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Biomedical subjects

I G Martin

Publications and source records attributed to I G Martin.

At least 19 recordsLinked to original sources

Evaluation of POSSUM in patients with oesophageal cancer undergoing resection.

BACKGROUND: The Physiogical and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) has been used to produce a numerical estimate of expected mortality and morbidity after a variety of general surgical procedures. The aim of this study was to evaluate the ability of POSSUM to predict mortality and morbidity in patients undergoing oesophagectomy. METHODS: POSSUM predictor equations for morbidity and mortality were applied retrospectively to 204 patients who had undergone oesophagectomy for cancer. Observed morbidity and mortality rates were compared with rates predicted by POSSUM using the Hosmer-Lemeshow goodness-of-fit test. Evaluation of the discriminative capability of POSSUM predictor equations was performed using receiver-operator characteristic (ROC) curve analysis. RESULTS: The observed and predicted mortality rates were 12.7 and 19.1 per cent respectively, and the respective morbidity rates were 53.4 and 62.3 per cent. However, the POSSUM model showed a poor fit with the data both for the observed 30-day mortality (chi2 = 16.26, P = 0.002) and morbidity (chi2 = 63.14, P < 0.001) using the Hosmer-Lemeshow test. ROC curve analysis revealed that POSSUM had poor predictive accuracy both for mortality (area under curve 0.62) and morbidity (area under curve 0.55). CONCLUSION: These data suggest that POSSUM does not accurately predict mortality and morbidity in patients undergoing oesophagectomy and must be modified.

Adult↗

Multivariate analysis of clinical, operative and pathologic features of esophageal cancer: who needs adjuvant therapy?

The failure of adjuvant therapy to significantly improve the prognosis of patients undergoing esophago-gastrectomy for cancer may be because of poor patient selection. We sought prognostic factors that would identify those patients who could benefit from adjuvant therapy. Data on 15 possible prognostic factors were prospectively collected on 225 patients undergoing esophago-gastrectomy at a single institution, and univariate and multivariate analyzes performed. T, N, M and overall UICC stage, differentiation, involvement of the circumferential resection margin and number of metastatic of lymph nodes were identified as significant prognostic factors by univariate analysis. Multivariate analysis revealed that the completeness of resection (R-category), ratio of metastatic to total nodes resected and the presence of vascular invasion were independently significant prognostic factors. Following R0 or R1 resection, patients with a metastatic to total lymph node ratio > 0.2 and /or the presence of vascular invasion have a poor prognosis, and the effects of adjuvant therapy in these patients should be studied.

Adult↗

Dietary antioxidants and DNA damage in patients on long-term acid-suppression therapy: a randomized controlled study.

Free radicals and reactive species produced in vivo can trigger cell damage and DNA modifications resulting in carcinogenesis. Dietary antioxidants trap these species limiting their damage. The present study evaluated the role of vitamins C and E in the prevention of potentially premalignant modifications to DNA in the human stomach by supplementing patients who, because of hypochlorhydria and possible depletion of gastric antioxidants, could be at increased risk of gastric cancer. Patients undergoing surveillance for Barrett's oesophagus (n 100), on long-term proton pump inhibitors were randomized into two groups: vitamin C (500 mg twice/d) and vitamin E (100 mg twice/d) for 12 weeks (the supplemented group) or placebo. Those attending for subsequent endoscopy had gastric juice, plasma and mucosal measurements of vitamin levels and markers of DNA damage. Seventy-two patients completed the study. Plasma ascorbic acid, total vitamin C and vitamin E were elevated in the supplemented group consistent with compliance. Gastric juice ascorbic acid and total vitamin C levels were raised significantly in the supplemented group (P=0.01) but supplementation had no effect on the mucosal level of this vitamin. However, gastric juice ascorbic acid and total vitamin C were within normal ranges in the unsupplemented group. Mucosal malondialdehyde, chemiluminescence and DNA damage levels in the comet assay were unaffected by vitamin supplementation. In conclusion, supplementation does not affect DNA damage in this group of patients. This is probably because long-term inhibition of the gastric proton pump alone does not affect gastric juice ascorbate and therefore does not increase the theoretical risk of gastric cancer because of antioxidant depletion.

Achlorhydria↗

Does pneumatic dilatation affect the outcome of laparoscopic cardiomyotomy?

