Enhancement of cardiac allografts in rats. Comparison of host responses to different treatment protocols.

Immunological responses to heterotopic (L X BN)F1 cardiac allografts placed in untreated L rats were compared with those grafts enhanced by different treatment regimens. Host pretreatment by antigen and antibody (Ag-Ab) 11 and 10 days before transplantation, respectively, was the most effective treatment regimen for prolongation of graft function; active or passive immunization alone increased survival only modestly. A late dose of antiserum administered to Ag-Ab-pretreated animals significantly shortened graft survival. Patterns of cellular responsiveness were measured serially by lymphocyte-mediated cytotoxicity; humoral immunity by Ab-lymphocyte-mediated cytotoxicity, capillary hemagglutination, and complement-dependent cytotoxicity. Allograft rejection in animals of all groups was heralded in vitro by increasing immunological activity. All cellular and humoral responses were depressed consistently in Ag-Ab-pretreated recipients. Cellular but not humoral responses were decreased in Ag-pretreated hosts, while humoral but not cellular responses were decreased in Ab-treated animals. The results suggest that the in vitro determinants of immunological activity used in this study generally followed clinical patterns of rejection or enhancement of cardiac allografts in the rat. Recipient pretreatment with Ag and Ab is more effective in graft prolongation than treatment with Ag or Ab alone, and in vitro data suggest an additive effect of these two regiments.

Site distribution of oesophagogastric cancer.

AIMS: It has been suggested that adenocarcinomas of the lower oesophagus and gastric cardia should be reclassified as oesophagogastric junction (OGJ) cancers. This study aimed to define the frequency of OGJ cancers in a geographically defined population of 4.3 million people. METHODS: All cases of oesophageal and gastric cancer occurring in 1993 were identified by the North Western Regional Cancer Registry. A total of 1192 hospital case notes were reviewed and a study group of 1067 patients was defined. Tumour involvement was documented at individual subsites in the oesophagus and stomach, allowing for tumour presence in more than one oesophageal/gastric subsite. RESULTS: There were 627 tumours in men and 440 in women. The tumour was confined to the oesophagus in 281 (26.3%) cases and to the stomach in 454 (42.6%) cases. The tumour encroached upon or crossed the OGJ in 332 (31.1%) cases. Overall, tumours involved the cardia, OGJ, or lower oesophagus in 633 (59.3%) cases; in 179 (18.5%) cases the tumour involved the lower oesophagus but not the OGJ, and in another 122 (11.4%) cases the cardia was involved but not the OGJ. CONCLUSIONS: Oesophagogastric cancers in this population predominantly involve the OGJ, lower oesophagus, and/or cardia.

Identification of the optimal parameters for recording cortical evoked potentials to human oesophageal electrical stimulation.

Cortical evoked potentials in response to stimulation of the oesophagus may prove to be a powerful technique for assessing the oesophageal afferent pathway in health and disease. However, in order to maximize the potential of this technique it is essential that the optimal parameters for recording oesophageal CEP are established. The aim was to determine the optimal parameters required to record reproducible CEP. CEP were recorded from the vertex in eight subjects (age range 23-44 years). Electrical stimulation was performed 5 cm above the lower oesophageal sphincter using a bipolar ring electrode at 0.2 Hz. Protocol 1: to determine the stimulation intensity which generates the largest amplitude and shortest latency, two runs of 50 stimuli were applied at increasing intensities. Protocol 2: to determine the number of stimuli for optimal signal to noise ratio, 10 runs of 50 stimuli were recorded. Individual runs were averaged. Protocol 3: to determine the optimal inter-run interval, CEP evoked by 200 stimuli were averaged using randomly chosen inter-run intervals. Protocol 4: CEP reproducibility using parameters determined from Protocols 1-3 was assessed in three subjects on three separate occasions. The results were as follows: Protocol 1; P1 latency was shortest and P1-N1 amplitude largest at an intensity of 75% above threshold. Protocol 2; optimal signal-to-noise was achieved by averaging four runs of 50 stimuli. Protocol 3; the optimal interstudy interval was 10 min. Protocol 4; highly reproducible CEP were obtained in all individuals. Using these optimal parameters, it is possible to obtain highly reproducible oesophageal CEP to ES which can now be used for clinical study.

