54) or hydroxycarbamide (prerandomization dose/schedule; n = 56); crossover to ruxolitinib was permitted after Week 16. The primary endpoint, ≥50% improvement from baseline in myeloproliferative neoplasm ‐symptom assessment form total symptom score cytokine symptom cluster (TSS‐C; sum of tiredness, itching, muscle aches, night sweats, and sweats while awake) at Week 16, was achieved by 43·4% vs. 29·6% of ruxolitinib‐ and hydroxycarbamide‐treated patients, respectively (odds ratio, 1·82; 95% confidence interval, 0·82–4·04; P = 0·139). The primary endpoint was achieved by 34% of a subgroup who maintained their hydroxycarbamide dose from baseline to Weeks 13–16. In a post hoc analysis, the primary endpoint was achieved by more patients with stable screening‐to‐baseline TSS‐C scores (ratio ≤ 2) receiving ruxolitinib than hydroxycarbamide (47·4% vs. 25·0%; P = 0·0346). Ruxolitinib treatment after unblinding was associated with continued symptom score improvements. Adverse events were primarily grades 1/2 with no unexpected safety signals. Ruxolitinib was associated with a nonsignificant trend towards improved PV‐related symptoms versus hydroxycarbamide, although an unexpectedly large proportion of patients who maintained their hydroxycarbamide dose reported symptom improvement.

Abstract Background: Common cancers develop through a multistep process often including inherited susceptibility. Collaboration among multiple institutions, and funding from multiple sources, has allowed the development of an inexpensive genotyping microarray, the OncoArray. The array includes a genome-wide backbone, comprising 230,000 SNPs tagging most common genetic variants, together with dense mapping of known susceptibility regions, rare variants from sequencing experiments, pharmacogenetic markers, and cancer-related traits. Methods: The OncoArray can be genotyped using a novel technology developed by Illumina to facilitate efficient genotyping. The consortium developed standard approaches for selecting SNPs for study, for quality control of markers, and for ancestry analysis. The array was genotyped at selected sites and with prespecified replicate samples to permit evaluation of genotyping accuracy among centers and by ethnic background. Results: The OncoArray consortium genotyped 447,705 samples. A total of 494,763 SNPs passed quality control steps with a sample success rate of 97% of the samples. Participating sites performed ancestry analysis using a common set of markers and a scoring algorithm based on principal components analysis. Conclusions: Results from these analyses will enable researchers to identify new susceptibility loci, perform fine-mapping of new or known loci associated with either single or multiple cancers, assess the degree of overlap in cancer causation and pleiotropic effects of loci that have been identified for disease-specific risk, and jointly model genetic, environmental, and lifestyle-related exposures. Impact: Ongoing analyses will shed light on etiology and risk assessment for many types of cancer. Cancer Epidemiol Biomarkers Prev; 26(1); 126–35. ©2016 AACR.