Photodynamic therapy with porfimer sodium versus thermal ablation therapy with Nd:YAG laser for palliation of esophageal cancer: a multicenter randomized trial.

BACKGROUND: Photodynamic therapy (PDT) is a different type of laser treatment from Nd:YAG thermal ablation for palliation of dysphagia from esophageal cancer. METHODS: In this prospective, multicenter study, patients with advanced esophageal cancer were randomized to receive PDT with porfimer sodium and argon-pumped dye laser or Nd:YAG laser therapy. RESULTS: Two hundred thirty-six patients were randomized and 218 treated (PDT 110, Nd:YAG 108) at 24 centers. Improvement in dysphagia was equivalent between the two treatment groups. Objective tumor response was also equivalent at week 1, but at month 1 was 32% after PDT and 20% after Nd:YAG (p < 0.05). Nine complete tumor responses occurred after PDT and two after Nd:YAG. Trends for improved responses for PDT were seen in tumors located in the upper and lower third of the esophagus, in long tumors, and in patients who had prior therapy. More mild to moderate complications followed PDT, including sunburn in 19% of patients. Perforations from laser treatments or associated dilations occurred after PDT in 1%, Nd:YAG 7% (p < 0.05). Termination of laser sessions due to adverse events occurred in 3% with PDT and in 19% with Nd:YAG (p < 0.05). CONCLUSIONS: Photodynamic therapy with porfimer sodium has overall equal efficacy to Nd:YAG laser thermal ablation for palliation of dysphagia in esophageal cancer, and equal or better objective tumor response rate. Temporary photosensitivity is a limitation, but PDT is carried out with greater ease and is associated with fewer acute perforations than Nd:YAG laser therapy.

Photodynamic therapy for obstructing esophageal cancer: light dosimetry and randomized comparison with Nd:YAG laser therapy.

BACKGROUND & AIMS: Light dosimetry analysis to achieve predictable tumor necrosis has not been performed for photodynamic therapy (PDT) in the gastrointestinal tract. We evaluated dihematoporphyrin ethers for sensitizing esophageal carcinomas to 630 nm light and compared PDT with neodymium:yttrium-aluminum-garnet (Nd:YAG) laser therapy in a randomized trial. METHODS: Of 52 patients with dysphagia, 32 received palliative PDT. Ten patients treated with PDT participated in a preliminary trial using various doses of 630-nm light, and 22 patients treated with PDT participated in a randomized trial using a derived standardized light dose for comparison with 20 patients treated with the Nd:YAG laser. RESULTS: Light dosimetry correlated with depth of tumor necrosis (r = 0.664; P < 0.001). PDT activity was similar for squamous cell and adenocarcinoma. Among randomized patients, both PDT and Nd:YAG therapy relieved dysphagia, but PDT resulted in improved Karnofsky performance status at 1 month (+7 vs. -7; P < 0.001) and longer duration of response (84 vs. 57 days; P = 0.008). Skin photoreactions were unique to PDT. CONCLUSIONS: The extent of PDT tumor ablation correlates with light dosimetry, enabling selection of a standardized light dose. PDT can relieve esophageal obstruction from squamous cell and adenocarcinoma and is an alternative to Nd:YAG thermal necrosis with a longer duration of response. However, PDT requires patient precautions to minimize skin photoreactions.

Tissue sensitizers.

A second generation of tissue sensitizers has been formulated for the photodynamic ablation of cancer. The photophysical and biologic properties of these agents will determine their activity and clinical use. Investigations of sensitizer properties are discussed, providing a foundation for sensitizer selection, followed by a summary of clinical reports. Tissue sensitizers may be particularly effective for the noninvasive ablation of early cancers.

The safety and efficacy of gi endoscopy in patients with acute-leukemia - a review of 27 cases.

