Iain G. Martin

Early increase in intestinal permeability in patients with severe acute pancreatitis: Correlation with endotoxemia, organ failure, and mortality

Sepsis accounts for 80% of deaths from acute pancreatitis. This study aimed to investigate early changes in intestinal permeability in patients with acute pancreatitis, and to correlate these changes with subsequent disease severity and endotoxemia. The renal excretion of enterally administered polyethylene glycol (PEG) 3350 and PEG 400 was measured within 72 hours of onset of acute pancreatitis to determine intestinal permeability. Severity was assessed on the basis of APACHE II scores and C-reactive protein measurements. Serum endotoxin and antiendotoxin antibodies were measured on admission. Eight-five patients with acute pancreatitis (mild in 56, severe in 29) and 25 healthy control subjects were studied. Urinary excretion of PEG 3350 (median) was significantly greater in patients who had severe attacks (0.61%) compared to those with mild disease (0.09%) and health control subjects (0.12%) (P <0.0001), as was the permeability index (PEG 3350/400 excretion) (P <0.00001). The permeability index was significantly greater in patients who subsequently developed multiple organ system failure and/or died compared with other severe cases (0.16 vs. 0.04) (P = 0.0005). The excretion of PEG 3350 correlated strongly with endotoxemia (r = 0.8; P = 0.002). Early increased intestinal permeability may play an important role in the pathophysiology of severe acute pancreatitis. Therapies that aim to restore intestinal barrier function may improve outcome.

Gastric cancer: a curable disease in Britain.

OBJECTIVE--To determine whether more vigorous efforts aimed at earlier diagnosis allied to radical surgical resection lead to improved survival of patients with gastric cancer. DESIGN--Prospective audit of all cases of gastric cancer treated during 1970-89. SETTING--Department of surgery, general hospital. SUBJECTS--493 consecutive patients with gastric adenocarcinoma. MAIN OUTCOME MEASURES--Operative mortality, postoperative morbidity, and five year survival after radical potentially curative resection. RESULTS--207 (42%) patients underwent potentially curative resection. The proportion of all patients in whom this was possible increased significantly (p < 0.01) from 31% in the first five year period to 53% in the last five year period. The proportion of patients who had early gastric cancer rose from 1% to 15% (p < 0.01) and stage I disease rose from 4% to 26% (p < 0.001). After potentially curative resection, mortality 30 days after operation was 6%. Operative mortality decreased from 9% in the 1970s to 5% in the 1980s. Likewise, the incidence of serious postoperative complications decreased from 33% in the 1970s to 17% in the 1980s (p < 0.01). Five year survival was 60% in patients who underwent curative resection, 98% in patients with early gastric cancer, and 93%, 69%, and 28% in stage I, II, and III disease respectively. By the late 1980s five year survival after operation was about 70%. CONCLUSIONS--These findings suggest that an increasing proportion of patients with gastric cancer could be diagnosed at a relatively early pathological stage when about two thirds are curable by means of radical surgery.

Total or subtotal gastrectomy for gastric carcinoma? A study of quality of life.

Abstract. The aim of this study was to compare quality of life after total gastrectomy (TG) with that after subtotal gastrectomy (STG) for gastric carcinoma. The value of the routine use of TGde principe in the treatment of gastric carcinoma, wherever the tumor may be sited in the stomach, remains controversial. The advocates of TG contend that when it can be performed safely, with relatively low operative mortality and morbidity, it yields better long-term survival than STG. Most surgeons, however, believe that the routine use of TG increases both operative mortality and morbidity and the risk of nutritional deficiency in the long term, without improving survival. TG may also be associated with poorer outcome in terms of quality of life (QOL), but the evidence for this is tenuous. Forty-seven consecutive patients who had undergone potentially curative (R0) gastric resection for carcinoma were studied: 26 had undergone TG and 21 STG. A radical D2 lymph node dissection had been performed in each, and all patients were free from recurrence at the time of the study. QOL was measured before operation and 1, 3, 6, and 12 months after operation by means of five questionnaires to measure functional outcome: the Rotterdam symptom checklist (RSCL), the Troidl index, the hospital anxiety and depression (HAD) scale, activities of daily living score, and Visick grades. Before operation there was no significant difference in QOL between the two groups of patients. At 1 year after operation, however, patients who had undergone STG had a significantly better QOL than patients who had undergone TG: Their median RSCL score was lower (10 versus 19 respectively, p < 0.05), and their Troidl index was higher (11 versus 9 respectively,p < 0.05). The QOL of patients who underwent STG was also significantly better after operation than it had been before operation, whereas the QOL of the TG group was not significantly better after operation than before operation. The QOL of patients was found to be significantly better after STG than after TG for gastric carcinoma. Because operative mortality is greater and long-term survival is no better after TG than after STG, the latter is recommended as the treatment of choice for tumors of the distal stomach.

Dendritic cells: Immunological sentinels with a central role in health and disease

Immunological effector cells must be sensitive to the antigens or environmental signals that indicate that a pathogen is present. To this end, a group of cells known as the professional antigen‐presenting cells have the ability to educate T, B and NK cells as to the fingerprints of specific infections. The most adept of these cells are a closely related family termed dendritic cells (DC). A subset of these act as peripheral sentinels, specializing in the uptake, processing and presentation of antigenic material combined with an ability to detect a wide variety of ‘danger’ signals. These ‘danger’ or activation signals induce profound changes in dendritic cell physiology, facilitating the efficient stimulation of both adaptive and innate immunity. In the present review, a number of recent advances in the understanding of DC biology are discussed. These advances offer insights into the pathogenesis of a wide variety of diseases and point towards future strategies for immunotherapy.

