Denis A. Cortese

Photodynamic Therapy for Early Stage Squamous Cell Carcinoma of the Lung

OBJECTIVE To study the effectiveness of photodynamic therapy (PDT) as a therapeutic strategy in roentgenographically occult squamous cell carcinoma of the lung. MATERIAL AND METHODS A carefully selected group of 21 patients (with 23 cancers) who had early stage squamous cell carcinoma of the lung and were eligible for surgical treatment were offered PDT as an alternative to resection. Patients underwent close follow-up with bronchoscopic surveillance and were offered resection if cancer persisted after no more than two sessions of PDT. RESULTS A complete response was identified in 15 patients (16 cancers) after an initial PDT session. A complete response that lasted longer than 12 months was noted in 11 patients (52%). After PDT, the minimal follow-up period was 24 months. A subsequent primary lung cancer developed in 5 of the 21 patients (24%). Ten patients ultimately had surgical treatment, in 3 (30%) of whom N1 disease was identified at the time of resection. Two patients refused a surgical procedure and received alternative therapy. Therefore, nine patients (43%) were spared an operation (95% confidence interval, 21.8 to 66.6%). The mean duration of follow-up for these nine patients was 68 months (range, 24 to 116). CONCLUSION On the basis of this investigation, we can conclude with 95% confidence that at least 22% of patients with early stage squamous cell lung cancer who are candidates for PDT can be spared surgical resection.

Photoradiation therapy in the treatment of malignant brain tumors: a phase I (feasibility) study.

Hematoporphyrin derivative accumulates in malignant brain tumors and. when activated by light. can produce a cytotoxic reaction. A system for utilizing this concept in the treatment of human malignant brain tumors has been developed and tested in a small series of patients. No significant adverse re

Pulmonary Aspects of Chronic Liver Disease and Liver Transplantation

A vast spectrum of pulmonary pathologic conditions occurs in association with chronic liver diseases, and clinically important manifestations, such as arterial hypoxemia, can result. Both pulmonary vascular and parenchymal abnormalities can contribute to the dysfunction, as evidenced by results of pulmonary function tests and gas exchange studies. The clinical implications of identifying such pulmonary problems range from alleviation of symptoms, especially dyspnea, to comprehensive assessment of patients before and after liver transplantation. Physicians should be aware of these potential pulmonary disorders that can complicate liver disease and liver transplantation so that management of affected patients can be improved.

Bronchoscopic Phototherapy With Hematoporphyrin Derivative for Treatment of Localized Bronchogenic Carcinoma: A 5-Year Experience

Between December 1980 and April 1986 at our institution, 38 patients with cancer that involved the tracheobronchial tree (a total of 40 carcinomas) completed at least one course of hematoporphyrin derivative phototherapy. A complete response occurred in 13 patients (with 14 carcinomas). Eleven of these carcinomas did not recur during follow-up periods that ranged from 3 to 53 months. Three carcinomas recurred at 9, 12, and 35 months, respectively. For 26 carcinomas, the response was less than complete, and alternative therapy was necessary. The carcinomas in patients with a complete response were radiographically occult, were less than 3 cm2 in surface area, and appeared superficial at bronchoscopy. Our experience supports the use of hematoporphyrin derivative phototherapy as an alternative to surgical resection in carefully selected patients.

Failure of hepatopulmonary syndrome to resolve after liver transplantation and successful treatment with embolotherapy

The hepatopulmonary syndrome is an uncommon accompaniment of chronic liver disease. The outcome of this disorder after orthotopic liver transplantation is variable. We describe a patient with the hepatopulmonary syndrome who underwent orthotopic liver transplantation for autoimmune hepatitis. Her platypnea and orthodeoxia failed to improve postoperatively. Pulmonary angiography showed large pulmonary arteriovenous shunts that were successfully treated with coil embolotherapy.

Treatment of Transitional Cell Carcinoma of the Bladder with Hematoporphyrin Derivative Phototherapy

The demonstration that intravenously administered hematoporphyrin derivative concentrates preferentially in dysplastic and neoplastic transitional cells in the human bladder prompted a trial of hematoporphyrin derivative phototherapy in patients with transitional cell cancer of the bladder. A dose of 2.5 mg. per kg. was given intravenously 3 to 48 hours before treatment with light of a wavelength of 630 nm. from an argon ion pumped dye laser. Total light dose approximated 150 joules per cm.2. Four patients with resistant carcinoma in situ have been treated and all have had disappearance of the tumors proved by biopsy. Although there are many technical problems we believe that hematoporphyrin derivative phototherapy holds promise as an effective treatment modality, primarily for patients with resistant, recurrent in situ transitional cell carcinoma of the bladder.

