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Subtotal deglovement injuries with delayed presentation give rise to the question: how to treat the mangled soft tissue to best keep the digit alive and functioning. We hereby present a case of a 59-year-old woman who was referred to our clinic 7 h after initial trauma from a peripheral hospital where an instant repositioning of a subtotal degloved skin envelop of her left middle finger had taken place with only minimal adhesion and circulation at the top of the finger left intact. On X-ray, a small avulsion fracture of her distal interphalangeal joint was visible but flexion and extension was intact at proximal interphalangeal (PIP) joint level on examination. On arrival, we saw a finger with minimal reconstituted blood circulation and livid skin. Further treatment consisted of onsite debridement and primary suturing of the involved skin, followed by leech therapy the next week, and consecutive split-skin grafting 6 weeks later to cover minor residual defects. Further clinical course was uneventful and showed good clinical and esthetic results. We hereby present the patient’s clinical outcome and review of the literature for further evidence of our treatment regime. Level of evidence: Level V, therapeutic study.

Background The component separation technique (CST) is considered an excellent technique for complex ventral hernia repair. However, postoperative infectious complications and reherniation rates are significant. Risk factor analysis for postoperative complication and reherniation has focused mostly on patient history and co-morbidity and shows equivocal results. The use of abdominal morphometrics derived from CT scans to assist in risk assessment seems promising. The aim of this study is to determine the predictability of reherniation and surgical site infections (SSI) using pre-operative CT measurements. Methods Electronic patient records were searched for patients who underwent CST between 2000 and 2013 and had a pre-operative CT scan available. Visceral fat volume (VFV), subcutaneous fat volume (SFV), loss of domain (LOD), rectus thickness and width (RT, RW), abdominal volume, hernia sac volume, total fat volume (TFV), sagittal distance (SD) and waist circumference (WC) were measured or calculated. Relevant variables were entered in multivariate regression analysis to determine their effect on reherniation and SSI as separate outcomes. Results Sixty-five patients were included. VFV (p = 0.025, OR = 1.65) was a significant predictor regarding reherniation. Hernia sac volume (p = 0.020, OR = 2.10) and SFV per 1000 cm3 (p = 0.034, OR = 0.26) were significant predictors of SSI. Conclusion Visceral fat volume, subcutaneous fat volume and hernia sac volume derived from CT scan measurements may be used to predict reherniation and SSI in patients undergoing complex ventral hernia repair using CST. These findings may aid in optimizing patient-tailored preoperative risk assessment.

Background The surgical treatment of patients with complex ventral hernias is challenging. The aim of this study was to present an international overview of expert opinions on current practice. Methods A survey questionnaire was designed to investigate preoperative risk management, surgical approach and mesh choice in patients undergoing complex hernias repair, and treatment strategies for infected meshes. Geographical location of practice, experience and annual volumes of the surgeons were compared. Results Of 408 surgeons, 234 (57.4 per cent) were practising in the USA, 116 (28.4 per cent) in Europe, and 58 (14.2 per cent) in other countries. Some 412 of 418 surgeons (98.6 per cent) performed open repair and 322 of 416 (77.4 per cent) performed laparoscopic repair. Most recommended preoperative work-up/lifestyle changes such as smoking cessation (319 of 398, 80.2 per cent) and weight loss (254 of 399, 63.7 per cent), but the consequences of these strategies varied. American surgeons and less experienced surgeons were stricter. Antibiotics were given at least 1 h before surgery by 295 of 414 respondents (71.3 per cent). Synthetic and biological meshes were used equally in contaminated primary hernia repair, whereas for recurrent hernia repair synthetic mesh was used in a clean environment and biological or no mesh in a contaminated environment. American surgeons and surgeons with less experience preferred biological mesh in contaminated environments significantly more often. Percutaneous drainage and antibiotics were the first steps recommended in treating mesh infection. In the presence of sepsis, most surgeons favoured synthetic mesh explantation and further repair with biological mesh. Conclusion There remains a paucity of good-quality evidence in dealing with these hernias, leading to variations in management. Patient optimization and issues related to mesh choice and infections require well designed prospective studies., This manuscript displays a good overview of current practice among difficult subjects in ventral hernia repair on which limited guidelines exist in two continents (Europe and USA). Based on our findings we would recommend that more attention should be paid on pre-operative optimization and specifically pre-operative diabetic control and adequate administration of antibiotic prophylaxis. Prehabilitation programs should be implemented together with patient education on the importance of risk reduction and the impact of complications. Reaching goals set to optimize patients before hernia surgery should be a quality control parameter. The use of biologic mesh in ventral hernia repair should be critically appraised. To improve adherence to guidelines and protocol decision tools, guideline training, easy ways of data sharing, feedback loops and apps may be helpful. Since there is a gap in knowledge concerning mesh infection (abscess) a standardized animal model needs to be developed to assess different treatment options and analyze different meshes for their susceptibility to infection and the ability to clear an infection. Lack of high quality evidence This survey provided a good overview of current practice among difficult subjects in ventral hernia repair on which limited guidelines exist in two continents (Europe and USA). Based on the findings, the authors recommend that more attention should be paid to preoperative optimization, specifically preoperative diabetic control and adequate antibiotic prophylaxis. Prehabilitation programmes should be implemented together with patient education on the importance of risk reduction and the impact of complications. Reaching goals set to optimize patients before hernia surgery should be a quality control parameter. The use of biological mesh in ventral hernia repair should be appraised critically. To improve adherence to guidelines and protocol decision tools, guideline training, easy ways of data-sharing, feedback loops and apps may be helpful.