BACKGROUND: Controversy surrounds the choice of laparoscopic cardiomyotomy as the primary treatment for achalasia or a second-line treatment following the failure of nonsurgical treatment. Laparoscopic cardiomyotomy can be more difficult technically following pneumatic dilatations. The aim of this study was to compare the outcome obtained with primary laparoscopic cardiomyotomy to that achieved when the procedure is performed following failed pneumatic dilatation. METHODS: Laparoscopic cardiomyotomy was performed in seven patients following a median of four pneumatic dilatations (group A) and in five patients as their primary treatment (group B). Outcome was measured using manometry, a modified DeMeester symptom scoring system, and a quality-of-life questionnaire. RESULTS: There were no significant differences between groups A and B in sex, age, preoperative modified DeMeester score, or mean barrier pressure. Six of seven group A patients had evidence of periesophageal and submucosal fibrosis at surgery, but this condition was not seen in group B patients. The operative time was slightly longer in group A patients. There was no difference in complication rates (one primary hemorrhage in group A and one esophageal perforation in group B), and both groups had a significantly improved modified DeMeester score at 6 weeks and at long-term follow-up (median, 26 months). Eleven of 12 patients said that they would choose laparoscopic cardiomyotomy as their primary treatment if newly diagnosed with achalasia. CONCLUSIONS: Laparoscopic cardiomyotomy is safe and effective as a primary or second-line treatment following pneumatic dilatations in patients with achalasia.

Adult↗

Laparoscopic cholecystectomy in morbidly obese patients.

BACKGROUND: Morbid obesity is generally regarded as a risk factor for laparoscopic cholecystectomy due to increases in operative time, morbidity, and conversion rate to open cholecystectomy. The aim of this study was to evaluate the feasibility and outcome of laparoscopic cholecystectomy (LC) in morbidly obese patients. METHODS: A total of 864 consecutive patients underwent LC at our institution between 1990 and 1997. This series represents a continuing policy of LC for all comers. Data were collected prospectively. There were 659 nonobese (NO: BMI 40 kg/m2). Laparoscopic bile duct exploration was performed in 28 (4.2%), nine (4.8%), and one (5.9%) patients, respectively. RESULTS: Obesity and morbid obesity were associated with trends toward an increased conversion rate (2.3% NO; 4.3% OB; 5.9% MO), a longer operative time (median, 80, 85, and 107 mins, respectively), greater postoperative morbidity (4.7%, 5.9%, and 11.8%, respectively), and a reduced ability to obtain cholangiography (86.1%, 80.1%, and 71.4%, respectively). None of these differences, however, were statistically significant (c2 test, p > 0.05). Postoperative hospital stay for LC was similar for all three groups (median, 1 day). CONCLUSION: LC in morbidly obese patients is a safe procedure, but it may be associated with increased operative difficulty and morbidity, as compared with nonobese and obese patients.

Adult↗

Circumferential resection margin involvement: an independent predictor of survival following surgery for oesophageal cancer.

BACKGROUND: For rectal carcinoma, the presence of tumour within 1 mm of the circumferential margin is an important independent prognostic factor for both local recurrence and survival. Similar prospective data have not been reported for oesophageal carcinoma and we wished to ascertain the prognostic importance of this variable following potentially curative resection for oesophageal carcinoma. AIM: To prospectively assess the impact of circumferential margin involvement (tumour within 1 mm) following potentially curative resection for oesophageal carcinoma. PATIENTS AND METHODS: In a prospective study, resection specimens of 135 patients treated with potentially curative oesophageal resection alone were studied for the presence of tumour within 1 mm of the circumferential margin (margin positive), using inked margins and cross sectional slicing of the specimen. All tumours were also staged using the 1987 UICC TNM classification. Patients were followed for a mean of 19 months, and overall and cancer specific survival analysed. RESULTS: The finding of tumour cells within 1 mm of the circumferential margin (CRM+) was a significant and independent predictor of survival following potentially curative oesophageal resection. Overall, 64 (47%) patients were CRM+. Median survival in this group was 21 months compared with 39 months in the CRM- group (p=0.015). The impact of CRM status on survival was only seen in patients with a low nodal metastatic burden (<25% nodes positive). The odds ratio for the risk of dying from oesophageal cancer was 2.08 when the CRM was involved (p=0.013). CONCLUSIONS: The presence of tumour within 1 mm of the circumferential margin following potentially curative resection for oesophageal carcinoma is an important independent prognostic variable and should be reported routinely.

