C. Campisi

Collagen (NeuraGen®) nerve conduits and stem cells for peripheral nerve gap repair

Collagen nerve guides are used clinically for peripheral nerve defects, but their use is generally limited to lesions up to 3 cm. In this study we combined collagen conduits with cells as an alternative strategy to support nerve regeneration over longer gaps. In vitro cell adherence to collagen conduits (NeuraGen(®) nerve guides) was assessed by scanning electron microscopy. For in vivo experiments, conduits were seeded with either Schwann cells (SC), SC-like differentiated bone marrow-derived mesenchymal stem cells (dMSC), SC-like differentiated adipose-derived stem cells (dASC) or left empty (control group), conduits were used to bridge a 1cm gap in the rat sciatic nerve and after 2-weeks immunohistochemical analysis was performed to assess axonal regeneration and SC infiltration. The regenerative cells showed good adherence to the collagen walls. Primary SC showed significant improvement in distal stump sprouting. No significant differences in proximal regeneration distances were noticed among experimental groups. dMSC and dASC-loaded conduits showed a diffuse sprouting pattern, while SC-loaded showed an enhanced cone pattern and a typical sprouting along the conduits walls, suggesting an increased affinity for the collagen type I fibrillar structure. NeuraGen(®) guides showed high affinity of regenerative cells and could be used as efficient vehicle for cell delivery. However, surface modifications (e.g. with extracellular matrix molecule peptides) of NeuraGen(®) guides could be used in future tissue-engineering applications to better exploit the cell potential.

Evolution of chylous fistula management after neck dissection.

Purpose of reviewThe present review is focused on the management of lymphatic, chylous, and thoracic duct lesions following head and neck surgery, with particular attention to these complications after neck dissection. Postoperative scenarios may include chylous fistula, chylothorax, chylomediastinum, chylopericardium, lymphocele, persistent lymphorrhea, and secondary lymphedema. Recent findingsThere is a paucity of literature on the treatment of lymphatic, chylous, and thoracic duct injuries following head and neck surgery; however, this review suggests that the most appropriate treatment should include both conservative and surgical approaches. Nonsurgical options consist of low-fat diet with medium-chain triglycerides, total parenteral nutrition, careful monitoring of fluid and electrolytes, drainage of the leakage, somatostatin analogs such as octreotide, and negative-pressure wound therapy. On the other hand, surgical management includes therapeutic percutaneous lymphography-guided thoracic duct cannulation and embolization, thoracic duct ligation, excision and imbrication of leaking lymphatics, chylous fistula surgical/microsurgical repair, fistula closure by locoregional flaps, video-assisted thoracoscopic surgery, thoracotomy, pleurodesis and decortication, pericardial ‘window’, and pleura–venous/pleura–peritoneal shunts. In addition, single or, preferably, multiple lymphovenous anastomoses may be taken into account. SummaryThe various possible clinical presentations of such challenging lymphatic, chylous, and thoracic duct injuries require an appropriate multidisciplinary approach by experienced teams. Primary prevention of these complications can be achieved through adequate surgical planning to minimize lesions, including structured and thorough patient assessment, and centralization of resources and teams.

Lymphatic microsurgery to treat lymphedema: techniques and indications for better results.

AbstractThis study aimed to report new clinical approaches to the treatment of lymphatic disorders by microsurgical techniques based on histological and immunohistochemical findings. The authors’ wide clinical experience in the treatment of patients with peripheral lymphedema by microsurgical techniques is reported. Microsurgical methods included derivative lymphatic-venous anastomoses and lymphatic reconstruction by interpositioned vein grafted shunts. In all patients, lymphatic and lymph nodal tissues were sent for histological assessment, together with specimen of the interstitial matrix. Diagnostic investigations consisted in venous duplex scan and lymphoscintigraphy. Results were assessed clinically by volumetry performed preoperatively and postoperatively at 3 to 6 months and at 1, 3, and 5 years. The outcome obtained in treating lymphedemas at different stages was analyzed for volume reduction, stability of results with time, reduction of dermatolymphangioadenitis attacks, necessity of wearing elastic supports, and use of conservative measures postoperatively. Microsurgical lymphatic derivative and reconstructive techniques allow bringing about positive results in the treatment of peripheral lymphedema, above all in early stages when tissular changes are slight and allow almost a complete restore of lymphatic drainage.

