Surgical options for lymphedema after gynecological cancer treatment: current trends and advances.

Lower leg lymphedema is an important complication after gynecological treatment that can severely affect the quality of life of long-term survivors of these malignancies. As a chronic and progressive disease, affected patients will require life-long therapy centered on compression. Although conventional compressive treatments can be effective, they are extremely burdensome and time-consuming for most patients and adherence is challenging. With advances in the field of reconstructive microsurgery, new procedures have been developed in the past decades to help these patients in their continuous care and have been offered at many oncological centers around the world as a first line of treatment. We performed a PubMed search using the Mesh terms 'Lymphedema/surgery' and 'Lower extremity' yielding a total of 508 articles. Of these, 35 articles were included for analysis. Articles that failed to provide a comprehensive analysis of outcomes following surgical treatment, studies examining treatment for upper limb lymphedema, primary lymphedema, or lower extremity lymphedema resulting from non-gynecologic etiologies, and studies that failed to have a minimum of 6 months follow-up were excluded. A comprehensive review of these 35 articles including over 1200 patients demonstrated large variability on the outcomes reported; however, an overall benefit from these procedures was found. Surgical options including lymphovenous anastomosis, vascularized lymph node transfers, and excisional procedures can be performed in patients with lower leg lymphedema, depending on staging and findings in indocyanine green lymphography. Surgical treatment of lymphedema is an effective option that can improve symptoms and quality of life of patients suffering from lymphedema following gynecologic cancers.

Indocyanine Green Fluorescent Lymphography During Open Inguinal Hernia Repair: Relationship Between Lymphatic Vessel Injury and Postoperative Hydrocele.

BACKGROUND: This prospective case series analyzed patients who underwent indocyanine green (ICG) fluorescent lymphography during open inguinal hernia repair. The aim of this study was to investigate the association between ICG leakage and postoperative hydroceles in patients who underwent inguinal hernia repair. MATERIALS AND METHODS: Data were analyzed from 40 patients who underwent primary open hernia repair between October 2020 and June 2021 (44 cases in total). Hydroceles were categorized into two types: symptomatic and "ultrasonic" (detected only by ultrasound imaging). RESULTS: In the univariate analysis, hernia type (p = 0.044) and ICG leakage (p = 0.007) were independent risk factors for postoperative ultrasonic hydroceles. Additionally, mesh type (p = 0.043) and ICG leakage (p = 0.025) were independent risk factors for postoperative symptomatic hydroceles. In the multivariate analysis, ICG leakage (p = 0.034) was an independent risk factor for postoperative ultrasonic hydroceles. CONCLUSIONS: ICG leakage after inguinal hernia repair was independently associated with postoperative ultrasonic and symptomatic hydroceles. These findings suggest a relationship between lymphatic vessel injury and the incidence of postoperative hydroceles.

Primary Prevention of Cancer-Related Lymphedema Using Preventive Lymphatic Surgery: Systematic Review and Meta-analysis.

Background Several studies have proven prophylactic lymphovenous anastomosis (LVA) performed after lymphadenectomy can potentially reduce the risk of cancer-related lymphedema (CRL) without compromising the oncological treatment. We present a systematic review of the current evidence on the primary prevention of CRL using preventive lymphatic surgery (PLS). Patients and Methods A comprehensive search across PubMed, Cochrane-EBMR, Web of Science, Ovid Medline (R) and in-process, SCOPUS, and ScienceDirect was performed through December 2020. A meta-analysis with a random-effect method was accomplished. Results Twenty-four studies including 1547 patients fulfilled the inclusion criteria. Overall, 830 prophylactic LVA procedures were performed after oncological treatment, of which 61 developed lymphedema. The pooled cumulative rate of upper extremity lymphedema after axillary lymph node dissection (ALND) and PLS was 5.15% (95% CI, 2.9%-7.5%; p < 0.01). The pooled cumulative rate of lower extremity lymphedema after oncological surgical treatment and PLS was 6.66% (95% CI < 1-13.4%, p-value = 0.5). Pooled analysis showed that PLS reduced the incidence of upper and lower limb lymphedema after lymph node dissection by 18.7 per 100 patients treated (risk difference [RD] - 18.7%, 95% CI - 29.5% to - 7.9%; p < 0.001) and by 30.3 per 100 patients treated (RD - 30.3%, 95% CI - 46.5% to - 14%; p < 0.001), respectively, versus no prophylactic lymphatic reconstruction. Conclusions Low-quality studies and a high risk of bias halt the formulating of strong recommendations in favor of PLS, despite preliminary reports theoretically indicating that the inclusion of PLS may significantly decrease the incidence of CRL.

