Evaluation of Locoregional Recurrence Patterns Following Adjuvant (Chemo)Radiotherapy for Oral Cavity Carcinoma.

AIMS: To evaluate patterns of locoregional recurrence following adjuvant (chemo)radiotherapy for oral cavity squamous cell carcinomas. MATERIALS AND METHODS: One hundred and one patients who received adjuvant radiotherapy ± chemotherapy for oral cavity squamous cell carcinoma between 2013 and 2016 were analysed. For documented locoregional recurrence, recurrence imaging was deformably co-registered to the planning computed tomography scan. The volume of recurrence was delineated (Vrec). Vrec coverage by 95% of the corresponding planning target volume prescription dose was determined and the location compared with planning target volumes. Sites of recurrence were classified using a combined volume and centroid-based method: (A) central high dose, (B) peripheral high dose, (C) central low dose, (D) central peripheral dose, (E) extraneous. RESULTS: The median follow-up was 36 months. Forty-three per cent and 53% of patients received radiotherapy to the ipsilateral neck only and bilateral neck, respectively. Three-year overall survival, disease-free survival, local control, regional control and distant metastases-free survival were 63.0, 65.6, 88.0, 85.1 and 85.3%, respectively. Of 10 episodes of primary site recurrences, five were type A, four type B and one was type E. Of 14 episodes of regional recurrence, five were type A, two type C, two type D and five type E. Five of 21 (24%) patients with oral tongue carcinoma with an undissected/unirradiated contralateral neck had a type E contralateral neck recurrence, including 2/11 with pN0, 1/4 with pN1 and 2/6 with pN2 disease. CONCLUSIONS: Marginal and out-of-field recurrences remain a significant pattern of failure. We advocate generous target delineation postoperatively and, for oral tongue carcinomas, a comprehensive approach with bilateral neck irradiation.

A double-blind controlled trial of the effect of sodium cromoglycate in preventing relapse in ulcerative colitis.

A double-blind controlled trial of the effect of sodium cromoglycate (SCG) in preventing relapse in ulcerative colitis has been completed in 100 subjects. In patients already taking sulphasalazine, SCG did not prove to be of any additional benefit. However, in patients not on any other maintenance therapy, the relapse rate was 40% for SCG as compared with 75% for placebo. A large study of the effect of SCG in patients intolerant of sulphasalazine is indicated.

Serum, cerebrospinal fluid, and brain levels of bile acids in patients with fulminant hepatic failure.

Bile acid levels were measured in the sera, cerebrospinal fluid (CSF), and brain tissue of 10 patients immediately after death from fulminant hepatic (FHF). Serum bile acids in FHF were predominantly conjugated, and total bile acid levels were higher in all 10 patients than in normal controls (85.9 +/- SE 8.4 compared with 5.7 +/- 0.4 nmol/ml, P less than 0.001). Small but significant amounts could be detected in CSF (range 1.2-5.3 nmol total bile acid/ml) and brain biopsies (1.0-18.8 nmol/g wet weight) of FHF patients, whereas none could be detected in CSF and brain biopsies of patients dying without evidence of liver disease. There was no relationship between serum, CSF, or brain levels and duration of coma, or presence of cerebral oedema found in five FHF patients at necropsy. However, serum bile acid levels were similar in FHF to those found in chronic liver disease without encephalopathy and lower than those found to inhibit brain respiration in vitro. A primary role for these compounds in the pathogenesis of coma in FHF therefore seems unlikely.

Detection and grading of oesophageal varices by fibre-optic endoscopy and barium swallow with and without Buscopan.

Detection of oesophageal varices is important in the diagnosis of portal hypertension. We have, therefore, compared the results of fibre-optic endoscopy and barium swallow in 56 patients with chronic liver disease. Oesophageal varices were graded as small, moderate or gross by independent observers for each technique. In 12 patients varices were not detected by either method, and in six cases varices were detected by endoscopy when the barium swallow was negative. In 15 of the remaining 38 patients varices were found to be one grade larger at endoscopy than on barium swallow. Since it is possible that varices appear larger at endoscopy because of the Buscopan (hyoscine N-butyl bromide) used as a relaxant, we carried out barium examinations after Buscopan 20 mg i.v. in 23 of the patients. In eight cases varices were one grade larger after Buscopan than on the standard barium swallow, and in two were only detected after Buscopan had been given. Eight cases negative after Buscopan were also negative at endoscopy. Although emergency endoscopy has particular value in locating the site of bleeding in patients with portal hypertension and acute gastrointestinal haemorrhage, the results of the present study suggest that a barium meal with Buscopan is as accurate as endoscopy in the detection of oesophageal varices.

Kinetics of [14C]cholic acid in fulminant hepatic failure: a prognostic test.

