Effects of organophosphorus, carbamate, pyrethroid and organochlorine pesticides, and a heavy metal on survival and cholinesterase activity of Chironomus riparius Meigen

BACKGROUND & AIMS: The first therapeutic experiences with the conventional photosensitizer dihematoporphyrinester in the treatment of Barrett's esophagus show the curative potential of photodynamic therapy (PDT). The aim of this study was to test 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX, a photosensitizer with a high mucosa specificity without phototoxic side effects on the skin, as a new form of PDT. METHODS: Thirty-two patients (mean age, 68.5 years) with histologically proven high-grade dysplasia (n = 10) and mucosal cancer (n = 22) in Barrett's esophagus were treated. Four to 6 hours after oral ingestion of 5-ALA (dose, 60 mg/kg body wt), irradiation was conducted with a dye laser system (635 nm) with a light dose of 150 J/cm2. The patients received 20-80 mg omeprazole daily after PDT. RESULTS: High-grade dysplasia was eradicated in all patients (10 of 10), and mucosal cancer was eliminated in 17 of 22 patients (77%) at a mean follow-up of 9.9 months (range, 1-30 months). All tumors < or = 2 mm in thickness were completely ablated (17 of 17). The method-related mortality and morbidity was 0%. CONCLUSIONS: Severe dysplasia and thin (< or = 2 mm) mucosal cancer of Barrett's esophagus can be completely ablated. PDT might offer a minimally invasive treatment modality as an alternative to esophagectomy.     

Rapid tapering of cyclosporine for cytogenetic relapse shortly after bone marrow transplantation in a patient with chronic myeloid leukemia

A new therapy for the treatment of oral leukoplakia by 5-aminolevulinic acid (ALA) and photodynamic therapy (PDT) is presented. ALA, a precursor in the biosynthesis of haeme, induces the production of the endogenous photosensitizer protoporphyrin IX which can be used for PDT. Twelve patients, who had been suffering from leukoplakia of the oral mucosa for several years, were treated by ALA-mediated PDT. ALA was used as a topical photosensitizer and 20% ALA cream was applied to the leukoplakia lesion of the oral mucosa for two hours and then light activated at 630 nm, 100 mW/cm2 and 100 J/cm2. Five patients showed complete response to the treatment, four patients showed a partial response and in three patients treatment was unsuccessful. One patient with partial response was retreated, after which the lesion disappeared.     

Design and evaluation of a portable rigid forced-air warming cover for prehospital transport of cold patients

Although villous lesions comprise only about 5 per cent of all adenomas, 40 per cent are premalignant. Complete colonic evaluation and resection of all villous lesions should be performed. The purpose of this study is to examine our experience with transanal excision and low anterior resection as treatment options for large villous adenomas of the rectum. A retrospective review of all cases of villous adenomas of the rectum at this institution from January 1991 to February 1997 was performed. A total of 16 patients were identified; fourteen underwent transanal excision and two underwent low anterior resection. The average lesion size was 5 cm, and 50 per cent extended proximal to 8 cm from the anal verge. Thirty-seven per cent (six patients) had villous lesions containing adenocarcinoma. Thirty-one per cent (five patients) have required treatment for residual disease noted within 6 months of resection. Twelve per cent (two patients) have received treatment for recurrent disease presenting 6 months after resection. The minor complications included two episodes of urinary retention. The serious complications included one perforation and one postoperative hemorrhage for a 12 per cent complication rate. In summary, large villous adenomas of the rectum can be removed by sphincter-preserving techniques with low morbidity and an acceptable recurrence rate.     

11 cases of anal Bowen's disease

Bowen's disease of the anal region is a rare, slow-growing, intraepidermal squamous-cell carcinoma (carcinoma in situ). If surgical excision is incomplete, there is a risk of subsequent development of malignancy and metastasis. Between 1980 and 1995 we treated 11 patients (8 female, 3 male) with anal Bowen's disease. The mean age was 55 (34-75) years. The main reason for excision was: pain (4), itching (3), bleeding (3) and a disturbing lump (3). The intraoperative findings were in all cases a lesion at the anocutaneous line: perianal or intra-anal tumor (6), erosion (2) or ulceration (2) as well as lichenoid lesion (4) or hyperpigmentation (3). The procedure was excision of the lesion in 10 cases. Only in one case was a biopsy taken. 3 patients had to be operated on a second time for reasons of radicality. 5 years after primary diagnosis, one patient developed a recurrent invasive squamous-cell carcinoma and had to undergo perineo-abdominal rectum amputation with postoperative radiotherapy (2 years after operation). Only one patient underwent a biopsy, which produced the diagnosis of invasive squamous-cell carcinoma. He underwent combined chemo-radiotherapy. The symptoms of anal Bowen's disease are unspecific and the clinical findings are uncharacteristic. The recommended therapy is complete surgical excision. With complete excision no recurrences do occur.     

