A novel therapy to promote axonal fusion in human digital nerves.

BACKGROUND: Peripheral nerve injury can have a devastating impact on our military and veteran population. Current strategies for peripheral nerve repair include techniques such as nerve tubes, nerve grafts, tissue matrices, and nerve growth guides to enhance the number of regenerating axons. Even with such advanced techniques, it takes months to regain function. In animal models, polyethylene glycol (PEG) therapy has shown to improve both physiologic and behavioral outcomes after nerve transection by fusion of a portion of the proximal axons to the distal axon stumps. The objective of this study was to show the efficacy of PEG fusion in humans and to retrospectively compare PEG fusion to standard nerve repair. METHODS: Patients with traumatic lacerations involving digital nerves were treated with PEG after standard microsurgical neurorrhaphy. Sensory assessment after injury was performed at 1 week, 2 weeks, 1 month, and 2 months using static two-point discrimination and Semmes-Weinstein monofilament testing. The Medical Research Council Classification (MRCC) for Sensory Recovery Scale was used to evaluate the level of injury. The PEG fusion group was compared to patient-matched controls whose data were retrospectively collected. RESULTS: Four PEG fusions were performed on four nerve transections in two patients. Polyethylene glycol therapy improves functional outcomes and speed of nerve recovery in clinical setting assessed by average MRCC score in week 1 (2.8 vs 1.0, p = 0.03). At 4 weeks, MRCC remained superior in the PEG fusion group (3.8 vs 1.3, p = 0.01). At 8 weeks, there was improvement in both groups with the PEG fusion cohort remaining statistically better (4.0 vs 1.7, p = 0.01). CONCLUSION: Polyethylene glycol fusion is a novel therapy for peripheral nerve repair with proven effectiveness in animal models. Clinical studies are still in early stages but have had encouraging results. Polyethylene glycol fusion is a potential revolutionary therapy in peripheral nerve repair but needs further investigation. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Difficult Diagnosis of Colon Adenocarcinoma Metastasis to Retina: A Case Report and Literature Review.

Intraocular metastatic tumors have been increasingly reported in the recent past. Unlike choroidal metastasis, metastasis to retina is very rare and so far has been reported in very few case reports only. A 56 year-old male who presented with a history of adenocarcinoma of the cecum and underwent lap colectomy for the primary cecal tumor, received adjuvant chemotherapy for a year after surgery and decided to stop. He was also diagnosed with metastasis to liver and lung at this time. He presented with left eye pain, pressure and decreased vision suspicious for retinal metastasis from cecal primary lesion, 2 years after initial diagnosis. A mass of 5 x 10 mm was found on ophthalmoscopic examination and on ultrasound of the eye, in spite of normal results of MRI of the orbit. Palliative radiation therapy of the left eye resulted in decreased eye pressure and improved vision. As retinal metastasis carries a poorer prognosis due to higher risk of spread to central nervous system, the diagnosis of retinal metastasis in case of gastrointestinal cancers patients who present with vision changes should be made urgently. These patients should be thoroughly investigated with a synergistic approach of opthalmoscopic examination, ultrasound of the eye along with other imaging modalities like MRI of the orbit and just not MRI of orbit. Immediate action in the form of surgical or radiation treatments of the metastatic tumors of the eye should be instituted early on for a better prognosis.

Adjuvant neurotrophic factors in peripheral nerve repair with chondroitin sulfate proteoglycan-reduced acellular nerve allografts.

BACKGROUND: Acellular nerve allografts are now standard tools in peripheral nerve repair because of decreased donor site morbidity and operative time savings. Preparation of nerve allografts involves several steps of decellularization and modification of extracellular matrix to remove chondroitin sulfate proteoglycans (CSPGs), which have been shown to inhibit neurite outgrowth through a poorly understood mechanism involving RhoA and extracellular matrix-integrin interactions. Chondroitinase ABC (ChABC) is an enzyme that degrades CSPG molecules and has been shown to promote neurite outgrowth after injury of the central and peripheral nervous systems. Variable results after ChABC treatment make it difficult to predict the effects of this drug in human nerve allografts, especially in the presence of native extracellular signaling molecules. Several studies have shown cross-talk between neurotrophic factor and CSPG signaling pathways, but their interaction remains poorly understood. In this study, we examined the adjuvant effects of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor (GDNF) on neurite outgrowth postinjury in CSPG-reduced substrates and acellular nerve allografts. MATERIALS AND METHODS: E12 chicken DRG explants were cultured in medium containing ChABC, ChABC + NGF, ChABC + GDNF, or control media. Explants were imaged at 3 d and neurite outgrowths measured. The rat sciatic nerve injury model involved a 1-cm sciatic nerve gap that was microsurgically repaired with ChABC-pretreated acellular nerve allografts. Before implantation, nerve allografts were incubated in NGF, GDNF, or sterile water. Nerve histology was evaluated at 5 d and 8 wk postinjury. RESULTS: The addition of GDNF in vitro produced significant increase in sensory neurite length at 3 d compared with ChABC alone (P < 0.01), whereas NGF was not significantly different from control. In vivo adjuvant NGF produced increases in total myelinated axon count (P < 0.005) and motor axon count (P < 0.01), whereas significantly reducing IB4+ nociceptor axon count (P < 0.01). There were no significant differences produced by in vivo adjuvant GDNF. CONCLUSIONS: This study provides initial evidence that CSPG-reduced nerve grafts may disinhibit the prosurvival effects of NGF in vivo, promoting motor axon outgrowth and reducing regeneration of specific nociceptive neurons. Our results support further investigation of adjuvant NGF therapy in CSPG-reduced acellular nerve grafts.

