Cost-effectiveness of N-butyl-2-cyanoacrylate (histoacryl) glue injections versus transjugular intrahepatic portosystemic shunt in the management of acute gastric variceal bleeding.

UNLABELLED: The management of bleeding gastric varices has not been standardized. Although transjugular intrahepatic portosystemic shunt (TIPS) is used in most centers, endoscopic treatment with N-butyl-2-cyanoacrylate (cyanoacrylate) glue has recently been shown to be effective. Cost-effectiveness analyses of these methods are lacking. METHODS: We performed a retrospective review of patients with bleeding gastric varices treated either by TIPS or cyanoacrylate glue injection. Economic analysis was based on direct costs for a fixed financial year. The two groups were compared for a period of 6 months follow-up, to liver transplantation, or death for each patient. RESULTS: Between January, 1995 and December, 1999, 20 patients with bleeding gastric varices had TIPS; 23 patients had cyanoacrylate glue injection from January, 2000 to October, 2001. There were no significant differences between the two groups in patient characteristics, transfusion requirement, and gastric variceal anatomy. In the TIPS group, 15/20 patients had the procedure performed within 24 h of hemorrhage, and 90% of stent insertions were successful. Complications consisted of two cases of pulmonary edema, two cases of severe encephalopathy, and a 15% stenosis rate at 6 months. In the glue group, there were 3 +/- 1.5 endoscopies and 2 +/- 1 injections per patient, with a 96% initial hemostasis. There was one case of (glue) pulmonary embolism and one blocked front endoscope lens, which required repair. The initial rebleed rate was significantly lower in patients who had TIPS (15% vs 30%, p = 0.005). The inpatient stay was shorter in the glue group (13 +/- 1 vs 18 +/- 2 days, p = 0.05), but there was no difference in the overall mortality rate. The median cost within 6 months of initial gastric variceal bleeding was $4,138 US dollars ($3,009-$8,290 US dollars) for glue versus $11,906 US dollars ($8,200-$16,770 US dollars) for TIPS (p < 0.0001). CONCLUSION: In this comparable group of patients, cyanoacrylate glue injection was more cost effective than TIPS in the management of acute gastric variceal bleeding. A prospective, randomized trial would be required to confirm our analysis.

Safety of pancreatic surgery in a small DGH.

The Combined Gastroenterology Service at Scarborough Hospital has a particular interest in pancreatic disease. The claim that pancreatic surgery should only be performed in larger, specialised units prompted a review of our experience in a small district general hospital (DGH). The case notes of 63 patients who had undergone pancreatic surgery over a 7-year period were examined retrospectively. The 30-day mortality was 8%, while 14 complications were recorded. Of 16 patients with acute pancreatitis, three died before discharge and three had long-term complications. Five patients who underwent surgery for chronic pancreatitis were discharged safely. There were 11 curative and 29 palliative procedures for patients with malignant disease. Median survival was 8 months (range 1-32 months) and median hospital stay was 16.8 days (range 7-89 days). Successful pancreatic surgery can be performed safely in a DGH setting. Patient selection and expertise are more important than numbers.

Photodynamic therapy for gastrointestinal tumors using three photosensitizers--ALA induced PPIX, Photofrin and MTHPC. A pilot study.