The use of bioceramic materials and cryosurgery in the treatment of patients with the Gorlin-Goltz syndrome

Therapeutic response to treatment (vaginal and external cryotherapy, drugs) in 97 patients with chronic salpingo-oophoritis at reproductive age provides the conclusion on effectiveness of various cryotherapeutic regimens in this disease. Cryotherapy improves regional blood circulation, restores contractility of the uterine tubes.     

Inhibition of 5-fluorouracil-cisplatin-induced stomatitis by oral cryotherapy: use of an ice-bar containing fibrinolysin and deoxyribonuclease combine (Elase)

Stomatitis caused by a combined chemotherapy with 5-fluorouracil (5-FU) and cisplatin (CDDP) is a serious problem in the course of treatment for patients with oral carcinoma. In the present study, we proposed a form of cryotherapy using an ice-bar containing fibrinolysin and deoxyribonuclease (Elase) to inhibit the stomatitis. The therapeutic effect of the ice-bar cryotherapy was evaluated in 20 patients with oral squamous cell carcinoma who were undergoing 5-FU-CDDP chemotherapy. Nine of the 20 patients were given the ice-bar cryotherapy while the remaining patients were not. As a result, although there was no significant difference between the incidence of stomatitis in the groups with and without the ice-bar cryotherapy, the incidence of severe stomatitis with ulcers and/or eating disturbance in the 11 cases without the ice-bar cryotherapy (90%) was significantly higher than that in the 9 cases with the cryotherapy (44%) (p < 0.05). However, no significant difference in the clinical response rate of the 5-FU-CDDP chemotherapy was observed between the two groups.     

Cryotherapy for trichiasis in ocular cicatricial pemphigoid

Trichiasis is a common and potentially sight threatening complication of ocular cicatricial pemphigoid and is usually secondary to cicatricial entropion. This study aimed to assess the success and complications of eyelid cryotherapy for trichiasis in a group of patients with long term follow up. The case records of all patients with ocular cicatricial pemphigoid that attended the external disease clinic at Moorfields Eye Hospital from 1980 to 1992 were reviewed. Each eyelid was divided into three horizontal zones. Cryotherapy was delivered with an Amoilette cryoprobe for approximately 30 seconds. Failure of the cryotherapy was defined as a regrowth of the eyelashes within the treated zone that either required epilation for symptom control or caused keratopathy. Ninety two lid zones were treated, involving 25 lids of 12 patients. The cumulative chance of success decreased rapidly to 40% over the first year. Thereafter, the chance of success declined slowly to 34% at 4 years. Complications included lid notching (n = 2), tarsal atrophy (n = 1), altered lid contour (n = 1), and temporarily raised intraocular pressure (n = 1). All patients had quiescent disease at the time of the cryotherapy and no patients showed increased conjunctival disease activity after treatment. Six patients were taking systemic immunosuppression medication. When ocular cicatricial pemphigoid is quiescent, lid cryotherapy has an acceptable complication rate. The major reason for recurrence of the trichiasis was attributed to inadequate follicle freezing.     

