Primary intra-abdominal malignant fibrous histiocytoma presenting as pyrexia of unknown origin--report of a case with review of literature.

Primary intra-abdominal malignant mesenchymal tumours are very rare and there are not many cases of visceral malignant fibrous histiocytoma in the English literature. We report a new case of abdominal malignant fibrous histiocytoma presenting as abdominal pain and pyrexia of unknown origin in a 54 year old female followed by a brief review of literature. Presentation with pyrexia of unknown origin is extremely rare in this condition.

Appraisal of compliance with the UICC/AJCC staging system in the staging of gastric cancer. Union Internacional Contra la Cancrum/American Joint Committee on Cancer.

BACKGROUND: In the surgical management of gastric carcinoma, regional lymphatic spread is of prognostic importance. The fifth edition of the Union Internacional Contra la Cancrum classification has been shown to be reproducible, practical and of significant prognostic use. The tumour node metastasis (TNM) system requires at least 15 lymph nodes to be acquired and examined for staging to be accurate. This has raised concern over the consistency with which the requisite numbers of nodes would be acquired. This study was performed to assess how consistently surgically managed cases of gastric cancer in the West Midlands fulfilled this requirement to allow accurate staging. METHODS: Data from the West Midlands Cancer Intelligence Unit on all cases of gastric cancer registered from 1998 to 1999 were obtained and the number of lymph nodes documented for each surgically managed case was assessed. RESULTS: Overall, only 31.0 per cent of surgically resected cases could be assessed accurately according to the TNM system. The proportion staged accurately varied widely across hospitals from 10.9 to 76.0 per cent. CONCLUSION: These results reflect the need for improved N staging across the region to aid the appropriate multimodal treatment of patients.

Marimastat as maintenance therapy for patients with advanced gastric cancer: a randomised trial.

This randomised, double-blind, placebo-controlled study was designed to evaluate the ability of the orally administered matrix metalloproteinase inhibitor, marimastat, to prolong survival in patients with non-resectable gastric and gastro-oesophageal adenocarcinoma. Three hundred and sixty-nine patients with histological proof of adenocarcinoma, who had received no more than a single regimen of 5-fluorouracil-based chemotherapy, were randomised to receive either marimastat (10 mg b.d.) or placebo. Patients were treated for as long as was tolerable. The primary endpoint was overall survival with secondary endpoints of time to disease progression and quality of life. At the point of protocol-defined study completion (85% mortality in the placebo arm) there was a modest difference in survival in the intention-to-treat population in favour of marimastat (P=0.07 log-rank test, hazard ratio=1.23 (95% confidence interval 0.98-1.55)). This survival benefit was maintained over a further 2 years of follow-up (P=0.024, hazard ratio=1.27 (1.03-1.57)). The median survival was 138 days for placebo and 160 days for marimastat, with 2-year survival of 3% and 9% respectively. A significant survival benefit was identified at study completion in the pre-defined sub-group of 123 patients who had received prior chemotherapy (P=0.045, hazard ratio=1.53 (1.00-2.34)). This benefit increased with 2 years additional follow-up (P=0.006, hazard ratio=1.68 (1.16-2.44)), with 2-year survival of 5% and 18% respectively. Progression-free survival was also significantly longer for patients receiving marimastat compared to placebo (P=0.009, hazard ratio=1.32 (1.07-1.63)). Marimastat treatment was associated with the development of musculoskeletal pain and inflammation. Events of anaemia, abdominal pain, jaundice and weight loss were more common in the placebo arm. This is one of the first demonstrations of a therapeutic benefit for a matrix metalloproteinase inhibitor in cancer patients. The greatest benefit was observed in patients who had previously received chemotherapy. A further randomised study of marimastat in these patients is warranted.

The long term results of endoscopic surveillance of premalignant gastric lesions.

BACKGROUND: A large proportion of patients attending open access endoscopy have histological and gross pathological findings that are potentially premalignant. The proportion of these patients who go on to develop malignancies and the timescale over which this occurs are uncertain. AIMS: This study aims to discover the incidence of gastric cancers in this "high risk" group and to examine the potential for their early diagnosis and treatment. PATIENTS: A total of 1753 patients attended open access endoscopy. From these, 166 patients with dysplasia, intestinal metaplasia, atrophic gastritis, foveolar hyperplasia, regenerative changes, polyps, or ulcers who agreed to undergo annual surveillance endoscopy were studied. METHODS: Patients were endoscoped annually. Additionally, patients with ulcers were re-examined at two monthly intervals until ulcer healing. Cancers detected were treated by gastrectomy. RESULTS: Twenty two of 1753 patients attending open access endoscopy had gastric cancer (1.3%). In the study population, 14 cancers were detected over 10 years (8.4 %). These were of an earlier stage than those detected at open access (stage I and II 67% v 23%; p<0.05) and five year survival was significantly higher (50% v 10%; p=0.006). In atrophic gastritis and intestinal metaplasia the risk of malignancy was 11%. CONCLUSIONS: In patients with atrophic gastritis or intestinal metaplasia, annual surveillance can detect most new tumours at an early stage with a major improvement in survival. Potential benefits of such a surveillance programme are large and warrant further investigation in a multicentre randomised controlled trial.