Contains fulltext : 251695.pdf (Publisher’s version ) (Open Access) BACKGROUND: Vascularized lymph node transfer (VLNT) has become an increasingly popular technique for treating lymphedema. However, although many studies have been performed, its efficacy in increasing patients' quality of life (QoL) and reducing lymphedema in the affected body part has remained controversial. In the present systematic review, we summarized the evidence for VLNT for treating breast cancer-related lymphedema. METHODS: The MEDLINE, Embase, and Cochrane Central databases were searched for studies of patients with breast cancer-related lymphedema who had received VLNT. The study methods were assessed using the MINORS (methodologic index for nonrandomized studies) tool. The primary outcomes were the change in volume difference between the arms and QoL. The secondary outcomes were skin infection, complications, and discontinuation of compression garment use. RESULTS: A total of 17 studies were included for qualitative synthesis and 8 for meta-analysis. The average reduction rate between the healthy and affected arms in the studies included in the meta-analysis was 40.31%. Five studies had evaluated QoL, and all five studies had reported that QoL was significantly increased. Eight studies had evaluated skin infections, of which three had reported the annual infection rates before and after surgery. In these studies, infection rate had decreased significantly. Three studies had described usage of compression garments. When the patients were pooled, 27 of 60 were able to discontinue use of the compression garment. The donor and recipient complication rates were 12.1% and 7.3%, respectively. CONCLUSIONS: The current evidence indicates that VLNT can improve the volume differences between the arms in patients with unilateral lymphedema by ∼40%. In addition, although determined from a few studies, it is likely that VLNT has a positive effect on patients' QoL, the number of skin infections, and compression garment usage and coincided with a low complication rate.

Introduction The profunda artery perforator (PAP) flap can be an alternative to the deep inferior epigastric artery flap. However, in some cases, the PAP may not be adequate to perfuse the whole flap. In this study, we describe 3 cases in which an alternative perforator was used for PAP flap perfusion. In addition, we describe an anatomical study to explore the perforasome of the PAP and alternative perforators. Materials and methods Three cases are described in which an alternative perforator was used to successfully perfuse the pap flap. For the anatomical study, 7 PAP flaps were raised from cadavers. Ink was injected in the PAP, the gracilis perforator (GP) and the descending branch of the inferior gluteal artery perforator (DBIGA). Then, perfused area of the flap by each perforator was calculated. Results The 3 patients with alternative perforators recovered without complications, in addition, no signs of fat necrosis were observed. Concerning the anatomical study, mean perfusion area of the PAP pedicle was 204 ± 90 cm (range, 141-364 cm). The GP and the DBIGA had a perfusion area of 182 ± 42 cm (range, 123-235 cm) and 157 ± 22 cm (range, 136-192), respectively. Conclusion Although the PAP flap has considerable benefits over the more traditional inferior gluteal artery perforator and transverse upper gracilis flaps, a plastic surgeon might encounter a PAP flap perforator that is not deemed viable for flap perfusion. In these cases, the GP and DBIGA may be suitable "escape" alternatives to complete the reconstruction.

BACKGROUND: The deep inferior epigastric artery perforator (DIEP) flap is one of the most common techniques for breast reconstruction. Body mass index (BMI) is considered as an important predictor of donor site healing complications such as wound dehiscence. The use of computed tomography (CT) proved to be a precise and objective method to assess visceral adipose tissue. It remains unclear whether quantification of visceral fat provides more accurate predictions of abdominal wound healing complications than BMI.PATIENTS AND METHODS: A total of 97 patients with DIEP flap were retrospectively evaluated. Patients' abdominal visceral fat (AVF) was quantified on CT angiography (CTA). The patients were postoperatively assessed for abdominal wound healing complications. We analyzed for the correlations between AVF, BMI, and dehiscence and established a logistic regression model to assess the potential high-profile predictors in anatomic and patient characteristics such as weight, smoking, and diabetes.RESULTS: We included 97 patients, and of them, 24 patients (24.7%) had some degree of abdominal dehiscence. No significant differences were observed between the dehiscence group and the non-dehiscence group, except for smoking (p = 0.002). We found a significant correlation between AVF and BMI (R = 0.282, p = 0.005), but neither was significant in predicting donor site dehiscence. Smoking greatly increased the likelihood of developing wound dehiscence (OR = 11.4, p = CONCLUSIONS: AVF and BMI were not significant predictors of abdominal wound healing complications after DIEP flap reconstruction. This study established active smoking (OR = 11.4, p =

Contains fulltext : 181803.pdf (Publisher’s version ) (Open Access)

BACKGROUND AND OBJECTIVES Lymphedema is a condition that can greatly affect patient's quality of life. Promising results have been described with lymphaticovenular anastomosis (LVA) in the treatment of lymphedema. It is currently unknown at what rate anastomoses remain functional after a longer follow-up. The aim of this study was to determine LVA patency at 1-year follow-up. METHODS Retrospective chart review was performed on patients who underwent LVA surgery. Patients who had indocyanine green lymphography performed at 12 months' follow-up after LVA were included in this study. Volume measurements were performed prior to surgery and at 6 and 12 months' follow-up. Patients quality of life was measured prior to surgery and at 6 months' follow-up. RESULTS Twelve patients met inclusion criteria. In total, 15 (56.5%) of 23 LVAs were considered patent. In 8 patients (66.7%), at least 1 patent LVA was visible. The volume difference between the healthy and affected arms decreased 32.3% on average. Quality of life increased with 1.4 points on average. CONCLUSIONS This study is, to our knowledge, the first to evaluate long-term patency of LVA in upper limb lymphedema. Our study demonstrates that at least 56.5% of the anastomoses created are patent after 1-year follow-up.