Lymphatic complications in surgery: Possibility of prevention and therapeutic options

The problem of prevention of lymphatic complications in surgery is extremely important if we think about the frequency of both early complications such as lymphorrhea, lymphocele, wound dehiscence and infections and late complications such as lymphangitis and lymphedema. Nowadays, it is possible to identify risk patients and prevent these lesions or treat them at an early stage. This report helps to demonstrate how it is important to integrate diagnostic and clinical findings to better understand how to properly identify risk patients for lymphatic injuries and, therefore, when it is useful and proper to do prevention. Authors report their experiences in the prevention and treatment of lymphatic injuries after surgical operations and trauma. After an accurate diagnostic approach, prevention is based on different technical procedures among which microsurgical procedures. It is very important to follow-up the patient not only clinically but also by lymphoscintigraphy. A protocol of prevention of secondary limb lymphedema was proposed and it includes, from the diagnostic point of view, lymphoscintigraphy and, as concerns therapy, it recognizes also a role to early microsurgery. It is necessary to accurately follow-up the patient who has undergone an operation at risk for the appearance of lymphatic complications and, even better, to assess clinically and by lymphoscintigraphy the patient before surgical operation.

LYMPHA Technique to Prevent Secondary Lower Limb Lymphedema

BackgroundInguinofemoral lymphadenectomy carries a high risk of lower limb lymphedema. This report describes the feasibility of performing multiple lymphatic-venous anastomoses (MLVA) after inguinofemoral lymph node completion (LYMPHA technique) and the possible benefit of LYMPHA for preventing lymphedema.MethodsBetween February, 2011 and October, 2014, 11 patients with vulvar cancer and 16 patients with melanoma of the trunk requiring inguinofemoral lymphadenectomy underwent lymph node dissection and the LYMPHA technique. Blue dye was injected into the thigh 10 min before surgery. Lymphatics afferent to the blue nodes were used to perform MLVA using a collateral branch of the great saphenous vein.ResultsThe mean age of patients in the vulvar cancer group was 52 years (range, 48–75 years). The melanoma group comprised seven men and nine women with a mean age of 41 years (range, 37–56 years). Of the 16 patients, 5 with vulvar cancer underwent bilateral inguinofemoral lymphadenectomy, whereas the remaining 6 patients with vulvar cancer and all 16 patients with melanoma of the trunk had unilateral node dissection. All the patients were treated by the LYMPHA technique. No lymphocele or infectious complications occurred. Transient lower-extremity edema occurred for one melanoma patient (6.25 %), which resolved after 2 months, and permanent lower-extremity edema occurred for one patient (9 %) with vulvar cancer.ConclusionsThe LYMPHA technique appears to be feasible, safe, and effective for the prevention of lower limb lymphedema, thereby improving the patient’s quality of life and decreasing health care costs.

Surgical Treatment for Lymphedema: Optimal Timing and Optimal Techniques

and may have indicated a fundamental difference in approach of some surgeons undertaking OPD. We do share the authors’ views on LPD and believe it does have an important role to play in the management of periampullary carcinomas. However, before its widespread adoption to clinical practice, we feel a multicenter randomize controlled trial of LPD vs OCD for patients with periampullary carcinomas (head of pancreas, ampullary, and distal common bile duct) should be performed using a strict protocol for documenting histopathology and perioperative morbidity to be certain of the benefits of this technically challenging operation.

Fibro-Lipo-Lymph-Aspiration With a Lymph Vessel Sparing Procedure to Treat Advanced Lymphedema After Multiple Lymphatic-Venous Anastomoses: The Complete Treatment Protocol.

Background In lymphedema, excess adipose tissue occurs with progression of the disease because of chronic lymph stasis, impeding lymphatic flow. Recently, liposuction has been used as a less-invasive procedure to remove this excess tissue. Given the existing poor lymph drainage in patients with lymphatic diseases, extra caution should be taken to avoid damaging lymphatic vessels during liposuction. We developed a new technique (Fibro-Lipo-Lymph-Aspiration with a Lymph Vessel Sparing Procedure [FLLA-LVSP]) to improve chronic swelling in patients with advanced lymphedema. The FLLA-LSVP highlights the superficial lymphatic pathways in the treated limb. This visibility allows surgeons to avoid these pathways, while removing the maximum amount of excess tissue. Method One hundred forty-six patients with primary or secondary lymphedema that had already been treated by lymphatic microsurgery, in Genoa, Italy, were included in this retrospective study. All patients had residual fibrotic/adipose tissue, resistant to conservative treatments. Indocyanine green fluorescent dye and Blue Patent Violet dye were injected laterally/medially to the main superficial veins at the wrist/ankle of the limb to be treated. Using a photodynamic camera, the superficial lymphatic network was made visible and sketched onto the skin in indelible ink. After the microlymphography, the excess adipose tissue was carefully aspirated. Preoperative and postoperative excess limb volume was calculated using circumferential measurements and the formula of a frustum. Results For the upper limb, 0.80 L, on average, and 2.42 L for the lower limb were removed with the FLLA-LVSP. For the upper limb, there was an average presurgery excess volume of 20.19%, which reduced to 2.68% after the FLLA-LVSP (Z score = −6.90, P < 0.001). Similarly, for the lower limb, there was an average presurgery excess limb volume of 21.24% and a reduction to 2.64% postoperatively (Z score = −3.57, P < 0.01). Immediate postoperative microlymphography and Blue Patent Violet test confirmed no lymphatic complications. No episodes of postoperative infection occurred. Conclusions The FLLA-LVSP is efficient. An entire leg can be completed within 90 minutes. Recovery time is short, and cosmetic results are immediate. More importantly, the removal of excess tissue is completed without further damage to lymphatic vessels. When used after microsurgery, FLLA-LVSP offers the possibility of removing almost all obstacles to lymphatic flow.