Laparoscopic peritoneal lavage in staging gastric and oesophageal cancer.

AIMS: Accurate staging of gastric, oesophageal and oesophagogastric cancer is essential to avoid unnecessary laparotomies in patients where only palliation is appropriate. This requires a multimodal approach utilizing endoscopy, computed tomography and laparoscopy. Previous authors have found that the presence of free peritoneal tumour cells (FPTCs) detected at laparoscopy or laparotomy confers a poorer prognosis. However, various methods of peritoneal lavage are described. The aim of this study was to evaluate the prognostic value of our technique of peritoneal lavage. MATERIALS AND METHODS: 88 staging laparoscopies with peritoneal lavage were carried out between March 1997 and February 1999 on patients eligible for attempted curative resection of a gastric, oesophageal or oesophagogastric cancer. During laparoscopy the pelvis was irrigated with 200 ml of normal saline, with 100 ml aspirated and examined cytologically. Patients were followed-up until September, 1999. RESULTS: 11 patients had FPTC-positive cytology with a median survival following laparoscopy of 122 days (95% CI 82-161) with only a single patient surviving more than one year. In the FPTC-negative group, median survival was 378 days (95% CI 256,-). Log-rank Chi(2)=16.7, P<0.001. CONCLUSIONS: The presence of FPTCs detected by our technique is a contraindication to attempted curative resection - palliation only (medical or surgical) is appropriate.

Prospective, double-blind, placebo-controlled randomized trial of cimetidine in gastric cancer. British Stomach Cancer Group.

Cimetidine is thought to inhibit suppressor T-lymphocyte function and preliminary evidence from a randomized trial indicated that it might prolong survival for patients with operable and inoperable gastric cancer. The British Stomach Cancer Group conducted a randomized, double-blind, placebo-controlled trial examining the effects of cimetidine (400 mg or 800 mg twice a day) on the survival of patients with early (stages I, II and III: n = 229) and advanced (stages IVa and IVb: n = 201) gastric cancer. The primary end point was death. A total of 442 patients were randomized by 59 consultants in 39 hospitals between February 1990 and March 1995. Log-rank survival analysis was used to assess differences between the groups. Three hundred and forty patients died during the study: 166 (49%) in the cimetidine treatment groups and 174 (51%) in the placebo groups. Median survival for patients receiving cimetidine was 13 months (95% confidence interval (CI) 9-16 months) and 11 months in the placebo arm (95% CI 9-14 months). There was no significant difference in survival between the two treatment groups (P = 0.42) or between different doses of cimetidine tablets (P = 0.46). Five-year survival of those patients randomized to cimetidine was 21% compared to 18% for those patients randomized to placebo. Cimetidine at a dose of 400 mg or 800 mg twice a day does not have a significant influence on the survival of patients with gastric cancer compared to placebo.

Phase II trial of radical surgery for locally advanced pelvic neoplasia.

BACKGROUND: Reported operative mortality and survival rates following total pelvic exenteration (TPE) for recurrent pelvic neoplasia are now as good as those for many primary treatments. The currently accepted primary treatments for these tumours are, however, still either radiotherapy alone or radiotherapy and chemotherapy. The primary aim of this study was to evaluate the safety and tolerability of TPE and secondarily to ascertain survival after TPE. METHODS: This was a phase II study of 50 patients with locally advanced pelvic tumours who underwent TPE. RESULTS: Thirty-two patients (64 per cent) underwent TPE for recurrent carcinoma of the cervix, seven (14 per cent) for rectal cancer, three (6 per cent) for vulval carcinoma, three (6 per cent) for vaginal carcinoma, two (4 per cent) for prostate cancer and three (6 per cent) for other tumours. The 30-day mortality rate was 8 per cent with an in-hospital mortality rate of 16 per cent. The crude morbidity rate was 62 per cent, with 23 patients (46 per cent) having grade III or IV toxicity. A complete response was achieved in 63 per cent and a partial response in 37 per cent of patients. The overall median survival time was 86 weeks; it was 111 weeks in patients in whom a complete response was achieved. CONCLUSION: The survival and operative mortality rates that are now attainable with TPE are comparable to those achieved with chemoradiotherapy in advanced pelvic neoplasia. TPE should no longer be reserved for salvage therapy and should perhaps be compared with chemoradiotherapy as first-line treatment in a phase III randomized trial in patients with these tumours.