To provide guidelines for all surgical specialists who deal with the open abdomen (OA) or the burst abdomen (BA) in adult patients both on the methods used to close the musculofascial layers of the abdominal wall, and regarding possible materials to be used. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach including publications up to January 2017. When RCTs were available, outcomes of interest were quantitatively synthesized by means of a conventional meta-analysis. When only observational studies were available, a meta-analysis of proportions was done. The guidelines were written using the AGREE II instrument. For many of the Key Questions that were researched, there were no high quality studies available. While some strong recommendations could be made according to GRADE, the guidelines also contain good practice statements and clinical expertise guidance which are distinct from recommendations that have been formally categorized using GRADE. When considering the OA, dynamic closure techniques should be prioritized over the use of static closure techniques (strong recommendation). However, for techniques including suture closure, mesh reinforcement, component separation techniques and skin grafting, only clinical expertise guidance was provided. Considering the BA, a clinical expertise guidance statement was advised for dynamic closure techniques. Additionally, a clinical expertise guidance statement concerning suture closure and a good practice statement concerning mesh reinforcement during fascial closure were proposed. The role of advanced techniques such as component separation or relaxing incisions is questioned. In addition, the role of the abdominal girdle seems limited to very selected patients.

Item does not contain fulltext OBJECTIVE: To evaluate the safety and long-term durability of 1-stage repair of enteric fistulas in the presence of an abdominal wall defect. BACKGROUND: Patients with enteric fistulas and an abdominal wall defect present an extreme challenge to surgeons and have been associated with significant morbidity and mortality. Durability of repair is unknown as studies fail to report this or use limited follow-up periods. METHODS: Chart review was done of consecutive patients who underwent 1-stage repair. Short-term outcomes included morbidity (wound and medical) and mortality. Long-term durability of repair was determined by prospective outpatient follow-up at least 3 years after surgery. RESULTS: Thirty-nine patients were included with a mean age of 61.2 years, a mean BMI of 24.4 kg/m2, and a mean abdominal wall defect size of 247.9 cm2. Component separation technique was used in 34 (87.2%) and synthetic mesh in 13 (33.3%) patients. There was 1 (2.6%) postoperative death. Twenty-four wound complications developed in 18 (46.2%) patients, including surgical-site infection in 8 (20.5%) patients. Two (5.1%) enteric fistulas recurred and were treated conservatively resulting in closure. Medical complications were seen 36 times in 23 (59%) patients. Twelve of 33 (36.4%) living patients developed a recurrent hernia after a mean follow-up of 62.7 months (range: 36-130). CONCLUSIONS: One-stage abdominal wall reconstruction with enteric fistula takedown is feasible at the cost of considerable morbidity. Our treatment strategy including component separation technique with synthetic mesh on-demand results in a durable repair in 6 to 7 of 10 patients.

Contains fulltext : 178004.pdf (Publisher’s version ) (Open Access) INTRODUCTION: Lymphedema can be a debilitating condition, causing a great decrease in a person's quality of life (QoL). Treatment with lymphaticovenular anastomosis (LVA), in which an anastomosis is created between the lymphatic and venous system, may attenuate lymphedema symptoms and reduce swelling. In this study, we share the results using LVA to treat breast cancer-related lymphedema (BCRL) at our institution. MATERIALS AND METHODS: Patients were eligible for inclusion if they suffered from unilateral BCRL, if functional lymphatics were available, if compression therapy was used for at least 6 months, and if the follow-up was 12 months at minimum. Lymph vessel functionality was assessed preoperatively using indocyanine green (ICG). During surgery, 1-3 anastomoses were created and shunt patency was confirmed using ICG. Arm volumes were measured before surgery and at 6- and 12-month follow-up. QoL was measured before surgery and at 6-month follow-up. Arm volume differences between the healthy arm and affected arm were compared between the time points. RESULTS: Twenty-nine consecutive female patients with unilateral BCRL were included. The preoperative mean difference in arm volumes was 701 +/- 435 ml (36.9%). This was reduced to 496 +/- 302 ml (24.7%) at 6-month follow-up (p = 0.00). At 12-month follow-up, the mean difference in arm volume was 467 +/- 303 ml (23.5%) (p = 0.02). The overall perceived QoL was increased from 5.8 +/- 1.1 to 7.4 +/- 0.7 (p = 0.00). The functionality score decreased from 2.2 to 1.8 (p = 0.00), the appearance score decreased from 2.6 to 1.9 (p = 0.00), the symptoms score decreased from 2.8 to 1.8 (p = 0.00), and the mood score decreased from 2.7 to 1.5 (p = 0.00). Fifteen patients (53.6%) were able to discontinue the use of compression garment. CONCLUSION: Treatment with LVAs is effective in reducing arm volume difference in patients suffering from BCRL. Although no complete reduction of the edema was achieved at 12-month follow-up, the procedure significantly increased the patients' QoL.

