Breast Angiosarcoma Surveillance Study: UK national audit of management and outcomes of angiosarcoma of the breast and chest wall.

BACKGROUND: Breast angiosarcomas are rare tumours of vascular origin. Secondary angiosarcoma occurs following radiotherapy for breast cancer. Angiosarcomas have high recurrence and poor survival rates. This is concerning owing to the increasing use of adjuvant radiotherapy for the treatment of invasive breast cancer and ductal cancer in situ (DCIS), which could explain the rising incidence of angiosarcoma. Outcome data are limited and provide a poor evidence base for treatment. This paper presents a national, trainee-led, retrospective, multicentre study of a large angiosarcoma cohort. METHODS: Data for patients with a diagnosis of breast/chest wall angiosarcoma between 2000 and 2015 were collected retrospectively from 15 centres. RESULTS: The cohort included 183 patients with 34 primary and 149 secondary angiosarcomas. Median latency from breast cancer to secondary angiosarcoma was 6 years. Only 78.9 per cent of patients were discussed at a sarcoma multidisciplinary team meeting. Rates of recurrence were high with 14 of 28 (50 per cent ) recurrences in patients with primary and 80 of 124 (64.5 per cent ) in those with secondary angiosarcoma at 5 years. Many patients had multiple recurrences: total of 94 recurrences in 162 patients (58.0 per cent). Median survival was 5 (range 0-16) years for patients with primary and 5 (0-15) years for those with secondary angiosarcoma. Development of secondary angiosarcoma had a negative impact on predicted breast cancer survival, with a median 10-year PREDICT prognostic rate of 69.6 per cent, compared with 54.0 per cent in the observed cohort. CONCLUSION: A detrimental impact of secondary angiosarcoma on breast cancer survival has been demonstrated. Although not statistically significant, almost all excess deaths were attributable to angiosarcoma. The increased use of adjuvant radiotherapy to treat low-risk breast cancer and DCIS is a cause for concern and warrants further study.

The sensitivity of needle core biopsy in combination with other investigations for the diagnosis of phyllodes tumours of the breast.

BACKGROUND: The sensitivity of needle-core biopsy (NCB) in diagnosing phyllodes tumours has only been addressed by a handful of small studies. The aim of this study was to analyse the sensitivity of NCB in the diagnosis of phyllodes tumours and to compare this to the sensitivity of other commonly performed investigations. A secondary aim was to assess the effect of various patient and disease factors on the rate of false negative test results. METHODS: Pathology databases were interrogated to identify all patients with the SNOMED term M-9020 or the word phyllodes in specimen reports. Excisional specimen reports were matched to prior FNAC reports, NCB reports and imaging reports. RESULTS: Ninety-one patients had a confirmed phyllodes tumour on excision. The sensitivity of FNAC, NCB and imaging for diagnosing phyllodes tumours was 40%, 63% and 65% respectively. The sensitivity of imaging and NCB was greater for borderline and malignant lesions. Combining cytohistological and radiological tests improved sensitivity to 76%. A younger age was associated with a greater false negative rate for all tests. Borderline and malignant phyllodes tumours were significantly associated with advancing age and greater lesion size on imaging and histology. CONCLUSIONS: This is the largest report to date assessing the sensitivity of NCB in the diagnosis of phyllodes tumours. Increased sensitivity in the diagnosis of phyllodes tumours can be achieved by combining cytohistological and radiological test results. The novel association between younger age and false negative results warrants further investigation. The most likely explanation is a reluctance to diagnose phyllodes tumours in young women given the increased prevalence of cellular fibroadenomas in this age group.

Oesophageal adenocarcinoma is associated with a deregulation in the MYC/MAX/MAD network.

Oesophageal adenocarcinoma, which arises from an acquired columnar lesion, Barrett's metaplasia, is rising in incidence more rapidly than any other cancer in the Western world. Elevated expression of c-MYC has been demonstrated in oesophageal adenocarcinoma; however, the expression of other members of the MYC/MAX/MAD network has not been addressed. The aims of this work were to characterise the expression of c-MYC, MAX and the MAD family in adenocarcinoma development and assess the effects of overexpression on cellular behaviour. mRNA expression in samples of Barrett's metaplasia and oesophageal adenocarcinoma were examined by qRT-PCR. Semi-quantitative immunohistochemistry and western blotting were used to examine cellular localisation and protein levels. Cellular proliferation and mRNA expression were determined in SEG1 cells overexpressing c-MYCER or MAD1 using a bromodeoxyuridine assay and qRT-PCR, respectively. Consistent with previous work expression of c-MYC was deregulated in oesophageal adenocarcinoma. Paradoxically, increased expression of putative c-MYC antagonists MAD1 and MXI1 was observed in tumour specimens. Overexpression of c-MYC and MAD proteins in SEG1 cells resulted in differential expression of MYC/MAX/MAD network members and reciprocal changes in proliferation. In conclusion, the expression patterns of c-MYC, MAX and the MAD family were shown to be deregulated in the oesophageal cancer model.

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.

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.

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.

Subphrenic abscess caused by gallstones "lost" at laparoscopic cholecystectomy one year previously: management by minimally invasive techniques.

Gallstones lost into the peritoneal cavity rarely cause symptoms. This case report describes the development of a subphrenic abscess 1 year after laparoscopic cholecystectomy due to lost gallstones, and it's management by the adaptation of routine urological minimally invasive techniques.

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.

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.

The second British Stomach Cancer Group trial of adjuvant radiotherapy or chemotherapy in resectable gastric cancer: five-year follow-up.

The overall survival in patients with gastric cancer is low, even among those undergoing resection. It has been hoped that the development of adjuvant therapy might improve survival in patients following surgery when tumour burden was minimal and both chemotherapy and radiotherapy have been proposed as suitable for use in gastric cancer. Their value has been evaluated by the British Stomach Cancer Group Second adjuvant therapy trial. 436 patients entered a prospective, randomised, controlled trial of adjuvant radiotherapy or cytotoxic chemotherapy with mitomycin, doxorubicin, and fluorouracil after gastrectomy for adenocarcinoma. After at least 5 years, there have been 372 deaths of which 7 were due to surgical complications and 327 from recurrent cancer. Following stratified randomisation, 145 patients were allocated to surgery alone, 153 to receive adjuvant radiotherapy, and 138 to adjuvant combination chemotherapy. The overall 2-year and 5-year survival were 33% (95% confidence interval 31-35%) and 17% (13-21%). No survival advantage has been shown for those patients receiving either adjuvant therapy compared to those undergoing surgery alone. The 5-year survival for surgery alone was 20%, for surgery plus radiotherapy 12%, and for surgery plus chemotherapy 19%. Surgery, therefore, remains the standard treatment for this condition and the use of adjuvant treatments should be restricted to controlled trials.