Palliation in oesophageal neoplasia.

Oesophageal cancer is an increasingly common disease in the UK. Sadly, the overall results of treatment remain poor with overall 5 year survival of approximately 10%. More than 50% of patients receive purely palliative care from the outset. Of those having potentially curative treatment, 40% will not survive the first year and 70% will not survive 5 years. Good quality palliation is, therefore, required for the majority of patients.

The surgical management of pancreatic abscess.

In the past 6 years we have operated on 13 patients with pancreatic abscess. Sepsis recurred in all 12 in whom the primary procedure was closed drainage. Following further surgical debridement of these recurrent abscesses 2 patients had further closed drainage and in 10 the cavities were packed open to heal by granulation. One patient underwent primary open packing which eliminated the pancreatic abscess but the patient subsequently died. Six patients (46%) died: one of lung abscesses after recovering completely from secondary open packing, one of an unsuspected carcinoma of the pancreas after secondary closed drainage and 4 of multiple organ failure after secondary open packing. There were no residual intraabdominal abscesses in any of these at autopsy. Four of those who died had initially presented with catastrophic pancreatitis according to Ranson's criteria and all 3 patients with initial sepsis scores of greater than or equal to 15 died. Open packing, whilst appearing to provide better drainage of pancreatic abscesses than closed drainage does not have a dramatic influence on mortality. Future reports of the results of open and closed methods of treating pancreatic abscesses should take account of both the severity of pancreatitis and of sepsis.

Adjuvant chemotherapy and immunotherapy for colorectal cancer: preliminary communication.

Following surgical resection of Dukes' B or C colorectal cancers 72 patients have been randomly allocated to receive: 5-fluorouracil; or 5-fluorouracil and levamisole; or no treatment. Adjuvant treatment was continued for one year. 66 patients remain evaluable for up to 24 months. Preliminary results show no significant differences in survival or recurrence rates. Two patients receiving 5-fluorouracil and levamisole developed severe, but reversible, neutropenia. Other side effects were uncommon.

Intravenous feeding - complications - their prevention and management.

Intravenous feeding is a potentially hazardous and expensive form of nutritional treatment. Complications may be associated with the intravenous catheter and delivery system, mainly injury to the great vessels or adjacent structures including the pleura. Sepsis is a constant threat and meticulous technique is required to minimise the danger. Deficiency states may be seen if nutritional requirements are not met. Other metabolic problems which may arise are hyperglycaemia and rebound hypoglycaemia, jaundice and a recently described respiratory distress syndrome due to an increase in carbon dioxide production.

Ureteric obstruction due to pelvic actinomycosis.

PIP: Since 1973 several reports of pelvic actinomycosis arising in association with modern types of IUDs have appeared. Various presentations occur such as vaginal discharge, tubo-ovarian abscess, or "frozen pelvis." Ureteric obstruction is uncommon and its management unclear. A case is presented of ureteric obstruction due to pelvic actinomycosis associated with an IUD. A 34 year old woman presented with a 6 month history of alternating constipation and diarrhea, weight loss, amenorrhea, and laterally, a vaginal discharge. A Lippes loop had been inserted 2 years earlier. On examination, she was anemic, cachectic, pyrexial and had a frozen pelvis. There was a stricture of the midrectum but the mucosa was intact. The strings of the IUD could be felt and the cervix appeared normal. There was skin redness and induration over the right ischiorectal fossa. Intravenous urogram showed bilateral hydronephrosis with hydroureter. Examination under anesthesia confirmed the midrectal stricture. Biopsies showed mild inflammatory changes only. The IUD was removed and curettings revealed an acute endometritis. At laparotomy, apparently normal small bowel loops were adherent to a friable mass in the pelvis, which displaced the bladder forwards. The colon and uterus appeared normal but bilateral pyosalpinges were present and were resected. Neither ovary could be identified. Despite the tubal infection, pelvic malignancy was suspected and a sigmoid colostomy fashioned in view of impending rectal obstruction. Histology of the mass showed a large amount of fibrous tissue infiltrated by acute and chronic inflammatory cells and containing micro-abscesses. In 2 places only, colonies of actinomycetes surrounded by polymorphs were observed. No sulphur granules were identified. No growth was obtained on aerobic and anaerobic culture of the tissue and the pyosalpinges. Treatment with penicillin V 500 mg q.d.s. produced an allergic reaction and was changed to tetracycline 250 mg q.d.s. which was continued for 2 months at home. 4 months later, the rectal stricture had resolved and the colostomy was closed. 9 months after the initial presentation a urogram showed complete resolution of the left hydronephrosis. There was slight residual right hydronephrosis but no evidence of ureteric obstruction.^ieng