Despite increasing use of lateral lower leg perforator flaps, comprehensive anatomical data are still lacking. The aim of this article was to comprehensively document the pattern of usable lateral lower leg perforators. Systematic mapping of 16 cadaver leg perforators in a well-defined area was performed to elucidate location, course, length, diameter, and origin. Overall, 197 perforators were found in 16 lateral lower legs. The mean number of perforators per leg with a diameter >/= 0.3 mm was 13.4 +/- 3.6. Most perforators were found in the distal third (39.0%), followed by the middle third (32.0%), and proximal third (29.0%). A musculocutaneous course was found in 26.9% of the perforators, whereas 73.1% revealed a septocutaneous course. Most septocutaneous perforators (50.0%) were found in the distal third and most musculocutaneous perforators (58.5%) in the proximal third (P < 0.001). The majority of perforators originated from the anterior tibial artery (53.0%), followed by the peroneal artery (41.6%), and the popliteal artery (5.1%). Popliteal artery perforators (1.64 mm) were significantly larger than anterior tibial artery (0.91 mm) and peroneal artery perforators (1.02 mm; P < 0.001). These results may facilitate tissue transfer around the lateral lower leg.

Item does not contain fulltext PURPOSE: A clear definition of "complex (abdominal wall) hernia" is missing, though the term is often used. Practically all "complex hernia" literature is retrospective and lacks proper description of the population. There is need for clarification and classification to improve patient care and allow comparison of different surgical approaches. The aim of this study was to reach consensus on criteria used to define a patient with "complex" hernia. METHODS: Three consensus meetings were convened by surgeons with expertise in complex abdominal wall hernias, aimed at laying down criteria that can be used to define "complex hernia" patients, and to divide patients in severity classes. To aid discussion, literature review was performed to identify hernia classification systems, and to find evidence for patient and hernia variables that influence treatment and/or prognosis. RESULTS: Consensus was reached on 22 patient and hernia variables for "complex" hernia criteria inclusion which were grouped under four categories: "Size and location", "Contamination/soft tissue condition", "Patient history/risk factors", and "Clinical scenario". These variables were further divided in three patient severity classes ('Minor', 'Moderate', and 'Major') to provide guidance for peri-operative planning and measures, the risk of a complicated post-operative course, and the extent of financial costs associated with treatment of these hernia patients. CONCLUSION: Common criteria that can be used in defining and describing "complex" (abdominal wall) hernia patients have been identified and divided under four categories and three severity classes. Next step would be to create and validate treatment algorithms to guide the choice of surgical technique including mesh type for the various complex hernias.

Lmo2 is an oncogenic transcription factor that is frequently overexpressed in T-cell acute lymphoblastic leukemia (T-ALL), including early T-cell precursor ALL (ETP-ALL) cases with poor prognosis. Lmo2 must be recruited to DNA by binding to the hematopoietic basic helix-loop-helix factors Scl/Tal1 or Lyl1. However, it is unknown which of these factors can mediate the leukemic activity of Lmo2. To address this, we have generated Lmo2-transgenic mice lacking either Scl or Lyl1 in the thymus. We show that although Scl is dispensable for Lmo2-driven leukemia, Lyl1 is critical for all oncogenic functions of Lmo2, including upregulation of a stem cell-like gene signature, aberrant self-renewal of thymocytes, and subsequent generation of T-cell leukemia. Lyl1 expression is restricted to preleukemic and leukemic stem cell populations in this model, providing a molecular explanation for the stage-specific expression of the Lmo2-induced gene expression program. Moreover, LMO2 and LYL1 are coexpressed in ETP-ALL patient samples, and LYL1 is required for growth of ETP-ALL cell lines. Thus, the LMO2-LYL1 interaction is a promising therapeutic target for inhibiting self-renewing cancer stem cells in T-ALL, including poor-prognosis ETP-ALL cases.

Contains fulltext : 172527.pdf (Publisher’s version ) (Open Access) A 23-year-old male student presented to our clinic with a traumatic complex ring avulsion of his right dominant index finger. Clinical evaluation revealed a complete distal amputation of the DIP joint with a laceration of the soft tissue at the middle phalanx and a rupture of the FDP-2-tendon far proximally. We hereby present the patient's clinical outcome after reconstruction with a distally based extended DMCA-II flap. To our own knowledge, this is the first report of an extended distally based DMCA flap for coverage of a class IVd ring avulsion injury in combination with autologous amputate skin transplantation. LEVEL OF EVIDENCE: Level V, therapeutic study.