Laparoscopic cryoablation of hepatic metastases

OBJECTIVE: To evaluate the feasibility of laparoscopic cryoablation for the management of hepatic metastases. DESIGN: Retrospective review. SETTING: Tertiary referral center. PATIENTS: Nine patients were evaluated by laparoscopy for planned laparoscopic cryoablation of hepatic metastases at The Cleveland Clinic Foundation, Cleveland, Ohio, from April 1996 to May 1997. RESULTS: Laparoscopic exploration revealed diffuse extrahepatic disease not identified by preoperative studies in 2 patients. The remaining 7 patients underwent 9 cryotherapy sessions. During 4 of the cryotherapy sessions, ultrasonography demonstrated unrecognized additional treatable hepatic lesions. An average of 3 lesions (range, 2-5) were treated. Operative time averaged 3.5 hours with a mean intraoperative blood loss of 235 mL. One patient had significant intraoperative hemorrhage requiring conversion to open hepatic resection for bleeding control. Eight of the 9 patients tolerated normal diets and ambulated independently on the first postoperative day. Following cryotherapy, 4 of the patients developed fever without an infectious source. One patient developed a postoperative bile leak requiring percutaneous biliary stenting. Postoperative hospital stay averaged 4.5 days (median, 4 days; range, 2-14 days). At a mean follow-up of 9 months, 4 of the 7 patients treated are alive without evidence of disease, 2 are alive with disease, and 1 patient with a pancreatic primary tumor has died of disease. CONCLUSIONS: Laparoscopy with laparoscopic ultrasonography is a useful tool in evaluating patients with hepatic metastases. Laparoscopic cryoablation is feasible and may result in lower postoperative morbidity in patients receiving aggressive treatment for inoperable hepatic metastases.     

Intrathecal clonidine alleviates allodynia in neuropathic rats: interaction with spinal muscarinic and nicotinic receptors

PURPOSE: There has been a significant shift toward multimodality therapy to try to eradicate extracapsular disease better in patients with locally advanced prostate cancer. We assess the feasibility and complications of initial cryotherapy followed by radical prostatectomy, and evaluate the frequency and location of viable benign and malignant prostate tissue and positive surgical margins after this treatment combination. MATERIALS AND METHODS: A total of 12 patients with clinical stage T3 cancer or clinical stages T1c to T2, Gleason score 8 to 10 cancer on the initial biopsy were treated with initial cryotherapy followed by open surgical exploration 2 to 8 days later. If pelvic lymph nodes were negative, radical prostatectomy was performed. Prostate specific antigen was measured approximately every 3 months postoperatively, and complications were assessed by retrospective chart review and a quality of life survey. RESULTS: Radical prostatectomy was aborted in 5 patients with positive pelvic lymph nodes. Of the 7 patients who underwent prostatectomy 4 had no residual prostate cancer in the specimen (pathological stage pT0 disease). All 7 of these patients had focal areas of viable normal prostate glands. Only 1 of the 7 patients had a positive surgical margin and biochemical failure (mean followup 22.6 months). The main complications of cryotherapy followed by radical prostatectomy were urinary incontinence and impotence. CONCLUSIONS: Neoadjuvant cryotherapy achieved complete tumor destruction in 4 of 7 patients with locally advanced prostate cancer. Cryotherapy followed by radical prostatectomy was associated with substantial morbidity, mainly in terms of urinary incontinence.     

Vascularization of purified pancreatic islet-like cell aggregates (pseudoislets) after syngeneic transplantation

OBJECTIVE: To determine, in vivo, the effect of radiofrequency ablation (RFA) treatment time and tissue blood flow on the size and shape of the resulting necrotic lesion in porcine liver. SUMMARY BACKGROUND DATA: Radiofrequency ablation is an electrosurgical technique that uses a high frequency alternating current to heat tissues to the point of desiccation (thermal coagulation). Radiofrequency ablation is well established as the treatment of choice for many symptomatic cardiac arrhythmias because of its ability to create localized necrotic lesions in the cardiac conducting system. Until recently, a major limitation of RFA was the small lesion size created by this technique. Development of bipolar and multiple-electrode RFA probes has enabled the creation of larger lesions and therefore has expanded the potential clinical applications of RFA, which includes the treatment of liver tumors. A basic understanding of factors that influence RFA lesion size in vivo is critical to the success of this treatment modality. The optimal RFA technique, which maximizes liver lesion size, has yet to be determined. Theoretically, lesion size varies directly with time of application of the RF current, and inversely with blood flow, but these relationships have not been previously studied in the liver. METHODS: Six animals underwent hepatic RFA (460 kHz), for 5, 7.5, 10, 12.5, 15, and 20 minutes. Identical, predetermined anatomic areas of the liver were ablated in each animal. Two additional animals underwent 12 RFA treatments -- 6 with vascular inflow occlusion (Pringle maneuver) and 6 with uninterrupted hepatic blood flow. Animals were euthanized and the livers were removed for gross pathologic examination. All lesions were measured in three dimensions and photographed. Tissues were examined by routine histology and by histochemistry to determine viability. RESULTS: Increasing duration of RFA application from 5 through 20 minutes did not create lesions of larger diameter, but this time increase did predict deeper lesion production (beta = 0.34, p = 0.04). A range of lesion shapes were created from four separate ovals (corresponding to each electrode), to larger ovals intersecting to form a cross, to spheroid lesions. The number of blood vessels in close proximity to the probe tip (within a 1-cm radius from the center of the lesion) strongly predicted minimum lesion diameter (beta = -0.61, p = 0.0001) and lesion volume (beta = -0.56, p = 0.0004). This negative effect of blood flow on lesion size was confirmed experimentally. Radiofrequency ablation lesions created during a Pringle maneuver were significantly larger in all three dimensions than lesions created without a Pringle maneuver: minimum diameter was 3.0 cm (with Pringle) versus 1.2 cm (p = 0.002), maximum diameter was 4.5 cm (with Pringle) versus 3.1 cm (p = 0.002), depth was 4.8 cm (with Pringle) versus 3.1 cm (p < 0.001), and lesion volume was 35.0 cm3 (with Pringle) versus 6.5 cm3 (p < 0.001). CONCLUSIONS: Blood flow is a strong predictor of all RFA lesion dimensions in porcine liver in vivo, whereas a change of treatment time from 5 to 20 minutes is predictive only of lesion depth, but not diameter or volume.     