The lower oesophageal sphincter after floppy Nissen fundoplication.

The pressure and intra-abdominal length of the lower oesophageal sphincter (LOS) were measured by oesophageal manometry before and after floppy Nissen fundoplication (FNP) for intractable gastrooesophageal reflux. Control of reflux was assessed by 24 h pH recording and endoscopy. It was complete in 67 cases (84.8 per cent) in this non-consecutive series. In the group as a whole LOS pressure increased significantly after FNP, but the intra-abdominal length did not. LOS pressure decreased in 21 cases of whom 16 (76.2 per cent) still had perfect reflux control. Likewise, intra-abdominal length decreased in 41 cases of whom 36 (87.8 per cent) had good reflux control. There was no evidence of a compensatory increase in length to account for reflux control when LOS pressure decreased. When a length-pressure diagram was plotted for the postoperative measurements no clear separation of those with persistent reflux could be seen. These results suggest that the measured changes in LOS pressure and length following FNP are an artefact of surgery rather than the means by which the operation controls gastro-oesophageal reflux.

Clinical implications of abnormal oesophageal motility.

The usefulness of oesophageal manometry as a clinical tool has been assessed in 202 patients requiring detailed investigation for troublesome oesophageal symptoms, who first presented between June 1979 and May 1982. Only 12 were found to have specific motility disorders such as achalasia and scleroderma. A total of 147 had a variety of non-specific motility disorders and, of these, 112 (76.2 per cent) had coexistent gastro-oesophageal reflux. There was a significant association between the symptoms of dysphagia and the occurrence of predominantly non-propagated motor activity in the oesophagus. A similarly significant relationship existed between crushing chest pain and oesophageal spasm. Despite this statistical association, detection and treatment of gastro-oesophageal reflux was found to be the most useful part of clinical management. Symptoms of associated motility disorders resolved in more than 90 per cent of patients treated by Nissen fundoplication. Preoperative assessment of motility was of no value in detecting those who might develop postoperative dysphagia. Oesophageal manometry is useful for the assessment of a small proportion of patients with oesophageal symptoms in whom gastro-oesophageal reflux has been excluded by vigorous investigation, including 24 h pH recording.

Endoscopic diagnosis of a bleeding ileal carcinoid tumour.

Carcinoid tumour accounts for one per cent of all gastrointestinal neoplasms and has been reported in 0.5% of appendicectomy specimens. Local gastrointestinal complications occur infrequently and we report a case of repeated and massive gastrointestinal haemorrhage from a non-metabolically active carcinoid tumour of the distal ileum diagnosed by colonoscopy.

Endoscopic appearance of the gastroesophageal valve and competence of the cardia.

