Richard E. Hayden

Recurrent respiratory papillomatosis: Progression to invasion and malignancy

Recurrent respiratory papillomatosis is the most common benign tumor of the larynx in children. The disease often runs a protracted course necessitating multiple endolaryngeal procedures. Rarely, these papillomata become invasive and/or undergo malignant degeneration. A case report of malignant degeneration and widespread invasion in long-standing laryngeal papillomatosis and a review of the relevant literature are presented.

Supraglottic carcinoma: impact of radiation therapy on outcome of patients with positive margins and extracapsular nodal disease.

Seventy‐nine patients with supraglottic carcinoma treated between 1966 and 1985 are reviewed. All patients were treated with surgery and postoperative radiation therapy. Thirty‐five percent of the patients had positive margins at the site of resection of the primary tumor. Of the 25 patients who had positive nodal disease, 13 patients (52%) had either extracapsular extension or soft‐tissue or adjacent organ invasion, referred to in composite as “grave signs.” The median follow‐up of the patients was 4.9 years and all patients were followed for a minimum of 3 years. The disease‐free survival for all patients was 76% at 2 years and 71% at 3 years. The locoregional control rate for all patients was 70%.

Cutaneous photoprotection using a hydroxyl radical scavenger in photodynamic therapy.

Photodynamic therapy (PDT) is emerging as an effective therapy for a variety of malignant diseases, including head and neck cancer. Prolonged cutaneous photosensitivity following therapy, however, remains the most significant side effect. The biochemical mechanism of this sensitivity, and indeed of the tumoricidal effect of PDT, is uncertain, but is believed to involve formation of singlet oxygen and possibly other oxygen-derived free radicals. This laboratory recently reported that a singlet oxygen scavenger, diphenylisobenzofuran (DPIBF), afforded cutaneous photoprotection to 67% of animals treated with PDT. Those results, the first from an in vivo study, supported the idea that singlet oxygen plays a significant role in PDT and its associated toxicity. They also, however, suggested that it is not the sole intermediate. The current study looks at the photoprotective effects of the hydroxyl radical scavenger dimethyl thiourea, alone and in conjunction with DPIBF. Our results strongly support a role for the hydroxyl radical in producing the cutaneous phototoxicity associated with PDT.

FREE FLAP RECONSTRUCTION OF RECALCITRANT HYPOPHARYNGEAL STRICTURE

A case report is presented of the use of a jejunal microvascular free flap for the reconstruction of a hypopharyngeal stricture caused by caustic ingestion. Although the airway was reestablished, there was aspiration and diplophonia. This case is discussed as an example of an effective treatment of a difficult problem, but one posing secondary problems arising from the use of jejunum.

Prevention of cutaneous phototoxicity in photodynamic therapy

Photodynamic therapy using hematoporphyrin derivative (Hpd), or its semipurified form, dihematoporphyrin ether (DHE), in combination with light, has proven effective in the treatment of several types of neoplasms including squamous cell carcinoma. A major disadvantage of this therapy is the long-term retention of these drugs in skin, which may result in cutaneous phototoxicity for weeks after treatment. Singlet oxygen has been identified as the primary cytotoxic product in the reaction of Hpd and light in vitro. This study demonstrates the protective effect in vivo of the singlet oxygen scavengers 1,3 diphenylisobenzofuran and L-tryptophan on the skin of young rats exposed to light after receiving DHE.

Tolerance of gastric mucosal flap to postoperative irradiation

When malignant lesions of the oral cavity, base of tongue, and oropharynx are treated with radical resection, adequate reconstruction is required. The free gastric mucosal flap with microvascular transfer is being used with increasing frequency at Washington University Medical Center. Because of the advanced nature of the primary lesions, most patients also require postoperative radiation therapy. In this paper the tolerance of the gastric mucosal flap to postoperative radiation therapy is reviewed. The changes resulting from radiation therapy in the mucosal flap were found to be acceptable, and no major complications were encountered.

Thrombolysis with systemically administered t-PA in a new venous thrombosis model

Early thrombosis of either the arterial or venous supply of a free flap or island pedicle flap results in total flap necrosis. Until very recently, the only option for flap salvage was surgical intervention and, often, revision of the vascular pedicle. Current advances in the pharmacologic treatment of coronary artery and deep leg vein thrombosis have kindled interest in the field of reconstructive surgery for pharmacologic treatment of thromboses that compromise flaps.

The effect of hydroxyl radical scavenging on acute axial-random skin flap survival

Dimethyl thiourea (DMTU), a known hydroxyl radical scavenger, was tested for its ability to improve survival in acute island skin flaps. Rats receiving 500 mg/kg DMTU 1 hour after flap elevation showed a 23.5% improved survival over saline controls. The role of the hydroxyl radical in ischemia/reperfusion injury, and its proposed mechanism, is discussed.

Verdins in photodynamic therapy of squamous cell carcinoma

Photodynamic therapy (PDT) is a relatively new treatment modality employing photoactive drugs in combination with light to destroy malignant tissue. Porphyrins (ie, hematoporphyrin derivative and dihematoporphyrin ether) have been the most thoroughly investigated photoactive drugs. The primary limitation of the use of porphyrins in PDT is the shallow depth of effective tumor kill. Each photoactive drug is activated maximally by light of a particular wavelength, and longer wavelengths are able to penetrate tissue to a greater depth. Hematoporphyrin derivative and its semipurified form, dihematoporphyrin ether, are activated by light at 630 nm, which penetrates tissue to a maximum of 8 mm. The search for more effective photosensitizers is under way. Verdins, photoactive compounds in the class of chlorins, have recently been synthesized with activating wavelengths near 700 nm. This longer activation wavelength should theoretically allow a greater depth of tumor kill. Verdins have been shown to be effective photosensitizers in a urothelial carcinoma model in rats. In this study, we investigated the effectiveness of these compounds on squamous cell carcinoma in the hamster cheek pouch model.

Real time multivariable laser Doppler analysis of arterial and venous compromise

Laser Doppler perfusion monitoring was used to assess microcirculatory blood flow, volume, and velocity before and after total arterial or total venous occlusion in 18 buttock island flaps. Critical analysis of these three laser Doppler perfusion values was found to be useful in differentiating adequately perfused skin from inadequately perfused skin, as well as in distinguishing arterial from venous compromise. Multivariable laser Doppler analysis demonstrated that arterial occlusion produced a more rapid and greater percentage decrease in flow and volume values than did venous occlusion. Arterial occlusion produced an insignificant percentage change in velocity values, whereas venous occlusion produced a substantial percentage decrease in velocity values. The substantial intrasubject and intersubject variability in absolute laser Doppler perfusion values suggests that normalized or percentage change values are more revealing than absolute values, although they require the acquisition of reliable baseline data.