Dual antivascular function of human fibulin-3 variant, a potential new drug discovery strategy for glioblastoma.

The ECM protein EFEMP1 (fibulin-3) is associated with all types of solid tumor through its cell context-dependent dual function. A variant of fibulin-3 was engineered by truncation and mutation to alleviate its oncogenic function, specifically the proinvasive role in glioblastoma multiforme (GBM) cells at stem-like state. ZR30 is an in vitro synthesized 39-kDa protein of human fibulin-3 variant. It has a therapeutic effect in intracranial xenograft models of human GBM, through suppression of epidermal growth factor receptor/AKT and NOTCH1/AKT signaling in GBM cells and extracellular MMP2 activation. Glioblastoma multiforme is highly vascular, with leaky blood vessels formed by tumor cells expressing endothelial cell markers, including CD31. Here we studied GBM intracranial xenografts, 2 weeks after intratumoral injection of ZR30 or PBS, by CD31 immunohistochemistry. We found a 70% reduction of blood vessel density in ZR30-treated xenografts compared with that of PBS-treated ones. Matrigel plug assays showed the effect of ZR30 on suppressing angiogenesis. We further studied the effect of ZR30 on genes involved in endothelial transdifferentiation (ETD), in 7 primary cultures derived from 3 GBMs under different culture conditions. Two GBM cultures formed mesh structures with upregulation of ETD genes shortly after culture in Matrigel Matrix, and ZR30 suppressed both. ZR30 also downregulated ETD genes in two GBM cultures with high expression of these genes. In conclusion, multifaceted tumor suppression effects of human fibulin-3 variant include both suppression of angiogenesis and vasculogenic mimicry in GBM.

Emerging importance of molecular pathogenesis of vascular malformations in clinical practice and classifications.

Vascular malformations occur during early vascular development resulting in abnormally formed vessels that can manifest as arterial, venous, capillary or lymphatic lesions, or in combination, and include local tissue overdevelopment. Vascular malformations are largely caused by sporadic somatic gene mutations. This article aims to review and discuss current molecular signaling pathways and therapeutic targets for vascular malformations and to classify vascular malformations according to the molecular pathways involved. A literature review was performed using Embase and Medline. Different MeSH terms were combined for the search strategy, with the aim of encompassing all studies describing the classification, pathogenesis, and treatment of vascular malformations. Major pathways involved in the pathogenesis of vascular malformations are vascular endothelial growth factor (VEGF), Ras/Raf/MEK/ERK, angiopoietin-TIE2, transforming growth factor beta (TGF-ß), and PI3K/AKT/mTOR. These pathways are involved in controlling cellular growth, apoptosis, differentiation, and proliferation, and play a central role in endothelial cell signaling and angiogenesis. Many vascular malformations share similar aberrant molecular signaling pathways with cancers and inflammatory disorders. Therefore, selective anticancer agents and immunosuppressants may be beneficial in treating vascular malformations of specific mutations. The current classification systems of vascular malformations, including the International Society of the Study of Vascular Anomalies (ISSVA) classification, are primarily observational and clinical, and are not based on the molecular pathways involved in the pathogenesis of the condition. Several molecular pathways with potential therapeutic targets have been demonstrated to contribute to the development of various vascular anomalies. Classifying vascular malformations based on their molecular pathogenesis may improve treatment by determining the underlying nature of the condition and their potential therapeutic target.

