Scott W. Taber

Resection of the metatarsal head for diabetic foot ulcers

BACKGROUND Diabetic foot ulceration is a worldwide health problem. Approximately 15% of the 10 million diabetic patients in the United States will develop a foot ulceration at some time in their lives. The presence of a foot ulcer in this population is extremely debilitating and dramatically increases the risk of lower extremity amputation, accounting for approximately 67,000 lost limbs each year. Additionally, the costs associated with treating foot ulcers in diabetic patients is a major expense in the overall care of this patient group. METHODS An 11-year retrospective study was conducted to evaluate 101 consecutive patients with diabetic ulcers of the forefoot who were treated using resection of the metatarsal head as the primary means of obtaining wound closure. RESULTS The results indicate that 88% of the ulcers were healed by using this technique, and relatively more rapidly than would be expected when compared with historical norms. CONCLUSIONS Resection of the metatarsal head is a safe and relatively inexpensive procedure that facilitates closure of the lesion, helps to control infection, and prevents countless and costly amputations.

Mortality, major amputation rates, and leukopenia after isolated limb perfusion with phenylalanine mustard for the treatment of melanoma

AbstractBackground: Isolated limb perfusion (ILP) is a treatment for cutaneous melanoma performed by several centers worldwide. The final data analysis of the World Health Organization and European Organization for Research and Treatment of Cancer in the use of ILP as adjuvant treatment for cutaneous melanoma is pending. ILP is effective to treat recurrent cutaneous melanoma. We determined the published rates of morbidity and mortality of ILP and put that component of the procedure into contemporary perspective. Methods: A MEDLINE search was conducted of the English-language literature from 1980 to 1995 for all publications reporting perfusion with phenylalanine mustard alone or combined with other agents. Patients treated by staged perfusion or fractional doses of chemotherapy were excluded. All published series were analyzed for the rate of mortality, number of major amputations, and presence of leukopenia. Results: The 30-day mortality rate for >2,000 patients was 0.6%. Death often resulted from cardiopulmonary complications or overwhelming sepsis from leukopenia. Leukopenia occurred in 0.7% of patients reviewed, caused by leakage of chemotherapeutic agents into the systemic circulation. Major amputations occurred in 0.8% of patients, and most were of the lower extremity. Conclusions: The definition of efficacy of ILP in the treatment of extremity melanomas remains to be clearly defined. However, based on this review of worldwide publications, the risk of death, amputation, and leukopenia is low.

The treatment of malignant endobronchial obstruction with laser ablation

BACKGROUND We compared a new endoscopic treatment for malignant endobronchial obstruction known as photodynamic therapy (PDT) with the more established therapy of neodymium: yttrium-aluminum garnet laser (Nd:YAG) therapy. METHODS A retrospective review was conducted of the medical records at our institution from 1988 to 1999 of patients treated for bronchial obstruction by thermal laser vaporization (Nd:YAG) or by PDT using the tunable dye laser in combination with a light-sensitive dye (PDT). The Nd:YAG procedure vaporized the obstructing neoplasm, whereas the PDT procedure photoablated the obstruction. Thirty-day mortality and morbidity rates were analyzed for both treatment groups using chi-square analysis. RESULTS Of the 102 patients who were suitable for review, 83 received treatment with the Nd:YAG laser and 19 patients received treatment with PDT. Morbidity rates were comparable in both groups (22% for Nd:YAG vs 31% for PDT; P > .05). Equally common complications in both groups were respiratory failure and hypoxemia. Five Nd:YAG patients (6%) died within 30 days after treatment (3 of respiratory failure, 2 of massive hemoptysis), whereas 2 patients (10%) in the PDT group (1 of massive hemoptysis, 1 of acute myocardial infarction) died (P > . 05). CONCLUSIONS PDT and Nd:YAG have similar mortality and morbidity rates. In our experience, PDT is a better choice for the treatment of malignant bronchial obstruction because it is technically easier, potentially safer, and does not require general anesthesia.

Photodynamic therapy for palliation of chest wall recurrence in patients with breast cancer

Background and Objectives: Chest wall recurrence occurs in 5–20% of breast cancer patients. Until recently, the only treatments available were surgical resection or radiotherapy. Photodynamic therapy (PDT) is a new modality that uses a photosensitizer and light to destroy tumor cells selectively. We report here our experience with PDT as a treatment for chest wall recurrence.

Photodynamic Therapy Trials with Lutetium Texaphyrin (Lu-Tex) in Patients with Locally Recurrent Breast Cancer

Photodynamic therapy (PDT) of locally recurrent breast cancer has been limited to treatment of small lesions because of non- selective necrosis of adjacent normal tissues in the treatment field. Lutetium Texaphyrin (PCI-0123, Lu-Tex) is a photosensitizer with improved tumor localization that is activated by 732 nm light, which can penetrate through larger tumors. We have evaluated Lu-Tex in a Phase I trial and in an ongoing Phase II trial in women with locally recurrent breast cancer with large tumors who have failed radiation therapy. Patients received Lu-Tex intravenously by rapid infusion 3 hours before illumination of cutaneous or subcutaneous lesions. In Phase I, Lu-Tex doses were escalated from 0.6 to 7.2 mg/kg in 7 cohorts. Sixteen patients with locally recurrent breast cancer lesions were treated. Dose limiting toxicities above 5.5 mg/kg were pain in the treatment field during therapy, and dysesthesias in light exposed areas. No necrosis of normal tissues in the treated field was noticed. Responses were observed in 60% of evaluable patients [n equals 15, 27% complete remission (CR), 33% partial remission (PR)], with 63% of lesions responding (n equals 73: 45% CR, 18% PR). In Phase II, 25 patients have been studied to date, receiving two treatments ranging from 1.0 to 3.0 mg/kg at a 21 day interval. Treatment fields up to 480 cm2 in size were treated successfully and activity has been observed. Patients have experienced pain at the treatment site but no tissue necrosis. These studies demonstrate the feasibility of Lu-Tex PDT to large chest wall areas in women who have failed radiation therapy for the treatment of locally recurrent breast cancer. Treatment conditions are currently being optimized in the ongoing Phase II trials.

