Latissimus dorsi seroma prevention with running quilting suture using barbed suture.

Dorsal seroma is a common complication of autologous latissimus dorsi flap (ALDF) in breast reconstruction, and has limited the use of this technique, despite its aesthetic success. It is important to find a right technique to limit the incidence of seroma formation after ALDF. The aim of this study was to evaluate the effectiveness and tolerance of a dorsal quilting technique called "running quilting" using barbed resorbable suture in seroma prevention. Three hundred patients who underwent ALDF breast reconstruction in the period between 2004 and 2014 were included in this study. The population was divided in 3 groups; without quilting, with simple quilting suture, and with running quilting using barbed suture. The incidence of small seromas (requiring 1 or 2 aspirations during routine postoperative visits without adding additional appointments to the follow-up routine) was not significantly decreased: it was 54% in the non-quilted group, 47% in group 2 Quilting, and 34% in group 3 running quilting. However, quilting reduced the duration of drainage, and the rate of late seromas (from 8% to 0%), and chronic sero-hematomas completely disappeared in our experience. Running quilting using barbed suture is highly effective in preventing late and refractory donor-site seromas. Its effectiveness is expected to increase the use of ALDF in breast reconstruction, which we consider currently as one of the best autologous reconstruction techniques.

[Breast restoration by the lipomodeling technique after breast sequelae following complications of reduction mammoplasty]. / Rattrapage des séquelles esthétiques de réduction mammaire par la technique du lipomodelage.

BACKGROUND: Complications of reduction mammoplasty can lead to aesthetic sequelae, which are known to be difficult and delicate to treat, and only a few articles deal with this subject. PURPOSE: The objective of this article is to present and analyze our experience of lipomodeling for the secondary management of aesthetic sequelae occurring after a complication of reduction mammoplasty. MATERIAL AND METHODS: An uniform and consecutive series of 22 female patients, operated with the lipomodeling technique from December 2003 to March 2019 by the last author, to correct aesthetic sequelae after secondary complications of reduction mammoplasty was studied analyzing the efficiency and the tolerance of this technique. RESULTS: The results showed 86.4% of very good results and 13.6% of good results. Seventeen patients (77.3%) were highly satisfied with the postoperative outcome, and 5 patients were satisfied (22.7%). The number of procedures varied from 1 to 3: 15 patients (68.2%) underwent only one session of lipomodeling, 5 patients (22.7%) underwent two sessions, and 2 patients (9.1%) underwent three sessions. The mean time between two interventions was 4 months (3-12). No patient of this series initiates any medico-legal proceeding towards the first surgeon. CONCLUSION: After this study, lipomodeling, in association with ancillary procedures, seems to be an effective and safe solution to correct aesthetic sequelae following secondary complications of reduction mammoplasty. It should have a key role for the correction of these sequelae. An effective and appropriate care of these patients leads to good results and patients' final satisfaction, and manages to avoid any medico-legal proceeding, always badly lived as much for the patient as for the first surgeon.

Titanium plates salvage in irradiated facial areas with the lipomodeling technique.

Major defects of the facial structures cause severe functional and aesthetic impairment. For composite defects with bone loss, the use of a titanium plate bridging the bony defect, associated or not to a soft tissue pedicled flap is to be considered in complex cases, or for patients with high comorbidities. The principal limit of this technique is the risk of plate exposure, especially for patients who had adjuvant radiation therapy. We present two clinical cases of patients who had a facial reconstruction using a titanium plate associated with a locoregional soft tissue flap, and who presented a near-exposed plate a few years after the first surgery and adjuvant radiation therapy. In order to prevent plate exposure, we performed several lipomodeling sessions between skin and plate. Our results are very encouraging, with no plate exposure and thickening of the soft tissues which cover the plate at 10-years follow-up. The knowledge of the possibility to use fat grafting transfer could therefore lead to a strong return to the use of titanium plates in facial reconstruction.

A novel LKB1 isoform enhances AMPK metabolic activity and displays oncogenic properties.

The LKB1 tumor suppressor gene encodes a master kinase that coordinates the regulation of energetic metabolism and cell polarity. We now report the identification of a novel isoform of LKB1 (named ΔN-LKB1) that is generated through alternative transcription and internal initiation of translation of the LKB1 mRNA. The ΔN-LKB1 protein lacks the N-terminal region and a portion of the kinase domain. Although ΔN-LKB1 is catalytically inactive, it potentiates the stimulating effect of LKB1 on the AMP-activated protein kinase (AMPK) metabolic sensor through a direct interaction with the regulatory autoinhibitory domain of AMPK. In contrast, ΔN-LKB1 negatively interferes with the LKB1 polarizing activity. Finally, combining in vitro and in vivo approaches, we showed that ΔN-LKB1 has an intrinsic oncogenic property. ΔN-LKB1 is expressed solely in the lung cancer cell line, NCI-H460. Silencing of ΔN-LKB1 decreased the survival of NCI-H460 cells and inhibited their tumorigenicity when engrafted in nude mice. In conclusion, we have identified a novel LKB1 isoform that enhances the LKB1-controlled AMPK metabolic activity but inhibits LKB1-induced polarizing activity. Both the LKB1 tumor suppressor gene and the oncogene ΔN-LKB1 are expressed from the same locus and this may account for some of the paradoxical effects of LKB1 during tumorigenesis.

Molecular chaperone complexes with antagonizing activities regulate stability and activity of the tumor suppressor LKB1.

LKB1 is a tumor suppressor that is constitutionally mutated in a cancer-prone condition, called Peutz-Jeghers syndrome, as well as somatically inactivated in a sizeable fraction of lung and cervical neoplasms. The LKB1 gene encodes a serine/threonine kinase that associates with the pseudokinase STRAD (STE-20-related pseudokinase) and the scaffolding protein MO25, the formation of this heterotrimeric complex promotes allosteric activation of LKB1. We have previously reported that the molecular chaperone heat shock protein 90 (Hsp90) binds to and stabilizes LKB1. Combining pharmacological studies and RNA interference approaches, we now provide evidence that the co-chaperone Cdc37 participates to the regulation of LKB1 stability. It is known that the Hsp90-Cdc37 complex recognizes a surface within the N-terminal catalytic lobe of client protein kinases. In agreement with this finding, we found that the chaperones Hsp90 and Cdc37 interact with an LKB1 isoform that differs in the C-terminal region, but not with a novel LKB1 variant that lacks a portion of the kinase N-terminal lobe domain. Reconstitution of the two complexes LKB1-STRAD and LKB1-Hsp90-Cdc37 with recombinant proteins revealed that the former is catalytically active whereas the latter is inactive. Furthermore, consistent with a documented repressor function of Hsp90, LKB1 kinase activity was transiently stimulated upon dissociation of Hsp90. Finally, disruption of the LKB1-Hsp90 complex favors the recruitment of both Hsp/Hsc70 and the U-box dependent E3 ubiquitin ligase CHIP (carboxyl terminus of Hsc70-interacting protein) that triggers LKB1 degradation. Taken together, our results establish that the Hsp90-Cdc37 complex controls both the stability and activity of the LKB1 kinase. This study further shows that two chaperone complexes with antagonizing activities, Hsp90-Cdc37 and Hsp/Hsc70-CHIP, finely control the cellular level of LKB1 protein.