Microsatellite instability in colorectal cancer: Improved assessment using fluorescent polymerase chain reaction

BACKGROUND & AIMSnMicrosatellite instability was first described in hereditary nonpolyposis colorectal cancers and sporadic colorectal cancers, in which it was associated with a good prognosis. The aim of this study was to assess the advantages of a novel fluorescent assay for detecting microsatellite instability.nnnMETHODSnEleven fluorescently tagged microsatellites and an automated DNA sequencer were used to investigate 54 sporadic colorectal adenocarcinomas.nnnRESULTSnThis fluorescent assay combined accurate allele sizing with cross-sectional data display and allowed improved assessment of microsatellite instability. Twenty-two percent of cancers (12 of 54) showed microsatellite instability with at least one marker. For tumors showing microsatellite instability, results were obtained for a minimum of eight markers. Six tumors showed microsatellite instability at high frequency (at least 63% of markers affected), and 42% of the patients who had a tumor showing microsatellite instability had a synchronous and/or metachronous colorectal tumor (vs. 7% of patients whose tumor did not show microsatellite instability). Patients with a microsatellite instability-positive tumor had an improved prognosis (P = 0.03).nnnCONCLUSIONSnThe use of this fluorescent assay improved the assessment of microsatellite instability with the automated analysis and cross-sectional data display. The assay identified a subgroup of patients who showed microsatellite instability and who also showed clinical features that differed from the microsatellite instability-negative cases.

Delays in the diagnosis of oesophagogastric cancer: a consecutive case series

Abstract Objectives: To examine the time taken to diagnose oesophageal or gastric cancer, identify the source of delay, and assess its clinical importance Design: Study of all new patients presenting to one surgical unit with carcinoma of the oesophagus or stomach. Setting: University department of surgery in a large teaching hospital. Subjects: 115 consecutive patients (70 men, mean age 66 years) with carcinoma of the oesophagus (27) or stomach (88). Main outcome measures: Interval from the onset of symptoms to histological diagnosis, final pathological stage of the tumour, and whether potentially curative resection was possible. Results: The median delay from first symptoms to histological diagnosis was 17 weeks (range 1 to 168 weeks). 25% (29/115) of patients had a delay of over 28 weeks (median 39 weeks). Total delay was made up of the following components: delay in consulting a doctor (29%), delay in referral (23%), delay in being seen at hospital (16%), and delay in establishing the diagnosis at the hospital (32%). No relation was found between delay in diagnosis and tumour stage in patients with gastric cancer, but for oesophageal cancer those with stage I and II disease were diagnosed within 7 weeks compared with 21 weeks (P<0.02) for those with stage III and IV disease. Conclusions: Long delays still occur in the diagnosis of patients with cancer of the stomach or oesophagus. Streamlined referral and investigation pathways are needed if patients with gastric and oesophageal carcinomas are to be diagnosed early in the course of the disease. Key messages Survival of oesophagogastric cancer is most likely if the tumour is caught early The median delay in diagnosis for patients with oesophagogastric cancer was 17 weeks but 25% of patients had delays of more than 28 weeks For patients with oesophageal cancer this delay was associated with tumours of more advanced stage Patient delay in seeking medical help was relatively short; the biggest reductions in delays could be produced by streamlined referral and investigation. Open access endoscopy service reduced delays in diagnosis compared with standard referral

Benefiting from clinical experience: the influence of learning style and clinical experience on performance in an undergraduate objective structured clinical examination.

To assess the relationship between clinical experience, learning style and performance in an objective structured clinical examination (OSCE) in medical students at the end of their first clinical year.

Effect of endoscopic ultrasonography on the management of 100 consecutive patients with oesophageal and junctional carcinoma.

Endoscopic ultrasonography (EUS) offers very accurate tumour and node staging information for oesophagogastric cancer. The aim was to determine whether the addition of EUS directly influenced the definitive management plan for individual patients.

Relaparoscopy for the detection and treatment of complications of laparoscopic cholecystectomy.

BACKGROUNDnLaparotomy remains the commonest intervention in patients with abdominal complications of laparoscopic surgery. Our own policy is to employ relaparoscopy to avoid diagnostic delay and unnecessary laparotomy. The results of using this policy in patients with suspected intra-abdominal complications following laparoscopic cholecystectomy are reviewed.nnnMETHODSnData were collected from laparoscopic cholecystectomies carried out by five consultant surgeons in one center. Details of relaparoscopy for complications were analyzed.nnnRESULTSnThirteen patients underwent relaparoscopy within 7 days of laparoscopic cholecystectomy for intra-abdominal bleeding (2 patients) or abdominal pain (11 patients). The causes of pain were subhepatic haematoma (1), acute pancreatitis (1), small bowel injury (1), and minor bile leakage (6). In 2 patients no cause was identified. Twelve patients were managed laparoscopically and 1 patient required laparotomy. Median stay after relaparoscopy was 7 days (range 2 to 19).nnnCONCLUSIONSnExploratory laparotomy can be avoided by prompt relaparoscopy in the majority of patients with abdominal complications of laparoscopic cholecystectomy.

Assessment of microsatellite alterations in young patients with gastric adenocarcinoma

Genetic factors are probably important in the development of gastric carcinoma in young patients (younger than 40 years). The authors investigated early onset primary gastric adenocarcinomas for the presence of microsatellite instability, which is a phenotypic marker for the hereditary nonpolyposis colon carcinoma syndrome.