The endoscopic appearance of the gastroesophageal valve, viewed by the retroflexed gastroscope, has been studied in 51 patients with and without reflux esophagitis. Esophagitis was graded according to its severity, and the yield pressure (YP) was measured in all patients to assess the competence of the cardia. There was a close relationship between the YP and the grades of the gastroesophageal valve. YP was significantly lower in patients with endoscopic oesophagitis than in patients with no evidence of reflux esophagitis (p <0.0001). An increased abnormality of the gastroesophageal valve was associated with all grades of esophagitis and with a low YP. The valve mechanism at the cardia has an important role in determining its competence. YP is possibly a measure of the flap valve component of the gastroesophageal junction.

Perforation of the oesophagus: experience in a general hospital.

The results of a retrospective study of 62 patients who sustained perforation of the oesophagus during the period 1956--78 are reviewed. Oesophageal instrumentation was implicated in 40 patients. A total of 69 per cent of perforations occurred in the lower third; 45 per cent of patients remained undiagnosed for at least 24 h and in 23 patients remained undiagnosed for at least 24 h in 23 per cent the diagnosis was made only at post-mortem examination. Operative and non-operative management resulted in mortality rates of 48 per cent and 62 per cent respectively. Delay in operative treatment for more than 6 h was associated with increased mortality. However, 5 of 8 patients in whom diagnosis was delayed for more than 48 h recovered. The reason for this is discussed. The indications for conservative treatment are few and well defined; surgery is the treatment of choice. Early diagnosis and treatment are required if the mortality from oesophageal perforation is to be reduced.

Yield pressure, anatomy of the cardia and gastro-oesophageal reflux.

The yield pressure at which the cardia opens in response to gastric distension was measured in 155 subjects with and without gastro-oesophageal reflux (GOR) and after Nissen fundoplication. Yield pressure was measured by endoscopy or during oesophageal manometry. The median pressure was significantly lower in subjects with GOR than in those without (P < 0.0001). After successful Nissen fundoplication this pressure increased to supranormal values (P < 0.0001). There was a close relationship between yield pressure and the presence and size of hiatus hernia and also between yield pressure and the valvular appearance of the cardia at endoscopy. There was a significant correlation between yield pressure and oesophageal acid exposure. However, no relationship was observed between yield pressure and lower oesophageal sphincter pressure or intra-abdominal length. These results suggest that yield pressure is useful for assessment of the competence of the cardia, particularly after antireflux surgery. The competence of the cardia is greatly influenced by its anatomical structure.

Yield pressure: a new concept in the evaluation of GERD?

This study evaluates the yield pressure at the gastroesophageal junction in a group of 73 patients undergoing diagnostic endoscopy and in another group of 82 patients during the course of manometry for suspected GERD. The group included 17 patients who had previously undergone a successful Nissen fundoplication and eight patients who had a failed Nissen fundoplication. Air is insufflated into the stomach, and a water perfused pressure transducer is used to detect intragastric pressure. The pressure at which the cardia was seen to open at endoscopy, or when a common cavity phenomenon was detected at manometry, was taken as the opening pressure. Yield pressure was calculated as the difference between the opening pressure of the cardia and the resting gastric pressure. Results indicated a significant decrease in yield pressure in 65 patients with esophagitis compared with 65 patients with no evidence of reflux or esophagitis. A significant inverse correlation was found between yield pressure and the size of the hiatus hernia noted in these patients. There was also a correlation between valvular appearance of the cardia at endoscopy and the yield pressure. A progressive decrease in yield pressure occurred with an increasing deterioration in the physical appearance of the valve. There was no significant relationship found between yield pressure and lower esophageal sphincter (LES) pressure or intra-abdominal length. A small but significant relationship was found between yield pressure and acid exposure of the lower esophagus. The 17 patients with a successful Nissen showed a significantly increased yield pressure to supranormal values. In contrast, the eight patients with a failed Nissen had yield pressures within the range of the patients with esophagitis. In eight patients, yield pressure was measured by both manometry and endoscopy and showed no significant differences between the two methods.

Sarcoma after injection of intramuscular iron.

Two cases are presented of sarcomata arising at the site of previous iron dextran injections. One of the tumours showed a histological pattern associated with iron dextran administration in animal experiments.