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.

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.

Expression of proliferating cell nuclear antigen (PCNA) in gastric carcinoma: no evidence for prognostic value.

It has been proposed that immunostaining with PC10, a monoclonal antibody against proliferating cell nuclear antigen (PCNA), is of prognostic value in gastric carcinoma. Gastric carcinomas from a series of 90 patients in whom survival data were known have been studied. There was no relation between the degree of PC10 immunostaining assessed semiquantitatively and survival.

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.

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.

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.

Paraoesophageal hiatus hernia: surgery for all ages.

The results of surgery for paraoesophageal hiatus hernia over a 10-year period have been studied. From a group of 26 symptomatic patients, elective repair has been undertaken in 20 (mean age of 65.6 years) and emergency repair in four (mean age of 73.1 years). Emergency surgery was associated with a fivefold increase in mortality, and anatomical repair gave a satisfactory result in 90% (CI 77-100) of survivors. Surgical treatment should be considered for all symptomatic patients with paraoesophageal hiatus hernia.

Blood transfusion: an overused resource in colorectal cancer surgery.

The use of blood transfusion was examined in 476 patients who underwent curative surgery for large bowel cancer. Of these patients, 128 were not transfused while 348 received a total of 1174 units of blood. A patient was considered over-transfused if the predischarge haemoglobin was more than 12 g/dl. Using this criteria and accepting that single unit transfusions should be avoided, transfusion could have been avoided in 30% of the patients and a total of 377 units were given unnecessarily. Major under-transfusion did not occur; no patient being discharged with a haemoglobin of less than 9 g/dl. This study shows that blood transfusion is overused and the reasons for its use rarely recorded. In view of the morbidity related to transfusion, it is suggested that surgeons and anaesthetists reappraise their transfusion policy and the first step in this must be to record the reason for transfusion.

Early detection of gastric cancer.

OBJECTIVE: To see whether investigation of dyspeptic patients aged over 40 after their first consultation with the general practitioner would increase the proportions with early and operable gastric cancers. DESIGN: Prospective study of gastric cancer in dyspeptic patients aged over 40 from a defined population. SETTING: 10 General practices (six in central Birmingham, four in Sandwell); the Queen Elizabeth Hospital, Birmingham; and Sandwell District General Hospital. PATIENTS: 2659 Patients aged 40 or over referred with dyspepsia. MAIN OUTCOME MEASURE: Increase in early and operable gastric cancers detected in middle aged patients with dyspepsia. RESULTS: Disease was identified in 1992 patients (75%). Fifty seven were found to have gastric cancer, 36 being treated by potentially curative resection, including 15 with early cancer. CONCLUSIONS: The investigation of dyspeptic patients over 40 at first attendance can increase the proportion of early gastric cancers detected to 26% and the proportion of operable cases to 63%. Such a policy has the potential to reduce mortality from gastric cancer in the population.

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.

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.

Adjuvant chemotherapy in operable gastric cancer. 5 year follow-up of first British Stomach Cancer Group trial.

411 patients were entered into a prospective, randomised controlled trial of adjuvant chemotherapy after gastrectomy for adenocarcinoma. After a follow-up of at least 5 1/2 years there has been no survival advantage for those receiving adjuvant 5-fluorouracil and mitomycin C with or without an induction course of 5-fluorouracil, vincristine, cyclophosphamide, and methotrexate compared with those undergoing surgery only. There have been 366 deaths, including 22 from treatment-related conditions. A multivariate analysis of prognostic factors demonstrated that stage of disease, nodal and resection margin involvement, and the presence of residual disease are significant determinants of survival. Weight loss before surgery had a significant independent influence on survival. The combination of preoperative symptoms and intraoperative findings may be used to select patients for radical or palliative procedures.

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.

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.

Resection-line involvement in gastric cancer: a continuing problem.

Surgeons are aware of the adverse effect that resection-line disease has on anastomotic leakage, perioperative mortality and long-term survival. In an attempt to assess the effect of this knowledge on surgical practice, patients entered into the second British Stomach Cancer Group adjuvant therapy trial were studied. The presence of resection-line disease was compared with the operative stage. Of 555 patients for whom complete data were available, resection-line disease was present in 105 (19 per cent). Of 424 patients undergoing what the surgeon considered to be a potentially curative operation, 55 (13 per cent) had involvement of one or both resection lines, rendering the surgery palliative. Only 9 per cent of patients with stage I-III disease and resection-line involvement survived beyond 5 years, compared with 27 per cent of those with clear lines. Despite knowledge of the adverse effects of resection-line disease, surgeons continue to perform inadequate resections. This demonstrates the need for a more aggressive approach to assessment of resection margins at operation.

A controlled, prospective, randomised trial of adjuvant chemotherapy or radiotherapy in resectable gastric cancer: interim report. British Stomach Cancer Group.

A prospective, randomised controlled trial of surgery, surgery with adjuvant radiotherapy and surgery with adjuvant chemotherapy (5-fluorouracil, adriamycin and mitomycin C) in operable gastric cancer is described. Four hundred and thirty-six patients were randomly allocated to one of three treatment groups. With 12 months' minimum follow-up, 334 patients have died, 292 from recurrent cancer. The median survival for all patients was 15 months. Neither form of adjuvant therapy provides any survival advantage. Surgery remains the principal treatment for operable gastric cancer. Care should be taken to standardise surgical treatment and any adjuvant treatments must be compared within the confines of controlled, randomised trials.

Palliative surgery for gastric cancer.

Most patients with gastric carcinoma have a disease that is too advanced for radical surgery. A Review was made of 13,175 cases of gastric carcinoma registered at the Birmingham Cancer Registry during the period of 1960-1969. Of the patients, 79.6% had disease that was not radically resected, and few of these patients survived to 2 years. Those who had a palliative resection or bypass had the lowest 30-day mortality rate when compared to all other palliative measures (P less than 0.001). Furthermore, palliative resection gave the best survival in the presence of both locally advanced and metastatic disease (P less than 0.001). This suggests that the best palliative procedure for those with a disease unsuitable for radical surgery is a resection.

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.