Endoscopic cryotherapy: experimental results and first clinical use.

BACKGROUND: Cryotherapy or the application of extreme cold has many potential applications in gastroenterology including tissue destruction and hemostasis but until now its development has been prevented by the lack of a delivery device suitable for use through the endoscope. We report here our experience with prototype devices using both liquid nitrogen driven by a cryosurgical system and cryogenic refrigerants (nitrous oxide and carbon dioxide) at or near ambient temperature. METHODS: Cryotherapy was applied to the distal esophageal mucosa of dogs via a flexible catheter passed through an upper endoscope. In other dogs, cryotherapy was used for hemostasis in a bleeding ulcer model. The procedure was also used for palliation in a 58-year-old man with unresectable adenocarcinoma of the stomach with pyloric channel obstruction. RESULTS: Freezing of the superficial mucosa was nearly instantaneous. All dogs survived the procedure and appeared to thrive. Histologic evaluation revealed significant necrosis of the superficial epithelial layer accompanied by a fibrinocellular infiltrate on the surface. These markers of acute injury subside by the fourth to sixth day and are replaced by regenerating epithelium, a process that is virtually complete by day 10. In the hemostasis experiments, bleeding ceased immediately after cryospraying of the lesions but resumed on thawing in most cases. Application of cryotherapy in the patient resulted in reduction of the pyloric mass with no immediately apparent adverse effects. CONCLUSIONS: These data, although preliminary, demonstrate the feasibility of endoscopic cryotherapy using a simple hand-held device. This device has broad potential for use in gastroenterology including ablation of superficial epithelium, debulking of large tumors and hemostasis.

Clinical usefulness of 3% hydrogen peroxide in acute upper GI bleeding: a pilot study.

BACKGROUND: A major problem in the endoscopic management of acute upper gastrointestinal (GI) bleeding is the presence of blood and clots overlying the bleeding source, preventing visualization of the lesion. A simple alternative is to alter the characteristics of blood such that it not only becomes easier to remove but also becomes translucent. We report the results of a pilot study on the use of hydrogen peroxide in patients with acute upper GI bleeding. METHODS: Patients with acute upper GI bleeding were studied if the presence of blood or clots obscured the site of bleeding. The potential site of bleeding was initially sprayed with 200 mL water and then with 200 mL 3% hydrogen peroxide mixed with simethicone. RESULTS: In 6 patients with acute upper GI bleeding, hydrogen peroxide spray resulted in good to excellent visualization of the bleeding source. Hemostasis occurred in 2 patients who were actively bleeding. There were no adverse effects or complications. CONCLUSIONS: Hydrogen peroxide significantly enhanced clot dissolution and endoscopic visualization in patients with acute upper GI bleeding.

Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure.

The objective of this pilot controlled study was to evaluate the extracorporeal liver assist device (ELAD) in patients with acute liver failure who were judged to still have a significant chance of survival (approximately 50%) and in those who had already fulfilled criteria for transplantation. Twenty-four patients were divided into two groups, 17 with a potentially recoverable lesion (group I) and 7 listed for transplantation (group II), and then randomly allocated to ELAD haemoperfusion or control. The median period of ELAD haemoperfusion was 72 hours (range 3-168 h). Biocompatibility of the device was good, with no acceleration in platelet consumption, and haemodynamic stability was maintained. Two patients were withdrawn from the study because of worsening of preexisting disseminated intravascular coagulation in one case and a hypersensitivity reaction in the other. Deterioration with respect to encephalopathy grade was more frequent in the control patients, 7 of 12 (58%), than in the ELAD-treated patients, 3 of 12 (25%). In group I where survival for the ELAD cases was 7 of 9 (78%), there was a higher than expected survival in the controls, 6 of 8 (75%). For group II cases, survival was 1 of 3 (33%) for the ELAD-treated patients, and 1 of 4 (25%) for the controls. Both of the survivors underwent transplantation. Assessment of additive function for the device revealed an improvement in galactose elimination capacity after 6 hours of haemoperfusion. Based on the results of this pilot-controlled trial, better indices of prognosis will be required, in addition to those used to select for transplantation, if patients at an earlier stage of clinical deterioration are to be included in future studies.

Extracorporeal liver support. Application to fulminant hepatic failure.

Artificial liver support is urgently needed. Mechanical devices such as hemodialysis and hemoperfusion do not correct the metabolic abnormalities that exist in endstage liver disease, and biologically active devices have been impracticable because of limitations in the availability and viability of cultured liver cells. This deficit in the medical armamentarium is a major concern best illustrated by current management of fulminant hepatic failure (FHF). Medical treatment for FHF is largely unsuccessful, and orthotopic liver transplantation (OLT) is the intervention against which all future therapeutic interventions must be judged. The OLT procedure, however, is not benign. The cost is high, and survivors face a lifetime of immunosuppression and medical supervision. By comparison, patients who survive without surgery recover full liver function and have a normal life expectancy. A device that provides liver support during the critical stages of FHF would stabilize patients until a suitable donor organ was found and might negate the need for transplant altogether if the liver were able to regenerate. We review theoretical and practical aspects of biologically active devices using FHF as a paradigm of liver disease.

A treatment system for implementing an extracorporeal liver assist device.

Biologically active devices are receiving increasing attention, especially in the management of endocrine pancreatic failure (diabetes) and acute liver failure. In both instances, mechanical devices have been unable to replace the function of the original organ, and consequences range from inconvenient (e.g., regular insulin shots, diabetic vasculopathy) to fatal (e.g., fulminant hepatic failure). In developing a cell-based liver assist device, we concluded that currently available extracorporeal blood treatment systems are not suited to the delivery of high molecular weight substances and that they do not adequately address the metabolic needs of the device. We therefore developed a system that provides safe, continuous perfusion of an extracorporeal organ. We detail the design and first clinical use of the system.

The Hepatix extracorporeal liver assist device: initial clinical experience.

Eleven patients were treated with the Hepatix extracorporeal liver assist device (ELAD) between June 1991 and August 1993. The first 2 patients were treated according to Food and Drug Administration guidelines ("Emergency Use of Unapproved Medical Devices," October 22, 1985), and the remaining 9 were treated according to an Investigational Device Exemption (IDE). The goal of the study was to establish the short-term safety of ELAD therapy, with a focus on acute medical complications such as hemodynamic instability, complement activation, and deterioration of vital organ function. As secondary goals, the metabolic capacity of ELAD cartridges and their clinical impact were assessed. Treatment was considered successful if the patient recovered sufficient liver function to survive weaning from the ELAD or was stabilized until orthotopic liver transplantation was performed. No short-term safety problems were associated with ELAD use. In addition, metabolic support was documented in 10 of the 11 patients, and 6 patients reached a successful end-point. The Hepatix ELAD is safe, and it provides measurable metabolic support in patients with late-stage liver failure. This pilot study provides the impetus to perform controlled trials of ELAD therapy in the treatment of various types of end-stage liver disease.