Reconstructive Microsurgery for Lymphedema: While the Early Bird Catches the Worm, the Late Riser Still Benefits

We read with interest Doscher and colleagues’ collective review, especially given the citations relevant to our group. Although we agree with the general principle that patients with chronic, end-stage lymphedema with fibrotic components are more difficult to treat than those with earlier stages, we cannot completely agree with the premise that microsurgical reconstructive techniques are not appropriate in the treatment of these chronic cases. A thorough understanding of the underlying cause of lymphedema is necessary to illustrate our point of view. Lymphedema, by definition, occurs when the transport capacity of the lymphatic system falls below the overall volume of fluid in the system, resulting in lymph-stasis in the interstitial space. Recent mouse models show the physiologic effects of this lymph-stasis with regard to both primary (lymphatic malformations) and secondary (obstructive) lymphedemas. Lymph-stasis, in models of secondary lymphedema (eg, from damage to lymph nodes in mouse tails), leads to hyperplasia of lymph channels in the tail as a response to increased fluid. These hyperplastic channels are less efficient and leak fluid, further increasing the swelling. Lymph-stasis is followed, in some models, by a rapid accumulation of lipids in the extracellular matrix, which is likely to be a physiologic response to increased hydraulic conductivity of the cells from dermal swelling as an attempt to normalize this conductivity through increased tissue formation; however, in reality, this tissue further impedes the removal of the fluid in the interstitial space. Taken together, these studies provide a good explanation of end-stage lymphedema in humans, in whom recent models state that chronic swelling is a result of both lymph-stasis and an overgrowth of adipose and fibrotic tissue. This lymph-stasis is also implicated in decreased immune-cell trafficking, where dendritic cells accumulate in the dermis and fail to migrate as usual to the nodes,

Lymphedema staging and surgical indications in geriatric age

Background Lymphedema, refractory to non-operative methods [1], may be managed by surgical treatment. Indications include insufficient lymphedema reduction by well performed medical and physical therapy (less than 50%), recurrent episodes of lymphangitis, intractable pain, worsening limb function, patient unsatisfied of the results obtained by non-operative methods and willing to proceed with surgical options. In this study Authors report a new lymphedema staging and their wide clinical experience in the microsurgical treatment of peripheral lymphedema [2,3] in geriatric age. Materials and methods More than 500 patients with peripheral lymphedema in geriatrics have been treated with microsurgical techniques. Derivative lymphatic micro-vascular procedures recognize today its most exemplary application in multiple lymphatic-venous anastomoses (LVA). In the case of associated venous disease reconstructive lymphatic microsurgery techniques have been developed. Objective assessment was undertaken by water volumetry and lymphoscintigraphy. Lymphedema staging is reported in Table 1. Results Subjective improvement was noted in 87% of patients. Objectively, volume changes showed a significant improvement in 83%, with an average reduction of 67% of the excess volume (Figure 1). Of those patients followed-up, 85% have been able to discontinue the use of conservative measures, with an average follow-up of more than 10 years and average reduction in excess volume of 69%. There was a 87% reduction in the incidence of cellulitis after microsurgery. Conclusions

Obesity and lymphedema in geriatrics: combined therapeutical approaches

Background Obesity combined with lymphedema, especially in geriatrics, is more than the sum of the two diseases [1] because it causes the diaphragm to be above its normal position, impairing its movement. As a consequence, a fundamental mechanism that supports lymph flow is significantly decreased. Obesity associated with lymphedema represents a cause of a highly invalidating condition. The purpose of this preliminary report is to propose a system of treatment, assessing the efficacy of a combined approach of lymphostatic disease in obese geriatric patients.