Item does not contain fulltext BACKGROUND: Under ideal circumstances, creation of the anastomosis during free flap transfer is a routine task and can be performed under short ischemia time. However, vessels may be in suboptimal state due to atherosclerosis, radiotherapy or trauma, increasing difficulties regarding receptor vessel identification, and anastomosis which in turn may lead to lengthening of ischemia time resulting in postoperative wound problems or even flap loss. In the current pilot study, a modified heart-lung machine was assembled to achieve continuous oxygenated extracoporeal perfusion using porcine myocutaneous rectus abdominis flaps, aimed at minimizing tissue damage occurring during ischemia time. MATERIALS AND METHODS: Different pilot test groups with n = 2 were created, including oxygenated perfusion with heparinized autologous blood or organ preservation solutions. Control groups included short flush with preservation solution followed by cold storage. RESULTS: Flaps were successfully attached to the modified heart-lung machine while maintaining stable flow throughout the 24-h experiments. Flaps undergoing continuous oxygenated perfusion with preservation solutions showed minimal or no signs of cell necrosis during the 24-h experiment, in contrast to using heparinized autologous blood or flushing and cold storage. CONCLUSIONS: The use of a modified heart-lung machine for oxygenated perfusion of free flaps provides new possibilities to minimize tissue damage during ischemia time, and further study of its use is warranted.

Item does not contain fulltext BACKGROUND AND AIM: Coverage of soft-tissue defects of the knee due to multiple operations, trauma, and infection remains a surgical challenge. Often, these defects are repaired using free tissue transfer. The aim of this study was to find an easy and reliable local method of repair for small to medium-sized defects. The authors describe a new surgical option for tissue coverage using a proximally based long peroneal muscle turnover flap (LPTF) with split-thickness skin graft. METHODS: Proximally based LPTFs were harvested and transposed into same-size created defects in five cadavers. After optimizing this technique, it was clinically used in two patients with defects secondary to total knee replacement revisions. RESULTS: Average cadaver flap size was 4.7 x 15.8 cm allowing reach of all knee joint areas and was based consistently on a sufficient (2-mm-diameter average) proximal arterial branch of the anterior tibial artery. Donor sites were closed without tension. Subsequent application of the flap on two patients resulted in good functional outcome. CONCLUSION: The proximally based LPTF is a new option available in the reconstruction of knee defects and should be added to the reconstructive surgeon's armamentarium of pedicled flaps, providing short operating time and promising clinical outcome.

Item does not contain fulltext BACKGROUND: Occasionally, the deep inferior epigastric perforator flap is unavailable for autologous breast reconstruction. Alternative options, such as gluteal artery perforator flaps, the transverse upper gracilis flap, and the profunda artery perforator (PAP) flap, have been well documented. In our initial experience, the PAP flap was associated with limitations at the donor site. Therefore, a geometrically modified PAP flap was evaluated. METHODS: Forty geometrically modified PAP flap reconstructions were performed on 30 patients. Our modification comprised flap harvest from a more cranial area, hereby adding abundant inferior gluteal tissue to the flap while sparing superior thigh tissue. Patient characteristics, anatomical variables, and clinical outcome were prospectively evaluated. RESULTS: Mean patient age was 44 years, and mean body mass index (BMI) was 23.3 kg/m. Mean flap size was 32 x 12 cm, and mean weight was 385 g. Mean number of suitable perforators (diameter >/= 0.5 mm) in the adductor magnus area was 1.7 per thigh. All flaps survived completely. Wound dehiscence at the donor site occurred after 4 unilateral reconstructions. Transient lymphedema of the leg occurred after 4 other unilateral reconstructions. Other wound morbidity or systemic complications did not occur. Secondary breast surgery for symmetry and volume was indicated after 16 reconstructions. Preoperative bra size was unchanged or larger in 36 reconstructions. Scar position in the crease was achieved after 39 reconstructions. Sensibility changes of the posteromedial thigh region were not observed. CONCLUSIONS: The geometrically modified PAP flap ensures in-the-crease scar positioning and provides sufficient tissue to restore preoperative bra size.

The prevention and treatment of wound dehiscence and incisional hernia is a constant challenge to surgeons and other specialists operating in the abdomen. This paper discusses the risk factors and proposed mechanisms of pathophysiology of wound dehiscence and incisional hernia, followed by a discussion of the evidence regarding the best surgical technique of incision and closure of the abdomen in open surgery with focus on prevention of dehiscence and hernia. Lastly, the principles of management when faced with wound dehiscence and incisional hernia are addressed along with the treatment algorithm used at our institution. The focus of this paper is on median incisions and ventral median incisional hernia repair, being most common and extensively studied in the literature.