The kinetics of intravenously injected [14C]cholic acid have been investigated in 14 patients with fulminant hepatic failure, 24 to 36 hr after the development of grade IV encephalopathy. Radioactivity was measured in plasma samples and in the individual plasma bile acid fractions after separation by thin layer chromatography. Plasma disappearance curves of the free [14C]cholic acid were calculated by an iterative nonlinear least squares fitting procedure using a computer. The disappearance of total plasma radioactivity was similar in all patients and greatly prolonged compared with healthy subjects. However, the plasma disappearance of free [14C]cholic acid was significantly faster in the 8 patients who recovered consciousness than in the 6 who did not. Plasma disappearance of free [14C]cholic acid correlated highly significantly with the proportion of conjugated [14C]cholate in plasma. All patients in whom more than 70% of plasma radioactivity was in the conjugated fraction 3 hr after injection survived and left hospital, whereas all of those in whom less than 55% was conjugated died. Measuring the percentage conjugation of [14C]cholate 3 hr after injection may therefore be a useful test of residual liver function in hepatic failure, as a guide to prognosis and in evaluating new forms of treatment.

Bile composition and bile cast formation after transplantation of the liver in man.

Transplantation of the liver in man is frequently complicated by biliary fistula and obstruction of the biliary tree by casts, which suggests that the composition of the bile may be abnormal. In part of the present study, bile composition was investigated in three recipients during the first few weeks after transplantation, when a T tube was in place. Supersaturation of bile with cholesterol was found in two patients immediately after surgery and during episodes of acute rejection, but bile was never lithogenic in the third. There was no evidence of bile stasis in the absence of acute rejection and bile viscosity was normal in all three patients throughout the study. Free bile acids and free bilirubin, which are relatively insoluble products of bacterial metabolism, were not present in the bile of any patient. However, chemical analysis of casts found at autopsy in a fourth recipient showed that the major component was free bilirubin. Escherichia coli was grown in cultures of the casts and the organisms were shown to possess glucuronidase activity, thus providing an explanation for the high bilirubin content. There was also some evidence in one case that damage to the bile duct mucosa has led to the precipitation of material upon it, and it is concluded that a number of factors, including infection, supersaturation with cholesterol, and mucosal damage, may be involved in bile case formation after transplantation of the liver.

Chronic pancreatitis, sclerosing cholangitis, and sicca complex in two siblings.

A new syndrome of chronic pancreatitis, sclerosing cholangitis, sicca complex, and other features was found in a brother and sister. Leucocyte-migration inhibition in the presence of a bile antigen in both patients suggested that immune mechanisms may be involved.

Mechanisms of lipid loss from the small intestinal mucosa.

Many water-soluble compounds have been shown to pass from the small intestinal mucosa into the lumen. In this work, the loss of lipids from the mucosa was investigated by perfusion experiments in rats, using 0-15M NaCl or buffer solutions over range of pH, with or without the addition of 5-7 or 11-4mM taurocholic acid. Perfusates were extracted for the estimation of individual lipids and for DNA, which is a measure of cell loss. The results suggest that free fatty acids reach the lumen by diffusion and that their solubility in the luminal fluid is a factor determining their rate of loss. Triglycerides, cholesterol, phosphatidyl ethanolamine, and phosphatidly choline are present onlyas the result of desquamation of mucosal cells.

Salmonella heidelberg infection in Caroli's syndrome.

A PATIENT IS DESCRIBED IN WHOM DIARRHEA AND FEVER DUE TO Salmonella heidelberg was followed by a series of episodes of cholangitis due to the same organism. Cholecystectomy and prolonged courses of antibiotics failed to eradicate the infection, and the presence of multiple intrahepatic biliary cysts (Caroli's syndrome) was eventually discovered by endoscopic retrograde cholangiography.

Emergency endoscopy after gastrointestinal haemorrhage in 50 patients with portal hypertension.

Endoscopy was carried out in 50 patients with oesophageal varices within 24 hours of a major haematemesis or melaena. Sources of bleeding were identified in 42 of the cases and in only 19 patients was bleeding due to oesophageal varices. Bleeding from gastric varices was present in 11 patients, and a variety of acute and chronic lesions made up the remainder. In contrast with previous series haemorrhage from erosive gastric lesions was seen in only five patients and was no more common in 23 patients with alcoholic cirrhosis than in the group as a whole.

Early endoscopy of oesophagus, stomach, and duodenal bulb in patients with haematemesis and melaena.

Oesophago-gastro-duodenoscopy was successfully performed in 196 of 208 patients admitted with haematemesis or melaena, or both. A precise visual diagnosis was made in 80% of all patients and in 96% of those where the final diagnosis lay within the oesophagus, stomach, and first two parts of the duodenum. Bleeding oesophagitis was more common and bleeding duodenal ulcer less common than in other series using mainly radiology. Altogether, 26% of all patients with endoscopically-proved duodenal ulcers were bleeding from another site, and 15.4% of all patients had more than one lesion. This fact, and inability to detect surface lesions limits the value of acute barium radiology, which was performed in only 81 patients. Accurate diagnosis should lead to better understanding of individual lesions and more rational management of individual patients. Where a good service is available oesophago-gastro-duodenoscopy should be performed on all bleeding patients within 24 hours of admission.