Dissolving Microneedle Arrays for Transdermal Delivery of Amphiphilic Vaccines.

Amphiphilic vaccine based on lipid-polymer conjugates is a new type of vaccine capable of self-delivering to the immune system. When injected subcutaneously, amphiphilic vaccines efficiently target antigen presenting cells in the lymph nodes (LNs) via a unique albumin-mediated transport and uptake mechanism and induce potent humoral and cellular immune responses. However, whether this new type of vaccine can be administrated via a safe, convenient microneedle-based transdermal approach remains unstudied. For such skin barrier-disruption systems, a simple application of microneedle arrays (MNs) is desired to disrupt the stratum corneum, and for rapid and pain-free self-administration of vaccines into the skin, the anatomic place permeates with an intricate mesh of lymphatic vessels draining to LNs. Here the microneedle transdermal approach is combined with amphiphilic vaccines to create a simple delivery approach which efficiently traffic molecular vaccines into lymphatics and draining LNs. The rapid release of amphiphilic vaccines into epidermis upon application of dissolving MNs to the skin of mice generates potent cellular and humoral responses, comparable or superior to those elicited by traditional needle-based immunizations. The results suggest that the amphiphilic vaccines delivered by dissolving MNs can provide a simple and safer vaccination method with enhanced vaccine efficacy.

Outcomes of vascularized versus non-vascularized lymph node transplant in animal models for lymphedema. Review of the literature.

Lymph node transfer has been performed to treat lymphedema for several years. The goal of this procedure is to provide a bridge between the lymphatic system distal and proximal to the lymph node dissection. There is a lack of consensus about the necessity of an additional vascular anastomosis for the transplanted lymph nodes. A systematic literature search in Cochrane Library database CENTRAL, MEDLINE, and EMBASE of animal studies using lymph node transplantation with and without additional vascularization was performed in March 2016. The strategy used for the search was: (("Models, Animal"[Mesh]) AND (("Lymphedema"[Mesh]) OR "Lymph Nodes"[Mesh]) OR "Lymph Node Excision"[Mesh])) AND ((vascularized lymph node transfer) OR ((non-vascularized lymph node transfer) OR lymph node graft)). The primary outcomes were: survival of transplanted lymph node and lymphatic vessel regeneration. Sixteen studies were included. Vascularization and the use of growth factors were significantly associated with lymph node survival. Lymphatic vessels regeneration was independent from vascularization. According to the results of the current study, additional vascular anastomosis might improve the transplanted lymph node survival. Further studies in both experimental and clinical setting are needed in order to support it. J. Surg. Oncol. 2017;115:32-36. © 2016 Wiley Periodicals, Inc.

Spontaneous activity in peripheral diaphragmatic lymphatic loops.

The spontaneous contractility of FITC-dextran-filled lymphatics at the periphery of the pleural diaphragm was documented for the first time "in vivo" in anesthetized Wistar rats. We found that lymphatic segments could be divided into four phenotypes: 1) active, displaying rhythmic spontaneous contractions (51.8% of 197 analyzed sites); 2) stretch-activated, whose contraction was triggered by passive distension of the vessel lumen (4.1%); 3) passive, which displayed a completely passive distension (4.5%); and 4) inert, whose diameter never changed over time (39.6%). Smooth muscle actin was detected by immunofluorescence and confocal microscopy in the vessel walls of active but also of inert sites, albeit with a very different structure within the vessel wall. Indeed, while in active segments, actin was arranged in a dense mesh completely surrounding the lumen, in inert segments actin decorated the vessels wall in sparse longitudinal strips. When located nearby along the same lymphatic loop, active, stretch-activated, and passive sites were always recruited in temporal sequence starting from the active contraction. The time delay was ∼0.35 s between active and stretch-activated and 0.54 s between stretch-activated and passive segments, promoting a uniform lymph flux of ∼150/200 pl/min. We conclude that, unlike more central diaphragmatic lymphatic vessels, loops located at the extreme diaphragmatic periphery do require an intrinsic pumping mechanism to propel lymph centripetally, and that such an active lymph propulsion is attained by means of a complex interplay among sites whose properties differ but are indeed able to organize lymph flux in an ordered fashion.