Redefining surgery for gastric cancer.

BACKGROUND: Despite encouraging retrospective and non-randomized trials, two large prospective, randomized trials of D1 vs D2 resections show double the mortality in the D2 group, with no increase in long-term survival. However, the D2 resection still offers the only hope of cure when N2 nodes are involved. We propose a reclassification of the International Union Against Cancer TNM "N" staging to a system with an anatomical basis that is useful in defining the surgery performed. Junctional nodes lying between the N1 and N2 tiers will act as a guide to surgery. Where these nodes are uninvolved, the probability of gastric bed (N2) involvement is low and the radical D2 dissection with its higher mortality and morbidity can be avoided.CONCLUSION: Such "stage-appropriate" surgery will reduce the number of D2 resections while ensuring that patients with N2 disease are not denied curative surgery. A prospective, randomized, controlled trial of targeted surgery is required.

Propofol sedation for oesophago-gastro-duodenoscopy.

A questionnaire was sent to 53 patients who had undergone an upper gastrointestinal endoscopy under total intravenous anaesthesia (TIVA) using intermittent Propofol. All of the patients would accept the same technique again. Out of 20 patients who had previously had the procedure performed under Diazepam sedation, 18 preferred the use of Propofol. This technique can only be used with an anaesthetist present.

Radical surgery for early gastric cancer.

The role of radical surgery for early gastric cancer has become a topic of considerable debate. Despite excellent results from Japan and several retrospective and uncontrolled trials, results from two large prospective randomized trials appear to demonstrate no benefit from D2 compared to the D1 resections. These trials have prompted a move away from radical lymph-node dissection. We argue that this reasoning is flawed and based not on the lack of efficacy of the D2 resection but in an attempt to reduce post-operative mortality and morbidity. Post-operative complications are largely a result of distal pancreatectomy and splenectomy and the relative inexperience of surgeons performing the operations. By preserving these organs and concentrating surgery to specialized centres the complication rate of radical surgery can be significantly reduced to approximate that of non-radical surgery. Lymph-node metastasis to the N2 nodes in early gastric cancer has been shown to be as high as 23%. Non-radical surgery poses significant risks of leaving residual disease. Radical surgery must remain the operation of choice if non-curative surgery for a curable condition is to be avoided.

Screening for gastric cancer by Helicobacter pylori serology: a retrospective study.

BACKGROUND: Screening by serology for Helicobacter pylori in young dyspeptic patients has been shown to be effective in reducing demand for endoscopy. H. pylori has been implicated in the causation of gastric cancer and the reported seropositivity rate in patients with gastric cancer ranges from 69 to 94 per cent. The aim of this study was to assess the potential value of Helicobacter antibodies as a method of selecting dyspeptic patients over the age of 45 years for endoscopy. METHODS: A retrospective comparison of the antibody status to H. pylori was made between 154 patients with gastric cancer and a sex- and date of birth-matched dyspeptic control group. Results from the former group were correlated with demographic data and tumour characteristics. RESULTS: Significantly more patients with gastric cancer were seropositive than controls (77 versus 66 per cent). H. pylori was not related to the Laurén classification of the tumour. Tumour site was significant: body and antrum tumours were associated with Helicobacter whereas cardial tumours appeared to be unrelated. CONCLUSION: Screening by antibody assays to H. pylori would miss more than 30 per cent of current gastric cancers. The increasing incidence of cardial cancer would cause this percentage to rise in the future.

Vulvoperineal reconstruction after excision of anogenital multifocal intraepithelial neoplasia ("MIN").

Over the past 7 years, 12 women have been treated utilising a radical surgical approach for extensive vulval involvement as a component of multifocal intraepithelial neoplasia (MIN) of the female genital tract. The patients were analysed with respect to the anatomical site of involvement, age, presenting complaints and their duration, colposcopic examination, histopathology and surgical treatment. Gynaecologists, general surgeons and plastic surgeons were involved in the surgical treatment which was an initial colostomy followed by a definitive vulvoperineal resection and simultaneous vulval reconstruction using meshed split skin grafts or a combination of skin grafts and local flaps. 17 vulvoperineal reconstructions were done for 12 patients. Three had an incomplete histopathological clearance at the initial operation. Apart from these three patients, one had recurrence of symptoms alone, without any evidence of MIN, which was possibly due to human papilloma virus infection. One patient developed malignant squamous invasion 4 years later, which was cured with surgical excision and reconstruction. Colostomy closure was done after achieving local control of the disease. This staged approach does achieve the objectives of eliminating disease and alleviating symptoms. It preserves function and attempts to reconstruct normal anatomy without compromising the principles of surgical oncology and results in a high patient satisfaction.

