Insights into pediatric rhabdomyosarcoma research: Challenges and goals.

Overall survival rates for pediatric patients with high-risk or relapsed rhabdomyosarcoma (RMS) have not improved significantly since the 1980s. Recent studies have identified a number of targetable vulnerabilities in RMS, but these discoveries have infrequently translated into clinical trials. We propose streamlining the process by which agents are selected for clinical evaluation in RMS. We believe that strong consideration should be given to the development of combination therapies that add biologically targeted agents to conventional cytotoxic drugs. One example of this type of combination is the addition of the WEE1 inhibitor AZD1775 to the conventional cytotoxic chemotherapeutics, vincristine and irinotecan.

Thoracic outlet syndrome: a review.

BACKGROUND: : Arterial and venous thoracic outlet syndrome (TOS) were recognized in the late 1800s and neurogenic TOS in the early 1900s. Diagnosis and treatment of the 2 vascular forms of TOS are generally accepted in all medical circles. On the other hand, neurogenic TOS is more difficult to diagnose because there is no standard objective test to confirm clinical impressions. REVIEW SUMMARY: : The clinical features of arterial, venous, and neurogenic TOS are described. Because neurogenic TOS is by far the most common type, the pathology, pathophysiology, diagnostic tests, differential and associate diagnoses, and treatment are detailed and discussed. The controversial area of objective and subjective diagnostic criteria is addressed. CONCLUSION: : Arterial and venous TOS are usually not difficult to recognize and the diagnosis can be confirmed by angiography. The diagnosis of neurogenic TOS is more challenging because its symptoms of nerve compression are not unique. The clinical diagnosis relies on documenting several positive findings on physical examination. To date there is still no reliable objective test to confirm the diagnosis, but measurements of the medial antebrachial cutaneous nerve appear promising.

Etiology and pathology.

Until the 1920s, TOS was believed to be a vascular condition caused by compression of the subclavian artery by a congenital anomaly, either a cervical rib or tight anterior scalen muscle. Today it is regarded primarily as a neurologic condition caused by neck trauma injuring and scarring the scalene muscles.

Supraclavicular first rib resection and total scalenectomy: technique and results.

The supraclavicular approach has been a successful route for thoracic outlet decompression. It permits many more options than the transaxillary route. Anterior and middle scalenectomy, together with brachial plexus neurolysis can be performed with excellent exposure. The same incision can be used to perform cervical or first rib resection, although the success rate is not significantly improved by removing ribs. The 5-year success rate for scalenectomy with or without first rib resection using life table methods is approximately 70%.

Venous thoracic outlet syndrome.

Venous thoracic outlet syndrome is caused by subclavian vein obstruction with or without thrombosis. The primary symptom is arm swelling, frequently accompanied by cyanosis, pain, and occasionally paresthesias. Venography is the only reliable diagnostic tool. Therapy has three goals: (1) remove the thrombus (in thrombotic cases), (2) remove the extrinsic compression, and in a minority of cases, (3) remove the intrinsic stenosis.

Observations on the use of seprafilm on the brachial plexus in 249 operations for neurogenic thoracic outlet syndrome.

PURPOSE: Seprafilm was initially used successfully as a membrane to reduce abdominal adhesions. Subsequently it was tried in a number of other areas to reduce postoperative scarring. Seprafilm was employed in this study to see if it would reduce postoperative scarring after supraclavicular thoracic outlet decompression for neurogenic thoracic outlet syndrome (NTOS). MATERIAL AND METHODS: There were 249 operations for primary NTOS (185) and recurrent NTOS (64). Seprafilm was applied to the nerve roots at the end of each procedure. Diagnosis was established by careful history and extensive physical exam consisting of several provocative maneuvers. Scalene muscle block confirmed the diagnosis. RESULTS: Success rates for primary operations, 1-2 years postoperation were 74% for scalenectomy without first rib resection and 70% for scalenectomy with first rib resection. For reoperations, success rate for scalenectomy and neurolysis after transaxillary rib resection was 78% whereas success rate for neurolysis after supraclavicular scalenectomy was 68%. Seprafilm did not significantly improve overall results compared to our results 15 years ago, although in reoperations there was a trend toward improvement with Seprafilm. Observations in 10 reoperations after use of Seprafilm revealed that there were fewer adhesions between fat pad and nerve roots, making it much easier to find the nerve roots. Recurrence was because of scar formation around individual nerve roots. CONCLUSION: Seprafilm made reoperations easier by reducing scarring between scalene fat pad and brachial plexus. However, it did not prevent scar tissue forming around the individual nerve roots nor did it significantly lower the failure rate for primary operations. The trend supported the use of Seprafilm in reoperations.

Diagnosis of thoracic outlet syndrome.

