Bergein F. Overholt

Spectroscopic diagnosis of esophageal cancer: New classification model, improved measurement system

Laser-induced fluorescence spectroscopy was used to measure fluorescence emission of normal and malignant tissue during endoscopy in patients with esophageal cancer and volunteers with normal esophagus. The spectroscopy system consisted of a nitrogen-pumped dye-laser tuned at 410 nm for excitation source, an optical multichannel analyzer for spectrum analysis, and a fiberoptic probe designed for both the delivery of excitation light and the collection of fluorescence emission from tissue. The fluorescence lineshape of each spectrum was determined and sampled at 15-nm intervals from 430 to 716 nm. A calibration set of spectra from normal and malignant spectra was selected. Using stepwise discriminate analysis, significant wavelengths that separated normal from malignant spectra were selected. The intensities at these wavelengths were used to formulate a classification model using linear discriminate analysis. The model was then used to classify additional tissue spectra from 26 malignant and 108 normal sites into either normal or malignant spectra. A sensitivity of 100% and specificity of 98% were obtained.

Barrett's esophagus: photodynamic therapy for ablation of dysplasia, reduction of specialized mucosa and treatment of superficial esophageal cancer

Fifteen patients with Barretts esophagus and dysplasia were treated with photodynamic therapy. Four patients also had early, superficial esophageal cancers and 5 had esophageal polyps. Light was delivered via a standard diffuser or a centering esophageal balloon. Eight patients maintained on omeprazole and followed for 6 - 54 months are the subject of this report. Photodynamic therapy ablated dysplastic or malignant mucosa in patients with superficial cancer. Healing and partial replacement of Barretts mucosa with normal squamous epithelium occurred in all patients and complete replacement with squamous epithelium was found in two. Side effects included photosensitivity and mild-moderate chest pain and dysphagia for 5 - 7 days. In three patients with extensive circumferential mucosal ablation in the proximal esophagus, healing was associated with esophageal strictures which were treated successfully by esophageal dilation. Strictures were not found in the distal esophagus. Photodynamic therapy combined with long-term acid inhibition provides effective endoscopic therapy of Barretts mucosal dysplasia and superficial (Tis-T1) esophageal cancer. The windowed centering balloon improves delivery of photodynamic therapy to diffusely abnormal esophageal mucosa.

Flexible fiberoptic sigmoidoscopy: Technique and preliminary results†

Currently available flexible, controlled‐tip fibersigmoidoscopes for visualization of the rectum, sigmoid, and descending colon are reviewed. The technique of insertion includes patient medication and positioning, manipulation of the distal tip, rotation of the instrument, “persuasive pressure,” air insufflations, and water instillation. Insertion to 70 cm or greater was accomplished in 66% of patients. Fibersigmoidoscopy frequently provides information that influences the diagnosis and treatment in many patients with diseases of the colon and rectum.

Balloon photodynamic therapy of esophageal cancer: Effect of increasing balloon size

Photodynamic therapy is currently being used to treat various malignancies including esophageal cancer. The effect of photodynamic therapy depends upon the concentration of photosensitizing drug, light energy delivered to tissue, and the presence of oxygen in the targeted tissue. We have found that an esophageal centering balloon improves light delivery to esophageal mucosa. However, balloon pressure on esophageal mucosa could possibly reduce mucosal blood flow and oxygenation, therefore reducing the effect of photodynamic therapy. This study was conducted to investigate the effect of balloon pressure on the esophageal wall during photodynamic therapy in the canine esophageal model.

A centering balloon for photodynamic therapy of esophageal cancer tested in a canine model.

Delivery of uniform circumferential light is desirable during photodynamic therapy of early or advanced esophageal cancer in human beings. Studies were performed in the canine esophagus to investigate whether use of a centering balloon would improve circumferential illumination of esophageal mucosa for photodynamic therapy of esophageal cancer. When the centering balloon was used, photodynamic therapy produced uniform and circumferential injury. With the cylindrical diffuser used in human studies, non-uniform and focal esophageal injury occurred. Placement of isotropic probes on the balloon wall allowed measurement and verification of relatively uniform light doses delivered to esophageal mucosa during balloon photodynamic therapy. The centering balloon has a potential role in improving light dosimetry during esophageal photodynamic therapy.