Machine learning techniques in early screening for gastric and oesophageal cancer.

A database on 2692 dyspeptic patients over the age of 40 was established, consisting of 73 epidemiological and clinical variables. A tree-based machine learning algorithm (PREDICTOR) was applied to this database, in order to attempt to find rules which would classify patients into 2 groups, i.e., those suffering from gastric or oesophageal cancer, and the remainder. The results were encouraging. The cross-validated classification performance figure showed that by classifying 61.3% of the patients as high risk, a sensitivity of 94.9% and a specificity of 39.8% could be achieved. It is planned to construct an expert system based on the rules produced by the machine learning algorithm, in order to provide preliminary screening for cancer in dyspeptic patients.

The influence of age on the surgical management of carcinoma of the stomach.

The medical records of 31,808 patients with gastric cancer registered with the West-Midlands Cancer Registry between 1957-1981 were reviewed to determine the influence of age on presentation, stage assessment, management, survival and mortality rates. When analysed by stage, and excluding post-operative deaths, survival was similar in all age groups. This study confirms stage of disease to be the single most important prognostic factor. The inverse relationship between laparotomy and age implies inadequate assessment of stage in the elderly. The poor prognosis in unresected cases suggests that increased precise staging by laparotomy or laparoscopy will have minimal adverse effects. On the other hand this may result in increased resections and survival.

Prognostic factors for gastric cancer influencing clinical practice.

Despite a slow decline in the incidence of gastric cancer over the last 90 years, we can still expect to see over 100,000 patients die of this disease each decade in England and Wales. The 5-year survival rate has not improved during this century, which is largely due to the stage at diagnosis being unchanged. There are a number of prognostic determinants in gastric cancer which have clinical relevance. Age is an important determinant; patients under 40 years commonly have more advanced diffuse lesions than older patients so that a higher index of suspicion needs to be maintained in younger patients with persistent symptoms. Conflicting reports make it unclear whether the duration of symptoms bears any relationship to tumor stage, but there is some evidence that actively shortening the symptom duration by early investigation can have a beneficial effect in the proportion of patients diagnosed with early cancers. The site of the tumor is important; unfortunately, the proportion of patients with cardia lesions is increasing and this has had the effect of reducing the overall survival. Tumor size should not play a part in the decision to resect a lesion as most studies show no clear relationship between tumor size and stage. Tumor stage is the most important prognostic determinant and efforts to increase the proportion of stage I cancers presenting for surgery can be shown to alter the natural history of the disease, by diagnosing it when it is still surgically curable.

Pathologic prognostic factors for gastrointestinal cancer.

Numerous clinicopathologic factors have been reported to have prognostic significance for gastrointestinal cancer. Many problems, however, confront the surgeon assessing the extent of disease and the clinical and molecular pathologist distinguishing differences in tumor differentiation, behavior, and defining important prognostic markers of cancer. This review assesses current pathologic prognostic variables of gastric and colorectal cancer that have been reported to influence survival.

Evaluation of pepsinogen A and gastrin-17 as markers of gastric cancer and high-risk pathologic conditions.

BACKGROUND: Gastric cancer remains a major cause of mortality and will remain so for the lifetime of current clinicians. Many cancers are diagnosed at a stage when current therapy cannot provide the hope of cure. A method for early detection of gastric cancer which can be widely applied is needed. The serum levels of pepsinogen A and gastrin-17 have been shown to vary in the presence of pathologic conditions of the gastric mucosa and may provide such a tool. METHODS: Serum samples were obtained from 432 patients undergoing endoscopy for undiagnosed dyspepsia. The levels of pepsinogen I and gastrin-17 were estimated by radioimmunoassay and compared with the final diagnosis. Discriminant analysis was performed to assess the value of the peptides predicting the presence of gastric cancer and the high-risk mucosal changes. RESULTS: Abnormal levels of gastrin-17 or pepsinogen A were found in 60% of patients with gastric cancer and 60% of those with one of the high-risk mucosal changes, the latter figure rising to 75% when the changes were in the upper third of the stomach. Discriminant analysis showed the log of gastrin-17 and log of pepsinogen A to be the best predictors of the high-risk mucosal changes, gastric cancer, and benign disease. CONCLUSIONS: These results confirm gastrin-17 and pepsinogen A as markers of pathologic gastric conditions and suggest that these peptides are potential screening tools worthy of further assessment.