Search PubMed⌕ Search

Biomedical subjects

I G Martin

Publications and source records attributed to I G Martin.

At least 37 records · Page 2Linked to original sources

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↗

Laparoscopic cholecystectomy after pancreatic debridement.

BACKGROUND: Pancreatic debridement is a lifesaving operation in patients with severe acute pancreatitis and pancreatic or peripancreatic necrosis. Even in the presence of gallstones, cholecystectomy may be avoided during the procedure, but definitive treatment of the stones is needed at a later stage. METHODS: Five patients (median age 58 years) underwent laparoscopic cholecystectomy, at a median time interval of 15 months, after pancreatic debridement via a dome-shaped upper abdominal incision for severe acute pancreatitis. The use of alternative methods for primary access, additional cannulae to enable division of adhesions, the harmonic scalpel, and the fundus first technique made the laparoscopic approach possible and safe. RESULTS: The median operating time was 130 min. Four patients were discharged home the first or second postoperative day. One patient required a "mini-laparotomy" for drainage of a periumbilical hematoma and was discharged on the 13th day. CONCLUSIONS: Laparoscopic cholecystectomy can be considered an effective and safe approach for the treatment of gallstones in patients who have undergone pancreatic debridement.

Adult↗

Diaphragmatic rupture resulting from gastrointestinal barotrauma in a scuba diver.

A fit young man sustained a ruptured diaphragm during a recreational scuba dive three months after undergoing an uncomplicated laparoscopic Nissen fundoplication for gastro-oesophageal reflux disease. It is proposed that this rare occurrence was attributable to gastrointestinal barotrauma. The injury was treated by laparotomy, mobilisation of herniated abdominal viscera back into the abdomen, repair of the crura and gastropexy. He made a full postoperative recovery. It is concluded that scuba diving should be avoided in patients who have undergone fundoplication.

Adult↗

Assessment of microsatellite alterations in young patients with gastric adenocarcinoma.

BACKGROUND: 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. METHODS: DNA was extracted from archival microdissected carcinoma and corresponding normal tissue from 10 British gastric carcinoma patients age 19 to 39 years at the time of diagnosis. A panel of 12 microsatellite loci were amplified by fluorescent polymerase chain reaction and analyzed using an automated DNA sequencer. RESULTS: There was no evidence of microsatellite instability. In contrast, allelic imbalance was recorded at D3S966, D3S1076, D10S197, D11S904, P53, NM23, and DCC microsatellite loci. CONCLUSIONS: The authors reported ten cases of early onset gastric carcinoma that demonstrated allelic imbalance but no evidence of instability at microsatellite loci. It is unlikely that defective DNA mismatch repair is important in this group of young patients.

Adenocarcinoma↗

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

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.

Aged↗

Prognostic significance of microsatellite instability in patients with gastric carcinoma.

A proportion of gastric adenocarcinomas exhibit replication errors manifested as microsatellite instability. The clinicopathological and prognostic significance of this abnormality remains uncertain. This study aimed to determine the importance of microsatellite instability by analysing a large series of gastric carcinomas from an English population. Using a novel fluorescent polymerase chain reaction technique, we amplified 11 microsatellite sequences from paired normal and carcinoma DNA from 101 patients who underwent a potentially curative resection for gastric carcinoma. Overall, 21% of cases demonstrated microsatellite instability in at least one locus. At least four loci were examined in each case. A replication error positive phenotype (minimum of 29% of loci affected) was detected in 9% of cases. There was no statistically significant association between the presence of microsatellite instability or replication error positive phenotype and the patient's age, sex, tumour site, stage, node status, histological subtype or grade. Carcinomas confined to the mucosa or submucosa (T1) showed a significantly higher frequency of instability and replication error positive phenotypes than T3 lesions (P = 0.03 and P = 0.05, respectively). A larger proportion of patients who were microsatellite instability or replication error positive were alive at 5 years compared with those who were negative but this did not reach statistical significance (P = 0.15 and P = 0.16, respectively). We identified a subset of gastric carcinomas from a relatively low-risk population which showed evidence of microsatellite instability. There were no statistically significant 5-year survival advantages in cases demonstrating microsatellite instability or replication error positive phenotypes. The detection of microsatellite instability is of limited prognostic value in gastric carcinoma.