Thyroidectomy as primary treatment optimizes body mass index in patients with hyperthyroidism.

OBJECTIVE: The purpose of this study was to determine how the timing of thyroidectomy influenced postoperative weight change. METHODS: We conducted a two-institution study, identifying patients treated with total thyroidectomy for hyperthyroidism. Patients were classified as 'early' if they were referred for surgery as the first treatment option, or 'delayed' if they were previously treated with radioactive iodine (RAI). Groups were compared with the Student's t-test or χ (2) test where appropriate. RESULTS: There were 204 patients undergoing thyroidectomy for hyperthyroidism. Of these, 171 patients were classified as early and 33 were classified as delayed. Overall, patients gained 6.0 % ± 0.8 of their preoperative body weight at last follow-up. Preoperative body mass indexes (BMIs) were similar between groups (p = 0.98), and the median follow-up time was 388 days (range 15-1,584 days). Both groups gained weight until they achieved a normal thyroid-stimulating hormone (TSH) postoperatively. After achieving a normal TSH, the early group stabilized or lost weight (-0.2 lbs/day), while the delayed group continued to gain weight (0.02 lbs/day; p = 0.61). At last follow-up, there were significantly more patients in the delayed group who increased their BMI category compared with the early group (42.4 vs. 21.6 %; p = 0.01). Twice as many patients in the delayed group moved up or into an unhealthy BMI category (overweight or obese) compared with the early group (39.4 vs. 19.3 %; p = 0.01). CONCLUSIONS: Compared with patients initially treated with RAI, patients with hyperthyroidism who underwent surgery as the first treatment were less likely to become overweight or obese postoperatively.

Total thyroidectomy for Graves' disease: compliance with American Thyroid Association guidelines may not always be necessary.

BACKGROUND: Total thyroidectomy (TT) is the preferred operative approach to Graves' disease. Current guidelines of the American Thyroid Association call for the administration of potassium iodide (KI) and achievement of euthyroid state before operation. Small numbers and a mixture of operative approaches spanning several decades hinder previous operative series. We present the outcomes for TT at a single high-volume center. METHODS: A retrospective cohort study was conducted on 165 patients undergoing TT for Graves' disease from July 2007 to May 2012. RESULTS: Mean age was 43 years (range, 17-78), and 128 patients (78%) were female. A total of 95% of patients were on methimazole or propylthiouracil, and 42% remained hyperthyroid at time of TT. Only 3 (2%) patients received KI. Mean operative time was 132 minutes (range, 59-271). Mean gland size and blood loss were 41 g (range, 8-180) and 55 mL (range, 10-1050), respectively. No patient developed thyroid storm. Median follow-up was 7.5 months. Temporary and permanent hypocalcemia developed in 51 (31%) and 2 patients (1.2%), respectively. Temporary and permanent recurrent laryngeal nerve paresis occurred in 12 (7%) and one (0.6%) patient, respectively. Sixty-one (37%) patients experienced at least one complication. On multivariate analysis, patient age younger than 45 years (odds ratio 2.93, 95% confidence interval 1.39-6.19) and obesity (odds ratio 2.11, 95% confidence interval 1.00-4.43) were associated with the occurrence of complications. CONCLUSION: This high-volume surgeon experience demonstrates no appreciable detriment to patient outcomes when recommendations of the American Thyroid Association for routine use of KI and euthyroid state before thyroidectomy are not met. Transient hypocalcemia and hoarseness are frequent complications of TT for Graves' disease, resolving within 6 months in most patients. Age younger than 45 years and obesity are risk factors for postoperative complications.

Toxic nodular goiter and cancer: a compelling case for thyroidectomy.

BACKGROUND: Recent American Thyroid Association guidelines call for thyroidectomy or (131)I (Recommendation 31) in managing hyperthyroidism due to toxic nodular goiter (TNG). Concern for concomitant malignancy favors surgery. A 3 % thyroid cancer incidence in TNG patients has been reported, yet recent studies suggest this rate is underestimated. This multi-institutional study examined cancer incidence in TNG patients referred to surgery. METHODS: Patients referred for thyroidectomy at three tertiary-care institutions were included (2002-2011). Patients with concurrent indeterminate or malignant diagnosis by fine-needle aspiration (FNA) were excluded. Cancer incidence in TNG patients was determined. Fisher's exact and chi-square tests and nonparametric t tests were used. RESULTS: Among 2,551 surgically treated patients, 164 had TNG (6.4 %). Median age at presentation was 49.7 years, and 86 % were female. Overall cancer incidence was 18.3 % (30 of 164), and rates were not significantly different between institutions. A significantly greater cancer rate was noted in toxic multinodular goiter versus single toxic nodule patients (21 vs. 4.5 %, P < 0.05). Mean tumor size was 0.71 cm (range 0.1-1.5 cm; 23 % ≥1 cm). Most patients underwent total or near-total thyroidectomy. There were no significant differences in tumor sizes among institutions (P > 0.05). No significant cancer association was noted with age, preoperative dominant nodule size, lymphocytic thyroiditis or preoperative FNA (P > 0.05). CONCLUSIONS: These data demonstrate a higher than expected incidental cancer rate in TNG patients compared to historical reports (18.3 vs. 3 %). This higher cancer incidence may alter the risk/benefit analysis regarding TNG treatment. This information should be provided to TNG patients before decision making regarding treatment.