Interdisciplinary aspects of abdominal and plastic surgery - what does the (abdominal) surgeon need to know?

Introduction: The aim was to reflect the established interdisciplinary aspects of general/abdominal and plastic surgery by means of a narrative review. Methods: (i) With specific references out of the medical literature and (ii) own clinical and perioperative as well as operating technical and tactical management experiences obtained in surgical daily practice, we present a choice of options for interdisciplinary cooperation that could be food of thought for other surgeons. Content: - Decubital ulcers require pressure relieve, debridement and plastic surgery coverage, e.g., by a rotation flap plasty, V-Y flap or "tensor-fascia-lata" (TFL) flap depending on localization (sacral/gluteal defects, ischiadic tuber). - Coverage of soft tissue defects, e.g., after lymph node dissection, tumor lesions or disturbance of wound healing can be managed with fasciocutaneous or muscle flaps. - Bariatric surgery: Surgical interventions such as butt lift, tummy tuck should be explained and demonstrated in advance and performed commonly after reduction of the body weight. - Abdominoperineal rectum extirpation (APE): Holm's procedure with greater circumferential extent of resection at the mesorectum and the insertion site of the levator muscle at the anal sphicter muscle resulting in a substantial defect is covered by myocutaneous flap plasty. - Hernia surgery: Complicated/recurrent hernias or abdominal wall defect can be covered by flap plasty to achieve functional reconstruction, e.g., using innervated muscle. Thus, abdominal wall can respond better onto changes of pressure and tension. - Necrotising fasciitis: Even in case of suspicious fasciitis, an immediate radical debridement must be performed, followed by intensive care with calculated antibiotic treatment; after appropriate stabilization tissue defects can be covered by mesh graft of flap plasty. - Soft tissue tumor lesions cannot be resected with primary closure to achieve appropriate as intended R0 resection status by means of local radical resection all the time - plastic surgery expertise has to be included into interdisciplinary tumor concepts. - Liposuction/-filling: Liposuction can be used with aesthetic intention after bariatric surgery or for lipedema. Lipofilling is possible for reconstruction and for aesthetic purpose. - Reconstruction of lymphatic vessels: Lymphedema after tumor operations interrupting or blocking lymphatic drainage can be treated with microsurgical reconstructions (such as lympho-venous anastomoses, lympho-lymphatic anastomoses or free microvascular lymph node transfer). - Microsurgery: It is substantial part of modern reconstructive plastic surgery, i.e., surgery of peripheral nerves belongs to this field. For visceral surgery, it can become important for reconstruction of the recurrent laryngeal nerve. - Sternum osteomyelitis: Radical debridement (eventually, complete sternal resection) with conditioning of the wound by vacuum-assisted closure followed by plastic surgery coverage can prevent chronification, threatening mediastinitis, persisting infectious risk, long-term suffering or limited quality of life. Summary: The presented selection of single topics can only be an excerpt of all the options for surgical cooperation in daily clinical and surgical practice. Outlook: An interdisciplinary approach of abdominal and plastic surgery is characterized by a highly developed cooperation in common surgical interventions including various techniques and tactics highlighting the specifics of the two fields.

The Internal Conduit System of the Swine Inverted Lymph Node.