Adenocarcinoma↗

Prospective study of cyclin D1 overexpression in Barrett's esophagus: association with increased risk of adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma commonly arises from a precancerous condition, Barrett's esophagus, in which the normal squamous epithelium is replaced by a columnar cell-lined epithelium. Genetic alterations occurring in this process could serve as biomarkers for the risk of malignant progression, improve surveillance, and contribute to early diagnosis. We examined two potential biomarkers, cyclin D1 and p53, in a prospective cohort of Barrett's esophagus patients. METHODS: A total of 307 patients were enrolled in an endoscopic surveillance cohort, and esophageal biopsy specimens were collected at each endoscopy. Incident cases of adenocarcinoma were matched to control patients within the cohort by duration of follow-up, age, sex, and length of columnar cell-lined epithelium at recruitment. Biopsy specimens were analyzed for cyclin D1 and p53 protein levels by immunohistochemistry. Statistical tests were two-sided. RESULTS: A total of 12 cases of adenocarcinoma occurred within the follow-up period, and tumor biopsy specimens from 11 cases stained positive for cyclin D1. Biopsy specimens from eight of these patients taken at recruitment also stained positive for cyclin D1. A case-control analysis of biopsy specimens obtained at recruitment revealed a statistically significantly increased risk of progression to adenocarcinoma in Barrett's esophagus patients whose biopsy specimens were cyclin D1 positive (odds ratio [OR] = 6. 85; 95% confidence interval [CI] = 1.57-29.91; P =.0106) but not in patients whose biopsy specimens were p53 positive (OR = 2.99; 95% CI = 0.57-15.76; P =.197). CONCLUSIONS: Cyclin D1-positive staining could be a useful biomarker in identifying Barrett's esophagus patients at high risk of esophageal adenocarcinoma. Given the complexity of genetic alterations in the natural history of this cancer, additional biomarkers will be required to increase the sensitivity and specificity of molecular diagnosis.

Adenocarcinoma↗

A comparison of microsatellite instability in early onset gastric carcinomas from relatively low and high incidence European populations.

We have investigated the genetic basis of gastric carcinomas occurring in patients aged under 40 years from a Portuguese population with a relatively high incidence of gastric cancer. We analysed a panel of 12 microsatellite loci in DNA extracted from gastric carcinomas arising in 16 patients aged 24-39 years from Braga, Portugal. Overall, microsatellite instability (MI) in at least 1 locus was detected in 44% (7 of 16) of carcinomas. A single patient demonstrated a mutator phenotype suggestive of the hereditary nonpolyposis colorectal cancer syndrome with instability in 82% of loci. This carcinoma showed loss of expression of the hMLH1 mismatch repair protein. In a previous study, we found no evidence of MI among 10 cases of early onset gastric carcinomas from an English population, which has a relatively low incidence of gastric cancer. Comparing the 2 series, we found that there was a significant difference (p = 0.04) in the prevalence of MI (at least 1 marker affected). This geographical difference in low-level MI may be related to a significantly higher prevalence of background chronic atrophic gastritis (8 of 16 vs. 0 of 8) and Helicobacter pylori infection (15 of 16 vs. 2 of 8) in Portuguese carcinomas compared with English cases. Genetic mechanisms underlying the hereditary non-polyposis colorectal cancer syndrome may play a role in a small number of early onset gastric carcinomas. The difference in prevalence of low-level MI between these relatively high and low incidence European populations requires further investigation.

Adult↗

Intraoperative cholangiography during laparoscopic cholecystectomy.

BACKGROUND: The routine use of intraoperative cholangiography (IOC) during laparoscopic cholecystectomy remains controversial. METHODS: A retrospective review of 950 consecutive laparoscopic cholecystectomies performed during an 8-year period was performed. For the first 2 years, IOC was performed selectively, and thereafter routinely. RESULTS: Attempted in 896 patients, IOC was successful in 734 (82%). Bile duct stones were found in 77 patients (10%), dilated ducts without stones in 47 patients (6%), and anatomic variations in 4 patients (0.5%). There were four (0.4%) minor intraoperative complications related to the IOC, with no consequences for the patients. There were three (0.3%) minor injuries of the bile duct, which were identified with IOC and repaired at the time of cholecystectomy without any consequences for the patients. In two of these patients, the structure recognized and catheterized as the cystic duct was revealed by IOC to be the bile duct. Thus IOC prevented extension to a major common bile duct (CBD) injury. CONCLUSIONS: Findings show that IOC is a safe technique. Its routine use during laparoscopic cholecystectomy may not prevent bile duct injuries, but it minimizes the extent of the injury so that it can be repaired easily without any consequences for the patient. The prevention of a major bile duct injury makes IOC cost effective.