Item does not contain fulltext BACKGROUND: Large ventral hernia repair represents a major reconstructive surgical challenge, especially under contaminated conditions. Synthetic mesh is usually avoided in these circumstances because of fear of mesh infection, although evidence is outdated and does not regard new materials and techniques. The authors evaluated the safety of synthetic mesh in large contaminated ventral hernia repair. METHODS: All large ventral hernias repaired with the components separation technique and polypropylene mesh were included in analysis. Primary outcomes were wound and medical complications, with a focus on surgical-site infection and mesh removal. For risk analysis, patients were stratified by surgical wound class, Ventral Hernia Working Group grade, and modified Ventral Hernia Working Group grade. RESULTS: One hundred thirty-seven patients were included, with a mean age of 58.6 years, mean body mass index of 26.6 cm, and mean defect size of 235.6 cm. Surgical-site infection and total wound complication rates were 16.1 and 48.9 percent, respectively. The surgical wound class distribution of surgical-site infections was as follows: clean, five of 56 (9.1 percent); clean-contaminated, five of 34 (14.7 percent); contaminated, three of 19 (15.8 percent); and dirty/infected, nine of 28 (32.1 percent). Seven meshes (5.1 percent) needed removal, two after clean repairs, three after clean-contaminated repairs, and two after dirty/infected repairs. Surgical wound class (OR, 1.77; 95 percent CI, 1.20 to 2.61) and Ventral Hernia Working Group grade (OR, 2.31; 95 percent CI, 1.24 to 4.28) were predictors of surgical-site infection. CONCLUSION: Rate of surgical-site infection after large contaminated ventral hernia repair with synthetic mesh is considerable but with a low mesh removal rate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Item does not contain fulltext BACKGROUND: Recurrence rates after component separation technique (CST) are low in the literature but may be underestimated because of inadequate follow-up methods. METHODS: Prospective patient follow-up was performed of consecutive patients who underwent repair of large and complex ventral hernias using CST without mesh utilization. Primary outcome was recurrent hernia determined by clinical examination at least 1 year after surgery in all living patients. Current literature underwent meta-analysis regarding outcomes and mode of follow-up. RESULTS: Seventy-five patients were included with a mean age of 52.2 years and a mean defect size of 214.9 cm(2), respectively. Twenty-nine patients (38.7%) had a recurrent hernia after a mean of 40.9-month follow-up, and this was significantly higher than in the literature (14.0%, P < .01). Sixty-four percent of studies in the literature were unclear about the method of determining recurrent hernia or included telephone follow-up and questionnaires. CONCLUSIONS: CST coincides with a high recurrence rate when clinical follow-up is longer than a year. Reported recurrence rates are probably underestimated because the method and duration of follow-up are inadequate.

Abdominal wall defects often complicate the postoperative course of patients after abdominal surgery in the form of wound dehiscence in the short term and incisional hernia in the long term. Prevention and treatment remain a significant challenge to surgeons. This paper provides an update regarding the most recent insights regarding the pathogenesis of these common abdominal wall defects. In the ‘How to’ sections, the best methods of opening and closing the abdomen are presented, with a focus on prevention of short- and long-term complications. Also, the various options and indications for synthetic and autologous abdominal wall reconstructions are discussed. Finally, a treatment algorithm based on our extensive experience and the best available evidence in the literature is presented for the various forms of incisional hernias discussed in this paper.

Objective The aims of this study were, first, to determine if granulocyte colony-stimulating factor (G-CSF) and stem cell factor (SCF) improved left ventricular function in the setting of a reperfusion model of myocardial infarction (MI) and, second, to evaluate the effects of G-CSF/SCF on cellular repair and, in particular, the fate of bone marrow cells homing to the site of tissue injury. Methods MI was induced in mice by transient ligation of the left descending coronary artery. G-CSF/SCF were administered for 5 days after MI. Cardiac function was assessed 28 days after MI. The effect of G-CSF/SCF on the cellular composition of the infarct region was assessed by immunohistochemistry. MI was performed in mice reconstituted with bone marrow cells expressing DsRed to track the fate of bone marrow-derived cells within the infarct region. Results G-CSF/SCF-treated mice had significantly improved left ventricular (LV) function as determined by LV developed pressure, LV±d p /d t max/min, and LV end-diastolic pressure. G-CSF alone produced similar improvements in cardiac function. These improvements in LV function were associated with 70% more blood vessels and a doubling of cells expressing cardiomyocyte-specific transcription factors GATA-4, Nkx2.5 and alpha-actinin cells within the infarct zone. Cells within the infarct expressing stromal-derived factor also increased by 200%. To elucidate the origin of these cells, bone marrow chimeras, where hematopoietic cells expressed the fluorescent marker DsRed, were treated with G-CSF/SCF after MI. Bone marrow-derived, DsRed-expressing cells in the infarct region of G-CSF/SCF-treated chimeras increased by an average of 12-fold; however, the vast majority of DsRed cells expressed the hematopoietic-specific marker CD45 but not blood vessel or cardiomyocyte markers. Conclusions G-CSF/SCF therapy improved cardiac function when delivered after MI, increasing the number of blood vessels and cells of cardiomyogenic lineage. However, these cells were of myocardial rather than bone marrow origin.

A number of alternatively spliced isoforms of haemopoietic growth factor receptors (HGFRs) have been described, but their role in human haemopoiesis remains undetermined. We have investigated the relative expression of the alpha1 and alpha2 isoforms of human granulocyte/macrophage colony-stimulating factor receptor (hGM-CSFR) during haemopoietic cell differentiation, and have shown that both subunits are independently regulated during differentiation of CD34+ human haemopoietic progenitor cells. To further investigate these ex-vivo observations, we established a series of murine FDCP mix cell lines, which, as a consequence of the ectopic expression of alpha1 or alpha2 hGM-CSFR, demonstrated differential differentiation responses to hGM-CSF. In this model system, hGM-CSFR-alpha2-expressing cells showed increased hGM-CSF-mediated erythroid/megakaryocytic differentiation compared with hGM-CSFR-alpha1-expressing cells.

Mutations in the Wilms tumor suppressor 1 (WT1) gene are as frequent in acute myeloid leukemia (AML) as in nephroblastma and predict poor prognosis. However, the role of WT1 in hematopoiesis remains unclear. We show that Wt1-deficient mouse embryonic stem cells exhibit reduced hematopoietic potential caused by vascular endothelial growth factor A (Vegf-a)-dependent apoptosis of hematopoietic progenitor cells associated with overproduction of the Vegf-a120 isoform. We demonstrate that Wt1 promotes exon inclusion using a Vegf-a minigene-based splicing assay. These data identify a critical role for Wt1 in hematopoiesis and Vegf-a as a cellular RNA whose splicing is potentially regulated by Wt1. The correction of Wt1 deficiency by treatment with exogenous Vegf-a protein indicates that the Wt1/Vegf-a axis is a molecular pathway that could be exploited for the management/treatment of poor prognosis AMLs.