The effects of aspirin on microvasculature after photodynamic therapy.

Abstract— The effects of aspirin (acetylsalicylic acid: ASA) on vessel behavior and tumor response were measured during and after photodynamic therapy (PDT). Changes to vessel constriction, macromolecular leakage, tumor interstitial pressure, and tumor response were examined. Animals were randomly placed into treatment groups and injected with 0–25 mg/kg Photofrin® and given 0 or 135 J/cm2 light treatment. The light treatment was standardized to 75 mW/cm2 at 630 nm over a 30 min treatment interval (135 J/cm2). The treatment groups were further subdivided to receive Photofrin® alone or Photofrin® plus 100 mg/kg ASA. A cremaster muscle model in Sprague‐Dawley rats was used to directly observe microvascular response and changes in vessel permeability to macromolecules. A tumor interstitial pressure model was designed to measure pressure changes in a chondrosarcoma tumor over time. This model indirectly measures macromolecular leakage, among other factors, in the tumor tissue. Groups of 10–20 rats were implanted subcutaneously with chondrosarcoma and were subjected to PDT to assess tumor response to the various treatments. Statistically significant differences in vessel leakage and changes in interstitial pressure were observed between animals given ASA plus PDT as compared to animals given PDT alone. The administration of ASA significantly inhibited venule leakage of albumin and reduced increases in interstitial pressure after treatment. The use of ASA had no effect on vessel constriction or tumor response after PDT. These findings suggest that the increases in vessel permeability observed during and after PDT, using Photofrin®, do not significantly contribute to tumor response.

ANALYSIS OF PULMONARY MICROVASCULATURE CHANGES AFTER PHOTODYNAMIC THERAPY DELIVERED TO DISTANT SITES

Abstract— Photodynamic therapy (PDT) can exert local damage by direct tumor cytotoxicity, by disruption of the microvas‐culature or by a combination of these effects. Although systemic effects after PDT of small tissue areas (< 1% total body surface area) are unlikely, treatment of larger areas may result in an accumulated effect leading to toxicity. Several investigators have described animal death after high dose PDT to tumors on the hind limb of animals and hypothesized that a toxic shock syndrome caused by vasoactive agents released after PDT is responsible. Because one of the most vulnerable organs to toxic shock injury is the lung, we studied the systemic effects of local PDT to this organ by intravital microscopy using a pulmonary window chamber. The PDT treatment conditions (25 mg/kg Photofrin®, 24 h, 150 J/cm2 630 nm, maximum area 6.28 cm2) were chosen that produce systemic toxicity and lethality in rats. Adhesion of leukocytes in the lung was monitored in vivo using anti‐CD‐13‐labeled microspheres. The progression of pulmonary edema was assessed by monitoring the leakage of rhodamine‐labeled albumin and by wet‐to‐dry lung weight ratios. Although an increased leukocyte adherence was observed and a significant number of animals died after the extensive PDT treatment, no biologically significant lung edema could be demonstrated. These data indicate that lung edema and acute respiratory distress syndrome is not the cause of death in these animals and that the toxicity is related to other mechanisms including circulatory shock after extensive muscle damage.

Use of scanning Doppler velocimetry to monitor vascular changes during photodynamic therapy

We are investigating the use of Scanning Doppler Velocimetry to evaluate changes in tissue perfusion that occur during Photodynamic Therapy (PDT). In initial studies, this technique was used to assess changes in tissue perfusion in mice given PDT using Photofrin, Purlytin, or Lutrin. There was a rapid and complete loss of perfusion in both normal tissue and tumor in animals given PDT using Photofrin. Using Purlytin, there was immediate loss of perfusion at the tumor site. For PDT using Lutrin, there was a lot of perfusion in the tumor with relatively no change in the surrounding normal skin, confirming the high degree of selectivity of PDT with this photosensitizer. These reductions in persistent through at least 24 h after PDT.

Automatic segmentation and quantification of fluorescing microspheres adhering to capillary endothelial cells in the rat lung

Adhesion molecules present in the cellular membrane of the endothelium provide sites of leukocyte adherence as a first step in the process of leukocyte migration into the interstitium. New evidence suggests the same adhesion proteins may be responsible for the spread of metastatic tumors by providing a location for tumor cell attachment. A method was sought to quantitate the degree of adhesion molecule expression in the pulmonary capillary endothelium using a recently developed animal model which allows for viewing the lung surface in vivo. Videoimages of the pulmonary vascular system were gathered using this new lung chamber technique. A fully automated digital image processing and analysis (DIPA) system was also developed to estimate the level of intercellular adhesion molecule-1 (ICAM-1) expression on the capillary endothelial cells in these videoimages. Fluorescent microspheres were immunologically bound to the ICAM-1 molecules present on the endothelial cell surface. The DIPA system then located and quantified the fluorescent spots present in the videoimages. The ability of this system to locate and measure the fluorescence was compared with human measurements of the same images.