Oncogenic Ras modulates epidermal growth factor responsiveness in endometrial carcinomas

OBJECTIVE: To compare cryotherapy, laser vaporization, and loop electrical excision for treatment of squamous intraepithelial lesions (SILs). METHODS: Women at least 18 years old with biopsy-proven SIL, negative pregnancy tests, negative findings on endocervical curettage, satisfactory colposcopy examinations, and congruent Papanicolaou smear and biopsy results were assigned randomly to treatment after stratification by SIL grade, endocervical gland involvement, and lesion size; they were evaluated 1, 4, 8, 12, 16, 20, and 24 months after treatment. Data were analyzed using chi2 statistics, logistic regression analysis, and the Cox proportional hazards model. RESULTS: Of 498 patients assigned, 108 were excluded (most because of inadequate follow-up), leaving 390 (139 cryotherapy, 121 laser vaporization, 130 loop excision) for analysis. All were followed 6-37 months (mean 16). There were no statistically significant differences in complications, persistence (disease present less than 6 months after treatment), or recurrence (disease present more than 6 months after treatment). Risk of persistent disease was higher among women with large lesions (risk ratio [RR], 18.9; 95% confidence interval [CI], 3.2, 110.6). Recurrence risk was higher among women aged 30 years and older (RR, 2.1; 95% CI, 1.2, 4.3), those with human papillomavirus type 16 or 18 (RR, 2.1; 95% CI, 1.1, 4.0), and those who had had prior treatment (RR, 2.1; 95% CI, 1.1, 3.9). CONCLUSION: The data support a high success rate with all three modalities. No significant difference in success rates was observed between the three treatments in our population. Additional attention and research should be directed toward the higher risk patients identified above.     

Reduction of tumour oxygenation during and after photodynamic therapy in vivo: effects of fluence rate

It has been proposed that the generation of O2 during photodynamic therapy (PDT) may lead to photochemical depletion of ambient tumour oxygen, thus causing acute hypoxia and limiting treatment effectiveness. We have studied the effects of fluence rate on pO2, in the murine RIF tumour during and after PDT using 5 mg kg(-1) Photofrin and fluence rates of 30, 75 or 150 mW cm(-2). Median pO2 before PDT ranged from 2.9 to 5.2 mmHg in three treatment groups. Within the first minute of illumination, median tumour pO2 decreased with all fluence rates to values between 0.7 and 1.1 mmHg. These effects were rapidly and completely reversible if illumination was interrupted. During prolonged illumination (20-50 J cm(-2)) pO2 recovered at the 30 mW cm(-2) fluence rate to a median value of 7.4 mmHg, but remained low at the 150 mW cm(-2) fluence rate (median pO2 1.7 mmHg). Fluence rate effects were not found after PDT, and at both 30 and 150 mW cm(-2) median tumour pO2 fell from control levels to 1.0-1.8 mmHg within 1-3 h after treatment conclusion. PDT with 100 J cm(-2) at 30 mW cm(-2) caused significantly (P = 0.0004) longer median tumour regrowth times than PDT at 150 mW cm(-2), indicating that lower fluence rate can improve PDT response. Vascular perfusion studies uncovered significant fluence rate-dependent differences in the responses of the normal and tumour vasculature. These data establish a direct relationship between tumour pO2, the fluence rate applied during PDT and treatment outcome. The findings are of immediate clinical relevance.     