Photodynamic therapy (PDT) produces localized necrosis with light after prior administration of a photosensitizing drug. As PDT lesions in the gastrointestinal tract heal well, the technique is suitable for repeated endoscopic use. In this study we used PDT to treat benign and malignant gastrointestinal tumors in esophagus, duodenum and rectum in 22 patients, who refused or were not suitable for surgery. Patients were sensitized with 0.15 mg/kg of body weight with mesotetrahydroxyphenylchlorin i.v. m-THPc (2 patients), with 2.0 mg/kg Photofrin i.v. (4 patients) or 60 mg/kg 5-aminolevulinic acid orally ALA (which is converted in vivo to active derivate protoporphyrin IX-PRIX) in fractionated doses (16 patients). Laser treatment was performed 2 days after Photofrin, 2 and 4 days after mTHPc and 4 hours after ALA, using a metal vapour laser (628 nm, 50-150 J/cm2 for ALA and Photofrin, 650 nm and 10-15 J/cm2 for mTHPc). Using ALA, the necrosis was only superficial (up to 1.8 mm depth). Four patients treated with Photofrin showed deeper necrosis, in one case of 8 mm colon cancer complete response, in three cases 1-1.5 cm adenomatous polyps involving the ampulla Vateri 50% longer term reduction in size-seen endoscopically. Two patients with rectal villous adenomas treated with mTHPc showed 60-80% reduction in size (observed endoscopically) within few days after PDT, with better effects for treatment carried out 4 rather than 2 days after the sensitization. In all patients the healing was without any complications. Photofrin and mTHPc work better, but cause cutaneous photosensitivity lasting 12 and 5 weeks, respectively. Better results with ALA are possible when using higher drug doses or modified light dosimetry. PDT is a promising treatment for small localized tumors in patients unsuitable for surgery, but further work is required to optimize the treatment conditions.

A prospective study of serum pancreatic elastase-1 in the diagnosis and assessment of acute pancreatitis.

BACKGROUND: Serum amylase gives a poor estimate of both the true incidence and the severity of acute pancreatitis (AP). METHODS: We evaluated serum pancreatic elastase-1 (PE-1) prospectively in 567 patients in whom AP was suspected. In established AP, severity was assessed using the Glasgow Criteria, and C-reactive protein, amylase, and serum PE-1 were evaluated over 5 days. RESULTS: The sensitivity, specificity, and diagnostic efficiency of serum PE-1 were 0.66, 0.85, and 0.84, respectively. The diagnostic accuracy of serum PE-1 was 0.80, and that of amylase 0.97. Serum PE-1 did not correlate with disease severity or the development of complications, but it fell more slowly than the serum amylase in the week after admission. CONCLUSIONS: The serum PE-1 level correlated closely with the serum amylase but conferred no benefit as a diagnostic test, nor did it provide further prognostic information.

Distribution and photodynamic effects of meso-tetrahydroxyphenylchlorin (mTHPC) in the pancreas and adjacent tissues in the Syrian golden hamster.

Photodynamic therapy (PDT) has the potential to destroy small tumours with safe healing of adjacent normal tissue. This study looks at the effects of PDT on the normal pancreas and adjacent tissues in hamsters using the photosensitiser meso-tetrahydroxyphenylchlorin (mTHPC). Pharmacokinetic studies used fluorescence microscopy on sections of pancreas, stomach and duodenum 1 h to 6 days after mTHPC. Highest levels of sensitiser were seen in the gastric and duodenal mucosa and in the acinar pancreas after 2-4 days. For PDT, light at 652 nm was delivered by placing a 0.2 mm diameter bare-ended fibre against the tissue. An energy of 50 J was used 2 or 4 days after 0.1 or 0.3 mg kg-1 mTHPC and animals killed 1 to 7 days later. Maximum necrosis was seen 3 days after PDT with lesions up to 4 mm in pancreas, 4.5 mm in duodenum and 2.5 mm in stomach. By fractionating the light dose, the lesion size could be increased by 30%. The main complication was free or sealed duodenal perforation (avoided by shielding the duodenum). Partial, reversible bile duct obstruction was seen occasionally. There was no macroscopic damage to the bile ducts or major blood vessels. Apart from the duodenum, all lesions healed safely. In this animal model, only the duodenum was at risk of serious, irreversible damage. Treatment is likely to be safer in the much thicker human duodenum. mTHPC is a powerful photosensitiser and suitable for further study for tumours in the region of the pancreas although care is required near the duodenum.

The killing of Helicobacter pylori by low-power laser light in the presence of a photosensitiser.