Severe Hypoxemia Associated With Liver Disease: Mayo Clinic Experience and the Experimental Use of Almitrine Bismesylate

Severe hypoxemia associated with chronic liver disease is an uncommon disorder most likely due to an intrapulmonary vascular abnormality that has characteristics of both ventilation-perfusion mismatching and diffusion limitation. Anatomically, the intrapulmonary vascular abnormalities can occasionally be detected by angiography. Physiologically, the gas exchange abnormalities can be substantiated by contrast-enhanced two-dimensional echocardiography. Although orthodeoxia and platypnea have frequently been found in these patients, echocardiographic data suggest that vascular abnormalities can exist in the absence of orthodeoxia. We describe 11 patients who had severe hypoxemia and chronic liver disease and review their pulmonary angiographic, contrast echocardiographic, and arterial blood gas findings. Among five of these patients who were given almitrine bismesylate, an experimental medication thought to alter ventilation-perfusion relationships in patients with chronic obstructive pulmonary disease, one had improved oxygenation. We recommend that patients with hypoxemia associated with chronic liver disease have detailed studies to rule out reversible forms of hypoxemia and that those with severe hypoxemia undergo testing to determine the existence of intrapulmonary vascular abnormalities, especially if liver transplantation is considered.

Management of malignant airway obstruction: Clinical and dosimetric considerations using an iridium-192 afterloading technique in conjunction with the neodymium-YAG laser

Fourteen patients with malignant airway obstruction have had 21 placements of a flexible nylon catheter for afterloading Iridium-192 using the flexible fiberoptic bronchoscope. Prescribed therapy was completed in 13 patients (18 courses). All patients had prior full-dose external irradiation, and no effective surgical or chemotherapeutic options remained. While many have had a trial of neodymium-YAG (yttrium-aluminum-garnet) laser therapy alone, eight patients received laser treatment one to three weeks prior to planned brachytherapy to provide immediate relief of symptoms and/or facilitate access and safe catheter placement. Most patients (64%) had recurrent squamous cell lung cancer. A dose of 3000 cGy is currently specified to 5 mm and 10 mm in the bronchus and trachea, respectively. Nine of the 13 treated patients have had follow-up bronchoscopy at approximately three months post-treatment with improvement documented in seven and progression in two patients. One patient was clinically improved without follow-up bronchoscopy, and three patients have had insufficient follow-up. A single patient treated with laser and 6000 rad at 5 mm developed a bronchoesophageal fistula. No other complication has been observed. The technique is simple and safe with the use of laser therapy when needed and appears to offer effective palliation in most patients even when standard therapy is exhausted.

Ancillary Therapies in the Management of Lung Cancer: Photodynamic Therapy, Laser Therapy, and Endobronchial Prosthetic Devices

Endoscopic therapy for cancer that involves the tracheobronchial tree is currently available for two distinct types of lesions: radiographically occult superficial squamous cell carcinoma and advanced malignant tumors that cause severe airway obstruction. Photodynamic therapy, which uses a photosensitizing agent, is effective for managing early superficial squamous cell carcinoma. Neodymium:yttrium-aluminum-garnet laser therapy has been effective in the palliative management of patients with advanced or recurrent malignant obstructive airway lesions, either alone or in combination with intraluminal radiation therapy. Most recently, endobronchial prosthetic devices (stents) have been used in patients with advanced airway obstruction. The use of each of these modalities in the management of lung cancer is reviewed.

Managing Conflict of Interest in Clinical Practice

Conflict of interest, even the appearance of potential conflict, has long been a concern for physicians and scientists. Conflict of interest arises when an activity is accompanied by a divergence between personal or institutional benefit when compared to the responsibilities to patients and to society; it arises in the context of research, purchasing, leadership, and investments. Conflict of interest is of concern because it compromises the trust of the patient and of society in the individual physician or the medical center.