Item does not contain fulltext BACKGROUND: Biologic grafts hold promise of a durable repair for ventral hernias with the potential for fewer complications than synthetic mesh. This systematic review was performed to evaluate the effectiveness and safety of biologic grafts for ventral hernia repair. METHODS: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched for studies on biologic grafts for the repair of ventral hernias. Outcomes are presented as weighted pooled proportions. RESULTS: Twenty-five retrospective studies were included. Recurrence depended on wound class, with an overall rate of 13.8% (95% confidence interval [CI], 7.6-21.3). The recurrence rate in contaminated/dirty repairs was 23.1% (95% CI, 11.3-37.6). Abdominal wall laxity occurred in 10.5% (95% CI, 3.7-20.3) of patients. The surgical morbidity rate was 46.3% (95% CI, 33.3-59.6). Infection occurred in 15.9% (95% CI, 9.8-23.2) of patients but only led to graft removal in 4.9% of cases. CONCLUSIONS: No randomized trials are available to properly evaluate biologic grafts for ventral hernia repair. The current evidence suggests that biologic grafts perform similarly to other surgical options. Biologic grafts are associated with a high salvage rate when faced with infection.

Contains fulltext : 109648.pdf (Publisher’s version ) (Closed access) BACKGROUND: Parastomal hernias are a frequent complication of enterostomies that require surgical treatment in approximately half of patients. This systematic review aimed to evaluate and compare the safety and effectiveness of the surgical techniques available for parastomal hernia repair. METHODS: Systematic review was performed in accordance with PRISMA. Assessment of methodological quality and selection of studies of parastomal hernia repair was done with a modified MINORS. Subgroups were formed for each surgical technique. Primary outcome was recurrence after at least 1-year follow-up. Secondary outcomes were mortality and postoperative morbidity. Outcomes were analyzed using weighted pooled proportions and logistic regression. RESULTS: Thirty studies were included with the majority retrospective. Suture repair resulted in a significantly increased recurrence rate when compared with mesh repair (odds ratio [OR] 8.9, 95% confidence interval [CI] 5.2-15.1; P < 0.0001). Recurrence rates for mesh repair ranged from 6.9% to 17% and did not differ significantly. In the laparoscopic repair group, the Sugarbaker technique had less recurrences than the keyhole technique (OR 2.3, 95% CI 1.2-4.6; P = 0.016). Morbidity did not differ between techniques. The overall rate of mesh infections was low (3%, 95% CI 2) and comparable for each type of mesh repair. CONCLUSIONS: Suture repair of parastomal hernia should be abandoned because of increased recurrence rates. The use of mesh in parastomal hernia repair significantly reduces recurrence rates and is safe with a low overall rate of mesh infection. In laparoscopic repair, the Sugarbaker technique is superior over the keyhole technique showing fewer recurrences. 01 april 2012

Contains fulltext : 98303.pdf (Publisher’s version ) (Open Access) BACKGROUND: Biologic grafts are increasingly used instead of synthetic mesh for parastomal hernia repair due to concerns of synthetic mesh-related complications. This systematic review was designed to evaluate the use of these collagen-based scaffolds for the repair of parastomal hernias. METHODS: Studies were retrieved after searching the electronic databases MEDLINE, EMBASE and Cochrane CENTRAL. The search terms 'paracolostomy', 'paraileostomy', 'parastomal', 'colostomy', 'ileostomy', 'hernia', 'defect', 'closure', 'repair' and 'reconstruction' were used. Selection of studies and assessment of methodological quality were performed with a modified MINORS index. All reports on repair of parastomal hernias using a collagen-based biologic scaffold to reinforce or bridge the defect were included. Outcomes were recurrence rate, mortality and morbidity. RESULTS: Four retrospective studies with a combined enrolment of 57 patients were included. Recurrence occurred in 15.7% (95% confidence interval [CI] 7.8-25.9) of patients and wound-related complications in 26.2% (95% CI 14.7-39.5). No mortality or graft infections were reported. CONCLUSIONS: The use of reinforcing or bridging biologic grafts during parastomal hernia repair results in acceptable rates of recurrence and complications. However, given the similar rates of recurrence and complications achieved using synthetic mesh in this scenario, the evidence does not support use of biologic grafts.

Runx1 is essential for the homeostatic control of normal hematopoiesis and is required for lymphoid development. Translocations or point mutations that result in RUNX1 loss or disrupted function predispose to leukemia but data derived from model systems suggests that Runx genes can also be pro-oncogenic. Here we investigate the effects of enforced Runx1 expression in lymphoid lineages both in vivo and in vitro and show that transgene expression enhanced cell survival in the thymus and bone marrow but strongly inhibited the expansion of hematopoietic and B cell progenitors in vitro. Despite this, modestly enhanced levels of Runx1 accelerated Myc-induced lymphomagenesis in both the B cell and T cell lineages. Together these data provide formal proof that wild type Runx1 can promote oncogenesis in lymphoid tissues and that, in addition to loss of function, gain of function may have an aetiological role in leukemia.