Adolescent↗

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

BACKGROUND: Laparotomy 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. METHODS: Data were collected from laparoscopic cholecystectomies carried out by five consultant surgeons in one center. Details of relaparoscopy for complications were analyzed. RESULTS: Thirteen 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). CONCLUSIONS: Exploratory laparotomy can be avoided by prompt relaparoscopy in the majority of patients with abdominal complications of laparoscopic cholecystectomy.

Adult↗

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

OBJECTIVE: 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. DESIGN: Prospective study of undergraduate students taking an OSCE examination at the end of their first clinical year. SUBJECTS: 194 undergraduate medical students (95 male). MAIN OUTCOME MEASURES: Performance in the OSCE examination, the Entwhistle Learning Style Inventory1 and a composite self-reported score of clinical activity during the students first clinical year. RESULTS: Performance in the OSCE examination was related to well-organized study methods but not to clinical experience. A significant relationship between clinical experience and organized deep-learning styles suggests that knowledge gained from clinical experience is related to learning style. CONCLUSIONS: The relationship between clinical experience and student performance is complex. Well-organized and strategic learning styles appear to influence the benefits of increased clinical exposure. Further work is required to elucidate the most beneficial aspects of clinical teaching.

Adult↗

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.

Animals↗

Barrett's oesophagus: results from a 13-year surveillance programme.

OBJECTIVES: To review the results of a 13-year surveillance programme of patients with Barrett's oesophagus to determine the incidence of adenocarcinoma. Although the risk of cancer in Barrett's oesophagus is well established, the magnitude of this risk is still controversial. DESIGN: Records of all patients with histologically confirmed Barrett's oesophagus in our 13-year surveillance programme were examined retrospectively. SETTING: Integrated gastroenterology and gastrointestinal surgical service in a large teaching hospital. PARTICIPANTS: During the study period, 597 patients had a diagnosis of Barrett's oesophagus; of these, 357 entered a yearly endoscopy and biopsy surveillance programme. MAIN OUTCOME MEASURES: The development of oesophageal adenocarcinoma. RESULTS: After a mean follow-up of 43 months, 12 patients, all with specialized epithelium, developed adenocarcinoma (11 men), an incidence for men of one cancer per 69 patient-years; and for women, one cancer per 537 patient-years follow-up (P < 0.01). If only patients with specialized mucosa were included the incidence of cancer was one per 95 patient-years of follow-up (men, one per 61 patient-years; women, one per 468 patient-years). CONCLUSIONS: Whilst the role of screening patients with Barrett's oesophagus remains controversial, this study supports the routine surveillance of male patients with specialized epithelium.

Adenocarcinoma↗

Laparoscopic enucleation of a solitary pancreatic insulinoma.

Insulinomas are usually small, benign tumors of the pancreas, often found in obese patients, which require an incision that is out of all proportion to the size of the lesion. A laparoscopic technique for enucleation of a pancreatic insulinoma is described.

Aged↗

Expression of the 17-1A antigen in gastric and gastro-oesophageal junction adenocarcinomas: a potential immunotherapeutic target?

BACKGROUND: A murine monoclonal antibody against the 17-1A epithelial antigen has been shown to be a useful adjuvant therapy in colorectal cancer. Its clinical use could be extended to patients with upper gastrointestinal adenocarcinoma. AIM: To determine the distribution of the antigen in gastric and oesophageal adenocarcinoma. METHODS: The activity of two monoclonal antibodies active against 17-1A epithelial antigen was studied in gastric and gastro-oesophageal junction adenocarcinomas: fresh frozen tissue from both the carcinoma and adjacent mucosa was stained using immunocytochemistry with a murine monoclonal antibody (17-1A edrecolomab, Glaxo Wellcome); paraffin embedded tissue was stained using the humanised monoclonal antibody 3622W94 (Glaxo Wellcome). RESULTS: 29 of 33 cancers (88%) stained with the murine antibody and 39 of 40 (98%) with the humanised antibody. The degree of staining was greater in well differentiated and moderately differentiated tumours. There was no staining of the normal background gastric or oesophageal mucosa, but areas of intestinal metaplasia stained intensely. The humanised monoclonal 3622W94 antibody produced more intense staining than the murine antibody. CONCLUSIONS: The high incidence of expression of the 17-1A antigen in patients with gastric and gastro-oesophageal junction adenocarcinomas suggests a potential role for these antibodies as an adjuvant treatment for these common cancers.

Adenocarcinoma↗