Hyperthermia treatment using a computer-controlled Nd:YAG laser system in combination with surface cooling

An Nd:YAG laser hyperthermia system was used to induce hyperthermia in chemically-induced rat mammary adenocarcinomas. Excessive heating of the surface tissue limits the depth of heating during laser-induced hyperthermia. To determine whether surface cooling would allow heating of deeper tissues, treatment surfaces were cooled using two different techniques. (1) an IV drip in conjunction with oxygen flow directed toward the surface, and (2) moisture saturated oxygen flow from a nebulizer. The laser was interfaced to a computer and a thermometer that provided feedback to maintain the tumor temperature between 43.2- 43.5 degree(s)C. The thermocouple was placed in the base of the tumor and its temperature was used via the feedback system to control laser exposure. All tumors were 1.0 to 2.0 cm in diameter. While both cooling techniques lowered the surface temperature effectively, nebulizer technique was preferred due to better control of surface cooling and less fluid accumulation around the treatment area. Nd:YAG laser hyperthermia delivered in conjunction with surface cooling using the nebulizer technique produced efficient heating of rat mammary adenocarcinomas to an approximate depth of 15 mm without overheating the surface tissue.

Interstitial hyperthermia treatment using Nd:YAG laser

Treatment of tumors with hyperthermia with other agents can be effective under certain circumstances. However, often it is impossible to adequately treat tumors because of the difficulties in delivering uniform thermal doses throughout the entire tumor volume. This difficulty may be caused by many different factors including perfusion differences between tumor and normal tissue and differences in thermal properties between these tissues. With interstitial techniques however, some of these difficulties can be overcome. We have developed an interstitial laser system for delivery of heat to tissue. The system utilizes the output of an Nd:YAG laser directed into a fiberoptic probe which can be inserted into a tumor. Sapphire contact tips are used to deliver laser energy into the tissue. A series of animals were heated with a single probe. Temperature measured by small implanted thermocouples was controlled via a feedback circuit to a constant value over this interval. The control system was able to maintain temperature to within 0.3°C. This pilot study showed that this technique was suitable for interstitial hyperthermia. Continued work into the characterization of thermal profiles in tissue resulting from laser treatment must be performed. Ultimately, light from the interstitial probes will be used in combination with specific photosensitizers for delivery of photodynamic therapy in conjunction with hyperthermia.

In-vivo fluorescence spectropscopy for diagnosis of skin cancer

Laser-induced fluorescence spectroscopy is a noninvasive technique previously used for detection of cancer in a variety of organ systems. The objective of this study was to determine whether in vivo laser-induced fluorescence can be used to detect malignant skin lesions.

Laser-induced fluorescence quantitation of choloroaluminum phthalocyanine tetrasulfonate concentration in rat tissue

The determination of photosensitizer concentration in tissue will allow improved planning of photodynamic therapy. Laser-induced fluorescence (LIF) has been used to measure fluorescence of drugs in tissue. This study was designed to determine if in-vivo fluorescence intensities could be correlated with tissue concentration of chloroaluminum phthalocyanine tetrasulfonate in rat tissues. Following LIF measurement, the animals were euthanized and the concentration of AlPcs in different tissues were determined using chemical extraction technique. In-vivo fluorescence intensities were correlated with the extracted AlPcs for several tissues. A linear relationship between concentration and in-vivo fluorescence intensity was found for all tissues examined with correlation coefficient being highest in tissues such as liver, spleen, kidney and tumor. The correlation coefficient in skin, leg muscle and tongue was lower.

Treatment of spontaneously occurring veterinary tumors with photodynamic therapy

Chloroaluminum phthalocyanine tetrasulfonate was administered intravenously (1.0 mg/kg) to client owned cats and a dog with spontaneously occurring squamous cell carcinoma of head and neck. Light was delivered 48 hours post injection of the photosensitizer. An argon- pumped dye-laser was used to illuminate the lesions with 675 nm light delivered through a microlens fiber and/or a cylindrical diffuser. The light dose was 100 J/cm2 superficially or 300 J/cm interstitially. Eleven photodynamic therapy treatments in seven cats and one dog were performed. Two cats received a second treatment in approximately sixty days after the initial treatment. The superficial dose of light was increased to 200 J/cm2 for the second treatment. While the longest follow-up is twelve months, the responses are encouraging. The dog had a complete response. Among the cats, three showed complete response, three showed partial response and one showed no response. One cat expired two days post treatment. It is early to evaluate the response in two cats that received second treatments. Photodynamic therapy with chloroaluminum phthalocyanine tetrasulfonate was effective in treating squamous cell carcinoma in pet animals.