Lymph nodes (LN) are the crossroad where naïve lymphocytes, peripheral antigens and antigen presenting cells contact together in order to mount an adaptive immune response. For this purpose, LN are highly organized convergent hubs of blood and lymphatic vessels that, in the case of B lymphocytes, lead to the B cell follicles. Herein take place the selection and maturation of B cell clones producing high affinity antibodies directed against various antigens. Whereas the knowledge on the murine and human LN distribution systems have reached an exquisite precision those last years, the organization of the antigens and cells circulation into the inverted porcine LN remains poorly described. Using up to date microscopy tools, we described the complex interconnections between afferent lymphatics and blood vessels, perifollicular macrophages, follicular B cells and efferent blood vessels. We observed that afferent lymphatic sinuses presented an asymmetric Lyve-1 expression similar to the one observed in murine LN, whereas specialized perifollicular sinuses connect the main afferent lymphatic sinus to the B cell follicles. Finally, whereas it was long though that mature B cells egress from the inverted LN in the T cell zone through HEV, our observations are in agreement with mature B cells accessing the efferent blood circulation in the efferent, subcapsular area. This understanding of the inverted porcine LN circuitry will allow a more accurate exploration of swine pathogens interactions with the immune cells inside the LN structures. Moreover, the mix between similarities and differences of porcine inverted LN circuitry with mouse and human normal LN shall enable to better apprehend the functions and malfunctions of normal LN from a new perspective.

Indocyanine green fluorescent lymphography during open inguinal hernia repair in a patient who developed postoperative ultrasonic hydrocele: A case report.

BACKGROUND: To our knowledge, no reports of indocyanine green (ICG) fluorescent lymphography during inguinal hernia repair currently exist. We report the case of a patient who underwent ICG fluorescent lymphography during open inguinal hernia repair. CASE PRESENTATION: A 63-year-old man was referred to our department for treatment of a right inguinal hernia, during which an ICG lymphography was performed. The patient had a history of robot-assisted radical prostatectomy for prostate cancer. Following induction of general anesthesia, 0.25 mg of ICG was injected into the right testicle and the scrotum was gently massaged, after which an open inguinal hernia repair was performed. During the operation, fluorescence from the ICG was observed in two lymphatic vessels in the spermatic cord. The ICG fluorescent vessels were resected due to the strong adhesion between the lymphatic vessels and the hernia sac. ICG leakage was observed in the resected vessels. An open tension-free technique was performed using an open mesh plug. The patient was discharged one day postoperatively. The histological diagnosis of the resected vessel was a lymphatic vessel. He had a slight postoperative hydrocele that was detected at the follow-up clinic 10 days postoperatively during ultrasonic examination (ultrasonic hydrocele). CONCLUSION: We report the use of ICG fluorescent lymphography during open inguinal hernia repair in a patient who developed postoperative ultrasonic hydrocele. This case may indicate a relationship between lymphatic vessel injury and hydrocele.

Prognostic Relevance of Lymphatic Vessel Density in Squamous Cell Carcinomas of the Oral Cavity: A Systematic Review and Meta-Analysis.

BACKGROUND: Oral Squamous Cell Carcinoma (OSCC), a major debilitating illness demands focus in recent times due to a constant upsurge in cases and poor prognostic implications. An urgent mandate upon finding evidence of relevant prognostic markers is the need of the hour. This systematic review and meta-analysis, therefore, elect an objective assessment of Lymphatic Vessel Density (LVD) as a pertinent parameter governing OSCC prognosis. METHODS: The study protocol was registered at the International Prospective Register Of Systematic Reviews (PROSPERO). Databases were searched using the MeSH keywords for all study types following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The exposure under consideration was the evaluation of LVD in patients of OSCC. The outcome was measured as pooled Hazard/Odd's/Risk ratios in survived versus non-survived OSCC population. The risk of bias assessment was performed using the QUIPS tool. Heterogeneity was assessed by Chi-square and I2 statistics whereas publication bias was investigated using Egger's test of significance. All the statistical analysis was conducted using STATA version 13.0. RESULTS: The initial search of 226 records were screened and filtered through the inclusion and exclusion criteria to achieve an outcome of 15 studies for qualitative synthesis out of which seven studies were eligible for meta-analysis. Pooled Hazard of enhanced Lymphatic Vessel Density was not found to be statistically significant (HR = 1.98, p = 0.553); contrary to the pooled Odd's/Risk for patient survival which was statistically significant (RR = 1.33, p = 0.046). The I2 test of heterogeneity was also significant (58.8%, p = 0.046). CONCLUSIONS: This meta-analysis helps to generate pathfinding evidence for a noteworthy role of Lymphatic Vessel Density evaluation in suggesting OSCC prognosis.