In the course of aggressive treatment for acute leukemia, the ensuing pancytopenia and intensive medical support may be accompanied by severe gastrointestinal (GI) complications. Therefore, to assess the safety and efficacy of GI endoscopy as a means of diagnosis, we analyzed the records of 16 patients undergoing 27 endoscopies a mean (+/-S.D.) of 18.4 +/- 11.9 days post chemotherapy. There were 6 procedures performed in patients with acute lymphocytic, 18 with acute myelogenous, including 3 with acute promyelocytic and 3 with blastic phase chronic myelogenous leukemia. 10/27 procedures were performed in patients with less than 1000 WBC/mm3 and 19/27 had less than 100,000 platelets. 15 patients had 25 upper endoscopies done for: bleeding (twenty-one), abdominal pain (two), and persistent vomiting (two). The principal bleeding sources were: esophagitis (eleven), Mallory Weiss tear (one), gastritis (three), gastric ulcer (one), duodenal ulcer (five). In the non-bleeding cases 2 exams were normal and the others had gastritis (one) and esophagitis (one). 15/25 procedures (64%) resulted in new diagnosis and 20/25 (80%) in additional therapies. 47% of patients undergoing upper GI endoscopy received specific new therapies as a result of that procedure. Nd: YAG laser photocoagulation was effective in stopping bleeding lesions in 4/6 cases. 10/12 bleeding patients had persistent or recurrent bleeding and 2 died from bleeding. None had surgery. Two patients underwent colonoscopy, both for colonic distention. One patient, who had been recently treated for Cl. difficile had submucosal petechiae. The other had non-specific colitis. No biopsies were done and both cases were successfully decompressed..No complications occurred from any GI endoscopy. We conclude that GI endoscopy can be safely performed in patients with acute leukemia, resulting in specific diagnoses and therapies. Esophagitis is a principal cause of GI bleeding in these patients. The role of therapeutic endoscopy in controlling bleeding is promising but requires further evaluation.

Upper gastrointestinal bleeding following open heart surgery. Predominant finding of aggressive duodenal ulcer disease.

We reviewed our experience with endoscopically evaluated severe upper gastrointestinal hemorrhage following open heart surgery. Of 4892 patients undergoing open heart surgery, 18 (0.4%) sustained upper gastrointestinal hemorrhage requiring endoscopic evaluation. Endoscopy identified the source of bleeding in all cases. No significant complications of endoscopy were observed. Duodenal ulcers (DUs) were found in 16 (89%) of cases and were felt to be the source of bleeding in 15 (83%). Aggressive features, such as multiplicity, large size, or distal location were associated with 13 (81%) of the DU cases. Complications necessitated endoscopic or surgical therapy in eight (44%) patients with DUs. We conclude that aggressive DU disease accounts for the majority of severe upper gastrointestinal bleeding following open heart surgery.

The hepatobiliary manifestations of human immunodeficiency virus infection.

Liver abnormalities are common in patients with acquired immune deficiency syndrome. These relate to 1) coincident exposure to hepatotropic viruses, 2) complications, either infectious, neoplastic, or iatrogenic, of the immunosuppressed state, or 3) nonspecific changes associated with chronic debilitating illness. We review the hepatobiliary manifestations of acquired immune deficiency syndrome, and discuss our approach to the clinical evaluation of these problems.

Gastrointestinal manifestations of the acquired immunodeficiency syndrome: a review of 22 cases.

Patients with acquired immunodeficiency syndrome (AIDS) frequently have diarrhea and weight loss. We prospectively examined the upper and lower gastrointestinal tracts in 22 AIDS patients, although severe medical problems often precluded full evaluation. Ninety-six percent (21 of 22) lost weight, and 55% (12 of 22) had diarrhea. The mean (+/- SD) weight loss was 34 +/- 19 lb. Steatorrhea was found in 4 of 14 patients, and D-xylose tests were abnormal in 8 of 14 patients. Mean serum albumin was 3.3 +/- 0.8 g/dl. A significantly diminished plasma selenium level, which can influence immune function, was noted in these AIDS patients. Gastrointestinal infections were identified in 45% of patients. Although diarrhea and malabsorption were more common in the infected group, weight loss and albumin were similar in those with and without demonstrated infections. Flexible sigmoidoscopy showed that of 15 patients, there were two with Kaposi's sarcoma, 10 normals, and three with nonspecific endoscopic changes of colitis. Infection was documented in all patients with colitis. Panendoscopy of the upper gastrointestinal tract was positive for AIDS-related pathology in five of 10 patients, including two with Kaposi's sarcoma, one with Candida esophagitis, one with herpetic esophagitis, and one with gastroduodenitis (biopsy positive for cryptosporidia); five patients had a normal-appearing tract. Small bowel or colonic biopsies frequently showed nonspecific inflammatory changes, although pathogens were identified in six patients (27% of all biopsies). We conclude that a wide variety of gastrointestinal pathology, which includes infectious agents, neoplasms, and inflammatory changes, may occur in AIDS patients. Therefore, AIDS patients, particularly those with diarrhea or weight loss, deserve an intensive evaluation for remediable lesions of their gastrointestinal tracts.