R J Polson

Ninety-three patients with malignant disease underwent orthotopic liver transplantation between May 1968 and April 1987 in the Cambridge/King's College Hospital program. Of 50 patients with primary hepatocellular carcinoma (HCC) (19 with cirrhosis, 31 without cirrhosis, including 7 with fibrolamellar variant), 37 (74%) survived for more than 3 months, and in this group evidence of tumor recurrence was obtained in 24 (64.9%), the longest survivor being 11.8 years post-transplant, and three survived for more than 5 years. Although there is no correlation between the frequency of tumor recurrence and underlying cirrhosis, or histologic type (except fibrolamellar variant), it was observed earlier in those with moderate/poorly differentiated tumors and also when prednisolone and azathioprine was used for immunosuppression. Tumor recurred in all but two of those with peripheral or central cholangiocarcinoma (one alive at 6.1 years) with median survival times of 34 weeks and 56 weeks for the central and peripheral types, respectively. Among the unusual primary tumors, one with epithelioid haemangioendothelioma developed tumor recurrence at 2 years, one of two patients with apudoma is tumor-free at 2.2 years, and the one patient with bile-duct papillary cystadenocarcinoma is alive at 1.7 years. For the secondary hepatic malignancy group, survival times were shorter with little palliation except for two patients with carcinoid syndrome who were free of associated symptoms at 6 and 10 months. Despite the overall high frequency of tumor recurrence in most categories of hepatic malignancy, liver transplantation gave worthwhile survival with a number of patients cured and in the others considerable palliation of symptoms.

BACKGROUND AND AIMS: Helicobacter pylori infection is the major cause of peptic ulceration and gastric adenocarcinoma. To address the hypothesis that the human acquired immune response to H. pylori influences pathogenesis, we characterised the gastric T helper (Th) and regulatory T cell (Treg) response of infected patients. METHODS: The human gastric CD4(+) T cell response of 28 donors who were infected with H. pylori and 44 who were not infected was analysed using flow cytometry. The T cell associated mucosal cytokine response was analysed by real-time polymerase chain reaction assay of samples from 38 infected and 22 uninfected donors. Recombinant interleukin 10 (IL10) was added to co-cultures of H. pylori and AGS cells and its suppressive effects upon inflammatory responses were measured. RESULTS: We found that the H. pylori-specific response consists of both T helper 1 and 2 subsets with high levels of IL10-secreting Tregs. People with peptic ulcer disease had a 2.4-fold reduced CD4(+)CD25(hi)IL10(+) Treg response (p = 0.05) but increased Th1 and Th2 responses (Th1: 3.2-fold, p = 0.038; Th2: 6.1-fold, p = 0.029) compared to those without ulcers. In vitro studies showed that IL10 inhibited IL8 expression and activation of nuclear factor kappa B induced by H. pylori in gastric epithelial cells, and enhanced H. pylori growth in a bacterial-cell co-culture model. CONCLUSIONS: Together our data suggest that H. pylori induces a regulatory T cell response, possibly contributing to its peaceful coexistence with the human host, and that ulcers occur when this regulatory response is inadequate.

In a prospective, randomized clinical trial, immediate injection sclerotherapy was compared with treatment by a combined infusion of vasopressin (0.4 unit per min) and nitroglycerin (40 to 400 micrograms per min) in 50 consecutive patients with 64 episodes of endoscopy-proven variceal hemorrhage. Control of bleeding was assessed over a 12-hr period following entry into the trial. Patients in the vasopressin + nitroglycerin group were then treated by sclerotherapy, as were those in the sclerotherapy group who continued to bleed. At 12 hr, bleeding was controlled in 29 (88%) of the 33 episodes treated by sclerotherapy compared with 20 (65%) of 31 episodes treated by vasopressin + nitroglycerin (p less than 0.05). Recurrence of variceal bleeding occurred at the same frequency (31%). Although admission mortality was less in those initially treated by sclerotherapy compared to those managed by vasopressin + nitroglycerin, this did not reach statistical significance (27 and 39%, respectively, p greater than 0.20). Sclerotherapy carried out as the first treatment of the active variceal hemorrhage proved both safe and effective, even in the presence of major hemorrhage, and as compared to combined vasopressin and nitroglycerin it proved superior.

There is no ideal method for detecting Helicobacter pylori. The 'standard' 13Carbon urea breath test (13C-UBT), which involves collecting eight to 15 breath samples and subsequent costly analysis, was modified by pooling 21 samples of expired breath taken at five minute intervals for 40 minutes into a collecting bag, from which a single 20 ml aliquot was taken and analysed by mass spectrometry. This test was evaluated on 50 patients after routine upper gastrointestinal endoscopy, and results were compared with those from the standard 13C-UBT, bacteriology, ELISA serology, and histology--the latter being taken as the gold standard. H pylori were seen in 34 of 50 (68%) patients (in three it was detected in biopsy specimens from the corpus alone). The modified 13C-UBT was positive (pooled excretion delta 13CO2 greater than 5 per mil) in 31 patients and negative in 19 (three false negative results), specificity was 100% (standard 13C-UBT 94%) and sensitivity 92% (standard 13C-UBT 93%). The modified 13C-UBT had a coefficient of variation within subjects of 3.7%. For the ELISA serology and culture the specificities were both 100%, but the sensitivities were 82% and 68% respectively. The 13C-UBT results correlated with the grade of histological gastritis. The modified 13C-UBT is simpler, cheaper, more reproducible, and provides an easy non-invasive method for the detection of H pylori.