Adult↗

Spiral computed tomography and operative staging of gastric carcinoma: a comparison with histopathological staging.

BACKGROUND: Much controversy exists as to the value of computed tomography (CT) in the preoperative staging of gastric cancer, because of its limited ability to identify correctly lymph node (LN) metastases, invasion of adjacent organs, or hepatic and peritoneal metastases. Spiral CT scanners have a number of potential advantages over conventional scanners, including the absence of respiratory misregistration, image reconstruction smaller than scan collimation permitting overlapping slices and optimisation of intravenous contrast enhancement. AIM: To compare the performance of spiral CT and operative assessment against formal (TNM) pathological staging. PATIENTS AND METHODS: A study of 105 consecutive patients who underwent both spiral CT and operative staging was performed. All CT scans were reviewed by a radiologist who commented on tumour location and size, evidence of adjacent organ invasion, lymph node metastases to both N1 and N2 nodes, and evidence of hepatic and peritoneal metastases. All patients underwent careful operative assessment at the time of surgery, along the lines suggested by Rohde and colleagues. RESULTS: Spiral CT remained poor at identifying LN metastases to both N1 and N2 lymph nodes, with sensitivity ranging from 24 to 43%; specificity, however, was 100%. Operative staging was superior, with sensitivities between 84 and 94%, but specificity was much lower (63-74%). Spiral CT correctly detected 13 of 17 cases of invasion of either the colon or the mesocolon (sensitivity 76%) compared with 16 of 17 cases at operative staging (sensitivity 94%). Spiral CT correctly identified three of six cases with invasion of the pancreas (sensitivity 50%) compared with six of six cases on operative staging (sensitivity 100%). Spiral CT correctly identified 12 of 17 cases of peritoneal metastases (sensitivity 71%) and four of seven cases of hepatic metastases (sensitivity 57%). CONCLUSION: Whilst spiral CT remains poor at identifying lymph node metastases, it correctly identified most cases with invasion of either the colon or the mesocolon and half the cases of pancreatic invasion. It was of value in detecting peritoneal metastases and some cases with hepatic metastases. At present, at Leeds General Infirmary spiral CT is performed routinely on all patients with gastric cancer and a selective staging laparoscopy policy is adopted in those patients in whom the status of the peritoneal cavity and liver is in doubt.

Adult↗

Long operation and the risk of complications from laparoscopic cholecystectomy.

BACKGROUND: Data collected prospectively from patients undergoing laparoscopic cholecystectomy under one consultant surgical team were analysed to examine the influence of duration of operation on postoperative complications. METHODS: Between June 1990 and March 1994, 411 consecutive patients underwent laparoscopic cholecystectomy, of which nine (2.2 per cent) were converted to open operation. Patients whose laparoscopic operation took 3 h or more (32 patients) were compared with those whose operation took less than 3 h (370 patients) with respect to postoperative complications. RESULTS: There was a higher incidence of acute biliary disease (28 versus 7.0 per cent), upper abdominal adhesions (16 versus 3.2 per cent), significant gallbladder adhesions (69 versus 25.4 per cent) and common bile duct exploration (16 versus 1.4 per cent) in patients having a long operation. Complications were divided into "surgical' and "general', and included cardiovascular, respiratory and thromboembolic events. The overall complication rate was 9 per cent in the long operation group and 3.8 per cent in the short operation group (P not significant) (4.2 per cent for both groups combined). No general complications occurred in those having a longer operation. CONCLUSION: The duration of operation does not affect the risk of general complications after laparoscopic cholecystectomy, so enabling the advantages of the minimally invasive approach to be realized in patients with more advanced biliary disease.