Human microvascular lymphatic and blood endothelial cells produce fibrillin: deposition patterns and quantitative analysis.

Fibrillin microfibrils constitute a scaffold for elastin deposition in the wall of arteries and form the anchoring filaments that connect the lymphatic endothelium to surrounding elastic fibers. We previously reported that fibrillin is deposited in a honeycomb pattern in bovine arterial endothelial cells, which also deposit microfibril-associated glycoprotein (MAGP)-1, whereas thoracic duct endothelial cells form an irregular web. The present immunohistochemical study was designed to verify whether lymphatic and blood human dermal microvascular endothelial cells (HDMECs) isolated from human foreskin by the sequential use of a pan-endothelial marker, CD31, and the lymphatic specific marker, D2-40, deposit fibrillin and MAGP-1. In both cell types, fibrillin and MAGP-1 co-localized and were deposited with different patterns of increasing complexity co-existing in the same culture. Fibrillin microfibrils formed a wide-mesh honeycomb leaving fibrillin-free spaces that were gradually filled. This modality of fibrillin deposition, similar to that of bovine large artery endothelial cells, was basically the same in blood and lymphatic HDMECs. In some lymphatic HDMECs, fibrillin was initially deposited as uniformly scattered short fibrillin strands probably as a result of anchoring filaments carried over from the vessels of origin. Our findings show that blood and lymphatic endothelial cells participate in fibrillin deposition in human skin.

Engineering drug delivery systems to overcome mucosal barriers for immunotherapy and vaccination.

Mucosal surfaces protect our bodies from pathogens and external irritants using a system of biological barriers. Overcoming these barriers is a significant drug delivery challenge, particularly for immunotherapies that aim to modulate the local immune response. Reaching local lymphoid tissues and draining lymph nodes (LNs) requires crossing the mucus mesh, mucosal epithelium, and either targeting M cells covering lymphoid tissues or utilizing lymphatic transport that shuttles molecules and particulates from the periphery to the LN. We first highlight the barrier properties of mucus and mucosal epithelium, and the function of the mucosal immune system. We then dive into existing drug delivery technologies that have been engineered to overcome each of these barriers. We particularly focus on novel strategies for targeting lymphoid tissues, which has been shown to enhance immunotherapies and vaccinations, via directly targeting LNs, lymphatic vessels, and M cells that transport samples of mucosal content to the lymphoid tissues.

Retroperitoneal exploration with Vicryl mesh and fibrin tissue sealant for refractory chylous ascites.

BACKGROUND: Congenital chylous ascites poses a significant challenge in neonatal care, and often results in prolonged, complex hospital stays and increased mortality. Few effective options exist in refractory cases. METHODS: Patients aged 0 to 12 months with refractory chylous ascites underwent retroperitoneal exploration after medical treatment and minimally invasive therapies were unsuccessful. The retroperitoneum was completely exposed via left and right medial visceral rotation and opening the lesser sac. Visible leaks were ligated, and alternating layers of fibrin glue and Vicryl mesh were used to cover the entire retroperitoneum. RESULTS: All 4 patients had resolution of their chylous ascites. None required reoperation or reintervention for chyle leaks. All achieved goal enteral feeds at a median of 29 days postoperatively and were discharged from hospital at a median of 42 days postoperatively. CONCLUSIONS: Management of chylous ascites is extremely challenging in refractory cases. Complete retroperitoneal exposure with fibrin glue and Vicryl mesh application offers a definitive, reliable therapy for achieving cessation of lymphatic leakage and ultimate recovery for patients who fail all nonoperative approaches. STUDY TYPE: Therapeutic. LEVEL OF EVIDENCE: IV.