Application of Raney nickel to measure adducts of styrene oxide with hemoglobin and albumin

BACKGROUND: Although peripheral cryotherapy decreases the incidence of unfavorable anatomic outcomes in threshold retinopathy of prematurity (ROP), apnea, bradycardia, and lid edema can occur. Argon laser indirect ophthalmoscope photocoagulation has been used as an alternative to cryotherapy, with fewer adverse effects. Retinal lesions placed with diode lasers are deeper than similar argon laser lesions, and it is not known whether this difference could influence the response to ablative therapy. METHODS: Patients were enrolled under a prospective, randomized protocol. One eye of each patient with symmetric, threshold ROP was treated with an 814/815 nm diode laser, while the other eye was treated with cryotherapy. Patients with asymmetric diseases also were randomized for treatment in the threshold eye. RESULTS: Nineteen infants (33 eyes) were treated, ranging from 485 to 863 g birth weight (23 to 27 weeks gestational age); 18 patients (32 eyes) were followed for 3 months or longer. Four patients (8 eyes) had bilateral zone 1 disease. Postconceptional age was 36 to 45 weeks at the time of treatment. The diode laser treatment was better tolerated than cryotherapy, and the treatment apparatus was more easily transported. Apneic episodes requiring intubation resulted from two cryotherapy sessions but no diode laser sessions. Five cryotherapy-treated eyes required retreatment because of persistent disease with adjacent skip areas. In the group followed for 3 to 15 months, 1 cryotherapy-treated eye and 1 diode laser-treated eye progressed to stage 5 retinal detachment. CONCLUSION: Compared with cryotherapy, the diode laser was more convenient, technically easier to administer, and better tolerated by the patient. Although the number of patients was too small for meaningful statistical analysis of outcome, diode laser peripheral retinal ablation appeared to be as effective as cryotherapy for the treatment of threshold ROP.     

Treatment of cutaneous Bowen's disease with particular emphasis on the problem of lower leg lesions

Bowen's disease has a particular predilection for the lower leg, especially in women. A review of the literature for treating Bowen's disease is presented and the problems associated with treating the lower leg emphasized. Evidence for the various treatment modalities used to treat Bowen's disease largely comes from studies that lack good methodology in terms of standardized techniques, patient controls and adequate follow-up. In particular the widely accepted recommendation for excision is not supported by evidence that this treatment is superior to other modalities. The choice of treatment for Bowen's disease should take into account the patient's general condition, the site and size of the lesion.     

Local resection of pulmonary lesions by Nd-YAG laser without suturing

Local excision of 67 pulmonary lesions in 5 patients was performed with the Nd-YAG laser. There were 2 women and 3 men with an average age of 68 years. The patients consisted of three cases of metastatic lung cancer (65 lesions), one hamartoma (One lesion) and one organized pneumonitis (one lesion). The lesion was first enucleated by a contact method using an Nd-YAG laser scalpel, then the crater of the resected lesion in the normal lung tissue was coagulated with a defocused laser beam. The craters of 52 of the 67 resected lesions which were shallow seated in the lung were left open, but the other 15 resected lesions were closed with sutures. Total blood loss was less than 100 ml. There was no bleeding or air leakage (30 cm water pressure) during the post operative days in 4 of the 5 patients, but one patients (one lesion) had to be treated by bronchoscopic endobronchial embolization against a persistent air leak. This lesion was 2.5 cm in diameter and 4 cm deep in the lung on CT. The other lesions were also measured by CT. The tumor size was 1.4 +/- 0.7 cm and the depth was 2.4 +/- 1.0 cm. The Nd-YAG laser is very suitable for local resection of peripheral lung lesions without suturing.     