Adult↗

Radical thoracoscopic esophagectomy for cancer.

BACKGROUND: Much of the morbidity of conventional esophagectomy for cancer is thought to relate to the thoracotomy wound and while transhiatal esophagectomy removes the need for a thoracotomy, it is not oncologically sound. Videothoracoscopy could potentially provide an oncologically sound means for resecting the thoracic esophagus without the need for a thorcotomy. METHODS: Between June 1991 and June 1994, thoracoscopic mobilization of the thoracic esophagus combined with radical lymphadenectomy was attempted in 24 patients as part of three-stage esophagectomy for cancer (5 squamous and 19 adenocarcinomas). Mean age was 59 years (range 43-76). Eight patients were ASA grade I, 10 were ASA II, and 6 ASA III. Two patients had early lesions (T1N0) but all other cancers were T2 or T3. Dissection of the thoracic esophagus was attempted via a right-sided approach, followed by a laparotomy and a cervical incision. RESULTS: The thoracoscopic procedure was successful in 22 patients; it was abandoned in one patient with dense pleural adhesions and in another with inoperable tumor. Mean duration of the thoracic component was 184 min(120-330). There were three post-operative deaths. Ten further patients had major complications. Median post-operative stay was 18 days(9-129). Mean node harvest was 13 nodes(6-28). Two-year survival (cancer specific) was 33%. CONCLUSIONS: Radical thoracoscopic mobilization of the esophagus is feasible, but the potential for complications remains high and requires further study.

Adenocarcinoma↗

Laparoscopic cholecystectomy in pregnancy. A safe option during the second trimester?

BACKGROUND: Laparoscopic cholecystectomy is now the standard treatment for symptomatic gallstones; while symptomatic gallstones during pregnancy are not frequent they are by no means rare. The role of laparoscopic cholecystectomy during pregnancy is controversial but initial reports suggest it is both safe and feasible. METHODS: During a consecutive series of 500 laparoscopic cholecystectomies, 3 patients have undergone laparoscopic cholecystectomy during pregnancy. The 3 patients were 16-27 weeks pregnant with an average age of 32 years. The indication for laparoscopic cholecystectomy was severe pain in two patients and gallstone pancreatitis in one patient. Following standard obstetric anesthesia, laparoscopic cholecystectomy was performed. Open cannulation was used to establish peritoneal access, following which "standard," four-port laparoscopic cholecystectomy was performed without complication. The insufflation pressure used was 8-10 mmHg CO2 and a liver retractor was employed to facilitate access. RESULTS: In each case the postoperative recovery was rapid and uneventful for both mother and fetus. The patients were discharged on the first or second postoperative day. CONCLUSIONS: Laparoscopic cholecystectomy during the second trimester of pregnancy is both safe and feasible provided both suitable surgical and anesthetic expertise are available. Even up to the end of the second trimester there is sufficient access for the technique to be employed.

Adult↗

Laparoscopic splenectomy. The suspended pedicle technique.

BACKGROUND: Elective splenectomy is often performed for hematological diseases, some of which cause only moderate enlargement of the spleen. The avoidance of an extensive upper abdominal incision is desirable in such cases and laparoscopic splenectomy offers significant potential advantages over the open operation if it can be performed safely and economically. METHODS: Eight consecutive patients underwent laparoscopic splenectomy. The operation was carried out with the patient at 40 degrees in the right lateral position so that rotating the operating table would make a full right lateral position possible. After fenestration of the gastrocolic omentum and division of the short gastric vessels, this position allowed the spleen to be pushed up under the diaphragm to facilitate access to the splenic vessels and the hilum. Vessels were divided individually between clips. RESULTS: All eight cases were completed laparoscopically. Mean length of operation was 259 min (range 230-285). Postoperative stay ranged from 2 to 7 days (median 4 days). There was no mortality, although minor complications did occur in three patients. CONCLUSIONS: We found laparoscopic splenectomy to be a safe and feasible procedure for the elective removal of the moderately enlarged spleen.

Adult↗