What does a (general and abdominal) surgeon need to know on plastic surgery?

BACKGROUND: Plastic surgery was first introduced as a sub-specialty of general surgery in Germany in 1978. Since then, this surgical subspecialty/discipline has evolved enormous potential, e.g. in collaboration with other disciplines such as general andabdominal surgery. AIM: To highlight and summarize the basic potential, technical options and novel aspects of plastic surgery, which are relevant for the common interdisciplinary surgical strategies of plastic and general as well as abdominal surgery in clinical practice. METHOD: Short and compact narrative review based on 1) a selection of relevant references from the medical scientific literature and 2) surgical experiences obtained in daily practice. R esults (selected corner points): 1) Biological protection procedures in vascular surgery by flap coverage after meticulous debridement with or without autogenic vascular reconstruction are used to overcome infection of a vascular prosthesis, a serious problem, associated with the risk of anastomotic rupture and bleeding by transfer of immunological competence due to tissue coverage and finally to induce healing in the area of an infected vascular prosthesis. 2) Fistula treatment for aorto-tracheal or aorto-duodenal fistulas, a big challenge for the referring general surgeon, can be treated by flap coverage, i.e. interposition of the pectoralis-major flap and the omentum-majus flap, respectively. 3) With regard to nerve surgery, encouraging results have been reported after early microsurgical recurrent laryngeal nerve repair, i.e. improved subjective voice quality or reconstitution of respiratory capacity in diaphragmatic. 4) Lymphatic surgery for lymphedema occurring either primarily due to an absence or lack of lymphatic vessels or secondarily due to infection, trauma, radiation therapy or surgery can be indicated in specialized microsurgical centers, e.g. for surgical repair of the lymphatic pathway: I) the interrupted lymphatic system can be reconstructed by an interposition, or II) the lymphatic fluid can be drained extraanatomically (e.g. by a lymphatic-venous anastomosis). Further techniques are the following: free lymph node transplantation included in a free vascularized groin flap or autologous lymphatic vessel transfer or vein graft interposition (used for lymphatic vessel interposition). 5) Mass reduction such as dermolipectomy with subsequent split-thickness is a valuable option, which provides excellent volume reduction. 6) Defect coverage: A. Split- or full-thickness skin grafts are a common method of defect coverage (in cases of clean and well-vascularized wound bed and lacking donor skin, or if the graft bed is of questionable quality) using various allogenic or xenogenic skin substitute materials. B. Further methods offer a wide-range armamentarium of local and free fasciocutaneous and musculocutaneous flaps, e.g. after abdomino-perineal rectum extirpation using the vertical rectus-abdominis myocutaneous flap (VRAM) or propeller flaps according to the "angiosome". 7) Abdominal wall hernia closure with instable skin coverage, flap closure, either alone or in combination with mesh is superior to mesh closure only. 8) Free flaps: If there is no option for a local or pedicled flap available, free flaps can be well used for abdominal wall defect closure (complication rate in experienced hands is low). CONCLUSION: Plastic surgery is an indispensable partner for specific surgical problems and clinical situations of general and abdominal surgery, which indicates that each general and abdominal surgeon should be well notified on great options and surgical techniques offered by modern plastic surgery to achieve best outcomes and quality of life for patients and should combine the expertise of these two surgical disciplines.

A hybrid model for three-dimensional simulations of sprouting angiogenesis.

Recent advances in cancer research have identified critical angiogenic signaling pathways and the influence of the extracellular matrix on endothelial cell migration. These findings provide us with insight into the process of angiogenesis that can facilitate the development of effective computational models of sprouting angiogenesis. In this work, we present the first three-dimensional model of sprouting angiogenesis that considers explicitly the effect of the extracellular matrix and of the soluble as well as matrix-bound growth factors on capillary growth. The computational model relies on a hybrid particle-mesh representation of the blood vessels and it introduces an implicit representation of the vasculature that can accommodate detailed descriptions of nutrient transport. Extensive parametric studies reveal the role of the extracellular matrix structure and the distribution of the different vascular endothelial growth factors isoforms on the dynamics and the morphology of the generated vascular networks.