Trends in surgical management of astrocytomas and other brain gliomas

PURPOSE: Retrospective analysis of the influence of clinical and technical factors on local control and survival after radiosurgery for brain metastasis. PATIENTS AND METHODS: From January 1994 to December 1996, 42 patients presenting with 71 metastases underwent radiosurgery for brain metastasis. The median age was 56 years and the median Karnofsky index 80. Primary sites included: lung (20 patients), kidney (seven), breast (five), colon (two), melanoma (three), osteosarcoma (one) and it was unknown for three patients. Seventeen patients had extracranial metastasis. Twenty-four patients were treated at recurrence which occurred after whole brain irradiation (12 patients), surgical excision (four) or after both treatments (eight). Thirty-six sessions of radiosurgery have been realized for one metastasis and 13 for two, three or four lesions. The median metastasis diameter was 21 mm and the median volume 1.7 cm3. The median peripheral dose to the lesion was 14 Gy, and the median dose at the isocenter 20 Gy. RESULTS: Sixty-five metastases were evaluable for response analysis. The overall local control rate was 82% and the 1-year actuarial rate was 72%. In univariate analysis, theoretical radioresistance (P = 0.001), diameter less than 3 cm (P = 0.039) and initial treatment with radiosurgery (P = 0.041) were significantly associated with increased local control. Only the first two factors remained significant in multivariate analysis. No prognostic factor of overall survival was identified. The median survival was 12 months. Six patients had a symptomatic oedema (RTOG grade 2), only one of which requiring a surgical excision. CONCLUSION: In conclusion, 14 Gy delivered at the periphery of metastasis seems to be a sufficient dose to control most brain metastases, with a minimal toxicity. Better results were obtained for lesions initially treated with radiosurgery, theoretically radioresistant and with a diameter less than 3 cm.     

Cryotherapy of basal cell carcinoma in oculoplastic surgery

Cryotherapy was an effective modality in the treatment of basal cell carcinoma in the eyelid and periorbital area and cured 93% of the 29 lesions in 25 patients. This method was especially advantageous in patients with blood clotting disorders; those with medical contraindications to, or who refused, classical surgery; patients who had prior radiation or surgery; patients with the basal cell nevus syndrome or xeroderma pigmentosa; and in patients with medial canthal tumors. Experimental cryotherapy in the albino rabbit showed their lacrimal system is not adversely affected by freezing in the temperature range required for tumor death.     

Cryotherapy treatment of patients with hepatic metastases from neuroendocrine tumors

BACKGROUND: Liver metastases from neuroendocrine tumors often present with disabling symptoms due to syndromes of hormonal excess. A locally destructive technique such as hepatic cryotherapy not only alleviates symptoms but may improve survival in this group of patients. METHODS: Six patients with metastatic neuroendocrine tumors were treated with hepatic cryotherapy. Four patients were symptomatic and three of these had elevated tumor markers from ectopic hormone production. RESULTS: All patients are alive and asymptomatic, with a median follow-up of 24 months (range, 6 months to 6 years). All have had a complete radiologic response. All with elevated preoperative markers have had a greater than 89% decrease in tumor markers. Coagulopathy occurred in two patients necessitating additional surgery, but there was no other morbidity attributable to the cryotherapy. CONCLUSION: To the authors' knowledge, this study demonstrates for the first time that hepatic cryotherapy offers supportive treatment for patients with neuroendocrine tumors metastatic to the liver. Cryotherapy alleviates symptoms and may improve survival.     

Photodynamic therapy of human glioma (U87) in the nude rat

We measured the response of normal brain and the human U87 glioma implanted in the brain of rats (n = 65) to photodynamic therapy (PDT) using Photofrin as the sensitizer. Normal brain and U87 tumor implanted within brain of athymic (nude) rats were subjected to PDT (12.5 mg/kg of Photofrin) at increasing optical energy doses (35 J/cm2, 140 J/cm2, 280 J/cm2) of 632 nm light. Photofrin concentration in tumor, brain adjacent to tumor and normal brain were measured in a separate population of rats. Twenty-four hours after PDT, the brains were removed, sectioned, stained with hematoxylin and eosin (H&E), and the volumes of the PDT-induced lesion measured. Photofrin concentration in tumor greatly exceeded that of normal brain and brain adjacent to tumor (> 20x). Both normal brain and U87 tumor exhibited superficial tissue damage with PDT at 35 J/cm2. However, both normal and tumor-implanted brain exhibited tissue damage with increasing optical dose. A heterogeneous pattern of pannecrosis along with a uniform volume of pannecrosis was detected in the tumor. In contrast, normal brain exhibited a uniform sharply demarcated volume of necrosis. Our data indicate that the U87 human brain tumor model and the normal brain in the athymic rat are sensitive to PDT and Photofrin with an optical dose-dependent response to treatment.