The stem cell leukemia (SCL) gene encodes a basic helix-loop-helix transcription factor expressed in erythroid, megakaryocyte, and mast-cell lineages. SCL is essential for growth of megakaryocyte and erythroid progenitors. We have used a conditional knockout of SCL (SCL−/Δ) to examine its function in mast cells, critical effectors of the immune system. SCL−/Δ mice had markedly increased numbers of mast-cell progenitors (MCPs) within the peritoneal fluid, bone marrow, and spleen. Fractionation of bone marrow myeloid progenitors demonstrated that these MCPs were present in the megakaryocyte-erythroid–restricted cell fraction. In contrast, unilineage MCPs from control mice were present in the cell fraction with granulocyte-macrophage potential. The aberrant mast-cell differentiation of SCL−/Δ megakaryocyte-erythroid progenitors was associated with increased expression of GATA-2. Despite increased numbers of MCPs in SCL−/Δ mice, numbers of mature tissue mast cells were not increased unless SCL−/Δ mice were treated with IL-3 and stem-cell factor. In part, this may be due to a requirement for SCL in normal mast-cell maturation: SCL−/Δ mast cells had reduced expression of the high-affinity IgE receptor and mast cell proteases, MCP-5 and MCP-6. Together, these studies suggest that loss of SCL leads to aberrant mast-cell differentiation of megakaryocyte-erythroid progenitors.

The generation of platelets from megakaryocytes in the steady state is regulated by a variety of cytokines and transcription factors, including thrombopoietin (TPO), GATA-1, and NF-E2. Less is known about platelet production in the setting of stress thrombopoiesis, a pivotal event in the context of cytotoxic chemotherapy. Here we show in mice that the transcription factor Scl is critical for platelet production after chemotherapy and in thrombopoiesis induced by administration of TPO. Megakaryocytes from these mice showed appropriate increases in number and ploidy but failed to shed platelets. Ultrastructural examination of Scl-null megakaryocytes revealed a disorganized demarcation membrane and reduction in platelet granules. Quantitative real-time polymerase chain reaction showed that Scl-null platelets lacked NF-E2, and chromatin immunoprecipitation analysis demonstrated Scl binding to the NF-E2 promoter in the human megakaryoblastic-cell line Meg-01, along with its binding partners E47, Lmo2, and the cofactors Ldb1 and GATA-2. These findings suggest that Scl acts up-stream of NF-E2 expression to control megakaryocyte development and platelet release in settings of thrombopoietic stress.

Erythroid and megakaryocyte progenitors express a number of transcription factor genes in common, including the Stem Cell Leukemia (SCL) gene. The SCL gene encodes a 45 kDa protein that contains two distinct functional domains, a basic DNA-binding domain (b) and a helix-loop-helix domain (HLH) required for heterodimerisation with E proteins. We have used a conditional SCL-knockout mouse strain (SCLloxP) to demonstrate that SCL is essential for the growth of erythroid (BFU-E) and megakaryocyte (Mk-CFU) progenitors. To further address the role of SCL in these two related lineages, we have used bone marrow cells from SCL-conditional knockout mice as a source of SCL-null progenitors to perform structure-function analyses. Consistent with the absence of BFU-E, SCL-null bone marrow cells were unable to generate erythroblasts when grown in erythroid cultures (stem cell factor, erythropoietin, insulin-like growth factor 1 and dexamethasone). We subsequently infected SCL-null bone marrow cells with retroviruses expressing wild type or mutant forms of SCL. Expression of wild-type SCL completely rescued the erythroid growth defect of SCL-null bone marrow cells. A truncation mutant containing only the bHLH region was also sufficient for complete rescue of erythropoiesis. However, an HLH only mutant, which lacked the DNA binding domain was unable to rescue erythroid growth, suggesting that SCL directly regulates target genes required for erythropoiesis. To further define the function of SCL in erythropoiesis, we generated immortal cell lines with erythroid potential from SCLloxP mice. In vitro deletion of SCL at the time of initiating erythroid cultures led to rapid cell death that was not rescued by expression of BclXL, suggesting that SCL was not functioning to promote erythroid cell survival. In contrast to the effects on early erythroid cell growth, deletion of SCL after the establishment of erythroblasts had no significant effect on cell growth or survival. This indicates that SCL is required for the initiation or growth of early erythroid progenitors but is dispensable for more mature erythroid progenitor cells. Parallel experiments examining megakaryocytic progenitor growth yielded contrasting results to the erythroid progenitors. Complete rescue of in vitro megakaryopoiesis was observed with both the bHLH and HLH only mutants, with the DNA-binding mutant exhibiting more potent activity than wild-type SCL in this context. The differential DNA-binding requirements of erythroid and megakaryocyte progenitors were even more evident when the HLH only mutant was expressed in wild type cells. In this setting, the DNA-binding mutant increased growth of Mk-CFU but actively inhibited erythroid cell growth. Together, these results indicate that SCL functions to promote erythroid and megakaryocyte cell growth by differing mechanisms. In early erythroid cell growth, SCL functions as a classical transactivator of key target genes, while in megakaryocyte growth, it functions by either sequestration of repressor E proteins, or as a critical, but non DNA-binding, component of a transactivation complex.