Critical roles of VEGF-C-VEGF receptor 3 in reconnection of the collecting lymph vessels in mice.

Molecular mechanisms of reconnection of collecting lymph vessels were analyzed by using murine popliteal prenodal lymph vessels. At 1 and 2 weeks after being divided by cutting the lymph vessel, lymphatic reconnection was frequently observed accompanied by mesh-like lymphatic channels. Electron microscopic study also showed a monolayer of endothelial cells in the newly developed lymph vessels. Smooth muscle markers were immunofluorescently demonstrated in the wall of the new vessels. At 1 week after the procedure of cutting, augmented expressions of VEGF receptors 1, 2 and 3 were found immunohistochemically at the site of the reconnected lymph vessels. The expression of mRNA for VEGF receptor 3 was enhanced at 5 days and 1 week in small pieces of the tissues containing the reconnected lymph vessels, compared with that in the corresponding tissues obtained with sham operated ones. The administration of VEGF-C at the cutting site of the collecting lymph vessel significantly increased the rate of the reconnected lymph vessels, whereas additional treatment with Flt4/Fc chimera protein significantly reduced the rate of the reconnected ones. These results suggest that activation of VEGF-C-VEGF receptor 3 has critical roles in reconnection of the collecting lymph vessels in adult mice.

Simulation of Multispecies Desmoplastic Cancer Growth via a Fully Adaptive Non-linear Full Multigrid Algorithm.

A fully adaptive non-linear full multigrid (FMG) algorithm is implemented to computationally simulate a model of multispecies desmoplastic tumor growth in three spatial dimensions. The algorithm solves a thermodynamic mixture model employing a diffuse interface approach with Cahn-Hilliard-type fourth-order equations that are coupled, non-linear, and numerically stiff. The tumor model includes extracellular matrix (ECM) as a major component with elastic energy contribution in its chemical potential term. Blood and lymphatic vasculatures are simulated via continuum representations. The model employs advection-reaction-diffusion partial differential equations (PDEs) for the cell, ECM, and vascular components, and reaction-diffusion PDEs for the elements diffusing from the vessels. This study provides the details of the numerical solution obtained by applying the fully adaptive non-linear FMG algorithm with finite difference method to solve this complex system of PDEs. The results indicate that this type of computational model can simulate the extracellular matrix-rich desmoplastic tumor microenvironment typical of fibrotic tumors, such as pancreatic adenocarcinoma.

Laminin-332 (Laminin-5) is the major motility ligand for B cell chronic lymphocytic leukemia.

Cell adhesion and motility are central aspects in the pathophysiology of B cell chronic lymphocytic leukemia (B-CLL), but the role of specific extracellular matrix proteins is still to be completely unveiled. Purified peripheral blood neoplastic cells of B-CLL patients migrated poorly on laminins-111,-411,-511, but showed pronounced motility on laminin (LM)-332 in a high percentage of cases. B-CLL cell motility on LM-332 was mediated by the alpha3beta1 integrin and was preferentially observed in cells carrying a mutated IgV(H) gene profile. Within normal lymph nodes, LM-332 was circumscribed around blood vessels and to areas corresponding to marginal zones, where it was deposited in a pattern reminiscent of reticular fibers. Conversely, in B-CLL involved lymph nodes, a positive LM-332 reticular mesh was diffusely evident, throughout the disrupted nodal architecture. In the present study we identified LM-332 as a crucial motility-promoting factor for B-CLL lymphocytes and as a potential constituent favoring the dissemination of B-CLL lymphocytes through vascular basement membranes and possibly lymph node compartments.