Long-Term Outcomes after Double Free Flap Reconstruction for Locally Advanced Head and Neck Cancer.

BACKGROUND: The use of simultaneous, multiple free flaps has become a reliable reconstructive option in patients with extensive composite defects after resection of locally advanced head and neck cancer. However, some reluctance remains among reconstructive surgeons with concerns regarding flap outcomes and limited patient survival. Therefore, we evaluated complications, long-term patient survival, and patient-reported outcomes following these extensive head and neck reconstructions. METHODS: All consecutive patients treated with multiple free flaps for reconstruction of extensive composite defects after resection of locally advanced head and neck cancer between 1999 and 2014 were retrospectively reviewed. Patient charts were evaluated for demographics, treatment details, complications, and patient survival. In addition, all patients alive at the start of the study were asked to complete the 10-item Eat Assessment Tool (EAT-10) and the Intelligibility Rating Scale (IRS). RESULTS: Eighty-four simultaneous, multiple free flaps were performed in 42 patients. The predominant free flap combination consisted of a fibula with either an anterolateral thigh (n = 22) or a radial forearm flap (n = 14). Complete flap survival was 95%. Nineteen patients were still alive with a mean follow-up of 55 months. Five-year patient survival was 46.3%. Mean EAT-10 score was 8.4 (range: 0-29), with only one patient reporting problematic swallowing. Ninety percent of the patients had moderate to good speech intelligibility with the IRS. CONCLUSION: Multiple, simultaneous free flaps can be performed safely, leading to acceptable long-term patient survival and patient-reported functional outcomes. Our study demonstrates that it is worthwhile to perform these challenging microvascular reconstructions in patients with locally advanced head and neck cancer.

An early diagnostic tool for diabetic peripheral neuropathy in rats.

The skin's rewarming rate of diabetic patients is used as a diagnostic tool for early diagnosis of diabetic neuropathy. At present, the relationship between microvascular changes in the skin and diabetic neuropathy is unclear in streptozotocin (STZ) diabetic rats. The aim of this study was to investigate whether the skin rewarming rate in diabetic rats is related to microvascular changes and whether this is accompanied by changes observed in classical diagnostic methods for diabetic peripheral neuropathy. Computer-assisted infrared thermography was used to assess the rewarming rate after cold exposure on the plantar skin of STZ diabetic rats' hind paws. Peripheral neuropathy was determined by the density of intra-epidermal nerve fibers (IENFs), mechanical sensitivity, and electrophysiological recordings. Data were obtained in diabetic rats at four, six, and eight weeks after the induction of diabetes and in controls. Four weeks after the induction of diabetes, a delayed rewarming rate, decreased skin blood flow and decreased density of IENFs were observed. However, the mechanical hyposensitivity and decreased motor nerve conduction velocity (MNCV) developed 6 and 8 weeks after the induction of diabetes. Our study shows that the skin rewarming rate is related to microvascular changes in diabetic rats. Moreover, the skin rewarming rate is a non-invasive method that provides more information for an earlier diagnosis of peripheral neuropathy than the classical monofilament test and MNCV in STZ induced diabetic rats.

Long-term follow-up of peptidergic and nonpeptidergic reinnervation of the epidermis following sciatic nerve reconstruction in rats.

OBJECT: Peripheral nerve injuries are a commonly encountered clinical problem and often result in long-term functional deficits. The current gold standard for transected nerves is an end-to-end reconstruction, which results in the intermittent appearance of neuropathic pain. METHODS: To improve our understanding of the relation between this type of reconstruction and neuropathic pain, the authors transected and immediately end-to-end reconstructed the sciatic nerve in rats. The effect of this procedure on neuropathic pain, as measured by thermal and mechanical hypersensitivity at 4 different time points (5, 10, 20, and 30 weeks), was related to the density of peptidergic and nonpeptidergic fiber innervation in the glabrous skin of rats' hind paws. RESULTS: Thermal hypersensitivity occurring 20 weeks after reconstruction was accompanied by a significant increase in peptidergic epidermal fibers. However, the lesion-induced reduction in the density of nonpeptidergic epidermal fibers remained decreased at all experimental time points. Moreover, temporal collateral sprouting by undamaged saphenous nerve was visualized using the recently revised Evans blue extravasation technique. Strikingly, as the sciatic nerve repopulated rats' hind paw, the saphenous nerve withdrew to its original territory. CONCLUSIONS: The authors conclude that the transient thermal hypersensitivity is related to increased density of epidermal peptidergic fibers, which mainly originate from regenerating fibers. Furthermore, a changed composition in the peptidergic and nonpeptidergic epidermal fibers is demonstrated following end-to-end reconstruction of the sciatic nerve.

Spatiotemporal dynamics of re-innervation and hyperinnervation patterns by uninjured CGRP fibers in the rat foot sole epidermis after nerve injury.

The epidermis is innervated by fine nerve endings that are important in mediating nociceptive stimuli. However, their precise role in neuropathic pain is still controversial. Here, we have studied the role of epidermal peptidergic nociceptive fibers that are located adjacent to injured fibers in a rat model of neuropathic pain. Using the Spared Nerve Injury (SNI) model, which involves complete transections of the tibial and common peroneal nerve while sparing the sural and saphenous branches, mechanical hypersensitivity was induced of the uninjured lateral (sural) and medial (saphenous) area of the foot sole. At different time points, a complete foot sole biopsy was taken from the injured paw and processed for Calcitonin Gene-Related Peptide (CGRP) immunohistochemistry. Subsequently, a novel 2D-reconstruction model depicting the density of CGRP fibers was made to evaluate the course of denervation and re-innervation by uninjured CGRP fibers. The results show an increased density of uninjured CGRP-IR epidermal fibers on the lateral and medial side after a SNI procedure at 5 and 10 weeks. Furthermore, although in control animals the density of epidermal CGRP-IR fibers in the footpads was lower compared to the surrounding skin of the foot, 10 weeks after the SNI procedure, the initially denervated footpads displayed a hyper-innervation. These data support the idea that uninjured fibers may play a considerable role in development and maintenance of neuropathic pain and that it is important to take larger biopsies to test the relationship between innervation of injured and uninjured nerve areas.