Helicobacter pylori is associated with various gastrointestinal disorders. Lethal photosensitisation was investigated as a possible technique for killing H. pylori which might offer a better alternative to antibiotics. The susceptibility of H. pylori to lethal photosensitisation was determined by mixing suspensions of H. pylori with various photosensitisers and plating out on blood agar before irradiation with low-power laser light. Five sensitisers were studied further by mixing them with H. pylori in a tissue-culture plate and counting survivors after irradiation as a function of laser exposure time, dye concentration and pre-irradiation time. Crystal violet and thionine were ineffective as sensitisers, but zones of inhibition appeared with methylene blue (MB), protoporphyrin IX (PPIX), haematoporphyrin derivative (HPD), toluidine blue O (TBO) and disulphonated aluminium phthalocyanine (S2). Laser light or sensitiser alone did not affect bacterial viability. S2 (100 microg/ml) with a laser light energy density of 16 J/cm2, HPD (10O microg/ml) with 160 J/cm2, MB (100 microg/ml) with 21 J/cm2, PPIX (150 microg/ml) with 320 J/cm2 and TBO (50 microg/ml) with 160 J/cm2 all reduced bacterial viability by >99%. The killing of sensitised H. pylori by laser light offers a new approach to the treatment of localised infections when all colonised areas are accessible to light.

Ex-vivo treatment of gastric Helicobacter infection by photodynamic therapy.

Attempts to develop PDT for eradication of Helicobacter infection have only been successful in vitro. We have investigated the effect of topical sensitization (except ALA) of Helicobacter mustelae on explanted ferret gastric mucosa using one of five sensitizers (methylene blue (MB), toluidine blue O (TBO), phthalocyanine, haematoporphyrin derivative and 5-aminolavulinic acid), followed by irradiation with an appropriately tuned copper vapour pumped dye laser. A 90% reduction in counts of bacteria sensitized with 0.75 mg TBO kg-1 were seen after irradiation with 200 J cm-2. Concentrations of MB of 0.75 mg kg-1 and 7.5 mg kg-1 were not toxic to H. mustelae, but the further addition of 20 J cm-2 laser light reduced colony counts by more than 99%. MB at a concentration of 75 mg kg-1 exhibited significant dark toxicity towards H. mustelae, but further addition of 20 J cm-2 laser light resulted in near eradication of all colonies. The remaining three compounds were ineffective. Finally, we studied the microscopic fluorescence distribution of MB (7.5 mg kg-1) on ferret gastric mucosa after topical administration. Fluorescence was greatest in the superficial mucosal layer, upon which lies the bacteria. However, from experiments on rats, the energy required to kill the sensitized bacteria was insufficient to damage the underlying mucosa. We conclude that Helicobacter can be killed on host mucosal epithelium following topical administration of MB and subsequent exposure to laser light.

Sensitization and photodynamic therapy (PDT) of gastrointestinal tumors with 5-aminolaevulinic acid (ALA) induced protoporphyrin IX (PPIX). A pilot study.

5-Aminolaevulinic acid (ALA) is a promising agent for photodynamic therapy (PDT) sensitization as it can be given orally and only causes skin photosensitivity for 1-2 days. In fluorescence and photodynamic studies 26 patients with benign and malignant gastrointestinal tumors were given 30-60 mg ALA orally (single or divided doses) and biopsies were taken of tumor and normal tissue at 1-24 hours for fluorescence microscopy. With 30 mg/kg, highest protoporphyrin IX (PPIX) levels were seen in esophagus, duodenum and less in colon, but without tumor selectivity. Better tumor selectivity was seen in colon after 60 mg/kg (5:1). Six patients had transient rises in transaminases and five mild nausea. Sixteen patients were later treated (after further ALA) with red light (628 nm, bare or diffuser fibre, 50-100 J at 50 mW at each site). All but two showed subsequent necrosis, but only 0.5-1.5 mm of depth. PDT with ALA is simple, safe and promising for tumors in the gastrointestinal tract. Modification of treatment parameters may make it suitable for larger lesions.