Thoracic outlet syndrome (TOS) is a nonspecific label. When employing it, one should define the type of TOS as arterial TOS, venous TOS, or neurogenic TOS. Each type has different symptoms and physical findings by which the three types can easily be identified. Neurogenic TOS (NTOS) is by far the most common, comprising well over 90% of all TOS patients. Arterial TOS is the least common accounting for no more than 1%. Many patients are erroneously diagnosed as "vascular" TOS, a nonspecific misnomer, whereas they really have NTOS. The Adson Test of noting a radial pulse deficit in provocative positions has been shown to be of no clinical value and should not be relied upon to make the diagnosis of any of the three types. The test is normal in most patients with NTOS and at the same time can be positive in many control volunteers. Arterial TOS is caused by emboli arising from subclavian artery stenosis or aneurysms. Symptoms are those of arterial ischemia and x-rays almost always disclose a cervical rib or anomalous first rib. Venous TOS presents with arm swelling, cyanosis, and pain due to subclavian vein obstruction, with or without thrombosis. Neurogenic TOS is due to brachial plexus compression usually from scarred scalene muscles secondary to neck trauma, whiplash injuries being the most common. Symptoms include extremity paresthesia, pain, and weakness as well as neck pain and occipital headache. Physical exam is most important and includes several provocative maneuvers including neck rotation and head tilting, which elicit symptoms in the contralateral extremity; the upper limb tension test, which is comparable to straight leg raising; and abducting the arms to 90 degrees in external rotation, which usually brings on symptoms within 60 seconds.

Subclavian vein obstruction without thrombosis.

BACKGROUND: Unilateral arm swelling caused by subclavian vein obstruction without thrombosis is an uncommon form of venous thoracic outlet syndrome (TOS). In 87 patients with venous TOS, only 21 patients had no thrombosis. We describe the diagnosis and treatment of these patients. MATERIAL AND METHODS: Twenty-one patients with arm swelling, cyanosis, and venograms demonstrating partial subclavian vein obstruction were treated with transaxillary first rib resection and venolysis. RESULTS: Eighteen (86%) of 21 patients had good-to-excellent improvement of symptoms. There were two failures (9%). CONCLUSIONS: Unilateral arm swelling without thrombosis, when not caused by lymphatic obstruction, may be due to subclavian vein compression at the costoclavicular ligament because of compression either by that ligament or the subclavius tendon most often because of congenital close proximity of the vein to the ligament. Arm symptoms of neurogenic TOS, pain, and paresthesia often accompany venous TOS while neck pain and headache, other common symptoms of neurogenic TOS, are infrequent. Diagnosis was made by dynamic venography. First rib resection, which included the anterior portion of rib and cartilage plus division of the costoclavicular ligament and subclavius tendon, proved to be effective treatment.

Management of cervical ribs and anomalous first ribs causing neurogenic thoracic outlet syndrome.

OBJECTIVE: Cervical and anomalous first ribs are rare conditions, occurring in less than 1% of the population. This manuscript reviews our management of neurogenic thoracic outlet syndrome (TOS) associated with these congenital anomalies. METHODS: During the past 26 years, 65 operations were performed for abnormal ribs that produced symptoms of TOS. Of these, 54 operations were for neurogenic TOS and are covered in this paper. Indications for surgery were disabling pain and paresthesia and failure to respond to conservative treatment. Surgical technique for neurogenic TOS was supraclavicular cervical rib resection and scalenectomy without first rib resection in 22 cases, supraclavicular cervical and first rib resection in 17 cases, supraclavicular excision of anomalous first ribs in five cases, and transaxillary anomalous first rib resections in two cases (total, 46 cases). Eight reoperations were performed for recurrent TOS in patients who previously had undergone cervical and first rib resections. RESULTS: Neck trauma was the cause of neurogenic symptoms in 80% of patients with cervical or anomalous first ribs. The surgical failure rate was 28% for 46 primary operations. A significant variable in results was the etiology of the symptoms. The failure rate for patients in whom symptoms developed after work-related injuries or repetitive stress at work was 42%, and the failure rates for patients whose symptoms followed an auto accident or developed spontaneously were 26% and 18%, respectively. The failure rate in each etiology group also was affected by the operation performed. The failure rate for cervical rib resection without first rib resection in the work-related group was 75% compared with a failure rate of 38% in the non-work-related group. In contrast, when both cervical and first ribs were resected, the failure rate in the work-related group fell to 25% and in the non-work-related group to 20%. These failure rates for the work-related and non-work-related groups are similar to our failure rates in patients without cervical ribs. CONCLUSION: Surgery for neurogenic TOS in patients with cervical ribs should include both cervical and first rib resection. The presence of cervical or anomalous first ribs in patients with neurogenic TOS does not improve the success rate from surgery compared with patients without abnormal ribs. Neck trauma is the most common cause for neurogenic TOS in patients with abnormal ribs. Cervical and anomalous first ribs are the predisposing factors rather than the cause.